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Molecular And Functional Interaction Of Runx2 And Sp7 For Development Of The Osteoblast Phenotype, Harunur Rashid Jan 2014

Molecular And Functional Interaction Of Runx2 And Sp7 For Development Of The Osteoblast Phenotype, Harunur Rashid

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Runx2 and Sp7 transcription factors are essential for skeletogenesis. Deletion of either gene in mice results in failure of bone tissue development. However, underlying mechanisms responsible for a surprisingly similar phenotype by two distinctly unrelated proteins remain unknown. Sp7 is a Runx2 downstream target gene and is not expressed in Runx2 null mice. Thus, the Runx2 null model represents a compound phenotype of loss of both proteins. In contrast, normal levels of Runx2 mRNA are noted in Sp7 null mice. The failure of Runx2 to promote bone formation in Sp7 null mice suggests that Sp7 is required for Runx2 function …


Epithelial Sodium Channel Purification And X-Ray Crystallographic Studies, Bharat G. Reddy Jan 2014

Epithelial Sodium Channel Purification And X-Ray Crystallographic Studies, Bharat G. Reddy

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Epithelial sodium channels (ENaC) play a critical role in maintaining Na+ homeostasis in various tissues throughout our body. Understanding of ENaC structure is mediated from studies of the homologous acid sensing ion channel 1 (ASIC1). However, ENaC has sev-eral notable functional differences compared to ASIC1, thereby providing justification for determination of its three-dimensional structure. Unfortunately, this goal remains elu-sive due to several experimental challenges. Of the subunits that comprise a physiological hetero-trimeric ENaC (α, ß, and γ), the α-subunit alone is of significant interest. αENaC is unique in that it is capable of forming a homo-trimeric structure capable of conducting …


The Role Of The Planar Cell Polarity Pathway In The Second Heart Field During Outflow Tract Morphogenesis, Tanvi Sinha Jan 2014

The Role Of The Planar Cell Polarity Pathway In The Second Heart Field During Outflow Tract Morphogenesis, Tanvi Sinha

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Outflow Tract (OFT) malformations underlie a majority of congenital heart defects (CHD) in humans and are a leading cause of childhood mortality. The OFT, which gives rise to the aorta and pulmonary artery of the heart, relies on the contribution of the Second Heart Field (SHF) progenitors in the pharyngeal and the splanchnic mesoderm, outside of the initial heart. OFT morphogenesis requires highly regulated SHF development involving the proliferation, differentiation and deployment of the SHF progenitors to the heart. Extensive studies elegantly demonstrate how transcriptional networks integrating signaling input from multiple pathways finely balance the proliferation and differentiation of SHF …


The Role Of Gene Fragmentation And Loss In Poxvirus Evolution, Eneida Hatcher Jan 2014

The Role Of Gene Fragmentation And Loss In Poxvirus Evolution, Eneida Hatcher

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Members of the Poxviridae family of viruses have experienced several different evolutionary mechanisms to arrive at their large genomes, diverse host range, and complex replication cycle that we see today. Our work has focused on the identification of gene truncation, fragmentation, and deletion events. We have used genomic sequences for representative species throughout the Poxviridae family as our data set, and correctly annotated the gene set for each virus. We found that the number of truncated, fragmented, or missing genes in a genome is highly variable. We also identified the nucleotide changes which lead to gene loss, called early stop …


Clinical Evaluation Of Non-Carious Cervical Lesions- A Five Year Prospective Evaluation, Kanchan Sawlani Jan 2014

Clinical Evaluation Of Non-Carious Cervical Lesions- A Five Year Prospective Evaluation, Kanchan Sawlani

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Non-carious cervical lesions (NCCLs) have a non-bacterial origin and produce a loss of tooth structure at the cemento-enamel junction. A review of the literature reveals that these lesions may have a multifactorial etiology (chemical, abrasion, abfraction). The role of heavy biting forces in the pathogenesis of NCCLs is yet to be firmly established. Treatment and preventive measures for NCCLs can be improved if the etiology can be clearly identified and treated.Objective: This prospective clinical trial measured the volume loss (increase in size) of NCCLs and the occlusal biting forces applied to these teeth; diet and tooth brushing analysis, followed by …


