Calcium Independent Effect of Orai1 and STIM1 in Non-Hodgkin B Cell Lymphoma Dissemination

International audienceCa 2+ release-activated Ca 2+ channels, composed of Orai1 and STIM1 (stromal interaction molecule 1) proteins, are the main Ca 2+ entry mechanism in lymphocytes. Their role in cell migration and metastasis is demonstrated in solid cancers but it remains elusive in malignant hemopathies. Diffuse large B cell lymphoma (DLBCL) is characterized by the dissemination of neoplastic B cells throughout the organism which is under the control of chemokines such as Stromal Derived Factor 1 (SDF-1) and its receptor CXCR4. CXCR4 activation triggers a complex intracellular signaling including an increase in intracellular Ca 2+ concentration whose role is still unclear. Using pharmacological and genetic approaches, we revealed that STIM1 and Orai1 were responsible for Ca 2+ influx induced by SDF-1. Furthermore, we provide in vitro and in vivo evidence that they are necessary for basal or SDF-1-induced DLBCL cell migration which is independent of Ca 2+ entry. We identify that they act as effectors coupling RhoA and ROCK dependent signaling pathway to MLC2 phosphorylation and actin polymerization. Finally, we revealed an alteration of Orai1 and STIM1 expression in extra-nodal DLBCL. Thus, we discovered a novel Ca 2+-independent but Orai1 and STIM1-dependent signaling pathway involved in basal and CXCR4 dependent cell migration, which could be relevant for DLBCL physiopathology

MED12 Alterations in Both Human Benign and Malignant Uterine Soft Tissue Tumors

The relationship between benign uterine leiomyomas and their malignant counterparts, i.e. leiomyosarcomas and smooth muscle tumors of uncertain malignant potential (STUMP), is still poorly understood. The idea that a leiomyosarcoma could derive from a leiomyoma is still controversial. Recently MED12 mutations have been reported in uterine leiomyomas. In this study we asked whether such mutations could also be involved in leiomyosarcomas and STUMP oncogenesis. For this purpose we examined 33 uterine mesenchymal tumors by sequencing the hot-spot mutation region of MED12. We determined that MED12 is altered in 66.6% of typical leiomyomas as previously reported but also in 11% of STUMP and 20% of leiomyosarcomas. The mutated allele is predominantly expressed in leiomyomas and STUMP. Interestingly all classical leiomyomas exhibit MED12 protein expression while 40% of atypical leiomyomas, 50% of STUMP and 80% of leiomyosarcomas (among them the two mutated ones) do not express MED12. All these tumors without protein expression exhibit complex genomic profiles. No mutations and no expression loss were identified in an additional series of 38 non-uterine leiomyosarcomas. MED12 mutations are not exclusive to leiomyomas but seem to be specific to uterine malignancies. A previous study has suggested that MED12 mutations in leiomyomas could lead to Wnt/β-catenin pathway activation however our immunohistochemistry results show that there is no association between MED12 status and β-catenin nuclear/cytoplasmic localization. Collectively, our results show that subgroups of benign and malignant tumors share a common genetics. We propose here that MED12 alterations could be implicated in the development of smooth muscle tumor and that its expression could be inhibited in malignant tumors

Evaluación de competencias en lengua francesa conforme al Marco Común Europeo de Referencia para las lenguas (IIª fase)

Memoria ID12-0229. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2012-2013

Futuros filólogos (2): competencias digitales en tratamiento de textos y enseñanza de idiomas

Memoria ID-0098. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2014-2015

Genetic diversity, linkage disequilibrium and power of a large grapevine (Vitis vinifera L) diversity panel newly designed for association studies

