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Theses/Dissertations

Physiology

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Full-Text Articles in Biomedical Engineering and Bioengineering

Friend Or Foe? The Role Of Transforming Growth Factor-Β (Tgfβ) Signaling In Calcineurin Inhibitor-Induced Renal Damage, Adaku Ume Jan 2023

Friend Or Foe? The Role Of Transforming Growth Factor-Β (Tgfβ) Signaling In Calcineurin Inhibitor-Induced Renal Damage, Adaku Ume

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With its incorporation into clinical practice in the early 1980s, the class of pharmacological agents known as calcineurin inhibitors (CNIs) quickly became the cornerstone of immunosuppressive therapy post-organ transplantation. However, its use is limited by irreversible kidney damage in the form of renal fibrosis. The molecular mechanism by which CNIs induce renal fibrosis remains to be better understood, and to date, there are no specific therapeutic strategies to mitigate this damage. This dilemma presents a critical need to explain mechanisms by which CNIs cause renal damage. Kidneys of patients on chronic CNI therapy show increased expression of the proinflammatory cytokine …


Friend Or Foe? The Role Of Transforming Growth Factor-Β (Tgfβ) Signaling In Calcineurin Inhibitor-Induced Renal Damage, Adaku Uwe Jan 2023

Friend Or Foe? The Role Of Transforming Growth Factor-Β (Tgfβ) Signaling In Calcineurin Inhibitor-Induced Renal Damage, Adaku Uwe

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With its incorporation into clinical practice in the early 1980s, the class of pharmacological agents known as calcineurin inhibitors (CNIs) quickly became the cornerstone of immunosuppressive therapy post-organ transplantation. However, its use is limited by irreversible kidney damage in the form of renal fibrosis. The molecular mechanism by which CNIs induce renal fibrosis remains to be better understood, and to date, there are no specific therapeutic strategies to mitigate this damage. This dilemma presents a critical need to explain mechanisms by which CNIs cause renal damage. Kidneys of patients on chronic CNI therapy show increased expression of the proinflammatory cytokine …


Acute Oxygen-Sensing By The Carotid Bodies : The Thermal Microdomain Model, Ryan Joseph Rakoczy Jan 2021

Acute Oxygen-Sensing By The Carotid Bodies : The Thermal Microdomain Model, Ryan Joseph Rakoczy

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The carotid bodies (CB) are peripheral chemoreceptors that detect changes in arterial oxygenation and, via afferent inputs to the brainstem, correct the pattern of breathing to restore blood gas homeostasis. Elucidating the “signal” that couples carotid body sensory type I cell (CBSC) hypoxic mitochondrial inhibition with potassium channel closure has proven to be an arduous task; to date, a multitude of oxygen-sensing chemotransduction mechanisms have been described and altercated (Varas, Wyatt & Buckler, 2007; Gao et al, 2017; Rakoczy & Wyatt, 2018). Herein, we provide preliminary evidence supporting a novel oxygen-sensing hypothesis suggesting CBSC hypoxic chemotransductive signaling may in part …


Altered Skeletal Muscle Excitation-Contraction Coupling In The R6/2 Transgenic Mouse Model For Huntington's Disease, Daniel R. Miranda Jan 2021

Altered Skeletal Muscle Excitation-Contraction Coupling In The R6/2 Transgenic Mouse Model For Huntington's Disease, Daniel R. Miranda

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Huntington’s disease (HD) has classically been categorized as a neurodegenerative disorder. However, the expression of the disease-causing mutated huntingtin gene in skeletal muscle may contribute to the symptoms of HD, namely those that involve involuntary muscle contraction. In the R6/2 transgenic mouse model of HD, we previously observed ion channel defects that could contribute to involuntary muscle contraction. Here, in R6/2 muscle we investigated the consequence of these ion channel defects on action potentials (APs), the first step in excitation-contraction (EC) coupling. We found that the ion channel defects were associated with depolarizing the baseline membrane potential during AP trains. …


Als-Induced Excitability Changes In Individual Motorneurons And The Spinal Motorneuron Network In Sod1-G93a Mice At Symptom Onset, Christiana S.I. Draper Jan 2021

Als-Induced Excitability Changes In Individual Motorneurons And The Spinal Motorneuron Network In Sod1-G93a Mice At Symptom Onset, Christiana S.I. Draper

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Amyotrophic lateral sclerosis (ALS) is the most common motorneuron (MN) disease in adulthood. ALS is hallmarked by the progressive loss of MNs in the brain, brainstem, and spinal cord. Many hypotheses to explain the pathogenesis of ALS have been explored, but the exact mechanisms underlying the development of this disease remain unknown. However, abnormalities in MN excitability and glutamate excitotoxicity are the most widely studied. For decades, researchers have examined MN excitability in ALS, but the current literature is inconsistent, showing evidence of hyperexcitability, hypoexcitability, or no change in excitability of MNs in ALS. Many of these studies also focus …


Altered Skeletal Muscle Excitation-Contraction Coupling In The R6/2 Transgenic Mouse Model For Huntington's Disease, Daniel R. Miranda Jan 2021

Altered Skeletal Muscle Excitation-Contraction Coupling In The R6/2 Transgenic Mouse Model For Huntington's Disease, Daniel R. Miranda

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Huntington’s disease (HD) has classically been categorized as a neurodegenerative disorder. However, the expression of the disease-causing mutated huntingtin gene in skeletal muscle may contribute to the symptoms of HD, namely those that involve involuntary muscle contraction. In the R6/2 transgenic mouse model of HD, we previously observed ion channel defects that could contribute to involuntary muscle contraction. Here, in R6/2 muscle we investigated the consequence of these ion channel defects on action potentials (APs), the first step in excitation-contraction (EC) coupling. We found that the ion channel defects were associated with depolarizing the baseline membrane potential during AP trains. …


Biomarker-Performance Associations During Nutritional And Exercise Intervention In Air Force Personnel, Jennifer Jurcsisn Jan 2019

Biomarker-Performance Associations During Nutritional And Exercise Intervention In Air Force Personnel, Jennifer Jurcsisn

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This study evaluated the combined effects of an exercise intervention and nutritional supplement on biomarkers of stress and resilience, and the relationships of those markers with physical and cognitive performance. 130 healthy Active-Duty Air Force (AF) personnel were recruited to participate in a double-blind, placebo controlled 12-week exercise and nutritional intervention. Serum was collected at basal and high stress conditions pre- and post-intervention to track the following biomarkers: cortisol, dehydroepiandrosterone-sulfate (DHEA-S), norepinephrine (NE), neuropeptide Y (NPY), and serotonin. The exercise intervention significantly attenuated the cortisol response and peak stress cortisol levels. The nutritional intervention decreased peak stress NE. The selected …


Context-Dependence Of Physiological Systems: Environment-Physiology Interactions In The Respiratory Control System, Joseph M. Santin Jan 2017

Context-Dependence Of Physiological Systems: Environment-Physiology Interactions In The Respiratory Control System, Joseph M. Santin

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We know that animals are tuned to survive different environmental conditions or else life would not exist. Unfortunately, this is often forgotten or ignored when designing experiments. As Marsh Tenney articulated, "The physiologist keeps the whole always in mind. He accepts the tactical necessity of reductionism to understand parts, but, once done, for him it is only the beginning, never the end” (from Remmers, 2005). In an era when it is all too common to take environmental complexity out of the organism to understand physiology, my work puts some of that complexity back in the study of organisms. I take …