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Understanding The Relation Between Routines And Problem Behaviors In Children With Clinical Diagnoses, Mark Ryan Pennick Jan 2013

Understanding The Relation Between Routines And Problem Behaviors In Children With Clinical Diagnoses, Mark Ryan Pennick

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The current study investigated the impact of routines on problem behaviors in children with the clinical diagnoses of either PDD, ADHD, or depression/anxiety. Previous research has identified negative relations between externalizing behaviors and routines as well as a link between using routines and having positive parenting. The study extends these findings to children with these various diagnoses and also to internalizing symptoms. In our sample negative relations were found between routines, as measured by the Child Routines Inventory (CRI), and both internalizing and externalizing symptoms when all groups were examined together. Additionally routines were found to moderate the relation between …

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Msx1 Mutations And Their Binding Interactions, Divakar Prakash Jan 2013

Msx1 Mutations And Their Binding Interactions, Divakar Prakash

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Orofacial clefting (OFC), also called cleft lip and/or palate, is the most common congenital birth anomaly that involve the craniofacial region in humans. The etiology of Non-Syndromic OFC (NS-OFC) is complex and multifactorial; a slew of genetic mutations, standing alone or in combinations, along with several environmental factors, play a major role in the disease process. Numerous linkage and association studies in humans, as well as expression studies and knockout mouse models, have implicated Muscle segment homeobox gene 1 (MSX1), which encodes a homeodomain/DNA binding domain (HD) containing transcription factor as a strong candidate contributing to NS-OFC and Tooth Agenesis …

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The Role Of Complement In Experimental Cerebral Malaria, Theresa N. Ramos Jan 2013

The Role Of Complement In Experimental Cerebral Malaria, Theresa N. Ramos

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Cerebral malaria (CM) is one of the most severe clinical complications of P. falciparum malaria with a fatality rate of 15-30%, and 10% of CM survivors have permanent neurological sequelae. Since inflammation is a central pathophysiological tenet of CM, we began examining the role of the complement system in pathogenesis of experimental cerebral malaria (ECM) using Plasmodium berghei ANKA (PbA) model. Previous studies using this model indicated that mice naturally deficient in complement component C5 were protected from cerebral complications, and wild type mice treated with anti-C5aR antibody were also protected. To determine the protective mechanism of naturally-C5 deficient mice, …

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Mesocorticolimbic Abnormalities In Schizophrenia: A Magnetic Resonance Spectroscopy And Diffusion Tensor Imaging Study, Meredith A. Reid Jan 2013

Mesocorticolimbic Abnormalities In Schizophrenia: A Magnetic Resonance Spectroscopy And Diffusion Tensor Imaging Study, Meredith A. Reid

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Schizophrenia is a complex, often debilitating chronic mental disorder that affects approximately 1% of people worldwide. Recently, there has been growing interest in identifying non-invasive biomarkers of schizophrenia. Understanding the molecular and structural mechanisms underlying clinical features of schizophrenia and patients' drug response is an important step in identifying biomarkers and potential targets for novel medications, treatment strategies, and interventions. The primary objective of this dissertation research was to use non-invasive magnetic resonance imaging techniques, specifically magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI), to examine the neurochemical and structural correlates of symptoms, cognition, and treatment response to antipsychotic …

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Commensal Microbiota And Its Impact On Health And Autoimmune Diabetets, Kyle James Wolf Jan 2013

Commensal Microbiota And Its Impact On Health And Autoimmune Diabetets, Kyle James Wolf

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Environmental exposures such as diet, use of antibiotics, and lifestyle have significant impact on the health of an individual. One mechanism that acts as a major pathway in these environmental exposures is the role intestinal commensal microbiota play in both metabolic and immunological responses. Metabolic pathways are altered through changes in metabolites provided by commensal microbiota; alterations in microbial make-up can have drastic impacts on metabolic function. Similarly, the development and maturation of the immune system is dependent on the intestinal microbes to induce tolerance and act as both an immune modulator as well as a barrier against pathogens. We …

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Characterization Of The Mumps Virus Replicase, Robert Marsden Cox Jan 2013

