Portail HAL du Collège de France
Not a member yet
22122 research outputs found
Sort by
Microglial colonization of the developing mouse brain is controlled by both microglial and neural CSF-1
No full textInternational audienceAbstract Microglia are brain-resident macrophages critical for cerebral development, function, and homeostasis. During development, yolk sac-derived microglial progenitor cells colonize and populate the brain following a well-defined spatiotemporal pattern. However, the mechanisms controlling microglial colonization and proliferation remain largely unknown. Here, we describe two broad waves of microglial proliferation in the developing mouse forebrain. Microglia accumulate in transient hotspots, in a proliferative axon tract-associated microglia (ATM)-like state. Prenatal and early postnatal patterns of microglial colonization do not rely on neuronal activity. Instead, using conditional inactivation of the microglial regulator colony-stimulating factor 1 ( Csf1 ) gene, we reveal that the distribution and proliferation of embryonic cortical microglia critically rely on neural CSF-1, mainly produced by cortical progenitor cells but also by post-mitotic neurons, with the action of CSF-1 being local, dose-dependent, and transient. In addition, intrinsic CSF-1 expressed by ATM microglia contributes to their sustained proliferation in developmental hotspots. Our study reveals that microglia rely on distinct, local, and cell-type-specific sources of CSF-1 for their developmental distribution, which has major implications for understanding how microglia colonize the brain in health and disease
Voies et voix de la philologie classique. Éditer les textes anciens : comment et pour quel public ?
No full textInternational audiencePhilology lies at the heart of a triangle formed by the author, the text, and the audience. This threefold relationship also involves the factor of time—time as embodied in the transmission of the text, which separates the author from the reader. The task of philology is precisely to confront the effects of time. On the one hand, it seeks to diminish, even erase these effects, by bringing the text closer to the original state in which it was conceived by its author, eliminating the errors accumulated over the centuries. On the other hand, philology is responsible for reactivating time, by enabling the reader to understand the text within the context in which it was created. It also bears the responsibility of making the text present—of allowing it to live on through the work of translation.These challenges form the thematic core of the contributions gathered in this volume, which stem from a conference held at the Collège de France on October 5–6, 2023. The first section, “Paths of Classical Philology,” examines the various ways of recounting the long history of the transmission of ancient texts, highlighting key figures, periodizations, concepts, and models. The second section, “Voices of Classical Philology,” gives the floor to several scholars engaged in editing classical works and studying the history of philology. Some contributions explore current trends in the art of editing, translating, and commenting on ancient texts. Others retrace the development of various journals and series that illuminate the history of this scholarly field.La philologie est au cœur d’un triangle, formé par l’auteur, le texte et le public. Cette relation à trois implique également le facteur du temps, celui rempli par la transmission du texte, qui sépare l’auteur du lecteur. Or la mission de la philologie est d’affronter les effets du temps. D’une part, elle doit en réduire, presque effacer les effets, en rapprochant le texte de l’état original dans lequel l’auteur l’avait conçu, en éliminant les erreurs accumulées au fil des siècles. D’autre part, il lui incombe de réactiver le temps, en plaçant le lecteur en condition de comprendre le texte dans le contexte où il a été conçu. Elle a en outre la tâche de rendre le texte présent, à le faire vivre encore, à travers l’œuvre de traduction. Soit autant d’enjeux qui nourrissent les contributions du volume, issues d’un colloque tenu au Collège de France les 5 et 6 octobre 2023. Le premier volet, « Voies de la philologie classique », analyse les manières de narrer la longue histoire de la transmission des textes antiques et d’évoquer ses figures marquantes, ses périodisations, ses concepts, ses modèles. Le second volet, « Voix de la philologie classique », donne la parole à plusieurs représentants de l’édition des œuvres classiques et des études d’histoire de la philologie. Certains se penchent sur les tendances actuelles de l’art d’éditer, traduire et commenter les textes anciens. D’autres retracent le parcours de plusieurs revues et collections éclairant l’histoire de ce domaine scientifique
