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Functions Of The Apical Na+/ K+/ 2cl- Cotransporter 1 In Choroid Plexus Epithelial Cells, Jeannine Marie Crum Gregoriades Jan 2017

Functions Of The Apical Na+/ K+/ 2cl- Cotransporter 1 In Choroid Plexus Epithelial Cells, Jeannine Marie Crum Gregoriades

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Choroid plexus epithelial cells (CPECs) secrete cerebrospinal fluid (CSF) and regulate its electrolyte composition. CPECs express both the Na+/ K+ ATPase and the Na+/ K+/ 2Cl- cotransporter 1 (NKCC1) on their apical membrane (CSF facing), deviating from the typical basolateral membrane location in chloride secretory epithelia. Given this unusual location of NKCC1 and the unknown intracellular Na+ and Cl- concentrations of CPECs, the cotransporter function in these cells is not understood. Further, the direction of net ion and associated water fluxes mediated by NKCC1 under basal physiological conditions in CPECs is controversial. Determining the direction of NKCC1- mediated fluxes is …


Sensorimotor Deficits Following Oxaliplatin Chemotherapy, Jacob Adam Vincent Jan 2017

Sensorimotor Deficits Following Oxaliplatin Chemotherapy, Jacob Adam Vincent

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Neurotoxicity is one of the most significant side effects diminishing clinical efficacy and patient quality of life during and following chemotherapy. Oxaliplatin (OX) is a platinum based chemotherapy agent used in the treatment of colorectal cancer. Colorectal cancer currently ranks as the 4th most common cancer, and the majority of patients receive OX as a part of their adjuvant therapy. OX based adjuvant therapies significantly improve 5 year survival rates, however in many cases patients must stop treatment early because of the neurotoxic side effects. OX causes two clinically distinct forms of neurotoxicity. Acutely, within hours and for days following …


Novel Mechanisms Underlying Warm-Up And Percussion Myotonia In Myotonia Congenita, Kevin Richard Nnovak Jan 2017

Novel Mechanisms Underlying Warm-Up And Percussion Myotonia In Myotonia Congenita, Kevin Richard Nnovak

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Patients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the ClC-1 chloride channel in skeletal muscle, which causes spontaneous firing of muscle action potentials (myotonia), producing muscle stiffness. Triggers for myotonia can occur voluntarily at the neuromuscular junction or involuntarily by striking the muscle with a reflex hammer (percussion myotonia). In patients, muscle stiffness lessens with exercise, a change known as the warm-up phenomenon. Our goal was to identify the mechanism underlying warm-up and percussion myotonia and to use this information to guide development of novel therapies. To determine these underlying mechanisms, we used a drug to …


Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash Jan 2017

Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash

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Myotonia congenita is a rare skeletal muscle channelopathy caused by a reduced chloride channel (ClC-1) current, which results in debilitating muscle hyperexcitability, prolonged contractions, and transient episodes of weakness. The excitatory events that trigger myotonic action potentials in the absence of stabilizing ClC-1 current are not fully understood. My in vitro intracellular recordings from a mouse homozygous knockout of ClC-1 revealed a slow after-depolarization (AfD) that triggers myotonic action potentials. The AfD is well-explained by a tetrododoxin-sensitive and voltage-dependent Na+ persistent inward current (NaPIC). Notably, this NaPIC undergoes slow inactivation over seconds, thus providing the first mechanistic explanation for the …


Functions Of The Apical Na+/ K+/ 2cl- Cotransporter 1 In Choroid Plexus Epithelial Cells., Jeannine Marie Crum Gregoriades Jan 2017

Functions Of The Apical Na+/ K+/ 2cl- Cotransporter 1 In Choroid Plexus Epithelial Cells., Jeannine Marie Crum Gregoriades

