Thesis (Ph. D.)--University of Wisconsin--Madison, 1969. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliography.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1959. / Typescript. Abstracted in Dissertation abstracts, v. 20 (1959) no. 2, p. 469-470. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves [107]-114).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1941. / Typescript. Includes abstract and vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves [81-87]).

Thesis (doctoral)--Katholieke Universiteit te Nijmegen.

Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.

Thesis (M.S.) in Biochemistry--University of Maine, 2006. / Includes vita. Includes bibliographical references (leaves 74-87).

Tissue maintenance requires a balance between cell production and cell death. The former is dependent on the activity of stem cells, which in turn are dependent on both extrinsic signals produced by surrounding somatic tissue and intrinsic signals to control their behaviour. Additionally, stem cell activity may be regulated by systemic factors, demonstrating the complexity of stem cell regulation. The ovary of Drosophila melanogaster is a useful model for understanding tissue function as production of a viable egg requires the coordination of two different stem cell populations, the germline stem cells and follicle stem cells. In a screen designed to identify genes which regulate early oogenesis in the Drosophila ovary, we identified the four candidate genes which are described in the three papers found in this thesis. The first paper demonstrates that two RNA associated proteins, Ataxin 2 binding protein 1 and Gemin3, are essential for germline stem cell and follicle cell production in a Sex lethal dependent manner. The second shows that Glucuronyl transferase I, which is important for regulating the synthesis of key components of the extracellular matrix known as proteoglycans, is able to regulate the activity of several different signalling pathways. Finally, the third paper suggests that Defective proboscis extension response 9, a brain expressed gene involved in the behavioural response to alcohol, is important for regulating both follicle cells and germline stem cells at a systemic level. Taken together, these papers highlight the importance of intrinsic, extrinsic and systemic signalling in regulating stem cell function during Drosophila oogenesis.

The aim of this research project was to investigate ways of improving the accuracy of dosimetric measurements in pion radiotherapy. Interest in this area was stimulated by the results of recent experimental work which revealed that materials from which dosimeters in pion radiotherapy are routinely constructed are not tissue equivalent for pi-. Two means of achieving the stated objective were identified: 1. To produce materials which are tissue equivalent for pions, to use in the construction of phantoms and dosimeters. 2. To evaluate correction factors necessary to convert dose recorded under non-tissue equivalent conditions to that for tissue. An attempt was made to produce muscle and bone equivalent phantom materials. The extent to which the materials produced could be considered tissue equivalent was judged by comparing experimentally determined carbon to oxygen (C:O) and nitrogen to oxygen (N:O) pion atomic capture ratios with those for the corresponding tissue type. Negative pion atomic capture ratios were also evaluated for sets of simple organic compounds to aid further development of the theoretical models necessary to determine correction factors.

Versican, a chondroitin sulfate proteoglycan, is one of the main components of the extracellular matrix and hence plays a central role in tissue morphogenesis and a number of pathologic processes. My main goal has been to investigate the mechanisms of versican gene regulation, focusing on the signal transduction pathways, promoter regions, cis-acting elements, and trans- factors. This thesis puts forth new knowledge regarding transcriptional regulation of the human versican gene. In chapter III, I present the cloning of a 752-bp fragment of the human versican promoter (- 634/+118 bp) and nine stepwise 5' deletion fragments in the PGL3-luciferase reporter plasmid. Furthermore, I identify three potential enhancer and two repressor regions in this promoter. I also demonstrate that both cAMP and C/EBPβ enhanced and repressed versican transcription in HeLa cells and rat aortic smooth muscle cells (SMC), respectively, suggesting that versican transcription is differentially regulated by the respective mediator and transcription factor in epithelial cells and SMC. In chapter IV, I reveal the role of PI3K/PKB/GSK-3β signaling pathway in regulating versican promoter activity and transcription. Furthermore, I identify that the β-catenin/TCF-4 transcription factor complex, one of the downstream targets of GSK-3β, mediates versican promoter activity and transcription. In chapter V, I identify that variations in C-terminal regions of TCF family members determine their repressor or enhancer properties on Wnt target genes. Furthermore, I show that curcumin is a strong inhibitor of the β-catenin/TCF-p300 mediated gene expression. In chapter VI, I demonstrate that the androgen receptor trans-activates versican transcription in prostate cancer cells. Furthermore, I show cross-talk between the androgen receptor and β-catenin in regulating versican transcription in prostate stromal fibroblasts. Overall, this study charts previously uncharacterized promoter elements, transcription factors, and signal transduction pathways involved in regulation of the versican gene. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

No description available.