Penguins, a highly specialized group of birds that have mastered underwater flight, evolved a unique body plan dramatically divergent from volant birds. We dissected two macaroni penguins (Eudyptes chrysolophus) to define appendicular myology in comparison to their aerial relatives. Macaroni penguins have unique and specific adaptations to underwater flight including: an m. supracoracoideus that is proportionally larger than in aerial birds, an annular retinaculum through which both mm. latissimus dorsi cranialis and caudalis pass-an unexpected configuration of the m. latissimus dorsi complex-and an unusual interconnection between several muscles of the pes. We also define a muscle that originates at the sternum and attaches on the proximal tibiotarsus, with the right and left muscles meeting at a midline raphe attaching to the distal sternal keel, functionally supporting the two tibiotarsi in adduction. This muscle has been discussed in the literature for over 100 years as either a slip from m. obliquus externus abdominus or possibly as a superficial head of m. flexor cruris medialis, historically called m. semimembranosus in birds. Our dissections reveal that this muscle is anatomically distinct and may play a specialized role underwater by adducting the hindlimbs to maintain a relatively effortless streamlined silhouette, and on land, by keeping the tibiotarsi adducted thereby supporting otherwise abducted femora. Therefore, we propose that we recognize this distinct muscle with the name m. adductor tibialis.
Numerous lineages of theropod dinosaurs display notable modification of the forelimb, particularly reduction in size and number of digits. Alvarezsauroids are one of the most striking examples of this, exhibiting extreme shortening and increased robusticity of forelimb elements, with a functionally monodactylous manus in late-diverging taxa. These features are generally interpreted as adaptations for digging, possibly as part of a myrmecophagous ecology. Here, we test this hypothesis, using computational range of motion analysis of the shoulder and elbow joints to demonstrate the feasibility of digging behaviours in Mononykus olecranus, a highly specialized alvarezsauroid, and the less specialized Bannykus wulatensis. We find that Bannykus has the capacity for various digging styles and generalized forelimb function, while Mononykus has more restricted motion and may have employed a highly specialized digging style. We also identify similarities in forelimb muscle moment arms between alvarezsaurs and specialized mammalian diggers, supporting adaptation for digging. These findings are consistent with interpretations of insectivory in alvarezsauroids, and suggest increasing specialization to myrmecophagy throughout their evolutionary history, shedding new light on the evolution of this enigmatic clade and the ecological diversity of non-avian theropod dinosaurs.
Recently, both Clarivate and Scopus announced improved metrics for the European Journal of Translational Myology (EJTM), bringing its Impact Factor to 2.0 and its CiteScore to 4.1. I am proud of these achievements and share the credit with the entire PAGEpress staff. Furthermore, many organizers and moderators for the "Padua Days on Muscle and Mobility Medicine" 2027 (2027 Pd3m) have accepted their roles and proposed improvements for the event, which will take place at the Euganean Thermal Baths (Padua, Italy) from March 9 to 12, 2027. The program remains open to numerous additional speakers. On the downside, rising operating costs are affecting both digital publishing and event organization; it is hoped that these increases will not negatively impact the submission of contributions to the EJTM and the 2027 Pd3m conference. Those interested can find further information and forms for active participation (registration, accommodation, abstract template, and participation details) at the following address: www.paduamuscledays.it. Undoubtedly, the 2027 Pd3m promises to be an engaging event, on par with all previous editions of the "Padua Days on Muscle and Mobility Medicine."
Postosuchus kirkpatricki was a large pseudosuchian archosaur from the Late Triassic period in North America. It is among several pseudosuchians proposed to have had derived aspects of locomotor function such as bipedalism or digitigrady, rather than plesiomorphic quadrupedalism or plantigrady, but disputes and inconsistencies about these propositions remain. These lingering disputes need resolution in order to formulate broader inferences about the evolution of bipedalism, limb posture, athleticism, and the end-Triassic mass extinctions. Here, we use 3D musculoskeletal modelling to address the disputes via a deep critical review of available evidence via multiple methods. We conclude that it is uncertain if Postosuchus spp. was quadrupedal or bipedal, plantigrade or digitigrade, due to conflicting evidence. Our analyses also reconstruct pelvic limb musculature that was relatively three times as massive as that in a similar-sized Nile crocodile, whereas the caudofemoralis was smaller than expected due to the gracile tail of Postosuchus. Aspects of hindlimb myology and morphofunctional analyses of the hindlimb joints suggest a mix of traits that are plesiomorphic archosaurian, derived "rauisuchian" and singular for Postosuchus. Our extensive modelling procedure and synthesis of current evidence forms a foundation for future studies such as predictive simulations or ichnological evidence of locomotor function.
