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Differential Effects Of Endocannabinoid Catabolic Inhibitors On Opioid Withdrawal In Mice, Thomas Gamage Dec 2013

Differential Effects Of Endocannabinoid Catabolic Inhibitors On Opioid Withdrawal In Mice, Thomas Gamage

Theses and Dissertations

The effects of cannabinoids in reducing somatic signs of opioid withdrawal have been known for some time. In morphine dependent rodents, opioid withdrawal following precipitation with the mu opioid antagonist naloxone elicits robust withdrawal behaviors including jumps, paw flutters, head shakes, diarrhea and weight loss. Delta-9-tetrahydrocannabinol has been shown to reduce this opioid withdrawal in mice via activation of the cannabinoid type-1 (CB1) receptor and recently it has been shown that inhibition of the catabolic enzymes for endocannabinoids also reduce somatic signs of opioid withdrawal. Specifically, inhibition the enzyme fatty acid amide hydrolase (FAAH), the catabolic enzyme for the endocannabinoid …


Clostridium Difficile Infection Occurrence In Academic Health Centers: Do Organizational Factors Matter?, Amy Pakyz Dec 2013

Clostridium Difficile Infection Occurrence In Academic Health Centers: Do Organizational Factors Matter?, Amy Pakyz

Theses and Dissertations

Healthcare-associated infections occur commonly in hospitals and have a major impact on patient well-being. The occurrence of the healthcare-associated infection, Clostridium difficile, has been occurring more frequently among hospitalized patients due to an epidemic strain, and is an important cause of antibiotic-associated diarrhea and colitis. This study examined the impact of several organizational factors on the occurrence of C. difficile infection (CDI) in hospitals using an institutional theory perspective. Administrative claims were utilized from University HealthSystem Consortium hospitals to obtain hospital-level data for the calendar year 2011. Data were available for 89 hospitals. Hospital-level analyses, negative binomial regression models, were …


Tobramycin Disposition In The Lung Following Airway Administration, Min Li Dec 2013

Tobramycin Disposition In The Lung Following Airway Administration, Min Li

Theses and Dissertations

Tobramycin disposition following airway administration was evaluated by meta-analysis of human data in the literature and, experimentally, using a realistic ex vivo model, the isolated perfused rat lung preparation (IPRL). Pulmonary bioavailability of inhaled tobramycin in published studies was re-evaluated separately for CF and healthy adults, with the drug’s intrinsic pharmacokinetic (PK) parameters obtained from intravenous (IV) studies in the literature. While large variations in tobramycin’s clearance precluded accurate assessment of its bioavailability, the results were indicative of substantial pulmonary absorption, in spite of its hydrophilic and poly cationic properties. To explore its disposition kinetics and mechanisms following airway administration, …


Transcriptional Crosstalk Between Helper Bacteriophages And Staphylococcal Aureus Pathogenicity Islands, Kristin Lane Dec 2013

Transcriptional Crosstalk Between Helper Bacteriophages And Staphylococcal Aureus Pathogenicity Islands, Kristin Lane

Theses and Dissertations

Acquisition of a superantigen pathogenicity island (SaPI) significantly increases virulence in Staphylococcus aureus. Horizontal transfer of SaPIs occurs at high frequency and depends upon a helper bacteriophage, either through direct infection or SOS-mediated induction of a lysogen. SaPIs hijack the packaging machinery of the helper phage, leading to the formation of SaPI-containing transducing particles that can introduce the pathogenicity island into neighboring SaPI-negative cells. All SaPIs contain a conserved core of genes, some of which are co-transcribed as an operon and encode functions involved in helper exploitation. The goal of this study was to more fully understand the intricate relationships …


Effects Of Thoracic Spinal Manipulative Therapy On Thoracic Spine And Shoulder Kinematics, Thoracic Spine Flexion/Extension Excursion, And Pressure Pain Sensitivity In Patients With Subacromial Pain Syndrome, Joseph Kardouni Dec 2013

