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Marcks Effector Domain: Functions In Glioblastoma Progression And Novel Cytolytic Therapy, Nicholas James Eustace Jan 2019

Marcks Effector Domain: Functions In Glioblastoma Progression And Novel Cytolytic Therapy, Nicholas James Eustace

All ETDs from UAB

Glioblastoma (GBM; grade IV astrocytoma) is the most common primary adult brain malignancy and remains incurable despite tremendous advances in our understanding of this heterogeneous disease. In this dissertation, we explore the challenges encountered in the treatment of GBM and discuss a promising new therapeutic approach gleaned from studies of the phospholipid binding “effector” domain (ED) of the protein Myristoylated alanine-rich protein C kinase substrate (MARCKS). Following an introduction to central nervous system (CNS) tumors and the grading of diffuse gliomas, we explain how recent advancements to our understanding of the cellular and molecular composition of CNS tu-mors, and the …

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Regulation Of St6gal-I In Cancer: Sox2 Identified As Novel Driver Of St6gal-I Expression, Kaitlyn Alexandra Dorsett Jan 2019

Regulation Of St6gal-I In Cancer: Sox2 Identified As Novel Driver Of St6gal-I Expression, Kaitlyn Alexandra Dorsett

All ETDs from UAB

ST6Gal-I is a sialyltransferase that functions to add an 2-6 linked sialic acid to N-linked glycoproteins. The expression of ST6Gal-I is upregulated in many cancers at both the mRNA and protein levels. ST6Gal-I has also been shown to promote cancer stem cell (CSC) characteristics including chemoresistance, tumor-initiating potential, and spheroid growth. However, the transcriptional drivers of ST6Gal-I expression in stem-like cells remain largely unknown. Herein we highlight that SOX2 and ST6GAL1 are both located on one of the most commonly amplified chromosomal segments in cancer, amplicon 3q26. Copy number gains in both SOX2 and ST6GAL1 are observed in roughly 25% …

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Identification Of Two Spop-Mediated Pathways In Prostate Cancer Progression, Joshua Fried Jan 2019

Identification Of Two Spop-Mediated Pathways In Prostate Cancer Progression, Joshua Fried

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Prostate cancer is one of the most common malignancies and causes of cancer related death in men. Morbidity is primarily attributed to late-stage and metastatic disease. Re-cent genomic screening studies have revealed that the Speckle type Poz Protein (SPOP) is the most frequently altered gene by missense mutations in prostate cancer. Interestingly, all of the identified mutations were located in the substrate binding domain of SPOP. Here, two pathways highlighting the impact of SPOP mutation on prostate cancer are pre-sented. First, evidence showing that one of the naturally occurring SPOP mutations, ser-ine 119 to asparagine (S119N), induces radiosensitivity and an …

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The Role Of Nudc In Rod Photoreceptor Cell Maintenance: A New Function For An Old Protein, Evan Boitet Jan 2019

The Role Of Nudc In Rod Photoreceptor Cell Maintenance: A New Function For An Old Protein, Evan Boitet

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The overall health and maintenance of rod photoreceptors depends on directed vectorial transport of rhodopsin from its synthesis within the inner segment to its target destination the outer segment disk membranes. Numerous proteins are known to be involved in molecular interactions with rhodopsin during transport, including the interaction of nuclear distribution protein C (nudC) with rhodopsin that was first described in Xenopus laevis. We found that the interaction of nudC and rhodopsin is conserved in mammalian retina. This interaction is direct and aberrant expression of nudC results in subcellular localization of rhodopsin. We show for the first time that nudC …

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Social Support And Self-Care Efficacy As Mediators Of Racial Disparities In Diabetes Health In Older Adults, Wesley Browning Jan 2019

Social Support And Self-Care Efficacy As Mediators Of Racial Disparities In Diabetes Health In Older Adults, Wesley Browning

