Creatine and L-carnitine attenuate muscular laminopathy in the LMNA mutation transgenic zebrafish.

Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this study, we delve into the investigations of five distinct LMNA mutations, including three novel variants and two pathogenic variants identified in patients with muscular laminopathy. Our approach employs zebrafish models to comprehensively study these variants. Transgenic zebrafish expressing wild-type LMNA and each mutation undergo extensive morphological profiling, swimming behavior assessments, muscle endurance evaluations, heartbeat measurement, and histopathological analysis of skeletal muscles. Additionally, these models serve as platform for focused drug screening. We explore the transcriptomic landscape through qPCR and RNAseq to unveil altered gene expression profiles in muscle tissues. Larvae of LMNA(L35P), LMNA(E358K), and LMNA(R453W) transgenic fish exhibit reduced swim speed compared to LMNA(WT) measured by DanioVision. All LMNA transgenic adult fish exhibit reduced swim speed compared to LMNA(WT) in T-maze. Moreover, all LMNA transgenic adult fish, except LMNA(E358K), display weaker muscle endurance than LMNA(WT) measured by swimming tunnel. Histochemical staining reveals decreased fiber size in all LMNA mutations transgenic fish, excluding LMNA(WT) fish. Interestingly, LMNA(A539V) and LMNA(E358K) exhibited elevated heartbeats. We recognize potential limitations with transgene overexpression and conducted association calculations to explore its effects on zebrafish phenotypes. Our results suggest lamin A/C overexpression may not directly impact mutant phenotypes, such as impaired swim speed, increased heart rates, or decreased muscle fiber diameter. Utilizing LMNA zebrafish models for drug screening, we identify L-carnitine treatment rescuing muscle endurance in LMNA(L35P) and creatine treatment reversing muscle endurance in LMNA(R453W) zebrafish models. Creatine activates AMPK and mTOR pathways, improving muscle endurance and swim speed in LMNA(R453W) fish. Transcriptomic profiling reveals upstream regulators and affected genes contributing to motor dysfunction, cardiac anomalies, and ion flux dysregulation in LMNA mutant transgenic fish. These findings faithfully mimic clinical manifestations of muscular laminopathies, including dysmorphism, early mortality, decreased fiber size, and muscle dysfunction in zebrafish. Furthermore, our drug screening results suggest L-carnitine and creatine treatments as potential rescuers of muscle endurance in LMNA(L35P) and LMNA(R453W) zebrafish models. Our study offers valuable insights into the future development of potential treatments for LMNA-related muscular laminopathy.

Insertions of the striated muscles in the skin and mucosa: a histological study of fetuses and cadavers.

Striated muscle insertions into the skin and mucosa are present in the head, neck, and pelvic floor. We reexamined the histology of these tissues to elucidate their role in transmission of the force. We examined histological sections of 25 human fetuses (gestational ages of ~11-19 weeks and ~26-40 weeks) and 6 cadavers of elderly individuals. Facial muscle insertion or terminal almost always formed as an interdigitation with another muscle or as a circular arrangement in which muscle fiber insertions were sandwiched and mechanically supported by other muscle fibers (like an in-series muscle). Our examination of the face revealed some limited exceptions in which muscle fibers that approached the dermis were always in the nasalis and mentalis muscles, and often in the levator labii superioris alaeque nasi muscle. The buccinator muscle was consistently inserted into the basement membrane of the oral mucosa. Parts of the uvulae muscle in the soft palate and of the intrinsic vertical muscle of the tongue were likely to direct toward the mucosa. In contrast, the pelvic floor did not contain striated muscle fibers that were directed toward the skin or mucosa. Although 'cutaneous muscle' is a common term, the actual insertion of a muscle into the skin or mucosa seemed to be very rare. Instead, superficial muscle insertion often consisted of interdigitated muscle bundles that had different functional vectors. In this case, the terminal of one muscle bundle was sandwiched and fixed mechanically by other bundles.

Integrated multi-omics approach reveals the role of striated muscle preferentially expressed protein kinase in skeletal muscle including its relationship with myospryn complex.

