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Il-17 Producing Cd4 T Cells In Spontaneous Germinal Center And Autoantibody Formation In Murine Lupus, Huixian Hong Jan 2020

Il-17 Producing Cd4 T Cells In Spontaneous Germinal Center And Autoantibody Formation In Murine Lupus, Huixian Hong

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IL-23 promotes autoimmune disease, including Th17 CD4 T-cell development and autoantibody (autoAb) production. Here, we show that a deficiency of the p19 component of IL-23 in the autoimmune BXD2 (BXD2-p19−/−) mouse leads to a shift of the follicular T-helper cell program from Tfh-IL-17 to Tfh-IFN-ɣ. Although the germinal center (GC) size and the number of GC B cells remained the same, BXD2-p19−/− mice exhibited a lower class-switch recombination (CSR) in the GC B cells, leading to lower serum levels of IgG2b. Single-cell transcriptomics analysis of GC B cells revealed that while Ifngr1, Il21r and Il4r genes exhibited a synchronized expression …

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Examining The Role Of Neighborhood Quality On The Association Of Mammography Adherence Among Racial/Ethnic Groups, Roman Johnson Jan 2020

Examining The Role Of Neighborhood Quality On The Association Of Mammography Adherence Among Racial/Ethnic Groups, Roman Johnson

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Although several racial/ethnic minority women groups (e.g., Latina, Black, Asian-American, and Native-American women) have lower breast cancer incidence than white women, they are more likely to die from breast cancer. One possible explanation for this discrepancy is racial/ethnic differences in mammography use. Mammography has been shown to contribute to the discovery of tumor proliferation earlier which translates to less breast cancer complications like greater risk of breast cancer-related mortality. Previous studies on racial/ethnic differences in mammography adherence (e.g., annual and biannual mammography adherence) have been inconclusive, and they generally overlook important contextual factors, namely neighborhood quality and geographic location (e.g., …

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Pharmacodynamic Responses And Efficacies Associated With Lrrk2 Inhibition, Kaela Kelly Jan 2020

Pharmacodynamic Responses And Efficacies Associated With Lrrk2 Inhibition, Kaela Kelly

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Parkinson’s disease (PD) is an age-related, progressive, movement disorder pathologically characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of proteinaceous aggregates, termed Lewy bodies, that are largely comprised of αSynuclein (αSyn). Missense mutations in the leucine-rich repeat kinase (LRRK2) gene are the most common genetic cause of PD and lead to gain-of-function increases in kinase activity. The G2019S-LRRK2 mutation is the most frequent mutation and elevates kinase activity by ~2-3 fold. Genetic and biochemical evidence suggest elevated LRRK2 kinase activity plays a pathogenic role in the development of PD, implicating LRRK2 …

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A Preliminary Analysis On The Effects Of Acute Beetroot Juice Intake On Glycemic And Blood Pressure Control In Type 2 Diabetes, Braxton Linder Jan 2020

A Preliminary Analysis On The Effects Of Acute Beetroot Juice Intake On Glycemic And Blood Pressure Control In Type 2 Diabetes, Braxton Linder

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Cardiometabolic diseases are becoming increasingly prevalent in modern society due to low activity lifestyles and poor nutrition. Inorganic dietary nitrate (diNO3) has shown to potentially improve cardiometabolic health in a number of different populations but remains to be corroborated in humans with type 2 diabetes (T2D). This preliminary analysis aimed to determine the effects of consuming an acute, concentrated dose of diNO3 containing beetroot juice (BRJ) on hemodynamic and glycemic responses in humans with T2D while controlling for pharmacological influences. Three participants with a clinical diagnosis of T2D were recruited into this study. Pulsewave Velocity (PWV) was used to assess …

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Protective Host Responses During Acute And Chronic Lung Exposure To Aspergillus Fumigatus, Joseph Mackel Jan 2020

Protective Host Responses During Acute And Chronic Lung Exposure To Aspergillus Fumigatus, Joseph Mackel

