Univ., Diss.--Köln, 2002.

No description available.

Bien que l'on ne sache pas (encore) quel phénomène unitarise la diffusion WLWL à l'échelle du TeV, les données indirecte actuelles favorise le boson de Higgs. Etant donné que cette particule scalaire pourrait être aussi lourde que la masse de Planck, comment peut-on expliquer sa légèreté ? La supersymmétrie (SUSY), brisée à l'échelle du TeV, peut effectuer cette stabilisation, et permettre du même coup l'existence de Théories de Grande Unifications (GUTs). Ces SUSY GUTs réalisées dans une dimension supplémentaire compactifiée, peuvent être particulièrement simples. De plus, elles peuvent être prises comme limite basse énergie d'une théorie de cordes. Cette thèse est consacrée à l'étude de tels modèles de SUSY GUTs. Nous avons étudié, développé et étendu certains aspects de la classe de modèle d'Unification Jauge-Higgs, et de la classe de modèle d'Unification Holographique. Différents aspects de la physique basse-énergie ont été étudiés, incluant spectre de masses, physique des saveur, matière noire, et phénoménologie au LHC. / Although one does not know (yet) which phenomenon unitarizes WLWL scattering at the TeV scale, indirect data currently favors the Higgs boson. Since such a scalar particle is susceptible to become as heavy as the Planck mass, how can one explain its lightness ? Supersymmetry (SUSY), broken at the TeV scale, can do this stabilization, providing in the same time models of Grand Uni fied Theories (GUTs). These SUSY GUTs, combined with extra spatial dimensions compacti fied on an interval, can be particularly simple. Moreover they can be seen as the low energy limit of some string theory. This thesis is devoted to the study of such models of SUSY GUTs on flat and warped orbifolds, trying to cover the range from models to experimental constraints. We studied, developed and extended certain aspects of two interesting frameworks of this type: a framework with gauge-Higgs uni fication, and the framework of holographic grand uni fication. We investigated several aspects of the low-energy implications, including mass spectra, flavour constraints, dark matter and LHC phenomenology

Introduction: Intestinal bacteria influence gut morphology by affecting epithelial cell proliferation, development of the lamina propria, villus length and crypt depth [1]. Gut microbiota-derived factors have been proposed to also play a role in the development of a 30 % longer intestine, that is characteristic of PRM/Alf mice compared to other mouse strains [2, 3]. Polyamines and SCFAs produced by gut bacteria are important growth factors, which possibly influence mucosal morphology, in particular villus length and crypt depth and play a role in gut lengthening in the PRM/Alf mouse. However, experimental evidence is lacking. Aim: The objective of this work was to clarify the role of bacterially-produced polyamines on crypt depth, mucosa thickness and epithelial cell proliferation. For this purpose, C3H mice associated with a simplified human microbiota (SIHUMI) were compared with mice colonized with SIHUMI complemented by the polyamine-producing Fusobacterium varium (SIHUMI + Fv). In addition, the microbial impact on gut lengthening in PRM/Alf mice was characterized and the contribution of SCFAs and polyamines to this phenotype was examined. Results: SIHUMI + Fv mice exhibited an up to 1.7 fold higher intestinal polyamine concentration compared to SIHUMI mice, which was mainly due to increased putrescine concentrations. However, no differences were observed in crypt depth, mucosa thickness and epithelial proliferation. In PRM/Alf mice, the intestine of conventional mice was 8.5 % longer compared to germfree mice. In contrast, intestinal lengths of C3H mice were similar, independent of the colonization status. The comparison of PRM/Alf and C3H