BACKGROUND: Autosomal-recessive mutations in SPEG (striated muscle preferentially expressed protein kinase) have been linked to centronuclear myopathy with or without dilated cardiomyopathy (CNM5). Loss of SPEG is associated with defective triad formation, abnormal excitation-contraction coupling, calcium mishandling and disruption of the focal adhesion complex in skeletal muscles. To elucidate the underlying molecular pathways, we have utilized multi-omics tools and analysis to obtain a comprehensive view of the complex biological processes and molecular functions. METHODS: Skeletal muscles from 2-month-old SPEG-deficient (Speg-CKO) and wild-type (WT) mice were used for RNA sequencing (n = 4 per genotype) to profile transcriptomics and mass spectrometry (n = 4 for WT; n = 3 for Speg-CKO mice) to profile proteomics and phosphoproteomics. In addition, interactomics was performed using the SPEG antibody on pooled muscle lysates (quadriceps, gastrocnemius and triceps) from WT and Speg-CKO mice. Based on the multi-omics results, we performed quantitative real-time PCR, co-immunoprecipitation and immunoblot to verify the findings. RESULTS: We identified that SPEG interacts with myospryn complex proteins CMYA5, FSD2 and RyR1, which are critical for triad formation, and that SPEG deficiency results in myospryn complex abnormalities (protein levels decreased to 22 ± 3% for CMYA5 [P < 0.05] and 18 ± 3% for FSD2 [P < 0.01]). Furthermore, SPEG phosphorylates RyR1 at S2902 (phosphorylation level decreased to 55 ± 15% at S2902 in Speg-CKO mice; P < 0.05), and its loss affects JPH2 phosphorylation at multiple sites (increased phosphorylation at T161 [1.90 ± 0.24-fold], S162 [1.61 ± 0.37-fold] and S165 [1.66 ± 0.13-fold]; decreased phosphorylation at S228 and S231 [39 ± 6%], S234 [50 ± 12%], S593 [48 ± 3%] and S613 [66 ± 10%]; P < 0.05 for S162 and P < 0.01 for other sites). On analysing the transcriptome, the most dysregulated pathways affected by SPEG deficiency included extracellular matrix-receptor interaction (P < 1e-15) and peroxisome proliferator-activated receptor signalling (P < 9e-14). CONCLUSIONS: We have elucidated the critical role of SPEG in the triad as it works closely with myospryn complex proteins (CMYA5, FSD2 and RyR1), it regulates phosphorylation levels of various residues in JPH2 and S2902 in RyR1, and its deficiency is associated with dysregulation of several pathways. The study identifies unique SPEG-interacting proteins and their phosphorylation functions and emphasizes the importance of using a multi-omics approach to comprehensively evaluate the molecular function of proteins involved in various genetic disorders.

Parkinson's disease is associated with low striated esophagus contractility potentially contributing to the development of dysphagia.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder, and more than 80% of PD patients will develop oropharyngeal dysphagia. Despite its striated histology, proximity to airway, and potential negative impact of its dysfunction on bolus transport and airway safety, the contractile function of the striated esophagus in PD patients has not been systematically studied. METHODS: Using our repository of clinical manometry and the Milwaukee ManoBank, we analyzed high-resolution manometry (HRM) studies of 20 PD patients, mean age 69.1 (range 38-87 years); 30 non-PD patients with dysphagia, mean age 64.0 (44-86 years); and 32 healthy volunteers, mean age 65.3 (39-86 years). Patients with abnormal findings based on Chicago Classification 4.0 were identified. Repeat analysis was performed in 20% of the manometric tracings by a different investigator with inter-rater concordance between 0.91 and 0.99. KEY RESULTS: The striated esophageal contractile integral in PD patients was significantly lower than that in non-PD dysphagic patients and healthy controls (p = 0.03 and <0.01, respectively). This significant difference persisted after excluding patients with concurrent Chicago Classification motility disorders (p = 0.02 and 0.01, respectively). In both analyses, the distal esophageal contractile integral did not show any significant difference between groups (p = 0.58 and 0.93, respectively). CONCLUSIONS & INFERENCES: PD is associated with a significant decrease in striated esophagus contractility compared to non-PD and healthy controls. This finding may play a pathophysiologic role in development of dysphagia in this patient population.