Effects Of Thoracic Spinal Manipulative Therapy On Thoracic Spine And Shoulder Kinematics, Thoracic Spine Flexion/Extension Excursion, And Pressure Pain Sensitivity In Patients With Subacromial Pain Syndrome, Joseph Kardouni

Theses and Dissertations

EFFECTS OF THORACIC SPINAL MANIPULATIVE THERAPY ON THORACIC SPINE AND SHOULDER KINEMATICS, THORACIC SPINE FLEXION/EXTENSION EXCURSION, AND PRESSURE PAIN SENSITIVITY IN PATIENTS WITH SUBACROMIAL PAIN SYNDROME By Joseph R. Kardouni, Ph.D., PT A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, at Virginia Commonwealth University. Virginia Commonwealth University, 2013. Major Director: Lori A. Michener, PhD, PT, ATC, Professor, Department of Physical Therapy In patients with shoulder pain, the use of manual therapy directed at the spine and shoulder have been reported to provide superior outcomes to exercise based interventions or usual care without …


Hybrid Pet/Mri Nanoparticle Development And Multi-Modal Imaging, David Hoffman Dec 2013

Hybrid Pet/Mri Nanoparticle Development And Multi-Modal Imaging, David Hoffman

Theses and Dissertations

The development of hybrid PET/MRI imaging systems needs to be paralleled with the development of a hybrid intrinsic PET/MRI probes. The aim of this work was to develop and validate a novel radio-superparamagnetic nanoparticle (r-SPNP) for hybrid PET/MRI imaging. This was achieved with the synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) that intrinsically incorporated 59Fe and manganese iron oxide nanoparticles (MIONs) that intrinsically incorporated 52Mn. Both [59Fe]-SPIONs and [52Mn]-MIONs were produced through thermal decomposition synthesis. The physiochemical characteristics of the r-SPNPs were assessed with TEM, DLS, and zeta-potential measurements, as well as in imaging phantom studies. The [59Fe]-SPIONs were evaluated …


Analysis Of Plasminogen Binding To Treponema Denticola, A Key Periopathogen, Brittney Tegels Nov 2013

Analysis Of Plasminogen Binding To Treponema Denticola, A Key Periopathogen, Brittney Tegels

Theses and Dissertations

Periodontitis is a chronic inflammatory disease that affects over 116 million adults in the United States. A shift in the normal microflora occurs as periodontal disease develops resulting in a larger number of Gram-negative anaerobes and spirochetes. An increase in the oral spirochete, Treponema denticola, is highly correlated with periodontal disease progression and severity. The ability of this periopathogen to thrive in the subgingival crevice is dependent on complement evasion mechanisms. Earlier analyses demonstrated that the primary mechanism of T. denticola serum resistance is binding of the human complement regulatory protein, Factor H (FH), to the factor H-binding protein (FhbB). …


Sirt6 And Premature Aging Of Hutchinson-Gilford Progeria Syndrome Fibroblasts., Helal Endisha Nov 2013

Sirt6 And Premature Aging Of Hutchinson-Gilford Progeria Syndrome Fibroblasts., Helal Endisha

Theses and Dissertations

The genetic disease Hutchinson-Gilford Progeria Syndrome (HGPS) arises from a de novo single nucleotide mutation (1824CàT) in the LMNA gene. As a result, the mutated lamin A protein (progerin) remains farnesylated and permanently attached to the nuclear membrane. Progerin accumulates and deforms the nuclear membrane leading to an array of cellular abnormalities driving the cells to enter a state of permanent cell-cycle arrest early on in replicative age i.e. premature cellular senescence. Cellular senescence has been extensively studied as one of the contributing factors to aging in HGPS patients and other age-related diseases. There has also been evidence to show …


Identification Of Human Pgc-1Α-B Isoforms Using A Novel Pgc-1Α-B Specific Antibody, Shannon Hedrick Nov 2013

Identification Of Human Pgc-1Α-B Isoforms Using A Novel Pgc-1Α-B Specific Antibody, Shannon Hedrick

