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Articles 61 - 90 of 186

Full-Text Articles in Physiology

Mitochondrial Therapeutics During Ischemia-Reperfusion; Modulation Of Complex I: Effect Of Metformin., Shawn Y. Sunu Jan 2015

Mitochondrial Therapeutics During Ischemia-Reperfusion; Modulation Of Complex I: Effect Of Metformin., Shawn Y. Sunu

Theses and Dissertations

The modulation of the electron transport during ischemia-reperfusion has been shown to be protective. We hypothesized that metformin, a Complex I inhibitor, may exhibit characteristics of a pharmacological agent that could achieve long-term therapeutic intervention against ischemia-reperfusion injury. Mitochondria were harvested from adult male mice and incubated with or without metformin at 30oC for 15 minutes, while being shaken at 300 rpm. Metformin decreased Complex I oxidative phosphorylation and Complex I activity. However, metformin also increased injury and decreased the maximum membrane potential. Even though there was a decrease in maximum membrane potential, the proton motive force (PMF) …


Increased Circulatory Lipopolysaccharide From A High Fat Diet Aggravates Inflammation And Exacerbates Renal Failure, Samuel Righi Apr 2014

Increased Circulatory Lipopolysaccharide From A High Fat Diet Aggravates Inflammation And Exacerbates Renal Failure, Samuel Righi

Theses and Dissertations

Kidney failure is frequently associated with the risk factors linked to metabolic syndrome. Lipopolysaccharide (LPS) is a potent inflammatory molecule, which has increased absorption from the gut into blood circulation following a high fat and high-energy diet. We hypothesized that LPS from a high fat diet can amplify inflammation, thereby exacerbating chronic kidney disease and associated disorders. We have found that adding a high fat diet to renal insufficient mice significantly progressed their kidney disease as well as associated disorders, compared to both a high fat diet and renal insufficiency alone. Additionally, we were able to demonstrate in vitro that …


Evaluation Of The Physiological Effects Of Reduced Hydroxocobalamin On Acute Carbon Monoxide Toxicity, Alden Newcomb Jan 2014

Evaluation Of The Physiological Effects Of Reduced Hydroxocobalamin On Acute Carbon Monoxide Toxicity, Alden Newcomb

Theses and Dissertations

Carbon monoxide (CO) poisoning represents a global health threat responsible for hundreds of thousands of hospital visits and tens of thousands of deaths annually. Oxygen therapy is the only current approved treatment for CO poisoning. Previous work published in the 1970’s and research conducted in the VCURES lab group has indicated that a reduced form of vitamin B12, hydroxocobalamin (B12r), can potentially serve as an antidote for CO poisoning by converting CO bound to hemoglobin to carbon dioxide (CO2) and mitigating the deleterious neurological effects of CO poisoning. For the first time in documented literature we successfully used a Clark-type …


Biochemical And Structural Studies Of Aav-2 Rep68-Aavs1 Complex Assembly, Clayton Bishop Jan 2014

Biochemical And Structural Studies Of Aav-2 Rep68-Aavs1 Complex Assembly, Clayton Bishop

Theses and Dissertations

Multiple DNA transactions are at the center of almost all processes regulating the AAV life cycle. A common feature shared by all transactions is the binding of the large AAV Rep proteins Rep78/Rep68 onto DNA sites harboring multiple GCTC repeats. AAV mediated site-specific integration is contingent upon the formation of a productive complex between Rep78/Rep68 and the AAVS1 site located at chromosome 19. In order to understand the mechanistic details of the initial assembly process we carried out equilibrium binding experiments of Rep68 and its individual domains with a 42-mer AAVS1 site. Results show that although Rep68 binds AAVS1 with …


Characterization Of The Biological Role Of A Putative Porphyromonas Gingivalis Rna-Binding Protein, Ramana Cvitkovic Jan 2014

Characterization Of The Biological Role Of A Putative Porphyromonas Gingivalis Rna-Binding Protein, Ramana Cvitkovic