Striated Musculature: Embryonic and Fetal Development

SUMMARY: The different embryological origins of striated muscle tissue make it an interesting tissue but at the same time difficult to understand, this is how the musculature of the face comes from the first pharyngeal arch, on the other hand. The muscles of the tongue derive from the somites. The muscles of the larynx come from the pharyngeal arches. The muscles of the spine come from the medial or internal myotome of the somite, while the muscles of the limbs and body wall come from the external myotome. The cardiac musculature originates from the lateral splanchnic mesoderm. In this work, the development of myoblasts in human, mouse and chicken fetuses was studied in the facial region, tongue, and spine, limbs, body wall and cardiac muscles using histological histochemical techniques and immunohistochemical technique. The objective of the work is to compare the histogenesis of striated muscle (skeletal, visceral and cardiac), indicating the differences in origin, evolution of the morphological characteristics in each of them and the signaling routes that are involved in its development.

Los distintos origenes embriológicos del tejido muscular estriado lo hace un tejido interesante, pero a la vez difícil de entender, es así como la musculatura de la cara proviene del primer arco faríngeo, en cambio, la musculatura de la lengua deriva de los somitos. La musculatura de la laringe proviene de los arcos faríngeos. La musculatura de la columna vertebral proviene del miotomo medial o interno del somito, en cambio la musculatura de los miembros y pared del cuerpo proviene del miotomo externo. La musculatura cardiaca se origina del mesoderma lateral esplácnico. En este trabajo se estudió el desarrollo de mioblastos en fetos humanos, de ratón y pollo, en la región facial, lengua, columna vertebral, miembros, pared del cuerpo y musculatura cardíaca mediante técnicas histológicas histoquímicas y técnica inmunohistoquímica. El objetivo del trabajo fue comparar la histogénesis del músculo estriado (esquelético, visceral y cardíaco), indicando las diferencias de origen, evolución de las características morfológicas en cada una de ellas y las rutas de señalización que se ven involucradas en el desarrollo del mismo.

Localization of sensory nerve terminals containing calcitonin gene-related peptide (CGRP) on striated muscle fibers in the rat esophagus: Evidence for triple innervation via motor endplates.

BACKGROUND: Many esophageal striated muscles of mammals are dually innervated by the vagal and enteric nerves. Recently, substance P (SP)-sensory nerve terminals with calcitonin gene-related peptide (CGRP) were found on a few striated muscle fibers in the rat esophagus, implying that these muscle fibers are triply innervated. In this study, we examined the localization and origin of CGRP-nerve endings in striated muscles to consider their possible roles in the esophagus regarding triple innervation. METHODS: Wholemounts of the rat esophagus were immunolabeled to detect CGRP-nerve endings in striated muscles. Also, retrograde tracing was performed by injecting Fast Blue (FB) into the esophagus, and cryostat sections of the medulla oblongata, nodose ganglion (NG), and the tenth thoracic (T10) dorsal root ganglion (DRG) were immunostained to identify the origin of the CGRP-nerve endings. RESULTS: CGRP-fine, varicose nerve endings were localized in motor endplates on a few esophageal striated muscle fibers (4 %), most of which received nitric oxide (NO) synthase nerve terminals, and most of the CGRP nerve endings were SP- and transient receptor potential vanilloid member 1 (TRPV1)-positive. Retrograde tracing showed many FB-labeled CGRP-neurons positive for SP and TRPV1 in the NG and T10 DGR. CONCLUSIONS: This study suggests that the CGRP-varicose nerve endings containing SP and TRPV1 in motor endplates are sensory, and a few esophageal striated muscle fibers are triply innervated. The nerve endings may detect acetylcholine-derived acetic acid from the vagal motor nerve endings and NO from esophageal intrinsic nerve terminals in the motor endplates to regulate esophageal motility.

