Ce travail à pour but de déterminer le mode d’acquisition des ressources carnées par les groupes d’hominidés au cours du Paléolithique inférieur en Europe. La présence du genre Homo en Europe, antérieur à l’épisode paléomagnétique de Jaramillo est attestée dans plusieurs sites archéologiques. Cette dispersion hors d’Afrique est signalée par des industries lithiques appartenant à l’horizon culturel du Préoldowayen et par des restes squelettiques affiliés au genre Homo. Cette étude est axée sur l’analyse taphonomique et archéozoologique, de trois assemblages fauniques associés à une industrie du mode 1 (Barranco León, Fuente Nueva 3, la grotte du Vallonnet) et un assemblage associé à une industrie du mode 2 (la Caune de l’Arago). Les analyses permettent de comprendre les processus de formation de ces assemblages en contexte de plein air et en grotte et d’estimer la part des agents qui sont intervenus. L’implication des Hommes est attestée dans la modification des carcasses de grands mammifères. Des ossements présentent des stries, qui impliquent que les éclats étaient bien utilisés pour prélever la chair et une fracturation caractéristique, liée à l’éclatement des os par les outils aménagés. L’analyse des assemblages osseux révèle une variabilité des systèmes d’approvisionnement en matière carnée. La comparaison de ces accumulations formées en grotte et en plein air, apportent une meilleure compréhension des comportements de subsistances et permet de proposer un aperçu de la variabilité et de la chronologie des comportements alimentaires des Hommes en Europe méridionale pendant le Pléistocène inférieur et moyen. / The purpose of this work is determinated the mode of acquisition of the meat-based resources by the groups of hominids during the lower Palaeolithic in Europe. The presence of the genus Homo in Europe previous to the paleomagnetic Jaramillo event, is attested in several archeological sites. This dispersal outside Africa is indicated by litic industry belonging to the cultural horizon of Préoldowayen and by human fossils affiliated to genus Homo. This study is centred on taphonomical and zooarcheological analysis, of three faunal assemblages associated with a mode 1 industry (Barranco León, Fuente Nueva 3, the Vallonnet cave) and an assemblage associated with a mode 2 industry (Caune de l' Arago). Analyses allow to understand the processes formation of these assemblages in open air site and in cave, and to estimate the part of the agents who intervened. The implication of human is attested in the modification of the carcasses of big mammals. Bones present cutmarks which imply that flakes were used to discard flesh and a characteristic fracturation connected to the percussion of bones by stones tools. The analysis of the bones assemblages reveals a variability of the systems of supply in meat-based subject. The comparison of theses accumulations, bring a better understanding of the subsistences behavior and allows to propose an outline of the variability and the chronology of the eating habits of the Paleolitic People in Southern Europe during Lower and Middle Pleistocene.

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<p>Atherosclerosis is a progressive inflammatory disease that is characterized by the accumulation of lipids, infiltrated cells and fibrous elements in large arteries.</p><p>This thesis focuses on the molecular mechanisms behind foam cell formation and inflammation, two central processes in the development of atherosclerosis. More specific, we studied the effects of proinflammatory cytokines on CXCL16 expression and its role as scavenger receptor on macrophages and smooth muscle cells in atherogenesis. CXCL16 is defined as a chemokine and a scavenger receptor, regulating adhesion and chemoattraction of CXCR6 expressing cells and uptake of oxLDL. We show that the expression of CXCL16 and its receptor CXCR6 are more pronounced in human atherosclerotic lesions compared with non-atherosclerotic vessels. Increased expression of CXCL16 was also seen in atherosclerotic aortas of apoE-/- mice compared with aortas of non-atherosclerotic, age-matched C57BL/6 mice. In vitro, IFN gamma induced CXCL16 expression in primary human monocytes and smooth muscle cells which resulted in an increased uptake of oxLDL. Treatment of mice with IFN gamma also induced CXCL16 expression in atherosclerotic lesions. Thus, we have demonstrated a role for IFN gamma in foam cell formation through upregulation of CXCL16. The expression of CXCR6 was defined to the same regions as for CXCL16 in the lesion, indicating the presence of cells able to respond to CXCL16. Consequently, CXCL16 could serve as a molecular link between lipid metabolism and immune activity in atherosclerotic lesion.</p><p>CD137 belongs to the TNF family and mediates several important processes in inflammation. CD137 is involved in the activation of T cells, NK cells, B cells and monocytes and regulate cytokine production, proliferation and apoptosis in these cells. A limited number of studies have demonstrated CD137 expression on smooth muscle cells and endothelial cells. Our results show that CD137 mRNA is higher expressed in human atherosclerotic lesions compared with unaffected vessels. We found that endothelial cells express CD137 in atherosclerotic lesions and that cultured endothelial cells and smooth muscle cells express CD137 and CD137 ligand in vitro. CD137 was regulated differentially by proinflammatory cytokines (i.e. IFN gamma, TNF alpha, IL-1 beta) and bacterial lipopolysaccharide depending on cell type. Furthermore, we investigated the effects of CD137 signalling, demonstrating that binding of the CD137 ligand to its receptor increases proliferation and migration of smooth muscle cells.</p><p>In summary, this thesis has focused on the expression, regulation and role of CXCL16 and CD137, two genes that have not been described earlier in the concept of atherosclerosis. The findings demonstrate some of the molecular mechanisms involved in vascular inflammation and may increase our knowledge about the development of atherosclerosis.</p>

