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Resource landscape shapes the composition and stability of the human vaginal microbiota
No full textAbstract The vaginal microbiota is associated with the health of women and newborns alike. Despite its comparatively simple composition relative to other human microbiota systems, the mechanisms underpinning the dynamics and stability of vaginal microbial communities remain elusive. A crucial, yet so far underexplored, aspect of vaginal microbiota ecology is the role played by nutritional resources. Glycogen and its derivatives, produced by vaginal epithelia, are accessible to all bacterial constituents of the microbiota. Concurrently, free sialic acid and fucose offer supplementary nutritional resources to bacterial strains capable of cleaving them from glycans, which are structurally integral to mucus. Notably, bacteria adept at sialic acid exploitation are often correlated with adverse clinical outcomes and are frequently implicated in bacterial vaginosis (BV). In this study, we introduce a novel mathematical model tailored to human vaginal microbiota dynamics to explore the interactions between bacteria and their respective nutritional landscape. Our resource-based model examines the impact of the relative availability of glycogen derivatives (accessible to all bacterial species) and sialic acid (exclusive to some BV-associated bacteria) on the composition of the vaginal microbiota. Our findings elucidate that the success of BV-associated bacteria is intricately linked to their exclusive access to specific nutritional resources. This private access fortifies communities dominated by BV-associated bacteria, rendering them resilient to compositional transitions. We empirically corroborate our model prediction with longitudinal clinical data on microbiota composition and previously unpublished metabolomic profiles obtained from a North American cohort. The insights gleaned from this study shed light on potential pathways for BV prevention and treatment. Significance statement The vaginal microbiota has a notable impact on women’s health at various stages of life, namely puberty, infection protection, sexual health, fertility, pregnancy, and menopausal changes. At present, most non-anti-microbial products developed to mitigate adverse vaginal symptoms emphasise competitive interactions through acids (boric or lactic acid) or probiotics as a means to “rebalance” microbiota communities. Despite recent advances in profiling the composition of vaginal microbiota communities, there remains a major gap in our mechanistic understanding of how to maintain or reinstate a resilient Lactobacillus -dominated microbiota that improves vaginal health and outcomes. This study explores the role of nutritional resources in the vaginal microbiota by introducing a mathematical model that analyses how access to specific nutrients like glycogen derivatives and sialic acid affects the balance of bacterial vaginosis (BV) and non-BV-associated bacteria. Our findings, supported by original cohort-derived microbiological and metabolomics data, demonstrate that exclusive access to these nutrients is linked to the dominance and resilience of BV-associated bacteria, providing new insights for BV prevention and treatment
ALMA-JELLY. I. High Resolution CO(2–1) Observations of Ongoing Ram Pressure Stripping in NGC 4858 Reveal Asymmetrical Gas Tail Formation and Fallback
No full textInternational audienceAbstract We present new CO(2–1) observations (resolution ∼1″ = 460 pc) of the Coma cluster jellyfish galaxy NGC 4858 obtained from the ALMA-JELLY large program. Analyzing this data alongside complimentary Subaru H α and Hubble Space Telescope (F600LP / F350LP) observations, we find numerous structural and kinematic features indicative of the effects from strong, inclined ram pressure, including an asymmetric inner gas tail. We estimate a highly inclined disk-wind angle of ϕ DW = 7 5 − 27 + 10 . By subtracting a simple circular velocity model, we find (1): gas clumps that are being accelerated by ram pressure, and (2): signatures of gas clumps that had been previously pushed out of the disk but are now falling inward. We also discuss head-tail morphologies in star complexes within the stellar disk that appear to be ram pressure stripping (RPS)-influenced. Lastly, we compare this galaxy to state-of-the-art galaxy “wind tunnel” simulations. We find that this galaxy is one of the best nearby examples of strong and inclined ram pressure gas stripping, and of gas that is perturbed by ram pressure but not fully stripped and falls back. We emphasize the importance of torques due to ram pressure in highly inclined interactions, which help drive gas inward on the side rotating against the wind, contributing to the formation of asymmetric inner RPS tails
EXKALIBUR: Towards a Kaonic Atoms Periodic Table to test Fundamental Interactions
