Université de Sherbrooke

About: Université de Sherbrooke is a education organization based out in Sherbrooke, Quebec, Canada. It is known for research contribution in the topics: Population & Receptor. The organization has 14922 authors who have published 28783 publications receiving 792511 citations. The organization is also known as: Universite de Sherbrooke & Sherbrooke University.

β-Amyloid peptides display protective activity against the human Alzheimer’s disease-associated herpes simplex virus-1

Abstract: Amyloid plaques, the hallmark of Alzheimer’s disease (AD), contain fibrillar β-amyloid (Aβ) 1-40 and 1-42 peptides. Herpes simplex virus 1 (HSV-1) has been implicated as a risk factor for AD and found to co-localize within amyloid plaques. Aβ 1-40 and Aβ 1-42 display anti-bacterial, anti-yeast and anti-viral activities. Here, fibroblast, epithelial and neuronal cell lines were exposed to Aβ 1-40 or Aβ 1-42 and challenged with HSV-1. Quantitative analysis revealed that Aβ 1-40 and Aβ 1-42 inhibited HSV-1 replication when added 2 h prior to or concomitantly with virus challenge, but not when added 2 or 6 h after virus addition. In contrast, Aβ 1-40 and Aβ 1-42 did not prevent replication of the non-enveloped human adenovirus. In comparison, antimicrobial peptide LL-37 prevented HSV-1 infection independently of its sequence of addition. Our findings showed also that Aβ 1-40 and Aβ 1-42 acted directly on HSV-1 in a cell-free system and prevented viral entry into cells. The sequence homology between Aβ and a proximal transmembrane region of HSV-1 glycoprotein B suggested that Aβ interference with HSV-1 replication could involve its insertion into the HSV-1 envelope. Our data suggest that Aβ peptides represent a novel class of antimicrobial peptides that protect against neurotropic enveloped virus infections such as HSV-1. Overproduction of Aβ peptide to protect against latent herpes viruses and eventually against other infections, may contribute to amyloid plaque formation, and partially explain why brain infections play a pathogenic role in the progression of the sporadic form of AD.

IL-13 and IL-4 up-regulate cysteinyl leukotriene 1 receptor expression in human monocytes and macrophages.

Abstract: The cysteinyl (Cys) leukotrienes (LT)C(4), LTD(4), and LTE(4), are lipid mediators that have been implicated in the pathogenesis of asthma. The human LTD(4) receptor (CysLT(1)R) was recently cloned and characterized. The present work was undertaken to study the potential modulation of CysLT(1)R expression by the Th2 cytokines IL-13 and IL-4. In this study, we report that IL-13 up-regulates CysLT(1)R mRNA levels, with consequently enhanced CysLT(1)R protein expression and function in human monocytes and monocyte-derived macrophages. CysLT(1)R mRNA expression was augmented 2- to 5-fold following treatment with IL-13 and was due to enhanced transcriptional activity. The effect was observed after 4 h, was maximal by 8 h, and maintained at 24 h. IL-4, but not IFN-gamma, induced a similar pattern of CysLT(1)R up-regulation. Monocytes pretreated with IL-13 or IL-4 for 24 h showed enhanced CysLT(1)R protein expression, as assessed by flow cytometry using a polyclonal anti-CysLT(1)R Ab. They also showed enhanced responsiveness to LTD(4), but not to LTB(4), in terms of Ca(2+) mobilization, as well as augmented chemotactic activity. Our findings suggest a possible mechanism by which IL-13 and IL-4 can modulate CysLT(1)R expression on monocytes and macrophages, and consequently their responsiveness to LTD(4), and thus contribute to the pathogenesis of asthma and allergic diseases.

Context and Decision Making Autonomy in the Foreign Affiliates of U.S. Multinational Corporations1

Abstract: In a study of the autonomy of decision making in multinational corporations, 23 explanatory variables grouped in 11 dimensions were tested in 3 separate surveys conducted in France and in Mexico Degree of interchange of products among members, ownership, workflow integration, and size of the global group were found to be the main predictors of autonomy

Hepatocyte nuclear factor 4-alpha involvement in liver and intestinal inflammatory networks

Abstract: Hepatocyte nuclear factor 4-alpha (HNF4-α) is a nuclear receptor regulating metabolism, cell junctions, differentiation and proliferation in liver and intestinal epithelial cells. Mutations within the HNF4A gene are associated with human diseases such as maturity-onset diabetes of the young. Recently, HNF4A has also been described as a susceptibility gene for ulcerative colitis in genome-wide association studies. In addition, specific HNF4A genetic variants have been identified in pediatric cohorts of Crohn's disease. Results obtained from knockout mice supported that HNF4-α can protect the intestinal mucosae against inflammation. However, the exact molecular links behind HNF4-α and inflammatory bowel diseases remains elusive. In this review, we will summarize the current knowledge about the role of HNF4-α and its isoforms in inflammation. Specific nature of HNF4-α P1 and P2 classes of isoforms will be summarized. HNF4-α role as a hepatocyte mediator for cytokines relays during liver inflammation will be integrated based on documented examples of the literature. Conclusions that can be made from these earlier liver studies will serve as a basis to extrapolate correlations and divergences applicable to intestinal inflammation. Finally, potential functional roles for HNF4-α isoforms in protecting the intestinal mucosae from chronic and pathological inflammation will be presented.

Histone H2A.Z is essential for estrogen receptor signaling

Abstract: Incorporation of H2A.Z into the chromatin of inactive promoters has been shown to poise genes for their expression. Here we provide strong evidence that H2A.Z is incorporated into the promoter regions of estrogen receptor (ERa) target genes only upon gene induction, and that, in a cyclic pattern. Moreover, members of the human H2A.Z-depositing complex, p400, also follow the same gene recruitment kinetics as H2A.Z. Importantly, cellular depletion of H2A.Z or p400 leads to a severe defect in estrogen signaling, including loss of estrogenspecific cell proliferation. We find that incorporation of H2A.Z within TFF1 promoter chromatin allows nucleosomes to adopt preferential positions along the DNA translational axis. Finally, we provide evidence that H2A.Z is essential to allow estrogen-responsive enhancer function. Taken together, our results provide strong mechanistic insight into how H2A.Z regulates ERa-mediated gene expression and provide a novel link between H2A.Z–p400 and ERa-dependent gene regulation and enhancer function.