Physiology Commons^™

Biomechanical And Psychophysical Underpinnings Of Balance Dysfunction In Individuals With Traumatic Brain Injury, Naphtaly Ehrenberg

Dissertations

Falls are a major burden on healthcare infrastructure, especially in older adults and even more so in older individuals that are living in institutions. According to data from the Centers for Disease Control and Prevention (CDC), from 2010 to 2020, unintentional falls were the leading cause of nonfatal emergency department visits for all age groups except among individuals from 15-24 years of age, where unintentional falls ranked a very close second to being unintentionally struck by or against. Among older individuals living in the community, approximately 30-35% fall at least once in a given year, and around three times as …

Distinct Roles For Free Fatty Acid Receptor 3 (Ffar3) In Vagal And Spinal Afferents Regulating Energy Balance And Glucose Homeostasis, Tyler M. Cook

Dissertations

energy balance, glucose homeostasis, gut-brain axis, microbiome, nutrient sensing, satiety

The Role Of Gut Microbiome And Scfa Butyrate In The Development Of Obesity Associated Pre-Hfpef, Jomana Hatahet

Dissertations

No abstract provided.

From Young To Old: The Effects Of Sedentary-Aging And Exercise Interventions On Structural Plasticity Of Lumbar Motor Neurons, Nmj, And Glial Cell Line-Derived Neurotrophic Factor Expression, Alberto Felipe Cintron-Colon

Dissertations

Neuromuscular weakness has been associated with age progression. A possible reason is a disconnection between muscle and neuron, causing components from both the central and peripheral nervous systems to deteriorate. Exercise, however, has beneficial effects for both muscle and nervous tissue, inducing neuroprotection. Neurotrophic factors are powerful regulators of neuronal maintenance and synaptic strength. Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor that has been shown to be a potent survival factor for somatic motor neurons that innervate skeletal muscle.

This study aims to evaluate changes in structural plasticity of motor neurons in the lumbar spinal cord and …

The Role Of Glycogen Synthase Kinase 3 Β (Gsk-3Β) At The Cardiac Myofilament, Marisa Jean Stachowski

Dissertations

Altered kinase activity and localization is gaining appreciation as a mechanism contributing to cardiovascular disease. Previous work suggests that the kinase glycogen synthase kinase 3 β (GSK-3β) regulates contractile function of the myofilament, but this work was performed in vitro. The goal of this work was to investigate GSK-3β’s in vivo role in regulating myofilament function, the mechanisms involved, and the translational relevance in disease. GSK-3β’s myofilament localization was confirmed in wild type mouse and human tissue via western blot of myofilament enriched tissue and immunofluorescence. These experiments also revealed that GSK-3β phosphorylated at Y216 binds to the z-disc. We …

Mechanisms Of Oscillations And Polyglot Entrainment In Neuronal And Circadian Models, Emel Khan

Dissertations

Entrainment is a type of synchronization in which the period of an endogenous oscillator matches the period of an external forcing signal and a stable phase relationship is maintained between them. Entrainment patterns are described in terms of the number of input oscillations (N) that are phase-locked to a number of output oscillations (M), referred to as N:M patterns. Arnold tongue diagrams are used to depict the regions of N:M entrainment patterns in the input period-amplitude parameter space. Although the entrainment of self-sustained oscillators by periodic forcing are well investigated is a well-studied problem, entrainment of damped oscillators has been …

The Role Of The Co-Chaperone Protein Bcl-2-Associated Athanogene 3 (Bag3) At The Cardiomyocyte Sarcomere, Thomas Gwynn Martin

Dissertations

The co-chaperone protein Bcl-2-associated athanogene-3 (BAG3) is a central mediator of cellular protein quality control through autophagy. In the heart, decreased BAG3 activity through mutation or decreased expression are linked to dilated cardiomyopathy (DCM). Unfortunately, though clinical data indicates BAG3 mutations are a definitive cause of DCM, few mechanistic studies had been performed to decipher the fundamental role of BAG3 in cardiomyocytes. However, several studies suggested BAG3 was involved in maintenance of the sarcomere, the molecular contractile structure in muscle cells. The goals of this dissertation were to: 1. Determine the functional significance of BAG3 for the sarcomere, 2. Identify …

