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Étude de la compartimentalisation de la dystrophine dans le muscle squelettique et ses cellules souches résidentes
No full textDuchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by the loss of full-length dystrophin at the sarcolemma, resulting in myofiber fragility, degeneration, and impaired regeneration. Beyond this classical view, dysfunction of muscle stem cells (mSCs) has been proposed to contribute to disease progression, with studies suggesting that polarized dystrophin within mSCs regulates asymmetric division and self-renewal. My study aimed to elucidate the dynamic processes governing the establishment of dystrophin compartmentalization within muscle satellite cells. In this study, we reassessed the presence and distribution of dystrophin in mSCs using a mouse model expressing a dystrophin-EGFP fusion and tdTomato protein specifically in mSCs. Despite high Dmd transcription, no dystrophin protein was detected in mSCs at any activation state, as confirmed by in vivo imaging, histology, FACS, and capillary electrophoresis.Dystrophin accumulation observed near mSCs originated from the sarcolemma, rather than from the mSCs themselves, and showed no consistent polarity. These findings challenge the prevailing hypothesis that dystrophin plays a direct role in establishing muscle stem cell polarity, and question the requirement for mSC-intrinsic dystrophin expression as a prerequisite for effective muscle regeneration. While our results do not question the importance of polarized division in mSC biology or the existence of stem cell dysfunction in DMD, they argue against dystrophin as a regulator of these processes. Alternative mechanisms may underlie mSC impairment. This work refines our understanding of DMD pathophysiology and suggests that therapeutic restoration of dystrophin in mSCs may not be necessary for effective muscle regeneration.La dystrophie musculaire de Duchenne (DMD) est une pathologie récessive liée à l'X, causée par l'absence de dystrophine à la membrane des myofibres, entraînant leur fragilité, leur dégénérescence et une régénération musculaire altérée. Au-delà de cette vision classique, le dysfonctionnement des cellules souches musculaires (mSCs) a été suggéré comme un facteur contribuant à la progression de la maladie, certaines études proposant que la polarisation de la dystrophine au sein des mSCs régule leur division asymétrique et leur auto-renouvellement. Mon étude visait à élucider les processus dynamiques régissant l'établissement de la compartimentalisation de la dystrophine au sein des cellules satellites musculaires. Dans ce but, nous avons utilisé un modèle murin exprimant une protéine de fusion dystrophine-EGFP et le tdTomato spécifiquement dans les mSCs. Malgré une transcription élevée du gène Dmd, aucune protéine dystrophine n'a été détectée dans les mSCs, quel que soit leur état d'activation, comme l'ont confirmé l'imagerie in vivo, l'histologie, le FACS et l'électrophorèse capillaire. L'accumulation de dystrophine observée à proximité des mSCs provenait du sarcolemme, et non des mSCs elles-mêmes, sans présenter de polarité cohérente. Ces résultats remettent en question l'hypothèse selon laquelle la dystrophine jouerait un rôle direct dans l'établissement de la polarité des cellules souches musculaires, ainsi que la nécessité d'une expression intrinsèque de la dystrophine par ces cellules pour assurer une régénération musculaire efficace. Bien que nos résultats ne remettent pas en cause l'importance des divisions polarisées dans la biologie des mSCs ni l'existence d'un dysfonctionnement des cellules souches dans la DMD, ils réfutent l'idée selon laquelle la dystrophine jouerait un rôle dans ces processus. D'autres mécanismes pourraient sous-tendre le dysfonctionnement des mSCs. Cette étude affine notre compréhension de la physiopathologie de la DMD et suggère que la restauration thérapeutique de la dystrophine dans les mSCs n'est pas nécessaire pour une régénération musculaire efficace
Proposition de règlement European Space Act : les premiers pas de l'Union dans l'arène du NewSpace
No full textInternational audienc
Entre réputation et liberté d'expression : l'application du DSA par le Tribunal judiciaire de Paris
No full textInternational audienceIn two rulings handed down on September 3 and 5, 2025, the Paris Court of Justice ruled on the conditions under which a judge may order the removal of online content or its delisting. In the first case, a former journalist asked Google to de-index an article in Le Parisien implicating him in sexual violence, invoking his right to be forgotten (Art. 17 GDPR). In the second case, a tanning company requested the removal of a TikTok video in which a user claimed to have suffered burns, as well as the disclosure of her identification data (Art. 6-3 LCEN, DSA). In both cases, the court rejected the requests, due to a lack of conclusive evidence of the unlawful nature of the content, and in the name of protecting freedom of expression and the right to information. These decisions, in light of the DSA, confirm the rigorous approach of the judicial judge: only clearly unlawful infringements, established by solid evidence, can justify a restriction of digital content.