Dans son Historia Animalium en 343 av. J.C., Aristote proposait déjà deux critères qui continuent d’être les bases fondamentales de notre compréhension de la diversité des modes de reproduction : l’origine des nutriments des embryons (lécitotrophie vs. matrotrophie) et le mode de parition (oviparité vs. viviparité). Depuis plusieurs décennies la compréhension de la transition évolutive vers la viviparité a attiré un intérêt scientifique considérable. En effet les analyses phylogénétiques récentes reconnaissent une évolution indépendante de la viviparité dans plus de 150 lignées de vertébrés dont au moins 115 concernent uniquement le taxon des reptiles squamates actuels (lézards, serpents et amphisbènes). Les lignées présentant une transition évolutive de l’oviparité à la viviparité chez les squamates se retrouvent généralement associées aux climats froids, mais pas uniquement. Les explications proposées pour ce patron reposent sur le contrôle comportemental de la température de développement chez les femelles gestantes, offrant ainsi des températures plus favorables que celles des sites de ponte situés sous la surface du sol. Durant cette thèse doctorale nous avons étudié une espèce à reproduction bimodale (Zootoca vivipara) chez qui coexistent des populations ovipares et vivipares disjointes. Ce contexte nous a permis de comparer les modes reproducteurs en minimisant les biais phylogénétiques. Nous avons pu mettre en évidence et quantifier différents coûts « potentiels » de la reproduction (énergétique, contrainte volumique, phénotype des nouveau-nés) et certains bénéfices (phénologie et performance des nouveau-nés) associés à la régulation maternelle du développement. Nos résultats nous amènent à discuter des différentes pressions de sélection s’exerçant sur la durée de rétention des embryons, dont les directions seraient opposées et/ou dont l’intensité serait variable au cours du développement embryonnaire. Dans ce schéma, la viviparité ne devrait être favorisée que dans des contextes plus contraignants et où les bénéfices thermiques compensent les coûts de prolongation de la rétention. Ce contexte sélectif aurait abouti chez les squamates à l’existence de deux modalités reproductives avec entre elles une instabilité évolutive des états intermédiaires. / In his Historia Animalium in 343 B.C., Aristotle proposed two fundamental distinguishing criteria for reproductive diversity: the source of nutrients for embryonic development (lecitotrophy vs. matrotrophy) and partuition mode (oviparity vs. viviparity). Understanding the evolutionary transition to viviparity attracted considerable scientific interest over the past few decades. Phylogenetic analyses indicate that viviparity has originated independently in more than 150 vertebrate lineages, including in a minimum of 115 clades of extant squamate reptiles (lizards, snakes and amphisbaenians). Transitions from oviparity to viviparity in squamate reptiles seem closely related to cold climates, but not exclusively. Explanations for this pattern are based on the fact that pregnant females can behaviouraly thermoregulate and thus offer more suitable developmental temperatures than those available in nests under the soil surface. During this PhD thesis we studied a reproductively bi-modal species (Zootoca vivipara) in which non-overlapping oviparous and viviparous populations exist. This context allowed us to compare oviparous and viviparous reproductive modes while minimizing phylogenetic biases. We identified and quantified potential reproductive costs (energy, volume constraints, offspring phenotype) and also benefits (phenology and offspring performances) associated with maternal thermoregulation. Our results provide support for multiple selective pressures on embryo retention, with variable intensities and opposite directions depending on embryonic developmental stage. In this scheme, viviparity should be selected in constraining environments where thermal advantages exceed the costs of increased retention. This context may explain the dichotomy observed in squamate reproductive modes and the evolutionary instability of intermediate stages.

