Thesis (Ph. D.)--University of Missouri-Columbia, 1999. / Typescript. Vita. Includes bibliographical references (leaves 111-127). Also available on the Internet.

Thesis (Ph.D)--Virginia Commonwealth University, 2009. / Prepared for: Dept. of Physiology. Title from title-page of electronic thesis. Includes bibliographical references.

Thesis (Ph. D.)--York University, 1999. Graduate Programme in Biology. / Typescript. Includes bibliographical references (leaves 135-144). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pNQ39261.

Thesis (Ph. D.)--University of Oregon, 2002. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 102-119). Also available for download via the World Wide Web; free to University of Oregon users.

Thesis--Ph. D., University of Hong Kong, 1981.

Rationale and hypothesis: Diabetic neuropathy involves dying back of nerve endings that reflects impairment in axonal plasticity and regenerative nerve growth. Metabolic changes in diabetes can lead to a dysregulation of hormonal mediators, such as cytokines. Thus I studied the effect of interleukin-17A (IL-17A), a proinflammatory cytokine produced by T-cells, on the phenotype of sensory neurons derived from control or diabetic rats. I hypothesized that IL-17A induces neurite outgrowth in sensory neurons through signaling pathways that enhance mitochondrial function. IL-17A can also reverse impaired nerve regeneration associated with diabetes Objectives: Determine the ability of IL-17A to enhance neurite outgrowth in cultured sensory neurons. Investigate the signalling pathways activated by IL-17A and mechanistically link to neurite outgrowth. Study the ability of IL-17A to improve mitochondrial function of sensory neurons (since axon outgrowth consumes high levels of ATP). Methodology: Cultured adult dorsal root ganglia (DRG) sensory neurons derived from age matched control or streptozotocin (STZ)-induced type 1 diabetic rats were fixed and stained for fluorescent imaging to determine total neurite outgrowth. Western blotting determined the levels of MAPK and PI-3K activation by IL-17A and for measuring levels of proteins of mitochondrial oxidative phosphorylation pathway. Mitochondrial bioenergetic function was tested in cultured DRG neurons using the Seahorse XF Analyzer. Results: I found that IL-17A (10 ng/ml; P<0.05) significantly increased total neurite outgrowth in cultures derived from both control and STZ-diabetic rat models. This enhancement was mediated by IL-17A-dependent activation of MAPK and PI-3K pathways with maximal effect at 15 minutes (P<0.05). Pharmacological blockade of one of these activated pathways led to total inhibition of neurite outgrowth. IL-17A improved mitochondrial bioenergetic function of sensory neurons. Bioenergetics function was associated with augmented expression of proteins of mitochondrial oxidative phosphorylation. Conclusion: IL-17A enhanced axonal plasticity through activation of MAPK and PI-3K pathways and was associated with augmented mitochondrial bioenergetics function in sensory neurons / October 2014

published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

No description available.

Resolving the phylogenetic tree of eukaryotes is an ongoing challenge for evolutionary biologists. One of the most intriguing questions is the phylogenetic status of Excavata, a group that is well supported by morphological evidence, yet usually not recovered as a clade in molecular phylogenies. The most problematic group of excavates are diplomonads (e.g., Giardia), which tend to have very highly divergent gene sequences, making any phylogenetic analyses that include these protists very susceptible to long branch attraction artifact. This thesis first explores which organisms are most closely related to diplomonads. Phylogenies of three marker genes demonstrate that enteromonads, formerly considered a possible sister group to diplomonads, are a polyphyletic group within diplomonads, suggesting complex evolution of cell morphology in this lineage. However, a large diversity of Carpediemonas-like organisms (CLOs) was discovered from marine/saline samples. Most of the major clades of CLOs had not been detected by previous environmental PCR studies. SSU rRNA gene phylogenies show that CLOs form a series of relatively short branches at the base of diplomonads. Phylogenomic analysis of eukaryotes (161 genes), incorporating EST data from 5 excavates, including 3 CLOs, shows that the non-monophyly of Excavata in phylogenomic studies is likely caused by long branch attraction artifact, since most of the methods used to suppress long branch attraction significantly weaken support for this topology. Furthermore, the shorter-branching CLOs represent valuable replacements for the long branching diplomonads; we recovered a robustly supported monophyletic Excavata, when long branches, including diplomonads (and parabasalids), were removed from the analysis. Subsequently, comparative analysis of the putative proteomes of three CLO isolates, the retortamonad Chilomastix, diplomonads and parabasalids was performed. Several putative evolutionary steps leading to the extremely reduced mitochondrial organelle of diplomonads were derived through the comparative analysis of predicted organellar proteomes. This thesis shows the importance of taxon sampling for inferring deep eukaryotic evolution. The more robust understanding of the phylogeny of Excavata, especially diplomonads and parabasalids, and the new availability of a number of deep branching relatives of diplomonads, provide a framework for comparative analyses exploring the evolution of anaerobic organelles or parasitism.

No description available.