Graduate Theses & Dissertations

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Immunotherapies Targeting the Amyotrophic Lateral Sclerosis-Associated Protein TDP-43
Transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) pathology, including fibrillar aggregates and mutations, develops in amyotrophic lateral sclerosis (ALS) and is characterized by hyperphosphorylation and aggregation patterns, a mechanism largely understudied. In addition, ALS remains without a cure. Herein, in vitro aggregation of phosphorylated TDP-43 was explored, and the anti-TDP-43 antibodies tested for their inhibitor efficacies. Additionally, in vitro phosphorylation of TDP-43 by protein kinases was conducted to identify which protein kinases catalyze phosphorylation. The aggregation of phosphorylated and unphosphorylated full-length TDP-43 protein (pS410) was monitored by transmission electron microscopy (TEM), turbidity absorbance, and thioflavin (ThT) fluorescence spectroscopy. The protein aggregates were largely insoluble, ThT-positive and characterized with heterogeneous morphologies. Antibodies specific to epitopes within the RNA-recognition motifs and the C-terminal domains reduced the formation of β-sheets and insoluble aggregates, with outcomes highly dependent on the type of antibodies, indicating dual functionality. The only protein kinase able to phosphorylate TDP-43 at S410 was MARK4, indicating its role in the onset of PTMs in the protein. Thus, targeting TDP-43 epitopes for inhibition of aggregation and in vitro phosphorylation represent viable biochemical assays for screening protein kinase inhibitors as potential drugs against ALS. Author Keywords: aggregation, ALS, antibody-based inhibition, phosphorylation, protein kinase, TDP-43
Demographic history and conservation genomics of caribou (Rangifer tarandus) in Québec
Genetic variation is the raw material and basis for evolutionary changes in nature. The loss of genetic diversity is a challenge many species are facing, with genomics being a potential tool to inform and prioritize decision making. Whole genome analysis can be an asset to conservation biology and the management of species through the generation of more precise and novel metrics. This thesis uses whole genome re-sequencing to characterize the demographic history and quantify genomic metrics relevant to conservation of caribou (Rangifer tarandus) in Québec, Canada. We calculated the ancestral and contemporary patterns of genomic diversity of five representative caribou populations and applied a comparative population genomics framework to assess the interplay between demographic events and genomic diversity. When compared to the census size, NC, the endangered Gaspésie Mountain caribou population had the highest ancestral Ne:NC ratio which is consistent with recent work suggesting high ancestral Ne:NC is of conservation concern. These ratios were highly correlated with genomic signatures (i.e. Tajima’s D) of recent population declines and explicit demographic model parameters. Values of contemporary Ne, estimated from linkage-disequilibrium showed Gaspêsie having among the highest contemporary Ne:NC ratio. Importantly, classic conservation genetics theory would predict this population to be of less concern based off this metric alone. Inbreeding measures suggested nuanced patterns of inbreeding and correlated to the demographic models. This study suggests that while the Québec populations are all under decline, they harbour enough ancestral genetic variation to replenish any lost diversity, if conservation decisions are made in favour of these populations, specifically supporting NC. Author Keywords:
Frequency-time and polarization considerations in spectral-focusing-based CARS microscopy
Spectral-focusing-based coherent anti-Stokes Raman scattering (SF-CARS) microscopy is a powerful imaging technique that involves temporally and spectrally stretching ultrashort laser pulses and controlling their frequency-time characteristics. However, a broader and more detailed understanding of the frequency-time characteristics of the laser pulses and signals involved, how they are related, and how they influence important aspects such as the spectral resolution is needed to understand the full potential of SF-CARS systems. In this work, I elucidate these relationships and discuss how they can be exploited to optimize SF-CARS microscopy setups. I present a theoretical analysis of the relationships between the spectral resolution, the degree of chirp-matching, and pulse bandwidth in SF-CARS. I find that, despite allowing better ultimate spectral resolution when chirp-matching is attained, the use of the broadest bandwidth pulses can significantly worsen the spectral resolution if the pulses are not chirp-matched. I demonstrate that the bandwidth of the detected anti-Stokes signal is minimized when the pump is twice as chirped as the Stokes, meaning that (perhaps counter-intuitively) a narrow anti-Stokes bandwidth