niryuu/sni-each-converted huggingface dataset:
Toll-like receptors (TLRs) are sentinel receptors of the host innate immune system that recognize conserved 'pathogen-associated molecular patterns' of invading microbes, including viruses. The activation of TLRs establishes antiviral innate immune responses and coordinates the development of long-lasting adaptive immunity in order to control viral pathogenesis. However, microbe-induced damage to host tissues may release 'danger-associated molecular patterns' that also activate TLRs, leading to an overexuberant inflammatory response and, ultimately, to tissue damage. Thus, TLRs have proven to be promising targets as therapeutics for the treatment of viral infections that result in inflammatory damage or as adjuvants in order to enhance the efficacy of vaccines. Here, we explore recent advances in TLR biology with a focus on novel drugs that target TLRs (agonists and antagonists) for antiviral therapy.
Output: Novel drugs targeting Toll-like receptors for antiviral therapy
Aims: This paper aims to summarise the growing literature concerning an imminent future influenza pandemic, from the primary care perspective. Methods: Sources of literature were scanned and relevant material short-listed for further study from: (1) WHO and CDC websites; (2) PUBMED; and (3) papers mentioned in references of full-text papers. Results: Outbreaks of avian influenza in Asia and elsewhere indicate that the world may be moving towards a pandemic influenza outbreak. The WHO Global Influenza Preparedness Plan 2005 unifies the world with the vision of tackling the next pandemic influenza outbreak as a global effort that includes healthcare provider and patient alike. Conclusions: We need to update ourselves and keep our staff and patients informed to make infection control measures part of our daily activities. In areas where there are contacts with animal reservoirs of influenza A, patients need to be reminded that they need to protect themselves from being infected.
Output: The pandemic influenza threat: a review from the primary care perspective
Background: Hepatitis C virus is a major cause of chronic liver diseases which can lead to permanent liver damage, hepatocellular carcinoma and death. The presently available treatment with interferon plus ribavirin, has limited benefits due to adverse side effects such as anemia, depression, fatigue, and "flu-like" symptoms. Herbal plants have been used for centuries against different diseases including viral diseases and have become a major source of new compounds to treat bacterial and viral diseases. Material: The present study was design to study the antiviral effect of Glycyrrhizin (GL) against HCV. For this purpose, HCV infected liver cells were treated with GL at non toxic doses and HCV titer was measured by Quantitative real time RT-PCR. Our results demonstrated that GL inhibit HCV titer in a dose dependent manner and resulted in 50% reduction of HCV at a concentration of 14 ± 2 μg. Comparative studies were made with interferon alpha to investigate synergistic effects, if any, between antiviral compound and interferon alpha 2a. Our data showed that GL exhibited synergistic effect when combined with interferon. Moreover, these results were verified by transiently transfecting the liver cells with HCV 3a core plasmid. The results proved that GL dose dependently inhibit the expression of HCV 3a core gene both at mRNA and protein levels while the GAPDH remained constant. Our results suggest that GL inhibit HCV full length viral particles and HCV core gene expression or function in a dose dependent manner and had synergistic effect with interferon. In future, GL along with interferon will be better option to treat HCV infection.
Output: Glycyrrhizin as antiviral agent against Hepatitis C Virus
An exacerbated immune response is one of the main causes of influenza-induced lung damage during infection. The molecular mechanisms regulating the fate of the initial immune response to infection, either as a protective response or as detrimental immunopathology, are not well understood. The purinergic receptor P2X7 is an ionotropic nucleotide-gated ion channel receptor expressed on immune cells that has been implicated in induction and maintenance of excessive inflammation. Here, we analyze the role of this receptor in a mouse model of influenza virus infection using a receptor knockout (KO) mouse strain. Our results demonstrate that the absence of the P2X7 receptor results in a better outcome to influenza virus infection characterized by reduced weight loss and increased survival upon experimental influenza challenge compared to wild-type mice. This effect was not virus strain specific. Overall lung pathology and apoptosis were reduced in virusinfected KO mice. Production of proinflammatory cytokines and chemokines such as interleukin-10 (IL-10), gamma interferon (IFN-␥), and CC chemokine ligand 2 (CCL2) was also reduced in the lungs of the infected KO mice. Infiltration of neutrophils and depletion of CD11b ϩ macrophages, characteristic of severe influenza virus infection in mice, were lower in the KO animals. Together, these results demonstrate that activation of the P2X7 receptor is involved in the exacerbated immune response observed during influenza virus infection. IMPORTANCE A hallmark of influenza virus infection is the development of lung pathology induced by an exacerbated immune response. The mechanisms shared by the antiviral host defense required for viral clearance and those required for development of immunopathology are not clearly understood. Purinergic receptors, and in particular the purinergic receptor P2X7 (P2X7r), are involved in activation of the immune response. We used mice lacking the P2X7r (P2X7r KO mice) to better understand the mechanisms that lead to development of lung pathology during influenza virus infection. In our studies, we observed that P2X7r KO mice developed less lung immunopathology and had better survival than the wild-type mice. These results implicate P2X7r in the induction of an exacerbated local immune response to influenza virus and help us to better understand the mechanisms leading to the lung immunopathology observed during severe viral infections. Citation Leyva-Grado VH, Ermler ME, Schotsaert M, Gonzalez MG, Gillespie V, Lim JK, García-Sastre A. 2017. Contribution of the purinergic receptor P2X7 to development of lung immunopathology during influenza virus infection. mBio 8:e00229-17. https://doi.
