Muscle RANK is a key regulator of calcium storage, SERCA activity, and function of fast-twitch skeletal muscles

Receptor-activator of nuclear factor kB (RANK), its ligand RANKL and the soluble decoy receptor osteoprotegerin (OPG)are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion (RANKmko) has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscle preventing the loss of maximum specific force while promoting muscle atrophy, fatigability and increased proportion of fast-twitch fibers. In denervated EDL muscles, RANK deletion markedly increased stromal interaction molecule 1 (Stim1) content, a calcium sensor, and altered activity of the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) modulating Ca2+ storage. Muscle RANK deletion had no significant effects on the sham or denervated slow-twitch soleus (Sol) muscles. These data identify a novel role for RANK as a key regulator of calcium storage and SERCA activity, ultimately affecting denervated skeletal muscle function

Communication changes following non-glottic head and neck cancer management: The perspectives of survivors and carers

Purpose. Head and neck cancer (HNC) survivors may experience functional changes to their voice, speech and hearing following curative chemoradiotherapy. However, few studies have explored the impact of living with such changes from the perspective of the HNC survivor and their carer. The current study employed a person-centred approach to explore the lived experience of communication changes following chemoradiotherapy treatment for HNC from the perspective of survivors and carers. Method. Participants included 14 survivors with non-glottic HNC and nine carers. All participants took part in in-depth interviews where they were encouraged to describe their experiences of living with and adjusting to communication changes following treatment. Interviews were analysed as a single data set. Result. Four themes emerged including: (1) impairments in communication sub-systems; (2) the challenges of communicating in everyday life; (3) broad ranging effects of communication changes; and (4) adaptations as a result of communication changes. Conclusion. These data confirm that communication changes following chemoradiotherapy have potentially negative psychosocial impacts on both the HNC survivor and their carer. Clinicians should consider the impact of communication changes on the life of the HNC survivor and their carer and provide adequate and timely education and management to address the needs of this population

Documenting an educational imaginary – representations of schooling in British documentary films.

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The changing role of the headteacher in England post academisation

The schooling landscape in England has changed significantly in the past decade as a result of ‘academisation’. Academy schools have moved from being locally administered to being independently run, and directly funded by national government. Conversion to academy status has been encouraged by the government on the premise that headteachers are afforded more autonomy over their schools with more effective lines of accountability. Such schools are frequently grouped in Multi-Academy Trusts (MATs), more recently called School Trusts, which has consequences for leadership practice. The research in this study presents the perceptions of policy impact on the role of the headteachers working within a MAT. The participants include two primary headteachers and the Chief Executive Officer (CEO) of the trust, a role which has emerged as a leadership position over the last decade. This article shares the leaders’ views on education policy trends, particularly how this has changed the central team, the MAT, and how collaboration within the trust has changed the role of the headteacher. This unique research examined a trust that has gone through that process and records the altering dynamics of a leadership team as a consequence

Serum metabolite signature predicts the acute onset of diabetes in spontaneously diabetic congenic BB rats

The clinical presentation of type 1 diabetes is preceded by a prodrome of beta cell autoimmunity. We probed the short period of subtle metabolic abnormalities, which precede the acute onset of diabetes in the spontaneously diabetic BB rat, by analyzing the serum metabolite profile detected with combined gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS). We found that the metabolite pattern prior to diabetes included 17 metabolites, which differed between individual diabetes prone (DP) BB rats and their age and sex matched diabetes resistant (DR) littermates. As the metabolite signature at the 40 days of age baseline failed to distinguish DP from DR, there was a brief 10-day period after which the diabetes prediction pattern was observed, that includes fatty acids (e.g. oleamide), phospholipids (e.g. phosphocholines) and amino acids (e.g. isoleucine). It is concluded that distinct changes in the serum metabolite pattern predict type 1 diabetes and precede the appearance of insulitis in spontaneously diabetic BB DP rats. This observation should prove useful to dissect mechanisms of type 1 diabetes

In Vivo, Fatty Acid Translocase (CD36) Critically Regulates Skeletal Muscle Fuel Selection, Exercise Performance, and Training-induced Adaptation of Fatty Acid Oxidation