Diaphragm dysfunction is an important and often unrecognized cause of dyspnea. The current gold standard, transdiaphragmatic twitch pressure (Pdi,tw), requires oesophageal and gastric balloon catheters and is infrequently used in routine care. We evaluated whether ultrafast ultrasound descriptors of costal diaphragm during bilateral phrenic magnetic stimulation can provide a noninvasive alternative for assessing diaphragm contractility. Thirty patients (19 men and 11 women) referred for suspected diaphragm dysfunction (median age 57 [42-63] years) underwent bilateral anterolateral magnetic stimulation with simultaneous ultrafast ultrasound and oesophageal/gastric pressure recordings. Peak diaphragm tissue velocity, acceleration and jerk were extracted. Associations with Pdi,tw were assessed using ridge regression. Diagnostic performance for detecting abnormal Pdi,tw (< 20 cmH2O) was evaluated using Bayesian receiver operating characteristic (ROC) analysis, including posterior mean AUC and 95% credible intervals. Agreement between predicted and measured Pdi,tw was assessed using Lin's concordance correlation coefficient and Passing-Bablok regression. Twenty four of 30 patients (80%) had abnormal Pdi,tw. Ultrafast ultrasound descriptors correlated with Pdi,tw (Spearman's ρ: velocity 0.77 [95% CI, 0.57-0.89], acceleration 0.70 [95% CI, 0.41-0.87], jerk 0.67 [95% CI, 0.43-0.85]; all p < 0.0001). The multivariable ridge model explained 66% of the variance in Pdi,tw and showed high agreement with measured values (Lin's concordance correlation coefficient = 0.87 [95% CI, 0.75-0.93]). Bayesian ROC analysis demonstrated strong discrimination of diaphragm dysfunction (AUC = 0.91; 95% credible interval [CrI], 0.76-0.98). Using the clinical threshold of 20 cmH2O, model-predicted Pdi,tw yielded a sensitivity of 75% and specificity of 100%. The optimal velocity threshold for discriminating abnormal Pdi,tw was 10.25 mm·ms-1 (95% CrI, 6.12-18.58 mm·ms-1). The corresponding thresholds for acceleration and jerk were 408.6 mm·ms-2 (95% CrI, 122.6-952.4) and 3073 mm·ms-3 (95% CrI, 1038.8-11541.4), respectively. Ultrafast ultrasound coupled with magnetic phrenic stimulation provides a feasible, noninvasive, nonvolitional assessment of diaphragm contractility. Diaphragm motion descriptors reliably predicted Pdi,tw and enabled accurate identification of diaphragm dysfunction. These findings support further clinical evaluation and warrant larger multicentre validation studies.