Estrogen Regulation Of Mir-9-5p And Mir-9-3p Stability And Localization In The Aging Female Brain, Chun Kim

Dissertations

In females, levels of estrogens fluctuate across the lifespan and rapidly decline during menopause. Hormone replacement therapy (HRT) has been introduced as a clinical alternative to replenish systemic levels of 17β-estradiol (E2), the primary estrogen in circulation. However, studies from the Women's Health Initiative revealed a critical period immediately following the onset of menopause where HRT is efficacious. Here, we identified the differential regulation of miRNAs, small non-coding RNAs that inhibit translation, as a potential mechanism for this temporal switch in estrogen action. Specifically, early - but not late - E2 administration following ovariectomy in a rat model of menopause …

"Understanding Lgbtq+ Intimate Partner Violence & Challenges In, Dr. Juanita Yates

Dissertations

This research project is a focus on Intimate Partner Violence (IPV) within LGBTQ+

community and the challenges associated with seeking family support. IPV is defined as a violent

or aggressive behavior within the home, typically involving the violent abuse of an intimate spouse

or partner. However, IPV can happen on the street, in one’s home or even in a public place. Those

exposed to IPV can be children, men and women. IPV is a prevalent issue in our society (Bright

2008). According to Ristock (2005), violence in LGBTQ+ relationships may be referred to as

partner violence, relationship violence, or LGBTQ+ …

Examining The Combined Effects Of Dissolved Oxygen, Temperature, And Body Size On The Physiological Responses Of A Model Macrobenthic Polychaete Species, Capitella Teleta, Kelsey Burns Gillam

Dissertations

While the scientific community is in consensus that coastal systems are threatened by climate change, few climate change studies test the effects of more than one variable directly related to climate change. The dissolved oxygen (DO) levels of the ocean are currently subject to both global warming and eutrophication; 94% of all hypoxia zones are expected to experience >2°C increase by 2035. This dissertation aims to examine how a model organism responds to simultaneous thermal and DO stress involving four levels of DO (100%, 70%, 50%, and 20%) saturation and three temperatures (15°C, 20°C, and 25°C).

The polychaete, Capitella teleta …

The Effect Of Auditory Stimulation On Sleep Disruption In West Indian Manatee (Trichechus Manatus Latirostris), Natalija Lace

Dissertations

Florida manatees inhabit waterways where motorized boats are common. Although manatee mortalities resulting from boat strikes are well documented, the effect of boat noise on some manatee behaviors, including rest, has not been investigated. This study focuses on rest behavior and used a playback experiment with four manatees at the Lowry Park Zoo in Florida. We tested their responses to playback stimuli of either boat noise, silence, or manatee calls. A playback trial was initiated when the focal animal showed behavioral characteristics of rest.

Results showed that rest was interrupted in response to the playback of boat noise for each …

Transition Between Phases Of The Annual Cycle: Spring Migration To Breeding In Nearctic-Neotropical Songbirds, Kristen Marie Covino

Dissertations

Appropriate timing of each life-history stage is crucial for seasonally migratory species. The temporal constraints faced by migratory songbirds require that they overlap preparation for breeding with spring migration. However, previous work has focused primarily on male birds and has produced inconsistent results regarding the degree of overlap between these two life-history stages. I study the degree to which migrating male and female songbirds prepare for breeding throughout spring migration as they move towards their breeding grounds. Overall, male migrants show a significant degree of breeding preparation during spring migration as determined by circulating testosterone levels and their ability to …

Critical Role Of C-Jun N-Terminal Kinase Signaling In Binge Alcohol-Driven Atrial Arrhythmic Remodeling, Jiajie Yan Yan

Dissertations

Holiday Heart Syndrome (HHS) is cardiac arrhythmia induced by binge alcohol consumption, a drinking pattern affects 38 million adults in our society. Atrial fibrillation (AF) is the most frequently diagnosed arrhythmia in HHS and causes significant morbidity and mortality. Despite the intensive prevention effort nationwide, the binge drinking population keeps rising. However, no effective treatment strategies are available for binge drinking induced AF due to the unknown underlying mechanisms. In this thesis, I aim to elucidate the mechanisms of binge alcohol-promoted atrial arrhythmogenicity by using a mouse model of repeated binge alcohol exposure established in the Ai Lab.

