The signalling cascade induced by the binding of neurotrophins (NGF, BDNF, NT3 and NT4) to their high-affinity tyrosine kinase receptors (TrkA, B and C) is well documented to be important for neuronal cell survival, proliferation and differentiation. Evidence has accumulated demonstrating the importance of these signalling pathways in nonneuronal tissues, including the ovary where all neurotrophins and their receptors are expressed. In the mouse, effects on ovulation have been demonstrated but the role of Trk signalling in neonatal ovary development is less clear. Previous work had found that TrkB expression is upregulated at the time of follicle formation in the mouse and transgenic mice null for the TrkB receptor demonstrate significant loss of oocytes neonatally (TrkB knockouts, KO, die shortly after birth). This thesis examines the phenotype of the TrkB KO using morphological, histological and surgical techniques with the aim being to further investigate the role of TrkB signalling in oocyte survival, and to contribute to our understanding of neonatal ovary development. The main questions addressed are: 1) what developmental defects are occurring on a morphological level that result in the phenotype of the TrkB KO; 2) can these defects be quantified; and 3) what are the longterm survival prospects for TrkB KO oocytes. Morphological assessment revealed that TrkB KO ovaries exhibit poorer follicle health than their Controls and this was confirmed by assessment of basement membrane (BM) composition. TrkB KO brain and kidney were also assessed and found to have similarly affected BM. It is well known that cells require contact with the BM to maintain survival, thus it is postulated that TrkB signalling contributes to oocyte survival through regulation of the BM. Due to the postnatal lethality of the mutation, TrkB KO ovaries were transplanted to ascertain long-term oocyte survival. Unexpectedly it was found that TrkB KO oocytes are able to survive and follicles grow as well as they do in the Control transplants. Consequently, the in vivo effect has to be indirect. It is known that oocytes in the neonatal ovary undergo an increased rate of cell death but it is not known how the cell debris is removed. A novel observation of a neonatal ovarian immune response has been made in this thesis and is postulated to be a physiological mechanism for cell debris clearance. In conclusion, this thesis has demonstrated that signalling through TrkB has an effect on regulating BM in the ovary and other organs, but that surprisingly it has an indirect effect on oocyte survival.

Cell migration is an important component of many physiological and pathological processes such as tissue and organ morphogenesis during development, wound healing, inflammatory immune response, and tumor metastasis. The actin cytoskeleton is the basic engine driving cell migration. In the present study, we elucidate the role of an important actin interacting proteins, Adducins, in motility of normal lung epithelium and lung cancer cells. Adducins are the family of cytoskeleton protein capping the fast growing end and facilitating the bundling of actin filaments. Adducins are encoded by the three closely related genes namely alpha (ADD1), beta (ADD2) and gamma (ADD3) Adducin. ADD1 and ADD3 are ubiquitously expressed, whereas ADD2 is most abundant in brain and erythrocytes. Adducins are also involved in recruiting spectrin to the actin filaments forming spectrin-actin membrane skeletal network. Its role in cell motility remains controversial. In this study, we observed that CRISPR/Cas9 mediated stable knockout of ADD1 and ADD3 in 16HBE normal lung epithelium cells significantly increases transfilter migration of cells. On the other hand, stable overexpression of ADD1 in H1299 Non-Small Cell lung cancer cells significantly decreases wound healing, transfilter migration and Matrigel invasion of the cells. Importantly, the effects of Adducin depletion and overexpression on cell motility were not due to altered cell proliferation. ADD1 overexpressed H1299 cells were characterized by the increased adhesion and spreading on the collagen matrix. Fluorescence microscopy revealed alterations in their cortical actin cytoskeleton that was manifested in the assembly of peripheral F-actin bundles and formation of filopodia-like protrusions. These findings suggest that Adducins are negative regulators of motility of normal lung epithelial and lung cancer cells that act by altering the architecture of submembranous actin cytoskeleton and modulating cell adhesion to the extracellular matrix.

We introduce the definition of 1-cotilting object in a Grothendieck category and investigate its relation to the analogue of the standard definition of 1-cotilting module. The 1-cotilting quasi-coherent sheaves on a Noetherian scheme are stud- ied in particular: using the classification of hereditary torsion pairs in the category of quasi-coherent sheaves on a Noetherian scheme X, to each hereditary torsion- free class F that is generating we assign a 1-cotilting quasi-coherent sheaf whose 1-cotilting class is F. This provides a family of pairwise non-equivalent 1-cotilting quasi-coherent sheaves which are parametrized by specialization closed subsets of X avoiding the set of associated points of a chosen generator of the category of quasi-coherent sheaves. In many cases (e.g. for separated schemes), this set of avoided points can be chosen as the set of associated points of the scheme. 1

