Thyroid hormones (THs) are essential signaling molecules for the postembryonic development of all vertebrates. THs are capable of initiating a diverse set of developmental programs across multiple tissues. The role of TH in regulating gene expression is well-known, but the initiation of TH signaling is still not fully understood. In amphibians, THs are the sole hormones required for the metamorphosis from tadpole to juvenile froglet. Amphibians are a useful model for studying TH signaling, as they undergo extensive, tissue-specific response programs in response to exogenous TH. The metamorphosis of the American bullfrog, Rana [Lithobates] catesbeiana is temperature sensitive. R. catesbeiana tadpoles do not undergo metamorphosis at cold temperatures (4-5 °C) even in the presence of THs that should otherwise prompt it. However, tadpoles undergo metamorphosis at an accelerated rate when returned to warm temperatures (24-25 °C) forty days after their initial TH exposure. R. catesbeiana tadpoles possess a “molecular memory” of TH exposure which establishes the TH signal at cold temperatures and prompts accelerated metamorphosis after a return to warmer temperatures. The mechanisms of the molecular memory which allow it to uncouple the initiation of TH signaling from the execution of the TH response program are not fully understood. Previous research has established that transcripts encoding transcription factors are a substantial component of the TH-dependent transcriptomic response of cultured tailfin (C-Fin) at cold temperatures. However, not all of these putative transcripts encoding transcription factors required active transcription and translation for their induction, which suggests that the initiation of a TH signal involves mechanisms other than regulating gene expression. Herein, we used quantitative polymerase chain reaction (qPCR) and RNA-Sequencing (RNA-Seq) to investigate the TH-dependent transcriptomic response of the back skin, a tissue that undergoes extensive remodeling during metamorphosis. Cultured back skin (C-Skin) was TH-responsive in warm, cold and temperature shift conditions. Forty-four transcripts underwent significant changes in abundance in response to TH in cold temperatures under which the molecular memory is established. Seven of these transcripts encoded putative transcription factors. Surprisingly, the only TH-responsive transcript significantly changed at 4 °C in both the C-Skin and the previously studied C-Fin was thyroid hormone-induced basic leucine zipper-containing protein (thibz). Thibz has been found to be TH-responsive at cold temperatures in the liver, lung, liver, brain, tailfin and back skin of whole animals, which suggests it may be an important regulator of initiating TH signaling. The lack of overlap in the transcriptomic responses of C-Skin and C-Fin may suggest that even the early initiation of TH signaling has tissue-specificity. Alternately, the molecular memory may include mechanisms that do not require active transcription and translation. Transcripts associated with epigenetic modifications and post-transcriptional changes to mRNA stability were also significantly expressed at 4 °C within the C-Skin. Previous investigation of the putative transcription factors in C-Fin revealed that active transcription and translation was not always required for changes in transcript abundance. Multiple mechanisms may be at play in the TH response at different temperatures. In cold temperatures, TH may modulate mRNA stability to influence transcript abundance as a part of initiating TH signaling without executing metamorphosis. Further research is needed to explore potential alternative mechanisms of establishing the molecular memory and the accelerated metamorphic response. The temperature sensitivity of R. catesbeiana’s TH response is incredibly valuable in investigating mechanisms of early TH signaling during postembryonic vertebrate development. / Graduate

Die Haut ist eine oft übersehene Komponente des angeborenen Immunsystems der Mücken. Die Haut der Mücke bildet eine physische Barriere, die die mikrobielle Homöostase aufrechterhält, das Eindringen von Toxinen wie Insektiziden verhindert und das Austrocknen verhindert. Die am meisten untersuchten Akteure des Immunsystems von Stechmücken sind das Fettgewebe und die Blutzellen, aber die Hauttalg-Fabriken, die Oenozyten, werden in Studien nur selten berücksichtigt. Mückenpuppen haben aktiv funktionierende immunitätsbezogene Organe, einschließlich derjenigen, die Hautbarrieren produzieren. Ihre biologische Rolle in diesem Entwicklungsstadium ist kaum bekannt, aber der Übergang von der Puppen- zur Erwachsenenhaut und die Auffälligkeit der talgproduzierenden Zellen machen dieses Stadium zu einem vielversprechenden Entwicklungsstadium für die Untersuchung der Hautbildung. Mit Hilfe der Transkriptomanalyse beschreiben wir die Rolle der Blutzellen bei der Entwicklung des chitinösen Teils der Insektenhaut, die Beteiligung des Fettkörpers an der Immunität und bestätigen die Rolle der talgproduzierenden Zellen im Lipidstoffwechsel. Darüber hinaus beschreiben wir talgsezernierende Zellen als einen bedeutenden Wirkungsort des NF-kappaB-ähnlichen IMD-Rel2-Pathway, in dem der Transkriptionsfaktor Rel2 die Retinoid-Homöostase reguliert. Schließlich bestätigen wir eine 100 Jahre alte Beobachtung, wonach sebumsezernierende Zellen der Stechmücke ihren Zellinhalt in einem Netzwerk von Vesikeln absondern. Wir beschreiben extrazelluläres Chromatin als Fracht in diesem