Les colonies de fourmis produisent occasionnellement des individus intermédiaires entre les reines et les ouvrières (c.-À-D. intercastes). Les intercastes pourraient être impliquées dans l'évolution de nouvelles castes par un processus de réorganisation des phénotypes ancestraux. Afin d'évaluer cette hypothèse, nous avons étudié la validité de trois corollaires de ce modèle évolutif chez la fourmi Mystrium rogeri: (i) les intercastes résultent de la réorganisation de caractères de reines et d'ouvrières; (ii) les intercastes sont susceptibles d'être fonctionnelles parce qu'elles recombinent des comportements qui ont déjà été testé par la sélection chez les reines et les ouvrières; (iii) certains phénotypes intercastes ressemblent à ceux des nouvelles castes ayant évolué de cette façon.Les résultats suggèrent que les intercastes sont générées par des niveaux intermédiaires de facteurs environnementaux induisant des réponses différentielles entre les modules. Les intercastes effectuent les mêmes tâches que les reines et les ouvrières et elles ne sont pas associées à des comportements aberrants. Elles sont plus impliquées que les reines et les ouvrières dans les interactions agonistes et peuvent ainsi entraîner des coûts à l'échelle de la colonie. Les intercastes peuvent attirer les mâles, s'accoupler et pondre des ¿ufs, présentant ainsi un fort potentiel reproducteur. Des changements de pressions de sélection sur les stratégies de reproduction sont alors susceptibles d'entrainer la fixation d'un phénotype intercaste par accommodation génétique. Nos résultats soutiennent l'hypothèse selon laquelle les intercastes peuvent être à l'origine de l'évolution des nouvelles castes. / Ant colonies occasionally produce individuals called intercastes. These are morphologically highly variable, but always intermediate between queens and workers. Because of their rarity, intercastes have been little studied. However, they may be involved in the evolution of novel castes through the reorganization of ancestral phenotypes (i.e. developmental recombination). In order to evaluate this hypothesis, we investigated the validity of three corollaries of this evolutionary model in the ant Mystrium rogeri: (i) intercastes must be produce by the reorganization of queen and workers characters following new genetic or environmental input; (ii) they are likely to be functional because they recombine behaviors that have already been tested by selection in queens and workers, unlike a random mutational process that mainly produces deleterious variants; (iii) some intercaste phenotypes may resemble those of new castes suspected to have evolved by this way. In agreement with the phenotypic reorganization hypothesis, our morphometric analyses suggest that intercastes are generated by intermediate levels of environmental factors inducing differential responses among modules. Behavioral records showed that intercastes perform the same tasks than queens and workers and therefore they are not associated with aberrant and costly behaviors. Nevertheless, they are more involved in agonistic interactions than queens and workers and thus may cause significant costs at the colonial level. Behavioral tests showed that some intercastes may attract males, mate, and lay diploid eggs, thereby demonstrating their high reproductive potential. Consequently, new selective pressures on the reproductive strategy may result in the selection of these intercastes and then the fixation of a new canalized phenotype by genetic accommodation of change. This process may explain the multiple evolutions of new reproductive castes (e.g. ergatoid queens). Overall, results presented in this work support the hypothesis that intercastes may be at the origin of the evolution of novel castes by developmental recombination.

L'échange et le partage d'informations est devenu de nos jours un acte de gestion courante pour l'ensemble du monde professionnel. Pour autant, du point de vue juridique, cette situation interpelle de par sa complexité. Au travers de la régulation de l'information, de la dématérialisation des échanges, la multiplication des acteurs, les professionnels du droit doivent s'interroger concernant l'interaction entre le possible technique et les impératifs réglementaires. Domaine parmi tant d'autres, le monde sanitaire constitue assurément un espace permettant d'étudier ce mouvement à deux temps, notamment lorsque l'on observe plus particulièrement la relation de soins. En effet, l'évolution numérique qui s'applique désormais à cette relation constitue véritablement une étape significative dans le long développement historique de la science médicale. Bien sûr, mêlant tout à la fois modernisation et transformation, elle oblige à une réflexion où s'entremêle banalité et originalité. Mais cette réflexion s'avère nécessaire, car si le développement numérique participe à une meilleure qualité des soins et à une meilleure coordination, il ne doit pas faire oublier qu'il est avant tout au service des individus. / The exchange and the sharing of information became nowadays an act of current management for the whole professional world. However, from the legal point of view, this situation calls due to its complexity. Through the regulation of the information, the dematerialization of the exchanges, the increase of the actors, the professionals of the law have to wonder concerning the interaction between the possible technical and the statutory imperatives. Domain among so many others, the sanitary world constitutes undoubtedly a space allowing to study this movement in two time, in particular when we observe more particularly the relation of care. Indeed, the digital evolution which applies henceforth to this relation really constitutes a significant stage in the long historic development of the medical science. Of course, mixing quite at once modernization and transformation, it obliges a reflection where becomes entangled commonness and originality. But this reflection turns out necessary, because if the digital development participates in a better quality of the care and in a better coordination, he does not have to make forget that he is above all in the service of the individuals.

