University of Lethbridge Theses

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    The molecular mechanisms of anti-inflammatory impact of three minor phytocannabinoids, eugenol and psilocybin and the protective effect of two major phyatocannabinoids, three minor phytocannabinoids, eugenol and psilocybin on high glucose-high lipid induced ß-cell loss, dysfunctionality and dedifferentiation
    (Lethbridge, Alta. : University of Lethbridge, Dept. of Biological Sciences, 2023) Ghasemi Gojani, Esmaeel; University of Lethbridge. Faculty of Arts and Science; Kovalchuk, Igor; Kovalchuk, Olga
    Type 2 Diabetes, a growing disorder worldwide, particularly in advanced countries, is closely associated with dysregulated inflammation. In our current research, we aimed to explore the molecular mechanisms behind the potential anti-inflammatory effects of major and minor phytocannabinoids, eugenol and psilocybin. We investigated their impact on mitigating proinflammatory responses in human macrophages, as well as their potential to counteract high glucose-high lipid-induced (HG-HL) loss and dedifferentiation of beta-cells, along with impaired glucose-stimulated insulin secretion. Our findings suggest that the anti-inflammatory effects of THCV, CBC, and CBN are likely mediated through the involvement of CB1R and PPARγ receptors. Furthermore, we identified PANX-1, TXNIP, and ADAR1 as potential contributors to the mitigation of Nlrp3 inflammasome and the anti-inflammatory effects exerted by these three minor phytocannabinoids. We also observed that THC, CBD, THCV, CBC, and CBN could inhibit HG-HL-induced loss of beta-cells, possibly by reducing apoptosis and pyroptosis. Additionally, all five phytocannabinoids displayed varying degrees of inhibitory effects on HG-HL-induced -cell dedifferentiation. Moreover, we found evidence suggesting that eugenol exerts its anti-inflammatory effects, at least in part, by mitigating NFκB activity. Eugenol also demonstrated the ability to inhibit apoptosis and dedifferentiation in HG-HL-induced beta-cell. As for psilocybin, it showed potential inhibitory effects on cytokine storm through the suppression of NFκB, STAT3, and STAT1 transcription factors. Psilocybin also exhibited a suppressive impact on beta-cell loss and dedifferentiation. In summary, our research sheds light on the molecular mechanisms underlying the anti-inflammatory properties of eugenol and psilocybin, as well as major and minor phytocannabinoids. These findings have implications for understanding the potential therapeutic benefits of these compounds in mitigating inflammation and preserving beta-cell function in the context of Type 2 Diabetes.
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    Topics in explicit number theory
    (Lethbridge, Alta. : University of Lethbridge, Dept. of Mathematics and Computer Science, 2023) Hasanalizade, Elchin; University of Lethbridge. Faculty of Arts and Science; Kadiri, Habiba; Ng, Nathan
    This doctoral thesis is made up of a collection of papers of the author. All of these papers are already published. The structure of this thesis is as follows. After the introduction, there are four chapters. In Chapters 2 and 3, we obtain explicit bounds for the number of non-trivial zeros of the Riemann zeta function and Dedekind zeta functions, which improve previous results of Trudgian. This improvement is based on ideas from previous works of Bennett et al., Kadiri and Ng and Trudgian. This is a joint work with Quanli Shen and Peng-Jie Wong. In Chapter 4, we apply explicit results from transcendental number theory due to Bugeaud, Laurent and Matveev to completely solve a Diophantine inequality involving the Fibonacci numbers and to study a particular case of the Terai-Shinsho conjecture. In Chapter 5, using elementary methods and explicit bounds for primes in arithmetic progressions due to Bennett et al. we study two Diophantine equations which involve multiplicative functions.
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    Biophysical and biochemical characterization of an HBV cccDNA g-quadruplex targeting therapeutic
    (Lethbridge, Alta. : University of Lethbridge, Dept. of Biochemistry and Chemistry, 2023) Balderas Figueroa, Gerardo K.; University of Lethbridge. Faculty of Arts and Science; Patel, Trushar
    Hepatitis B virus (HBV) has chronically infected 296 million people, and it is the leading cause of cirrhosis and hepatocellular carcinoma (HCC). Current treatments target post-transcriptional steps of the viral cycle, which leaves HBV’s covalently closed circular DNA (cccDNA) nuclear reservoirs unaffected. This allows patients to relapse if therapy ceases. We have previously identified a G-quadruplex (G4) forming region in the HBV preCore promoter involved in viral replication. Here, we develop recombinant single-domain antibodies (sdAbs) that can target this G4-forming region. The sdAbs are purified by chromatography, and their interaction with HBV G4 is characterized by biochemical binding assays as well as biophysical techniques. We conclude that sdAbs can be highly structure and sequence specific towards HBV G4. Overall, my work develops a pipeline for G4-targeting that can be used in future HBV cccDNA studies as well as be implemented in the study of other G4s involved in disease.
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    Population genetics and historical introgression of a North American passerine within the genus Sialia
    (Lethbridge, Alta. : University of Lethbridge, Dept. of Biological Sciences, 2023) Veale, Aaron L.; University of Lethbridge. Faculty of Arts and Science; Burg, Theresa; Reudink, Matthew
    This study analyzed the genetic structure of mountain bluebirds (Sialia currucoides) from across their range using restriction site-associated DNA sequencing to find single nucleotide polymorphisms. I found evidence of at least four distinct genetic clusters, two of which were in Alberta. I then went on to hypothesize current and historical barriers to gene flow. In the third chapter, I examined the mountain bluebird breeding populations in Alberta and Saskatchewan for signals of current and historical hybridization. Although I did not find evidence of recent hybridization, I did detect signals of ancient introgression from both bluebird congeners. I then used both nuclear and mitochondrial DNA to examine the Sialia polytomy containing all three species of bluebirds. The polytomy showed signs of both incomplete lineage sorting between mitochondrial genes and mitonuclear discordance. As such, it appears that hybridization and other potential factors may obscure the evolutionary history of the entire genus.
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    Gurmukhi Punjabi (PA) as a low resource-language through the lens of the BLARK model.
    (Lethbridge, Alta. : University of Lethbridge, Dept. of English, 2023) Kaur, Kirandeep; O'Donnell, Daniel Paul; Snoek, Conor
    We are venturing into the next phase of digital divide (unequal access to digital technology), where the languages which are not ready for Natural Language Processing (NLP) are at the most risk of losing out on the developments in the fields of Speech and Language technologies. This has brought forth a big gap between the readiness of different languages in terms of taking advantage of the recent developments in the field of computational technologies. Common Language Resources and Technology Infrastructure (CLARIN) - a large-scale pan-European collaborative effort to create, coordinate and make language resources and technology available and readily usable, has developed the Basic Language Resource Kit (BLARK) model to assess the readiness for speech and language technology developments in any language. Punjabi, despite being a major language with millions of native speakers and a significant diaspora population around the world, has received limited attention in the computational technologies. The thesis aims to provide a comprehensive overview of the existing resources, tools, and techniques for Punjabi NLP, as well as to identify the gaps and opportunities for future research using BLARK model as a framework. The thesis, after giving the current (sorry) state of Punjabi in terms of its readiness for computation technologies, concludes with some suggestions for directions and effort which are needed for making Punjabi ready for development of speech and language technologies. The thesis contributes to the field of Punjabi language processing by proposing a generic model for comparing and enhancing Punjabi linguistic resources.