The research was designed to investigate the effects of AIT-082, a derivative of the purine hypoxanthine containing a para-amino benzoic acid moiety, on neural cells. AIT-082 has been shown to possess a number of neurotrophic and neuroprotective properties and to enhance memory. Furthermore, AIT-082 is undergoing clinical trials as a potential treatment for Alzheimers disease.<p>The first part of the study investigated the ability of AIT-082 to influence cellular ATP levels in cortical neurons. Decreased energy metabolism is a key point in Yings (Ying, 1996a) theory of the development of Alzheimers disease. Previous work with AIT-082 had shown that it could protect hippocampal neurons from cellular damage caused by sublethal doses of glutamate. Specifically, AIT-082 prevented neurite degeneration. Also, AIT-082 was shown to increase mitochondrial membrane potential, especially at the distal tips of the neurites, in hippocampal neurons. I hypothesized that AIT-082 was protecting the neurons by increasing the ability of the mitochondria to generate ATP and thereby increasing the amount of ATP available to the cell. ATP was collected and measured from cortical neuron cultures that were exposed to glutamate, AIT-082, glutamate and AIT-082. The ATP levels were compared to the ATP levels from cortical neuron cultures that were exposed to vehicle for glutamate and AIT-082. The results did not significantly increase ATP levels in cortical neurons following glutamate exposure. <p>The next set of experiments involved investigations into the ability of AIT-082 to influence phosphorylation events in neural cells. AIT-082 shares some neurotrophic and neuroprotective properties with a group of drugs called the immunophilin ligands. The neuroprotective properties of the immunophilin ligands are mainly due to their ability to influence protein phosphorylation by inhibiting the activity of calcineurin a protein phosphatase. The first set of experiments used western blot techniques to measure serine peptide and threonine peptide phosphorylation levels in proteins from whole brain homogenates that were incubated with vehicle, AIT-082, and GMP. Both AIT-082 and GMP caused an increase in the level of serine peptide phosphorylation compared to vehicle but only the increase caused by GMP treatment proved to be significant. Further, threonine phosphorylation levels were significantly increased by GMP but not AIT-082. Phosphorylation levels of short peptide sequences containing either a phosphorylated serine or threonine residue were also measured in neuronal and astrocytic cultures. The neuronal cultures were exposed to 4 h of hypoxia to mimic the conditions of reduced energy availability observed in Alzheimers disease brains. Astrocyte cultures were exposed to 4 h of hypoxia/ischemia for the same reason. Both cell types were allowed to recover for 0, 1, 4, 12 and 24 hours with or without AIT-082 following the insult. AIT-082 treatment did not significantly affect phosphorylation levels of proteins harvested from either neuron or astrocyte cultures at any time period. I conclude therefore, that AIT-082 is not able to influence phosphorylation of the short amino acid sequences containing phosphorylated serine or threonine residues that could be detected by the primary antibodies used in my experiments.

