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Smartphones For Smart Eating: Evaluating The Effectiveness Of Smartphone Applications On Improving Adolescent Food Knowledge, Heather A. Jantzi

Electronic Thesis and Dissertation Repository

Many Canadian adolescents have unhealthy eating habits which are risk factors for developing chronic diseases later in life. Food literacy plays a role in healthy eating habits but teens in Ontario currently lack sufficient nutrition education learning opportunities in home and school environments. Across health research, smartphones have been utilized as a novel medium to promote learning and alter behaviour. This thesis seeks to understand the effectiveness of smartphone applications at improving food knowledge in adolescents through (i) a systematic review of published interventions, and (ii) by investigating the efficacy of a novel location-based smartphone application. Findings from this thesis …

The Modulation Of Lfp Characteristics In The Freely Moving Common Marmoset, William Jm Assis

Electronic Thesis and Dissertation Repository

The hippocampus is a neural structure critical for navigation. Neurons in this region, along with others, create a functional network which generates large-amplitude modulations known as local field potential (LFP) activity. Prior LFP research has predominantly used rodent animal models, however recent studies have shown that frequencies associated with navigation in other mammals do not correlate to those of the rodent. We hypothesized that LFP characteristics in the common marmoset are modulated by the speed and axis of travel of the animal. Two marmosets were placed in a free moving 3-dimensional environment where movement and neurological activity were recorded. Results …

The Ventilatory Response To Modified Rebreathing Is Unchanged By Hyperoxic Severity: Implications For The Hyperoxic Hyperventilation Paradox, Joshua D. Huggard

Electronic Thesis and Dissertation Repository

We measured the ventilatory response to hyperoxic CO₂ rebreathing with O₂ tension clamped at increasingly higher pressures. We hypothesized that the V̇_E versus PCO₂ relationship is fixed and independent of PO₂. Twenty participants (10 females; mean± SD age: 24±4 years) performed three repetitions of modified rebreathing in 4, randomized, isoxic-hyperoxic conditions: mild: PO₂=150 mmHg; moderate: PO₂=200 mmHg; high: PO₂=300 mmHg; and extreme: PO₂≈700 mmHg. For each rebreathing trial, the P_ETCO₂ at which V̇_E rose was identified as the ventilatory recruitment threshold (VRT, …

From Micro To Macro: Examining Potential Microbiome Mediated Influences On Human Growth And Health Outcomes Through Breastfeeding And Antibiotic Exposures, Nicole K. Phillips

Electronic Thesis and Dissertation Repository

Human microbiome research has rapidly developed over the past two decades yet absent from most research is the composition and dynamics of microbiomes within human populations. Given the limitations in longitudinal studies which requires decades of repeated microbe taxonomic testing of a population sample, an alternative option is to examine microbiomes and their influences via proxies using pre-existing health datasets. This research demonstrates preliminary associations between presumed disrupted and supportive microbiomes dynamics proxied by antibiotic and breastmilk exposure respectively. Using health record data across the life span from approximately 500,000 U.K. participants, this research demonstrates variable altered growth and health …

Extrinsic And Intrinsic Factors Influencing Homeostasis And Repair In Oral Tissues, Georgia Nikoloudaki

Electronic Thesis and Dissertation Repository

The oral tissues, including gingiva and buccal mucosa, heal rapidly with minimal scar formation. Although in the oral cavity, the palatal mucosa is associated with excessive scarring in response to injury. In this thesis, first, I investigated the complex relationship between cells and their microenvironment using wound healing models in which extracellular matrix composition and mechanical stiffness affect cellular responses during acute wound repair. I also determined how intrinsic differences of cells recruited during healing contribute to wound resolution.

