Life Sciences Commons^™

Corticotropin Releasing Factor Receptor Type 1 Signaling In Epilepsy And Traumatic Brain Injury, V V Chakravarthi Narla

Electronic Thesis and Dissertation Repository

Stress increases the frequency by which epileptic seizures occur. Corticotropin-releasing factor (CRF) coordinates neuroendocrine, autonomic and behavioral response to stress. This thesis sought to study the cellular and molecular mechanisms by which CRF regulates the activity of neural circuits in the piriform cortex (PC) in normal and epileptic states. The PC is richly innervated by CRF and 5-HT containing axons arising from the central amygdala and raphe nucleus. CRFR₁ and 5-HT_2A/CRs have been shown to interact in a manner where CRFR activation subsequently potentiates the activity of 5-HT_2A/CRs. The first purpose of this thesis was …

Identification Of A Novel Interaction Between Integrin-Linked Kinase And Beta-Arrestin 1, Hannah E. Murphy-Marshman

Electronic Thesis and Dissertation Repository

Integrin-linked kinase (ILK) is a ubiquitous scaffold protein essential for the development of front-rear polarity and directional migration of epidermal keratinocytes. β-arrestin 1 is another adaptor protein which has recently emerged as a key factor in modulating proliferation and migration of various cell types. Previous studies have demonstrated an association between β-arrestin 2 and ILK in cerebellar granule precursor cells. I have now identified a novel interaction between ILK and β-arrestin 1 in primary keratinocytes that occurs directly and without post-translational modifications. The N-terminal 67 residues of ILK and multiple regions in β-arrestin 1 are important for this interaction. This …

Role Of Anterior Cingulate Cortex In Saccade Control, Sahand Babapoor-Farrokhran

Electronic Thesis and Dissertation Repository

Cognitive control is referred to the guidance of behavior based on internal goals rather than external stimuli. It has been postulated that prefrontal cortex is mainly involved in higher order cognitive functions. Specifically, anterior cingulate cortex (ACC), which is part of the prefrontal cortex, is suggested to be involved in performance monitoring and conflict monitoring that are considered to be cognitive control functions.

Saccades are the fast eye movements that align the fovea on the objects of interest in the environment. In this thesis, I have explored the role of ACC in control of saccadic eye movements. First, I performed …

A Test Of The Effects Of Androgens On Immunity: No Relationship Between 11-Keto Testosterone And Immune Performance In Bluegill Sunfish (Lepomis Macrochirus), John W. Loggie

Electronic Thesis and Dissertation Repository

The posited immunosuppressive effects of androgens are a key component of the immunocompetence handicap hypothesis (ICHH). My thesis uses bluegill sunfish (Lepomis macrochirus) to test two predictions arising from this hypothesis: (1) natural concentrations of the androgen 11-keto testosterone (11-KT) will be negatively related with immunity, and (2) an immunochallenge will lower 11-KT concentration. I found no evidence for a relationship between natural 11-KT concentration and measures of immunity (leukocyte counts, respiratory burst, cytokine gene expression), and an immunochallenge with Vibrio vaccine did not affect 11-KT concentration. I performed a meta-analysis of immunochallenge studies to help interpret my …

The Role Of Gaba Signalling In Lung Macrophage Immune Response, Jacob W. Poirier

Electronic Thesis and Dissertation Repository

Lung macrophages (LMϕs) play a key role in pulmonary innate immunity. They polarize into different phenotypes adapting to the needs of the immediate pulmonary environment. Studies in our laboratory suggest that murine LMϕs are endowed with an autocrine gamma-aminobutyric acid (GABA) signaling system. My honors thesis study found that antagonizing the autocrine GABA signaling in alveolar macrophages (AMϕs) increased secretion of the M1 cytokine tumor necrosis factor-alpha (TNF-α), suggesting a role for GABA signaling in immune response. This project explored whether GABA signaling plays a role in LMϕ polarization. Results from this study confirmed that bacterial toxin lipopolysaccharide (LPS) and …

The Neuroprotective Effects Of Endurance Training On The Aging Brain, Katelyn Norton