Naturally competent bacterial species, which self-induce the recombination mechanism of transformation, are wide spread across the bacterial tree-of-life. However, it remains unclear why competence has evolved in these bacteria. Although it is likely that exact explanations will be different for each species, a common selective factor cannot be excluded. Currently, three dominant hypotheses, which focus on the transformation function, try to explain the benefits of competence. Firstly, competence is thought to increase the rate of adaptation by combining beneficial alleles in single genotypes. Secondly, competence can repair DNA-damage by replacing the damaged DNA fragments with undamaged ones. Thirdly, the DNA uptake during competence is used to recycle environmental DNA fragments for nutrients. One of the naturally competent species is the Gram-positive Streptococcus pneumoniae, which is an opportunistic pathogen generally inhabiting the naso-pharyngeal area of young children. Competence in S. pneumoniae is regulated via density dependent extracellular signaling peptide. Here I use a combination of experiments designed around knockout mutants of the signaling mechanism and next-generation sequencing methods to test the first two hypotheses in S. pneumoniae. First, I extend on the DNA-for-repair hypothesis by showing that competent populations of S. pneumoniae are better protected not only against a DNA-damaging agent, but also against protein synthesis inhibitors. However, the mechanisms underlying this protection differ between types of stress. DNA-damage requires the full process of transformation, while protection against protein synthesis inhibitors only requires the activation of the competent cell state. This shows that benefits of competence cannot be totally explained by the benefits of transformation. Second, I use a long-term evolution experiment, where competent and non-competent strains are kept in the presence and absence of periodic stress, to determine the importance of competence for the generation of genetic variation. I find that competence does not increase the rate of adaptation in S. pneumoniae. The fitness of evolved competent populations was significantly lower than those of non-competent populations evolved over the same period of time. However, the intrinsic costs of competence are mitigated by the addition of short periods of stress exposure. These results confirm the prediction of the fitness associated recombination (FAR) hypothesis that competence is favoured in low-fitness situations. Thirdly, whole genome re-sequencing of the evolved populations allowed me to explore genomic evolution next to fitness changes. The genomic data revealed that competence reduces the mutational load of deleterious mutations rather than generating combinations of beneficial alleles. In addition I show several case of parallel genomic evolution within each treatment and across treatments. This shows that parallel evolution is not restricted by genotypic background (competence) or environment (periodic stress). Finally, these results show that competence has evolved in populations of S. pneumoniae as a mechanism to deal with various forms of stress.

The purpose of this study is to examine the theory of workmen's compensation, tracing its historical development and showing how the law evolved in the United States. Pertinent statutes and administrative and judicial decisions will be given to the evolution of the theory of compensable occupational diseases. Following an analysis of the occupational disease concept and the significance of this concept in modifying the basic theory, an effort will be made to evaluate the effect of this concept upon the meaning of the laws.

