Life Sciences Commons^™

A Behavioral Study On The Adult Marmoset Interference Control In Spatial Working Memory, Mohadese Khosravi Najafabadi

Electronic Thesis and Dissertation Repository

Interference control deficit in Working Memory (WM) is associated with neurodevelopmental disorders. The common marmoset (Callithrix jacchus) is an ideal non-human animal model for studying WM disorders. Previous studies of marmoset WM have used a touch-screen self-ordered sequencing task (SOST), which resembles an n-back paradigm and targets updating processes in internal interference control. However, the training time for the marmoset to reach proficiency on this paradigm is long given the short marmoset lifespan. In an attempt to accelerate marmoset learning of the task, we developed a new version of SOST that relied on foraging behaviour. The goal of …

Assessment Of Executive Function Using A Series Of Operant Conditioning Based Tasks In T1dm Rodents, Kevin T. Murphy

Electronic Thesis and Dissertation Repository

This study examined the impact of Type 1 Diabetes Mellitus (T1DM) on executive function using a series of operant conditioning based tasks in rats. Sprague Dawley rats were randomized to either non-diabetic (n = 12; 6 male) or diabetic (n = 14; 6 male) groups. Diabetes was induced using multiple low-dose streptozotocin injections. All diabetic rodents were insulin-treated using subcutaneous insulin pellet implants. At week 14 of the study, rats were placed on a food restricted diet to induce 5 - 10% weight loss. Rodents were familiarized and tested on a series of tasks that required continuous adjustments to novel …

Investigating Social Dynamics Using Automated Radiotracking Of Winter Flocks Of Black-Capped Chickadees (Poecile Atricapillus), Christopher J. Course

Electronic Thesis and Dissertation Repository

The major forces that govern social groups, namely fission-fusion dynamics, cohesion and maintenance, are nearly ubiquitous across animal groups. The field of animal collective behaviour has recently been married with automated radiotracking producing a ‘re-wilding’ of field research into sociality. The combination of this with Social Network Analysis has led to discoveries such as population wide information transfer and the flexibility of animal groups to change social connectivity based on environmental context. However, these networks are constructed, and do not include the dynamic environmental, spatio-temporal, and social contexts which directly affect sociality. I conducted the first automated radiotracking study I …

Insights Into O-Glcnac-Mediated Regulation Of Galectin Expression And Secretion In Promyelocytic Hl-60 Cells, Adam J. Mctague

Electronic Thesis and Dissertation Repository

Galectins are a family of -galactoside-binding proteins involved in cell stress responses and differentiation. Galectins are multifunctional proteins widely studied in many cell models including acute myeloid leukemia HL-60 cells where they mediate numerous intra- and extracellular functions in response to many stress-inducing stimuli. O-GlcNAcylation is a dynamic post-translational modification implicated in the regulation of many cellular diseases including cancers. The O-GlcNAc mediated expression and secretion of galectins during neutrophilic differentiation was examined in HL-60 cells. Galectin gene (LGALS), galectin protein expression, and galectin secretion were determined by RT-qPCR, immunoblotting, and ELISA, respectively. Inhibition of O-GlcNAcylation induced markers of differentiation …

Direct Electrical Stimulation Of Prefrontal Cortex Modulates The Transient Heart Rate Response To Exercise In Conscious Humans, Bartek Kulas

Electronic Thesis and Dissertation Repository

Prefrontal cortical regions play an essential role in generating appropriate cardiovascular adjustments, particularly in cardio-vagally mediated heart rate (HR) responses to active tasks. Functional imaging studies provide correlational evidence that this region coordinates HR responses to exercise, however, direct experimental evidence of prefrontal cortical HR regulation in humans is not available. Seven persons with epilepsy implanted with intracranial electroencephalography (iEEG) completed 2-second isometric handgrip (IHG) contractions at no-stimulation (NO-STIM) or sham-stimulation (SHAM) conditions, and during direct electrical stimulation (STIM) of the orbitofrontal and medial prefrontal cortex. HR responses to IHG during NO-STIM and SHAM increased HR by Δ4.9±2.7 bpm, compared …

Developing A Toolbox To Engineer Quantitative Trait Variation In Legume Species Using Crispr/Cas Technologies., Petar Miletic

Electronic Thesis and Dissertation Repository

The impact of intensive agriculture on the environment is immense. This is especially dire with regard to the natural nitrogen (N) cycle, where the human driven interference, primarily associated with industrial fertilization, has reached unsustainable levels. Unlike cereals, legumes, such as soybean, alfalfa and common bean, have the ability to use atmospheric nitrogen, which limits the need for industrial fertilization. A more wide-spread use of legumes could alleviate some of the negative impacts on the biogeochemical cycle while also providing a useful alternative to meat consumption, an important factor in sustainability. To reach this goal, further improvements of legume crops …

