Medicine and Health Sciences Commons^™

Target Validation And Pharmacological Characterization Of Novel Nmdar Modulators, Kiran Sapkota

Theses & Dissertations

The N-methyl-D aspartate receptors (NMDARs) are ligand-gated ion channels, which play important roles in learning and memory. Excessive activity of NMDARs is implicated in damage due to stroke and neurodegenerative diseases, whereas hypoactivity of NMDARs contributes to schizophrenia. The initial goal of my dissertation is to evaluate the potential role of the GluN2D-containing NMDARs in neuropathological, behavioral and cognitive alterations associated with schizophrenia and characterize the pharmacology and mechanisms of action of NMDAR modulators which could potentially be used to modulate these receptors in schizophrenia.

A subanesthetic dose of the NMDAR antagonist ketamine elicits symptoms of schizophrenia. This property led …

Inflammatory Gene Expression In Women Diagnosed With Polycystic Ovarian Syndrome, Myles K. Taylor

Electronic Theses & Dissertations

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The pathophysiology of PCOS has conventionally thought to originate from androgen excess. However, recent evidence suggests that androgen excess is a downstream consequence to inflammatory dysregulation and subsequent metabolic abnormalities. Inflammatory mRNA gene expression of TNFa and IL-1ß in mononuclear cells isolated from women diagnosed with PCOS was explored using qPCR. Additionally, the correlations between body mass index (BMI) and fasting glucose on mRNA expression of TNFa and IL-1ß were explored. mRNA expression of both TNFa and IL-1ß were found to be significantly higher in PCOS …

Follicular Dynamics In Insulin Resistant Mares, Julio Cesar Prado

Masters Theses

Obesity and insulin resistance have been linked to prolonged interovulatory period, aberrations in the estrous cycle, and continuous reproductive activity during the non-breeding season. EMS has been determined to influence the intrafollicular environment of mare ovaries. In humans, insulin resistance has been linked to polycystic ovaries as part of Polycystic Ovarian Syndrome (PCOS). A study was conducted to determine 1) the impact of insulin resistance on follicle growth and size at ovulation, and 2) whether predicted ovulatory follicles respond to hCG administration in Insulin-resistant (IR) mares. Mares were selected for the study based on insulin sensitivity and separated into an …

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 …

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 …

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. …

Novel Mechanisms Of Β-Adrenergic Signaling In Prostate Cancer Progression, Mohit Hulsurkar

Dissertations & Theses (Open Access)

Prostate cancer is the second leading cause of cancer death among American men. The American Cancer Society estimates that 180,890 men will be will be diagnosed with prostate cancer in 2016 in the USA. (http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-key-statistics). Androgen deprivation therapy (ADT) is the standard treatment for early stage prostate cancer. But most patients relapse with aggressive variants of prostate cancer, with survival time between 1-3 years. In order to develop cure for such aggressive variants of prostate cancer, our present understanding of the mechanisms underlying its progression needs to be advanced.

Recently, it has been found that activation of β-adrenergic signaling pathway …

The Role Of O-Glcnacase During Heart Failure., Sujith Dassanayaka

Electronic Theses and Dissertations

Global augmentation of protein O-GlcNAcylation occurs in response to a myriad of stressors and confers a survival advantage at the cellular level. This protective phenomenon has been demonstrated to mediate cardioprotection through various in vitro and in vivo studies during ischemia-reperfusion, myocardial infarction, and oxidative stress; however, relatively little is known of the regulation of protein O-GlcNAcylation. Protein O-GlcNAcylation is regulated by two antagonistic enzymes, namely, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Ablation of cardiomyocyte OGT, the enzyme that catalyzes the addition of O-GlcNAc to proteins, exacerbates cardiac dysfunction during infarct-induced heart failure (HF). However, little is known of the …

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 …

Tubulin Post-Translational Modifications Are Altered By Changes In Actin-Myosin Contractility In Non-Muscle Cells, James Mcgee

Honors Theses

All cells regulate their contractility by the interaction of actin and myosin. In non-muscle cells, however, this interaction is regulated by rho, a GTPase, which is the upstream effector for multiple pathways. Cell contractility increases when rho is active, and prior research has shown the depolymerization of microtubules (MTs) activates rho. Microtubules play a role in many cellular functions and it is thought that either associations with MT-associated proteins and/or post-translational modifications to tubulin regulate MT functions. Numerous post-translational modifications (PTMs) to microtubules have been identified, but their roles are not well understood. A possible relationship between changes in cell …