In Chapter 2, I first investigated cell-extrinsic factors, specifically the influence of the pro-fibrotic matricellular protein periostin on palatal healing. Using …

Identification Of Dna Methylation Episignatures For Classification And Phenotype/Genotype Correlation In Mendelian Neurodevelopmental Disorders, John Reilly

Electronic Thesis and Dissertation Repository

ABSTRACT: Diagnosis for neurodevelopmental disorders poses numerous challenges, related to the lack of specific findings and limited understanding of clinical impact of the majority of genetic variation. Epigenomics mechanisms involve chemical modifications in DNA that involve a range of cellular mechanisms. DNA methylation is an epigenetic mechanism involving addition and removal of methyl groups to cytosine residues. These methylation signals form episignatures; patterns of methylation that can be used as biomarkers capable of differentiating neurodevelopmental disorders. EpiSigns have enabled molecular diagnosis of a number of genetic conditions, classification of variants of unknown significance, and provided insights into the pathophysiology of …

Characterizing The Structural, Biophysical And Functional Effects Of S-Glutathionylation On Stim1 Ca2+ Sensing, Christian Michael Sirko

Electronic Thesis and Dissertation Repository

Stromal interaction molecule 1 (STIM1) is an endo/sarcoplasmic reticulum (ER/SR) calcium (Ca²⁺) sensing protein that initiates cytoplasmic Ca²⁺ influx via store-operated calcium entry (SOCE). STIM1, in conjunction with Orai, a plasma membrane (PM) protein, function as mediators of SOCE through the formation of calcium-release activated calcium (CRAC) channels. S-Glutathionylation of STIM1 at Cys56 has been shown to evoke constitutive Ca²⁺ entry in DT40 cells, however no studies have carefully investigated the biophysical and structural effects of this covalent modification to the luminal domain, which are critical for understanding the molecular mechanism underlying the regulation of …

The Effects Of Decellularized Adipose Tissue Constructs On Mesenchymal Stromal/Stem Cell Phenotype And Pro-Angiogenic Secretory Function., Yehia Moharrem

Electronic Thesis and Dissertation Repository

Due to limited treatment options for critical limb ischemia (CLI), cellular-based therapies have been investigated to induce blood vessel regeneration. Bone marrow-mesenchymal stromal/stem cells (BM-MSC) have shown pre-clinical success in animal models of CLI as they possess pro-angiogenic and immunomodulatory functions. However, clinical translation has been hindered by inadequate expansion and delivery strategies. This project aimed to characterize the phenotype and pro-angiogenic secretory function of BM-MSC on decellularized adipose tissue (DAT) bioscaffolds as expansion platforms. Compared to cells grown on tissue-culture plastic, DAT substrates supported BM-MSC growth, regenerative marker expression, and pro-angiogenic secretory function. Conditioned media generated by BM-MSC cultured …

A Workflow To Analyze Ethcd Mass Spectrometry Data For Studying Hiv Gp120 Glycosylation, Yingxue Sun

Electronic Thesis and Dissertation Repository

The great heterogeneity of HIV populations and richness of surface glycan clouds makes it difficult to locate a conserved and exposed protein epitope as an effective vaccine target. However, more than 80% new infections result from single transmitted founder (T/F) viruses. We set out to design a workflow to study the traits of T/Fs that allow for their superior infectivity, specifically, the glycosylation patterns of gp120, a subunit of HIV envelope protein responsible for binding to host cell receptors. Our main research methods include Western blot and mass spectrometry. Our current understanding of the mass spectrometry data indicates that our …

The Role Of Gsk3 Alpha And Beta In Embryonic Craniofacial Development, Harman Jassar

Electronic Thesis and Dissertation Repository

Background: The GSK-3 genes (Gsk3a and Gsk3b) have been known to affect many cellular processes and signaling pathways some of which are implicated in the growth and development of the craniofacial skeleton.

Aim: The purpose of this study was to assess the effect of chondrocyte-specific deletion of Gsk3a and Gsk3b on the size of the mandible and craniofacial skeleton in embryonic mice.

