Key points• If skeletal muscle fibres are subjected to excessive activation, or stretched whilst contracting, they subsequently display long-term reductions in their force response, apparently due in part to structural or molecular changes at the triad junction, where excitation of the surface membrane triggers Ca 2+ release from the internal Ca 2+ store.• The changes appear to be due to excessive or prolonged increases in intracellular Ca 2+ levels, which activate Ca 2+ -dependent proteases known as calpains, but their target proteins are currently unknown.• This study shows that excessive muscle stimulation, or directly raising intracellular Ca 2+ levels, causes calpain activation in tandem with proteolysis of junctophilin, a key protein thought to hold the triad junction together.• Proteolysis of junctophilin is also seen in muscle of mice with muscular dystrophy and in cardiac muscle following ischaemic damage.• Proteolysis of junctophilin may be a major factor causing muscle weakness and cardiac dysfunction in a range of circumstances.Abstract Excessive increases in intracellular [Ca 2+ ] in skeletal muscle fibres cause failure of excitation-contraction coupling by disrupting communication between the dihydropyridine receptors in the transverse tubular system and the Ca 2+ release channels (RyRs) in the sarcoplasmic reticulum (SR), but the exact mechanism is unknown. Previous work suggested a possible role of Ca 2+ -dependent proteolysis in this uncoupling process but found no proteolysis of the dihydropyridine receptors, RyRs or triadin. Junctophilin-1 (JP1; ∼90 kDa) stabilizes close apposition of the transverse tubular system and SR membranes in adult skeletal muscle; its C-terminal end is embedded in the SR and its N-terminal associates with the transverse tubular system membrane. Exposure of skeletal muscle homogenates to precisely set [Ca 2+ ] revealed that JP1 undergoes Ca 2+ -dependent proteolysis over the physiological [Ca 2+ ] range in tandem with autolytic activation of endogenous μ-calpain. Cleavage of JP1 occurs close to the C-terminal, yielding a ∼75 kDa diffusible fragment and a fixed ∼15 kDa fragment. Depolarization-induced force responses in rat skinned fibres were abolished following 1 min exposure to 40 μM Ca 2+ , with accompanying loss of full-length JP1. Supraphysiological stimulation of rat skeletal muscle in vitro by repeated tetanic stimulation in 30 mM caffeine also produced marked proteolysis of JP1 (and not RyR1). In dystrophic mdx mice, JP1 proteolysis is seen in limb muscles at 4 and not at 10 weeks of age. Junctophilin-2 in cardiac and skeletal muscle also undergoes Ca 2+ -dependent proteolysis, and junctophilin-2 levels are reduced following cardiac ischaemia-reperfusion. Junctophilin proteolysis may contribute to skeletal muscle weakness and cardiac dysfunction in a range of circumstances.

2 ABSTRACTPurpose: Cross-education of strength has been proposed to be greater when completed by the dominant limb in right handed humans. We investigated whether the direction of cross-education of strength and corticospinal plasticity are different following right or left limb strength training in right-handed participants. Methods: Changes in strength, muscle thickness and indices of corticospinal plasticity were analyzed in 23 adults who were exposed to 3-weeks of either right-hand strength training (RHT) or left-hand strength training (LHT). Results: Maximum voluntary wrist extensor strength in both the trained and untrained limb increased, irrespective of which limb was trained, with TMS revealing reduced corticospinal inhibition. Conclusions: Cross-education of strength was not limited by which limb was trained and reduced corticospinal inhibition was not just confined to the trained limb.Critically, from a behavioral perspective, the magnitude of cross-education was not limited by which limb was trained.

Recent studies report that depletion and repletion of muscle taurine (Tau) to endogenous levels affects skeletal muscle contractility in vitro. In this study, muscle Tau content was raised above endogenous levels by supplementing male Sprague-Dawley rats with 2.5% (wt/vol) Tau in drinking water for 2 wk, after which extensor digitorum longus (EDL) muscles were examined for in vitro contractile properties, fatigue resistance, and recovery from fatigue after two different high-frequency stimulation bouts. Tau supplementation increased muscle Tau content by approximately 40% and isometric twitch force by 19%, shifted the force-frequency relationship upward and to the left, increased specific force by 4.2%, and increased muscle calsequestrin protein content by 49%. Force at the end of a 10-s (100 Hz) continuous tetanic stimulation was 6% greater than controls, while force at the end of the 3-min intermittent high-frequency stimulation bout was significantly higher than controls, with a 12% greater area under the force curve. For 1 h after the 10-s continuous stimulation, tetanic force in Tau-supplemented muscles remained relatively stable while control muscle force gradually deteriorated. After the 3-min intermittent bout, tetanic force continued to slowly recover over the next 1 h, while control muscle force again began to decline. Tau supplementation attenuated F(2)-isoprostane production (a sensitive indicator of reactive oxygen species-induced lipid peroxidation) during the 3-min intermittent stimulation bout. Finally, Tau transporter protein expression was not altered by the Tau supplementation. Our results demonstrate that raising Tau content above endogenous levels increases twitch and subtetanic and specific force in rat fast-twitch skeletal muscle. Also, we demonstrate that raising Tau protects muscle function during high-frequency in vitro stimulation and the ensuing recovery period and helps reduce oxidative stress during prolonged stimulation.

