Thesis (Ph. D.)--Ohio State University, 2008. / Title from first page of PDF file. Includes bibliographical references (p. 102-122).

Thesis (Ph. D.)--Carleton University, 1999. / Also available in electronic format on the Internet.

Thesis (M. Sc.)--Carleton University, 2001. / Includes bibliographical references (p. 113-138). Also available in electronic format on the Internet.

Thesis (Ph.D.)--Victoria University of Wellington, 2009. / Includes bibliographical references.

Thesis (Ph. D.)--Illinois State University, 1994. / Title from title page screen, viewed March 21, 2006. Dissertation Committee: H. Tak Cheung (chair), Herman E. Brockman, Lynne A. Lucher, Philip D. Morse, Anthony J. Otsuka. Includes bibliographical references (leaves 101-111) and abstract. Also available in print.

Thesis (M.S.)--Brigham Young University. Dept. of Microbiology and Molecular Biology, 2006. / Includes bibliographical references (p. 42-43).

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 201-220).

The main aim of this thesis was to examine the hypothesis that the A/J strain variant of H55N substitution affects citrate synthase (CS) enzyme activity and metabolic health in mice fed a high fat diet (HFD). C57BL/6J (B6) mice and congenic B6.A-(rs3676616-D10Utsw1)/KjnB6 (B6.A) mice, a strain which carries the A/J allele of Cs on the B6 strain background, were fed a HFD (45% kcal from fat) for 12 weeks. CS activity, but not that of ß-hydroxyacyl-coenzyme dehydrogenase was lower in the gastrocnemius muscle of B6.A mice compared to B6 mice (P< 0.001). During HFD feeding the glucose tolerance of mice decreased progressively and to a greater extent in B6.A females compared to B6 females, with males showing a similar trend. Interestingly, after 12 weeks of HFD feeding only B6.A males showed increases (P< 0.05) in their resting metabolic rate; moreover; core body temperature were also increased (P< 0.05) for congenic B6.A of both sexes by the end of the study. However, body weight and fat gain did not differ between B6.A and B6 mice. The second aim of the thesis was to test the hypothesis that low CS activity promotes palmitate-induced lipotoxicity in muscle cells. After 18 hours of incubation in 0.8 mM palmitate, C2C12 muscle cells with a ~50% reduction in CS activity showed low (P< 0.001) viability, increased (P< 0.001) levels of cleaved Caspase-3, high levels of AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation (P< 0.05), low levels of protein kinase B phosphorylation, high mitogen-activated protein kinases activation (P< 0.001) compared to the control shRNA cells. This was coupled with higher levels of mitochondrial proteins (P< 0.05), which are involved in oxidative phosphorylation. C2C12 cells with reduced CS activity also showed high reactive oxygen species production (P< 0.05), low intracellular ATP levels (P< 0.05), and lower basal mitochondrial respiration (P< 0.001). In summary, the A/J strain variant of H55N is associated with low CS enzyme activity and impaired metabolic health when fed HFD. Palmitate has a lipotoxic effect on Cs shRNA transfected cells and can lead to cell death.