Three-Dimensional Photography Of Facial Morphology Of African-American Children Compared To Welsh Children, Don Franklin Norris Jan 2014

Three-Dimensional Photography Of Facial Morphology Of African-American Children Compared To Welsh Children, Don Franklin Norris

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The purpose of this study is to compare the facial morphology of African-American children to Welsh children using three-dimensional imaging. Materials and Methods: Three-dimensional images were captured using a stereo-photogrammatic camera system (3dMDfaceTM). 107 African-American children were imaged with the 3dMDfaceTM system and were compared with 64 Welsh children which were previously imaged using two Minolta Vivid VI900 3D laser scanners arranged in a stereo pair. The subjects were between 10 and 13 years old, presented with a normal BMI, and had no major craniofacial deformity. The images were aligned, combined and averaged using Rapidform 2006 Plus Pack 2 software …


Evaluation Of Tau As A Target For Alzheimer Disease And Other Conditions With Epileptiform Activity, Zhiyong Li Jan 2014

Evaluation Of Tau As A Target For Alzheimer Disease And Other Conditions With Epileptiform Activity, Zhiyong Li

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Alzheimer disease (AD) is a devastating neurological condition that slowly destroys memory and thinking skills of the affected patients. No disease-modifying medications are available. While all the treatment against Aߒ (major component of one hallmark pathology of AD) failed in clinical trials, tau (major component of the other hallmark pathology of AD) is emerging as a better alternative. Germline knockout of tau does not cause overt abnormalities in young mice and prevents AD-like deficits in mouse models of AD. Germline knockout of tau also confers resistance to epileptiform activity in models of both AD and epilepsy. Therefore tau is proposed …


Mechanisms Of At101 [(-)-Gossypol] Induced Cytotoxicity In Malignant Peripheral Nerve Sheath Tumors, Niroop Kaza Jan 2014

Mechanisms Of At101 [(-)-Gossypol] Induced Cytotoxicity In Malignant Peripheral Nerve Sheath Tumors, Niroop Kaza

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Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive Schwann cell-derived sarcomas and are the leading cause of mortality in patients with neurofibromatosis type 1 (NF1). Current treatment modalities have been largely ineffective resulting in a high rate of MPNST recurrence and poor five year patient survival. This necessitates the exploration of alternative chemotherapeutic options for MPNST patients. By evading apoptosis and utilizing protective mechanisms such as autophagy, cancer cells develop resistance to chemo- and radio-therapy. The overall goal of my thesis studies is to evaluate chemotherapeutic agents that can modulate both apoptosis and autophagy, thus target both cell death pathways …


Type I Interferons-Induced Follicular Translocation Of Lymphotoxin-Expressing Marginal Zone B Cells Initiates Lupus, Hao Li Jan 2014

Type I Interferons-Induced Follicular Translocation Of Lymphotoxin-Expressing Marginal Zone B Cells Initiates Lupus, Hao Li

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Systemic lupus erythematosus (SLE) is characterized by elevation of type I interferon (IFN) signature genes and production of autoantibodies against apoptotic self-antigens. The complex nature of SLE, however, suggests that multiple immune dysregulations must integrate to initiate the disease. Here, we provided evidence that lupus can be initiated via type I IFNs-induced follicular translocation of membrane lymphotoxin (mLT)-expressing marginal zone (MZ) B cells in the spleen of lupus prone BXD2 mice. The mislocation of mLT+ MZ B cells induces two important pathogenic effects including deteriorations of marginal zone macrophages (MZMs) in the MZ, leading to defective clearance of apoptotic debris, …


Association Of Blood Pressure Phenotypes With Kidney Disease, Rikki M. Tanner Jan 2014

Association Of Blood Pressure Phenotypes With Kidney Disease, Rikki M. Tanner

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Kidney disease is common, with recent estimates indicating a prevalence of 13% among US adults. Furthermore, the vast majority of individuals with kidney disease have hypertension. Apparent treatment-resistant hypertension (aTRH), 24-hour blood pressure (BP) variability, and inter-arm differences (IADs) in BP have been identified as risk factors for cardiovascular disease, and there is increasing evidence that these phenotypes provide prognostic information above and beyond mean clinic BP. However, these phenotypes have not been extensively studied among individuals with kidney disease. The goal of this dissertation was to determine the association of kidney disease with BP phenotypes in the context of …


