Life Sciences Commons^™

Characterizing The Function Of B Cells That Accumulate In The Inflamed Central Nervous System In Anti-Myelin Autoimmunity, Lika Chowdhury

Electronic Thesis and Dissertation Repository

While the role of autoimmune T cells has been extensively studied in anti-myelin

autoimmunity, little is known about the function of B cells in multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS). B cells form clusters with T cells in the meninges directly adjacent to demyelinating lesions. Previous studies have shown that disease progression is dependent on the depletion of specific populations of B cells, but it is not clear which contributes to pathology or how. The purpose of this thesis is to characterize the population of meningeal B cells to determine how they differ …

Nitrogen Transfer From Cover Crops To The Subsequent Grain Crop And The Influence Of Variability In Winter Conditions, Spencer Heuchan

Electronic Thesis and Dissertation Repository

Cover crops, which are used to provide ground cover after the harvest of the grain crop, can potentially improve the sustainability of agroecosystems by reducing nutrient losses. However, few data are available to document the extent to which cover crops improve both the retention of soil nitrogen (N) and the transfer of this N to the grain crop. The efficiency of this N transfer may be further influenced by variation in winter soil temperature; for example, reduced snow cover can increase the frequency and intensity of soil freezing, which can affect the survival of cover crops and the timing of …

Using Stable Isotope Techniques To Complement Existing Northern Pintail Management., Dariusz Wojtaszek

Electronic Thesis and Dissertation Repository

The Northern Pintail (Anas acuta) is a waterfowl game species with North American population levels consistently below long-term management goals. Native habitat loss to agriculture likely reduced recruitment and limits population growth. My objective was to provide a proof-of-concept approach to using stable isotope ratios (δ²H, δ¹³C, δ¹⁵N) in feathers to infer spatial origins and habitat selection to complement existing pintail management. I found 46% of all sampled pintails had likely moult origins in the boreal biome, compared to 32% estimated by breeding population survey and 55% of recruitment of young …

The Effect Of Postural Perturbations On Cardiovascular And Skeletal Muscle Function In Healthy Adults, Patrick Siedlecki

Electronic Thesis and Dissertation Repository

Maintenance of standing balance is vital to daily living. Traditionally, perspectives on maintaining balance are achieved through the study of visual, vestibular and somatosensory inputs on motor outputs. While evidence suggests cardiovascular regulation also functions to assist postural control during orthostatic stress, how the cardiovascular system responds to postural perturbations is not well established. This dissertation includes four studies that investigated the effects of postural perturbations on the cardiovascular system and skeletal muscle responses in healthy adults. All of the studies involved exposing standing participants to surface-translation perturbations at different velocities, with known or unknown timing, and occurred while spontaneously …

Selection Pressure On Surface Exposed Virus Proteins, Sareh Bagherichimeh

Electronic Thesis and Dissertation Repository

Viral infection requires the interaction between virus surface-exposed (SE) proteins and host cell receptors. This can result in an “arms race” that is assumed to drive accelerated rates of evolution, and some well known examples of diversifying selection involve surface pro- teins (HIV-1 env, influenza hemagglutinin). We conducted a systematic analysis to determine whether this is truly a distinctive feature of SE virus proteins, in comparison to non-SE proteins encoded by the same genomes.

We obtained reference and all neighbour genomes of 52 human viruses from the NCBI Viral Genomes database. The coding sequences (CDS) of each genome extracted by …

Gene Regulatory Context Of Honey Bee Worker Sterility, Rahul Choorakkat Unnikrishnan

Electronic Thesis and Dissertation Repository

Honey bee workers deactivate their ovaries and are functionally sterile when a queen is present in the colony. I adopt a bioinformatics approach to up-date a model transcriptional regulatory network (TRN) to study gene-regulatory processes that regulate fecundity in workers. On splitting the network, I obtained nine clusters and each cluster conformed to properties associated with real-world networks. Two of the nine clusters are enriched for 'sterility genes' and contained single well-connected hub genes (GB44769, ftz-f1). The genes in the two clusters were functionally enriched for nucleic acid binding (GO:0003676) and nucleotide binding (GO:0000166). I identified homologous genes for …

On The Spatial Modelling Of Biological Invasions, Tedi Ramaj

Electronic Thesis and Dissertation Repository

We investigate problems of biological spatial invasion through the use of spatial modelling. We begin by examining the spread of an invasive weed plant species through a forest by developing a system of partial differential equations (PDEs) involving an invasive weed and a competing native plant species. We find that extinction of the native plant species may be achieved by increasing the carrying capacity of the forest as well as the competition coefficient between the species. We also find that the boundary conditions exert long-term control on the biomass of the invasive weed and hence should be considered when implementing …