Output: Contribution of the Purinergic Receptor P2X7 to Development of Lung Immunopathology during Influenza Virus Infection
Motivation: Deep sequencing of clinical samples is now an established tool for the detection of infectious pathogens, with direct medical applications. The large amount of data generated produces an opportunity to detect species even at very low levels, provided that computational tools can effectively profile the relevant metagenomic communities. Data interpretation is complicated by the fact that short sequencing reads can match multiple organisms and by the lack of completeness of existing databases, in particular for viral pathogens. Here we present metaMix, a Bayesian mixture model framework for resolving complex metagenomic mixtures. We show that the use of parallel Monte Carlo Markov chains for the exploration of the species space enables the identification of the set of species most likely to contribute to the mixture. Results: We demonstrate the greater accuracy of metaMix compared with relevant methods, particularly for profiling complex communities consisting of several related species. We designed metaMix specifically for the analysis of deep transcriptome sequencing datasets, with a focus on viral pathogen detection; however, the principles are generally applicable to all types of metagenomic mixtures. Availability and implementation: metaMix is implemented as a user friendly R package, freely available on CRAN: http://cran.r-project.org/web/packages/metaMix Contact: sofia.morfopoulou.10@ucl.ac.uk Supplementary information: Supplementary data are available at Bionformatics online.
Output: Bayesian mixture analysis for metagenomic community profiling
A bacterial target-specific titanium oxide (TiO 2 ) photocatalyst was developed for the enhancement of selective inactivation of targeted bacteria. An antibacterial composition comprising TiO 2 particles immobilized with a bacterial-specific antibody having affinity to bacteria of interest was prepared via a carbodiimide hydrochloride/N-hydroxysulfosuccinimide (EDC/NHS) coupling reaction between polyacrylic acid (PAA) coated TiO 2 and an antibody. As a model case, an antibody to Escherichia coli was conjugated with the PAA-coated TiO 2 (TiO 2 -Ab E ). We evaluated the enhancement of the antibacterial effect of TiO 2 -Ab E against target E. coli, compared with its effect on other bacteria that lack affinity for the antibody used. The TiO 2 -Ab E inactivated approximately 90% of the E. coli at 15 min, whereas the raw TiO 2 inactivated approximately 20% of the E. coli after the same period of time under UV irradiation. The TiO 2 -Ab E did not show an enhanced antibacterial effect against non-target bacteria. We infer that close contact between TiO 2 particles and E. coli, as a result of the specificity of the antibody, can enhance the direct transfer of reactive oxygen species (ROS) generated by TiO 2 particles to the cellular surface under UV irradiation and result in rapid and efficient inactivation of the targeted bacteria. The strategy presented here will facilitate the combination of other receptors and TiO 2 particles for the preparation of highly selective and photocatalytic composites to prevent or remediate contamination by unwanted bacteria in a wide variety of natural and man-made systems.
Output: Bacterial target-specific photocatalyst for the enhancement of antibacterial property to targets
Regulations (IHR) aim to prevent, detect and respond to such threats, through increase in national public health core capacities, but whether IHR core capacity implementation is necessary and sufficient has been contested. With a longitudinal study we relate changes in national IHR core capacities to changes in cross-border infectious disease threat events (IDTE) between 2010 and 2016, collected through epidemic intelligence at the European Centre for Disease Prevention and Control (ECDC). By combining all IHR core capacities into one composite measure we found that a 10% increase in the mean of this composite IHR core capacity to be associated with a 19% decrease (p = 0.017) in the incidence of cross-border IDTE in the EU. With respect to specific IHR core capacities, an individual increase in national legislation, policy & financing; coordination and communication with relevant sectors; surveillance; response; preparedness; risk communication; human resource capacity; or laboratory capacity was associated with a significant decrease in cross-border IDTE incidence. In contrast, our analysis showed that IHR core capacities relating to point-of-entry, zoonotic events or food safety were not associated with IDTE in the EU. Due to high internal correlations between core capacities, we conducted a principal component analysis which confirmed a 20% decrease in risk of IDTE for every 10% increase in the core capacity score (95% CI: 0.73, 0.88). Globally (EU excluded), a 10% increase in the mean of all IHR core capacities combined was associated with a 14% decrease (p = 0.077) in cross-border IDTE incidence. We provide quantitative evidence that improvements in IHR core capacities at country-level are associated with fewer cross-border IDTE in the EU, which may also hold true for other parts of the world. epidemic, infectious diseases, International Health Regulations, outbreak, pandemic, threat events This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Output: Systemic resilience to cross-border infectious disease threat events in Europe
• The M2 protein of influenza A is a proton-gated proton channel that is required for viral replication • Current influenza strains are resistant to licensed M2 antivirals, so new therapies that target M2 are needed • The structure and function of M2, rise of drug resistance mutations, and current antiviral strategies are discussed The ongoing threat of seasonal and pandemic influenza to human health requires antivirals that can effectively supplement existing vaccination strategies. The M2 protein of influenza A virus (IAV) is a proton-gated, proton-selective ion channel that is required for virus replication and is an established antiviral target. While licensed adamantane-based M2 antivirals have been historically used, M2 mutations that confer major adamantane resistance are now so prevalent in circulating virus strains that these drugs are no longer recommended. Here we review the current understanding of IAV M2 structure and function, mechanisms of inhibition, the rise of drug resistance mutations, and ongoing efforts to develop new antivirals that target resistant forms of M2.
