Affichage des résultats 1061 à 1080 sur 1579 au total
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After a brief introduction to algorithmic complexity and some examples of graph problems in biology, I will present the formalism and algorithm we developed for the large-scale reconstruction of a signalling network, based on protein-protein interaction and transcriptomics data. The model we developed in consisted in modeling this reconstruction as a combinatorial optimization problem called the "Prize-collecting Steiner tree problem", and our algorithm, was applied to the reconstruction of the pheromone pathway in S. cerevisiae, with results that we were able to verify experimentally.
Some trypanosomatids harbor a symbiotic bacterium, which maintains a close association with the host, constituting an excellent model to study organelle origin and cellular evolution. Molecular data show that all endosymbiont containing trypanosomatids are grouped together in a single phylogenetic branch. Endosymbionts of different species are similar, being classified in the beta division of Proteobacteria, thus suggesting that a single evolutionary event gave rise to the symbiosis in the Trypanosomatidae family. The bacterium is enclosed by two unit membranes and presents a reduced peptidoglycan layer, which is essential for cell division and morphological maintenance. Regarding the protein composition, the number of intramembrane particles in the endosymbiont envelope is similar to that described for Gram-negative bacteria. Lipid analyses of purified endosymbionts show absence of sterols and indicate phosphatidylcholine as a major component of the envelope, as described in other intracellular bacteria. The endosymbiont promotes ultrastructural and physico-chemical alterations in the trypanosomatid and its presence influences the protozoan interaction with the insect host and mammalian cells. Symbiont-containing trypanosomatids are able to infect and to replicate inside fibroblasts and macrophages, whose microbicidal activity was deactivated by HIV-1 infection. The symbiosis in trypanosomatids is characterized by intensive metabolic exchanges; the bacterium contains enzymes and metabolic precursors that complete essential biosynthetic pathways of the protozoan. Conversely, the symbiont is capable of obtaining part of the required energetic molecules from the host glycosomes. Taken together, data suggest that the endosymbiont in trypanosomatids represents an intermediate evolutionary step between bacteria and eukaryotic cell organelles..
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Understanding how phenomenological behaviors observed in biological systems emerge from molecular interactions of many individual unit and how these interactions shape the response of living systems to a changing environment are challenging questions which lie at the interface between multiple disciplines. In this talk I will draw an example from the human gut microbiome, the full consortium of microbes living in association with the human gut. Recent developments in DNA sequencing have made it possible to monitor how the compositions of microbial species change in time. Analysis of healthy adults under antibiotic treatment showed that the gut microbiota could take several weeks to recover after treatment cessation. This suggests that the combination of inter-species and host-microbe interactions and external perturbations could lead to hysteresis phenomena. We investigate this possibility and propose an out of equilibrium stochastic model able to explain this phenomenon. Our study reveals the importance of noise-activated dynamics in the recovery from antibiotic-perturbed states.
Les modèles mathématiques basés sur des systèmes d'équations différentielles ont permis des avancées majeures dans l'infection par le VIH au milieu des années 1990 notamment en quantifiant la production et la disparition du virus et des cellules infectées. Depuis des progrès ont été réalisés dans l'estimation des paramètres de ce type de modèle. Concomitamment, la prise en charge des patients infectés par le VIH avec des traitements antirétroviraux et des immuno-interventions est en constante amélioration. Nous présenterons les nouveaux développements et les applications en cours notamment pour l'optimisation des traitements antirétroviraux et le développement clinique des immuno-interventions dont l'interleukine 7.
L'évaluation de l'efficacité d'une intervention repose principalement sur des essais contrôlés randomisés (ECR), dont le plan d'expérience permet d'inférer la causalité. A l'inverse, les études observationnelles sont généralement considérées comme permettant d'étudier une association mais pas de relation causale entre une exposition et le devenir des sujets. Cet exposé présente deux différentes méthodes permettant une inférence causale dans les études observationnelles (scores de propension et variables instrumentales), et illustre leur utilisation à l'aide d'exemples.
Deux équipes présentent des résultats ou des questions qui leurs sont propres afin de favoriser de nouvelles discussions au sein du laboratoire.
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Papers evaluating measures of explained variation, or similar indices, invariably use independence from censoring as the most important criterion. And they invariably end up suggesting that some measures meet this criterion, and some don't, leading to a conclusion that the first are better than the second. As a consequence, users are offered measures that cannot be used with time-dependant covariates and effects, not to mention extensions to repeated events or multi state models. We explain in this paper that the above mentioned criterion is of no use in studying such measures, since it simply favours those that make an implicit assumption of a model being valid everywhere. Measures not making such an assumption are disqualified, even though they are better in every other respect. We show that if these, allegedly inferior, measures are allowed to make the same assumption, they are easily corrected to satisfy the `independent-from-censoring' criterion. Even better, it is enough to make such an assumption only for the times greater than the last observed failure time $tau$. Which, in contrast with the `preferred' measures, makes it possible to use all the modelling flexibility up-to $tau$, and assume whatever one wants after $tau$. As a consequence, we claim that measures being proffered as better in the existing reviews, are exactly those that are inferior
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