No full textInternational audienceKaonic atoms, formed when a negatively charged kaon replaces an electron, provide a unique laboratory to test fundamental interactions at low energies. EXKALIBUR (EXtensive Kaonic Atoms research: from LIthium and Beryllium to URanium) is a program to perform systematic, high-precision X-ray spectroscopy of selected kaonic atoms across the periodic table at the DANE accelerator at the National Laboratory of Frascati (INFN-LNF). Here, we outline its detector-driven strategy: Silicon Drift Detectors for 10-40 keV transitions in light targets (Li, Be, B, O), CdZnTe detectors for 40-300 keV lines in intermediate- systems (Mg, Al, Si, S), and a High-Purity Germanium detector for high- atoms (Se, Zr, Ta, Mo, W, Pb), complemented by VOXES, a high-resolution crystal spectrometer for sub-eV studies. EXKALIBUR plans to (i) reduce the charged-kaon mass uncertainty below 10 keV, (ii) produce a database of nuclear shifts and widths to constrain multi-nucleon K-nucleus interaction models, and (iii) provide precision data for testing bound-state QED in strong fields. We summarize the planned measurements and expected sensitivities within DANE luminosities
Eliminating separase inhibition reveals absence of robust cohesin protection in oocyte metaphase II
No full textInternational audienceThe meiotic segregation pattern to generate haploid gametes is mediated by step-wise cohesion removal by separase, first from chromosome arms in meiosis I, and then from the pericentromere in meiosis II. In mammalian oocytes, separase is tightly controlled during the hours-long prometaphase and until chromosome segregation in meiosis I, activated for a short time window, and again inhibited until metaphase II arrest is lifted by fertilization. Centromeric cohesin is protected from cleavage by Sgo2-PP2A in meiosis I. It remained enigmatic how tight control of alternating separase activation and inactivation is achieved during the two divisions in oocytes, and when cohesin protection is put in place and removed. Using complementation assays in knock-out mouse models, we established the contributions of cyclin B1 and securin for separase inhibition during both divisions. When eliminating separase inhibition, we found that cohesin is not robustly protected at meiosis I resumption and during metaphase II arrest. Importantly, in meiosis II, the sole event required for cleavage of pericentromeric cohesin besides separase activation is prior kinetochore individualization in meiosis I
Recent progress in classical string cosmology
No full textInternational audienceI will summarise recent work on constructing regular bouncing string cosmologies in the framework of Hohm and Zwiebach’s classification of all order corrections compatible with O(d, d) symmetry
Mathematical modeling of the feather follicle morphogenetic wave in birds
No full textInternational audienceDuring the development of the avian skin, feather follicles are produced in a medio-lateral morphogenetic wave that results in their spatial arrangement in typical patterns. This wave involves the timely acquisition of pattern-forming competence followed by a row-by-row produc tion of feather follicles. While several mathematical models combining self-organizing systems accurately reproduced dynamics of feather follicle pattern formation, the events that control timely parameters of wave propagation remain poorly understood. Here, we built on previous modeling work to theoretically calculate the speed at which tissue competence progresses. Using a weakly non-linear analysis, we calculated the speed at which follicles emerge once competence is attained. We produced numerical simulations of our model to predict the respective influences of competence acquisition and follicle emergence on each other and on wave propagation. Our results show that the theoretical speed of follicle emergence is limited by competence acquisition, but that, in turn, competence acquisition is not constrained by follicle emergence. This modeling work provides an approximation of the timely parameters of the morphogenetic wave, and sheds light on the interplay between competence and patterning events in the developing skin
Contemporanéités du Parnasse contemporain. Contextualisation historique et réactualisation critique
No full textInternational audienceLe Parnasse contemporain. Recueil de vers nouveaux is a periodical anthology gathering three generations of poets, representative of new aesthetic orientations: it is a project by Catulle Mendès, financed by Louis-Xavier Ricard and published by Alphonse Lemerre in eighteen weekly issues, on Saturdays, from March 3rd to June 30th 1866. Henri Scepi and Seth Whidden propose the first critical edition of this editorial and poetical undertaking, restoring its seriality and updating, thanks to critical notes, its status as a turning point in the history of literature. Therefore, the contemporary reader has access to the poems as a 19th century reader and can, at the same time, grasp them in a historical critical perspective.Le Parnasse contemporain. Recueil de vers nouveaux est une anthologie périodique réunissant trois générations de poètes représentatifs de nouvelles orientations esthétiques : il s’agit d’un projet de Catulle Mendès, financé par Louis-Xavier Ricard et édité par Alphonse Lemerre en dix-huit livraisons hebdomadaires, le samedi, du 3 mars au 30 juin 1866. Henri Scepi et Seth Whidden proposent la première édition critique de cette entreprise éditoriale et poétique, en en restituant la sérialité et en en réactualisant, grâce aux notices critiques, le statut de tournant dans l’histoire littéraire. Le lecteur contemporain a donc accès aux poèmes comme un lecteur du xixe siècle et peut, en même temps, les saisir dans une perspective critique historique