Long-Term Vs. Short-Term Plant Responses To Warming And Nitrogen Addition In A Temperate Old Field, Breanna Craig

Electronic Thesis and Dissertation Repository

Climate warming and atmospheric nitrogen (N) deposition are expected to have strong effects on plant productivity in temperate ecosystems over the next century. However, short-term experiments may not adequately address their potential effects because of lags in changes in species composition. I added new plots to a pre-existing field experiment to compare the short-term (1-2 year; new plots) vs. long-term (14-15 year; old plots) effects of warming and N addition on plant productivity, relative species abundances, plant tissue N content, and litter decomposition. In 2020, N addition increased aboveground plant productivity most in old plots and only increased belowground biomass …

Validation Of Arterial Spin Labeling For Longitudinal Monitoring And Differential Diagnosis Of Frontotemporal Dementia, Tracy Ssali

Electronic Thesis and Dissertation Repository

Frontotemporal dementia (FTD) is a devastating neurodegenerative disease characterized by a rapid decline in behavioural, language, and motor abilities. Advances in the understanding of FTD genetics and pathophysiology, and the subsequent development of novel disease modifying treatments have highlighted the need for tools to assess their efficacy. While structural magnetic resonance imaging (MRI) and functional imaging with ¹⁸F-flurodeoxyglucose (FDG) positron emission tomography (PET) are used for clinical diagnosis, structural changes are subtle at the early stages and PET imaging is expensive and access limited. Given the coupling of cerebral blood flow (CBF) to energy metabolism, an attractive alternative is …

Phase Imaging For Reducing Macrovascular Signal Contributions In High-Resolution Fmri, Olivia W. Stanley

Electronic Thesis and Dissertation Repository

High resolution functional MRI allows for the investigation of neural activity within the cortical sheet. One consideration in high resolution fMRI is the choice of which sequence to use during imaging, as all methods come with sensitivity and specificity tradeoffs. The most used fMRI sequence is gradient-echo echo planar imaging (GE-EPI) which has the highest sensitivity but is not specific to microvasculature. GE-EPI results in a signal with pial vessel bias which increases complexity of performing studies targeted at structures within the cortex. This work seeks to explore the use of MRI phase signal as a macrovascular filter to correct …

Motor Unit Firing Rate Control Of Agonist Skeletal Muscle During Voluntary Isometric And Shortening Contractions With Limb Movement, Eric A. Kirk

Electronic Thesis and Dissertation Repository

Voluntary movements throughout mammalian lifespan require skeletal muscle contractions that are controlled by time- and recruitment-dependent firing rate patterns. Single motor unit (MU) activity reflects the final efferent neural drive to the muscle, yet the underlying neural control of movement at the MU level is not well understood. Using intramuscular electromyography single MU recordings, relationships between voluntary contraction kinematics and MU firing rates were evaluated in vivo, in groups of young and older adult participants.

The purpose of study one was to characterize how MU firing rates are differently scaled among muscles relative to voluntary contraction intensity. Across 12 …

The Expression Of Guilt, Chloe A. Stewart

Electronic Thesis and Dissertation Repository

Though aversive, the experience and expression of guilt is important to healthy social functioning. Guilt is often described as visceral, and nonverbal guilt expressions are anecdotally observed, yet much remains unknown about how guilt is expressed. The present work aimed to explore the visceral experience of guilt via the autonomic nervous system (ANS), and the nonverbal display of guilt via facial, gestural, and postural expressions. Using a novel film paradigm, we explored ANS activity during guilt in healthy adults and adults with neurodegenerative disorders (NDs). We further explored the nonverbal behaviours associated with guilt in healthy adults. We hypothesized that, …

Metschnikowia Mitochondria, Dong Kyung Lee

Electronic Thesis and Dissertation Repository

Mitochondrial genomes are known for their diverse characteristics and are an attractive model to study genome evolution. Draft nuclear genomes of 71 Metschnikowia yeast strains are publicly available but their mitochondrial genome assemblies are incomplete, thereby making genome studies difficult. To remediate this shortcoming, complete mitochondrial genomes of 71 Metschnikowia strains were assembled from the draft nuclear genomes. Metschnikowia mitochondrial genomes exhibit an unprecedented amount of diversity, particularly with respect to the frequency and distribution of introns, which is often reflected upon overall genome size variations. Additionally, loss of synteny between strains of the same species further strengthens the notion …