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Aspergillus fumigatus is an environmental airborne fungus that acts as both an opportunistic pathogen and an allergen. In immunocompromised hosts, A. fumigatus can germinate in the lung, cause tissue damage and pneumonia, and disseminate to other organs, causing a disease termed invasive aspergillosis (IA). In severe asthma, sensitization to fungi such as A. fumigatus is associated with more severe disease. Determination of host and fungal factors that drive immunoprotection versus immunopathogenesis in both of these settings will ultimately enable therapeutic modulation of immune responses to improve disease outcomes. In this body of work, we build on recent findings that implicate …

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Gp44, A Minor Protein With A Major Role In Bacteriophage 80Α Infection, Keith Allen Manning Jan 2020

Gp44, A Minor Protein With A Major Role In Bacteriophage 80Α Infection, Keith Allen Manning

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Bacteriophage 80α is a temperate double-stranded DNA phage that infects Staphylococcus aureus and is capable of mobilizing a variety of mobile genetic elements named S. aureus Pathogenicity Islands. The capsid of the mature virion is composed of subunits of the capsid protein, portal protein, and a minor capsid protein gp44 as well as packaged phage genomic DNA. The loss of the gp44 protein completely eliminates the phage titer of 80α but does not eliminate the transduction of the pathogenicity islands. In this dissertation, I show that the minor capsid protein is primarily active in a post-ejection role. Without gp44 the …

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The Role Of The Β-Catenin Signaling Pathway In Modulating The Nucleolar Proteome Of Triple Negative Breast Cancer, Shannon E. Meier Jan 2020

The Role Of The Β-Catenin Signaling Pathway In Modulating The Nucleolar Proteome Of Triple Negative Breast Cancer, Shannon E. Meier

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Previously, abnormal nucleoli were noted as indicators of cancerous lesions andused as a pathologic readout of neoplasia. Nucleolar hypertrophy and increased nucleolar number have been correlated with increased breast cancer (BC) mortality rates. Although various functions of the nucleolus have been investigated, it remains widely understudied in the context of cancer. The nucleolus was initially thought to be solely the site of ribosome biogenesis. However, over half of the proteins found in the nucleolus are associated with other biological functions. It is evident that the nucleolus plays major roles in stress response, DNA repair, and critical cellular aspects that influence …

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Advancing Single Cell And Crispr/Dcas9 Technologies For The Study Of Reward Learning And Addiction, Corey Grant Duke Jan 2020

Advancing Single Cell And Crispr/Dcas9 Technologies For The Study Of Reward Learning And Addiction, Corey Grant Duke

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Drug addiction is a chronic relapsing condition inflicting tremendous harm to individuals and society with ineffective treatment options available to most people. Drugs of abuse elevate dopamine levels in a brain region known as the nucleus accumbens (NAc), and activate gene programs considered essential for producing lasting synaptic and cell state changes which underlie the generation of addictive behavior. These gene expression changes remain poorly understood due to a complex heterogenous cellular architecture, and the rapidly fluctuating nature of the transcriptional processes themselves which make investigation difficult. Recent technical advances increase access to both profiling and manipulating these transcriptional changes …

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An Augmented Framework For Validating Neural Network Predictions Based On Statistical Modeling, William Stonewall Monroe Jan 2020

An Augmented Framework For Validating Neural Network Predictions Based On Statistical Modeling, William Stonewall Monroe

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The Parkinson's Progression Markers Initiative (PPMI) dataset (which includes several types of imaging datasets) was created to generate biomarkers for diagnosing the presence and severity of Parkinson’s Disease (PD). Unlike some conditions, PD is not intuitively diagnosed directly from brain imaging. As such, it is vital to understand as well as classify PD. Deep learning techniques are becoming increasingly prevalent in medical imaging workflows. In some cases, deep learning outperforms human diagnostic ability. However, the black-box nature of many machine learning models can be troubling, particularly in a medical context since the results could imply alternate treatments and a human …

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Deficiency Of Tumor Suppressor Merlin Induces Metabolic Reprogramming In Breast Cancer, Mateus Mota Jan 2020

Deficiency Of Tumor Suppressor Merlin Induces Metabolic Reprogramming In Breast Cancer, Mateus Mota