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Choroid plexus epithelial cells (CPECs) secrete cerebrospinal fluid (CSF) and regulate its electrolyte composition. CPECs express both the Na+/ K+ ATPase and the Na+/ K+/ 2Cl- cotransporter 1 (NKCC1) on their apical membrane (CSF facing), deviating from the typical basolateral membrane location in chloride secretory epithelia. Given this unusual location of NKCC1 and the unknown intracellular Na+ and Cl- concentrations of CPECs, the cotransporter function in these cells is not understood. Further, the direction of net ion and associated water fluxes mediated by NKCC1 under basal physiological conditions in CPECs …


Novel Cell Killing Mechanism Of Hydroxyurea In The Fission Yeast Schizosaccharomyces Pombe And Its Implications In Improving Antifungal Therapy, Amanpreet Singh Jan 2016

Novel Cell Killing Mechanism Of Hydroxyurea In The Fission Yeast Schizosaccharomyces Pombe And Its Implications In Improving Antifungal Therapy, Amanpreet Singh

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Hydroxyurea (HU, also known as hydroxycarbamide) is a well known ribonucleotide reductase (RNR) inhibitor that depletes cellular deoxyribonucleoside triphosphates (dNTPs, the building blocks of DNA). Depleted dNTP pools inside the proliferating cells stalls ongoing DNA replication forks, leading to the activation of the well-conserved DNA replication checkpoint (also known as intra-S phase checkpoint) pathway. One of the major functions of the checkpoint pathway is to protect ongoing forks from collapsing. Stalled forks, if not protected by the checkpoint pathway, lead to DNA damage and ultimately cell death. Thus it is believed that DNA damage resulting from collapsed forks is the …


Modification Reactivity Analysis Of Human Replication Protein A In Biologically Important States, Ryan James Yoakum Jan 2016

Modification Reactivity Analysis Of Human Replication Protein A In Biologically Important States, Ryan James Yoakum

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Human Replication Protein A (RPA) is a heterotrimeric protein consisting of 70, 32, and 14 kDa subunits. RPA is the predominant single stranded DNA binding protein within the cell. It is involved in all forms of the DNA metabolic pathways, including but not limited to, replication, recombination, damage repair, as well as cell cycle and DNA check point signaling. RPA is phosphorylated (pRPA) during G1-S phase and is dephosphorylated during M phase. Further, RPA is hyperphosphorylated during DNA damage. Through the use of x-ray crystallography and nuclear magnetic resonance, researchers have proposed models and structures based on truncated portions of …


Extension Of Multivariate Analyses To The Field Of Microbial Ecology, Vijay Shankar Jan 2016

Extension Of Multivariate Analyses To The Field Of Microbial Ecology, Vijay Shankar

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Ground-breaking advancements in molecular and analytical techniques in the past decade have enabled researchers to accumulate data at an extraordinary rate. Especially in the field of microbial ecology, the introduction of technologies such as high-throughput sequencing, quantitative microarrays, nuclear magnetic resonance and mass spectrometry has led to the interrogation of diverse and previously unexplored microbial communities at unparalleled depth. Analysis and interpretation of patterns within datasets acquired with such high-throughput methods require powerful statistical approaches. A class of such techniques called multivariate statistical analyses is an excellent choice for analysis of complex microbiota-related datasets. This field of statistics is constantly …


Novel Therapeutic Approach For Regulating The Susceptibility Of Epitheliato Adenovirus Infection, Mahmoud Soliman Salem Alghamri Jan 2016

Novel Therapeutic Approach For Regulating The Susceptibility Of Epitheliato Adenovirus Infection, Mahmoud Soliman Salem Alghamri

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Human Adenoviruses (AdVs) are etiologic agents for respiratory tract, digestive tract, heart, and eye infections. Although most AdV infections are self-resolving, some infections progress to acute respiratory disease with up to 50% mortality, particularly in immunosuppressed people. Except for vaccines for serotypes, 4 and 7, serotypes that are prevalent in the military, no vaccines or therapeutics that specifically prevent or treat AdV infection exist. On the other hand, AdV remains the most common vector system used in gene therapy clinical trials worldwide and several AdV vectors show promise in phase III clinical trials. The majority of AdVs use the coxsackievirus …


