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Etude des programmes transcriptionnels impliqués dans le développement des neurones somatosensoriels et leur état après axotomie / Transcription programs in the development of somatosensory neurons and their state after axotomyMoussa, Salim 16 December 2013 (has links)
La sensation du toucher permet de détecter des stimuli mécaniques via des neurones mécanosensitifs dont les corps cellulaires sont localisés dans le ganglion rachidien dorsal. Ces neurones projettent vers la peau en périphérie et font leurs synapses avec les interneurones dorsaux de la moelle épinière. L'étude de ces neurones était difficile à cause du manque de marqueurs spécifiques pour ces neurones, jusqu'à la découverte du gène MafA dans le ganglion rachidien dorsal. En effet, mon équipe a montré que MafA est un marqueur spécifique des neurones mécanosensitifs à bas seuil de type Rapidly adapting. Le gène c-Maf, de la même famille que MafA, est aussi exprimé dans ces neurones et il est l'acteur principal de leur développement et de leur fonction. Afin de comprendre comment c-Maf contrôle le développement des neurones somatosensoriels, la première partie de mon travail visait à identifier de nouveaux gènes cibles du facteur de transcription c-Maf et à savoir comment l'expression de ce dernier est régulée dans les neurones du ganglion rachidien dorsal. Concernant la recherche des gènes cibles de c-Maf, j'ai réalisé l'étude de l'expression de gènes candidats dans le contexte de perte de fonction de c-Maf chez la souris. J'ai pu identifier deux cibles : p-cadhérine et mab21/L2, parmi une liste de gènes candidats. J'ai par la suite analysé l'expression de P-cadhérine au cours du développement et j'ai observé qu'elle est exprimée dans la sous-population de neurones sensoriels myélinisés exprimant c-Maf ainsi que dans certains interneurones des laminae III/IV de la moelle épinière. Une expression particulière de P-cadherine est observée dans les cellules des capsules frontières dans les zones d'entrée et de sortie des racines rachidiennes. Suite à ces observations, nous avons émis l'hypothèse suivante : l'expression de la p-cadhérine est régulée par c-Maf dans les neurones sensoriels ainsi que dans les interneurones pour assurer la connexion synaptique entre eux. Concernant, la régulation du gène c-maf, la question reste ouverte. La deuxième partie de mon étude concernait l'analyse du rôle de facteurs de transcription MafA, c-Maf, Runx3 et Er81 dans la plasticité neuronale induite chez la souris adulte après axotomie du nerf sciatique. Ces facteurs sont impliqués dans le développement des neurones somatosensoriels. Cette analyse a montré que l'expression de MafA et Er81 diminue trois jours après axotomie du nerf périphérique, alors que celle de Runx3 et de c-Maf n'est pas affectée. On peut suggérer que chez l'adulte, la régulation de l'expression de MafA et Er81 dépend des facteurs neurotrophiques libérés par les cibles de ces neurones tandis que celle de c-Maf et Runx3 en est indépendante. / The sense of touch relies on the detection of mechanical stimuli by specialized cutaneous mechanosensory neurons whose cell bodies are located in the dorsal root ganglia. These neurons project peripherally to the skin and synapse on target interneurons in the spinal cord. Until the discovery of MafA expression in the dorsal root ganglion, the lack of molecular markers of mechanoreceptor neurons has made it difficult to analyze the development of these neurons. My team showed that MafA is a specific molecular marker for low-threshold mechanoreceptor neurons RAM. C-Maf gene is a member of the Maf family and it is expressed in the MafA sensory neurons. The transcription factor c-Maf controls touch receptor development and function.In order to understand how c-Maf controls somatosensory neurons development, the first objective of my study was to find new targets for c-Maf transcription factor and to know how c-Maf expression is regulated in the dorsal root ganglion. Therefore, I have analysed the expression of different candidate genes in a loss of function context of c-Maf in the mice. I identified two targets: p-cadherin and Mab21/L2 among a list of candidates. Then, I analysed the p-cadherin expression during development and found that this target of c-Maf is expressed in a sub-population of c-Maf sensory neurons and interneurons of the laminae III/IV of the spinal cord. A particular expression of p-cadherin was noticed in the boundary cap cells at the dorsal root entry zone and the motor exit point of the spinal cord. These observations let us put the following hypothesis: c-Maf regulates p-cadherin expression in the sensory neurons and the interneurons to enable specific connections between these neurons. No identified factors were found to regulate c-Maf expression. In the second part of my study, I focused my efforts on the analysis of the role of MafA, c-MAf, Runx3 and Er81 transcription factors in neuronal plasticity induced in the adult mice three days after sciatic nerve axotomy. These factors are involved in the development of somatosensory neurons. The analysis showed that MafA and Er81 expression are down-regulated after peripheral nerve axotomy but the c-Maf and Runx3 expression did not change. We suggest that at adult stage the regulation of MafA and Er81 expression depend on neurotrophic factors released by the targets of these neurons but it's not the case for c-Maf and Runx3 expression.
