Characterization of Long Non-coding RNAs Modified by m6A RNA Methylation in Skeletal Myogenesis

Proper development of mammalian skeletal muscle relies on precise gene expression regulation. Our previous studies revealed that muscle development is regulated by both mRNA and long non-coding RNAs (lncRNAs). Accumulating evidence has demonstrated that N6-methyladenosine (m6A) plays important roles in various biological processes, making it essential to profile m6A modification on a transcriptome-wide scale in developing muscle. Patterns of m6A methylation in lncRNAs in developing muscle have not been uncovered. Here, we reveal differentially expressed lncRNAs and report temporal m6A methylation patterns in lncRNAs expressed in mouse myoblasts and myotubes by RNA-seq and methylated RNA immunoprecipitation (MeRIP) sequencing. Many lncRNAs exhibit temporal differential expression, and m6A-lncRNAs harbor the consensus m6A motif “DRACH” along lncRNA transcripts. Interestingly, we found that m6A methylation levels of lncRNAs are positively correlated with the transcript abundance of lncRNAs. Overexpression or knockdown of m6A methyltransferase METTL3 alters the expression levels of these lncRNAs. Furthermore, we highlight that the function of m6A genic lncRNAs might correlate to their nearby mRNAs. Our work reveals a fundamental expression reference of m6A-mediated epitranscriptomic modifications in lncRNAs that are temporally expressed in developing muscle.

Dysregulation of the Tweak/Fn14 pathway in skeletal muscle of spinal muscular atrophy mice

Spinal muscular atrophy (SMA) is a childhood neuromuscular disorder caused by depletion of the survival motor neuron (SMN) protein. SMA is characterized by the selective death of spinal cord motor neurons, leading to progressive muscle wasting. Loss of skeletal muscle in SMA is a combination of denervation-induced muscle atrophy and intrinsic muscle pathologies. Elucidation of the pathways involved is essential to identify the key molecules that contribute to and sustain muscle pathology. The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/TNF receptor superfamily member fibroblast growth factor inducible 14 (Fn14) pathway has been shown to play a critical role in the regulation of denervation-induced muscle atrophy as well as muscle proliferation, differentiation and metabolism in adults. However, it is not clear whether this pathway would be important in highly dynamic and developing muscle. We thus investigated the potential role of the TWEAK/Fn14 pathway in SMA muscle pathology, using the severe Taiwanese Smn-/-;SMN2 and the less severe Smn2B/- SMA mice, which undergo a progressive neuromuscular decline in the first three post-natal weeks. Here, we report significantly dysregulated expression of the TWEAK/Fn14 pathway during disease progression in skeletal muscle of the two SMA mouse models. In addition, siRNA-mediated Smn knockdown in C2C12 myoblasts suggests a genetic interaction between Smn and the TWEAK/Fn14 pathway. Further analyses of SMA, Tweak-/- and Fn14-/- mice revealed dysregulated myopathy, myogenesis and glucose metabolism pathways as a common skeletal muscle feature, and providing further evidence in support of a relationship between the TWEAK/Fn14 pathway and Smn. Finally, a pharmacological intervention (Fc-TWEAK) to upregulate the activity of the TWEAK/Fn14 pathway improved disease phenotypes in the two SMA mouse models. Our study provides novel mechanistic insights into the molecular players that contribute to muscle pathology in SMA and into the role of the TWEAK/Fn14 pathway in developing muscle.

Fibroblast fusion to the muscle fiber regulates myotendinous junction formation

Vertebrate muscles and tendons are derived from distinct embryonic origins yet they must interact in order to facilitate muscle contraction and body movements. How robust muscle tendon junctions (MTJs) form to be able to withstand contraction forces is still not understood. Using techniques at a single cell resolution we reexamine the classical view of distinct identities for the tissues composing the musculoskeletal system. We identify fibroblasts that have switched on a myogenic program and demonstrate these dual identity cells fuse into the developing muscle fibers along the MTJs facilitating the introduction of fibroblast-specific transcripts into the elongating myofibers. We suggest this mechanism resulting in a hybrid muscle fiber, primarily along the fiber tips, enables a smooth transition from muscle fiber characteristics towards tendon features essential for forming robust MTJs. We propose that dual characteristics of junctional cells could be a common mechanism for generating stable interactions between tissues throughout the musculoskeletal system.

Developing muscle power for combat sports athletes

<p>In combat sports, the specificity of the training requires that the athlete improve all performance indicators associated with the match. For this reason, muscle power seems to be determinant during the application of the techniques that result in scores, specifically punches, kicks, elbows, knees, throwing techniques, transitions to the groundwork and some groundwork techniques and sometimes, the win match by knockout. Based in these information’s, the present chapter will approach items referring to the muscle power manifestation and monitoring, and to the training prescription of exercises for the grappling, striking and mixed combat sports.</p>

Profile of Muscle Strength and Physical Performance with the Incidence of Urinary Incontinence in Elderly Women

