University of Lethbridge Theses
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- ItemSulfur diimides and their tin(IV) complexes, and contributions to improved models for X-ray crystal structures(Lethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistry, 2025) Hill, Nathan D. D.; University of Lethbridge. Faculty of Arts and Science; Boeré, René T.; Dibble, Peter W.Modernization of X-ray crystallographic structure model refinement using NoSpherA2 and an extensive investigation of the chemical and electrochemical properties of sulfur diimides (SDIs) and their tin(IV) chloride complexes are described. NoSpherA2, an X-ray model refinement tool recently integrated into the free-to-use Olex2 program, is shown by thorough comparative analysis to significantly outperform conventional Independent Atom Model (IAM) methods. Consistent improvements in hydrogen atom placement and non-H bond precisions demonstrate the benefits of incorporating NoSpherA2 into routine processing of crystallographic data. The synthesis of a systematic series of SDIs is presented alongside a comprehensive study of their fundamental properties, both on their own and as ligands in tin(IV) complexes. Their voltammetric behaviour is meticulously documented and suggests the SDIs are acting as redox-active ligands. This foundational work positions SDIs as promising candidates in this very active field of research, and provides warrant and clear direction for future endeavours therein.
- ItemThe factors associated with suicidality among Canadian youth: a cross-sectional secondary analysis(Lethbridge, Alta. : University of Lethbridge, Faculty of Health Sciences, 2025) Doctor, Jenessa; University of Lethbridge. Faculty of Health Sciences; Sanders, JamesThe focus of this thesis was to examine the association between vulnerable youth and suicidality. This was done by conducting a secondary analysis on youth aged 15 to 29. A secondary data analysis took place utilizing the Statistics Canada 2022 Mental Health and Access to Care Survey for two separate papers. In the first paper exposure to childhood maltreatment was examined as an exposure variable for the outcome suicidality among the age group 18 to 29. Results indicated that those exposed to childhood maltreatment were more likely to experience suicidality than those not exposed. Additionally, the odds of suicidality increased with the number of maltreatment types experienced, suggesting a potential dose-response relationship. This association showed evidence for being partially mediated by mental health conditions, specifically meeting diagnostic criteria for depression or anxiety. In the second paper, minority status was created as an exposure variable for the outcome suicidality by combining racialized minorities (including Indigenous groups), and sexual identity minorities for the age group 15 to 24. These results showed minorities were more likely to experience suicidality compared to non-minority youth. This association appeared to be partially mediated by childhood maltreatment, which consisted of experiencing any form of maltreatment in the past. Findings from both studies suggest that vulnerable youth are more likely to experience suicidality, placing them at an increased risk for negative health outcomes. This emphasizes the importance of reducing systemic inequalities and developing context specific interventions to support these groups of youth. Policy makers, governments, and the community should aim to use proactive measures for prevention rather than implementing more crisis interventions in the future.
- ItemUnderstanding Indigenous data governance when collaborating with post-secondary institutions(Lethbridge, Alta. : University of Lethbridge, Faculty of Health Sciences, 2025) Shouting, Melissa A.; University of Lethbridge. Faculty of Health Sciences; Vogelsang, Laura; Rice, JackieBackground: The Blood Tribe Department of Health (BTDH), with support from the Blood Tribe’s Chief and Council, are moving toward self-determination by establishing a collaborative partnership with a local post-secondary institution to create sustainable models of governance. This thesis is a small but essential piece of the work being conducted to determine best practices for developing data collection tools to assess and evaluate the community needs of Kainai Nation while understanding the resources needed for BTDH to enact the Ownership, Control, Access, and Possession (OCAP) Principles of data storage and management. Objective: This scoping review aimed to explore and describe what exists in the current literature on Indigenous Data Governance principles, and how the information is understood and utilized in collaborative health research initiatives. A goal and purpose for this review are to explore and understand the role that Indigenous populations or communities assume in collaborative research with academics and scholars. Methodology: The search was conducted using nine databases from inception until May 2024. Two reviewers independently screened for inclusion and exclusion using the Arksey & O’Malley (2005) scoping review framework. The principal investigator conducted the final review for full-text articles, based on content and findings, with additional criteria added. Results: Fifteen reports were included. Our included reports consisted of qualitative research (n=7), mixed methods approach (n=6), and quantitative studies (n=2). Findings are presented within a framework that discusses IDG in six areas: 1) study characteristics and demographics; 2) study objectives, designs and theoretical frameworks; 3) Indigenous data governance: an overview of community engagement; 4) ethical practices in research and data governance; 5) enacting community collaboration to guide and support Indigenous data governance; 6) limitations. Conclusion: Themes identified related to Indigenous Data Governance (IDG), as well as challenges and barriers to implementing IDG in collaborative health research projects that are situated within universities. A collaborative approach involving stakeholders, culturally competent training and capacity building are approaches to move forward, but the establishment of Indigenous-led research institutes, a source of stable funding, and further collaborative research opportunities focusing on building and supporting IDG through building nation-specific data ecosystems are needed.
