Digital Commons Network^™

Amyloid Β Peptides, Signalling And Trafficking Of The Α7 Nicotine Receptor, Kirk Young

Electronic Thesis and Dissertation Repository

The α7 nicotinic acetylcholine receptor (nAChR) is an ionotropic receptor for the neurotransmitter acetylcholine and its precursor, choline. Interestingly, α7 nAChR binds amyloid β 42 (Aβ42) peptide, which has a primary role in Alzheimer’s disease pathology. Aβ42 peptide forms aggregates and different structural forms elicit different physiological outcomes. Oligomeric, fibrillar and non-aggregated preparations of Aβ42 were characterized by atomic force microscopy. Immunoblotting of neuronal cells exposed to these preparations determined oligomeric aggregates of Aβ42 mediate ERK1/2 intracellular signalling through α7 nAChR. Cell surface ionotropic receptors are regulated through endocytosis to maintain the integrity of neurotransmission. Cellular pathways for endocytosis of …

Maximal Motor Unit Discharge Rates Of The Medial And Lateral Gastrocnemeii Of Young Males, Mitchell T. Graham

Electronic Thesis and Dissertation Repository

The triceps surae is composed of the mono-articular soleus and the bi-articular gastrocnemeii. Mean maximal motor unit discharge rates (MUDRs) reported for the soleus (~16Hz) are lower than other limb muscles tested (Dalton et al., 2009). Because of differences in fibre-type and functional anatomy it is important to determine maximal MUDRs in the two heads of gastrocnemeii, as compared with the soleus, to fully understand the interplay of these three muscles for plantar flexion. The purpose of the study was to record maximal MUDRs of the medial (MG) and lateral gastrocnemeii (LG) in 9 recreationally active, young men (age 24.2 …

Advances In Image Acquisition And Filtering For Mri Neuroimaging At 7 Tesla, Andrew T. Curtis

Electronic Thesis and Dissertation Repository

Performing magnetic resonance imaging at high magnetic field strength promises many improvements over low fields that are of direct benefit in functional neuroimaging. This includes the possibility of improved signal-to-noise levels, and increased BOLD functional contrast and spatial specificity. However, human MRI at 7T and above suffers from unique engineering challenges that limit the achievable gains. In this thesis, three technological developments are introduced, all of which address separate issues associated with functional magnetic resonance neuroimaging at very high magnetic field strengths.

First, the image homogeneity problem is addressed by investigating methods of RF shimming — modifying the excitation portion …

The Effects Of Global Climate Change On Canadian Boreal Forest Collembola Communities, Matthew S. Turnbull

Electronic Thesis and Dissertation Repository

Soil fauna are an integral component of terrestrial ecosystem function. The effects of global environmental change on soil biodiversity are poorly studied, particularly interactions among temperature, atmospheric CO₂, precipitation intensity, and nutrient loading. Body size distributions can be used to quantify soil community responses to perturbation and consequences for ecosystem function. I quantified top-down and bottom-up effects of environmental change on the abundance, richness, and size distribution of the soil microarthropod group Collembola. I demonstrated negative effects in a lab experiment of increased precipitation on collembolan density and richness across all size groups. I demonstrated positive effects in …

Decreased Peak Muscle Power Is Associated With Motor Unit Loss In The Lower Limb Of Older Adults, Neal B. Mckinnon

Electronic Thesis and Dissertation Repository

This study investigated the relationship between motor unit (MU) properties and the strength and power of two lower limb muscles in healthy young and old adults. Twelve older adults (mean age, 77 ± 5 yrs) and twelve young adults (mean age, 24 ± 3 yrs) were studied. MU properties of the tibialis anterior (TA) and vastus medialis (VM) muscles were determined using decomposition-enhanced spike-triggered averaging (DE-STA). Motor unit number estimates (MUNE) of the TA were significantly reduced (p>0.05) in older adults (102 ± 76) compared to young adults (234 ± 109), primarily as a result of significantly larger surface-detected …

