206,116 research outputs found

    TSE pathogenesis in cattle and sheep

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    Many studies have been undertaken in rodents to study the pathogenesis of transmissible spongiform encephalopathies (TSE). Only a few studies have focused on the pathogenesis of bovine spongiform encephalopathy (BSE) and scrapie in their natural hosts. In this review, we summarize the most recent insights into the pathogenesis of BSE and scrapie starting from the initial uptake of TSE agents and crossing of the gut epithelium. Following replication in the gut-associated lymphoid tissues (GALT), TSE agents spread to the enteric nervous system (ENS) of the gut. Infection is then carried through the efferent fibers of the post-ganglionic neurons of the parasympathetic and sympathetic nervous system to the pre-ganglionic neurons in the medulla oblongata of the brain and the thoracic segments of the spinal cord. The differences between the pathogenesis of BSE in cattle and scrapie in sheep are discussed as well as the possible existence of additional pathogenetic routes

    Ativismo no judiciário eleitoral: análise crítica dos julgamentos e das resoluções expedidas pelo TSE

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    TCC(graduação) - Universidade Federal de Santa Catarina. Centro de Ciências Jurídicas. Direito.A monografia objetiva estudar o Ativismo na Justiça Eleitoral em relação ao poder normativo que lhe compete. O objetivo principal da pesquisa, coincidente ao problema, reside em avaliar se as resoluções expedidas com base nesse poder do Judiciário Eleitoral que criam direitos, penalidades, inelegibilidades, obrigações, competências são consideradas inconstitucionais por violarem os princípios da separação de poderes, da legalidade, da segurança jurídica, as normas de organização judiciária e demais dispositivos legais. A hipótese é de que sim, tais instruções vão de encontro à Constituição Federal. Ademais, os objetivos secundários perpassam a exacerbação do Judiciário frente aos demais poderes estatais, apontando-se o ativismo judicial e suas causas, consequências e distinções. O trabalho averigua, também, os limites à regulamentação do Tribunal Superior Eleitoral – fonte considerável de posturas ativistas – e critica a desarmonia instalada no sistema constitucional de freios e contrapesos quando da usurpação da competência do Congresso Nacional pelos magistrados. Quanto à atualidade da pesquisa, é perceptível a tentativa contínua e recente do Judiciário em deixar sua passividade e atuar no intuito de moralizar a política brasileira por meio de normas gerais, abstratas e prospectivas, impedindo candidatos de concorrerem às eleições e também alterando o resultado do pleito. Concluiu-se que as resoluções analisadas, as quais instituíram a perda do mandato eletivo por infidelidade partidária e o requisito de aprovação das contas para se obter a certidão negativa eleitoral (Resolução TSE nº. 22.610/2007 e nº. 23.376/2012, respectivamente), devem ser expurgadas do ordenamento por serem inconstitucionais

    Mutations in the Aeromonas salmonicida subsp. salmonicida type III secretion system affect Atlantic salmon leucocyte activation and downstream immune responses

