Producing competent and fertilizable oocytes from in vitro grown primordial follicles could revolutionize female infertility treatment, particularly using fertility preservation approaches that use cryopreserved ovarian tissue. However, the protracted length of folliculogenesis in humans makes follicular culture complex, and the mechanisms controlling the tightly-regulated activation of primordial follicles remain largely unknown. The delicate balance between follicular recruitment and quiescence might be affected by preservation procedures, such as ovarian fragmentation or in vitro culture, that disrupt crucial pathways, such as the Hippo and PI3K/Akt/mTOR signaling pathways, that are involved in this process. When activated, these pathways induce massive recruitment of primordial follicles and accelerate follicular growth in vitro, with potential negative consequences on future oocyte developmental competence. Therefore, we hypothesized that the inhibition of the PI3K/Akt/mTOR pathway might improve follicular growth by slowing down the activation process.In the first part of this thesis, we explored the potential benefit of inhibiting PI3K/Akt/mTOR signaling on the regulation of in vitro follicular activation and growth, as well as its impact on the Hippo pathway. The effect of everolimus (EVE), a specific mTORC1 inhibitor, was compared to the PI3K/Akt activators recently used to reinitiate the growth of residual follicles in the ovarian tissue of patients with premature ovarian insufficiency. We showed that short-term incubation of ovarian cortex with EVE partially delayed follicular recruitment while supporting follicle survival and steroidogenesis. However, morphological abnormalities were observed in all conditions, suggesting that EVE failed to protect follicles from accelerated in vitro growth-related defects.Our findings also provided evidence that ovarian fragmentation, which disrupts the Hippo pathway, contributes to the triggering of primordial follicle recruitment and early development of quiescent human follicles. Moreover, our data suggested that both PI3K/Akt and Hippo signaling could act synergistically to promote follicular activation and growth.In the second part of the project, we further investigated the integrity of EVE-treated follicles based on their ultrastructural and functional status. Our observations indicate that the integrity of oocyte and granulosa cells, as well as their physical contacts, were preserved in EVE and control conditions, although some in vitro grown follicles sustained cryopreservation- and culture- induced damage. We also found that short exposure to EVE allowed the maintenance of intra-follicular communication while preserving follicular developmental potential. Importantly, results obtained suggested that, at a similar developmental stage, cell coupling and oocyte growth may be improved in EVE-treated follicles.Altogether, these data provide better insight into the regulation of the follicular activation process and emphasize the importance of getting closer to physiological conditions to preserve follicle integrity. They also provide proof-of-concept evidence that reducing the initiation of growth is feasible, and suggest that mTORC1 inhibitors are a potentially useful pharmacological tool to regulate in vitro follicular growth. / La production d'ovocytes compétents et fécondables à partir de follicules primordiaux développés in vitro pourrait révolutionner les traitements liés à l'infertilité féminine, en particulier les approches de préservation de la fertilité à partir du tissu ovarien cryopréservé. Cependant, la longue durée de la folliculogenèse chez l'Homme rend la culture folliculaire complexe, et les mécanismes contrôlant l'activation des follicules primordiaux restent largement inconnus. L’équilibre fragile entre quiescence folliculaire et entrée en croissance pourrait être affecté par la fragmentation ovarienne ou la culture in vitro elle-même, qui perturbent deux voies de signalisation cruciales: les voies Hippo et PI3K/Akt/mTOR, respectivement. Lorsqu'elles sont activées, elles induisent un recrutement massif de follicules primordiaux et accélèrent la croissance folliculaire in vitro, avec des conséquences potentiellement néfastes sur la capacité future des ovocytes à devenir compétents. Par conséquent, nous avons émis l’hypothèse que l’inhibition de la voie PI3K/Akt/mTOR pourrait améliorer la croissance folliculaire via un ralentissement du processus d’activation.Dans la première partie de cette thèse, nous avons exploré le potentiel bénéfice d’une inhibition de la voie PI3K/Akt/mTOR sur la régulation de l'activation et de la croissance folliculaire in vitro, ainsi que son impact sur la voie Hippo. L’effet de l’évérolimus (EVE), un inhibiteur spécifique de mTORC1, a été comparé à ceux d’activateurs de PI3K/Akt, récemment utilisés afin d’initier la croissance des follicules résiduels au sein de tissus ovarien de patientes en insuffisance ovarienne précoce. Nous avons montré que l'exposition à court terme de cortex ovarien à l'EVE retardait partiellement le recrutement folliculaire tout en préservant la survie et la stéroidogenèse des follicules. Toutefois, des anomalies morphologiques ont été observées dans toutes les conditions, ce qui suggère que l’EVE ne préserve pas les follicules de défauts liés à une croissance accélérée.Nos résultats ont également prouvé que la fragmentation ovarienne, en perturbant la voie Hippo, contribue au recrutement et au développement précoce des follicules primordiaux. De plus, les données obtenues suggèrent que les voies PI3K/Akt/mTOR et Hippo pourraient agir de manière synergique pour promouvoir l'activation et la croissance folliculaire.Dans la deuxième partie du projet, nous avons étudié la qualité des follicules traités avec de l’EVE en se basant sur des critères ultrastructural et fonctionnel. Nos observations ont indiqué que l'intégrité des ovocytes et des cellules de la granulosa ainsi que leurs contacts physiques était préservée dans les conditions EVE et contrôle, bien que certains follicules en croissance présentent des signes de dommages induits par la cryopréservation et la culture. Nous avons également constaté qu'une courte exposition à l’EVE permettait de maintenir les communications intra-folliculaires tout en préservant le potentiel de développement des follicules. De façon importante, les résultats obtenus suggèrent qu’à un stade de développement similaire, le couplage cellulaire et la croissance des ovocytes pourraient être améliorés dans les follicules traités à l’EVE.En conclusion, ces données contribuent à une meilleure compréhension de la régulation de l'activation folliculaire in vitro, et soulignent l'importance de mimer les conditions physiologiques pour préserver l'intégrité des follicules. Elles apportent également la preuve qu’un ralentissement de l’initiation de la croissance est réalisable, et suggèrent que l’utilisation d’inhibiteurs de mTORC1 pourrait représenter un outil pharmacologique efficace pour réguler la croissance folliculaire in vitro. / Doctorat en Sciences biomédicales et pharmaceutiques (Médecine) / info:eu-repo/semantics/nonPublished