Evaluating The Similarity In Postures Between Forklift Operators In Virtual Reality And The Workplace, Youngmin Jun

Electronic Thesis and Dissertation Repository

Forklift operators must adopt awkward postures in order to gain appropriate lines of sight; these postures are associated with musculoskeletal injuries and disorders such as low back pain and neck pain. The purpose of this thesis was to evaluate the similarity in postures between forklift operators in virtual reality simulation of forklift loading and unloading operations and a corresponding real world workplace. This evaluation will help determine whether the virtual reality system is a useful tool for performing controlled laboratory-based investigations of ergonomics issues in heavy mobile machinery. One certified forklift operator and one uncertified individual performed two cycles of …

Post Exercise Ingestion Of Plant Vs Animal Protein Enhances Exercise Performance Outcomes Similarly, Adam N. Upshaw

Electronic Thesis and Dissertation Repository

Recently, the ingestion of a carbohydrate-protein supplement after exercise has garnered considerable interest among both athletes and scientists. However, debate exists about whether the type of protein consumed, animal vs plant, affects exercise performance differently. Thus, it is the purpose of this dissertation to compare performance outcomes following carbohydrate (CHO)-plant or CHO-animal protein ingestion utilizing a variety of exercise conditions (acute bouts of aerobic exercise, 10 weeks of strength training and six weeks of concurrent training).

Study 1 demonstrated that following a glycogen depleting bout of cycling, dairy chocolate, soy chocolate, hemp chocolate or dairy milk ingestion all enhanced the …

Regulation Of Saga By The N-Terminus Of Spt7 In Saccharomyces Cerevisiae, Dominik Dobransky

Electronic Thesis and Dissertation Repository

Spt7 is a 1,332 residue protein critical for maintaining structural integrity of the SAGA complex. I demonstrated that the extreme N-terminus of Spt7 plays an important role in SAGA function. Deletion of the first 73 (Spt7_73-1332) and 121 (Spt7_121-1332) N- terminal residues resulted in slow growth, decreased transcriptional activation at PHO5 and INO1, and a partial decrease in acetylation at lysine 18 of histone H3 at PHO5. The Spt7_121-1332 mutant did not affect Spt7’s association with Gcn5 or Tra1, or its localization within the cell. Mutation of the first four positively charged residues …

Biosteel High Performance Sports Drink Improves Exercise Performance Following A Simulated Hockey Game, Kolten C. Abbott

Electronic Thesis and Dissertation Repository

INTRODUCTION: BioSteel High Performance Sports Drink (BioSteel) is one of the most popular sports supplements consumed by professional and amateur athletes. BioSteel Inc^® claims that consumption of BioSteel before and during exercise will result in “enhanced energy while delaying the onset of muscular and mental fatigue”. PURPOSE: Assess the efficacy of BioSteel supplementation on anaerobic and aerobic exercise performance as well as sport-specific cognition throughout exercise. METHODS: Eleven exercise-trained men completed a simulated hockey game on a cycle ergometer under two experimental conditions: BioSteel and isoenergetic placebo. Measures of exercise performance and cognition were assessed before, throughout and after …

Identification And Characterization Of Cysteine Protease Genes In Tobacco For Use In Recombinant Protein Production, Kishor Duwadi

Electronic Thesis and Dissertation Repository

Plants are an attractive host system for pharmaceutical protein production. Many therapeutic proteins have been produced and scaled up in plants at a low cost compared to the conventional microbial and animal based systems. The main technical challenge during this process is to produce sufficient level of proteins in plants. Low yield is generally caused by proteolytic degradation during expression and downstream processing of recombinant proteins. The yield of a human therapeutic protein interleukin (IL) -10 produced in transgenic tobacco leaves was found to be below the critical level, and is potentially due to degradation by tobacco cysteine proteases (CysPs). …

Two Spotted Spider Mite (Tetranychus Urticae) Selection To Arabidopsis Thaliana, Huzefa Ratlamwala