Output: Journal Pre-proof Put a cork in it: Plugging the M2 viral ion channel to sink influenza Put a cork in it: Plugging the M2 viral ion channel to sink influenza
In this paper, we represent a label-free biosensor based on immobilization of serum antibodies for rapid detection of viral antigens. Human serum containing specific antibodies against Japanese encephalitis virus (JEV) was immobilized on a silanized surface of an interdigitated sensor via protein A/glutaraldehyde for electrical detection of JEV antigens. The effective immobilization of serum antibodies on the sensor surface was verified by Fourier transform infrared spectrometry and fluorescence microscopy. The signal of the biosensor obtained by the differential voltage converted from the change into non-Faradic impedance resulting from the specific binding of JEV antigens on the surface of the sensor. The detection analyzed indicates that the detection range of this biosensor is 1-10 g/ml JEV antigens, with a detection limit of 0.75 g/ml and that stable signals are measured in about 20 min. This study presents a useful biosensor with a high selectivity for rapid and simple detection of JEV antigens, and it also proposes the biosensor as a future diagnostic tool for rapid and direct detection of viral antigens in clinical samples for preliminary pathogenic screenings in the case of possible outbreaks.
Output: A novel biosensor based on serum antibody immobilization for rapid detection of viral antigens
Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) as interaction partners of the CoV non-structural protein 1 (Nsp1). These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA) blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock. Citation: Pfefferle S, Schö pf J, Kö gl M, Friedel CC, Mü ller MA, et al. (2011) The SARS-Coronavirus-Host Interactome: Identification of Cyclophilins as Target for Pan-Coronavirus Inhibitors. PLoS Pathog 7(10): e1002331.
Output: The SARS-Coronavirus-Host Interactome: Identification of Cyclophilins as Target for Pan-Coronavirus Inhibitors
Background: Although allergic asthma is a complex area with many interacting factors involved, the 'hygiene hypothesis' proposes that a lack of exposure to infection during childhood may polarise the immune system towards allergen-reactive Th2-type responses in genetically susceptible individuals. Toll-like receptors (TLRs) play a key role within the innate immune system and TLR7 agonists have previously been shown to up-regulate Th1 responses and down-regulate Th2 responses to allergens in murine models of allergic or chronic asthma. This study aimed to examine the efficacy and safety of the novel TRL7 agonist AZD8848, which has been developed as an antedrug. Methods: In this double-blind, randomised, parallel-group study, AZD8848 60 μg or placebo was administered intranasally once-weekly for 8 weeks in patients with mild-to-moderate allergic asthma (NCT00999466). Efficacy assessments were performed at 1 and 4 weeks after the last dose. The primary outcome was the late asthmatic response (LAR) fall in forced expiratory volume in 1 s (FEV 1 ) after allergen challenge at 1-week post-treatment. Results: AZD8848 significantly reduced average LAR fall in FEV 1 by 27% vs. placebo at 1 week after treatment (p = 0.035). This effect was sustained at 4 weeks post-treatment; however, it did not reach clinical significance. AZD8848 reduced post-allergen challenge methacholine-induced airway hyper-responsiveness (AHR) vs. placebo at 1 week post-dosing (treatment ratio: 2.20, p = 0.024), with no effect at 4 weeks. There was no significant difference between the two groups in plasma cytokine, sputum Th2 cytokine or eosinophil responses post-allergen challenge at 1 week after treatment. The incidence of adverse events was similar in the two groups. AZD8848 was generally well tolerated. Conclusions and clinical relevance: In patients with allergic asthma, TLR7 agonists could potentially reduce allergen responsiveness by stimulating Type 1 interferon responses to down-regulate the dominant Th2 responses. Trial registration: clinicaltrials.gov identifier NCT00999466.
