RIPK3-mediated cell death is involved in DUX4-mediated toxicity in facioscapulohumeral dystrophy

BACKGROUND: Facioscapulohumeral dystrophy (FSHD) is caused by mutations leading to the aberrant expression of the DUX4 transcription factor in muscles. DUX4 was proposed to induce cell death, but the involvement of different death pathways is still discussed. A possible pro‐apoptotic role of DUX4 was proposed, but as FSHD muscles are characterized by necrosis and inflammatory infiltrates, non‐apoptotic pathways may be also involved. METHODS: We explored DUX4‐mediated cell death by focusing on the role of one regulated necrosis pathway called necroptosis, which is regulated by RIPK3. We investigated the effect of necroptosis on cell death in vitro and in vivo experiments using RIPK3 inhibitors and a RIPK3‐deficient transgenic mouse model. RESULTS: We showed in vitro that DUX4 expression causes a caspase‐independent and RIPK3‐mediated cell death in both myoblasts and myotubes. In vivo, RIPK3‐deficient animals present improved body and muscle weights, a reduction of the aberrant activation of the DUX4 network genes, and an improvement of muscle histology. CONCLUSIONS: These results provide evidence for a role of RIPK3 in DUX4‐mediated cell death and open new avenues of research

Modélisation d’appui au contrôle des invasions biologiques Une application à la gestion de la Jussie en Pays de Loire: rapport final

Afin de répondre a l’objectif des gestionnaires de milieux d’assurer un contrôle efficace et financièrement soutenable des invasions biologiques, une intégration des connaissances et des outils d’évaluation des politiques de mesures est nécessaire afin de rationaliser les décisions de gestion dans un contexte budgétaire tendu. Les gestionnaires de milieux concernés par des invasions biologiques ont exprimé régulièrement une demande d’outils d’aide a la décision ainsi que de référentiels en termes de coûts et bénéfices leur permettant de guider leurs décisions. Cette action fait suite a une analyse économique des invasions biologiques en milieux aquatiques, et plus particulièrement la Jussie (L. Peploides, L. Grandiflora), de 2012 a 2015, qui avait déjà mis en évidence la nécessite de préciser les éléments constitutifs d’une analyse coût-bénéfice (Issanchou et Thomas, 2012). . L’action proposée vise a définir la structure théorique et l’application empirique d’un outil de gestion d’une invasion biologique, outil destine aux gestionnaires de milieux, que nous appliquons aux stratégies de gestion de la Jussie dans le marais Briérons (Pays de la Loire). En matière de contrôle des invasions biologiques, quatre questions centrales se posent lorsqu’on s’engage dans la mise en œuvre d’une politique de contrôle : quelles espèces invasives contrôler en priorité, ou les contrôler, comment le faire et selon quel agenda ? Afin d’y répondre, l’optimisation sous contrainte permet de définir formellement le problème et d’évaluer des priorités en matière de gestion, qu’il s’agisse de savoir quelles espèces contrôler ou bien ou les contrôler. Pour répondre a ces questions, l’enjeu en matière de recherche est de coupler des analyses sur les bénéfices du contrôle, les coûts de ce contrôle et les dynamiques écologiques, que ce soit les dynamiques de reproduction et de dispersion spatiale des espèces ou les interrelations entre espèces. Bien que théoriquement, les approches que nous développons dans ce projet admettent des applications possibles en matière de priorisation entre espèces, le focus du projet porte sur le problème de priorisation entre sites. En d’autres termes, l’objet de l’outil que nous développons vise a choisir ou contrôler en priorité une espèce envahissante installée, étant donne un budget limite. Nous nous plaçons dans la perspective d’un gestionnaire ayant une enveloppe budgétaire limitée et choisissant comment l’allouer afin de maximiser le ratio bénéfice-coût de son action. Bien que simple en apparence, ce problème de choix se révèle conceptuellement complexe dans la mesure ou les coûts et les bénéfices du contrôle de l’espèce sont susceptibles de varier dans l’espace. De plus, par définition, l’espèce envahissante se reproduit dans le temps et se disperse dans l’espace. Il est donc nécessaire de tenir compte de la dynamique spatiale de l’invasion dans la mesure ou cette dynamique impacte indirectement les bénéfices associes au contrôle

