Muscle Structure Research Articles

Effect of insulin insufficiency on ultrastructure and function in skeletal muscle.

Decreased insulin availability and high blood glucose levels, the hallmark features of poorly controlled diabetes, drive disease progression and are associated with decreased skeletal muscle mass. We have shown that mice with β-cell dysfunction and normal insulin sensitivity have decreased skeletal muscle mass. This project asks how insulin deficiency impacts on the structure and function of the remaining skeletal muscle in these animals. Skeletal muscle function was determined by measuring exercise capacity and specific muscle strength prior to and after insulin supplementation for 28days in 12-week-old mice with conditional β-cell deletion of the ATP binding cassette transporters ABCA1 and ABCG1 (β-DKO mice). Abca1 and Abcg1 floxed (fl/fl) mice were used as controls. RNAseq was used to quantify changes in transcripts in soleus and extensor digitorum longus muscles. Skeletal muscle and mitochondrial morphology were assessed by transmission electron microscopy. Myofibrillar Ca2+ sensitivity and maximum isometric single muscle fibre force were assessed using MyoRobot biomechatronics technology. RNA transcripts were significantly altered in β-DKO mice compared with fl/fl controls (32 in extensor digitorum longus and 412 in soleus). Exercise capacity and muscle strength were significantly decreased in β-DKO mice compared with fl/fl controls (P=0.012), and a loss of structural integrity was also observed in skeletal muscle from the β-DKO mice. Supplementation of β-DKO mice with insulin restored muscle integrity, strength and expression of 13 and 16 of the dysregulated transcripts in and extensor digitorum longus and soleus muscles, respectively. Insulin insufficiency due to β-cell dysfunction perturbs the structure and function of skeletal muscle. These adverse effects are rectified by insulin supplementation.

Numerical investigation of a finite element abdominal wall model during breathing and muscular contraction

Background and ObjectiveVentral hernia repair is faced with high recurrence rates. The personalization of the diagnosis, the surgical approach and the choice of the prosthetic implant seem relevant axes to improve the current results. Numerical models have the potential to allow this patient-specific approach, yet currently existing models lack validation. This work extensively investigated a realistic finite element abdominal wall model including the implementation of muscle activation. MethodsA parametric 3D finite element model composed of bone, muscle and aponeurotic structures was introduced. Hyperelastic anisotropic materials were implemented. Two loading scenarios were simulated: passive inflation of the abdominal cavity to represent, e.g., breathing, and passive inflation followed by muscular activation to simulate other daily activities such as cough. The impact of the inter-individual variability (e.g., BMI, tissue thickness, material properties, intra-abdominal pressure (IAP) and muscle contractility) on the model outputs was studied through a sensitivity analysis. ResultsThe overall model predictions were in good agreement with the experimental data in terms of shape variation, muscles displacements, strains and midline forces. A total of 34 and 41 runs were computed for the passive and active sensitivity analysis respectively. The regression model fits rendered high R-squared in both passive (84.0 ± 6.7 %) and active conditions (82.0 ± 8.3 %). IAP and muscle thickness were the most influential factors for the selected outputs during passive (breathing) activities. Maximum isometric stress, muscle thickness and pre-activation IAP were found to drive the response of the simulations involving muscular contraction. The material properties of the connective tissue were essential contributors to the behaviour of the medial part of the abdominal wall. ConclusionsThis work extensively investigated a realistic abdominal wall model and evaluated its robustness using experimental data from literature. Such a model could improve patient-specific simulation for ventral hernia surgical planning, prevention, and repair or implant evaluation. Further investigations will be conducted to evaluate the impact of the surgical technique and the mechanical characteristic of prosthetic meshes on the model outputs.

Effect of isokinetic eccentric training on the human shoulder strength, flexibility, and muscle architecture in physically active men: A preliminary study.

