Bruceleonard8045

α-synuclein (aSyn) is a major player in Parkinson's disease and a group of other disorders collectively known as synucleinopathies, but the precise molecular mechanisms involved are still unclear. aSyn, as virtually all proteins, undergoes a series of posttranslational modifications during its lifetime, which can affect its biology and pathobiology. We recently showed that glycation of aSyn by methylglyoxal (MGO) potentiates its oligomerization and toxicity, induces dopaminergic neuronal cell loss in mice, and affects motor performance in flies. Small heat-shock proteins (sHsps) are molecular chaperones that facilitate the folding of proteins or target misfolded proteins for clearance. Importantly, sHsps were shown to prevent aSyn aggregation and cytotoxicity. Upon treating cells with increasing amounts of methylglyoxal, we found that the levels of Hsp27 decreased in a dose-dependent manner. Therefore, we hypothesized that restoring the levels of Hsp27 in glycating environments could alleviate the pathogenicity of aSyn. Consistently, we found that Hsp27 reduced MGO-induced aSyn aggregation in cells, leading to the formation of nontoxic aSyn species. Remarkably, increasing the levels of Hsp27 suppressed the deleterious effects induced by MGO. Our findings suggest that in glycating environments, the levels of Hsp27 are important for modulating the glycation-associated cellular pathologies in synucleinopathies. © 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.AIM Linguistic diversity is increasing nationally; patients with limited English proficiency require provision of professional interpreters. We reviewed hospital-wide use of interpreters for low English proficiency in a tertiary hospital across emergency (ED), outpatient and inpatient presentations. METHODS Two cohorts with low English proficiency presenting to Princess Margaret Hospital were audited. Records of new Refugee Health Service patients (presenting between January and July 2015) and non-Refugee Health Service low English proficiency patients (obtained through Language Services bookings) were reviewed to assess demographic profiles and use of interpreters for any occasion of service over the following 12 months (for each patient). RESULTS Data from 188 patients were reviewed (Refugee Health Service 119 patients; non-Refugee Health Service 69 patients; total 1027 occasions of service); all were under 18 years of age. High socio-economic disadvantage and limited education was noted. Almost all (98.5%) including impact on clinical handover, informed consent and non-compliance with state language services policy. Further staff education and quality improvement work is essential. © 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).Effective receptor signaling is anchored on the preferential localization of the receptor in lipid rafts, which are plasma membrane platforms replete with cholesterol and sphingolipids. We hypothesized that the dopamine D1 receptor (D1 R) contains structural features that allow it to reside in lipid rafts for its activity. Mutation of C347 palmitoylation site and Y218 of a newly identified Cholesterol Recognition Amino Acid Consensus motif resulted in the exclusion of D1 R from lipid rafts, blunted cAMP response, impaired sodium transport, and increased oxidative stress in renal proximal tubule cells (RPTCs). Kidney-restricted silencing of Drd1 in C57BL/6J mice increased blood pressure (BP) that was normalized by renal tubule-restricted rescue with D1 R-wild-type but not the mutant D1 R 347A that lacks a palmitoylation site. Kidney-restricted disruption of lipid rafts by β-MCD jettisoned the D1 R from the brush border, decreased sodium excretion, and increased oxidative stress and BP in C57BL/6J mice. Deletion of the PX domain of the novel D1 R-binding partner sorting nexin 19 (SNX19) resulted in D1 R partitioning solely to non-raft domains, while silencing of SNX19 impaired D1 R function in RPTCs. Kidney-restricted silencing of Snx19 resulted in hypertension in C57BL/6J mice. Our results highlight the essential role of lipid rafts for effective D1 R signaling. © 2020 Federation of American Societies for Experimental Biology.Mountain sports are becoming more and more popular. In these sports activities, exposure to high altitude results in physiological changes of the human body that may lead to acute mountain sickness (AMS). The autonomic nervous system (ANS) plays an important role in adaptive changes after acute altitude exposure. Recent studies support the concept of a withdrawal of vagal activity as well as an increase of sympathetic activity after altitude exposure. This article is protected by copyright. All rights reserved.Motives for physical activity may vary considerably by age, sex, and the level of physical activity. We aimed to examine motives for physical activity in older men and women with different physical activity levels as well as whether genetic and/or environmental factors explain those motives. Finnish twins (mean age 72.9 years, 262 full twin pairs) self-reported their motives for physical activity. Time spent on moderate-to-vigorous physical activity was monitored using a hip-worn accelerometer. Comparisons between the different physical activity groups of older twins (n = 764-791/motive dimension) were analyzed using the Wald test, and effect sizes were calculated as Cohen's d. Quantitative genetic modeling was used to estimate genetic and environmental contributions. For both sexes, the most frequently reported motives for physical activity were physical fitness, health maintenance, and psychological well-being. Conforming to others' expectations was more important for men than for women (P  less then  .001, Cohen's d = 0.38), while appearance (P = .001 Cohen's d = -0.24) and psychological well-being (P = .02, Cohen's d = -0.17) were highlighted by women. Most of the motive dimensions differed significantly between the physically active and inactive individuals. It was estimated that 5%-42% of the variation in motives was contributed by genetic factors and 58%-95% by environmental factors. The result that environmental factors contribute in a great deal to motives indicates that interventions to motivate physically inactive older individuals to be physically active can be successful. However, personalized interventions are needed because sex and the level of physical activity were found to be associated with older individuals' motives for physical activity. © 2020 The Authors. Apoptosis inhibitor Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.