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The tumor suppressor Merlin is encoded by Neurofibromin 2 (NF2) gene. Merlin is predominantly located in the cell cortex where regulates cell proliferation by mediating cell contact-dependent growth inhibition. Metastatic breast cancer tissues presented with a remarkable loss of Merlin protein, revealing clinical relevance of Merlin. In order to examine the cellular effect of Merlin deficiency, breast cancer cell lines were silenced for NF2. Additionally, to assess the impact of Merlin loss at the organismal level, a mammary-specific NF2 knockout mouse mammary tumor model was engineered. Merlin deficiency induced a metabolic shift from mitochondrial oxidative phosphorylation to aerobic glycolysis. Furthermore, …

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Protective Effects Of Thioredoxin Reductase Inhibition In The Murine Lung: The Regulation And Contribution Of Heme Oxygenase-1, Katelyn Louise Dunigan-Russell Jan 2020

Protective Effects Of Thioredoxin Reductase Inhibition In The Murine Lung: The Regulation And Contribution Of Heme Oxygenase-1, Katelyn Louise Dunigan-Russell

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Endogenous antioxidant responses defend the lung against oxygen toxicity. In premature neonates, oxygen toxicity and impaired antioxidant defenses contribute to the development of bronchopulmonary dysplasia (BPD), the leading cause of long-term morbidity among premature infants. In adults, oxygen toxicity and impaired antioxidant defense contributes to the pathogenesis of acute lung injury (ALI). Acute Respiratory Distress Syndrome (ARDS), a severe form of ALI, can cause permeant lung damage and mortality. Our lab has established that pharmacologic thioredoxin reductase-1 (TXNRD1) inhibition attenuates lung injury in murine BPD and ALI models. The protective effects of TXNRD1 inhibition are mediated by the activation of …

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Peace. Love. Youth. (In) Yoga: Development Of A Mental Health Program Among Adolescents Living In The Inner City, Sherilyn Jonnell Garner Jan 2020

Peace. Love. Youth. (In) Yoga: Development Of A Mental Health Program Among Adolescents Living In The Inner City, Sherilyn Jonnell Garner

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Adolescence is a unique developmental stage during which physical, cognitive, social, and emotional changes occur simultaneously and the traumatic effects of adverse childhood experiences (ACEs) can be particularly salient for the emotional and cognitive development of adolescents as they navigate and adjust to the social environment (Blakemore & Mills, 2014). Seventy-seven percent of Black adolescents have unmet mental health needs, and only 13% of those adolescents receive services compared to 31% of White adolescents. Meeting mental health needs of Black adolescents is imperative as their mental health needs continue to grow and resources become increasingly scarce. Innovative, culturally acceptable, accessible …

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The Non-Protostegid Cretaceous Marine Turtles Of Alabama And Their Bearing On The Evolution Of Extant Chelonioids, Andrew Gentry Jan 2020

The Non-Protostegid Cretaceous Marine Turtles Of Alabama And Their Bearing On The Evolution Of Extant Chelonioids, Andrew Gentry

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The non-protostegid marine turtle fossils recovered from the Late Cretaceous of Alabama may represent some of the most recent common ancestors of modern marine turtles. Despite their evolutionary significance, almost no formal studies have been conducted on these animals for more than 60 years. Many of these species are known from incomplete holotypes which has led to decades of systematic ambiguity and made specific referrals of recently collected fossil material exceedingly challenging. The aim of this study is to review and describe the specimens of Cretaceous marine turtles collected from Alabama to determine if this material can be used to …

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Immunopathogenesis In Fungal Asthma, Matthew Stephen Godwin Jan 2020

Immunopathogenesis In Fungal Asthma, Matthew Stephen Godwin

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Asthma patients are increasingly presenting with asthma that is more difficult to control and treat than in years past. A subset of these patients who are sensitive to fungal species are described as having severe asthma with fungal sensitization (SAFS). Given the severity of disease, there is ever increasing interest in identifying the immune processes underlying SAFS disease pathology and the development of novel therapeutics to improve management. While sensitivity to multiple fungal species has been described in SAFS, none is more common than Aspergillus fumigatus. Here, we describe two previously unrecognized contributors to the amelioration of disease pathology in …

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A Comparison Of Collection Materials And Differential Dna Extraction Methods Used To Extract Sperm And Buccal Cell Mixtures, Tyler Lawayne Corbin Jan 2020

A Comparison Of Collection Materials And Differential Dna Extraction Methods Used To Extract Sperm And Buccal Cell Mixtures, Tyler Lawayne Corbin