Theses and Dissertations

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is known as the master regulator of mitochondrial biogenesis. PGC-1α holds this role by acting as a transcriptional coactivator for an array of transcription factors and nuclear hormone receptors, such as NRF-1/2 and ERRα/γ, whose downstream targets function in mitochondrial biogenesis and oxidative phosphorylation. PGC-1α is regulated both at the transcriptional and post-translational level in several signaling pathways, including p38 MAPK and AMPK. This regulation affects which transcription factor binding events can occur in a given tissue, and thus affects regulation of PGC-1α target genes. PGC-1α is downregulated in many neurodegenerative disorders as …


Beta 2 Nicotinic Acetylcholine Receptor Contributions To Anxiety-Like Behavior, Shawn Anderson Nov 2013

Beta 2 Nicotinic Acetylcholine Receptor Contributions To Anxiety-Like Behavior, Shawn Anderson

Theses and Dissertations

Nicotine is a major psychoactive ingredient in tobacco that is thought to promote smoking behavior via nicotinic acetylcholine receptors (nAChRs) in the brain. Given reports that people smoke to relieve anxiety and that anxiety precipitates relapse, the overarching goal of this dissertation research is to assess beta 2 subunit containing nAChR (beta2*nAChR) contributions to anxiety-like behavior. Nicotine’s activity at beta2*nAChRs is concentration-dependent, with high concentrations facilitating activation followed by rapid desensitization and low concentrations preferentially desensitizing beta2*nAChRs; hence, activation or inhibition of beta2*nAChRs may support smoking behavior. Rodent studies reveal that nicotine affects anxiety-like behavior dose-dependently: low doses promote anxiolysis- …


Alcohol And Medication Use In Community-Dwelling Older Adults: Understanding The Effect Of Alcohol And Central Nervous System-Acting Medications On The Risk For Falls, Maitreyee Mohanty Nov 2013

Alcohol And Medication Use In Community-Dwelling Older Adults: Understanding The Effect Of Alcohol And Central Nervous System-Acting Medications On The Risk For Falls, Maitreyee Mohanty

Theses and Dissertations

Introduction: Aging, comorbid conditions, and use of medications render older adults more susceptible to alcohol-disease or alcohol-drug interactions that may lead to harmful outcomes. In this dissertation project the risk profile of alcohol and medications use among older adults was investigated. Considering the rise in CNS-acting medication use and the adverse effect profile linked to CNS-acting medications, it was also of interest to find if older adults were at risk of falling due to interactions between alcohol and CNS-acting medication. Objectives: The objectives were as follows: 1) to determine the prevalence, pattern and factors associated with at-risk drinking, 2) to …


Behavioral And Genomic Characterization Of Scheduled Ethanol Deprivation, Jonathan Warner Nov 2013

Behavioral And Genomic Characterization Of Scheduled Ethanol Deprivation, Jonathan Warner

Theses and Dissertations

Alcoholism is a persistent substance abuse disorder that is associated with negative health, social, and economic outcomes. Treatment strategies for alcohol use disorders are limited, and only three drugs have been approved by the FDA for treatment. Although behavioral therapy and drug combination strategies improve abstinence outcomes, the majority of those in treatment will not achieve long-term abstinence. Therefore, better treatment strategies are needed. While much progress has been made toward understanding the neurobiology of alcoholism, this knowledge has not been effectively translated into treatment strategies. Animal models of alcohol drinking have been crucial to this research effort, but until …


Analyzing The Functions Of Human Polynucleotide Phosphorylase (Hpnpaseold-35), Upneet K. Sokhi Nov 2013

Analyzing The Functions Of Human Polynucleotide Phosphorylase (Hpnpaseold-35), Upneet K. Sokhi

Theses and Dissertations

RNA degradation plays a fundamental role in maintaining cellular homeostasis, along with being a part of normal regulatory mechanisms, whether it occurs as a surveillance mechanism eliminating aberrant mRNAs or during RNA processing to generate mature transcripts. 3’-5’ exoribonucleases are essential mediators of RNA decay pathways, and one such evolutionarily conserved enzyme is polynucleotide phosphorylase (PNPase). The human homologue of this fascinating enzymatic protein (hPNPaseold-35) was cloned a decade ago in the context of terminal differentiation and senescence through a novel ‘overlapping pathway screening’ approach. Since then, significant insights have been garnered about this exoribonuclease and its repertoire of expanding …