Strengthening the rotator cuff muscles is important for injury prevention and rehabilitation. Since muscle fascicle length improves motor performance and is suggested to reduce the risk of injury for the hamstring, it may be an important variable to promote multidirectional changes in the function and macroscopic structure for the shoulder. Recent literature reviews overwhelmingly suggest that eccentric exercises improve fascicle length and functional measures for the lower limb. However, there is a research gap for the shoulder. Since ultrasound imaging is the most commonly used imaging technique to quantify muscle structure, but has yielded heterogeneous results in different studies, there is another issue and a research gap for the imaging method. Based on the research gaps, the purpose of this study was to evaluate the effects of standardized eccentric strength training on the function and structure of the external rotator cuff muscles using an isokinetic dynamometer and MRI. Therefore, a preliminary pre-post intervention study was conducted and 16 physically active men were recruited in October 2021. For the right shoulder, an eccentric isokinetic training was performed twice a week for almost six weeks. The primary outcome measures (external rotators) were active and passive range of motion, eccentric and concentric torque at 30, 60, and 180°/s isokinetic speed, and fascicle length and fascicle volume for the supraspinatus and infraspinatus muscles. The findings show a training effect for the absolute mean values of eccentric strength (+24%, p = .008). The torque-angle relationship increased, especially in the final phase of range of motion, although a 4% (p = .002) decrease in passive range of motion was found in the stretch test. Positive changes in muscle structure were shown for the supraspinatus muscle fascicle length (+16%, p = .003) and fascicle volume (+19%, p = .002). Based on the study results, we can conclude that eccentric isokinetic training has a significant positive effect on the shoulder. To our knowledge, this is the first eccentric training study using both isokinetic dynamometer and muscle diffusion tensor imaging to access functional and structural changes in the human shoulder rotator cuff muscles. The methods were shown to be applicable for interventional studies. Based on these results, populations such as high-performance handball players with highly trained shoulders should be included in future studies.

Unravelling anisotropic nonlinear shear elasticity in muscles: Towards a non-invasive assessment of stress in living organisms

Acoustoelasticity theory describes propagation of shear waves in uniaxially stressed medium and allows the retrieval of nonlinear elastic coefficients of tissues. In transverse isotropic medium such as muscles the theory leads to 9 different configurations of propagating shear waves (stress axis vs. fibers axis vs. shear wave polarization axis vs. shear wave propagation axis). In this work we propose to use 4 configurations to quantify these nonlinear parameters ex vivo and in vivo. Ex vivo experiments combining ultrasound shear wave elastography and mechanical testing were conducted on iliopsoas pig muscles to quantify three third-order nonlinear coefficients A, H and K that are possibly linked to the architectural structure of muscles. In vivo experiments were performed with human volunteers on biceps brachii during a stretching exercise on an ergometer. A combination of the third order nonlinear elastic parameters was assessed. The knowledge of this nonlinear elastic parameters paves the way to quantify in vivo the local forces produced by muscle during exercise, contraction or movements.

Soft Finger Rehabilitation Exoskeleton of Biomimetic Dragonfly Abdominal Ventral Muscles: Center Tendon Pneumatic Bellows Actuator.

The development of soft robotics owes much to the field of biomimetics, where soft actuators predominantly mimic the movement found in nature. In contrast to their rigid counterparts, soft robots offer superior safety and human-machine interaction comfort, particularly in medical applications. However, when it comes to the hand rehabilitation exoskeletons, the soft devices have been limited by size and material constraints, unable to provide sufficient tensile strength for patients with high muscle tension. In this paper, we drew inspiration from the muscle structure found in the tail of dragonflies and designed a novel central tendon-based bellows actuator. The experimental results demonstrated that the central tendon-based bellows actuator significantly outperforms conventional pneumatic bellows actuators in terms of mechanical output. The tensile strength of the central tendon-based bellows actuator exceeded that of pneumatic actuators more than tenfold, while adding only 2 g to the wearable weight. This finding suggests that the central tendon-based bellows actuator is exceptionally well-suited for applications demanding substantial pulling force, such as in the field of exoskeleton robotics. With tensile strength exceeding that of pneumatic bellows actuators, this biomimetic design opens new avenues for safer and more effective human-machine interaction, revolutionizing various sectors from healthcare to industrial automation.