mice, both associated with SIHUMI + Fv, demonstrated that PRM/Alf mice had a 35.9 % longer intestine than C3H mice. However, intestinal SCFA and polyamine concentrations of PRM/Alf mice were similar or even lower, except N acetylcadaverine, which was 3.1-fold higher in PRM/Alf mice. When germfree PRM/Alf mice were associated with a complex PRM/Alf microbiota, the intestine was one quarter longer compared to PRM/Alf mice colonized with a C3H microbiota. This gut elongation correlated with levels of the polyamine N acetylspermine. Conclusion: The intestinal microbiota is able to influence intestinal length dependent on microbial composition and on the mouse genotype. Although SCFAs do not contribute to gut elongation, an influence of the polyamines N acetylcadaverine and N acetylspermine is conceivable. In addition, the study clearly demonstrated that bacterial putrescine does not influence gut morphology in C3H mice. / Einleitung: Die intestinale Mikrobiota beeinflusst die Morphologie des Darmes durch Beeinflussung der Epithelzellproliferation, Entwicklung der Lamina Propria, Zottenlänge und Kryptentiefe [1]. Zudem stehen bakterielle Faktoren im Verdacht, die Entwicklung eines 30 % längeren Darmes in der PRM/Alf Maus gegenüber anderen Mausstämmen zu begünstigen [2, 3]. Die von der intestinalen Mikrobiota produzierten Polyamine und kurzkettigen Fettsäuren (SCFA) stellen wichtige Wachstumsfaktoren dar, die bei der Ausbildung des Darmes sowie an der Darmverlängerung in der PRM/Alf Maus beteiligt sein könnten. Zielstellung: Ziel dieser Arbeit war, den Einfluss von bakteriell-produzierten Polyaminen auf die Kryptentiefe, Schleimhautdicke und Epithelzellproliferation zu untersuchen. Zu diesem Zweck wurden keimfreie C3H Mäuse mit einer vereinfachten menschlichen Mikrobiota (SIHUMI) assoziiert und mit C3H Mäusen, die mit einer SIHUMI plus dem polyaminproduzierendem Fusobacterium varium (SIHUMI + Fv) besiedelt worden waren, verglichen. Weiterhin sollte der mikrobielle Einfluss sowie die Rolle von SCFAs und Polyaminen bei der Ausbildung eines verlängerten Darms in der PRM/Alf Maus untersucht werden. Ergebnisse: Die SIHUMI + Fv Mäuse zeigten eine bis zu 1,7 fach höhere intestinale Polyaminkonzentration im Vergleich zu SIHUMI-Mäusen, welche vor allem auf eine Erhöhung von Putrescin zurückzuführen war. Trotz der höheren Polyaminkonzentrationen wurden keine Unterschiede in der Kryptentiefe, Schleimhautdicke und Epithelzellproliferation beobachtet. Die Untersuchung der Darmlänge in PRM/Alf Mäusen in Abhängigkeit vom Besiedlungsstatus ergab einen 8,5 % längeren Darm in konventionell besiedelten PRM/Alf Mäusen im Vergleich zu keimfreien PRM/Alf Mäusen. Im Gegensatz dazu wurden in C3H-Mäusen keine Unterschiede in der Darmlänge in Abhängigkeit von der Besiedlung beobachtet. Der Vergleich zwischen PRM/Alf und C3H Mäusen, die beide mit der SIHUMI + Fv Mikrobiota assoziiert wurden, zeigte einen 35,9 % längeren Darm in PRM/Alf Mäusen. Trotz des längeren Darmes waren die intestinalen SCFA- und Polyaminkonzentrationen vergleichbar bzw. geringer als in C3H Mäusen, mit einer Ausnahme: Die Konzentration von N Acetylcadaverin war in PRM/Alf Mäusen 3,1-fach erhöht. Wurden keimfreie PRM/Alf Mäuse mit einer komplexen PRM/Alf Mikrobiota assoziiert, so war ihr Darm ein Viertel länger als bei PRM/Alf Mäusen, die mit einer C3H Mikrobiota besiedelt wurden. Dieser längere Darm korrelierte mit der N Acetylsperminkonzentration. Schlussfolgerung: Die intestinale Mikrobiota ist in der Lage, die Darmlänge abhängig von der mikrobiellen Zusammensetzung und von dem Genotyp des Wirtes zu beeinflussen. Obwohl SCFAs die Darmlänge nicht beeinflussten, ist eine Beteiligung der Polyamine N Acetylcadaverin und N Acetylspermin denkbar. Darüber hinaus zeigte die Studie, dass Putrescin die Anatomie des Darmes in C3H Mäusen nicht beeinflusst.