Spinal Muscular Atrophy (SMA) is a phenotypically heterogenous disease. The Survival Motor Neuron 2 (SMN2) gene copy number can partially predict the clinical severity of SMA, with a single SMN2 copy generally associated with the most severe phenotypes. The aim of this retrospective observational study was to explore the spectrum of phenotypes associated with one SMN2 copy and the possible association with genotype and outcome. We conducted a retrospective observational study of individuals with genetically confirmed SMA (biallelic Survival Motor Neuron 1 [SMN1] variants) and one SMN2 copy, recruited from 36 Italian neuromuscular centres and additional 28 centres from nine other countries (Austria, Belgium, Brazil, Chile, Germany, Netherlands, Spain, United Kingdom and United States) between January 2015 and November 2025.Individuals were included irrespective of age or phenotype; those with incomplete genetic data or confounding diagnoses were excluded. The primary outcome was the phenotypic spectrum associated with a single SMN2 copy, including clinical severity, genotype, treatment exposure, and survival at last follow-up. Sixty-five individuals with one SMN2 copy were included. Neonatal onset was observed in 50/65 (77%). The predominant phenotype was type 0 (39/50, 78%), followed by type 1.1 (6/50, 12%). Five individuals with neonatal onset had prenatal signs (reduced foetal movements and cardiac malformation), but no contractures reported. All individuals with neonatal onset had homozygous deletions of SMN1. The remaining 15/65 (23%) had later onset, with milder phenotypes and all but two presented either with an heterozygous SMN1 deletion associated with a point mutation, or with c.859G>C(p.Gly287Arg) variant in SMN2. Our findings confirm that type 0 is the most frequent phenotype associated with one SMN2 copy, but the boundaries between neonatal-onset phenotypes appear to be fluid. The individuals with one SMN2 copy with milder phenotypes carried variants known to mitigate disease severity. Further prospective studies are needed to better define genotype-phenotype correlations and inform treatment decisions in this population. Some of the data in this study originate from disease registries at least partially funded by Biogen, Novartis and Roche.
Glucosylated-sterols can be synthetized endogenously, absorbed through the diet or derive from bacterial infection. Their clinical relevance is currently underestimated, even though their imbalance has been associated with an increased risk of neurodegeneration over the lifespan. We studied the detrimental effects elicited by dietary consumption of the plant-derived β-sitosterol β-D-glucoside (BSSG), known to be associated with the occurrence of ALS-PDC, to elucidate its potential mechanism of action. Zebrafish larvae and adults, as well as mice, were treated with BSSG administered directly in the water or via customized food pellet, respectively. Since the intestine was identified as the primary target tissue, its morphological and functional characteristics were assessed, together with transcriptional profiling and gut microbiota sequencing. Ex vivo analysis of zebrafish gut contractility was applied to evaluate intestinal neuromuscular responses. Mutant and transgenic zebrafish lines were used to explore a potential BSSG mechanism of action. BSSG induced intestinal inflammation in both zebrafish and mouse models. This previously unknown effect was evidenced by gut dysmotility and inflammatory response. Transcriptomic analyses revealed increased expression of inflammation-related genes in the intestine of both zebrafish and mice, while preliminary gut microbiota analyses suggested the onset of dysbiosis. Transgenic and mutant zebrafish lines, depleted of genes involved in glucocorticoids synthesis and activity, evidenced that BSSG likely interacts with the glucocorticoid receptor, potentially impairing its canonical anti-inflammatory activity. We identified novel pathways altered by dietary BSSG exposure. This molecule appears to initially induce gut inflammation, leading to changes in intestinal morphology and function, and may contribute to neurodegeneration through disruption of the well-known gut-brain axis.
Emery-Dreifuss Muscular Dystrophy (EDMD) is a progressive disease characterized by cardiac and skeletal muscle dysfunction. A primary cause of EDMD is loss of function of the X-chromosome gene emerin (EMD). Although emerin mutations were discovered over three decades ago, X-linked EDMD (X-EDMD) remains understudied largely due to the absence of an animal model with pathological features found in humans. Here, we show that rats lacking emerin (EMD(-/y)) develop motor issues and suddenly die, a major risk factor for patients with X-EDMD. Additionally, EMD(-/y) rats present with other hallmarks of X-EDMD. We found significant fibrosis, abnormal nuclear morphologies, functional deficits and left ventricular wall thinning in the heart of EMD(-/y) rats. Skeletal muscles of EMD(-/y) rats also exhibit altered myonuclei morphology in addition to reduced muscle fiber size. In both cardiac and skeletal muscles of EMD(-/y) rats, we identified altered expression of genes with roles in the cytoskeleton, fibrosis, and muscle contraction. Some of these genes have been previously found to be dysregulated in human muscles lacking emerin. Altogether, these findings identify EMD(-/y) rats as a preclinical model of X-EDMD that phenocopies many aspects of the disease in humans. This work also revealed genes that could potentially be used as biomarkers and targets to treat X-EDMD.
