Altered Muscle Research Articles

Quantitative magnetic resonance imaging of paraspinal muscles for assessing chronic non-specific low back pain in young adults: a prospective case-control study.

This study aimed to investigate the application of quantitative magnetic resonance imaging of paraspinal muscles in assessing the young CNLBP with unilateral symptom. This prospective study enrolled 107 young individuals with unilateral symptomatic CNLBP (56 cases) and a normal cohort (51 cases). All subjects underwent conventional lumbar sequences, T2 mapping, and IDEAL-IQ scans at 3T. T2 values and fat fraction (FF) of bilateral multifidus (mid-levels of L2-L5 vertebrae) and erector spinae (mid-levels of L1-L4 vertebrae) were measured. CNLBP severity, Japanese Orthopedic Association (JOA) score, and Visual Analogue Scale (VAS) score were recorded. Wilcoxon signed-rank tests were used to compare parameter differences between painful and non-painful sides in the case group. Mann-Whitney U tests were employed to evaluate differences between the case and normal group. Logistic regression analysis was conducted to identify predictive factors and to establish a combined model. In the case group, erector spinae FF values (L4 level), erector spinae T2 values (L1, L2, and L4 levels), and multifidus T2 values (L4 and L5 levels) were higher on the painful side (P<0.05). Multifidus T2 values (L5 level) and FF values (L2-L5 levels) were higher in the case group compared to the normal group (P<0.05). The optimal performance in differentiating young CNLBP was the combination of L5 level multifidus T2 value with FF (AUC = 91.81%). Negative correlation existed between T2 values and FF of multifidus at L5 level and JOA scores (r=-0.41, P < 0.05), and positive correlation with VAS scores (r = 0.46, P < 0.05). The combination of T2 value and FF may provide deeper insights into the pathological alterations of paraspinal muscles in young CNLBP, providing an important imaging basis for clinical judgment and preventive treatment of non-painful side in unilateral symptomatic patients.

Acute effects of resistance exercise on the muscle architecture and tissue organization of the maximal isometrically contracted and uncontracted gastrocnemius medialis muscle

ABSTRACT This study aimed to investigate the acute effects of resistance exercise on muscle architecture and tissue organization at rest and during isometric maximum voluntary contraction (iMVC) of the gastrocnemius medialis muscle. In 16 healthy adults (25 ± 3 y), ultrasound scans were captured before (pre), immediately after (post), and 15 min after (post_15) single-leg calf raises during rest and iMVCs. Measurements included muscle thickness (MT), pennation angle (PA), and fascicle length (FL). Spatial frequency analysis (SFA) assessed tissue organization (e.g. peak spatial frequency radius (PSFR), quality factor (Q6)). MT increased significantly from pre to post (+5.7%) and post_15 (+5.6%) at rest. During iMVC, MT and FL increased significantly from pre to post (MT: +8.1%, FL: +14.9%) and post_15 (MT: +5.2%, FL: +10.5%), while PA decreased significantly from pre to post_15 (−10.2%). PSFR and Q6 decreased significantly from pre to post (−7.0-8.2%) and increased from post to post_15 (+10.3-10.6%) at rest, with no significant changes during iMVC. Resistance exercise led to altered muscle architecture for more than 15 min, while SFA parameters reverted to baseline within 15 min. Thus, SFA potentially enables early differentiation of potential physiological alterations in muscle micro-morphology.

Exploration of the triceps surae muscle in ambulatory children with cerebral palsy using instrumented measurements of stiffness and diffusion tensor magnetic resonance imaging for muscle architecture

