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Chemical inhibition of SUMOylation activates the FSHD locus
No full textInternational audienceFacioscapulohumeral muscular dystrophy (FSHD) is a progressive and debilitating muscle disease for which no cure currently exists. In the majority of cases, FSHD is associated with the contraction of the D4Z4 macrosatellite repeat array at the 4q35 locus, leading to the inappropriate activation of DUX4 , normally expressed during early embryogenesis. In FSHD, the genetic contraction is accompanied by hypomethylation of the D4Z4 array. Although a connection between DNA hypomethylation and DUX4 expression has been suggested, the precise mechanisms that regulate DUX4 transcription remain incompletely defined. The post-translational modification by SUMO was shown previously to repress the expression of Dux , the DUX4 homolog, in mouse embryonic stem cells. Based on these findings, we explored here the contribution of SUMOylation in the regulation of DUX4 in human muscle cells. We demonstrate that TAK‑981 (subasumstat), a selective SUMOylation inhibitor, promotes transcriptional reprogramming of the 4q35 locus and induces DUX4 expression. Importantly, this activation occurs independently of changes in DNA methylation or SMCHD1 ATPase activity. Our findings identify SUMOylation inhibition as a novel regulatory process driving DUX4 expression. This work uncovers the importance of SUMOylation in the epigenetic control of the 4q35 locus and DUX4 transcription, providing a potential therapeutic strategy to modulate DUX4 expression in FSHD
De l'intérêt de la recherche foncière pour la détermination de la propriété : le « bien communal » et la loi révolutionnaire
No full textInternational audienc
Broadband quasistatic passive cloaking: bounds and limitations in the near-field regime
No full textWe consider here several aspects of the following challenging question: is it possible to use a passive cloak to make invisible a dielectric inclusion on a finite frequency interval in the quasistatic regime of Maxwell's equations for an observer close to the object? In this work, by considering the Dirichlet-to-Neumann (DtN) map, we not only answer negatively this question, but we go further and provide some quantitative bounds on this map that provide fundamental limits to both cloaking as well as approximate cloaking. These bounds involve the following physical parameters: the length and center of the frequency interval, the volume of the cloaking device, the volume of the obstacle, and the relative permittivity of the object. Our approach is based on two key tools: i) variational principles from the abstract theory of composites and ii) the analytic approach to deriving bounds from sum rules for passive systems. To use i), we prove a new representation theorem for the DtN map which allows us to interpret this map as an effective operator in the abstract theory of composites. One important consequence of this representation is that it allows one to incorporate the broad and deep results from the theory of composites, such as variational principles, and to apply the bounds derived from them to the DtN map. These results could be useful in other contexts other than cloaking. Next, to use ii), we show that the passivity assumption allows us to connect the DtN map (as function of the frequency) with two important classes of analytic functions, namely, Herglotz and Stieltjes functions. The sum rules for these functions, combined with the variational approach, allows us to derive new inequalities on the DtN map which impose fundamental limitations on passive cloaking, both exact and approximate, over a frequency interval. We consider both cases of lossy and lossless cloaks
Beyond single nanomaterial exposure: investigating the fate of a TiO 2 and CeO 2 nanomaterial mixture in freshwater mesocosms
No full textInternational audienceAssessing the environmental risks of emerging contaminants related to new technologies remains a major challenge due to the diversity of pollutants, their complex interactions, and the limitations of conventional testing frameworks. Among these contaminants, engineered nanomaterials (ENMs) stand out for their unique surface reactivities and transformation pathways, which can significantly alter their behavior and that of co-occurring pollutants. Although many studies have addressed the toxicity and fate of individual ENMs, real-world scenarios often involve complex mixtures, whose combined effects are less investigated. This study addresses this gap by investigating the fate, behavior, and ecological impacts of a mixture of two representative metal oxide ENMs i.e. an industrial TiO2 and a combustion-derived CeO2. This study shows that under environmentally relevant conditions using