Bouddhisme et mobilité. Les monastères-ger de Mongolie, xvie-xixe siècle
No full textInternational audienceBeside stationary Buddhist monasteries, the Mongols also had itinerant monasteries with felt and wooden temples that periodically moved in the steppes and mountains of Inner Asia. Most of them eventually settled down in the course of the 18th and 19th centuries, but up to the early 20th century, a few mobile monasteries continued to nomadise in western Mongolia. This paper first argues that there is no reason for a Buddhist monastery not to be made up of felt tents and frequently change locations, and that lightweight, demountable architecture is not restricted to the ger (yurt) but includes prestigious large structures. Finally, it examines the mobility patterns of itinerant monasteries and the various reasons for their moves to determine whether their migration was a matter of choice or necessity.Outre des monastères fixes, les Mongols avaient également des monastères bouddhiques itinérants avec des temples en feutre et en bois qui se déplaçaient périodiquement dans les steppes d’Asie intérieure. La plupart d’entre eux ont fini par se sédentariser au cours des xviiie et xixe siècles, mais jusqu’au début du xxe siècle, quelques monastères itinérants ont continué à nomadiser dans l’ouest de la Mongolie. Cet article montre tout d’abord qu’il n’y a pas de contre-indication à ce qu’un monastère bouddhique soit constitué de tentes en feutre et change fréquemment d’emplacement, et que l’architecture légère et démontable ne se limite pas à la ger (yourte) mais inclut également de grandes structures prestigieuses. Enfin, il examine les schémas de mobilité des monastères itinérants et les diverses raisons qui motivaient leurs déplacements afin de déterminer si la migration était une question de choix ou de nécessité
Assessing Geological Hazards in a Changing World Through Regional Multidisciplinary Approaches to European Glacial Lakes (Northern Pyrenees, Northern and Western Alps)
No full textInternational audienceThis study combines a multidisciplinary approach to Pyrenean and Alpine glacial lakes to characterize the sensitivity of Late Glacial to Holocene subaquatic flood deposits in deltaic environments to slope failures triggered either by earthquakes, rockfalls, or snow avalanches. To clarify the possible interactions between environmental changes and these natural hazards in mountain and piedmont lakes, we analyze the lacustrine sedimentary records of key historical events and discuss the recurrence of similar regional events in the past. High-resolution seismic profiles and sediment cores from large perialpine lakes (Bourget, Geneva, and Constance) and from small mountain lakes in the French Alps and the Pyrenees were used to establish a conceptual model linking environmental changes, tributary flood sedimentary processes, subaquatic deltaic depocenters, and potentially tsunamigenic mass-wasting deposits. These findings illustrate the specific signatures of the largest French earthquakes in 1660 CE (northern Pyrenees) and in 1822 CE (western Alps) and suggest their recurrence during the Holocene. In addition, the regional record in the Aiguilles Rouges massif near Mont Blanc of the tsunamigenic 1584 CE Aigle earthquake in Lake Geneva may be used to better document a similar Celtic event ca. 2300 Cal BP at the border between Switzerland and France
Tail Modulo Async-Await
No full textThis article extends tail-call optimisation by applying it to asynchronous calls. We first introduce Tail-Modulo-Await, a novel code transformation for asynchronous tail recursive functions that prevents the creation of unnecessary tasks. We then show how to combine Tail-Modulo-Await with the existing Tail-Modulo-Cons optimisation; we obtain an optimisation able to turn a recursive function with multiple tail calls under constructors into a parallel version of the function, also optimised in space.We formalise both optimisations over representative calculi, and prove them correct through backward simulations. Finally, we provide a proof-of-concept implementation as an OCaml syntax extension and evaluate it experimentally, showing our approach optimises both memory and execution time
Data for Mathematical Copilots: Better Ways of Presenting Proofs for Machine Learning