A Molecular Mechanism Regulating The Timing Of Corticogeniculate Innervation, Justin Brooks Oct 2013

A Molecular Mechanism Regulating The Timing Of Corticogeniculate Innervation, Justin Brooks

Theses and Dissertations

Visual system development requires the formation of precise circuitry in the dorsal lateral geniculate nucleus (dLGN) of the thalamus. Although much work has examined the molecular mechanisms by which retinal axons target and form synapses in dLGN, much less is known about the mechanisms that coordinate the formation of non-retinal inputs in dLGN. These non-retinal inputs represent ~90% of the terminals that form in dLGN. Interestingly, recently reports show that the targeting and formation of retinal and non-retinal inputs are temporally orchestrated. dLGN relay neurons are first innervated by retinal axons, and it is only after retinogeniculate synapses form that …


Exploring Substance Use Disorders Community Outpatient Counselors’ Experiences Treating Clients With Co-Occurring Medical Conditions: An Interpretative Phenomenological Analysis, Lauretta Cathers Sep 2013

Exploring Substance Use Disorders Community Outpatient Counselors’ Experiences Treating Clients With Co-Occurring Medical Conditions: An Interpretative Phenomenological Analysis, Lauretta Cathers

Theses and Dissertations

Abstract EXPLORING SUBSTANCE USE DISORDERS COMMUNITY OUTPATIENT COUNSELORS’ EXPERIENCES TREATING CLIENTS WITH CO-OCCURRING MEDICAL CONDITIONS. AN INTERPRETATIVE PHENOMENOLOGICAL ANALYSIS Lauretta Anne Cathers, Ph.D. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2013 Major Director: Amy Armstrong, PhD, Chair, Rehabilitation Counseling The Interpretative Phenomenological Analysis study presents the findings from a qualitative study examining substance use disorders (SUD) community outpatient treatment counselors’ experiences treating clients with co-occurring medical conditions. Interviews from five SUD community outpatient treatment counselors resulted in four emerging super-ordinate themes. The findings illustrate …


The Role Of Outer Membrane Protein A In Anaplasma Marginale Cellular Invasion And Its Potential As A Cross-Protective Antigen, Sarvani Emani Sep 2013

The Role Of Outer Membrane Protein A In Anaplasma Marginale Cellular Invasion And Its Potential As A Cross-Protective Antigen, Sarvani Emani

Theses and Dissertations

Anaplasma phagocytophilum and A. marginale are the etiologic agents of human granulocytic anaplasmosis and bovine anaplasmosis, respectively. Both diseases can be severe, even fatal, and protective vaccines for each are lacking. We recently identified A. phagocytophilum outer membrane protein A (ApOmpA) as being critical for cellular invasion and is expressed during infection of mammalian but not tick cells. Disrupting ApOmpA-host cell interactions significantly inhibits A. phagocytophilum entry into host cells. ApOmpA and its A. marginale ortholog, AM854 (A. marginale OmpA; AmOmpA) exhibit 44% amino acid identity. The ApOmpA invasin domain is highly conserved between both proteins. In this study, we …


The Role Of Nitric Oxide Dysregulation In Tumor Maintenance, Christopher Rabender Sep 2013

The Role Of Nitric Oxide Dysregulation In Tumor Maintenance, Christopher Rabender

Theses and Dissertations

The inflammatory nature of the tumor microenvironment provides a cytokine and chemokine rich proliferative environment. Much of the responsibility of this environment is due to the production of Reactive Oxygen Species (ROS). These studies examined the proliferative rich tumor environment from a new perspective of Nitric Oxide Synthase (NOS) dysregulation. NOS’s have the ability to become uncoupled and generate superoxide in lieu of nitric oxide (NO). A requirement of NOS for the production of NO is the cofactor tetrahydrobiopterin (BH4) and when it is missing NOS becomes uncoupled and turns into a peroxynitrite synthase. Here I demonstrate that NOS is …