Electronic Thesis and Dissertation Repository

Dysregulation of autonomic control often develops with advancing age, favoring a chronic state of heightened sympathetic outflow with parasympathetic withdrawal. However, the mechanisms of this age-related autonomic impairment are not known and may relate to alterations in brain structure (e.g. cortical atrophy) and/or altered neural function, particularly in regions related to the cortical autonomic network, namely, the medial prefrontal cortex (MPFC), insula cortex (IC), and hippocampus (HC). Exercise exerts beneficial effects on brain structure and, in the case of cognition, neurologic function; however, how exercise affects regions of the brain related to autonomic function are not known. This thesis tested …

The Cardiovascular Benefits Of Regular Exercise In Type 1 Diabetes Mellitus And The Risk Of Exercise-Induced Hypoglycemia, Matthew W. Mcdonald

Electronic Thesis and Dissertation Repository

Type 1 diabetes mellitus (T1DM) is associated with compromised glycemic control and a heightened risk for cardiovascular disease. The common treatment of T1DM with strict glycemic control through intensive insulin therapy can be problematic (weight gain, insulin resistance, hypoglycemia). Regular exercise is known to improve cardiovascular health, yet most individuals with T1DM remain sedentary, and identify the risk of exercise-induced hypoglycemia as a significant barrier. The investigation into the use of different forms of exercise (higher intensity, resistance) for preventing exercise-induced hypoglycemia in populations with T1DM has been promising, however, little work has investigated their cardiovascular benefit or whether the …

Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad

Electronic Thesis and Dissertation Repository

PDZ (PSD95/Disc Large/Zona Occludens) domain-containing proteins are scaffolding proteins that play important roles in regulating the activity of G protein-coupled receptors. Corticotropin Releasing Factor Receptor 1 (CRFR1) and Serotonin 2A Receptor (5-HT_2AR) are two GPCRs that are commonly associated with mental disorders. Both receptors also contain a class I PDZ-binding motif at the carboxyl terminal tail. In the first chapter, we investigate the effects of CAL (CFTR-associated ligand) on regulating the trafficking and signaling of CRFR1. We demonstrate a role for CAL in inhibiting CRFR1 endocytosis, cell surface expression, and CRF-mediated ERK1/2 signaling via the CRFR1 PDZ-binding motif. …

Glycosylation On Stromal Interaction Molecule-1 Ca2+ Sensing Region Enhances Store Operated Ca2+ Entry, Yoo Jung Choi

Electronic Thesis and Dissertation Repository

A major intracellular calcium (Ca²⁺) uptake pathway in excitable and non-excitable eukaryotic cells is store-operated Ca²⁺ entry (SOCE). Stromal interaction molecule-1 (STIM1) is the key regulator of SOCE and responds to changes in endoplasmic reticulum (ER)-stored Ca²⁺ through luminal sensing machinery composed of EF-hand and SAM domains (EFSAM). EFSAM can undergo N-glycosylation at Asn131 and Asn171 sites; however, the exact molecular and functional effects of N-glycosylation are unclear. By establishing a site-specific chemical approach to covalently linking glucose to EFSAM and subsequently examining EFSAM biophysical properties, I found that this modification enhances STIM1 activation …

Non-Invasive Determination Of Vascular Reactivity: A New Approach To An Important Measure, Kaitlin M. Mclay

Electronic Thesis and Dissertation Repository

Vascular impairments at both the macro- and the micro-circulatory level are known to be associated with cardiovascular disease (CVD) and may be one of the earlier signs of disease. As such, it is important to have a means of non-invasively assessing vascular reactivity, however accurate assessment remains challenging. Tests of flow-mediated dilation (FMD) have been widely used to non-invasively determine endothelium-dependent vasodilation in humans; however, the use of this technique poses some challenges. Thus, the purpose of this thesis was to explore new strategies to non-invasively determine the magnitude and dynamic adjustment of vascular responses in humans. Using near-infrared spectroscopy …

Comprehensive Topological, Geometric, And Hemodynamic Analysis Of The Rat Gluteus Maximus Arteriolar Networks, Mohammed K. Al Tarhuni

Electronic Thesis and Dissertation Repository

The objective of this thesis was to measure the geometric and topological properties of complete arteriolar networks within skeletal muscle, and to use these data as ideal inputs in a computational blood flow model in order to analyze the corresponding hemodynamic properties. Specifically, we sought to measure the levels of structural and hemodynamic heterogeneity exhibited within and between arteriolar networks. Intravital videomicroscopy was used to image and construct photomontages of complete arteriolar networks of the rat gluteus maximus muscle under baseline conditions. Arteriolar diameters, lengths, and inter-connections were analyzed and grouped according to a centrifugal ordering scheme. For all networks …

