1,074 research outputs found

    Modulation of experimental autoimmune encephalomyelitis by endogenous Annexin A1

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    Abstract Background Autoimmune diseases, like multiple sclerosis, are triggered by uncontrolled activation of cells of the immune system against self-antigen present, for instance, in the central nervous system. We have reported novel biological functions for Annexin A1, an effector of endogenous anti-inflammation, to produce positive actions on the adaptive immune system by reducing the threshold of T cell activation. In this study, we investigated the potential modulatory role of Annexin A1 in the development of experimental autoimmune encephalomyelitis, a model of multiple sclerosis. Methods Male control C57/BL6 and AnxA1 null mice were immunized subcutaneously with an emulsion consisting of 300 μg of MOG35-55 in PBS combined with an equal volume of CFA. Lymph node cells obtained from mice immunized with MOG33-55 for 14 days were re-stimulated in vitro with MOG33-55 (100 μg/ml) for 4 days and the Th1/Th17 cytokine profile measured by ELISA. Spinal cords were processed either to isolate the infiltrated T cells or fixed and stained with haematoxylin and eosin. Statistical analyses were performed using two-tailed, unpaired Student's t tests or ANOVA. Results Our results show a direct correlation between Annexin A1 expression and severity of EAE. Analysis of MOG35-55-induced EAE development in Annexin A1 null mice showed decreased signs of the disease compared to wild type mice. This defect was significant at the peak of the disease and accompanied by reduced infiltration of T cells in the spinal cord. Finally, analysis of the T cell recall response in vitro following stimulation with MOG35-55 showed a decrease proliferation of Annexin A1 null T cells, with a significantly reduced Th1/Th17 phenotype, compared to wild type cells. Conclusion Together these findings suggest that Annexin A1 null mice have an impaired capacity to develop EAE. Furthermore strategies aiming at reducing Annexin A1 functions or expression in T cells might represent a novel therapeutic approach for multiple sclerosis.</p

    A portable hand-operated sampler for shallow-water surface sediments with special reference to epipelic communities

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    A convenient, portable, hand-operated surface-sediment sampler for use in shallow water is described. Collection of replicable, undisturbed surface sediment samples from shallow-water locations is made simple. The sampler is highly portable for use at remote sites and can be operated by one person. It is especially useful for sampling in the 0.3–1.3 m water depth range where other samplers are often unsuccessful. This sampler consists of a PVC tube (about 33-cm length, 7.1-cm diameter) attached to a 1-m-long supporting rod. A lever system is used to close off the PVC core tube. In the open position, the core tube is inserted into the sediment to an optimal depth (typically 1-cm) so that a 1-cm disc of surface sediment is enclosed. This disc is then isolated by operating the lever and tube closure plate. The sampler and sediment sample (with an intact epipelon biofilm) are removed carefully so that most of the enclosed water drains away and the sample is retained intact. <br/

    Rod Korns

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    Photo showing J. Roderic ("Rod") Korns, a historian of western trails and author of "West from Fort Bridger

    Lipocortin-1: Cellular mechanisms and clinical relevance

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    Lipocortin-1, a 37 kDa member of the annexin superfamily of proteins, originally evoked interest as one of the 'second messengers' of the antiinflammatory actions of the glucocorticoids. Subsequent research has shown that the protein plays a major regulatory role in systems as diverse as cell-growth regulation and differentiation, neutrophil migration, CNS responses to cytokines, neuroendocrine secretion and neurodegeneration. The role of lipocortin-1 in mediating glucocorticoid-induced effects in these systems has been demonstrated using immunoneutralization strategies and by mimicking steroid actions with highly purified or recombinant lipocortin-1 or its biologically active peptide fragments. Originally the mode of action of lipocortin-1 seemed to be largely through inhibition of prostaglandin formation, but it is now clear that it can modify other aspects of cell function, perhaps pointing to a more fundamental mechanism than was originally envisaged. In this article Rod Flower and Nancy Rothwell review the nature, possible mechanisms and clinical relevance of these diverse actions of lipocortin-1

    golden-rod

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    golden. . . spiked willow-weed; golden rod; the sweet flower of the bake-apple, and other pretty things grow quietly upon this ground, which is scarce habitable for man.PRINTED ITEM W. J. KIRWIN AUG 1973JH AUG 1973Used INot usedWithdrawnTyped. Head used, but not in this sense

    Synergetic strengthening far beyond rule of mixtures in gradient structured aluminum rod

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    Gradient structured metals have been reported to exhibit high strength and high ductility. Here we report that the strength of gradient structured aluminum rod is much higher than the value calculated using the rule of mixtures. The mechanical incompatibility in the gradient structured round sample produced 3D stress states, extraordinary strengthening and good ductility. An out of plane {111) wire texture was developed during the testing, which contributes to the evolution of the stress state and mechanical behavior. (C) 2016 Elsevier Ltd. All rights reserved

    Retinitis Pigmentosa GTPase Regulator (RPGR) protein isoforms in mammalian retina:insights into X-linked Retinitis Pigmentosa and associated ciliopathies

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    Mutations in the cilia-centrosomal protein Retinitis Pigmentosa GTPase Regulator (RPGR) are a frequent cause of retinal degeneration. The RPGR gene undergoes complex alternative splicing and encodes multiple protein isoforms. To elucidate the function of major RPGR isoforms (RPGR 1-19 and RPGR ORF15), we have generated isoform-specific antibodies and examined their expression and localization in the retina. Using sucrose-gradient centrifugation, immunofluorescence and co-immunoprecipitation methods, we show that RPGR isoforms localize to distinct sub-cellular compartments in mammalian photoreceptors and associate with a number of cilia-centrosomal proteins. The RCC1-like domain of RPGR, which is present in all major RPGR isoforms, is sufficient to target it to the cilia and centrosomes in cultured cells. Our findings indicate that multiple isotypes of RPGR may perform overlapping yet somewhat distinct transport-related functions in photoreceptors

    Of platelets and aggregometers: personal reminiscences of Gus Born (1921–2018)

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    This paper recounts the author’s personal reminiscences of the late Gustav Born and details some of his major influences on the field of platelet biology and mechanisms of hemostasis. In particular, it focuses on his development of the ‘Born aggregometer’ and the differences that are seen in the aggregation response to certain stimuli when aggregation is recorded using other techniques such as the impedance method
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