Modeling Effects Of Diet On Human Gut Microbiota, Richard Thomas Agans Jan 2016

Modeling Effects Of Diet On Human Gut Microbiota, Richard Thomas Agans

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The human gut microbiota is integrally involved in the metabolism of nutrients contained within the human diet. Studies into human nutrition have primarily been carried out using human and animal models. These studies are extremely important in our understanding of human nutrition, however, suffer from inherent limitations including unique microbial compositions between individuals, compliance in human studies, inability to carry out mechanistic studies, and inability to interrogate proximal regions of the gut without applying invasive techniques. In vitro gut simulator systems circumvent many of these limitations in animal and human models by allowing control of gut environmental conditions, decreasing variability …


A Functional Analysis Of The 3’ Regulatory Region Of The Immunoglobulin Heavy Chain Gene, Andrew David Snyder Jan 2016

A Functional Analysis Of The 3’ Regulatory Region Of The Immunoglobulin Heavy Chain Gene, Andrew David Snyder

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The immunoglobulin heavy chain (IGH) locus is partially responsible for immunoglobulin (Ig) production in B cells. The human IGH locus contains two 3’ regulatory regions (3’IghRR) that each contain three enhancers, which are thought to help drive overall transcription of the locus and also influence class switching to alternative Ig isotypes. The hs1.2 enhancer within the 3’IghRR is polymorphic in humans, containing a 53 bp invariant sequence (IS) that can be repeated up to four times. In vitro, the human hs1.2 enhancer is a sensitive target of exogenous chemicals, particularly 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin), a potent inhibitor of Ig expression …


The Role Of Interleukin-2 In Directing Vascular Smooth Muscle Cell Function And Its Implications For Understanding The Progression Of Atherosclerosis, Prakash Arumugam Jan 2016

The Role Of Interleukin-2 In Directing Vascular Smooth Muscle Cell Function And Its Implications For Understanding The Progression Of Atherosclerosis, Prakash Arumugam

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Atherosclerosis is an inflammatory disorder of the vasculature leading to the development of plaques within vessel walls. A critical component of atherosclerosis involves migration and proliferation of vascular smooth muscle cells (VSMCs) into the developing plaque, however, its mechanism is not yet understood. Previous studies have reported that IL-2 is deposited within the vasculature and IL-2 accumulates within atherosclerotic plaques due to secretion by infiltrating Th-1 cells. A limited number of studies suggest that VSMCs express a partial IL-2 receptor, comprising the ß and ¿ subunit. This suggests that IL-2 may elicit a physiological response in VSMCs. Considering IL-2’s proliferative …


Interaction Of Due-B And Treslin During The Initiation Of Dna Replication, Sumeet Poudel Jan 2016

Interaction Of Due-B And Treslin During The Initiation Of Dna Replication, Sumeet Poudel

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The initiation of DNA replication is a highly regulated and coordinated process. To ensure that the entire genome is replicated only once per cell cycle, many replication proteins are assembled on the chromatin in a step-wise and cell cycle dependent manner. This process is controlled by interaction of replication proteins, post-translational modifications of the replication factors, control of cellular localization of the proteins, or replication factor degradation after their function terminates. Two kinases, CDK (cyclin dependent kinase) and DDK (Dbf4/Drf1 dependent kinase), play important roles during the initiation stage of DNA replication. The c-myc DNA unwinding element-binding protein (DUE-B) is …


Evidence That Myo-Inositol Plus Ethanolamine Elevates Plasmalogen Levels And Lends Protection Against Oxidative Stress In Neuro-2a Cells, Isaie Sibomana Jan 2016

