HAL-ENS-LYON
Not a member yet
104280 research outputs found
Sort by
Col6 deficiency in a zebrafish model of Bethlem myopathy leads to dysfunction of the muscle dihydropyridine receptor
No full textBethlem myopathy (BM) is an incurable muscle disease characterized by joint contractures and muscle weakness worsening with age. BM results from mutations in genes encoding one of the three α chains of collagen VI (ColVI), a component of the skeletal muscle extracellular matrix produced by interstitial fibroblasts. A still unresolved issue in BM is how alteration in ColVI present outside muscle fibers induces dysfunction within muscle fibers. In the present study, we explored properties of excitationcontraction coupling on isolated fast skeletal muscle fibers from one-year old zebrafish col6a1 Δex14 harboring an exon-skipping mutation (col6a1 Δex14 ) that is the most frequently found in BM patients. Col6a1 Δex14 fish muscle exhibited age-dependent progressive loss of ColVI deposition, accompanied with defects in basement membrane organization and ColVI intracellular accumulation. Muscle action potentials were found to be unchanged in col6a1 Δex14 fish as compared to wild-type. The density of charge movements produced by depolarization-induced activation of dihydropyridine receptors (DHPRs), that control sarcoplasmic reticulum (SR) Ca 2+ release, was found to be reduced and their voltage-dependence shifted toward negative potentials in col6a1 Δex14 fish. Concomitantly, the voltage dependence of depolarization-evoked intracellular Ca 2+ transients was also shifted toward negative voltages, promoting in this way an elevated pathogenic SR Ca 2+ leak at resting membrane potentials, as evidenced by higher density of Ca 2+ sparks at rest, larger SR Ca 2+ release in response to long-duration depolarizations between -70 and -40 mV and reduced twitch muscle force and swimming performance. Finally, clusters of α1S subunits of DHPR were found to be mis-localized in mutant fibers t-tubules. These data suggest that Col6 deficiency in BM leads to an alteration of the DHPR function that contributes to promote a pathogenic SR Ca 2+ leak. DHPR could represent the still elusive link that allows altered myomatrix to transduce pathogenic signals within muscle.</div
Single-cell transcriptomic profiling of zebrafish primary motor neurons reveals subtype-specific gene expression signatures
No full textInternational audienceMotor neurons (MNs) connect the central nervous system to skeletal muscles, enabling movement. In zebrafish, the three MN subtypes, RoP, MiP, and CaP, are defined anatomically, but their molecular identities remain underexplored. Using single-cell transcriptomics of developing Tg(mnx1:gfp) zebrafish embryos, where MNs are specifically labeled, we identified 14 clusters, including differentiating primary MNs.Subclustering and pseudotime analysis resolved seven primary MN subtypes, that were assigned to early, intermediate, and terminal differentiation states, each with distinct gene expression profiles, involving transcription factors and membrane receptors associated with axon pathfinding and cell fate. Spatial validation using smiFISH confirmed subtype-specific marker expression within the spinal cord. Proteinprotein interaction analysis revealed potential interactions between subtype-specific receptors and extracellular signaling molecules present in the motor axon environment.These findings define molecular signatures of primary MN subtypes, providing new insights into their identity and roles in motor axon decision-making during zebrafish development.</div
Evaluation of ZT Scan DIA for the diagnosis of bloodstream infections
No full textInternational audienc
Real life study of ivosidenib in either monotherapy or combined with azacytidine for first line mutant IDH1 AML: A study from the french AML intergroup ALFA/filo
