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2014

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Articles 9211 - 9240 of 9579

Full-Text Articles in Medicine and Health Sciences

Identification Of A New Schwannomatosis-Predisposing Gene And Study Of Splicing Defects Caused By Deep Intronic Nf1 Mutations Causing Neurofibromatosis Type 1, Jing Xie Jan 2014

Identification Of A New Schwannomatosis-Predisposing Gene And Study Of Splicing Defects Caused By Deep Intronic Nf1 Mutations Causing Neurofibromatosis Type 1, Jing Xie

All ETDs from UAB

Schwannomatosis is the third major form of the neurofibromatoses. Constitutional mutations in the SMARCB1 gene have been found only in ~50% of familial and <10% of sporadic schwannomatosis patients, suggesting additional predisposing genes exist. In the present study, we sequenced 3.72 Mb of evolutionary conserved sequences along 22q in 8 schwannomatosis patients without a SMARCB1 mutation in blood or schwannomas, and had a molecular signature consisting of somatic partial loss of 22q and a different NF2 mutation in every schwannoma. We identified LZTR1 germline mutations in 7/8 patients. Targeted sequencing of LZTR1 in 12 further patients with the same molecular signature identified 9 additional germline mutations. Loss of heterozygosity with retention of the LZTR1 mutation was present in all 25 schwannomas studied. Mutations segregated with disease in all available affected first-degree relatives. Our findings identify LZTR1 as a gene predisposing to an autosomal dominant inherited disorder of multiple schwannomas in ~80% SMARCB1-negative 22q-related schwannomatosis patients. Neurofibromatosis type 1, another major form of neurofibromatoses, is caused by loss-of-function mutations in the NF1 gene. Approximately 2% of identified NF1 mutations are deep intronic splice mutations causing the inclusion of an intronic cryptic exon in the mature mRNA. In the present study, we identified 12 different deep intronic splice mutations in 15 unrelated probands, resulting in exonization of different fragments from intron 30(23.2) or 31(23a). This study describes the largest collection of deep intronic mutations in NF1 reported so far, and pinpoints specifically the intronic sequences flanking the alternatively spliced exon 31(23a) as a hotspot for NF1 intronic splice defects. Further investigation by fragment and cloning analysis uncovered that the deep intronic mutations residing either 5' or 3' of exon 31(23a) predominantly or preferentially affect the type II isoform including exon 31(23a), suggesting that alternative splicing of exon 31(23a) depends and is regulated by multiple flanking intronic sequences.

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Statistical Methods For Set-Based Association Tests In Genetic Studies, Qi Yan Jan 2014

Statistical Methods For Set-Based Association Tests In Genetic Studies, Qi Yan

All ETDs from UAB

This dissertation research focuses on developing statistical methods for set-based association tests at both pathway and gene levels in genetic studies. Set based analysis considers the biological hierarchical structure, while traditional genome-wide association studies usually focus on single-marker analysis which only access marginal effect. Therefore, pathway analysis may potentially complement single-marker analysis and provide additional insights for the genetic architecture of complex diseases. In the first study, we propose a novel way for pathway analysis that assesses the effects of genes using the sequence kernel association test (SKAT) and the effects of pathways via an extended adaptive-rank-truncated product statistic. For …

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Targeting Reactive Oxygen Species Production To Prevent Left Ventricle Remodeling In Volume Overload, Danielle Marie Yancey Jan 2014

Targeting Reactive Oxygen Species Production To Prevent Left Ventricle Remodeling In Volume Overload, Danielle Marie Yancey

All ETDs from UAB

Mechanisms of left ventricular dysfunction in cardiac volume overload (VO) are not well understood and currently, no medical therapy exists to treat this condition. Cardiac VO is marked by eccentric remodeling and contractile dysfunction ultimately resulting in cardiac failure. Oxidative stress is implicated in the pathophysiology of heart failure and recent evidence suggests mitochondrially- produced reactive oxygen species play a role in VO. To study VO, we used a rat model of aortocaval fistula (ACF). ACF results in early diastolic stress on the left ventricle (LV) and recapitulates the progressive nature of heart failure with contractile function being initially maintained …

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Gut Microbiome And Its Role In Obesity And Aging In C57bl/6j Mice, Yongbin Yang Jan 2014

Gut Microbiome And Its Role In Obesity And Aging In C57bl/6j Mice, Yongbin Yang

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turtles and its’ ecological and evolutionary significance regarding certain aspects of