Characterization Of The Mumps Virus Replicase, Robert Marsden Cox

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Negative strand RNA viruses (NSV) are unique because their nucleocapsids are used directly as the template for both transcription and replication. The viral genomic RNA is coated by the nucleoprotein (N) for the entirety of the NSV replication cycle. The viral polymerase, which is composed of the L and P proteins, can only recognize encapsidated RNA as the template for RNA synthesis. Our previous studies have solved the EM structure of the MuV N-RNA complex at 25Ņ. This structure revealed how the nucleocapsid is assembled and provides an initial model for examining how the viral polymerase may recognize the …

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Sulindac Sulfide Amide As A Novel Agent For The Prevention And Treatment Of Lung Cancer, Evrim Gurpinar Jan 2013

Sulindac Sulfide Amide As A Novel Agent For The Prevention And Treatment Of Lung Cancer, Evrim Gurpinar

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Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac sulfide (SS) have shown promising antineoplastic activity in multiple tumor types, but toxicities resulting from cyclooxygenase (COX) inhibition limit their use in cancer prevention. We recently described a N,N-dimethylethyl amine derivative of SS, sulindac sulfide amide (SSA), that does not inhibit COX-1 or -2, yet displays potent tumor cell growth inhibitory activity. Here, we studied the basis for the growth inhibitory effects of SSA on human lung adenocarcinoma cell lines and evaluated its preclinical pharmacology. SSA potently inhibited the growth of lung tumor cells with IC50 values of 2-5 μ compared with 44-52 …

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Clinical Consequences Of Micrornas In Colorectal Cancer, Liselle C. Bovell Jan 2013

Clinical Consequences Of Micrornas In Colorectal Cancer, Liselle C. Bovell

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Colorectal cancer (CRC) is a heterogeneous disease, and factors such as tumor location, the environment, genetics, and ethnic differences, can influence its development and progression. Over the last few decades, overall CRC mortality rates have declined; however, racial disparities in mortality rates have increased. The discovery of biomarkers that focus on identifying individual differences based on confounders such as tumor stage and patient race/ethnicity is needed, for such biomarkers can lead to development of personalized therapeutic approaches to target these molecules. MicroRNAs (miRNAs) are a class of small molecules that regulate genes at the post-transcriptional level. Altered miRNA expression levels …

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Therapeutic Potential Of Genetically-Engineered Mesenchymal Stem Cells In Multiple Myeloma, Jerome T. Higgs Jan 2013

Therapeutic Potential Of Genetically-Engineered Mesenchymal Stem Cells In Multiple Myeloma, Jerome T. Higgs

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ABSTRACT Multiple Myeloma (MM) remains the second most common hematologic malig-nancy occurring in adults, which primarily affects the skeletal system causing severe bone destruction, spinal cord compression and hypercalcemia. Current therapies, which include chemotherapy, radiotherapy, autologouos stem cell transplantation and in some cases surgery, have extended the median survival between 3 and 10 years. However, MM is still incurable and therefore improving current therapies or developing newer ones to reduce the burden of osteolytic damage and extend survival rate will be highly beneficial for patient management. The long-term goal of this study is to develop a novel therapeutic approach to …

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Exploring Rti Reading Intervention For Hispanic English Learning Kindergarten Students In Central Alabama:, Kelly Leah Hill Jan 2013

Exploring Rti Reading Intervention For Hispanic English Learning Kindergarten Students In Central Alabama:, Kelly Leah Hill

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This study addressed issues in implementing RTI Tier II reading intervention in kindergarten classrooms which contained Hispanic students learning English. In addition, the scope of reading progress of Hispanic students learning English was explored. The purpose of this research was to examine the frequency in providing RTI reading interventions and how they were implemented in kindergarten with Hispanic children who are learning English. This study employed an explanatory sequential (Quan QUAL) mixed methods design (Creswell & Plano Clark, 2011). To address the purpose of the study, the overarching mixed methods question was: What is the frequency of RTI Tier II …

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Determinant Of G-Chain Mediated Fc Receptor Signaling, Spandan Shah Jan 2013

Determinant Of G-Chain Mediated Fc Receptor Signaling, Spandan Shah

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Fc receptors provide an interface between humoral immunity and cellular immunity by binding to the Fc portion of immunoglobulin and mediating effector functions. Cells expressing Fc receptors play a major role in immune complex clearance via phagocytosis, leading to a context dependent pro- or anti-inflammatory environment. Signaling by multi-chain Fc receptor complexes, including FcgRI, FcgRIII, FceRI and FcaRI is mediated by the ITAM-containing common FceRIg (g-chain) subunit. However, despite the use of a common g-chain, different Fc receptor complexes elicit specific cellular programs, suggesting additional layers of regulation of tyrosine based signaling by g-chain. We hypothesized that the unique g-chain …

