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Rnf111 has a pivotal role in regulating development of definitive hematopoietic stem and progenitor cells through the Smad2/3-Gcsfr/NO axis in zebrafish
No full textInternational audienceThe ubiquitination or SUMOylation of hematopoietic related factors plays pivotal roles in hematopoiesis. RNF111, known as a ubiquitin ligase (Ubl), is a newly discovered SUMO-targeted ubiquitin ligase (STUbl) involved in multiple signaling pathways mediated by TGF-β family members. However, its role in hematopoiesis remains unclear. Herein, a heritable Rnf111 mutant zebrafish line was generated by CRISPR/Cas9-mediated genome editing. Impaired hematopoietic stem and progenitor cells (HSPC) of definitive hematopoiesis was found in Rnf111 deficient mutants. Ablation of Rnf111 resulted in decreased phosphorylation of Smad2/3 in HSPC. Definitive endoderm 2 inducer (IDE2), which specifically activates TGF-β signaling and downstream Smad2 phosphorylation, can restore the definitive hematopoiesis in Rnf111-deficient embryos. Further molecular mechanism studies revealed that Gcsfr/NO signaling was an important target pathway of Smad2/3 involved in Rnf111-mediated HSPC development. In conclusion, our study demonstrated that Rnf111 contributes to the development of HSPC by maintaining Smad2/3 phosphorylation and the Gcsfr/NO signaling pathway activation. Keywords: Rnf111, Ubiquitin ligase (UbL), HSPC, Smad2/3, Gcsfr/N
Pic de Drude déplacé par les corrections de vertex π-ton
No full textInternational audienceCorrelated electron systems often show strong bosonic fluctuations, e.g., of antiferromagnetic nature, around a large wave vector such as q = (π, π . . .). These fluctuations can give rise to vertex corrections to the optical conductivity through the (transversal) particle-hole channel, coined π -ton contributions. Previous numerical results differed qualitatively on how such vertex corrections alter the optical conductivity. Here we clarify that π -ton vertex corrections lead to a displaced Drude peak, by studying the weakly correlated regime of a onedimensional single-orbital Hubbard model. The proximity and enhancement of the effect when approaching a phase transition of, e.g., antiferromagnetic nature can be utilized for discriminating π -tons in experiments from other physics leading to a displaced Drude peak.Les systèmes électroniques corrélés présentent souvent de fortes fluctuations bosoniques, par exemple de nature antiferromagnétique, autour d'un grand vecteur d'onde tel que q = (π, π . . .). Ces fluctuations peuvent donner lieu à des corrections de vertex à la conductivité optique par le biais du canal (transversal) particule-trou, appelées contributions π -ton. Les résultats numériques précédents différaient qualitativement sur la manière dont ces corrections de vertex modifient la conductivité optique. Nous clarifions ici que les corrections de vertex π -ton conduisent à un pic de Drude déplacé, en étudiant le régime faiblement corrélé d'un modèle Hubbard à une bande unidimensionnel. La proximité et l'amplification de l'effet à l'approche d'une transition de phase, par exemple de nature antiferromagnétique, peuvent être utilisées pour distinguer les π -tons dans les expériences d'autres phénomènes physiques conduisant à un pic de Drude déplacé
Specialized replication mechanisms maintain genome stability at human centromeres
No full textInternational audienceThe high incidence of whole-arm chromosome aneuploidy and translocations in tumors suggests an intrinsic instability of centromeres, unique chromosomal loci built on large stretches of repetitive sequences that are essential for chromosome separation. The causes behind this fragility and the molecular mechanisms acting to preserve centromere integrity remain elusive. Here, we show that replication stress, a hallmark of pre-cancerous and cancer lesions, promotes non-random breakage of repetitive centromeres in mitosis due to spindle forces and endonuclease activities.Mechanistically, we unveil that the centromeric replisome follows a finely tuned replication dynamics that is distinct from the rest of the genome. By locus-specific proteomics we identify specialized DNA replication and repair proteins acting at centromeres, suggesting that these sites are difficult-to replicate regions. Some of these factors, among which is the translesion synthesis pathway, act to sustain normal centromere replication and to maintain their integrity. Finally, we show that prolonged replication stress causes centromeric alterations. Accordingly, we find centromere ruptures and whole-arm chromosome translocations in a panel of ex-vivo patientderived ovarian cancer models, known to suffer from replication stress. Our results provide an unprecedented molecular view on how centromeres are replicated and their integrity is preserved and propose a mechanism on the cause of centromere alterations that give rise to abnormal karyotypes in cancer.</div
Voile sur les villes, briques sur le Nil : au Soudan, la construction en terre crue du Néolithique… à nos jours !
