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Full-Text Articles in Life Sciences

Examination Of Platelet Adhesion By Streptococcus Sanguinis, Brian Mahoney Nov 2009

Examination Of Platelet Adhesion By Streptococcus Sanguinis, Brian Mahoney

Theses and Dissertations

Streptococcus sanguinis is a leading cause of infective endocarditis. Bacterial adhesion to platelets is likely important in the pathogenesis of infective endocarditis. Bacterial cell wall-anchored (Cwa) proteins may mediate this adhesion. To begin to test this hypothesis, S. sanguinis adhesion to platelets was examined in vitro. The requirement of 12 Cwa proteins for S. sanguinis-platelet adhesion was individually assessed, measuring adhesion of purified platelets to polystyrene wells coated with S. sanguinis strain SK36 or 12 isogenic Cwa protein mutants. Significantly fewer platelets adhered to wells coated with one mutant strain, VT1614. However, results of a whole-cell enzyme-linked immunosorbent assay (ELISA) …


The Role Of Cannabinoids And Cannabinoid Receptors In Enteric Neuronal Survival, Yan Li Nov 2009

The Role Of Cannabinoids And Cannabinoid Receptors In Enteric Neuronal Survival, Yan Li

Theses and Dissertations

The Endocannabinoid system has been found in the gastrointestinal tract, where it plays an important role in gut under both physiological and pathological conditions. Although the major effects of cannabinoids in the gut are mediated through effects on enteric neurons, the role of cannabinoids in the enteric nervous system is poorly understood. In the present study, we have used the primary cultures of myenteric ganglia and a newly developed fetal enteric neuronal cell line to identify whether the endocannabinoid, anandamide, affects ganglionic and neuronal survival and the pathways involved. Anandamide had a biphasic effect on ganglionic survival, increasing survival at …


Sphingolipid-Induced Activation Of The Volume-Sensitive Cl− Current Is Mediated By Mitochondrial Reactive Oxygen Species, Frank Raucci Oct 2009

Sphingolipid-Induced Activation Of The Volume-Sensitive Cl− Current Is Mediated By Mitochondrial Reactive Oxygen Species, Frank Raucci

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 a number of models of cardiovascular disease. Previously we showed that angiotensin II (Ang II), endothelin-1 (ET-1), endothelial growth factor receptor (EGFR), and reactive oxygen species (ROS) produced by NADPH oxidase (NOX) and mitochondria are involved in the activation of ICl,swell by both osmotic swelling and Beta1 integrin stretch. Sphingolipid metabolism is modulated in several cardiopathologies and because sphingolipids are bioactive lipids …


The Role Of Porphyromonas Gingivalis Lysine Specific Protease, Kgp In Hemin Transport And Pigment Accumulation, Anuj Phull Aug 2009

The Role Of Porphyromonas Gingivalis Lysine Specific Protease, Kgp In Hemin Transport And Pigment Accumulation, Anuj Phull

Theses and Dissertations

Porphyromonas gingivalis, a gram-negative anaerobic bacterium, is implicated as a major etiological agent in the initiation and progression of severe forms of periodontal disease. It has been reported that gingivitis and periodontal disease affect roughly 50.3% and 35% of the adult population, respectively. Therefore, approximately over 85% of the adult population may suffer from some form of gingival disease. Porphyromonas gingivalis, an established periodontopathogen, requires hemin for growth. Although multiple hemin uptake systems appear to be present in this organism, their specific role in hemin uptake and virulence remains unknown. Pigmentation is thought to result from the accumulation of iron …


Ion Channel Modulation By Photocaged Dioctanoyl Pip2, Junghoon Ha Aug 2009

Ion Channel Modulation By Photocaged Dioctanoyl Pip2, Junghoon Ha

Theses and Dissertations

Phosphatidylinositol bisphosphate (PIP2) directly regulates electrophysiological activity in a diverse family of ion channels whether the effect is stimulatory or inhibitory. Much has been unveiled about the apparent affinity and modulatory function of PIP2 using a chemically modified dioctanoyl PIP2 (diC8), a membrane delimited cytosolic co-factor in inside-out macropatch experiments. Yet, the scarcity of molecular tools that permit fine external control in whole-cell systems has precluded future studies from probing the physiological role of PIP2 in cells in the presence of a fully intact cytoplasm. Here we introduce light as an external control for PIP2 through photocaging of diC8, and …