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Neuropathological Alterations In Alzheimer's Disease: An Up Close Look At Sympathetic Sprouting, Amy Renee Nelson Jan 2013

Neuropathological Alterations In Alzheimer's Disease: An Up Close Look At Sympathetic Sprouting, Amy Renee Nelson

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Pathological hallmarks of AD include neurofibrillary tau tangles, amyloid beta (Abeta) accumulation and cholinergic degeneration. Cholinergic degeneration can be mimicked in rats by lesioning cholinergic neurons in medial septum. Hippocampal cholinergic denervation disrupts retrograde transport of nerve growth factor (NGF), leading to its accumulation, which subsequently triggers sprouting of noradrenergic sympathetic fibers from the superior cervical ganglia into hippocampus. Dr. McMahon's lab previously reported that coincident with this sprouting, there is an increase in cholinergic innervation that correlates with a recovery of M1 muscarinic receptor dependent plasticity at CA3-CA1 synapses and visual cortex. These findings suggest that noradrenergic sympathetic sprouting …

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Hepatic Effect Of Inhaled Ozone In Sprague-Dawley Rat, Whitney Slone Theis Jan 2012

Hepatic Effect Of Inhaled Ozone In Sprague-Dawley Rat, Whitney Slone Theis

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Ozone (O3) is a primary component of photochemical smog and represents a serious public health concern as more than 50% of the U.S. population lives in areas exceeding national ambient air quality standards for this toxic pollutant. Recent findings indicate that the effects of inhaled O3 extend to extra-pulmonary tissues like the heart and liver. We hypothesize that inhaled O3 exposure-related events in the lung will cause downstream alterations in the liver proteome. To test this, we exposed male Sprague-Dawley rats to 0.5 ppm ozone for 8 hr a day for 5 days. After exposures, livers were removed and proteomic …

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Hepatic Effect Of Inhaled Ozone In Sprague-Dawley Rat, Whitney Slone Theis Jan 2012

Hepatic Effect Of Inhaled Ozone In Sprague-Dawley Rat, Whitney Slone Theis

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Ozone (O3) is a primary component of photochemical smog and represents a serious public health concern as more than 50% of the U.S. population lives in areas exceeding national ambient air quality standards for this toxic pollutant. Recent findings indicate that the effects of inhaled O3 extend to extra-pulmonary tissues like the heart and liver. We hypothesize that inhaled O3 exposure-related events in the lung will cause downstream alterations in the liver proteome. To test this, we exposed male Sprague-Dawley rats to 0.5 ppm ozone for 8 hr a day for 5 days. After exposures, livers were removed and proteomic …

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Environmental Enrichment Recouples Histone Methylation In The Hippocampus To Restore Cognition In Aging, Sarah Jean Morse Jan 2012

Environmental Enrichment Recouples Histone Methylation In The Hippocampus To Restore Cognition In Aging, Sarah Jean Morse

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It is hypothesized that age-related memory deficits arise in part due to altered gene transcription within the hippocampus. These aberrations in gene transcription can lead to alterations in the induction of synaptic plasticity and subsequently interrupt the process of memory formation. Histone methylation-mediated chromatin remodeling mechanisms have recently emerged as crucial regulators of gene transcription in the hippocampus during memory formation. In the present study, we examined the contributions of histone methylation to cognitive deficits and transcriptional aberrations in the hippocampus throughout aging. We found that aging is associated with reduced histone acetylation and an increase in tri-methylation of histone …

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Structural Investigations Of Retinoid X Receptor Transcriptional Activation By Anti-Cancer Rexinoids, Leeann J. Boerma Jan 2012

Structural Investigations Of Retinoid X Receptor Transcriptional Activation By Anti-Cancer Rexinoids, Leeann J. Boerma

