The ER-Bound RING Finger Protein 5 (RNF5/RMA1) Causes Degenerative Myopathy in Transgenic Mice and Is Deregulated in Inclusion Body Myositis

Growing evidence supports the importance of ubiquitin ligases in the pathogenesis of muscular disorders, although underlying mechanisms remain largely elusive. Here we show that the expression of RNF5 (aka RMA1), an ER-anchored RING finger E3 ligase implicated in muscle organization and in recognition and processing of malfolded proteins, is elevated and mislocalized to cytoplasmic aggregates in biopsies from patients suffering from sporadic-Inclusion Body Myositis (sIBM). Consistent with these findings, an animal model for hereditary IBM (hIBM), but not their control littermates, revealed deregulated expression of RNF5. Further studies for the role of RNF5 in the pathogenesis of s-IBM and more generally in muscle physiology were performed using RNF5 transgenic and KO animals. Transgenic mice carrying inducible expression of RNF5, under control of β-actin or muscle specific promoter, exhibit an early onset of muscle wasting, muscle degeneration and extensive fiber regeneration. Prolonged expression of RNF5 in the muscle also results in the formation of fibers containing congophilic material, blue-rimmed vacuoles and inclusion bodies. These phenotypes were associated with altered expression and activity of ER chaperones, characteristic of myodegenerative diseases such as s-IBM. Conversely, muscle regeneration and induction of ER stress markers were delayed in RNF5 KO mice subjected to cardiotoxin treatment. While supporting a role for RNF5 Tg mice as model for s-IBM, our study also establishes the importance of RNF5 in muscle physiology and its deregulation in ER stress associated muscular disorders

Morphological, physiological and behavioural evaluation of a ‘Mice in Space’ housing system

Environmental conditions likely affect physiology and behaviour of mice used for life sciences research on Earth or in Space. Here, we analysed the effects of cage confinement on the weightbearing musculoskeletal system, behaviour and stress of wild-type mice (C57BL/6JRj, 30 g b.wt., total n = 24) housed for 25 days in a prototypical ground-based and fully automated life support habitat device called “Mice in Space” (MIS). Compared with control housing (individually ventilated cages) the MIS mice revealed no significant changes in soleus muscle size and myofiber distribution (type I vs. II) and quality of bone (3-D microarchitecture and mineralisation of calvaria, spine and femur) determined by confocal and micro-computed tomography. Corticosterone metabolism measured non-invasively (faeces) monitored elevated adrenocortical activity at only start of the MIS cage confinement (day 1). Behavioural tests (i.e., grip strength, rotarod, L/D box, elevated plus-maze, open field, aggressiveness) performed subsequently revealed only minor changes in motor performance (MIS vs. controls). The MIS habitat will not, on its own, produce major effects that could confound interpretation of data induced by microgravity exposure during spaceflight. Our results may be even more helpful in developing multidisciplinary protocols with adequate scenarios addressing molecular to systems levels using mice of various genetic phenotypes in many laboratories

Estudo comparativo da força muscular da mão entre cadetes homens e mulheres da Força Aérea Brasileira Grip and pinch strength in Brazilian Air Force cadet pilots: a comparative study between men and women

O objetivo do estudo foi quantificar a força muscular da mão, nos movimentos de preensão palmar e três tipos de pinça, comparando os cadetes homens e mulheres. Foram avaliados 31 cadetes da Academia da Força Aérea Basileira, sendo 17 homens e 14 mulheres, com os dinamômetros Jamar e Preston Pinch Gauge. A média de preensão das mulheres foi de 31,4 kgf no lado dominante e 29,3 kgf no lado não-dominante; nos homens, foi 43,6 e 41,2 kgf, respectivamente (p<0,01). Na pinça lateral, a média feminina foi de 7,4 kgf e masculina, 10,2 kgf, no lado dominante (p<0,01); na pinça trípode, a média das mulheres foi de 7,2 kgf no lado dominante e 7,1 kgf do lado não-dominante; nos homens, foi respectivamente de 9,8 kgf e 9,5 kgf (p<0,01); na pinça polpa-a-polpa, as médias femininas foram de 4,9 e 4,6 kgf nos lados dominante e não-dominante; dos homens, foram de 6,5 e 5,7 kgf nos lados dominante e não-dominante, respectivamente (p<0,01). A força de preensão palmar, pinça lateral, pinça trípode e pinça polpa-a-polpa foi significantemente maior nos cadetes masculinos do que nas mulheres. Ambos os sexos mostraram mais força do lado dominante do que no não-dominante, exceto na pinça trípode. Quando comparados à população em geral, há pouca diferença dos valores obtidos nos cadetes, tanto em relação ao sexo quanto à dominância. Esses achados podem ser relevantes na avaliação fisioterapêutica e para o desempenho desses pilotos.<br>The aim of this study was to quantify the hand muscle strength during grip and pinch movements, and to compare results between men and women. Thirty-one cadet pilots (17 men and 14 women) from the Brazilian Air Force Academy were assessed by means of Jamar dynamometer (grip) and Preston Pinch Gauge (pinch). Female cadets mean grip was 31.4 kgf at dominant hand and 29.3 kgf at non-dominant hand; in male subjects, corresponding values were 43.6 kgf and 41.2 kgf. Mean female lateral pinch at the dominant hand was 7.4 kgf and men's, 10.2 kgf (p<0.01); tripod pinch values were 7.2 kgf at dominant side and 7.1 kgf at non-dominant for women, and 9.8 kgf and 9.50 kgf for men, respectively (p<0.01); women pinch values were 4.9 kgf and 4.6 at dominant and non-dominant hands, and men's, 6.5 kgf and 5.7 kgf respectively (p<0.01). Grip, pinch, lateral pinch, and tripod pinch were all significantly higher (p<0.01) in men than in women. Both sexes showed higher strength at the dominant side, except of the tripod pinch. When compared to the population in general, there are little differences among cadets, both as to sex and dominance. These findings may be of relevance both for pilots performance and physical therapy assessment

Progressive resistance training for persons with intellectual disabilities and visual impairment

Background Knowledge concerning the feasibility and effects of progressive resistance training (PRT) for persons with intellectual disabilities and visual impairment who are categorized in Gross Motor Function Classification System (GMFCS) Level 1 is limited. The aim of our study was to evaluate feasibility and effect of PRT on participants' Quadriceps strength and personal goals. Methods Eight Participants followed a PRT program for 10 weeks. Feasibility was determined by percentage of attendance and compliance. The effect of PRT was analyzed with a linear mixed model (p <0.05) and by normalized bootstrap (95% CI). Results Participants attended 87.8% of the sessions and trained according to the PRT program, indicating sufficient compliance. Quadriceps strength increased significantly by 69%, and participants' personal goals were achieved. Conclusion PRT is a feasible and potentially effective method for increasing Quadriceps strength as well as achieving personal goals in persons with intellectual disabilities and visual impairment with GMFCS Level 1