Free Fatty Acid Treatment Alters Autophagy During Mouse Preimplantation Embryo Development, Zuleika C. L. Leung

Electronic Thesis and Dissertation Repository

Obesity-induced hyperlipidemia is one of the main factors for female infertility. Hyperlipidemia, specifically with high levels of palmitic acid (PA) and oleic acid (OA), interferes with preimplantation development. Autophagy is essential in early embryo development but, it is unknown whether hyperlipidemia affects autophagic mechanisms in preimplantation embryos. It was hypothesized that PA will alter autophagy in preimplantation mouse embryos and that the subsequent effects will be reversed by OA. PA impaired blastocyst development by arresting embryos at the 8-cell stage. PA also elevated early embryo autophagy by increasing autophagosome formation, decreasing maturation, and disrupting degradation. Co-treatment with OA showed developmental …

Understanding Neural Signals Related To Speech Processing In Humans During Sleep, Ashwin Harimohan

Electronic Thesis and Dissertation Repository

Many cognitive processes are surprisingly preserved during sleep, including the processing of basic language stimuli. However, whether the sleeping brain can process complex, natural speech is not yet known. The present study used regularized linear regression to understand which features of narrative speech, ranging from low-level acoustic information to higher-level linguistic information, are processed during sleep. Participants were exposed to an intact and scrambled narrative story while they were napping or lying awake. Temporal response functions (TRFs) mapped the relationship between participants’ EEG neural responses and the (1) auditory envelope, (2) word onsets and (3) semantic dissimilarity of words. For …

Regional Lipid Expression Abnormalities Identified Using Maldi Ims Correspond To Mri-Defined White Matter Hyperintensities Within Post-Mortem Human Brain Tissue., William J. Pinsky

Electronic Thesis and Dissertation Repository

Periventricular white matter hyperintensities (pvWMHs) are a neurological feature detected with magnetic resonance imaging (MRI) and are clinically associated with an increased risk of stroke and dementia. pvWMHs are characterized by white matter lesions with myelin and axon rarefaction, and as such likely involve changes in lipid composition, however these alterations remain unknown. Lipids are critical in determining cell function and survival, although their detection within tissue, until recently has been challenging. Perturbations in lipid expression have previously been associated with neurological disorders. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an emerging technique for untargeted, high-throughput investigation of …

Exogenous Surfactant As A Delivery Vehicle For Intrapulmonary Therapeutics, Brandon J. Baer

Electronic Thesis and Dissertation Repository

As an organ system, the lung has unique advantages and disadvantages for direct drug delivery. Its contact with the external environment allows for the airways to be easily accessible to intrapulmonary delivery. However, its complex structure, which divides into more narrow airways with each branch, can make direct delivery to the remote alveoli challenging. The objective of this thesis was to overcome this issue by using exogenous surfactant, a lipoprotein complex used to treat neonatal respiratory distress syndrome, as a carrier for pulmonary therapeutics. It was hypothesized that therapeutics administered with a surfactant vehicle would display enhanced delivery to the …

Establishment Of A Pesticide Resistance Monitoring Tool For The Two-Spotted Spider Mite, Tetranychus Urticae, Hanna Varonina

Electronic Thesis and Dissertation Repository

Two-spotted spider mite (TSSM), or Tetranychus urticae (Koch), is a major agriculture pest known for its rapid development of resistance to pesticides. The analysis of spider mites’ pesticide resistance demonstrated that resistance patterns and frequencies vary between T. urticae strains collected from different geographic locations and host plants. This research aims at characterization of pesticide resistance patterns in mite populations present in greenhouses in the Southwestern Ontario by identifying genetic and metabolic markers of their pesticide resistance. The establishment of these markers lays the basis for development of a pesticide resistance diagnostic tool that will enable prediction of population resistance …

Development Of 3d Bioartificial Human Tissue Models Of Periprosthetic Shoulder Joint Infection, Tony B. Huang

Electronic Thesis and Dissertation Repository

Periprosthetic joint infection (PJI) is a devastating and costly post-surgical complication that is not well understood due to the scarcity of physiologically representative experimental models. This thesis outlines the development of two 3D bioartificial human tissue models designed to study the cellular and biochemical interactions between primary fibroblasts from the shoulder capsule (SC) and infectious microorganisms. Using the Fibroblast-Bacteria Co-culture in 3D Collagen model, we demonstrated a global gene repression of metabolic and homeostatic processes in SC fibroblasts following 48 hours of co-culture with Cutibacterium acnes – the most common microbial cause of PJI in the shoulder. These cellular changes …

