Müllerzellen - die dominierenden Gliazellen der Netzhaut - üben vielfältige Funktionen und Aufgaben im retinalen „Zellnetzwerk“ aus. Ihre wohl wichtigste Funktion ist die Aufrechterhaltung der Volumen- und Ionenhomöostase der Retina. Forschungsergebnisse der letzten Jahre deuten darauf hin, dass pathologische Veränderungen in der Volumenregulation von Müllerzellen bei vielen Erkrankungen der Netzhaut eine bedeutende Rolle spielen. Diese Promotionsarbeit befasst sich mit morphologischen Veränderungen in der Netzhaut von Wildtypmäusen sowie von drei Mausstämmen mit genetischen Veränderungen (Überexpression von dnSNARE, P2Y1-defizient, IP3-R2-defizient) unter pathologischen Bedingungen. In den experimentellen Untersuchungen fand das in Vorarbeiten bereits etablierte Ischämie-Reperfusions-Modell Anwendung. Es ist bekannt, dass Müllerzellen nach retinaler Ischämie Veränderungen durchmachen, die als reaktive Gliose bezeichnet werden. Reaktive Müllerzellen sind nicht mehr in der Lage, bestimmte Funktionen zu erfüllen, die sie in der gesunden Netzhaut haben, dazu gehört eine Einschränkung der Fähigkeit zur Volumenregulation. Ziel der Arbeit war es erstens, eine Charakterisierung der Mausnetzhäute hinsichtlich der zellulären Zusammensetzung der Retina vorzunehmen und zweitens zu untersuchen, inwiefern sich eine Störung der Müllerzellfunktion – wie sie bei allen drei genetisch veränderten Mauslinien vorliegt – auf das Überleben der Nervenzellen unter extremen Stressbedingungen wie z.B. einer Ischämie auswirkt. Denn gerade unter den mit einer Ischämie einhergehenden Bedingungen sollte die Funktion der Müllerzellen zum Erhalt der retinalen Ionen- und Volumenhomöostase von entscheidender Bedeutung sein.

This study was designed as an attempt to extend Schneider and Shiffrin's (1977) automatic versus controlled processing distinction into the area of visual perception. Hasher and Zacks (1979) proposed a continuum of automatic processes, with processes which encode the fundamental aspects of the flow of information as the anchor of the continuum. They presented evidence that depressed people perform more poorly than nondepressed on effortful (controlled) memory tasks, but not on automatic tasks. Tachistoscopic and free inspection presentation of Piaget's (1961/1969) primary geometric illusions meet two of Hasher and Zack's criteria for automatic and effortful tasks, respectively. Consequently, multiple regression techniques were used to determine the relationship between depression (operationally defined as score on the Beck Depression Inventory) and method of presentation of a Piagetian primary illusion, the Müller-Lyer. Furthermore, correlations were determined between tachistoscopic versus free inspection of the Müller-Lyer illusion and forward versus backward digit span (operationally defined as score on the WAIS Digit Span subtest), since forward and backward digit span have been linked theoretically to automatic and effortful processing, respectively.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

When translating a stylistic written language there are lot to consider, in particular metaphors are said to be one of the most specific challenges. Herta Müllers writing is known to be filled with rhetorical devices. As metaphors belong to one of the major characteristics in Müllers texts, the novel Atemschaukel was studied to find out whether the readers comprehension and experience would differ when reading the text in German language or reading it translated into Swedish.The analysis was based on which strategies was used for the translation and if, and in that case how, it effects the reception of the text by the readers. It showed that most parables and metaphors were directly translated and that the difference in understanding and reading experience mainly didn’t differ much from reading the original text.