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Diabetes is a health problem that affects millions of Americans annually, and Black Americans have a higher prevalence with more complications than White Americans. A disparity exists between Black and White older adults living with diabetes in distress related to symptoms, treatment, and complications associated with the disease. Additionally, there are differences in levels of performing diabetes self-care behaviors between Blacks and Whites. One series of factors that may predict better diabetes self-care and diabetes distress in older adults are self-care efficacy and components of social support. This study used linear regression models to predict racial differences between Blacks and …

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Peruvian Medical Students' Attitudes Toward People With Disabilities, Shane Daniel Burns Jan 2019

Peruvian Medical Students' Attitudes Toward People With Disabilities, Shane Daniel Burns

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Patients with disabilities often interpret health care providers’ skills and facilities inadequate, are denied health care services, and report poor treatment in the medical setting. Key stakeholders in reforming this process are medical students, a demographic that currently provides services for patients with disabilities and will shape tomorrow’s health care systems. Past research has demonstrated that medical students often hold negative attitudes toward people with disabilities with much of this research being conducted in the developed world and none in Latin America. As a result, this study pursued to understand Peruvian medical students’ attitudes toward people with disabilities and how …

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Bioactive Materials: Ion Release & Recharge, Wear, Gloss & Hydroxyapatite Formation, Mohammed Badahman Jan 2019

Bioactive Materials: Ion Release & Recharge, Wear, Gloss & Hydroxyapatite Formation, Mohammed Badahman

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Introduction : Dental caries is one of the most prevalent chronic diseases 1. Unfortunately, there have been numerous failures with the treatment rendered, the materials used and how they are used. One significant cause for dental restoration failure is secondary caries and the need to replace the existing restoration. It has been reported that more than half of the restorations placed have been replaced because of recurrent caries. New materials and techniques have been developed to enhance adhesives in dentistry and improve the bonded interface however that interface still remains the weakest component of composite restorations. Marginal degradation and the …

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Role Of Developmental Protein, Nudc, In The Retina, Skyler Boehm Jan 2019

Role Of Developmental Protein, Nudc, In The Retina, Skyler Boehm

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Rod photoreceptors are the most prominent light sensitive cell in the retina of most mammals. The outer segments of photoreceptors contain the cellular machinery necessary for phototransduction to occur. The process of generating the phototransduction components occurs in the inner segment before being trafficked to the outer segment. These processes are highly regulated and require many different trafficking proteins and chaperones. The developmental protein nuclear distribution gene C (nudC) was found to be present in the photoreceptor, but its function is yet to be determined. Here we confirm that nudC is present in the retina and necessary in the photoreceptors. …

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Vagal Mediated Heart Rate Variability And Cognitive Impairments In Hiv-Seropositive Women, William C. Nicholson Jan 2019

Vagal Mediated Heart Rate Variability And Cognitive Impairments In Hiv-Seropositive Women, William C. Nicholson

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Regardless of sufficient viral suppression, HIV exerts an ongoing inflammatory process that promotes chronic autonomic nervous system (ANS) dysfunction, accelerates physiological aging, and increases the risk of developing a spectrum of cognitive disorders (known as HIV-associated neurocognitive disorders [HAND]). Given this, identifying pathological mediators of this inflammatory response could provide insight into the mechanisms driving HAND. The vagus nerve (indexed by vagal-mediated heart rate variability [vmHRV]) could provide such a mediator as it regulates ANS activity via reciprocal cardio-neural pathways, which regulate inflammation and homeostasis. Vagal dysfunction is associated with persistent inflammatory signaling (e.g., stress or inflammatory-based disorders [such as …

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Early Life Stress And Immune Responses In Adult Rat Kidneys, Ijeoma E. Obi Jan 2019

Early Life Stress And Immune Responses In Adult Rat Kidneys, Ijeoma E. Obi

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Globally, human studies show overwhelming associations between adverse childhood experiences and cardiovascular disease (CVD) and CVD risks throughout adult life. As early as 6 years old, there are significant associations between childhood adversity and inflammation, and those association are observed throughout adult life as well. Over a decade ago, rodent models were used to establish the importance of the immune cells in hypertension, which is the major risk factor in developing CVD. Although these associations in humans are important, they pose several limitations that can be overcome by the use of animal models to study the molecular mechanisms that are …