Theses and Dissertations

Porphyromonas gingivalis, a gram-negative anaerobic bacterium, is a major etiological agent in the initiation and progression of severe forms of periodontal disease. Oral bacteria like P. gingivalis are subject to continually changing conditions as a consequence of host eating, oral hygiene patterns and subgingival temperatures. As such survival requires an adaptive response to environmental cues, but little is known about the mechanism by which P. gingivalis controls co- and post-transcriptional regulation of RNA levels and potentially protein expression. RNA-binding proteins (RBPs) are evolutionarily conserved across species and are involved in such regulatory mechanisms. However, P. gingivalis currently has no identified …


Comparison Of Two Different Sprint Interval Training Work-To-Rest Ratios On Acute Metabolic And Inflammatory Responses, Christopher R. Harnish Jan 2014

Comparison Of Two Different Sprint Interval Training Work-To-Rest Ratios On Acute Metabolic And Inflammatory Responses, Christopher R. Harnish

Theses and Dissertations

High intensity exercise is believed to yield greater results on health and human performance than moderate intensity exercise. Extensive research indicates that not only do high-intensity interval training (HIT) and sprint interval training (SIT) produce significant improvements in cardiovascular fitness and disease, they may be more effective at improving long-term metabolic function, including insulin sensitivity (Si), by producing more mitochondria. Moreover, compliance rates for HIT and SIT participation are reported to be the same or better than traditional moderate intensity exercise. Because lack of time is often cited as major hindrance to exercise participation, SIT is also seen as a …


Regulation Of Pancreatic Α And Β Cell Function By The Bile Acid Receptor Tgr5, Divya Prasanna Kumar Jan 2014

Regulation Of Pancreatic Α And Β Cell Function By The Bile Acid Receptor Tgr5, Divya Prasanna Kumar

Theses and Dissertations

The discovery that bile acids act as endogenous ligands of the membrane receptor TGR5 and the nuclear receptor FXR increased their significance as regulators of cholesterol, glucose and energy metabolism. Activation of TGR5, expressed on enteroendocrine L cells, by bile acids caused secretion of GLP-1, which stimulates insulin secretion from pancreatic β cells. Expression of TGR5 on pancreatic islet cells and the direct effect of bile acids on the endocrine functions of pancreas, however, are not fully understood. The aim of this study was to identify expression of TGR5 in pancreatic islet cells and determine the effect of bile acids …


Differential Effects Of Short-Chain Fatty Acids On Motility Of Guinea Pig Proximal And Distal Colon, Norman Hurst Nov 2013

Differential Effects Of Short-Chain Fatty Acids On Motility Of Guinea Pig Proximal And Distal Colon, Norman Hurst

Theses and Dissertations

NTRODUCTION: Colonic bacteria produce short-chain fatty acids (SCFAs) by fermentation of dietary carbohydrates and fiber. The production of SCFAs is greatest in proximal colon where propulsion is likely to be highly dependent on chemical/nutrient stimuli. Unabsorbed SCFAs entering the distal colon are likely to modify peristalsis initiated by fecal pellet-induced distension. AIM: To determine the effect of individual SCFAs on propulsive contractions in guinea pig proximal colon and on pellet propulsion in distal colon. METHODS: Proximal colon was excised, cannulated and placed in Krebs buffer in an organ bath. After equilibration, the colon was distended with 1ml of Krebs buffer …


Effects Of Nitrite And Oxygen On Angiogenesis In Vascular Networks Of The Chicken Embryo, Michael Connery Oct 2013

Effects Of Nitrite And Oxygen On Angiogenesis In Vascular Networks Of The Chicken Embryo, Michael Connery

Theses and Dissertations

Nitric oxide (NO) is an important mediator of angiogenesis and is primarily produced endogenously through the action of nitric oxide synthase (NOS). An alternate pathway for NO production is the conversion of nitrite to NO, which depends on the presence of hemoglobin (Hb) and hypoxic conditions. The angiogenic effects of topically applied sodium nitrite on two vascular beds in the ex ovo chicken embryonic model of angiogenesis were assessed. Gas barrier films were used to modulate local oxygen levels in the chorioallantoic membrane (CAM), a respiratory vascular network, and the area vasculosa (AV) on the yolk sac, a typical peripheral …