No full textInternational audienceBackground: IDH1 mutations are found in 6-10% of acute myeloid leukemia (AML) cases. Ivosidenib (IVO), an oral mIDH1 inhibitor, is approved for newly diagnosed mIDH1 AML in patients (pts) aged ≥75 years or unfit for intensive chemotherapy as monotherapy (US), based on the results of the AG120-C-001 study (Roboz, Blood, 2020, median overall survival (mOS) 12.6 months) or with azacitidine (AZA) (US and Europe) based on the results of the AGILE study (Montesinos, NEJM, 2022, mOS 29.3 months). However, data available on IVO+/-AZA in real-life are limited. Method: This retrospective study (IVOOBS, NCT06377579)included pts treated in France between 01/2017 and 02/2024 through a compassionate use program with IVO+/-AZA for mIDH1 AML, front-line or at time of relapse or for a refractory disease. Here we focused only on newly diagnosed pts. The primary objective was OS and secondary objectives included response rate (ELN-2022 criteria) and toxicity. Results: 49 pts from 17 centers were included; 16 (33%) received IVO alone (IVO-mono cohort) and 33 (67%) the combination (IVO+AZA cohort). IVO-mono cohort (n=16) : The median age was 72 yo (IQR: 60 - 83.25), 62.5% were male. Most of the pts were unfit (PS > 2 in 92%) with high-risk disease (secondary AML n=14, including 8 pts who have already received AZA for prior hematologic disease; adverse (adv)-risk according to ELN-2022 classification n=7, 43%, intermediate (int)-risk n= 9, 57%). The median white blood count (WBC) was 2.67 Giga/L. The majority of pts started IVO at the recommended dose of 500 mg/day (d) (n=13, 81%), while 3 started at 250 mg/d (concomitant prescription of azole). Median duration of IVO treatment was short (3.25 months, IQR: 1.6-7.07) as 77% % (n=10) of IVO discontinuations occurred within 4 months (3 allo-HCT, 3 progressions, 2 differentiation syndrome (DS), 1 QT prolongation (QTp), 1 death). Any grades of DS and QTp were reported in 25% (n=4) and 7% (n=1) of pts, respectively, while grade 3-4 hepatic, infection and hematologic adverse events (AE) occurred in 0, 4 and 3 pts, respectively. Two deaths were linked to IVO (DS). Mortality at D30 and D60 was 6% and 25%, respectively. Composite complete remission (CCR) (CR/CRh/CRi) rate was 37% (31%/6%/0%), with no MLFS and 44% of non-responders (19% of pts not assessed (NA)). For pts receiving IVO at 500mg/d, CCR was 46% (38%/8%/0%). At 250mg/d, 2 pts did not respond and 1 was NA. Four pts (3 in CR, 1 in no response) received an allo-HCT after IVO. Among responders (n=6), 1 pt relapsed at 10.8 months. With a median follow-up (mFU) of 4.5 months, mOS was 4.5 months (95% CI: 2.07-not reached (NR)) and 2y OS 31.25% (95% CI: 15.11-64.64). IVO+AZA cohort (n=33): The median age was 78 yo (IQR: 75 – 80), 60% were male. The majority of pts were unfit (PS > 2 in 93%) and classified as int-risk (83%) according to ELN-2022 classification (adv-risk 17%). However, according to ELN-2024 classification, most pts had favourable-risk (n=22, 67%) (adv-risk n=2, NA n=9). The median WBC was 2.15 Giga/L. Nine pts (27%) had a secondary AML. The majority of pts started IVO at the dose of 500 mg/d (n=27, 82%), while 6 pts started at 250 mg/d (concomitant prescription of azole (n=5), previous cardiac history (n=1)). Median number of AZA cycles was 6 (range: 1; 28). Median duration of IVO treatment was 13.1 months (IQR: 8.4-18.4) and 26% (n=5) of IVO discontinuations occurred within 4 months (3 progressions, 2 deaths). Mortality at D30 and D60 was 3% and 9%, respectively. DS was reported in 3 pts (9%) and QTp in 2 (7%), any grades, while grade 3-4 hepatic, infection and hematologic AE occurred in 0, 5 and 8 pts, respectively. No death was linked to IVO. CCR was 73% (55%/12%/6%), 3% showed MLFS, 21% were non-responders and 3% NA. CCR was 78% (56%/15%/7%) and 50% (50%/0%/0%) for those receiving IVO at 500 mg/d and 250mg/d, respectively. Among responders (n=24), only 1 pt was consolidated with an allo-HCT and 8 (33%) relapsed at a median of 11.4 months. At relapse, 4 were treated with AZA+BCL2 inhibitor and 1 obtained CR. With a mFU of 16.6 months, mOS was NR (95% CI: 16.62-NR) and 2y OS 52% (95% CI: 35.55-76.56). Conclusion: This retrospective real-life study shows the reproducibility of the results of the AGILE study (IVO+AZA). Pts receiving IVO mono had poorer outcome compared to those of the AG120-C-001 study, likely because pts were at higher risk. The dose of 500 mg/d should also be preferred questioning the role of azole prophylaxis
Mettre le genre à distance, Tenir les victimes à l’écart, Occulter la violence masculine : Ethnographie de la mise en place des Centres de Prise en Charge des Auteurs de violences conjugales
No full textThis doctoral research focuses on the implementation of the Centres de Prise en Charge des Auteurs de Violences Conjugales (CPCA), introduced in France in 2020. These programmes aim to hold perpetrators of domestic violence accountable for their behaviour and to prevent recidivism. They bring together professional groups from various sectors — justice, probation administration, healthcare and social work—who are expected to collaboratively shape this public policy. Using an ethnographic approach, the research reconstructs these professional networks through 80 interviews with a wide range of stakeholders: public prosecutors, sentence enforcement judges, probation officers, psychologists, social workers, and directors of specialized facilities. These interviews are completed by 120 hours of field observations across varied settings, including perpetrator accountability sessions, professional training courses, interprofessional and partner meetings, criminal court hearings, and one-on-one probation monitoring.Using a network-based approach, an interactionist sociology of professions, and a feminist epistemology, this thesis examines how the interplay between criminal justice, public policy, and gender regimes serves to obscure gender as a system of power and domination. It highlights how victims are sidelined in the process of offender treatment and how masculine violence, which underpins broader social structures, is rendered invisible.The thesis is structured in three parts. The first part offers a socio-historical account of domestic violence perpetrator programs in France, tracing how feminist theories have been progressively diluted through institutional norms and logics. This shift has led to a framing of domestic violence primarily as deviance, interpreted through disciplinary knowledges that tend to conceal malsculine violence. This first section emphasises the importance of analysing such public policies through a feminist lens.The second part investigates how professionals organise their work within these networks and how they contribute to co-construct public policy. Support workers face constraints in terms of financial, material, and temporal resources, yet are expected to demonstrate the programs’ effectiveness. They are thus compelled to adopt an “entrepreneurial ethos,” assuming roles that extend well beyond their original mandates in mental health and social work. In an overburdened public service landscape—and under growing scrutiny of public responses to domestic violence—the network operates as a form of collective protection. It diffuses individual accountability in cases of reoffending—what might be called “opening the umbrellas”—and ultimately fosters a system of distributed irresponsibility.The final part analyses how professionals perceive gender, relationships, and family norms, and how these perceptions shape their understanding of domestic violence. Lacking specific training on gender-based violence, professionals rely on personal interpretations and dominant social norms. These norms often reinforce perpetrators’ own narratives, making it difficult to recognize coercive control or to challenge the “feeling rules” that legitimise such behaviours. As a result, violence is viewed and addressed primarily from the perpetrator’s perspective.The research also finds that the judiciary disproportionately targets men from specific socio-demographic backgrounds—particularly working-class men, those with low levels of education, and racialized individuals. These men are portrayed as “cultural others” and perceived as lacking civic competence. This leads to a reconfiguration of subordinated or marginalized masculinities in line with a republican ideal of the family, ultimately leaving hegemonic masculinity intact — or even reinforced.Cette recherche doctorale s’intéresse à la création et la mise en place des Centres de Prise en Charge des auteurs de violences conjugales (CPCA), lancés en 2020 afin de responsabiliser les auteurs pour lutter contre la récidive. Ces dispositifs mettent en réseau des catégories professionnelles plurielles — celles de la justice, de l’administration pénitentiaire, du soin (psychologues principalement) et du travail social — qui doivent coconstruire cette action publique. L’enquête ethnographique a reconstitué ces réseaux de « prise en charge » et s’appuie sur 80 entretiens menés avec une diversité d’acteur·ices : procureur·es et substitut·es ; juges de l’application des peines ; conseiller·ères pénitentiaires d’insertion et de probation ; psychologues ; travailleur·ses