Gametophytic self-incompatibility limits the ability to derive inbred lines of potato through self-pollination and is prevalent in diploid potato. Within a population of F1 hybrids between two genotypes used in potato genome sequencing, we observed fruit set on many greenhouse-grown plants. Subsequently, after controlled self-pollinations, we confirmed fruit set in 32 of 103 F1 plants. Our goal was to identify genes responsible for self-compatibility in this population and to advance selfed progeny to develop highly homozygous inbred lines. The F1 population was genotyped using a single nucleotide polymorphism (SNP) array. Polymorphic and robust SNPs were analyzed by Fisher\'s Exact Test to identify allelic states segregating with the self-compatible phenotype. Filtering 1966 SNPs to retain only those with p-values less than 0.0001 yielded 95 highly significant SNPs, with all SNPs on anchored scaffolds located on chromosome 12. Candidate genes encoding for multiple notable proteins including an S-protein homologue were identified near highly significant SNPs on the Potato Genome Browser. Seeds obtained after self-pollination of self-compatible individuals were used to advance the population for three generations. SNP chip genotyping of the S3 generation revealed entirely different SNPs segregating for self-compatibility on nine different chromosomes. Comparison of the allelic state of SNPs in the F1 and S3 generations revealed a heterozygosity reduction by 80%, with fixation of many SNPs including those surrounding the S-protein homologue. We conclude that the genes responsible for segregation of self-compatibility in the S3 generation are different from those in the F1 generation. / Master of Science

La perfusion intraveineuse occupe une large place dans les services de soins cliniques. Les patients reçoivent de nombreux médicaments simultanément dans la même voie centrale, où des problèmes de compatibilité entre les médicaments peuvent survenir. La maitrise de ces incompatibilités médicamenteuses, génératrices de particules, représente donc un enjeu majeur dans la prise en charge des patients polymédiqués.La première partie de ce travail est une analyse de la littérature portant sur les incompatibilités médicamenteuses et leurs principales conséquences sur le plan clinique. A ce titre, un chapitre est dédié à l’ensemble des moyens de prévention de ces problèmes, parmi lesquels l’usage de filtres en ligne de perfusion ou de dispositifs de perfusion multi-lumières.La première partie de nos travaux expérimentaux est consacrée à l’évaluation de la filtration terminale comme stratégie de prévention de l’administration de particules aux patients. Dans ce contexte, nos travaux ont porté sur le noircissement des filtres en ligne observé dans un service de réanimation néonatale. L’objectif était de définir la nature de l’incompatibilité en cause et de s’assurer, dans un second temps, de l’efficacité des filtres malgré les phénomènes de noircissement. Les filtres ont été examinés par microscopie électronique et comptage particulaire. Un aminogramme de la nutrition parentérale a également été réalisé. Une interaction spécifique a été mise en évidence entre un acide aminé (la cystéine) et un oligoélément (le cuivre) dans les poches. De plus, le maintien de la fonction des filtres en ligne a été démontré.La seconde partie de nos travaux est axée sur l’évaluation de l’intérêt d’un dispositif médical multi-lumières innovant dans la prévention des incompatibilités médicamenteuses. Le premier travail mené dans cette thématique a montré in vitro son intérêt à prévenir la survenue d’incompatibilités physiques entre plusieurs associations médicamenteuses, allant de deux à six médicaments administrés simultanément. Nos résultats indiquent que la conception de ces nouveaux dispositifs de perfusion et notamment leur géométrie interne permet de minimiser le temps de contact entre les produits, et ainsi d’améliorer la compatibilité entre les produits, au même titre que le type de solution d’hydratation. Le second travail consistait à poursuivre l’évaluation de ces dispositifs de perfusion multi-lumières en reproduisant un protocole de perfusion utilisé habituellement en hématologie pédiatrique et associant plusieurs médicaments incompatibles à l’origine de précipité. Un comptage particulaire réalisé de manière dynamique a permis de montrer que l’emploi de ces dispositifs permettait de réduire significativement la charge particulaire administrée aux patients, en comparaison avec les dispositifs standard de perfusion (rampes de robinets).Les résultats de l’ensemble de nos travaux sont prometteurs pour l’amélioration de la prise en charge des patients. Ils doivent être maintenant confirmés au travers d’une étude clinique. / Intravenous infusions are extensively used in clinical wards. Patients simultaneously receive many drugs through a limited number of venous accesses, thus increasing the risk of physical drug incompatibilities. Preventing incompatibility is therefore important for the safe administration of injectable drugs of polymedicated patients.The first part of this work consisted in analysing published literature on drug incompatibilities and their clinical consequences. This chapter includes a review of tools preventing drug incompatibilities, which include in-line filtration or the use of multi-lumen infusion sets.The first part of our experimental work is dedicated to the evaluation of terminal in-line filtration for preventing the injection of drug particles to patients. In this context, our research has focused on the blackening of in-line filters, which have been observed during the infusion of binary parenteral nutrition (BPN) delivered in a neonatal intensive care unit. The purposes of our study were, first, to examine the elemental content of precipitates isolated from infused BPN bags and so determine the main physicochemical interactions occurring in them and, second, to evaluate the blackening effect of in-line filters on filtration capacity. Filter membranes were examined by scanning electron microscopy and energy dispersion spectroscopy. Amino acid (AA) profiles were obtained from BPN mixtures to determine the concentrations of each AA. A specific interaction was identify between cysteine and copper in our BPN. Despite the gradual blackening of in-line filters during BPN bag infusion, the filter membranes continued to filter solutions efficiently and safely.The second part of our work focused on the assessment of the impact of new multilumen infusion access devices on the occurrence of known drug incompatibility.The first study used a well-documented incompatible combination of two to six drugs and three different carrier fluids. The multilumen infusion access device was able to prevent the occurrence of drug incompatibilities in nearly half of the drug combinations tested. This study confirmed that the characteristics of an infusion device have an impact on drug physical incompatibilities. The main hypothesis is those fluid dynamics differ according to infusion device and accesses, which modify the contact time between drugs and the infusion vehicle.The second in vitro study focused on a pediatric multidrug protocol for patients diagnosed with lymphoblastic leukemia and receiving allogeneic transplantation. A dynamic particle count test was used over 24 hours to evaluate the overall particulate contamination. The use of a multi-lumen infusion set reduces significantly overall particulate contamination compared to the standard infusion set.These results pave the way to performing a randomized controlled clinical trial assessing the multilumen infusion access device.

