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Full-Text Articles in Physiology

The Effect Of Oatp2b1-Mediated Statin Transport On Beta Cell Dysfunction, Jihoon Kwon Oct 2022

The Effect Of Oatp2b1-Mediated Statin Transport On Beta Cell Dysfunction, Jihoon Kwon

Electronic Thesis and Dissertation Repository

Statins are a class of cholesterol-lowering drugs which work by inhibiting the mevalonate pathway. Statin treatment has been linked to an increase in the risk of new-onset diabetes mellitus, and previous studies have suggested impairment in insulin secretion following statin treatment. Recent work from our laboratory confirmed the expression of organic anion transporting polypeptide 2B1 (OATP2B1), an important statin uptake transporter, in human pancreatic beta cells. Our study examined the role of OATP2B1 in statin-associated beta cell toxicity using INS-1 cells as a beta cell model. We showed that OATP2B1 augments cellular accumulation of rosuvastatin and atorvastatin, but not pravastatin. …


Prefrontal Coding Of Naturalistic Working Memory: Mechanisms During Normal Maintenance And Modelled Disease, Megan P. Roussy Aug 2022

Prefrontal Coding Of Naturalistic Working Memory: Mechanisms During Normal Maintenance And Modelled Disease, Megan P. Roussy

Electronic Thesis and Dissertation Repository

Neural activity in the primate lateral prefrontal cortex (LPFC) has been causally linked to working memory (WM) ⁠— the brief maintenance and mental manipulation of information. Primates use WM to perform tasks in complex contexts; however, neural mechanisms of WM and the pathophysiology related to WM deficits have traditionally been studied using simple tasks that deviate from naturalistic conditions. This raises the question, how is WM processed in naturalistic conditions? To explore this, I trained two macaque monkeys on a spatial WM task set in a naturalistic virtual environment. During the task, a target was presented in 1 of 9 …


The Effect Of Breathing Patterns Common To Competitive Swimming On Gas Exchange And Muscle Deoxygenation During Heavy-Intensity Fartlek Exercise, Kevin J. Grossman May 2022

The Effect Of Breathing Patterns Common To Competitive Swimming On Gas Exchange And Muscle Deoxygenation During Heavy-Intensity Fartlek Exercise, Kevin J. Grossman

Electronic Thesis and Dissertation Repository

The purpose of this study was to compare the respiratory and muscle deoxygenation (HHb) responses of regulated breathing versus free-breathing, during continuous exercise (CONLD) and intermittent 5s breath holds (BH) (CONLD-BH), intermittent 5s sprint (FLK) and combined 5s BH and sprint (FLK-BH) followed by 25s of free-breathing. Oxygen uptake(V̇O2)was unchanged between CONLD (2.12±0.35L/min) and CONLD-BH (2.15±0.42L/min; p=0.116), and FLK (2.24±0.40L/min) and FLK-BH (2.20±0.45L/min; p=0.861). Δ[Hbtot]: CONLD (3.3±1.6µM) > CONLD-BH (-2.5±1.2µM; ∆177%; p<0.001), but unchanged between FLK (2.0±1.6µM) and FLK-BH (0.82±1.4µM; p=0.979). Δ[HHb]: CONLD (7.3±1.8µM) > CONLD-BH (7.0±2.0µM; ∆4%; p=0.011), and FLK (6.7±1.8µM) < FLK-BH (8.7±2.4µM; p<0.001). It is suggested that the unchanged V̇O2 between CONLD and CONLD-BH was supported by increased deoxygenation, reflected by decreased ∆[Hbtot] and blunted …


Biochemistry Of Trehalose Accumulation In The Spring Field Cricket, Gryllus Veletis, Alyssa R. Stephens May 2022

Biochemistry Of Trehalose Accumulation In The Spring Field Cricket, Gryllus Veletis, Alyssa R. Stephens

Electronic Thesis and Dissertation Repository

The freeze tolerant spring field cricket, Gryllus veletis, accumulates trehalose in the blood and tissues during cold acclimation. Trehalose is the main blood sugar in insects, thus its blood concentration is tightly regulated, and trehalose is readily metabolized. How do crickets modify their metabolism to accumulate trehalose in their hemolymph and tissues? I hypothesized that trehalose production, transport, and consumption were modified during the cold acclimation to facilitate trehalose accumulation. Trehalose and the trehalose-specific transporter, TRET-1, are distributed among all tissues, and trehalose accumulates in the hemolymph, fat body, Malpighian tubules, and gut. Trehalose production increases during cold acclimation …


The Hydrophobic Residues In Amino Terminal Domains Of Cx46 And Cx50 Are Important For Their Gap Junction Channel Ion Permeation And Gating, Roa'a Jaradat May 2022

The Hydrophobic Residues In Amino Terminal Domains Of Cx46 And Cx50 Are Important For Their Gap Junction Channel Ion Permeation And Gating, Roa'a Jaradat