Electronic Thesis and Dissertation Repository

Spider mite feeding on A. thaliana induces the production of indole glucosinolates (IGs), plant secondary metabolites that negatively affect mite performance. In this study I conducted selection experiments on A. thaliana with varying levels of IGs, to determine if mites could adapt to IGs and other defense compounds. After 12 months, mites reared on host with IGs performed significantly better on A. thaliana than mites maintained on beans. However, an adaptation cost was detected between selected mite lines and their ancestral host. The qRT-PCR data on different mite lines revealed that the detoxification genes previously identified may only be involved …

The Role Of The Pre-Sensor 1 Β Hairpin In Minichromosome Maintenance 2-7 Function, Simon K. W. Lam

Electronic Thesis and Dissertation Repository

The pre-sensor 1 (PS1) hairpin is found in helicases of the AAA+ family (ATPases associated with a variety of cellular activities) of proteins and is implicated in DNA translocation during DNA unwinding. To determine whether the PS1 b hairpin is required in the eukaryotic replicative helicase, Mcm2-7 (also comprised of AAA+ proteins), we mutated the conserved lysine residue in the PS1 hairpin in each of the S. cerevisiae Mcm subunits to alanine. Only the PS1 hairpin of Mcm3 was essential for viability, while mutation of the PS1 hairpin in the remaining Mcm subunits resulted in minimal phenotypes, with the exception …

Characterizing The Interaction Between Ranbpm And C-Raf, Wesley Berube-Janzen

Electronic Thesis and Dissertation Repository

RanBPM/RanBP9 is a multi-domain nucleocytoplasmic protein which has been linked to numerous cellular processes including cell adhesion, migration, transcription and apoptosis. Although RanBPM is a member of the mammalian CTLH complex, the counterpart of a conserved yeast E3 ubiquitin ligase complex, its exact function remains unknown. Previous work in our laboratory has shown that RanBPM inhibits the ERK pathway by interacting with the kinase c-Raf and downregulating c-Raf levels. Here, we show that the N-terminus, LisH/CTLH and CRA domains of RanBPM are required for downregulation of c-Raf and that RanBPM interacts directly with c-Raf through its CRA domain. We also …

A Philosophical Analysis Of Ethics Education In The Canadian National Coaching Certification Program For Rowing, Mark M. Williams

Electronic Thesis and Dissertation Repository

This dissertation applies a conception of rationality from the philosophy of science to the coaching education context. The purpose of this dissertation is to present an account of how the exercise of judgment by coaches facing ethical dilemmas can be rational. The discussion in this dissertation begins with a traditional account of rationality that has long been a staple of moral philosophy. Next, the influence of this model in the current Canadian rowing coach education program are highlighted, as are its limitations in providing a complete account of rational ethical-decision making in the coaching context. After establishing these limitations, an …

Elucidating The Signalling Pathway Of Mer Tyrosine Kinase Receptor In Efferocytosis, Ekenedelichukwu Azu

Electronic Thesis and Dissertation Repository

Efferocytosis is the clearance of apoptotic cells and is necessary for homeostasis. Mer Tyrosine Kinase (MerTK) is a crucial efferocytic receptor whose loss is associated with chronic inflammatory diseases and autoimmunity. While previous studies have shown that MerTK mediates efferocytosis through a unique mechanism that requires integrins, MerTK signalling pathway remains unknown. Given this unusual internalization mechanism, I hypothesized that MerTK signals and engages integrins through a novel signalling pathway different from that used by other phagocytic receptors. Therefore, this study aimed to identify the signalling pathways activated by MerTK, utilizing conventional cell biology and pharmacological approaches.