Materials & Methods: Mice were bred to generate cartilage-specific Gsk3a and Gsk3b KO mice. On embryonic day 18.5 (E18.5) the offspring were gathered by caesarian section. Whole mount skeletal staining was completed on the specimens using …

Discovery Of Novel Mechanisms Regulating Cancer Extravasation In The Chorioallantoic Membrane Model, Yohan Kim

Electronic Thesis and Dissertation Repository

Cancer metastasis is a multistep process that begins with the invasion of tumour cells into the stroma and migration towards the blood vessels. Tumour cells that have entered the bloodstream must then survive and leave by a process known as extravasation. Finally, extravasated cells proliferate and establish the secondary site in the metastatic cascade. Although extravasation encompasses key events during cancer cell invasion to aid in the development of effective treatments, an in vivo model that rapidly, reproducibly and economically recapitulates cancer cell extravasation is needed. Therefore, the objectives of my research were to 1) establish and validate an in …

The Characterization Of The Rat Bone Sialoprotein Knockout Phenotype, Benjamin Harvey

Electronic Thesis and Dissertation Repository

Bone sialoprotein (BSP) is an extracellular phosphoprotein that has been associated with mineralizing tissues, such as the periodontium, the fibrocartilaginous enthesis, and long bone formation. In this study, we characterized the phenotype of BSP-deficient rats. Histomorphometric analysis discovered a thinning of the acellular cementum in both 20 and 50 week-old Bsp^-/- rats with no related periodontal defects and an organized periodontal ligament. Analysis of the mature quadriceps tendon (QCT) enthesis determined that BSP and osteopontin are present in the calcified fibrocartilage of wild-type rats at 14 weeks. The developing QCT enthesis of Bsp^-/- rats appears similar in mineral …

Encountering Lectins In The Recipient Mucosa: Implications Of N-Linked Glycosylation On Hiv-1 Transmission, Adam Meadows

Electronic Thesis and Dissertation Repository

Although several studies have determined key differences in envelope motifs between TF and chronic HIV-1, it is still not known what the overall glycosylation profile is that is selected for in a transmission event, as well as what contributes to this selection. Using a bottom-up approach of modifying specific viruses, determining their transmission fitness in an ex vivo tissue explant assay, and determining their glycan content, we have laid the basis for determining the overall glycan structure which is selected for in TF HIV-1. Preliminarily, we have shown that C-type lectins represent a stringent barrier to transmission and have several …

Endogenous, Controlled Expression Of Anti-Hiv-1 Broadly Neutralizing Antibody, Darshit Patel

Electronic Thesis and Dissertation Repository

Recently, researchers have identified a number of anti-HIV broadly neutralizing antibodies (bNAbs), such as VRC01 and N6, capable of targeting a broad range of HIV-1 strains. Passive immunization using these patient-derived bNAbs could provide temporary protection but are limited by the short antibody half-life. While current gene transfer technology allows sustained bNAb expression, it lacks the ability to control bNAb production in vivo resulting in possible autoimmunity. To address this issue of achieving controlled bNAb expression in vivo, we hypothesize that bNAb expression from transduced Flu-specific B cells can be activated and modulated by subsequent Flu immunizations in the …

Maternal Nicotine Exposure Induces Congenital Heart Defects In The Offspring Of Mice, Elizabeth Greco

Electronic Thesis and Dissertation Repository

Congenital heart defects are the most prevalent birth defect, and maternal cigarette smoking is a known risk factor. Nicotine replacement therapies are recommended to pregnant women who smoke to aid in smoking cessation, as this alternative is thought to be much safer compared to cigarette smoking. However, these products contain nicotine, and the safety of nicotine on the developing heart is not well known. In this thesis, a mouse model was used to test the hypothesis that maternal nicotine exposure (MNE) during pregnancy leads to congenital heart defects and coronary artery defects in the offspring of mice. MNE resulted in …

The Role Of C-Kit And Insulin Receptor Tyrosine Kinases In Beta Cell Function And Insulin Secretion, Amanda Oakie

