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Systematic yeast two-hybrid screening identifies novel functions for SET1C/COMPASS
No full textInternational audienceABSTRACT Set1 is the catalytic subunit of SET1C or COMPASS, which methylates histone H3K4 and serves as a scaffold for the association of seven tightly bound polypeptides. We have employed yeast two-hybrid screenings to determine the interactome of Set1 and each subunit, providing a unique resource for exploring known and novel roles of the complex. Our screenings identified a multitude of interactors involved in chromatin regulation, DNA replication, meiotic breaks, and Ty transposition, processes previously associated with SET1C. Consistent with Set1 being an RNA-binding protein, the screens link SET1C to multiple aspects of RNA biogenesis, including pre-mRNA splicing and polyadenylation. The results reveal that Set1 interacts with several importins and with RGG motif-containing proteins, providing insights into the mechanisms by which Set1 moves between cytoplasmic and nuclear compartments. We demonstrate that the transcriptional corepressor Nrm1 is methylated by SET1C in vitro suggesting that H3K4-like domains may represent a class of non-histone substrates for SET1C. We further reveal that reconstituted SET1C interacts with the AT hook domain of the chromatin remodeler Snf2 and methylates multiple arginines within this domain. In vivo , we report that the ARTSTRGR AT-hook motif is methylated in a Set1-dependent manner revealing new interplay between lysine and arginine methylation
Mas Aguilhon Saint-Marcel-d’Ardèche Retour sur la question gravettienne dans la vallée du Rhône
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Calixarenes meet (TG4T)4 G-quadruplex: Exploring reciprocal interactions to develop innovative biotechnological applications
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Two pore domain THIK2 channel is involved in acute and chronic pain signal regulation
No full textInternational audienceAbstract Two-pore domain potassium channels (K 2P ) regulate neuronal excitability by acting as hyperpolarizing leak channels. Among them, THIK2 remain poorly characterized. Although no study has yet clearly linked them to excitability or pain, their selective expression in nociceptive neurons of the Dorsal Root Ganglia (DRG) suggests a role in nociception and pain regulation. This project investigates THIK2 channels in pain pathophysiology through molecular, electrophysiological, and behavioral approaches. We mapped THIK expression patterns and in THIK2 knock-out mice, we examined DRG neuron excitability and pain sensitivity. Results reveal thermal hypersensitivity under both naive and inflammatory conditions, indicating that THIK2 normally limits neuronal hyperexcitability. These findings position THIK2 as a potential therapeutic target in chronic inflammatory pain, with peripheral inhibition potentially offering analgesia without central opioid side effects
Incorporating FATES Principles in Continuous Development of ML-Integrated Systems: Importance of Requirements
No full textInternational audienceThe MLOps movement adopts the DevOps objective of reducing the gap between development and operations teamsby integrating data scientist teams and Machine Learning (ML) models. The initial FATES-MLOps project aims to apply andadapt good software engineering practices to enhance both the quality of the ML model construction processes and the software systems produced, particularly with regard to extra-functional properties that will be critical issues: Fairness, Accountability, Transparency, Ethics, and Security (FATES). This paper focuses specifically on the formalization, measurement, and management of these properties throughout the MLOps process
The Non-covalent Stereocontrol of Disulfide bonds
No full textDisulfide bonds are pivotal in shaping the structure and function of both natural proteins and synthetic architectures, yet the stereochemical control of their axial chirality has only very recently garnered focused attention. In this perspective article, we have (re)-examined the published structures of natural and synthetic disulfide-containing com-pounds to uncover the non-covalent interactions that can bias the chirality of the S-S bond toward specific P or M con-formations. Building on these insights, we provide here a conceptual toolbox that could inspire various communities, from molecular biologists exploring the role of disulfide bridges in transmitting stereochemical information within protein structures to organic chemists designing disulfide-based architectures of increased complexity
TERT expression attenuates metabolic disorders in obese mice by promoting adipose stem and progenitor cell expansion and differentiation