Protein Kinase C Dependent Inhibition Of Kir3.2 (Girk2) Channel Activity And Its Molecular Determinants, Scott Adney Sep 2013

Protein Kinase C Dependent Inhibition Of Kir3.2 (Girk2) Channel Activity And Its Molecular Determinants, Scott Adney

Theses and Dissertations

Inwardly rectifying potassium (Kir) channels are critically important for regulating resting membrane potential in excitable cells, a job underscored by the severe pathophysiology associated with channel dysfunction. While all Kir channels require the activating lipid PIP2, many of these channels have diverse modulatory factors that couple to PIP2-dependent gating. Channels in the Kir3 (GIRK) family, in particular, have several co-activating elements, including G-protein betagamma subunits, ethanol, and sodium. During stimulation of Gq-coupled receptors, downstream activation of Protein Kinase C can phosphorylate and inhibit Kir3 channels, yet the mechanism of inhibition and phosphorylation sites are incompletely understood. We took a combined …


The Effects Of Neurotensin On The Rat Distal Colon, Rick Chainani Sep 2013

The Effects Of Neurotensin On The Rat Distal Colon, Rick Chainani

Theses and Dissertations

The enteric nervous system controls the gut through the release of specific neurotransmitter and neuromodulators at specific sites such as mucosal secretory cell or smooth muscle cell. In the present study, we have examined the response to one of these neurohumoral agents, Neurotensin, in the rat distal colon. Neurotensin is a paracrine and endocrine modulator of the digestive tract. Even though these effects have been seen in colonic preparations, there are very few functional studies of the effects of Neurotensin in the rat colon, especially the distal colon. In the current study we propose the following hypothesis that Neurotensin will …


Paired Interactions Between Kir Channels And Tertiapin-Q, Chul Ho Yang Jul 2013

Paired Interactions Between Kir Channels And Tertiapin-Q, Chul Ho Yang

Theses and Dissertations

Kir channels serve diverse and important roles throughout the human body and malfunctions of these channels are implicated in various channelopathies. Specific inhibitors for different subtypes of Kir channels are not available. However, Tertiapin-Q (TPNQ), a polypeptide isolated from honey bee venom, differentially inhibits certain subtypes of Kir channels with nanomolar affinity: ROMK1 (Kir1.1) and GIRK1/GIRK4 (Kir3.1/Kir3.4). Modification of TPNQ to increase selectivity for target channels bears great therapeutic potential. The in silico studies based on TPNQ-docked channel models, ROMK1_IRK2 (Kir1.1_Kir2.2) and GIRK2 (Kir3.2), predicted specific paired residue interactions and were experimentally validated here. In ROMK1 E123A mutant, the TPNQ …


S3-S4 Linker Modulation Of Voltage Sensor Relaxation In Voltage Gated Potassium Channels, W. Everett Fox Jul 2013

S3-S4 Linker Modulation Of Voltage Sensor Relaxation In Voltage Gated Potassium Channels, W. Everett Fox

Theses and Dissertations

It is commonly assumed that the voltage dependence for activation of voltage-gated channels is an intrinsic characteristic of the protein that remains unchanged during electrical activity. However, sporadic reports have suggested otherwise by showing that voltage dependence changes in a use-dependent manner resulting in a voltage dependence shift towards negative potentials (Bezanilla et al., 1982; Bruening-Wright and Larsson, 2007; Kuzmenkin et al., 2004; Labro et al., 2012; Larsson and Elinder, 2000; Olcese et al., 1997; Piper et al., 2003; Shirokov et al., 1992). Although the mechanism underlying the shift in voltage dependence remains unclear, this process seems to have two …


