HAL-ENS-LYON
Not a member yet
104280 research outputs found
Sort by
Giraud (Anne-Sophie), L’être anténatal. Dynamiques parentales, médicales et juridiques . Préface d’Irène Théry.
No full textInternational audienceCompte rendu de l'ouvrage d'Anne-Sophie Giraud, L'être anténatal. Dynamiques parentales, médicales et juridiques (éditions de la MSH, 2024).
Conservation et évolution du positionnement des nucléosomes médié par la séquence d'ADN chez les eucaryotes
No full textThe nucleosome is a complex of histones and ~150 bp of DNA. It is a major constituent of chromatin in eukaryotes, covering 75-90% of genomes . Histones are present in all eukaryotes analyzed. The positioning of nucleosomes by the DNA sequence is a parameter studied since the 80s and the discovery that nucleosomes did not form on polyA. Multiple models exploiting the sequences experimentally associated with histones have been proposed to predict nucleosome positioning. Our team has developed a polymer model where the elastic parameters depend on the sequence of the DNA wrapped around histones, allowing the prediction of the positioning of nucleosomes “ab initio”.This model was first exploited in yeast, then in humans. It has been shown that the sequence encodes Nucleosome Inhibitory Energy Barriers (NIEBs) that are bordered on each side by 2 - 3 nucleosomes. We studied experimental data from Mus musculus, Danio rerio, Caenorhabditis elegans, Drosophila melanogaster, Saccharomyces cerevisiae, Arabidopsis thaliana, Oryza sativa and Trypanosoma brucei. We confirm that the NIEBs correspond to sequences refractory to nucleosome formation in all eukaryotes studied. NIEBs in all these organisms are associated with similar oscillations in GC-content levels in relation to substitution profiles in their evolutionary lineages.Transcription termination sites (TTS) are associated with NIEBs in yeast and humans. In contrast, the relationship of NIEBs to transcription start sites (TSS) varies: those of H. sapiens are anti-correlated with TSS, while those of S. cerevisiae are directly associated. Our analysis shows that while NIEBs are associated with TTS in all species studied, they are associated with TSS in some species (S. cerevisiae, A. thaliana, C. elegans, T. brucei), and in other anti-associated (H. sapiens, M. musculus, D. rerio, O. sativa). These results suggest that genome size influences the relationship between NIEBs and TSS.It has also been shown that Alu retroelements in humans and chimpanzees are associated with the creation of new barriers, which they generate by the insertion of their polyA tail during retrotransposition. We show that NIEBs are associated with AT-rich microsatellites and transposable elements (TEs) in all species studied. We show that L1 retroelements are associated with NIEBs in humans, pigs and mice, thus allowing inter-species comparisons. Other specific TEs are also associated with NIEBs, such as the B1 retroelements in mice or the Harbinger DNA transposons in Danio rerio. This relationship between TEs and NIEBs raises the question of their coevolution. We can propose two hypotheses, that are not mutually exclusive. Firstly, nucleosome-free regions could be used for the integration of these TEs into eukaryotic genomes. Secondly, NIEBs could also be mobilized and even created by the insertion of these TEs.In conclusion, this work reveals the existence of sequences positioning nucleosomes in the genome of all eukaryotic species analyzed, thus revealing a general principle of chromatin organization by the DNA sequence in these organisms. They also reveal how repeated sequences such as microsatellites and transposable elements can modulate this chromatin structure through their instability and mobility. Thus, this study paves the way for a comparative genomics approach to better understand the evolution of chromatin in eukaryotes.Le nucléosome est un complexe d'histones et de ~150 bp d'ADN. C'est un constituant majeur de la chromatine chez les eucaryotes, couvrant 75 - 90% des génomes. Les histones sont présentes dans l'intégralité des eucaryotes analysés. Le positionnement des nucléosomes par la séquence d'ADN est une question étudiée dès les années 80 et la découverte que les nucléosomes ne se forment pas sur les polyA. De multiples modèles exploitant les séquences expérimentalement associées aux histones ont été proposés pour prédire le positionnement des nucléosomes. Notre équipe a développé une méthode alternative reposant sur les paramètres physico-élastiques de la séquence génomique (corrélant avec le contenu en GC), permettant ainsi la prédiction du positionnement des nucléosomes « ab initio ».Ce modèle a d'abord été exploité chez la levure, puis chez l'humain. Il a été ainsi montré que la séquence d'ADN code pour des barrières inhibitrices de la formation des nucléosomes (NIEBs, pour Nucleosome Inhibitory Energy Barriers), qui sont bordées de chaque côté par 2 - 3 nucléosomes. Nous avons étudié les données expérimentales disponibles pour Mus musculus, Danio rerio, Caenorhabditis elegans, Drosophila melanogaster, Saccharomyces cerevisiae, Arabidopsis thaliana, Oryza sativa et Trypanosoma brucei. Nous confirmons que les NIEBs correspondent à des séquences réfractaires à la formation de nucléosomes chez tous les eucaryotes étudiés. Les NIEBs chez tous ces organismes sont associés à des oscillations similaires du contenu en GC en lien avec les profils de substitutions de bases dans leurs lignées évolutives.Les signaux de terminaison de transcription (TTS) sont associés aux NIEBs chez la levure et l'humain. En revanche, la relation des NIEBs aux éléments de démarrage de la transcription (TSS) varie : ceux de H. sapiens sont anti-corrélés aux TSS, tandis que ceux de S. cerevisiae sont directement associés. Notre analyse montre que si les NIEBs sont associés aux TTS dans toutes les espèces étudiées, ils sont associés aux TSS chez certaines espèces (S. cerevisiae, A. thaliana, C. elegans, T. brucei), et chez d'autres anti-associés (H. sapiens, M. musculus, D. rerio, O. sativa). Ces résultats suggèrent que la taille du génome influe sur la relation entre NIEBs et TSS.Il a été aussi montré que les retroéléments Alu chez l'humain et le chimpanzé sont associés à la création de nouvelles barrières, qu'ils génèrent par l'insertion de leur queue polyA lors de la rétrotransposition. Nous montrons que les NIEBs sont associés aux microsatellites riches en AT et à certains éléments transposables (TE) dans toutes les espèces étudiées. Nous montrons que les retroéléments L1 sont associés aux NIEBs chez l'humain, le porc et la souris, permettant ainsi des comparaisons inter-espèces. D'autres TE spécifiques sont également associés aux NIEBs, comme les retroéléments B1 chez la souris ou bien le transposon à ADN Harbinger chez Danio rerio. Cette relation entre TE et NIEBs soulève la question de leur coévolution. On peut supposer (a) une utilisation des régions libres en nucléosomes pour l'intégration de ces TE dans les génomes eucaryotes et / ou (b) la création ou mobilisation des NIEBs par l'insertion de ces TE.En conclusion, ces travaux révèlent l'existence de séquences positionnant les nucléosomes dans le génome de toutes les espèces eucaryotes analysées, révélant ainsi un principe général d'organisation de la chromatine par la séquence d'ADN chez ces organismes. Ils révèlent également comment les séquences répétées comme les microsatellites et les éléments transposables peuvent moduler cette structure de la chromatine par leur instabilité et mobilité. Ainsi, cette étude ouvre la voie d'une approche de génomique comparative pour mieux comprendre l'évolution de la chromatine chez les eucaryotes
Formalization of Brownian motion in Lean
No full textBrownian motion is a building block in modern probability theory. In this paper, we describe a formalization of Brownian motion using the Lean theorem prover. We build on the existing measure-theoretic foundations in Lean's mathematical library, Mathlib, and we develop several key components needed for the construction of Brownian motion, including the Carathéodory and Kolmogorov extension theorems, Gaussian measures in Banach spaces, and the Kolmogorov-Chentsov theorem for path continuity
« Je deviens le plant de tabac (...) mon tronc c’est la tige ». Étude micro-phénoménologique d'interactions avec des végétaux en transe cognitive auto-induite
No full textEcdysone-mediated intestinal growth contributes to microbiota-driven developmental plasticity under malnutrition