Our lab has shown that conditionally disrupting the tcfap2beta gene, responsible for the activating protein-2beta (AP-2beta) transcription factor, exclusively in the craniofacial neural crest cells, leads to anterior segment dysgenesis. Subsequent loss of the corneal endothelium results in the adherence of the iris to the corneal stroma, causing closure of the iridocorneal angle. The activating protein-2beta neural crest cell knockout (AP-2beta NCC KO) model involves a complete blockage of the both the conventional (through the trabecular meshwork) and non-conventional (uveoscleral) pathways for aqueous humor drainage, and therefore it could be used as a powerful experimental model for glaucoma. As shown by our previous work, elevated intraocular pressure (IOP) and a 35% decrease in the number of cells in the retinal ganglion cell (RGC) layer was observed in AP-2beta NCC KO mice by 2 months; 6 to 11 months sooner than other reported mouse models of glaucoma. These observations suggested that the AP-2beta NCC KO mouse could be a novel and cost-effective experimental model for glaucoma if the RGC loss occurred progressively rather than due to a congenital defect. The purpose of this research project was to investigate how the retinal ganglion cell layer and macroglial activity changes with respect to age in the AP-2beta NCC KO mutant through immunofluorescence. Specifically, it was investigated whether the loss of RGCs was progressive and due to the increased IOP caused by the blockage of the uveoscleral drainage pathway. A significant decrease in the number of RGCs was observed between P4 and P10 in the retinal periphery of both WT and AP-2beta NCC KO mice (p<0.05), which is indicative of the programmed cell death that occurs due to retinal pruning during development. No statistical difference between WT and AP-2beta NCC KO mice phenotypes was observed at postnatal day 4 (P4), suggesting that no developmental defect resulted in the significant loss of RGCs at 2 months. In all other time points investigated, while no statistical difference was found between WT and the AP-2 NCC KO mutant, a clear downward trend was present in the AP-2 NCC KO mutant retinal ganglion cell layer from P10 to P40. There was also an expression of glial fibrillary acidic protein (GFAP) by Müller cells, indicating the presence of neuroinflammation at P35 and P40. This substantiates the potential P42 starting point of neurodegeneration our lab previously observed. This was further corroborated with Müller cell-associated expression of GFAP at P35 and P40 exclusively in the AP-2beta NCC KO mouse. Overall, we have shown that the retinal damage observed in our AP-2beta NCC KO mouse is not due to a developmental defect, but rather occurs over time. Thus, this mouse model, which appears to block both the conventional and unconventional uveoscleral pathways, has a profound effect on aqueous humor drainage. As a result, the model requires relatively little time to observe an increase in IOP and subsequent RGC loss. Our findings suggest that the AP-2beta NCC KO mouse can be a novel, powerful, and extremely cost-effective experimental model for glaucoma. / Thesis / Master of Science (MSc)

Las enfermedades neurodegenerativas de la retina son la principal causa de disfunción visual en el mundo desarrollado. En ellas se produce la degeneración y muerte de las neuronas fotorreceptoras, originando una disminución o pérdida total de la visión, en los casos más severos. Las células gliales de Müller (CGM), el principal tipo de células gliales en la retina, y las células del epitelio pigmentario de la retina (EPR) desempeñan un papel clave tanto en la prevención como en el progreso de estas enfermedades. En condiciones fisiológicas las CGM y las células del EPR son las encargadas del mantenimiento estructural, fisiológico y funcional de la retina. Ante alteraciones fisiológicas o frente a daños de diferentes tipos, las CGM y las células del EPR modifican levemente sus funciones a fin de restablecer las condiciones normales o reparar los daños existentes. La proliferación y la migración se activan como parte de una respuesta inespecífica, pero cuando el daño persiste por mecanismos aún desconocidos estos procesos se descontrolan y exacerban, tornándose contraproducentes. A su vez, la localización de estas células en lugares inadecuados distorsiona severamente la estructura y función de la retina, contribuyendo al desarrollo de la disfunción visual, particularmente en las patologías retinoproliferativas. Dilucidar los mecanismos de regulación de la proliferación y la migración, como así también las moléculas que intervienen, es clave para lograr un tratamiento integral de estas enfermedades. Los esfingolípidos bioactivos son