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This study focuses on two areas of interest when performing differential extractions for sexual assault kit analysis. By choosing different collection substrates, a traditional cotton swab, a nylon flocked swab, and a teased cotton swab, cellular elution capabilities were compared using two different semen dilutions. Nylon flocked swabs showed the most promise in obtaining a better male DNA yield compared to other swab types of similar dilution sets. Differential extraction methods introducing enzymatic digestion steps were modified and paired with the Qiagen DNA Investigator kit protocol to investigate their effects on cellular elution, cell separation, and time. These modified methods …

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Adolescent Fast Food Consumption: Underlying Factors And Related Health Outcomes, Lindsay Marie Stager Jan 2020

Adolescent Fast Food Consumption: Underlying Factors And Related Health Outcomes, Lindsay Marie Stager

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Obesity represents one of our nation’s leading public health issues. In 2017, over 30% of U.S. high school students presented with either overweight (15.6%) or obesity (14.8%). These trends are alarming as early childhood and adolescence are critical developmental periods for establishing healthy eating and exercise behaviors. Though past research has uncovered many factors related to adolescent eating behaviors, few studies have examined the longitudinal impacts of parenting and family variables on diet across the transition from adolescence to adulthood. Further, there is a lack of longitudinal research regarding health outcomes of fast food consumption during this same developmental period. …

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Novel Methods For Establishing The Capacity For Nociception And Cognition In The Zebrafish Danio Rerio, Chris Taylor Jan 2020

Novel Methods For Establishing The Capacity For Nociception And Cognition In The Zebrafish Danio Rerio, Chris Taylor

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Here we demonstrate the utility of a zebrafish-based model of nociception to serve as a novel screening tool for analgesic drugs. Zebrafish swimming behavior was measured following administration of various algogens used in rodent research. All compounds reduce distance traveled, thought to be an expression of nociception. Furthermore, we undertook to investigate the contribution of sex and feeding history on the acetic acid-evoked nociceptive response in zebrafish. Data suggest that male fish were more sensitive to pain than females, and that females recovered from pain faster than males. Dietary restriction increased pain sensitivity in zebrafish. We then tested the viability …

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Effect Of Cement Selection On Retention Of Zirconia And Lithium Disilicate Crowns, Chan-Te Huang Jan 2020

Effect Of Cement Selection On Retention Of Zirconia And Lithium Disilicate Crowns, Chan-Te Huang

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Background: Ceramic crowns (lithium disilicate and zirconia) have become the most prescribed material for the restoration of anterior and posterior teeth due to the esthetic concerns of patients and the high cost of noble alloys. Different types of cements are used for luting crowns such as zinc phosphate, glass ionomer, resin modified glass ionomer (RMGI), resin cements and bioactive cements. Selection of different cements and bonding protocols for zirconia or lithium disilicate crowns to increase their bonding strength remains a clinical challenge for dentists. Objectives: To measure the retention strength of lithium disilicate and zirconia crowns cemented with different cements. …

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C-Reactive Protein Subverts The Myeloid Lineage: Implications For Renal Injury, Rachel Jimenez Jan 2020

C-Reactive Protein Subverts The Myeloid Lineage: Implications For Renal Injury, Rachel Jimenez

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C-reactive protein (CRP) is an evolutionarily conserved pattern recognition molecule that was first characterized for its participation in the acute phase response to bacterial infection. In the last 90 years, knowledge of CRP biology in innate immunity has expanded significantly. CRP is known to bind and activate the classical pathway of complement, to opsonize bacteria and inflamed tissue, and to modulate myeloid cell functions. CRP is normally present in the blood at low levels with its biosynthesis and serum concentration rapidly rises upon systemic inflammation. For example, high levels of serum CRP are found following acute kidney injury (AKI) in …

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Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby Jan 2020

Understanding And Targeting Glucose Transporter 3 In Glioblastoma, Catherine Jeanne Libby

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Glioblastoma (GBM) is the most common adult primary malignant brain tumor with a median survival of about 15 months, even after aggressive treatment. Treatment of GBM is difficult for multiple reasons including the location of the tumor, tumor invasiveness, and the high degree of both inter-and intra-tumoral heterogeneity. Contributing to intratumoral heterogeneity are highly tumorigenic, stem-like tumor cells, with the capacity to self-renew and propagate the tumor, termed brain tumor initiating cells (BTICs). BTICs are also commonly therapy resistant, highly invasive, and metabolically plastic with elevated expression of glucose transporter 3 (GLUT3) allowing them to preferentially survive in low nutrient …