Output: Effects of the Toll-like receptor 7 (TLR7) agonist, AZD8848, on allergen-induced responses in patients with mild asthma: a double-blind, randomised, parallel-group study
Background: The outbreak of the 2019 novel coronavirus has attracted global attention. In the early stage of the outbreak, the most important question concerns some meaningful milepost moments, including (1) the time when the number of daily confirmed cases decreases, (2) the time when the number of daily confirmed cases becomes smaller than that of the daily removed (recovered and death), (3) the time when the number of daily confirmed cases becomes zero, and (4) the time when the number of patients treated in hospital is zero, which indicates the end of the epidemic. Intuitively, the former two can be regarded as two important turning points which indicate the alleviation of epidemic to some extent, while the latter two as two "zero" points, respectively. Unfortunately, it is extremely difficult to make right and precise prediction due to the limited amount of available data at a early stage of the outbreak. Method: To address it, in this paper, we propose a flexible framework incorporating the effectiveness of the government control to forecast the whole process of a new unknown infectious disease in its early-outbreak. Specially, we first establish the iconic indicators to characterize the extent of epidemic spread, yielding four periods of the whole process corresponding to the four meaningful milepost moments: two turning points and two "zero" points. Then we develop the tracking and forecasting procedure with mild and reasonable assumption. Finally we apply it to analyze and evaluate the COVID-19 using the public available data for mainland China beyond Hubei Province from the China Centers for Disease Control (CDC) during the period of Jan 29th, 2020, to Feb 29th, 2020, which shows the effectiveness of the proposed procedure. Results: Results show that our model can clearly outline the development of the epidemic at a very early stage. The first prediction results on Jan 29th reveal that the first and second milepost moments
Output: Tracking and forecasting milepost moments of the epidemic in the early-outbreak: framework and applications to the COVID-19
Bovine toroviruses (BToVs), belong to the subfamily Toroviridae within the family Coronaviridae, and are pathogens, causing enteric disease in cattle. In Japan, BToVs are distributed throughout the country and cause gastrointestinal infection of calves and cows. In the present study, complete genome sequences of two Japanese BToVs and partial genome sequences of two Japanese BToVs and one porcine torovirus (PToV) from distant regions in Japan were determined and genetic analyses were performed. Pairwise nucleotide comparison and phylogenetic analyses revealed that Japanese BToVs shared high identity with each other and showed high similarities with BToV Breda1 strain in S, M, and HE coding regions. Japanese BToVs showed high similarities with porcine toroviruses in ORF1a, ORF1b, and N coding regions and the 5′ and 3′ untranslated regions, suggestive of a natural recombination event. Recombination analyses mapped the putative recombinant breakpoints to the 3′ ends of the ORF1b and HE regions. These findings suggest that the interspecies recombinant nature of Japanese BToVs resulted in a closer relationship between BToV Breda1 and PToVs.
Output: Whole genome analysis of Japanese bovine toroviruses reveals natural recombination between porcine and bovine toroviruses
The major structural protein VP2 of porcine parvovirus (PPV) was used as the model parvovirus antigen, which has been expressed in Lactobacillus casei fusing with Escherichia coli heat-labile enterotoxin B subunit (LTB) as mucosal adjuvant. The VP2-LTB DNA fragment was cloned into vector pPG611 or pPG612 to generated inducible surface-displayed and secretion expression systems based on xylose promoter, designated as rLc:pPG611-VP2-LTB (recombinant L. casei) and rLc:pPG612-VP2-LTB, respectively. Expression of the fusion protein was verified by SDS-PAGE, Western blot immunofluorescence and electron microscopy. It was observed that the level of IgG or sIgA from mice orally immunized with VP2-LTB was higher than that from mice received VP2 and negative control, which demonstrated significantly statistically different. Especially, the titer of IgG or sIgA in mice immunized with rLc:pPG612-VP2-LTB is the highest in this study. In summary, LTB as mucosal adjuvant was able to effectively facilitate induction of mucosal and systemic immunity by L. casei-expressing VP2 fusion protein.
Output: Comparison of the immune responses induced by oral immunization of mice with Lactobacillus casei-expressing porcine parvovirus VP2 and VP2 fused to Escherichia coli heat-labile enterotoxin B subunit protein
Toona sinensis (TS), which is also known as Cedrela sinensis, belongs to Meliaceae family, the compounds identified from this TS leaves possess a wide range of biologic functions, such as hypoglycemic effects, anti-LDL glycative activity, antioxidant activities, and inhibition of sudden acute respiratory syndrome (SARS) coronavirus replication. However, their effect against cancer cells is not well explored. In this study, to understand the cytotoxic effect and molecular mechanism stimulated by TSL-1 (TS leaf extract fraction) we employed three different non-small-cell lung cancer (NSCLC) cell lines: H441 cells (lung adenocarcinoma), H661 cells (lung large cell carcinoma) and H520 cells (lung squamous cell carcinoma). IC50 value was varied between these three cell lines, the least IC 50 value was observed in TSL-1-treated H661cells. Exposure of NSCLC cells to TSL-1 caused cell-cycle arrest in subG1 phase and caused apoptosis. Moreover, TSL-1 treatment decreased the cell-cycle regulators; cyclin D1 and CDK4 proteins by up regulating p27 expression in a dosedependent manner. Thus, the TSL-1-induced apoptosis was further confirmed by cell morphology, subG1 peak accumulation, poly(adenosine diphosphate [ADP]ribose) polymerase (PARP) cleavage, propidium iodide (PI)-Annexin-V double staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The decreased Bcl2 protein level was concurrent with an increased Bax protein level in all 3 cell lines. Additionally, the tumoricidal effect of TSL-1 was measured using a xenograft