freshwater mesocosms, these two ENMs undergo primary hetero-aggregation. Co-exposure of the freshwater snail Planorbarius corneus revealed that ENM aggregates (homo- or primary hetero-aggregates) interact with egg layings, potentially affecting early developmental stages, while slight but measurable uptakes were also observed in co-exposed adult snails. Importantly, no quenching of reactive oxygen species generated by the photocatalytic TiO2 was detected in the presence of CeO2, suggesting that the combusted CeO2 does not mitigate potentially TiO2-induced phototoxicity. These findings underscore the importance of considering ENM mixtures in environmental risk assessments and the relevance of mesocosm experiments to capture realistic exposure scenarios. Future studies should prioritize investigating how unique surface reactivities and transformation mechanisms of ENM mixtures shape their ecological impacts throughout their life cycles
Liberté de choix, consommation et limites planétaires : généalogie d’une confusion sociohistorique
No full textInternational audienc
Qui a le monopole de la petite phrase ? Analyse du phénomène médiatique de la petite phrase politique
No full textInternational audience"Fais tes valises Liliane !", "Casse-toi pauv'con !", "Aujourd'hui on rapporte une histoire abracadabrantesque", "on met un pognon de dingue dans des minima sociaux". Notre communication portera sur ces énoncés politico-médiatiques singuliers par le métadiscours et les polémiques qu'ils génèrent, et que les journalistes nomment "petite phrase". Nous montrerons la manière dont ces énoncés sont co-construits, par un contrat de communication particulier entre acteurs politiques et journalistes. Cette co-construction met en jeux des paramètres syntaxiques, énonciatifs et pragmatiques qui expliquent la mise en circulation virale de ces énoncés spectaculaires. Pour comprendre cette fabrique médiatique de la petite phrase, nous la situerons dans les dispositifs de communication qui ont permis sa naissance, et chercherons l'origine du figement "petite phrase"
Extreme Mediterranean rainfall impact on sedimentary routing systems: what can we learn from Storm Alex using in situ detrital 10Be?
No full textInternational audienceUnderstanding how extreme meteorological events influence sediment transport is critical for predicting landscape evolution under a changing climate. Detrital cosmogenic 10Be can provide insights into sediment dynamics following extreme rainfall, but high-resolution datasets tracking 10Be variations before and after a storm, alongside long-term records, remain rare.The Var catchment (French Southern Alps) presents a unique case study, as its 10Be signal was well-documented before the October 2020 Storm Alex (>500 mm of rainfall/24 h), which triggered flash floods, mobilized large sediment volumes, and formed a 10 km-long sediment plume in the Mediterranean Sea. We compare 10Be concentrations in river sediments collected pre-storm (2016–2018), and at +7 days, +21 days, +4 months, and +7 months post-storm. We also use a historical offshore sample and contextualize these results with a 75 ka-long 10Be record from deep-sea sediment cores.At the Var outlet, 10Be concentrations initially increased by ∼25 % at +7 and +21 days, attributed to the mobilization of 10Be-rich sediments from the upstream Var and Tinée sub-catchments. Concentrations returned to pre-storm levels within four months, primarily due to dilution with 10Be-poor sediments from the Vésubie sub-catchment fluvioglacial terraces. While short-term 10Be fluctuations at the Var outlet reflect complex sediment sourcing, our comparison with the 0–75 ka record confirms that major glaciation events and potential anthropic influences remain distinguishable, demonstrating that 10Be is a robust proxy of denudation changes, even when extreme events are involved
Search for planetary-mass ultra-compact binaries using data from the first part of the LIGO--Virgo--KAGRA fourth observing run
No full textInternational audienceWe present a search for gravitational waves from inspiraling, planetary-mass ultra-compact binaries using data from the first part of the fourth observing run of LIGO, Virgo and KAGRA. Finding no evidence of such systems, we determine the maximum distance reach for such objects and their merger rate densities, independently of how they could have formed. Then, we identify classes of primordial black-hole mass distributions for which these rate limits can be translated into relevant constraints on the mass distribution of primordial black holes, assuming that they compose all of dark matter, in the mass range . Our constraints are consistent with existing microlensing results in the planetary-mass range, and provide a complementary probe to sub-solar mass objects