does not imply good spectral resolution. I present approximate expressions that relate the bandwidths of the pump, Stokes, and anti-Stokes pulses to the degree of chirp-matching and outline how these could be used to estimate the amount of glass needed to attain chirp-matching. I develop a spectral-focusing-based polarization-resolved (SFP-CARS) setup, by modifying our existing system, to explore the merits of integrating polarization-dependent detection as an add-on to existing SF-CARS setups. By using the system to study polarization-dependent features in the CARS spectrum of benzonitrile, I assess its capabilities and demonstrate its ability to accurately determine Raman depolarization ratios. Ultimately, the detected anti-Stokes signals are more elliptically polarized than desired, hindering a complete suppression of the non-resonant background. Nevertheless, I find that the SFP-CARS setup is a useful tool for studying polarization-dependent features in the CARS spectra of various samples and is worthy of further investigation. This work clarifies several technical aspects of SF-CARS microscopy and provides researchers with valuable information to consider when working with SF-CARS microscopy systems. Author Keywords: coherent anti-Stokes Raman scattering, nonlinear microscopy, polarization, spectral focusing, spectroscopy
Experiencing buhts’an qu’inal from sHachel jwohc’ a’tel through sna'el ya'beyel stuc te bin ay ma'yuc
This thesis shows and emphasizes the importance of Indigenous Knowledge (IK) in informing collaborative efforts that promote sustainable economic development in Indigenous communities. It tells the story of a participative research study undertaken with six Tseltal communities located in the Region Selva of Chiapas, Mexico, in the context of the Covid19 pandemic of 2020 and early 2021. In this study, the research participants reflect on their endeavours pursuing projects focused on the economic self-sufficiency of their communities. Their initiatives, which are deeply grounded in Tseltal practices while accompanied by the local non-profit organization IXIM AC, focus on developing economically self-sustaining enterprises in self-organized groups led by local Indigenous women. The findings offer a deep immersion into two aspects that emerge from Tseltal knowledge: The Nucleus of Tseltal community wellbeing and the Four Elements of Buhts’an qu’inal (Tseltal community wellbeing). The study’s results show that these two IK grounded aspects guide the participants’ endeavours in developing sHachel jwohc’ a’tel (Tseltal initiatives of entrepreneurship) while also enabling opportunities for gender transformative collaborative work and sustained engagement in local initiatives of sna'el ya'beyel stuc te bin ay ma'yuc (Tseltal economic development oriented to community wellbeing). Author Keywords: Community Wellbeing, Indigenous Entrepreneurship, Indigenous Knowledges, Indigenous Women, Participative Action Research, Sustainable Development
Evidence for hybrid breakdown in the cattail (Typha) hybrid swarm in southern Ontario
Heterosis, expressed as phenotypic superiority over parental species, typically peaks in first generation hybrids (F1s), while later generations (F2 +) exhibit lower fitness. The decrease in hybrid fitness is called hybrid breakdown. The overall incidence of hybrid breakdown in invasive hybrid zones remains poorly understood. The Laurentian Great Lakes (LGL) region contains a hybrid zone comprised of: native Typha latifolia, Typha angustifolia, and hybrid Typha × glauca. F1 T. × glauca display heterosis and are invasive, while later generation hybrids are relatively rare. To investigate possible hybrid breakdown, I compared seed germination and plant growth of backcrossed and advanced-generation (F2) hybrids to F1s and T. latifolia. I found evidence for hybrid breakdown in F2s and backcrossed hybrids, expressed as reduced growth and germination rates. Expression of hybrid breakdown in F2s and backcrosses may explain their relative rarity in the LGL hybrid zone. Author Keywords: Advanced-generation hybrids, Backcrossed hybrids, Hybridization, introgression, Invasive species, plant competition
Forging Masks Through Perceptions of the Maskless in Benjamin Britten’s 'Peter Grimes'
This thesis proposes that Benjamin Britten’s 'Peter Grimes' leads its audience toward actively constructing an attitude toward its maskless protagonist. Grimes’s tragedy results from the social construction of his character from ambiguous and unseen actions. Utilizing the theories of Hannah Arendt and Carl Jung, this thesis proposes that Grimes may have resisted tragedy by constructing a public persona for himself. This thesis analyses the opera’s music and narrative according to the difference between Grimes’s lack of a public persona and the Borough- members’ construction of a mask for him. A central contention of the thesis is that as another element of Britten’s persona, Peter Grimes permitted the composer’s entrance into the public sphere, despite his private inclinations and illegal sexuality. Like the opera’s drama, the opera’s “Sea Interludes” reveals the tragedy resulting from the failure to construct an attitude toward the public world. These “Sea Interludes” work alongside the opera’s drama to induce the audience into a common perception of the opera’s whole. Through ironic relation to the opera’s musical and narrative parts, Benjamin Britten induces his audience’s construction of personae, thereby bringing himself and them into a shared public realm. Author Keywords: Benjamin Britten, E. M. Forster, English Opera, Montagu Slater, Peter Grimes, W. H. Auden