For ∼40 years it has been widely accepted that (i) the exercise-induced increase in muscle fatty acid oxidation (FAO) is dependent on the increased delivery of circulating fatty acids, and (ii) exercise training-induced FAO up-regulation is largely attributable to muscle mitochondrial biogenesis. These long standing concepts were developed prior to the recent recognition that fatty acid entry into muscle occurs via a regulatable sarcolemmal CD36-mediated mechanism. We examined the role of CD36 in muscle fuel selection under basal conditions, during a metabolic challenge (exercise), and after exercise training. We also investigated whether CD36 overexpression, independent of mitochondrial changes, mimicked exercise training-induced FAO up-regulation. Under basal conditions CD36-KO versus WT mice displayed reduced fatty acid transport (−21%) and oxidation (−25%), intramuscular lipids (less than or equal to −31%), and hepatic glycogen (−20%); but muscle glycogen, VO(2max), and mitochondrial content and enzymes did not differ. In acutely exercised (78% VO(2max)) CD36-KO mice, fatty acid transport (−41%), oxidation (−37%), and exercise duration (−44%) were reduced, whereas muscle and hepatic glycogen depletions were accelerated by 27–55%, revealing 2-fold greater carbohydrate use. Exercise training increased mtDNA and β-hydroxyacyl-CoA dehydrogenase similarly in WT and CD36-KO muscles, but FAO was increased only in WT muscle (+90%). Comparable CD36 increases, induced by exercise training (+44%) or by CD36 overexpression (+41%), increased FAO similarly (84–90%), either when mitochondrial biogenesis and FAO enzymes were up-regulated (exercise training) or when these were unaltered (CD36 overexpression). Thus, sarcolemmal CD36 has a key role in muscle fuel selection, exercise performance, and training-induced muscle FAO adaptation, challenging long held views of mechanisms involved in acute and adaptive regulation of muscle FAO

Saturation of SERCA's lipid annulus may protect against its thermal inactivation.

The sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) pumps are integral membrane proteins that catalyze the active transport of Ca2+ into the sarcoplasmic reticulum, thereby eliciting muscle relaxation. SERCA pumps are highly susceptible to oxidative damage, and cytoprotection of SERCA dampens thermal inactivation and is a viable therapeutic strategy in combating diseases where SERCA activity is impaired, such as muscular dystrophy. Here, we sought to determine whether increasing the percent of saturated fatty acids (SFA) within SERCA's lipid annulus through diet could protect SERCA pumps from thermal inactivation. Female Wistar rats were fed either a semi-purified control diet (AIN93G, 7% soybean oil by weight) or a modified AIN93G diet containing high SFA (20% lard by weight) for 17 weeks. Soleus muscles were extracted and SERCA lipid annulus and activity under thermal stress were analyzed. Our results show that SERCA's lipid annulus is abundant with short-chain (12–14 carbon) fatty acids, which corresponds well with SERCA's predicted bilayer thickness of 21 Å. Under control-fed conditions, SERCA's lipid annulus was already highly saturated (79%), and high-fat feeding did not increase this any further. High-fat feeding did not mitigate the reductions in SERCA activity seen with thermal stress; however, correlational analyses revealed significant and strong associations between % SFA and thermal stability of SERCA activity with greater %SFA being associated with lower thermal inactivation and greater % polyunsaturation and unsaturation index being associated with increased thermal inactivation. Altogether, these findings show that SERCA's lipid annulus may influence its susceptibility to oxidative damage, which could have implications in muscular dystrophy and age-related muscle wasting.Analyses supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada to PJL. The in vivo portion of the study was funded by start-up funding from Brock University to WEW. VAF was supported through a Canadian Institutes of Health Research (CIHR) Doctoral Award; NT and PM were both supported through CIHR Master's Awards; LC was supported through an Ontario Graduate Scholarship. WEW holds a Canada Research Chair in Bone and Muscle Development

Does ligament balancing technique affect kinematics in rotating platform, PCL retaining knee arthroplasties?: A prospective randomized study

The goal of this prospective, randomized, blinded trial was to determine if ligament balancing techniques for rotating platform TKA affect postoperative knee kinematics. Sixteen patients with unilateral rotating platform TKA consented to participate in this institutional review board approved study. Eight patients were randomly selected to receive ligament balancing with an instrumented joint spreader device and eight patients received ligament balancing using fixed thickness spacer blocks. A single plane shape matching technique was used for kinematic analysis of static deep knee flexion and dynamic stair activities. There were no differences in knee kinematics between groups during static deep flexion activities. The spreader group demonstrated kinematics more similar to the normal knee during the ascending phase of the dynamic stair activity. Knee kinematics in static knee flexion were unaffected by ligament balancing technique, while knees balanced with the spreader demonstrated a medial pivot motion pattern during stair ascent. This medial pivot motion pattern may improve long-term results by more closely replicating normal knee kinematics