The development of multifunctional dressings capable of actively orchestrating the complex wound microenvironment remains a critical challenge in regenerative medicine. Although leucocyte cell-derived chemotaxin-2 (LECT2) has been implicated in inflammation and angiogenesis, its therapeutic potential in wound healing remains unexplored. Here, we report a novel, portable coaxial electrospinning system for the in situ fabrication of a bioactive nanofiber dressing that continuously delivers functional LECT2. This dressing features a unique polyvinyl butyral (PVB)/polyvinylpyrrolidone (PVP) core and a polyvinyl alcohol (PVA)/PVP shell, which together ensure sustained LECT2 release. We demonstrate that LECT2 acts as a potent multi-target agent: it directly scavenges reactive oxygen species by upregulating the NRF2/SOD axis in keratinocytes and fibroblasts, promotes angiogenesis under oxidative stress, and exerts antimicrobial activity against S. aureus and Methicillin-resistant Staphylococcus aureus. Crucially, LECT2 drives immune reprogramming by polarizing macrophages toward a pro-regenerative M2 phenotype. The resulting dressing exhibits excellent mechanical properties and air permeability, and facilitates rapid wound closure in vivo by simultaneously enhancing re-epithelialization, neovascularization, and M2 macrophage polarization. Conclusions: This work not only unveils LECT2 as a master regulator of wound healing but also establishes a versatile platform for in situ fabrication of advanced dressings, with great promise for the treatment of complex skin wounds.
Fibro/adipogenic progenitors (FAPs) are multipotent stromal cells that support myofiber regeneration, but can also give rise to intramuscular adipose tissue (IMAT) and fibrotic scar tissue. While the Hedgehog pathway suppresses FAP adipogenesis and promotes myofiber repair through ligand Desert Hedgehog, the key cell type that senses this signal has remained unclear. Here, we demonstrate through FAP-specific deletion of the Hedgehog signal transducer Smoothened that FAPs are the primary Hedgehog-responding cells during muscle regeneration. Loss of Smoothened in FAPs increases IMAT, causes persistent fibrosis, reduces the Hedgehog-dependent effectors TIMP3 and GDF10, and impairs myofiber regeneration. FAPs lacking Smoothened also fail to support in vitro myoblast differentiation and fusion as efficiently as control FAPs, showing that Hedgehog signaling helps establish a pro-myogenic FAP state early after injury. Pharmacological Hedgehog activation via the Smoothened agonist SAG fails to rescue adipocyte accumulation or myofiber regeneration when FAPs lack Smoothened. Together, these findings provide direct genetic evidence that FAPs are the primary cellular mediators of Hedgehog signaling in muscle and establish FAP Hedgehog signaling competence as a key determinant of regenerative outcome and a target for restoring muscle repair in disease.
Peripheral artery disease is a major manifestation of atherosclerotic cardiovascular disease (ASCVD) that affects both men and women. In women, menopause increases the ASCVD risk. However, preclinical ASCVD research has historically been conducted predominantly in males, with relatively few studies focused on females and even fewer incorporating menopause models that more closely reflect human ASCVD pathobiology. Herein, we tested whether the chemical 4-vinylcyclohexene diepoxide (4-VCD)-induced ovarian failure or ovariectomy (OVX) would drive atherosclerotic development and worsen ischemic limb pathophysiology. Female C57BL/6J mice were injected with adeno-associated virus-mediated encoding a gain-of-function mutant PCSK9 and fed an atherogenic diet for 23 weeks. Based on the baseline body weight, mice were randomly assigned to normally cycling controls (CON), 4-VCD, or OVX groups. Three weeks after the conformation of ovarian failure (4-VCD) or surgical ovarian removal (OVX), hindlimb ischemia (HLI) was induced via femoral artery ligation, and limb perfusion recovery and limb muscle performance were assessed. Both 4-VCD treatment and OVX reduced uterus mass, without impacting body weight or composition, or circulating cholesterol levels compared to CON mice. Despite the similar metabolic and cholesterol profiles, atherosclerotic lesion areas were 1.5-1.7-fold greater in 4-VCD and OVX mice than CON mice. Perfusion recovery following HLI and plantar flexor muscle function in the ischemic limb were similar across groups, though muscle oxygenation was reduced in 4-VCD and OVX groups. Ovarian failure and removal exacerbated atherosclerotic development but had minimal impacts on perfusion recovery and limb function following HLI. These findings confirm the inclusion of menopausal models, whether through ovarian failure or OVX, should be carefully considered to improve translatability of preclinical ASCVD studies, especially for women's health.