La Maladie d’Alzheimer est une maladie multifactorielle dont l’apparition peut être influencée par divers facteurs génétiques ou environnementaux, tels l’allèle ApoEɛ4, différents polymorphismes ainsi que le vieillissement ou la ménopause, par exemple. Depuis une dizaine d’années des études épidémiologiques ont mis en évidence l’existence d’une relation entre le statut métabolique des individus durant leur vie adulte et l’augmentation du risque de développer la MA à un âge plus avancé. Les travaux présentés dans cette thèse visent à étudier l’impact d’un régime riche en graisse, permettant le développement d’une obésité, sur le développement physiopathologique d’un modèle transgénique mimant le versant Tau de la MA, la souris THY-Tau22. Cette souris surexprime dans les neurones du cerveau la protéine Tau humaine mutée en 2 sites favorisant sa phosphorylation et son agrégation et présente une pathologie Tau hippocampique évolutive qui s'exprime en parallèle d'altérations mnésiques. Ainsi, ce modèle murin constitue un modèle particulièrement adapté à l'étude des conséquences comportementales, anatomo-pathologiques, biochimiques et transcriptomiques de la tauopathie de la MA. L'induction d'une obésité et de ses conséquences métaboliques chez la souris THY-Tau22 de 7 mois a engendré une diminution des performances d'apprentissage accompagnée d'une aggravation de la pathologie Tau hippocampique. De façon intéressante, ces modifications pathologiques ont eu lieu en parallèle du maintien d'une bonne sensibilité à l'insuline périphérique et en présence d'une activation de la voie de signalisation du récepteur à l'insuline dans l'hippocampe. Ces données remettent en cause le dogme établit dans la littérature, et suggèrent que les conséquences délétères d'une obésité sur Tau dans la MA peuvent être dissociées d'une résistance à l'insuline périphérique et centrale. Sur le plan métabolique, lorsque nourries par un régime obésifiant, les souris THY-Tau22 de 7 mois présentent au contraire de leurs contrôles de portées wild-type une homéostasie glucidique peu détériorée. Afin de contrôler la véracité de ce phénotype nous avons entrepris la caractérisation métabolique de la lignée de souris THY-Tau22 via une étude longitudinale de 2 à 9 mois. Cette caractérisation a permis de mettre en évidence le caractère plus maigre de la souris THY-Tau22 comparé aux WT avec des différences de paramètres métaboliques qui s'accentuent au cours de la vie de la souris THY-Tau22. Afin de décrypter si cette particularité métabolique est le fruit du gain de fonction lié à la surexpression de la protéine Tau dans le cerveau de cette souris, un suivi longitudinal identique a été réalisé chez la souris Knock-out pour le gène Tau (KO-Tau). Les résultats indiquent que la souris KO-Tau présente un phénotype métabolique inverse à celui de la souris THY-Tau22, avec poids corporel augmenté et homéostasie glucidique altérée, suggérant que Tau puisse posséder un rôle dans l'homéostasie métabolique. En conclusion l’ensemble des résultats de cette thèse suggère par conséquent qu'une obésité provoque l'aggravation de la pathologie Tau de la MA, et ce, en l'absence d'une résistance à l'insuline. De plus, nous révélons l'existence d'une potentielle fonction inédite de la protéine Tau dont l'action au niveau central aurait des conséquences métaboliques périphériques. / Alzheimer's disease (AD) is a multifactorial disease that can be influenced by several genetic or environnemental factors, such as ApoEɛ4 allele, genetic polymorphisms and ageing and menopause, for instance. Since a decade epidemiological studies have pointed out the existence of a relationship between the metabolic status of individuals during their adult's life and an increased risk of developing AD at an advanced age. Indeed, type 2 diabetes doubles the risk to have AD. Mid-life overweight and obesity are also important risk factors for the development of AD. The work presented in this thesis aim at studying the impact of an obesity induced by a high-fat diet on physiopathological development of a transgenic mouse model reproducing AD-like Tau pathology, the THY-Tau22 mouse. This mouse overexpresses in the neurons a human Tau protein, mutated on two sites favoring its phosphorylation and aggregation and exhibits a progressive hippocampal Tau pathology in parallel with learning and memory impairment. This mouse model therefore constitutes an appropriate model to study the behavioral, anatomo-pathologic, biochemical and transcriptomic consequences of AD-like Tauopathy. Diet induced obesity and its metabolic disturbances in 7 months THY-Tau22 mice impaired learning and induced an aggravation of hippocampal Tau pathology. Interestingly, this pathological worsening occurred in parallel with healthy peripheral insulin sensitivity and activation of central insulin signaling. These data question the current dogma of the literature and suggest that deleterious consequences of obesity on Tau pathology could happen dissociated from peripheral and central insulin signaling. On the metabolic point of view, when fed high-fat, 7 months THY-Tau22 mice present, on the contrary of their littermate controls, a relative healthy glucose homeostasis. To control this phenotype we undertook the characterization of THY-Tau22 mice with a longitudinal study from 2 to 9 months. This characterization led us to underscore the leaner phenotype of THY-Tau22 compared to their WT counterparts, with increasing differences in metabolic parameters over age. In order to decipher if this metabolic feature is due to a gain of function induced by the neuronal overexpression of Tau we realized the same phenotyping on a Tau knock-out mouse (KO-Tau). The results indicate that, in contrary to THY-Tau22 mice, KO-Tau mice present a mirrored metabolic phenotype with higher body weight and impaired glucose homeostasis, suggesting a possible role for Tau in metabolic homeostasis. In conclusion, all the data presented in this thesis therefore suggest that obesity induces a worsening of AD-like Tau pathology that occurs dissociated from insulin resistance. Moreover, our study reveals the existence of a potential unpublished function of Tau protein whose action at central level could have peripheral metabolic consequences.