No full textAbstract Organ and systemic growth must remain coordinated during development, even under nutritional stress. In Drosophila larvae, the intestinal microbiota contributes to this coordination by promoting growth and maturation under chronic undernutrition. Using gnotobiotic models, we show that association with Lactiplantibacillus plantarum ( Lp ) selectively enhances midgut growth relatively to other organs, providing an adaptive mechanism that buffers the impact of dietary restriction. Transcriptomic profiling of larval midguts revealed a strong Ecdysone signaling signature upon Lp association. Functional analyses showed that local conversion of Ecdysone to its active form, 20-hydroxyecdysone, by the cytochrome P450 enzyme Shade, together with enterocyte Ecd receptor activity, is required for Lp -dependent intestinal and systemic growth. Pharmacological activation of Ecd signaling partially mimicked the bacterial effect, confirming its sufficiency to drive adaptive midgut expansion. Our results uncover an unexpected role of intestinal Ecd signaling in microbiota-driven developmental plasticity, revealing how commensal bacteria modulate local steroid signaling to fine-tune organismal growth and maturation
Deciphering lentiviral Vpr/Vpx determinants required for HUSH and SAMHD1 antagonism highlights the molecular plasticity of these evolutionary conflicts
No full textInternational audienceSAMHD1 and the HUSH complex constitute two blocks during primate lentivirus infection, the first by limiting reverse transcription and the second by inhibiting proviral expression. Vpr and Vpx of specific lentiviral lineages have evolved to antagonize these antiviral proteins. While the antagonism of SAMHD1 has been well characterized, the evolutionary and molecular determinants of the antagonism against HUSH are unknown. We used chimeric Vpr proteins between SIVagm.Ver and SIVagm.Gri lentiviruses infecting two African green monkey species to investigate viral determinants involved in HUSH and SAMHD1 antagonisms. We found that different interfaces of closely related Vpr proteins are engaged to degrade different SAMHD1 haplotypes. In addition, we identified distinct viral determinants in SIVagm.Ver Vpr for SAMHD1 and HUSH degradation. The substitution of one residue in SIVagm.Gri Vpr is sufficient to gain the capacity to degrade SAMHD1, while the substitution of α-helix 3 confers HUSH antagonism. We also found that Vpx proteins of HIV-2 from people living with HIV have different abilities to degrade HUSH. These phenotypes rely on small changes in either the N or C terminal part of Vpx, depending on the context. On the host side, we found that HIV-2 and SIVsmm Vpx degrading HUSH from human and vervet monkey cells cannot degrade HUSH in owl monkey cells, suggesting some host species specificity. Altogether, we highlight the molecular plasticity and constraints of viral proteins to adapt to host restrictions. HUSH, like SAMHD1, may have been engaged in ancient and more recent coevolution conflicts with lentiviruses and a player in viral fitness. IMPORTANCE Antiviral host proteins, the so-called restriction factors, block lentiviruses at different steps of their viral replication cycle. In return, primate lentiviruses may counteract these immune proteins to efficiently spread in vivo . HIV-2 and some simian immunodeficiency viruses (SIVs), but not HIV-1, inactivate SAMHD1 and HUSH, two host antiviral proteins, thanks to their Vpx or Vpr viral proteins. First, we uncovered viral determinants involved in the function of closely related Vpr proteins from SIVs of African green monkeys and of HIV-2 Vpx alleles from people living with HIV-2. We show how these small viral proteins differently adapted to SAMHD1 polymorphism or to HUSH restriction and highlight their molecular plasticity. Finally, the capacity of divergent lentiviral proteins, including HIV-2 Vpx, to induce the degradation of HUSH depends on the cell/host species. Altogether, our results suggest that HUSH has been engaged in a molecular arms race along evolution, and therefore is a key player in host–pathogen interaction
Compte rendu de : Anthony Saudrais, « Imaginaires et techniques du merveilleux. Les machines de théâtre dans les planches de l’ Encyclopédie », dossier thématique de l'Édition numérique collaborative et critique de l’Encyclopédie (ENCCRE), 2024, URL : https://enccre.academie-sciences.fr/encyclopedie/dossier/D00-5f96962100ec/
No full textCompte rendu d'ouvrage
On the Minimisation of Deterministic and History-Deterministic Generalised (Co)Büchi Automata
No full textInternational audienceWe present a polynomial-time algorithm minimising the number of states of history-deterministic generalised coBüchi automata, building on the work of Abu Radi and Kupferman on coBüchi automata. On the other hand, we establish that the minimisation problem for both deterministic and history-deterministic generalised Büchi automata is NP-complete, as well as the problem of minimising at the same time the number of states and colours of history-deterministic generalised coBüchi automata