model, after 5 weeks of TSL-1 treatment by various regimen caused regression of tumor. Taken together both these in vitro and in vivo studies revealed that TSL-1 is a potent inhibitor against NSCLC growth and our provoking result suggest that TSL-1 can be a better nutriceutical as a singlet or along withdoublet agents (taxane, vinorelbine, and gemcitabine) for treating NSCLC. (Translational Research 2010;155:305-314) Abbreviations: CDK ¼ cyclin-dependent kinase; ECL ¼ enhanced chemiluminescence; FACS ¼ fluorescence-activated cell sorting; FBS ¼ fetal bovine serum; IC 50 ¼ half maximal inhibitory concentration; MTT ¼ tetrazolium dye; NSCLC ¼ non-small-cell lung cancer; PARP ¼ poly(adenosine diphosphate [ADP]-ribose) polymerase; PBS ¼ phosphate-buffered saline; PI ¼ propidium iodide; SKOV3 ¼ human ovarian cancer cell; RT ¼ room temperature; TS ¼ Toona sinensis; TSL-1 ¼ TS leaf extract fraction-1; TUNEL ¼ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling
Output: Antiproliferative effect of Toona sinensis leaf extract on non-small-cell lung cancer
Influenza was detected in 308 of 1027 (30%) samples tested; influenza A in 157 (15.3%), influenza B in 149 (14.5%) and RSV in 28 (2.7%). When compared against Fast Track Diagnostics Respiratory Pathogens 21 multiplex polymerase chain reaction and Cepheid Xpert Xpress Flu/RSV assay, Liat performance for the detection of influenza A or B was: sensitivity 85% [95% confidence interval (CI) 76e92)], specificity 98% (95% CI 97e99), negative predictive value 94% (95% CI 92e96) and positive predictive value 95% (95% CI 91e97). ª
Output: Implementation of the cobas Liat influenza point-of-care test into an emergency department during a high-incidence season: a retrospective evaluation following real-world implementation The cobas Liat influenza A/B and respiratory syncytial virus (RSV) assay (Liat) was used in the adult emergency department of a large London hospital from 21 st
It is well known that piglets congenitally infected with porcine reproductive and respiratory syndrome virus (PRRSV) can be viremic at birth, and that preweaning mortality due to secondary infections often increases during acute outbreaks of PRRS. Therefore, an immunosuppressive effect of in utero infection has been suggested. The aim of the present study was to characterise the changes of leukocyte populations in piglets surviving in utero infection with PRRSV. A total of 27 liveborn uninfected control piglets and 22 piglets infected transplacentally with a Danish strain of PRRSV were included. At 2 and 4 weeks of age, 21 of 22 (96%) and 7 of 14 (50%) examined infected piglets were still viremic, whereas PRRSV could not be detected in the six infected piglets examined at 6 weeks of age. Flow cytometry analysis was used to determine the phenotypic composition of leukocytes in peripheral blood and bronchoalveolar lavage fluid (BALF) of 2-, 4-and 6-week-old infected piglets and age-matched uninfected controls. The key observation in the present study is that high levels of CD8 þ cells constitute a dominant feature in peripheral blood and BALF of piglets surviving in utero infection with PRRSV. In BALF, the average high level of CD8 þ cells in 2-week-old infected piglets (33:4 AE 12:6%) was followed by a decline to 7:3 AE 3:0 and 11:1 AE 3:0% at 4 and 6 weeks of age. BALF of control piglets contained 1:6 AE 0:9, 2:3 AE 1:8 and 1:9 AE 0:5% CD8 þ cells, only. In peripheral blood, however, the average number of CD8 þ cells remained at high levels in the infected piglets throughout the post-natal experimental period (2:8 AE 1:9, 2:9 AE 1:8 and 3:2 AE 1:7 Â 10 6 CD8 þ cells/ml at 2, 4 and 6 weeks, respectively). In the controls, the average levels of CD8 þ cells were 0:9 AE 0:2, 1:9 AE 1:7 and 1:6 AE 0:5 Â 10 6 /ml, respectively. Furthermore, the numbers of CD2 þ , CD4 þ CD8 þ and SLA-classII þ cells, respectively, in peripheral blood, together with the levels of CD2 þ and CD3 þ cells in BALF were increased in the infected piglets infected in utero compared to the uninfected controls. Veterinary Immunology and Immunopathology 93 (2003) 135-151 Abbreviations: SLA, swine leukocyte antigen; FSC, forward light scattering; SSC, side light scattering; BALF, bronchoalveolar lavage fluid; PPAM, porcine pulmonary alveolar macrophages; WBC, white blood cells; CD, cluster of differentiation The kinetic analyses carried out in the present study reflect that in utero infection with PRRSV modulates immune cell populations in peripheral blood and BALF of surviving piglets. The observed changes are characterised by high levels of CD8 þ cells supporting an important role of these cells in PRRSV infection. The present results, however, do not support the existence of post-natal immunosuppression following in utero infection with PRRSV. #
Output: In utero infection with porcine reproductive and respiratory syndrome virus modulates leukocyte subpopulations in peripheral blood and bronchoalveolar fluid of surviving piglets
Background: Respiratory tract infections (RTIs) are a major morbidity factor contributing largely to health care costs and individual quality of life. The aim of the study was to test whether obesity (BMI ≥ 30 kg/m 2 ) is one of the risk factors underlying frequent RTIs in the German adult population. Methods: We recruited 1455 individuals between 18 to 70 years from a cross-sectional survey on airway infections in Germany and invited them to self-report in diaries incident RTIs experienced during three consecutive winter/ spring seasons. RTIs reported in these 18 months and summary measures adding-up individual RTIs were the outcomes of interest. Results: Compared to individuals with normal weight, obese individuals reported a consistently higher frequency of upper and lower RTIs and predominantly fell in the upper 10% group of a diary sumscore adding-up 10 different RTI symptoms over time. Obesity was associated both with lower RTIs ( adjusted OR = 2.02, 95%CI = 1.36-3.00) and upper RTIs ( adjusted OR = 1.55, 95%CI = 1.22-1.96). Adjusting for demographic and lifestyle variables did only marginally affect ORs. Stratified analyses suggested a stronger association for women and effect modifications by sports activity and dietary habits. We confirm the association of obesity with infection burden and present evidence for putative interaction with sports activity and dietary patterns.
