Human Muscle Synergy Analysis to Approach the Understanding of Brain Control Algorithm

Purpose: Muscle synergy is a functional unit that coordinates the activity of a number of muscles. In this study, the extraction of muscle synergies in three types of hand movements in the horizontal plane is investigated. Materials and Methods: So, after constructing the tracking pattern of three signals, by LabVIEW, the Electromyography (EMG) signal from six muscles of hand was recorded. Then time-constant muscle synergies and their activity curves from the recorded EMG signals were extracted using Non-negative Matrix Factorization (NMF) method. Results: Comparison of these patterns showed that the non-random motions’ synergies were more similar than the random motions among different individuals. It was observed that in all movements, the similarity of the synergies in one cluster was greater than the similarity of their corresponding activation curves. Conclusion: The results showed that the complexity of the recurrence plot in random movement is greater than that of the other movements.

Genotype Score for Iron Status Is Associated with Muscle Fiber Composition in Women

Human muscle fiber composition is heterogeneous and mainly determined by genetic factors. A previous study reported that experimentally induced iron deficiency in rats increases the proportion of fast-twitch muscle fibers. Iron status has been reported to be affected by genetic factors. As the TMPRSS6 rs855791 T/C and HFE rs1799945 C/G polymorphisms are strongly associated with iron status in humans, we hypothesized that the genotype score (GS) based on these polymorphisms could be associated with the muscle fiber composition in humans. Herein, we examined 214 Japanese individuals, comprising of 107 men and 107 women, for possible associations of the GS for iron status with the proportion of myosin heavy chain (MHC) isoforms (I, IIa, and IIx) as markers of muscle fiber composition. No statistically significant correlations were found between the GS for iron status and the proportion of MHC isoforms in all participants. When the participants were stratified based on sex, women showed positive and negative correlations of the GS with MHC-IIa (age-adjusted p = 0.020) and MHC-IIx (age-adjusted p = 0.011), respectively. In contrast, no correlation was found in men. In women, a 1-point increase in the GS was associated with 2.42% higher MHC-IIa level and 2.72% lower MHC-IIx level. Our results suggest that the GS based on the TMPRSS6 rs855791 T/C and HFE rs1799945 C/G polymorphisms for iron status is associated with muscle fiber composition in women.

Acute RyR1 Ca2+ leak enhances NADH-linked mitochondrial respiratory capacity

Sustained ryanodine receptor (RyR) Ca2+ leak is associated with pathological conditions such as heart failure or skeletal muscle weakness. We report that a single session of sprint interval training (SIT), but not of moderate intensity continuous training (MICT), triggers RyR1 protein oxidation and nitrosylation leading to calstabin1 dissociation in healthy human muscle and in in vitro SIT models (simulated SIT or S-SIT). This is accompanied by decreased sarcoplasmic reticulum Ca2+ content, increased levels of mitochondrial oxidative phosphorylation proteins, supercomplex formation and enhanced NADH-linked mitochondrial respiratory capacity. Mechanistically, (S-)SIT increases mitochondrial Ca2+ uptake in mouse myotubes and muscle fibres, and decreases pyruvate dehydrogenase phosphorylation in human muscle and mouse myotubes. Countering Ca2+ leak or preventing mitochondrial Ca2+ uptake blunts S-SIT-induced adaptations, a result supported by proteomic analyses. Here we show that triggering acute transient Ca2+ leak through RyR1 in healthy muscle may contribute to the multiple health promoting benefits of exercise.

Recent Trends in Biofabrication Technologies for Studying Skeletal Muscle Tissue-Related Diseases

In native skeletal muscle, densely packed myofibers exist in close contact with surrounding motor neurons and blood vessels, which are embedded in the fibrous connective tissue. In comparison to conventional two-dimensional (2D) cultures, the three-dimensional (3D) engineered skeletal muscle models allow structural and mechanical resemblance with native skeletal muscle tissue by providing geometric confinement and physiological matrix stiffness to the cells. In addition, various external stimuli applied to these models enhance muscle maturation along with cell–cell and cell–extracellular matrix interaction. Therefore, 3D in vitro muscle models can adequately recapitulate the pathophysiologic events occurring in tissue–tissue interfaces inside the native skeletal muscle such as neuromuscular junction. Moreover, 3D muscle models can induce pathological phenotype of human muscle dystrophies such as Duchenne muscular dystrophy by incorporating patient-derived induced pluripotent stem cells and human primary cells. In this review, we discuss the current biofabrication technologies for modeling various skeletal muscle tissue-related diseases (i.e., muscle diseases) including muscular dystrophies and inflammatory muscle diseases. In particular, these approaches would enable the discovery of novel phenotypic markers and the mechanism study of human muscle diseases with genetic mutations.

Tension-driven multi-scale self-organisation in human iPSC-derived muscle fibers

Human muscle is a hierarchically organised tissue with its contractile cells called myofibers packed into large myofiber bundles. Each myofiber contains periodic myofibrils built by hundreds of contractile sarcomeres that generate large mechanical forces. To better understand the mechanisms that coordinate human muscle morphogenesis from tissue to molecular scales, we adopted a simple in vitro system using induced pluripotent stem cell-derived human myogenic precursors. When grown on an unrestricted two-dimensional substrate, developing myofibers spontaneously align and self-organise into higher-order myofiber bundles, which grow and consolidate to stable sizes. Following a transcriptional boost of sarcomeric components, myofibrils assemble into chains of periodic sarcomeres that emerge across the entire myofiber. By directly probing tension we found that tension build-up precedes sarcomere assembly and increases within each assembling myofibril. Furthermore, we found that myofiber ends stably attach to other myofibers using integrin-based attachments and thus myofiber bundling coincides with stable myofiber bundle attachment in vitro. A failure in stable myofiber attachment results in a collapse followed by a disassembly of the myofibrils. Overall, our results strongly suggest that mechanical tension across sarcomeric components as well as between differentiating myofibers is key to coordinate the multi-scale self-organisation of muscle morphogenesis.