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    Deletion mutants of Aeromonas salmonicida subsp. salmonicida were used to determine the effect of the type three secretion system (TTSS) on Atlantic salmon anterior head kidney leucocytes (AHKL). One strain had a deletion in the outer membrane pore gene, ascC; and the other in three effector genes: aopO, aopH and aexT (we call this strain Δaop3). Host cell invasion success and 24h survival were depressed in ΔascC, as was 24h survival of Δaop3, when compared to the wild type strain. Challenge of AHKLs with A449 or TTSS mutants stimulated expression of the inflammatory mediators IL-8, IL-1 and TNFα at two bacterial concentrations (A600 0.1, 0.01). Expression of IL-12 was not stimulated in ΔascC challenged cells, whereas A449 and Δaop3 challenge resulted in an up-regulation of IL-12 in AHKLs, 2- and 4-fold higher than PBS, respectively. Only the wild type strain elicited a significant increase in IL-10 expression (5.5× at A600 0.1). Inducible nitric oxide synthetase (iNOS) and arginase (I+II) genes were also significantly up-regulated upon exposure to all strains. However, iNOS:arginase ratio was elevated in the effector mutant challenge. These results suggest that A. salmonicida subsp. salmonicida may enhance survival within the host cell through polarization of macrophages/leucocytes to an alternative, rather than classical, activation state. Furthermore, the short-term survival and lack of T-cell signalling cytokine stimulation in ΔascC, may help explain its inefficiency at providing protection to subsequent wild type challenge.ID: S1050464809002988; M3: Article; Accession Number: S1050464809002988; Author: Mark D. Fast (a, ∗); Author: Brenda Tse (b); Author: Jessica M. Boyd (c); Author: Stewart C. Johnson (d); Affiliation: School of Marine and Atmospheric Sciences, Stony Brook University, Stony Brook, New York 11794-5000, USA; Affiliation: Department of Biology, Dalhousie University, Halifax, Nova Scotia, Canada; Affiliation: Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada; Affiliation: Pacific Biological Station, Fisheries and Oceans Canada, Nanaimo, British Columbia, Canada; Keyword: Aeromonas salmonicida; Keyword: Type three secretion system; Keyword: Atlantic salmon; Keyword: SHK-1; Keyword: Gene expression; Keyword: Inflammation; Keyword: Activation; Keyword: Interleukin-1β; Keyword: (IL-1β); Keyword: Interleukin-10; Keyword: Interleukin-12; Number of Pages: 8; Language: English;Source type: Electronic(1

    TSE surveillance in small ruminants and pigs: a pilot study

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    Switzerland is controlling Transmissible Spongiform Encephalopathies (TSE) in cattle (BSE) and small ruminants (scrapie). Since BSE is potentially transmissible to sheep, goats or pigs through feeding of contaminated meat and bone meal, implementation of an active surveillance programme for TSE in these species is discussed. The aim of this pilot study was to obtain preliminary data on the prevalence ofTSE and other neurological disorders in these populations. For that purpose, a total of 398 perished and 825 slaughtered adult small ruminants and pigs was examined for the presence of neuropathological changes. None of these animals revealed positive for TSE. However, the investigations demonstrated that perished sheep and goats exhibited a higher prevalence of relevant neuropathological changes when compared with slaughtered animals. From these results, it is concluded that perished small ruminants are probably a risk population for TSE and should be considered as target populations for an active surveillance programme

    From Halfspace M-Depth to Multiple-output Expectile Regression

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    Despite the importance of expectiles in fields such as econometrics, risk management, and extreme value theory, expectile regression—or, more generally, M-quantile regression—unfortunately remains limited to single-output problems. To improve on this, we define hyperplane-valued multivariate M-quantiles that show strong advantages over their point-valued competitors. Our M-quantiles are directional in nature and provide centrality regions when all directions are considered. These regions define new statistical depths, the halfspace M-depths, that include the celebrated Tukey depth as a particular case. We study thoroughly the proposed M-quantiles, halfspace M-depths, and corresponding regions. M-depths not only provide a general framework to consider Tukey depth, expectile depth, Lr-depths, etc., but are also of interest on their own. However, since our original motivation was to consider multiple-output expectile regression, we pay more attention to the expectile case and show that expectile depth and multivariate expectiles enjoy distinctive properties that will be of primary interest to practitioners: expectile depth is maximized at the mean vector, is smoother than the Tukey depth, and exhibits surprising monotonicity properties that are key for computational purposes. Finally, our multivariate expectiles allow defining multiple-output expectile regression methods, that, in riskoriented applications in particular, are preferable to their analogs based on standard quantiles

    Mechanisms of action of antiviral drugs: the interferons

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    -Edmund Tse and Michael R. Bear

    Teacher self-efficacy (TSE) of recently graduated emergency medicine physicians and the factors influencing TSE