Effects of Protein Structure Changes on Texture of Scallop Adductor Muscles under Ultra-High Pressure

In order to investigate the effect of protein structure changes on the texture of scallop adductor muscles under ultra-high pressure, the protein structure, hardness, elasticity, cohesion, and chewing properties of untreated scallops maintained at 200 MPa for 60 s, 120 s, and 180 s were measured and compared. At the same time, sensory indicators were evaluated to verify the effect of ultra-high pressure treatment on the quality of scallop adductor muscles. The results indicated that the mass fraction of the α-helix was decreased by 13.70% and the mass fraction of β–folding was 2.72 times higher in the adductor muscle of scallops compared to the fresh adducts without ultra-high pressure treatment, maintained for 180 s at an ultra-high pressure of 200 MPa. At the same time, the value of I850/I830 of protein tyrosine residues was 1.094, which weakened the water retention ability of the protein, the elasticity of the scallop adduct was reduced from the original 7.16 N to 6.17 N, the cohesion was reduced by 3.76%, and the hardness was increased by 17.45%. This improved the cooking quality of scallops, which was consistent with the sensory evaluation results. Therefore, under ultra-high pressure treatment, changes in the protein structure of the adductor muscle of scallops had a certain impact on their texture, which was able to provide support for in-depth research on the mechanism of ultra-high pressure action.

Three-dimensional freehand ultrasonography to measure muscle volume of the lumbar multifidus: Reliability of processing technique and validity through comparison to magnetic resonance imaging.

There is a growing interest in muscle characteristics of the lumbar multifidus related to low back pain, but findings between studies are inconsistent. One of the issues explaining these conflicting findings might be the use of two-dimensional measures of cross-sectional area and thickness of the lumbar multifidus in most studies, which might be a suboptimal representation of the entire muscle volume. A three-dimensional volumetric assessment, combined with standardized imaging and processing measurement protocols, is highly recommended to quantify spinal muscle morphology. Three-dimensional freehand ultrasonography is a technique with large potential for daily clinical practice. It is achieved by combining conventional two-dimensional ultrasound with a motion-tracking system, recording the position and orientation of the ultrasound transducer during acquisition, resulting in a three-dimensional reconstruction. This study investigates intra- and interprocessor reliability for the quantification of muscle volume of the lumbar multifidus based on three-dimensional freehand ultrasound and its validity, in 31 patients with low back pain and 20 healthy subjects. Two processors manually segmented the lumbar multifidus on three-dimensional freehand ultrasound images using Stradwin software following a well-defined method. We assessed the concurrent validity of the measurement of multifidus muscle volume using three-dimensional freehand ultrasound compared with magnetic resonance imaging in 10 patients with low back pain. Processing reliability and agreement were determined using intraclass correlation coefficients, Bland-Altman plots, and calculation of the standard error of measurement and minimal detectable change, while validity was defined based on correlation analysis. The processing of three-dimensional freehand ultrasound images to measure lumbar multifidus volume was reliable. Good to excellent intraclass correlation coefficients were found for intraprocessor reliability. For interprocessor reliability, the intraclass correlation coefficients were moderate to good, emphasizing the importance of processing guidelines and training. A single processor analysis is preferred in clinical studies or when small differences in muscle volume are expected. The correlation between magnetic resonance imaging and three-dimensional freehand ultrasound measurements of lumbar multifidus volume was moderate to good but with a systematically smaller multifidus volume measured on three-dimensional freehand ultrasound. These results provide opportunities for both researchers and clinicians to reliably assess muscle structure using three-dimensional freehand ultrasound in patients with low back pain and to monitor changes related to pathology or interventions. To allow implementation in both research and clinical settings, guidelines on three-dimensional freehand ultrasound processing and training were provided.