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Multiple Human Itgam Variants Alter Mac-1, Fcgamma Receptor And Tlr Functions On Neutrophils, Yebin Zhou Jan 2014

Multiple Human Itgam Variants Alter Mac-1, Fcgamma Receptor And Tlr Functions On Neutrophils, Yebin Zhou

All ETDs from UAB

Multiple studies have demonstrated that single-nucleotide polymorphisms (SNPs) in the ITGAM locus (including the non-synonymous SNPs rs1143679, rs1143678 and rs1143683) are associated with SLE. ITGAM encodes the protein CD11b, a subunit of the ß2 integrin Mac-1. The purpose of this work was to determine the effects of ITGAM genetic variation on the biological functions of neutrophil Mac-1. Neutrophils from ITGAM genotyped and sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement coated erythrocytes, serum treated zymosan, heat treated zymosan and IgG coated erythrocytes. The adhesion capacity of ITGAM variants, in …

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Calreticulin Regulates Tgf-Ss Stimulated Extracellular Matrix Production, Kurt Zimmerman Jan 2014

Calreticulin Regulates Tgf-Ss Stimulated Extracellular Matrix Production, Kurt Zimmerman

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Calreticulin (CRT) is an ER chaperone and regulator of Ca2+ signaling which is increased following ER stress and in fibrotic and vascular fibroproliferative disorders. Previously, we demonstrated that ER CRT regulates type I collagen transcript, trafficking, secretion, and processing into the extracellular matrix (ECM). These studies investigated the role of CRT in regulating ECM production through control TGF-ß dependent signaling pathways. Our studies show that CRT -/- mouse embryonic fibroblasts (MEFs), rat lung fibroblasts, and human IPF lung fibroblasts with siRNA knockdown of CRT had impaired production of type I collagen and fibronectin when stimulated with TGF-ß. Similarly, knockdown of …

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Parent Perspectives Of Neonatal Intensive Care At The End-Of-Life And Subsequent Bereavement And Coping Experiences After Infant Death, Erin Currie Jan 2014

Parent Perspectives Of Neonatal Intensive Care At The End-Of-Life And Subsequent Bereavement And Coping Experiences After Infant Death, Erin Currie

All ETDs from UAB

produced an overall female bias. The fifth chapter addressed the effects of arribada

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Actions Of Grape Seed Extract In Rodent Brain And Differences In Metabolism Of Its Polyphenols In A Rodent Model Of Menopause, John Kenneth Cutts Jan 2014

Actions Of Grape Seed Extract In Rodent Brain And Differences In Metabolism Of Its Polyphenols In A Rodent Model Of Menopause, John Kenneth Cutts

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Grape seed extract (GSE), a dietary supplement, has potential in the treatment and prevention of human chronic age-related diseases including cancers, cardiovascular diseases, and neurodegenerative diseases. GSE and adult hippocampal neurogenesis, independently, have enhanced learning and memory in rodents. We hypothesized that GSE enhances learning and memory, at least partially, by enhancing hippocampal neurogenesis. However, adult mice given GSE did not exhibit increased number of progenitor cells or new neurons, established markers of neurogenesis, in the dentate gyrus (DG). Also, 26-day-old pups whose mother was given GSE only while nursing had fewer new neurons in the DG compared to control …

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Gene Expression Signatures In Tree Shrew Sclera In Different Visual Conditions, Lin Guo Jan 2014

Gene Expression Signatures In Tree Shrew Sclera In Different Visual Conditions, Lin Guo

All ETDs from UAB

The sclera is a target tissue that receives signals that are initiated in the retina, cascade through retinal pigment epithelium (RPE) and choroid, and cause scleral extra cellular matrix remodeling. Biomechanical alterations of the sclera are produced by these biochemical changes, and in turn control the axial length of the eye. This dissertation project examined scleral gene expression changes in mRNA level of juvenile tree shrews. Three specific aims were investigated: specific aim one tested the hypothesis that three different GO visual conditions that all produce axial elongation and myopia: minus-lens wear, form deprivation, and continuous darkness, will produce similar …

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Risk Assessment And Staging Of Cardiometabolic Diseases, Fangjian Guo Jan 2014

