La longue séquence pliocène de Marchésieux - Résultats analytiques et premiers résultats

National audienceLe sondage intégralement carotté de Marchésieux a permis d'atteindre l'objectif fixé dans le projet AR42 du BRGM : l'analyse paléoclimatique du premier épisode glaciaire de l'hémisphère nord (Prétiglien, -2,4 Ma) et probablement le premier rafraîchissement de -3,1 Ma. Les 159,3 m de sédiments datés du Reuvérien et du Prétiglien ont déjà livré une quantité importante d'informations aussi bien climatiques que paléoenvironnementales. De par sa position géographique privilégiée et de par son environnement côtier, la "Longue sequence" de Marchésieux a précisé les modalités de la séquence de dégradation climatique en milieu continental et marin à nos latitudes moyennes. La méthodologie fortement pluridisciplinaire, le plus souvent il très haute résolution, permet d'affiner notablement les modalités de la réponse de chaque environnement au changement climatique, et apparaît, en ce sens, beaucoup plus riche que les études monodisciplinaires classiques. Ainsi, les réponses zoologiques, phytosociologiques, sedimentologiques et géochimiques au stimulus climatique externe peuvent être comparées et calibrées

Missense variant contribution to USP9X-female syndrome

USP9X is an X-chromosome gene that escapes X-inactivation. Loss or compromised function of USP9X leads to neurodevelopmental disorders in males and females. While males are impacted primarily by hemizygous partial loss-of-function missense variants, in females de novo heterozygous complete loss-of-function mutations predominate, and give rise to the clinically recognisable USP9X-female syndrome. Here we provide evidence of the contribution of USP9X missense and small in-frame deletion variants in USP9X-female syndrome also. We scrutinise the pathogenicity of eleven such variants, ten of which were novel. Combined application of variant prediction algorithms, protein structure modelling, and assessment under clinically relevant guidelines universally support their pathogenicity. The core phenotype of this cohort overlapped with previous descriptions of USP9X-female syndrome, but exposed heightened variability. Aggregate phenotypic information of 35 currently known females with predicted pathogenic variation in USP9X reaffirms the clinically recognisable USP9X-female syndrome, and highlights major differences when compared to USP9X-male associated neurodevelopmental disorders.Lachlan A. Jolly … Alison E. Gardner, Mark A. Corbett, Luis A. Pérez-Jurado, Marie Shaw … Jozef Gec

Genomic and phenotypic characterization of 404 individuals with neurodevelopmental disorders caused by CTNNB1 variants

Purpose: Germline loss-of-function variants in CTNNB1 cause neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV; OMIM 615075) and are the most frequent, recurrent monogenic cause of cerebral palsy (CP). We investigated the range of clinical phenotypes owing to disruptions of CTNNB1 to determine the association between NEDSDV and CP. Methods: Genetic information from 404 individuals with collectively 392 pathogenic CTNNB1 variants were ascertained for the study. From these, detailed phenotypes for 52 previously unpublished individuals were collected and combined with 68 previously published individuals with comparable clinical information. The functional effects of selected CTNNB1 missense variants were assessed using TOPFlash assay. Results: The phenotypes associated with pathogenic CTNNB1 variants were similar. A diagnosis of CP was not significantly associated with any set of traits that defined a specific phenotypic subgroup, indicating that CP is not additional to NEDSDV. Two CTNNB1 missense variants were dominant negative regulators of WNT signaling, highlighting the utility of the TOPFlash assay to functionally assess variants. Conclusion: NEDSDV is a clinically homogeneous disorder irrespective of initial clinical diagnoses, including CP, or entry points for genetic testing.Sayaka Kayumi, Luis A. Perez-Jurado, María Palomares, Sneha Rangu, Sarah E. Sheppard, Wendy K. Chung, Michael C. Kruer, Mira Kharbanda, David J. Amor, George McGillivray, Julie S. Cohen, Sixto García-Minaúr, Clare L. van Eyk, Kelly Harper, Lachlan A. Jolly, Dani L. Webber, Christopher P. Barnett, Fernando Santos-Simarro, Marta Pacio-Míguez, Angela del Pozo, Somayeh Bakhtiari, Matthew Deardorff, Holly A. Dubbs, Kosuke Izumi, Katheryn Grand, Christopher Gray, Paul R. Mark, Elizabeth J. Bhoj, Dong Li, Xilma R. Ortiz-Gonzalez, Beth Keena, Elaine H. Zackai, Ethan M. Goldberg, Guiomar Perez de Nanclares, Arrate Pereda, Isabel Llano-Rivas, Ignacio Arroyo, María Angeles Fernandez-Cuesta, Christel Thauvin-Robinet, Laurence Faivre, Aurore Garde, Benoit Mazel, Ange-Line Bruel, Michael L. Tress, Eva Brilstra, Amena Smith Fine, Kylie E. Crompton, Alexander P.A. Stegmann, Margje Sinnema, Servi C.J. Stevens, Joost Nicolai, Gaetan Lesca, Laurence Lion-Francois, Damien Haye, Nicolas Chatron, Amelie Piton, Mathilde Nizon, Benjamin Cogne, Siddharth Srivastava, Jennifer Bassetti, Candace Muss, Karen W. Gripp, Rebecca A. Procopio, Francisca Millan, Michelle M. Morrow, Melissa Assaf, Andres Moreno-De-Luca, Shelagh Joss, Mark J. Hamilton, Marta Bertoli, Nicola Foulds, Shane McKee, Alastair H. MacLennan, Jozef Gecz, Mark A. Corbet

Combination of searches for Higgs boson decays into a photon and a massless dark photon using pp collisions at √s = 13 TeV with the ATLAS detector

A combination of searches for Higgs boson decays into a visible photon and a massless dark photon (H → γγd) is presented using 139 fb−1 of proton-proton collision data at a centre-of-mass energy of √s = 13 TeV recorded by the ATLAS detector at the Large Hadron Collider. The observed (expected) 95% confidence level upper limit on the Standard Model Higgs boson decay branching ratio is determined to be B(H → γγd) < 1.3% (1.5)%. The search is also sensitive to higher-mass Higgs bosons decaying into the same final state. The observed (expected) 95% confidence level limit on the cross-section times branching ratio ranges from 16 fb (20 fb) for mH = 400 GeV to 1.0 fb (1.5 fb) for mH = 3 TeV. Results are also interpreted in the context of a minimal simplified model