No full textInternational audienceDans la vallée du Nil, on construit en terre depuis le Néolithique. Vestiges archéologiques et architecture locale sont les témoins de la façon dont on gère et sélectionne cette ressource au fil des millénaires. Aujourd’hui, les matériaux industriels, les grands projets d’infrastructures et les changements environnementaux remettent pourtant en cause les pratiques traditionnelles
Athènes était-elle la cité d'Athéna ?: Les Douze dieux et autres configurations divines. Nouvelle histoire d'Athènes. La cité vue de l'Agora, Ve-IVe siècle av. J.-C. Siron, Nicolas, Perrin, pp.235-255, 2024, 9782262103439.
No full textInternational audienceLe monde grec est plein de dieux et Athènes n’échappe pas à ce constat. Athéna, déesse éponyme, joue un rôle important dans la protection de la cité, mais elle n’est jamais seule à le faire. Même sur l’Acropole où elle reçoit plusieurs cultes, Zeus et Poséidon l’accompagnent. En contrebas, sur l’Agora, l’autel des Douze dieux construit par les Pisistratides en 522 offre l’image d’une configuration divine alliant l’unité du groupe divin à la multiplicité de ses composantes. Ce monument est un bel exemple de la plasticité du polythéisme et des combinaisons qui s’y rejouent sans cesse, entre le singulier et le pluriel, que ce soit dans les récits ou dans les cultes
Force balance of opposing diffusive motors generates polarity-sorted microtubule patterns
No full textInternational audienceThe internal organization of cells is largely determined by the architecture and orientation of the microtubule network. Microtubules serve as polar tracks for the selective transport of specific molecular motors toward either their plus or minus ends. How both motors reciprocally move microtubules and organize the network’s arrangement and polarity is unknown. Here, we combined experiments on reconstituted systems and theory to study the interaction of microtubules with both plus- and minus-end directed motors bound to a fluid membrane. Depending on motor concentrations, the system could lead either to the constant transport of microtubules or to their alignment, stacking, and immobilization in regular bands that separate motors into domains of opposite polarities. In bands, microtubules shared the same polarity and segregated the two opposing motors accordingly. These regular patterns resulted from the balance of forces produced by the two motors as they walked in opposite directions along microtubules. The system was maintained in a dynamic steady state in which the directional transport of microtubule-bound motors compensates for the random diffusion of lipid-bound motors. The size of motor domains depended on their respective concentrations. The constant flow of motors allowed the system to respond to variations in motor concentrations by moving microtubules to adapt to the new force balance. The polar sorting and linear arrangement of microtubules associated with the segregation of motors of opposite polarity are typical of cellular architectures, which these data may help to better understand
Depositional and cultural contexts of Late Pleistocene Homo sapiens fossils from Rabat-Témara caves in Morocco
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Constraining the chronology of glacial fluctuations in the upper Garonne basin through multimethod dating of Pleistocene fluvioglacial sequences
No full textInternational audience•Maximum phases of glacial expansion are well documented in the Pyrenees but understanding the behavior of former glaciers during the interstadial periods remains limited. To address this gap, we focused on the upper Garonne Valley, integrating our own mapping and chronological data from glacial and fluvioglacial deposits with previous studies on terraces and moraines. This approach provides new insights into the Pleistocene chronology of Pyrenean glacial fluctuations.•Our research employed four dating methods, including OSL, ESR, 14C, and 10Be, to date Pleistocene fluvio-glacial sequences and glacial erratic boulders. This multi-method approach allowed to discuss potential methodological issues and establish the chronology of fluvial aggradation and incision phases in a proglacial context from the Late Pleistocene to the Holocene. Bayesian modeling, guided by relative stratigraphy, helped us to statistically identify specific events for each aggradation phase.•Key findings include the precise chronological constraints on terrace levels, such as Fx which aggraded during MIS6 and can be linked to an external moraine dated at 124.3 ± 10.3 ka. Terrace levels from the Fy generation were identified during MIS5, MIS3, and MIS2. The Bayesian model favored OSL ages due to their consistency with relative stratigraphy, highlighting somehow poor bleaching conditions for ESR measurements in a proglacial context.•These results prompted a reassessment of terrace chronology based on previous 10Be vertical profiles. We identified a major glacial expansion during MIS6, forming external moraines and terrace Fx, followed by retreat and incision and then a subsequent advance during the Late Pleistocene, corresponding to the Local Last Glacial Maximum, forming terraces Fya and Fyb. While the glacier front during the LLGM remains unspecified, a new glacial advance at the end of MIS3 formed the terrace level Fyc. Radiocarbon dating indicated terrace Fyd, formed during the MIS2, served as a floodplain until the mid-Holocene.•This multi-method dating approach precisely constrains Pleistocene fluvial sequences in a proglacial context, shedding light on local glacier impacts on river systems. Future data in the lower Garonne and the Ariege will further elucidate how glacial fluctuations affected downstream fluvial dynamics