Integrative analysis reveals chemokines CCL2 and CXCL5 mediated shear stress-induced aortic dissection formation

BackgroundAortic dissection (AD) is a critical emergency in cardiovascular disease. AD occurs only in specific sites of the aorta, and the variation of shear stress in different aortic segments is a possible cause not reported. This study investigated the key molecules involved in shear stress-induced AD through quantitative bioinformatic analysis of a public RNA sequencing database and clinical tissue sample validation. MethodsGene expression data from the GSE153434, GSE147026, and GSE52093 datasets were downloaded from the Gene Expression Omnibus. Next, differently expressed genes (DEGs) in each dataset were identified and integrated to identify common AD DEGs. STRING, Cytoscape, and MCODE were used to identify hub genes and crucial clustering modules, and Connectivity Map (CMap) was used to identify positive and negative agents. The same procedure was performed for the GSE160611 dataset to obtain shear stress-induced human aortic endothelial cell (HAEC) DEGs. After the integration of these two DEGs sets to identify shear stress-associated hub DEGs in AD, Gene Ontology Enrichment Analysis was performed. The common chemokine receptors and ligands in AD were identified by analyzing AD's three RNA sequencing datasets. Their origin was verified by analyzing AD single-cell sequencing data and validated by immunoblotting and immunofluorescence. ResultsWe identified 100 down-regulated and 50 up-regulated AD common DEGs. Enrichment results showed that common DEGs were closely related to blood vessel morphogenesis, muscle structure development, muscle tissue development, and chemotaxis. Among those DEGs, MYC, CCL2, and SPP1 are the three molecules with the highest degree. A crucial cluster of 15 genes was identified using MCODE, which contained inflammation-related genes with elevated expression and muscle cell-related genes with decreased expression, and CCL2 is central to immune-related genes. CMap confirmed MEK inhibitors and ALK inhibitors as possible therapeutic agents for AD. Moreover, 366 shear stress-associated DEGs in HAEC were identified in the GSE160611 dataset. After taking the intersection, we identified five shear stress-associated hub DEGs in AD (ANGPTL4, SNAI2, CCL2, GADD45B, and PROM1), and the enrichment analysis indicated they were related to the endothelial cell apoptotic process. Chemokine CCL2 was the molecule with a high degree in both DEG sets. Besides CCL2, CXCL5 was the only chemokine ligand differentially expressed in the three datasets. Additionally, immunoblotting confirmed the increased expression of CCL2 and CXCL5 in clinical tissue samples. Further research at the single-cell level revealed that CCL2 has multiple origins, and CXCL5 is macrophage-derived. ConclusionThrough integrative analysis, we identified core common AD DEGs and possible therapeutic agents based on these DEGs. We elucidated that the chemokine CCL2 and CXCL5-mediated “Endothelial-Monocyte-Neutrophil” axis may contribute to the development of shear stress-induced AD. These findings provide possible therapeutic targets for the prevention and treatment of AD.

Impact of Prepectoral vs. Subpectoral Tissue Expander Placement on Post-mastectomy Radiation Therapy Delivery: A Retrospective Cohort Study.

Implant-based reconstruction is the most common method of postmastectomy reconstruction. Many patients require postmastectomy radiation (PMRT). Tissue expanders (TEs), typically inserted as a first stage, have historically been placed subpectorally. More recently, prepectoral reconstruction has gained popularity, but its impact on PMRT is unknown. Prior studies focus on complication rates and aesthetic outcomes. This study examines whether there is a difference in radiation dosimetry among patients undergoing prepectoral versus subpectoral TE reconstruction. Electronic medical records and radiation plans of 50 patients (25 prepectoral, 25 subpectoral) who underwent mastectomy with immediate TE reconstruction at our institution or affiliate site were reviewed. Pectoralis major muscle and chest wall structures were contoured and mean percentage volumes of these structures receiving less than 95%, 100%, and more than 105% target radiation dose were calculated, as were heart and ipsilateral lung doses. Welch two sample t test, Fisher exact test, and Pearson chi-squared tests were performed. The groups had comparable patient and tumor characteristics and underwent similar ablative and reconstructive procedures and radiation dosimetry. Subpectoral patients had larger mean areas receiving less than 95% target dose ("cold spots"); prepectoral patients had larger mean areas receiving greater than 105% ("hot spots") and 100% target doses. There were no differences in chest wall, heart, and lung doses. Our results demonstrate an increased mean percentage area of pectoralis cold spots with subpectoral reconstruction and increased area of hot spots and 100% dose delivery to the pectoralis in prepectoral patients. Larger studies should analyze long-term effects of prepectoral reconstruction on radiation dosing and recurrence rates.