Mechanism Of Chimeric Vaccine Mediated Immune Suppression Of Human Dendritic Cells, Jacques Christian Mbongue

Loma Linda University Electronic Theses, Dissertations & Projects

Type 1 diabetes mellitus is a chronic inflammatory disease in which insulin producing β-cells of the pancreatic islets are killed by autoreactive cells of the immune system in response to a loss of tolerance. Dendritic cells (DC) interact predominantly with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this dissertation, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of …

The Effects Of Hypohydration On Neurocognitive, Balance, Vestibular Ocular Motor Functions And Mood State, Satoshi Iida

Graduate Theses and Dissertations

Inconsistent findings have been observed on the impact of hydration state on cognitive functions. The isolated effect of hypohydration on neurocognitive performance, balance, vestibular ocular motor function and mood outcomes in widely used concussion assessment tools has not been studied. The purpose of this study was to investigate how hypohydration affected the results in concussion testing batteries. A single-blind randomized crossover design was used. Thirteen healthy males (22 ± 4y, 180.9 ± 5.7cm) without history of concussion within the past six months or any condition or disease that could influence outcome measurements participated in this study. Each subject completed concussion …

Validation Of The Use Of Doubly Labeled Water For Measuring Metabolic Rate In Timber Rattlesnakes (Crotalus Horridus), Caitlin Hirsh

Biological Sciences Undergraduate Honors Theses

The doubly labeled water method is an isotopic technique for measuring field metabolic rate and water flux rates of free-living animals. We present a validation of the use doubly labeled water for measuring metabolic rate and water loss in Timber Rattlesnakes (Crotalus horridus). For this study seven animals of varying body size were used with masses ranging from 148 to 650 grams. Prior to dosing, blood samples were taken to establish background isotope levels for each animal. Snakes were injected with water enriched with isotopes of oxygen (18O) and hydrogen (2H, deuterium). The injected isotopes were then allowed to equilibrate …

The Effects Of Whole Body High-Intensity Interval Training On Collegiate Female Soccer Players 2016, Whitney Frary

Master's Theses

Soccer is considered a high intensity sport that requires a high level of both aerobic and anaerobic fitness. A whole body high-intensity interval training adaptation has been shown to benefit both of these systems over a short period of time. The purpose of this study was to examine the effects of a five week whole-body high intensity interval training program on female collegiate soccer players performance in speed, acceleration, agility, vertical jump, aerobic capacity, physical self perception, and physical enjoyment. Participants were from the SUNY Cortland women’s soccer team who participated in a five- week training protocol three days a …

Power Output And Loads On The Lumbar Vertebrae During A Power Clean 2016, Joseph Keleher

Master's Theses

The purpose of the present study was to compare the peak resultant torque, shear, and compressive forces acting at the L3/L4 junction of the lumbar vertebrae and the peak power output during 40% one repetition maximum (1RM) and 80% 1RM attempts of the power clean. It was hypothesized that performance of a power clean at 80% 1RM will result in greater peak resultant compressive force, torque and shear force at the L3/L4 junction of the lumbar spine than that of a 40% 1RM attempt. Power cleans at 80% 1RM will also result in higher maximum instantaneous power outputs than that …

Determining The Optimal Combination Of Lifting Method And Intensity For Power Production During The Hang Clean 2016, Thomas P. Murray

Master's Theses

The purpose of this study was to determine the optimal combination of lifting method and load intensity for power production during the hang clean. Twenty college students (18 male, 2 female) performed one set of three repetitions of the hang clean at four different intensities for each method while standing on a force platform embedded in the floor. Intensities were set at 50%, 60%, 70%, and 80% 1RM and the methods tested were Contact, where the participant maintained contact with the force platform throughout the lift, and Jump, where the participant jumped through the pull phase of the lift and …

The Thioredoxin Trx-1 Regulates The Major Oxidative Stress Response Transcription Factor, Skn-1, In Caenorhabditis Elegans, Katie C. Mccallum

Dissertations & Theses (Open Access)

The ability to respond to hostile environmental conditions is critical for the survival of an organism. Oxidative stress is an adverse state in which reactive oxygen species (ROS) accumulate to a harmful level and, if left unresolved, can lead to cellular dysfunction and organismal disease. Sophisticated detoxification systems, characterized by a battery of enzymatic antioxidants, are utilized to neutralize ROS thereby reducing stress. However, ROS are also purposefully produced by designated cellular enzymes to facilitate the signaling and regulation of critical physiological processes. Therefore, both the production and neutralization of ROS must be tightly controlled. Indeed, the expression of detoxification …

