Skeletal Muscle最新文献

{"title":"Macroglossia and less advanced dystrophic change in the tongue muscle of the Duchenne muscular dystrophy rat.","authors":"Keitaro Yamanouchi,&nbsp;Yukie Tanaka,&nbsp;Masanari Ikeda,&nbsp;Shizuka Kato,&nbsp;Ryosuke Okino,&nbsp;Hiroki Nishi,&nbsp;Fumihiko Hakuno,&nbsp;Shin-Ichiro Takahashi,&nbsp;James Chambers,&nbsp;Takashi Matsuwaki,&nbsp;Kazuyuki Uchida","doi":"10.1186/s13395-022-00307-7","DOIUrl":"https://doi.org/10.1186/s13395-022-00307-7","url":null,"abstract":"<p><strong>Background: </strong>Duchenne muscular dystrophy (DMD) is an X-linked muscle disease caused by a complete lack of dystrophin, which stabilizes the plasma membrane of myofibers. The orofacial function is affected in an advanced stage of DMD and this often leads to an eating disorder such as dysphagia. Dysphagia is caused by multiple etiologies including decreased mastication and swallowing. Therefore, preventing the functional declines of mastication and swallowing in DMD is important to improve the patient's quality of life. In the present study, using a rat model of DMD we generated previously, we performed analyses on the masseter and tongue muscles, both are required for proper eating function.</p><p><strong>Methods: </strong>Age-related changes of the masseter and tongue muscle of DMD rats were analyzed morphometrically, histologically, and immunohistochemically. Also, transcription of cellular senescent markers, and utrophin (Utrn), a functional analog of dystrophin, was examined.</p><p><strong>Results: </strong>The masseter muscle of DMD rats showed progressive dystrophic changes as observed in their hindlimb muscle, accompanied by increased transcription of p16 and p19. On the other hand, the tongue of DMD rats showed macroglossia due to hypertrophy of myofibers with less dystrophic changes. Proliferative activity was preserved in the satellite cells from the tongue muscle but was perturbed severely in those from the masseter muscle. While Utrn transcription was increased in the masseter muscle of DMD rats compared to WT rats, probably due to a compensatory mechanism, its level in the tongue muscle was comparable between WT and DMD rats and was similar to that in the masseter muscle of DMD rats.</p><p><strong>Conclusions: </strong>Muscular dystrophy is less advanced in the tongue muscle compared to the masseter muscle in the DMD rat.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"24"},"PeriodicalIF":4.9,"publicationDate":"2022-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40339240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Megaconial congenital muscular dystrophy due to novel CHKB variants: a case report and literature review.","authors":"Francesca Magri,&nbsp;Sara Antognozzi,&nbsp;Michela Ripolone,&nbsp;Simona Zanotti,&nbsp;Laura Napoli,&nbsp;Patrizia Ciscato,&nbsp;Daniele Velardo,&nbsp;Giulietta Scuvera,&nbsp;Valeria Nicotra,&nbsp;Antonella Giacobbe,&nbsp;Donatella Milani,&nbsp;Francesco Fortunato,&nbsp;Manuela Garbellini,&nbsp;Monica Sciacco,&nbsp;Stefania Corti,&nbsp;Giacomo Pietro Comi,&nbsp;Dario Ronchi","doi":"10.1186/s13395-022-00306-8","DOIUrl":"https://doi.org/10.1186/s13395-022-00306-8","url":null,"abstract":"<p><strong>Background: </strong>Choline kinase beta (CHKB) catalyzes the first step in the de novo biosynthesis of phosphatidyl choline and phosphatidylethanolamine via the Kennedy pathway. Derangement of this pathway might also influence the homeostasis of mitochondrial membranes. Autosomal recessive CHKB mutations cause a rare form of congenital muscular dystrophy known as megaconial congenital muscular dystrophy (MCMD).</p><p><strong>Case presentation: </strong>We describe a novel proband presenting MCMD due to unpublished CHKB mutations. The patient is a 6-year-old boy who came to our attention for cognitive impairment and slowly progressive muscular weakness. He was the first son of non-consanguineous healthy parents from Sri Lanka. Neurological examination showed proximal weakness at four limbs, weak osteotendinous reflexes, Gowers' maneuver, and waddling gate. Creatine kinase levels were mildly increased. EMG and brain MRI were normal. Left quadriceps skeletal muscle biopsy showed a myopathic pattern with nuclear centralizations and connective tissue increase. Histological and histochemical staining suggested subsarcolemmal localization and dimensional increase of mitochondria. Ultrastructural analysis confirmed the presence of enlarged (\"megaconial\") mitochondria. Direct sequencing of CHKB identified two novel defects: the c.1060G > C (p.Gly354Arg) substitution and the c.448-56_29del intronic deletion, segregating from father and mother, respectively. Subcloning of RT-PCR amplicons from patient's muscle RNA showed that c.448-56_29del results in the partial retention (14 nucleotides) of intron 3, altering physiological splicing and transcript stability. Biochemical studies showed reduced levels of the mitochondrial fission factor DRP1 and the severe impairment of mitochondrial respiratory chain activity in patient's muscle compared to controls.