Risk Assessment And Staging Of Cardiometabolic Diseases, Fangjian Guo

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Obesity is associated with elevated risk for morbidity and mortality and has become an epidemic both in the United States and around the world. Insulin resistance is essentially involved in the pathogenic process of cardiometabolic diseases in obese people, which involves defects in glucose production by the liver and insulin-stimulated glucose uptake and utilization by peripheral tissues. Insulin resistance appears at an early stage of life and is the first step in the development of cardiometabolic diseases. Long-term insulin resistance will induce metabolic syndrome and prediabetes and eventually will cause type 2 diabetes and cardiovascular diseases. Obesity may exacerbate insulin …

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Studies Of The Effect Of Nicotine On Color Vision In Color Deficient Humans, Warren Gwynn Jan 2014

Studies Of The Effect Of Nicotine On Color Vision In Color Deficient Humans, Warren Gwynn

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Previous research showed that oral nicotine use in non-smoking color normal individuals significantly improved color discrimination scores on the F-M 100 and both white and red increment thresholds of the Red Test. Our research sought to determine if similar results could be found when oral nicotine was administered to color deficient individuals. Ten color deficient individuals were first screened with both the HRR and Nagel Anomaloscope. Next, the F-M 100 and Red Test were performed before and after chewing nicotine gum (four mg). Subjects were introduced to testing procedures in one visit; a second visit, at least 24 hours later, …

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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 …

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Alpha-Camkii-Induced Vegf Expression Is Critical For The Growth Of Human Osteosarcoma, Paul Glenn Daft Jan 2014

Alpha-Camkii-Induced Vegf Expression Is Critical For The Growth Of Human Osteosarcoma, Paul Glenn Daft

All ETDs from UAB

Osteosarcoma (OS) is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. Despite improvements in OS treatment, more specific molecular targets are needed. One target of interest is alpha-Ca2+/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca2+-linked signaling, which has been shown to regulate tumor cell proliferation. Here, we show that α-CaMKII is highly expressed in primary OS tissue, and α-CaMKII deletion in human OS cell lines significantly reduces tumor burden in vivo. This inhibition of α-CaMKII results in decreased vascular endothelial growth factor (VEGF) protein secretion. Highly aggressive OS cells express VEGF receptor …

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Patient And System Level Factors As Predictors Of Adherence To Antiretroviral Therapy Appointment Schedules In Cambodia, Gary T. Daigle Jan 2014

Patient And System Level Factors As Predictors Of Adherence To Antiretroviral Therapy Appointment Schedules In Cambodia, Gary T. Daigle

All ETDs from UAB

PATIENT AND SYSTEM LEVEL FACTORS AS PREDICTORS OF ADHERENCE TO ANTIRETROVIRAL THERAPY APPOINTMENT SCHEDULES IN CAMBODIA GARY T. DAIGLE EPIDEMIOLOGY / INTERNATIONAL HEALTH ABSTRACT On-time attendance at clinical appointments by patients on antiretroviral therapy (ART) is essential to the prevention of medication interruptions, viral rebound, drug resistance, and long term mortality. An observational study conducted in 2010, Enablers and Adherence to Antiretroviral Therapy in Cambodia, sought to identify factors that predict on-time clinical appointment attendance by patients on ART. These factors were classified as either ART patient level factors (e.g. demographic, clinical) or patient care and support system level factors …

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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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Comparisons Between The Nod And Nor Mouse: Insight Into Diabetes Pathogenesis And Protection, Joseph Guy Daft Jan 2014

Comparisons Between The Nod And Nor Mouse: Insight Into Diabetes Pathogenesis And Protection, Joseph Guy Daft

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Type 1 Diabetes (T1D) is defined as the selective immune destruction of insulin producing beta cells within the islet. A new emphasis has been put on the role of the gastrointestinal (GI) tract in T1D; however, there is much more to learn about this relationship. Distinct differences have been observed in the intestinal permeability, barrier function, commensal microbiota, and mucosal innate and adaptive immunity of patients and animals with T1D, when compared to healthy controls. The non-obese diabetic (NOD) mouse and the BioBreeding diabetes prone (BBdp) rat are commonly used to models to study T1D in humans. Most murine studies …

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Contribution Of Kv4.2 To Neuronal Hyperexcitability In A Mouse Model Of Alzheimer's Disease, Alicia Marie Hall Jan 2014

Contribution Of Kv4.2 To Neuronal Hyperexcitability In A Mouse Model Of Alzheimer's Disease, Alicia Marie Hall

All ETDs from UAB

may be advantageous for increasing seasonal and yearly variability in sex ratios.

