Physiology Commons^™

Life-History And Energetics Of The Diamond-Backed Watersnake, Jeremy David Chamberlain

Theses and Dissertations

Life-history research explores how environmental variation and physiological constraints shift the energy allocation decisions to competing functions of the body among individuals and populations. Variation in the energy available across the environmental landscape is of particular interest as it dictates the amount energy available for organisms to acquire and allocate to their life-history. Additionally, individuals vary in their ability to capture and assimilate energy from the environment. This dissertation seeks to understand how environmental variation in energy availability and physiological constraints of attaining this energy shape allocation decisions among individuals and populations. I examined diamond-backed watersnakes (Nerodia rhombifer) from five …

Alterations In Tight Junctional Proteins And Their Effects On Pulmonary Inflammation, Joshua B. Lewis

Theses and Dissertations

The lungs represent one of the earliest interfaces for pathogens and noxious stimuli to interact with the body. As such, careful maintenance of the permeability barrier is vital in providing homeostasis within the lung. Essential to maintaining this barrier is the tight junction, which primarily acts as a paracellular seal and regulator of ionic transport, but also contributes to establishing cell polarity, cell-to-cell integrity, and regulating cell proliferation and differentiation. The loss of these tight junctions has been documented to result in alterations in inflammation, and ultimately the development of many respiratory disorders such as COPD, Asthma, ARDS, and pulmonary …

Lkb1 Regulation Of High-Fat Diet-Induced Adaptation In Mouse Skeletal Muscle, Ting Chen

Theses and Dissertations

Ad libitum high-fat diet (HFD)-induced obesity leads to insulin resistance in skeletal muscle, altered gene expression, and altered growth signaling, all of which contributes to pathological changes in metabolism. Liver kinase B1 (LKB1) is an important metabolism regulator. The purpose of this dissertation was to understand how knocking out LKB1 influences HFD induced adaptations in mouse skeletal muscle. To do so, control and skeletal muscle LKB1 knock-out (LKB1-KO) mice were put on either standard diet (STD) or HFD for 1 week or 14 weeks, or put on the HFD for 14 weeks and then switched to STD for 1 week …

Identification Of Expression And Function Of The Glucagon-Like Peptide-1 Receptor In Gastrointestinal Smooth Muscle, Alexander T. May

Theses and Dissertations

In response to ingestion of nutrients, enteroendocrine L cells secrete the incretin hormone, glucagon-like peptide-1 (GLP-1), to enhance glucose-dependent insulin release. Therapies related to GLP-1 are approved for type 2 diabetes. The GLP-1 receptor (GLP-1R) is expressed in cells of the gastrointestinal tract and elsewhere. In pancreatic beta cells, GLP-1R are coupled to the Gs/cAMP/PKA pathway. The expression and function of GLP-1R in gastrointestinal smooth muscle are not known. Aim. To test the hypothesis that GLP-1 regulates smooth muscle function by acting on GLP-1R expressed on smooth muscle. Methods. Smooth muscle cells (SMC) were isolated and cultured. Expression of GLP-1R …

N-Alkyl 4-Methylamphetamine Enantiomers And The Implication For Potential Modulation Of Abuse Liability And Enhancement Of Psychoactive Drug Targeting., Ramsey Sitta

Theses and Dissertations

Drugs of abuse have a long history in humanity. Currently however, a subject of great interest is the phenylalkylamine family of drugs. Not only is the abuse liability of interest but also the potential therapeutic expansion of the capabilities of this family of drugs by utilizing the unique stereospecific effects of the newly discovered hybrid compounds. Based upon prior data of N-Alkyl 4-MA the enantiomers of N-Methyl, N-Ethyl, and N-Propyl were analyzed in hDAT, hNET, and hSERT. It was found that there was a negative correlation between chain length and potency and dopaminergic component. In agreement with the currently established …