No full textInternational audienceThe suite of datasets commonly used to train and evaluate the mathematical capabilities of AI-based mathematical copilots (primarily large language models) exhibit several shortcomings. These limitations include a restricted scope of mathematical complexity, typically not exceeding lower undergraduate-level mathematics, binary rating protocols and other issues, which makes comprehensive proof-based evaluation suites difficult. We systematically explore these limitations and contend that enhancing the capabilities of large language models, or any forthcoming advancements in AI-based mathematical assistants (copilots or "thought partners"), necessitates a paradigm shift in the design of mathematical datasets and the evaluation criteria of mathematical ability: It is necessary to move away from result-based datasets (theorem statement to theorem proof) and convert the rich facets of mathematical research practice to data LLMs can train on. Examples of these are mathematical workflows (sequences of atomic, potentially subfield-dependent tasks that are often performed when creating new mathematics), which are an important part of the proof-discovery process. Additionally, we advocate for mathematical dataset developers to consider the concept of "motivated proof", introduced by G. Pólya in 1949, which can serve as a blueprint for datasets that offer a better proof learning signal, alleviating some of the mentioned limitations. Lastly, we introduce math datasheets for datasets, extending the general, dataset-agnostic variants of datasheets: We provide a questionnaire designed specifically for math datasets that we urge dataset creators to include with their datasets. This will make creators aware of potential limitations of their datasets while at the same time making it easy for readers to assess it from the point of view of training and evaluating mathematical copilots
A New Approach to Radiocarbon Summarisation: Rigorous Identification of Variations/Changepoints in the Occurrence Rate of Radiocarbon Samples using a Poisson Process
No full textInternational audienceA commonly-used paradigm to estimate changes in the frequency of past events or the size of populations is to consider the occurrence rate of archaeological/environmental samples found at a site over time. The reliability of such a "dates-as-data" approach is highly dependent upon how the occurrence rates are estimated from the underlying samples, particularly when calendar age information for the samples is obtained from radiocarbon (14C). The most frequently used "14C-dates-as-data" approach of creating Summed Probability Distributions (SPDs) is not statistically valid, or coherent, and can provide highly misleading inference. Here, we provide an alternative method with a rigorous statistical underpinning that also provides valuable additional information on potential changepoints in the rate of events. Furthermore, unlike current SPD alternatives, our summarisation approach does not restrict users to pre-specified, rigid, summary formats (e.g., exponential or logistic growth) but instead flexibly adapts to the dates themselves. Our methodology ensures more reliable "14C-dates-as-data" analyses, allowing us to better assess and identify potential signals present. We model the occurrence of events, each assumed to leave a radiocarbon sample in the archaeological/environmental record, as an inhomogeneous Poisson process. The varying rate of samples over time is then estimated within a fully-Bayesian framework using reversible-jump Markov Chain Monte Carlo (RJ-MCMC). Given a set of radiocarbon samples, we reconstruct how their occurrence rate varies over calendar time and identify if that rate contains statistically-significant changes, i.e., specific times at which the rate of events abruptly changes. We illustrate our method with both a simulation study and a practical example concerning late-Pleistocene megafaunal population changes in Alaska and Yukon
The Galaxy Activity, Torus, and Outflow Survey (GATOS). VI. Black hole mass estimation using machine learning
No full textInternational audienceThe detailed feeding and feedback mechanisms of active galactic nuclei (AGNs) are not yet well known. For low-luminosity AGNs, obscured AGNs, and late-type galaxies, the masses of their central black holes (BH) are difficult to determine precisely. Our goal with the GATOS sample is to study the circum-nuclear regions and, in the present work, to better determine their BH mass, with more precise and accurate estimations than those obtained from scaling relations. We used the high spatial resolution of ALMA to resolve the CO(3–2) emission within ∼100 pc around the supermassive black hole (SMBH) of seven GATOS galaxies and try to estimate their BH mass when enough gas is