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Método para instalação robusta do sensor medidor de vazão mássica de ar (MAFS) em sistemas de admissão de ar para motores de combustão interna. / Method for installing robust sensor mass air flow meter (MAFS) in air intake systems for internal combustion engines.Bernardo, Giovanni Francisco 15 December 2010 (has links)
A utilização do sensor medidor de vazão mássica de ar (MAFS) para controlar a vazão em massa de ar admitida pelo motor de combustão interna é relativamente nova no Brasil. Dentre os veículos comercializados no mercado brasileiro é possível encontrar uma série de exemplos que aplicam tal tecnologia. Acredita-se ainda, que este sensor em breve será adotado pela totalidade dos fabricantes de veículos nacionais. Este trabalho aborda uma metodologia prática para instalação robusta deste sensor em sistemas de admissão de ar para motores de combustão interna veiculares. Esta metodologia foi baseada em recentes projetos de desenvolvimento de sistemas de admissão de ar realizados por uma das principais montadoras brasileiras que utiliza este tipo de sensor para auxiliar no gerenciamento do sistema eletrônico de controle do motor. Este trabalho inclui ainda informações sobre os principais testes de validação para a instalação do sensor nos sistemas de admissão veicular, bem como algumas das práticas adotadas na execução do processo de desenvolvimento. Além disso, serão abordados também os efeitos de modificações realizadas nos sistemas de admissão e como estas afetam os resultados obtidos. / The usage of Mass Air Flow Sensor (MAFS) to control the mass air flow intake by the internal combustion engine is relatively new in Brazil. Among the vehicles sold in the Brazilian market it is possible to find a number of examples that apply this technology. It is believed, however, that this sensor will soon be embraced by all domestic vehicle manufacturers. This document presents a practical methodology for robust installation of this sensor in air intake systems for a vehicle internal combustion engine. This methodology was based on recent development projects of air intake systems developed by one of the main Brazilian companies that use this type of sensor to help the electronic control system to manage the engine. This work also includes information about the main validation tests for installing the sensor in the vehicle air intake systems, as well as some of the practices adopted in the implementation of the development process. There will also be addressed the effects of modifications in the intake systems and how these modifications affect the results.
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Método para instalação robusta do sensor medidor de vazão mássica de ar (MAFS) em sistemas de admissão de ar para motores de combustão interna. / Method for installing robust sensor mass air flow meter (MAFS) in air intake systems for internal combustion engines.Giovanni Francisco Bernardo 15 December 2010 (has links)
A utilização do sensor medidor de vazão mássica de ar (MAFS) para controlar a vazão em massa de ar admitida pelo motor de combustão interna é relativamente nova no Brasil. Dentre os veículos comercializados no mercado brasileiro é possível encontrar uma série de exemplos que aplicam tal tecnologia. Acredita-se ainda, que este sensor em breve será adotado pela totalidade dos fabricantes de veículos nacionais. Este trabalho aborda uma metodologia prática para instalação robusta deste sensor em sistemas de admissão de ar para motores de combustão interna veiculares. Esta metodologia foi baseada em recentes projetos de desenvolvimento de sistemas de admissão de ar realizados por uma das principais montadoras brasileiras que utiliza este tipo de sensor para auxiliar no gerenciamento do sistema eletrônico de controle do motor. Este trabalho inclui ainda informações sobre os principais testes de validação para a instalação do sensor nos sistemas de admissão veicular, bem como algumas das práticas adotadas na execução do processo de desenvolvimento. Além disso, serão abordados também os efeitos de modificações realizadas nos sistemas de admissão e como estas afetam os resultados obtidos. / The usage of Mass Air Flow Sensor (MAFS) to control the mass air flow intake by the internal combustion engine is relatively new in Brazil. Among the vehicles sold in the Brazilian market it is possible to find a number of examples that apply this technology. It is believed, however, that this sensor will soon be embraced by all domestic vehicle manufacturers. This document presents a practical methodology for robust installation of this sensor in air intake systems for a vehicle internal combustion engine. This methodology was based on recent development projects of air intake systems developed by one of the main Brazilian companies that use this type of sensor to help the electronic control system to manage the engine. This work also includes information about the main validation tests for installing the sensor in the vehicle air intake systems, as well as some of the practices adopted in the implementation of the development process. There will also be addressed the effects of modifications in the intake systems and how these modifications affect the results.
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