evolutionary ecology of Alaska's mountain goats with management implications
The integration of genetic and environmental information can help wildlife managers better understand the factors affecting a species’ population structure and their response to disturbance. This thesis uses genetic techniques to assess the broad and fine scale population structure of mountain goats in Alaska. The first chapter aims to determine the number of genetically distinct subpopulations and model the demographic history of mountain goats in Alaska. The second chapter investigates the population structure and demographic history of mountain goats in Glacier Bay National Park and examines the impact that climate change will have on these mountain goats. My results indicate that Alaska has eight subpopulations which diverged during the Wisconsin glaciation. In Glacier Bay, population structure is reflective of the landscape during colonization, and mountain goat population density and movement corridors are likely to decline due to future climate change. Author Keywords: Alaska, biogeography, gene flow, landscape genetics, mountain goat, population genetic structure
Anthropogenic particles and microplastics in headwater lake catchments in Muskoka-Haliburton, Canada
Microplastics, plastic particles less than 5 mm in diameter, are ubiquitous in the environment. This study estimated the abundance of microplastics (MP) in atmospheric deposition from four background monitoring stations in Muskoka-Haliburton, south-central Ontario, Canada and quantified the fate of microplastics to three background headwater lake catchments in Muskoka-Haliburton. Microplastics were observed across all sample media with polyethylene terephthalate and polyamide being predominant. The average atmospheric deposition of anthropogenic particles was 57 particles/m2/day with a plastic deposition rate of 7 MP/m2/day. Atmospheric deposition represented the highest daily microplastic flux rate to the three headwater lake catchments compared, 1.5 to 4 times greater than the flux rate for the inflow streams suggesting that atmospheric deposition can account for all the inflowing microplastics. A large fraction of the microplastics from atmospheric deposition (41 – 73%) were retained in the terrestrial catchment and there was a high retention of microplastics in each of the study lakes (1.44 – 7.39 million MP/day; 30 – 45%) suggesting that a large fraction of the terrestrial catchment export is retained by the lakes and that lakes are a reservoir for microplastics. Author Keywords: Atmospheric deposition, Microplastics, Ontario, Plastic pollution, Sinks, Sources
Archaeology and Reconciliation in the Williams Treaties Territory
This thesis examines the history of Indigenous inclusion in the discipline of archaeology and how archaeologists can provide reconciliation when working with Indigenous peoples in their territory. This thesis focuses on the territory of the Williams Treaties with a particular focus on the location of Nogojiwanong (Peterborough). My data consists of in-depth interviews from ten informants and studying three case studies that happened in the area. I take my informants’ suggestions and apply them to my case studies, to show practical examples of how we can provide reconciliation in the field of archaeology. Author Keywords: Decolonization , Heritage Management , Indigenous, Reconciliation
Electrochemical Biosensors for Neurodegenerative Disease Biomarkers
The onset of neurodegenerative diseases such as Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS) are typically characterised by the aggregation of protein biomarkers into cytotoxic fibrils. Novel means of analysing these biomarkers are needed to expand the literature toward earlier diagnosis of these conditions. Electrochemical sensors could offer the sensitivity and selectivity needed for specialised analysis, including potential point-of-care applications. The AD biomarker Tau, and ALS biomarker TDP-43 proteins are explored here by using a label-free electrochemical sensors. Tau protein was covalently bound to gold electrode surface to study the in vitro mechanisms of aggregation for this protein. An immunosensor to TDP-43 was developed by covalently binding primary TDP-43 antibodies (Abs) on gold electrode surface. A novel direct ELISA sensor for TDP-43 with visual detection and electrochemical quantification was also developed. The results validated the experimental designs toward specialised and selective analysis of these biomarkers and their aggregation mechanisms. Author Keywords: ALS, Alzheimer's, Biosensors, Electrochemistry, Tau, TDP-43