Loss of a single allele for Ku80 leads to progenitor dysfunction and accelerated aging in skeletal muscle

In this note we classify the simple modules of the Ariki--Koike algebras when q = 1 and also describe the classification for those algebras considered in [3, 14], together with the underlying computation of the computing canonical bases of an affine quantum group. In particular, this gives a classification of the simple modules of the Iwahori--Hecke algebras of type B

Moderate and intense muscular exercises induce marked intramyocellular metabolic acidosis in sickle cell disease mice

International audienceSickle cell disease (SCD) is associated with an impaired oxygen delivery to skeletal muscle that could alter ATP production processes. The present study aimed to determine the effects of sickle hemoglobin (HbS) on muscle pH homeostasis in response to exercise in homozygous (HbSS, n = 9) and heterozygous (HbAS, n = 10) SCD (Townes) mice in comparison to control (HbAA, n = 10) littermates. Magnetic resonance spectroscopy of phosphorus 31 enabled to measure intramuscular pH and phosphocreatine (PCr) concentration during rest-stimulation-recovery protocols at two different intensities. Maximal activity of some enzymes involved in muscle energetics and content of proteins involved in pH regulation were also investigated. HbSS mice presented a more pronounced exercise-induced intramuscular acidosis, whatever the intensity of exercise. Moreover, the depletion of PCr was also exacerbated in HbSS mice in response to intense exercise as compared with both HbAA and HbAS mice ( P < 0.01). While no difference was observed concerning proteins involved in muscle pH regulation, the activity of enolase (a glycolytic enzyme) was higher in both HbSS and HbAS mice as compared with controls ( P < 0.05). Interestingly, HbAS mice presented also metabolic impairments as compared with their control counterparts. This study has identified for the first time an exacerbated exercise-induced intramuscular acidosis in SCD mice. NEW & NOTEWORTHY The main finding of the present study was that the exercise-induced intramuscular acidosis was systematically more pronounced in sickle cell disease (SCD) mice as compared with their control counterparts. This result is important since it has been demonstrated in vitro that acidosis can trigger hemoglobin polymerization. From that point of view, our results tend to support the idea that high-intensity exercise may increase the risk of hemoglobin polymerization in SCD

Force-Velocity-Endurance (FoVE) Model: a new in situ method for functional muscle evaluation in murine models.

International audienc

Corrigendum to “Single Bout Exercise in Children with Juvenile Idiopathic Arthritis: Impact on Inflammatory Markers”

Corrigendum to "Single Bout Exercise in Children with Juvenile Idiopathic Arthritis: Impact on Inflammatory Markers" DOI: 10.1155/2018/9365745; PubMed ID: 30008613; WOS:000436285900001 In the article titled “Single Bout Exercise in Children with Juvenile Idiopathic Arthritis: Impact on Inflammatory Markers” [1], the first and last names of all the authors were reversed. The revised authors’ list is shown above.Objective. In a context of inflammatory disease such as juvenile idiopathic arthritis (JIA), we do not know what impact physical activity may have on a deregulated immune system. The objective is to measure the impact of a single bout of exercise on plasma inflammatory markers such as calprotectin, IL-6, sIL-6R, sgp130, and the hypothalamic-pituitary-adrenal axis in children with juvenile idiopathic arthritis. Methods. Twelve children with JIA performed a nonexercise control day and a consecutive day that included a 20 min exercise bout at 70% of max-HR at 08:30 am. Venous blood samples were taken at 08:30, 08:50, 09:30, 10:30 am, and 12:00 pm to measure plasma concentrations of calprotectin, IL-6, sIL-6R, sgp130, cortisol, and ACTH. Pain was evaluated at 08:30, 08:50 am, and 06:00 pm. Results. There was a transient twofold increase in postexercise self-evaluated pain () that disappeared in the evening. A single bout of exercise resulted in a 1.7-fold increase in plasma calprotectin () but not IL-6 and its soluble receptors. Calprotectin levels returned to baseline within 3 hours after cessation of exercise. Conclusion. Acute exercise in children with JIA induced slightly musculoskeletal leg pain and transient increased plasma calprotectin levels but not IL-6 levels

Single Bout Exercise in Children with Juvenile Idiopathic Arthritis: Impact on Inflammatory Markers"