The Effects Of Gain Of Function Mutant P53 And P63 On Eps8 And Cxcl5 Expression In Head And Neck Squamous Cell Carcinoma, Rubana Masood Jul 2013

The Effects Of Gain Of Function Mutant P53 And P63 On Eps8 And Cxcl5 Expression In Head And Neck Squamous Cell Carcinoma, Rubana Masood

Theses and Dissertations

Head and neck squamous cell carcinoma (HNSCC) is one of the ten most common cancers worldwide, with a survival rate of less than 50%. A class of mutant p53, known as gain of function (GOF) mutant p53, has been found to be expressed in tumors in these patients. GOF mutant p53 not only loses the wild type tumor suppressor functions, but also gains aberrant functions that have been linked to tumorigenesis. In this current study, we utilized a model system consisting of cells derived from HNSCC tumors in order to investigate our hypothesis that GOF mutant p53 enhances, and p63 …


Intra-Mitochondrial Injury During Ischemia-Reperfusion, Hema Aluri May 2013

Intra-Mitochondrial Injury During Ischemia-Reperfusion, Hema Aluri

Theses and Dissertations

Cardiac injury is increased following ischemia-reperfusion. Mitochondria are the “effector organelles” that are damaged during ischemia (ISC) when there is no blood flow. Resumption of metabolism by damaged mitochondria during reperfusion (REP) results in increased cell injury. Current therapeutic interventions to pre-condition and post-condition the heart during ISC are ineffective during certain conditions like aging and diabetes due to defects in the signaling cascades. In contrast, mitochondrial-based strategies are effective in protecting the heart during ISC-REP. Hence direct therapeutic targeting of dysfunctional mitochondria will provide the potential to bypass the upstream signaling defects and intervene directly upon the effector organelle. …


Effects Of Ischemia And Reperfusion On The Local Regulation Of Oxygen Consumption, Tissue Oxygenation And Blood Supply In Rat Skeletal Muscle., Sami Dodhy May 2013

Effects Of Ischemia And Reperfusion On The Local Regulation Of Oxygen Consumption, Tissue Oxygenation And Blood Supply In Rat Skeletal Muscle., Sami Dodhy

Theses and Dissertations

In resting muscle, blood flow is regulated to meet the demand for O2 by the tissue. A modified ischemia (I)/reperfusion(R) investigation was systematically run and PISFO2, PaO2, Q and VO2 were observed. Twenty-nine spinotrapezius muscles from male Sprague-Dawley rats (284±20 grams) were surgically exteriorized for intravital microscopy to test a model relating blood flow, O2 supply and O2 demand. The model can aid in the understanding of the regulation of tissue PO2. The interstitial PO2 (PISFO2) and perivascular PO2 (PaO2) measurements were made using phosphorescence quenching microscopy (PQM). O2 consumption (VO2) values were obtained with a quasi-continuous, flash-synchronized, pressurized airbag …


The Effects Of Tarsh Overexpression On Lung Carcinomas, Young Kim Apr 2013

The Effects Of Tarsh Overexpression On Lung Carcinomas, Young Kim

Theses and Dissertations

Lung cancer arises from epithelial cells that line the air passages of the lungs. It is the second most common malignancy in the United States; trends suggest that over 228,000 new patients will be diagnosed with lung cancer in 2013. Due to the fact that lung cancer is highly aggressive, it has proven difficult to control. The 5-year survival rate has been shown to be only 15.9%, despite the advances made in terms of diagnosis and treatment. Therefore, we are faced with the problem of finding more effective methods that allow for an earlier diagnosis and the improved treatment of …


The Inflammasome In Acute Myocarditis, Harsha Kannan Apr 2013

The Inflammasome In Acute Myocarditis, Harsha Kannan

Theses and Dissertations

Acute myocarditis is an acute inflammatory syndrome characterized by myocardial damage and dysfunction often due to a viral infection followed by a variable development over time. There are currently no specific treatments and standard treatments for heart failure are generally applied. The inflammasome is a recently identified macromolecular structure that occupies a central role in the amplification of the inflammatory response and promotion of cell death during acute and chronic infections. We hypothesized the formation of the inflammasome in acute myocarditis. To investigate, samples of patients were collected from the Cardiomyopathy Registry in Trieste, with 12 cases of biopsy-proven myocarditis …