Functional Characterization Of Crip1a Knockout Mice, Joanna Jacob Aug 2013

Functional Characterization Of Crip1a Knockout Mice, Joanna Jacob

Theses and Dissertations

CB1 cannabinoid receptors are G-protein-coupled receptors that mediate the central nervous system (CNS) effects of marijuana and endocannabinoids. Recently, cannabinoid receptor interacting protein 1a (CRIP1a) was discovered as a novel protein that binds to the CB1 receptor C-terminus and inhibits CB1 receptor activity without affecting CB1 expression. This thesis investigated the functions of CRIP1a by characterizing the first CRIP1a knockout (KO) mouse line. The absence of CRIP1a was confirmed in KO mice using quantitative PCR and immunoblotting. I hypothesized that CRIP1a KO mice would exhibit enhanced CB1 receptor-mediated G-protein activity in the CNS, as well as cannabimemetic phenotypes and enhanced …


Positron Emission Tomography For Pre-Clinical Sub-Volume Dose Escalation, Christopher Bass Aug 2013

Positron Emission Tomography For Pre-Clinical Sub-Volume Dose Escalation, Christopher Bass

Theses and Dissertations

Purpose: This dissertation focuses on establishment of pre-clinical methods facilitating the use of PET imaging for selective sub-volume dose escalation. Specifically the problems addressed are 1.) The difficulties associated with comparing multiple PET images, 2.) The need for further validation of novel PET tracers before their implementation in dose escalation schema and 3.) The lack of concrete pre-clinical data supporting the use of PET images for guidance of selective sub-volume dose escalations. Methods and materials: In order to compare multiple PET images the confounding effects of mispositioning and anatomical change between imaging sessions needed to be alleviated. To mitigate the …


Osteopontin Expression During The Acute Immune Response Mediates Reactive Synaptogenesis And Adaptive Outcome, Julie Chan Aug 2013

Osteopontin Expression During The Acute Immune Response Mediates Reactive Synaptogenesis And Adaptive Outcome, Julie Chan

Theses and Dissertations

Traumatic brain injury (TBI) is a worldwide epidemic as the number of victims living with the resulting cognitive and physical impairment continues to rise, principally due to limited treatment options which fail to address its multifaceted sequelae. By approaching TBI therapy from a molecular standpoint, we have the opportunity to develop a better understanding of the mechanisms which prevent effective recovery. With this information, we can move toward the identification of novel therapeutic treatments which target specific molecules to improve patient outcome following TBI. Here, we have focused on the therapeutic potential of osteopontin (OPN), an extracellular matrix (ECM) protein …


Assessment Of The Drug-Drug Interaction Potential Of Anionic Components In The Diet And Herbal Medicines On Organic Anion Transporters (Slc22 Family), Li Wang Aug 2013

Assessment Of The Drug-Drug Interaction Potential Of Anionic Components In The Diet And Herbal Medicines On Organic Anion Transporters (Slc22 Family), Li Wang

Theses and Dissertations

Numerous natural products are widely used as first-line/alternative therapeutics and dietary supplements in both western and eastern society. However, the safety and efficacy profiles for herbal products are still limited. Organic anion transporters (OATs; SLC22 family) are expressed in many barrier organs and mediate in vivo body disposition of a broad array of endogenous substances and clinically important drugs. As some dietary flavonoids and phenolic acids were previously demonstrated to interact with OATs, it is necessary to explore the potential interaction of such components found in natural products in order to avoid potential OAT-mediated drug-drug interactions (DDIs). The inhibitory effects …


A Novel Biorelevant In Vitro System To Predict The In Vivo Performance Of Oral Transmucosal Products, Poonam Delvadia Jul 2013

A Novel Biorelevant In Vitro System To Predict The In Vivo Performance Of Oral Transmucosal Products, Poonam Delvadia

