-
Clinical Neurophysiology : Official... Aug 2019This document is the consensus of international experts on the current status of Single Fiber EMG (SFEMG) and the measurement of neuromuscular jitter with concentric... (Review)
Review
This document is the consensus of international experts on the current status of Single Fiber EMG (SFEMG) and the measurement of neuromuscular jitter with concentric needle electrodes (CNE - CN-jitter). The panel of authors was chosen based on their particular interests and previous publications within a specific area of SFEMG or CN-jitter. Each member of the panel was asked to submit a section on their particular area of interest and these submissions were circulated among the panel members for edits and comments. This process continued until a consensus was reached. Donald Sanders and Erik Stålberg then edited the final document.
Topics: Animals; Electrodes; Electromyography; Humans; Myofibrils; Neuromuscular Junction; Practice Guidelines as Topic
PubMed: 31080019
DOI: 10.1016/j.clinph.2019.04.005 -
The Journal of Physiology Sep 2016Skeletal muscle hypertrophy is one of the main outcomes from resistance training (RT), but how it is modulated throughout training is still unknown. We show that changes...
KEY POINTS
Skeletal muscle hypertrophy is one of the main outcomes from resistance training (RT), but how it is modulated throughout training is still unknown. We show that changes in myofibrillar protein synthesis (MyoPS) after an initial resistance exercise (RE) bout in the first week of RT (T1) were greater than those seen post-RE at the third (T2) and tenth week (T3) of RT, with values being similar at T2 and T3. Muscle damage (Z-band streaming) was the highest during post-RE recovery at T1, lower at T2 and minimal at T3. When muscle damage was the highest, so was the integrated MyoPS (at T1), but neither were related to hypertrophy; however, integrated MyoPS at T2 and T3 were correlated with hypertrophy. We conclude that muscle hypertrophy is the result of accumulated intermittent increases in MyoPS mainly after a progressive attenuation of muscle damage.
ABSTRACT
Skeletal muscle hypertrophy is one of the main outcomes of resistance training (RT), but how hypertrophy is modulated and the mechanisms regulating it are still unknown. To investigate how muscle hypertrophy is modulated through RT, we measured day-to-day integrated myofibrillar protein synthesis (MyoPS) using deuterium oxide and assessed muscle damage at the beginning (T1), at 3 weeks (T2) and at 10 weeks of RT (T3). Ten young men (27 (1) years, mean (SEM)) had muscle biopsies (vastus lateralis) taken to measure integrated MyoPS and muscle damage (Z-band streaming and indirect parameters) before, and 24 h and 48 h post resistance exercise (post-RE) at T1, T2 and T3. Fibre cross-sectional area (fCSA) was evaluated using biopsies at T1, T2 and T3. Increases in fCSA were observed only at T3 (P = 0.017). Changes in MyoPS post-RE at T1, T2 and T3 were greater at T1 (P < 0.03) than at T2 and T3 (similar values between T2 and T3). Muscle damage was the highest during post-RE recovery at T1, attenuated at T2 and further attenuated at T3. The change in MyoPS post-RE at both T2 and T3, but not at T1, was strongly correlated (r ≈ 0.9, P < 0.04) with muscle hypertrophy. Initial MyoPS response post-RE in an RT programme is not directed to support muscle hypertrophy, coinciding with the greatest muscle damage. However, integrated MyoPS is quickly 'refined' by 3 weeks of RT, and is related to muscle hypertrophy. We conclude that muscle hypertrophy is the result of accumulated intermittent changes in MyoPS post-RE in RT, which coincides with progressive attenuation of muscle damage.
Topics: Adult; Humans; Hypertrophy; Male; Muscle Proteins; Muscular Diseases; Myofibrils; Protein Biosynthesis; Resistance Training
PubMed: 27219125
DOI: 10.1113/JP272472 -
Nature Communications Jun 2021A comprehensive transcriptomic survey of pigs can provide a mechanistic understanding of tissue specialization processes underlying economically valuable traits and...