moléculas señal que regulan una gran cantidad de procesos biológicos como la supervivencia, proliferación, migración e inflamación. Entre éstos, la ceramida-1-fosfato (C1P) es un esfingolípido que regula numerosas funciones biológicas en diferentes tipos de células. La C1P es generada por la acción de la ceramida quinasa (CerK), enzima encargada de sintetizar C1P a través de la fosforilación de la ceramida (Cer). La actividad de CerK es clave para la señalización celular mediada por C1P y está regulada por niveles bajos de Ca+2, fosforilación y diversos estímulos. La C1P promueve la proliferación través de la activación de diferentes vías de señalización intracelular y la inflamación mediante la unión y activación de la fosfolipasa A2 citosólica (cPLA2), que interviene en la síntesis de prostaglandinas. Para promover la migración, se ha propuesto que la C1P activa un receptor extracelular específico (parcialmente identificado). Trabajos previos de nuestro laboratorio demuestran que la esfingosina-1-fosfato (S1P), un esfingolípido bioactivo muy relacionado a la C1P, promueve la migración de las CGM (Simón et al. 2015). Dada la estrecha interacción metabólica y funcional entre los esfingolípidos, es de gran interés establecer si la C1P, cuyas funciones son semejantes a las de S1P, interviene en la regulación de los procesos que contribuyen a las patologías retinoproliferativas. El objetivo de esta Tesis es investigar si la C1P y la CerK participan en la migración y en la proliferación de las CGM y las células del EPR. Mediante el ensayo de la herida y utilizando cultivos gliales puros de retina de rata y la línea celular humana de EPR, ARPE-19 investigamos los posibles efectos de C1P/CerK en la migración de estos dos tipos celulares. En estos ensayos de motilidad celular, consideramos la reducción del ancho de la herida como un indicador de la migración. Al evaluar el efecto de C1P sobre la migración de las CGM, determinamos que la C1P aumentó la migración a través de la reorganización del citoesqueleto de actina y la formación de filopodios y lamelipodios. Mediante ensayos de incorporación del nucleótido Bromo-deoxiuridina (BrdU) establecimos que la migración no contribuyó al cierre de la herida. Luego investigamos las vías de señalización involucradas en el efecto de C1P. La inhibición de las vías PI3K/Akt y JNK con LY294002 y SP600125, respectivamente, disminuyó la migración glial, tanto en los controles como en los cultivos tratados con C1P. Mediante ensayos de Western blot comprobamos que el agregado de C1P aumentó los niveles de p-Akt, forma activa de la Akt, respecto a los controles, confirmando la activación de la vía de la PI3K. Al inhibir la vía de ERK / MAPK con el inhibidor U0126 disminuyó la migración promovida por la C1P, pero no se alteró la migración en los controles. A continuación, evaluamos el papel de la cPLA2, mediador de C1P en la inflamación, que es activada por su unión a C1P. El tratamiento con ATK, un inhibidor de cPLA2, redujo notablemente la migración glial en cultivos tratados con C1P, mientras que en los cultivos controles la migración no fue alterada. Demostramos así que la C1P promueve la migración de las CGM mediante la activación de cPLA2 y JNK, PI3K y ERK / MAPK. Además, el agregado conjunto de C1P y S1P, evidenció que estos esfingolípidos tuvieron juntos el mismo efecto promotor de la migración glial que cuando fueron suplementados por separado, evidenciando una interrelación entre ellos en la regulación de los mecanismos que activan río abajo. Como la realización de la herida activó la migración celular, decidimos evaluar si la síntesis endógena de C1P estaba involucrada en dicha migración. Para ello, establecimos en primer término, mediante RT-PCR que las CGM expresaban CerK. Incubando los cultivos gliales con NVP231, un inhibidor de la CerK, demostramos que la síntesis endógena de C1P fue necesaria para la migración glial en los controles y para la estimulación de la migración por C1P. Para descartar que la inhibición de la motilidad reflejara una pérdida de viabilidad celular, evaluamos dicha viabilidad por ensayo de MTT. Determinamos que el tratamiento de los cultivos gliales con NVP231 no alteró la viabilidad celular. En las células del EPR el tratamiento con C1P aumentó la migración, mediante la reorganización del citoesqueleto de actina y el desarrollo de extensos lamelipodios. Al evaluar el rol de la síntesis endógena en la migración del EPR, comprobamos que el tratamiento de los cultivos con NVP231 inhibió la formación de lamelipodios y bloqueó la migración de las células epiteliales. Determinamos, mediante el ensayo de MTT, que el tratamiento con NVP231 no alteró la viabilidad de las células del EPR. La C1P y la S1P promovieron la migración