BackgroundMusculoskeletal alterations causing reduced range of motion of the ankle joint are common in children with cerebral palsy (CP). Objective measurements of passive joint resistance and three-dimensional skeletal muscle volume and muscle architecture can lead to a comprehensive understanding of which factors influence joint range of motion.Research questionTo investigate the relation between the passive dorsiflexion of the ankle joint, biomechanical contributing factors to the passive joint resistance, and muscular architectural properties of the triceps surae muscle in children with CP.MethodsIn this cross-sectional observational study, 14 children with spastic CP (bilateral: 5, unilateral: 9, Gross Motor Function Classification System (GMFCS) level I:11, II:3) naïve to intramuscular tone reducing treatment, and 14 TD children were included. The passive dorsiflexion of the ankle was measured with a goniometer. Passive joint resistance and related parameters were estimated based on a biomechanical model and measurements using a motorized device, the Neuroflexor. Three-dimensional muscle architecture was quantified with diffusion tensor magnetic resonance imaging (DT-MRI).ResultsIn the CP group, the median [min, max] passive dorsiflexion was decreased in the most affected leg (MAL) compared to the less affected leg (LAL) (2.5° [-25°, 20°] vs. 12.5° [5°, 30°], p = 0.001). The stiffness coefficient (Nm/rad) in the MAL was significantly higher in children with CP compared to TD children (7.10 [3.39, 62.00] vs. 2.82 [1.24, 10.46], p = 0.015). Muscle architecture properties did not differ between CP and TD, except for pennation angle in the medial gastrocnemius (MG) of the MAL (CP 17.64° (2.29) vs. TD 21.46° (3.20), p = 0.017). The stiffness coefficient, in the MAL, correlated negatively to passive dorsiflexion (rs=-0.638) and pennation angle in medial gastrocnemius (rs=-0.964), and the non-linear coefficient (Non-linear 1) correlated negatively to the fascicle length of the medial gastrocnemius (rs=-0.857).ConclusionThis study shows that stiffness of the plantarflexors is related to decreased passive dorsiflexion of the ankle and muscle structure of the MG in high-functioning children with spastic CP. Assessments of how dynamic components as well as microscopic muscle alterations contribute to joint stiffness in the plantarflexors in individuals with CP are warranted.Trial registrationRetrospectively registered in ClinicalTrials.gov, NCT05447299. Observational study. Study start: 2019-01-15, register date: 2022-07-01.

648P MRI demonstrates altered skeletal muscle membrane permeability in Becker muscular dystrophy, representing a potential biomarker for disease activity

648P MRI demonstrates altered skeletal muscle membrane permeability in Becker muscular dystrophy, representing a potential biomarker for disease activity

Comprehensive Proteomic Analysis of Dysferlinopathy Unveiling Molecular Mechanisms and Biomarkers Linked to Pathological Progression.

Previous proteomics studies in dysferlinopathy muscle have been limited in scope, often utilizing 2D-electrophoresis and yielding only a small number of differential expression calls. To address this gap, this study aimed to employ high-resolution proteomics to explore the proteomic landscapes of dysferlinopathy and analyze the correlation between muscle pathological changes and alterations in protein expression in muscle biopsies. We conducted a comprehensive approach to investigate the proteomic profile and disease-associated changes in the muscle tissue proteome from 15 patients with dysferlinopathy, exhibiting varying degrees of dystrophic pathology, alongside age-matched controls. Our methodology encompasses tandem mass tag (TMT)-labeled liquid chromatography-mass spectrometry (LC-MS/MS)-based proteomics, protein-protein interaction (PPI) network analysis, weighted gene co-expression network analysis, and differential expression analysis. Subsequently, we examined the correlation between the expression of key proteins and the clinical characteristics of the patients to identify pathogenic targets associated with DYSF mutations in dysferlinopathy. A total of 1600 differentially expressed proteins were identified, with 1321 showing high expression levels and 279 expressed at lower levels. Our investigation yields a molecular profile delineating the altered protein networks in dysferlinopathy-afflicted skeletal muscle, uncovering dysregulation across numerous cellular pathways and molecular processes, including mRNA metabolic processes, regulated exocytosis, immune response, muscle system processes, energy metabolic processes, and calcium transmembrane transport. Moreover, we observe significant associations between the protein expression of ANXA1, ANXA2, ANXA4, ANXA5, LMNA, PYGM, and the extent of histopathologic changes in muscle biopsies from patients with dysferlinopathy, validated through immunoblotting and immunofluorescence assays. Through the aggregation of expression data from dysferlinopathy-impacted muscles exhibiting a range of pathological alterations, we identified multiple key proteins associated with the dystrophic pathology of patients with dysferlinopathy. These findings provide novel insights into the pathogenesis of dysferlinopathy and propose promising targets for future therapeutic endeavors.

