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Articles 1 - 21 of 21
Full-Text Articles in Physiology
Cardioprotective Role Of The Cholinergic System, Mouhamed Dakroub
Cardioprotective Role Of The Cholinergic System, Mouhamed Dakroub
Electronic Thesis and Dissertation Repository
The process of aging is an irreversible continuum experienced by all individuals. A large number of physiological transformations occur to the cardiovascular system as one ages. These changes result in increased risk of developing cardiovascular diseases, many of which are frequently seen in geriatric populations. While the exact mechanisms of age-related cardiac dysfunction have not been established, abnormal cholinergic dysfunction has been implicated in the pathology of other age related diseases; therefore, we have hypothesized that age induced cholinergic dysfunction is detrimental to cardiac function and health. This study seeks to identify whether increased cholinergic signaling, either by transgenic overexpression …
Brain Injury And Inflammation And Placental Inflammation In Response To Repetitive Umbilical Cord Occlusions In The Near Term Ovine Fetus, Alex Xu
Electronic Thesis and Dissertation Repository
We hypothesized that repetitive umbilical cord occlusions (UCOs) leading to severe acidemia will stimulate a placental and fetal inflammatory response associated with brain injury, which will be exacerbated by chronic hypoxemia and low-grade infection. Chronically instrumented fetal sheep served as controls or underwent repetitive UCOs for up to 4 hours or until fetal arterial pH was2saturation pre-UCOs of >55% and
Dexamethasone Regulates Gene Expression Induced By The Mechanosensitive P2x7 Receptor In Osteoblasts, Meena Na
Dexamethasone Regulates Gene Expression Induced By The Mechanosensitive P2x7 Receptor In Osteoblasts, Meena Na
Electronic Thesis and Dissertation Repository
Orthodontic tooth movement involves activation of osteoblasts and osteoclasts in response to mechanical forces. Extracellular nucleotides, released in response to mechanical stimuli, signal through P2 receptors in osteoblasts. P2X7 receptors are ATP-gated cation channels implicated in mechanotransduction in bone. Corticosteroids such as dexamethasone exhibit anti-inflammatory effects and their chronic use has been linked to serious side-effects such as osteoporosis. We investigated gene expression following P2X7 receptor activation with benzoylbenzoyl-ATP (P2X7 receptor agonist) in osteoblast precursor cells in the presence or absence of dexamethasone. We hypothesized that dexamethasone inhibits the ability of ATP to stimulate the expression of anabolic (bone forming) …
Degrees Of Damage: Quantifying Male Vs. Female Exercise-Induced Muscle Damage Through Magnetization Transfer Ratios, Nicholai Michael Clausius Crawford
Degrees Of Damage: Quantifying Male Vs. Female Exercise-Induced Muscle Damage Through Magnetization Transfer Ratios, Nicholai Michael Clausius Crawford
Electronic Thesis and Dissertation Repository
No direct, quantitative, and non-invasive markers presently exist to assess exercise-induced muscle damage (EIMD). However, magnetization transfer ratios (MTR), an emerging measurement quantified via magnetic resonance imagery, provide more direct indication of muscle integrity following EIMD. This study compares and correlates the temporal pattern of the MTR to alternative indirect markers of EIMD in male vs. female populations, and subsequently establishes whether there are sex differences in biochemical activity during recovery. The antioxidant properties of estrogen hypothetically minimize muscle trauma, maintain membrane stability, and limit swelling resulting in heightened tissue integrity and resilience to EIMD. Six males and three females …
Engineered Cx26 Variant Established Functional Heterotypic Cx26/Cx43 And Cx26/Cx40 Gap Junction Channels, Levent Berk Karademir
Engineered Cx26 Variant Established Functional Heterotypic Cx26/Cx43 And Cx26/Cx40 Gap Junction Channels, Levent Berk Karademir
Electronic Thesis and Dissertation Repository
Two hexameric connexin hemichannels dock together to from a whole gap junction (GJ) channel. The mechanisms of docking specificity in forming homotypic and heterotypic GJ channels are not fully clear. To reveal the key differences between Cx26 and Cx43 (or Cx40) in their docking residues, we aligned and analyzed ten well studied connexin sequences. Five of them are docking compatible with Cx26 and the rest (including Cx43 and Cx40) are not. According to Cx26 crystal structure at the docking interface, we identified two putative docking residues on the second extracellular domain (E2) that are well conserved within docking compatible connexins, …
Examination Of The Non-Linear V̇O2p Response To Exercise: Non-Invasive Evidence Of Linear Systems Control Using V̇O2p Kinetic Analyses, Daniel A. Keir