Vesikelnetzwerk und sein antimikrobielles Potenzial. / The skin is an often overlooked component of the mosquito's innate immune system. The mosquito skin provides a physical barrier that maintains microbial homeostasis, prevents the entry of toxins like insecticides, and avoids desiccation. The most studied players in the immune system of mosquitoes are the adipose tissue and blood cells, but studies rarely consider the skin sebum factories, oenocytes. Mosquito pupae have actively functional immunity-related organs, including those producing skin barriers. Their biological roles at this developmental stage are poorly understood, but the pupae-to-adult metamorphic skin transition and the conspicuity of sebum-secreting cells make it a promising developmental stage to study skin formation. We use transcriptomics to describe the role of blood cells in the development of the chitinous section of the insect skin, the involvement of the fat body in immunity, and confirm the lipid metabolism role of sebum-secreting cells. Furthermore, we describe sebum-secreting cells as a significant action site of the NF-kappaB-like IMD-Rel2 pathway where the transcription factor Rel2 regulates retinoid homeostasis. Finally, we confirm a 100-year-old observation of how mosquito sebum-secreting cells secrete their cellular contents in a network of vesicles. We describe extracellular chromatin as cargo inside this vesicle network and its antimicrobial potential.

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La plasticité du système nerveux central face aux contraintes environnementales ou morphologiques est un processus fondamental mis en place afin de permettre à l’animal de maintenir des comportements adaptés. Parce que le comportement locomoteur est essentiel à la survie de l'animal, les mécanismes neuronaux permettant sa genèse doivent s’adapter aux modifications morphologiques de l’organisme pendant son développement. Pour aborder cette question, nous avons développé un nouveau modèle expérimental pour lequel les modifications morphologiques au cours du développement sont extrêmes et impliquent des reconfigurations à long terme du système nerveux. L'amphibien Xenopus laevis lors de sa métamorphose est, en effet, un modèle pertinent pour étudier (par des approches comportementales, neuroanatomiques, électro-physiologiques et pharmacologiques), les mécanismes impliqués dans la réorganisation des réseaux neuronaux locomoteurs de la moelle épinière face à des modifications extrêmes du schéma corporel. En effet, pendant sa métamorphose, l'animal passe d'un mode de locomotion ondulatoire mettant en jeu sa musculature axiale, à un mode de locomotion appendiculaire grâce aux membres néo-formés. Il existe de plus des stades intermédiaires où les deux modes de locomotion coexistent et expriment des relations fonctionnelles variables. Nos expériences d’électrophysiologie extracellulaire nous ont permis de dégager la dynamique temporelle de l’émergence du réseau de neurones commandant la locomotion appendiculaire adulte et de ses relations fonctionnelles avec le réseau locomoteur commandant la nage larvaire lorsque ces deux réseaux coexistent. D’après les résultats présentés, il apparaît un changement de l’équilibre fonctionnel et des interactions entre les commandes locomotrices ondulatoire et appendiculaire, faisant des stades intermédiaires de la métamorphose les témoins privilégiés du passage de relais progressif entre les deux systèmes locomoteurs. Nos travaux ont également démontré que l’activité de chaque réseau ainsi que leurs relations fonctionnelles sont sujettes à modulation glutamatergique et aminergique destinées à adapter la locomotion aux besoins de l'animal. Nous montrons que certains modulateurs (tels que le glutamate, la sérotonine et la noradrénaline) exercent des effets opposés sur les réseaux locomoteurs larvaires et adultes, alors qu'à l'inverse, la dopamine conserve les mêmes propriétés modulatrices sur ces réseaux malgré les profonds bouleversements subis pendant le développement. Outre leur rôle modulateur, nos résultats suggèrent aussi un rôle des afférences aminergiques dans la maturation des réseaux locomoteurs et ouvrent de nombreuses interrogations quant aux mécanismes impliqués dans la plasticité des afférences neuromodulatrices elles-mêmes au cours de la métamorphose. L’apparition et la disparition de neurones sérotoninergiques intraspinaux concomitantes avec la croissance des membres postérieurs, et précédant la régression de l'appendice caudal laissent envisager un rôle de la sérotonine dans la maturation du réseau locomoteur appendiculaire ou dans la chronologie de la régression du réseau axial. / Plasticity of the central nervous system is fundamental to an animal's capacity to adapt to continually changing biomechanical and environmental demands. Although the neuronal mechanisms underlying such essential behaviours as locomotion must adapt to an organism's morphological modifications during growth and development, the associated changes that occur in central nervous function remain poorly understood. To address this issue, we have developed a new experimental model - the amphibian Xenopus laevis during its metamorphosis - in which the extreme biomechanical modifications occurring during this critical period necessitate a correspondingly extensive and long-term reorganisation of locomotor neural circuitry within the animal's spinal cord. During metamorphosis, the locomotory strategy of Xenopus shifts from undulatory swimming involving