Evidence That Myo-Inositol Plus Ethanolamine Elevates Plasmalogen Levels And Lends Protection Against Oxidative Stress In Neuro-2a Cells, Isaie Sibomana

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Plasmalogens are glycerophospholipids abundant in brain and heart tissues. Evidence suggests that they have antioxidant properties. Studies from our laboratory showed that rats treated with myo-inositol plus ethanolamine (ME) have elevated ethanolamine plasmalogens (PE-Pls) in brain and are protected against phosphine-induced oxidative stress. We hypothesized that ME elevates PE-Pls levels and protects against oxidative stress through oxidation of its vinyl ether bond. We tested this hypothesis in Neuro-2A cell culture and assessed the effects of treatments with myo-inositol (M), ethanolamine (Etn), or a combination (ME) on the: (1) effects on phospholipid (PL) classes, especially Etn PLs; (2) effects on cell …


Refining A Post-Stroke Pharmacological And Physical Treatment To Reduce Infarct Volume Or Improve Functional Recovery, Using Gene Expression Changes In The Peri-Infarct Region To Examine Potential Mechanisms In Male And Female Rats, Moner A. Ragas Jan 2016

Refining A Post-Stroke Pharmacological And Physical Treatment To Reduce Infarct Volume Or Improve Functional Recovery, Using Gene Expression Changes In The Peri-Infarct Region To Examine Potential Mechanisms In Male And Female Rats, Moner A. Ragas

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Stroke, a life-threatening medical condition, is the fifth-leading cause of death in the United States with an estimated annual cost of treatments above $70 billion. A combination of innovative approaches was used in our lab to optimize the pre-clinical stroke research design by choosing the most appropriate animal model and methodologies to increase the translational capability of the stroke research. The first study, modeled after ongoing clinical trials using fluoxetine, refined the appropriate timing of fluoxetine and ascorbic acid delivery if a rat was on simvastatin for 7 days pre-stroke and throughout the remainder of the study. Administration of fluoxetine …


Co-Transplantation Of Endothelial Progenitor Cells And Neural Progenitor Cells For Treating Ischemic Stroke In A Mouse Model, Jinju Wang Jan 2016

Co-Transplantation Of Endothelial Progenitor Cells And Neural Progenitor Cells For Treating Ischemic Stroke In A Mouse Model, Jinju Wang

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Ischemic stroke (IS) is a major cause of death and disability with limited and less effective therapeutics. Transplantation of stem cells, such as neuronal progenitor cells (NPCs) and endothelial progenitor cells (EPCs), is promising for treating IS. It is well known that neurogenesis and angiogenesis are critical for cerebral repair following ischemic injury. However, whether co-transplantation of EPCs and NPCs has synergistic effects remains unclarified. In addition, the PI3K/Akt pathway participates in modulating a widely range of cellular functions such as anti-apoptotic and anti-oxidant. The signal pathways responsible for the effects of grafted NPCs and EPCs are also waiting for …


Measuring The Acute Physiological Effects Of Leptin In The Carotid Body, Richard Laurence Pye Jan 2015

Measuring The Acute Physiological Effects Of Leptin In The Carotid Body, Richard Laurence Pye

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Obesity is the healthcare crisis of our generation. Circulating levels of the adipokine leptin are proportional to adiposity and in addition to its role as a satiety factor leptin has been shown to have a host of pleiotropic effects. Among these effects is its role as a respiratory stimulant where it has been shown to have both whole body and central stimulatory effects on breathing. Porzionato et al. (2011) showed that leptin and leptin receptors are selectively expressed in the chemosensing type I cells of the carotid body. Carotid bodies are small chemosensitive organs that act as the primary peripheral …


The Guinea Pig Model For Organophosphate Toxicology And Therapeutic Development, Christopher Daniel Ruark Jan 2015

The Guinea Pig Model For Organophosphate Toxicology And Therapeutic Development, Christopher Daniel Ruark