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The Role Of Protein Synthesis Attenuation And Eif2-Alpha Phosphorylation In Retinal Degeneration, Christopher Ryan Starr Jan 2019

The Role Of Protein Synthesis Attenuation And Eif2-Alpha Phosphorylation In Retinal Degeneration, Christopher Ryan Starr

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Inherited retinal degeneration is a class of diseases in which there is no cure and very few treatment options available. An activated unfolded protein response has been detected in various animal models of retinal degenerative diseases. Several groups have found heightened activation of one pathway of the unfolded protein response in particular, the protein kinase R-like endoplasmic reticulum kinase signaling cascade, which converges on and phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 to transiently halt protein synthesis and allow the cell to reestablish homeostasis. Although it is widely accepted that this signaling is inherently protective, hyperactivity or …

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Dysregulation In The Central Nervous System Upon Mcmv Infection In Newborn Mice, Cathy Yea Won Sung Jan 2019

Dysregulation In The Central Nervous System Upon Mcmv Infection In Newborn Mice, Cathy Yea Won Sung

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Human cytomegalovirus (HCMV) infection is a major cause of morbidity in infants and children throughout the world. Between 0.2-1.2% of all live births is infected with HCMV in the United States. Approximately 5-15% of these newborn babies will develop long-term neurological damage resulting in motor disorders, mental retardation, and sensorineural hearing loss. Although the neurological sequelae associated with congenital HCMV infections are well characterized, little is known about the pathogenesis of the damage to the central nervous system (CNS). To study the pathogenesis of congenital HCMV infection, we have developed a mouse model in which newborn mice are infected intraperitoneally …

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Therapeutic Mechanisms In Sickle Cell Nephropathy, Crystal Taylor Jan 2019

Therapeutic Mechanisms In Sickle Cell Nephropathy, Crystal Taylor

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Sickle cell disease (SCD) is a commonly inherited genetic blood disorder that causes hypoxia-induced polymerization of mutant hemoglobin resulting in erythrocyte sickling, transient microvascular occlusion, ischemic injury, and end-organ damage. Systemic endothelial dysfunction and vaso-occlusive episodes observed in SCD are particularly deleterious to the kidney, where the hypoxic, hyperosmotic environment of the medulla makes it particularly susceptible to ischemic injury. Over recent decades, chronic kidney disease has emerged as a significant contributor to mortality and morbidity in SCD patients. Despite a growing interest in the importance of sickle cell nephropathy (SCN), therapeutic options are limited and much remains undiscovered regarding …

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The Role Of Protein O-Glcnacylation In Regulating Mitochondrial Function, Jalessa Nicole Wright Jan 2019

The Role Of Protein O-Glcnacylation In Regulating Mitochondrial Function, Jalessa Nicole Wright

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The attachment of O-linked-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins has emerged as an important regulatory mechanism in transcriptional regulation, protein activation as well as cell survival. Several studies have reported that elevated O-GlcNAc levels have adverse effects on mitochondrial function. These negative effects have been linked to O-GlcNAc modification of mitochondrial proteins that are integral across multiple metabolic cell processes i.e. VDAC, NDUFA9 and DRP-1. Mitochondrial complexes I, III and IV all contain subunit proteins that are O-GlcNAc modified and increased O-GlcNAcylation of these proteins is associated with deficits in oxidative phosphorylation in these models. Conversely, it has …

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Methods For The Establishment Of A Dss-Induced Ibd Model In Adult Zebrafish, Ningxiang Zeng Jan 2019

Methods For The Establishment Of A Dss-Induced Ibd Model In Adult Zebrafish, Ningxiang Zeng