Ocular neovascularization (NV) associated with corneal NV, ischemic retinopathies and age-related macular degeneration is a leading cause of severe vision loss. While numerous contributing factors have been identified, the potential role of the CD36 scavenger receptor has been largely overlooked notwithstanding its crucial involvement in normal retinal function. Accordingly, the central aim of this work was to elucidate the contribution and regulation of CD36 during ocular NV using the cornea as a model. / Initial work investigating the role of CD36 10 maintaining corneal avascularity, an important feature of the normal cornea, revealed that genetic ablation of CD36 elicits age-related corneal NV. Subsequent studies using a pathophysiologically relevant model of inflammatory corneal NV showed constitutive expression of CD36 in the normal cornea with marked induction in the neovascularized cornea. Importantly, activation of CD36 suppressed and induced regression of corneal NV, effects that proceeded via concerted inhibition of VEGFA, JNK-1, and cJun. / Because hypoxia is a fundamental stimulus for angiogenesis, it was pertinent to explore the role and regulation of CD36 during hypoxia. We demonstrate that CD36 expression was significantly elevated in hypoxia-exposed corneal and retinal tissue and in hypoxic retinal pigment epithelial cells. Essential contributions of hypoxia-inducible factor (HIF)-1 and reactive oxygen species were also established. Functional consequences were depicted by augmentations in CD36 phagocytic and anti-angiogenic activities. / Collectively, data disclose CD36 as an important modulator of corneal avascularity and inflammatory corneal NV; this imparts several interesting avenues for future research on the involvement of CD36 in neovascular diseases of the eye. Novel data further identify CD36 as a hypoxia and HIF-1 regulated gene thus creating a framework for future elucidation of the regulatory aspects of this receptor.

T cells, which constitute an essential arm in the adaptive immunity, complete their development in the thymus through a process called thymopoiesis. However, thymic involution can be induced by a couple of factors, which impairs T cell functions and is slow to recover. Therefore, understanding how thymopoiesis is regulated may lead effort to accelerate thymic recovery and improve immune functions in thymocyte-depleted patients. In this project, we identified scavenger receptor BI (SR-BI), a high density lipoprotein (HDL) receptor, as a novel modulator in thymopoiesis. In mice, absence of SR-BI causes a significant reduction in thymus size after puberty and a remarkable decrease in thymic output. Consequently, SR-BI-null mice show a narrowed naïve T cell pool in the periphery and blunted T cell responses, indicating that the impaired thymopoiesis due to SR-BI deficiency leads to compromised T cell homeostasis and functions. The impaired thymopoiesis of SR-BI-null mice is featured by a significant reduction in the percentage of earliest T progenitors (ETPs) but unchanged percentages of other thymocyte subtypes, suggesting that SR-BI deficiency causes a reduction in progenitor thymic entry. Further investigations reveal that SR-BI deficiency impairs thymopoiesis through affecting bone marrow progenitor thymic homing without influencing the lymphoid progenitor development in bone marrow. Importantly, SR-BI-null mice exhibit delayed thymic recovery after sublethal irradiation, indicating that SR-BI is also required for thymic regeneration. Using bone marrow transplantation models, we elucidate that it is non-hematopoietic rather than hematopoietic SR-BI deficiency that results in the defects in thymopoiesis. However, SR-BI deficiency-induced hypercholesterolemia is not responsible for the impaired thymopoiesis. Using adrenal transplantation models, we found that absence of adrenal SR-BI is responsible for the impaired thymopoiesis, as shown by that adrenalectomized mice transplanted with SR-BI-null adrenal gland display reduced thymus size, decreased percentage of ETPs and delayed thymic regeneration compared with those transplanted with wild-type adrenal. Altogether, results from this study elucidate a previously unrecognized role of SR-BI in thymopoiesis. We reveal that SR-BI expressed in adrenal gland is critical in maintaining normal T cell development and enhancing thymic regeneration, providing novel links between adrenal functions and T cell development.