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Organophosphates (OPs) are highly toxic insecticides and nerve agents that have been designed to inhibit the hydrolysis of acetylcholine by binding to the serine active site of acetylcholinesterase (AChE). They are one of the most common causes of human poisoning worldwide and are frequently intentionally used in suicides in agricultural areas. For this reason, there is a need for therapeutics to rescue those from intoxication. Obvious ethical concerns prevent humans from being subjected to OP exposure for therapeutic efficacy and safety testing. Therefore, animal surrogates for humans must be appropriately selected. A new paradigm, described herein, incorporating both in silico …


Vitamin D Receptor And 1Α, 25-Dihydroxyvitamin D3 Mediated Regulation Of Δnp63Α, Hill Tremayne Natasha Jan 2015

Vitamin D Receptor And 1Α, 25-Dihydroxyvitamin D3 Mediated Regulation Of Δnp63Α, Hill Tremayne Natasha

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1alpha, 25-dihydroxyvitamin D3 (VD3), the ligand for the Vitamin D Receptor (VDR), functions to both inhibit cell growth and promote cell survival. High-dose VD3 is being utilized as a cancer preventive therapy for melanoma, breast and colorectal cancers, without a complete understanding of VD3/VDR signaling. DeltaNp63alpha, considered to be a proto-oncogene, is overexpressed in non-melanoma skin cancers (NMSCs), induces VDR gene expression and promotes keratinocyte proliferation, and may serve to exacerbate non-melanoma skin cancer. The objective of this dissertation was to determine whether VDR/VD3 signaling promotes keratinocyte proliferation by up-regulating DeltaNp63alpha. I showed that VDR increases DeltaNp63alpha expression at both …


Manipulation Of Gold Nanorod Physicochemical Properties To Enhance Biocompatibility, Uptake And Intracellular Preservation Of Optical Properties For Bio-Imaging And Plasmonic Photo-Therapeutic Applications, Anthony B. Polito Jan 2015

Manipulation Of Gold Nanorod Physicochemical Properties To Enhance Biocompatibility, Uptake And Intracellular Preservation Of Optical Properties For Bio-Imaging And Plasmonic Photo-Therapeutic Applications, Anthony B. Polito

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Gold nanorods (GNRs) due to their tunable optical properties within the near infrared (NIR) region have been identified as strong candidates for new nano-based biomedical applications. Unfortunately, many have reported GNR cytotoxicity and it is still unclear how GNR aspect ratio (AR), surface charge and surface chemistry contribute to cellular association and cytotoxicity. GNR surface chemistry modifications have been reported to reduce cytotoxicity, however they can result in poor cellular uptake and loss of NIR optical properties preventing efficiency with bio-imaging and photo-thermal applications. The aim of this study was to determine if manipulation of GNR physicochemical properties could enhance …


The Organization Of Kv2.1 Channel Proteins In The Membrane Of Spinal Motoneurons: Regulation By Injury And Cellular Activity, Shannon Hunt Romer Jan 2015

The Organization Of Kv2.1 Channel Proteins In The Membrane Of Spinal Motoneurons: Regulation By Injury And Cellular Activity, Shannon Hunt Romer

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The intrinsic membrane properties of neurons in the central nervous system are controlled by the tight regulation of membrane-bound ion channels. Rather than existing as static entities operating only in opened or closed states in fixed locations, ion channels are dynamic molecules with the capacity to adopt multiple functional states through conformational changes and/or post-translational modification - enabling flexibility in their activity. Furthermore, the location of ion channels within certain membrane compartments and/or signaling ensembles is critical to synaptic integration and shaping of firing properties, and can also be dynamically modified by changes in neuronal activity and pathology. In mammalian …


Regulation Of Motoneuron Firing Properties: Intrinsic And Circuit-Based Mechanisms, Adam S. Deardorff Jan 2015

Regulation Of Motoneuron Firing Properties: Intrinsic And Circuit-Based Mechanisms, Adam S. Deardorff