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Inflammatory Bowel Disease (IBD) is a group of idiopathic chronic inflammatory intestinal conditions. To reveal its pathogenesis, several different animal models have been established. Although no single model captures the complexity of human IBD, each model provides valuable insights into one or another major aspect of disease, and together they have led to the establishment of a generally accepted understanding for human IBD pathogenesis. Recently, zebrafish have become an important platform for IBD research, and several murine IBD outcomes have been adapted to the zebrafish. Dextran Sulfate Sodium (DSS) -induced colitis, the most widely used murine IBD model, has never …

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Exploring The Link Between Dietary Fiber, The Gut Microbiota And Estrogen Metabolism Among Women With Breast Cancer, Ayse G. Zengul Jan 2019

Exploring The Link Between Dietary Fiber, The Gut Microbiota And Estrogen Metabolism Among Women With Breast Cancer, Ayse G. Zengul

All ETDs from UAB

Breast cancer continues to be a very prevalent disease and impacts over 260,000 new patients per year in the United States. The gut microbiota composition may affect breast cancer risk by modulating various hormonal metabolites including endogenous estrogens. Dietary factors impact gut microbial ecology and influence the regulation of estrogen metabolism. Current evidence supports the potential role of dietary fiber in breast cancer prevention and its possible modulating influence on serum estrogen levels through the gut microbiota associated with β-glucuronidase activity. However, this mechanism is not clearly understood. In this study, we aimed to explore the associations between dietary fiber, …

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Delayed Diagnosis Of Pheochromocytoma: The Importance Of Reevaluating The Differential And The Dangers Of Patient Labeling., Nabeel Ali, Joseph Granade, Gayatri Venketraman Jan 2019

Delayed Diagnosis Of Pheochromocytoma: The Importance Of Reevaluating The Differential And The Dangers Of Patient Labeling., Nabeel Ali, Joseph Granade, Gayatri Venketraman

UAB Huntsville Research Day - All Presentations

2019 clinical vignette poster

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A Case Of An Increased Factor Viii Activity And Its Relationship To Cryptogenic Stroke, Syeda Sabeeka Batool, Mohammed Abdulhaleem, Swetha Srialluri, Alan Baggett Jan 2019

A Case Of An Increased Factor Viii Activity And Its Relationship To Cryptogenic Stroke, Syeda Sabeeka Batool, Mohammed Abdulhaleem, Swetha Srialluri, Alan Baggett

UAB Huntsville Research Day - All Presentations

2019 clinical vignette poster

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Sjogren's Syndrome: A Case Presentation, J Johnson, L Burch, P Yedla Jan 2019

Sjogren's Syndrome: A Case Presentation, J Johnson, L Burch, P Yedla

UAB Huntsville Research Day - All Presentations

2019 clinical vignette poster

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Prevalence Of Drugs In Blood Alcohol Concentrations Above Versus Below 0.08% In Alabama Driving Under The Influence Cases, Charity Buggs Jan 2019

Prevalence Of Drugs In Blood Alcohol Concentrations Above Versus Below 0.08% In Alabama Driving Under The Influence Cases, Charity Buggs

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Driving under the influence of drugs combined with alcohol has become an increasing problem in the United States. When a person provides a breath test that results in less than the 0.08% per se limit, their driving may still be impaired from drug use. Over the past decade, more blood samples from DUI cases involving motor vehicle crashes have tested positive for drugs than for alcohol. Cases with previously analyzed blood samples were taken from the Laboratory Information Management System at the Alabama Department of Forensic Sciences for statistical analysis. The aim of this study was to review reported DUI …

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Predictors Of School Weapon Carrying Among Adolescents, Jonathan Adams Jan 2019

Predictors Of School Weapon Carrying Among Adolescents, Jonathan Adams

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The presence of weapons threatens the safety of all individuals on school grounds. Emergent research suggests factors linked to school weapon carrying may stem from both within and outside the school environment; however, few efforts have been made to identify a comprehensive set of risk and protective factors associated with school weapon carrying. To address this gap, the first manuscript serves as a comprehensive, systematic review of variables associated with higher or lower likelihood an adolescent will carry weapons to school. Results indicated higher rates of weapon carrying among individuals who are male, sexual minority, children of single parents; exhibit …