A comprehensive transcriptomic survey of pigs can provide a mechanistic understanding of tissue specialization processes underlying economically valuable traits and accelerate their use as a biomedical model. Here we characterize four transcript types (lncRNAs, TUCPs, miRNAs, and circRNAs) and protein-coding genes in 31 adult pig tissues and two cell lines. We uncover the transcriptomic variability among 47 skeletal muscles, and six adipose depots linked to their different origins, metabolism, cell composition, physical activity, and mitochondrial pathways. We perform comparative analysis of the transcriptomes of seven tissues from pigs and nine other vertebrates to reveal that evolutionary divergence in transcription potentially contributes to lineage-specific biology. Long-range promoter-enhancer interaction analysis in subcutaneous adipose tissues across species suggests evolutionarily stable transcription patterns likely attributable to redundant enhancers buffering gene expression patterns against perturbations, thereby conferring robustness during speciation. This study can facilitate adoption of the pig as a biomedical model for human biology and disease and uncovers the molecular bases of valuable traits.
Topics: Adipose Tissue; Alternative Splicing; Animals; Biological Evolution; Cell Line; Cell Lineage; Cell Nucleus; Enhancer Elements, Genetic; Evolution, Molecular; Gene Expression Profiling; Gene Regulatory Networks; MicroRNAs; Mitochondria; Molecular Conformation; Muscle, Skeletal; Myofibrils; Phylogeny; Promoter Regions, Genetic; RNA, Circular; RNA, Long Noncoding; RNA, Messenger; Spatial Analysis; Swine; Transcriptome
PubMed: 34140474
DOI: 10.1038/s41467-021-23560-8 -
The Journal of Clinical Investigation May 2022Passive stiffness of the heart is determined largely by extracellular matrix and titin, which functions as a molecular spring within sarcomeres. Titin stiffening is...
Passive stiffness of the heart is determined largely by extracellular matrix and titin, which functions as a molecular spring within sarcomeres. Titin stiffening is associated with the development of diastolic dysfunction (DD), while augmented titin compliance appears to impair systolic performance in dilated cardiomyopathy. We found that myofibril stiffness was elevated in mice lacking histone deacetylase 6 (HDAC6). Cultured adult murine ventricular myocytes treated with a selective HDAC6 inhibitor also exhibited increased myofibril stiffness. Conversely, HDAC6 overexpression in cardiomyocytes led to decreased myofibril stiffness, as did ex vivo treatment of mouse, rat, and human myofibrils with recombinant HDAC6. Modulation of myofibril stiffness by HDAC6 was dependent on 282 amino acids encompassing a portion of the PEVK element of titin. HDAC6 colocalized with Z-disks, and proteomics analysis suggested that HDAC6 functions as a sarcomeric protein deacetylase. Finally, increased myofibril stiffness in HDAC6-deficient mice was associated with exacerbated DD in response to hypertension or aging. These findings define a role for a deacetylase in the control of myofibril function and myocardial passive stiffness, suggest that reversible acetylation alters titin compliance, and reveal the potential of targeting HDAC6 to manipulate the elastic properties of the heart to treat cardiac diseases.
Topics: Animals; Connectin; Histone Deacetylase 6; Humans; Mice; Myocardium; Myocytes, Cardiac; Myofibrils; Rats; Sarcomeres
PubMed: 35575093
DOI: 10.1172/JCI148333 -
Circulation. Genomic and Precision... Oct 2020Pathogenic variants in , encoding cardiac MyBP-C (myosin binding protein C), are the most common cause of familial hypertrophic cardiomyopathy. A large number of unique...
BACKGROUND
Pathogenic variants in , encoding cardiac MyBP-C (myosin binding protein C), are the most common cause of familial hypertrophic cardiomyopathy. A large number of unique variants and relatively small genotyped hypertrophic cardiomyopathy cohorts have precluded detailed genotype-phenotype correlations.
METHODS
Patients with hypertrophic cardiomyopathy and variants were identified from the Sarcomeric Human Cardiomyopathy Registry. Variant types and locations were analyzed, morphological severity was assessed, and time-event analysis was performed (composite clinical outcome of sudden death, class III/IV heart failure, left ventricular assist device/transplant, atrial fibrillation). For selected missense variants falling in enriched domains, myofilament localization and degradation rates were measured in vitro.