axial tail-based movements, to appendicular propulsion that uses the newly formed limbs. At intermediate metamorphic stages, moreover, the two locomotor strategies coexist within the same animal as the secondary limb-based motor circuitry is progressively replaces the primary axial network as the limbs are added and the tail regresses. By making extracellular recordings of spontaneous "fictive" locomotor patterns generated by isolated brainstem/spinal cord preparations, we have charted the temporal dynamics of the emergence of the appendicular neuronal network and determined its functional relationship with larval axial locomotor circuitry through the metamorphic period. Our results have shown that the limb circuitry is initially present but not functional, functional but subordinate to the embryonic axial network, functionally independent from the axial network, and ultimately alone after axial circuitry disappears with tail resorption. Furthermore, the use of pharmacological approaches established that during the metamorphic transition, the coexisting spinal locomotory networks and their functional interactions are subject to glutamatergic and aminergic modulation in order to adapt locomotory performance to the immediate behavioural needs of the animal. Interestingly, the neuromodulators glutamate, serotonin and noradrenaline exert directly opposing influences on the larval and adult locomotor networks, while dopamine preserves a similar modulatory action on the two circuits in spite of their profound remodelling during metamorphic development. Finally, in addition to a short-term modulatory role, our immunocytochemical evidence suggested that descending aminergic systems may contribute to the long-term maturation of spinal locomotor circuitry during metamorphosis in parallel with their own developmental reconfiguration. Specifically, the appearance and disappearance of a population of intraspinal serotonergic neurons concomitant with hindlimb growth and preceding tail regression suggested a role of serotonin in the maturation of the appendicular locomotor network and/or in the chronology of axial network regression.

Au cours d’une infection, l’intensité et la durée de la réaction immunitaire doivent être étroitement contrôlées au risque de devenir délétère pour l’hôte. Chez la drosophile Drosophila Melanogaster, une infection bactérienne conduit à l’activation de voies de signalisation de type NFκ-B, conservées au cours de l'évolution, via la détection du peptidoglycane, un composant de la paroi bactérienne, par des récepteurs PGRPs (« Peptidoglycan Recognition Proteins »). Durant ma thèse, j’ai étudié les conséquences d’une activation non contrôlée d'une de ces voies, la voie IMD, sur la physiologie de la drosophile. Le premier projet auquel j’ai participé montre que l’inactivation de PGRP-LF, un régulateur négatif de la voie, conduit à l'activation de la voie IMD dans les tissus larvaires dérivés de l’ectoderme en absence d’infection. Cette activation entraine l’expression ectopique dans ces tissus de la protéines DIAP1 («Drosophila Inhibitor of Apoptosis 1»), suffisante pour induire la malformation de certains tissus de la drosophile adulte démontrant une fonction développementale jusqu'alors inconnue de la voie IMD au cours de la métamorphose de la drosophile. Dans la seconde partie de ma thèse, j’ai pu observer que durant une infection chronique, le maintien de l’activation de la voie IMD entraine l’apparition de nombreux phénotypes tels qu’une baisse de l’espérance de vie, des troubles locomoteurs, de la neurodégénérescence et l’atrophie du corps gras et des ovaires. Mes résultats montrent que l’activation de la voie IMD spécifiquement au niveau de la glie périneuriale, un composant de la barrière hématoencéphalique, participe activement à l’apparition des phénotypes observés. / Upon infection, the intensity and duration of the immune response must be tightly controlled at the risk of becoming harmful for the host. In the fruit fly Drosophila Melanogaster, a bacterial infection leads to the activation of evolutionary conserved NFk-B signalling pathways, through detection of a bacterial cell wall component, the peptidoglycan (PG), by PGRPs ("Peptidoglycan Recognition Proteins") receptors. During my thesis, I studied the consequences of uncontrolled activation of one of these NFk-B pathways, the IMD pathway, on the physiology of Drosophila. The first project I took part in shows that inactivation of PGRP-LF, a negative regulator of the pathway, leads to the activation of the IMD pathway in ectodermal derived larval tissues without any infection. This pathway activation in those tissues leads to an ectopic expression of the DIAP1 ("Drosophila Inhibitor of Apoptosis 1") protein, wich is sufficient to induce some adult Drosophila structures malformations, demonstrating a previously unknown developmental function of the IMD pathway during Drosophila metamorphosis. In the second part of my thesis, I was able to demonstrate that during chronic infection, maintenance of IMD pathway activation leads to the appearance of many deleterious phenotypes such as a decreased lifespan, locomotor disorders, neurodegeneration and atrophy of the fat body and ovaries. My results show that IMD pathway activation specifically in the perineurial glia, a component of the blood-brain barrier, actively contributes to the development of the observed phenotypes. Demonstrating for the first time that fhe fly's brain is able to detect circulating PG in the hemolymph.