de las células del EPR, pero cuando los cultivos fueron tratados con NVP231 antes del agregado de estos esfingolípidos, el aumento de la migración que promovían fue bloqueado. Estos resultados demuestran que la síntesis endógena de C1P fue necesaria para la migración promovida por C1P y S1P, evidenciando que la síntesis de C1P es clave en la estimulación de la migración por estos dos esfingolípidos. A continuación evaluamos el rol de C1P en la proliferación. Ensayos de incorporación del nucleótido BrdU en cultivos no confluentes demostraron que el agregado de C1P no alteró la proliferación ni en los cultivos gliales ni en los epiteliales. La inhibición de la síntesis de C1P redujo la proliferación en las CGM, mientras que no alteró la tasa de proliferación de los cultivos epiteliales, lo que sugiere que la C1P sería un mediador necesario para la proliferación glial en el período activo de mitogénesis de estas células. En conclusión, en este trabajo evidenciamos por primera vez que la C1P agregada exógenamente como así también aquella sintetizada por CerK en el interior celular, potenciaron la migración de las CGM y de las células del EPR. Demostramos también que la síntesis de C1P fue necesaria para la proliferación glial. Considerando la importancia del proceso de migración y proliferación en los dos tipos celulares de la retina decisivos en la mayoría de las enfermedades retinianas, proponemos a C1P/CerK como clave en el desarrollo y avance de las retinopatías proliferativas. / Retinal neurodegenerative diseases are the main cause of visual dysfunction in the developed world. Their common feature is the degeneration and eventual death of photoreceptors, which leads to visual impairment and eventual blindness in the most severe cases. Müller Glial Cells (MGC) are the main type of retinal glia and along with the Retinal Pigmented Epithelium (RPE) these cell types are two key factors in both the prevention and progression of these diseases. Under physiological conditions, MGCs and the RPE are in charge of the structural, physiological and functional maintenance of the retina. When faced with physiological changes or different damages, they alter their regular functions in order to either reestablish a proper environment or repair the existing damages; however, if the damage persists, the long-term changes of their aforementioned functions can be counterproductive and contribute to the development of retinal neurodegenerative pathologies. Proliferation and migration are activated as an unspecific response upon different damages in order to repair them but, due to unknown mechanisms, these processes finally provoke retina structural and functional loss, thus contributing to the progression of the visual dysfunction. The elucidation of the regulatory mechanisms involved in controlling migration and proliferation, including the molecules involved, is crucial for developing an integral treatment of these diseases. Bioactive sphingolipids are signaling molecules that regulate a wide array of biological processes, such as survival, proliferation, migration and inflammation. Among them, ceramide-1-phospate (C1P) is a sphingolipid generated by ceramide kinase (CerK), the enzyme responsible of phosphorylating ceramide (Cer) molecules. CerK activity has a central role in C1P-mediated cellular signaling, and is regulated by low levels of Ca2+, phosphorylation and many other stimuli. C1P promotes proliferation by activating several intracellular signaling pathways, as well as promoting inflammation by coupling with and activating the cytosolic phospholipase A2 (cPLA2), which participates in prostaglandin synthesis. Both for proliferation and migration, it has been proposed that C1P activates a (partially identified) specific extracellular receptor. Previous work from our group has shown that sphingosine-1-phospate (S1P), which is metabolically closely related to C1P, promotes MGC migration (Simón et al. 2015). Due to the close interconversions and functions of sphingolipids, uncovering the role of C1P in the processes involved in proliferative retinopathies is highly relevant. The purpose of this thesis is to investigate whether C1P and CerK participate in the regulation of migration and proliferation of MGC and RPE. By using the scratch wound assay in pure rat glial cultures and the RPE cell line ARPE-19, we assessed the effects of C1P/CerK in the migration of these two cell types. In these cellular motility assays we considered the reduction on the wound width as a positive indicator of cell migration. When evaluating the effect of C1P on migration, we determined that C1P enhanced migration by reorganizing the actin cytoskeleton and the formation of filopodia and lamellipodia. By quantifying