Thesis (doctoral)--Rijksuniversiteit te Utrecht.

Thesis (doctoral)--Ludwig Maximilians-Universität zu München, 1978.

Thesis--University of Lund. / Extra t. p. with thesis statement inserted. Includes bibliographical references (p. 19-21).

Thesis (M.S.)--University of Wisconsin--Madison. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 90-96).

Thesis--University of Lund. / Extra t. p. with thesis statement inserted. Includes bibliographical references (p. 19-21).

Thesis (doctoral)--Rijksuniversiteit te Utrecht.

Thesis (Ph. D.)--University of Missouri-Columbia, 2005. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file viewed on (May 22, 2006) Vita. Includes bibliographical references.

Thesis (M.Sc.(Clinical Epidemiology))--University of Pretoria, 2006. / Summary in English and Afrikaans. Includes bibliographical references. Also available online.

Dissertation submitted in compliance with the requirements of the Master's Degree in Technology in Biotechnology, Technikon Natal, 1999. / Sugarcane mosaic potyvirus (SCMV) IS the causal agent of the most important viral disease of sugarcane in South Africa, mosaic. Accurate knowledge of the prevalent SCMV strain(s) in the South African sugar industry is lacking and has never been determined using molecular analysis. Identification of SCMVstrains at the genomic level would provide valuable information for the development of appropriate in vitro diagnostic tests and in the genetic engineering of sugarcane for coat protein (CP) mediated resistance. / M

Retinoic acid-inducible gene-I (RIG-I) is a putative RNA helicase and recently identified as a cytosolic RNA receptor in mammalian cells. The role of RIG-I in the regulation of vascular function under physiological and pathological conditions is unknown. Recent studies have shown that the inflammasome serves as a crucial initiator of cytokine-mediated inflammation mediating the pathogenesis of cardiovascular disease. The present study tested whether RIG-I activation triggers inflammasome formation and subsequent cytokine-mediated inflammation in the endothelium of mice coronary arteries. Using both genetic and pharmacological interventions of the RIG-I inflammasome, we first characterized whether specific activation of RIG-I via 3pRNA transfection induced the formation of an ASC-containing inflammasome in mouse vascular endothelial cells (MVECs). We confirmed that 3pRNA dose-dependently increased RIG-I protein levels and release of of type I IFNβ and IL-1b (a prototype cytokine from inflammasome activation), confirming RIG-I activation. We found that MVECs transfected with 3pRNA exhibited increased colocalization of RIG-I with apoptosis-associated speck-like protein (ASC) or caspase-1 and elevated active caspase-1 and IL-1β levels, indicating the formation and activation of the RIG-I inflammasome. This RIG-I inflammasome activation was accompanied by endothelial barrier dysfunction. In the presence of 3pRNA, ZO-1 and ZO-1 and VE-Cadherin expression diminished, and inhibiting caspase-1 and silencing inflammasome components attenuated this effect. To test the functional role of RIG-I and its affect on the permeability of mouse ECs, we performed a transwell permeability assay. Results confirmed that 3pRNA induced increased permeabilization of these mouse ECs, which was attenuated when inhibiting and silencing inflammasome components. These data indicate that increased expression and activity of RIG-I activate IL-1b producing inflammasomes in ECs, which may represent an early molecular mechanism mediating vascular inflammation and endothelial dysfunction independent of Nlrp3. Furthermore, we investigated the role of anti-aging gene Klotho in the regulation of RIG-I inflammasome activation. The Klotho protein has been shown to directly interact with RIG-I in senescent cells to block RIG-I multimerization and downstream production of pro-inflammatory cytokines. Administration of D-saccharic acid 1,4-lactone (saccharolactone) in vitro, a pharmacological inhibitor of Klotho activity, substantially increased inflammasome activation. In addition, mice injected with saccharolactone exhibited increased RIG-I inflammasome formation and activation within the coronary artery endothelium. These results suggest that decreased Klotho activity may activate RIG-I and thereby increase inflammasome activity. Therefore, the present study defines a novel role for RIG-I inflammasome activation in vascular dysfunction.