Dissecting the Mechanism of Biosynthesis of Sulfurated Biomolecules: The Case of tRNA Sulfuration
No full textInternational audienceCONSPECTUS: Sulfuration of biomolecules is a crucial biochemical process responsible for producing essential organic cofactors, coenzymes, vitamins, and other sulfurated biomolecules. In particular, thiomodified nucleosides in tRNA play a key role in ensuring the accuracy and efficiency of genetic translation. Although sulfurating enzymes have been studied structurally and biochemically since the early 2000s, detailed mechanistic analyses remain limited. In particular, the importance of reductants used in catalytic assays is often underappreciated. In recent years, the use of anaerobic conditions has led to the discovery, in many of these enzymes, of an air-sensitive iron-sulfur cluster that is essential for catalysis. This led to the proposal of a catalytic mechanism involving a [4Fe-5S] intermediate, distinct from the previously accepted persulfide-based pathway. As this remains a debated topic, the current understanding of both mechanisms and the role of reductants warrants a critical evaluation. The sulfur atom for the reaction is usually extracted from cysteine by a cysteine desulfurase (CD) and then used as the sulfur source by sulfurating enzymes, as noted by E throughout the article. Two main E classes are distinguished by their catalytic centers:1. Class I Es use a key cysteinyl residue to form a persulfide intermediate. After deprotonation (pK a 6.2), the nucleophilic persulfide attacks the activated carbonyl group on the substrate, to form a disulfide (S-S) intermediate. To regenerate the active cysteinyl form and permit multiple turnovers, a two-electron reducing system is required. In vitro assays often use dithiothreitol (DTT) as the reductant. However, DTT can prematurely reduce persulfides into free hydrosulfide (HS -) that can itself react with substrates, complicating interpretation. Thus, DTT-containing assays may reflect sulfide-dependent rather than genuine persulfide-dependent catalysis.2. Class II Es contain a [4Fe-4S] cluster with a free coordination site that can bind sulfur donors such as persulfides to form a disulfide-containing iron-sulfur intermediate. A two-electron reducing system is again necessary to reduce the disulfide bond and generate a reactive [4Fe-5S] species capable of transferring sulfur to the substrate and supporting multiple turnovers.Thiocarboxylates are alternative sulfur donors that likewise require a two-electron reducing system for their formation.Without reductants, only one turnover is possible. In vitro, sodium sulfide can serve as a sulfur source by directly forming the [4Fe-5S] catalytic intermediate.Overall, both E classes critically depend on two-electron reducing systems to sustain catalytic cycling. The presence or absence of reductants strongly influences enzyme activity and mechanisms, so that in vitro results, especially those using nonphysiological reductants like DTT, should be interpreted with caution.Understanding the fundamental chemistry of Es is essential not only for elucidating their role in metabolism and cellular regulation but also for potential therapeutic targeting and biotechnological applications. A key remaining challenge is the identification of physiological reducing systems, a critical yet unresolved aspect of sulfuration biochemistry.</div
La connaissance métaphysique
No full textCe livre est la réédition par le Collège de France de l'ouvrage publié sous le même titre en 2011 (Collège de France/Fayard).International audienceOn avait proclamé la métaphysique archaïque ou dépassée. En fait, elle n'est jamais " morte ". Elle connaît même un renouveau international considérable, dont on est loin en France d'avoir pris encore la mesure. Parce qu'elle s'interroge, de la manière la plus générale et la plus précise à la fois, sur " ce qu'il y a ", elle est essentielle à toute entreprise de connaissance, entendue non comme la reconnaissance de vérités éternelles, mais comme une enquête sur le monde et la réalité.Aux antipodes du spiritualisme obscurantiste comme du relativisme postmoderne, Claudine Tiercelin expose ici le programme d'une métaphysique scientifique et réaliste, ancrée dans la tradition rationaliste