UMR-AGAP Equipe DAVV (Diversité, adaptation et amélioration de la vigne) ; équipe ID (Intégration de Données)International audienceAbstractBackgroundAs for many crops, new high-quality grapevine varieties requiring less pesticide and adapted to climate change are needed. In perennial species, breeding is a long process which can be speeded up by gaining knowledge about quantitative trait loci linked to agronomic traits variation. However, due to the long juvenile period of these species, establishing numerous highly recombinant populations for high resolution mapping is both costly and time-consuming. Genome wide association studies in germplasm panels is an alternative method of choice, since it allows identifying the main quantitative trait loci with high resolution by exploiting past recombination events between cultivars. Such studies require adequate panel design to represent most of the available genetic and phenotypic diversity. Assessing linkage disequilibrium extent and panel power is also needed to determine the marker density required for association studies.ResultsStarting from the largest grapevine collection worldwide maintained in Vassal (France), we designed a diversity panel of 279 cultivars with limited relatedness, reflecting the low structuration in three genetic pools resulting from different uses (table vs wine) and geographical origin (East vs West), and including the major founders of modern cultivars. With 20 simple sequence repeat markers and five quantitative traits, we showed that our panel adequately captured most of the genetic and phenotypic diversity existing within the entire Vassal collection. To assess linkage disequilibrium extent and panel power, we genotyped single nucleotide polymorphisms: 372 over four genomic regions and 129 distributed over the whole genome. Linkage disequilibrium, measured by correlation corrected for kinship, reached 0.2 for a physical distance between 9 and 458 Kb depending on genetic pool and genomic region, with varying size of linkage disequilibrium blocks. This panel achieved reasonable power to detect associations between traits with high broad-sense heritability (> 0.7) and causal loci with intermediate allelic frequency and strong effect (explaining > 10 % of total variance).ConclusionsOur association panel constitutes a new, highly valuable resource for genetic association studies in grapevine, and deserves dissemination to diverse field and greenhouse trials to gain more insight into the genetic control of many agronomic traits and their interaction with the environment

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

La place des femmes dans le vignoble bordelais

Les femmes sont massivement entrées, en France, dans le monde du travail après la Seconde Guerre mondiale, continuant à participer à « l’effort de guerre ». Pendant la période de guerre, il vaut mieux parler d’une entrée par défaut puisqu’elles se substitueront aux hommes absents. En réalité, il faudra attendre les trente glorieuses pour qu’elles y trouvent véritablement une place (Battagliola, 2004). Il ne s’agira pas d’y prendre une place à part entière où elles auraient exprimé la totalité..

La vigne, le vin et la ville. Expériences bordelaises d'une trilogie vécue

The vineyard, wine and the city. experiments of Bordeaux of a lived trilogy. Bordeaux, a city which bears the name of wine, a wine which bears the name of a city, this close alliance born in Antiquity and which has developed along the centuries, is still the world capital of wine to this day. In this article, we will try to understand, going beyond the traditional clichés, how wine-producing and winegrowing activities take up the urban space and how local actors have used this spatial capital to build an attractive image of Bordeaux and its wine. We will also attempt to show how public and private actions contribute to making living the city truly exceptional.Bordeaux, ville qui porte un nom de vin, vin qui porte un nom de ville, cette alliance intime, née dès l'Antiquité, construite au fil des siècles, se maintient aujourd'hui encore, alors que Bordeaux affirme, malgré la crise d'une partie de son vignoble, son rôle de capitale mondiale du vin. Mais au-delà des clichés couramment véhiculés, nous découvrons quelles formes prennent, dans l'espace urbain, les activités vitivinicoles et comment les acteurs locaux utilisent ce capital spatial pour construire l'image vivante d'une ville qui se définit, en partie, par ses vins. Enfin, au fil de ce travail, nous montrons comment des actions tant publiques que privées contribuent à la construction d'un vécu de la ville singulier, riche de représentations vitivinicoles.La vina, el vino y la ciudad. experiencia Bordelesa de la vivencia de una trilogía. Burdeos, ciudad que lleva un nombre de vino, vino que ¡leva un nombre de ciudad. Esta alianza íntima, nacida desde la Antigüedad, construida con los siglos, sigue manteniéndose todavía, mientras que Burdeos afirma, a pesar de la crisis de una parte de sus viñedos, su papel de capital mundial del vino. Pero más allá de los clichés habituales, descubrimos qué formas toman en el espacio urbano, las actividades vitivinícolas y cómo los actores locales utilizan ese capital espacial para construir la imagen viva de una ciudad que se define, en parte, por sus vinos. En este trabajo se comprueba cómo las acciones tanto públicas como privadas contribuyen a la construcción de una vivencia de la ciudad, singular, rica de representaciones vitivinícolas.Kociemba Valérie, Roy Charlotte, Vélasco-Graciet Hélène. La vigne, le vin et la ville. Expériences bordelaises d'une trilogie vécue. In: Sud-Ouest européen, tome 22, 2006. Vivre la ville, vivre Bordeaux (Coordonné par Guy Di Méo) pp. 13-25