sociaux·ales ; directeur·ices de structures spécialisées. Ces entretiens s’articulent à 120 heures d’observations réalisées dans différents contextes : stages de responsabilisation ; formations de professionnel·les ; réunions entre professionnel·les et/ou partenaires ; comités de pilotage ; audiences correctionnelles ; suivis individuels SPIP. Sur la base d’une sociologie interactionniste des professions et de l’action publique et d’une épistémologie féministe, cette thèse montre en quoi l’articulation des régimes pénaux, de l’action publique et du genre concourent à mettre à distance le genre en tant que système de pouvoir et de domination ; à tenir les victimes à l’écart du traitement des auteurs ; à occulter la violence masculine structurelle.La thèse s’articule en trois parties. Une première partie reconstruit une socio-histoire des dispositifs pour les auteurs de violence conjugale en France en retraçant la manière dont les théories et savoirs féministes ont été progressivement dilués dans des logiques institutionnelles normatives où la violence conjugale est perçue au prisme de la déviance par des catégories de savoirs disciplinaires qui tendent à occulter la violence masculine.Une deuxième partie se concentre sur la co-construction de l’action publique en réseau. Les professionnel·les de l’accompagnement se retrouvent dans une situation où les ressources (économiques, matérielles, temporelles) sont insuffisantes pour répondre à l’injonction de prouver la « plus-value » et l’efficacité du dispositif. Elles/ils doivent développer un « ethos d’entrepreneur·es » et endosser des missions qui débordent largement celles de leurs missions premières. Par ailleurs, dans un contexte à la fois de saturation des services publics et, dans le même temps, de vigilance sociale accrue sur les pratiques professionnelles eu égard au traitement de la violence conjugale, le réseau apparait comme un moyen de se prémunir d’une responsabilité individuelle du/de la professionnel·le en cas de récidive ; d’ouvrir les parapluies et, in fine, de former une chaîne de déresponsabilisation.Une dernière partie propose l’analyse des normes de genre, de couple, de famille et des représentations de la violence conjugale véhiculées par les professionnel·les. Sans formation à l’approche sur le genre en tant que système de domination, elles/ils s’appuient largement sur leurs propres représentations de la violence et sur des normes de genre dominantes. Ces normes et représentations rendent difficiles la reconnaissance du contrôle coercitif ainsi que la remise en question des règles de sentiment qui légitiment la violence : c’est par le prisme de l’agresseur qu’est perçue et traitée la violence. Par ailleurs, l’enquête relève l’interception d’hommes aux profils socio-démographiques spécifiques, avec une sur-représentation d’hommes provenant des classes populaires et/ou peu diplômés et/ou racisés. Les auteurs de violence, altérisés, sont perçus comme des citoyens déficitaires et c’est vers un ethos républicain du couple et de la famille que s’opère un recadrage des masculinités subordonnées ou marginalisées, laissant intacte, voire renforçant la masculinité hégémonique
Avec quelles représentations lit-on (ou non) des violences sexuelles dans un récit de fiction ? À propos d’une lecture de Disgrâce de J. M. Coetzee sur France Culture
No full textDate de mise en ligne réelle : Décembre 2025International audienceThe article investigates the idea that we should transform the way cultural productions represent sexual violence, by shifting the emphasis toward the representations we use to make sense of these productions. A case study of how Coetzee’s novel Disgrace was read on an hour-long programme on the radio channel France Culture provides a way to explore differences in the novel’s reception regarding the interpretation of rape: according to the critics on the radio programme, there is only one "real rape" in the novel, as opposed to a teacher-student relationship unfairly "re-characterized" as rape. Through this case study, the article raises two questions: first, does the problem come from the fact that the victim’s perspective is missing from Disgrace and should we include it to achieve better literary depictions of sexual violence? Secondly, should we transform literary representations or should we focus on how we interpret them?L’article questionne