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The Multifaceted Role Of Neutrophils In Hiv-1-Infection, Nathan Bowers Jan 2014

The Multifaceted Role Of Neutrophils In Hiv-1-Infection, Nathan Bowers

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In recent years, a new appreciation of the role of neutrophils in regulating the immune system has emerged. Neutrophils are the most abundant leukocyte population and are traditionally recognized as essential effector cells of the innate immune system in the host defense against invading organisms. Neutrophils play a critical role in controlling bacterial and fungal infections by multiple mechanisms including phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs). Neutrophils have been shown to play important roles in viral pathogenesis, a knowledge gap exists in our understanding of the function of neutrophils in individuals infected with human immunodeficiency virus-1 (HIV-1). …

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Assessing System Congruence By Analyzing The Relationship Between Employee And Patient Driven Outputs, Timothy J. Harlin Jan 2014

Assessing System Congruence By Analyzing The Relationship Between Employee And Patient Driven Outputs, Timothy J. Harlin

All ETDs from UAB

Patients are at risk for employee driven preventable adverse events during hospital stays. These adverse events are varied and include such things as medication errors, pressure ulcers, hospital acquired infections, and falls. Preventable adverse events continue at alarming frequency despite significant academic, regulatory, and management attention to the topic over the past 14 years since the Institute of Medicine's (IOM) To Err is Human report. In addition to being at risk for preventable adverse events, patients experience aspects of the health care system such as ease of access, employee attitude, skill and efficiency of staff, and perceived value. Although purporting …

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Sialic Acid: A Signal For Pneumococcal Egress From The Nasal Mucosa Into The Central Nervous System, Brandon L. Hatcher Jan 2014

Sialic Acid: A Signal For Pneumococcal Egress From The Nasal Mucosa Into The Central Nervous System, Brandon L. Hatcher

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Streptococcus pneumoniae (pneumococcus) is one of the leading causes of bacterial meningitis world-wide. The classic paradigm in the establishment of bacterial meningitis is that in the absence of physical trauma, infection in the peripheral blood is needed to cause invasion of the central nervous system (CNS). Our previous studies have shown that pneumococci, a frequent colonizer of the nasopharynx, can cause bacterial meningitis through a nonhematogenous route by which bacteria appear to travel along the olfactory nerves, through the cribriform plate to the olfactory bulbs and into the rest of the CNS. However, with the frequency of nasopharyngeal colonization and …

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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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temperatures were near pivotal. The second chapter addresses the effects of fluctuating

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Gene Expression Signatures In Tree Shrew Retina, Rpe, And Choroid During Experimental Myopia And Recovery, Li He Jan 2014

Gene Expression Signatures In Tree Shrew Retina, Rpe, And Choroid During Experimental Myopia And Recovery, Li He

All ETDs from UAB

During the development of induced myopia and recovery, the emmetropization mechanism is stimulated to modulate ocular growth. Emmetropization signals originate in the retina, are transmitted and transformed by retinal pigment epithelium (RPE) and choroid, and reach sclera to induce tissue remodeling. Induced myopia occurs in response to myopiagenic stimuli - minus lens, form deprivation, and darkness - (three GO conditions) which increase ocular elongation; recovery from lens-induced myopia (STOP) occurs when minus-lens wear is discontinued after complete compensation, slowing ocular elongation. This dissertation examined gene expression signatures in the retina, RPE, and choroid under GO and STOP conditions to examine …

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Proteomic Analysis Of Rosenthal Fibers And The Development Of Software For Proteomics, Michael Raymond Heaven Jan 2014

Proteomic Analysis Of Rosenthal Fibers And The Development Of Software For Proteomics, Michael Raymond Heaven

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The first aim of my thesis was to identify the protein composition of the protein aggregates, called Rosenthal fibers, which are the defining feature of Alexander disease (AxD). AxD is a rare neurodegenerative disease caused by mutations in the astrocyte specific protein, glial fibrillary acidic protein (GFAP). GFAP is a type III intermediate filament protein that is overexpressed in AxD. A guiding hypothesis of this project was that sequestration of vital cell proteins in the aggregates contributed to disease. The results of my research do not support this hypothesis, but do provide an in depth characterization of the protein composition …

