المؤلفون: Glenn Carrington, Abbi Hau, Sarah Kosta, Hannah F. Dugdale, Francesco Muntoni, Adele D’Amico, Peter Van den Bergh, Norma B. Romero, Edoardo Malfatti, Juan Jesus Vilchez, Anders Oldfors, Sander Pajusalu, Katrin Õunap, Marta Giralt-Pujol, Edmar Zanoteli, Kenneth S. Campbell, Hiroyuki Iwamoto, Michelle Peckham, Julien Ochala

المصدر: JCI Insight, Vol 8, Iss 21 (2023)

مصطلحات موضوعية: Muscle biology, Medicine

الوصف: Myosin heavy chains encoded by MYH7 and MYH2 are abundant in human skeletal muscle and important for muscle contraction. However, it is unclear how mutations in these genes disrupt myosin structure and function leading to skeletal muscle myopathies termed myosinopathies. Here, we used multiple approaches to analyze the effects of common MYH7 and MYH2 mutations in the light meromyosin (LMM) region of myosin. Analyses of expressed and purified MYH7 and MYH2 LMM mutant proteins combined with in silico modeling showed that myosin coiled coil structure and packing of filaments in vitro are commonly disrupted. Using muscle biopsies from patients and fluorescent ATP analog chase protocols to estimate the proportion of myosin heads that were super-relaxed, together with x-ray diffraction measurements to estimate myosin head order, we found that basal myosin ATP consumption was increased and the myosin super-relaxed state was decreased in vivo. In addition, myofiber mechanics experiments to investigate contractile function showed that myofiber contractility was not affected. These findings indicate that the structural remodeling associated with LMM mutations induces a pathogenic state in which formation of shutdown heads is impaired, thus increasing myosin head ATP demand in the filaments, rather than affecting contractility. These key findings will help design future therapies for myosinopathies.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2379-3708Test

الوصول الحر: https://doaj.org/article/59ff4fd339fd4cbaa9a588a2470f9192Test

المؤلفون: Danique Beijer, Hong Joo Kim, Lin Guo, Kevin O’Donovan, Inès Mademan, Tine Deconinck, Kristof Van Schil, Charlotte M. Fare, Lauren E. Drake, Alice F. Ford, Andrzej Kochański, Dagmara Kabzińska, Nicolas Dubuisson, Peter Van den Bergh, Nicol C. Voermans, Richard J.L.F. Lemmers, Silvère M. van der Maarel, Devon Bonner, Jacinda B. Sampson, Matthew T. Wheeler, Anahit Mehrabyan, Steven Palmer, Peter De Jonghe, James Shorter, J. Paul Taylor, Jonathan Baets

المصدر: JCI Insight, Vol 6, Iss 14 (2021)

مصطلحات موضوعية: Genetics, Neuroscience, Medicine

الوصف: Mutations in HNRNPA1 encoding heterogeneous nuclear ribonucleoprotein (hnRNP) A1 are a rare cause of amyotrophic lateral sclerosis (ALS) and multisystem proteinopathy (MSP). hnRNPA1 is part of the group of RNA-binding proteins (RBPs) that assemble with RNA to form RNPs. hnRNPs are concentrated in the nucleus and function in pre-mRNA splicing, mRNA stability, and the regulation of transcription and translation. During stress, hnRNPs, mRNA, and other RBPs condense in the cytoplasm to form stress granules (SGs). SGs are implicated in the pathogenesis of (neuro-)degenerative diseases, including ALS and inclusion body myopathy (IBM). Mutations in RBPs that affect SG biology, including FUS, TDP-43, hnRNPA1, hnRNPA2B1, and TIA1, underlie ALS, IBM, and other neurodegenerative diseases. Here, we characterize 4 potentially novel HNRNPA1 mutations (yielding 3 protein variants: *321Eext*6, *321Qext*6, and G304Nfs*3) and 2 known HNRNPA1 mutations (P288A and D262V), previously connected to ALS and MSP, in a broad spectrum of patients with hereditary motor neuropathy, ALS, and myopathy. We establish that the mutations can have different effects on hnRNPA1 fibrillization, liquid-liquid phase separation, and SG dynamics. P288A accelerated fibrillization and decelerated SG disassembly, whereas *321Eext*6 had no effect on fibrillization but decelerated SG disassembly. By contrast, G304Nfs*3 decelerated fibrillization and impaired liquid phase separation. Our findings suggest different underlying pathomechanisms for HNRNPA1 mutations with a possible link to clinical phenotypes.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2379-3708Test

الوصول الحر: https://doaj.org/article/47cf72fa59a4478a90634b78aa5718fdTest

المؤلفون: Vincent Tiffreau, Christine Detrembleur, Peter Van Den Bergh, Anne Renders, Virginie Kinet, André Thevenon, Etienne Allart, Thierry Lejeune

المصدر: The Journal of the International Society of Physical and Rehabilitation Medicine, Vol 1, Iss 2, Pp 65-71 (2018)

مصطلحات موضوعية: electromyography, gait analysis, kinematics, kinetics, myotonic dystrophy type 1, treadmill, Orthopedic surgery, RD701-811, Medicine

الوصف: Objective: The objective was to characterize the gait abnormalities in myotonic dystrophy type 1 patients. Material and Methods: Outcomes variables were kinematic and kinetic parameters, timing of muscles, mechanical work and energy cost, and the motor function measure. Results: Despite a high cadence and a low ankle range of motion ratio, ankle extension power, and first extension moment of the knee during the stance, the mechanical work and energy cost were normal. The duration of electromyography activation of the gastrocnemius lateralis (GL) muscle was abnormally long. Conclusion: The hypothesis of a myotonic activity of the GL during the swing phase should be investigated.