Hydrogen Sulfide Regulation Of Kir Channels, Junghoon Ha

Theses and Dissertations

Inwardly rectifying potassium (Kir) channels establish and regulate the resting membrane potential of excitable cells in the heart, brain and other peripheral tissues. Phosphatidylinositol- 4,5-bisphosphate (PIP2) is a key direct activator of ion channels, including Kir channels. Gasotransmitters, such as carbon monoxide (CO), have been reported to regulate the activity of Kir channels by altering channel-PIP2 interactions. We tested, in a model system, the effects and mechanism of action of another important gasotransmitter, hydrogen sulfide (H2S) thought to play a key role in cellular responses under ischemic conditions. Direct administration of sodium hydrogen sulfide (NaHS), as an exogenous H2S source, …

Po2 Dependence Of Oxygen Consumption In Skeletal Muscle Of Hypertensive And Normotensive Rats, Habiba Shah

Theses and Dissertations

Human essential hypertension affects over 75 million people in the United States, and can lead to death due to its several serious health complications such as hypertension-related cardiovascular disease. The purpose of this research was to understand how hypertension could cause physiological changes to the microcirculation, specifically the PO₂ dependence of oxygen consumption (VO₂) in skeletal muscle of normotensive and hypertensive rats. The Spontaneously Hypertensive Rat (SHR) strain was used as the diseased model, and Wistar-Kyoto (WKY) rats were used as controls to conduct this study. The SHR strain develops hypertension between 5-6 weeks after birth with …

Deletion Of Cardiac Mir-17-92 Cluster Increases Ischemia/ Reperfusion Injury Via Pten Upregulation, Meeta B. Prakash

Theses and Dissertations

The miR-17- 92 cluster is necessary for cell proliferation and development of the cardiovascular system. Deletion of this cluster leads to death in neonatal mice. The role of this cluster still needs to be defined following ischemia and reperfusion. Methods and Results: Adult male mice were injected with Tamoxifen- was to induce inducible cardiac-specific miR-17- 92-deficient (miR-17- 92-def: MCM:TG:miR-17- 92 flox/flox ) and wild type (WT: MCM:NTG:miR-17-92 flox/flox ) mice were subjected to 30 minutes of myocardial ischemia via left anterior descending coronary artery ligation followed by reperfusion for 24 hours. Post I/R survival (48%) and ejection fraction were reduced, …

The Role Of Human Msc Derived Exosomes In The Treatment Of Periodontal Diseases, Sonia S. Talegaonkar

Theses and Dissertations

Periodontal disease affects 47% of Americans over 30. Characterized by microbial dysbiosis and unregulated inflammation, severe periodontitis causes degradation of bone and soft tissue around teeth. Current treatments have limited regenerative outcomes and frequent reinfection by harmful bacteria. Human mesenchymal stem cells (hMSCs) have been shown to promote wound healing and tissue regeneration. Many therapeutic benefits of hMSCs are due to their secretome products, like exosomes. Our long-term goal is to develop periodontal therapies with hMSC exosomes. The objectives of this study were to determine the effect of hMSC-derived exosomes on cellular activity of hMSCs and investigate whether hMSC exosome …

Diabetes-Induced Expression And Regulation Of Glp-1 Levels By Bile Acid Receptors (Tgr5 & Fxr), Joseph R. Spengler

Theses and Dissertations

Diabetes Mellitus has continued to drastically affect the health of the world and many complications can prove fatal. As long as this metabolic disease persist, research discoveries will need to continue to be made so that patient outcomes and healthcare are dramatically enhanced. In recent years, GLP-1 has been the topic of conversation for diabetes research, due to its promising effects in promoting insulin sensitivity. Furthermore, bile acids and their receptors (TGR5 & FXR) have shown promise in their actions in the regulation of GLP-1, and thus glucose homeostasis. Here we have shown the detection and increased expression of TGR5 …

Hydrogen Peroxide And Pharmacological Agent Modulation Of Trpv2 Channel Gating, Tuoxin Cao

Theses and Dissertations

Transient receptor potential vanilloid 2 channel (TRPV2) is a Ca²⁺-permeable ion channel that is highly expressed in leukocytes but is also present in skeletal and cardiac muscle and endocrine cells. The TRPV2 function is implicated in a number of physiological processes, including bacterial phagocytosis, pro-inflammatory cytokine production, cardiac hypertrophy, and cancer development. TRPV2 knockout mice exhibit a high incidence of perinatal mortality, arguing that the channel plays essential roles in physiology. Despite the importance of TRPV2 for normal homeostasis, the mechanisms that control TRPV2 gating in response to pharmacological agonists, heating, membrane stretch, bioactive lipids and reactive oxygen …

