Physiology Commons^™

A Novel Role For Enos In Regulating Lymphatic Valve Development During Embryogenesis, Drishya Iyer

USF Tampa Graduate Theses and Dissertations

Lymphedema is a disease that occurs when lymph flow is impaired, resulting in tissue swelling, fibrosis, chronic inflammation and recurrent secondary infections. Lymphatic valves play a critical role in maintaining unidirectional lymph flow and evidence for valve defects have been reported in lymphedema patients. The lack of drugs that can correct lymphatic valve defects warrants a better understanding of the molecular regulators of lymphatic valve development and maintenance. Lymphatic valves first develop during embryogenesis in response to mechanotransduction signaling pathways triggered by oscillatory lymph flow. Since eNOS (gene name: Nos3) is a well characterized mechanotransduction signaling molecule in blood vessels, …

Atrial Fibrillation In Aging: Mechanisms And Potential Therapeutics, Mengmeng Chang

USF Tampa Graduate Theses and Dissertations

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias seen in the clinics, and currently available antiarrhythmic pharmacotherapies in AF are not very effective. Although AF has been recognized as an aging-mediated disease, our understanding of the electrophysiological pathways that link aging and AF remain incomplete, which limits breakthroughs in the development of novel antiarrhythmic treatments for this disease. Studies have shown that aging increases the generation of reactive oxygen species (ROS) in the heart, and high levels of ROS have been associated with development of AF in animals and patients. Additionally, in some forms of AF, the …

A Holistic Investigation Of Acidosis In Breast Cancer, Bryce Ordway

USF Tampa Graduate Theses and Dissertations

In the early 20th century, Nobel laureate Otto Warburg made the observation that cells of a carcinoma had considerably higher glycolytic metabolism and considerably lower oxidative metabolism compared to cells of a normal tissue. He postulated that within this observation was the key to deciphering the differences between malignant and normal tissue. It is now well established that tumors of the breast are unequivocally acidic, caused by an abnormal amount of aerobic glycolysis, colloquially known as the Warburg effect. Over the last decades, our group, led by Dr. Robert J. Gillies, has set out to characterize the causes and consequences …

The Effects Of Temperature And Oxygen Availability On Aerobic Performance In Three Coastal Shark Species; Squalus Acanthias, Carcharhinus Limbatus, And Carcharhinus Leucas, Alyssa M. Andres

USF Tampa Graduate Theses and Dissertations

Anthropogenically driven climate changes are altering marine habitats globally. Rising sea surface temperatures and coastal eutrophication, arising from global warming and coastal nutrient loading, have resulted in progressive ocean deoxygenation. This may restrict available habitat of marine organisms as studies suggest that the balance between metabolic oxygen demand and environmental supply plays an important role in limiting viable habitat and species fitness. As ectothermic predators, with temperature-dependent metabolism and high metabolic demands, coastal shark species may be susceptible to shifts in ocean temperature and oxygen. Such environmental changes may alter metabolic performance and ultimately success and survival within shark habitat. …

Phenotypic Variability In Ipsc-Induced Cardiomyocytes And Cardiac Fibroblasts Carrying Diverse Lmna Mutations, Jiajia Yang

USF Tampa Graduate Theses and Dissertations

Mutations in the LMNA gene (encoding lamin A/C) are the second most common cause of familial arrhythmogenic cardiomyopathy. Diverse LMNA variants in cardiomyocytes have been associated with cardiac phenotypes. Moreover, cardiac fibroblasts make up a large fraction of the myocardium's non-myocyte component, intrinsically linked to extracellular matrix synthesis and turnover as well as secreting large amounts of bioactive metabolites. However, our understanding of how different mutation sites and the non-myocyte niche mediate cardiomyocyte function is limited. To fill this gap, in this thesis I investigated the hypothesis that variable LMNA mutations have significant effects on the genetic, structure and electrophysiological …