Orientador: Leila Peres / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Quimica / Made available in DSpace on 2018-08-08T09:28:02Z (GMT). No. of bitstreams: 1 Nogueira_FernandaCunhaClementoni_M.pdf: 3177527 bytes, checksum: f32df709760fd5cc5454138d0affb90d (MD5) Previous issue date: 2005 / Resumo: Estudos indicam que o principal fator a ser controlado para garantir a qualidade de produtos embalados é a concentração de oxigênio. Este controle poderá ser determinante na vida de prateleira do produto. Neste trabalho sistema (¿célula de absorção¿) e metodologia foram desenvolvidos para caracterizar um filme ativo contendo polietileno de baixa densidade e aditivo absorvedor de oxigênio disperso em sua matriz polimérica, o qual, na aplicação, compõe um sistema de embalagens multicamadas. Este aditivo é ativado pelo contato com a umidade e age de forma a seqüestrar o oxigênio dentro da embalagem. A caracterização do filme consistiu na determinação da capacidade e da velocidade de absorção de oxigênio pelo filme ativo, que foi acondicionado na célula, onde se realizou o controle da concentração de oxigênio via análises cromatográficas. O estudo da influência da temperatura e da umidade relativa na absorção do oxigênio foi conduzido segundo um planejamento fatorial composto 22. A dispersão do aditivo na matriz polimérica (microscopia óptica), a rugosidade da superfície do filme (MEV), a transmissão de luz (espectrofotometria UV-visível) e o grau de cristalização da resina (DSC) também foram estudadas. Os resultados indicaram que a variável de maior influencia na absorção de oxigênio é a umidade e que o filme apresenta sua máxima absorção e altas velocidades em temperaturas acima de 15°C e umidade acima de 81,2%. A dispersão do aditivo e a rugosidade na superfície do filme indicam melhores resultados em filmes em concentrações de aditivo acima de 5%. O filme ativo apresenta perda de transparência mesmo em baixas concentrações de aditivo (1%). O grau de cristalização do filme diminui com o aumento da concentração de aditivo, o que pode promover a difusão do oxigênio na resina favorecendo o contato entre o oxigênio e o aditivo, e assim, aumentar a absorção pelo filme / Abstract: Studies indicate that the main factor to be controlled to warrant the quality in packaged products is the oxygen concentration. This controlling can be determinant in the products shelf life. In this work, system (¿absorption cell¿) and methodology had been developed for characterize an active film containing low density polyethylene and a kind of oxygen scavenger additive dispersed throughout the polymer carrier, that, in the application, is part of a multilayer system packaging. This additive is activated by humidity contact and acts in a way of scavenging oxygen inside the packaging. The active film characterization consisted in determining the capacity and speed of oxygen scavenging by the film, that was kept inside the cell, where was carried out the oxygen concentration controlling by gas chromatography. The study of the temperature and the relative humidity influence in the oxygen scavenging was conducted by an experimental design composite 22. The additive dispersion in the polymer carrier (Optical microscopy), the surface roughness (MEV), the light transmission (spectrophotometry UV-visible) and the resin crystallization degree (DSC) were studied as well. The results indicated that the variable with the most influence in the oxygen scavenging was the relative humidity and the film showed the maxim scavenging and speed in temperatures above 15°C and relative humidity above 81,2%. The additive dispersion and the film surface roughness showed better results in film with concentrations above 5%. The film shows transparence lost even for low additive concentration (1%). The film crystallization degree reduces with the increase of additive concentration, this can promote the oxygen diffusion in the resin benefiting the contact between the additive and the oxygen and, though, it increases the scavenging by the film / Mestrado / Ciencia e Tecnologia de Materiais / Mestre em Engenharia Química

La fonctionnalisation de surface par réduction de précurseurs diazoniums est une puissante méthode de fonctionnalisation de surface. Cependant, bien que cette approche permette l’obtention de matériaux robustes, elle reste encore mal maîtrisée et conduit systématiquement à l’élaboration de films organiques épais, non reproductibles, et structurellement désorganisés. Dans ce contexte, nous avons développé une méthodologie permettant le contrôle du greffage dans le but de réaliser des matériaux organisés et reproductibles. Basée sur l’utilisation de piégeur de radicaux, cette méthode a permis l’obtention d’une monocouche sur un substrat carboné. La stratégie de contrôle a ensuite été exploitée pour bloquer sélectivement le mécanisme radicalaire et évaluer le rôle des mécanismes non-radicalaires dans le processus de greffage. Cette étude a permis une meilleure caractérisation du processus de greffage et mis en lumière l’impact du substituant du précurseur diazonium sur le processus de croissance du film organique. L’exploitation de ces connaissances a été mise à profit via la réalisation d’une plateforme monocouche multifonctionnelle. L’étude des relations structures/propriété a révélé des performances accrues en matière de transfert électronique et d’électro catalyse. Pour finir, la transposition de la méthode de contrôle à un greffage de type spontané a fourni un résultat similaire à celui observé pour le greffage électro-induit. L’approche a été validée par l’optimisation des performances d’un super condensateur réalisé à base de matériaux carbonés dispersés. / The surface functionalization by diazonium salt reduction is a powerful grafting method. However, despite that this approach allows the preparation of robust materials, it leads to thick and unorganized organic films. In this context, we have developped a method allowing the grafting control in order to obtain films having controlled thickness. Based on the use of radical scavengers, this method gives access to monolayer formations on carbon substrates. The control strategy was then exploited to selectively block the radical grafting mechanism and allows to assess the role of non-radical mechanisms in the process. This study provided a better understanding of the layer growth, highlighting the impact of precursor substituent.This knowledge has been used to elaborate a multifunctional platform monolayer. The establishment of sutructure/properties relathionships revealed better performances for electronic transfert and electrocatalysis. Finally, the control method was transposed to the spontaneous grafting and gives similar results than those obtained for the electrochemical one. This approach was validated by the performance optimization of supercapacitor made of carbon powder.

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