Alterations of whole body glucose metabolism in a feline SARS-CoV-2 infection model.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been especially devastating to patients with comorbidities, including metabolic and cardiovascular diseases. Elevated blood glucose during SARS-CoV-2 infection increased mortality of patients with COVID-19, although the mechanisms are not well understood. It has been previously demonstrated that glucose transport and utilization is a crucial pathway for other highly infectious RNA viruses. Thus, we hypothesized that SARS-CoV-2 infection could lead to alterations in cellular and whole body glucose metabolism. Specific pathogen-free domestic cats were intratracheally inoculated with USA-WA1/2020 (wild-type) SARS-CoV-2 or vehicle-inoculated, then euthanized at 4- and 8-days postinoculation (dpi). Blood glucose and cortisol concentrations were elevated at 4 and 8 dpi. Blood ketones, insulin, and angiotensin II concentrations remained unchanged throughout the experimental timeline. SARS-CoV-2 RNA was detected in the lung and heart, without changes in angiotensin-converting enzyme 2 (ACE2) RNA expression. In the lung, SARS-CoV-2 infection increased glucose transporter 1 (GLUT1) protein levels at 4 and 8 dpi, whereas GLUT4 level was only upregulated at 8 dpi. In the heart, GLUT-1 and -4 protein levels remained unchanged. Furthermore, GLUT1 level was upregulated in the skeletal muscle at 8 dpi, and AMPK was activated in the hearts of infected cats. SARS-CoV-2 infection increased blood glucose concentration and pulmonary GLUT protein levels. These findings suggest that SARS-CoV-2 infection induces metabolic reprogramming primarily in the lung to support viral replication. Furthermore, this translational feline model mimicked human COVID-19 and could be used to explore novel therapeutic targets to treat metabolic disease during SARS-CoV-2 infection.NEW & NOTEWORTHY Our study on a feline model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, mirroring human COVID-19, revealed alterations in whole body and cellular glucose metabolism. Infected cats developed mild hyperglycemia, increased protein levels of glucose transporters in the lung, and AMPK activation in the heart. These findings suggest that SARS-CoV-2 infection induces metabolic reprogramming in the cardiorespiratory system to support viral replication. Understanding these mechanisms could lead to novel antiviral therapeutic strategies.

An Overview of the Effect of Aging on the Female Urethra.

Urethral function declines by roughly 15% per decade and profoundly contributes to the pathogenesis of urinary incontinence. Individuals with poor urethral function are more likely to fail surgical management for stress incontinence that focus on improving urethral support. The reduced number of intramuscular nerves and the morphologic changes in muscle and connective tissue collectively impact urethral function as women age. Imaging technologies like MRI and ultrasound have advanced our understanding of these changes. However, substantial knowledge gaps remain. Addressing these gaps can be crucial for developing better prevention and treatment strategies, ultimately enhancing the quality of life for aging women.

Correlation between congenital pelvic floor muscle development assessed by magnetic resonance imaging and postoperative defecation.

OBJECTIVE: Children with congenital anorectal malformation (CAM) experience challenges with defecation. This study aims to assess defecation in preschool-age children with CAM and to evaluate the correlation between pelvic floor muscle developed assessed by magnetic resonance imaging (MRI) and postoperative defecation. METHODS: We collected clinical data and MRI results from 89 male children with CAM. The bowel function scores for children with Perineal (cutaneous) fistula, Rectourethral fistula(Prostatic or Bulbar), and Rectovesical fistula were computed. MRI scans were subjected to image analysis of the striated muscle complex (SMC). The association between pelvic floor muscle score and bowel function score was examined using the Cochran-Armitage Trend Test. RESULTS: We observed that 77.4% of the SMC scores by MRI for Perineal fistula were good. The Rectourethral fistula SMC score was 40.6% for moderate and 59.4% for poor. The SMC score for Rectovesical fistula was 100% for moderate. Furthermore, 77.4% of patients with Perineal fistula had bowel function scores (BFS) ≥ 17 points. Among those with Rectourethral fistula and Rectovesical fistula, 12.5% and 0 had BFS ≥ 17 points, respectively. An analysis of muscle development and bowel function in patients with Rectovesical fistula, Rectourethral fistula, and Perineal fistula revealed a correlation between SMC development and BFS. Subgroup analysis showed that the Perineal fistula had statistical significance; however, the Rectourethral fistula and Rectovesical fistula were not statistically significant. CONCLUSION: A correlation exists between pelvic floor muscle development and postoperative defecation in children with Perineal fistula.

The parabasal filaments of Trichomonas vaginalis: A new filament and observations using 0.8 nm-resolution scanning electron microscopy.

Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common nonviral sexually transmitted infection worldwide, with an estimated 260 million new cases annually. T. vaginalis contains organelles common to all eukaryotic cells, uncommon cell structures such as hydrogenosomes, and a complex and elaborate cytoskeleton constituting the mastigont system. The mastigont system is mainly formed by several proteinaceous structures associated with basal bodies, the pelta-axostylar complex made of microtubules, and striated filaments named the costa and the parabasal filaments (PFs). Although the structural organization of trichomonad cytoskeletons has been analyzed using several techniques, observation using a new generation of scanning electron microscopes with a resolution exceeding 1 nm has allowed more detailed visualization of the three-dimensional organization of the mastigont system. In this study, we have investigated the cytoskeleton of T. vaginalis using a diverse range of scanning probe microscopy techniques, which were complemented by electron tomography and Fast-Fourier methods. This multi-modal approach has allowed us to characterize an unknown parabasal filament and reveal the ultrastructure of other striated fibers that have not been published before. Here, we show the differences in origin, striation pattern, size, localization, and additional details of the PFs, thus improving the knowledge of the cell biology of this parasite.

Structure of mavacamten-free human cardiac thick filaments within the sarcomere by cryoelectron tomography.

Heart muscle has the unique property that it can never rest; all cardiomyocytes contract with each heartbeat which requires a complex control mechanism to regulate cardiac output to physiological requirements. Changes in calcium concentration regulate the thin filament activation. A separate but linked mechanism regulates the thick filament activation, which frees sufficient myosin heads to bind the thin filament, thereby producing the required force. Thick filaments contain additional nonmyosin proteins, myosin-binding protein C and titin, the latter being the protein that transmits applied tension to the thick filament. How these three proteins interact to control thick filament activation is poorly understood. Here, we show using 3-D image reconstruction of frozen-hydrated human cardiac muscle myofibrils lacking exogenous drugs that the thick filament is structured to provide three levels of myosin activation corresponding to the three crowns of myosin heads in each 429Å repeat. In one crown, the myosin heads are almost completely activated and disordered. In another crown, many myosin heads are inactive, ordered into a structure called the interacting heads motif. At the third crown, the myosin heads are ordered into the interacting heads motif, but the stability of that motif is affected by myosin-binding protein C. We think that this hierarchy of control explains many of the effects of length-dependent activation as well as stretch activation in cardiac muscle control.

Sequences in the myosin A rod interact with UNC-89/obscurin and the zinc-finger protein UNC-98 during thick filament assembly and M-line formation in C. elegans striated muscle.

The M-line of striated muscle is a complex structure that anchors myosin-containing thick filaments and also participates in signaling and proteostasis. While the physical associations among many M-line components have been defined, the mechanism of thick filament attachment is not completely understood. In Caenorhabditis elegans, myosin A is essential for viability and forms the site of M-line attachment at the center of the filament, whereas myosin B forms the filament arms. Using a mutant myosin A that forms ectopic filaments, we examined interactions between myosin A and M-line proteins in intact muscle cells. Ectopic myosin A recruits the giant kinase UNC-89/obscurin, a presumed scaffolding protein, in an interaction that requires the zinc-finger protein UNC-98, but not UNC-82/NUAK, UNC-97/PINCH, or UNC-96. In myosin A mutants, UNC-89/obscurin patterning is highly defective in embryos and adults. A chimeric myosin containing 169 residues of the myosin A C-terminal rod, coincident with the UNC-98/ZnF binding site, is sufficient for colocalization of UNC-89/obscurin and UNC-98/ZnF in M-line structures whereas a myosin chimera lacking these residues colocalizes with UNC-89/obscurin in M-lines that lack UNC-98. Thus, at least two myosin A rod regions contribute independently to M-line organization. We hypothesize that these M-line-organizing functions correspond to the essential "filament initiation function" performed by this isoform.

Ketone flux through BDH1 supports metabolic remodeling of skeletal and cardiac muscles in response to intermittent time-restricted feeding.