Amyotrophic lateral sclerosis (ALS) shows marked clinical heterogeneity, while standard clinical assessments may fail to capture its multidimensional burden. Integrating quantitative muscle strength, functional tests and patient-reported outcomes (PROs) may improve disease characterization. Ten ambulant adults with ALS were enrolled in a cross-sectional pilot study. Functional performance was assessed with the Revised ALS Functional Rating Scale (ALSFRS-R), Six-Minute Walk Test (6MWT), Ten-Meter Walk Test, Timed Up and Go, Berg Balance Scale and a fatigability index, lower-limb strength with dynamometry, and PROs with ALS Assessment Questionnaire-40 (ALSAQ-40), Hospital Anxiety and Depression Scale, Fatigue Severity Scale and Modified Fatigue Impact Scale (MFIS). Despite relatively preserved ALSFRS-R scores (40.6 ± 2.8), participants showed reduced 6MWT (61.3 ± 21.7% predicted), marked fatigability (- 47.3 ± 112.3%) and a lower-limb strength index of 58.2 ± 13.8% predicted. The ALSAQ-40 score averaged 183.1 ± 59.5. Fatigue was prominent, while anxiety and depression remained mild. Muscle strength correlated positively with ALSFRS-R gross motor score and inversely with anxiety. ALSAQ-40 and MFIS components showed significant associations with both functional and walking performance. Even at ambulant stages, measurable muscle weakness and fatigability co-occur with functional and PROs changes in ALS, supporting the use of multidomain, sensitive clinical assessment. The trial was registered at ClinicalTrials.gov (NCT06199284) on 29/12/2023.
Severe COVID-19 infection leads to profound pulmonary, cardiovascular, and neuromuscular impairments, resulting in marked exercise deconditioning and reduced functional walking capacity after hospital discharge. Eccentric cycling offers high mechanical load with low metabolic cost and may therefore represent a relevant rehabilitation strategy to restore functional capacity in people after COVID-19. To compare functional recovery after 8 weeks of eccentric (ECC) or concentric (CON) training in individuals discharged 1 month previously after a COVID-19 infection. The CovExc trial was a multicenter, randomized, controlled, open-label study conducted in 3 centers. Adults (<80 years) at least 1 month after hospital discharge for severe COVID-19 were randomized (1:1) to 8 weeks of ECC or concentric CON ergometer training (3 30-min sessions per week). The primary outcome was change in the 6-minute walk test (6MWT) distance between baseline and post-intervention (M2). Secondary outcomes included physical performance, muscle strength (handgrip), fatigue, and quality of life. Analyses were conducted in the modified intention-to-treat (mITT) population using mixed models. Of the 60 participants enrolled, 56 (median age (IQR): 54.5 (48; 62)) were included in the modified intention-to-treat population, including 33 men (59%). Forty-four participants completed the program. Intergroup analysis showed no significant differences between the ECC and CON for any variable. However, within-group analyses of the primary endpoint (mITT and per-protocol) revealed a significant change between baseline and 2 months (P = 0.002 and P = 0.001 for ECC and CON groups on mITT and P = 0.001 for ECC and CON groups on per-protocol). 6MWT improved by 18 m in ECC (0; 72) and 28 m in CON (0; 53) (median difference -10 m; 95% CI (-42 to 22). Both eccentric and concentric training improved walking distance in participants after COVID-19, with no difference between groups. Further randomized controlled trials are needed to confirm the effectiveness of these approaches for people who survived COVID-19. NCT04649086.
Idiopathic inflammatory myopathies (IIMs) are autoimmune disorders defined by persistent muscle inflammation, fibrosis, and frequent resistance to current therapies. However, the mechanisms perpetuating disease activity despite immunosuppressive treatment remain elusive. Here, we describe a novel role for tissue-resident stromal cells, specifically fibro-adipogenic progenitors (FAPs), in sustaining skeletal muscle inflammation. Utilizing single-nucleus and spatial transcriptomics in 24 IIM patients and six non-diseased controls, we describe how FAPs adapt to their tissue context, favoring T-cell-centric programs in T-cell environments and myeloid programs in macrophage environments. At the spatial level, FAPs form inflammatory niches by co-localizing with muscle stem cells and activated macrophages, positioning them to participate in cell-to-cell communication with both immune and muscle cells. Trajectory and ligand-receptor analyses suggest a dual-input mechanism whereby infiltrating immune cells (via TGF-β) and myofibers (via epidermal growth factor (EGF)) converge on the AP-1 transcription factor to drive FAP differentiation toward a pro-inflammatory and pro-fibrotic phenotype. Mechanistically, exposure of primary human FAPs to TGF-β and EGF induces a primed state by altering the accessibility to AP-1 regulatory elements. Together, our findings reveal a previously unrecognized role of tissue-resident stromal cells in IIM, highlighting microenvironmental cross-talk centered on FAPs as a promising and actionable therapeutic target.
Open muscle biopsy (OMB) is a key diagnostic tool for neuromuscular diseases, though patients often worry about risks and discomfort. This study aimed to assess pain during and after OMB, factors influencing pain perception, and adverse events. In this single-center prospective study at the Neuropathology Unit of the Pitié-Salpêtrière Hospital, Paris, 100 patients (68 women; mean age 55.4 years) aged ≥ 18 years with suspected myopathy were enrolled from August 2024 to June 2025. Exclusion criteria were inability to understand French, pregnancy, and no social security coverage. Patients completed the numerical rating scale (NRS) for pain assessment and the Patient Health Questionnaire-9. Descriptive statistics summarized patient characteristics. Univariate and multivariate linear regression analyses identified factors associated with procedural pain. Follow-up phone calls were performed at 15 and 30 days postbiopsy. Procedural pain was mild (median NRS = 2) with moderate and weak positive correlations with preprocedural anxiety (r = 0.54, p < 0.01) and Clinical Frailty Scale scores (r = 0.32, p = 0.02), respectively. Weak negative correlations were observed with satisfaction with staff communication (r = -0.29, p = 0.02) and comfort with medical staff (r = -0.27, p = 0.05). Postprocedural discomfort occurred in 42/83 patients, mostly short-lived. No major complications occurred. OMB is a safe procedure. Pain intensity was lower than that generally reported in the literature. Frailty may influence acute pain perception. Preprocedural anxiety emerged as the strongest predictor of pain intensity. Therefore, preprocedural anxiety should be routinely addressed in patients undergoing OMB.
Muscle fibrosis is a major driver of progression in diverse myopathies, yet the conserved molecular mediators of this process in humans remain poorly defined. Here, we identify collagen VI as a common regeneration-impairing extracellular matrix (ECM) component across three distinct human myopathies: Duchenne Muscular Dystrophy (DMD), Oculopharyngeal Muscular Dystrophy (OPMD), and Inclusion Body Myositis (IBM). Proteomic profiling of fibrotic biopsies reveals consistent upregulation of collagen VI and laminin γ1, alongside disease-specific alterations. Fibroadipogenic progenitors (FAPs) are the predominant source of these ECM components, including collagen VI and laminin γ1. Functionally, xenotransplantation of patient-derived FAPs into regenerating mouse muscle induces localized collagen deposition, myofiber atrophy, and depletion of Pax7⁺ muscle stem cells. Mechanistic assays demonstrate that FAP-derived collagen VI is sufficient to impair myogenic fusion, while silencing COL6 in patient FAPs restores fusion capacity, directly linking pathological collagen VI deposition to regeneration failure. Our findings uncover collagen VI as a conserved effector of fibrosis and stem cell niche disruption in human myopathies, positioning it as a potential therapeutic target across genetically and clinically distinct muscle diseases.