Notre équipe a précédemment rapporté que l'utilisation d'un traitement d'induction lympho-déplétant [les globulines anti-lymphocytaires polyclonales (GALP)], peut entrainer une lymphopénie T CD4 persistante chez certains transplantés rénaux. Celle-ci est associée à certaines anomalies biologiques telles que la présence d'un syndrome inflammatoire chronique. Ce travail de thèse s'intéresse aux facteurs impliqués dans l'induction de ces anomalies puisqu'elles sont associées à une augmentation de l'incidence d'infections, de maladies cardiovasculaires et de décès, habituellement retrouvés chez les personnes âgées. Nous avons montré que les GALP entrainent une diminution de la fonction thymique et une expansion de lymphocytes T à un stade avancé de différenciation pouvant traduire une immunosénescence prématurée. Par ailleurs, une rupture de la barrière intestinale semble favoriser la translocation bactérienne digestive et l'activation d'une inflammation chronique observée en transplantation, via les lipopolysaccharides libérés dans la circulation périphérique. La composition du rnicrobiote intestinal pourrait jouer un rôle dans l'initiation, le maintien et la sévérité de l'inflammation. Nous avons observé des modifications du microbiote après transplantation et après l' antibioprophylaxie utilisée en transplantation. Les mécanismes à l'origine de toutes ces observations restent à élucider mais ce travail permet d'améliorer la compréhension des facteurs impliqués dans le développement de l'immunosénescence et de l'inflammation chronique en transplantation rénale, ouvrant potentiellement la voie à d'intéressantes perspectives thérapeutiques. / We bave previously described that polyclonal anti-lymphocytic globulins (GALP) may contribute to prolonged CD4 T­cell lymphopenia in some renal transplant recipients, associated with some biological abnormalities, such as a chronic inflammatory syndrome. Our work focuses on the factors involved in the induction of tbese abnormalities and susceptible to increase the incidence of infections, cardiovascular diseases and deatb, comparable to the incidence observed in the elderly. We showed that GALP are implicated in the decrease in thymie output and the expansion ofT cells at an advanced stage of differentiation. Both are hallmarks of premature immune senescence. Moreover, the dysfunction of the gut epithelial barrier is responsible for gut bacterial translocation (GBT) and the activation of chronic inflammation observed in chronic kidney disease as well as in renal transplant recipients. The composition of the intestinal microbiota may play a role in the initiation, maintenance and severity of GBT and systernic inflammation. We reported the existence of a dysbiosis a.fier transplantation. The mechanisms involved remain to be elucidated, yet, this work contributes to the understanding of the potential factors involved. in the progression of immune senescence and the persistence of chronic inflammation after kidney transplantation paving the way to new fields of therapeutic research in transplantation

Submitted by Sandra Pereira (srpereira@ufrrj.br) on 2017-06-05T14:54:01Z No. of bitstreams: 1 2010 - Samuel_Ribeiro_Passos.pdf: 16768295 bytes, checksum: 38c2614ad26085e9a101652551af84b5 (MD5) / Made available in DSpace on 2017-06-05T14:54:01Z (GMT). No. of bitstreams: 1 2010 - Samuel_Ribeiro_Passos.pdf: 16768295 bytes, checksum: 38c2614ad26085e9a101652551af84b5 (MD5) Previous issue date: 2010-02-23 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior, CAPES, Brasil. / The increasing demand for biological processes alternative, environmentally friendly and efficient in converting lignocellulosic material, expanding their application potential for agribusiness, motivates researches worldwide. Thus, organisms isolated in nature, in specific ecosystems, become increasingly important because of their physiological and metabolic diversity, which gives them a great potential in the development of biotechnological processes of interest to society. The aim of this study was to assess the microbial community associated with the intestinal tract of millipede Trigoniulus corallinus and bioprospecting for microorganisms with cellulolytic capacity. The millipedes were