Melanoma, ancestralidad y variantes MC1R en la población mestizada uruguaya

Malignant melanoma (MM) is the most dangerous type of skin cancer and the main cause of death produced by skin diseases. In Uruguay, the incidence rate is 3.8/100,000, one of the highest in Latin America. We analyzed the contribution of ancestry and MC1R as a candidate gene for sporadic melanoma in Uruguay. Our objective wasto investigate the possible associations between ancestry and the MC1R gene with sporadic melanoma in the Uruguayan population. To that end, one hundred patients with sporadic MM and 107 controls were recruited. Phenotypic factors and lifestyle were evaluated as risk factors. At the same time, we analyzed fiveancestry informative markers, the MC1R variants (R151, R160 and D294H) and five tag-SNPs. Phototype, atypical nevi, sunburns and recreational exposure were the main risk factors for MM in the Uruguayan population. We confirmed 16q as a candidate region for MM. R151C, and R160W showed an important association with risk of melanoma (OR= 3.85, P= 1 x 10-2; OR= 10.15, P= 7 x 10-3, respectively). Furthermore, three novel MC1R haplotypes from the promoter region were detected,and the two most common haplotypes for the coding region were different to the ones found in Europeans through HapMap. However, MC1R coding region haplotypes revealed a highly similar frequency to that of the Spanish population. Our results showed that the chromosomal 16q region confers susceptibility to MM risk in the Uruguayan population. In addition, the admixed genome structure of the MC1R region could be part of the explanation of melanoma etiology.El melanoma maligno (MM) es uno de los más peligrosos, y la principal causa de muerte producida por tumores de piel. En el Uruguay, la tasa de incidencia es de 3,8/100.000, una de las más altas de América Latina. En este trabajo analizamos la ancestría y el gen candidato MC1R entre los pacientes con MM del Uruguay. Nuestro objetivo fue investigar la posible asociación entre ancestría y el gen MC1R en pacientes con melanoma esporádico en la población uruguaya. Con tal finalidad, se reclutaron 100 pacientes con MM esporádico y 107 controles. Se evaluó el riesgo de factores fenotípicos y de estilo de vida. Además se analizaron cinco marcadores informativos de ancesdencia, variantes del gen MC1R (R151, R160 y D294H) y cinco tagSNPs. El fototipo, los nevos atípicos, quemaduras solares y la exposición recreativa fueron los principales factores de riesgo para MM en la población uruguaya. La región cromosómica 16q es candidata para MM, mientras que R151C y R160W mostraron una importante asociación con el riesgo para MM (OR= 3,85, P= 1 x 10-2; OR= 10,15, P= 7 x 10-3, respectivamente). Por otra parte, se detectaron tres nuevos haplotipos en la región promotora y los dos haplotipos más frecuentes en la región codificante son diferentes a los encontrados en la población europea. Sin embargo, los haplotipos de la región codificante presentan una frecuencia muy similar a las encontradas en la población española. Los resultados muestran que la región cromosómica 16q confiere susceptibilidad al riesgo de MM en la población uruguaya. Por otra parte, la estructura genómica mestizada de la región del MC1R podría explicar la etiología del melanoma

Approche historique des classifications en psychiatrie

International audienceDès le milieu du siècle s'est posée la question des critères de classification des maladies. Pour les maladies mentales, diverses classifications ont alors été proposées par des auteurs français (Morel) et allemands (Kahlbaum, Kraepelin). À partir de la fin du siècle, le Bureau International de Statistique (Paris) a publié à une Classification Internationale des Maladies, à révision décennale (J. Bertillon). Cette tâche a été poursuivie dans l'entre-deux-guerres par le Bureau de Santé de la Société des Nations (Genève) puis, après la Seconde Guerre mondiale, par l'OMS à partir de la 5 édition. Un chapitre spécial V (F) a ensuite été réservé aux troubles mentaux. Plusieurs classifications nationales ont été révisées et modifiées pour établir des concordances avec les successives éditions de la CIM, et en particulier, dans le domaine de la psychiatrie infanto-juvénile, la Classification Française des Troubles Mentaux de l'Enfant et de l'Adolescent dans sa version 2010