present in the nuclear regions. We studied the seven bright ( L AGN (14 − 150 keV)≥10 42 erg/s) and nearby (< 28 Mpc) galaxies from the GATOS core sample. For the sake of comparison, we first searched the literature for previous BH mass estimations. We also made additional estimations using the M BH – σ relation and the fundamental plane of BH activity. We developed a new method using supervised machine learning to estimate the BH mass either from position-velocity diagrams or from first-moment maps computed from ALMA CO(3–2) observations. We used numerical simulations with a large range of parameters to create the training, validation, and test sets. Seven galaxies had sufficient gas detected, thus, we were able to make a BH estimation from the ALMA data: NGC 4388, NGC 5506, NGC 5643, NGC 6300, NGC 7314, NGC 7465, and NGC 7582. Our BH masses range from 6.39 to 7.18 log( M BH / M ⊙ ) and are consistent with the previous estimations. In addition, our machine learning method has the advantage of providing a robust estimation of errors with confidence intervals. The method has also more growth potential than scaling relations. This work represents the first step toward an automatized method for estimating M BH using machine learning
Rôles de H2Av, unique variant de H2A chez la drosophile D. melanogaster, dans l'ovogenèse et le maintien de l'intégrité du génome
No full textTransposable Elements (TEs) are major components of genomes. TEs are able to move in genomes, generating mutations which can be involved in the development of numerous diseases. Fortunately, several defense mechanisms exist against TEs, such as Piwi-associated RNAs (piRNAs) in gonads. piRNAs are small non-coding RNAs (sncRNAs) targeting TEs by sequence complementarity. tRNA fragments (tRFs) are other sncRNAs with a capacity to target TEs, but their biogenesis and silencing mechanisms are mostly unknown. Therefore, during my PhD, I carried out a targeted genetic screen with a tRF-based TEs-silencing biosensor, tagged with GFP. I took advantage of the powerful Drosophila genetics to uncover genes that would be relevant to other species as well. H2Av emerged as a very strong and interesting candidate. Chromatin structure is crucial for TEs silencing. Deposition of heterochromatin marks at TEs loci impedes their transcription by compacting DNA. Paradoxically, heterochromatin drives piRNAs production. Yet, despite histone variants being numerous and playing critical roles in diverse functions, their contribution to TEs silencing is mostly unexplored. In many organisms, H2A variants are crucial for DNA repair (H2A.X) and transcription control (H2A.Z). Curiously, Drosophila has only one H2A variant called H2Av.Therefore, I conducted a phenotypic characterization of H2Av mutation in the Drosophila female germline, at the cellular and developmental levels, by combining RNA FISH, immunostaining, confocal imaging with Drosophila genetics and RNA and small RNA-sequencing analyses. I showed that H2Av is required for TEs silencing. H2Av is important for the transcription of piRNA pathway genes and of piRNAs precursors. Yet, H2Av is not involved in heterochromatin establishment but in the recruitment of the chromatin-binding protein rhino, a key determinant of piRNAs production. Besides, H2Av is required in a narrow developmental window only, highlighting the tight intrication of TEs silencing with developmental processes.H2Av is also important for the expression of oogenesis genes, their localization in the differentiating germline (Orb, gurken, C(3)G) and for the regulation of cell divisions. The structure of the nucleolus, a nuclear organelle involved in ribosome maturation, is impaired in H2Av germline knock-down (GLKD) flies even though nuclear components like chromosome territories are correctly specified. As a result, ovaries are atrophied and H2Av GLKD flies are sterile. DNA damage accumulate in these ovaries, leading to the activation of DNA damage checkpoints (Chk1, Chk2). Mutating each one of these checkpoint proteins rescue oogenesis growth, indicating that these pathways are at the origin of oogenesis arrest. DNA damage comes from several sources, among which meiotic DNA double-strand breaks and replication stress. Alleviating these sources rescues ovary growth.Importantly, H2Av C-terminal tail phosphorylation is crucial for DNA damage repair, similarly to H2A.X phosphorylation. However, in homozygous mutants with a deletion of the phosphorylation site, there are no developmental defects or no TEs up-regulation. This suggests that it is H2Av transcriptional function that is required for oogenesis. Indeed, over-expression