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.

This study investigated the transplantation of understory plants within the Cu-Ni smelterdamaged urban forest of Sudbury, Ontario, Canada, to increase plant biodiversity in an area where natural colonization of understory species is delayed. The goal of my study was to evaluate establishment of 16 m2 vegetation mats along a gradient of smelter disturbance and to relate successful establishment to abiotic and biotic site characteristics. Specific investigations were conducted to determine whether soil quality influenced root growth and transplant establishment. Variables associated with smelter emissions and soil temperature were the best predictors of successful transplant establishment of understory plant species, but relationships were species specific. Also, root growth was not limited to organic soils of the transplant mat and roots were able to grow into receptor site soil. Knowledge of environmental factors influencing establishment will help to determine site locations and to select species to introduce when transplanting understory species in future reclamation projects.

This thesis explores the process of remediation and renewal in the context of decommissioned gold mining operations in Yellowknife, Northwest Territories, Canada. The work aims to demonstrate that architecture can facilitate understanding and bring awareness to the processes involved in reclaiming industrial sites by creating places for observation, interaction and refl ection. Existing mine infrastructure will be adapted and augmented to support phytoremediation processes, clean energy generation and municipal waste treatment for adjacent Yellowknife residents. These interventions are based on a series of studies involving mineral extraction processes, historic mine development and geological formations. The architectural interventions are phased and are intended to be prototypical strategies for decommissioned mine sites in general, but are specifi cally relevant to those located in sub-arctic climates.

Aggregate mining in Ontario is a highly contentious landuse activity between many stakeholder groups. Land use activities, within a watershed, including anthropogenic infrastructure and anthropogenic changes to the natural infrastructure (such as aggregate pits and quarries), may increase susceptibility of an aquifer by modifying contaminant migration pathways, which is an issue of water security. The purpose of this research is to apply the Vulnerability Scoring Tool to test its utility in the field of water security. The methodology is applied to an aggregate extraction site in the Grand River Watershed in Ontario, and presents an example of how changing land use may change exposure pathways. In particular, the case study results indicate an increase in vulnerability once the aquitard had been penetrated, through aggregate excavation. Applying vulnerability and risk models to future aggregate mining sites can be a useful decision-making tool when investigating impacts of aggregate extraction sites on water security. / Canadian Water Network

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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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