The Ai …

The Amino Terminal Region Of Cardiac Myosin Binding Protein-C Is Necessary For Cardiac Function, Thomas Lawrence Lynch

Dissertations

Cardiac myosin binding protein-C (cMyBP-C) is a thick filament-associated protein that has been suggested to regulate cardiac contraction via its amino terminal (N’) region. Following ischemic injury to the heart, cMyBP-C is cleaved into a predominant N’ fragment consisting of domains C0 through C1 and the first 17 residues of the M-domain that is referred to as C0-C1f. However, the necessity of the N’-C0-C1f region of cMyBP-C in regulating cardiac function in vivo has not been elucidated. I hypothesized that the N’-C0-C1f region of cMyBP-C is critical for normal cardiac function in vivo. To test this hypothesis, transgenic (TG) mice …

Cardiac Calcium Atpase Dimerization Measured By Fluorescence Resonance Energy Transfer And Chemical Cross-Linking, Daniel Blackwell

Dissertations

The cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA) establishes the intracellular calcium gradient across the sarcoplasmic reticulum membrane. It has been proposed that SERCA forms homo-oligomers that increase the catalytic rate of calcium transport. We investigated SERCA oligomerization in rabbit left ventricular myocytes using a photoactivatable cross-linker. Western blotting of cross-linked SERCA revealed higher molecular weight species consistent with SERCA oligomerization. Fluorescence resonance energy transfer (FRET) measurements in cells transiently transfected with fluorescently-labeled SERCA2a revealed that SERCA readily forms homo-dimers. These dimers formed in the absence or presence of the SERCA regulatory partner, phospholamban (PLB) and were unaltered by PLB phosphorylation …

Regulation Of Micrornas By 17Β-Estradiol In The Aging Female Brain, Yathindar Satya Giffin-Rao

Dissertations

Hormone Therapy (HT) is used to increase the 17β-estradiol (E2) levels in women who are going through the menopausal transition to alleviate the negative symptoms associated with menopause and decrease the risk of chronic diseases. Clinical and basic science research had previously shown that HT provided protection from cognitive decline and reduced the risk of dementia. However the Women's Health Initiative (WHI) clinical trial demonstrated that HT had no beneficial effects for cognitive decline and, in some cases increased the risk of dementia in post-menopausal women. However, further analysis of WHI data showed that when HT was given to women …

L30a Mutation Of Phospholemman Mimics Effects Of Cardiac Glycosides On Isolated Cardiomyocytes, Ryan David Himes

Dissertations

In order to determine if mutations made to phospholemman (PLM) could increase PLM binding to the Na/K-ATPase (NKA) and cause positive inotropy we performed scanning mutagenesis of the transmembrane domain of PLM and measured FRET between each mutant and NKA. We observed increased binding to NKA for several PLM mutants compared to WT, including L27A, L30A, and I32A. In isolated cardiomyocytes, overexpression of WT PLM increased the amplitude of the Ca2+ transient compared to GFP control. Ca2+ transient amplitude was further increased by L30A PLM overexpression. L30A mutation also delayed Ca2+ extrusion and increased the duration of the cardiomyocyte contraction. …

Mechanisms Of Estrogen Receptor Alternative Splicing And The Consequences For Aging In The Female Brain, Cody Lee Shults

Dissertations

The advances in healthcare and scientific knowledge have resulted in longer life expectancies in women. These advanced ages in women now means that they are experiencing the effects of age-related changes in the body for much longer periods of time, mainly reproductive senescence, resulting in the loss of circulating ovarian hormones. The age at which menopause occurs has not changed, resulting in women now living over a third of their lives in a postmenopausal state.

The major circulating estrogen produced by the ovaries, 17β-estradiol (E2), has many homeostatic effects in the body like neuroprotection and cardioprotection. Hormone replacement therapy (HT) …

Haploinsufficiency Of Cardiac Myosin Binding Protein-C In The Development Of Hypertrophic Cardiomyopathy, David Barefield

Dissertations

Heart Failure is one of the leading causes of morbidity and mortality in the human population and represents a common endpoint for several diseases including inherited cardiomyopathies. Hypertrophic Cardiomyopathy (HCM) is characterized by left ventricular wall thickening, diastolic dysfunction, and sarcomere disarray. Mutations in sarcomeric protein encoding genes have been established as causative for HCM.