</p><p><strong>Conclusions: </strong>This report expands the molecular findings associated with MCMD and confirms the importance of considering CHKB variants in the differential diagnosis of patients presenting with muscular dystrophy and mental retardation. The clinical outcome of MCMD patients seems to be influenced by CHKB molecular defects. Histological and ultrastructural examination of muscle biopsy directed molecular studies and allowed the identification and characterization of an intronic mutation, usually escaping standard molecular testing.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"23"},"PeriodicalIF":4.9,"publicationDate":"2022-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9524117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40383594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mouse models of SMA show divergent patterns of neuronal vulnerability and resilience.","authors":"Victoria Woschitz,&nbsp;Irene Mei,&nbsp;Eva Hedlund,&nbsp;Lyndsay M Murray","doi":"10.1186/s13395-022-00305-9","DOIUrl":"https://doi.org/10.1186/s13395-022-00305-9","url":null,"abstract":"<p><strong>Background: </strong>Spinal muscular atrophy (SMA) is a form of motor neuron disease affecting primarily children characterised by the loss of lower motor neurons (MNs). Breakdown of the neuromuscular junctions (NMJs) is an early pathological event in SMA. However, not all motor neurons are equally vulnerable, with some populations being lost early in the disease while others remain intact at the disease end-stage. A thorough understanding of the basis of this selective vulnerability will give critical insight into the factors which prohibit pathology in certain motor neuron populations and consequently help identify novel neuroprotective strategies.</p><p><strong>Methods: </strong>To retrieve a comprehensive understanding of motor neuron susceptibility in SMA, we mapped NMJ pathology in 20 muscles from the Smn^2B/- SMA mouse model and cross-compared these data with published data from three other commonly used mouse models. To gain insight into the molecular mechanisms regulating selective resilience and vulnerability, we analysed published RNA sequencing data acquired from differentially vulnerable motor neurons from two different SMA mouse models.</p><p><strong>Results: </strong>In the Smn^2B/- mouse model of SMA, we identified substantial NMJ loss in the muscles from the core, neck, proximal hind limbs and proximal forelimbs, with a marked reduction in denervation in the distal limbs and head. Motor neuron cell body loss was greater at T5 and T11 compared with L5. We subsequently show that although widespread denervation is observed in each SMA mouse model (with the notable exception of the Taiwanese model), all models have a distinct pattern of selective vulnerability. A comparison of previously published data sets reveals novel transcripts upregulated with a disease in selectively resistant motor neurons, including genes involved in axonal transport, RNA processing and mitochondrial bioenergetics.</p><p><strong>Conclusions: </strong>Our work demonstrates that the Smn^2B/- mouse model shows a pattern of selective vulnerability which bears resemblance to the regional pathology observed in SMA patients. We found drastic differences in patterns of selective vulnerability across the four SMA mouse models, which is critical to consider during experimental design. We also identified transcript groups that potentially contribute to the protection of certain motor neurons in SMA mouse models.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"22"},"PeriodicalIF":4.9,"publicationDate":"2022-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33464624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of the co-differentially expressed hub genes involved in the endogenous protective mechanism against ventilator-induced diaphragm dysfunction.","authors":"Dong Zhang,&nbsp;Wenyan Hao,&nbsp;Qi Niu,&nbsp;Dongdong Xu,&nbsp;Xuejiao Duan","doi":"10.1186/s13395-022-00304-w","DOIUrl":"https://doi.org/10.1186/s13395-022-00304-w","url":null,"abstract":"<p><strong>Background: </strong>In intensive care units (ICU), mechanical ventilation (MV) is commonly applied to save patients' lives. However, ventilator-induced diaphragm dysfunction (VIDD) can complicate treatment by hindering weaning in critically ill patients and worsening outcomes. The goal of this study was to identify potential genes involved in the endogenous protective mechanism against VIDD.