Effects Of Methylmercury And Unpredictable Food Stress Exposure On Songbirds’ Physiology And Seasonal Transition, Claire L.J. Bottini

Electronic Thesis and Dissertation Repository

Organisms regularly adjust their physiology to respond to predictable seasonal or environmental variation. However, annual cycle transitions could be disrupted by contaminants or stressors. For example, methylmercury and stress exposure can independently disrupt birds’ neural and endocrine systems, energy balance, metabolism, or behaviour, all necessary for seasonal transitions. Although, the effects of combined exposure to stressors and methylmercury (MeHg), and how long they last after exposure ends, are poorly understood. The objective of my PhD was to evaluate the impact of MeHg exposure on songbirds’ physiology and its potential carry-over effects on seasonal transitions. I exposed song sparrows (Melospiza …

Postexercise Executive Function Benefits And Cerebral Blood Flow: In The Lab And At Home, Benjamin Tari

Electronic Thesis and Dissertation Repository

A single bout of aerobic exercise improves executive function; however, the mechanism, or mechanisms, supporting this improvement remain unclear. One candidate mechanism is an exercise-mediated increase in cerebral blood flow (CBF) that enhances the efficiency of executive-related frontoparietal networks. To evaluate the link between exercise, CBF and executive function, three separate experiments were conducted. In the first study, separate 10-min sessions of moderate-to-heavy-intensity aerobic exercise, and a hypercapnic environment (i.e., 5% CO₂) were implemented. The hypercapnic condition was included because it increases CBF independent of the metabolic demands of exercise. The second study investigated whether exercise intensity-specific changes …

Chromatin Regulation By Rb-Interacting Proteins In Cellular Immune Functions, Seung June Kim

Electronic Thesis and Dissertation Repository

The retinoblastoma protein (RB) is historically known for its function in cell cycle control. However, mice carrying targeted Rb1 mutations have revealed that RB serves various non-cell cycle control roles. Notably, RB acts as a scaffold that recruits chromatin regulatory proteins, condensin II and enhancer of zeste homolog 2 (EZH2). These complexes protect the genome integrity through maintaining proper chromosome condensation, long range contacts, and transcriptionally repressive histone modification. This thesis explores the mechanistic links that regulate such RB-condensin II complex or that are leveraged upon pharmacological inhibition of the RB-EZH2 complex. First, I identified potential phosphorylation sites in the …

Regulation Of Hedgehog And Wnt Signaling In Neural Differentiation Of P19 Embryonal Carcinoma Cells, Danielle Margaret Spice

Electronic Thesis and Dissertation Repository

The Hedgehog (Hh) and Wnt protein signaling pathways are essential in the differentiation of neurons and astrocytes. As there are many known and new players involved in regulating these pathways, the role of the regulators Suppressor of Fused (SUFU) and Never in Mitosis Kinase 2 (Nek2) have either not been previously reported or have not been thoroughly explored. To address this shortfall CRISPR gene editing was used to target SUFU and Nek2 in the mouse P19 embryonal carcinoma cell model of neural differentiation. Hh and Wnt signaling were explored in normal P19 neural differentiation, which occurs in the presence of …

The Clinical Value Of Oculomotor Assessments Across The Continuum Of Concussion, Dillon Richards

Electronic Thesis and Dissertation Repository

Concussions are complex conditions that are difficult to manage medically. Variations in symptom presentation, intricate neurophysiological processes, and the availability of a variety of possible assessment tools may contribute to this complexity. Clinicians must use a broad approach, employing both subjective symptom assessment and objective assessments to confirm a diagnosis and/or monitor progression and recovery. Oculomotor function after concussion may be an important indicator of injury, given the interconnectedness of oculomotor function, vestibulo-ocular and visual systems, and even cognition. Oculomotor function may be assessed objectively or indirectly using patient-reported symptom checklists as part of subjective assessments. One way of objectively …

Tracing The Fate Of Cytokeratin 19+ Cells During Beta Cell Regeneration Stimulated By Multipotent Stromal Cell-Secreted Effectors, Nazihah Rasiwala