Electronic Thesis and Dissertation Repository

The receptor tyrosine kinases (RTKs) c-Kit and insulin receptor (IR) initiate similar intracellular signalling pathways in pancreatic beta cells to regulate beta cell proliferation, survival, and insulin secretion. Mice with a c-Kit overexpression specifically in beta cells (c-KitβTg) demonstrated improved beta cell proliferation and insulin secretion compared to control mice, and islets from c-KitβTg mice also demonstrated increased IR expression. The potential interplay between c-Kit and IR and their roles during ageing and metabolic stress are not currently known. This work reports the examination of c-Kit and IR signalling using in vitro and in vivo models to determine their effects …

Mucosa-Associated Invariant T Cell Roles And Local Responses In Cell-Mediated Immunity To Influenza A Virus, Christine Marie Wardell

Electronic Thesis and Dissertation Repository

Mucosa-associated invariant T (MAIT) cells are innate-like T cells that are activated by microbial vitamin B metabolites and/or cytokine stimulation to produce pro-inflammatory cytokines and cytotoxic granules. Influenza A viruses (IAVs) activate MAIT cells in a by-stander manner, and their abundance negatively correlates with infection-induced morbidity and mortality. However, how MAIT cells directly contribute to anti-viral immunity is ill-defined. I hypothesized that MAIT cells’ presence in mice enhances antigen-specific CD8⁺ T cell responses. I observed a trend that MAIT cell-deficient mice generally developed smaller populations of antigen-specific CD8⁺ T cells following IAV exposure than mice abundant in MAIT …

A Ph-Sensitive Delivery System For The Prevention Of Dental Caries Using Salivary Proteins, Yi Zhu

Electronic Thesis and Dissertation Repository

Dental caries remains one of the most common chronic diseases worldwide. Salivary proteins such as histatins have demonstrated biological functions directly related to tooth homeostasis and prevention of dental caries. However, histatins are susceptible to the high proteolytic activities in the oral environment. Therefore, pH-sensitive chitosan nanoparticles (CNs) have been proposed as potential carriers to target major oral diseases that occur under acidic conditions (e.g. dental caries and dental erosion). Four different types of chitosan polymers were investigated and the optimized CNs successfully loaded histatin 3 and released it selectively under acidic conditions. Through loading the survival time of histatin …

Hyperactive Torc1 Sensitizes Yeast Cells To Endoplasmic Reticulum Stress By Compromising Cell Wall Integrity, Khadija Ahmed

Electronic Thesis and Dissertation Repository

The disruption of protein folding homeostasis in the endoplasmic reticulum (ER) results in an accumulation of toxic misfolded proteins and activates a network of signaling events collectively known as the unfolded protein response (UPR). While UPR activation upon ER stress is well characterized, how other signaling pathways integrate into the ER proteostasis network is unclear. Here, I sought to investigate how the target of rapamycin complex 1 (TORC1) signaling cascade acts in parallel with the UPR to regulate ER stress sensitivity. Using S. cerevisiae, I found that TORC1 signaling is attenuated during ER stress and constitutive activation of TORC1 …

Hiv-1 Group M Subtype Fitness, Disease Progression, And Entry Efficiency, Colin M. Venner

Electronic Thesis and Dissertation Repository

Human immunodeficiency virus type 1 (HIV-1) emerged in the human population shortly after the turn of the 19th century. Distribution of HIV-1 across the globe over the past 30–35 years can be traced to founder events with primordial HIV strains from sub-Saharan Africa. Even considering the burden of HIV in Africa, our knowledge of HIV-1 disease is still largely limited to subtype B HIV-1, a strain responsible for 3 million infections in North America and Europe as compared to the 33 million that are infected with HIV-1 subtypes A, C, D, and circulating and unique recombinant forms.