the main transcriptional activator of oogenesis and piRNA pathway genes, Ovo, is able to rescue ovary growth and even fertility in H2Av GLKD flies.Finally, to better understand the mechanism by which H2Av regulates TEs, I studied a protein of the chromatin remodeling complex incorporating H2Av in chromatin: Arp6 (Actin-related protein 6). Arp6 GLKD flies are also sterile. They have mild oogenesis defects but up-regulate strongly TEs. Arp6 is therefore a new and unexpected factor involved in TEs silencing upstream of H2Av.Altogether, I identified a new role of H2Av in genome integrity control during oogenesis, and revealed for the first time the importance of the Arp6/H2Av axis for TEs regulation in gonads.Les éléments transposables (ETs) constituent une part importante des génomes. Leurs déplacements créent des mutations à l'origine de nombreuses maladies. Des mécanismes de défense existent, tels que les petits ARNs associés à Piwi (piRNAs) dans les gonades. D'autres petits ARN non codants ont cette capacité, comme les fragments d'ARNt (tRFs), qui sont encore peu étudiés. Lors de ma thèse, j'ai réalisé un crible génétique orienté à l'aide d'un biosenseur de l'activité des ETs basé sur un tRF. et j'ai identifié un candidat particulièrement intéressant, H2Av.La structure de la chromatine est cruciale pour la répression des ETs. En effet, la mise en place d'hétérochromatine aux loci des ETs empêche leur transcription en compactant l'ADN. Paradoxalement, l'hétérochromatine est aussi nécessaire à la production des piRNAs. Alors même que les variants d'histones sont très diversifiés et jouent des rôles cruciaux dans de nombreux processus cellulaires, leur contribution à la répression des ETs est peu documentée. Ainsi les variants de H2A sont fondamentaux pour la réparation des dommages à l'ADN (H2A.X) et la régulation de la transcription (H2A.Z) mais curieusement, la drosophile n'a qu'un unique variant, H2Av. J'ai donc réalisé une caractérisation phénotypique de la mutation de H2Av dans la lignée germinale femelle, en combinant immunomarquages, hybridation in situ d'acides nucléiques et imagerie confocale avec la génétique de la drosophile et des expériences de séquençage des ARNs et petits ARNs. J'ai montré qu'H2Av est requis pour la répression des ETs. H2Av est important à la fois pour la transcription de gènes de la voie des piRNA et des précurseurs des piRNAs. H2Av n'est pas requis pour la mise en place de l'hétérochromatine mais pour le recrutement de rhino, protéine déterminant les loci produisant des piRNAs.H2Av est également important pour l'expression de gènes de l'ovogenèse, leur localisation lors de la différenciation de la lignée germinale (Orb, Gurken, C(3)G) et la régulation des divisions cellulaires. La structure du nucléole, une organelle nucléaire impliquée dans la maturation du ribosome, est altérée dans les mutants germinaux (MG) pour H2Av alors que d'autres composants structurels du noyau comme les territoires chromosomiques, sont correctement établis. En conséquence, les ovaires des MG pour H2Av sont atrophiés, les femelles sont stériles. Les MG pour H2Av accumulent des dommages à l'ADN, ce qui active des protéines ‘checkpoints' (Chk1, Chk2). Muter chacune de ces protéines sauve la croissance des ovaires, ce qui signifie que l'activation de ces voies est à l'origine de l'arrêt de l'ovogenèse. Les cassures méiotiques et le stress réplicatif sont les principales sources de dommages à l'ADN ; les affaiblir permet de restaurer la croissance ovarienne des MG de H2AvUne fonction importante de H2Av est la réparation des dommages à l'ADN, médiée par sa phosphorylation, de manière analogue à H2A.X. Cependant, des mutants homozygotes avec une délétion du site de phosphorylation ne présentent ni défauts développementaux, ni dérégulation des ETs. C'est donc principalement la fonction transcriptionnelle d'H2Av qui est requise pour l'ovogenèse. La sur-expression d'Ovo, le principal facteur de transcription contrôlant l'expression de la voie des piRNA et des gènes de l'ovogenèse, permet de restaurer la croissance ovarienne et même la fertilité des MG pour H2Av.Afin de mieux comprendre le mécanisme par lequel H2Av réprime les ETs, j'ai finalement étudié Arp6, un membre du complexe intégrant H2Av à la chromatine. Les MG pour Arp6 ont de légers défauts développementaux et dérégulent très fortement les ETs. Arp6 est donc un nouveau facteur, inattendu, requis pour la répression des ETs en amont de H2Av.En conclusion, j'ai identifié un nouveau rôle de H2Av dans l'ovogenèse et le maintien de l'intégrité du génome et décrit pour la première fois l'importance d'Arp6 en amont dans ce processus