Electronic Thesis and Dissertation Repository

Human bone marrow-derived multipotent stromal cells expanded under Wnt pathway stimulation secrete beta cell-regenerative factors collected as conditioned media (Wnt+ CdM). We used the cytokeratin 19 (CK19)-CreERT Rosa26-mTomato lineage tracing mouse to observe CK19+ cell conversion to insulin+ beta cells following intra-pancreatic injection of Wnt+ CdM. Tamoxifen treatment in mice induced labelling of CK19+ ductal and acinar cells with tdTomato and streptozotocin (50 mg/kg/day x 5 days) induced hyperglycemia. Injection of Wnt+ CdM preserved beta cell mass, reduced non-fasted blood glucose levels, and improved glucose tolerance over a 28-day period compared to controls. Insulin+/tdTomato+ cells in mice given Wnt+ CdM …

Conformational Dynamics And Aggregation Of Thermally Stressed Proteins Studied By Hydrogen/Deuterium Exchange Mass Spectrometry, Nastaran Nosrat Tajoddin

Electronic Thesis and Dissertation Repository

Proteins perform various biological functions, e.g., as enzymes or transporters. In addition to naturally occurring proteins, the use of protein therapeutic drugs for treating cancer and other diseases is a rapidly growing area. A thorough biophysical characterization of proteins and protein therapeutics opens the door to a more comprehensive understanding of their role in health and disease. This dissertation aims to expand the capabilities of an existing technique (Hydrogen Deuterium Exchange Mass Spectrometry, HDX-MS), which is widely used for probing protein structure and dynamics. Conventionally, HDX-MS experiments are performed as a function of labelling time. Here we aim to establish …

Root-Inhabiting And Rhizosphere Mycobiomes And Crop Yield Of Corn And Wheat, Marianna E. Wallace

Electronic Thesis and Dissertation Repository

The root mycobiome plays a direct role in plant productivity, and the study of its community composition allows for identification of organisms that influence plant health. To better understand the role of fungal community composition in crop productivity, the root-associated mycobiomes of historically high and low yield sites of corn and wheat planted in rotation were characterized and analyzed along with soil physicochemical variables and crop yield. In each field studied, root and rhizosphere mycobiomes reflected significant differences in fungal species composition. Several soil variables were found to be predictors of differences in composition of sample types including soil texture …

Rhamm As A Biomarker And Therapeutic Target In Triple-Negative Breast Cancer, Britney Messam

Electronic Thesis and Dissertation Repository

Triple-negative breast cancer (TNBC) is a heterogeneous group of tumours characterized by early metastases and poor prognosis. Discovering novel biomarkers and therapeutic targets is necessary to improve TNBC patient outcomes as resistance to chemotherapy, the main therapeutic approach for TNBC, is common. In my study, RHAMM promoted proliferation of TNBC MDA-MB-231 tumour cells. RHAMM expression increased sensitivity to doxorubicin (p=0.0002) and strongly increased sensitivity to the FDA-approved MEK1/2 inhibitor trametinib (p≤0.0001). Doxorubicin and trametinib selectively killed RHAMM^+/+ MDA-MB-231 tumour cells grown as co-cultures with RHAMM^-/- MDA-MB-231 tumour cells. RHAMM-loss or trametinib decreased phosphorylated ERK1/2 protein levels and …

Herbicide Mediated Selection Of Sulfonamide Resistant E. Coli, Laura P. Muntz

Electronic Thesis and Dissertation Repository

Asulam is an herbicide that is structurally analogous to sulfonamide antibiotics (sulfas), with the potential to contribute to the global antibiotic resistance crisis by cross-selecting for sulfa-resistant bacteria. To determine if asulam can select for antibiotic resistant bacteria, isothermal titration calorimetry (ITC) was used to assess the binding affinity of asulam with the target protein of sulfas, dihydropteroate synthase (DHPS). ITC confirmed asulam interacts with DHPS, and in vitro directed evolution experiments showed that prolonged asulam exposure can select for sulfa-insensitive DHPS in E. coli. Since mobile sul genes also encode for sulfa-insensitive DHPS, the potential effect of asulam on …

Localization And Function Of Pannexin2 Isoform 202, Marina D. Sertsis

Electronic Thesis and Dissertation Repository

Pannexins (PANX) are a family of membrane glycoproteins comprised of 3 members: pannexin 1 (PANX1), pannexin 2 (PANX2), and pannexin 3 (PANX3). Oligomerized pannexin proteins form channels that allow for the passage of ions and small molecules. While PANX1 and PANX3 mostly localize to the cell surface, PANX2 remains intracellular within the endoplasmic reticulum (ER). Recently, a splice variant of PANX2 termed Panx2-202, was detected during development of murine skin. However, the localization and function of this shorter Panx2-202 isoform remains unknown. We found that Panx2-202 localizes to the ER in immortalized rat epidermal keratinocytes. We also found that expression …

The Effect Of Active Learning On Viewpoint Dependence For Novel Objects, Cassandra Wallace Bacher