No full textInternational audienceBackground and aims: Adipose tissue (AT) senescence, induced by obesity or aging, leads to a reduced capacity for tissue remodeling and a chronic pro-inflammatory state, which leads to the onset of metabolic pathologies. Cellular senescence is triggered by various stresses, in particular excessive shortening of telomeres, which activates the p21 pathway and leads to the arrest of the cell cycle. We used the mouse model p21 +/Tert expressing TERT from the Cdkn1a locus to investigate whether counteracting telomere shortening by telomerase (TERT) specifically in pre-senescent cells could improve obesity-induced metabolic disorders. Results: Our study demonstrates that conditional expression of TERT reduces insulin-resistance and glucose intolerance associated with obesity. In AT, this is accompanied by a decrease in the number of senescent p21-positive cells, very short telomeres, and oxidative DNA damage. Single nucleus RNA-seq data reveal TERT expression attenuates senescence induced by HFD in particular in adipose stem and progenitor cells (ASPC). We demonstrate that ASPC expansion and differentiation are promoted in p21 +/Tert obese mice, thereby improving AT plasticity. Furthermore, we show that TERT expression enhances mitochondrial function and alleviates oxidative stress in ASPC. This process contributes to the AT hyperplasia with increased number of adipocytes which has been shown to have a protective effect against obesityassociated metabolic disorders. Conclusions: These results underscore TERT's role in mitigating obesity-related metabolic dysfunction. Conditional TERT expression may therefore represent as a promising therapeutic strategy for obesity-associated metabolic disorders.</div
Print exposure and reading development in the French educational context: A systematic review
No full textInternational audienceThis systematic review investigates the role of print exposure in reading development within the French education system and discusses its implications for international research. Background: France’s declining performance in international reading assessments highlights the need to better understand literacy-related factors. Objectives and Methods: We synthesized findings from studies on diverse forms of print exposure—including home literacy environments and educational interventions—focusing on how these factors predict literacy outcomes. We also critically evaluated common measures of print exposure, from self-reports to print exposure checklists, and assessed their conceptual clarity and predictive validity. Results: Consistent with international evidence, print exposure and, more broadly, the home literacy environment support literacy development. However, in France, their impact appears more limited, likely due to the strong influence of socioeconomic factors and a centralized, school-driven educational system that reduces parental involvement. Conclusion/Implications: We propose an integrative framework that distinguishes direct measures of print exposure from distal indicators (e.g., number of books at home) often confounded with socioeconomic status. We also suggest incorporating additional variables, such as non-print activities that foster language and cognitive development, such as music training, play, and high-quality parent–child interactions. To strengthen future research, we recommend adopting a nested incremental approach to identify a parsimonious set of predictors that maximize both reliability and explanatory power
Interactive Audio Sculpting: Plugin Customization and UI Affordances in Immersive Environments
No full textInternational audienceWAM Jam Party is a collaborative WebXR platform for creating 3D musical installations using Web Audio Modules (WAM) plugins. Expanding on earlier work, this paper introduces major improvements focused on usability, expressiveness, and interaction design. A new 3D GUI editor allows users to attach interactive, custom graphical interfaces to existing WAM plugins without modifying their source code, enabling representations such as synths with distinctive textures, labels, 3D knobs etc. or physics-based instruments like a guitar with a body shaped like a real acoustic guitar. The design offers a "3D Plugin Shop" and floating menus with preview thumbnail images as alternative means to select and assemble audio components. The system allows dynamic code injection for advanced behaviors, including animated parameter modulators, piano roll sequencers or an animated drum kit. User studies report higher engagement, faster onboarding, and creative workflows. This study also gives some practical insights for building collaborative audio tools in immersive web-based environments.</div
Les ONG internationales en quête de performance : comment coordonner et contrôler les relations entre siège et entités subsidiaires ?
No full textNational audienceLa multiplication et l’amplification des crises rappellent le rôle crucial qui est joué par les Organisations Non Gouvernementales (ONG) internationales dans nos sociétés. Elles jouent un rôle clé dans l’atteinte des objectifs de développement durable, mais manquent de moyens pour faire face aux besoins importants qui existent dans de nombreux pays. Cette recherche s’intéresse à la quête d’efficience pour soutenir la performance opérationnelle à travers les mécanismes de coordination et de contrôle au sein des ONG internationales afin de comprendre comment ces organisations particulières gèrent leurs relations entre siège et entités subsidiaires. Nous avons adopté la perspective de la théorie de l’agence. Notre étude exploratoire menée auprès des ONG Action Contre la Faim, Première Urgence Internationale, et Solidarités International met en lumière les objectifs alignés entre siège et entités subsidiaires, en contraste avec le postulat de la théorie de l’agence. Nous constatons aussi une évolution dans l’autonomie déléguée par les sièges à leurs entités subsidiaires, avec une plus forte décentralisation qui influence les mécanismes de coordination et de contrôle. La coordination s’appuie sur une collaboration étroite dans la définition de la stratégie et le contrôle repose sur des logiques de normalisation et de socialisation. Notre travail offre des pistes de réflexion sur la définition de la performance et l’articulation des mécanismes de coordination et de contrôle dans les ONG internationales