Role Of Bmi1 In Acute Lung Injury, María Helena Hernández-Cuervo

USF Tampa Graduate Theses and Dissertations

Acute Lung Injury (ALI) is a set of signs and symptoms that lead to acute hypoxemic respiratory failure characterized by bilateral pulmonary infiltrates not attributed to cardiogenic origin. It is caused by a massive innate immune response, with the migration of white blood cells (neutrophils and macrophages principally) and a cytokine storm, followed by alterations in mitochondrial function, increase in reactive oxygen species production, and oxidative stress that in turn induces more mitochondrial damage. Several studies have shown that mitochondrial alterations are key events in the mechanism of ALI and reducing mitochondrial dysfunction could be a possible target in the …

Effects Of Exogenous Ketone Therapy On Performance, Cardiorespiration, And Seizure Genesis During Exposure To Hbo2 In The Sprague Dawley Rat, Nicole M. Stavitzski

USF Tampa Graduate Theses and Dissertations

Hyperbaric oxygen (HBO2) is used for clinical HBO2 therapy and in undersea and aerospace medicine. HBO2 is a humanmade extreme environment and protracted exposures can cause several adverse physiological effects on the body. For example, HBO2 increases the partial pressure of oxygen (PO2) in the body leading to redox stress. Redox stress is, in part, a cause of oxygen toxicity that manifests as seizures in its most severe form (central nervous system oxygen toxicity, CNS-OT). This dissertation focuses on strategies to be employed specifically for the warfighter breathing HBO2. Currently, the only way to prevent CNS-OT is to lower the …

Moving In Fluid: Exploring How Fishes Manipulate Water To Swim Efficiently, Nils B. Tack

USF Tampa Graduate Theses and Dissertations

Moving through a dense fluid such as water presents some unique challenges to minimizing energy use and maximizing performance (i.e., speed). Due to animal-fluid interactions during swimming (drag and thrust production) fish have evolved a variety of morphological structures and locomotor mechanisms. For instance, fish rely on body bending and/or fins to interact with the surrounding water such that energy can be transferred to generate thrust. Typically, this synergy promotes morphologies and behaviors aimed at enhancing propulsive efficiency and/or minimizing metabolic activity to lessen the cost of transport (COT). This work focuses on quantifying the energetic and hydromechanical benefits of …

Mitigation Strategies For Central Nervous System Oxygen Toxicity In Rodents: Ketone Metabolic Therapy And Mitochondrial Antioxidant Therapy, Christopher Manuel Hinojo

USF Tampa Graduate Theses and Dissertations

Hyperbaric oxygen (HBO2) is a frequently encountered condition in undersea medicine and hyperbaric oxygen therapy (HBOT). The risk of CNS oxygen toxicity (CNS-OT) seizures limits its use in hyperbaric medicine and limits bottom time for diving operations. In this study, we sought to understand the role of reactive oxygen species (ROS) in two mitigation strategies for CNS-OT; ketone metabolic therapy (KMT), which is known to delay onset of CNS-OT seizures, and mitochondria targeted antioxidant therapy (MitoTAT), which has never been tested under HBO2 conditions. We specifically focused on superoxide anions, one of the early reduction products of molecular oxygen, and …

Role Of Nhe3 In The Intestine And Thick Ascending Limb Of The Kidneys, Jianxiang Xue

USF Tampa Graduate Theses and Dissertations

The sodium-hydrogen exchanger isoform 3 (NHE3, SLC9A3) mediates most Na+/H+ exchange in the gastrointestinal tract and the kidney, where it plays crucial roles in Na+ and fluid absorption as well as acid-base homeostasis. Whole body NHE3 knockout (NHE3-/-) mice show overt absorptive defects in both the intestine and kidneys. Genetic mutations of NHE3 gene in humans are associated with congenital sodium diarrhea (CSD). In the kidneys, NHE3 is expressed in the proximal tubule (PT) and the thick ascending limb (TAL). Whole kidney-specific (PT and TAL) NHE3 knockout (NHE3Pax8cre) mice and PT-specific NHE3 knockout (PT-NHE3-/-) mice have shown the importance of …

