16 research outputs found

    Local Increase of Arginase Activity in Lesions of Patients with Cutaneous Leishmaniasis in Ethiopia

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    The leishmaniases are a complex of diseases caused by Leishmania parasites. Currently, the diseases affect an estimated 12 million people in 88 countries, and approximately 350 million more people are at risk. The leishmaniases belong to the most neglected tropical diseases, affecting the poorest populations, for whom access to diagnosis and effective treatment are often not available. Leishmania parasites infect cells of the immune system called macrophages, which have the capacity to eliminate the intracellular parasites when they receive the appropriate signals from other cells of the immune system. In nonhealing persistent leishmaniasis, lymphocytes are unable to transmit the signals to macrophages required to kill the intracellular parasites. The local upregulation of the enzyme arginase has been shown to impair lymphocyte effector functions at the site of pathology. In this study, we tested the activity of this enzyme in skin lesions of patients presenting with localized cutaneous leishmaniasis. Our results show that arginase is highly upregulated in these lesions. This increase in arginase activity coincides with lower expression of a signalling molecule in lymphocytes, which is essential for efficient activation of these cells. These results suggest that increased arginase expression in the localized cutaneous lesions might contribute to persistent disease in patients presenting with cutaneous leishmaniasis

    An Open-Section Shell Designed for Customized Bending and Twisting to Ease Sitting and Rising in a Chair

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    This paper is concerned with a compliant-hinge mechanism in an assistive chair that does not use external power in aiding the elderly and arthritics in stand-to-sit and sit-to-stand manoeuvres. The mechanism, attached to the seat of the chair, acts like a nonlinear torsion spring that is effectively pivoted to the frame. A pair of semi-circular open-section shells that are rigidly connected to each other and fastened to the chair frame comprise the spring. A cam profile on a guide plate enables the shells to deform transversely even as they twist to provide customized torque-angle characteristic as per the weight of the occupant. The formulation of the design specification based on biomechanical considerations, kinetics of sitting and rising in a chair, kinetoelastic modelling of open-section shells, a new energy mapping method of designing the guideway for the shells, and simulation of the entire unitized compliant spring mechanism are presented

    Gaining more than just vocational skills: Evaluating women learners’ aspirations through the capability approach

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    Vocational education and training had been a popular choice for women learners in the English Further Education sector. However, policy makers and policy researchers have characterized these women learners as providing a poor return on investment due to their failure to enter immediate employment. As a result, there have been significant cuts to funding. Such policy processes have not engaged with why these women returned to education and what they stood to gain from participation. This major absence is the focus of this chapter. Framed using a capabilities approach, women learners were asked why they had returned to FE and how they were going to use their knowledge and training. Using capabilities as a lens reveals a nuanced and complex picture of how education helps them to expand their well-being, agency, and freedom achievement.This work was funded by the Economic and Social Research Council (UK) [grant number 151171]

    Combined lipidomic and proteomic analysis of isolated human islets exposed to palmitate reveals time-dependent changes in insulin secretion and lipid metabolism

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    Studies on the pathophysiology of type 2 diabetes mellitus (T2DM) have linked the accumulation of lipid metabolites to the development of beta-cell dysfunction and impaired insulin secretion. In most in vitro models of T2DM, rodent islets or beta-cell lines are used and typically focus is on specific cellular pathways or organs. Our aim was to, firstly, develop a combined lipidomics and proteomics approach for lipotoxicity in isolated human islets and, secondly, investigate if the approach could delineate novel and/or confirm reported mechanisms of lipotoxicity. To this end isolated human pancreatic islets, exposed to chronically elevated palmitate concentrations for 0, 2 and 7 days, were functionally characterized and their levels of multiple targeted lipid and untargeted protein species determined. Glucosestimulated insulin secretion from the islets increased on day 2 and decreased on day 7. At day 7 islet insulin content decreased and the proinsulin to insulin content ratio doubled. Amounts of cholesterol, stearic acid, C16 dihydroceramide and C24: 1 sphingomyelin, obtained from the lipidomic screen, increased time-dependently in the palmitate-exposed islets. The proteomic screen identified matching changes in proteins involved in lipid biosynthesis indicating up-regulated cholesterol and lipid biosynthesis in the islets. Furthermore, proteins associated with immature secretory granules were decreased when palmitate exposure time was increased despite their high affinity for cholesterol. Proteins associated with mature secretory granules remained unchanged. Pathway analysis based on the protein and lipid expression profiles implicated autocrine effects of insulin in lipotoxicity. Taken together the study demonstrates that combining different omics approaches has potential in mapping of multiple simultaneous cellular events. However, it also shows that challenges exist for effectively combining lipidomics and proteomics in primary cells. Our findings provide insight into how saturated fatty acids contribute to islet cell dysfunction by affecting the granule maturation process and confirmation in human islets of some previous findings from rodent islet and cell-line studies
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