Output: Obesity and risk of respiratory tract infections: results of an infection-diary based cohort study
Although border quarantine is included in many influenza pandemic plans, detailed guidelines have yet to be formulated, including considerations for the optimal quarantine length. Motivated by the situation of small island nations, which will probably experience the introduction of pandemic influenza via just one airport, we examined the potential effectiveness of quarantine as a border control measure. Analysing the detailed epidemiologic characteristics of influenza, the effectiveness of quarantine at the borders of islands was modelled as the relative reduction of the risk of releasing infectious individuals into the community, explicitly accounting for the presence of asymptomatic infected individuals. The potential benefit of adding the use of rapid diagnostic testing to the quarantine process was also considered. We predict that 95% and 99% effectiveness in preventing the release of infectious individuals into the community could be achieved with quarantine periods of longer than 4.7 and 8.6 days, respectively. If rapid diagnostic testing is combined with quarantine, the lengths of quarantine to achieve 95% and 99% effectiveness could be shortened to 2.6 and 5.7 days, respectively. Sensitivity analysis revealed that quarantine alone for 8.7 days or quarantine for 5.7 days combined with using rapid diagnostic testing could prevent secondary transmissions caused by the released infectious individuals for a plausible range of prevalence at the source country (up to 10%) and for a modest number of incoming travellers (up to 8000 individuals). Conclusion: Quarantine at the borders of island nations could contribute substantially to preventing the arrival of pandemic influenza (or at least delaying the arrival date). For small island nations we recommend consideration of quarantine alone for 9 days or quarantine for 6 days combined with using rapid diagnostic testing (if available).
Output: BMC Infectious Diseases Quarantine for pandemic influenza control at the borders of small island nations
Suspensions of transmissible gastroenteritis virus (TGEV), a porcine coronavirus, were nebulized at rates of 0.1-0.2 ml/min into moving air using a Collison nebulizer or a plastic medical nebulizer operating at pressures ranging from 7 to 15 psi. The airborne viruses were collected on heating, ventilating, and air conditioning (HVAC) filters in an experimental apparatus and also sampled upstream of these test filters using AGI-30 and BioSampler impinger samplers. To study the effects of relative humidity (RH) on TGEV collection by the filters and samplers, the virus was nebulized into air at 30, 50, 70, and 90% RH. There were no significant changes in virus titer in the nebulizer suspension before and after nebulization for either nebulizer at any of the pressures utilized. Aerosolization efficiency -the ratio of viable virus sampled with impingers to the quantity of viable virus nebulizeddecreased with increasing humidity. BioSamplers detected more airborne virus than AGI-30 samplers at all RH levels. This difference was statistically significant at 30 and 50% RH. Nebulizer type and pressure did not significantly affect the viability of the airborne virus. Virus recovery from test filters relative to the concentration of virus in the nebulizer suspension was less than 10%. The most and the least virus were recovered from filter media at 30% and 90% RH, respectively. The results suggest that TGEV, and perhaps other coronaviruses, remain viable longer in an airborne state and are sampled more effectively at low RH than at high humidity.
Output: Effects of humidity and other factors on the generation and sampling of a coronavirus aerosol
A newly identified novel coronavirus (2019-nCoV) has caused numerous acute respiratory syndrome cases in Wuhan China from December 2019 to Feb 2020. Its fast spreading to other provinces in China and overseas is very likely causing a pandemic. Since the novel coronavirus has been reported to be capable of endangering thousands of lives, it is extremely important to find out how the coronavirus is transmitted in human organs. Apart from fever and respiratory complications, gastrointestinal symptoms are observed in some patients with 2019-nCoV but the significance remains undetermined. The cell receptor angiotensin covering enzyme II (ACE2), which is the major receptor of SARS-nCoV, has been reported to be a cellular entry receptor of 2019-nCoV as well. Here, to more precisely explore the potential pathogen transmission route of the 2019-nCoV infections in the gastrointestinal tract, we analyzed the ACE2 RNA expression profile in the colon tissue of healthy adults and colorectal cancer patients of our cohort and other databases. The data indicates that ACE2 is mainly expressed in epithelial cells of the colon. The expression of ACE2 is gradually increased from healthy control, adenoma to colorectal cancer patients in our cohort as well as in the external Asian datasets. According to the expression profile of ACE2 in colon epithelial cells, we speculate adenoma and colorectal cancer patients are more likely to be infected with 2019-nCoV than healthy people. Our data may provide a theoretical basis for the classification and management of future 2019-nCoV susceptibility people in clinical application.