Characterization Of Phosphatidylinositol 4,5-Bisphosphate Regulation Of The Electrogenic Na/Bicarbonate Cotransporter Nbce1, Ian Michael Thornell Jan 2014

Characterization Of Phosphatidylinositol 4,5-Bisphosphate Regulation Of The Electrogenic Na/Bicarbonate Cotransporter Nbce1, Ian Michael Thornell

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The electrogenic Na/bicarbonate cotransporter (NBCe1) is an acid/base regulator that is also involved in coordinating epithelial ion transport. Splice variants of NBCe1 differ at their cytosolic amino- (N-) and/or carboxy- (C-) termini. These different cytosolic termini impart differential regulation for each variant. For example, the N-terminus of NBCe1-A is autostimulatory, whereas the N-terminus of NBCe1-B and -C is autoinhibitory. We examine the regulatory role of PIP2 for NBCe1 splice variants. In the first study of this dissertation, we characterize the effect of increasing PIP2 on the activity of NBCe1-A, -B, and -C expressed in Xenopus laevis oocytes. Injecting PIP2 stimulated …


Evaluation Of Environmental Factors And Dengue Fever In Sri Lanka Using Geospatial Tools, Meghan Tipre Jan 2014

Evaluation Of Environmental Factors And Dengue Fever In Sri Lanka Using Geospatial Tools, Meghan Tipre

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The incidence of dengue fever has increased exponentially in Sri Lanka, from 24.4 cases per 100,000 in 2003 to 165.3 per 100,000 population in 2013. Despite concerted effort by the Sri Lankan government, dengue control remains a challenge in the country, indicating a need for novel approach for dengue prevention and control. The aim of this research was to identify environmental risk factors that may be associated with dengue incidence rate at the Gram Niladhari Divisions level (smallest administrative unit) in Colombo city, Sri Lanka, using geospatial tools such as remote sensing and geographic information system. These factors included climate …


Socio-Demographic Characteristics, Medical Indications, And Perinatal Outcomes Associated With Interventional Early Term Delivery, Kelley Swatzell Jan 2014

Socio-Demographic Characteristics, Medical Indications, And Perinatal Outcomes Associated With Interventional Early Term Delivery, Kelley Swatzell

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Non-medically indicated deliveries, resulting from obstetrical intervention in an effort to avoid delivery at a later date, are frequently referred to as elective deliveries. These were increasingly occurring in early term gestations of 37.0 to 38.7 and frequently resulting in adverse neonatal outcomes such as sepsis, hypoglycemia, respiratory distress disorder the need for mechanical ventilation. In addition to concerns regarding adverse neonatal and maternal health outcomes, elective early term delivery increases health care costs due to prolonged hospital stays and NICU admissions. Efforts taken to reduce elective early term deliveries include public service announcements, educational programs, performance incentives and reimbursement …


Effects Of Storage On The Red Blood Cell And Its Implications For Transfusion, Ryan D. Stapley Jan 2014

Effects Of Storage On The Red Blood Cell And Its Implications For Transfusion, Ryan D. Stapley

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Transfusion with red blood cells (RBC) remains a frontline therapy in critically ill patients. Recent studies have documented an association between storage duration and an increased incidence of transfusion-related toxicities. This transfusion-related toxicity is characterized by both a pro-inflammatory state and a microcirculatory dysfunction and is associated with changes that occur to the RBC and its media during storage referred to as the storage lesion. These changes that occur to the RBC include an increase in cell-free hemoglobin, heme, free iron, microparticles, as well as changes to the RBC itself. This thesis explores how these elements could contribute to transfusion-related …


Modulation Of The Immune Response To Aspergillus Fumigatus By Antibodies To Conserved Bacterial Polysaccharides, Emily Stefanov Jan 2014

Modulation Of The Immune Response To Aspergillus Fumigatus By Antibodies To Conserved Bacterial Polysaccharides, Emily Stefanov

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The incidence of asthma, allergies and autoimmune diseases has increased dramatically in developed countries. The hygiene hypothesis postulates that excessively sanitary conditions lead to a lack of critical immune stimulation during early life, leading to inappropriate responses to self or harmless antigens later in life. Many bacteria and potential allergens share common polysaccharide epitopes. We investigated the ability of antibodies against these shared polysaccharides to dampen the immune response to the ubiquitous fungus and potent allergen, Aspergillus fumigatus. We found that antibodies against these polysaccharides, specifically of the IgM isotype, induced by neonatal bacterial immunization or passive antibody transfer, dampened …


