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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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The Effects Of Sleep Restriction On Adolescents' Pedestrian Safety, Aaron Leah Davis Jan 2013

The Effects Of Sleep Restriction On Adolescents' Pedestrian Safety, Aaron Leah Davis

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Introduction. Over 8,000 American adolescents ages 14 and 15 require medical attention due to pedestrian injury annually. Psychosocial factors contributing to pedestrian safety include reaction time, impulsivity, risk-taking, attention, and decision-making. These characteristics are also influenced by sleep restriction. Adolescents require 8.5 hours of uninterrupted sleep each night. Despite requiring more sleep than other children, adolescents often do not obtain adequate sleep due to delayed circadian, academic demands, extracurricular activities, media use, and minimal parental supervision. This combination of factors may place adolescents at risk for pedestrian injury. Method. This study investigated whether sleep restriction reduces adolescents' pedestrian safety. Using …

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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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Regulation Of Glioma Cell Migration And Proliferation By A Non-Selective Cation Channel., Arun Kumar Rooj Jan 2013

Regulation Of Glioma Cell Migration And Proliferation By A Non-Selective Cation Channel., Arun Kumar Rooj

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Two of the most striking features of brain tumors are their unusual ability to robustly proliferate and migrate in the brain. Previous results from our laboratory suggest that glioma cells express a non-selective cation channel that is composed of Epithelial Sodium Channel (ENaC) and Acid Sensing Ion Channel (ASIC) subunits. We hypothesize that this glioma specific current regulates glioma cell migration and proliferation by modulating an intracellular signaling pathway. To test our hypothesis, we have attenuated this cationic conductance by either pharmacological blockers (psalmotoxin-1 and benzamil), or by knocking down expression of a particular subunit of this cross-clade ion channel …

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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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Down-Modulation Of Mica On Malignant Glioma Cells By Herpes Simplex Virus, Carl Irwin Odom Jan 2012

Down-Modulation Of Mica On Malignant Glioma Cells By Herpes Simplex Virus, Carl Irwin Odom

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Glioblastoma Multiforme is a primary malignancy of the central nervous system and is fatal for patients despite surgical resection and radiotherapy. Oncolytic Herpes Simplex Virus (oHSV) vectors deleted of the γ134.5 neurovirulence gene are potential therapies for treating glioblastoma tumors. Although replication in permissive cells is considered the primary mechanism of oHSV mediated tumor clearance, there is evidence that the immune system is part of the tumor clearance mechanism during treatment with oncolytic viruses. Specifically, natural killer (NK) cells may be important for tumor clearance during oHSV therapy. NK cell activation relies partially on the stimulation of activating or inhibitory …

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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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Childhood Obesity: The Role Of Genetic Admixture, Parental Feeding Practices, And The School Food Environment, Michelle Cardel Jan 2012

Childhood Obesity: The Role Of Genetic Admixture, Parental Feeding Practices, And The School Food Environment, Michelle Cardel

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Disentangling the etiology of pediatric obesity continues to challenge researchers due to the interconnecting of behavioral, physiological, environmental, and genetic factors. Studies have focused on the role of the obesogenic environment, characterized by excess energy intake and sedentary behavior, as it relates to weight and fat gain in children. Although these factors certainly have an impact on fat accumulation, increased energy intake and decreased physical activity do not solely account for the increasing trends in obesity prevalence. Less explored genetic and environmental factors may contribute independently and/or synergistically to the current obesity epidemic, and that, these factors could vary in …

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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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Characterization Of Pleiotrophin And Receptor Protein Tyrosine Phosphatase Beta/Zeta In Odontoblast And Osteoblast Cell Lines, Amena Tamkenath Jan 2012

Characterization Of Pleiotrophin And Receptor Protein Tyrosine Phosphatase Beta/Zeta In Odontoblast And Osteoblast Cell Lines, Amena Tamkenath

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Pleiotrophin (PTN) is an extracellular matrix-associated growth factor and chemokine expressed in mesodermal and ectodermal cells. It plays an important role in osteoblast recruitment and differentiation. PTN has two well-known physiological receptors, protein tyrosine phosphatase beta/zeta (RPTPRZ1), and N-syndecan. Protein tyrosine phosphatases are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins. Protein tyrosine phosphorylation is a common post-translation modification that can create novel recognition motifs for protein interactions and cellular localization, affect protein stability and regulate enzyme activity. Osteoblasts have recently been found to express the short transmembrane isoform of RPTP beta/zeta but nothing …

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A Case Study Of Second-Grade Teachers' Comprehension Instruction, Rebecca Burdette Mckay Jan 2012

A Case Study Of Second-Grade Teachers' Comprehension Instruction, Rebecca Burdette Mckay