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Nuclear receptor (NR) protein retinoid X receptor (RXR) is a ligand-inducible transcription factor that binds retinoids for regulation of target genes. Agonist binding induces a major structural rearrangement in the ligand binding domain (LBD) and formation of the coactivator binding interface. RXR-signaling pathways control proliferation, differentiation, and growth in epithelial tissues. To understand how RXR agonists enhance signaling at the molecular level requires an understanding of how agonists induce structural and dynamical changes in the LBD to recruit coactivators for activation of anti-cancer relevant transcription. While most studies of NR activation center on the position of Helix 12 (H12)/activation function-2 …

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Complex Interactions Between Marine Sponges And Their Symbiotic Microbial Communities, Christopher John Freeman Jan 2012

Complex Interactions Between Marine Sponges And Their Symbiotic Microbial Communities, Christopher John Freeman

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Microbial communities spanning nearly all evolutionary lineages of bacteria and archaea are found within many species of marine sponges. Although diverse microbial metabolic pathways may benefit sponge hosts, minimal experimental evidence exists supporting host assimilation of symbiont-derived nutrients. By coupling manipulative shading experiments with stable isotope analyses of isolated microbial and sponge cell fractions, I provide evidence that some sponge hosts assimilate a large proportion of their C and N from microbial symbionts and that these inputs are crucial to host performance. Interestingly, however, these interactions are highly variable across host species, suggesting that overall symbiont abundance alone does not …

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Investigating Potential Novel Angiogenic And Immunogenic Properties Of Heme Oxygenase-1, Carl Antonio Frizell Jan 2012

Investigating Potential Novel Angiogenic And Immunogenic Properties Of Heme Oxygenase-1, Carl Antonio Frizell

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INVESTIGATING POTENTIAL NOVEL ANGIOGENIC AND IMMUNOGENIC PROPERTIES OF HEME OXYGENASE-1 According to the American Heart Association and Centers of Disease Control and Prevention, cardiovascular diseases comprise the primary causes of death in the United States. Heme oxygenase-1 (HO-1), an inducible microsomal enzyme, catalyzes the rate limiting step in heme degradation releasing equimolar amounts of biliverdin, iron and carbon monoxide. Importantly, the induction of HO-1 is an adaptive response that affords protection in these disease states and several others. Expression of HO-1 has been demonstrated in several disease states and pathophysiological processes, including ischemia-reperfusion, inflammation and organ transplantation. This protection is …

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Myosin Ii Regulates Actin Dynamics Critical For Structural Plasticity And Fear Memory Formation, Cristin Gavin Jan 2012

Myosin Ii Regulates Actin Dynamics Critical For Structural Plasticity And Fear Memory Formation, Cristin Gavin

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Dynamic changes to the actin cytoskeleton are required for synaptic plasticity and long-term memory formation. However, the molecular mechanisms that mediate filamentous actin (F-actin) dynamics during both activity-dependent synaptic potentiation and long-term memory encoding are poorly understood. Myosin II motor proteins are highly expressed in actin-rich growth structures in neurons, including dendritic spines. Recent work demonstrates that these molecular machines mobilize F-actin in response to synaptic stimulation and are required for memory encoding in CA1 hippocampus of rodents. The aims of this project were two-fold. First, we sought to establish if myosin II regulates actin filament polymerization necessary for structural …

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Calcium Signaling And The Regulation Of Ecdysteroid Hormone Synthesis By Blue Crab (Callinectes Sapidus) Molting Glands, Hsiang-Yin Chen Jan 2012

Calcium Signaling And The Regulation Of Ecdysteroid Hormone Synthesis By Blue Crab (Callinectes Sapidus) Molting Glands, Hsiang-Yin Chen

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In crustaceans, cellular events that lead to molting are triggered by steroid molting hormones, ecdysteroids. The synthesis of ecdysteroids is negatively regulated by molt-inhibiting hormone (MIH) mediated by one or more cyclic nucleotide second messengers. Existing data indicate ecdysteroidogenesis is positively regulated by Ca2+ through the activation of phosphodiesterases (PDEs). The studies presented in this dissertation composed the first report of intracellular Ca2+ measurement in Y-organ cells from any crustacean species. Studies demonstrated that elevated cytosolic Ca2+ levels in Y-organ cells were associated with increased hemolymphatic ecdysteroid titer. Measurement of Ca2+ levels in Y-organ cells in a natural molting cycle …

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Localization Of Proteins Involved In Trafficking In Frog And Mouse Retina, Amie Marsh Jan 2012

Localization Of Proteins Involved In Trafficking In Frog And Mouse Retina, Amie Marsh

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The connecting cilium serves as the major route for protein transport from the inner to outer segment of photoreceptor cells. The hypothesis that all Congenital Stationary Night Blindness (CSNB) rhodopsin mutants travel properly to the rod outer segment in Xenopus laevis will be tested by preparing transgenic X. laevis expressing a rhodopsin mutation found in human CSNB, A295V. In addition, probing for the existence of potential proteins involved in regulating rhodopsin trafficking and monitoring their localization will contribute to a better understanding of the underlying pathway of intracellular photoreceptor trafficking.