RESULTS
Among 4756 genotyped patients with hypertrophic cardiomyopathy in Sarcomeric Human Cardiomyopathy Registry, 1316 patients were identified with adjudicated pathogenic truncating (N=234 unique variants, 1047 patients) or nontruncating (N=22 unique variants, 191 patients) variants in . Truncating variants were evenly dispersed throughout the gene, and hypertrophy severity and outcomes were not associated with variant location (grouped by 5'-3' quartiles or by founder variant subgroup). Nontruncating pathogenic variants clustered in the C3, C6, and C10 domains (18 of 22, 82%, <0.001 versus Genome Aggregation Database common variants) and were associated with similar hypertrophy severity and adverse event rates as observed with truncating variants. MyBP-C with variants in the C3, C6, and C10 domains was expressed in rat ventricular myocytes. C10 mutant MyBP-C failed to incorporate into myofilaments and degradation rates were accelerated by ≈90%, while C3 and C6 mutant MyBP-C incorporated normally with degradation rate similar to wild-type.
CONCLUSIONS
Truncating variants account for 91% of pathogenic variants and cause similar clinical severity and outcomes regardless of location, consistent with locus-independent loss-of-function. Nontruncating pathogenic variants are regionally clustered, and a subset also cause loss of function through failure of myofilament incorporation and rapid degradation. Cardiac morphology and clinical outcomes are similar in patients with truncating versus nontruncating variants.
Topics: Adolescent; Adult; Cardiomyopathy, Hypertrophic; Carrier Proteins; Child; Female; Genotype; Humans; Male; Middle Aged; Myofibrils; Phenotype; Polymorphism, Genetic; Registries; Severity of Illness Index; Spatial Analysis; Young Adult
PubMed: 32841044
DOI: 10.1161/CIRCGEN.120.002929 -
Cells & Development Dec 2021Muscles generate forces for animal locomotion. The contractile apparatus of muscles is the sarcomere, a highly regular array of large actin and myosin filaments linked... (Review)
Review
Muscles generate forces for animal locomotion. The contractile apparatus of muscles is the sarcomere, a highly regular array of large actin and myosin filaments linked by gigantic titin springs. During muscle development many sarcomeres assemble in series into long periodic myofibrils that mechanically connect the attached skeleton elements. Thus, ATP-driven myosin forces can power movement of the skeleton. Here we review muscle and myofibril morphogenesis, with a particular focus on their mechanobiology. We describe recent progress on the molecular structure of sarcomeres and their mechanical connections to the skeleton. We discuss current models predicting how tension coordinates the assembly of key sarcomeric components to periodic myofibrils that then further mature during development. This requires transcriptional feedback mechanisms that may help to coordinate myofibril assembly and maturation states with the transcriptional program. To fuel the varying energy demands of muscles we also discuss the close mechanical interactions of myofibrils with mitochondria and nuclei to optimally support powerful or enduring muscle fibers.
Topics: Animals; Biophysics; Morphogenesis; Myofibrils; Myosins; Sarcomeres
PubMed: 34863916
DOI: 10.1016/j.cdev.2021.203760 -
Mechanisms of Development Apr 2017Muscles are the major force producing tissue in the human body. While certain muscle types specialize in producing maximum forces, others are very enduring. An extreme... (Review)
Review
Muscles are the major force producing tissue in the human body. While certain muscle types specialize in producing maximum forces, others are very enduring. An extreme example is the heart, which continuously beats for the entire life. Despite being specialized, all body muscles share similar contractile mini-machines called sarcomeres that are organized into regular higher order structures called myofibrils. The major sarcomeric components and their organizational principles are conserved throughout most of the animal kingdom. In this review, we discuss recent progress in the understanding of myofibril and sarcomere development largely obtained from in vivo models. We focus on the role of mechanical forces during muscle and myofibril development and propose a tension driven self-organization mechanism for myofibril formation. We discuss recent technological advances that allow quantification of forces across tissues or molecules in vitro and in vivo. Although their application towards muscle development is still in its infancy, these technologies are likely to provide fundamental new insights into the mechanobiology of muscle and myofibril development in the near future.
Topics: Actins; Animals; Biomechanical Phenomena; Connectin; Drosophila melanogaster; Gene Expression Regulation, Developmental; Humans; Integrins; Muscle Development; Muscle Tonus; Myofibrils; Signal Transduction; Tendons
PubMed: 27913119
DOI: 10.1016/j.mod.2016.11.003 -
Circulation Research Feb 2024Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disorder. However, the pathogenesis of HCM, especially its nongenetic mechanisms, remains largely...