A Study Of Trpa1 Activation Via Covalent Electrophilic Modification Of Cysteines, Thomas A. Parks

USF Tampa Graduate Theses and Dissertations

A subset of sensory nerves called nociceptors are stimulated by noxious stimuli and evoke nocifensive responses in different organ systems. Transient Receptor Potential Ankyrin 1 (TRPA1) is a tetrameric, nonselective, cation channel that initiates the generator potential that evokes afferent signaling in nociceptive nerves. TRPA1 is activated many harmful irritants, such as food chemicals, environmental pollutants, reactive oxygen species and other endogenous mediators. Most TRPA1 agonists have electrophilic properties, which covalently modify cysteine residues on the cytosolic side of the channel. Biochemical studies in our lab have identified four cysteines (C273, C621, C665, C1085) that rapidly bound iodoacetamide (irreversible electrophile); …

Metabolic Rate, Critical Oxygen Partial Pressure, And Oxygen Supply Capacity Of Farfantepenaeus Duorarum At Their Lower Thermal Limit, Alexandra L. Burns

USF Tampa Graduate Theses and Dissertations

Temperature and environmental oxygen availability affect oxygen supply and demand in ectotherms, which are hypothesized to control the geographic limits of many marine species. The oxygen supply capacity (α) is calculated from commonly measured metabolic traits, including the standard metabolic rate (SMR) and critical oxygen partial pressure at SMR (Pcrit). It may be used to estimate the metabolic capacity and aerobic scope across changes in temperature and oxygen partial pressures as α reflects adaptations of the cardiorespiratory system to meet maximum energy demands at a given oxygen partial pressure (PO2). In this study, α was measured for the Tampa Bay …

An Examination Of Changes In Muscle Thickness, Isometric Strength, And Body Water Throughout The Menstrual Cycle, Tayla E. Kuehne

USF Tampa Graduate Theses and Dissertations

Women are often excluded from research studies interested in changes in muscle size and strength due to confounding influence that the menstrual cycle may have on these variables. Although there is considerable data showing that strength may fluctuate throughout the menstrual cycle, the thesis that muscle size changes throughout the cycle is based on the premise that changes in body water throughout the menstrual cycle may influence the size of the muscle. Despite this suggestion there is no experimental data demonstrating that the menstrual cycle has any influence on muscle size. Purpose: The purpose of this study is to examine …

Targeting Cancer-Anorexia Cachexia Syndrome And Septic Inflammatory-Based Atrophy With R/S 1,3 Butanediol Acetoacetate Diester, Andrew P. Koutnik

USF Tampa Graduate Theses and Dissertations

Cancer anorexia cachexia syndrome (CACS) is a distinct atrophy disease negatively influencing multiple aspects of clinical care and patient quality of life. Although it directly causes 20% of all cancer-related deaths, there are currently no model systems that encompass the entire multifaceted syndrome, nor are there any effective therapeutic treatments. Here, we show that the VM-M3 mouse model of systemic metastasis demonstrates a novel, immunocompetent, logistically feasible, repeatable phenotype with progressive tumor growth, spontaneous metastatic spread, and the full multifaceted CACS with expected sex dimorphisms across tissue wasting. We also demonstrate that the ubiquitin proteasomal degradation pathway was significantly upregulated …

Functional Significance Of Endothelial Sigma-1 Receptors In Vascular Reactivity And Barrier Function, Zeinab Y. Motawe

