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Combined Effects Of Corexit Ec 9500a With Secondary Abiotic And Biotic Stressors In The Rotifer Brachionus Plicatilis, Michael Britt Williams Jan 2014

Combined Effects Of Corexit Ec 9500a With Secondary Abiotic And Biotic Stressors In The Rotifer Brachionus Plicatilis, Michael Britt Williams

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Following the Deepwater Horizon oil spill the dispersant Corexit EC 9500A (C-9500) was applied to facilitate rapid oil degradation. C-9500 toxicity has been evaluated on a number of marine species; however, many of these studies do not account for environmental conditions that may increase negative outcomes related to dispersant exposure in the wild. We examined lethality and behavioral effects of C-9500 exposure on the model marine zooplankton Brachionus plicatilis. We also evaluated interactions of abiotic and biotic stressors that may alter outcomes of exposure. C-9500 exposure at standard husbandry conditions (17.5ppt, 24°C, 200 rotifer*ml-1 density) produced a 24 hr median …

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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

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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

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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

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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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Nonlinear Optical Characterizations Of Bithiophenes With Phosphorus Containing Substituents, Yuanli Zhang Jan 2014

Nonlinear Optical Characterizations Of Bithiophenes With Phosphorus Containing Substituents, Yuanli Zhang

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This dissertation describes experimental and theoretical studies of the nonlinear optical (NLO) absorption mechanisms in chalcogenidodiphenylphosphino-substituted bithiophenes and phosphonato-substituted bithiophenes. The NLO properties of these compounds were studied by measurements of NLO absorption versus input energy and Z-scan experiments. Both of these NLO experiments were performed in the picosecond (ps) and nanosecond (ns) time regimes in the blue spectral region. These experiments demonstrate that these compounds exhibit both high linear transmissions and strong nonlinear absorptions in the blue spectral region. Saturated solutions of the bithiophenes monosubstituted with chalcogenatodiphenylphosphino groups exhibit the highest NLO absorbances of picosecond laser pulses that have …

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

High Spatiotemporal Resolution Mapping Of Retinal Physiology, Qiuxiang Zhang

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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 …

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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

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

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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

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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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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

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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 …

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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

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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

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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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Imaging Biomarkers For Prediction Of Treatment Response In Schizophrenia, Jennifer Ann Hadley Jan 2014

Imaging Biomarkers For Prediction Of Treatment Response In Schizophrenia, Jennifer Ann Hadley

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Schizophrenia affects approximately 1% of the population and is one of the top five causes of disability worldwide. Patient response to any particular drug is variable and currently unpredictable. Our overall goal is to identify imaging biomarkers that will distinguish patients with schizophrenia who will respond to an antipsychotic drug from those who will not. When considering potential biomarkers, it is important to note that schizophrenia is known to involve altered neuronal connections, thought to reflect pathologically relevant changes associated with the disease. We propose to utilize functional connectivity as a biomarker for treatment response to antipsychotic drugs in schizophrenia. …

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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

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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 …

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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

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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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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

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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 …

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

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

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

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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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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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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

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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 …

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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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Nanodiamond Mediated Therapies For Prostate Cancer, Amanee Salaam Jan 2014

Nanodiamond Mediated Therapies For Prostate Cancer, Amanee Salaam

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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 …

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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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Dihydrofolate Reductase Inhibitors - Applications To Chagas Disease And Dental Caries, Thao Nguyen Jan 2014

Dihydrofolate Reductase Inhibitors - Applications To Chagas Disease And Dental Caries, Thao Nguyen

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significantly influenced sex ratios by increasing the production of males when

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Coevolution Of Sponges And Microbial Symbionts Across Ocean Basins, Zachary Lee Nolen Jan 2014

Coevolution Of Sponges And Microbial Symbionts Across Ocean Basins, Zachary Lee Nolen

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Sponges (phylum Porifera) can comprise a large portion of benthic communities in freshwater and marine environments. Because sponges possess simple body plans and can have substantial phenotypic plasticity within species, reconstructing phylogenies of Porifera based upon morphologies alone has proven difficult. With the advent of nucleic acid sequencing technologies, interest in sponge phylogenetics has significantly increased among researchers. Additionally, sponges host a wide range of microbial symbionts, including the cyanobacterium Synechococcus spongiarum. This study examined the evolution of both sets of organisms in the symbiotic relationship between Aplysina sponges and Synechococcus cyanobacteria. In Chapter 3, gene sequences coding for the …

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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 …

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Substrate Recognition And Translocation Catalyzed By Aaa+ Chaperones, Tao Li Jan 2013

Substrate Recognition And Translocation Catalyzed By Aaa+ Chaperones, Tao Li

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Both E. coli ClpA and E. coli ClpB belong to the Clp/Hsp100 chaperone family. They share many common features, such as the same conserved motifs (Walker A, Walker B, Arginine finger, Pore loop, etc.), hexameric ring-shaped structure, and double nucleotide binding domains. ClpA and ClpB are closely related to each other. However, they participate in different protein quality control pathways. ClpA regulates cellular functions by either associating with ClpP to form the ClpAP complex (an ATP-dependant protease) to degrade unwanted polypeptides or remodeling inactive proteins to their biological active forms. ClpA can recognize specific sequences located on either N- or …

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Intramural Electrical Uncoupling During Long-Duration Ventricular Fibrillation In Rabbit, Trenika A. Madden Jan 2013

Intramural Electrical Uncoupling During Long-Duration Ventricular Fibrillation In Rabbit, Trenika A. Madden

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Ventricular fibrillation is a lethal cardiac arrhythmia which alters electrophysiological properties of the myocardium while concurrently inducing global ischemia and is associated with high mortality rates. Studies on the organization of long-duration ventricular fibrillation (LDVF) have shown that an endocardial to epicardial (i.e. transmural) activation rate gradient exists during ventricular fibrillation in canine and human myocardium; however, the underlying mechanism is unknown. This study tested the hypothesis that the activation rate gradient reflects heterogeneous changes in tissue electrical resistivity resulting in differential transmural electrical uncoupling of the ventricular myocardium. LDVF (>5min) was electrically induced in anesthetized, open-chest rabbits using …

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