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disorder. However, the pathogenesis of HCM, especially its nongenetic mechanisms, remains largely unclear. Transcription factors are known to be involved in various biological processes including cell growth. We hypothesized that SP1 (specificity protein 1), the first purified TF in mammals, plays a role in the cardiomyocyte growth and cardiac hypertrophy of HCM.
METHODS
Cardiac-specific conditional knockout of mice were constructed to investigate the role of SP1 in the heart. The echocardiography, histochemical experiment, and transmission electron microscope were performed to analyze the cardiac phenotypes of cardiac-specific conditional knockout of mice. RNA sequencing, chromatin immunoprecipitation sequencing, and adeno-associated virus experiments in vivo were performed to explore the downstream molecules of SP1. To examine the therapeutic effect of SP1 on HCM, an SP1 overexpression vector was constructed and injected into the mutant allele of Myh6 R404Q/+ ( c. 1211C>T) HCM mice. The human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with HCM were used to detect the potential therapeutic effects of SP1 in human HCM.
RESULTS
The cardiac-specific conditional knockout of mice developed a typical HCM phenotype, displaying overt myocardial hypertrophy, interstitial fibrosis, and disordered myofilament. In addition, knockdown dramatically increased the cell area of hiPSC-CMs and caused intracellular myofibrillar disorganization, which was similar to the hypertrophic cardiomyocytes of HCM. Mechanistically, was identified as the key target gene of SP1. The hypertrophic phenotypes induced by knockdown in both hiPSC-CMs and mice could be rescued by TUFT1 (tuftelin 1) overexpression. Furthermore, SP1 overexpression suppressed the development of HCM in the mutant allele of Myh6 R404Q/+ mice and also reversed the hypertrophic phenotype of HCM hiPSC-CMs.
CONCLUSIONS
Our study demonstrates that SP1 deficiency leads to HCM. SP1 overexpression exhibits significant therapeutic effects on both HCM mice and HCM hiPSC-CMs, suggesting that SP1 could be a potential intervention target for HCM.
Topics: Humans; Mice; Animals; Induced Pluripotent Stem Cells; Cardiomyopathy, Hypertrophic; Myofibrils; Myocytes, Cardiac; Cardiomegaly; Transcription Factors; Mammals
PubMed: 38197258
DOI: 10.1161/CIRCRESAHA.123.323272 -
Biochimica Et Biophysica Acta.... Mar 2020The sarcomere is the basic unit of the myofibrils, which mediate skeletal and cardiac Muscle contraction. Two transverse structures, the Z-disc and the M-band, anchor... (Review)
Review
The sarcomere is the basic unit of the myofibrils, which mediate skeletal and cardiac Muscle contraction. Two transverse structures, the Z-disc and the M-band, anchor the thin (actin and associated proteins) and thick (myosin and associated proteins) filaments to the elastic filament system composed of titin. A plethora of proteins are known to be integral or associated proteins of the Z-disc and its structural and signalling role in muscle is better understood, while the molecular constituents of the M-band and its function are less well defined. Evidence discussed here suggests that the M-band is important for managing force imbalances during active muscle contraction. Its molecular composition is fine-tuned, especially as far as the structural linkers encoded by members of the myomesin family are concerned and depends on the specific mechanical characteristics of each particular muscle fibre type. Muscle activity signals from the M-band to the nucleus and affects transcription of sarcomeric genes, especially via serum response factor (SRF). Due to its important role as shock absorber in contracting muscle, the M-band is also more and more recognised as a contributor to muscle disease.
Topics: Actins; Connectin; Humans; Muscle Contraction; Myofibrils; Myosins; Sarcomeres; Serum Response Factor; Transcription, Genetic
PubMed: 30738787
DOI: 10.1016/j.bbamcr.2019.02.003 -
Archives of Biochemistry and Biophysics May 2019
Topics: Animals; Humans; Muscle Contraction; Muscle Proteins; Myofibrils
PubMed: 31051122
DOI: 10.1016/j.abb.2019.04.011