USF Tampa Graduate Theses and Dissertations

The sigma-1 receptor (σ1) is a single 25 kD polypeptide that acts as a chaperone protein residing primarily in the endoplasmic reticulum Its interaction with mitochondria at the mitochondria-associated ER membrane domain is well-documented. Following activation, σ1 binds to the inositol trisphosphate receptor (Hayashi & Su), and modulates intracellular calcium homeostasis. Also, the activated σ1 modulates plasma membrane receptors and ion channel functions, and may regulate cellular excitability. Further, σ1 affects trafficking of lipids and proteins essential for neurotransmission, cell growth and motility. Activation of σ1 provides neuroprotection and cardio-protection in various models. Examples of neuroprotection include but not limited …

Investigating Student Conceptual Understanding Of Structure And Function By Using Formative Assessment And Automated Scoring Models, Kelli Patrice Carter

USF Tampa Graduate Theses and Dissertations

There has been a call from the national community of biologists and biology educators to increase biological literacy of undergraduate students, including understanding and application of core concepts. The structure and function relationship is a core concept identified by the wider biology community and by physiology faculty. Understanding of the core concept structure and function across multiple levels of organization may promote biological literacy. My research focused on the development of formative written assessment tools to provide insight into student understanding of structure and function in anatomy and physiology.

In chapter two I developed automated scoring tools to facilitate the …

Evaluation Of Novel Hemocompatible Surface Coatings For Extracorporeal Life Support: A Biocompatible Alternative To Systemic Anticoagulation, Teryn Rose Roberts

USF Tampa Graduate Theses and Dissertations

Extracorporeal life support (ECLS) is a class of technologies used to support or replace the function of failing organs. During ECLS, blood is withdrawn from systemic circulation and circulated through an artificial organ or “treatment membrane” that performs the function of the failing organ, prior to return to systemic circulation. While ECLS provides life-saving therapy to wide patient populations from pre-term infants to combat-wounded soldiers, this therapy is limited due to secondary thrombotic and bleeding complications that result from: 1) exposure of blood to the foreign surfaces in the device circuit and 2) administration of anticoagulant drugs to prevent clot …

Neutrophil Extracellular Traps And Vascular Barrier Injury, Jamie E. Meegan

USF Tampa Graduate Theses and Dissertations

Sepsis is a life-threatening inflammatory condition with high morbidity and mortality rates. Though improvements to diagnosis and management of sepsis have been made, the complexity of the disease process and an incomplete understanding of its endpoint mechanisms have prevented major breakthroughs for early diagnosis and treatment. Representing a common endpoint in a number of inflammatory injuries including sepsis, endothelial barrier dysfunction causes fluid leakage and leukocyte infiltration that leads to tissue damage and multiple organ failure. Therefore, elucidating mechanisms of endothelial barrier regulation is needed to further develop targeted therapies in inflammatory disease.

Sepsis is characterized by a hyperinflammatory response …

The Role Of Pulmonary Stretch Receptor Afferents In Swallow-Breathing Coordination: A Comparison Of Central Respiratory Rhythm Versus Mechanical Ventilation On Swallow In A Decerebrate Feline Model, Kofi-Kermit A. Horton

USF Tampa Graduate Theses and Dissertations

Swallowing is an essential motor act that coordinates the movement of food or saliva from the mouth through the pharynx and into the esophagus while protecting the upper airways from aspiration of those materials. Disordered swallowing, or dysphagia, results when bolus movement from the oropharyngeal phase into the esophageal phase is uncoordinated. Dysphagia directly causes or increases the risk of aspiration during swallowing in many clinical pathologies including Parkinson’s disease, Alzheimer’s disease, cerebrovascular incidents (stroke) in addition to being prevalent among the elderly population. The coordination between breathing and swallowing is mediated through the interaction of the swallow and respiratory …

Ecophysiology Of Oxygen Supply In Cephalopods, Matthew A. Birk

USF Tampa Graduate Theses and Dissertations

Cephalopods are an important component of many marine ecosystems and support large fisheries. Their active lifestyles and complex behaviors are thought to be driven in large part by competition with fishes. Although cephalopods appear to compete successfully with fishes, a number of their important physiological traits are arguably inferior, such as an inefficient mode of locomotion via jet propulsion and a phylogenetically limited means of blood-borne gas transport. In active shallow-water cephalopods, these traits result in an interesting combination of very high oxygen demand and limited oxygen supply. The ability to maintain active lifestyles despite these metabolic constraints makes cephalopods …

