Open Access. Powered by Scholars. Published by Universities.®

Digital Commons Network™

Open Access. Powered by Scholars. Published by Universities.®

2014

Discipline
Institution
Keyword
Publication
Publication Type
File Type

Articles 46951 - 46980 of 48977

Full-Text Articles in Entire DC Network

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.

Go to article

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 …

Go to article

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 …

Go to article

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

All ETDs from UAB

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

Go to article

High Spatiotemporal Resolution Mapping Of Retinal Physiology, Qiuxiang Zhang Jan 2014

High Spatiotemporal Resolution Mapping Of Retinal Physiology, Qiuxiang Zhang

All ETDs from UAB

The objective of my PhD dissertation research is to explore high resolution imaging of retinal function using transient intrinsic optical signals (IOSs) correlated with retinal physiological activation. The retina is responsible for capturing photons and preliminary visual information processing. Functional examination of retinal neural cells is important for eye disease detection and treatment evaluation. It is known that different diseases can target different retinal cell types, and thus high resolution imaging of retinal function is desirable. Fast IOSs with time courses comparable to retinal electroretinogram (ERG) kinetics can act as a unique biomarker to map physiological distortions correlated with eye …

Go to article

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

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

All ETDs from UAB

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 …

Go to article

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

Go to article

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 …

Go to article

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

Risk Assessment And Staging Of Cardiometabolic Diseases, Fangjian Guo

All ETDs from UAB

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 …

Go to article

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

All ETDs from UAB

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, …

Go to article

Evaluation Of Municipal Wastewater In The Vicinity Of Birmingham, Alabama For Estrogens Using Vitellogenin Gene Expression In Largescale Stonerollers (Campostoma Oligolepis), Shara Blackwell Legg Jan 2014

Evaluation Of Municipal Wastewater In The Vicinity Of Birmingham, Alabama For Estrogens Using Vitellogenin Gene Expression In Largescale Stonerollers (Campostoma Oligolepis), Shara Blackwell Legg

All ETDs from UAB

Environmental endocrine disrupting compounds (EDCs) have become a growing threat to the health of humans and wildlife. Numerous studies have demonstrated the presence of EDCs in freshwater aquatic environments. Environmental estrogens, both natural and synthetic, appear to be posing a threat to the reproductive fitness of aquatic organisms. Wastewater treatment plants (WWTPs) have been identified as significant routes by which the EDCs enter waterways. The egg yolk precursor protein vitellogenin (VTG) has proven to be a useful biomarker that can be used to identify organisms that have been exposed to environmental estrogens. In this study, a quantitative RT-PCR assay for …

Go to article

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

All ETDs from UAB

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 …

Go to article

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 …

Go to article

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 …

Go to article

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

All ETDs from UAB

none

Go to article

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

All ETDs from UAB

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 …

Go to article

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.

Go to article

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

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

All ETDs from UAB

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). …

Go to article

Depression And Alcohol Use Disorders As Gendered Phenotypes Of 5-Httlpr, Bryant Walker Hamby Jan 2014

Depression And Alcohol Use Disorders As Gendered Phenotypes Of 5-Httlpr, Bryant Walker Hamby

All ETDs from UAB

The serotonin transporter linked polymorphic region (5-HTTLPR) has been associated with both depression and alcohol use disorders in previous gene-environment interaction studies, but these associations have not been consistent. Previous research on mental health has posited that depression and alcohol use disorders are functionally equivalent manifestations of distress, with men displaying alcohol use disorders and women displaying depression in response to stress. This paper assesses whether the presence of the risk-conferring serotonin gene alleles increase an individual's chance of expressing distress as either depression or alcohol use disorders, depending on gender. The hypotheses that more symptoms of depression would be …

Go to article

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 …

Go to article

An Evaluation Of The Healthy Eating Active Living (Heal) Alabama Program For Prevention Of Childhood Obesity Among Fifth Grade Students, Kelley Devane Hart Jan 2014