Altered Muscle Bioenergetic in CKD: Focus on Inorganic Phosphate and Acidosis

Altered Muscle Bioenergetic in CKD: Focus on Inorganic Phosphate and Acidosis

The prevalence of sarcopenic obesity in older adults with obesity differs between the use of the chair stand test and handgrip strength as measure of altered muscle function

The prevalence of sarcopenic obesity in older adults with obesity differs between the use of the chair stand test and handgrip strength as measure of altered muscle function

An open-source toolbox for enhancing the assessment of muscle activation patterns during cyclical movements

Objective.The accurate temporal analysis of muscle activations is of great importance in several research areas spanning from the assessment of altered muscle activation patterns in orthopaedic and neurological patients to the monitoring of their motor rehabilitation. Several studies have highlighted the challenge of understanding and interpreting muscle activation patterns due to the high cycle-by-cycle variability of the sEMG data. This makes it difficult to interpret results and to use sEMG signals in clinical practice. To overcome this limitation, this study aims at presenting a toolbox to help scientists easily characterize and assess muscle activation patterns during cyclical movements.Approach.CIMAP(Clustering for the Identification of Muscle Activation Patterns) is an open-source Python toolbox based on agglomerative hierarchical clustering that aims at characterizing muscle activation patterns during cyclical movements by grouping movement cycles showing similar muscle activity.Main results.From muscle activation intervals to the graphical representation of the agglomerative hierarchical clustering dendrograms, the proposed toolbox offers a complete analysis framework for enabling the assessment of muscle activation patterns. The toolbox can be flexibly modified to comply with the necessities of the scientist.CIMAPis addressed to scientists of any programming skill level working in different research areas such as biomedical engineering, robotics, sports, clinics, biomechanics, and neuroscience. CIMAP is freely available on GitHub (https://github.com/Biolab-PoliTO/CIMAP).Significance.CIMAPtoolbox offers scientists a standardized method for analyzing muscle activation patterns during cyclical movements.

Fiber-type composition and 3D capillary analysis of the human splenius capitis muscle.

Despite the significance of neck muscles in musculoskeletal disorders, their microscopic anatomy remains poorly characterized. This study examined the splenius capitis muscle, focusing on its fiber-type composition, fiber size, and capillary network characteristics. For comparison and validation, the vastus lateralis muscle was also analyzed. Muscle samples from 13 young male subjects (mean age ± SD: 35.7 ± 8.6 years) were collected within 24-h post-mortem during autopsy. Myosin heavy chain (MyHC) isoform expression was characterized immunohistochemically in 10 μm sections, while the capillary network architecture was assessed in 100 μm sections. Immunofluorescence staining, confocal microscopy, and 3D image analysis were employed to quantify capillary tortuosity, anisotropy, branch density (Br dens), and the length of capillaries per muscle volume (LV), per muscle fiber length (LL), per fiber surface area (LS), and per fiber volume (LVf). Compared to the vastus lateralis muscle, the splenius capitis muscle had a higher percentage of type 1 fibers (51.2% vs 39.7%), fewer type 2a fibers (16.2% vs 31.4%), and smaller fiber diameters (35.5-40.9 μm vs 47-56.1 μm). It also displayed lower Br dens (P = 0.0069), higher anisotropy (P = 0.0004), and lower LL (P < 0.0001) but higher LVf (P = 0.0486). In the splenius capitis muscle, body mass index (BMI) negatively correlated with LV (P = 0.0155), LS (P = 0.0091), LVf (P = 0.0137), and anisotropy (P = 0.0425), and positively correlated with tortuosity (P = 0.0473), indicating a reduction in the capillary network. In the vastus lateralis muscle, only LV (P = 0.0161) decreased with high BMI. This study characterized the fiber-type composition, fiber size, and 3D capillary network of the splenius capitis muscle, establishing a baseline for investigations into pathological muscle alterations.

Functional Food Mixture Extricates D-Galactose-Induced Skeletal Muscle Impairment in Rats.