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    This study examines the Teaching Self-Efficacy (TSE) of Emergency Medicine (EM) physicians who graduated from the EM residency programs accredited by the Canadian Royal College of Physicians from 2008-2017, and evaluates the factors influencing these TSE beliefs. Eighty EM physicians participated in this study, providing data on their TSE beliefs using the Emergency Physician Teacher Self-Efficacy Scale (EP-TSES). Factors affecting TSE were assessed using the Influencing Factors of EM Physician TSE questionnaire. These factors include mastery experience, working experience, feedback on teaching performance, interpersonal support from colleague physicians, interpersonal support from department leadership, vicarious experiences, formal teaching training, and informal teaching training. The study also explores other possible factors, pertaining to the clinical environment, which could influence the TSE beliefs. Both instruments were validated before use in this study. Correlation analysis, and multiple regression analysis were conducted to answer the research questions. The results reveal that the mean EP-TSES score of participating physicians is 35.1 out of 50. The correlation analysis shows the EP-TSES score has a significant positive correlation with mastery experience, vicarious experience, informal teaching training, feedback on teaching performance, and more shifts with learners. The regression analysis reveals that mastery experience is the strongest predictor of TES of EM physicians, followed by vicarious experience, informal teaching training, and feedback on teaching performance. This study suggests that stakeholders in training EM physicians should consider employing strategies that foster TSE, to improve teaching and learning outcomes, and, by extrapolation, to improve healthcare outcomes.Cette étude se penche sur l'enseignement de l'auto-efficacité (ou TSE pour son sigle en anglais) aux médecins diplômés en médecine d'urgence (EM en anglais), ayant suivi les programmes de résidence en médecine d'urgence accrédités par le Collège Royal des Médecins et Chirurgiens du Canada, entre 2008 et 2017, et évalue les facteurs qui influencent les croyances en matière de TSE. Quatre-vingts médecins d'urgence ont participé à cette étude, lesquels ont fourni des données sur leurs croyances en matière de TSE à l'aide de l'échelle Enseignant d'auto-efficacité pour les médecins d'urgence, ou EP-TSES pour son sigle en anglais (Emergency Physician Teacher Self-Efficacy Scale). Les facteurs jouant un rôle dans le TSE ont été évalués sur la base d'un questionnaire portant sur les facteurs d'influence du TSE pour les médecins d'urgence, comprenant notamment l'expérience de maîtrise, l'expérience professionnelle, un feedback sur la performance de l'enseignement, le soutien interpersonnel de la part de collègues médecins, le soutien de la direction du département, les expériences vicariantes, et la formation pédagogique formelle et informelle. L'étude explore également d'autres facteurs possibles, liés à l'environnement clinique, susceptibles d'influencer les croyances en matière de TSE. Les deux outils ont été validés avant d'être utilisés dans cette étude. Une analyse de corrélation et une analyse de régression multiple ont été effectuées pour répondre aux questions posées par le travail de recherche. Les résultats obtenus montrent que le score moyen de l'EP-TSES des médecins participants est de 35,1 sur 50. L'analyse de corrélation montre que le score EP-TSES garde un lien significatif et positif avec l'expérience de maîtrise, l'expérience vicariante, la formation pédagogique informelle, le feedback sur la performance de l'enseignement et un plus grand nombre de gardes avec les apprenants. L'analyse de régression révèle que l'expérience de maîtrise est le meilleur prédicteur de TSE au niveau des médecins d'urgence, suivie de l'expérience vicariante, de la formation pédagogique informelle et du feedback sur la performance de l'enseignement. Cette étude permet de conclure que les intervenants dans la formation des médecins d'urgence devraient envisager l'emploi de stratégies encourageant le TSE, afin d'améliorer les résultats des processus d'enseignement et d'apprentissage et, par extrapolation, d'améliorer les retombées sur les soins de santé

    State-of-the-art review of goat TSE in the European Union, with special emphasis on PRNP genetics and epidemiology