Theses and Dissertations

In vitro dissolution, release and permeation testing is a common practice during drug product research and development. These in vitro tests, if predictive, are referred to as biorelevant tests and can play diverse roles to facilitate and expedite product development in a cost effective manner. Oral transmucosal products (OTPs) are currently tested using compendial and modified in vitro tests which may or may not be good predictors of in vivo performance due to a lack of biorelevance. A critical need for a broadly applicable and biorelevant in vitro system for OTPs has been expressed in the literature and the goal …


Anti-Cytomegalovirus Activity Of Atanyl Blue Prl, An Anthraquinone Derivative, Zohaib Alam Jul 2013

Anti-Cytomegalovirus Activity Of Atanyl Blue Prl, An Anthraquinone Derivative, Zohaib Alam

Theses and Dissertations

Cytomegalovirus (CMV) is a significant cause of mortality and morbidity in immunocompromised patients and an important cause of birth defects if acquired in utero. The licensed CMV antivirals, ganciclovir, cidofovir and foscarnet, all target the viral DNA polymerase. For each drug prolonged use is associated with significant toxicities and development of drug resistance. None are approved for use during pregnancy. Therefore, development of new anti-CMV drugs that target different pathways would be beneficial. All herpesviruses encode an alkaline nuclease. That genetic disruption of the CMV alkaline nuclease, UL98, reduces CMV replication by 1,000-fold suggests that UL98 may be a useful …


Role Of Crc In The Regulation Of Alginate In Pseudomonas Aeruginosa, Arfeen Alam Jul 2013

Role Of Crc In The Regulation Of Alginate In Pseudomonas Aeruginosa, Arfeen Alam

Theses and Dissertations

As Pseudomonas aeruginosa adapts to the Cystic Fibrosis (CF) and chronic obstructive pulmonary disease (COPD) lung environments, mucoid strains often appear as a result of alginate overproduction. Such mucoid conversion is associated with the establishment of a chronic pulmonary infection. Alginate confers resistance to phagocytosis and has other pathogenic properties. The regulation of alginate production is complex and involves an alternate sigma factor, anti-sigmas and several DNA-binding transcriptional regulators. Here we examined the possibility that the catabolic repression control (Crc) protein repressor may affect alginate gene expression. A putative Crc binding site was observed adjacent to the ribosome binding site …


Exploring Electric Field-Induced Changes In Astrocyte Behavior, Doel Dhar Jul 2013

Exploring Electric Field-Induced Changes In Astrocyte Behavior, Doel Dhar

Theses and Dissertations

Electric fields, which are generated by the movement of charged ions across membranes, are found in all biological systems and can influence cellular components ranging from amino acids to biological macromolecules. Physiological field strengths range from 1 – 200 mV/mm, and these electric fields are especially elevated at sites of cellular growth during development and regeneration. It has previously been demonstrated that elevated electric fields induce alignment of astrocyte processes in vitro, enhancing the rate of neurite outgrowth. It is believed that electric fields of varying physiological strength affect other astrocytic responses associated with regeneration. To characterize the duration over …


Characterization Of Cyclic Di-Gmp Binding By The Sole Borrelia Burgdorferi And Borrelia Hermsii Pilz Domain-Containing Proteins, Katherine Louise Mallory Jul 2013

Characterization Of Cyclic Di-Gmp Binding By The Sole Borrelia Burgdorferi And Borrelia Hermsii Pilz Domain-Containing Proteins, Katherine Louise Mallory

Theses and Dissertations

Borrelia burgdorferi and Borrelia hermsii cause Lyme disease and relapsing fever, respectively. These spirochetes are maintained in an enzootic cycle, involving tick vectors and mammalian hosts. Differential gene expression is central in their survival in various environmental conditions. C-di-GMP has been demonstrated to be important in bacterial adaptation. Borrelia deletion mutant phenotypes have shown that c-di-GMP regulates motility, infectivity, and enzootic cycle progression. As the only known receptors encoded by Borrelia, PlzA and PlzC characterization is necessary in delineating c-di-GMP roles within the cell. In this study, biochemical, biophysical, and FRET methods demonstrated that these proteins exhibit a structural rearrangement …


