Thesis (Ph.D.) - University of St Andrews, December 2007. / Restricted until 12th December 2008.

Reproduction de : Thèse de doctorat : Chimie organique biologique : Clermont-Ferrand 2 : 2005. / Titre provenant de l'écran-titre. Bibliogr. p. 302-306.

Staphylococcus aureus (S. aureus) is a bacterium commonly found on the skin and associated with minor skin and soft tissue infections. It is possible for S. aureus to infect the bloodstream, which can lead to serious illness and possibly death. Endothelial cells line all blood vessels in the body and serve as the last defense against pathogens attempting to invade the bloodstream. We have found that S. aureus requires a cellular pathway, called the phosphoinositide 3-kinase (PI3K) pathway, to be active in order to invade endothelial cells. PI3K has multiple isoforms and we hypothesize that one isoform, p1 l Oa, is specifically utilized for infection. We have gathered strong evidenceto suggest that p 1 l Oa plays a significant role in the infection process of S. aureus; however more experiments are needed to conclude that our hypothesis is supported. / Department of Biology

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 84-106).

Staphylococcus aureus (S. aureus) is a medically important bacterial pathogen associated with many diseases and infections of the respiratory system, wound sites, surgical incisions, and other portals of entry and exit. S. aureus is able to invade cells via mechanisms that have yet to be fully characterized. Vimentin, a protein filament of the animal cell cytoskeleton, and phosphoinositide 3-kinase (PI3K), a family of kinases responsible for initiating several cell signaling events, were found to be associated with S. aureus invasion. Confocal microscopy revealed that the vimentin network in human umbilical vein endothelial cells (HUVECs) undergoes dynamic rearrangement in steady state under control conditions. However, cells infected with S. aureus demonstrated peri-nuclear collapse of the vimentin network. Pre-treatment with LY294002, a drug that inhibits PI3K activity, decreased invasion of S. aureus and paralyzed the vimentin network. These data suggest that PI3K mediates S. aureus infection and vimentin rearrangement. / Department of Biology

Thesis (Ph. D.)--University of Virginia, 2000. / Spine title: Serine phosphorylation of FAK. Includes bibliographical references (p. 209-231). Also available online through Digital Dissertations.

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 201-231).

Phosphoinositide 3-kinases (PI3Ks) are a family of proteins involved in many different aspects of cell signaling. To date, eight different human PI3K isoforms have been identified, and distinct roles are beginning to emerge for each family member. Statins, HMG co-A reductase inhibitors used clinically to lower LDL cholesterol levels, also act through the PI3K signaling pathway to regulate cholesterol independent of their lipid-lowering effects. In an effort to discover the role of pl 10f3 in mediating non-lipid lowering effects of pravastatin, a mutant of p110(3 was overexpressed in human coronary artery endothelial cells (HCAEC) to form a dominant negative model (p110(3 DN). Silence si-RNA as an alterative tool was also optimized to diminish p110(3 protein expression successfully. HepG2 3: RE was used to monitor statins function by assaying luciferase expression. Results from these studies will determine the contribution of p110f3 in mediating selective cellular responses to statin. / Department of Biology

Thesis (Ph.D.) -- McMaster University, 1998. / Includes bibliographical references (p. 134-135). Also available via World Wide Web.

Thesis (Ph.D.) -- McMaster University, 1999. / Includes bibliographical references (leaves 216-244). Also available via World Wide Web.