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Apolipoprotein E Mimetic Peptide Improves Hdl Functionality And Inhibits Atherosclerosis Progression In Mouse Models Of Atherosclerosis, Gaurav Nayyar Jan 2012

Apolipoprotein E Mimetic Peptide Improves Hdl Functionality And Inhibits Atherosclerosis Progression In Mouse Models Of Atherosclerosis, Gaurav Nayyar

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Despite major advances in diagnosis and treatment, coronary artery disease (CAD) is still the number one cause of morbidity and mortality in United States. An ideal treatment for lipid-mediated inflammatory disorders would not only reduce plasma cholesterol dramatically but also improve high density lipoproteins (HDL) function. Apolipoprotein E (apo E), a protein component of HDL and very low density lipoprotein (VLDL), is necessary for the receptor mediated hepatic uptake of apolipoprotein-B (apo B) containing remnant lipoproteins and also possesses strong anti-inflammatory properties. We hypothesized that a synthetic dual domain apo E mimetic peptide, Ac-hE18A-NH2 (a 28-residue peptide) containing receptor binding …

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Berry G. Jackson, Alias Berry Clyatt: Murder Witness And Murderer, Jessica Eileen Parker Newman Jan 2012

Berry G. Jackson, Alias Berry Clyatt: Murder Witness And Murderer, Jessica Eileen Parker Newman

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This study examines the life of an escaped slave named Berry G. Jackson, alias Berry Clyatt. Jackson was born approximately 1851 in Levy County, Florida, on the Samuel Clyatt plantation. Jackson's is a success story of how a teenage slave escaped his young master, boarded a Union steamer, and served in the Civil War. After the war, Jackson claimed to have met General Ulysses S. Grant in Washington, D.C. and received encouragement to continue north where Grant hoped he would become a farmer. Jackson ended up owning several properties and ultimately possessed 21 acres with a farmhouse in Gates, New …

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The Role Of Primary Cilia In Articular Cartilage And Growth Plate, Ching-Fang Chang Jan 2012

The Role Of Primary Cilia In Articular Cartilage And Growth Plate, Ching-Fang Chang

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Primary cilia are now considered an important organelle required for many key steps during developmental processes including skeletal development. Articular cartilage and growth plate are two cartilage compartments whose functions are important postnatally. Articular cartilage is a think cartilage layer which serves as a cushion to protect the joint space, whereas growth plate is important for postnatal long bone growth. Both articular cartilage and growth plate need to be developed properly to ensure the normal bone function. Here, we show an important role of primary cilia in development of both articular cartilage and growth plate using genetic modified mouse model …

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Neuropharmacology Of The Α2a Adrenergic Receptor In Disorders Of Mood And Cognition, Christopher Cottingham Jan 2012

Neuropharmacology Of The Α2a Adrenergic Receptor In Disorders Of Mood And Cognition, Christopher Cottingham

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Depressive disorders carry relatively high lifetime risks of greater than 10%, and the antidepressant drugs used in the pharmacotherapy of these mood/cognitive disorders are among the most-prescribed pharmacological agents. However, a detailed understanding of both depressive etiology and the pharmacological mechanisms of action for antidepressant drugs remain elusive. The overall goal of this dissertation research is to provide novel in-sights through a detailed study of the neuropharmacology of the α2A adrenergic receptor (AR). α2ARs, as key regulators of noradrenergic neurotransmission, have been broadly understood to have some ill-defined role in both the neurobiology and neuropharmacology of depressive disorders. The studies …

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The Conformational Analysis And Biophysical Studies Of Retinoic Acid Interactions With Nuclear Receptor Homodimers And Heterodimers, Bryan Dean Cox Jan 2012