Molecular And Cellular Mechanisms Whereby The Apical Ectodermal Ridge (Aer), Via Wnt5a, Mediates Directional Migration Of The Adjacent Mesenchyme During Vertebrate Limb Development, Kate E. Kmetzsch Aug 2009

Molecular And Cellular Mechanisms Whereby The Apical Ectodermal Ridge (Aer), Via Wnt5a, Mediates Directional Migration Of The Adjacent Mesenchyme During Vertebrate Limb Development, Kate E. Kmetzsch

Theses and Dissertations

The vertebrate embryonic limb is a key model in elucidating the genetic basis underlying the three dimensional morphogenesis of structures. Despite the wealth of insights that have been generated from this model, many long-standing questions remain. For example, it has been known for over 70 years that the apical ectodermal ridge (AER) of the embryonic limb is essential for distal outgrowth and patterning of the adjacent limb mesenchyme. The mechanisms whereby the AER does accomplish outgrowth and patterning are still poorly understood. We propose that secreted FGFs from the AER activate Wnt5a expression in gradient fashion, which in turn provides …


Marrying Immunotherapy And Chemotherapy: A Cancer Therapy Based On T Lymphocyte Expansion Augmented By Alternate Gamma Chain Cytokines And Gemcitabine-Mediated Inhibition Of Myeloid Derived Suppressor Cells, Esther Cha Aug 2009

Marrying Immunotherapy And Chemotherapy: A Cancer Therapy Based On T Lymphocyte Expansion Augmented By Alternate Gamma Chain Cytokines And Gemcitabine-Mediated Inhibition Of Myeloid Derived Suppressor Cells, Esther Cha

Theses and Dissertations

Successful adoptive immunotherapy (AIT) for cancer relies on the infusion of in vitro expanded, tumor-reactive lymphocytes with a goal of generating productive tumor immunity. Previously, our lab has developed a protocol to activate selectively tumor-reactive T lymphocytes in vitro using two pharmacologic agents, bryostatin-1 and ionomycin. Following the pharmacological stimulation, conventionally, IL-2 is added to stimulate in vitro proliferation. In this report, alternate cytokines from the common cytokine receptor γ-chain family, namely IL-7 and IL-15, were explored as the alternative cytokine supplements. We found that tumor DLN cells activated in vitro with B/I and cultured in IL-7/15 alternate common γ-chain …


Zyxin Regulates Epithelial-Mesenchymal Transition By Mediating Actin-Membrane Linkages At Cell-Cell Junctions, Liv Rebecca Sperry Aug 2009

Zyxin Regulates Epithelial-Mesenchymal Transition By Mediating Actin-Membrane Linkages At Cell-Cell Junctions, Liv Rebecca Sperry

Theses and Dissertations

Development is punctuated by morphogenetic rearrangements of epithelial tissues, including complete detachment of individual motile cells during epithelial-mesenchymal transition (EMT). Dramatic actin rearrangements occur as cell-cell junctions are dismantled and cells become independently motile during EMT. Characterizing dynamic actin rearrangements and identifying actin machinery driving these rearrangements is essential for understanding basic mechanisms of cell-cell junction remodeling; yet, neither the precise series of actin rearrangements at cell-cell junctions that accompany EMT, nor the machinery that controls actin rearrangement during EMT, have been identified. This work represents a detailed study of junctional actin reorganization in cells undergoing EMT, identifies actin regulatory …


Schizophrenia Candidate Genes Study, Grace Lee Jul 2009

Schizophrenia Candidate Genes Study, Grace Lee

Theses and Dissertations

Schizophrenia is a debilitating disorder caused by the interaction of genetic and environmental factors. In this study, we identified candidate genes and single nucleotide polymorphisms from two genome-wide association studies, GAIN and CATIE. Nine SNPs representing four candidate genes were selected for replication studies with our Irish samples: Irish Case-Control Study of Schizophrenia (ICCSS), the Irish Study of High-Density Schizophrenia Families (ISHDSF), and the Irish Trio Study of Schizophrenia (ITRIO). In the ITRIO sample, rs4704591 (CMYA5 gene) showed nominal significance (p = 0.0447947). Combining ICCSS, ISHDSF, and ITRIO samples for rs4704591 increased sample size and power and yielded a p-value …