The Effect Of Descriptive Norms On Resistance Exercise Self-Efficacy In College-Aged Females 2016, Justin Kompf

Master's Theses

Resistance training is a form of physical activity that provides substantial health benefits. Despite these widespread benefits, participation in resistance training is considerably low, particularly among females. To engage in a skill-related activity such as resistance training, individuals need to have confidence in their abilities. Self-efficacy is a cognitive construct that is used to describe situation-specific self-confidence. Descriptive norms are a type of social norm that describes the behavior of others. Descriptive norms have been useful in positively changing health related behaviors. The exact mechanism of how descriptive norms alter behavior is unknown. However, it has been show in research …

Do Running Kinematics Change On The Alter-G Treadmill? [2016], Brittany Lavaute

Master's Theses

The Alter-G lower body positive pressure treadmill, also known as the antigravity treadmill, provides a unique means of exercising for rehabilitation patients and low-impact training in athletes. The purpose of this study was to examine the interaction effect of four different treadmill weighted conditions and three different running velocities (2.68 m.s-1, 3.13 m.s-1, and 3.58 m.s-1) on the kinematic variables of step length, step rate, contact time, and flight time on the Alter-G treadmill (AG) and on the regular treadmill (TM). Fifteen participants completed two separate days of testing. All individuals ran at four different conditions (100%, 80%, 60%, and …

Investigating The Role Of The Basic Helix-Loop-Helix Transcription Factor Mist1 In Pancreatic Diseases, Anju Karki

Open Access Dissertations

Acinar cells of the exocrine pancreas are dedicated to synthesize, package and secrete immense quantities of pro-digestive enzymes to maintain proper metabolic homeostasis for the organism. Dysregulation of enzyme secretion in acinar cells can give rise to exocrine diseases including acute pancreatitis (AP), a disease that targets acinar cells, leading to acinar-ductal metaplasia (ADM), inflammation and fibrosis—events that can transition into the earliest stages of pancreatic ductal adenocarcinoma (PDAC). The focus of this thesis is to interrogate transcriptional regulatory networks that are susceptible to AP and the role that these networks play in acinar cell and exocrine pancreas responses. The …

The Relationship Between Landing Error Scoring System-Real Time And Dorsiflexion Range Of Motion In Recreational Athletes, Hannah M. Twiddy

Human Movement Sciences & Special Education Theses & Dissertations

Participation in physical activity is important for overall health; however, lower extremity injuries are a major risk associated with physical activity. Injuries can lead to time away from physical activity and be associated with negative health consequences. The most common injuries are traumatic injuries to the knee and ankle; which may be related to poor landing mechanics and decreased range of motion. Previous research utilizing motion analysis systems have determined people with greater dorsiflexion range of motion (DROM) demonstrated smaller ground reaction forces and greater knee and hip flexion displacement while landing; indicating a softer landing strategy. The ability to …

The Effects Of Fitness Level And Sex On Epoc Following High Intensity Interval And Moderate Intensity Aerobic Exercise, Rachel Lauren Simmons

Human Movement Sciences & Special Education Theses & Dissertations

In the past few years, much attention has been directed toward shorter-duration vigorous intensity aerobic exercise as opposed to longer-duration moderate intensity exercise. There is conflicting evidence as to whether vigorous exercise can result in a greater excess post-exercise oxygen consumption (EPOC) and thus more calories burned when compared to moderate continuous exercise performed for a longer duration. In addition, the literature contains a dearth of information isolating and investigating male and female response to these exercises, as well as fit and unfit subjects. The purpose of this study was to quantify EPOC following moderate intensity aerobic exercise (MOD) and …

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 …

The Effects Of Two Different Resistance Training Protocols With Similar Volume On Muscular Strength, Muscle Thickness, And Fat-Free Mass, Cory Worthey

Theses and Dissertations

The manipulation of exercise volume, intensity, and order is associated with producing different musculoskeletal changes. These resistance training program variables affect mechanical tension and metabolic stress associated with resistance training, therefore affecting strength and hypertrophic outcomes. PURPOSE: The purpose of this study was to examine the effects of two different volume-equated total body exercise protocols over 9 weeks using compound exercises on muscular strength, muscle thickness, and fat-free mass. METHODS: Eight well-trained men were randomly assigned to a hypertrophy-style protocol (HG) performing 3 sets of 10 repetitions with 90 seconds rest between sets (n = 4) or a strength-style protocol …