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Identifying Associated Risk With Exposure Ti Weapon Carrying Among Emerging Adults Living In Disadvantaged Urban Areas In Birmingham, Tolulope Aduroja Jan 2019

Identifying Associated Risk With Exposure Ti Weapon Carrying Among Emerging Adults Living In Disadvantaged Urban Areas In Birmingham, Tolulope Aduroja

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IDENTIFYING ASSOCIATED RISK WITH EXPOSURE TO WEAPON CARRYING AMONG EMERGING ADULTS LIVING IN DISADVANTAGED URBAN AREAS IN BIRMINGHAM TOLULOPE ADUROJA HEALTH EDUCATION/HEALTH PROMOTION ABSTRACT Weapon carrying is a public health concern due to its association with a serious injury, disability or death, and adverse health-related outcomes. Weapon carrying among youth is associated with both intrinsic or internalizing and extrinsic or externalizing factors (Stayton, 2011). Violence in youth and young adults is the 2nd leading cause of death (homicide) in Alabama. Health behavior theories posit that health-relevant attitudes, beliefs, and behavioral skills drive subsequent actions people take to protect themselves from …

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Identification And Application Of Gingival Mesenchymal Stem Cells For Dental Tissue Regenration, Yousuf Al-Aboosi Jan 2019

Identification And Application Of Gingival Mesenchymal Stem Cells For Dental Tissue Regenration, Yousuf Al-Aboosi

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Mesenchymal stem cells have been very attractive treatment modality in regenerative medicine, but not so much in regenerative dentistry. This can be attributed to the difficulty in obtaining dental origin stem cells without extracting a tooth or other invasive procedures. Autogenous gingival graft harvested from palatal tissue is used as the gold standard for treating single tooth recession. The healing of the gingival graft has been shown to be mostly depended on the recipient side more than the graft itself. This study is aiming to find if the palatal tissue has cells with mesenchymal characteristics that are helping in the …

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Assessment Of A Bdnf Mimetic To Improve Behavioral Deficits In Female Mecp2 Heterozygous Mice, A Model Of Rett Syndrome, Karen Nataly Ayala Baylon Jan 2019

Assessment Of A Bdnf Mimetic To Improve Behavioral Deficits In Female Mecp2 Heterozygous Mice, A Model Of Rett Syndrome, Karen Nataly Ayala Baylon

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Rett syndrome (RTT) is a neurodevelopmental disorder representing the second most common cause of intellectual disability in women. Most RTT cases are caused by mutations in the gene coding for the transcriptional regulator Methyl-CpG-binding Protein 2 (MeCP2). The neurotrophin BDNF (Brain-Derived Neurotrophic Factor) has therapeutic potential for RTT because BDNF levels are lower in RTT autopsy brains and in Mecp2 deficient mice, while conditional Bdnf deletion results in phenotypes similar to those of Mecp2 knockout (KO) mice. In addition, Bdnf overexpression in forebrain excitatory neurons in Mecp2 KO mice significantly improved their lifespan, locomotor function, and brain weight. However, BDNF …

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Regulation Of Intestinal Innate Lymphoid Cells In Acute And Chronic Inflammation, Sarah Dulson Jan 2019

Regulation Of Intestinal Innate Lymphoid Cells In Acute And Chronic Inflammation, Sarah Dulson

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The Innate Lymphoid Cell (ILC) population encompasses five subpopulations that are increasingly appreciated to participate in immune responses to inflammation and injury as well as directly influence homeostasis in tissues throughout the body. ILCs are enriched at mucosal surfaces, such as the gastrointestinal tract, where they are transcriptionally poised for rapid activation. Therefore, ILCs contribute significantly to protective responses to infection, and can exacerbate inflammation and disease when dysregulated. Herein, we demonstrate two pathways that regulate intestinal ILC phenotype and function and delineate the impact of these pathways on both protective and pathogenic roles of ILCs. Using a murine model …