Objective. In a context of inflammatory disease such as juvenile idiopathic arthritis (JIA), we do not know what impact physical activity may have on a deregulated immune system. The objective is to measure the impact of a single bout of exercise on plasma inflammatory markers such as calprotectin, IL-6, sIL-6R, sgp130, and the hypothalamic-pituitary-adrenal axis in children with juvenile idiopathic arthritis. Methods. Twelve children with JIA performed a nonexercise control day and a consecutive day that included a 20 min exercise bout at 70% of max-HR at 08:30 am. Venous blood samples were taken at 08:30, 08:50, 09:30, 10:30 am, and 12:00 pm to measure plasma concentrations of calprotectin, IL-6, sIL-6R, sgp130, cortisol, and ACTH. Pain was evaluated at 08:30, 08:50 am, and 06:00 pm. Results. There was a transient twofold increase in postexercise self-evaluated pain () that disappeared in the evening. A single bout of exercise resulted in a 1.7-fold increase in plasma calprotectin () but not IL-6 and its soluble receptors. Calprotectin levels returned to baseline within 3 hours after cessation of exercise. Conclusion. Acute exercise in children with JIA induced slightly musculoskeletal leg pain and transient increased plasma calprotectin levels but not IL-6 levels

Single Bout Exercise in Children with Juvenile Idiopathic Arthritis: Impact on Inflammatory Markers"

Objective. In a context of inflammatory disease such as juvenile idiopathic arthritis (JIA), we do not know what impact physical activity may have on a deregulated immune system. The objective is to measure the impact of a single bout of exercise on plasma inflammatory markers such as calprotectin, IL-6, sIL-6R, sgp130, and the hypothalamic-pituitary-adrenal axis in children with juvenile idiopathic arthritis. Methods. Twelve children with JIA performed a nonexercise control day and a consecutive day that included a 20 min exercise bout at 70% of max-HR at 08:30 am. Venous blood samples were taken at 08:30, 08:50, 09:30, 10:30 am, and 12:00 pm to measure plasma concentrations of calprotectin, IL-6, sIL-6R, sgp130, cortisol, and ACTH. Pain was evaluated at 08:30, 08:50 am, and 06:00 pm. Results. There was a transient twofold increase in postexercise self-evaluated pain () that disappeared in the evening. A single bout of exercise resulted in a 1.7-fold increase in plasma calprotectin () but not IL-6 and its soluble receptors. Calprotectin levels returned to baseline within 3 hours after cessation of exercise. Conclusion. Acute exercise in children with JIA induced slightly musculoskeletal leg pain and transient increased plasma calprotectin levels but not IL-6 levels

Diabetes provides an unfavorable environment for muscle mass and function after muscle injury in mice.

It is of common knowledge that diabetes decreases skeletal muscle contractility and induces atrophy. However, how hyperglycemia and insulin deficiency modify muscle mass and neuromuscular recovery after muscle injury is not well known. We have analyzed two models of diabetes: streptozotocin (STZ)-treated Swiss mice and Akita mice that spontaneously develop diabetes. A fast muscle, the tibialis anterior, was injured following injection of a myotoxic agent (cardiotoxin). Neuromuscular function was evaluated by examining in situ isometric contractile properties of regenerating muscles in response to nerve stimulation 14, 28 and 56 days after myotoxic injury. We found that STZ-induced diabetes reduces muscle weight and absolute maximal tetanic force in both regenerating and uninjured muscles (p = 0.0001). Moreover, it increases specific maximal tetanic force and tetanic fusion in regenerating and uninjured muscles (p = 0.04). In the Akita mice, diabetes decreases muscle weight and absolute maximal tetanic force, and increases tetanic fusion in both regenerating and uninjured muscles (p < or = 0.003). Interestingly, STZ-induced diabetes exerts more marked effects than diabetes of genetic origin, in particular on muscle weight. This reduction in muscle mass was not due to an increased expression of the atrogenes MuRF1 and atrogin-1 during STZ-induced diabetes. The present study in mice demonstrates that both models of diabetes impair regenerating muscles as well as uninjured muscles. Regenerating fast muscles are weaker, lighter and slower in diabetic compared with nondiabetic mice

Force-Velocity-Endurance (FoVE) Model: a new in situ method for functional muscle evaluation in murine models.

International audienc