Evaluation Of Association Of Microrna-122 With Histological Severity Of Recurrent Hcv Infection In Liver Transplant Recipients, Jihee Suh Jul 2009

Evaluation Of Association Of Microrna-122 With Histological Severity Of Recurrent Hcv Infection In Liver Transplant Recipients, Jihee Suh

Theses and Dissertations

Hepatitis C virus recurrence (which is defined by detection of HCV RNA in serum) in post-transplanted liver is universal but the progression of infection remains unpredictable, varying from case to case. It has been estimated that 75%-80% of the HCV recurrence patients will suffer chronic hepatitis C infection and up to a third of them will progress into the development of fibrosis and cirrhosis within 5 years post-transplantation. Therefore, finding ways to predict early on the progression of fibrosis can contribute to better prognoses. Recent literatures have mentioned that the hepatitis C virus relies on the host microRNA-122 (miR-122) for …


A Cellular Mechanism For Dendritic Spine Loss Following Traumautic Brain Injury In Rat, Brian Low Jul 2009

A Cellular Mechanism For Dendritic Spine Loss Following Traumautic Brain Injury In Rat, Brian Low

Theses and Dissertations

Traumatic brain injury is a leading cause of death and disability in the United States. The injury is often composed of two processes: the primary injury, which can involve irreversible loss of tissue, and the secondary injury, which involves a cascade of reactive processes such as excitotoxicity that occur in the hours and days after the initial insult. Excitotoxic stimulation of neuronal circuits can lead to cellular dysfunction and modulation of neuronal sensitivity. One mechanism of dysfunction involves the calcium-regulated phosphatase, calcineurin. Calcineurin has been shown to be involved in the modulation of the neuronal post-synaptic structures known as dendritic …


Role Of Endothelin-1 In The Regulation Of The Swelling-Activated Cl- Current In Atrial Myocytes, Wu Deng Jul 2009

Role Of Endothelin-1 In The Regulation Of The Swelling-Activated Cl- Current In Atrial Myocytes, Wu Deng

Theses and Dissertations

Swelling-activated Cl- current (ICl,swell) is an outwardly rectifying Cl- current that influences cardiac electric activities and acts as a potential effector of mechanoelectrical feedback that antagonizes the effects of stretch-activated cation channels. Persistent activation of ICl,swell has been observed in multiple models of cardiovascular diseases. Previously we showed that angiotensin II (AngII) signaling and reactive oxygen species (ROS) produced by NADPH oxidase (NOX) are involved in the activation of ICl, swell by both beta1-integrin stretch and osmotic swelling. Because endothelin-1 (ET-1) is a potential downstream mediator of AngII and ETA receptor blockade abrogates AngII-induced ROS generation, we studied how ET-1 …


Adaptation At A Shortened Length In Rabbit Femoral Artery, Melissa Bednarek Jul 2009

Adaptation At A Shortened Length In Rabbit Femoral Artery, Melissa Bednarek

Theses and Dissertations

It is well known that the overlap between the thick and thin filaments in striated muscle is responsible for the single active length-tension (L-T) curve. With the lack of visible striations, a sarcomeric unit has not been identified in smooth muscle. Though once thought to function like striated muscle via a sliding filament mechanism of contraction, recent studies on length-adaptation (L-adaptation) in airway smooth muscle (ASM), in which increased tension is generated with repeated contraction, have led to the hypothesis of a dynamic L-T curve in smooth muscle. Although more established in ASM, two studies have shown L-adaptation in vascular …


Function Of The Notch/Delta Pathway In Ophthalmic Trigeminal Placode Development, Matthew K. Ball Jul 2009

Function Of The Notch/Delta Pathway In Ophthalmic Trigeminal Placode Development, Matthew K. Ball

Theses and Dissertations

The ophthalmic trigeminal placode (opV) is the birth place of one cell type of sensory neurons contributing to the trigeminal ganglion. Signals from the neural tube induce placodal identity within the surface ectoderm. Specified opV placode cells then up-regulate neuron differentiation markers and migrate to the ganglion. Several molecular pathways have been shown to act in opV placode cell development. Despite this, signals that specify individual neurons from within the opV placode remain unknown. However, it is known that components of the Notch signaling pathway are expressed in the opV placode. I tested the role of Notch signaling in opV …