Development And Testing Of The Primary Care Homeless Organizational Assessment Tool (Pc-Hoat) To Evaluate Primary Care Services For The Homeless, Jocelyn Louise Steward Jan 2014

Development And Testing Of The Primary Care Homeless Organizational Assessment Tool (Pc-Hoat) To Evaluate Primary Care Services For The Homeless, Jocelyn Louise Steward

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The purpose of this dissertation is to develop and test an organizational assessment tool that can used to evaluate primary care services for the homeless. The research evaluates the importance, feasibility, reliability, and validity of organizational processes and structures of primary care services for the homeless. The final product is the validated Primary Care Homeless Organizational Assessment Tool (PC-HOAT). This tool provides stakeholders with information regarding the organizational structures and processes associated with greater quality of primary care for the homeless. This tool will help managers better understand their organization's strengths and weaknesses, guide discussions regarding operations, and provide information …


Urbanization And Land-Use Change In Puerto Maldonado, Peru: Categorizing The Landscape Using High-Resolution Satellite Imagery For Potential Use In Public Health Research, Laura Brianna Gast Jan 2014

Urbanization And Land-Use Change In Puerto Maldonado, Peru: Categorizing The Landscape Using High-Resolution Satellite Imagery For Potential Use In Public Health Research, Laura Brianna Gast

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Environmental change, especially rapid urbanization, has measurable effects on human health. Over 70 percent of the global population is expected to live in urban areas by 2025, and at least 1 in 3 of these individuals will live in extreme poverty. Living in a slum or shantytown exposes individuals to health and safety risks including inadequate sanitation, lack of access to clean water, air pollution, violence, over-crowding and risk of infectious disease. Remote sensing technologies are an effective tool for detection and prediction of areas with significant land use change, which enables identification of populations with the highest risk of …


The Expression And Function Of Icam-2 In Neuroblastoma, Joseph Feduska Jan 2014

The Expression And Function Of Icam-2 In Neuroblastoma, Joseph Feduska

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Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, accounting for 15% of all childhood cancer deaths. At the time of initial diagnosis, the majority of patients present with NB that has already metastasized. While initial remission is often achieved following treatment, roughly 50% of these patients will relapse and die from the development of intractable metastatic progression. Intercellular adhesion molecule-2 (ICAM-2) is a transmembrane glycoprotein, normally expressed only in endothelial cells and subsets of leukocytes. ICAM-2 expression in cancer cells had not been previously investigated, until our lab recently reported the novel finding of endogenous ICAM-2 expression …


Mitochondrial Genetics And Cellular Metabolism Regulate Tumorigenicity And Metastatic Potential, Kyle Paul Feeley Jan 2014

Mitochondrial Genetics And Cellular Metabolism Regulate Tumorigenicity And Metastatic Potential, Kyle Paul Feeley

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Current paradigms of carcinogenic risk suggest that genetic, hormonal, and environmental factors combine to influence an individual's predilection for breast cancer and related metastatic tumor formation. The genetic component, in particular, has become the focus of many emergent studies. A renewed focus on cancer metabolism and the Warburg effect has similarly cast a spotlight on the role, if any, of the mitochondrion in directing disease progression. Analysis of the direct contribution of mitochondrial DNA on tumorigenicity is made possible through the use of mitochondrial-nuclear exchange (MNX) mice in which nuclei from normal FVB mice (the background strain of the tg: …


Elucidating The Role Of Gsk3 In Synaptic And Cognitive Deficits In Fragile X Syndrome, Aimee Vinson Franklin Jan 2014

Elucidating The Role Of Gsk3 In Synaptic And Cognitive Deficits In Fragile X Syndrome, Aimee Vinson Franklin

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Fragile X Syndrome (FX) is the most common inherited form of mental retarda-tion. Prominent characteristics of FX are mimicked in a mouse model with deleted fmr1 including hyperactivity, anxiety, developmental delay and social deficits. Additionally, FX mice display deficits in n-methyl-d-aspartate receptor (NMDAR) dependent long-term potentiation (LTP) at medial perforant path synapses onto dentate granule cells (MPP-DGC synapses). Because LTP is a cellular correlate of learning and memory, defi-cits in LTP at this synapse are thought to underlie impairments in pattern separation, a form of learning and memory dependent on proper DG function. Identifying the patho-logical mechanisms that cause impaired …