Introduction: The 200 million people in the world experience urinary incontinence. In general, with increasing age, the capacity of the bladder decreases. The remaining urine in the bladder tends to increase and irregular contraction of the bladder muscles becomes more frequent. This situation often makes the elderly experience problems with the fulfillment of urine elimination needs, namely urinary incontinence. Efforts to overcome urinary incontinence in the form of bladder training programs are aimed at developing muscle tone and bladder sphincter so that it can function optimally. Objective: Knowing the profile of muscle strength and physical performance with the incidence of urinary incontinence in elderly women. Methods: This research was a retrospective descriptive study based on the results of filling out the questionnaire and evaluating it directly. Based on tabulated data, 38 elderly women were selected as the study sample. Results: There were (42.1%) urinary incontinence on elderly with very poor left hand muscle strength and (50%) urinary incontinence on elderly with very poor right hand muscle strength. In physical performance with urinary incontinence as many as (57.8%) were normal and (42.1%) were poor. Conclusions: Muscle strength and physical performance can be used as a measurement to early detection of the urinary incontinence. Keywords: urinary incontinence; muscle strength; physical performance; descriptive retrospective study

Review on Effects of Conventional Physiotherapy in Muscle Strength using Meta-Analytic Critical Conventional Physiotherapy Method

This examination expected to efficiently survey distributed exploration written works to distinguish and assess the viability of Conventional Physiotherapy (CP) training on progress in muscle quality in moderately aged and old female people analyzed as having Osteoarthritis (OA) of the knee. Different information bases having articles distributed somewhere in the range of 2000 and 2016, for example, - PubMed, Web of Science, ProQuest, CINAHL, &Ebscohost are deliberately looked for articles identified with knee OA. Just unmistakable, meta-systematic and interventional investigation articles are held. Generally, impact size with 95% “confidence intervals (CIs)” is utilized to survey the quality of connection among intercessions and development in muscle quality between old OA of knee patients, by utilizing an arbitrary impacts model. Heterogeneity was likewise assessed. Nine exploratory investigations were chosen and remembered for the audit, out of 4 are randomized controlled preliminaries & remaining are pseudo-randomized controlled preliminaries. The surveys deliberating drug co-mediations are prohibited. Normalized impact sizes with 95% CIs are determined from pre-mediation and post-intercession methods for CP preparing gathering and other mediation or no-mediation gathering. Accordingly, the valuable effect of CP preparing in developing muscle-quality in OA patients didn't get affirmed. This discovery suggests that next investigations following thorough approach are needed to infer complete proof to affirm the gainful impacts of CP preparing on progress in muscle quality between old patients experiencing OA of the knee.

Methods of Strength Building of Qualified Weightlifters

The article shows that in the training process of modern weightlifters of high qualification, combinations of several most effective methods of developing muscle strength are used. During the preparation of the article, the analysis of scientific and methodological literature on the research topic was carried out. The training plans of qualified weightlifters were also studied. The results of the study allow us to conclude that from 70% to 90% of the total training load of qualified weightlifters falls on exercises performed using the method of repeated effort and the method of short-term maximum stress

Fibroblast fusion to the muscle fiber regulates myotendinous junction formation

SummaryVertebrate muscles and tendons are derived from distinct embryonic origins yet they must interact in order to facilitate muscle contraction and body movements. How robust muscle tendon junctions (MTJs) form to be able to withstand contraction forces is still not understood. Using techniques at a single cell resolution we reexamined the classical view of distinct identities for the tissues composing the musculoskeletal system. We identified fibroblasts that have switched on a myogenic program and demonstrate these dual identity cells fuse into the developing muscle fibers along the MTJs facilitating the introduction of fibroblast-specific transcripts into the elongating myofibers. We suggest this mechanism resulting in a hybrid muscle fiber, primarily along the fiber tips, enables a smooth transition from muscle fiber characteristics towards tendon features essential for forming robust MTJs. We propose that dual characteristics of junctional cells could be a common mechanism for generating stable interactions between tissues throughout the musculoskeletal system.

Reverse-engineering forces responsible for dynamic clustering and spreading of multiple nuclei in developing muscle cells

During Drosophila muscle development, multiple nuclei transition from being clustered together, to splitting into two smaller clusters, to spreading along the cell length. Computational screening reveals that initial short-ranged internuclear attraction and final long-ranged repulsion, overlapping in time, are responsible for the nuclear dynamics.

Cerebral peak alpha frequency reflects average pain severity in a human model of sustained, musculoskeletal pain

Heightened pain sensitivity, the amount of pain experienced in response to a noxious event, is a known risk factor for development of chronic pain. We have previously reported that pain-free, sensorimotor peak alpha frequency (PAF) is a reliable biomarker of pain sensitivity for thermal, prolonged pains lasting tens of minutes. To test whether PAF can provide information about pain sensitivity occurring over clinically relevant timescales (i.e., weeks), EEG was recorded before and while participants experienced a long-lasting pain model, repeated intramuscular injection of nerve growth factor (NGF), that produces progressively developing muscle pain for up to 21 days. We demonstrate that pain-free, sensorimotor PAF is negatively correlated with NGF pain sensitivity; increasingly slower PAF is associated with increasingly greater pain sensitivity. Furthermore, PAF remained stable following NGF injection, indicating that the presence of NGF pain for multiple weeks is not sufficient to induce the PAF slowing reported in chronic pain. In total, our results demonstrate that slower pain-free, sensorimotor PAF is associated with heightened sensitivity to a long-lasting musculoskeletal pain and also suggest that the apparent slowing of PAF in chronic pain may reflect predisease pain sensitivity. NEW & NOTEWORTHY Pain sensitivity, the intensity of pain experienced after injury, has been identified as an important risk factor in the development of chronic pain. Biomarkers of pain sensitivity have the potential to ease chronic pain burdens by preventing disease emergence. In the current study, we demonstrate that the speed of pain-free, sensorimotor peak alpha frequency recorded during resting-state EEG predicts pain sensitivity to a clinically-relevant, human model of prolonged pain that persists for weeks.