Investigating The Role Of Electric Fields In Directing Schwann Cell Behavior, Nishant Magar Jun 2009

Investigating The Role Of Electric Fields In Directing Schwann Cell Behavior, Nishant Magar

Theses and Dissertations

This study examines the potential of Schwann cells (SCs) to be manipulated by electric fields (EFs) in order to improve recovery from spinal cord injury (SCI). It had long been believed that the central nervous system (CNS) is incapable of regeneration, but recent studies have proven otherwise. SC transplants are known to be useful in promoting axon regeneration after SCI, but is not sufficient for functional recovery. EFs are known to exist in vivo, and have been known to drastically affect the morphology and behavior of cells in various tissues. It was the hypothesis of this study that the conditioning …


Tacrolimus Is Not Neuroprotective Against Bilirubin Induced Auditory Impairment, Lori Walker Apr 2009

Tacrolimus Is Not Neuroprotective Against Bilirubin Induced Auditory Impairment, Lori Walker

Theses and Dissertations

In newborns, unconjugated bilirubin (UCB) is not readily excreted, and when bilirubin levels exceed the serum albumin binding capacity, pathological levels of UCB exist. Hyperbilirubinemia may lead to auditory damage and ultimately cause a hearing disorder called auditory neuropathy/dys-synchrony, characterized by absent or abnormal brainstem auditory evoked potentials (BAEPs) with evidence of normal inner ear function assessed by either otoacoustic emissions or cochlear microphonic responses. Phototherapy and double volume exchange transfusion are used as treatment methods for neonatal hyperbilirubinemia. Spontaneously jaundiced Gunn rat pups given sulfadimethoxine to displace bilirubin from serum albumin develop bilirubin encephalopathy and have abnormal BAEPs comparable …


Role Of Hepatic Cholesterol Ester Hydrolase (Ceh) In Hydrolyzing Cholesterol Esters (Ce) Delivered Via Sr-Bi (Scavenger Receptor Class B Type I) And Sr-Bii, Saurabh Bajpai Apr 2009

Role Of Hepatic Cholesterol Ester Hydrolase (Ceh) In Hydrolyzing Cholesterol Esters (Ce) Delivered Via Sr-Bi (Scavenger Receptor Class B Type I) And Sr-Bii, Saurabh Bajpai

Theses and Dissertations

Reduction of cholesterol ester (CE) from lipid burden lesion-associated macrophage foam cells has been shown to reduce plaque volumes. Hydrolysis of CE to free cholesterol (FC) in macrophages is an essential step for removal of CE from the macrophage and its transport to the liver by high density lipoprotein (HDL) for further metabolism. Since CE must again be hydrolyzed into FC in the liver catalyzing this hydrolysis, it becomes imperative to find the identity of these enzymes. In this study the role of key enzyme in catalyzing the hydrolysis of CE to FC, neutral cholesterol ester hydrolase (CEH) was evaluated. …


Matrix Metalloproteinase Expression In Models Of Parkinson's Disease, Justin Mcclain Apr 2009

Matrix Metalloproteinase Expression In Models Of Parkinson's Disease, Justin Mcclain

Theses and Dissertations

Parkinson’s disease (PD) is a devastating neurodegenerative disorder characterized by progressive loss of dopaminergic neurons located in the substantia nigra. Accumulating evidence indicates that microglia-driven neuroinflammation contributes significantly to chronic neurodegeneration in PD. The matrix metalloproteinases (MMPs) play an important role in several neuroinflammatory paradigms; however, their relationship to dopaminergic neurodegeneration in PD remains relatively unexplored. To address this, the temporal relationship between MMP-2, MMP-3, MMP-9, and MMP-13 expression and dopaminergic neurodegeneration was compared in the 6-hydroxydopamine (6-OHDA) and lipopolysaccharide (LPS) models of PD. In dopaminergic SH-SY5Y cells, 6-OHDA treatment significantly increased MMP-13 mRNA expression; however, examination of 6-OHDA-lesioned rats …