the uptake of Bromide-deoxyuridine (BrdU) by MGC we determined that proliferation did not contribute to the reduction in the scratch width. We also investigated the signaling pathways involved in this process. Inhibition of PI3K/Akt and JNK pathways with the selective inhibitors LY294002 and SP600125, respectively, showed a decrease in glial migration in both control and C1Ptreated cultures. Western Blot assays showed that the addition of C1P increased the levels of p-Akt (the active form of Akt) when compared to controls, therefore confirming the activation of this pathway. Selective inhibition of the ERK/MAPK pathway with U0126 showed a decrease in C1P-induced migration, but did not alter it in control conditions. We also evaluated the role of cPLA2, a mediator of C1P in inflammation, which is activated by C1P binding. Treatment with ATK, a selective inhibitor of cPLA2, showed a substantial decrease in migration on C1P-treated cultures, while there was no alteration of the migrating capabilities in control conditions. We therefore showed that C1P is a promotor of MGC migration by activating cPLA2 as well as the JNK, PI3K and ERK/MAPK pathways. In addition, the combined addition of C1P and S1P showed that these sphingolipids had the same effect together than when they were added separately, suggesting either a direct relation between them or with the downstream mechanisms they trigger. Since we determined a basal reduction in the scratch width in control conditions, we evaluated whether the endogenous synthesis of C1P was involved in this migration. Initially, we established by RT-PCR assays that CGM expressed CerK. By incubating glial cultures with NVP231, a selective inhibitor of CerK, we showed that endogenous C1P synthesis was necessary for glial migration under control conditions, and that when this synthesis was inhibited addition of C1P did not restore cell migration. In order to verify that NVP231 did not affect cell viability, we evaluated viability by the MTT assay. We determined that treatment of glial cultures with NVP231 did not alter cell viability. On RPE cells, treatment with C1P increased cell migration by inducing actin cytoskeleton reorganization and extensive development of lamellipodia. When evaluating the role of the endogenous synthesis on RPE migration, we concluded that treating cultures with NVP231 inhibited lamellipodia formation and blocked RPE migration. We also determined that the viability of NVP231-treated RPE cells was not altered. Both C1P and S1P promoted RPE cell migration, but treating the cultures with NVP231 beforehand, abolished the migratory stimulus. These results show that endogenous C1P synthesis is essential for C1P and S1P-promoted migration, establishing that C1P synthesis is crucial to promote the migration of these two sphingolipids. Furthermore, we evaluated the possible role of C1P on cell proliferation. BrdU uptake assays on non-confluent cultures showed that the addition of C1P did not alter the proliferating capabilities on either MGC or RPE cultures. The inhibition of C1P synthesis impaired proliferation of MGCs, but did not affect that of RPE cells, suggesting that C1P might be a necessary mediator for glial proliferation in the active mitogenic stage of these cells. In this work we showed for the first time that both addition of C1P as well as the endogenous C1P produced by CerK promote migration of MGC and RPE cells. We also demonstrated that C1P synthesis is required for glial proliferation. Taking into consideration the relevance of migration and proliferation of both cell types in the development of most retinal diseases, we propose that C1P/CerK is instrumental in the development and progression of proliferative retinopathies.

O objetivo principal de nosso trabalho é descrever e analisar criticamente o núcleo da teoria da gastrea de Ernst Haeckel. Ele gira em torno de duas noções principais: forma gastrular e metazoário. A teoria da gastrea é um conjunto de formulações que visa estabelecer uma definição de metazoário a partir da noção de forma gastrular. O argumento central da teoria da gastrea articula essas duas noções para organizar a partir de estudos de embriologia comparativa uma visão geral da história evolutiva do reino animal. / The main goal of our work is to describe and critically analyze the core of the gastrea theory of Ernst Haeckel. It centers around two main notions: gastrula form and metazoan. The gastrea theory is a set of formulations designed to establish a definition of metazoan from the notion of gastrula form. The central argument of the gastrea theory articulates these two notions to organize from studies of comparative embryology an overview of evolutionary history of the animal kingdom.