Lateral ankle sprain (LAS) is one of the most common injuries incurred during sporting activities, and effective rehabilitation programs for this condition are challenging to develop. The purpose of this research was to compare the effect of 6 weeks of balance training on either a mini-trampoline or a dura disc on postural sway and to determine if the mini-trampoline or the dura disc is more effective in improving postural sway. Twenty subjects (11 men, 9 women) with a mean age of 25.4 +/- 4.2 years were randomly allocated into a control group, a dura disc training (DT) group, or a mini-trampoline (MT) group. Subjects completed 6 weeks of balance training. Postural sway was measured by subjects performing a single limb stance on a force plate. The disbursement of the center of pressure was obtained from the force plate in the medial-lateral and the anterior-posterior sway path and was subsequently used for pretest and posttest analysis. After the 6-week training intervention, there was a significant (p < 0.05) difference in postural sway between pre- and posttesting for both the MT (pretest = 56.8 +/- 20.5 mm, posttest = 33.3 +/- 8.5 mm) and DT (pretest = 41.3 +/- 2.6 mm, posttest = 27.2 +/- 4.8 mm) groups. There was no significant (p > 0.05) difference detected for improvements between the MT and DT groups. These results indicate that not only is the mini-trampoline an effective tool for improving balance after LAS, but it is equally as effective as the dura disc.

This study investigated the effect of taurine and β-alanine supplementation on muscle function and muscle taurine transporter (TauT) protein expression in mdx mice. Wild-type (WT) and mdx mice (5 months) were supplemented with taurine or β-alanine for 4 weeks, after which in vitro contractile properties, fatigue resistance and force recovery, and the expression of the TauT protein and proteins involved in excitation-contraction (E-C) coupling were examined in fast-twitch muscle. There was no difference in basal TauT protein expression or basal taurine content between mdx than WT muscle. Supplementation with taurine and β-alanine increased and reduced taurine content, respectively, in muscle from WT and mdx mice but had no effect of TauT protein. Taurine supplementation reduced body and muscle mass, and enhanced fatigue resistance and force recovery in mdx muscle. β-Alanine supplementation enhanced fatigue resistance in WT and mdx muscle. There was no difference in the basal expression of key E-C coupling proteins [ryanodine receptor 1 (RyR1), dihydropyridine receptor (DHPR), sarco(endo)plasmic reticulum Ca-ATPase 1 (SERCA1) or calsequestrin 1 (CSQ1)] between WT and mdx mice, and the expression of these proteins was not altered by taurine or β-alanine supplementation. These findings suggest that TauT protein expression is relatively insensitive to changes in muscle taurine content in WT and mdx mice, and that taurine and β-alanine supplementation may be viable therapeutic strategies to improve fatigue resistance of dystrophic skeletal muscle.

These findings show that the corticospinal responses to strength training of a proximal upper limb muscle are not spatially restricted, but rather, results in a change in connectivity, among an agonist and a synergistic muscle relevant to force production.

Northumbria University has developed Northumbria Research Link (NRL) to enable users to access the University's research output. Copyright © and moral rights for items on NRL are retained by the individual author(s) and/or other copyright owners. Single copies of full items can be reproduced, displayed or performed, and given to third parties in any format or medium for personal research or study, educational, or not-for-profit purposes without prior permission or charge, provided the authors, title and full bibliographic details are given, as well as a hyperlink and/or URL to the original metadata page. The content must not be changed in any way. Full items must not be sold commercially in any format or medium without formal permission of the copyright holder. The full policy is available online: http://nrl.northumbria.ac.uk/policies.html This document may differ from the final, published version of the research and has been made available online in accordance with publisher policies. To read and/or cite from the published version of the research, please visit the publisher's website (a subscription may be required.) men, aged 18-35 years; training group; n = 10 and control group; n = 10) before and after 3-weeks of strengthtraining the right biceps brachii at 80% of 1-repetition maximum (1-RM). Recruitment-curves for corticomotor excitability and inhibition of the untrained homologous and non-homologous muscle were constructed and assessed by examining the area under the recruitment curve (AURC). Strength-training increased strength of the trained elbow flexors (29%), resulting in a 18% increase in contralateral strength of the untrained elbow flexors (P <0.0001). The trained wrist flexors increased by 19%, resulting in a 12% increase in strength of the untrained wrist flexors (P = 0.005). TMS showed increased corticomotor excitability and decreased corticomotor inhibition for the untrained homologous muscle (P < 0.05); however, there were no changes in the untrained non-homologous muscle (P > 0.05). These findings show that the cross-education of muscular strength is spatially distributed; however, the neural adaptations are confined to the motor pathway ipsilateral to the untrained homologous agonist.

Growth in online higher education offerings has been significant in recent years, with many Australian Universities launching programs to extend into new markets and meet the student demand for greater flexibility in delivery modes. Further, it is well understood that good support is an essential component to student success, satisfaction and retention. Despite this, orientation, including non-academic support, is often overlooked in online education systems. Therefore, the current study aimed to develop an orientation program to increase student preparedness and facilitate ongoing support, in addition to developing evidence-based best-practice strategies to support academic’s when developing new online courses.