The Relationship Between Emergency Department Wait Times And Inpatient Satisfaction, Polly Jean Davenport Jan 2014

The Relationship Between Emergency Department Wait Times And Inpatient Satisfaction, Polly Jean Davenport

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Examining The Role Of G Protein-Coupled Estrogen Receptor 1 (Gper) Activation In 17beta-Estradiol-Mediated Protection In Traumatic Brain Injury, Nicole Day Jan 2014

Examining The Role Of G Protein-Coupled Estrogen Receptor 1 (Gper) Activation In 17beta-Estradiol-Mediated Protection In Traumatic Brain Injury, Nicole Day

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Traumatic brain injury (TBI) affects millions of persons per year, potentially leading to permanent disability or death, and exacts a staggering financial toll. Despite the severity of this public health problem, there are no clinically proven pharmacotherapeutics available that effectively attenuate the secondary neurochemically-mediated damage that follows the initial biomechanical insult. In addition, the heterogeneous nature of TBI and complexity of secondary injury cascades suggest that a polytherapeutic approach could be a powerful strategy with which to simultaneously target more than one deleterious pathway. Recently, sex steroid hormones have sparked interest as possible neuroprotective agents after traumatic injury. One of …


Mitochondrial Dysfunction In Response To Neurotoxins And The Role Of Mitophagy, Samantha Giordano Jan 2014

Mitochondrial Dysfunction In Response To Neurotoxins And The Role Of Mitophagy, Samantha Giordano

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Parkinson's disease (PD) is the second most common neurodegenerative disorder. Two major factors in both familial and sporadic PD are mitochondrial dysfunction and insufficient autophagy. My thesis research focuses on the interplay between these activities in PD. To investigate the common and differential effects of PD-inducing neurotoxins on mitochondrial bioenergetics and their relationships to cell survival, we used an in vitro culture system, differentiated dopaminergic SH-SY5Y neuroblastoma cells. We found that the neurotoxins rotenone, 1-methyl-4- phenylyridinium (MPP+) and 6-hydroxydopamine (6-OHDA), decreased mitochondrial respiration and induced cell death in these cells. The extent and characteristics of mitochondrial dysfunction in response to …


Assessing Patient Care Quality From Hospital Employed Physicians, Kerry Gil Gillihan Jan 2014

Assessing Patient Care Quality From Hospital Employed Physicians, Kerry Gil Gillihan

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ASSESSING PATIENT CARE QUALITY FROM HOSPITAL EMPLOYED PHYSICIANS KERRY GILLIHAN ADMINISTRATION-HEALTH SERVICES ABSTRACT Background: Physician employment by hospitals and healthcare systems has become a growing phenomenon in America. Also the emphasis on improving patient care quality is receiving increasing attention. Moreover, recent changes in federal regulation and reimbursement have made improving patient care quality an imperative for hospitals and their medical staffs. The purpose of this study was to determine if there is a demonstrable relationship between hospital employed physicians and the quality of their patient care. Methods: Physician quality measurements were obtained from a prominent community hospital with roughly …


Three Studies On Family Meals: Examining The Predictors Of Family Meals And Its Impact On Adolescent Health, Samantha Sittig Goldfarb Jan 2014

Three Studies On Family Meals: Examining The Predictors Of Family Meals And Its Impact On Adolescent Health, Samantha Sittig Goldfarb

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This three-manuscript dissertation addresses gaps in the literature related to the predictors of family meals and its impact on adolescent health behavior. Sharing dinner as a family has been promoted by the media and many researchers as an ideal environment to enrich the parent-child bond and subsequently reduce adolescent risk behaviors such as substance use and delinquency. This dissertation centers on three topics, in particular: (1) the nature of the family meal literature given the multiple adolescent health behavior outcomes, study designs, and model types investigated and used by researchers, (2) the impact of family dinners on adolescent school problems, …


Cutting Effectiveness Of Diamond Burs On Dental Zirconia., Ching-Kai Lin Jan 2014