Population Genetics and Gut Microbiome Composition Reveal Subdivisions and Space Use in a Generalist and Specialist Ungulate
Natural populations are often difficult and costly to study, due to the plethora of confounding processes and variables present. This is of particular importance when dealing with managed species. Ungulates, for example, act as both consumers and prey sources; they also provide economic benefit through harvest, and as such, are of high ecological and economic value. I addressed conservation and management concerns by quantifying subdivision in wild populations and combined movement with non-invasive sampling to provide novel insight on the physiological drivers of space use in multiple species. This thesis explored biological patterns in ungulates using two distinct approaches: the first used molecular genetics to quantify gene flow, while the second examined the relationship between movement and the gut microbiome using high-throughput sequencing and GPS tracking. The goal of the first chapter was to quantify gene flow and assess the population structure of mountain goats (Oreamnos americanus) in northern British Columbia (BC) to inform management. I used microsatellites to generate genotype data and used a landscape genetics framework to evaluate the possible drivers behind genetic differentiation. The same analyses were performed at both a broad and fine scale, assessing genetic differentiation between populations in all of northern BC and in a case management study area northeast of Smithers BC. The results indicated panmixia among mountain goats regardless of scale, suggesting distance and landscape resistance were minimally inhibiting gene flow. Therefore, management at local scales can continue with little need for genetically informed boundaries, but regulations should be tailored to specific regions incorporating data on local access and harvest pressure. My second chapter aimed to determine the extent to which the gut microbiome drives space-use patterns in a specialist (mountain goat) and generalist (white-tailed deer, Odocoileus virginianus) ungulate. Using fecal samples, we generated genomic data using 16S rRNA high-throughput sequencing to evaluate gut diversity and gut microbiome characteristics. Additionally, individuals were fitted with GPS collars so that we could gain insight into movement patterns. Gut microbiome metrics were stronger predictors of space use and movement patterns with respect to home range size, whereas they were weaker predictors of habitat use. Notably, factors of both the gut microbiome and age of a given species were correlated with changes in space use and habitat use. Ultimately, this research linked high-throughput sequencing and GPS data to better understand ecological processes in wild ungulates. Author Keywords: gene flow, genomics, gut microbiome, home range, population genetic structure, ungulates
Automated Separation and Preconcentration of Ultra-Trace Levels of Radionuclides in Complex Matrices by Online Ion Exchange Chromatography Coupled with Inductively Coupled Plasma Mass Spectrometry (ICP-MS)
Radionuclides occur in the environment both naturally and artificially. Along with weapons testing and nuclear reactor operations, activities such as mining, fuel fabrication and fuel reprocessing are also major contributors to nuclear waste in the environment. In terms of nuclear safety, the concentration of radionuclides in nuclear waste must be monitored and reported before storage and/or discharge. Similarly, radionuclide waste from mining activities also contains radionuclides that need to be monitored. In addition, a knowledge of ongoing radionuclide concentrations is often required under certain ‘special’ conditions, for example in the area surrounding nuclear and mining operations, or when nuclear and other accidents occur. Thus, there is a huge demand for new methods that are suitable for continuously monitoring and rapidly analyzing radionuclide levels, especially in emergency situations. In this study, new automated analytical methods were successfully developed to measure ultra trace levels of single or multiple radionuclides in various environmental samples with the goal of faster analysis times and less analyst involvement while achieving detection limits suitable for typical environmental concentrations. Author Keywords: automation, ICP-MS, ion exchange, radionuclide

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Graduate student theses produced at Trent University. You may also browse theses and dissertations by year, program, or author.

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