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Analyzing Spinach Growth Using Vertical Garden Techniques And Local Water Sources For Urban Gardens, Julia Ashlyn Manzella Jan 2020

Analyzing Spinach Growth Using Vertical Garden Techniques And Local Water Sources For Urban Gardens, Julia Ashlyn Manzella

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The University of Alabama at Birmingham undergraduate and graduate programs’ continued involvement in the Birmingham-Jefferson County community have identified food insecure areas, known as food deserts, and associated health issues negatively impacting the community due to poor diets and lack of access to healthy foods. Farm stands and community gardens around the Birmingham-metropolitan area have increased healthy food availability during the past several years to encourage healthier eating habits. To combat food insecurity, sustainable alternative growing techniques for urban agriculture need to be implemented and incorporated into local community gardens. Alternative gardening techniques such as vertical gardens maximize yield in …

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A Computational Method For The Analysis Of Magnetic Resonance Images Using Morphological Analysis, Jon Rolf Marstrander Jan 2020

A Computational Method For The Analysis Of Magnetic Resonance Images Using Morphological Analysis, Jon Rolf Marstrander

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Neurodegenerative diseases are an increasingly significant source of health problems in recent years. The prevalence and severity of these diseases is only expected to grow with the aging of the population. There is a large and and growing research effort to understand, diagnose and develop treatments for this class of diseases. Many of these diseases are not well understood, and there is a dearth of approved biomarkers and other techniques to definitively diagnose these diseases. The field of computational neuroimaging has been developed as part of the effort to study and diagnose these diseases. This field has undergone explosive growth …

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Translating Public Health Strategies To Examine Hypertensive Disorders Of Pregnancy In Alabama, Matthew Dean Moore Jan 2020

Translating Public Health Strategies To Examine Hypertensive Disorders Of Pregnancy In Alabama, Matthew Dean Moore

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Hypertensive disorders of pregnancy (HDP) are on the rise in the United States and contribute significantly to maternal and infant morbidity and mortality. The impact of such disorders is especially burdensome for women insured by Medicaid, for those who live in the South, and for those representing racial and ethnic minorities. It is evident across the aims of this dissertation that HDP remains an important public health concern to stakeholders in Alabama, its diagnosis is influenced by various maternal characteristics, and it can result in disparate severe outcomes for some populations. The first aim examines systems level decision-making in the …

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Single Cell Proteins Affect Growth Performance And Body Composition Of Pacific White Shrimp Litopenaeus Vannamei, Yuan Yuan Jan 2020

Single Cell Proteins Affect Growth Performance And Body Composition Of Pacific White Shrimp Litopenaeus Vannamei, Yuan Yuan

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The globally growing human population has increased the needs for protein based food. Single cell proteins (SCPs) as unconventional protein source, when coupled to aq-uaculture production, offer a means to ensure future protein needs can be met. To demon-strate a given type of SCP has potential as a protein source for use in aquaculture feed; a number of investigations are needed including demonstrating that the SCP is attractable and accepted by the animals, leads to equivalent survival, growth and nutritional compo-sition. This dissertation represents a series of investigations designed to evaluate the fea-sibility of using a bacterial based (MRD-Pro) and …

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Copper Dependent Inhibitors Subvert Common Resistance Mechanisms In Staphylococcus Aureus And Inhibit Crucial Metabolic Pathways, Cameron Crawford Jan 2020

Copper Dependent Inhibitors Subvert Common Resistance Mechanisms In Staphylococcus Aureus And Inhibit Crucial Metabolic Pathways, Cameron Crawford

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The effective antibiotic pool is shrinking with antibiotic resistance a constant problem that threatens to make our current therapies obsolete. To combat this, new drug screening methodologies are required since the traditional drug screens are offering limited results or only improvements upon current treatments. This work expands upon the idea that transition metal toxicity can be preferentially targeted towards bacteria. Specifically, the focus is on copper dependent inhibitors that quickly work to eliminate Staphylococcus aureus. S. aureus is a particularly threatening bacteria with high strain variability, a litany of survival and virulence factors, and multiple drug resistance mechanisms that are …