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Body and limb movements are controlled by regulating the activity of motor pools and their constituent motoneurons. An extensive complement of tightly regulated ion channels and second messenger systems determine active motoneuron spiking behavior, while segmental propriospinal circuits ensure the faithful execution of motor commands by providing real time sensory feedback to motoneurons and other somatosensory centers. However, current mechanistic understanding is incomplete for critical factor regulating motoneuron firing properties. Fundamental gaps in knowledge exist regarding (a) the spatial distribution and organization of specific ion channels in motoneurons, (b) the contribution of specific channels to motoneuron intrinsic properties, (c) the …


A Novel Function For Fancj Helicase In Microsatellite Stabilization During Replication Stress, Joanna Barthelemy Jan 2015

A Novel Function For Fancj Helicase In Microsatellite Stabilization During Replication Stress, Joanna Barthelemy

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Noncanonical DNA structure-forming sequences, such as hairpin structures, stall replication forks in vivo, expand or contract during DNA replication, and colocalize with chromosome fragile sites. Since the frequency of hairpin formation is higher than the frequency of expansion or contraction, the cell may possess mechanisms to resolve hairpin structures prior to replication fork stalling. One possible activity for hairpin resolution is the FANCJ DNA helicase, known to unwind noncanoncial DNA structures in vitro. Indeed, mutations or loss of any of the nineteen FANC genes, including FANCJ, leads to genome instability and the cancer-prone syndrome Fanconi anemia (FA). To test whether …


Silver Nanoparticles: The Immediate Benefits Of Low Bacterial Resistance And The Long-Term Risk Of Persistent Stress In Mammalian Cells, David Harold Ellis Jan 2015

Silver Nanoparticles: The Immediate Benefits Of Low Bacterial Resistance And The Long-Term Risk Of Persistent Stress In Mammalian Cells, David Harold Ellis

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Silver nanoparticles (AgNPs) are the fastest growing sector of nanotechnology, due mostly to their antibacterial properties. The antibacterial effectiveness of AgNPs is well known and derives from the shedding of silver ions which have multiple antibacterial targets in the bacterial cell. Due to their continuous release of ions and demonstrated antibacterial potency, some predict that AgNPs have a low potential for resistance development, which would make them a valuable asset in wound management. The ability for AgNPs to cause oxidative imbalance in mammalian cells is also well known, but the potential long-term impact of such a stress has not been …


The Regulation Of The Eight-Exon Isoform Of The Coxsackievirus And Adenovirus Receptor (CarEx8) And Its Biological Relevance, Poornima Kotha Lakshmi Narayan Jan 2014

The Regulation Of The Eight-Exon Isoform Of The Coxsackievirus And Adenovirus Receptor (CarEx8) And Its Biological Relevance, Poornima Kotha Lakshmi Narayan

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The airway epithelium poses a formidable barrier for the entry of pathogenic viruses due to the formation of tight junctions between adjacent epithelial cells. The coxsackievirus and adenovirus receptor (CAR), a member of the Ig superfamily of cell junction adhesion proteins, is the primary receptor for adenovirus entry and infection. As a result of alternative splicing, two transmembrane isoforms of CAR are generated. While the seven-exon isoform of CAR (CAREX7) is hidden on the basolateral surface of polarized epithelia, the eight-exon isoform of CAR (CAREX8) localizes within the sub-apical region and at the air-exposed apical surface. …


Chemosensitive Neurons Of The Locus Coeruleus And The Nucleus Tractus Solitarius: Three Dimensional Morphology And Association With The Vasculature, Cathy D. Graham Jan 2014

Chemosensitive Neurons Of The Locus Coeruleus And The Nucleus Tractus Solitarius: Three Dimensional Morphology And Association With The Vasculature, Cathy D. Graham