Motivated by the desire to investigate two of the largest outstanding problems in galactic evolution -- stellar feedback and galactic chemical evolution -- we develop the first set of galaxy-scale simulations that simultaneously follow star formation with individual stars and their associated multi-channel stellar feedback and multi-element metal yields. We developed these simulations to probe the way in which stellar feedback, including stellar winds, stellar radiation, and supernovae, couples to the interstellar medium (ISM), regulates star formation, and drives outflows in dwarf galaxies. We follow the evolution of the individual metal yields associated with these stars in order to trace how metals mix within the ISM and are ejected into the circumgalactic and intergalactic media (CGM, IGM) through outflows. This study is directed with the ultimate goal of leveraging the ever increasing quality of stellar abundance measurements within our own Milky Way galaxy and in nearby dwarf galaxies to understand galactic evolution. Our simulations follow the evolution of an idealized, isolated, low mass dwarf galaxy (Mvir ∼ 10^9 M ) for ∼ 500 Myr using the adaptive mesh refinement hydrodynamics code Enzo. We implemented a new star formation routine which deposits stars individually from 1 M to 100 M . Using tabulated stellar properties, we follow the stellar feedback from each star. For massive stars (M∗ > 8 M ) we follow their stellar winds, ionizing radiation (using an adaptive ray-tracing radiative transfer method), the FUV radiation which leads to photoelectric heating of dust grains, Lyman-Werner radiation, which leads to H2 dissociation, and core collapse supernovae. In addition, we follow the asymptotic giant branch (AGB) winds of low-mass stars (M∗ < 8 M ) and Type Ia supernovae. We investigate how this detailed model for stellar feedback drives the evolution of low mass galaxies. We find agreement with previous studies that these low mass dwarf galaxies exhibit bursty, irregular star formation histories with significant feedback-driven winds. Using these simulations, we investigate the role that stellar radiation feedback plays in the evolution of low mass dwarf galaxies. In this regime, we find that the local effects of stellar radiation (within ~ 10 pc of the massive, ionizing source star) act to regulate star formation by rapidly destroying cold, dense gas around newly formed stars. For the first time, we find that the long-range radiation effects far from the birth sites are vital for carving channels of diffuse gas in the ISM which dramatically increase the effect of supernovae. We find this effect is necessary to drive strong winds with significant mass loading factors and has a significant impact on the metal content of the ISM. Focusing on the evolution of individual metals within this galaxy, it remains an outstanding question as to what degree (if any) metal mixing processes in a multi-phase ISM influence observed stellar abundance patterns. To address this issue, we characterize the time evolution of the metal mass fraction distributions of each of the tracked elements in our simulation in each phase of the ISM. For the first time, we demonstrate that there are significant differences in how individual metals are sequestered in each gas phase (from cold, neutral gas up to hot, ionized gas) that depend upon the energetics of the enrichment sources that dominate the production of a given metal species. We find that AGB wind elements have much broader distributions (i.e. are poorly mixed) as compared to elements released in supernovae. In addition, we demonstrate that elements dominated by AGB wind production are retained at a much higher fraction than elements released in core collapse supernovae (by a factor of ~ 5). We expand upon these findings with a more careful study of how varying the energy and spatial location of a given enrichment event changes how its metal yields mix within the ISM. We play particular attention to events that could be associated with different channels of r-process enrichment (for example, neutron star - neutron star mergers vs. hypernovae) as a way to characterize how mixing / ejection differences may manifest themselves in observed abundance patterns in low mass dwarf galaxies. We find that -- on average -- the injection energy of a given enrichment source and the galaxy's global SFR at the time of injection play the strongest roles in regulating the mixing and ejection behavior of metals. Lower energy events are retained at a greater fraction and are more inhomogeneously distributed than metals from more energetic sources. However, the behavior of any single source varies dramatically, particularly for the low energy enrichment events. We further characterize the effect of radial position and local ISM density on the evolution of metals from single enrichment events. Finally, we summarize how this improved physical model of galactic chemical evolution that demonstrates that metal mixing and ejection from galaxies is not uniform across metal species can be used to improve significantly upon current state of the art galactic chemical evolution models. These improvements stand to help improve our understanding of galactic chemical evolution and reconcile outstanding disagreements between current models and observations.

Le neuroblastome est le cancer solide extra-cranial le plus fréquent chez l’enfant. Il est caractérisé par une très grande hétérogénéité tant au niveau clinique que moléculaire. Alors que certains patients rentrent spontanément en rémission, on peut se demander quels facteurs permettent la réémergence du cancer chez d’autres malgré traitement. Pour répondre à cette question, il convient d’identifier chez les patients ayant rechuté, les différentes populations clonales coexistant au diagnostic et/ou à la rechute. Cela permet, entre autre, d’étudier les voies différemment altérées entre ces deux temps. Dans cette optique, nous présentons ici QuantumClone, un algorithme de reconstruction clonal à partir de données de séquençage, ainsi que son application à une cohorte de patients souffrant d’un neuroblastome. Sur ces données, l’application de notre méthode a permis d’identifier des différences dans le ratio de variants prédits fonctionnels par rapport à ceux prédits passagers entre les populations ancestrales, enrichies à la rechute ou appauvries à la rechute. / Neuroblastoma is the most frequent solid extra-cranial cancer of childhood. This cancer displays a high heterogeneity both at clinical and molecular levels. Even though in some patients spontaneous remission can be observed, some others relapse despite treatment and surgical resection. It may be wondered which are the factors that distinguish these two cases. In order to answer this question, identification of populations coexisting at diagnosis and/or relapse in the patients which have relapsed is a prerequisite. This would allow, between other things, to study the pathways differently altered in clones that are specific to each time point. With this in mind, we hereby present QuantumClone, a clonal reconstruction algorithm from sequencing data. In addition, we applied this method to a cohort of patients suffering from neuroblastoma. On these data, our method identified differences in the functional mutation rate, i.e. the number of putative functional variants by total number of variants, between the ancestral clones, clones expanding at relapse, and clones shrinking at relapse.