Effects of Pilates on inter-recti distance, thickness of rectus abdominis, waist circumference and abdominal muscle endurance in primiparous women

BackgroundPilates is expected to have a positive effect on women with weakened abdominal muscles after childbirth. Pilates may have a beneficial effect on the structure and function of the abdominal muscles in pregnant women. Therefore, the objective of this study was to investigate the effects of Pilates on inter-recti distance, thickness of the rectus abdominis, waist circumference, and abdominal muscle endurance in primiparous women.MethodsThirty-five primiparous postpartum women were assigned to either the Pilates exercise group (n = 20) or the control group (n = 15). Pilates was undertaken by the exercise group for 50 min/day, 5 days/week, for 4 weeks. The control group maintained their daily activities without any intervention. The inter-recti distance was measured at three locations along the linea alba, and the thickness of the rectus abdominis was measured using ultrasound. Abdominal muscle endurance was measured using a repeated 1-min curl-up test. Waist circumference was also measured.ResultsThe exercise group showed significant improvements from baseline in inter-recti distance, waist circumference, and abdominal muscle endurance (p < 0.05). The control group showed no significant improvement in these variables. Compared with the control group, the exercise group showed significantly improved performance in terms of inter-recti distance, waist circumference, and abdominal muscle endurance (p < 0.05).ConclusionsThe results of this study demonstrate that Pilates was effective in reducing inter-recti distance and waist circumference and improving abdominal muscle endurance in primiparous postpartum women. Pilates is considered an effective exercise for improving muscle structure and function in primiparous postpartum women, helping in the recovery from, and preventing, diastasis rectus abdominis.

DNA hydroxymethylation differences underlie phenotypic divergence of somatic growth in Nile tilapia reared in common garden

ABSTRACTPhenotypic plasticity of metabolism and growth are essential for adaptation to new environmental conditions, such as those experienced during domestication. Epigenetic regulation plays a key role in this process but the underlying mechanisms are poorly understood, especially in the case of hydroxymethylation. Using reduced representation 5-hydroxymethylcytosine profiling, we compared the liver hydroxymethylomes in full-sib Nile tilapia with distinct growth rates (3.8-fold difference) and demonstrated that DNA hydroxymethylation is strongly associated with phenotypic divergence of somatic growth during the early stages of domestication. The 2677 differentially hydroxymethylated cytosines between fast- and slow-growing fish were enriched within gene bodies (79%), indicating a pertinent role in transcriptional regulation. Moreover, they were found in genes involved in biological processes related to skeletal system and muscle structure development, and there was a positive association between somatic growth and 5hmC levels in genes coding for growth factors, kinases and receptors linked to myogenesis. Single nucleotide polymorphism analysis revealed no genetic differentiation between fast- and slow-growing fish. In addition to unveiling a new link between DNA hydroxymethylation and epigenetic regulation of growth in fish during the initial stages of domestication, this study suggests that epimarkers may be applied in selective breeding programmes for superior phenotypes.

Mammary fibromatosis in a female dog: case report

Fibromatosis, or desmoid tumour, is characterized by excessive and infiltrative proliferation of connective tissue originating from aponeurotic muscle structures. Mammary fibromatosis is rare in humans and animals and its precise aetiology is unknown. A 10-year-old mixed-breed female dog developed a mass in the right cranial thoracic mammary gland (M1) and underwent lumpectomy. The mass was firm, with an irregular surface and distinct limits. Microscopically, it was a neoplastic proliferation of fusiform cells with low atypia, interspersed with abundant dense collagenous tissue, confirmed by histochemical staining with Gomori's trichrome and Masson's trichrome and immunopositivity for vimentin and smooth muscle actin, confirming mammary fibromatosis. Mammary fibromatosis in dogs needs further studies to elucidate its clinical, epidemiological and aetiopathogenic aspects.