Electronic Thesis and Dissertation Repository

Active learning of novel objects can facilitate subsequent object recognition and discrimination, but the reasons for its beneficial effects remain unclear. One potential explanation is that active learning enables the formation of a more detailed, realistic, or useful neural object representation than does passive learning. The current study addressed the question of whether active vs. passive learning of objects affects viewpoint discrimination. Participants learned novel wire-like objects either actively or passively and then completed a psychophysical task which they discriminated object orientation. This study did not find a significant difference in viewpoint discrimination between actively and passively learned object representations, …

Using Machine Learning To Identify Neural Mechanisms Underlying The Development Of Cognition In Children And Adolescents With Adhd, Brian Pho

Electronic Thesis and Dissertation Repository

Childhood and adolescence are marked by improvements to cognition and by the emergence of neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD). What neural mechanisms are associated with cognitive development in ADHD? In this study, I applied machine learning models to functional connectivity profiles to identify patterns of network connectivity that predict various cognitive abilities in a group of participants ages 6 to 16 with ADHD. The models successfully predicted IQ, visual spatial, verbal comprehension, and fluid reasoning in children ages 6 to 11, but not adolescents. Furthermore, the models identified connections with the default mode, memory retrieval, and …

Effects Of The Brain Nonapeptides Arginine-Vasotocin And Isotocin On Shoaling Behaviour In The Guppy (Poecilia Reticulata), Babak Ataei Mehr

Electronic Thesis and Dissertation Repository

Brain nonapeptides have been suggested to regulate social behaviours. However, the contribution of Arginine-Vasotocin (AVT) and Isotocin (IT) to social behaviour in fishes is not well-characterized. Using the guppy (Poecilia reticulata), I first measured association preference for conspecifics in individuals injected with either AVT, an AVT-antagonist, or saline. The time spent associating with conspecifics did not differ significantly among the injection treatments. However, individuals injected with AVT performed more movement among areas of the tank than individuals injected with either the AVT-antagonist or saline, consistent with an effect of AVT on anxiety-related behaviours (i.e. hyperactivity). Second, I measured …

The Express Sensorimotor Response Selects Visual Features Based On Instruction, David Youhanna Mekhaiel

Electronic Thesis and Dissertation Repository

In time-sensitive situations, orienting reflexes allow us to move rapidly in response to stimuli. The express sensorimotor response (ESR) is an orienting reflex presenting as a brief burst of muscle recruitment. Previous studies have identified commonalities between ESRs and express saccades, another orienting reflex.

In this study, we investigate if ESRs share in a characteristic of express saccades: preference for faces. In separate blocks, participants were instructed to reach toward one of two simultaneously appearing targets: a face and another image. Muscle activity in the pectoralis major muscle of the reaching arm was recorded using skin surface EMGs.

We …

Probing The Genetic Code With Leucine Trna Variants, Peter Anderson Hall

Electronic Thesis and Dissertation Repository

Mistranslation is an error in protein synthesis whereby the amino acids specified by the genetic code are misplaced by others in the growing polypeptide chain. The anticodon of tRNA^Leu can be altered allowing for the misincorporation of leucine at non-leucine codons. Observing the effect of tRNA^Leu variants on the viability of yeast and mammalian cells will provide information on their ability to cause mistranslation and potential relationship to genetic diseases. To explore this, a random pool of tRNA^Leu anticodonvariants was expressed in Saccharomyces cerevisiae. Furthermore, three mutant tRNA^Leu already sequenced from humans were expressed in …

The Effect Of Oatp2b1-Mediated Statin Transport On Beta Cell Dysfunction, Jihoon Kwon

Electronic Thesis and Dissertation Repository

Statins are a class of cholesterol-lowering drugs which work by inhibiting the mevalonate pathway. Statin treatment has been linked to an increase in the risk of new-onset diabetes mellitus, and previous studies have suggested impairment in insulin secretion following statin treatment. Recent work from our laboratory confirmed the expression of organic anion transporting polypeptide 2B1 (OATP2B1), an important statin uptake transporter, in human pancreatic beta cells. Our study examined the role of OATP2B1 in statin-associated beta cell toxicity using INS-1 cells as a beta cell model. We showed that OATP2B1 augments cellular accumulation of rosuvastatin and atorvastatin, but not pravastatin. …

Cadmium Uptake In Plants As Influenced By Selenium Uptake And Sulphate Availability, Marnie J. Demand

