Multiple lines of evidence suggest that elevated plasma lipoprotein(a) (Lp(a)) concentrations are a significant risk factor for the development of a number of vascular diseases including coronary heart disease and stroke. Lp(a) consists of a low-density lipoprotein (LDL)-like moiety and an unique glycoprotein, apolipoprotein(a) (apo(a)), that is covalently attached to the apolipoproteinB-100 (apoB-100) component of LDL by a single disulfide bond. Many studies have suggested a role for Lp(a) in the process of endothelial dysfunction. Indeed, Lp(a) has been shown to increase both the expression of adhesion molecules on endothelial cells (EC), as well as monocyte and leukocyte chemotactic activity in these cells. We have previously demonstrated that Lp(a), through its apo(a) moiety, increases actomyosin-driven EC contraction which, as a consequence, increases EC permeability. In this thesis, we have demonstrated a role for the strong lysine-binding site in the kringle IV type 10 domain of apo(a) in increasing EC permeability, which occurs through a Rho/Rho kinase-dependent pathway. We have further validated these findings using mouse mesenteric arteries in a pressure myograph system. We also have dissected another major signaling pathway initiated by apo(a) that involves in a disruption of adherens junctions in EC. In this pathway, apo(a)/Lp(a) activates the PI3K/Akt/GSK3β-dependent pathway to facilitate nuclear translocation of beta-catenin. In the nucleus beta-catenin induced the expression of cyclooxygenase-2 (COX-2) and the secretion of prostaglandin E2 (PGE2) from the EC. Finally, we have presented data to suggest a novel inflammatory role for apo(a) in which it induces the activation of nuclear factor-kappaB through promotion of the dissociation of IkappaB from the inactive cytoplasmic complex; this allows the nuclear translocation of NFkappaB with attendant effects on the transcription of pro-inflammatory genes. Taken together, our findings may facilitate the development of new drug targets for mitigating the harmful effects of Lp(a) on vascular EC which corresponds to an early step in the process of atherogenesis. / Thesis (Ph.D, Biochemistry) -- Queen's University, 2009-09-22 19:24:04.594

Of the organisms with sequenced genomes, plants appear to possess the most rhomboid protease-encoding genes. However, our knowledge of processes in plants that involve Regulated Intramembrane Proteolysis (RIP) and rhomboid proteases remains low. As expressed recently by other researchers, finding a natural substrate for a rhomboid protease represents the biggest experimental challenge. Using yeast mitochondria-based assays, a potential link between the plastid translocon component Tic40 and organellar rhomboid proteases was recently uncovered. In this particular link, rhomboid proteases appear capable of influencing the pattern of imported Tic40 in yeast mitochondria. Tic40 may thus represent a natural plant target of organellar rhomboid proteases. Here, we obtained further motif-oriented evidence supporting Tic40 as a natural plant rhomboid substrate. A comparative analysis of sequences revealed that Tic40 may also possess similar TMD motifs found in the model substrate, Spitz. Rhomboid proteases often require these motifs to cleave substrates within intramembrane environments. Using site-directed mutagenesis and yeast mitochondria assays, the impact of mutations occurring in the motifs ASISS, GV, QP, and GVGVG of Tic40 was assessed. In terms of cleavage and changing the pattern of imported Tic40, some of the mutations showed decreased activities and a few showed enhancements. More importantly, the overall observed pattern associated with select Tic40 mutations resembled the characteristics reported for the model substrates. In particular, mutations in the Tic40 GV motif produced similar results as that observed with Spitz, by drastically decreasing or increasing cleavage as a function of amino acid sequence. / Thesis (Master, Biology) -- Queen's University, 2010-05-30 10:22:07.72

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The goal of the present study is the description and analysis of the material found on the E. H. II site (Area A) situated near Lake Vouliagméni on the Perakhora peninsula. The study includes a description of the stratigraphy and architecture of the site and of the material (ceramics, lithics) found in the building. For the analysis of the material, statistics were widely used to give more precision to the descriptions. The objects were also compared to contemporaneous material. The conclusion consist of a functional analysis of each of the rooms of the building. / La présente étude a pour but de décrire et d’analyser le matériel retrouvé sur le site H. A. II (secteur A) situé près du lac Vouliagméni, dans la péninsule de Perakhora. L’ étude comprend une description de la stratigraphie et de l’architecture du site, ainsi que du matériel (céramique, lithique) contenu dans l’édifice. Au cours de l’analyse du matériel, on a fait un abondant usage des statistiques afin de donner plus de précision aux descriptions. Les objets ont aussi été mis en parallèle avec leurs contemporains. La conclusion consiste en une analyse fonctionnelle de chacune des pièces de l’édifice découvert.

Tree growth is influenced by environment and genetic factors. The same tree growing in different areas will have different growth patterns. Trees with different genetic material, e.g. pine and Eucalyptus trees, growing under the same environmental conditions have different growth patterns. Plantation trees in South Africa are mainly used for pulp and paper production. Growth is an important economic factor in the pulp and paper industry. Plantations with fast growth will be available for processing earlier compared to a slow growth plantation. Consequently, it is important to understand the role played by environmental factors, especially climatic factors, on tree growth. This thesis investigated the climatic effects on the radial growth of two Eucalyptus clones using growth data collected daily over five years by Sappi. The general linear model and the time series models were used to assess the effects of climate on radial growth of the two clones. It was found that the two clones have similar overall growth patterns over time, but differ in growth rates. The growth pattern of the two clones appears to be characterized by substantial jumps/changes in growth rates over time. The times at which the jumps/changes in growth rate occur are referred to as the “breakpoints”. The piecewise linear regression model was used to estimate when the breakpoints occur. After estimating the breakpoints, the climatic effects associated with these breakpoints were investigated. The linear and time series modeling results indicated that the contribution of climatic factors on radial growth of Eucalyptus clones was small. Most of the variation in radial growth was explained by the age of the trees. Consequently, this thesis also investigated the appropriate functional relationship between radial growth and age. In particular, this nonlinear growth models were used to model the radial growth process. The investigated growth curve models were those which included the maximum radius and the age at which the radial growth rate is largest as some of the parameters. The maximum growth rate was calculated from the estimated model of each clone. The results indicated that the two clones reach the maximum growth rate at different times. In particular, the two clones reach the maximum growth rates at around 368 and 376 days, respectively. Furthermore, the maximum radius was found to be different for the two clones. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2009.

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Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Transposons are DNA segments that can move or transpose themselves to new positions within the genome of an organism. Biologists need to predict preferred insertion sites of transposons to devise strategies in functional genomics and gene therapy studies. It has been found that the deformability property of the local DNA structure of the integration sites, called Vstep, is of significant importance in the target-site selection process. We considered the Vstep profiles of insertion sites and developed predictors based on Artificial Neural Networks (ANN) and Support Vector Machines (SVM). We trained our ANN and SVM predictors with the Sleeping Beauty transposonal data, and used them for identifying preferred individual insertion sites (each 12bp in length) and regions (each 100bp in length). Running a five-fold cross-validation showed that (1) Both ANN and SVM predictors are more successful in recognizing preferred regions than preferred individual sites; (2) Both ANN and SVM predictors have excellent performance in finding the most preferred regions (more than 90% sensitivity and specificity); and (3) The SVM predictor outperforms the ANN predictor in recognizing preferred individual sites and regions. The SVM has 83% sensitivity and 72% specificity in identifying preferred individual insertion sites, and 85% sensitivity and 90% specificity in recognizing preferred insertion regions.