The research was designed to investigate the effects of AIT-082, a derivative of the purine hypoxanthine containing a para-amino benzoic acid moiety, on neural cells. AIT-082 has been shown to possess a number of neurotrophic and neuroprotective properties and to enhance memory. Furthermore, AIT-082 is undergoing clinical trials as a potential treatment for Alzheimers disease.<p>The first part of the study investigated the ability of AIT-082 to influence cellular ATP levels in cortical neurons. Decreased energy metabolism is a key point in Yings (Ying, 1996a) theory of the development of Alzheimers disease. Previous work with AIT-082 had shown that it could protect hippocampal neurons from cellular damage caused by sublethal doses of glutamate. Specifically, AIT-082 prevented neurite degeneration. Also, AIT-082 was shown to increase mitochondrial membrane potential, especially at the distal tips of the neurites, in hippocampal neurons. I hypothesized that AIT-082 was protecting the neurons by increasing the ability of the mitochondria to generate ATP and thereby increasing the amount of ATP available to the cell. ATP was collected and measured from cortical neuron cultures that were exposed to glutamate, AIT-082, glutamate and AIT-082. The ATP levels were compared to the ATP levels from cortical neuron cultures that were exposed to vehicle for glutamate and AIT-082. The results did not significantly increase ATP levels in cortical neurons following glutamate exposure. <p>The next set of experiments involved investigations into the ability of AIT-082 to influence phosphorylation events in neural cells. AIT-082 shares some neurotrophic and neuroprotective properties with a group of drugs called the immunophilin ligands. The neuroprotective properties of the immunophilin ligands are mainly due to their ability to influence protein phosphorylation by inhibiting the activity of calcineurin a protein phosphatase. The first set of experiments used western blot techniques to measure serine peptide and threonine peptide phosphorylation levels in proteins from whole brain homogenates that were incubated with vehicle, AIT-082, and GMP. Both AIT-082 and GMP caused an increase in the level of serine peptide phosphorylation compared to vehicle but only the increase caused by GMP treatment proved to be significant. Further, threonine phosphorylation levels were significantly increased by GMP but not AIT-082. Phosphorylation levels of short peptide sequences containing either a phosphorylated serine or threonine residue were also measured in neuronal and astrocytic cultures. The neuronal cultures were exposed to 4 h of hypoxia to mimic the conditions of reduced energy availability observed in Alzheimers disease brains. Astrocyte cultures were exposed to 4 h of hypoxia/ischemia for the same reason. Both cell types were allowed to recover for 0, 1, 4, 12 and 24 hours with or without AIT-082 following the insult. AIT-082 treatment did not significantly affect phosphorylation levels of proteins harvested from either neuron or astrocyte cultures at any time period. I conclude therefore, that AIT-082 is not able to influence phosphorylation of the short amino acid sequences containing phosphorylated serine or threonine residues that could be detected by the primary antibodies used in my experiments.

Le blog est un catalyseur idéal des transformations sociales et technologiques définitoires pour les sociétés occidentales. Il traduit une double prise de distance des individus: la première anti-hégémonique, par le refus du monopole de la production de modèles de genre et de l’information, et la deuxième expressiviste et identitaire liée à la prise de parole non-médiée des femmes dans l’espace public digital. Cette recherche prolonge les questionnements sur la possibilité de manifestation dans le numérique d’un expressivisme de genre. En ce sens, le blog personnel de mode est questionné comme une voie d’intervention dans la culture, un nouveau média de mode et un genre discursif émergent, un espace d’affirmation des contre-publics et une nouvelle technologie de genre qui permet la redéfinition de la féminité contemporaine. Son objectif majeur a été de comprendre comment les femmes se présentent, parlent et agissent dans le numérique en rapport avec le contexte, leur condition de femmes et surtout leurs intentions. Il s’agit de la mise en question de leur investissement numérique en tant qu’actrices qui assument les épreuves de la nouvelle socialité féminine.L’analyse exploratoire, qui a été à la base de la construction du corpus d’analyse, dévoile l’ampleur de la fragmentation de la blogosphère de mode. Il s’agit d’un travail de pionnier qui a le grand avantage de ne pas rester à la surface du phénomène investigué. La fragmentation de la blogosphère annonce moins la disparition du phénomène, mais son évolution dans des tendances qui anticipent des changements futurs et qui sont en synergie avec le développement d’Internet. Les blogs sont une source riche de données qualitatives qui nous a permis une triangulation méthodologique efficace: une observation ethnographique en ligne, une analyse de discours cadrée par l’éthos et une analyse visuelle. Ainsi, nous avons analysé un répertoire diversifié de l’éthos féminin (corporel, contestataire, professionnel et familial), dont l’intérêt a été de prouver qu’il y a une forme de détachement