Study of the specific features in the histological structure of the longissimus muscle dorsi in animals of the genus &lt;i&gt;Ovis&lt;/i&gt;

Relevance. Interspecific hybridization of domestic animals with wild related species is considered as one of the promising directions in animal husbandry in the framework of improving the quality and nutrient biodiversity of livestock products. The article shows the research results of the specific features in the histological structure of the longissimus muscle dorsi in animals of the genus Ovis with different genotypes.Methods. The object of research was sheep of the Romanov breed and interspecific hybrids of domestic sheep (Romanov breed) with argali. Histological studies of the longissimus dorsi muscle of purebred and hybrid animals at the age of 12 months were carried out in a comparative aspect. The thickness and area of muscle fibers, muscle bundles, the number of muscle fibers per unit cross-sectional areas were studied.Results. Differences in a number of morphometric parameters in the main structural units of the longissimus dorsi muscle in hybrid animals depending on the genotype were revealed. In hybrid animals, in comparison with purebred sheep, a decrease in the thickness and area of muscle fibers by 12% and 25% was found (p &lt; 0.01). An increase in the number of muscle fibers per 1 mm2 of the cut and a decrease in the proportion of connective tissue in the structure of the longissimus dorsi muscle in interspecific hybrids were shown in comparison with those in sheep of the Romanov breed (p &lt; 0.01). These biological features of hybrid animals should be taken into account when breeding, selecting and using them to obtain meat and meat products.

Fine-needle percutaneous muscle microbiopsy technique as a feasible tool to address histological analysis in young children with cerebral palsy and age-matched typically developing children.

Cerebral palsy (CP) is a heterogeneous group of motor disorders attributed to a non-progressive lesion in the developing brain. Knowledge on skeletal muscle properties is important to understand the impact of CP and treatment but data at the microscopic levels are limited and inconsistent. Currently, muscle biopsies are collected during surgery and are restricted to CP eligible for such treatment or they may refer to another muscle or older children in typically developing (TD) biopsies. A minimally invasive technique to collect (repeated) muscle biopsies in young CP and TD children is needed to provide insights into the early muscle microscopic alterations and their evolution in CP. This paper describes the protocol used to 1) collect microbiopsies of the medial gastrocnemius (MG) and semitendinosus (ST) in CP children and age-matched TD children, 2) handle the biopsies for histology, 3) stain the biopsies to address muscle structure (Hematoxylin & Eosin), fiber size and proportion (myosin heavy chain), counting of the satellite cells (Pax7) and capillaries (CD31). Technique feasibility and safety as well as staining feasibility and measure accuracy were evaluated. Two microbiopsies per muscle were collected in 56 CP (5.8±1.1 yr) and 32 TD (6±1.1 yr) children using ultrasound-guided percutaneous microbiopsy technique. The biopsy procedure was safe (absence of complications) and well tolerated (Score pain using Wong-Baker faces). Cross-sectionally orientated fibers were found in 86% (CP) and 92% (TD) of the biopsies with 60% (CP) and 85% (TD) containing more than 150 fibers. Fiber staining was successful in all MG biopsies but failed in 30% (CP) and 16% (TD) of the ST biopsies. Satellite cell staining was successful in 89% (CP) and 85% (TD) for MG and in 70% (CP) and 90% (TD) for ST biopsies, while capillary staining was successful in 88% (CP) and 100% (TD) of the MG and in 86% (CP) and 90% (TD) for the ST biopsies. Intraclass coefficient correlation showed reliable and reproducible measures of all outcomes. This study shows that the percutaneous microbiopsy technique is a safe and feasible tool to collect (repeated) muscle biopsies in young CP and TD children for histological analysis and it provides sufficient muscle tissue of good quality for reliable quantification.