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Stimuli Response In Ph And Temperature-Responsive Hydrogels As Probed By Neutron Reflectivity, William Todd Higgins Jan 2020

Stimuli Response In Ph And Temperature-Responsive Hydrogels As Probed By Neutron Reflectivity, William Todd Higgins

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Polymer materials can be used as platforms to incorporate sensing materials, and increasingly the structure and chemistry of polymer chains is exploited in new and novel way and the unique nanoscale properties are studied. Polymers which can be dissolved in water are particularly interesting as primary components or for modifications in biomaterial applications, as many of them can have variable solubility in response to pH, temperature, or other solution conditions. This can allow the formation of microcapsules, for example, which can release drug triggered via specific solution conditions to release chemotherapeutic drug; in comparison to traditional injection or slow-release bulk …

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Pathogen Manipulation Of Arabidopsis Interaction Networks, Timothy Howton Jan 2020

Pathogen Manipulation Of Arabidopsis Interaction Networks, Timothy Howton

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Under normal conditions, plants devote resources for growth, development, and reproduction. These processes require finely tuned coordination between multiple physio logical pathways. In this dissertation, we explore the connectivity of these pathways as well as what happens when the plant is challenged by biotic stress such as a bacterial pathogen. We are able to use network biology approaches in conjunction with yeast two hybrid and BiFC assays to construct a network of leucine-rich repeat receptor kinases. Furthermore, we elucidated novel effector-host interactions through the aforementioned network. Lastly, we explored the role of the glyoxylate cycle, in particular peroxisomal citrate synthase …

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Rna Polymerase I Elongation Kinetics: A Biochemical And Global Study Of A Cancer Therapeutic Target, Catherine Elizabeth Scull Jan 2020

Rna Polymerase I Elongation Kinetics: A Biochemical And Global Study Of A Cancer Therapeutic Target, Catherine Elizabeth Scull

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My graduate research has focused on understanding the elongation kinetics of RNA polymerase I (Pol I), the enzyme responsible for synthesizing ribosomal RNA (rRNA), and defining how inhibition of ribosome biogenesis may be used as a cancer therapeutic strategy. Here, I have defined key biophysical features of Pol I and I have expanded the field’s understanding of Pol I elongation by: 1) characterizing the enzymatic properties of Pol I by mutational analysis of the polymerase itself, and by 2) elucidating the role of DNA sequence on Pol I arrest and nucleolytic cleavage activity. In recent years, Pol I has become …

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Smoke Inhalation, Lung Function, And Heart Rate In Wildland Firefighters, Jordan E. Nelson Jan 2020

Smoke Inhalation, Lung Function, And Heart Rate In Wildland Firefighters, Jordan E. Nelson

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Given the close proximity to the fire front and limited use of respiratory protection, wildland firefighters are exposed to elevated levels of biomass smoke during regular occupational shifts. Due to the complex composition of biomass smoke, the relationships relating biomass smoke exposure to health outcomes has yet to be elucidated. In addition to occupational exposures, increasing intensity of wildfire events may place communities within close proximity to wildfires at risk of biomass smoke exposure. This study aimed to assess exposures to biomass smoke particles and quantify respiratory and cardiovascular health responses during active fire events using novel monitoring techniques. Personal …

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A Structure Based Approach For Defining Ligand Interaction Requirements With Atp-Binding Cassette Proteins, Christina A. Le Jan 2019

A Structure Based Approach For Defining Ligand Interaction Requirements With Atp-Binding Cassette Proteins, Christina A. Le

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Membrane proteins belonging to the ATP-Binding Cassette (ABC) superfamily are responsible for transporting substrates into or out of cells. ABC transporters, such as P-glycoprotein (Pgp/ABCB1) defend cells by the active efflux of many chemically diverse cytotoxic compounds. The ABC protein, CFTR/ABCC7, is a passive chloride ion channel that provides fluid homeostasis. Pgp and CFTR of are high clinical interest since mutations in CFTR can result in Cystic Fibrosis (CF) and upregulation of Pgp in tumor cells can result in multidrug resistance (MDR). There has been a major effort to develop clinical drugs to treat CF by either repairing defects in …

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