Bibliography: leaves 276-298.

Bibliography: leaves 276-298. / 298 leaves ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of European Studies, 2001

Pope Benedict XVI, since his election to the papacy, has urged Catholic clergy and theologians to interpret the documents of the second Vatican Council using a "hermeneutic of continuity." This thesis seeks to answer whether such a hermeneutic is possible by focusing on one aspect of the Dogmatic Constitution on the Church, Lumen Gentium. The methodology here employed is a critical analysis of one of the major patristic sources of Lumen Gentiums teaching, St. Augustine of Hippo. In claiming St. Augustines support for its doctrine, Lumen Gentium also offers an interpretation of his thought. For Lumen Gentiums teaching to be plausible, we must be able to conclude that Augustines teaching is essentially identical to it. In that connection, Lumen Gentiums claim that the Church is both a spiritual and visible reality forces us to consider a controverted topic in Augustinian studies: can Augustines city of God be identified with the hierarchical Church? In order to resolve that question, we will examine both the historical and eschatological aspects of the Church in Augustines thought, with some reference (treated in an appendix) to the compatibility between his theory of predestination and his ecclesiology. Further, what the Council meant when it said that the Church of Christ subsists in the Catholic Church, and whether this change in terminology, along with its implications in the field of ecumenism, can be reconciled with St. Augustines ecclesiology must be determined with a view to establishing the continuity between pre and post conciliar Catholic ecclesiology. St. Augustine developed his understanding of the nature of the Church in the early years of his ecclesiastical career through his polemical battles with the Donatist schismatics, and so the history of that schism is related in an appendix.

