Organization and post-transcriptional processing of focal adhesion kinase gene

BACKGROUND: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase critical for processes ranging from embryo development to cancer progression. Although isoforms with specific molecular and functional properties have been characterized in rodents and chicken, the organization of FAK gene throughout phylogeny and its potential to generate multiple isoforms are not well understood. Here, we study the phylogeny of FAK, the organization of its gene, and its post-transcriptional processing in rodents and human. RESULTS: A single orthologue of FAK and the related PYK2 was found in non-vertebrate species. Gene duplication probably occurred in deuterostomes after the echinoderma embranchment, leading to the evolution of PYK2 with distinct properties. The amino acid sequence of FAK and PYK2 is conserved in their functional domains but not in their linker regions, with the absence of autophosphorylation site in C. elegans. Comparison of mouse and human FAK genes revealed the existence of multiple combinations of conserved and non-conserved 5'-untranslated exons in FAK transcripts suggesting a complex regulation of their expression. Four alternatively spliced coding exons (13, 14, 16, and 31), previously described in rodents, are highly conserved in vertebrates. Cis-regulatory elements known to regulate alternative splicing were found in conserved alternative exons of FAK or in the flanking introns. In contrast, other reported human variant exons were restricted to Homo sapiens, and, in some cases, other primates. Several of these non-conserved exons may correspond to transposable elements. The inclusion of conserved alternative exons was examined by RT-PCR in mouse and human brain during development. Inclusion of exons 14 and 16 peaked at the end of embryonic life, whereas inclusion of exon 13 increased steadily until adulthood. Study of various tissues showed that inclusion of these exons also occurred, independently from each other, in a tissue-specific fashion. CONCLUSION: The alternative coding exons 13, 14, 16, and 31 are highly conserved in vertebrates and their inclusion in mRNA is tightly but independently regulated. These exons may therefore be crucial for FAK function in specific tissues or during development. Conversely pathological disturbance of the expression of FAK and of its isoforms could lead to abnormal cellular regulation

Sciences, politiques institutionnelles et public

Pietro Corsi, directeur d’étudesJean-Marc Drouin, professeur au Muséum national d’histoire naturelle Le séminaire a été consacré à un examen détaillé des débats sur les systèmes de classification au XVIIIe siècle, et en particulier sur les conceptions de l’histoire naturelle proposées par Linné et Buffon. Thierry Hoquet, maître de conférences à l’Université Paris-X, auteur de plusieurs ouvrages sur Buffon, a été associé à nos travaux, ainsi que plusieurs collègues qui travaillent sur l’histoi..

Sciences, politiques institutionnelles et public

Pietro Corsi, directeur d’étudesJean-Marc Drouin, professeur au Muséum national d’histoire naturelleThierry Hoquet, maître de conférences à l’Université Paris-X Acteurs et pratiques de l’histoire naturelle. Les transformations de la vie (1800-1858) Le séminaire a proposé un itinéraire dans les courants profonds de l’évolutionnisme européen. Ce parcours s’arrête en 1858, et sera poursuivi en 2008-2009 par une étude approfondie de l’année 1859 et des travaux de Darwin envisagés sous leurs nombr..

Sciences, politiques institutionnelles et public

Pietro Corsi, directeur d’étudesJean-Marc Drouin, professeur au Muséum national d’histoire naturelleThierry Hoquet, maître de conférences à l’Université Paris-X/Nanterre Acteurs et pratiques de l’histoire naturelle. Les transformations de la vie (1858-1900) Le séminaire « Acteurs et pratiques de l’histoire naturelle » a proposé un itinéraire dans les courants profonds de l’évolutionnisme européen. Dans le séminaire de l’année 2007-2008, ce parcours s’est achevé avec la présentation à la Linne..

Sciences, politiques institutionnelles et public

Pietro Corsi, directeur d’études avec Jean-Marc Drouin, maître de conférences au Muséum national d’histoire naturelle et Georges Métailié, directeur de recherche au CNRS Compte rendu non communiqué

Sciences, politiques institutionnelles et public

Pietro Corsi, directeur d’étudesJean-Marc Drouin, professeur au Muséum national d’histoire naturelleThierry Hoquet, maître de conférences à l’Université Paris-X Acteurs et pratiques de l’histoire naturelle. Les transformations de la vie (1800-1858) Le séminaire a proposé un itinéraire dans les courants profonds de l’évolutionnisme européen. Ce parcours s’arrête en 1858, et sera poursuivi en 2008-2009 par une étude approfondie de l’année 1859 et des travaux de Darwin envisagés sous leurs nombr..

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM