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Full-Text Articles in Biomedical Engineering and Bioengineering

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 …


A Novel System For Detection Of Dna Double Strand Breaks And Repair In Human Cells, Todd Warren Lewis Jan 2017

A Novel System For Detection Of Dna Double Strand Breaks And Repair In Human Cells, Todd Warren Lewis

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Imperative to genomic stability is the ability of the cell to repair damaged DNA which can occur from numerous endogenous byproducts of metabolism or exogenous components from the environment. The Fanconi anemia pathway is a DNA repair mechanism used by human cells to resolve multiple forms of DNA damage including interstrand crosslinks (ICL). Fanconi anemia (FA) is an autosomal recessive inherited disorder characterized by genome instability, developmental abnormalities, cancer predisposition and bone marrow failure. FA is attributed to a mutations in at least 18 genes (FANCA-FANCT) that play a concerted role in DNA repair. FANCT is the latest discovery in …


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 …


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 …


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 …


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 …


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 …


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 …


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 …


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 …


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 …


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 …


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 …


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 …


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 …


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 …


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 …


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 …


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 …


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 …


Peroxisome Proliferator-Activated Receptor Alpha: Insight Into The Structure, Function And Energy Homeostasis, Dhawal P. Oswal Jan 2014

Peroxisome Proliferator-Activated Receptor Alpha: Insight Into The Structure, Function And Energy Homeostasis, Dhawal P. Oswal

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Peroxisome proliferator-activated receptor alpha (PPAR alpha) belongs to the family of ligand-activated nuclear transcription factors and serves as a lipid sensor to regulate nutrient metabolism and energy homeostasis. The transcriptional activity of PPAR alpha is thought to be regulated by the binding of exogenous ligands (example, fenofibrate, TriCor), as well as endogenous ligands including fatty acids and their derivatives. Although long-chain fatty acids (LCFA) and their thioesters (long-chain fatty acyl-CoA; LCFA-CoA) have been shown to activate PPAR alpha of several species, the true identity of high-affinity endogenous ligands for human PPAR alpha (hPPAR alpha) has been more elusive. This two …


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. …


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 …


New Insights Into The Spinal Recurrent Inhibitory Pathway Normally And After Motoneuron Regeneration, Ahmed Zayed Obeidat Jan 2013

New Insights Into The Spinal Recurrent Inhibitory Pathway Normally And After Motoneuron Regeneration, Ahmed Zayed Obeidat

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Despite more than seven decades of intensive research, uncertainty is the hallmark of spinal recurrent inhibition. The simplest possible structure that is formed between the a-motoneuron and its inhibitory interneurons has been the subject of long lasting scientific debate. To date, there is no consensus on the functional significance of this circuit. Even the simplest assumption of a negative feedback loop does not hold true. The current work used the technique of in vivo intracellular recording from the adult rat a-motoneurons to study the normal function and the plasticity after nerve injury and regeneration of this simple, yet intricate spinal …


Elucidating A Role Of Btf And Trap150 In Pre-Mrna Processing And Cell Cycle Progression, Sapna N. Varia Jan 2013

Elucidating A Role Of Btf And Trap150 In Pre-Mrna Processing And Cell Cycle Progression, Sapna N. Varia

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Transcription of protein-coding genes is coordinated with pre-mRNA processing as well as mRNP assembly and nuclear export in mammalian cells. In this dissertation, I examined the functions of two homologous non-classical serine-arginine-rich (SR) proteins, Btf (BCLAF1) and TRAP150 in these steps of gene regulation. Since Btf and TRAP150 share 39% sequence identity and 66% sequence similarity, I also examined whether Btf and TRAP150 have overlapping or distinct functions in pre-mRNA processing. Using two different reporter loci, I showed in-situ recruitment of Btf and TRAP150 at reporter transcription sites, and I identified both Btf and TRAP150 being associated with a core …


Differential Regulation Of The Hippocampal Taurine Transporter Protein In Rat Brain: Mechanisms Contributing To Neuronal Volume Regulation, Amanda Noelle Freeman Jan 2013

Differential Regulation Of The Hippocampal Taurine Transporter Protein In Rat Brain: Mechanisms Contributing To Neuronal Volume Regulation, Amanda Noelle Freeman

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Background. In osmotic edema, net efflux of taurine from neurons and accumulation by astrocytes contributes to neuronal volume regulation and astrocytic swelling. Taurine is accumulated in both cell types by a sodium- and chloride-dependent 72-75 kDa protein transporter, TauT. TauT functional activity decreases in osmotically swollen neurons but is unaltered in swollen astrocytes, in vitro. This swelling-induced downregulation of neuronal TauT activity is blocked with the tyrosine kinase (TK) inhibitor, genistein. In contrast, PKC activation has no effect on neuronal TauT, but inhibits astrocytic TauT. Thus, we hypothesize that during osmotic swelling, neuronal TauT activity is regulated by a TK …


Reactive Oxygen Modulates B Lymphocyte Function Via The Nfκb/Rel Pathway, Eric J. Romer Jan 2013

Reactive Oxygen Modulates B Lymphocyte Function Via The Nfκb/Rel Pathway, Eric J. Romer

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Reactive Oxygen Intermediates (ROI) can significantly affect B Lymphocyte function, but the effects on key signaling pathways and gene expression in activated and non-activated B lymphocytes are largely undefined. This study demonstrates a concentration dependent effect of exogenous hydrogen peroxide on the transcriptional regulation of a 3' regulatory region of the Immunoglobulin heavy chain gene (3'IghRR). Specifically, low μM hydrogen peroxide induces an enhancing effect while higher μM hydrogen peroxide (greater than or equal to 100 μM) is suppressive. The enhancing effects of hydrogen peroxide on 3'IghRR activity are dependent on the NFκB/Rel pathway, and appear to be most prominent …


A Comprehensive Tool And Analytical Pathway For Differential Molecular Profiling And Biomarker Discovery, Claude Curtis Grigsby Jan 2013

A Comprehensive Tool And Analytical Pathway For Differential Molecular Profiling And Biomarker Discovery, Claude Curtis Grigsby

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The key requirements to any empirically based study are to: (1) accurately measure and then compare the collected results in determining the result of the hypothesis being tested; and (2) collect a sample representative of the entities being studied. To demonstrate that an informatics tool can be designed that provides spectral registration, spectral and chromatographic alignment, visualization, and comparative analysis for data generated from multiple analytical platforms, e.g., LC-MS and GC-MS, the results and data analysis of five unique sets of experiments using a suite of novel informatics tools are presented. Comprehensive and reproducible sample collection techniques were developed concomitantly …