Chez les organismes pluricellulaires, la diversité morphologique observée à tous les niveaux est frappante, que ce soit au niveau de la taille, des couleurs, ou de la forme des individus, et des différentes parties qui les composent. La sélection naturelle, ainsi que les contraintes développementales, influencent l’évolution de ces différents attributs, sur le court terme comme sur le long terme. Le modèle choisi ici pour étudier l’évolution des formes est le grain de pollen des plantes à fleurs, qui présente une très grande diversité morphologique. Nous nous sommes focalisés sur un caractère morphologique, les apertures, qui sont des structures de la paroi du grain de pollen impliquées dans la survie et la reproduction. Nous avons étudié l’évolution des apertures à grande échelle taxonomique chez les angiospermes, et nous montrons que s’il existe de nombreuses variations, deux types principaux dominent : un pollen à une aperture chez les Monocotylédones et les angiospermes divergeant à la base, et un pollen à trois apertures chez les Eudicotylédones. En étudiant la dominance du pollen à trois apertures, nous avons pu montrer que la stase chez les Eudicotylédones était vraisemblablement due à une sélection stabilisante plutôt qu’à des contraintes développementales. Nous avons également montré, grâce à l’utilisation de mutants de la plante modèle Arabidopsis thaliana, qu’un nombre d’apertures élevé est défavorable face à un stress osmotique, ce qui pourrait suggérer que les pollens triaperturés représentent un bon compromis entre survie et germination. Enfin, nous nous sommes intéressés à un type particulier de pollen possédant de nombreuses apertures, dont nous avons étudié la distribution chez les angiospermes. L’apparition de ce type de pollen est récurrente, mais il n’est que rarement fixé à grande échelle taxonomique, suggérant l’existence d’un mécanisme de sélection interphylétique éliminant ce type de pollen sur le long terme. / Multicellular organisms are morphologically very diverse at every scale, regarding size, color, and shape of individuals and of their different parts. Natural selection and developmental constraints influence evolution of these characteristics, on the short term as well as on the long term. The model chosen here to study form evolution is the pollen grain of flowering plants, which is very diversified morphologically. We focused on specific features called apertures, which are structures of the pollen wall involved in survival and reproduction. We studied aperture evolution at large taxonomic scale in angiosperms, and we showed that in spite of variations, two main pollen types dominate: a pollen with one aperture in Monocots and early diverging angiosperms, and a pollen with three apertures in Eudicots. The study of this pattern showed that the stasis of triaperturate pollen in Eudicots is likely due to stabilizing selection rather than developmental constraints. Experiments on Arabidopsis thaliana mutants also revealed that an increase in aperture number was associated with lower resistance to osmotic stress. This result could suggest that triaperturate pollen grains represent a good trade-off between survival and germination. Moreover, we focused on a particular pollen type with many apertures, to determine its distribution in angiosperms. This type of pollen has many origins, however it is seldom fixed at large taxonomical scale, suggesting the intervention of lineage selection, eliminating this pollen type in the long run.

L’objectif de cette thèse est d’étudier le rôle de neuropeptides cérébraux, telle que la Neurokinin B codée par le gène tac3, dans le contrôle de la reproduction d’une espèce en danger, l’anguille Européenne, Anguilla anguilla. La maturation sexuelle de l’anguille est bloquée à un stade prépubertaire avant la migration océanique. Etant donnée sa position phylogénétique basale parmi les téléostéens, l’anguille est un modèle pertinent pour étudier l’évolution moléculaire et fonctionnelle de neuropeptides d’intérêt. Deux gènes paralogues tachykinine 3 (tac3) ont été identifiés dans le génome de l’anguille, chacun codant pour deux peptides. Ces gènes paralogues résultent de la duplication complète du génome spécifique aux téléostéens, comme le montrent les analyses phylogénétiques et synténiques. Les analyses de qPCR montrent que les deux gènes sont exprimés dans le cerveau. Les quatre peptides d’anguille ont été synthétisés et testés sur des cultures primaires de cellules hypophysaires d’anguille. Les quatre peptides inhibent l’expression de l’hormone lutéinisante et d’un récepteur à la gonadolibérine, révélant un double rôle inhibiteur dans le contrôle de la reproduction. / The aim of this PhD is to investigate the role of brain neuropeptides, such as neurokinin B, encoded by tac3 gene, in the control of reproduction of an endangered species, the European eel, Anguilla anguilla. The sexual maturation of the eel is blocked at a prepubertal stage before the oceanic migration. Due to its basal phylogenetic position among teleosts, the eel is also a relevant model for studying molecular and functional evolution of key neuropeptides. Two tachykinin 3 (tac3) paralogous genes were identified in the eel genome, each encoding two peptides. These paralogs result from the teleost-specific whole genome duplication, as shown by phylogeny and synteny analyses. Both genes are expressed in the brain as shown by qPCR. The four eel peptides were synthesized and tested on primary cultures of eel pituitary cells. The four peptides inhibited the expression of luteinizing hormone and gonadotropin-releasing hormone receptor, revealing a dual inhibitory role in the control of reproduction.

No description available.