Eine Reihe literaturwissenschaftlicher Arbeiten seit Anfang der Neunzigerjahre bezeugt das lebhafte Interesse an der subjektiven Verfasstheit von Müllers Schreiben. Keine jedoch widmet sich erschöpfend Müllers als Autobiografie ausgewiesenem Text KRIEG OHNE SCHLACHT – LEBEN IN ZWEI DIKTATUREN. Zu Ehren kam der Text bislang nur als Zitatsteinbruch, Interpretationshilfe und umfangreiche poetologische Materialsammlung. Zumeist wird das Werk als gültiger Beleg der Intention müllerschen Schreibens herangezogen und erlangt damit einen unzulässigen Grad an Deutungshoheit. Dabei wird die poetische Dimension des Textes oft nur unzureichend reflektiert oder gänzlich missachtet. Die vorliegende textkritische Untersuchung soll dazu beitragen, die Forschungslücke in der einschlägigen Sekundärliteratur zu schließen und dazu anregen, das Potenzial Müllers enormen und vielgestaltigen Werkes jenseits seiner als Theaterarbeiten ausgewiesenen Texte wahrzunehmen und in Bewegung zu setzen. Nach einführenden Darstellungen zu Rezeptionssituation und Forschungsstand, der Diskussion spezifischer poetologischer Fragestellungen im Allgemeinen wie solcher der Autobiografieforschung im Besonderen, der Untersuchung der Genese und formaler Besonderheiten des Textes, analysiert die vorliegende Arbeit vor allem die strukturellen Wirkungsmechanismen, die Müllers disparate Selbstexplikation zum Auto-Drama werden lassen. Die Rückführung der Bedeutungsgeneration auf die strukturästhetischen Wirkungsmechanismen scheint insofern geeignet, als sie durch Textnähe und punktuelle Analyse der Textgenese Müllers Strategie der Selbst-Dekonstruktion sehr nahe kommt. Zumal Müller seine »Lebenserzählung« nach ähnlichen Strukturprinzipien aufbaut, wie seine anderen »poetischen« Texte auch. Aus der Beschreibung der disparaten Äußerungsformen des autobiografischen Ichs ergeben sich die textimmanenten Strategien der überaus komplexen Selbstinszenierung Müllers, sein »Theater der Schrift«. / Since the early 1990s a number of literary papers testify the vivid interest in the subjective composition of Müller’s writing. But none of these detailed devotes to Müller’s as autobiography assigned text WAR WITHOUT BATTLE – LIFE IN TWO DICTATORSHIPS. Until now the text has been only used as quarry of quotations, aid of interpretation and extensive poetological collection of material. Mainly the work is used as evidence of the intention of Müller’s writing and therefore receives an inadmissible degree of sovereignty of interpretation. The poetical dimension of the text is often inadequately reflected or even totally neglected and ignored. This text-critical examination will contribute to close this gap of research within the relevant secondary literature and encourage the recognition and discussion of the potential of Müller’s enormous and multifarious work beyond his as theatre work assigned texts. After the introduction of the situation of reception and the status of current research, the discussion of specific poetological questions in general such as autobiographical research, examination of genesis and formal specific features of texts, this paper will analyse the structural mechanisms of effect, which turn Müller’s disparate self-explication into an auto-drama. It seems suitable to return the meaning of generation on the structure-esthetical mechanisms of effect, as the proximity of text and selective analysis of the genesis of text is very close to Müller’s strategy of self-deconstruction. Particularly as Müller constructs his »Lebenserzählung« to similar structural principals as well as others of his »poetical« texts. The description of the disparate form of expression of the autobiographic I result in the text-immanent strategies of the enormous complex self-dramatisation of Müller; his »Theater der Schrift«.