Examination Of The Non-Linear V̇O2p Response To Exercise: Non-Invasive Evidence Of Linear Systems Control Using V̇O2p Kinetic Analyses, Daniel A. Keir
Electronic Thesis and Dissertation Repository
The pulmonary O2 uptake (V̇O2p) response to exercise has been characterized by exponential kinetics that remain constant regardless of the exercise protocol used to force the change in V̇O2p (kinetics are invariant). A system that responds in this way is classified as “dynamically linear”, implying that a first-order rate reaction controls V̇O2 at the muscle level (V̇O2m). However, slowed V̇O2p kinetics when initiating exercise from raised baseline intensities challenges this notion. The purpose of this thesis was to characterize the rate (τV̇O2p) and magnitude (gain) of adjustment of V̇O2p …
Role Of Rgs2 In Cellular Stress, Chang-Hui Wang
Role Of Rgs2 In Cellular Stress, Chang-Hui Wang
Electronic Thesis and Dissertation Repository
Stresses from the external environment can disrupt cellular processes and result in damaging effects, such as the misfolding of proteins, which have been linked to several diseases. Regulator of G protein signalling 2 (RGS2) is upregulated by several forms of stress and can inhibit protein synthesis, an established response to stress typically achieved via the phosphorylation of the initiation factor, eIF2, to conserve energy and resources. Under reduced translation, some factors are selectively expressed via alternative translation mechanisms and these factors consequently may promote apoptosis. The molecular mechanisms mediating such opposing responses to stress are not well understood. Here, we …
Non-Invasive Determination Of Pre-Clinical Markers Of Cardiovascular Diseases In Low Birth Weight And Maternal Western Diet Guinea Pig Offspring Exposed To A Postnatal Western Diet, Jacky Chiu
Electronic Thesis and Dissertation Repository
Low birth weight (LBW), and maternal Western Diet (WD) consumption have both been independently implicated to increase the risk of developing cardiovascular diseases (CVDs) in later life. These fetal programmed risks are also believed to exacerbate the effects of a postnatal WD pattern. Therefore, resulting in the development of pre-clinical markers of CVDs, such as insulin resistance (IR), coronary circulation disruptions. This thesis aimed to elucidate the roles of sub-optimal in utero growth through placental insufficiency, or chronic maternal WD consumption, and postnatal WD consumption on the long-term programming of CVDs in a guinea pig model. Early pre-clinical markers of …
Fibulin-3 Promotes Triple Negative Breast Cancer Cell Invasion, Michelle M. Noonan
Fibulin-3 Promotes Triple Negative Breast Cancer Cell Invasion, Michelle M. Noonan
Electronic Thesis and Dissertation Repository
Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer, and metastasis is a leading cause of mortality in these patients. Fibulin-3, a secreted extracellular matrix protein, has a pro-invasive role in other cancers. However, a role for fibulin-3 in TNBC invasion is unknown. We have previously shown that KISS1R signaling promotes TNBC cell invasion through EGFR and MMP-9 activity, via β-arrestin2. Thus, we hypothesized that KISS1R signaling promotes TNBC cell invasion via fibulin-3. Our clinical data suggests that plasma fibulin-3 levels are elevated in metastatic TNBC patients. Additionally, we found that invasive breast cancer cells have increased …
Stability And Activity Of Naturally Occurring Rgs2 Variants, Patrick Stockwell
Stability And Activity Of Naturally Occurring Rgs2 Variants, Patrick Stockwell
Electronic Thesis and Dissertation Repository
Regulator of G protein signaling protein 2 (RGS2) attenuates G Protein-Coupled Receptor (GPCR) signaling by promoting the hydrolysis of GTP in the activated Gα subunit to GDP, thereby governing many physiological and pathophysiological signals. However, how RGS2 itself is regulated remains to be elucidated. In this study, our principal goal was to discover the molecular mechanisms controlling RGS2 degradation and if altered degradation affects Gα signaling. RGS2 has four initiation sites (at residues 1, 5, 16, and 33), resulting in the existence of four distinct N-terminal initiation site variants. Additionally, there are naturally occurring mutations in this region at residues …
The Effect Of A Multiple Modality Mind-Motor Exercise Intervention On Single And Dual-Task Gait, Balance, And Executive Function, In Community Dwelling Older Adults With A Subjective Cognitive Complaint: A Randomized Controlled Trial., John P. Bocti
Electronic Thesis and Dissertation Repository