Cutting Effectiveness Of Diamond Burs On Dental Zirconia., Ching-Kai Lin

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Monolithic zirconia restorations are popular but removing these crowns is difficult. The purpose of the study is to measure and compare the cutting effectiveness of 10 types of diamond burs through monolithic sintered zirconia. Ten types of diamond burs (n=8) were compared for the cutting effectiveness in Zirconia (CERCON; DeguDent) using a high speed computer controlled cutting device with water spray (5.45L/min). The turbine used to cut the blocks rotated at 150,000 rpm and with the burs at a depth of 2mm into the zirconia during cutting. A 100 gm load was applied during cutting for each bur which made …


Ksrp Ablation Enhances Lipolysis In White Adipose Tissue Through Reduced Mir-145 Expression, Yi-Yu Lin Jan 2014

Ksrp Ablation Enhances Lipolysis In White Adipose Tissue Through Reduced Mir-145 Expression, Yi-Yu Lin

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White adipose tissue (WAT) releases fatty acids from stored triacylglycerol (TAG) for energy source. Here, we report that null mice for KH-type splicing regulatory protein (KSRP), an RNA-binding protein, resisted high fat diet (HFD) induced obesity. Target of deletion of KSRP regulates gene expression at multiple levels and enhances lipolysis in epididymal WAT (eWAT) due to up-regulation of genes promoting lipolytic activity. Expression of miR-145 is decreased due to impaired pri-miR-145 processing in Ksrp-/- eWAT. We show that miR-145 directly targets and represses Foxo1 and Cgi58, activators of lipolytic activity, and forced expression of miR-145 attenuates lipolysis. This study reveals …


Expression Of The Influenza Protein M2 During Viral Infection Inhibits Cftr Activity, James David Londino Jan 2014

Expression Of The Influenza Protein M2 During Viral Infection Inhibits Cftr Activity, James David Londino

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The purpose of these dissertation studies was to 1) determine whether influenza infection alters CFTR activity in polarized epithelium; 2) measure CFTR expression and activity in cells co-expressing influenza M2 protein; and 3) examine the role of M2 on the alteration of CFTR during viral infection. We determined that infection of polarized primary epithelial cells with influenza decreases CFTR expression and activity. In addition, individual cells infected with influenza had decreased CFTR conductance as measured by whole-cell patch clamp. We also found that the influenza ion channel, matrix protein 2 (M2), alone reduced CFTR expression and activity. M2 is expressed …


Detection Of Scardovia Genus From Oral Samples In Children Using Real-Time Quantitative Polymerase Chain Reaction, Jungyi Alexis Liu Jan 2014

Detection Of Scardovia Genus From Oral Samples In Children Using Real-Time Quantitative Polymerase Chain Reaction, Jungyi Alexis Liu

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Streptococcus mutans (Sm) and Streptococcus sobrinus (Ss) , are considered the major bacterium associated with dental caries. However, recent findings identify Scardovia species (Sc) is associated with early childhood caries, with or without the presence of Sm or Ss. This IRB approved study quantified the presence of Sm and Sc in saliva by real-time quantitative PCR (qPCR) in relation to caries. Saliva samples were collected from 72 preschool children in a high-caries risk community in rural Alabama. SYBR Green-based qPCR using extracted DNA and primers specific for Sm, Ss, Sc and total bacteria determined the copy number (CN/ml). Twenty two …


Transmitted/Founder Siv In The Rhesus Macaque Model Of Hiv-1 Infection, Mike Lopker Jan 2014

Transmitted/Founder Siv In The Rhesus Macaque Model Of Hiv-1 Infection, Mike Lopker

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Vitally important to HIV-1 vaccine and prevention studies is a well-characterized animal model that recapitulates the salient features of HIV infection in humans. SIVmac and SIVsmm infection of rhesus macaques share key virological and pathological parallels with HIV-1 infection of humans including target cell entry via CD4 and CCR5 (Edinger et al., 1997), progressive T cell loss (Swanstrom & Coffin, 2012), generalized immune activation and preferential loss of mucosal Th17 cells (Brenchley et al., 2008; Klatt & Brenchley, 2010), and a vigorous but ultimately ineffective adaptive immune response. Though commonly used as a vaccine challenge strain in the macaque model, …