BLISS: an artificial language for learnability studies

To explore neurocognitive mechanisms underlying the human language faculty, cognitive scientists use artificial languages to control more precisely the language learning environment and to study selected aspects of natural languages. Artificial languages applied in cognitive studies are usually designed ad hoc, to only probe a specific hypothesis, and they include a miniature grammar and a very small vocabulary. The aim of the present study is the construction of an artificial language incorporating both syntax and semantics, BLISS. Of intermediate complexity, BLISS mimics natural languages by having a vocabulary, syntax, and some semantics, as defined by a degree of non-syntactic statistical dependence between words. We quantify, using information theoretical measures, dependencies between words in BLISS sentences as well as differences between the distinct models we introduce for semantics. While modeling English syntax in its basic version, BLISS can be easily varied in its internal parametric structure, thus allowing studies of the relative learnability of different parameter sets

Autisme, psychose précoce, troubles envahissants du développement

International audienceDans la nouvelle version de la classification française des troubles mentaux de l'enfant et de l'adolescent (CFTMEA-R2010), la notion de psychose précoce a été conservée dans le cadre de la catégorie "Troubles envahissants du développement (TED)", définis par les classifications internationales (DSM-IV et CIM-10). Au sein des TED, les catégories diagnostiques "Psychose précoce déficitaire" ("retard mental avec troubles autistiques ou psychotiques") et "Dysharmonie Multiple et Complexe du Développement (MCDD) -Dysharmonie psychotique", restent individualisées. Un effort particulier a été fait pour faciliter les correspondances entre ces catégories diagnostiques de la CFTMEA-R2010 et de la CIM-10, en vue du relevé informatisé d'activité (RIM-Psy) et des travaux de recherche internationaux

ADP-ribosylation of arginine

Arginine adenosine-5′-diphosphoribosylation (ADP-ribosylation) is an enzyme-catalyzed, potentially reversible posttranslational modification, in which the ADP-ribose moiety is transferred from NAD+ to the guanidino moiety of arginine. At 540 Da, ADP-ribose has the size of approximately five amino acid residues. In contrast to arginine, which, at neutral pH, is positively charged, ADP-ribose carries two negatively charged phosphate moieties. Arginine ADP-ribosylation, thus, causes a notable change in size and chemical property at the ADP-ribosylation site of the target protein. Often, this causes steric interference of the interaction of the target protein with binding partners, e.g. toxin-catalyzed ADP-ribosylation of actin at R177 sterically blocks actin polymerization. In case of the nucleotide-gated P2X7 ion channel, ADP-ribosylation at R125 in the vicinity of the ligand-binding site causes channel gating. Arginine-specific ADP-ribosyltransferases (ARTs) carry a characteristic R-S-EXE motif that distinguishes these enzymes from structurally related enzymes which catalyze ADP-ribosylation of other amino acid side chains, DNA, or small molecules. Arginine-specific ADP-ribosylation can be inhibited by small molecule arginine analogues such as agmatine or meta-iodobenzylguanidine (MIBG), which themselves can serve as targets for arginine-specific ARTs. ADP-ribosylarginine specific hydrolases (ARHs) can restore target protein function by hydrolytic removal of the entire ADP-ribose moiety. In some cases, ADP-ribosylarginine is processed into secondary posttranslational modifications, e.g. phosphoribosylarginine or ornithine. This review summarizes current knowledge on arginine-specific ADP-ribosylation, focussing on the methods available for its detection, its biological consequences, and the enzymes responsible for this modification and its reversal, and discusses future perspectives for research in this field

Impact of Diabetes on Postinfarction Heart Failure and Left Ventricular Remodeling

Diabetes mellitus, the metabolic syndrome, and the underlying insulin resistance are increasingly associated with diastolic dysfunction and reduced stress tolerance. The poor prognosis associated with heart failure in patients with diabetes after myocardial infarction is likely attributable to many factors, important among which is the metabolic impact from insulin resistance and hyperglycemia on the regulation of microvascular perfusion and energy generation in the cardiac myocyte. This review summarizes epidemiologic, pathophysiologic, diagnostic, and therapeutic data related to diabetes and heart failure in acute myocardial infarction and discusses novel perceptions and strategies that hold promise for the future and deserve further investigation

Analogical cognition: an insight into word meaning

Analogical cognition, extensively researched by Dedre Gentner and her colleagues over the past thirty five years, has been described as the core of human cognition, and it characterizes our use of many words. This research provides significant insight into the nature of word meaning, but it has been ignored by linguists and philosophers of language. I discuss some of the implications of the research for our account of word meaning. In particular, I argue that the research points to, and helps account for, a key explanatory role that linguistic meaning must play. The research also shows how words contribute to thought as opposed to merely being a means of conveying thought