Single fiber curvature for muscle impairment assessment: Phase contrast imaging of stroke-induced animals.

There are technical challenges in imaging studies that can three-dimensionally (3D) analyze a single fiber (SF) to observe the functionality of the entire muscle after stroke. This study proposes a 3D assessment technique that only segments the SF of the right stroke-induced soleus muscle of a gerbil using synchrotron radiation x-ray microcomputed tomography (SR-μCT), which is capable of muscle structure analysis. Curvature damage in the SF of the left soleus muscle (impaired) progressed at 7-day intervals after the stroke in the control; particularly on the 7 days (1 week) and 14 days (2 weeks), as observed through visualization analysis. At 2 weeks, the SF volume was significantly reduced in the control impaired group (p = .033), and was significantly less than that in the non-impaired group (p = .009). We expect that animal post-stroke studies will improve the basic field of rehabilitation therapy by diagnosing the degree of SF curvature. RESEARCH HIGHLIGHTS: Muscle evaluation after ischemic stroke using synchrotron radiation x-ray microcomputed tomography (SR-μCT). Curvature is measured by segmenting a single fiber (SF) in the muscle. Structural changes in the SF of impaired gerbils at 7-day intervals were assessed.

UNC-82/NUAK kinase is required by myosin A, but not myosin B, to assemble and function in the thick filament arms of C. elegans striated muscle.

The mechanisms that ensure proper assembly, activity, and turnover of myosin II filaments are fundamental to a diverse range of cellular processes. In Caenorhabditis elegans striated muscle, thick filaments contain two myosins that are functionally distinct and spatially segregated. Using transgenic double mutants, we demonstrate that the ability of increased myosin A expression to restore muscle structure and movement in myosin B mutants requires UNC-82/NUAK kinase activity. Myosin B function appears unaffected in the kinase-impaired unc-82(e1220) mutant: the recessive antimorphic effects on early assembly of paramyosin and myosin A in this mutant are counteracted by increased myosin B expression and exacerbated by loss of myosin B. Using chimeric myosins and motility assays, we mapped the region of myosin A that requires UNC-82 activity to a 531-amino-acid region of the coiled-coil rod. This region includes the 264-amino-acid Region 1, which is sufficient in chimeric myosins to rescue the essential filament-initiation function of myosin A, as well as two sites that interact with myosin head domains in the Interacting Heads Motif. A specific physical interaction between myosin A and UNC-82::GFP is supported by GFP labeling of ectopic myosin A filaments but not thin filaments. We hypothesize that UNC-82 regulates assembly competence of myosin A during parallel assembly in the filament arms.

Effects of voluntary exercise on muscle structure and function in cerebral palsy.

Linked Article: https://onlinelibrary.wiley.com/doi/10.1111/dmcn.15173

Assessment of multi-trait analysis of GWAS (MTAG) for discovery of novel genetic variants and mechanistic insight in common cardiovascular diseases