Electronic Thesis and Dissertation Repository

Connexins are ubiquitous transmembrane proteins that assemble to form intercellular channels, called gap junctions (GJs). The amino terminal (NT) domain and residues within this domain have been shown to be important for both Vj-gating and single channel conductance (γj) of several GJs including Cx46 and Cx50. High-resolution structures of Cx46 and Cx50 GJs were recently resolved showing that NT domain folds into the inner pore where hydrophobic residues are packed against M1/2 domains stabilizing open-state conformation. We studied functional properties of GJs formed by several point variants at NT (Cx46 L10I, N13E, A14V, Q15N and Cx50 …


Increased Corticospinal Inhibition Following Submaximal And Maximal Muscle Activation In Humans, Alexander D. Paish Apr 2022

Increased Corticospinal Inhibition Following Submaximal And Maximal Muscle Activation In Humans, Alexander D. Paish

Electronic Thesis and Dissertation Repository

Following short duration, high intensity muscle activation, there is an enhancement of muscle contractile properties, termed postactivation potentiation (PAP). Corticospinal inhibition, assessed by an increased silent period (SP), was shown previously to increase following voluntary or electrically evoked PAP. Although these changes coexist, the direct effect of PAP on corticospinal inhibition has not been systematically evaluated. In 10 participants, SP duration was measured pre and post 10s maximal and submaximal, voluntary and electrically stimulated contractions. Following maximal contractions, mean twitch torque was enhanced ~180% with no enhancement at submaximal levels (~102%). The SP duration was prolonged following all conditions: ~12% …


The Impact Of Excess Nutrients, Fatty Acids Or Glucose, On Bewo Placental Trophoblast Metabolic Function, Zachary Jw Easton Apr 2022

The Impact Of Excess Nutrients, Fatty Acids Or Glucose, On Bewo Placental Trophoblast Metabolic Function, Zachary Jw Easton

Electronic Thesis and Dissertation Repository

An adverse intrauterine environment high in circulating nutrients in pregnancies complicated by maternal obesity and diabetes mellitus has been well linked with the development of metabolic health disorders in the exposed offspring. Impairments in placental development, mitochondrial respiration, and nutrient processing are thought to specifically underlie the in-utero programming of these metabolic diseases. In these “at-risk” pregnancies a maternal diet high in fat as well as poor glycemic control have been highlighted to be important regulators of placental metabolic functions (including the transport, storage, and oxidation of dietary nutrients), and consequently regulators of offspring metabolic health outcomes. However, the independent …


Collagen Iv-Β1integrin Regulation Of Exocytotic Machinery In Pancreatic Beta-Cell Insulin Secretion, Malina Barillaro Mar 2022

Collagen Iv-Β1integrin Regulation Of Exocytotic Machinery In Pancreatic Beta-Cell Insulin Secretion, Malina Barillaro

Electronic Thesis and Dissertation Repository

Diabetes is a prevalent metabolic disease characterized by impaired insulin secretion, action, or both. β1-integrin is a key receptor that regulates cell-ECM interactions and is important in maintaining beta-cell functions, including insulin secretion. However, little is reported about the relationship between β1-integrin and the exocytotic proteins involved in insulin secretion. This study examined the influence of ECM-mediated β1-integrin activation on exocytotic machinery involved in insulin secretion using rat insulinoma (INS-1) cells. Collagen IV (COL IV) promoted INS-1 cell adhesion, spreading, and insulin secretion. Additionally, these cells displayed changes in levels and localization of exocytotic proteins involved in insulin secretion. β1-integrin …


Temperature-Dependent Developmental Plasticity In The Cardiorespiratory System Of Atlantic Salmon, Carlie A. Muir Mar 2022

Temperature-Dependent Developmental Plasticity In The Cardiorespiratory System Of Atlantic Salmon, Carlie A. Muir

Electronic Thesis and Dissertation Repository

Anthropogenic climate change is expected to have pervasive impacts on the performance and viability of fishes, as increasing temperatures create aerobically constrained environments for many species. Given the rapid rates of projected temperature increases, it is critical to evaluate the capacity for fish to respond to a changing thermal environment through phenotypic plasticity. In this thesis, I examined the capacity for developmental plasticity in the thermal performance of juvenile Atlantic salmon (Salmo salar) reared under two thermal regimes from fertilization, and investigated potential mechanistic underpinnings within the cardiorespiratory system. Cardiac performance was examined using a noninvasive Doppler echocardiograph …


Mechanisms Of Diapause And Cold Tolerance In The Colorado Potato Beetle, Jacqueline E. Lebenzon Jan 2022

Mechanisms Of Diapause And Cold Tolerance In The Colorado Potato Beetle, Jacqueline E. Lebenzon

Electronic Thesis and Dissertation Repository

Many temperate insects enter diapause (a state of dormancy) and enhance their cold tolerance to survive the winter. During diapause, the Colorado potato beetle (CPB, Leptinotarsa decemlineata, Coleoptera: Chrysomelidae) stops developing, lowers its metabolism, and changes its physiology to avoid freezing. The extent to which diapause confers cold tolerance in CPB is currently unknown. In my thesis, I used CPB to improve our understanding of the mechanisms underlying metabolic suppression during diapause and cellular protection at sub-zero temperatures in insects. First, I used RNA-sequencing (RNA-seq) to compare gene expression in two metabolically important tissues (the fat body and flight muscle) …