Glomerular Hyperfiltration And Hypertension In Diabetes, Jie Zhang

USF Tampa Graduate Theses and Dissertations

In the present study, we investigated the pathophysiological mechanisms of the hemodynamic alteration in diabetes. Glomerular hyperfiltration occurs in the early stage of diabetes mellitus and has been recognized to promote the pathogenesis of diabetic nephropathy. We determine the role of TGF response and the vascular tone of Af-Art in diabetic hyperfiltration and we found that 1) tubular high glucose directly activates NOS1 and increases NO generation in the macula densa, which inhibits TGF response and increases GFR; 2) high glucose dilates renal Af-Art through GLUT1 and mediated by NOS3-derived NO generation; 3) in diabetes, blunted TGF mediated by NOS1 …

Identifying New Treatment Options And Risk Factors For Type 2 Diabetes: The Potential Role Of Thymoquinone And Persistent Organic Pollutants, Shpetim Karandrea

USF Tampa Graduate Theses and Dissertations

Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, which develops as a consequence of peripheral insulin resistance and defective insulin secretion from pancreatic β-cells. A high calorie diet coupled with physical inactivity are known risk factors for the development of T2DM; however, these alone fail to account for the rapid rise of the disease. Recent attention has turned to the role of environmental pollutants in the development of metabolic diseases. PBDEs (polybrominated diphenyl ethers) are environmental pollutants that have been linked to the development of type 2 diabetes (T2D), however, the precise mechanisms are not …

The Interaction Of Scale And Temperature In Elastically Powered Movements, Jeffrey P. Olberding

USF Tampa Graduate Theses and Dissertations

For many animals, rapid movements place high power demands on underlying muscles. Storage of muscle energy in elastic structures and the subsequent rapid release of that energy can effectively amplify muscle power. Elastic recoil can also confer thermal robustness to performance in behaviors occurring at variable temperatures. Muscle contractile performance tends to decrease at lower temperatures, but elastic recoil is less affected by temperature. Here I examine the impacts of temperature and scale in systems using elastic recoil and I explore possible interactive effects on movement performance.

I explored the role that muscle contractile properties play in the differences in …

Acute Kidney Injury And Chronic Kidney Disease, Jin Wei

USF Tampa Graduate Theses and Dissertations

Ischemia and reperfusion are natural steps during kidney transplantation, and IRI is considered one of the most important nonspecific factors affecting allograft dysfunction. Transplanted organs experience several episodes of ischemia, in which cold ischemia occurs during allograft storage in preservation solutions.

Even though cold ischemia has been studied extensively, all of the studies have been carried out in vitro and ex vivo models. There is no in vivo model available to examine renal IRI induced solely by cold ischemia.

In the present study, we developed an in vivo mouse model to study renal IRI induced exclusively by cold ischemia through …

Hypercapnic Hyperoxia Increases Free Radical Production And Cellular Excitability In Rat Caudal Solitary Complex Brain Slice Neurons, Geoffrey Edward Ciarlone

USF Tampa Graduate Theses and Dissertations

The caudal solitary complex (cSC) is a cardiorespiratory integrative center in the dorsal medulla oblongata that plays a vital role in the central CO₂-chemoreceptive network. Neurons in this area respond to hypercapnic acidosis (HA) by a depolarization of the membrane potential and increase in firing rate, however a definitive mechanism for this response remains unknown. Likewise, CO₂-chemoreceptive neurons in the cSC respond to hyperoxia in a similar fashion, but via a free radical mediated mechanism. It remains unknown if the response to increased pO₂ is merely an increase in redox signaling, or if it’s the …