Output: Profiling ACE2 expression in colon tissue of healthy adults and colorectal cancer patients by single-cell transcriptome analysis
The shift of wildlife trade from brick-and-mortar markets to virtual online marketplaces is reported 8 ). We compared information on asking 12 prices and what species were traded using two comparative approaches to analyze how species 13 composition may have changed over time (physical markets and online platforms; pre-Internet and 14 Internet era). In comparison to the five previous market surveys, we did not find a statistically 15 significant difference between species and availability of species offered for sale when comparing 16 physical birds market and online markets. In all datasets biological factors such as wingspan were 17 significant factors in explaining price variation. We conclude that sustained monitoring is needed to 18 make direct comparisons between the trade platforms. With a continued increase of wildlife trade on 19 online platforms, we recommend increased regulation and enforcement of wildlife trade laws. 20 21 42 challenges in making direct comparisons between physical markets and online platforms range from 43 disjointed time periods, nuanced social differences in consumer buying behaviour, as well as 44 differences in survey methods and efforts. Nijman et al (2019) directly compared open animal 45 markets and online markets in trade of wild cats and revealed that there is indeed a directional shift of 46 trade towards online platforms but this differs generally between countries. An increased presence of 47 enforcement agencies in many traditional markets may have also contributed to the shift, however, the 48 rate of change occurs at varying degrees dependent on factors such as geographic location and 49 infrastructure limitations. 65 This poses a threat to wild populations. A recent analysis of the global raptor trade from 1975 to 2015 66 revealed that though current legal commercial trade seems to not pose large conservation concern, 67 there remains a lack of quantifiable evidence on the extent and impact of unregulated trade (Panter et
Output: Journal Pre-proof Wildlife trade shifts from brick-and-mortar markets to virtual marketplaces: A case study of birds of prey trade in Thailand Wildlife trade shifts from brick-and-mortar markets to virtual marketplaces: A case study of 1 birds of prey trade in Thailand 2
This is an extensive review on epiphytic plants that have been used traditionally as medicines. It provides information on 185 epiphytes and their traditional medicinal uses, regions where Indigenous people use the plants, parts of the plants used as medicines and their preparation, and their reported phytochemical properties and pharmacological properties aligned with their traditional uses. These epiphytic medicinal plants are able to produce a range of secondary metabolites, including alkaloids, and a total of 842 phytochemicals have been identified to date. As many as 71 epiphytic medicinal plants were studied for their biological activities, showing promising pharmacological activities, including as anti-inflammatory, antimicrobial, and anticancer agents. There are several species that were not investigated for their activities and are worthy of exploration. These epipythes have the potential to furnish drug lead compounds, especially for treating cancers, and thus warrant indepth investigations.
Output: biomolecules Vascular Epiphytic Medicinal Plants as Sources of Therapeutic Agents: Their Ethnopharmacological Uses, Chemical Composition, and Biological Activities
Radix of Isatis indigotica (indigowood root, IR) has been used in traditional medicine for its potential anti-inflammatory effect. The purpose of this study is to investigate the radioprotective effects of radiation caused damages in hematopoietic system and normal tissues in mice. A total of 57 BALB/c mice were randomized into six treatment groups: control, IR treatment (0.195, 0.585 and 1.170 g/kg, p.o. daily), L-glutamine (0.520 g/kg) and sham group. All mice except the sham group were irradiated and then administered for one week. The radioprotective effect on hematopoietic system, serum cytokines, and intestinal toxicity was studied. Protective effects on spleen and thymus are found in IR-treated groups. IR assisted in restoration of leukocytopenia after whole mice irradiation with significant reduction of serum TNF-a, IL-1b, and IL-6. These enhancements of hematopoietic effects are due to an increase in the serum G-CSF concentration in IR treated groups. In histopathological assessment, significant improvement of intestine toxicity is observed in high-dose IR and L-glutamine group. Evidences show that IR has potentials to be a radioprotector, especially in recovery of hematopoietic system, reduction of inflammatory cytokines and intestinal toxicity. Indirubin may play a crucial role, but the underlying mechanism is not very clear and warrants further studies.
Output: Indigowood root extract protects hematopoietic cells, reduces tissue damage and modulates inflammatory cytokines after total-body irradiation: Does Indirubin play a role in radioprotection?