وصف الملف: electronic resource

العلاقة: http://www.jisprm.org/article.asp?issn=2349-7904;year=2018;volume=1;issue=2;spage=65;epage=71;aulast=TiffreauTest; https://doaj.org/toc/2589-9457Test

الوصول الحر: https://doaj.org/article/c872e31f3eff4be28fdd84e0816886f8Test

المؤلفون: Samuel Arends, Judith Drenthen, Peter Van den Bergh, Hessel Franssen, Robert D.M. Hadden, Badrul Islam, Satoshi Kuwabara, Ricardo Reisin, Nortina Shahrizaila, Hiroshi Amino, Giovanni Antonini, Shahram Attarian, Claudia Balducci, Fabio Barroso, Tulio E. Bertorini, Davide Binda, Thomas H. Brannagan, Jan Buermann, Carlos Casasnovas, Guido Cavaletti, Chi‐Chao Chao, Mazen M. Dimachkie, E. Fulgenzi, Giuliana Galassi, Gerardo Gutiérrez-Gutiérrez, Thomas Harbo, Hans‐Peter Hartung, Sung‐Tsang Hsieh, Lynette Kiers, Helmar C. Lehmann, Fiore Manganelli, Girolama Alessandra Marfia, Giorgia Mataluni, Julio Pardo, Yann Péréon, Yusuf A. Rajabally, Lucio Santoro, Yukari Sekiguchi, Beth E. Shubin Stein, S. Clements Mark, Antonino Uncini, Christine Verboon, Camiel Verhamme, Michal Vytopil, Waqar Waheed, Min Wang, Sasha Živković, Bart C. Jacobs, David R. Cornblath, Jean Addington

مصطلحات موضوعية: Guillain-Barré Syndrome and Related Neuropathies, Neurology, Medicine, Health Sciences, Diagnosis and Management of Carpal Tunnel Syndrome, Radiology, Nuclear Medicine and Imaging, Genetic Basis of Neuropathies and Related Disorders, Cellular and Molecular Neuroscience, Neuroscience, Life Sciences, Electrodiagnostic Studies, Interquartile range, Guillain-Barre syndrome, Multinational corporation, Acute flaccid paralysis, Reference values, Internal medicine, Pediatrics, Political science, FOS Political science, Immunology, FOS Clinical medicine, Virus, Law, FOS Law, Poliovirus

الوصف: To describe the heterogeneity of electrodiagnostic (EDx) studies in Guillain-Barré syndrome (GBS) patients collected as part of the International GBS Outcome Study (IGOS).Prospectively collected clinical and EDx data were available in 957 IGOS patients from 115 centers. Only the first EDx study was included in the current analysis.Median timing of the EDx study was 7 days (interquartile range 4-11) from symptom onset. Methodology varied between centers, countries and regions. Reference values from the responding 103 centers were derived locally in 49%, from publications in 37% and from a combination of these in the remaining 15%. Amplitude measurement in the EDx studies (baseline-to-peak or peak-to-peak) differed from the way this was done in the reference values, in 22% of motor and 39% of sensory conduction. There was marked variability in both motor and sensory reference values, although only a few outliers accounted for this.Our study showed extensive variation in the clinical practice of EDx in GBS ... : لوصف عدم تجانس الدراسات التشخيصية الكهربائية (EDx) في مرضى متلازمة غيلان باريه (GBS) التي تم جمعها كجزء من الدراسة الدولية لنتائج متلازمة غيلان باريه (IGOS). كانت البيانات السريرية و EDx التي تم جمعها بشكل استباقي متاحة في 957 مريضًا بمتلازمة غيلان باريه من 115 مركزًا. تم تضمين دراسة EDx الأولى فقط في التحليل الحالي. كان التوقيت الوسيط لدراسة EDx هو 7 أيام (النطاق الربيعي 4-11) من ظهور الأعراض. اختلفت المنهجية بين المراكز والبلدان والمناطق. تم اشتقاق القيم المرجعية من 103 مراكز مجيبة محليًا في 49 ٪، ومن المنشورات في 37 ٪ ومن مزيج من هذه المراكز في 15 ٪ المتبقية. اختلف قياس السعة في دراسات EDx (من خط الأساس إلى الذروة أو من الذروة إلى الذروة) عن الطريقة التي تم بها ذلك في القيم المرجعية، في 22 ٪ من الحركة و 39 ٪ من التوصيل الحسي. كان هناك تباين ملحوظ في كل من القيم المرجعية الحركية والحسية، على الرغم من أن عددًا قليلاً فقط من القيم المتطرفة يمثل هذا. أظهرت دراستنا تباينًا واسعًا في الممارسة السريرية لـ EDx في مرضى GBS بين مراكز IGOS في جميع أنحاء المناطق. إلى جانب تباين EDx في مرضى GBS المشاركين في IGOS، من ...

العلاقة: https://dx.doi.org/10.60692/rs7e3-q4w90Test

الإتاحة: https://doi.org/10.60692/tgd0q-nff7310.60692/rs7e3-q4w90Test