Tissue Factor Expression, Regulation, And Signaling In Human Airway Cells, Michael D. Davis

Theses and Dissertations

Rationale: Tissue Factor (TF) is a transmembrane glycoprotein that canonically functions as the initiator of the coagulation cascade. Increased levels of TF have been associated with inflammatory airway diseases. Since lipopolysaccharide (LPS) is known to elicit and inflammatory response in airway epithelium, we hypothesized that airway epithelial cells release TF when exposed to LPS. Since TF aids in local wound healing, we also hypothesized that inhibition of TF would decrease NHBE growth. The specific aim of this work was to evaluate the effects of LPS exposure on TF production and release from airway epithelia and determine the signaling pathways involved. …

Po2 Dependence Of Oxygen Consumption In Skeletal Muscle Of Diabetic And Non-Diabetic Rats, Alexander C. Liles

Theses and Dissertations

Abstract

PO₂ DEPENDENCE OF OXYGEN CONSUMPTION IN SKELETAL MUSCLE OF DIABETIC AND NON-DIABETIC RATS

By: Alexander C. Liles

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at the Medical College of Virginia Campus, Virginia Commonwealth University

Virginia Commonwealth University, 2017

Advisor: Roland N. Pittman, Ph.D.

Department of Physiology and Biophysics

Type 2 diabetes mellitus (T2DM) is a major medical problem around the world, affecting nearly 6% of the world’s population. This study was an attempt to better understand physiological changes the disease may cause to the microcirculation and more specifically, to …

The Effects Of L-Cysteine On Alzheimer's Disease Pathology In Apoe2, Apoe3, And Apoe4 Homozygous Mice, Stephen Gerard Cieslak

Theses and Dissertations

The APOE gene is of profound importance regarding the onset of Alzheimer's disease (AD). From the small physical differences among the protein products of the isoforms of this gene arises a profound difference in their physiologies. For example, the APOE2 isoform confers resistance to AD, the APOE3 isoform confers neutral susceptibility to AD, and the APOE4 isoform confers proneness to AD. L-cysteine is an amino acid that has several anti-AD properties, among which are its ability to sequester iron and form glutathione – a powerful antioxidant – and therefore may be a promising potential dietary supplement for ameliorating AD …

Endocannabinoid-Mediated Synaptic Plasticity In The Ventral Tegmental Area And Hippocampus, Lindsey Nicole Friend

Theses and Dissertations

Synaptic plasticity is the process whereby connections between neurons can be altered in an experience dependent manner. For example, drugs of abuse alter plasticity in the ventral tegmental area (VTA) of the midbrain. A large amount of research has been applied to uncovering the mechanism whereby synapses on the reward signaling dopamine cells is altered, however, less is known regarding the VTA inhibitory GABA neurons. Our objective was to examine the ability of GABA neurons to exhibit plasticity, and determine how drugs of abuse could influence it. Here we report a novel type of plasticity of excitatory neurotransmission onto VTA …

Dopamine Effects Of Stimulant And Non-Stimulant Drugs Used In The Treatment Of Attention Deficit Hyperactivity Disorder, Preeti Chalwadi

Theses and Dissertations

Attention deficit hyperactivity disorder (ADHD) is thought to be associated with dysfunction of ascending catecholamine neuronal systems, particularly dopamine (DA) and norepinephrine (NE). Dysfunction of these catecholamine neurons innervating the prefrontal cortex is hypothesized to underlie impaired executive functions. Dysfunction of the DA neurons innervating the striatum is additionally hypothesized to underlie deficits in motivation and reinforcement learning. However, mechanisms of action of therapeutic drugs used for treating ADHD have mainly focused on catecholamines in the prefrontal cortex and have not adequately addressed the role played by DA signaling in the striatum. Stimulants such as Adderall® and Ritalin® are chemically …

Glutamate And Gaba Receptor-Mediated Plasticity In The Mesolimbic Dopamine System By Alcohol, Ashley Cerise Nelson