An Evaluation Of The Healthy Eating Active Living (Heal) Alabama Program For Prevention Of Childhood Obesity Among Fifth Grade Students, Kelley Devane Hart

All ETDs from UAB

Childhood obesity is a major public health concern. The multiple effects of obesity in childhood are long-reaching. Since weight loss and maintenance are very difficult, prevention of obesity is important. Schools have been identified as an important environment for obesity prevention interventions since most children spend a large portion of the day at school. The purpose of this secondary data analysis was to determine if the Healthy Eating Active Living (HEAL) Alabama intervention improved weight status, fitness levels, and health knowledge and behaviors. A 2-by-2 repeated measures ANOVA was performed to determine whether differences exist between intervention and comparison students …

Go to article

Autism And Work: The Impact Of Comorbidity On Employment, Karen Harris Jan 2014

Autism And Work: The Impact Of Comorbidity On Employment, Karen Harris

All ETDs from UAB

included sex ratio predictions for every nest in the main egg corral for 2007 and 2008.

Go to article

An Examination Of The Services That Contribute To Positive Vocational Outcomes In Adults With Developmental Disabilities, Abbey N. Harris Jan 2014

An Examination Of The Services That Contribute To Positive Vocational Outcomes In Adults With Developmental Disabilities, Abbey N. Harris

All ETDs from UAB

One of the most pressing issues concerning persons with developmental disabilities is making sure their needs are met once they reach adulthood. As adults, they should have the abilities and skills to be as independent as possible and to be contributing members of society. Without the proper services and help, though, this may not be possible for a large portion of this population. Research suggests that supportive employment services alone may not be enough to meet their unique vocational needs and to improve the likelihood of their achieving personal and financial independence. The purpose of this study was to determine …

Go to article

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

All ETDs from UAB

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 …

Go to article

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

All ETDs from UAB

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

Go to article

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

All ETDs from UAB

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 …

Go to article

Sex Differences In Ss-Adrenergic Responsiveness Of Isolated Rabbit Hearts, Gregory Hoeker Jan 2014

Sex Differences In Ss-Adrenergic Responsiveness Of Isolated Rabbit Hearts, Gregory Hoeker

All ETDs from UAB

Stimulation of adrenergic receptors by catecholamines is the predominant regulatory mechanism for cardiovascular performance. Many cardiovascular diseases involve changes in ß-adrenergic signaling that often lead to decreased cardiac performance, cardiac arrhythmias, and/or sudden cardiac death. This has made ß-adrenergic receptors (ß-ARs) a significant therapeutic target in cardiovascular disease. Sex differences in ß-adrenergic responsiveness have been associated with cardioprotection in females, conferring a survival benefit in female patients with heart failure (HF). The heart contains three distinct ß-ARs: ß1-, ß2-, and ß3-AR. It is not known how each ß-AR subtype contributes to the sex differences in ß-responsiveness, let alone how this …

Go to article

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

All ETDs from UAB

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 …

Go to article

Nanodiamond Mediated Therapies For Prostate Cancer, Amanee Salaam Jan 2014

Nanodiamond Mediated Therapies For Prostate Cancer, Amanee Salaam

All ETDs from UAB

Enhancing therapeutic efficacy is essential for successful treatment of chemoresistant cancers such as metastatic hormone-refractory prostate cancer. Current chemotherapy regimens are plagued with issues such as toxicity, low bioavailability, and lack of specificity. To combat these issues, the feasibility of using nanodiamond particles (ND) to enhance the therapeutic efficacy of doxorubicin and resveratrol was investigated. The enhancement of chemotherapy using NDs was evaluated with three unique approaches: (1) drug mediation, (2) combination therapy, and (3) targeted drug delivery. The ND mediated doxorubicin system achieved a 50% improvement in therapeutic efficacy with over 60% cell death. The ND resveratrol combination therapy …

Go to article

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

All ETDs from UAB

iv

Go to article

First Prev Next Last