Characterization Of The Neurotrophic Factor Brain-Derived Neurotrophic Factor (Bdnf) In Intestinal Smooth Muscle Cells, Mohammad Alqudah Apr 2013

Characterization Of The Neurotrophic Factor Brain-Derived Neurotrophic Factor (Bdnf) In Intestinal Smooth Muscle Cells, Mohammad Alqudah

Theses and Dissertations

Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of secreted proteins, which include in addition to BDNF, nerve growth factor (NGF) and neurotrophin 3-6 (NT-3-6). BDNF mediates its functions by activating two cell surface receptors, pan-neurotrophin receptor (P75NTR) and tropomyosin-related kinase B (TrkB) and their downstream intracellular cascades. BDNF is best known for its role in neuronal survival, regulation of neuronal differentiation, migration and activity-dependent synaptic plasticity. However, BDNF is widely expressed in non-neuronal tissues as well. The localization and the function of BDNF in intestinal smooth muscle cells (SMCs) are not well defined. Thus, the main purpose of …


Sildenafil Attenuates Ethanol-Induced Cardiomyocyte Injury And Preserves Cardiac Function Through Protein Kinase G-Dependent Signaling, Gregory R. Sturz Apr 2013

Sildenafil Attenuates Ethanol-Induced Cardiomyocyte Injury And Preserves Cardiac Function Through Protein Kinase G-Dependent Signaling, Gregory R. Sturz

Theses and Dissertations

Background: Ethanol is a cardiotoxic substance that damages the heart by increasing apoptosis, free radical formation and calcium overloading. Consequently, there is an increase in cell death leaving fewer functioning myocytes leading to heart failure. Sildenafil is a phosphodiesterase type-5 (PDE-5) inhibitor approved for treatment of erectile dysfunction. Studies from our lab have demonstrated that PDE-5 inhibition reduces myocardial infarct size and attenuates post-ischemic cardiac dysfunction in both ischemia-reperfusion and permanent coronary artery ligation models. Therefore, in the present study, we hypothesized that treatment with sildenafil will prevent cardiotoxicity associated with acute alcohol exposure by reducing myocyte apoptosis and preserving …


Regulation Of Gastrointestinal Smooth Muscle Function By Hydrogen Sulfide, Ancy Nalli Apr 2013

Regulation Of Gastrointestinal Smooth Muscle Function By Hydrogen Sulfide, Ancy Nalli

Theses and Dissertations

Inhibitory neurotransmitters, chiefly nitric oxide and vasoactive intestinal peptide, cause MLC20 dephosphorylation and muscle relaxation via inhibition of myosin light chain (MLC) kinase and activation of MLC phosphatase. Hydrogen sulfide (H2S) produced as a byproduct by luminal sulfate-reducing commensal bacteria or as an endogenous signaling molecule synthesized from L-cysteine via cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) regulates muscle contraction. However, the role of H2S in the regulation of MLC phosphatase activity and MLC20 phosphorylation is not known. The aim of the present study was to examine the expression of CSE and CBS in smooth muscle cells and to elucidate the molecular …


Studies On The Reaction Of High-Dose Hydroxocobalamin And Ascorbic Acid With Carbon Monoxide: Implications For Treatment Of Carbon Monoxide Poisoning, Joseph Roderique Apr 2013

Studies On The Reaction Of High-Dose Hydroxocobalamin And Ascorbic Acid With Carbon Monoxide: Implications For Treatment Of Carbon Monoxide Poisoning, Joseph Roderique