The gene MYBPC3, encoding cardiac myosin binding protein-C (cMyBP-C), is the second most commonly mutated gene in HCM cases. As a majority of these mutations have been determined to result in a null allele which does not produce any protein, it is thought that haploinsufficiency …

Functional Importance Of Oxidative Post-Translational Modifications Of Ryanodine Receptor In Cardiac Sarcoplasmic Reticulum Ca2+ Handling During Oxidative Stress, Stefan R. Mazurek

Dissertations

Free ionic calcium (Ca2+) plays an essential role as a second messenger that initiates muscle contraction in the heart. Ryanodine receptor (RyR2) acts as the primary Sarcoplasmic Reticulum (SR) Ca2+ release channel in the heart. In the event that intracellular SR Ca2+ handling is compromised, both the contractility and electrical excitability of the heart can be altered. As a consequence, heart function may not be able to maintain the necessary cardiac output to meet the metabolic demand of the body.

Increased oxidation of RyR2 has been implicated in abnormal Ca2+ handling that promotes the onset and progression of cardiovascular disease. …

Exercise Alters Glial Cell Line-Derived Neurotrophic Factor (Gdnf) Protein Content In The Spinal Cord, Monica Janine Mccullough

Dissertations

Neurotrophic factors may play a role in exercise-induced neuroprotective effects; however, it is not known if exercise mediates changes in glial cell line-derived neurotrophic factor (GDNF) protein levels in the spinal cord. The aim of the studies described herein was to determine if exercise alters GDNF protein expression in the lumbar spinal cord of healthy and diseased animals. The lumbar spinal cord was analyzed from adult rats aged 6-, 12-, 18- and 24-months, and from transgenic amyotrophic lateral sclerosis (ALS) mice and wild-type mice aged 3 months. Animals had undergone either forced wheel running, voluntary wheel running or swimming for …

Serine 910 Phosphorylation Of Focal Adhesion Kinase Is Critical For Costamere Assembly, Miensheng Chu

Dissertations

Tyrosine-phosphorylated FAK is required for the hypertrophic response of cardiomyocytes to growth factors and mechanical load, but the role of FAK serine phosphorylation in this process is unknown. Endothelin-1 (ET-1; 1-100nM, 2-30min) and other hypertrophic factors induced a time- and dose-dependent increase in FAK-S910 phosphorylation in neonatal rat ventricular myocytes (NRVM). FAK-S910 phosphorylation required ET_AR-dependent activation of PKCδ and Src via parallel Raf-1→MEK1/2→ERK1/2 and MEK5→ERK5 signaling pathways. Using co-immunoprecipitation, TIRF-microscopy and FRAP, ET-1 stimulation of NRVM expressing a nonphosphorylatable, S910A-FAK mutant decreased the interaction of paxillin and vinculin within costameres. This interaction was important in stabilizing α-actinin within …

Receptor-Mediated Hypertrophic Signaling Via Protein Kinase D And Histone Deacetylase 5 In Adult Myocytes, Chia-Wei Jenny Chang

Dissertations

Hemodynamic stress and neurohumoral signaling are common causes of cardiac hypertrophy. These extrinsic stress stimuli typically act on GPCR and induce a cascade of signal transduction to re-program terminally differentiated myocytes to grow in length or width. The compensatory hypertrophic response can enhance cardiac output briefly due to increased work load. However, prolonged stress results in maladaptive changes in the heart and gradually deteriorates ventricular function to supply blood throughout the body. Sustained hypertrophic signaling can also progress toward heart failure.