Ex Vivo Reprogramming Of Tumor-Reactive Immune Cells From Fvbn202 Mice Bearing Lung Metastatic Mammary Carcinoma: An Immunotherapeutic Opportunity Revealed Against Recurrence, Charles Hall Jul 2013

Ex Vivo Reprogramming Of Tumor-Reactive Immune Cells From Fvbn202 Mice Bearing Lung Metastatic Mammary Carcinoma: An Immunotherapeutic Opportunity Revealed Against Recurrence, Charles Hall

Theses and Dissertations

Metastatic breast cancer treatment has seen few advances in recent years, yet treatment resistance continues to rise, causing disease recurrence. A pilot study was performed to determine the efficacy of ex vivo expansion and reprogramming of tumor-reactive immune cells from experimental metastatic tumor-sensitized mice. Also, phenotypic changes in tumors due to metastasis or tumor microenvironment influences were characterized. Metastatic neu+ mouse mammary carcinoma (mMMC) and its distant relapsing neu-antigen-negative variant (mANV) were investigated in FVBN202 mice. Tumor-reactive central memory CD8+ T cells and activated NK/NKT cells were successfully reprogrammed and expanded during 6-day expansion from mMMC- and/or mANV-sensitized mice, resulting …


Genetic Dissection Of Quantitative Trait Loci For Substances Of Abuse, Jo Lynne Harenza Jul 2013

Genetic Dissection Of Quantitative Trait Loci For Substances Of Abuse, Jo Lynne Harenza

Theses and Dissertations

It has been reported that an individual’s initial level of response to a drug might be predictive of his or her future risk of becoming dependent, thus basal gene expression profiles underlying those drug responses may be informative for both predicting addiction susceptibility and determining targets for intervention. This dissertation research aims to elucidate genetic risk factors underlying acute alcohol and nicotine dependence phenotypes using mouse genetic models of addiction. Phenotyping, brain region-specific mRNA expression profiling, and genetic mapping of a recombinant inbred panel of over 25 mouse strains were performed in order to identify quantitative trait loci (QTL) harboring …


Identification And Characterization Of Ethanol Responsive Genes In Acute Ethanol Behaviors In Caenorhabditis Elegans, Joseph Alaimo Jul 2013

Identification And Characterization Of Ethanol Responsive Genes In Acute Ethanol Behaviors In Caenorhabditis Elegans, Joseph Alaimo

Theses and Dissertations

Alcohol abuse and dependence are complex disorders that are influenced by many genetic and environmental factors. Acute behavioral responses to ethanol have predictive value for determining an individual’s long-term susceptibility to alcohol abuse and dependence. These behavioral responses are strongly influenced by genetics. Here, we have explored the role of genetic influences on acute behavioral responses to ethanol using the nematode worm, Caenorhabditis elegans. First, we explored the role of ethanol metabolism in acute behavior responses to ethanol. Natural variation in human ethanol metabolism machinery is one of the most reported and reproducible associations found to alter drinking behavior. Ethanol …


Validation Of Copy Number Variants Associated With Schizophrenia Risk In An Irish Population And Implications To Clinical Practice, Rachel L. Elves Jul 2013

Validation Of Copy Number Variants Associated With Schizophrenia Risk In An Irish Population And Implications To Clinical Practice, Rachel L. Elves

Theses and Dissertations

Schizophrenia is a complex disorder affecting 1% of the population and is highly heritable, but the majority of contributing genetic factors has remained elusive. Current risk estimates for clinical practice are primarily determined by family history and associated empirical risk. Copy number variants (CNVs) may hold the key to explaining the missing heritability in schizophrenia research; schizophrenia risk estimates as high as 30% have been found for the most-studied CNV associated with schizophrenia, 22q11. Currently, there are methods to identify CNVs though previously collected data from SNP microarrays that would facilitate these types of studies. To determine if algorithms that …