Ce travail de doctorat s’inscrit dans un projet de recherche destiné à évaluer la charge particulaire issue des incompatibilités physico-chimiques d’origine médicamenteuse de patients admis en réanimation pour un état de choc septique ou un syndrome de détresse respiratoire aigüe. Le corollaire est de faire le lien avec la survenue de certaines complications (syndrome inflammatoire et dysfonction d’organe) susceptibles de menacer le pronostic vital. En effet, la dysfonction microcirculatoire caractéristique de ces patients pourrait être majorée par la contamination particulaire aboutissant ainsi à une aggravation de l’hypo-perfusion tissulaire et à la survenue du syndrome de défaillance multi viscérale.La première partie de ce travail a consisté en une analyse de la littérature portant sur les incompatibilités médicamenteuses et leurs principales conséquences cliniques sous forme d’une revue systématique. Un des messages essentiels est l’intérêt grandissant de la filtration en ligne comme moyen de prévention de la contamination particulaire bien mis en évidence par certains essais contrôlés randomisés en particulier pédiatriques.La seconde partie de ce travail était de mener, dans une première phase, une étude d’observation clinique au lit du malade des dispositifs de perfusion intraveineux habituellement utilisés et des médicaments le plus souvent administrés à ces patients de réanimation du CHU de Lille. La deuxième phase consistait à reproduire in vitro le montage de perfusion utilisé en clinique avec les différentes solutions médicamenteuses dans le but de quantifier la charge particulaire à laquelle sont exposés les patients. Le comptage particulaire a été réalisé de manière dynamique, selon une technique innovante, grâce à un analyseur de particule connecté au montage de perfusion.Ce travail nous a permis finalement d’évaluer le risque particulaire pour ces patients fragiles et de proposer une stratégie de prévention des incompatibilités médicamenteuses. / Our PhD work aimed to evaluate the particulate exposure induced by drug incompatibilities in patients admitted in ICU for a septic shock or acute respiratory distress syndrome. The purpose was to establish a link with the occurrence of certain complications (inflammatory syndrome and organ dysfunctions) susceptible to aggravate life threatening. Indeed, the microcirculatory dysfunction characteristic of these patients could be increased by the particulate contamination, compromising tissue perfusion and leading to the occurrence of multi organ failureThe first part of this study consisted in a systematic literature review on the clinical implications of drug incompatibilities. One of the essential messages is the growing interest of inline filtration to prevent particulate contamination, highlighted by randomized controlled trials especially in pediatric ICU.The second part of the study was to conduct, in a first phase, an observational study, at the ICU patients’ bedsides, of the commonly used intravenous drugs and infusion sets. The second phase was to reproduce in vitro the previous observed infusion lines using the observed drugs combination, in order to quantify the particulate exposure, during a simulated 6-hour infusion period. The particle counting was performed using an innovative dynamic image analysis device.Our work indicates the amount of particulate matter potentially administered to critically-ill adult patients and paves the way to a strategy of prevention of drug incompatibilities.