Nas últimas décadas, o fenômeno urbano na cidade de Juazeiro do Norte, localizado no interior do Ceará, no nordeste brasileiro, reproduziu-se de forma tão acelerada em direção as cidades limítrofes, Barbalha e Crato, subordinando-as, de tal modo que atingiu no fim do século passado seu ponto crítico em face de uma metamorfose urbana que se processa impactando as formas, funções e estrutura do espaço urbano. Em razão disso, o espaço tornou-se uma das novas raridades, ora subsumido como valor de troca pelo mercado imobiliário como também pelos empreendimentos comerciais, ora sendo reivindicado como valor de uso pelos sujeitos subalternizados. Essa encruzilha inaugura um novo momento em que a vida cotidiana é atravessada por novos referenciais, sendo colonizada por uma ordem distante, que ganha materialidade nos espaços economicamente mais dinâmicos da cidade. Nesse sentido, o bairro, enquanto lugar cotidianamente vivido, não só reflete as transformações decorrentes dessa metamorfose urbana como dialeticamente a condiciona, seja como um resíduo, seja porque se torna potencialmente alvo dos interesses dos agentes hegemônicos que regem a produção do espaço urbano nesse momento atual. Para compreender essas transformações e conflitos que se desencadeiam no seio do cotidiano, emergentes nesse momento atual da cidade, elege-se o bairro João Cabral, um espaço popular originalmente periférico cuja formação se deu no último quartel do século passado. Esse recorte espacial específico está relacionado a dois aspectos pelos os quais esse bairro em questão revela-se um fio condutor da metamorfose urbana da cidade, analisada sob a ótica da vida cotidiana: a) sua localização atual privilegiada, contígua aos espaços que se configuraram como áreas que exercem centralidade ou são subcentros, concorrendo com o centro principal; b) a emergência de uma nova condição espacial cujo conteúdo pode ser apreendido por meio das práticas socioespacias dos moradores. Assim, esse estudo busca dar cabo da seguinte questão: Quais contradições e conflitos têm se manifestado no bairro João Cabral no contexto contemporâneo em que se processa uma metamorfose urbana na cidade de Juazeiro do Norte, considerando o plano do cotidiano? Para tanto, recorremos à teoria urbana crítica, bem como ao método progressivo-regressivo lefebvriano. / In the last decades, the urban phenomenon in the city of Juazeiro do Norte, located in the interior of Ceará, in northeastern Brazil, reproduced itself so fast towards the neighboring cities, Barbalha and Crato, subordinating them, in such a way that it reached at the end of the last century its critical point in the face of an urban metamorphosis that takes place impacting the forms, functions and structure of the urban space. Because of this, space has become one of the new rarities, now subsumed as exchange value by the real estate market as well as commercial ventures, now being claimed as use value by subalternized individuals. This crossroads inaugurates a new moment in which daily life is crossed by new references, being colonized by a distant order that gains materiality in the most economically dynamic spaces of the city. In this sense, the neighborhood, as a place lived daily, not only reflects the transformations arising from this urban metamorphosis, as a conditional condition, either as a residue, or because it becomes potentially a target of the interests of the hegemonic agents that govern the production of urban space at that moment current. In order to understand these transformations and conflicts that are unleashed within the daily life, emerging at this current moment of the city, the neighborhood is chosen João Cabral, an originally peripheral popular space whose formation occurred in the last quarter of the last century. This specific spatial clipping is related to two aspects by which this neighborhood in question proves to be a guiding thread of the urban metamorphosis of the city, analyzed from the point of view of everyday life: a) its present privileged location, contiguous to the spaces that have been configured as areas that exercise centrality or are subcenters, competing with the main center; b) the emergence of a new spatial condition whose content can be apprehended through the socio-spatial practices of the residents. Thus, this study seeks to answer the following question: What contradictions and conflicts have been manifested in the neighborhood of João Cabral in the contemporary context in which an urban metamorphosis in the city of Juazeiro do Norte takes place, considering the daily plan? For this, we resort to critical urban theory, as well as Lefebvre\'s progressive-regressive method.