Theses and Dissertations

Based upon experimental evidence from the 1970’s we proposed that a reduced form of hydroxocobalamin should be capable of producing carbon dioxide (CO2) from carbon monoxide (CO) in blood, and that this conversion should be detectable. Using resonance raman spectroscopy we demonstrated that a mixture of hydroxocobalamin and ascorbic acid could create the reduced form of hydroxocobalamin. We used a closed-loop circulation system with a hollow-fiber membrane oxygenator to produce carboxyhemoglobin. Using sensitive gas monitoring equipment to the gas-out port of the oxygenator we analyzed the CO and CO2 concentrations coming from the oxygenator. The mixture of hydroxocobalamin and ascorbic …


Sphingosine-1-Phosphate And Fingolimod (Fty720) Regulate Icl,Swell In Hl-1 Cardiac Myocytes Via Intracellular Binding And Mitochondrial Ros Production, Pooja Desai Jan 2013

Sphingosine-1-Phosphate And Fingolimod (Fty720) Regulate Icl,Swell In Hl-1 Cardiac Myocytes Via Intracellular Binding And Mitochondrial Ros Production, Pooja Desai

Theses and Dissertations

Swelling-activated Cl− current (ICl,swell) is an outwardly-rectifying current that plays an important role in cardiac electrical activity, cellular volume regulation, apoptosis, and acts as a potential effector of mechanoelectrical feedback. Persistent activation of ICl,swell has been observed in models of cardiovascular disease. We previously suggested sphingosine-1-phosphate (S1P) activates volume-sensitive Cl- current (ICl,swell) by ROS-dependent signaling. S1P and its analog, FTY720 (fingolimod), primarily act via G-protein coupled receptors (S1PR; S1PR1-3 in heart), but several intracellular S1P ligands are known. We investigated how these agents regulate ICl,swell. ICl,swell was elicited by bath S1P (500 nM), FTY720 (S1PR1,3 agonist; 10 μM), and SEW2871 …


Novel Strategies To Improve Metabolic Parameters And Precondition Diabetic Hearts Against Ischemia/Reperfusion Injury, Amit Varma Nov 2012

Novel Strategies To Improve Metabolic Parameters And Precondition Diabetic Hearts Against Ischemia/Reperfusion Injury, Amit Varma

Theses and Dissertations

Insulin resistance and chronic hyperglycemia promote vascular damage, increase circulating levels of inflammatory cytokines and lead to increased morbidity and mortality. MicroRNAs (miRs) -103/107 have been shown to negatively regulate insulin sensitivity and glucose homeostasis. Based on complimentary binding profiles, the downstream target gene of miR-103/107 is caveolin-1 (Cav-1). We hypothesized that daily administration of the phosphodiesterase-5 inhibitor tadalafil (TAD) ± the curcumin analogue (HO-3867) will attenuate inflammation, improve metabolic parameters and reduce infarct size after ischemia/reperfusion injury (IRI). Furthermore, we propose that TAD therapy will reduce myocardial expression of miR-103/107 and increase mRNA and protein levels of its target …


Regulation Of Excitation-Contraction And Excitation-Transcription Coupling In Gastrointestinal Smooth Muscle By Caveolin-1, Sayak Bhattacharya Oct 2012

Regulation Of Excitation-Contraction And Excitation-Transcription Coupling In Gastrointestinal Smooth Muscle By Caveolin-1, Sayak Bhattacharya

Theses and Dissertations

Caveolae are integral part of the smooth muscle membrane and caveolins, the defining proteins of caveolae, act as scaffolding proteins for several G protein-coupled receptor signaling molecules and regulate cellular signaling through direct and indirect interactions with signaling proteins. Caveolin-1 is the predominant isoform in the smooth muscle and drives the formation of caveolae. However, little is known about the role of caveolin-1 in the regulation of excitation-contraction and excitation-transcription coupling in gastrointestinal smooth muscle. In the present study we have characterized muscarinic m2 and m3 receptor signaling in gastric smooth muscle and tested the hypothesis that caveolin-1 positively regulates …


Mutant P53 Regulation Of Cxc-Chemokine Expression In Head And Neck Squamous Cell Carcinoma, Brittany Field Oct 2012