Cognitive decline disorders are becoming increasingly prevalent, with older adults at increased risk. Combined exercise has been recently explored as an intervention to help to prevent the decline, however cognitive activation in combination with physical activity has yet to be explored. Therefore, the purpose of the study is to determine the effects of multiple modality exercise programs in combination with a mind-motor task and their effects on mobility and cognitive variables. A total of (n=89) older adults (55+ yrs), with subjective cognitive complaints participated in a multiple modality exercise class, three days a week over six months, with the intervention …
Skeletal Muscle Lipid Metabolism And Markers Of Insulin Resistance In Young Male Low Birth Weight Offspring In Combination With A Postnatal Western Diet, Kristyn Pamela Dunlop
Skeletal Muscle Lipid Metabolism And Markers Of Insulin Resistance In Young Male Low Birth Weight Offspring In Combination With A Postnatal Western Diet, Kristyn Pamela Dunlop
Electronic Thesis and Dissertation Repository
Low birth weight offspring are at increased risk for developing metabolic syndrome in later life, specifically its precursor, insulin resistance (IR). Reduced mitochondrial lipid metabolism is implicated in IR pathogenesis, promoting accumulation of acylcarnitines, and potentiating alterations in phosphorylation status of insulin signaling intermediates. While high-energy Western diets are classically implicated in IR progression, the in utero environment was recently highlighted as a major programming mechanism of later life IR. Using a guinea pig model of placental insufficiency, we investigated how an adverse in utero environment impacts later life mitochondrial lipid metabolism and IR progression, as well as its interaction …
Freeze Tolerance In The Spring Field Cricket, Gryllus Veletis, Alexander H. Mckinnon
Freeze Tolerance In The Spring Field Cricket, Gryllus Veletis, Alexander H. Mckinnon
Electronic Thesis and Dissertation Repository
Many insects are able to survive internal ice formation. However, the mechanisms underlying freeze tolerance are not well-understood, perhaps because of a lack of suitable model organisms. I found that the spring field cricket, Gryllus veletis, seasonally acquires freeze tolerance in the fall when kept outside in London, Ontario. Moreover, individuals acquired freeze tolerance in the laboratory in response to a simulated fall thermophotoperiod. Lab-acclimated G. veletis freeze at -6.1 ± 0.7 ºC and the acquisition of freeze tolerance is accompanied by the accumulation of proline and trehalose. Crickets survived temperatures as low as -12 ºC (1.5 h), and …
The Ctcf Chromatin Organizer Is Required For Hindlimb Development, Katherine L. Rabicki
The Ctcf Chromatin Organizer Is Required For Hindlimb Development, Katherine L. Rabicki
Electronic Thesis and Dissertation Repository
Mutations in chromatin organizer CTCF were identified in patients with intellectual disability and skeletal defects. Previous studies demonstrated that depletion of CTCF in murine limb mesenchyme results in apoptosis in the forelimb. The role of CTCF in the hindlimb, however, is unknown. My objective was to investigate effects of CTCF deletion on chondrogenesis and skeletal development in the hindlimb. In vitro wild-type micromass cultures demonstrate that chondrocyte gene expression is delayed in the hindlimb when compared to forelimbs. Embryonic CtcfFl/Fl;Prx1Cre mice were investigated, and qRT-PCR and histology were performed on limb buds and long bones. Results show that …
Thermal Performance Covaries With Environmental Temperature Across Populations Of Atlantic Salmon (Salmo Salar), Kayla J. Harding Gradil
Thermal Performance Covaries With Environmental Temperature Across Populations Of Atlantic Salmon (Salmo Salar), Kayla J. Harding Gradil
Electronic Thesis and Dissertation Repository
Global climate change is projected to have widespread effects that could threaten the viability of natural populations. Physiological processes of aquatic ectotherms critically depend on their thermal environment, such that the optima for performance often correspond to environmental temperatures. Given predicted changes in aquatic thermal environments, it is increasingly important to understand organism’s underlying physiological mechanisms utilized to cope with these changes. Here, I show that three populations of Atlantic salmon (Salmo salar) are narrowly adapted to their native summer temperatures, such that thermal tolerance is optimized near average temperatures and collapses near peak temperatures. Further, I found …
Reactivity Of The Middle Cerebral Artery To Carbon Dioxide, Nicole Coverdale
Reactivity Of The Middle Cerebral Artery To Carbon Dioxide, Nicole Coverdale
Electronic Thesis and Dissertation Repository
Transcranial Doppler ultrasound (TCD) is used for the assessment of cerebral blood flow velocity (CBFV) at the middle cerebral artery (MCA) with the assumption that diameter of the artery does not change. Thus, CBFV is equivalent to cerebral blood flow (CBF). The purpose of this thesis was determine if the MCA dilates during hypercapnia (HC) and/or constricts during hypocapnia (HO) in healthy young and older adults using 3T magnetic resonance imaging (MRI). We also determined how these changes in MCA cross-sectional area (CSA) influence estimates of CBF and cerebrovascular reactivity (CVR) from TCD in young and older adults. Lastly, we …