Theses and Dissertations

Alcoholism is a devastating chronic relapsing disorder with significant costs to individuals and society. The mesolimbic dopamine (DA) system plays an important role in regulating reward and addiction. GABA neurons located in the ventral tegmental area (VTA) regulate VTA DA neuron activity, and are a relevant target for alcohol in the brain. VTA GABA neurons exhibit marked hyperexcitability during withdrawal from ethanol. Past research has demonstrated that the motivational effects of opiates cause a change in VTA GABA(A) receptors in opiate-dependent animals, which switch from a GABA-induced hyperpolarization of GABA neurons to a GABA-induced depolarization. The focus of this study …

A Semi-Automated Algorithm For Segmenting The Hippocampus In Patient And Control Populations, Nathan Mckay Muncy

Theses and Dissertations

Calculating hippocampal volume from Magnetic Resonance (MR) images is an essential task in many studies of neurocognition in healthy and diseased populations. The `gold standard' method involves hand tracing, which is accurate but laborious, requiring expertly trained researchers and significant amounts of time. As such, segmenting large datasets with the standard method is impractical. Current automated pipelines are inaccurate at hippocampal demarcation and volumetry. We developed a semi-automated hippocampal segmentation pipeline based on the Advanced Normalization Tools (ANTs) suite of programs to segment the hippocampus. We applied the semi-automated segmentation pipeline to 70 participant scans (26 female) from groups that …

Metabolic Limits And Adaptation In Humans: Daily Energy Expenditure In Race Across The Usa Athletes, Caitlin Thurber

Theses and Dissertations

A longitudinal doubly labeled water study of total energy expenditure (TEE) in Race Across the USA athletes, examining the effects of extremely high levels of activity on metabolic adaptation.

Total Energy Expenditure In Captive Sapajus Apella, Wren Edwards

Theses and Dissertations

Primates expend approximately 50% less energy (kcal/day) for their body size than other eutherians. Using the doubly labeled water method, I investigated total energy expenditure (TEE) and physical activity in Sapajus apella. S. apella TEE was similar (p=0.67) to other platyrrhines, but 54% lower than expected for body mass.

An Evaluation Of The Influences Of Extra-Hippocampal Processes On Pattern Separation, Malia L. Anderson

Theses and Dissertations

Long-term declarative memory depends on pattern separation, which reduces the degree of overlap between similar representations, to maintain memory specificity, and on pattern completion, which occurs when a degraded cue is used to retrieve a previously stored memory. Previous studies aimed at evaluating the underlying neuronal substrates of these computational processes have used a mnemonic discrimination paradigm and fMRI to focus on the hippocampus, to the exclusion of cortical processing. We aim to investigate the influences extra-hippocampal processes have on pattern separation in the following two studies. Study 1. Computational models of pattern completion suggest it occurs cortically and results …

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 …

The Role Of Hypoxia On Pyruvate Kinase M2, Mammalian Target Of Rapamycin, Mitochondrial Function, And Cell Invasion In The Trophoblast, Rebecca Lutz Kimball

Theses and Dissertations

This thesis will be organized into two chapters discussing the role of hypoxia in the human placenta. The goal of this thesis is to characterize pyruvate kinase M2, mammalian target of rapamycin, mitochondrial function, and cell invasion in hypoxic conditions in the trophoblast. Understanding the mechanisms of placental metabolism can lead to further treatments for placental diseases. Chapter one covers the background of intrauterine growth restriction, hypoxia, placental metabolism, and pyruvate kinase M2 (PKM2). Little is currently understood about the role of the mitochondria in placental diseases. Expression of PKM2, trophoblast cell invasion, and mitochondrial function is shown to be …

A Neuroimaging Investigation Of The Effects Of Age And Sleep On Pattern Separation, Christopher Robert Doxey

Theses and Dissertations

Effective memory representations must be specific to prevent interference between episodes that may overlap in terms of place, time, or items present. Pattern separation, a computational process performed by the hippocampus overcomes this interference by establishing non-overlapping memory representations. This project explores pattern separation and how it is impacted by age and sleep. Experiment 1. Structures of the medial temporal lobe (MTL) are known to be involved in declarative memory processes. However, little is known about how age-related changes in MTL structures, white matter integrity, and functional connectivity affect pattern separation processes in the MTL. In the present study, we …