Response Of The Soil Bacterial Community, Resistome, And Mobilome To A Decade Of Macrolide Antibiotic Contamination, Liam Paul Brown

Electronic Thesis and Dissertation Repository

Biosolids (treated sewage sludge) are used as agricultural fertilizer but are frequently contaminated with macrolide antibiotics, to which resistance is rising among historically susceptible bacteria. To determine if the land-application of macrolides carried in biosolids could promote antibiotic resistance in soil bacteria, soil plots were exposed annually to environmentally realistic or high doses of macrolides for ten years. I sequenced the bacterial 16S ribosomal DNA, metagenomic DNA, and integron gene cassettes within the treated and antibiotic-free soil to compare the compositions and diversities of the bacterial communities, antibiotic resistance genes, and mobile genetic elements. I determined that the high dose …

Fatty Acid Regulation Of The Nrf2/Keap1 Pathway During Mouse Preimplantation Embryo Development, Grace Dionne

Electronic Thesis and Dissertation Repository

Obese women experience frequent infertility; obesity-conditioned reproductive tracts expose embryos to stressors including free fatty acids (FFA). Palmitic acid (PA) exposure significantly impairs mouse preimplantation development and increases endoplasmic reticulum stress; oleic acid (OA) rescues these effects. To further understand FFA in preimplantation development, this thesis investigates the NRF2/KEAP1 pathway, which coordinates antioxidant stress response pathways. We hypothesize that PA induces the NRF2/KEAP1 pathway, while OA alleviates it. Female mice were super-ovulated, mated, and embryos were placed in culture treatments: bovine serum albumin (control), 100 µM PA, 100 µM OA, or 100 µM PA+OA. Protein localization and mRNA abundances were …

The Functional And Structural Consequences Of Aberrant Microglial Activity In Major Depressive Disorder, Jasmine D. Cakmak

Electronic Thesis and Dissertation Repository

Major depressive disorder (MDD) is a highly debilitating neuropsychiatric illness which has been linked with increases in both peripheral and central inflammation, as well as with changes in connectivity. Although countless studies have investigated these two topics, the relationship between neuroinflammation and functional/structural connectivity has not been explored. Using [¹⁸F]FEPPA PET imaging, we measured translocator protein-related (TSPO) microglial activity in the subgenual anterior cingulate cortex (sgACC) and insula and confirmed significantly increased [¹⁸F]FEPPA uptake in depressed patients (N=12) compared to healthy controls (N=23). Using a seed-based ROI analysis of fMRI data, we found that patients show …

Microstructural Alterations In Grey And White Matter Following Early-Onset Deafness In The Cat, Alessandra Sacco

Electronic Thesis and Dissertation Repository

Following sensory deprivation such as deafness, compensatory plasticity underlies the reorganization of sensory-specific brain areas to process remaining intact modalities. Previous studies have explored microstructural consequences throughout the brain following auditory deprivation, including the effect of deafness on cerebral water diffusion. However, nearly all investigations have studied these neuronal changes in humans rather than animal models. The present study investigates microstructural differences between 19 hearing and 27 early-deaf cats via diffusion tensor imaging (DTI). Diffusivity scalars were compared within 155 grey and 21 white matter regions. Results indicate structural plasticity in various regions throughout the deaf brain in both tissues, …

A Generative-Discriminative Approach To Human Brain Mapping, Deepanshu Wadhwa

Electronic Thesis and Dissertation Repository

During everyday behaviours, the brain shows complex spatial patterns of activity. These activity maps are very replicable within an individual, but vary significantly across individuals, even though they are evoked by the same behaviour. It is unknown how differences in these spatial patterns relate to differences in behavior or function. More fundamentally, the structural, developmental, and genetic factors that determine the spatial organisation of these brain maps in each individual are unclear. Here we propose a new quantitative approach for uncovering the basic principles by which functional brain maps are organized. We propose to take an generative-discriminative approach to human …

Fishing For The Right Probiotic: Investigating The Mechanism Of Mucosal-Bacterial Interactions At The Interface Of Health And Productivity In Salmonid Aquaculture, Luana Langlois

Electronic Thesis and Dissertation Repository

Aquaculture is vital for the global food supply, but the high incidence of infectious diseases threatens the industry’s productivity. The intestinal mucosa is a key port of entry for pathogens and provides an extensive interface for host-microbe interactions. Tight junctions are at the core of gut barrier function and the mucosal health of finfish. Disruption of these complexes gives rise to sepsis, which leads to systemic inflammation and death. The present study employs a combinatorial approach that integrates in vitro and in vivo analyses to gain actionable insights into the mechanism of microbial-mediated modulation of host health. The experiments outlined …