Time-restricted feeding (TRF) has gained attention as a dietary regimen that promotes metabolic health. This study questioned if the health benefits of an intermittent TRF (iTRF) schedule require ketone flux specifically in skeletal and cardiac muscles. Notably, we found that the ketolytic enzyme beta-hydroxybutyrate dehydrogenase 1 (BDH1) is uniquely enriched in isolated mitochondria derived from heart and red/oxidative skeletal muscles, which also have high capacity for fatty acid oxidation (FAO). Using mice with BDH1 deficiency in striated muscles, we discover that this enzyme optimizes FAO efficiency and exercise tolerance during acute fasting. Additionally, iTRF leads to robust molecular remodeling of muscle tissues, and muscle BDH1 flux does indeed play an essential role in conferring the full adaptive benefits of this regimen, including increased lean mass, mitochondrial hormesis, and metabolic rerouting of pyruvate. In sum, ketone flux enhances mitochondrial bioenergetics and supports iTRF-induced remodeling of skeletal muscle and heart.

A Case of Liver Cancer with Overlapping Myasthenia Gravis, Myocarditis, Seronegative Autoimmune Autonomic Ganglionopathy, and Myositis Symptoms Induced by Atezolizumab: A Case Report.

An 83-year-old man with hepatocellular carcinoma developed muscle weakness, ptosis, and dyspnea 3 weeks after receiving atezolizumab. Soon after, mechanical ventilation was initiated, which was followed by marked blood pressure spikes. The levels of creatine kinase and troponin-I were significantly elevated, and acetylcholine receptor antibodies were positive. The patient was diagnosed with immune checkpoint inhibitor (ICI)-induced myositis, myasthenia gravis (MG), myocarditis, and suspected autoimmune autonomic ganglionopathy (AAG). After immunotherapy, the serum markers and blood pressure normalized, and he was weaned from the ventilator after five months. To our knowledge, this is the first reported case of AAG secondary to ICI-induced myositis, MG, and myocarditis.

Desmin and its molecular chaperone, the αB-crystallin: How post-translational modifications modulate their functions in heart and skeletal muscles?

Maintenance of the highly organized striated muscle tissue requires a cell-wide dynamic network through protein-protein interactions providing an effective mechanochemical integrator of morphology and function. Through a continuous and complex trans-cytoplasmic network, desmin intermediate filaments ensure this essential role in heart and in skeletal muscle. Besides their role in the maintenance of cell shape and architecture (permitting contractile activity efficiency and conferring resistance towards mechanical stress), desmin intermediate filaments are also key actors of cell and tissue homeostasis. Desmin participates to several cellular processes such as differentiation, apoptosis, intracellular signalisation, mechanotransduction, vesicle trafficking, organelle biogenesis and/or positioning, calcium homeostasis, protein homeostasis, cell adhesion, metabolism and gene expression. Desmin intermediate filaments assembly requires αB-crystallin, a small heat shock protein. Over its chaperone activity, αB-crystallin is involved in several cellular functions such as cell integrity, cytoskeleton stabilization, apoptosis, autophagy, differentiation, mitochondria function or aggresome formation. Importantly, both proteins are known to be strongly associated to the aetiology of several cardiac and skeletal muscles pathologies related to desmin filaments disorganization and a strong disturbance of desmin interactome. Note that these key proteins of cytoskeleton architecture are extensively modified by post-translational modifications that could affect their functional properties. Therefore, we reviewed in the herein paper the impact of post-translational modifications on the modulation of cellular functions of desmin and its molecular chaperone, the αB-crystallin.

Monensin poisoning outbreak in free-ranging and captive birds.

Monensin poisoning is uncommon and has been rarely reported in birds. This work aimed to described clinical-pathological aspects of an outbreak of monensin poisoning in captive and free-ranging birds. Thirty-seven of 600 captive birds fed a diet containing 893.19 mg/kg of monensin died within 10 days (mortality 6.17%). There was no ionophore antibiotics on the feed label supplied to captive birds, which established an error in feed production. Necropsies were performed on twelve animals: Muscovy duck (Cairina moschata) (2/12), greater rhea (Rhea americana) (2/12), black-necked swan (Cygnus melancoryphus) (2/12), garganey (Anas querquedula) (1/12), ostrich (Struthio camelus) (1/12), and common pigeon (Columbus livia) (4/12). These four common pigeons were free-ranging birds and died after eating the same contaminated feed. Birds were mainly found dead, however in animals which clinical signs were observed (Columba livia, Rhea americana, Cairina moschata, Anas querquedula, and Struthio camelus), they included incoordination, inability to stand, and intense prostration, that ranged from 24 to 72 h until death. Grossly, five birds had focally extensive pale firm areas in the myocardium and two had in the skeletal muscles, one being concomitant lesions. Histologically, muscle necrosis and degeneration were observed in striated musculature (skeletal and/or heart) in all birds analyzed. Monensin poisoning outbreaks can affect free-ranging birds that are fed on external feeders, as well as captive birds, due to an error in the feed formulation.

