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Theses/Dissertations

2021

Western University

Physiology

Articles 1 - 12 of 12

Full-Text Articles in Life Sciences

Targeting Ccn Proteins In The Treatment Of Dermal Fibrosis, Alex Peidl Nov 2021

Targeting Ccn Proteins In The Treatment Of Dermal Fibrosis, Alex Peidl

Electronic Thesis and Dissertation Repository

Fibrotic disorders, including the inflammatory connective tissue disease systemic sclerosis (SSc), contribute to 45% of deaths in the Western world. Currently there is no universally agreed-upon treatment for fibrosis. The CCN family of matricellular proteins are tightly spatiotemporally regulated proteins involved in development and wound healing, and are aberrantly expressed in fibrotic disease, including in SSc. CCN1 and CCN2 are overexpressed in SSc and contribute to the progression of animal models of fibrosis. CCN3 is reciprocally regulated to CCN1 and CCN2 and has been shown to suppress CCN2-mediated fibrogenic activity in kidney fibrosis. This led to the development of therapeutic …

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Direct Electrical Stimulation Of Prefrontal Cortex Modulates The Transient Heart Rate Response To Exercise In Conscious Humans, Bartek Kulas Nov 2021

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 …

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Fatty Acid Regulation Of The Nrf2/Keap1 Pathway During Mouse Preimplantation Embryo Development, Grace Dionne Sep 2021

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 …

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Characterizing The Structural, Biophysical And Functional Effects Of S-Glutathionylation On Stim1 Ca2+ Sensing, Christian Michael Sirko Aug 2021

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 …

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Investigation Of The Hsp90 Co-Chaperone, Sti1, In Cellular Resilience And Neurodegenerative Diseases, Rachel E. Lackie Aug 2021

Investigation Of The Hsp90 Co-Chaperone, Sti1, In Cellular Resilience And Neurodegenerative Diseases, Rachel E. Lackie

Electronic Thesis and Dissertation Repository

In neurodegenerative diseases, certain proteins misfold and form toxic aggregates that cause brain matter atrophy, leading to decline in motor and/or cognitive functions. To maintain cellular proteostasis and survival, molecular chaperones regulate protein maturation and help to prevent aberrant protein aggregation. The molecular chaperone Hsp90 regulates hundreds of proteins and interestingly, several of those are misfolded in neurodegenerative diseases. Stress inducible-phosphoprotein-1 (STI1, STIP1), an Hsp90 co-chaperone, orchestrates client protein transfer between chaperones Hsp70 and Hsp90 through physical interactions with both chaperones. Notably, previous work in yeast, worms, and mouse neurons all showed that STI1 protects organisms against stressors and amyloid-like …

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Cerebrovascular Compliance In Humans, Marcy Erin Moir Jul 2021

Cerebrovascular Compliance In Humans, Marcy Erin Moir

Electronic Thesis and Dissertation Repository

Pulsatile blood flow consists of two components: steady flow and oscillatory flow. Steady blood flow is primarily regulated by vascular resistance while vascular compliance represents a key mediator of oscillatory blood flow. However, most studies investigating the regulation of cerebral blood flow in humans have focused on vascular resistance. Recently, emerging evidence has implicated vascular compliance as an important contributor to the regulation of cerebral perfusion. Therefore, the research contained herein aimed to i) quantify cerebrovascular compliance responses to blood pressure alterations and ii) explore mechanisms regulating cerebrovascular compliance in humans. The studies employed a Windkessel modelling approach to calculate …

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Examining The Feasibility Of Delivering A Multi-Component Virtual Lifestyle Medicine Program For Adults With Type 2 Diabetes, Madison S. Hiemstra Jul 2021

Examining The Feasibility Of Delivering A Multi-Component Virtual Lifestyle Medicine Program For Adults With Type 2 Diabetes, Madison S. Hiemstra

Electronic Thesis and Dissertation Repository

BACKGROUND: The virtual delivery of lifestyle medicine programs (e.g., via web-conferencing platforms) can increase program accessibility for adults living with type 2 diabetes (T2D). PURPOSE: To assess the feasibility of virtually delivering a multi-component group-based lifestyle medicine program that uses wearable technologies and exercise prescriptions in an adult population with T2D. METHODS: This was a six-week, single-cohort feasibility study. The virtual lifestyle medicine program included live-video delivery of group education classes, one-on-one exercise counselling phone calls, flash glucose monitors, wearable activity monitors, and exercise prescriptions. Several feasibility outcomes were assessed including recruitment and retention rates, acceptability (e.g., exit survey), and …

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21°C Is The Emerging Ideal Temperature For Kidney Preservation In The Presence Of Hydrogen Sulfide, Smriti Juriasingani Jul 2021