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Effect Of Protons On The Biology Of Human Gliomas, Avinash Vinayak Honasoge Jan 2014

Effect Of Protons On The Biology Of Human Gliomas, Avinash Vinayak Honasoge

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Gliomas are the most common and most deadly primary brain cancer. Patient outcome for the most malignant variety, the World Health Organization (WHO) Type IV glioblastoma multiforme (GBM), has stagnated over the last several decades - the best combination treatment of surgical resection, radiation, and chemotherapy results in median survival of just over a year. To escape treatment, GBM must multiply and migrate in a confined brain environment. Both of these aspects of tumor cell invasion rely on the cell's ability to volume regulate; cell division involves a stage called "pre-mitotic condensation" in which the cells shrink immediately prior to …

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Copper Homeostasis In Mycobacteria, Jennifer L. Rowland Jan 2014

Copper Homeostasis In Mycobacteria, Jennifer L. Rowland

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Mycobacterium tuberculosis, the causative agent on tuberculosis in humans, is a globally important pathogen. In 2013, nearly 1.2 million people died from tuberculosis. Drug treatments and effective vaccines are lacking for this pathogen. A better understanding of the basic physiology of M. tuberculosis is required to improve disease outcomes. Upon inhalation into the lungs, M. tuberculosis is taken up by macrophages, in a process called phagocytosis, which normally destroys invading bacteria. As the phagosome inside the macrophage matures, bactericidal mechanisms are activated including: lowering pH, and introducing reactive oxygen and nitrogen species and hydrolytic enzymes to degrade bacterial cell walls. …

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Molecular Profiling In Cervical Carcinogenesis And Progression, Kathryn Elizabeth Royse Jan 2014

Molecular Profiling In Cervical Carcinogenesis And Progression, Kathryn Elizabeth Royse

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Coexisting lesions can reduce genomic heterogeneity in precancer progression analysis by reducing variation and bias that can mask gene effects. Our goal was to use novel methodologies to depict the neoplastic stage effect (Normal v. LSIL v. HSIL) in cervical precancer. We analyzed the neoplastic stage effect via in silico and in vivo methodologies. For in silico analyses, we calculated differential expression (DE) estimates from a systematic review of DNA methylation and gene expression literature. Significant genes (FC≤2.0 or p-value≥0.05) were grouped by histology for pathway analysis. For in vivo analyses, we performed RNA-seq on microdissected FFPE coexisting cervical tissue …

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Rhodopsin As A Model For Gpcr Trafficking And Its Role In Outer Segment Formation, Joshua D. Sammons Jan 2014

Rhodopsin As A Model For Gpcr Trafficking And Its Role In Outer Segment Formation, Joshua D. Sammons

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Rhodopsin is a prototypical G-protein coupled receptor whose biological function has been well worked out, yet little is known about the mechanism by which it is so efficiently transported to the rod outer segment (ROS) after synthesis. If rhodopsin is not efficiently transported to the ROS, rod cells will apoptose leading to cone cell apoptosis as well which results in the blinding disease retinitis pigmentosa. Work has begun to elucidate proteins responsible for transporting rhodopsin to the ROS using Xenopus laevis as a model since the photoreceptors of this amphibian are large and transgenic animals are relatively easy to prepare. …

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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 …

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Measuring The Relationship Between Contextual Factors, Nurse Staffing Patterns, And Hospital Performance, Dong Yeong Shin Jan 2014

Measuring The Relationship Between Contextual Factors, Nurse Staffing Patterns, And Hospital Performance, Dong Yeong Shin

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Role Of Immunoregulatory Cytokines Il-12 And Il-23 In Skin Cancer, Tahseen H. Nasti Jan 2014

Role Of Immunoregulatory Cytokines Il-12 And Il-23 In Skin Cancer, Tahseen H. Nasti

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The incidence of new cases of skin cancer, which includes non-melanoma epithelial tumors and melanoma, has increased dramatically over the last few decades. Approximately 75% of all skin cancer-related deaths is due to melanoma, which is one of the most aggressive and difficult cancers to treat. The initiating events and mechanisms that influence melanoma development are not fully known, due in part to a paucity of animal models amenable to identifying new oncogenic mutations, and investigating mechanisms of immunosurveillance. Transgenic mouse models often harbor an activating mutation in a known oncogene in all somatic cells, and its widespread expression from …

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