Aging-related muscle atrophy/sarcopenia is the most common type of muscle impairment that affects the quality of life. In the current study, we examined the effect of a functional food mixture of amla, turmeric, black pepper, cinnamon, and ginger on D-galactose-induced muscle alterations in rats. Wistar rats were randomly divided into three groups: Control (C), D-galactose (G), and D-galactose + functional food mixture intervention (G + I). Rats in group-G and -G + I were injected with D-galactose (300 mg/kg/day) for 90 days. After 3 months of the experimental period, the rats were sacrificed to collect gastrocnemius muscle. Group-G rats showed elevated levels of inflammatory cytokines (TNFα and NF-kB), atrogenes (atrogin-1 and MuRF1), decreased insulin/IGF1 signaling (decreased AKT phosphorylation), altered mitochondrial dynamics (increased fission and decreased fusion proteins), increased apoptotic mediators (Bax/Bcl-2, and caspase-3), and decreased muscle cell cross-sectional area when compared with group-C (p < 0.05). Interestingly, supplementation with the functional food mixture prevented galactose-induced alterations in the muscle. The observed anti-inflammatory, insulin-sensitizing, mitochondria-protective, and antiapoptotic effects of the functional food could be the underlying mechanisms in displaying positive effects against galactose-induced muscle atrophy and, hence, may be useful for the prevention of age-related muscle disorders.

Acute Effects of Soft Tissue Modalities on Muscular Ultrasound Characteristics and Isometric Performance

Prior to training, many athletes perform different soft-tissue preparation protocols. Many of these protocols involve stretching, foam rolling, and/or percussion massage. Many of these modalities have been studied, but not as a group to observe muscle alterations and differences in males and females. In total, 40 (20 males, 20 females) participants performed five minutes of static stretching, foam rolling, and percussion massage. Pre- and post-isometric leg strength, muscle activation and ultrasound assessments (cross-sectional area, echo intensity, pennation angle, fascicle length, and muscle thickness) were taken. The results indicate that there is no significant difference among modalities, and that they do not significantly alter any muscle characteristic or improve performance. There is a significant difference in size between males and female, with males having larger muscle and greater pennation angles than females. This allows males to generate significantly more muscle force. However, they both respond similarly to each modality. In conclusion, the muscle response to static stretching, foam rolling, and percussion massage do not differ among modalities and do not contribute to an increase or decrease in maximal isometric knee extension with similar effects between males and females.

Aging Does Not Alter Ankle, Muscle, and Tendon Stiffness at Low Loads Relevant to Stance.

Older adults have difficulty maintaining balance when faced with postural disturbances, a task that is influenced by the stiffness of the triceps surae and Achilles tendon. Age-related changes in Achilles tendon stiffness have been reported at matched levels of effort, but measures typically have not been made at matched loads, which is important due to age-dependent changes in strength. Moreover, there has been limited investigation into age-dependent changes in muscle stiffness. Here, we investigate how age alters muscle and tendon stiffness and their influence on ankle stiffness. We hypothesized that age-related changes in muscle and tendon contribute to reduced ankle stiffness in older adults and evaluated this hypothesis when either load or effort were matched. We used B-mode ultrasound with joint-level perturbations to quantify ankle, muscle, and tendon stiffness across a range of loads and efforts in seventeen healthy younger and older adults. At matched loads relevant to standing and the stance phase of walking, there was no significant difference in ankle, muscle, or tendon stiffness between groups (all p > 0.13). However, at matched effort, older adults exhibited a significant decrease in ankle (27%; p = 0.008), muscle (37%; p = 0.02), and tendon stiffness (22%; p = 0.03) at 30% of maximum effort. This is consistent with our finding that older adults were 36% weaker than younger adults in plantarflexion (p = 0.004). Together, these results indicate that, at the loads tested in this study, there are no age-dependent changes in the mechanical properties of muscle or tendon, only differences in strength that result in altered ankle, muscle, and tendon stiffness at matched levels of effort.

Acute Myocarditis, the Dilemma in the General Practice Setting in the Years of the Coronavirus Pandemic Era: An Italian Experience