Patients with cytochrome c oxidase (COX) deficiency exhibit clinical heterogeneity, with onset ranging from infancy to adulthood. COA8-related disorders typically present in childhood with acute symptoms and cavitating posterior leukoencephalopathy, though milder, muscle-predominant forms have recently been reported. We describe a 54-year-old woman with a neuropathy with slow conduction velocities and leukoencephalopathy, associated with hearing loss and migraine. Neurological examination showed mildly high-arched feet, mild dysmetria without lateralization, and distal hypoesthesia. There was no gastro-intestinal involvement. Targeted NGS for hereditary neuropathies was unremarkable. The neurometabolic workup was negative. Whole genome sequencing identified a homozygous COA8 mutation (c.476 + 1G > A), confirmed by muscle biopsy showing COX deficiency and significantly reduced complex IV activity. This case expands the phenotypic spectrum of COA8-related diseases and suggests that a mitochondrial etiology should be considered in cases of neuropathy with intermediate conduction velocities associated with leukoencephalopathy, even with late onset.
Cardiomyocytes die and do not regenerate after an injury such as a myocardial infarction (MI), a leading cause of mortality worldwide. Following MI, cardiac fibroblasts (CFs) proliferate and differentiate into myofibroblasts, which then produce increased collagen and extracellular matrix (ECM) leading to fibrosis. Fibrosis can weaken cardiac output via excessive stiffening and interference with electric signal transmission, but can also prevent wall rupture under load (reviewed in (1)). Thus, dampening fibrosis has been investigated as a potential therapeutic intervention. Most mammalian cells possess a single primary cilium involved in intercellular communication. We investigated the role of CF primary cilia in sensing injury signals and initiating fibrotic remodeling. We found that deleting CF cilia reduced fibrosis and improved cardiac output after MI, demonstrating that cilia act as a signaling hub that amplifies the fibrotic response in the injured heart.
Inflammatory myopathies are a heterogeneous group of autoimmune diseases characterized by immune-mediated damage to skeletal muscle. They are classified into five major subtypes: inclusion-body myositis, immune-mediated necrotizing myopathies, antisynthetase syndrome, overlapping myositis, and dermatomyositis, each with distinct clinical features and outcomes. Inclusion-body myositis and immune-mediated necrotizing myopathies primarily affect muscle, with prognosis largely determined by functional impairment, whereas antisynthetase syndrome, overlapping myositis, and dermatomyositis are systemic diseases that can involve the skin, joints, and lungs and may be life-threatening. The majority of inflammatory myopathies are associated with myositis-specific autoantibodies, which inform diagnosis, subtype classification, and prognosis. Advances in understanding the distinct pathomechanisms underlying each subgroup now enable increasingly targeted therapeutic approaches.
Marsupials (Marsupialia, Mammalia) represent an ecologically diverse clade. This is particularly true for opossums (South American marsupials), which are, however, often difficult to observe and collect. Consequently, few studies have focused on their bite force and the muscles of their masticatory apparatus, and only scant information on the diet of many species exists. Here we describe the masticatory muscles of several previously unstudied opossum species including Caenolestes fuliginosus, Dromiciops gliroides and Monodelphis touan. We calculate the bite force of these species using data from both manual and digital dissections and compare their theoretical bite forces with literature data. Additionally, we explore the differences between manual and digital dissection to determine the muscle PCSA (physiological cross-sectional area). The results highlighted variation in the position of the muscular attachments and muscle size as well as in the distribution of each muscle in the masticatory apparatus, with a larger temporal complex in M. touan and a larger zygomasseteric complex in D. gliroides. The bite forces are coherent with estimates from the literature suggesting that our biomechanical model is reliable. The comparison between manual and digital dissections showed that while digital dissection allows an overall description of the masticatory muscles, it is more complex to accurately describe the different subdivisions of the muscle bundles. The use of digital volumes to calculate the PCSA remains to be evaluated. Digital dissection data can complement manual dissection data, provided that the composite structure of muscles and the physiological changes during impregnation with contrast agents are better understood.