collected and incubated with litter in diets of grass (Paspalum notatum) and ?sabia? (Mimosa caesalpinifolia). Sampling occurred at 15, 30, 45, and 75 days of incubation. The intestinal tract of five individuals was removed, sectioned the posterior third, processed and stored in ultrasound. DNA from microbes associated with the intestinal tract, litter and coprolite was extracted, and DGGE analysis using 16S rDNA, DGGE group actinomycetes, and it was evaluated the presence of nifH genes. The 16s gene analysis by DGGE revealed a microbial diversity conditioned by the diet offered to 45 days. After this period, this effect was no longer visible. The community associated with coprolites and the type of litter was distributed in separate clusters of samples from the intestinal tract. This effect was not observed in the community assessment of actinomycetes, where the big difference for division of groups was the diet. The animals fed on grass litter showed a diverse community, and they were not influenced by time or compartmentalization. The samples associated with litter and coprolites were 80% similar to samples from the intestinal tract. In millipedes fed with material form Mimosa caesalpinifolia, the result was different, the samples of litter and coprolites where 50% similar to the intestinal tract. All samples had nifH genes detected by polymerase chain reaction. Samples collected at 45 days were also inoculated in mineral minimum medium of Busnell-Hass added carboxymethyl-cellulose (CMC) as sole carbon source. Colonies were evaluated for their ability to breakdown cellulose enzyme and 15 had an index greater than 1. The isolate that showed the highest rate (3.65) was subjected to further analysis. The microscope observation suggested that this was not an isolated but a complex of microorganisms acting on the degradation of cellulose. There is evidence of BNF in the intestinal tract of the millipede and microorganisms proliferated in CMC through the proper amplification of nifH genes and proliferation in medium within nitrogen. The community of prokaryotes was influenced by the diet offered to the community up to 45 days, and the actinomycetes community was conditioned by the diet. It was possible to isolate microorganisms and complexes of microorganisms with cellulolytic capacity, with great potential in the search for environmentally friendly technologies in generating agrobioenergy. / A crescente demanda por processos biol?gicos alternativos, ambientalmente favor?veis e eficientes na transforma??o de material ligninocelul?sico, ampliando seu potencial de aplica??o agroindustrial, estimula pesquisas em todo o mundo. Assim, microrganismos isolados na natureza, em ecossistemas espec?ficos, tornam-se cada vez mais importantes pela sua diversidade metab?lica e fisiol?gica, que lhes confere grande potencialidade no desenvolvimento de processos biotecnol?gicos de interesse ? sociedade. O objetivo deste trabalho foi avaliar a comunidade microbiana associada ao trato intestinal do dipl?pode Trigoniulus corallinus e a bioprospec??o de microrganismos com capacidade celulol?tica. Os dipl?podes foram coletados e incubados em dietas com serrapilheira de grama batatais (Paspalum notatum) e sabi? (Mimosa caesalpinifolia). As amostragens aconteceram aos 15, 30, 45 e 75 dias de incuba??o. O trato intestinal de cinco indiv?duos foi removido e seccionado o ter?o posterior tratado em ultrasom e estocado. Procedeu-se a extra??o de DNA da microbiota associada ao trato intestinal, serrapilheira e copr?lito, com an?lise por DGGE utilizando o gene 16S rDNA, DGGE para grupo actinomicetos e avalia??o da presen?a de genes nifH. A an?lise do gene 16s por DGGE revelou diversidade microbiana condicionada pela dieta oferecida at? os 45 dias. Ap?s este per?odo o efeito n?o foi mais vis?vel. A comunidade associada aos copr?litos e ao tipo de serrapilheira distribui-se em grupamentos separados das amostras oriundas do trato intestinal. O mesmo n?o foi observado na avalia??o da comunidade de actinomicetos, onde o grande diferencial para divis?o de grupos foi a dieta. Os animais alimentados com serrapilheira de grama mostraram uma comunidade diversa e n?o influenciada pelo tempo ou compartimentaliza??o. As amostras associadas ? serrapilheira e aos copr?litos foram 80% similares ?s do trato intestinal. Nos dipl?podes alimentados com sabi?, o resultado foi diferente, sendo as amostras de serrapilheira e copr?litos 50% similares ?s do trato intestinal. Todas as amostragens tiveram genes nifH detectados via PCR. Amostras coletadas aos 45 dias foram tamb?m inoculadas em meio mineral m?nimo de Busnell-Hass adicionado de carboxi-metil-celulose (CMC) como ?nica fonte de carbono. Os microrganismos isolados foram avaliados quanto ? capacidade de degrada??o de celulose e 15 apresentaram ?ndice enzim?tico maior que 1. O isolado com o maior ?ndice (3,65) foi alvo de outras an?lises. A visualiza??o em microsc?pio sugeriu que n?o se tratava de um isolado e sim de um complexo de microrganismos atuando na degrada??o da celulose. H? evidencias de FBN no trato intestinal do dipl?pode e microrganismos proliferados em meio CMC pela boa amplifica??o de genes nifH e prolifera??o em meio com aus?ncia de nitrog?nio. A comunidade de procariotos foi influenciada pela dieta oferecida at? os 45 dias e a comunidade de actinomicetos foi condicionada em fun??o da dieta. Foram isolados microrganismos e complexos de microrganismos com capacidade celulol?tica, com grande potencial para a busca de tecnologias ambientalmente sustent?veis na gera??o de agrobioenergia.

Les maladies psychiatriques présentent de fortes comorbidités avec des désordres gastrointestinaux, ce qui suggère l’existence de bases physiopathologiques communes. Une littérature abondante démontre que l’adversité précoce (infection, stress) augmente la vulnérabilité aux désordres psychiatriques à l’âge adulte. Chez le rongeur, le modèle de séparation maternelle induit chez la descendance adulte des comportements hyperanxieux associés à une hypersensibilité au stress, ainsi que des dysfonctionnements de la sphère gastrointestinale. De plus, des études récentes rapportent une hyperperméabilité de la barrière intestinale chez les ratons soumis au stress de séparation, un effet conduisant potentiellement à une dysbiose et une perturbation de la communication intestin-cerveau. Le but de ma thèse était donc d’étudier le rôle de l’axe intestin-cerveau dans la mise en place des effets à long terme du stress précoce. Nos travaux récents ont montré que certains effets à long-terme de la séparation maternelle peuvent être atténués par l’exposition des mères à un régime hyperlipidique. Dans un premier temps, nous avons testé les effets du régime hyperlipidique maternel sur le cerveau et l’intestin de ratons soumis à la séparation maternelle. Nos résultats montrent que le régime maternel hyperlipidique protège de l’augmentation de la permeabilité intestinale induite par le stress. Nous avons ensuite testé le rôle causal de la perméabilité intestinale sur les comportements émotionnels à travers une approche pharmacologique et une approche génétique. Nous rapportons 1) que la restauration de la fonction barrière de l’intestin atténue certains effets de la séparation maternelle et 2) qu’une hyperperméabilité intestinale chez des souris transgéniques non soumises à un stress produit des effets similaires à ceux de la séparation maternelle. Enfin, nous avons examiné les effets d’une adversité précoce multifactorielle sur le cerveau et l’intestin (perméabilité et microbiote) chez la descendance adulte mâle et femelle dans un modèle combinant infection prénatale et séparation maternelle. Nos résultats mettent en évidence un effet sexe très marqué sur les phénotypes comportements et intestinaux. D’autres études sont nécessaires pour identifier les mécanismes sous-tendant les effets de la perméabilité et la dysbiose intestinale sur la vulnérabilité émotionnelle associée au stress précoce. / Early-life adversity is a main risk factor for psychiatric disorders at adulthood; however the mechanisms underlying the programming effect of stress during development are still unknown. In rodents, chronic maternal separation has long lasting effects in adult offspring, including hyper-anxiety and hyper-responsiveness to a novel stress, along with gastrointestinal dysfunctions. Moreover, recent studies report gut barrier hyper-permeability in rat pups submitted to maternal separation, an effect that could potentially