The Effects Of Caffeine On Reaction Time Of Two Neurocognitive Tests, Kyle Petit

Theses and Dissertations

Context: A concussion is defined as a traumatically induced transient disturbance of the brain caused by a biomechanical force. These problematic injuries can prevent athletes from participating in physical activity for a number of days, weeks, or even months. Caffeine is known for improving mental alertness in everyday tasks and is found in many popular drinks such as, coffee, tea, energy shots, and even soda. Due to its increase in memory, mental alertness, and concentration, caffeine could potentially be utilized to improve the outcomes of post-concussion neurocognitive testing. This improvement would allow athletes to return to play before they have …

Mathematical Modeling Of Heart Rate Deflection Point In Relation To Respiratory Compensation And Treadmill Running Performance, Kayla Baker

Electronic Theses and Dissertations

Heart rate deflection point (HRDP), identified as the second breakpoint in the "intensity / heart rate" relationship, is indicative of the anaerobic threshold (AT). This point can be determined via bi-segmental linear regression (2SEG) or through use of the maximal distance model (D-max); however, the relationship between these methods has yet to be investigated 2. Purpose: To compare the use of 2SEG and D-max methods to determine HRDP and to examine the relationship between these values with a metabolic threshold, respiratory compensation point (RCP), as well as running performance [5,000 meter treadmill time trial (5Ktime)]. Methods: Nineteen recreationally active men …

The Reproducibility And Validity Of Using The Dmax Method To Predict Physical Working Capacity At Fatigue Threshold, Joshua Riffe

Electronic Theses and Dissertations

Although the original (ORG) physical working capacity at fatigue threshold (PWCFT) assessment has demonstrated strong reliability and sensitivity to training and/or nutritional interventions, limitations may exist regarding the method of PWCFT estimation. However, a relatively new mathematical method, called Dmax, has been shown to be objective and reliable when estimating metabolic and neuromuscular fatigue thresholds. To date, however, no study has examined whether the Dmax method for estimating the work rate at PWCFT is similar to the ORG method. PURPOSE: The purpose of this study is to evaluate the reliability and validity of the Dmax-EMG method for estimating and tracking …

Evaluation Of Echogenicity Within And Between Ultrasonographic Images Of The Vastus Lateralis, Alyssa Varanoske

Electronic Theses and Dissertations

PURPOSE: The purpose of this study was to examine the echo intensity (EI) values of different ultrasound (US) images of the vastus lateralis (VL) using panoramic imaging in the transverse plane (PTI) and still imaging in the longitudinal plane (SLI). Secondary purposes of this study were to examine VL homogeneity and to determine relationships between subcutaneous adipose tissue thickness (SubQ) adjacent to the muscle and EI. METHODS: Twenty-four recreationally trained collegiate males (20.2 ± 1.6 years; height: 178.1 ± 6.6 cm; weight: 82.2 ± 13.4 kg) participated in this investigation. EI, cross-sectional area (CSA), muscle thickness (MT), and SubQ of …

Calponin And Cytoskeleton Dynamics In Macrophage Functions And The Pathogenesis Of Atherosclerosis, Rong Liu

Wayne State University Dissertations

Arterial atherosclerosis is an inflammatory disease. Macrophages play a major role in the pathogenesis and progression of atherosclerotic lesions. Modulation of macrophage function is a therapeutic target for the treatment of atherosclerosis. Calponin is an actin-filament-associated regulatory protein that inhibits the activity of myosin-ATPase and dynamics of the actin cytoskeleton. Encoded by the Cnn2 gene, calponin isoform 2 is expressed at significant levels in macrophages. Deletion of calponin 2 increases macrophage migration and phagocytosis. In the present study, we investigated the effect of deletion of calponin 2 in macrophages on the pathogenesis and development of atherosclerosis. The results showed that …

Muscle Metaboreflex And Arterial Baroreflex: Action, Interaction And Altered Control In Heart Failure, Jasdeep Kaur

Wayne State University Dissertations

Stimulation of skeletal muscle afferents by metabolites that accumulate in the exercising muscle elicits a large pressor response, termed the muscle metaboreflex. Muscle metaboreflex activation during submaximal exercise induces large increases in arterial pressure, cardiac output, heart rate and ventricular contractility however, the vascular responses have varied in previous studies. We addressed three specific questions: 1) what are the mechanism(s) regulating the non-ischemic vasculature during muscle metaboreflex activation in normal subjects, 2) whether muscle metaboreflex activation vasoconstricts the ischemic active muscle from which this reflex originates and if this vasoconstriction is exaggerated in heart failure and 3) how do the …