I found that …

Understanding Recurrent Disease: A Dynamical Systems Approach, Wenjing Zhang

Electronic Thesis and Dissertation Repository

Recurrent disease, characterized by repeated alternations between acute relapse and long re- mission, can be a feature of both common diseases, like ear infections, and serious chronic diseases, such as HIV infection or multiple sclerosis. Due to their poorly understood etiology and the resultant challenge for medical treatment and patient management, recurrent diseases attract much attention in clinical research and biomathematics. Previous studies of recurrence by biomathematicians mainly focus on in-host models and generate recurrent patterns by in- corporating forcing functions or stochastic elements. In this study, we investigate deterministic in-host models through the qualitative analysis of dynamical systems, to …

Dissociating The Psychoactive Effects Of Distinct Cannabis Compounds In The Mesocorticolimbic Circuitry, Jordan S. Zunder

Electronic Thesis and Dissertation Repository

The discovery of the endocannabinoid system propelled understanding of the mechanisms of action of cannabinoid compounds. While marijuana is the most widely used illicit substance in the world, the neuropsychopharmacological mechanisms that underlie the diffuse effects of cannabis in the brain remain poorly understood. This is because marijuana smoke represents a complex mixture of chemical components, possessing dissociable psychoactive properties. Clinical evidence suggests a functional dissociation between the two main pharmacological components of cannabis, Δ9- tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Using a combination of cortical microinfusions during two emotional learning paradigms, and single-unit in vivo electrophysiological recording, we investigated the …

In Vitro Functional Analysis Of Novel Single Nucleotide Polymorphisms In Oatp1b1 And Potential Clinical Relevance, Zhiyuan P. Yin

Electronic Thesis and Dissertation Repository

Statin-induced myopathy is a common adverse reaction of statin therapy. Patients with elevated plasma concentration of statins are thought to be at greater risk for myopathy. Statins are transported from the blood to hepatocytes via organic anion transporting polypeptide 1B1 (OATP1B1). Although single nucleotide polymorphisms (SNPs) in OATP1B1 have been associated with increased statin concentrations, we hypothesize that there may be other SNPs in OATP1B1 that can also contribute to reduced transport activity and increased plasma statin concentrations. OATP1B1 cDNA packaged in pEF6/V5-His TOPO was used as template, and 6 SNPs — c.298G>A, c.419C>T, c.463C>A (*4), c.1007C …

Characterization Of Human 82-Kda Choline Acetyltransferase Expression In A Newly Developed Transgenic Mouse Model, Silke M. Vanvaerenbergh

Electronic Thesis and Dissertation Repository

Expression of human 82-kDa choline acetyltransferase (ChAT) protein in nuclei of cultured neurons from Alzheimer’s disease model APP/PS1 transgenic mice results in a reduction in Aβ release, suggesting a protective role. This thesis characterizes the expression of human 82-kDa ChAT in 82-hChAT;NkCre transgenic mice by PCR-based examination of genomic DNA and localization of the protein in mice brains. First, I demonstrate in a cultured cell model that Cre recombinase-mediated excision of a floxed LacZ gene is necessary for human 82-kDa ChAT protein expression from pcCALL2:82-ChAT, the plasmid used to create founder transgenic mice. Second, I confirmed that human 82-kDa ChAT …

Mindfulness Meditation Versus Eeg-Alpha Neurofeedback: The Role Of Eeg-Alpha Enhancement In Attentional Control, Theodore Chow

Electronic Thesis and Dissertation Repository

This thesis directly compared two active interventions known to enhance the EEG-Alpha rhythm, mindfulness meditation (MM) with EEG-Alpha enhancement neurofeedback (NFB), relative to a non-active Sham-NFB control. Seventy-three university students were randomized to one of the three 15-minute single-session interventions. Participants were subsequently compared on their ability to enhance EEG-Alpha amplitude as well as regarding Stroop behavioural performance, EEG event-related potentials, and EEG-Alpha event-related desynchronization (ERD) as markers of attentional control. Participants randomized to MM, NFB, and Sham did not differ in their ability to modulate the EEG-Alpha rhythm post-intervention. However, enhancements in EEG-Alpha amplitude were seen within the MM …