À travers deux décisions rendues les 3 et 5 septembre 2025, le Tribunal judiciaire de Paris s’est prononcé sur les conditions dans lesquelles un juge peut ordonner le retrait d’un contenu en ligne ou son déréférencement. Dans la première affaire, un ancien journaliste demandait à Google le déréférencement d’un article du Parisien le mettant en cause pour des violences sexuelles, en invoquant son droit à l’oubli (art. 17 RGPD). Dans la seconde, une société de bronzage sollicitait la suppression d’une vidéo TikTok où une utilisatrice affirmait avoir subi des brûlures, ainsi que la communication de ses données d’identification (art. 6-3 LCEN, DSA). Dans les deux cas, le tribunal rejette les demandes, faute de démonstration probante du caractère illicite des contenus, et au nom de la protection de la liberté d’expression et du droit à l’information. Ces décisions, à la lumière de DSA, confirment l’approche rigoureuse du juge judiciaire : seules les atteintes manifestement illicites, établies par des preuves solides, peuvent justifier une restriction des contenus numériques
Job exposure matrix on the incidence of carpal tunnel release surgery in the CONSTANCES cohort
No full textInternational audienceBackground Most studies of Carpal Tunnel Syndrome have examined only current workplace exposures as risk factors. We examined the effects of both recent and past work exposures on the incidence of surgery for carpal tunnel release (CTR). Material and Methods Participants in a large prospective study (CONSTANCES) were surveyed. The survey included self-reported history of current and past jobs, allowing estimation of past and current workplace physical exposures using an existing job exposure matrix (JEM). CTR cases were ascertained through matching the surveys to national health insurance data. Poisson regression analyses (controlling for age, Body Mass Index, and sex) computed the relative risks (RR) of future CTR associated with different work exposures. Eleven exposures including physical force, repetition, posture, and keyboard use were categorized into quartiles. Models included different time periods of exposure and/or different exposure lag times. Results 777 cases of CTR were observed among the 56,289 person cohort. RR of CTR per 5 years of exposure in the upper quartile included 1.19[1.13-1.25] for pressing with the base of the hand, 1.17[1.12-1.23] for use of vibrating tools, 1.17[1.12-1.22] for rotation of the forearm, and 0.88[0.84-0.91] for keyboard use. Higher effect sizes were seen among current workers than among those who had not worked in 5 or more years. Lagging exposures by 3 and 5 years reduced the strengths of association. Discussion Use of a JEM in a large general population cohort allowed us to study the effects of both recent and past work exposures on the incidence of carpal tunnel syndrome. While more recent exposures had stronger associations with CTR, some past exposures were also associated with future risk of CTR
Monitoring reef metabolism for a better management – case study of Reunion Island
No full textInternational audienceMonitoring carbon budget is a major challenge to improve coral reefs management (protection, conservation or restoration), including predictions about their fates by 2100. It requires sensors deployment, a collection of seawater samples and consideration of local factors such as tide, wind and benthic cover. This study assessed the benthic metabolic processes (organic production, respiration, calcification and calcium carbonate -CaCO3- dissolution) at three sites on the main shallow fringing reef of La Reunion Island. Autonomous sensors (current speed, temperature, salinity, PAR, dissolved oxygen -DO- and pH) were deployed during the warm and cold seasons between 2020 and 2022 and were complemented by discrete sampling of seawater for DO, pH and total alkalinity (TA) analysis. Metabolic budgets were calculated using a one-dimensional Eulerian approach of flow respirometry (study of changes in seawater chemistry along an axis, between two points, using fixed moored sensors). Due to the reef geomorphology, the variation in current orientation and its unidirectionality, spatio-temporal variability of metabolic budgets could not be related to benthic cover (Pleiades satellite images). Those factors strongly influenced variations of seawater chemistry and our ability to estimate the seawater residence time. We will show here, for instance, that reef geomorphology creates conditions for a flow re-entrainment of TA-depleted seawater (due to reef calcification activity) exiting the reef. Such TA-depleted seawater is immediately redirected towards the reef flat leading to an overestimation of daily reef net calcification rates (Gnet). At one site (33% of coral cover), Gnet was estimated at 283 mmolCaCO3.m-2.d-1. Such rate characterizes reefs with a coral cover up to 60%. Gnet accounted for 40% of reef gross primary production GPP (GPP = 726 mmolC.m-2.d-1, similar to the Indo-Pacific median) while calcification usually corresponds to 15-20% of GPP for typical coral/algal reef flats. The Eulerian method that was used in our study is a punctual approach and can be a powerful tool for monitoring coral reefs metabolism, mainly through the use of autonomous sensors. However, accurate estimations on a large spatio-temporal scale need long-term surveys and may be limited due by the difficulty of integrating the specific hydrodynamic conditions of each coral reef studied