Rab8 Mediates Trpv4 Vesicle Trafficking To The Plasma Membrane In Hgf-Stimulated Mdck Cells, Hillary Jean Haws

Theses and Dissertations

Epithelial to mesenchymal transition (EMT) is a process whereby epithelial cells, which act collectively through robust cell–cell interactions, take on mesenchymal characteristics, breaking cell–cell junctions to become solitary, invasive and motile. Our previous results show that a transient increase in calcium influxes through TRP channels at the plasma membrane is required for hepatocyte growth factor (HGF)– stimulated EMT. Since this transient increase requires an intact microtubule cytoskeleton, we propose that HGF stimulation results in the mobilization of calcium channels to the plasma membrane from an intracellular compartment via microtubule–dependent vesicle trafficking. Through immunofluorescence, we show that prior to HGF treatment, …

Forward Chemical Genetics Drug Screen Yields Novel Proteases And Proteolytic Inhibitors Of Hgf–Induced Epithelial–Mesenchymal Transition, Jeffrey Thomas Schuler

Theses and Dissertations

Hepatocyte Growth Factor (HGF)–induced Epithelial–Mesenchymal Transition (EMT) is a complex cellular pathway that causes epithelial cell scattering by breaking cell–cell contacts, eliminating apical–basal polarity, and replacing epithelial markers and characteristics with mesenchymal markers. Early EMT events include a brief period of cell spreading, followed by cell compaction and cell–cell contact breaks. A forward chemical genetics drug screen of 50,000 unique compounds measuring HGF–induced cell scattering identified 26 novel EMT inhibitors, including 2 proteolytic inhibitors. Here, we show that B5500–4, one of the EMT inhibitors from the screen, blocks HGF–induced EMT by a predicted blocking of the protease furin, in addition …

Identification And Characterization Of Serum Biomarkers Associated With Breast Cancer Progression, Adhari Abdullah Alzaabi

Theses and Dissertations

Despite the recognized advances in the treatment of breast cancer, it still accounts for 15% of all cancer-related deaths. 90% of breast cancer deaths are due to unpredicted metastasis. There is neither successful treatment for metastatic patients nor a specific test to predict or detect secondary lesions. Patients with primary tumor will be either over-treated with cytotoxic side effects or under-treated and risk recurrence. This necessitates the need for personalized treatment, which is hard to offer for such heterogeneous disease. Obstacles in treating breast cancer metastasis are mainly due to the gaps exist in the understanding of the molecular mechanism …

A Mechanistic Study Of An Ipsc Model For Leigh’S Disease Caused By Mtdna Mutataion (8993 T>G), John P. Galdun

Theses and Dissertations

Mitochondrial diseases encompass a broad range of devastating disorders that typically affect tissues with high-energy requirements. These disorders have been difficult to diagnose and research because of the complexity of mitochondrial genetics, and the large variability seen among patient populations. We have devised and carried out a mechanistic study to generate a cell based model for Leigh’s disease caused by mitochondrial DNA mutation 8993 T>G. Leigh’s disease is a multi-organ system disorder that depends heavily on the mutation burden seen within various tissues. Using new reprogramming and sequencing technologies, we were able to show that Leigh’s disease patient fibroblasts …

The Effect Of Pre-Deployment Physiology As A Predictor Of Post-Traumatic Stress Disorder Among A Sample Of United States Army National Guard And Reserve Soldiers, David J. Rothman

Theses and Dissertations

Potential risk factors for development of Post-Traumatic Stress Disorder (PTSD) are still unclear. One potential risk factor for the development of PTSD is an individual’s cardiovascular reactivity and recovery in response to stressor tasks. The current study was conducted with 763 Army National Guard and Army Reserve soldiers. Participants completed a stressful induction along with self-report measures prior to deployment. Post-deployment, self-report measures were completed to assess PTSD symptomatology and experiences related to deployment and combat. Multiple regression was used to determine the ability of blood pressure response to stress to predict PTSD symptoms immediately and one-year after return from …