Meine Doktorarbeit behandelt hauptsächlich den todfeindlichen Kampf zwischen Nietzsches Philosophie und Jesus Lehre, im Nietzsches Worte, Judda gegen Rom, Rom gegen Judda. Ich habe versucht, die Quelle dieses Kampfes begrifflich zu erklären. Dafür habe ich den Begriff 'Inkompatibilität' verwendet und ich habe auch versucht, den scheinbaren Widerspruch der Begriffe von Nietzsche zu erklären, z. B., die Kritik an Willensfreiheit und die Freiheit des freien Geistes, der scheinbare Widerspruch zwischen Wille zur Macht und ewiger Wiederkehr des Gleichen und die begriffliche Beziehung zwischen Philosophie und Wissenschaft. Man kann nur einen Standpunkt von Judda gegen Rom haben, weil dieser Kampf keinen Kompromiß erlaubt. / My PhD thesis treat mainly deadly battle between Nietzschean philosophy and christian doctrine, in Nietzschean concept, Jew against Rome, Rome against Jew. The source of this battle has been conceptually explained. The incompatibility describes the source of that deadly battle. The seeming inconsistency of Nietzschean concepts has been explained on entire context of Nietzschean philosophy, for example, the critique of the freedom of will and the freedom of free spirit, the seeming contradiction between will to power and eternal recurrence and conceptual relationship between philosophy and science. Just one standpoint can be chosen between Jew against Rome, because this battle doesn't allow any compromise between them.

Wolbachia est une bactérie endosymbiotique, intracellulaire et exclusivement transmise maternellement qui infecterait au moins 106 espèces d'insectes. Wolbachia manipule fréquemment la reproduction de ses hôte à son avantage, notamment en induisant une forme de stérilité conditionnelle appelée incompatibilité cytoplasmique (IC). Chez les moustiques du complexe Culex pipiens, une grande diversité de souches de Wolbachia et de types d'IC a été précédemment identifiée, mais plusieurs aspects de la biologie de cette association restaient peu connus. Les travaux présentés dans cette thèse ont notamment permis de caractériser (i) l'impact de Wolbachia sur la structuration génétique des populations hôtes et (ii) la diversité des souches de Wolbachia et, plus précisément d'appréhender le mécanisme de l'IC. Par un suivi de populations naturelles, nous avons mis en évidence que Wolbachia induisait une forte structuration de la diversité mitochondriale, mais aussi qu'elle participait à des événements répétés d'introgression cytoplasmique entre les différents membres du complexe Cx. pipiens. Nous avons également mené une étude de génomique comparative basée sur le séquençage de quatre génomes complets de Wolbachia très proches phylogénétiquement. Pour cela, nous avons mis en place une série d'analyses approfondies utilisant un large panel d'outils bioinformatiques couplés à des vérifications moléculaires. Nous avons montré qu'il existait peu de polymorphisme entre les groupes de Wolbachia infectant Cx. pipiens. De plus, ces études nous ont permis de mettre en évidence des gènes candidats qui pourraient être directement impliqués dans le mécanisme de l'IC. / Wolbachia is an intracellular bacterial symbiont, exclusively maternally inherited, infecting at least 106 species of insects. Wolbachia commonly manipulates insect reproduction to its own advantage, as well illustrated by a phenomenon of conditional sterility called cytoplasmic incompatibility (CI). In mosquitoes of Culex pipiens complex, a great diversity of Wolbachia strains and of CI types was previously identified, but several aspects of the biology of this symbiotic association remained unknown. The aim of the studies presented in this thesis is to characterize (i) the impact of Wolbachia on the host genetic structure and (ii) the Wolbachia strains diversity in order to attempt an identification of CI molecular basis. By a survey of natural populations, we highlighted that Wolbachia deeply impacts the population structure of mitochondrial diversity, but is also associated with repeated events of cytoplasmic introgression between members of complex Cx. pipiens. We also conducted a study of comparative genomics based on the sequencing of four complete genomes of very closely related Wolbachia strains. For that purpose, we performed a series of analyses using a wide panel of bioinformatic tools coupled with molecular validations. We showed a low polymorphism between two groups of Wolbachia infecting Cx. pipiens. These studies also allowed us to highlight promising candidate genes which could be directly involved in the CI mechanism.