Made available in DSpace on 2015-08-20T17:10:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-05-25. Added 1 bitstream(s) on 2015-08-20T17:25:37Z : No. of bitstreams: 1 000841528.pdf: 469659 bytes, checksum: 2dd38d332ff2b50df196e07151da31a3 (MD5) / O objetivo deste estudo foi avaliar a preferência e efeito do fornecimento de materiais de nidificação sobre o desempenho reprodutivo de camundongos isogênicos da linhagem BALB/c e da linhagem heterogênica Swiss em sistema de acasalamento intensivo monogâmico. Primeiro foi realizado um estudo para avaliar a preferência dos camundongos pelo material oferecido para nidificação. Utilizou-se um sistema composto de quatro gaiolas, com livre acesso a água e ração, interligados por tubos de PVC que permitiam que os animais se locomovessem entre todas as gaiolas. Quatro tipos de materiais foram oferecidos para a construção do ninho: algodão, gaze, rolinho de papelão, e touca de polipropileno descartável. Cada um dos quatro materiais foi oferecido simultaneamente em uma das quatro gaiolas que compunham o sistema. Foram usados 10 sistemas iguais e cada um abrigou um casal da linhagem BALB/c, desde os 28 dias de idade até o terceiro ciclo reprodutivo. Os mais encontrados na confecção do ninho, em ordem decrescente, foram a touca, rolinho, algodão e gaze (P< 0,0083). Com base nestes resultados foram selecionados dois tipos de materiais para fornecimento aos animais no experimento 2. Embora o rolinho tenha sido o segundo material mais utilizado optou-se pelo algodão devido a inviabilidade de fornecimento do item durante todo o período de duração do experimento 2. O segundo experimento avaliou a eficiência reprodutiva em cinco ciclos reprodutivos do nascimento até o desmame. Usou-se 60 casais de irmãos completos da linhagem BALB/c (isogênica) e 60 casais formados por acasalamentos aleatórios da linhagem Swiss (heterogênica) de padrão sanitário controlado, criados e mantidos em ambiente padronizado. Eles foram distribuídos, num delineamento inteiramente casualizado, em arranjo fatorial 2x2 (duas linhagens em alojamento com ou sem material para nidificação). Como forma de ... / The objective of this study was to evaluate the preference and effect of nesting materials provision on performance of inbred mice of the BALB/c strain and of heterogenic Swiss in intensive monogamous mating system. Firstly, a study was conducted to evaluate the preference of mice for the material offered for nesting. A system composed of four cages was used, with free access to water and food, connected by PVC tubing, which allowed animal displacement among all cages. Four types of materials were available for construction of the nest: cotton, gauze, cardboard rolls, and disposable polypropylene cap. Each of the four materials was offered simultaneously in one of four cages that formed the system. Ten identical system were used and each one housed a BALB/c couple, from 28 days of age up to the third reproductive cycle. The most commonly found materials in nest making were cap, roll, cotton and gauze (P <0.0083). Based on these results, two types of materials were selected to be offered to the animals in experiment 2. Although the roll was the second most used material, we chose cotton due to unfeasibility supplying of the item throughout the duration of the second experiment. The second experiment evaluated the reproductive efficiency in five reproductive cycles from birth to weaning. Sixty BALB / c full siblings pairs (inbred) and 60 pairs formed by random mating of Swiss strain (outbred), bred and maintained in a standardized environment were used. They were distributed in a completely randomized design in a 2x2 factorial arrangement (two strains in housing with or without nesting material). As a way of cage enrichment, polypropylene disposable cap cut into 8 pieces of approximately 1 cm each and one piece of cotton about 3 g were used after being previously packaged and autoclaved . The following characteristics were evaluated: age at first parturition, litter intervals, pre-weaning mortality and ...

Historically, the role of immune cells in the nervous system was predominantly examined throughthe lens of disease. In recent years, studies have shown that the complex, orchestrated events of immune activity throughout embryonic and postnatal critical periods are crucial for proper nervous system development. While previous studies have suggested limited immune heterogeneity in the adult brain, the diverse roles of the hippocampus in cognition and pathological development would suggest variation of immune cells in this region. Specifically, the hippocampus is known to be a site of adult neurogenesis. However, fundamental traits of immune cells in this region have not been well characterized. In chapter one, I present a summary of literature that discusses what was previously known of immune regulation of adult neurogenesis during health and disease. In chapter two, I compare different reporter lines and marker genes to evaluate responses in various cell types in the neurogenic niche and in other regions of the brain in the context of injury and pharmacological modulation. I discuss preliminary evidence suggesting microglial depletion may result in phenotypic changes in astrocytes throughout the hippocampus. In chapter three, I provide evidence of heterogeneity in myeloid-lineage cells in the hippocampus. I leveraged the highthroughput nature of cell suspension based single cell RNA-sequencing to collect transcriptomes of over 20,000 myeloid lineage cells from murine hippocampi. Using a series of bioinformatic techniques, I was able to computationally dissect different populations within this system and found spatial mapping of one distinct subset specifically localized to the neurogenic niche of the hippocampus. The transcriptomic signature of these cells alongside immunoreactivity to candidate genes, and morphological properties of this population resemble those of reactive microglia associated with the restriction of neurodegenerative diseases. In chapter four, I discuss how the immune landscape of the hippocampus responds to perturbation using a model of Focused Ultrasound mediated Blood-Brain Barrier opening. Subtypes of myeloid lineage cells change in composition and in transcriptomic response. We find distinct, temporally defined transcriptional responses in microglial and macrophage populations, indicating discrete roles for microglia and macrophages in immune activity during the transition from acute to chronic response. Together, these findings point towards diverse properties of microglia in the adult hippocampus.