Showing results 181 to 200 on 1471 in total
Personalized medicine is defined by the National Cancer Institute as "a form of medicine that uses information about a person's genes, proteins, and environment to prevent, diagnose, and treat disease." In oncology, the term "personalized medicine" arose with the emergence of molecularly targeted agents. The prescription of approved molecularly targeted agents to cancer patients currently relies on the primary tumor location and histological subtype. Predictive biomarkers of efficacy of these modern agents have been exclusively validated in specific tumor types. A major concern today is to determine whether the prescription of molecularly targeted therapies based on tumor molecular abnormalities, independently of primary tumor location and histology, would improve the outcome of cancer patients. This new paradigm requires prospective validation before being implemented in clinical practice. In this communication, we will first review different designs, including observational cohorts, as well as nonrandomized and randomized clinical trials, that have been recently implemented to evaluate the relevance of this approach. We then focus on the SHIVA trial, a randomized proof-of-concept phase II trial comparing therapy based on tumL'inscription est gratuite mais obligatoire et doit se faire au plus tard le jeudi 28 septembre 2017 par courriel à stephanie.robert@chu-lyon.frecular profiling versus conventional therapy in patients with refractory cancer. We will present various aspects of implementation, underlying statistical and design questions, limits and strengths and review the results using this prism.
Depuis 2015, les avancées des technologies de séquençage PacBio et Oxford Nanopore ont bouleversé les projets de séquençages génomiques. Les chromosomes bactériens et les bras chromosomiques des génomes eucaryotes peuvent être assemblés en une seule séquence. La qualité des assemblages atteint si ce n'est dépasse les assemblages de références Sanger des années 2000, les centromères et télomères alors souvent non résolus deviennent désormais analysables. Les résultats sur plusieurs espèces de bactéries, champignons et plantes seront présentés afin d'illustrer les réussites de cette rupture technologique mais aussi les cas qui restent encore non parfaitement résolus.
Le séminaire présentera les trois axes de recherche en écologie évolutive et comportementale développés par Claire Doutrelant (CEFE, Montpellier). Le premier axe de recherche porte sur la variation spatio-temporelle et l'évolution des ornements colorés chez les oiseaux (en particulier chez les femelles). Le deuxième axe de recherche porte sur la coopération et la dynamique de populations d'une espèce d'oiseau à reproduction coopérative, le républicain social. Le 3ème axe porte sur l'évolution en milieu insulaire par des comparaisons de plusieurs espèces vivant en milieu insulaire et continental.
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Life on isolated oceanic islands often means life in the absence of (or at least with fewer) top predators and large herbivores. Such a change in prey-predator and plant-herbivore interactions likely translates into slackened natural selection on the animals and plants that are normally being eaten. One consequence is high population densities on islands. Another is that over evolutionary time island organisms lose their defenses against predation and herbivory. The extent to which similar dynamics underlie changes in host defenses against parasites (i.e., immune function) is less clear. The host-parasite interaction can be seen as ecologically analogous to prey-predator and plant-herbivore interactions, and some instances of island animals being hard hit by infectious diseases have been described. If the selective pressures imposed by parasites are reduced on islands compared to on continents and if immune defenses incur costs, then the immune system architecture is expected to differ between animal hosts on living on islands and continents. In my presentation, I will explore this hypothesis by reviewing current literature and examining the breadth and consistency of results. If the hypothesis is well supported, then changes in the immune system might be appropriately recognized as a physiological aspect of the island syndrome. I will end by introducing plans for a new direction in this line of research: an examination of immunological and physiological changes associated with the reverse island syndrome. Under this scenario, low or fluctuating population densities on islands, for example due to severe environmental variation, appears to lead to a reverse set of life history changes in island animals. To date, however, little is known about the interaction between parasites and hosts defenses in this system.