l’idée d’une nécessaire transformation de la façon dont les œuvres représentent la violence sexuelle en décalant le regard vers les représentations avec lesquelles les interprètes donnent sens à ces œuvres. L’exemple de la réception du roman Disgrâce du romancier sud-africain J. M. Coetzee dans l’émission Répliques en France permet d’explorer un cas de divergence dans la réception critique sur la façon dont le roman représente le viol : selon les interprètes de l’émission, il n’y a qu’un « vrai viol » dans le roman, opposé à une relation injustement « requalifiée » comme viol. L’article soulève à partir de cette analyse deux questions : premièrement, l’absence du point de vue des victimes dans une représentation littéraire, comme c’est le cas dans Disgrâce, est-elle un problème ? Deuxièmement, faut-il changer ces représentations littéraires, ou bien changer la façon dont nous les comprenons
Structural mechanisms of cellulose-based nanocomposites mimicking the structure of articular cartilage under uniaxial compression probed by in situ SAXS
No full textInternational audienceA new method combining frontal ultrafiltration and ultrasound, followed by UV photocrosslinking enabled the fabrication of orthotropic CNC/PEGDA (poly(ethylene glycol) diacrylate) nanocomposites with the structure of articular cartilage. In situ SAXS compression/relaxation mechanical tests demonstrated this orthotropic organization as well as elastic behavior with a Young's modulus of 0.76 MPa, similar to articular cartilage
Alerter sur les manquements à l’intégrité scientifique ?
No full textL’article pose la question de savoir si les scientifiques qui signalent des manquements à l’IS peuvent être qualifiés de “lanceurs d’alerte” au sens de la législation française relative à l’alerte. L’article part du constat que les dispositifs de signalement de manquements n’ont pas été construits en considération du droit applicable aux lanceurs d’alerte. Ces deux corpus normatifs peuvent pourtant s’éclairer l’un l’autre
Irreversible Transitions of the Ocean Circulation in Antarctic Ice-Shelf Cavities
No full textIce shelves fringing the Antarctic continent experience low or high basal melt rates depending on local shelf conditions, ocean circulation and intensity of ice-sea-air exchanges. Recent studies have uncovered potential cold-to-warm transitions in specific ice-shelf cavities, which could lead to a dramatic increase in sea-level rise. Here we demonstrate that brine rejection in coastal polynyas promotes bistable dynamics in ice-shelf cavities, which would be otherwise monostable, for a broad diversity of Circumpolar Deep Water temperatures. We develop a generic low-dimensional box model featuring warm and cold circulation modes and apply it to nine ice-shelf cavities. We find that most ice-shelf cavities are in a bistable regime and are therefore susceptible to irreversible abrupt transitions for a realistic range of sea-ice formation rates. Bistability is robust to changes in cavity parameterization. However, the vertical mixing scheme at the ice-shelf front can be tuned to make the transitions reversible
Pushing the Frontiers of Subexponential FPT Time for Feedback Vertex Set
No full textInternational audienceThe paper deals with the Feedback Vertex Set problem parameterized by the solution size. Given a graph G and a parameter k, one has to decide if there is a set S of at most k vertices such that G-S is acyclic. Assuming the Exponential Time Hypothesis, it is known that FVS cannot be solved in time in general graphs. To overcome this, many recent results considered FVS restricted to particular intersection graph classes and provided such algorithms.In this paper we provide generic conditions on a graph class for the existence of an algorithm solving FVS in subexponential FPT time, i.e. time poly, for some {\varepsilon}<1, where n denotes the number of vertices of the instance and k the parameter. On the one hand this result unifies algorithms that have been proposed over the years for several graph classes such as planar graphs, map graphs, unit-disk graphs, pseudo-disk graphs, and string graphs of bounded edge-degree. On the other hand it extends the tractability horizon of FVS to new classes that are not amenable to previously used techniques, in particular intersection graphs of "thin" objects like segment graphs or more generally s-string graphs