Mutant P53 Regulation Of Cxc-Chemokine Expression In Head And Neck Squamous Cell Carcinoma, Brittany Field

Theses and Dissertations

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common type of cancer in the western hemisphere with a five-year survival rate of only 50% for patients with a localized tumor, which decreases significantly to as low as 5% for those patients with tumors that have metastasized to distant sites of the body. It has been found that both mutant p53 and epidermal growth factor receptor (EGFR) signaling pathways function to increase the expression of CXCL5, which has been identified as a key mediator in the process of tumor metastasis. Previous data from our lab suggested that the …


Gβγ Acts At An Inter-Subunit Cleft To Activate Girk1 Channels, Rahul Mahajan Oct 2012

Gβγ Acts At An Inter-Subunit Cleft To Activate Girk1 Channels, Rahul Mahajan

Theses and Dissertations

Heterotrimeric guanine nucleotide-binding proteins (G-proteins) consist of an alpha subunit (Gα) and the dimeric beta-gamma subunit (Gβγ). The first example of direct cell signaling by Gβγ was the discovery of its role in activating G-protein regulated inwardly rectifying K+ (GIRK) channels which underlie the acetylcholine-induced K+ current responsible for vagal inhibition of heart rate. Published crystal structures have provided important insights into the structures of the G-protein subunits and GIRK channels separately, but co-crystals of the channel and Gβγ together remain elusive and no specific reciprocal residue interactions between the two proteins are currently known. Given the absence of direct …


Purification And Reconstitution Into Planar Bilayers Of The Human Dopamine Transporter, Yoori Kim Aug 2012

Purification And Reconstitution Into Planar Bilayers Of The Human Dopamine Transporter, Yoori Kim

Theses and Dissertations

The human dopamine transporter (hDAT) provides the primary mechanism for dopamine clearance in synapses and thus facilitates the regulation of dopaminergic functions in cognition and reward. It is the molecular target of many centrally-active agents including amphetamines and cocaine. Therefore, an understanding of hDAT function and its modulation by these therapeutic drugs and drugs of abuse can provide insight into the mechanisms of abuse and addiction. In the presented studies, hDAT is tagged with a hexahistidine construct and heterologously expressed in Xenopus laevis oocytes. The plasma membranes are isolated, solubilized, and applied to a Nickel affinity column to obtain purified …


Signal Transduction Effects Induced By Erythropoietin In A Hnscc Model System, Shreya Desai Jul 2012

Signal Transduction Effects Induced By Erythropoietin In A Hnscc Model System, Shreya Desai

Theses and Dissertations

Head and Neck Squamous Cell Carcinoma (HNSCC) is an epithelial skin cancer of the upper aerodigestive tract, and is the sixth most common malignancy in the U.S. HNSCC patients undergoing chemotherapy commonly develop anemia, a condition in which the body lacks mature red blood cells (RBCs). Erythropoietin (EPO) is a systemically circulating hormone in the body that regulates the production of RBCs and is applied to treat anemia. Recently, several studies implicated shortened life expectancy of cancer patients by EPO administration. It may be due to an unexpected activation of survival and proliferation pathways of cancer cells by EPO because …


The Effect Of Various Chemical Factors On Angiogenesis In The Chick Chorio-Allantoic Membrane, Heather Hammond Jun 2012

The Effect Of Various Chemical Factors On Angiogenesis In The Chick Chorio-Allantoic Membrane, Heather Hammond

Theses and Dissertations

The chick chorio-allantoic membrane (CAM) contains a complex vascular network commonly used to study angiogenesis. The application of chemical factors and oxygen barrier films onto this tissue can easily influence the process of angiogenesis. In this study, oxygen barrier film patches (Krehalon, polyvinylidene chloride, 12 μm thick, O2 transmission rate = 2.19 cm3•ml/100 in2•day•atm) were applied to areas of the CAM. Holes were made in the film and alginate beads incubated in various chemical factors were placed in the holes. After 24 and 48 hours of exposure to the alginate beads, images were taken of the tissue using a stereomicroscope …