The purposes of this study were to determine if the successful treatment of bovine respiratory disease (BRD) in suckling calves was associated with a long-term increase in mean pulmonary arterial pressure (mPAP) and, to screen for associations between blood leukogram variables and mPAP. A cohort of Red Angus calves (n = 74) were followed from birth to weaning at an altitude of 975 m. Calves were weaned at 172 ± 14 d when their mPAP was measured and whole blood collected. Thirty calves that had been treated for BRD (34 to 45 d prior) and 30 calves that had not required treatment for BRD were sampled. Treatment for BRD had no effect on mPAP (P = 0.37). Mean mPAP was 48 ± 8 mm Hg (± SD) with a minimum of 34 mm Hg and a maximum at 69 mm Hg. Weaning weight and sex tended to be associated with mPAP, but they explained just 5% of the variation in mPAP (P = 0.08; Adj. r 2 = 0.05). Fibrinogen (P = 0.008) and absolute lymphocyte count (P = 0.06) were negatively associated with mPAP, whereas absolute monocyte count was positively associated with mPAP (P = 0.01). The findings of this study suggest that pre-weaning treatment for BRD does not increase a calves' post-weaning risk of congestive right heart failure. Further, components of the immune and acute phase response system may play a role in the development and progression of pulmonary hypertension.
Output: Successful treatment of suckling Red Angus calves for bovine respiratory disease is not associated with increased mean pulmonary arterial pressures at weaning
In Infectious salmon anaemia virus (ISAV), deletions in the highly polymorphic region (HPR) in the near membrane domain of the haemagglutinin-esterase (HE) stalk, influence viral fusion. It is suspected that selected mutations in the associated Fusion (F) protein may also be important in regulating fusion activity. To better understand the underlying mechanisms involved in ISAV fusion, several mutated F proteins were generated from the Scottish Nevis and Norwegian SK779/06 HPR0. Co-transfection with constructs encoding HE and F were performed, fusion activity assessed by content mixing assay and the degree of proteolytic cleavage by western blot. Substitutions in Nevis F demonstrated that K276 was the most likely cleavage site in the protein. Furthermore, amino acid substitutions at three sites and two insertions, all slightly upstream of K276, increased fusion activity. Co-expression with HE harbouring a full-length HPR produced high fusion activities when trypsin and low pH were applied. In comparison, under normal culture conditions, groups containing a mutated HE with an HPR deletion were able to generate moderate fusion levels, while those with a full length HPR HE could not induce fusion. This suggested that HPR length may influence how the HE primes the F protein and promotes fusion activation by an ubiquitous host protease and/or facilitate subsequent post-cleavage refolding steps. Variations in fusion activity through accumulated mutations on surface glycoproteins have also been reported in other orthomyxoviruses and paramyxoviruses. This may in part contribute to the different virulence and tissue tropism reported for HPR0 and HPR deleted ISAV genotypes.
Output: Dual Mutation Events in the Haemagglutinin- Esterase and Fusion Protein from an Infectious Salmon Anaemia Virus HPR0 Genotype Promote Viral Fusion and Activation by an Ubiquitous Host Protease
The structural and intracellular proteins of the murine hepatitis viruses MHV-JHM and MHV-A59 were studied by tryptic peptide mapping. The results demonstrated that the virions contained three distinct proteins: the two related chains of the E2 complex, the nucleocapsid protein and the heterogeneous E1 complex. Five distinct virus-specific proteins were synthesized by infected cells. Three of the five intracellular proteins contained tryptic-peptides with properties similar to the three structural proteins. Models describing the evolution of the proteins are proposed. Although the pathogenic properties of MHV-JttM and MHV-A59 differ greatly, the tryptic peptide maps of the corresponding proteins of these MHV strMns were remarkably similar. 334 C.W. BOND, K. A~VD~,~SON, and J. L. LEIBOWITZ: at least seven virus-specific RNA species that function as mRNAs (12, 13, 20, 22) . Five of the seven mRNAs have been translated in vitro and coding assignments have been made (13, 20) . Five to nine virus-specific proteins have been identified in cells infected by MHV-JHM, MHV-A59 or MHV-3 (1, 3, 5, 18, 21) . The virus-specific proteins were identified by comparison of immunoprecipitates of infected and mock-infected cell lysates with purified virions by SDS-polyacryIamide gel electrophoresis (SDS-PAGE). STURMAN (26) proposed a model for the structure of MHV-A59. Three structural proteins were described; the nucleocapsid phosphoprotein (N), the transmembrane gtycoprotein (El) and the peplomerie glycoprotein complex (E 2), which consists of two related proteins. SIDDELL (19) analyzed the structural and intracellular proteins of MHV-JHYI by tryptic peptide mapping of ssS-methionine-labeled proteins. The results indicated that six distinct virus-specific proteins were synthesized by infected cells during the acute infection. The virus particles contained four of these proteins. WEiss and LEIBOWITZ (31) demonstrated by molecular hybridization that the genomes of MHV strains JHM and A59 are closely related in sequence. The molecular weights of the MHV-JHM and MHV-A 59 proteins are similar by SDS-PAGE (2, 3), yet the pathogenic properties of these two viruses are strikingly different (15, 17). In this communication we present tryptic peptide maps of MHV-JHM and MHV-A59 proteins.
Output: Archives of Virology Protein Synthesis in Cells Infected by Murine Hepatitis Viruses JHM and A 59: Tryptie Peptide Analysis