The theoretical investigation of how spatial structure affects the evolution of social behavior has mostly been done under the assumption that parent-offspring strategy transmission is perfect, i.e., for genetically transmitted traits, that mutation is very weak or absent. In this talk, we investigate the evolution of social behavior in structured populations under arbitrary mutation probabilities. We consider spatially structured populations of fixed size N, in which two types of individuals,A and B, corresponding to two types of social behavior, are competing. Under the assumption of small phenotypic differences (weak selection), we provide a formula for the expected frequency of type A individuals in the population, and deduce conditions for the long-term success of one strategy against another. We then illustrate this result with three common life-cycles (Wright-Fisher,Moran Birth-Death and Moran Death-Birth),and specific population structures. Qualitatively, we find that some life-cycles (Moran Birth-Death,Wright-Fisher, when social interactions affect fecundities) prevent the evolution of altruistic behavior, confirming previous results obtained with perfect strategy transmission. Imperfect strategy transmission also alters the balance between the benefits and costs of staying next to one's kin, leading to surprising results in subdivided populations, in that higher emigration probabilities can be favourable to the evolution of altruistic strategies.
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Normalization is essential to ensure accurate analysis and proper interpretation of sequencing data. Chromosome conformation data, such as Hi-C, is not different. The most widely used type of normalization of Hi-C data casts estimations of unwanted effects as a matrix balancing problem, relying on the assumption that all genomic regions interact as much as any other. Here, we show that these approaches, while very effective on fully haploid or diploid genome, fail to correct for unwanted effects in the presence of copy number variations. We propose a simple extension to matrix balancing methods that properly models the copy-number variation effects. Our approach can either retain the copy-number variation effects or remove it. We show that this leads to better downstream analysis of the three-dimensional organization of rearranged genome.
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Dans le cadre du projet France Médecine Génomique annoncé par le Premier ministre en juin 2016, deux projets pilotes de plateformes de séquençage très haut débit ont été retenues : les projets SeqOIA (Paris-Île-de-France) et AURAGEN (région Auvergne Rhône Alpes). Après quelques rappels sur le contexte du plan France Médecine génomique, le projet AURAGEN sera détaillé avec ses 5 axes : pré analytique, analytique, post analytique, médico-économique et formation. Il s'agit d'un projet de génomique qui sera inclus dans le parcours de soins des patients présentant une maladie rare ou un cancer. Nous présenterons également les projets pilotes en lien avec le plan France médecine génomique et les retombées attendues tant au niveau diagnostique que de la recherche.
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Sexual intimidation is frequent in humans, but its evolutionary origin remain speculative because few animal studies have investigated comparable, long-term forms of sexual violence. In our study, we focused on a population of wild chacma baboons and showed that males intimidate females to mate with them, and that sexual violence is the main source of injuries for females. Aggression and matings were found to be decoupled temporally, which may explain why some forms of sexual violence have been largely overlooked in well-studied animal populations. This study suggests that long-term sexual coercion may be widespread across mammalian societies, with important implications for understanding the evolution of mate choice and sexual conflict in mammals, as well as the origins of human sexual violence.
Yellow-bellied marmots (Marmota flaviventer) live in highly seasonal environments and have limited time for development and fat accumulation. An increase in body mass is a strong determinant of overwinter survival, thus immature marmots (juveniles and yearlings) starting the active season with low body mass may exhibit compensatory growth. Additionally, adults may exhibit accelerated fat accumulation to compensate for mass loss during hibernation. We investigated the potential costs of accelerated growth in a wild population of yellow-bellied marmots, using individual survival and longevity as proxies for fitness. Mass measurements from 2002-2015 were used to calculate individual seasonal growth rates. We estimated annual survival from 130 adults, 239 yearlings and 643 juveniles and longevity from 76 females. Individuals were distributed in two areas that differ in elevation, down- and up-valley, where the latter is an overall harsher environment. As results, juvenile survival increased with growth rate, with location and initial body mass changing the shape of this association. For yearlings, both location and initial body mass influenced the relationship between growth rate and survival. Yearlings exhibiting compensatory growth had had lower survival up-valley, and higher survival down-valley. No significant effect was found for longevity or adult annual survival. Thus, yearlings appear to represent the development stage in which the costs of rapid growth are the highest, and compensatory growth may be beneficial depending on the environmental conditions. Juveniles benefit from accelerated growth, which suggests that the conflicting demands of structural growth and fat accumulation vs. body maintenance may be less drastic at this developmental stage. Overall, the benefits and costs of rapid growth are age- and site- dependent and the costs of compensatory growth be seen in the short-term in this species, instead of paid later in life.
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