Innovative problem solving by wild falcons.

Innovation (i.e., a new solution to a familiar problem, or applying an existing behavior to a novel problem1,2) plays a fundamental role in species' ecology and evolution. It can be a useful measure for cross-group comparisons of behavioral and cognitive flexibility and a proxy for general intelligence.3,4,5 Among birds, experimental studies of innovation (and cognition more generally) are largely from captive corvids and parrots,6,7,8,9,10,11,12 though we lack serious models for avian technical intelligence outside these taxa. Striated caracaras (Phalcoboenus australis) are Falconiformes, sister clade to parrots and passerines,13,14,15 and those endemic to the Falkland Islands (Malvinas) show curiosity and neophilia similar to notoriously neophilic kea parrots16,17 and face similar socio-ecological pressures to corvids and parrots.18,19 We tested wild striated caracaras as a new avian model for technical cognition and innovation using a field-applicable 8-task comparative paradigm (adapted from Rössler et al.20 and Auersperg et al.21). The setup allowed us to assess behavior, rate, and flexibility of problem solving over repeated exposure in a natural setting. Like other generalist species with low neophobia,21,22 we predicted caracaras to demonstrate a haptic approach to solving tasks, flexibly switching to new, unsolved problems and improving their performance over time. Striated caracaras performed comparably to tool-using parrots,20 nearly reaching ceiling levels of innovation in few trials, repeatedly and flexibly solving tasks, and rapidly learning. We attribute our findings to the birds' ecology, including geographic restriction, resource unpredictability, and opportunistic generalism,23,24,25 and encourage future work investigating their cognitive abilities in the wild. VIDEO ABSTRACT.

Pembrolizumab-induced Myopathy with Anti-striated Muscle Antibodies Successfully Treated by Plasma Exchange.

A 70-year-old woman with advanced endometrial cancer developed right ptosis and muscle weakness in the right quadriceps after pembrolizumab administration. Serum creatine kinase (CK) levels were elevated, and anti-striated muscle antibodies were positive. On magnetic resonance imaging, the right vastus lateral muscle showed an abnormal signal. She was diagnosed with pembrolizumab-induced myopathy. We initiated plasma exchange (PE), and the ptosis immediately resolved. We then introduced oral corticosteroids, which improved her muscle weakness. We were able to rapidly diagnose her with ocular symptoms and serum CK level elevation. The early initiation of PE might prevent the exacerbation of pembrolizumab-induced myopathy.

Dysfunction of the aging female mouse urethra is associated with striated muscle loss and increased fibrosis: an initial report.

The decline of urethral function with advancing age plays a major role in urinary incontinence in women, impairing quality of life and economically burdening the health care system. However, none of the current urinary incontinence treatments address the declining urethral function with aging, and the mechanisms by which aging impacts urethra physiology remain little known or explored. Here, we have compared functional, morphometric, and global gene expression of urethral tissues between young and old female mice. Bladder leak point pressure (LPP) measurement showed that the aged female mice had 26.55% lower LPP compared to younger mice. Vectorized Scale-Invariant Pattern Recognition (VIPR) analysis of the relative abundance of different tissue components revealed that the mid-urethra of old female mice contains less striated muscle, more extracellular matrix/fibrosis, and diminished elastin fibers ratio compared to young mice. Gene expression profiling analysis (bulk RNA-seq of the whole urethra) showed more down-regulated genes in aged than young mice. Immune response and muscle-related (striated and smooth) pathways were predominantly enriched. In contrast, keratinization, skin development, and cell differentiation pathways were significantly downregulated in aged urethral tissues compared to those from young female mice. These results suggest that molecular pathways (i.e., ACVR1/FST signaling and CTGF/TGF-ß signaling) leading to a decreased striated muscle mass and an increase in fibrous extracellular matrix in the process of aging deserve further investigation for their roles in the declined urethral function.