21°C Is The Emerging Ideal Temperature For Kidney Preservation In The Presence Of Hydrogen Sulfide, Smriti Juriasingani

Electronic Thesis and Dissertation Repository

Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. However, the shortage of transplantable kidneys has led to ever-increasing waiting lists. As a result, kidneys obtained via donation after cardiac death (DCD) are being used more frequently for transplantation. However, they exhibit poorer outcomes due to ischemia-reperfusion injury (IRI) and cold preservation methods, such as static cold storage (SCS). Supplementing cold preservation solutions with hydrogen sulfide donors, such as AP39, has been shown to improve renal IRI and graft outcomes, but the injury associated with cold preservation remains. This thesis evaluates the effect of subnormothermic kidney …

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Spinal Excitability Changes Following Sensory Electrical Stimulation Of The Forearm, Devin K. Box Jun 2021

Spinal Excitability Changes Following Sensory Electrical Stimulation Of The Forearm, Devin K. Box

Electronic Thesis and Dissertation Repository

Sensory electrical stimulation can be used to suppress tremor in Parkinson’s disease. This study investigated the central mechanism underlying this suppression in healthy participants. Reciprocal inhibition (RI) of the wrist flexors before and after a session of sensory electrical stimulation (SES) applied to the antagonistic extensor muscles was assessed using electromyography. It was hypothesized that a 15-minute session of SES, rated by participants as a 3 on a 0-10 pain scale, would produce an increase in RI. Seven of the 18 participants experienced an increase in RI at 0-5 minutes post stimulation, which returned to baseline at 10-15 minutes. The …

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Characterizing The Effects Of Pyrroloquinoline Quinone (Pqq) Supplementation On Skeletal Muscle Mitochondrial Function And Myogenesis During Oxidative Stress And Iugr., Allyson J. Wood May 2021

Characterizing The Effects Of Pyrroloquinoline Quinone (Pqq) Supplementation On Skeletal Muscle Mitochondrial Function And Myogenesis During Oxidative Stress And Iugr., Allyson J. Wood

Electronic Thesis and Dissertation Repository

Intrauterine growth restriction (IUGR) affects 10-15% of births and is associated with placental insufficiency (PI), resulting in fetal oxidative stress (OS). This OS is a factor in the predisposition to postnatal noncommunicable disease (NCD) of which muscle mitochondrial dysfunctional is a key aspect. Pyrroloquinoline quinone (PQQ), an antioxidant-like compound, is capable of OS reduction and promotes mitochondrial function, though limited research has focused on its effects in in utero skeletal muscle. This study sought to investigate the impact of in vitro H2O2, a model of OS, and an in vivo model of OS associated IUGR, with …

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Inwardly Rectifying Potassium Channels: Regulators Of Myogenic Tone In Cerebrovascular Smooth Muscle, Jacob Fletcher Apr 2021

Inwardly Rectifying Potassium Channels: Regulators Of Myogenic Tone In Cerebrovascular Smooth Muscle, Jacob Fletcher

Electronic Thesis and Dissertation Repository

In cerebral arteries, inwardly rectifying potassium channels (KIR) contribute to smooth muscle hyperpolarization to control arterial diameter and tone. Emerging evidence highlighted their regulation by pressure, though the underlying mechanism remains unclear. This thesis explored this concept through examination of KIR channels in mouse and rat cerebral vascular smooth muscle (VSM). Experiments progressed from isolated cells to whole animals, employing electrophysiology, immunocytochemistry, proximity ligation assay, and arterial spin-labelling MRI techniques. Initial experiments indicated that KIR activity persists beyond KIR2.1 knockout in smooth muscle, clarifying their molecular composition. Our subsequent study identified key structural components …

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Sexual Dimorphism In Response To Repetitive Bouts Of Acute Exercise In Rodents With Type 1 Diabetes Mellitus, Jordan C. Larocque Feb 2021

Sexual Dimorphism In Response To Repetitive Bouts Of Acute Exercise In Rodents With Type 1 Diabetes Mellitus, Jordan C. Larocque

Electronic Thesis and Dissertation Repository

The purpose of this study was to examine sex-specific differences in the blood glucose (BG) response to recurrent aerobic exercise in type 1 diabetes. Specifically, we examined the role of peak estrogen (E2) concentrations during proestrus on BG response to prolonged aerobic exercise. To do so, nineteen Sprague-Dawley rats were assigned to four exercised groups: control female (CXF; n = 5), control male (CXM; n = 5), diabetic female (DXF, n = 5) and diabetic male (DXM, n = 4). Diabetes was induced in DX groups via subcutaneous injection of low dose streptozotocin. After four days of exercise, liver glycogen …

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