Abstract Background Variability in cardiovascular conditions is partly explained by common genomic variation identifiable by genome-wide association studies (GWAS). Genetic substrate may overlap in certain entities, this being quantified by genetic correlation. We aimed to leverage multi-trait analysis of GWAS (MTAG), (1) which boosts statistical power by joint analysis of genetically correlated traits, to improve genetic loci discovery in 3 common cardiovascular diseases: atrial fibrillation (AF), coronary artery disease (CAD), and heart failure (HF). Methods and Results Cardiovascular phenotypes with available GWAS summary statistics most correlated with the disease of interest were analysed jointly by MTAG (workflow depicted in Figure 1). These included body mass index and HF for AF (2); HF, LDL-cholesterol, and systolic blood pressure for CAD (3); and AF, CAD, and dilated cardiomyopathy for HF (4). MTAG increased statistical power for all 3 disease GWAS and allowed the identification of 19 new genomic loci for AF, 89 for CAD and 52 for HF (at a GWAS significance level P&amp;lt;5x10-8) (Figure 2). New loci were defined as not previously identified in the single trait original GWAS. Consistently, 19/19, 85/89 and 48/52 of new loci reached nominal significance (P&amp;lt;0.05) in the original studies; and 37%, 44% and 36% of new loci have been associated with AF, CAD and HF in GWAS and phenome wide association studies (PheWAS) in independent cohorts. MTAG summary statistics annotation and functional analysis integrated the distance to the canonical transcriptional start site, chromatin interaction experiments, quantitative molecular phenotype trait experiments and in silico functional prediction through OpenTargets Genetics. MAGMA gene-set functional analysis of the new MTAG results showed 87, 27 and 24 significant associated pathways to AF, CAD and HF respectively. Among the top associations, cardiac depolarization, repolarization, and muscle contraction in AF; macromolecular complex remodeling, triglyceride, chylomicron and LDL metabolism in CAD; and muscle structure, tissue development and RNA transcription initiation in HF. Among novel relevant genes in AF, SRR on chromosome 16 is involved in central nervous system development through regulation of NMDA receptors. This locus has been previously associated with QRS in another GWAS and SRR is related to reduction in heart rate variability and AF enhancement in rats. In CAD, RSPO3 and JAG1 genes, on chromosomes 6 and 20 respectively, have a relevant role in angiogenesis, where RSPO3 is a crucial regulator of coronary artery formation in the developing heart. Conclusions MTAG allows the discovery of new trait-specific loci involved in the pathogenesis of AF, CAD, and HF congruent with the mechanisms of each disease and consistent with independent external cohort PheWAS and GWAS. Thus, MTAG is an interesting tool to unravel relevant mechanisms and potential therapeutic targets in common cardiovascular diseases.

Impact of Human Recombinant Irisin on Tissue-Engineered Skeletal Muscle Structure and Function.

Tissue engineering of exogenous skeletal muscle units (SMUs) through isolation of muscle satellite cells from muscle biopsies is a potential treatment method for acute volumetric muscle loss (VML). A current issue with this treatment process is the limited capacity for muscle stem cell (satellite cell) expansion in cell culture, resulting in a decreased ability to obtain enough cells to fabricate SMUs of appropriate size and structural quality and that produce native levels of contractile force. This study determined the impact of human recombinant irisin on the growth and development of three-dimensional (3D) engineered skeletal muscle. Muscle satellite cells were cultured without irisin (control) or with 50, 100, or 250 ng/mL of irisin supplementation. Light microscopy was used to analyze myotube formation with particular focus placed on the diameter and density of the monotubes during growth of the 3D SMU. Following the formation of 3D constructs, SMUs underwent measurement of maximum tetanic force to analyze contractile function, as well as immunohistochemical staining, to characterize muscle structure. The results indicate that irisin supplementation with 250 ng/mL significantly increased the average diameter of myotubes and increased the proliferation and differentiation of myoblasts in culture but did not have a consistent significant impact on force production. In conclusion, supplementation with 250 ng/mL of human recombinant irisin promotes the proliferation and differentiation of myotubes and has the potential for impacting contractile force production in scaffold-free tissue-engineered skeletal muscle.

Artificial Muscles for Underwater Soft Robots: Materials and Their Interactions

Underwater soft robots are typically constructed from soft and flexible materials, which enable them to adapt to aquatic environments where the terrain can be complex. They are often inspired by soft-bodied aquatic animals and can be used for a range of tasks, such as underwater exploration, environmental monitoring, and rescue operations. However, the design of these robots presents significant challenges, as it requires soft materials and systems that can withstand the harsh and varied conditions of ocean environments. This review delves into the physics of soft materials and outlines the constitutive models for such materials. Through an exploration of the muscle structures in aquatic creatures like octopuses and stingrays, we highlight the interplay between the materials that make up artificial muscles and how these muscles interact with their external surroundings. Finally, we conclude by outlining unresolved challenges and providing potential avenues for future research.