Inflammation, childhood trauma, and symptom dimensions in schizophrenia: a path-analysis study
No full textInternational audienceIt has been postulated that immune dysregulations may establish a link between early risk factors, such as childhood trauma (CT), and the later development of schizophrenia. Schizophrenia and experience of childhood trauma (CT) have independently been associated with increased circulating levels of inflammatory biomarkers, while CT and inflammation have also been linked to particular clinical features of the disorder. We investigated whether increased levels of inflammatory biomarkers were underpinned by CT among subjects with schizophrenia, and whether this inflammation mediated the relationship between CT and symptom dimensions.Methods: 451 subjects from the FACE-SZ ("FondaMental Academic Centres of Expertise for Schizophrenia") cohort were included. Path-analysis was used to evaluate direct and indirect relationships between Childhood Trauma Questionnaire (CTQ) scores, serum concentrations of C-reactive protein (CRP), interleukin (IL)-6 and tumour necrosis factor (TNF)-α, and Positive And Negative Syndrome Scale of Schizophrenia (PANSS) scales.Results: Significant associations between CTQ and PANSS scales and between the former and inflammatory biomarkers were found. Notably, CRP was positively predicted by emotional abuse (β = 0.10) and physical neglect (β = 0.12), and negatively by emotional neglect while IL-6 (β = -0.18) was negatively predicted by sexual abuse (β = -0.05). No indirect associations between CT on PANSS through effects on the inflammatory biomarkers were found.Conclusions: Our study confirmed the association between CT and PANSS dimensions and identified novel links between CT and inflammation among patients with schizophrenia, highlighting the need for further elucidation of the complex relationships between early stress and chronic inflammation in psychiatry
Avoidant/restrictive food intake disorder-like syndrome and cerebellar tumor in an adolescent: a case report
No full textInternational audienceAvoidant/Restrictive Food Intake Disorder (ARFID) is a recently recognized eating disorder category in the DSM-5 and ICD-11classifications. Recent functional neuroimaging studies have suggested alterations in the cerebellar intrinsic connectivity networks in patients suffering from eating disorders. Associations between eating disorders and central nervous system tumors have been documented, but to date no studies have linked eating disorders to cerebellar lesions. This case report presents a 13-year-old boy with ARFID symptoms and a cerebellar tumor, exploring the potential connection between the two. A 13-year-old adolescent with a history of dental agenesis, escalating food restriction, severe abdominal pain, impaired weight gain and statural growth was initially diagnosed with ARFID. A brain magnetic resonance imaging revealed a large and threatening cerebellar tumor, leading to urgent neurosurgery. After tumor removal, the patient's eating behaviors, weight, and growth but also puberty improved dramatically. One year later, a tumor remnant was found, necessitating targeted therapy. This case underscores the possibility that cerebellar tumors can mimic ARFID-like syndrome, suggesting a neurological origin for the observed disordered eating behaviors. The marked improvement in eating patterns and growth after tumor removal strongly suggests a direct link between the cerebellar tumor and the patient's symptoms. Given the rarity and complexity of such cases, neurological evaluations, including brain magnetic resonance imaging, should be considered in any children and adolescents with eating disorder or severe disordered eating especially when growth is affected, or unusual symptoms are present
Pour une histoire de la protection sociale dans les fonctions publiques
No full textInternational audienc
First Global Spatial Analysis of Mesospheric Inversion Layers Using GOMOS Temperature Data
No full textInternational audienceThe mesosphere (45-80 km) suffers from a lack of global data. Consequently, research on extreme mesospheric phenomena was limited to single-point analysis using lidar or coarse modelling: Mesospheric Inversion Layers (MILs), which cause an inversion of the temperature gradient at around 70 km with an amplitude up to +30 K, had been a subject of studies capped by this lack of knowledge. Using a reinterpreted temperature product from the limb-sounding GOMOS instrument, we presented one of the first globally comprehensive spatial analyses of MILs