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    Scrapie is a fatal, neurodegenerative disease of sheep and goats. It is also the earliest known member in the family of diseases classified as transmissible spongiform encephalopathies (TSE) or prion diseases, which includes Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (BSE), and chronic wasting disease in cervids. The recent revelation of naturally occurring BSE in a goat has brought the issue of TSE in goats to the attention of the public. In contrast to scrapie, BSE presents a proven risk to humans. The risk of goat BSE, however, is difficult to evaluate, as our knowledge of TSE in goats is limited. Natural caprine scrapie has been discovered throughout Europe, with reported cases generally being greatest in countries with the highest goat populations. As with sheep scrapie, susceptibility and incubation period duration of goat scrapie are most likely controlled by the prion protein (PrP) gene (PRNP). Like the PRNP of sheep, the caprine PRNP shows significantly greater variability than that of cattle and humans. Although PRNP variability in goats differs from that observed in sheep, the two species share several identical alleles. Moreover, while the ARR allele associated with enhancing resistance in sheep is not present in the goat PRNP, there is evidence for the existence of other PrP variants related to resistance. This review presents the current knowledge of the epidemiology of caprine scrapie within the major European goat populations, and compiles the current data on genetic variability of PRNP

    Proteins as markers of TSE infection in sheep blood

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    Transmissible spongiform encephalopathies (TSEs) are a group of fatal infectious neurodegenerative diseases affecting both humans and agricultural animals. TSE transmission via blood transfusion has been demonstrated experimentally in rodent, primate and sheep models. Additionally, in humans, four variant Creutzfeld-Jakob disease (vCJD) cases have been reported which probably resulted from infected blood transfusions. Although TSEs can be transmitted via blood transfusion, little is known about which blood cells are involved in the replication of the TSE agent and how infectivity is spread throughout the body prior to neuroinvasion. There are no currently validated diagnostic tests for TSE infection in blood.Detection of PK-resistant PrPSc has been extensively used as a biochemical marker for TSE infectivity. However, when this project was started it was not known if PKresistant PrPSc was present in TSE-infected sheep blood in sufficient quantities to explain the infectivity levels shown by bioassay. Following the development of an optimised Western blot method, this project has demonstrated that the pattern of protein detected with novel anti-PrP monoclonal antibodies is very different from the conventional triple banded pattern of PK-resistant PrPSc. High molecular weight bands were apparent in phosphotungstic acid (NaPTA) concentrated scrapie-infected and uninfected blood and may represent a novel form of blood-specific PrP. PK-resistant PrPSc is not therefore a suitable marker for TSE infection in blood.Other proteins in TSE infected blood were also investigated. Using a proteomics approach three protein markers, lactate dehydrogenase, elongation factor 1 and annexin 1 had altered expression patterns in scrapie infected blood. These proteins, in addition to the novel forms of PrP found in blood, may provide new information on the mechanisms of pathogenesis in scrapie-infected sheep and might prove to be useful molecular indicators of diagnostic value

    Two Genetically Defined Tram-Acting Loci Coordinately Regulate Overlapping Sets of Liver-Specific Genes

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    Mice homozygous for deletions around the albino locus fail to activate expression of a set of neonatal liver functions and die shortly after birth. This phenotype is thought to result from the loss of a positive trans-acting factor, denoted alf, in deletion homozygotes. Using differential cDNA screening, we isolated and characterized genes whose cell type-specific transcription is affected by alf and found as a common feature that expression of these genes is induced by glucocorticoids and cAMP. Surprisingly, a subset of these alf-responsive genes is negatively controlled by the tissue-specific extinguisher locus Tse-1. Administration of glucocorticoids and cAMP leads to reversal of Tse-1—mediated extinction of these genes. These results show that two trans-acting factors coordinately regulate expression of overlapping sets of liver-specific genes. We suggest that both the lethal phenotype and the extinguished state result from interference with hormone signal transduction
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