My dissertation research focuses on the hypertrophic signaling in adult cardiac myocytes in response to neurohumoral stimuli, ET-1 and …

An Investigation Of The Phospholamban-Serca Regulatory Interaction With Fluorescence Resonance Energy Transfer, Philip Adam Bidwell

Dissertations

With Fluorescence Resonance Energy Transfer (FRET), we are able to detect changes in the structure and affinity of the PLB-SERCA regulatory complex in live cells. Using this approach, we have detected a high level of PLB-SERCA interaction even at Ca2+ concentrations known to fully relieve PLB inhibition of SERCA, suggesting that dissociation is not required for relief of inhibition. We also detect no real-time change in PLB-SERCA binding over the course of a single Ca2+ transient in paced myocytes. The effect of Ca2+ on the PLB-SERCA interaction is best described as a reduced affinity with no change in the structure …

Expression And Regulation Of Osteopontin In The Diabetic Heart, Abigail Goodman

Dissertations

Diabetes leads to several alterations in cardiac structure, one of which is fibrosis of the ventricular myocardium. Myocardial fibrosis is a common underlying factor in most cardiac pathologies. Osteopontin (OPN) is a small phospho-protein that has been implicated in fibrotic tissue remodeling. In the heart, the expression of OPN protein is increased after acute and chronic pathologies. Upregulation of OPN coincides with a transition to heart failure and a direct role for OPN in the progression of diabetic cardiomyopathy to heart failure has been reported.

The overall objective of this project is to determine if OPN is upregulated in the …

Camkii-Mediated Phosphorylation Of The Inositol 1,4,5-Trisphosphate Receptor At Serine-150 Results In Decreased Channel Activity, Joshua Thomas Maxwell

Dissertations

One mechanism by which calcium is mobilized from intracellular stores is via the activation of inositol 1,4,5-trisphosphate receptors (InsP3Rs) by the second messenger, inositol 1,4,5-trisphosphate (InsP3). InsP3 is produced when certain factors bind to G protein-coupled receptors on the plasma membrane, causing activation of phospholipase C which cleaves InsP3 from its membrane tether, allowing InsP3 to diffuse through the cytoplasm to bind to its receptor. Activation of InsP3Rs leads to release of calcium into the cytoplasm of the cell, where it can activate a multitude of signal transduction cascades and a variety of local and global cellular events. One such …

Female Collegiate Gymnasts And Experiences In Sport Retirement Due To Injury, Coleen Harrington Barry

Dissertations

There has been very limited research on sport retirement concerning the experiences that female collegiate athletes face when retiring from a sport due to injury. The purpose of this qualitative study was to explore, understand, and describe experiences that former NCAA Division I female gymnasts had when they retired from gymnastics, part-way through college, due to injury. The main objective of the study was to attempt to understand female collegiate gymnasts' sport retirement experiences and the impact these experiences may have had on their identity development and college experience. The study also considered female collegiate gymnasts' perceived needs and coping …

Mapk Survival Signaling In Melanoma, Matthew W. Vanbrocklin

Dissertations

Extracellular signals activate mitogen-activated protein kinase (MAPK) cascades potentiating biological activities such as cell proliferation, differentiation, and survival. Constitutive activation of MAPK signaling pathways is implicated in the development and progression of many human cancers, including melanoma. Mutually exclusive activating mutations in NRAS or BRAF are found in ∼85% of all melanomas resulting in constitutive activation of the MAPK pathway (RAS-BRAF-MEK-ERK-RSK). We have previously demonstrated that inhibition of this pathway with small molecule MEK inhibitors selectively induces apoptosis in human melanoma cells both in vitro and in vivo, but not in normal melanocytes. These results support the notion that the …

Molecular Analysis Of The Effects Of Atrazine On Xenopus Laevis Frogs, Ronald Edward Celestine

Dissertations

Atrazine, the most commonly used herbicide in the U.S., has been implicated as one of the factors that may be causing the worldwide decline of amphibians. First, I examined effects of atrazine on laboratory raised Xenopus laevis tadpoles, treated from 5 days post fertilization to NF stage 65/66 with a concentrationof 25 ppb of atrazine. This study showed no significant difference in body weight, length and metamorphic rate.

Second, I used DNA microarrays to examine mRNA expression levels of genes in atrazine treated and control Xenopus laevis tadpoles. I found significant changes in gene expression levels of 18 genes. These …

Cloning And Characterization Of A Novel Ion Channel, Jung-Ha Lee

Dissertations

No abstract provided.