Jacques Derrida a ouvert un nouvel horizon pour concevoir l’écriture, en insistant notamment sur la dynamique de la différence qu’elle met en œuvre. Pour penser cette différence et pour libérer le texte d’un sens présupposé univoque, il sollicite Friedrich Nietzsche, mais sans étudier, pour autant, le lien qui rattache l’écriture de ce dernier à la question du corps. Quant à sa propre conception de l’écriture, il est frappant qu’elle ait été abondamment étudiée, sans que le lien qui l’unit à la question du corps reçoive toute l’attention méritée. Ce présent travail vise donc à penser l’écriture du corps chez Nietzsche et chez Derrida, ou plus exactement entre eux, en étudiant la « corporalisation » de l’écriture et la « textualisation » du corps. Nous montrons que, chacun à sa façon, Nietzsche et Derrida puisent dans l’ambiguïté corporelle pour élaborer de nouvelles dynamiques d’écriture, tout en donnant à penser le corps lui-même en termes d’écriture. Pour étudier ce double geste, nous lisons différents textes de Derrida, à partir desquels nous proposons une réflexion sur l’écriture du corps chez Nietzsche, sans que ce dernier y soit nécessairement mentionné. En effet, c’est l’hospitalité de l’écriture de Derrida elle-même qui invite à une telle démarche, que nous abordons en termes d’intrusion. / Jacques Derrida has opened a new horizon to conceive writing by insisting on the dynamic of “difference” that it implements. To address the question of difference, as well as to liberate the text from a presupposed unambiguous meaning, he solicits Friedrich Nietzsche without examining, however, the link which connects the writing of the latter with the question of the body. As for Derrida’s own conception of writing, what is striking is that while it has been widely studied, its link to the question of the body has not received the attention it deserves. Therefore this present work aims to consider the writing of the body in Nietzsche’s and Derrida’s philosophies, and more precisely between them, by studying the “corporization” of the writing and the “textualization” of the corporeity. We demonstrate that both Nietzsche and Derrida, each in his own way, draw from the body’s ambiguity to develop new dynamics of writing, and think about embodiment, at the same time, in terms of writing. To discuss these two aspects, we read various texts of Derrida, through which we also suggest a reflection on Nietzsche’s writing of the body, without the latter being necessarily mentioned. It is actually the hospitality of Derrida’s writing that allows such a gesture, which could be perceived more in terms of intrusion.

[pt] Esta pesquisa tem como objetivo conhecer o trabalho desenvolvido pela instituicão Se Essa Rua Fosse Minha em relacão as identidades culturais. Dentro desta organização, o foco principal recaiu sobre o projeto Dando Bola para a Vida. Este projeto tem como finalidade o trabalho de arte-educação, utilizando a metodologia do Circo Social, com as crianças e jovens do complexo do Cerro-Corá, localizado na Zona Sul do Rio de Janeiro. Foram analisadas duas categorias principais que surgiram da própria lógica do universo estudado: autonomia e reciprocidade. A partir destas categorias a relação dialética entre individuo e seu meio social se estabelece contribuindo para o desenvolvimento da identidade, do potencial de metamorfose e do alargamento do campo de possibilidades. / [en] The objective of this research is to understand the work developed by the institution Se Essa Rua Fosse Minha in relation to cultural identities. Within this organization the main focus was based on the project Dando Bola para a Vida. This project works with the children from the community of Cerro-Corá, which is located in the South part of Rio de Janeiro. It uses an art-education perspective and applies the Social Circus method. Two categories, which arose from the focus group itself, were used: autonomy and reciprocity. Supported by these categories, the dialectics between individual and one´s social surroundings is established and contributes to the development of the identity, of the potential of metamorphoses and of the broadening of the field of possibilities.