Characterization Of Efferosome Maturation And The Processing Of Apoptotic Bodies, Yohan Kim

Electronic Thesis and Dissertation Repository

Every day billions of cells in our bodies undergo apoptosis and are cleared through efferocytosis – a phagocytosis-like process in which phagocytes engulf and degrade apoptotic cells. Proper processing of efferosomes prevents inflammation and immunogenic presentation of antigens. In this thesis I determined that the early stages of efferosome maturation parallel that of the pro-immunogenic phagocytosis of pathogens. Mass spectrometry analysis of later maturation stages identified unique regulatory proteins on efferosomes and phagosomes. Keys among these were Rab17 and Rab45 on efferosomes versus Rab6b and PI-4-Kinase on phagosomes. The later would allow for antigen presentation from phagosomes, while the former …

The Effects Of Oar-Shaft Stiffness And Length On Rowing Biomechanics, Brock Laschowski

Electronic Thesis and Dissertation Repository

This work investigates the effects of oar-shaft stiffness and length on rowing biomechanics. The mechanical properties of the oar-shafts were examined using an end-loaded cantilever system, and theoretical relations were proposed between the mechanics of the oar-shafts and rowing performance. On-water experiments were subsequently conducted and rowing biomechanics measured via the PowerLine Rowing Instrumentation System. The PowerLine system measures force and oar angle on the oarlock, as well as proper boat acceleration. The convergent validity and test-retest reliability of the PowerLine force measurements were determined prior to the on-water experiments. Thereafter, rowers were tested over a set distance using oar-shafts …

Mutations At The 46th Residue Change Properties Of Cx50 Gap Junction Channels, Xiaoling Tong

Electronic Thesis and Dissertation Repository

The interface of the first transmembrane domain and the first extracellular loop (TM1/E1 border) in several gap junction (GJ) channels is known to line a portion of the pore and plays an important role in determining GJ channel properties. By introduction of a charged residue into this domain of Cx50, the resultant mutant channels showed drastically altered unitary conductance (γ_j) and transjunctional voltage-dependent gating (V_j-gating). Specifically G46D and G46E increased the Cx50 γ_j from 201 to 256 and 293 pS, respectively and G46K channel showed a decreased γ_j of only 20 pS. Moreover, in …

The Roles Of Matrix-Associated Periostin In An In Vitro Model Of Hypertrophic Scarring, Justin D. Crawford

Electronic Thesis and Dissertation Repository

Abnormal scarring is a type of benign fibrosis of the skin that can restrict mobility, dexterity and quality of life. There are few, if any, truly effective treatment options for these conditions. Hypertrophic scarring is a common form of abnormal scarring characterized by increased fibroblast proliferation and differentiation of apoptosis-resistant and hyper-contractile myofibroblasts that promote excessive deposition and contracture of the extracellular matrix (ECM). Periostin, a secreted ECM protein, is transiently expressed during normal cutaneous wound repair, but is abnormally abundant and persistent in abnormal scars and other benign fibroses that display enhanced fibroblast proliferation and myofibroblast differentiation. The objectives …

Mechanistics Of Prothymosin Alpha And Nrf2 In The Keap1-Nrf2 Mediated Oxidative Stress Response, Halema Khan

Electronic Thesis and Dissertation Repository

In an effort to dissect the mechanism of interaction of IDPs, in this thesis we focus on Prothymosin a (ProTa) and nuclear factor erythroid 2-related factor 2 (Nrf2), intrinsically disordered proteins, in the Nrf2 mediated oxidative stress response. Kelch-like ECH-associated protein 1 (Keap1) is an inhibitor of Nrf2, a key transcription factor of cytoprotective genes. Under unstressed conditions, Keap1 interacts with Nrf2 in the cytoplasm via its Kelch domain and suppresses Nrf2 activity. During oxidative stress, Nrf2 is released from Keap1 and is shuttled to the nucleus, where it initiates pro cell survival gene transcription. ProTa also interacts with the …