</p><p><strong>Methods: </strong>Twelve adult male rabbits were assigned to either an MV group or a control group under the same anesthetic conditions. Immunostaining and quantitative morphometry were used to assess diaphragm atrophy, while RNA-seq was used to investigate molecular differences between the groups. Additionally, core module and hub genes were analyzed using WGCNA, and co-differentially expressed hub genes were subsequently discovered by overlapping the differentially expressed genes (DEGs) with the hub genes from WGCNA. The identified genes were validated by western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR).</p><p><strong>Results: </strong>After a VIDD model was successfully built, 1276 DEGs were found between the MV and control groups. The turquoise and yellow modules were identified as the core modules, and Trim63, Fbxo32, Uchl1, Tmprss13, and Cst3 were identified as the five co-differentially expressed hub genes. After the two atrophy-related genes (Trim63 and Fbxo32) were excluded, the levels of the remaining three genes/proteins (Uchl1/UCHL1, Tmprss13/TMPRSS13, and Cst3/CST3) were found to be significantly elevated in the MV group (P < 0.05), suggesting the existence of a potential antiproteasomal, antiapoptotic, and antiautophagic mechanism against diaphragm dysfunction.</p><p><strong>Conclusion: </strong>The current research helps to reveal a potentially important endogenous protective mechanism that could serve as a novel therapeutic target against VIDD.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"21"},"PeriodicalIF":4.9,"publicationDate":"2022-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9461262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33460739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged FOS activity disrupts a global myogenic transcriptional program by altering 3D chromatin architecture in primary muscle progenitor cells.","authors":"A Rasim Barutcu, Gabriel Elizalde, Alfredo E Gonzalez, Kartik Soni, John L Rinn, Amy J Wagers, Albert E Almada","doi":"10.1186/s13395-022-00303-x","DOIUrl":"10.1186/s13395-022-00303-x","url":null,"abstract":"<p><strong>Background: </strong>The AP-1 transcription factor, FBJ osteosarcoma oncogene (FOS), is induced in adult muscle satellite cells (SCs) within hours following muscle damage and is required for effective stem cell activation and muscle repair. However, why FOS is rapidly downregulated before SCs enter cell cycle as progenitor cells (i.e., transiently expressed) remains unclear. Further, whether boosting FOS levels in the proliferating progeny of SCs can enhance their myogenic properties needs further evaluation.</p><p><strong>Methods: </strong>We established an inducible, FOS expression system to evaluate the impact of persistent FOS activity in muscle progenitor cells ex vivo. We performed various assays to measure cellular proliferation and differentiation, as well as uncover changes in RNA levels and three-dimensional (3D) chromatin interactions.</p><p><strong>Results: </strong>Persistent FOS activity in primary muscle progenitor cells severely antagonizes their ability to differentiate and form myotubes within the first 2 weeks in culture. RNA-seq analysis revealed that ectopic FOS activity in muscle progenitor cells suppressed a global pro-myogenic transcriptional program, while activating a stress-induced, mitogen-activated protein kinase (MAPK) transcriptional signature. Additionally, we observed various FOS-dependent, chromosomal re-organization events in A/B compartments, topologically associated domains (TADs), and genomic loops near FOS-regulated genes.</p><p><strong>Conclusions: </strong>Our results suggest that elevated FOS activity in recently activated muscle progenitor cells perturbs cellular differentiation by altering the 3D chromosome organization near critical pro-myogenic genes. This work highlights the crucial importance of tightly controlling FOS expression in the muscle lineage and suggests that in states of chronic stress or disease, persistent FOS activity in muscle precursor cells may disrupt the muscle-forming process.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"12 1","pages":"20"},"PeriodicalIF":4.9,"publicationDate":"2022-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9838031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress-induced premature senescence and aggravated denervated skeletal muscular atrophy by regulating progerin-p53 interaction.","authors":"Yaoxian Xiang,&nbsp;Zongqi You,&nbsp;Xinying Huang,&nbsp;Junxi Dai,&nbsp;Junpeng Zhang,&nbsp;Shuqi Nie,&nbsp;Lei Xu,&nbsp;Junjian Jiang,&nbsp;Jianguang Xu","doi":"10.1186/s13395-022-00302-y","DOIUrl":"https://doi.org/10.1186/s13395-022-00302-y","url":null,"abstract":"<p><strong>Background: </strong>Progerin elevates atrophic gene expression and helps modify the nuclear membrane to cause severe muscle pathology, which is similar to muscle weakness in the elderly, to alter the development and function of the skeletal muscles. Stress-induced premature senescence (SIPS), a state of cell growth arrest owing to such stimuli as oxidation, can be caused by progerin. However, evidence for whether SIPS-induced progerin accumulation is connected to denervation-induced muscle atrophy is not sufficient.