Pope Benedict XVI, since his election to the papacy, has urged Catholic clergy and theologians to interpret the documents of the second Vatican Council using a "hermeneutic of continuity." This thesis seeks to answer whether such a hermeneutic is possible by focusing on one aspect of the Dogmatic Constitution on the Church, Lumen Gentium. The methodology here employed is a critical analysis of one of the major patristic sources of Lumen Gentiums teaching, St. Augustine of Hippo. In claiming St. Augustines support for its doctrine, Lumen Gentium also offers an interpretation of his thought. For Lumen Gentiums teaching to be plausible, we must be able to conclude that Augustines teaching is essentially identical to it. In that connection, Lumen Gentiums claim that the Church is both a spiritual and visible reality forces us to consider a controverted topic in Augustinian studies: can Augustines city of God be identified with the hierarchical Church? In order to resolve that question, we will examine both the historical and eschatological aspects of the Church in Augustines thought, with some reference (treated in an appendix) to the compatibility between his theory of predestination and his ecclesiology. Further, what the Council meant when it said that the Church of Christ subsists in the Catholic Church, and whether this change in terminology, along with its implications in the field of ecumenism, can be reconciled with St. Augustines ecclesiology must be determined with a view to establishing the continuity between pre and post conciliar Catholic ecclesiology. St. Augustine developed his understanding of the nature of the Church in the early years of his ecclesiastical career through his polemical battles with the Donatist schismatics, and so the history of that schism is related in an appendix.

Much has been said about the influence of Plotinus, the Platonist philosopher, on the ideas of Augustine of Hippo, the Western Church Father whose writings had the largest impact on Western Europe in the Middle Ages. This thesis considers both writers’ ideas concerning matter, evil, and language. It then considers the way in which these writers’ ideas influenced their style of writing in the Enneads and the Confessions. Plotinus’ more straightforward negative attitude towards the material word and its relationship to the One ultimately makes his writing more academic and less emotionally powerful. Augustine’s more complicated understanding of the material world and its relationship to God results in a more mystical and more emotionally powerful style, which derives its effectiveness especially from its use of antithesis and the first and second person.

Reading Augustine’s letters as a collection proves useful for understanding his theory in practice of the significance of others—the moral status of love for others—particularly since the conditions of the letter (absence, writing) engender expressions of lack and desire for the other. With Augustine, this desire is frequently in tension with his Neoplatonic and Christian philosophical commitments which valorise the Creator over the creature, universally-directed love over private love, and the soul over the body. Following these tensions between theory and practice chronologically through the letters shows his changing responses to the significance of the other, in terms of their bodily presence and their individual interior experience. Moreover, Augustine’s developing theory of the afterlife as a place of continued embodiment and the fulfilment of intimacy corresponds to and models Augustine’s responses to absence and longing in this life. / Graduate

Thesis (MA)--Stellenbosch University, 1964.

Within recent political theory, political liberalism has answered the question of how to deal with pluralism in contemporary society largely in terms of tolerance. Prompted by the same question, agonistic political theory has been in search of a way to move beyond liberal invocations of tolerance to a deeper celebration of difference. This project tells the story of the move within political theory from tolerance to difference, and the concomitant move from epistemology to ontology, through an exposition of the work of liberal theorists John Rawls and Richard Rorty and of agonistic, or post-Nietzschean, political theorists Chantal Mouffe and William Connolly. From a theological perspective, the ontological turn within recent theory can be seen as a welcome development, as can the desire to expand our capacity to engage with difference and to augment our current political imagination given contemporary conditions of pluralism. Yet the sufficiency of the answers and ontology put forward by both political liberalism and post-Nietzschean political thought needs to be seriously questioned. Indeed, the ontological turn in political theory opens the way for a theological turn, for theology is equally concerned with questions of human being and 'what there is' more generally. To make this 'theological turn,' I look to Saint Augustine, and the ontology disclosed though his writings, to see what theological resources he offers for an engagement with difference. Through this discussion we re-discover Augustine's Heavenly City as the place in which unity and diversity, harmony and plurality can come together in ways that are not possible outside of participation in the Triune God. Yet this does not mean that the Heavenly City is to take over the earthly city. By putting Augustine into conversation with more recent theologians such as John Milbank, Karl Barth, and William Cavanaugh, we consider the relationship between the Heavenly City and the earthly city and we offer a picture in which renewed and expanded conceptions of 'public' and 'conversation' open the way for rich engagement between the many different particularities that constitute a pluralist society.

Thesis (Ph.D.)--Boston University. / 1. Problem. The problem of this dissertation is to examine the doctrines of the will in the thought of Plato; Aristotle, Augustine, and Kant and to relate their conceptions of freedom to their doctrines of the will. 2. Method. The method consists in examining primary sources which define and interpret the will and its freedom. [TRUNCATED]