Os principais objetos de estudo dessa dissertação são uma estatística e um mapa da Província de São Paulo, ambos encomendados pela recém-instituída Assembleia Legislativa Provincial, em 1835, ao engenheiro-militar Daniel Pedro Müller (1785-1841). Planejados para serem utilizados como instrumentos de poder a serviço de grupos da elite paulista, no controle da administração provincial, a reconstituição dos contextos de sua produção, impressão e circulação permitem estabelecer nexos entre esses artefatos e a sociedade que os produziu e utilizou pela primeira vez, ampliando a compreensão da dinâmica política, econômica e social da Província paulista da primeira metade do Oitocentos. Para estudá-los buscou-se, inicialmente, reconstituir a trajetória de Daniel Pedro Müller, bem como caracterizar os grupos da elite paulista que passaram a ocupar os espaços de poder provincial a partir da transição do regime absolutista para a monarquia constitucional, no princípio da década de 1820, até o final da primeira metade daquele século. Em seguida, passou-se à análise dos artefatos propriamente ditos, buscando estabelecer relações entre esses objetos e os contextos político, econômico e social em que estavam inseridos. Por fim, a partir de dois exemplos concretos da economia política provincial a apropriação das terras indígenas para o avanço das culturas de exportação e subsistência em direção ao Oeste e a orientação da política econômica ao desenvolvimento da infraestrutura viária paulista buscou-se demonstrar como a construção territorial engendrada por estes artefatos serviu como instrumento de poder para a realização dos interesses e desígnios de autoridades administrativas em aliança com a elite mercantil-exportadora paulista. / The main study objects of this masters thesis are a statistic and a map of the Province of São Paulo, both commissioned in 1835 by the recently established Provincial Legislative Assembly to the military engineer Daniel Pedro Müller (1785-1841). Planned to be used as instruments of power to serve groups of the local elite in control of the provincial administration, the reconstitution of the contexts of its production, printing and circulation allows us to establish links between these artifacts and the society who produced and used them for the first time, expanding the comprehension of the political, economic and social dynamics of the Paulista province during the first half of the 19th century. In order to study these artifacts we sought, in the first place, to rebuild the trajectory of Daniel Pedro Müller as well as to characterize the Paulista elite groups that came to occupy the spaces of provincial power from the transition from the absolutist regime to the constitutional monarchy in the beginning of the 1820s, up to the end of the first half of that century. Afterwards we went to the analysis of the actual artifacts, aiming to establish relationships between these objects and the political, economic and social context in which they were entered. Finally, from two concrete examples of the provincial economic politics the appropriation of indigenous lands for the advancements of the exports and subsistence cultures towards the West part of the province and the guidance of the political economy for the development of the Paulista road infrastructure we aimed to demonstrate how the territorial construction engendered by these artifacts was used as an instrument of power to attend the interests and intends of administrative authorities in alliance with the São Paulo exporting-mercantile elite.

Staphylococcus aureus est une bactérie responsable de nombreuses infections. Divers facteurs de virulence sont décrits comme ayant un rôle aggravant dans l’infection staphylococcique. La leucocidine de Panton-Valentine (LPV) en est un. Elle interagit par l’intermédiaire du récepteur de C5a (C5aR) avec les leucocytes et les cellules neuronales dans différents tissus, mais son action au niveau rétinien est méconnue. Nous avons recherché des cibles rétiniennes cellulaires de l’intoxination à la LPV et étudié ses conséquences cellulaires et inflammatoires précoces dans les tissus rétiniens. AINSI, deux modèles de lapins ont été créés : l'injection intravitréenne in vivo et les explants rétiniens ex vivo. Dans les deux modèles, les cellules ganglionnaires étaient les principales cibles cellulaires rétiniennes de la LPV et le seul type de neurones rétiniennes qui exprimait C5aR. Les cellules de Müller comme la microglie étaient activées. L’explant rétinien était facilement manipulé, ils peuvent servir à la recherche de la LPV sur la rétine. La LPV seule pourrait induire une inflammation rétinienne après avoir ciblé spécifiquement les cellules neuronales. / Staphylococcus aureus is responsible for many infections. It secretes various virulence factors aggravating the staphylococcal infections. Panton-Valentine leucocidin (PVL) is a virulent leukotoxin from S. aureus and presents active effects towards leukocytes and neuronal cells via the C5a receptor (C5aR). The effects of PVL on retina is little known. We explored PVL retinal cell target and early retinal inflammation and tried to find the processes of bacterial toxins aggravating bacterial endophthalmitis. We employed two different rabbit models to study the PVL effects on retina: intravitreal injection in vivo and retinal explant ex vivo. In the two models, retinal ganglion cells were the only retinal neurons which express C5aR and the major cell targets of PVL in retina. PVL induced retinal Müller and microglial cell activation. The retinal explants were easily manipulated and showed obvious cellular targets of PVL and glial cell activations, they can contribute to research the effects of PVL on retina in future. PVL alone without S. aureus could induce great retinal inflammation after targeting specifically retinal neurons.