Transcriptional programming of translation by BCL6 controls skeletal muscle proteostasis.

Skeletal muscle is dynamically controlled by the balance of protein synthesis and degradation. Here we discover an unexpected function for the transcriptional repressor B cell lymphoma 6 (BCL6) in muscle proteostasis and strength in mice. Skeletal muscle-specific Bcl6 ablation in utero or in adult mice results in over 30% decreased muscle mass and force production due to reduced protein synthesis and increased autophagy, while it promotes a shift to a slower myosin heavy chain fibre profile. Ribosome profiling reveals reduced overall translation efficiency in Bcl6-ablated muscles. Mechanistically, tandem chromatin immunoprecipitation, transcriptomic and translational analyses identify direct BCL6 repression of eukaryotic translation initiation factor 4E-binding protein 1 (Eif4ebp1) and activation of insulin-like growth factor 1 (Igf1) and androgen receptor (Ar). Together, these results uncover a bifunctional role for BCL6 in the transcriptional and translational control of muscle proteostasis.

Nanoparticles from Microalgae and Their Biomedical Applications.

Over the years, microalgae have been a source of useful compounds mainly used as food and dietary supplements. Recently, microalgae have been used as a source of metabolites that can participate in the synthesis of several nanoparticles through inexpensive and environmentally friendly routes alternative to chemical synthesis. Notably, the occurrence of global health threats focused attention on the microalgae application in the medicinal field. In this review, we report the influence of secondary metabolites from marine and freshwater microalgae and cyanobacteria on the synthesis of nanoparticles that were applied as therapeutics. In addition, the use of isolated compounds on the surface of nanoparticles to combat diseases has also been addressed. Although studies have proven the beneficial effect of high-value bioproducts on microalgae and their potential in medicine, there is still room for understanding their exact role in the human body and translating lab-based research into clinical trials.

Alterations of skeletal muscle bioenergetics in a mouse with F508del mutation leading to a cystic fibrosis-like condition.

High energy expenditure is reported in cystic fibrosis (CF) animal models and patients. Alterations in skeletal muscle oxidative capacity, fuel utilization, and the creatine kinase-phosphocreatine system suggest mitochondrial dysfunction. Studies were performed on congenic C57BL/6J and F508del (Cftrtm1kth) mice. Indirect calorimetry was used to measure gas exchange to evaluate aerobic capacity during treadmill exercise. The bioenergetic function of skeletal muscle subsarcolemmal (SSM) and interfibrillar mitochondria (IFM) was evaluated using an integrated approach combining measurement of the rate of oxidative phosphorylation by polarography and of electron transport chain activities by spectrophotometry. CF mice have reduced maximal aerobic capacity. In SSM of these mice, oxidative phosphorylation was impaired in the presence of complex I, II, III, and IV substrates except when glutamate was used as substrate. This impairment appeared to be caused by a defect in complex V activity, whereas the oxidative system of the electron transport chain was unchanged. In IFM, oxidative phosphorylation and electron transport chain activities were preserved, whereas complex V activity was reduced, in CF. Furthermore, creatine kinase activity was reduced in both SSM and IFM of CF skeletal muscle. The decreased complex V activity in SSM resulted in reduced oxidative phosphorylation, which could explain the reduced skeletal muscle response to exercise in CF mice. The decrease in mitochondrial creatine kinase activity also contributed to this poor exercise response.

Functional abdominal wall reconstruction improves core physiology and quality-of-life.

INTRODUCTION: One of the goals of modern ventral hernia repair (VHR) is restoring the linea alba by returning the rectus muscles to the midline. Although this practice presumably restores native abdominal wall function, improvement of abdominal wall function has never been measured in a scientific fashion. We hypothesized that a dynamometer could be used to demonstrate an improvement in rectus muscle function after open VHR with restoration of the midline, and that this improvement would be associated with a better quality-of-life. METHODS: Thirteen patients agreed to dynamometric analysis before and 6 months after an open posterior component separation (Rives-Stoppa technique complimented with a transversus abdominis muscle release) and mesh sublay. Analysis done using a dynamometer (Biodex 3, Corp, Shirley, NY) included measurement of peak torque (PT; N*m) and PT per bodyweight (BW; %) generated during abdominal flexion in 5 settings: Isokinetic analysis at 45°/s and 60°/s as well as isometric analysis at 0°, -15°, and +15°. Power (W) was calculated during isokinetic settings. Quality-of-life was measured using our validated HerQles survey at the time of each dynamometric analysis. RESULTS: Thirteen patients (mean age, 54 ± 9 years; mean body mass index, 31 ± 7 kg/m(2)) underwent repair with restoration of the midline using the aforementioned technique. Mean hernia width was 12.5 cm (range, 5-19). Improvements in PT and PT/BW were significant in all 5 settings (P < .05). Improvement in power during isokinetic analyses at 45°/s and 60°/s was also significant (P < .05). All patients reported an improvement in quality-of-life, which was associated positively with each dynamometric parameter. CONCLUSION: Restoration of the linea alba during VHR is associated with improved abdominal wall functionality. Analysis of rectus muscle function using a dynamometer showed statistical improvement by isokinetic and isometric measurements, all of which were associated with an improvement in quality-of-life.

Model analysis of the relationship between intracellular PO2 and energy demand in skeletal muscle.

On the basis of experimental studies, the intracellular O(2) (iPo(2))-work rate (WR) relationship in skeletal muscle is not unique. One study found that iPo(2) reached a plateau at 60% of maximal WR, while another found that iPo(2) decreased linearly at higher WR, inferring capillary permeability-surface area (PS) and blood-tissue O(2) gradient, respectively, as alternative dominant factors for determining O(2) diffusion changes during exercise. This relationship is affected by several factors, including O(2) delivery and oxidative and glycolytic capacities of the muscle. In this study, these factors are examined using a mechanistic, mathematical model to analyze experimental data from contracting skeletal muscle and predict the effects of muscle contraction on O(2) transport, glycogenolysis, and iPo(2). The model describes convection, O(2) diffusion, and cellular metabolism, including anaerobic glycogenolysis. Consequently, the model simulates iPo(2) in response to muscle contraction under a variety of experimental conditions. The model was validated by comparison of simulations of O(2) uptake with corresponding experimental responses of electrically stimulated canine muscle under different O(2) content, blood flow, and contraction intensities. The model allows hypothetical variation of PS, glycogenolytic capacity, and blood flow and predictions of the distinctive effects of these factors on the iPo(2)-contraction intensity relationship in canine muscle. Although PS is the main factor regulating O(2) diffusion rate, model simulations indicate that PS and O(2) gradient have essential roles, depending on the specific conditions. Furthermore, the model predicts that different convection and diffusion patterns and metabolic factors may be responsible for different iPo(2)-WR relationships in humans.