lead to dysbiosis and altered gut-brain communication. Therefore, the aim of my PhD was to unravel the role of the gut-brain axis in the neurobehavioral effects of early-life stress. We recently reported that some neural, behavioral and endocrine alterations associated with maternal separation in rats could be prevented by maternal exposure to a high-fat diet. We first addressed the effects of maternal high-fat diet on brain and gut during development in the maternal separation model. We show that maternal high-fat diet prevents the stress-induced decrease in spine density and altered dendritic morphology in the medial prefrontal cortex. Moreover, maternal high-fat diet also attenuates the exacerbated intestinal permeability associated with maternal separation. To explore a potential causal impact of gut leakiness on brain functions, we then examined the impact of pharmacological and genetic manipulations of intestinal permeability on brain and behavior. We report 1) that restoration of gut barrier function attenuates some of the behavioral alterations associated with maternal separation and 2) that chronic gut leakiness in naive adult transgenic mice recapitulates the effects of maternal separation. Finally, we examined the effects of multifactorial early-life adversity on behavior, gut function and microbiota composition in males and females using a combination of prenatal inflammation and maternal separation in mice. At adulthood, offspring exposed to early adversity displayed sex-specific behavioral (social behavior deficits in males and increased anxiety in females) and intestinal phenotypes. In conclusion, our work demonstrates an impact of gut dysfunctions, in particular gut leakiness, on the emergence of emotional alterations. Further studies are needed to unravel the role of the gut dysbiosis in the expression of the behavioral phenotypes associated with early-life adversity.

With its unique consortium of microorganisms from all domains of life, termite gut is considered one of the most efficient lignocellulose degrading systems in nature. Recently, host diet and taxonomy as well as gut microenvironmental conditions have emerged as main factors shaping microbial communities in termite guts. The aim of this thesis was to investigate this highly efficient lignocellulolytic system at holobiont level, with a particular focus on gut microbiome function and composition in relation to the host diet. As a starting point, we optimised a complete framework for an accurate termite gut prokaryote-oriented metatranscriptomics, which was at the basis of all subsequent sequencing assay designs and analyses performed in the course of the work. Afterwards, we characterised the compositions and functions of biomass-degrading bacterial communities in guts of plant fibre- and soil-feeding higher termites, proving the existence of functional equivalence across microbial populations from different termite hosts. We also showed that each termite is a reservoir of unique microorganisms and their accompanying genes. We further extended above approach to metagenomics and bacterial genomes reconstruction and we applied it to explore the process of biomass digestion in the different sections of the highly compartmented gut of soil feeding Labiotermes labralis. We showed that primarily cellulolytic activity of the termite host was restricted to foregut and midgut, while bacterial contribution was most pronounced in P1 and P3 hindgut compartments and included activities targeting broad range of lignocellulose components. Finally, we investigated the adaptation of a laboratory-maintained grass-feeding higher termite colony of Cortaritermes spp. to Miscanthus diet at host and symbiont levels. A natural system of a termite gut was shown to progressively change in composition to yield a consortium of microbes specialised in degradation of a specific biomass. Overall, the integrative omics approach proposed here provide a framework for a better understanding of a complex lignocellulose degradation by a higher termite gut system and pave a road towards its future bioprospecting. / Doctorat en Sciences / info:eu-repo/semantics/nonPublished

No description available.

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