Electronic Thesis and Dissertation Repository

With cadmium uptake by plants posing a risk to plants and consumers alike, strategies to reduce metal uptake are desirable. One strategy may be to apply selenium (as selenate) to the growth medium. I hypothesized selenate would yield greater lignification, with a higher proportion of cadmium bound to root cell walls. Consequently, higher selenium in plants would result in greater tolerance to cadmium. Additionally, since selenate is taken up in place of sulphate, providing the plants with high sulphate would inhibit uptake and translocation of selenium, mitigating selenate’s benefits of reducing cadmium uptake and translocation. Experimental results did not support …

Absence Of Enhancer Of Zeste Homolog 2 Promotes The Progression Of Kras-Driven Pancreatic Ductal Adenocarcinoma, Xiaoyi Wang

Electronic Thesis and Dissertation Repository

Pancreatic ductal adenocarcinoma (PDAC) is estimated to be the second deadliest cancer by 2030. Previous studies showed constitutive activation of KRAS (KRAS^G12D) is a key genetic driver of PDAC, accelerated by deletion of the epigenetic regulator Enhancer of Zeste Homologue 2 (EZH2). However, contradictory findings suggest multiple roles for EZH2. The goal of this study was to define EZH2’s contributes to early KRAS^G12D-driven PDAC. I hypothesized that EZH2 restricts KRAS^G12D initiation of PDAC in response to injury. To address this hypothesis, genetically modified mice with targeted deletion of the SET domain of Ezh2 +/- KRAS …

The Role Of Il-12 And Il-27 In Modulating Cd39 Expression On Cd8⁺ T-Cells And Their Effector Function, Lara E. Gerhardt

Electronic Thesis and Dissertation Repository

CD8⁺ T-cells play a critical role in anti-tumour immunity, and cytokines IL-12 and IL-27 can modulate their phenotype and function. Tumour-specific CD8⁺ tumour-infiltrating lymphocytes (TILs) can be identified based on the surface expression of CD39, while CD8⁺ TILs that recognize cancer unrelated antigens do not. It is currently unclear how and why tumour-specific CD8⁺ T-cells uniquely express CD39. We hypothesize that IL-12 and IL-27 upregulate CD39 expression on CD8⁺ T-cells and improve effector activity of CD39⁺CD8⁺ T-cells, compared to their CD39^- counterparts. Using in vitro stimulation assays, we identified that CD8 …

The Biosynthesis Of Non-Protein Sulfur Amino Acid In Developing Seeds Of Common Bean, Zixuan Lu

Electronic Thesis and Dissertation Repository

The protein quality of common bean (Phaseolus vulgaris) is associated with the level of dietary essential sulphur amino acids – methionine and cysteine. Extra sulphur that cannot be stored in the protein pool accumulates as the non-protein amino acid S-methylcysteine (S-methylCys) and its dipeptide γ-glutamyl-S-methylcysteine (γ-Glu-S-methylCys). Previous studies have indicated that S-methylhomoglutathione (S-methylhGSH) is present in the developing seed of common bean. It is hypothesized that S-methylhGSH is the key intermediate in the biosynthetic pathway of the γ-Glu-S-methylCys that leads to …

Using High-Resolution Geospatial Datasets To Investigate The Role Of Geomagnetic Cues During Long-Distance Bird Migration, Aranya Iyer

Electronic Thesis and Dissertation Repository

The Earth’s magnetic field is an orientation and navigation cue for migratory animals, especially birds. However, current experiments used to test this hypothesis are limited. In my thesis, I compare different methods for combining animal tracking data with high-resolution satellite geomagnetic data by using an open-source software called MagGeo. I use the best-performing MagGeo algorithm to investigate if white storks Ciconia ciconia use geomagnetic cues to cross the eastern Sahara. Crossing this inhospitable and featureless habitat has likely selected for unique strategies that facilitate successful bird navigation during migration. I show that MagGeo can reliably be used to annotate animal …

Investigation Of Hd2 Family Histone Deacetylases Relationship In Drought Stress Response And Root Growth In Arabidopsis Thaliana, Muhammad Sufyan Tahir

Electronic Thesis and Dissertation Repository

Despite evidence that certain HD2 family histone deacetylases (HDACs) play an important role in plant growth and stress response, the coordination of HD2-type HDACs in these processes remains largely unknown. Arabidopsis contains four HD2s called HD2A, HD2B, HD2C, and HD2D. I found that HD2A and HD2C coordinate to positively regulate drought stress response. The hd2a.hd2c double mutant (Mac16) exhibits decreased survival and increased water loss under drought due to modified stomatal closure as compared to the single mutants hd2a and hd2c. Gene expression analysis showed that the expression of stomatal closure-related genes ABI1, ABI2, and …