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A CASE STUDY OF SECOND-GRADE TEACHERS' COMPREHENSION INSTRUCTION REBECCA BURDETTE MCKAY EARLY CHILDHOOD EDUCATION ABSTRACT The dilemma of reconciling developmentally appropriate, constructivist reading instruction with mandated high-stakes tests was confronted by four second-grade teachers through their selection of two active professional development methods. To continue and deepen their use of an interactive model of reading focused on comprehension, the teachers worked as a professional community to renegotiate and reconstruct their professional knowledge and adapt their pedagogy to the school context. The goal of this research was to investigate how the teachers described their comprehension instruction as well as how they …

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Real-Time Quantitative Pcr For Evaluation Of Mutans Streptococci And Dental Caries, Chanika Manmontri Jan 2012

Real-Time Quantitative Pcr For Evaluation Of Mutans Streptococci And Dental Caries, Chanika Manmontri

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Mutans streptococci (MS), e.g., Streptococcus mutans (Sm) and Streptococcus sobrinus (Ss), are associated with dental caries. Quantification of MS has been shown to predict caries risk. A new technology using PCR may streamline quantification compared to traditional culture methods. Purpose: To use real-time quantitative PCR (qPCR) and standard plate counting (SPC) for detection and quantification of levels of Sm, Ss and total streptococci (TS) in clinical samples from high-caries-risk children with no regular access to dental care and to study correlation of these bacterial levels and ratios to caries prevalence. Methods: Saliva and plaque samples were collected from school-aged children …

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Relationship Between Religiosity, Violent Behavior And Gang Activity In Economically Disadvantaged Adolescents, David Mckenzie Jan 2012

Relationship Between Religiosity, Violent Behavior And Gang Activity In Economically Disadvantaged Adolescents, David Mckenzie

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RELATIONSHIP BETWEEN RELIGIOSITY, VIOLENT BEHAVIOR AND GANG ACTIVITY AMONG ECONOMICALLY DISADVANTAGED ADOLESCENTS DAVID McKENZIE HEALTH EDUCATION & HEALTH PROMOTION ABSTRACT Few studies have examined the relationship between religiosity, violent behavior and gang activity in disadvantaged youth. This research study analyzed data from a population of low-income adolescents in Mobile, Alabama. The research objectives were to assess the relationship between adolescent religiosity and involvement in violent behavior and gang activity, and to determine if there were gender differences between boys and girls regarding religiosity, violent behavior and gang activity. It was hypothesized that there would be an inverse relationship between religiosity …

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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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The Influence Of Growth Factors Applied During Socket Conversion, On The Incidence Of Spontaneous Early Dental Implant Exposure, Michael Anh Minh Nguyen Jan 2012

The Influence Of Growth Factors Applied During Socket Conversion, On The Incidence Of Spontaneous Early Dental Implant Exposure, Michael Anh Minh Nguyen

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Spontaneous early exposure of a dental implant's cover screw can result in a nidus for plaque accumulation, which may result in inflammation, damage to the peri-implant mucosa, and possible peri-implant bone loss. This study aims to investigate the effect of the addition of growth factors, specifically recombinant human platelet-derived growth factor, and platelet-rich plasma, at the time of socket conversion, on the incidence of early implant exposures. This retrospective study utilized data from a study involving a total of 80 implants that were placed in 4 different types of sites (Groups 1,2,3, and 4). Group 1 sites were extraction sites …

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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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Centering Pregnancy And Adverse Pregnancy Outcome: An Evaluation Of Group Prenatal Care In A Rural Western Kentucky Clinic, Lorie Wayne Chesnut Jan 2012

Centering Pregnancy And Adverse Pregnancy Outcome: An Evaluation Of Group Prenatal Care In A Rural Western Kentucky Clinic, Lorie Wayne Chesnut

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CenteringPregnancySmiles [TM] (CPS), a group prenatal care program with an oral health component, has demonstrated promising results in urban communities with primarily low-income minority women. This study examined three questions: 1) Do women who participate in CPS have better birth outcomes than those who participate in traditional prenatal care, even after adjusting for maternal characteristics and risk factors? 2) Is level of exposure to the intervention associated with improved birth outcomes? 3) Do women with dental infection have an increased risk of poor birth outcomes? Data were abstracted from medical records and birth certificates. Birth outcomes for women enrolled in …

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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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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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Optimization Of A Biomimetic Poly(Lactic Acid) Ligament Scaffold, Andrew F. Uehlin Jan 2012

Optimization Of A Biomimetic Poly(Lactic Acid) Ligament Scaffold, Andrew F. Uehlin

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The anterior cruciate ligament (ACL) is the most commonly injured ligament of the knee, often requiring orthopedic reconstruction using autograft or allograph tissue, both with significant disadvantages. As a result, tissue engineering an ACL replacement graft has been heavily investigated. The present study attempts to replicate the morphology and mechanical properties of the ACL using a nanomatrix composite of highly-aligned poly(lactic acid) (PLA) fibers with various surface and biochemical modifications. Additionally, this study attempts to recreate the natural mineralization gradient found at the ACL enthesis onto the scaffold, capable of inducing a favorable cellular response in vitro. Unidirectional electrospinning was …

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