Cardiovascular Regulation By Kvβ1.1 Subunit, Jared Tur

USF Tampa Graduate Theses and Dissertations

Heterologous expression systems such as COS-7 cells have demonstrated the profound effects of KCNAB1-3 or Kvβ1-3 proteins on voltage gated potassium channels (Kv) channels. Indeed, in the presence of these β-subunits transiently expressed Kv channels are often modulated in multiple ways. Kv channel membrane expression is often increased in the presence of β-subunits. In addition, non-inactivating Kv currents suddenly become fast-inactivating and fast-inactivating channels become even faster. While much research has demonstrated the profound effects the β-subunits in particular the Kvβ1 subunit have on transiently expressed Kv currents little to date is known of the physiological role it may play. …

Sialylation And Cardiomyocyte Complex N -Glycosylation Protect Against Dilated Cardiomyopathy And Heart Failure, Wei Deng

USF Tampa Graduate Theses and Dissertations

Dilated cardiomyopathy (DCM) is the third most common cause of heart failure, often associated with arrhythmias and sudden cardiac death if not controlled. Metabolic and/or environmental factors, such as alcohol abuse, obesity, diabetes and Chagas disease, alter glycoprotein glycosylation, can lead to DCM. Inherited genetic disease, such as the human congenital disorders of glycosylation (CDG), causes multi-system manifestations including DCM. Non-congenital changes in glycosylation are also occurred in humans with and in animal models of DCM and heart failure. However, mechanisms responsible for glyco-dependent DCM are not understood. Here we sought to investigate the impact of sialylation and N-glycosylation …

Cardiovascular Effects Evoked By Airway Nociceptive Reflexes In Healthy And Cardiovascular Diseased Rats, Justin Shane Hooper

USF Tampa Graduate Theses and Dissertations

Acute inhalation of airborne pollutants alters cardiovascular function and has been shown to have its greatest affects on individuals with pre-existing cardiovascular disease. Evidence suggests that pollutant-induced activation of airway sensory nerves via the gating of ion channels is critical to these systemic responses. Here, we have investigated the cardiovascular responses evoked by inhalation of AITC (TRPA1 agonist) and capsaicin (TRPV1 agonist) in healthy Sprague Dawley (SD) and Wistar Kyoto (WKY) rats, and cardiovascular diseased Spontaneously Hypertensive (SH) rats. Inhalation of the agonists by healthy SD and WKY rats caused significant bradycardia, atrio-ventricular (AV) block and prolonged PR-Intervals. Inhalation of …

Modulation Of Whole Cell Currents In Human Neuroblastoma Cells Via The Hormone Aldosterone: An In Vitro Study, Harish Kumar Chittam

USF Tampa Graduate Theses and Dissertations

Ion channels play a critical role in maintaining homeostasis by moving various ions in and out of cells. The Na⁺-K⁺-2Cl^- or NKCC1 ion channel is involved in the regulation of Na⁺, K⁺, and Cl^- across cell membranes, and plays a key role in many forms of cellular physiology. In the cochlea, NKCC1 is involved in endolymph production and maintenance of the endocochlear potential. Our hypothesis is that blocking NKCC1 channels should directly impact auditory sensitivity causing hearing loss. Our lab has also shown that the hormone aldosterone (ALD) can upregulate …

Metabolic Therapy For Age-Dependent Impaired Wound Healing, Shannon Lynn Kesl

USF Tampa Graduate Theses and Dissertations

Chronic wounds represent an under-acknowledged socioeconomic epidemic, affecting 1.8 million new patients per year and costing the US health care system upwards of $25 billion annually. This substantial cost is rapidly growing due to a disproportionate occurrence in the ever-aging population. Key features associated with age-related impairment of wound healing include limited energy and nutrient exchange, unremitting inflammations, increased reactive oxygen species (ROS), and diminished blood flow. Most chronic wound therapies target specific molecular mechanisms; however, there are often multiple mitigating factors that prevent normal wound closure. This is likely one reason most wound therapies are minimally effective. In the …