Temperature-Dependent Alterations Of Brown Adipose Tissue Metabolism During Hibernation In The Thirteen-Lined Ground Squirrel, Ictidomys Tridecemlineatus., Sarah V. Mcfarlane

Electronic Thesis and Dissertation Repository

Brown adipose tissue (BAT) is the major thermogenic tissue in small eutherian mammals. In hibernators, seasonal modifications of BAT are well documented but little is known about its functional regulation during hibernation. BAT metabolism is activated by sympathetic stimulation, so I hypothesized that further regulation at the mitochondrial level, as seen in other hibernator tissues, would be of little advantage. Contrary to my predictions, respiration rates of BAT mitochondria isolated from torpid thirteen-lined ground squirrels were suppressed by up to 62% compared with rates from individuals that aroused to interbout euthermia (IBE), when measured at 37°C. At 10°C, however, these …

Cardiovascular Characterization Of Cx40/Panx1 Single And Double Knockout Mice, Meghan L. Jelen

Electronic Thesis and Dissertation Repository

Connexins (Cxs) and pannexins (Panxs) are protein families that form large-pore channels which exist at the plasma membrane for both intracellular and extracellular signaling. Given their potential for overlapping cellular signaling functions we proposed that mice lacking both a connexin and a pannexin would have a severe phenotype. To investigate this possibility we crossed Panx1 null mice with Cx40 knockout mice and characterized the first global connexin/pannexin double knockout mouse. Intriguingly, the combined ablation of both Cx40 and Panx1 caused decreased prenatal and newborn survival, but did not affect the fertility or lifespan of surviving mice. Cx40^-/- and Cx40 …

Putative Pore-Lining Residues And Intracellular Magnesium Influence Connexin50 Unitary Gap Junction Channel Conductance, Swathy Sudhakar

Electronic Thesis and Dissertation Repository

Gap junction channels (GJs) are oligomers of connexins forming channels linking neighbouring cells. GJs formed by different connexins show distinct unitary channel conductance (γ_j), transjunctional-voltage dependent gating (V_j-gating) properties, and magnesium modulation. We investigate here how pore-lining residues may influence these GJ properties. We mutated putative pore-lining residues in Cx50 GJ (G8E/G46E/V53E individually or in combination) to investigate γ_j, V_j-gating, and magnesium modulation. GJs formed by combination mutants (G8E-G46E, G46E-V53E, and G8E-G46E-V53E) were functional and showed a significantly increased γ_j with little change in V_j-gating, while G8E-V53E mutants failed …

Photosynthetic Acclimation To Warming And Elevated Co2 In Two Antarctic Vascular Plant Species, Vi Nt Bui

Electronic Thesis and Dissertation Repository

Climate change can affect the performance of the only two vascular plant species found in Antarctica, Deschampsia antarctica and Colobanthus quitensis. I investigated the response of these two species to warming and elevated CO₂ in terms of photosynthesis and leaf anatomy. While photosynthesis increased directly with rising temperature and CO₂, it showed no acclimation to changes in growth temperature, and a small degree of acclimation to growth under elevated CO₂. Likewise, leaf anatomy displayed little plasticity in response to changes in the growth environment, although D. antarctica’s stomatal groove structure was modified under …

Gene Expression Microarray Data From Human Microvascular Endothelial Cells Supplemented With A Low Concentration Of Niacin, Nica M. Borradaile, Jennifer M. Hughes-Large

Physiology and Pharmacology Publications

The systemic lipid modifying drug, niacin, can directly improve human microvascular endothelial cell angiogenic function under lipotoxic conditions, possibly through activation of niacin receptors [1]. Here we provide accompanying data collected using Affymetrix GeneChip microarrays to identify changes in gene expression in human microvascular endothelial cells treated with 10 μM niacin. Statistical analyses of robust multi-array average (RMA) values revealed that only 16 genes exhibited greater than 1.3-fold differential expression. Of these 16, only 5 were identified protein coding genes, while 3 of the remaining 11 genes appeared to be small nuclear/nucleolar RNAs. Altered expression of EFCAB4B, …