</p><p><strong>Methods: </strong>Flow cytometry and a reactive oxygen species (ROS) as well as inducible nitric oxide synthase (iNOS) inhibitors were used to assess the effect of oxidation on protein (p53), progerin, and nuclear progerin-p53 interaction in the denervated muscles of models of mice suffering from sciatic injury. Loss-of-function approach with the targeted deletion of p53 was used to assess connection among SIPS, denervated muscle atrophy, and fibrogenesis.</p><p><strong>Results: </strong>The augmentation of ROS and iNOS-derived NO in the denervated muscles of models of mice suffering from sciatic injury upregulates p53 and progerin. The abnormal accumulation of progerin in the nuclear membrane as well as the activation of nuclear progerin-p53 interaction triggered premature senescence in the denervated muscle cells of mice. The p53-dependent SIPS in denervated muscles contributes to their atrophy and fibrogenesis.</p><p><strong>Conclusion: </strong>Oxidative stress-triggered premature senescence via nuclear progerin-p53 interaction that promotes denervated skeletal muscular atrophy and fibrogenesis.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"19"},"PeriodicalIF":4.9,"publicationDate":"2022-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40559279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulation of Tweak and Fn14 in skeletal muscle of spinal muscular atrophy mice.","authors":"Katharina E Meijboom,&nbsp;Emma R Sutton,&nbsp;Eve McCallion,&nbsp;Emily McFall,&nbsp;Daniel Anthony,&nbsp;Benjamin Edwards,&nbsp;Sabrina Kubinski,&nbsp;Ines Tapken,&nbsp;Ines Bünermann,&nbsp;Gareth Hazell,&nbsp;Nina Ahlskog,&nbsp;Peter Claus,&nbsp;Kay E Davies,&nbsp;Rashmi Kothary,&nbsp;Matthew J A Wood,&nbsp;Melissa Bowerman","doi":"10.1186/s13395-022-00301-z","DOIUrl":"https://doi.org/10.1186/s13395-022-00301-z","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 Smn^2B/- SMA mice, which undergo a progressive neuromuscular decline in the first three post-natal weeks. We also used experimental models of denervation and muscle injury in pre-weaned wild-type (WT) animals and siRNA-mediated knockdown in C2C12 muscle cells to conduct additional mechanistic investigations.</p><p><strong>Results: </strong>Here, we report significantly dysregulated expression of Tweak, Fn14, and previously proposed downstream effectors 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, providing further evidence in support of a relationship between the TWEAK/Fn14 pathway and Smn. Finally, administration of the TWEAK/Fn14 agonist Fc-TWEAK improved disease phenotypes in the two SMA mouse models.</p><p><strong>Conclusions: </strong>Our study provides mechanistic insights into potential molecular players that contribute to muscle pathology in SMA and into likely differential responses of the TWEAK/Fn14 pathway in developing muscle.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"18"},"PeriodicalIF":4.9,"publicationDate":"2022-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40571245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-throughput muscle fiber typing from RNA sequencing data.","authors":"Nikolay Oskolkov,&nbsp;Malgorzata Santel,&nbsp;Hemang M Parikh,&nbsp;Ola Ekström,&nbsp;Gray J Camp,&nbsp;Eri Miyamoto-Mikami,&nbsp;Kristoffer Ström,&nbsp;Bilal Ahmad Mir,&nbsp;Dmytro Kryvokhyzha,&nbsp;Mikko Lehtovirta,&nbsp;Hiroyuki Kobayashi,&nbsp;Ryo Kakigi,&nbsp;Hisashi Naito,&nbsp;Karl-Fredrik Eriksson,&nbsp;Björn Nystedt,&nbsp;Noriyuki Fuku,&nbsp;Barbara Treutlein,&nbsp;Svante Pääbo,&nbsp;Ola Hansson","doi":"10.1186/s13395-022-00299-4","DOIUrl":"https://doi.org/10.1186/s13395-022-00299-4","url":null,"abstract":"<p><strong>Background: </strong>Skeletal muscle fiber type distribution has implications for human health, muscle function, and performance. This knowledge has been gathered using labor-intensive and costly methodology that limited these studies. Here, we present a method based on muscle tissue RNA sequencing data (totRNAseq) to estimate the distribution of skeletal muscle fiber types from frozen human samples, allowing for a larger number of individuals to be tested.</p><p><strong>Methods: </strong>By using single-nuclei RNA sequencing (snRNAseq) data as a reference, cluster expression signatures were produced by averaging gene expression of cluster gene markers and then applying these to totRNAseq data and inferring muscle fiber nuclei type via linear matrix decomposition. This estimate was then compared with fiber type distribution measured by ATPase staining or myosin heavy chain protein isoform distribution of 62 muscle samples in two independent cohorts (n = 39 and 22).