This dissertation analyzes …

Mass Spectrometry-Based Proteomics Analysis Of Bioactive Proteins In Emd That Modulate Adhesion Of Gingival Fibroblast To Improve Bio-Integration Of Dental Implants, David Zuanazzi Machado Jr

Electronic Thesis and Dissertation Repository

Titanium implants are used in dental practice to replace damaged or lost teeth. The implant needs to integrate with the surrounding gingiva to protect it against bacterial invasion that leads to implant loss. The biointegration is dependent on the implant surface that interacts with proteins from biological fluids to modulate tissues response. Tailoring the surface with specific proteins from the enamel matrix derivative (EMD) would be beneficial to improve the implant-gingiva interface since EMD can affect various cells including gingival fibroblasts. A surface-affinity approach using three different titanium surfaces and saliva was utilized as a model in combination with tandem …

Determining The Molecular Mechanisms Of Pacs-1-Mediated Protein Sorting, Brennan S. Dirk

Electronic Thesis and Dissertation Repository

Membrane trafficking events are required to direct proteins to their precise subcellular locations. The cellular Phosphofurin Acidic Cluster Sorting protein – 1 (PACS-1) has emerged as a protein of interest in controlling the localization of a multitude of cellular and viral proteins. Specifically, PACS-1 is hijacked by type-1 Human Immunodeficiency Virus (HIV-1) to contribute to immune evasion in addition to regulating neuroendocrine hormone storage and release. To accomplish this, PACS-1 connects the cytoplasmic tail of cellular receptors to the heterotetrameric adaptor proteins (APs) to form a functional trafficking unit. Throughout this dissertation, I explored the role of PACS-1 and AP-1 …

Interferon-Induced Herc5 Is A Novel And Potent Inhibitor Of Ebola Virus-Like Particle Production, Nina Hunt

Electronic Thesis and Dissertation Repository

Ebola’s severe pathogenesis can be attributed to its suppression of the Type I interferon (IFN) response, suggesting this pathway plays a role in restricting viral replication. One IFN-induced protein, HERC5, warrants further investigation as it inhibits the replication of evolutionarily diverse viruses. We showed that HERC5 drastically reduces the expression of structural protein VP40 at the protein and mRNA level. Mutagenesis of HERC5 demonstrated that the RCC-1-like domain is necessary and sufficient for restriction. This domain is also responsible for HERC5’s interaction with ZAP, a protein required for VP40 mRNA degradation. Finally, we showed that Ebola GP antagonizes HERC5 activity. …

Immunization With Recombinant Myelin Oligodendrocyte Glycoprotein Identifies Autoreactive T Cells As A Limiting Factor In Autoreactive Germinal Center Maintenance, Rajiv William Jain

Electronic Thesis and Dissertation Repository

Germinal center (GC) responses are responsible for the protection provided by immunizations but can also drive autoimmunity. B and T cells collaborate in the GC to target the same antigen (Ag) to inform B cell differentiation; however, the properties of Ags differ substantially in autoimmunity and foreign-Ag driven immunity. Currently, it is not well understood how properties of the Ag itself influence the initiation or progression of GC responses, limiting our ability to develop effective vaccinations and predict the progression of autoimmune responses. The purpose of this thesis is to assess how GC responses initiate and progress when immunizing with …

The 2Β Insert Perturbs Folding, Stability And Hydrophobic Exposure Of Stromal Interaction Molecules, Steve Chung

Electronic Thesis and Dissertation Repository

Stromal interaction molecule (STIM)1 and 2 regulate agonist-induced and basal cytosolic calcium (Ca2+) levels through oligomerization and translocation to endoplasmic reticulum (ER)-plasma membrane (PM) junctions. At these junctions, the STIM cytosolic coiled-coil domains couple to PM Orai1 protein subunits to form Ca2+ released activated Ca2+ (CRAC) channels that facilitate store-operated Ca2+ entry (SOCE). One splice variant of STIM2, STIM2β, contains an extra 8-residue (2β insert) located within the coiled-coils and inhibits SOCE through an unresolved mechanism, adding another layer of complexity to Ca2+ regulation in mammals. I hypothesize that the 2β insert perturbs the coiled-coil conformation and dynamics commensurate with …