Inter-Subject Correlation Using Movie-Driven Fmri In Drug-Resistant Epilepsy, Hana H. Abbas

Electronic Thesis and Dissertation Repository

Treating drug-resistant epilepsy with surgery requires the localization of the epileptic focus. We explored the potential for movie-driven functional magnetic resonance imaging (fMRI) to act as a sensitive, non-invasive, and cost-effective tool to identify functionally disturbed networks. We assessed neural synchronization (inter-subject correlation; ISC) between presurgical epilepsy patients (n = 18) and healthy controls (n = 24) as they watched a suspenseful movie clip in the scanner. To optimize denoising, we compared ISC values with and without an automated Independent Components Analysis-based denoising step (ICA-AROMA). We found that denoising with ICA-AROMA elicited augmented correlation values, supporting its use …

Microbial Innovations For Disease Management In Honey Bees, Brendan A. Daisley

Electronic Thesis and Dissertation Repository

Arguably the most important insect pollinator, honey bees (Apis mellifera) are threatened by infectious disease, pesticide exposure, and nutritional deficits resulting from habitat loss.

The major goals of this thesis were to advance our understanding of the immune and microbiota factors underpinning synergistic interactions between the threats, and to develop a honey bee-specific probiotic with strain-level functions to alleviate cumulative stress burden.

Drosophila melanogaster was used as a high-throughput discovery platform in molecularly characterizing the effects of candidate probiotic lactobacilli and neonicotinoid-neuroimmune-microbiota mechanisms prior to experimentation in honey bees. Imd pathway activation by lactobacilli was identified to be …

A Quantitative Assessment Of Hemodynamic And Histological Parameters In The Mdx Mouse Model, Sarah Hakim

Electronic Thesis and Dissertation Repository

Duchenne muscular dystrophy (DMD) is one of the most commonly inherited musculoskeletal disorders affecting 1 in 3500 boys worldwide. The disorder is due to a lack of functional dystrophin protein, which, in turn, results in a loss of cell membrane integrity in skeletal, cardiac muscle and the brain leading to changes in perfusion. As such, within DMD tissue, necrosis is commonly observed, and it has been previously hypothesized that this may be due to a reduction in regional blood supply. Here, we aim to measure hemodynamic changes during disease progression in DMD (Mdx/Utrn+/+) mice, using dynamic contrast enhanced …

Coevolution Of Hosts And Pathogens In The Presence Of Multiple Types Of Hosts, Evan J. Mitchell

Electronic Thesis and Dissertation Repository

How will hosts and pathogens coevolve in response to multiple types of hosts? I study this question from three different perspectives. First, I model a scenario in which hosts are categorized as female or male. Hosts invest resources in maintaining their immune system at a cost to their reproductive success, while pathogens face a trade-off between transmission and duration of infection. Importantly, female hosts are also able to vertically transmit an infection to their newborn offspring. The main result is that as the rate of vertical transmission increases, female hosts will have a greater incentive to pay the cost to …

Mucosa-Associated Invariant T Cells Undergo Phenotypic Changes Following Fecal Microbiota Transplantation, Jenna M. Benoit

Electronic Thesis and Dissertation Repository

Fecal microbiota transplantation (FMT) has emerged as the most effective therapy for recurrent Clostridioides difficile infections (rCDI); yet the role of immune cells in the response to FMT remains poorly understood. Mucosa-associated invariant T (MAIT) cells are bacterial metabolite-reactive T cells found in the peripheral blood and mucosal tissues. We posited that MAIT cells are in the perfect position to respond to the influx of microbial metabolites associated with FMT. We collected peripheral blood from rCDI patients prior to FMT, 1-week post-FMT, and 1-month post-FMT, to explore if MAIT cell phenotypic characteristics or functions change following treatment. Following FMT, MAIT …

Potential Sex-Related Differences In Neurophysiology Post-Concussion, Alexandra N. Pauhl

Electronic Thesis and Dissertation Repository

The purpose of this study was to examine potential sex-related differences in neurophysiology in concussed and healthy individuals. There was a total of 21(9 F) participants in each group. The concussion (CONC) group reported to the lab within 72 hours, 1- and 2-weeks post-injury. The control (CONT) group followed a similar measurement schedule once recruited. Motor evoked potential (MEP) amplitude and cortical silent period (CSP) duration was measured in the first dorsal interosseous muscle using transcranial magnetic stimulation. There were no significant differences in MEP amplitude or CSP duration between the CONC and CONT group. As well, there was no …