Like many other people I have thought about the biblical understanding of homosexuality. Because of my previous study on sexual purity before marriage and the exegetical work done on key biblical passages for that study, I thought I understood where the real issues lay regarding the subject of homosexuality. This study is an attempt to contribute to the current discussion in the Dutch Reformed Church in South Africa on the topic of homosexuality. In bringing this study to its final format I have received the indispensable help of others. First and foremost I wish to express my gratitude to my promoter, Professor Fika J van Rensburg. I am indebted to him beyond what mere words could convey in terms of gratitude. Our academic relationship spans five years and has developed into a warm friendship. It has been to my matchless benefit to be associated with him. I have profited much from his biblical knowledge, scholarly experience and overall passion and love for the Lord Jesus Christ. I also want to thank Reverend Erlo Stegen of Mission Kwasizabantu for his support and spiritual guidance. It is very special to be associated with a person who preaches the Word of God unambiguously and who has given and dedicated his life to Christ and Christ alone. Through his dedication Mission Kwasizabantu had become a home to the spiritual homeless and a refuge for the spiritual weary. The Mission has also been my home since 1994. I would like to express appreciation to Dr Andre van Niekerk and the North-West University for the financial support to complete this study. It is my prayer that the critical reader of this thesis will acknowledge that the money was well invested. I also wish to express my sincere gratitude to my friend, Reverend Frits van der Menve, for proofreading the manuscript. A special word of thanks to the personnel of the Ferdinand Postma and Jan Lion Cachet Libraries for their help and assistance. All my requests were always met with a smile and helpful attitude. All work done for me was executed in a spirit of kindness and benevolence. Lastly, I would like to thank my wife Andra and my son Chris, whose lives are inextricably bound with my own and who shared in the sacrifices associated with this study. / Thesis (Ph.D. (New Testament))--North-West University, Potchefstroom Campus, 2004.

The importance of arenavirus glycoprotein processing has only been understood within the past decade, with the majority of work focused on the Old World arenaviruses. Evidence has shown that SKI-1/S1P (subtilisin kexin isozyme-1/site 1 protease) is the cellular protease responsible for glycoprotein cleavage in Old and New World arenaviruses. Furthermore, glycoprotein cleavage is shown to be necessary for the production of infectious virus particles in Lassa and Junín viruses. In this thesis, evidence is provided that the recently emerged Chapare virus (New World) is also processed by SKI-1/S1P. Additionally, novel serpin-based SKI-1 inhibitors were shown to effectively prevent SKI-1 mediated cleavage. Using a wide panel of recombinant vesicular stomatitis viruses expressing New World arenavirus glycoproteins, these inhibitors were capable of significantly reducing viral titres. This provides strong evidence that SKI-1 inhibitors can be used as an effective treatment against the majority of New World Clade B arenaviruses and LASV in vivo.

Caveolin-1 is a marker protein for caveolae and can be a regulator of intracellular signaling pathways that contribute to the pathogenesis of human diseases. In the present study, the structural and functional changes of the lung in caveolin-1 null mice (Cav-1-/-) were assessed. Respiratory mechanics, measured using a small animal ventilator, revealed heightened central airway resistance (Rn), tissue resistance (G) and tissue elastance (H) in response to inhaled methacholine. The respiratory hyperreactivity is associated with increased collagen deposition around central and peripheral airways in Cav-1-/- mice; however, no difference was found in smooth muscle α-actin quantity between mouse strains. Similar to our in vivo findings, tracheal rings from Cav-1-/- mice mounted on an isometric wire myograph exhibited enhanced maximum active contractile force without a change in sensitivity (EC50) to methacholine. Rho kinase (ROCK1/2), protein kinase C (PKC) and extracellular signal regulated kinase 1/2 (ERK1/2) signaling were assessed as possible sources of the enhanced airway reactivity observed in Cav-1-/- mice. Inhibition of Rho kinase markedly blunted in vivo lung function responses (Rn) and (G) and ex vivo smooth muscle responses to methacholine. In fact, inhibition of Rho kinase completely eliminated any difference in response between mouse strains. Thus, our data indicate that Cav-1 may regulate mechanisms, such as Rho/Rho kinase signaling, that determine airway smooth muscle contraction and airway fibrosis; thus, it could be an important regulator of airway biology and physiology in health and disease.