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We studied the 3 dimensional structure of LC and cNTS neurons from neonatal rats. Neurons were identified as either chemosensitive or nonchemosensitive based on their firing rate response to hypercapnia, using whole-cell patch clamping and were passively loaded with Lucifer Yellow. The identified, loaded neurons were reconstructed and analyzed using Neurolucida Neuron Tracing Software. Chemosensitive LC neurons have less rounded soma than nonchemosensitive neurons, and they have dendrites arising from two poles to produce a fusiform appearance. The dendritic branches extend a greater distance from the soma of chemosensitive than nonchemosensitive neurons. Conversely, chemosensitive cNTS neurons were found to have …


Guanine Nucleotide Exchange Activity Of Phospholipase D2 And Its Regulation, Madhupriya Mahankali Jan 2014

Guanine Nucleotide Exchange Activity Of Phospholipase D2 And Its Regulation, Madhupriya Mahankali

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Phospholipase D2 (PLD2) is a cell membrane lipase that catalyzes the break down of phosphatidyl choline (PC) to phosphatidic acid (PA) and choline. PA is one of the major lipid second messengers that modulate a wide variety of signaling pathways, which are crucial for various cellular functions. In addition to this, PLD2 via binding to a large number of proteins and thereby regulates them independent of its lipase activity. Whereas PLD2 is involved in plethora of cellular functions, high levels of protein and/or activity of PLD2 are reported in variety of disease conditions, such as cancer metastasis and chronic inflammation …


Apelin Regulation Of K-Cl Cotransport In Vascular Smooth Muscle Cells., Neelima Sharma Jan 2014

Apelin Regulation Of K-Cl Cotransport In Vascular Smooth Muscle Cells., Neelima Sharma

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Atherosclerosis and high circulating levels of oxidized low density lipoproteins (oxLDL) are considered among the most important risk factors for the occurrence and development of cardiovascular disease (CVD). During the atherosclerotic lesion repair, phenotypic transition of vascular smooth muscle cells (VSMCs) from contractile to synthetic states plays a central role. In this process, enhanced proliferation/migration of VSMCs, from the tunica media to the intima, is required to sustain blood vessel endothelium integrity, and for inducing vessel wall remodeling in response to injury. At the molecular level, the activity of electroneutral potassium-chloride cotransporters or KCCs, is necessary to: a) allow changes …


Rab3a As A Modulator Of Homeostatic Synaptic Plasticity, Andrew G. Koesters Jan 2014

Rab3a As A Modulator Of Homeostatic Synaptic Plasticity, Andrew G. Koesters

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The nervous system is faced with perturbations in activity levels throughout development and in disease or injury states. Neurons need to adapt to these changes in activity, but also need to maintain circuit firing within a normal range to stabilize the network from becoming too excited or too depressed. Homeostatic synaptic plasticity, the compensatory increase or decrease in synaptic strength as a result of excessive circuit inhibition or excitation, is a mechanism that the nervous system utilizes to keep network activity at normal levels. Despite intense effort, little is known about the mechanisms underlying homeostatic synaptic plasticity. Numerous studies have …


The Role Of Subunit Iii In The Functional And Structural Regulation Of Cytochrome C Oxidase In Rhodobacter Spheroids, Khadijeh Salim Alnajjar Jan 2014

The Role Of Subunit Iii In The Functional And Structural Regulation Of Cytochrome C Oxidase In Rhodobacter Spheroids, Khadijeh Salim Alnajjar

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Cytochrome c oxidase (COX) catalyzes the oxidation of ferrocytochrome c and the reduction of oxygen to water while concomitantly translocating protons across the inner mitochondrial membrane. The catalytic core of COX consists of three subunits that are conserved from the bacterial to the mitochondrial forms of the enzyme. Subunits I and II (SUI and SUII) contain the metal centers where electrons are transferred and oxygen binds for reduction. Subunit III (SUIII) does not contain any metals and has an unknown function. It contains three conserved histidine residues (3, 7 and 10) that are surface exposed and are in close proximity …