Myocarditis is inflammation of the muscle tissue of the heart (myocardium) and unlike most heart disease it tends to affect young people more often. Myocarditis can go almost unnoticed, frequently heals without results, but can sometimes be very serious and life threatening. However, many symptoms are non-specific and difficult to evaluate in the general practice setting. In order to diagnose myocarditis it is necessary to carry out some instrumental tests, too. Very important are the EKG and the dosage of cardiac markers in the blood. The echocardiogram allows you to highlight the valvular and muscle alterations that occur during inflammation and the same thing can be done by myocardial magnetic resonance. For those reasons, myocarditis is difficult to diagnose in the setting of General Practitioner (GP) and therefore it is underdiagnosed or misdiagnosed. The presence of nonspecific symptoms, fatigue and dyspnea, especially in a young person, it can lead the GP to suspect a myocarditis. We present a case of myocarditis in a young person. The patient, without a clinical history of important pathologies, presented asthenic and respiratory symptoms with progressive worsening of the clinical picture. We described the reasons of the diagnostic and therapeutic procedures. The general medicine setting is currently unsuitable for taking care of patients of this type, as the waiting times for the necessary examinations. The evaluation and follow-up are not within the reach of local doctors in Italy or with too long waiting times, so monitoring and optimizing therapies remain difficult outside the hospital.

Anabolic deficits and divergent unfolded protein response underlie skeletal and cardiac muscle growth impairments in the Yoshida hepatoma tumor model of cancer cachexia.

Cancer cachexia manifests as whole body wasting, however, the precise mechanisms governing the alterations in skeletal muscle and cardiac anabolism have yet to be fully elucidated. In this study, we explored changes in anabolic processes in both skeletal and cardiac muscles in the Yoshida AH-130 ascites hepatoma model of cancer cachexia. AH-130 tumor-bearing rats experienced significant losses in body weight, skeletal muscle, and heart mass. Skeletal and cardiac muscle loss was associated with decreased ribosomal (r)RNA, and hypophosphorylation of the eukaryotic factor 4E binding protein 1. Endoplasmic reticulum stress was evident by higher activating transcription factor mRNA in skeletal muscle and growth arrest and DNA damage-inducible protein (GADD)34 mRNA in both skeletal and cardiac muscles. Tumors provoked an increase in tissue expression of interferon-γ in the heart, while an increase in interleukin-1β mRNA was apparent in both skeletal and cardiac muscles. We conclude that compromised skeletal muscle and heart mass in the Yoshida AH-130 ascites hepatoma model involves a marked reduction translational capacity and efficiency. Furthermore, our observations suggest that endoplasmic reticulum stress and tissue production of pro-inflammatory factors may play a role in the development of skeletal and cardiac muscle wasting.

Low-intensity aerobic training reduces macrophages infiltration and improves morphological characteristics of soleus skeletal muscle from mdx mice

Duchenne Muscular Dystrophy (DMD) is characterized by the absence of the dystrophin protein. The absence of this protein determines recurrent injuries in muscle tissue progressing to necrosis and generalized weakness, leading to the patient’s death due to respiratory and/or cardiac failure. There is no cure for DMD. However, some exercise programs could minimize the disease's progression. Low-intensity training has been used as a rehabilitation program for dystrophic muscles, although the effects are still unclear. This study aimed to analyze the effects of low-intensity aerobic training on the general morphological aspects of the skeletal muscle of mdx mice. Eighteen male mice were divided into three groups with six animals each: (mdx sedentary, mdx trained, and wild-type sedentary). The low-intensity training was performed on a treadmill running during the 37 sessions. After the experiments, the animals were euthanized, and the soleus muscle was excised for histological and immunofluorescence analyses. The training (37 sessions) showed an improvement intoning the morphological aspects of soleus mdx mice and a reduction of macrophage infiltration. The low-intensity training can minimize the inflammatory process and reverse morphological alteration in the soleus muscle of the mdx mice.

Added Value of Histological Evaluation of Muscle Biopsies in Porcine Vascularized Composite Allografts.