Previous studies of genes associated with retroviral-induced neoplasia have provided the foundation for much of our current knowledge of both tumor suppressor and oncogenes, and have contributed to our understanding of both gene function and malignant transformation. The study of Friend virus-induced erythroleukemia, a well-studied example of multistage malignancy, has led to the identification of several oncogenes, including the Ets transcription factor, fli-1. Fli-1 plays a vital role in hematopoiesis, and vasculogenesis through the transcriptional regulation of its target genes, some of which are critical for the control of cellular proliferation, differentiation, and survival. The aberrant regulation of Fli-1 is associated with a number of cancers and human diseases, including erythroleukemia, Ewing’s sarcoma, lupus, and Jacobsen or Paris Trousseau syndrome. The essential goal set out to be achieved by the research presented herein is to establish a better understanding of both the oncogenic and developmental roles of Fli-1 by investigating the molecular basis by which its deregulated expression leads to fundamental aberration in the fine balance between proliferation and differentiation.

VP16 initiates the HSV replication cycle by activating immediate early (IE) gene expression. It recruits the RNA pol II through an acidic C-terminal domain. The defective VP16 encoded by the V422 mutant of HSV-1 possesses a truncated C-terminal domain. Therefore, V422 replication is suppressed in most cell-lines, except U2OS osteosarcoma cells. The permissive phenotype of U2OS cells stems from a failure to express one or more inhibitory factors that are produced in restrictive cells. The initial project was designed to identify these host inhibitory factors in restrictive cells of V422, using siRNA silencing technology. To facilitate the siRNA screen, a GFP reporter gene has been inserted into the thymindine kinase (TK) gene of the V422 genome and the wild-type KOS genome. This thesis provides information about characterizing the kinetics of GFP expression from recombinant viruses at both protein and mRNA levels, during different infection times in HeLa and Vero cells. / Virology

国立情報学研究所で電子化したコンテンツを使用している。

Bibliography: p. 159-171. / xviii, 171 p., [61] leaves of plates : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 1996?

Thrombospondin 1 (TSP1) is a 450 kDa homotrimeric multidomain glycoprotein with fundamental roles in many cell-cell and cell-matrix interactions. These varied, and sometimes conflicting, functions are mediated by specific domains in TSP1. One region with diverse biological roles is the Ca2+ binding loops (or type 3 repeats). The biological activity of this region is determined through a complex assembly of disulfide bonds linking structure and function. Disulfide interchange in a protein is usually very specific and quite slow, unless catalysed. I have found that protein disulfide isomerase (PDI) is expressed on the surface of platelets and endothelial cells in a reduced active conformation. The presence of enzymatically active PDI on the surface of TSP1-secreting cells suggests PDI is well positioned to catalyse disulfide interchange in, and regulate the structure/function relationships of, TSP1. PDI was observed to form disulfide-linked complexes with TSP1. Moreover, incubation of platelet or fibroblast TSP1 with PDI enhanced binding of an isomer-specific anti-TSP1 antibody whose epitope is in the Ca2+ binding loops. These findings suggest that PDI may mediate disulfide bond rearrangement in both the soluble and extracellular matrix-bound forms of TSP1. TSP1 is a tight-binding competitive inhibitor of neutrophil cathepsin G; however, incubation with PDI increased the Ki for the interaction ???10-14-fold. TSP1 bound platelet-derived growth factor (PDGF) tightly in the region of the Ca2+ binding loops and supported binding of PDGF to its receptor. PDI-mediated disulfide interchange in TSP1 ablated PDGF binding, indicating that PDI-catalysed disulfide interchange in TSP1 may modulate PDGF-TSP1 complex formation and the biological activity of PDGF. Finally, PDI-catalysed isomerization of TSP1 potently affected its cell adhesive properties. Treatment of TSP1 with PDI enhanced adhesion and spreading of endothelial cells through the ??v??3 integrin receptor to TSP1, by exposure of a cryptic RGD sequence. Thus, endothelial cell surface PDI may be a physiological regulator of RGD-dependent binding to TSP1. These data suggest that cell-surface PDI may regulate the disulfide-bonded structure and certain biological functions of TSP1. In conclusion, I propose a novel mechanism for the post-translational regulation of TSP1 structure/function, which in turn may regulate certain aspects of TSP1 in vascular biology.

Zugl.: Münster (Westfalen), Univ., Diss., 2005

Univ., Diss., 2006--Frankfurt (Main)