546 research outputs found

    Exercise training prevents skeletal muscle plasma membrane cholesterol accumulation, cortical actin filament loss, and insulin resistance in C57BL/6J mice fed a western‐style high‐fat diet

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    Insulin action and glucose disposal are enhanced by exercise, yet the mechanisms involved remain imperfectly understood. While the causes of skeletal muscle insulin resistance also remain poorly understood, new evidence suggest excess plasma membrane (PM) cholesterol may contribute by damaging the cortical filamentous actin (F‐actin) structure essential for GLUT4 glucose transporter redistribution to the PM upon insulin stimulation. Here, we investigated whether PM cholesterol toxicity was mitigated by exercise. Male C57BL/6J mice were placed on low‐fat (LF, 10% kCal) or high‐fat (HF, 45% kCal) diets for a total of 8 weeks. During the last 3 weeks of this LF/HF diet intervention, all mice were familiarized with a treadmill for 1 week and then either sham‐exercised (0 m/min, 10% grade, 50 min) or exercised (13.5 m/min, 10% grade, 50 min) daily for 2 weeks. HF‐feeding induced a significant gain in body mass by 3 weeks. Sham or chronic exercise did not affect food consumption, water intake, or body mass gain. Prior to sham and chronic exercise, “pre‐intervention” glucose tolerance tests were performed on all animals and demonstrated that HF‐fed mice were glucose intolerant. While sham exercise did not affect glucose tolerance in the LF or HF mice, exercised mice showed an improvement in glucose tolerance. Muscle from sham‐exercised HF‐fed mice showed a significant increase in PM cholesterol, loss of cortical F‐actin, and decrease in insulin‐stimulated glucose transport compared to sham‐exercised LF‐fed mice. These HF‐fed skeletal muscle membrane/cytoskeletal abnormalities and insulin resistance were improved in exercised mice. These data reveal a new therapeutic aspect of exercise being regulation of skeletal muscle PM cholesterol homeostasis. Further studies on this mechanism of insulin resistance and the benefits of exercise on its prevention are needed

    Magnetodielectric coupling in Mn3O4

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    We have investigated the dielectric anomalies associated with spin ordering transitions in the tetragonal spinel Mn3_3O4_4, using thermodynamic, magnetic, and dielectric measurements. We find that two of the three magnetic ordering transitions in Mn3_3O4_4 lead to decreases in the temperature dependent dielectric constant at zero applied field. Applying a magnetic field to the polycrystalline sample leaves these two dielectric anomalies practically unchanged, but leads to an increase in the dielectric constant at the intermediate spin-ordering transition. We discuss possible origins for this magnetodielectric behavior in terms of spin-phonon coupling. Band structure calculations suggest that in its ferrimagnetic state, Mn3_3O4_4 corresponds to a semiconductor with no orbital degeneracy due to strong Jahn-Teller distortion.Comment: 6 pages, 7 figure

    GINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome

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    Time-resolved ChIP-chip can be utilized to monitor the genome-wide dynamics of the GINS complex, yielding quantitative information on replication fork movement.Replication forks progress at remarkably uniform rates across the genome, regardless of location.GINS progression appears to be arrested, albeit with very low frequency, at sites of highly transcribed genes.Comparison of simulation with data leads to novel biological insights regarding the dynamics of replication fork progressio

    Measuring Dissociation Rate Constants of Protein Complexes through Subunit Exchange: Experimental Design and Theoretical Modeling

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    Protein complexes are dynamic macromolecules that constantly dissociate into, and simultaneously are assembled from, free subunits. Dissociation rate constants, koff, provide structural and functional information on protein complexes. However, because all existing methods for measuring koff require high-quality purification and specific modifications of protein complexes, dissociation kinetics has only been studied for a small set of model complexes. Here, we propose a new method, called Metabolically-labeled Affinity-tagged Subunit Exchange (MASE), to measure koff using metabolic stable isotope labeling, affinity purification and mass spectrometry. MASE is based on a subunit exchange process between an unlabeled affinity-tagged variant and a metabolically-labeled untagged variant of a complex. The subunit exchange process was modeled theoretically for a heterodimeric complex. The results showed that koff determines, and hence can be estimated from, the observed rate of subunit exchange. This study provided the theoretical foundation for future experiments that can validate and apply the MASE method

    Access and utilisation of maternity care for disabled women who experience domestic abuse:a systematic review

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    BACKGROUND: Although disabled women are significantly more likely to experience domestic abuse during pregnancy than non-disabled women, very little is known about how maternity care access and utilisation is affected by the co-existence of disability and domestic abuse. This systematic review of the literature explored how domestic abuse impacts upon disabled women’s access to maternity services. METHODS: Eleven articles were identified through a search of six electronic databases and data were analysed to identify: the factors that facilitate or compromise access to care; the consequences of inadequate care for pregnant women’s health and wellbeing; and the effectiveness of existing strategies for improvement. RESULTS: Findings indicate that a mental health diagnosis, poor relationships with health professionals and environmental barriers can compromise women’s utilisation of maternity services. Domestic abuse can both compromise, and catalyse, access to services and social support is a positive factor when accessing care. Delayed and inadequate care has adverse effects on women’s physical and psychological health, however further research is required to fully explore the nature and extent of these consequences. Only one study identified strategies currently being used to improve access to services for disabled women experiencing abuse. CONCLUSIONS: Based upon the barriers and facilitators identified within the review, we suggest that future strategies for improvement should focus on: understanding women’s reasons for accessing care; fostering positive relationships; being women-centred; promoting environmental accessibility; and improving the strength of the evidence base

    The TeaComposition Initiative: Unleashing the power of international collaboration to understand litter decomposition

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    Collected harmonized data on global litter decomposition are of great relevance for scientists, policymakers, and for education of the next generation of researchers and environmental managers. Here we describe the TeaComposition initiative, a global and open research collaborative network to study organic matter decomposition in a standardized way allowing comparison of decomposition rate and carbon turnover across global and regional gradients of ecosystems, climate, soils etc. The TeaComposition initiative today involves 570 terrestrial and 300 aquatic ecosystems from nine biomes worldwide. Further, we describe how to get involved in the TeaComposition initiative by (a) implementing the standard protocol within your study site, (b) joining task forces in data analyses, syntheses and modelling efforts, (c) using collected data and samples for further analyses through joint projects, (d) using collected data for graduate seminars, and (e) strengthening synergies between biogeochemical research and a wide range of stakeholders. These collaborative efforts within/emerging from the TeaComposition initiative, thereby, will leverage our understanding on litter decomposition at the global scale and strengthen global collaborations essential for addressing grand scientific challenges in a rapidly changing world.This work was performed within the TeaComposition and TeaComposition H2O initiatives, carried by 290 institutions worldwide. We thank to UNILEVER for sponsoring the Lipton tea bags. The initiative is supported by the following grants: ILTER Initiative Grants, ClimMani Short-Term Scientific Missions Grants, INTERACT Remote Transnational Access and an Alfred Deakin Postdoctoral Research Fellowship. Nico Eisenhauer gratefully acknowledges the support of iDiv funded by the German Research Foundation (DFG– FZT 118, 202548816). ST-T was supported by the ARC DE210101029 and Deakin University’s ADPR Fellowship. Fernando T. Maestre acknowledges support from the European Research Council (ERC Grant agreement 647038 [BIODESERT]) and Generalitat Valenciana (CIDEGENT/2018/041)
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