<p>A fundamental goal in the diverse field of evolutionary biology is reconstructing the historical processes that facilitated lineage diversification and the current geographic distribution of species diversity. Oceanic islands provide a view of evolutionary processes that may otherwise be obscured by the complex biogeographic histories of continental systems, and have thus provided evolutionary biology with some of its most lasting and significant theories. The Indian Ocean island of Madagascar is home to an extraordinarily diverse and endemic biota, and reconstructing the historical processes responsible for this diversity has consumed countless academic careers. While the flowering plant genus <italic>Coffea</italic> is but one lineage contributing to Madagascar's staggering floral diversity, it is representative of the common evolutionary theme of adaptive radiation and local endemism on the island. In this dissertation, I employ the genus <italic>Coffea</italic> as a model for understanding historical biogeographic processes in the Indian Ocean using methods of molecular phylogenetics and population genetics. In the molecular phylogenetic study of <italic>Coffea</italic> presented in chapter 2, I show that Madagascan <italic>Coffea</italic> diversity is likely the product of at least two independent colonization events from Africa, a result that contradicts current hypotheses for the single origin of this group. </p><p>Species of <italic>Coffea</italic> are known to exhibit self-incompatibly, which can have a dramatic affect on the geographic distribution of plant genetic diversity. In chapter 3, I identify the genetic mechanism of self-incompatibility in <italic>Coffea</italic> as homologous to the canonical eudicot S-RNase system. Baker's Rule suggests that self-incompatible lineages are very unlikely to colonize oceanic islands, and in chapter 4, I test this hypothesis by characterizing the strength of self-incompatibility and comparing S-RNase polymorphism in <italic>Coffea</italic> populations endemic to isolated Indian Ocean islands (Grande Comore and Mauritius) with that of Madagascan/African species. My findings suggest that while island populations show little evidence for genetic bottleneck in S-RNase allelic diversity, Mauritian endemic <italic>Coffea</italic> may have evolved a type of "leaky" self-incompatibility allowing self-fertilization at some unknown rate. Through the application of traditional phylogenetic methods and novel data from the self-incompatibly locus, my dissertation contributes a wealth of new information regarding the evolutionary and biogeographic history of <italic>Coffea</italic> in the Indian Ocean.</p> / Dissertation

Antibody-mediated rejection is central to ABO incompatible transplantation as well as to xenotransplantation. The xenoantigen alpha-Gal has a highly analogous carbohydrate structure to the human blood group antigens, and both require memory B cell activation for antibody production. We hypothesize that B cells, reactive to the alpha-Gal xenoantigen and B blood group antigen, require the presence of fully activated T cells in order to survive and proliferate in vitro, contrary to the traditional theory that humoral response to carbohydrate antigens is a T cell-independent process. When we compared the capacity of B cells to proliferate, we observed that activated T cells were necessary for B cell proliferation even in the presence of carbohydrate-derived antigens. A relevant question was also to investigate the role of a specific class of T cells: the CD1d-restricted iNKT cells, in the activation of alpha-Gal and B blood group-reactive B cells. The iNKT cells have the specificity of being reactive to glycolipids and are capable of producing both T helper 1 and T helper 2 cytokine responses. We therefore wanted to determine the role of the iNKT cells as mediators of a T helper 2-type response when B cells were exposed to a glycolipid antigen expressing the alpha-Gal epitope or the human B blood group antigen. We observed that, if the interaction between B cells and iNKT cells is blocked, neither B cell proliferation nor antibody production occurs. These results suggest therefore the importance of the iNKT cell category of T helper cells in the response to alpha-Gal and ABO-blood group glycolipids.