Background: Machine perfusion (MP) offers extended preservation of vascularized complex allografts (VCA), but the diagnostic value of histology using hematoxylin and eosin (H&E) in detecting ischemia-reperfusion injury (IRI) in muscle cells remains unclear. This study aims to document the application of the Histology Injury Severity Score (HISS) and to assess whether additional staining for nicotinamide adenine dinucleotide (NADH) and membrane attack complex (MAC) improves IRI detection in a porcine limb replantation model. Methods: The forelimbs of 16 Dutch Landrace pigs were amputated and preserved for 24 h using hypothermic MP (n = 8) with Histidine-Tryptophan-Ketoglutarate (HTK) or for 4 h with SCS (n = 8) before heterotopic replantation and 7 days of follow-up. Muscle damage was assessed via biochemical markers and light microscopy using H&E, NADH, and MAC at baseline, post-intervention, and post-operative day (POD) 1, 3, and 7 timepoints, using the HISS and a self-developed NADH and MAC score. Results: H&E effectively identified damaged muscle fibers and contributed to IRI assessment in porcine limbs (p < 0.05). The highest HISS was measured on POD 3 between MP (4.9) and SCS (3.5) (p = 0.029). NADH scores of both preservation groups varied over the 7-day follow-up and were statistically insignificant compared with baseline measurements (p > 0.05). MAC revealed no to minimal necrotic tissue across the different timepoints. Conclusions: This study documents the application of the HISS with H&E to detect IRI in muscle fibers. NADH and MAC showed no significant added diagnostic utility. The 24 h MP showed similar muscle alterations using the HISS compared to that of the 4 h SCS after a 7-day follow up.

Serum proteomic profiling of physical activity reveals CD300LG as a novel exerkine with a potential causal link to glucose homeostasis

Background:Physical activity has been associated with preventing the development of type 2 diabetes and atherosclerotic cardiovascular disease. However, our understanding of the precise molecular mechanisms underlying these effects remains incomplete and good biomarkers to objectively assess physical activity are lacking.Methods:We analyzed 3072 serum proteins in 26 men, normal weight or overweight, undergoing 12 weeks of a combined strength and endurance exercise intervention. We estimated insulin sensitivity with hyperinsulinemic euglycemic clamp, maximum oxygen uptake, muscle strength, and used MRI/MRS to evaluate body composition and organ fat depots. Muscle and subcutaneous adipose tissue biopsies were used for mRNA sequencing. Additional association analyses were performed in samples from up to 47,747 individuals in the UK Biobank, as well as using two-sample Mendelian randomization and mice models.Results:Following 12 weeks of exercise intervention, we observed significant changes in 283 serum proteins. Notably, 66 of these proteins were elevated in overweight men and positively associated with liver fat before the exercise regimen, but were normalized after exercise. Furthermore, for 19.7 and 12.1% of the exercise-responsive proteins, corresponding changes in mRNA expression levels in muscle and fat, respectively, were shown. The protein CD300LG displayed consistent alterations in blood, muscle, and fat. Serum CD300LG exhibited positive associations with insulin sensitivity, and to angiogenesis-related gene expression in both muscle and fat. Furthermore, serum CD300LG was positively associated with physical activity and negatively associated with glucose levels in the UK Biobank. In this sample, the association between serum CD300LG and physical activity was significantly stronger in men than in women. Mendelian randomization analysis suggested potential causal relationships between levels of serum CD300LG and fasting glucose, 2 hr glucose after an oral glucose tolerance test, and HbA1c. Additionally, Cd300lg responded to exercise in a mouse model, and we observed signs of impaired glucose tolerance in male, but not female, Cd300lg knockout mice.Conclusions:Our study identified several novel proteins in serum whose levels change in response to prolonged exercise and were significantly associated with body composition, liver fat, and glucose homeostasis. Serum CD300LG increased with physical activity and is a potential causal link to improved glucose levels. CD300LG may be a promising exercise biomarker and a therapeutic target in type 2 diabetes.Funding:South-Eastern Norway Regional Health Authority, Simon Fougners Fund, Diabetesforbundet, Johan Selmer Kvanes’ legat til forskning og bekjempelse av sukkersyke. The UK Biobank resource reference 53641. Australian National Health and Medical Research Council Investigator Grant (APP2017942). Australian Research Council Discovery Early Career Award (DE220101226). Research Council of Norway (Project grant: 325640 and Mobility grant: 287198). The Medical Student Research Program at the University of Oslo. Novo Nordisk Fonden Excellence Emerging Grant in Endocrinology and Metabolism 2023 (NNF23OC0082123).Clinical trial number:clinicaltrials.gov: NCT01803568.

Fatiguing exercise reduces cellular passive Young's modulus in human vastus lateralis muscle.