</p><p><strong>Results: </strong>The correlation between the sequencing-based method and the other two were r_ATPas = 0.44 [0.13-0.67], [95% CI], and r_myosin = 0.83 [0.61-0.93], with p = 5.70 × 10^-3 and 2.00 × 10^-6, respectively. The deconvolution inference of fiber type composition was accurate even for very low totRNAseq sequencing depths, i.e., down to an average of ~ 10,000 paired-end reads.</p><p><strong>Conclusions: </strong>This new method ( https://github.com/OlaHanssonLab/PredictFiberType ) consequently allows for measurement of fiber type distribution of a larger number of samples using totRNAseq in a cost and labor-efficient way. It is now feasible to study the association between fiber type distribution and e.g. health outcomes in large well-powered studies.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"16"},"PeriodicalIF":4.9,"publicationDate":"2022-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40577681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Estrogen signaling effects on muscle-specific immune responses through controlling the recruitment and function of macrophages and T cells.","authors":"Zhao Hong Liao,&nbsp;Tao Huang,&nbsp;Jiang Wei Xiao,&nbsp;Rui Cai Gu,&nbsp;Jun Ouyang,&nbsp;Gang Wu,&nbsp;Hua Liao","doi":"10.1186/s13395-022-00298-5","DOIUrl":"https://doi.org/10.1186/s13395-022-00298-5","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"15"},"PeriodicalIF":4.9,"publicationDate":"2022-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40397270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Absence of the Z-disc protein α-actinin-3 impairs the mechanical stability of Actn3KO mouse fast-twitch muscle fibres without altering their contractile properties or twitch kinetics.","authors":"Michael Haug,&nbsp;Barbara Reischl,&nbsp;Stefanie Nübler,&nbsp;Leonit Kiriaev,&nbsp;Davi A G Mázala,&nbsp;Peter J Houweling,&nbsp;Kathryn N North,&nbsp;Oliver Friedrich,&nbsp;Stewart I Head","doi":"10.1186/s13395-022-00295-8","DOIUrl":"https://doi.org/10.1186/s13395-022-00295-8","url":null,"abstract":"<p><strong>Background: </strong>A common polymorphism (R577X) in the ACTN3 gene results in the complete absence of the Z-disc protein α-actinin-3 from fast-twitch muscle fibres in ~ 16% of the world's population. This single gene polymorphism has been subject to strong positive selection pressure during recent human evolution. Previously, using an Actn3KO mouse model, we have shown in fast-twitch muscles, eccentric contractions at L₀ + 20% stretch did not cause eccentric damage. In contrast, L₀ + 30% stretch produced a significant ~ 40% deficit in maximum force; here, we use isolated single fast-twitch skeletal muscle fibres from the Actn3KO mouse to investigate the mechanism underlying this.</p><p><strong>Methods: </strong>Single fast-twitch fibres are separated from the intact muscle by a collagenase digest procedure. We use label-free second harmonic generation (SHG) imaging, ultra-fast video microscopy and skinned fibre measurements from our MyoRobot automated biomechatronics system to study the morphology, visco-elasticity, force production and mechanical strength of single fibres from the Actn3KO mouse. Data are presented as means ± SD and tested for significance using ANOVA.</p><p><strong>Results: </strong>We show that the absence of α-actinin-3 does not affect the visco-elastic properties or myofibrillar force production. Eccentric contractions demonstrated that chemically skinned Actn3KO fibres are mechanically weaker being prone to breakage when eccentrically stretched. Furthermore, SHG images reveal disruptions in the myofibrillar alignment of Actn3KO fast-twitch fibres with an increase in Y-shaped myofibrillar branching.</p><p><strong>Conclusions: </strong>The absence of α-actinin-3 from the Z-disc in fast-twitch fibres disrupts the organisation of the myofibrillar proteins, leading to structural weakness. This provides a mechanistic explanation for our earlier findings that in vitro intact Actn3KO fast-twitch muscles are significantly damaged by L₀ + 30%, but not L₀ + 20%, eccentric contraction strains. Our study also provides a possible mechanistic explanation as to why α-actinin-3-deficient humans have been reported to have a faster decline in muscle function with increasing age, that is, as sarcopenia reduces muscle mass and force output, the eccentric stress on the remaining functional α-actinin-3 deficient fibres will be increased, resulting in fibre breakages.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"14"},"PeriodicalIF":4.9,"publicationDate":"2022-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40209835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}