SPECTROPHOTOPOLARIMETRY AS A METHOD FOR DETERMINING THE TIME DYNAMICS OF CHANGES IN THE MORPHOLOGICAL STRUCTURE OF MUSCLE TISSUE

Introduction: The article presents the current state of issues regarding the diagnosis of pathological conditions for forensic medical experts, in particular the study of normal muscle tissue and in the presence of hemorrhages. Particular attention is paid to biophysical research methods with evidence-based accuracy, objectivity, reproducibility, and rapid results. Objectives: The purpose of the research was to study the possibilities of using spectrophotopolyarimetric methods to analyze and determine the relationship of morphological structure of biological tissues with the temporal dynamics of changes in their optical parameters, to establish the possibility of differentiating necrotic changes and signs of damage by applying Mueller matrices of human muscle tissue samples. Results: During the study, we found a number of features and patterns of change in the properties of the laser beam as a result of passing through biological tissue. Polarization-correlation methods provide new, objective information about the dynamics of change in laser polarimetric imaging of morphological structure of biological tissues. By analyzing the statistical distributions of the ellipticity of polarization of laser images of normal human muscle tissue and in the presence of hemorrhages, the possibility of identifying the relationship between the development of statistically significant changes with increasing time of death and the possibility of differentiating them are considered. Conclusion: Based on these results, we can conclude that employing laser polarization methods will allow us to open new doors in the study of the biological tissues of the human body. The results showed the effectiveness of the studied methodology and the prospect of further research in this direction.

Matrigel 3D bioprinting of contractile human skeletal muscle models recapitulating exercise and pharmacological responses

A key to enhance the low translatability of preclinical drug discovery are in vitro human three-dimensional (3D) microphysiological systems (MPS). Here, we show a new method for automated engineering of 3D human skeletal muscle models in microplates and functional compound screening to address the lack of muscle wasting disease medication. To this end, we adapted our recently described 24-well plate 3D bioprinting platform with a printhead cooling system to allow microvalve-based drop-on-demand printing of cell-laden Matrigel containing primary human muscle precursor cells. Mini skeletal muscle models develop within a week exhibiting contractile, striated myofibers aligned between two attachment posts. As an in vitro exercise model, repeated high impact stimulation of contractions for 3 h by a custom-made electrical pulse stimulation (EPS) system for 24-well plates induced interleukin-6 myokine expression and Akt hypertrophy pathway activation. Furthermore, the known muscle stimulators caffeine and Tirasemtiv acutely increase EPS-induced contractile force of the models. This validated new human muscle MPS will benefit development of drugs against muscle wasting diseases. Moreover, our Matrigel 3D bioprinting platform will allow engineering of non-self-organizing complex human 3D MPS.

Effect of dietary nitrate on human muscle power: a systematic review and individual participant data meta-analysis

Background Previous narrative reviews have concluded that dietary nitrate (NO3−) improves maximal neuromuscular power in humans. This conclusion, however, was based on a limited number of studies, and no attempt has been made to quantify the exact magnitude of this beneficial effect. Such information would help ensure adequate statistical power in future studies and could help place the effects of dietary NO3− on various aspects of exercise performance (i.e., endurance vs. strength vs. power) in better context. We therefore undertook a systematic review and individual participant data meta-analysis to quantify the effects of NO3− supplementation on human muscle power. Methods The literature was searched using a strategy developed by a health sciences librarian. Data sources included Medline Ovid, Embase, SPORTDiscus, Scopus, Clinicaltrials.gov, and Google Scholar. Studies were included if they used a randomized, double-blind, placebo-controlled, crossover experimental design to measure the effects of dietary NO3− on maximal power during exercise in the non-fatigued state and the within-subject correlation could be determined from data in the published manuscript or obtained from the authors. Results Nineteen studies of a total of 268 participants (218 men, 50 women) met the criteria for inclusion. The overall effect size (ES; Hedge’s g) calculated using a fixed effects model was 0.42 (95% confidence interval (CI) 0.29, 0.56; p = 6.310 × 10− 11). There was limited heterogeneity between studies (i.e., I2 = 22.79%, H2 = 1.30, p = 0.3460). The ES estimated using a random effects model was therefore similar (i.e., 0.45, 95% CI 0.30, 0.61; p = 1.064 × 10− 9). Sub-group analyses revealed no significant differences due to subject age, sex, or test modality (i.e., small vs. large muscle mass exercise). However, the ES in studies using an acute dose (i.e., 0.54, 95% CI 0.37, 0.71; p = 6.774 × 10− 12) was greater (p = 0.0211) than in studies using a multiple dose regimen (i.e., 0.22, 95% CI 0.01, 0.43; p = 0.003630). Conclusions Acute or chronic dietary NO3− intake significantly increases maximal muscle power in humans. The magnitude of this effect–on average, ~ 5%–is likely to be of considerable practical and clinical importance.