The Implications Of Altered Cholinergic Signaling In Cardiac Health And Disease, Ashbeel Roy

Electronic Thesis and Dissertation Repository

­Cardiac remodeling and dysfunction occur prior to the onset of heart failure. Altered regulation of cardiac function by the autonomic nervous system has been implicated in the progression of heart disease. Both altered sympathetic and parasympathetic tone contribute to cardiac disease; however, the role of the parasympathetic nervous system, and specifically acetylcholine (ACh), in cardiac dysfunction has not been fully elucidated. In these studies, we sought to determine whether changes in neuronal and/or non-neuronal ACh release regulate cardiac activity and alter the progression of cardiac remodeling and dysfunction. A systemic decrease in the expression of the vesicular acetylcholine transporter …

Ilk Modulates Stress-Induced Apoptosis In Epidermal Keratinocytes, Michelle Im

Electronic Thesis and Dissertation Repository

Integrin-linked kinase (ILK) is a ubiquitous scaffold protein that mediates cellular responses to integrin stimulation by extracellular matrix proteins. Mice with inactivation of the Ilk gene in squamous epithelia display defects in skin regeneration after injury, failure to thrive, and perinatal death. ILK-deficient epidermis exhibits reduced adhesion to the basement membrane and impaired hair follicle morphogenesis. In culture, ILK-deficient keratinocytes fail to attach and spread efficiently, and demonstrate decreased survival. We now show that ILK-deficient keratinocytes exhibit lower proliferative capacity and increased apoptosis in the absence or presence of growth factors. This reduced viability appears to be independent of the …

Synaptic Architecture Of The Acoustic Startle Response Pathway, Mahabba Smoka

Electronic Thesis and Dissertation Repository

The acoustic startle response (ASR) is mediated by a simple pathway which includes the giant neurons of the caudal pontine reticular nucleus (PnC). Habituation is theorized to occur via hyperpolarizing big potassium (BK) channels localized at glutamatergic terminals of auditory afferents in the PnC. Prepulse inhibition is suggested to be mediated by cholinergic innervation of PnC giant neurons, with possible glutamate and/or GABA co-release. Animals were injected with Fluorogold at C3/C4 to label a subpopulation of PnC giant neurons, and following a startle experiment, brainstems were processed for pCREB expression. Using their respective markers, BK channels, glutamatergic, GABAergic, and cholinergic …

Evolutionary And In Silico Analysis Of The Antiviral Trim22 Gene, Jenna Kelly

Electronic Thesis and Dissertation Repository

Tripartite motif protein 22 (TRIM22) is an evolutionarily ancient interferon-induced protein that been shown to potently inhibit human immunodeficiency virus (HIV), hepatitis B virus (HBV), and influenza A virus (IAV) replication. Altered TRIM22 expression levels have also been linked to autoimmune disease, cancer, and cellular proliferation. Despite its important role in a number of biological processes, the factors that influence TRIM22 expression and/or antiviral activity remain largely unknown. To identify key functional sites in TRIM22, we performed extensive evolutionary and in silico analyses on the TRIM22 coding region. These tools allowed us to pinpoint multiple sites in TRIM22 that have …

Investigating The Multiple Hit Hypothesis Of Parkinson Disease Using Transgenic Lrrk2-R1441g Rats, Komal T. Shaikh

Electronic Thesis and Dissertation Repository

The ‘multiple hit’ hypothesis of Parkinson disease (PD) suggests that the combination of several risk factors leads to the development of PD. Here, we explore the interaction between two potential causes of PD; a genetic mutation in the leucine-rich repeat kinase 2 (LRRK2) gene and exposure to the neurotoxin, Paraquat. This project characterizes transgenic BAC rats expressing human LRRK2 bearing the familial PD mutation, R1441G. These rats were tested for PD-related deficits at 3, 6, 9 & 12 months. These rats were then exposed to intraperitoneal injections of Paraquat. We hypothesized that LRRK2^R1441G rats will show increased vulnerability …