No description available.

Spiders are host to a plethora of heritable endosymbiotic bacteria. Broad-taxa screening studies indicate that endosymbionts are particularly common among spiders, however, little is known about how these bacteria affect their spider hosts. In insects these bacteria ensure vertical transmission by either conveying a benefit to the host or manipulating host reproduction to eliminate males that serve as evolutionary dead-ends for maternally-inherited bacteria. Common modes of reproductive manipulation include parthenogenesis, male killing, feminization, and cytoplasmic incompatibility. Screening an assemblage of Mermessus genus spiders, I detected a high frequency and diversity of endosymbiont infection. Within a single species, M. fradeorum, I detected three endosymbionts in multiple combinations. Rearing two natural infection types of M. fradeorum demonstrated two distinct endosymbiotic reproductive manipulations. Mothers infected with Rickettsia and Wolbachia produced extremely female-biased offspring, and antibiotic elimination of the symbionts successfully restored the sex ratio to the expected 1:1 in subsequent generations. A two-way factorial mating assay detected strong cytoplasmic incompatibility induced by a different strain of Wolbachia: cured females mated with infected males produced 70% fewer offspring than all other pairings. These results show that M. fradeorum is subject to multiple layers of reproductive manipulation that likely drive host evolution and ecology.

Les contrariétés de décisions de justice sont extrêmement nocives. D’une part, elles représentent une menace pour la cohérence du droit. D’autre part, elles pèsent lourd sur la situation des parties, mettant ces dernières dans des situations inextricables. En tant que mode juridictionnel de règlement des litiges, l’arbitrage international n’échappe pas à ce phénomène. Au contraire, les spécificités de la matière en font un terrain de prédilection pour le développement des contrariétés de décisions. En effet, les contrariétés résultent de la conduite parallèle de procédures portant sur des questions litigieuses identiques, sur lesquelles sont portées des appréciations divergentes. Or, l’arbitrage international se présente comme un facteur d’aggravation de ces causes classiques de contrariété, à savoir la concurrence juridictionnelle et l’incohérence des solutions. Le risque de contrariété y est à la fois fréquent et varié. Il se présente dans diverses configurations, opposant tantôt des décisions étatiques d’encadrement de l’arbitrage, tantôt une sentence arbitrale et une décision étatique ou encore deux sentences arbitrales.En dépit de la gravité du problème et de la fréquence du risque de contrariété, l’arbitrage international paraît mal armé pour y faire face. Il est confronté d’une part aux limites de l’efficacité des remèdes curatifs, qui se contentent souvent d’écarter la contrariété d’un territoire donné, et, d’autre part aux difficultés de mise en œuvre des remèdes préventifs. / The phenomenon of conflicting decisions is extremely hazardous. On the one hand, they represent a threat to the coherence of the legal systems. On the other hand, it places a burden on the parties, putting them in an inextricable situation. Being a jurisdictional dispute resolution method, international arbitration does not escape this phenomenon. On the contrary, the specificities of arbitration make it the territory of predilection for the appearance of conflicting decisions. In fact, conflicting decisions result from the conduction of parallel proceedings concerning identical issues, which receive a different analysis. International arbitration aggravates the classical causes resulting in conflicting decisions. These causes are the competition between jurisdictions and the incoherence of the solutions.The risk of the existence of conflicting decisions is frequent and it presents itself is several manners. It can oppose national courts’ decisions assisting and controlling the arbitration, an arbitral award and a national court’s decision or even two arbitral awards.Despite the gravity of the problem and the frequency of the risk of having conflicting decisions, international arbitration seems unarmed to deal with it. Firstly, it is confronted with the limited efficiency of the curative solutions, and secondly, with the difficulties of applying preventive solutions.