Lung-Derived Selectins Interact With Cd44 And Enhance The Migration Of Breast Cancer Cells, Sami U. Khan

Electronic Thesis and Dissertation Repository

The lung is among the deadliest sites of breast cancer metastasis. Previous work from our laboratory demonstrated that aggressive CD44-expressing breast cancer cells preferentially metastasize to the lung in vivo, and observed the presence of multiple CD44-interacting proteins in the lung including E-, L- and P-selectin. We hypothesized that lung-derived selectins promote breast cancer migration and/or growth via interactions with CD44. Using an ex vivo model of the soluble lung-microenvironment, we demonstrate that lung-derived selectins enhance in vitro migration but not proliferation of breast cancer cells. Co-immunoprecipitation experiments reveal that CD44 expressed by breast cancer cells in vitro interacts …

The Role Of The Hiv-1 Accessory Proteins Nef And Vpu In Subverting Host Cellular Immunity, Emily N. Pawlak

Electronic Thesis and Dissertation Repository

The HIV-1 accessory proteins Nef and Vpu have no known enzymatic activity, yet these viral proteins are critical for HIV-1 viral spread and pathogenicity. To mediate this, these viral proteins bind to and hijack host cellular proteins, including proteins implicated in the membrane trafficking machinery. Key to the effects of these proteins is their ability to alter the subcellular localization of a plethora of cell surface receptors, including the key immune cell receptorsCD28 and MHC-I.However,the mechanism utilized by Nef and Vpu to modulate these proteins is not fully understood. Herein, we demonstrated that Nef and Vpu mediate a decrease in …

Mechanisms Underlying Freeze Tolerance In The Spring Field Cricket, Gryllus Veletis, Jantina Toxopeus

Electronic Thesis and Dissertation Repository

Freeze tolerance has evolved repeatedly across insects, facilitating survival in low temperature environments. Internal ice formation poses several challenges, but the mechanisms that mitigate these challenges in freeze-tolerant insects are not well understood. To better understand how insects survive freezing, I describe a novel laboratory model, the spring field cricket Gryllus veletis (Orthoptera: Gryllidae). Following acclimation to six weeks of decreasing temperature and photoperiod (mimicking autumn), G. veletis juveniles becomes moderately freeze-tolerant, surviving freezing at -8 °C for up to one week, and surviving temperatures as low as -12 °C. Acclimation is associated with increased control of the temperature and …

The Costs Of Fear: Integrating Fear Effects On Prey Into Population Ecology, Marek Charles Allen

Electronic Thesis and Dissertation Repository

Predators not only kill prey, but through the 'fear' of predation, predators induce costly anti-predatory responses in prey. Anti-predatory costs may scale up to effects on prey populations, through effects on prey reproduction and survival. This thesis aimed to quantify the net effect of predation risk effects on a prey population in a terrestrial vertebrate system for the first time. I manipulated the perceived risk of predation in multiple study years by exposing song sparrows (Melospiza melodia) to playbacks of either predator or non-predator calls. Females exposed to predator playbacks laid fewer eggs, had more eggs fail to …

Understanding The Impact Of Hiv-1 Genetic Diversity On The Function Of Nef And Its Role In Serinc5 Antagonism, Aaron Leslie Johnson

Electronic Thesis and Dissertation Repository

HIV-1 Nef is a key pathogenic protein, allowing HIV-1 to evade the host immune system by downregulating MHC-I and CD4. Furthermore, it was recently discovered that Nef counteracts the host factor SERINC5 to increase HIV-1 infectivity, but the mechanistic details of the Nef:SERINC5 interaction still need to be explored. Throughout this dissertation, I will explore the hypothesis that the genetic diversity that defines HIV-1 has a pronounced effect on the HIV-1 protein Nef, altering its function between and within group M subtypes. To address this hypothesis I investigated how MHC-I and CD4 downregulation differ among all non-recombinant group M subtypes. …