Previous studies demonstrated that acute fatiguing exercise transiently reduces whole-muscle stiffness, which might contribute to increased risk of injury and impaired contractile performance. We sought to elucidate potential intracellular mechanisms underlying these reductions. To that end, the cellular passive Young's modulus was measured in muscle fibres from healthy, young males and females. Eight volunteers (four male and four female) completed unilateral, repeated maximal voluntary knee extensions until task failure, immediately followed by bilateral percutaneous needle muscle biopsy of the post-fatigued followed by the non-fatigued control vastus lateralis. Muscle samples were processed for mechanical assessment and separately for imaging and phosphoproteomics. Fibres were passively (pCa 8.0) stretched incrementally to 156% of initial sarcomere length to assess Young's modulus, calculated as the slope of the resulting stress-strain curve at short (sarcomere length=2.4-3.0µm) and long (sarcomere length=3.2-3.8µm) lengths. Titin phosphorylation was assessed by liquid chromatography followed by high-resolution mass spectrometry. The passive modulus was significantly reduced in post-fatigued versus control fibres from male, but not female, participants. Post-fatigued samples showed altered phosphorylation of five serine residues (four located within the elastic region of titin) but did not exhibit altered active tension or sarcomere ultrastructure. Collectively, these results suggest that acute fatigue is sufficient to alter phosphorylation of skeletal titin in multiple locations. We also found reductions in the passive modulus, consistent with prior reports in the literature investigating striated muscle stiffness. These results provide mechanistic insight contributing to the understanding of dynamic regulation of whole-muscle tissue mechanics in vivo. HIGHLIGHTS: What is the central question of this study? Previous studies have shown that skeletal muscle stiffness is reduced following a single bout of fatiguing exercise in whole muscle, but it is not known whether these changes manifest at the cellular level, and their potential mechanisms remain unexplored. What is the main finding and its importance? Fatiguing exercise reducescellular stiffnessin skeletal muscle from males but not females, suggesting thatfatigue alters tissue compliance in asex-dependent manner. The phosphorylation status of titin, a potential mediator of skeletal muscle cellular stiffness, is modified by fatiguing exercise. Previous studies have shown that passive skeletal muscle stiffness is reduced following a single bout of fatiguing exercise. Lower muscle passive stiffness following fatiguing exercise might increase risk for soft-tissue injury; however, the underlying mechanisms of this change are unclear. Our findings show that fatiguing exercise reduces the passive Young's modulus in skeletal muscle cells from males but not females, suggesting that intracellular proteins contribute to reduced muscle stiffness following repeated loading to task failure in a sex-dependent manner. The phosphorylation status of the intracellular protein titin is modified by fatiguing exercise in a way that might contribute to altered muscle stiffness after fatiguing exercise. These results provide important mechanistic insight that might help to explain why biological sex impacts the risk for soft-tissue injury with repeated or high-intensity mechanical loading in athletes and the risk of falls in older adults.

Altered smooth muscle cell phenotypic switching in atherogenesis and -progression in a murine model of chemically induced colitis

Altered smooth muscle cell phenotypic switching in atherogenesis and -progression in a murine model of chemically induced colitis

Helminth infection driven gastrointestinal hypermotility is independent of eosinophils and mediated by alterations in smooth muscle instead of enteric neurons.

Intestinal helminth infection triggers a type 2 immune response that promotes a 'weep-and sweep' response characterised by increased mucus secretion and intestinal hypermotility, which function to dislodge the worm from its intestinal habitat. Recent studies have discovered that several other pathogens cause intestinal dysmotility through major alterations to the immune and enteric nervous systems (ENS), and their interactions, within the gastrointestinal tract. However, the involvement of these systems has not been investigated for helminth infections. Eosinophils represent a key cell type recruited by the type 2 immune response and alter intestinal motility under steady-state conditions. Our study aimed to investigate whether altered intestinal motility driven by the murine hookworm, Nippostrongylus brasiliensis, infection involves eosinophils and how the ENS and smooth muscles of the gut are impacted. Eosinophil deficiency did not influence helminth-induced intestinal hypermotility and hypermotility did not involve gross structural or functional changes to the ENS. Hypermotility was instead associated with a dramatic increase in smooth muscle thickness and contractility, an observation that extended to another rodent nematode, Heligmosomoides polygyrus. In summary our data indicate that, in contrast to other pathogens, helminth-induced intestinal hypermotility is driven by largely by myogenic, rather than neurogenic, alterations with such changes occurring independently of eosinophils. (<300 words).