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Impact Of Familial Chronic Illness On Adolescent Somatization, Lindsey Elliott Jan 2019

Impact Of Familial Chronic Illness On Adolescent Somatization, Lindsey Elliott

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Somatic symptoms, or physical symptoms that do not have an identifiable organic etiology, have a prevalence of 10-30% in children. They have been associated with poor psychosocial outcomes in children, including emotional and behavioral problems, school absences, and impaired social functioning. Further, these symptoms represent a burden on the health care system as patients with somatic symptoms are frequent users of both primary care physicians and specialists. The etiology of somatic symptoms is thought to be due to a combination of biological, psychological, interpersonal, and healthcare factors. Two theories exist regarding the etiology of somatic symptoms. Brown’s integrative conceptual model …

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Bet Bromodomain Inhibition As An Approach For Treatment Of Cholangiocarcinoma, Samuel Charles Fehling Jan 2019

Bet Bromodomain Inhibition As An Approach For Treatment Of Cholangiocarcinoma, Samuel Charles Fehling

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Cholangiocarcinoma (CCA) is a highly aggressive neoplasm which arises from the epithelial layer of the biliary tract. It is the second most common primary hepatic malignancy. As CCA is typically diagnosed at late disease stage, the current standard of care, resection followed by gemcitabine with cisplatin, is not effective. Further, up to 90% of CCA patients are ineligible for resection. Of those eligible for resection, postoperative chemotherapy does not prolong overall survival leading to a 5-year survival of ~30%. Previously, mutations have been identified in KRAS (17% of CCA cases), TP53 (44%) and SMAD4 (17%) but none have been recognized …

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Evaluation Of A Novel Monoclonal Antibody Based Therapy For Neuroendocrine Tumors, Daniel Flanigan Jan 2019

Evaluation Of A Novel Monoclonal Antibody Based Therapy For Neuroendocrine Tumors, Daniel Flanigan

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Neuroendocrine tumors (NETs) are malignancies that arise from genetic or sporadic abnormalities in the endocrine system. These cancers can be found in various organ systems but are most frequently expressed in the gastrointestinal (GI) tract and pancreas. The incidence rate of NETs has been steadily increasing in the past few decades, exhibiting a 6.4-fold increase from 1973 to 2012. Despite this observation, these cancers are still considered rare and as such there is a lack of appropriate treatments addressing them. Monoclonal antibodies (mAbs) that specifically bind to type 2 somatostatin receptor (SSTR2), a protein commonly overexpressed in NETs, could be …

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Utilization Of The Zebrafish Model System To Predict Effects Of Dietary Lipid Composition On Human Health, Lauren Adele Fowler Jan 2019

Utilization Of The Zebrafish Model System To Predict Effects Of Dietary Lipid Composition On Human Health, Lauren Adele Fowler

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Obesity is a disease that encompasses the interaction of both genetics and life-style factors, and the pathology behind its development remains unclear. Specifically, defining the influence of dietary lipid intake on adiposity and metabolic health continues to be a fundamental challenge, and the use of animal models will be required to gain a full understanding of the processes contributing to diet-induced obesity in humans. The zebrafish Danio rerio has emerged as a powerful model system to study diet-induced obesity and metabolic disease in humans, while simultaneously offering multiple advantages over rodent models. This dissertation addresses multiple aspects regarding the use …

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Rituals Of Reconciliation: The Use Of Peaceful Interactions To Repair Relationships, Sheila Renee Gainer Jan 2019

Rituals Of Reconciliation: The Use Of Peaceful Interactions To Repair Relationships, Sheila Renee Gainer

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Reconciliation is the process by which social animals maintain valuable social relationships. It has been documented in many species including humans and nonhuman primates. While evidence of rituals has been seen in other species, the primary aim of this research is to explore how ritual behaviors are interconnected to human acts of reconciliation. Rituals are habitual activities closely linked to important events and reaffirm the identity of those who practice them as a group or a society. They are found in every society, culture and religion. In this study, rituals specifically related to reconciliation were exhibited in 27 of 138 …

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