The Role Of Shroom3 In Kidney Development, Alexandra Sull
The Role Of Shroom3 In Kidney Development, Alexandra Sull
Electronic Thesis and Dissertation Repository
Chronic kidney disease (CKD) affects 10% of the population in industrialized nations. Recent genome wide association studies (GWAS) have correlated SHROOM3 with glomerular filtration rate and albuminuria. To elucidate Shroom3’s role in the kidney, I employed a gene trap mouse model (Shroom3Gt/Gt allele) that produces a non-functional Shroom3 protein. Shroom3 is expressed in the podocytes embryonically and in adulthood as well as other cell types. Shroom3 loss results in glomerular cysts and reduced glomerular number. Some Shroom3+/Gt and Shroom3Gt/Gt podocytes showed loss of apical ROCK1, pMLC and actin consistent with the role of Shroom3 in …
Novel Video Imaging To Examine Cardiac Function In Xenopus Embryos, Judith Sull
Novel Video Imaging To Examine Cardiac Function In Xenopus Embryos, Judith Sull
Electronic Thesis and Dissertation Repository
Congenital heart defects (CHDs) occur in approximately 1% of live births and the etiology has been associated with disturbances in cardiogenesis. However, the majority of research examining CHDs relies on static morphological data, which does not elucidate how defects alter cardiac function. I used Xenopus laevis embryos to examine the association between CHDs and functional alterations using a novel imaging system that can obtain high- resolution images through a non-invasive procedure. A high-speed video camera and software were used to assess cardiac function, permitting functional characterization of late Xenopus cardiogenesis. Verification of the imaging system’s ability to detect changes in …
Investigating The Role Of Ephrins And Their Receptors In Mouse Folliculogenesis And Ovulation, Adrian Buensuceso
Investigating The Role Of Ephrins And Their Receptors In Mouse Folliculogenesis And Ovulation, Adrian Buensuceso
Electronic Thesis and Dissertation Repository
Follicle stimulating hormone (FSH) promotes granulosa cell (GC) proliferation, differentiation, and steroidogenesis. This series of events is critical for female fertility, and culminates in the formation of mature follicles responsive to the surge of luteinizing hormone (LH) that triggers ovulation. Ephrins (Efn genes) and Eph receptors (Eph genes) are membrane-associated signaling molecules that mediate communication at sites of cell-cell contact, and have been extensively studied in the context of embryonic development. The published literature contains several reports of ovarian Eph and Efn expression, although their precise roles in the ovary are unknown. Dysregulation of Efna5 in GCs of …
Prenatal Exposure To Bisphenol A Disrupts Fetal Liver Maturation In A Sex-Specific Manner, Bianca Debenedictis
Prenatal Exposure To Bisphenol A Disrupts Fetal Liver Maturation In A Sex-Specific Manner, Bianca Debenedictis
Electronic Thesis and Dissertation Repository
Developmental exposure to BPA is associated with liver dysfunction and diseases in adulthood. However, the effects of BPA on liver development are unknown. To address this question, pregnant mice were exposed to BPA via diet from embryonic day 7.5 (E7.5) to E18.5. At E18.5, fetal livers were collected, and analyzed for changes in the expression of key hepatic maturation markers. We found the following significant protein alterations in BPA-exposed female but not male fetal livers: (a) mature hepatocyte markers, albumin and glycogen synthase, were decreased; (b) immature hepatocyte marker, alpha-fetoprotein, was increased; (c) master transcription factor of hepatocyte differentiation, C/EBP-α, …
Mechanisms Of Neural Precursor Cell Apoptosis By Microglia-Derived Cytokines, Jennifer Guadagno
Mechanisms Of Neural Precursor Cell Apoptosis By Microglia-Derived Cytokines, Jennifer Guadagno
Electronic Thesis and Dissertation Repository
The persistence of neural precursor cells (NPCs) in distinct niches of the adult brain and spinal cord provides an important opportunity for regeneration in the affected nervous system. In the adult brain, neural precursor cells (NPCs) generate new neurons that can be integrated into the CNS circuitry to replace damaged or lost neurons, and contribute to learning and memory processes. Deregulated neurogenesis has been observed under both acute and chronic neurological conditions including stroke, Alzheimer’s disease, and Parkinson’s disease. The extent to which neurogenesis contributes to brain repair is severely limited by the neuroinflammatory processes associated with these neurodegenerative conditions. …