Title: Electromyographic analysis of selected muscles of lower extremity of kitesurfers. Objective: The goal of thesis is to determine muscle groups, which are the most active during the kitesurfing position and compare the values in increasing time spent in this position. Furthermore, to determine a degree of co-contraction level between m. quadriceps femoris and m. biceps femoris. According to the enlarging number of riders in kitesurfing population the goal is to compare results between professional and recreant riders and determine statisticaly significant differences. Methods: This thesis is a case study, where is analyzed the degree of muscle aktivity of lower extremity during the kitesurfing position. The research involved 6 persons of very specific selection consisted of professional riders and recreants. As an objectification method surface electromyography had been chosen and the normalized value between m. quadriceps femoris, m. gluteus maximus, m. biceps femoris, m. tibialis anterior, m. gastrocnemius and m. trapezius had been evaluated. Findings: The measurement results showed that the most active muscle during the kitesurfing position is m. quadriceps femoris of stance lower extremity even though after long-term stay. Furthemore, the results showed that professional riders apply more...

My dissertation involves a critique of the concept of life or seimei as it emerged in modern use during the Meiji era (1868-1912). Specifically, I have outlined the conditions of possibility for thinking seimei at particular moments in the development of the modern, market-centered Japanese nation-state in historical and literary terms such that I can begin to use these conditions to think its impossibilities. In short, I argue that a central condition of possibility for thinking life in its modern, historical form is a process of individuation that takes hold of and shapes bodies at an ontological level. By critiquing life and its ontology of individuation, I unearth the traces of an impossible “apriori collectivism” - that is, a collectivism not merely reducible to a congregation of individuals, but originally collective – buried under the calls for individual freedom, self-help, and industrialization that were at the heart of the Meiji era’s modernization project. I track this apriori collectivism in a lineage relating (through non-relation) the mutual aid societies or mujin-kô of the Edo period to the life insurance industry of the Meiji 10s and 20s. I then use this material history of life as backdrop to my study of the literary trends in the latter decades of the Meiji era, and end with a consideration of the political and aesthetic implications seimei has for thought by taking up a study of Iwano Hômei’s Shinpiteki hanjûshugi (Mystical Demi-animalism).

Thesis (M.L.A.)--University of Hong Kong, 2002. / Includes bibliographical references.

No description available.

Vitamin D may have immunomodulatory effects in the intestine. Our objective was to determine if exposure to vitamin D mitigates intestinal inflammation in IL-10 KO mice. Mice were randomized to a diet containing 25 IU (low) or 5000 IU (high) of vitamin D/kg of diet in utero and offspring were maintained on the same diet or switched to the other diet at weaning. Fecal samples were collected at 3 months of age. Vitamin D did not affect intestinal inflammation in male and female mice and did not affect KC cytokine concentration or regulate colonic gene expression in male mice. Vitamin D modulated the gut microbiota in a sex-specific manner and depending on timing of exposure. Females in the HH group had significantly higher fecal counts of C. coccoides than the other vitamin D interventions. Therefore, vitamin D may favourably modulate microbiota composition without attenuating inflammation.

Vitamin D may have immunomodulatory effects in the intestine. Our objective was to determine if exposure to vitamin D mitigates intestinal inflammation in IL-10 KO mice. Mice were randomized to a diet containing 25 IU (low) or 5000 IU (high) of vitamin D/kg of diet in utero and offspring were maintained on the same diet or switched to the other diet at weaning. Fecal samples were collected at 3 months of age. Vitamin D did not affect intestinal inflammation in male and female mice and did not affect KC cytokine concentration or regulate colonic gene expression in male mice. Vitamin D modulated the gut microbiota in a sex-specific manner and depending on timing of exposure. Females in the HH group had significantly higher fecal counts of C. coccoides than the other vitamin D interventions. Therefore, vitamin D may favourably modulate microbiota composition without attenuating inflammation.