The Conformational Analysis And Biophysical Studies Of Retinoic Acid Interactions With Nuclear Receptor Homodimers And Heterodimers, Bryan Dean Cox

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Vitamin A metabolites are compounds that perform critical functions for mammalian life. The retinoic acid metabolites of vitamin A regulate genetic transcription. Retinoic acids function by binding to type II nuclear receptor proteins (NRs), which modulates interactions between nuclear receptors and transcription initiation machinery (such as coactivator proteins). It is the focus of this dissertation to expand our understanding of retinoic acids in their interactions with the nuclear receptor protein Retinoid X Receptor alpha (RXR&alpha). Retinoic acids are composed of a trimethylcyclohexenyl ring, polyene chain, and terminal carboxylic acid. The first chapter investigates the energetics of the ring-chain conformation using …

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Adhesion Molecule Interactions Influence The Implementation Of Immune Responses To Infection, Maureen Ann Cox Jan 2012

Adhesion Molecule Interactions Influence The Implementation Of Immune Responses To Infection, Maureen Ann Cox

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Interactions mediated by intercellular adhesion molecule-1 (ICAM-1) enhance both the antigenic and cytokine signals that CD8 T cells perceive, and these interactions have been suggested to be required for the formation of memory CD8 T cells. Following acute lymphocytic choriomeningitis virus (LCMV) infection of ICAM-1-/- mice, we observe elevated numbers of "effector-phenotype" (CD127lo KLRG-1hi IL-2-) virus-specific CD8 T cells well into the memory phase, while the development of memory-phenotype CD8 T cells (CD127hi KLRG-1lo IL-2 producing) is not impaired. The enhanced maintenance of effector-phenotype cells is due to ICAM-1 deficiency on non-T cell subsets, suggesting a role for ICAM-1 mediated …

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Modulation Of Alpha-Synuclein Metabolism And Toxicity By Cathepsin D, Donna Marlana Crabtree Jan 2012

Modulation Of Alpha-Synuclein Metabolism And Toxicity By Cathepsin D, Donna Marlana Crabtree

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Parkinson's disease (PD) is the most commonly occurring neurodegenerative movement disorder, and aberrant accumulation of the protein α-synuclein is thought to be a major contributing factor in disease development. Dysfunction of the autophagy lysosome pathway (ALP) has been implicated in PD pathogenesis. Our lab and others have shown that the lysosomal enzyme cathepsin D (CD) is an important regulator of α-synuclein degradation. The primary focus of this thesis is probing the structure/function dynamic that exists between α-synuclein and CD. We have found that lentiviral-mediated over expression of wild type CD (wtCD) leads to subtle alterations in the ALP in a …

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Regulation Of Clc-3 In Human Malignant Glioma, Vishnu Anand Cuddapah Jan 2012

Regulation Of Clc-3 In Human Malignant Glioma, Vishnu Anand Cuddapah

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Malignant gliomas are the most common and deadly form of primary brain cancer afflicting adults. Current treatment regimens, including surgical debulking, radiotherapy, and chemotherapy, have limited efficacy, and median patient survival remains only 14 months. Therefore, novel therapies must target different aspects of glioma biology. Two of the most striking features of this cancer are the unusual ability of glioma cells to robustly proliferate and migrate in the brain, and recent evidence suggests that ClC-3, a voltage-gated Cl- channel/transporter is implicated in both of these processes. We hypothesize that ClC-3 may facilitate proliferation and migration by promoting hydrodynamic shape and …

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Glutamate Release And Uptake At Cerebellar Synapses, Ming-Chi Tsai Jan 2012

Glutamate Release And Uptake At Cerebellar Synapses, Ming-Chi Tsai

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Glutamate mediates excitatory synaptic transmission in the central nervous system (CNS). Regulation of glutamate release and uptake shapes the spatiotemporal dynamics of glutamate at and around synapses to influence information transfer between neural cells. This dissertation focuses on the modulation of glutamate release and uptake at excitatory synapses of cerebellar Purkinje cells (PC). In the first project we show that differential expression of PC glutamate transporters controls the amount of glutamate entering the extrasynaptic space, thereby influencing the excitatory responses in surrounding Bergmann glia. This work provides the first evidence that neuronal glutamate uptake affects glial glutamatergic signaling. In the …

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