- ItemInvestigation of dengue virus RNA terminal region interactions with human host proteins(Lethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistry, 2025) Demeler, Aysha K.; University of Lethbridge. Faculty of Arts and Science; Patel, Trushar R.Dengue virus (DENV) is a globally important arthropod-borne pathogen responsible for dengue fever, which can range from mild fever to severe hemorrhagic fever and shock syndrome. With no specific antiviral treatments available, understanding the molecular mechanisms of DENV replication and its interactions with host proteins is essential. This study focuses on two interconnected projects that use advanced biophysical techniques to address these challenges. The first project assesses biophysical methods for studying protein-protein interactions (PPIs) in solution, using the sfGFP-anti-GFP nanobody system as a model. Techniques such as microscale thermophoresis, fluorescence correlation spectroscopy, analytical ultracentrifugation, isothermal titration calorimetry, and size exclusion chromatography coupled with multi-angle light scattering were systematically compared. This analysis creates a reliable framework for studying PPIs, which can be applied to protein-RNA and RNA-RNA interactions. The second project examines the interaction between DENV serotype 2 (DENV-2) and the human DEAD-Box Helicase 6 protein (DDX6), a host factor involved in viral replication and assembly. By exploring the molecular interactions between the terminal regions of DENV-2 RNA and DDX6, this work aims to provide mechanistic insights into how DENV hijacks host proteins. To support these studies, DDX6 was expressed recombinantly with a superfolder green fluorescent protein (sfGFP) tag, which facilitates detection in fluorescence-based assays and improves protein yield. Collectively, these findings establish that DDX6 recognizes each structural domain of the DENV-2 3′ UTR independently. Through a robust biophysical framework, we demonstrated this interaction using multiple complementary techniques, extending detailed characterization to a domain that has not been previously studied in depth.
- ItemUnderstanding PTPLP specificity: from atomic resolution to rational mutagenesis(Lethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistry, 2025) Cleland, Colyn P.; University of Lethbridge. Faculty of Arts and Science; Mosimann, Steven C.; Girodat, DylanTo understand substrate specificity of protein tyrosine phosphatase-like myo-inositol phosphatases (PTPLPs), I determined the X-ray crystallographic structures of two divergent PTPLP’s (30% sequence identity), PhyAdm from Solidesulfovibrio magneticus and PhyAlp from Legionella pneumophila str. Paris, in complex with InsP6. Both enzymes feature a CRGG phosphate-binding loop (P-loop) sequence, a shared InsP6 dephosphorylation pathway and a novel InsP6 binding mode. Comparison with the previously solved PhyAsr structure in complex with InsP6, which features a CEAG P-loop sequence, revealed that conformational differences in InsP6 binding were linked to the identity of the x2 residue in the P-loop. This finding prompted the investigation of additional novel PTPLPs containing similar and divergent naturally occurring x1x2 P-loop variants. The results established a relationship between InsP6 dephosphorylation pathways and P-loop x1x2 residues, identifying the P-loop as a primary determinant of PTPLP specificity. To demonstrate an understanding of PTPLP specificity, I rationally engineered P-loop mutants of PhyAdm and PhyAsr that swapped their x1x2 residues. Each mutant exhibited the InsP6 dephosphorylation pathway characteristic of the other enzyme. Structural analysis of the PhyAsr P-loop mutant in complex with its new dephosphorylation products confirmed that the x1x2 residue pairing influences substrate binding modes within the active site. These findings significantly advance our understanding of PTPLP substrate specificity and suggest a variety of novel research directions to further expand upon the structure-function relationship of these enzymes.