60 research outputs found

    Delayed Recovery of Skeletal Muscle Mass following Hindlimb Immobilization in mTOR Heterozygous Mice

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    The present study addressed the hypothesis that reducing mTOR, as seen in mTOR heterozygous (+/−) mice, would exaggerate the changes in protein synthesis and degradation observed during hindlimb immobilization as well as impair normal muscle regrowth during the recovery period. Atrophy was produced by unilateral hindlimb immobilization and data compared to the contralateral gastrocnemius. In wild-type (WT) mice, the gradual loss of muscle mass plateaued by day 7. This response was associated with a reduction in basal protein synthesis and development of leucine resistance. Proteasome activity was consistently elevated, but atrogin-1 and MuRF1 mRNAs were only transiently increased returning to basal values by day 7. When assessed 7 days after immobilization, the decreased muscle mass and protein synthesis and increased proteasome activity did not differ between WT and mTOR+/− mice. Moreover, the muscle inflammatory cytokine response did not differ between groups. After 10 days of recovery, WT mice showed no decrement in muscle mass, and this accretion resulted from a sustained increase in protein synthesis and a normalization of proteasome activity. In contrast, mTOR+/− mice failed to fully replete muscle mass at this time, a defect caused by the lack of a compensatory increase in protein synthesis. The delayed muscle regrowth of the previously immobilized muscle in the mTOR+/− mice was associated with a decreased raptor•4EBP1 and increased raptor•Deptor binding. Slowed regrowth was also associated with a sustained inflammatory response (e.g., increased TNFα and CD45 mRNA) during the recovery period and a failure of IGF-I to increase as in WT mice. These data suggest mTOR is relatively more important in regulating the accretion of muscle mass during recovery than the loss of muscle during the atrophy phase, and that protein synthesis is more sensitive than degradation to the reduction in mTOR during muscle regrowth

    Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

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    Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

    Accelerated surgery versus standard care in hip fracture (HIP ATTACK): an international, randomised, controlled trial

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    Assessing farmers’ perspectives on climate change for effective farm-level adaptation measures in Khyber Pakhtunkhwa, Pakistan

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    Agriculture is considered as the backbone of the economy of Pakistan. However, current changes in climate have been adversely affecting agricultural productivity. In this paper, perceived impacts of climate change on agriculture and adaptation towards it have been studied in Charsadda district (lowlands) of Khyber Pakhtunkhwa province of Pakistan through extensive field surveys, involving 116 farm households. Results have revealed that climate change factors including fluctuating temperature, evidence of yearly long droughts, and a steady shift in rainfall patterns have pressured the agriculture sector and livelihoods of the local peasants. The staggering floods of 2010 and 2011 in Pakistan have evidenced severe climatic changes in Pakistan. These countrywide floods have washed fertile soil in the study area that has directly contributed to losses in agricultural yield and increased vector-borne diseases in crops. The local farmers have commonly deployed adaptive measure such as crops diversification, changing fertilizer, and planting shaded trees to minimize the impacts of changes in climate. However, these adjustments measures are perceived as not appropriate for improving farm yield. Therefore, the study suggests that improved understanding of the climate change impacts and knowledge on adapting adequately will lead to no-regret adaptation. It will also help protecting farmer's lives and livelihoods and will boost their resilience towards changing climatic conditions
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