du modèle dominant de la féminité. A partir d’un corpus international de blogs personnels écrits par des femmes, nous avons identifié et analysé le modèle dominant de la blogueuse de mode, défini par la vision consensuelle sur la féminité et un positionnement de partenariat avec l’industrie de la mode, et toute une série de positionnements contre-hégémoniques. Cette recherche indique le passage de la féminité comme identité imaginée à une féminité conçue en relation avec le statut de l’acteur social. Dans ce basculement réside l’intérêt d’une pratique qui recèle un pouvoir représentationnel.Cette recherche propose la redéfinition des blogs personnels de mode en tant que nouvelles technologies de genre et contribue à l’analyse générique du blog de mode par l’identification des différentes scénographies dans la sous-catégorie visée. Celle-ci a produit la première typologie des blogs personnels de mode qui implique les catégories suivantes: male gaze, pratiques hédonistes, posture critique, activisme social. Suite à la neutralisation du social, à la réactivation persistante de la mascarade féminine et l’enfermement dans l’identité unique de femme, le blog personnel de mode devient un instrument d’aliénation participative. Par contre, suite au défigement de la mascarade féminine, la construction des communautés diasporiques en ligne, la mobilisation des identités féminine plurielles et des degrés variables d’ancrage social, le blog personnel de mode devient un instrument de soft power qui atteste de la prise en charge des femmes des représentations de leur propre genre. L’approche interdisciplinaire nous a permis d’analyser cet objet d’étude syncrétique qui est le résultat du développement technologique, de la transformation des conditions et des formes de communication et, finalement, des mutations sociales en cours. / Nowadays, the blog actively mobilizes social and technological transformations that are characteristic for the Western society. As such, it encompasses two directions: a counter- hegemonic one, dismissing the monopoly of gender models and of information production, and an identity-related one, aspiring to the promise of unaltered self-expressionin the public sphere. This study aims to contribute to the body of research about the online manifestation of gender expressivism. Personal fashion blogs are analyzed as a form of cultural intervention, an emergent discourse, and a space of affirmation for contra-audiences, as well as a new gender technology, that facilitates the redefinition of contemporary femininity. The purpose is to explore how women represent themselves, how they relate to their social context, their gendered status, and how they communicate their intentions. To this end, I depart from the premise that their interventions in the digital space are enacted as agents seeking to validate new forms of feminine sociality. The corpus is built on an exploratory analysis revealing the fragmentation characterizing personal fashion blogs. Although this is a pioneering work, it does not treat superficially the investigated phenomena. Beyond the analysis, it emphasizes the future shifts of personal fashion blogs, in synergy with Internet developments. The blogosphere has constituted a rich source of qualitative data, which has allowed a methodological triangulation: an online ethnographical observation, a discourse analysis centering on the notion of ethos and a visual analysis. I selected and analyzed a varied repertoire of the contemporary feminine ethos (physical, disruptive, professional and familial), which demonstrates that in this media there is a trend to detach oneself from dominant model of femininity. By employing a cross-national corpus of fashion blogs, owned by women, I have identified the traits of the dominant fashion blog – presenting what it appears to be a consensual view on femininity, in partnership with the fashion industry - but also a series of counterhegemonic positionings. This research signals the transition from an imaginary femininity towards a feminine identity which materializes in close relationship with social status. In this shift of perspective resides our interest in a practice which grants access to self-representation.The study suggests defining personal fashion blogs as new gender technologies. It starts with a generic analysis of fashion blogs by circumscribing various scenographies based on which a series of visual sub-categories can be distinguished. Thus, I introduce an original typology of personal fashion blogs: male gaze, hedonistic practices, critical stance and social activism. On the one hand, personal fashion blogs neutralize the social context through the continuous activation of the feminine masquerade and by claiming a monolithic feminine identity, the blog becomes an instrument of participative alienation. On the other hand, through the deconstruction of the feminine masquerade, by building online diasporic communities, and shifting between identities, personal fashion blogs become an instrument of soft power, a place of resistance that establishes women’s representations as something achieved by them, not imposed upon them. An inter-disciplinary approach has made possible the analysis of this syncretic object of study, which is the result of digital technologies, but also of existing social transformations / of evolving gender relations.