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Transcriptional Dysregulation In Interneurons Causes Altered Modulation Of Hippocampal Synaptic Transmission And Circuit Function By The Dopamine System, Lillian J. Brady

All ETDs from UAB

Genetic deletion of the transcriptional coactivator PGC-1α leads to transcriptional dysregulation in interneurons, and transcriptional dysregulation in interneurons lead to changes in hippocampal synaptic transmission and circuit function. Hippocampal circuit activity and synaptic transmission alterations have implications for symptoms of cognitive impairment in neurological disorders like schizophrenia. Modulation of dopamine receptor activity through pharmacologic application of haloperidol and the specific dopamine D4 receptor antagonist L-745,870 in PGC-1α-/- mice leads to altered effects on inhibitory/excitatory synaptic transmission balance, circuit function, and innate hippocampal dependent nesting behavior. These are key aspects underlying hippocampus dependent cognitive impairment. Specifically, bath application of haloperidol restores …

Strategies Early Childhood Elementary Teachers Use In Order To Provide A Welcoming Environment For Student Who They Perceive To Be Lgbtq Or Exhibit Stereotypical Characteristics, Felecia Brooks-Jones

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STRATEGIES EARLY CHILDHOOD TEACHERS USE IN ORDER TO PROVIDE A WELCOMING CLASSROOM ENVIRONMENT FOR STUDENTS WHO THEY PERCEIVE TO BE LGBTQ OR EXHIBIT STEREOTYPICAL CHARACTERISTICS FELECIA BROOKS-JONES EARLY CHILDHOOD EDUCATION ABSTRACT People who identify as Lesbian, gay, bisexual, transgender, and queer/questioning are becoming more socially accepted today than they were before. Laws have been passed to give same-sex couples equal rights as heterosexual couples. However, they are not always treated the same, especially here in the southeast, which is known as the Bible Belt. There is minimal research or literature in the field of education concerning early elementary LGBTQ students, …

Autism Spectrum Disorders And Social-Ecological Models: Understanding How Context Drives Prevalence, Anne Elizabeth Brisendine

All ETDs from UAB

Background: While there has been significant work done to explore disparities in autism spectrum disorder (ASD) diagnoses with respect to individual characteristics, little work has been done to examine the overall system and structure of the environment in which ASD identification is made and how it is related to diagnosis and services. The purpose of this study is to better understand the social-ecological factors that impact ASD diagnoses at the population level. Methods: In the first aim of this dissertation, a tailored social ecological model was developed and examined across variables in the 2011/12 National Survey of Children’s Health. In …

Immunobiology Of The Mucosal Response To Helicobacter Pylori In Children, Kyle Brawner

All ETDs from UAB

Helicobacter pylori colonizes the stomach of approximately one half of the world’s population. However, the vast majority of infected persons remain asymptomatic. The degree of H. pylori-induced gastric inflammation depends on a complex interaction of several factors. In this dissertation, we focus on age as a determinant of gastritis severity. Children are known to respond to H. pylori infection with a stronger T regulatory cell profile compared with infected adults, yet the reason remains unknown. The influence of the microbiota on, and the communication among, cells of the innate immune system shape the nature of the adaptive immune response to …

Interplay Of The Circadian Clock And Growth Hormone Signaling In The Heart, Ryan Darrell Berry

All ETDs from UAB

Growth hormone (GH) signaling plays a critical role in postnatal development and the details of its release, regulation, and influence on the development of a number of organs has been well studied. GH is released from the anterior pituitary in a pulsatile fashion with pulse amplitude being greater at night than during the day in a number of species, including humans. Once in circulation, GH binds to the GH receptor (GHR) on target tissues throughout the body altering gene expression and stimulating the local production of insulin-like growth factor 1 (IGF-1). IGF-1 primarily acts in an autocrine and paracrine fashion. …

Optimizing The Non-Ablative Conditioning Regimen For Bone Marrow Transplantation Using A Murine Model Of Sickle Cell Disease, Divya Devadasan

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In this dissertation, we sought to determine if a sub-myeloablative conditioning regimen followed by bone marrow transplantation/hematopoietic stem cell transplantation (HSCT) using syngeneic donor cells could facilitate donor chimerism using a clinically relevant mouse model of sickle cell disease (SCD). This pre-clinical study determined the feasibility of using sub-myeloablative conditioning in the context of autologous HSCT. The prospect of using less-intense conditioning is particularly appealing in the era of modern gene-editing technologies since its extension to use in humans will allow for HSCT to be less toxic and hence be applicable in all patients. We showed that using a sub-myeloablative …

Effect Of Antihypertensive Drugs On Left Ventricular Traits In Africam American, Anh N. Do

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The purpose of this dissertation is to evaluate the association of antihypertensive treatment as well genomic variants with left ventricular (LV) hypertrophy (LVH) -related traits among African Americans (AAs) in five cross-sectional epidemiology cohorts from the United States. AAs especially those with hypertension, are overburdened by left ventricular (LV) hypertrophy (LVH) compared to other ethnic groups. LVH is associated with increased risk for cardiovascular morbidity and mortality. Antihypertensive treatments have been found to improve LVH and related echocardiographic measures (i.e. LV traits) among hypertensive patients. However, the effect of antihypertensive treatments on LVH and related traits in AAs has not …

Factors Guiding Cd4 T Cell Fate Bifurcations, Daniel Francis Ditoro

All ETDs from UAB

Naïve CD4 T cells differentiate into a variety of phenotypically and functionally distinct subsets uniquely tailored to the specific inflammatory context. Despite the extraordinary heterogeneity of potential fate outcomes, two distinct but related functional bifurcations appear common to all inflammatory contexts. Following activation, CD4 T cells either home to the site of inflammation and influence peripheral events or remain in the secondary lymphoid tissue to modulate central processes. Similarly, activated cells either drive or suppress inflammation. These functional bifurcations are coincident and sufficiently independent to allow for the simultaneous generation of all four potential outcomes. Pro-inflammatory cells retained in the …

O-Acetyltransferase Functionality Mediates Pneumococcal Capsular Diversity, Brady Spencer

All ETDs from UAB

Streptococcus pneumoniae (pneumococcus) is an important human pathogen that asymptomatically colonizes the nasopharynx but can disseminate opportunistically to cause diseases such as otitis media, pneumonia, septicemia, or meningitis. The pneumo-coccal capsular polysaccharide is necessary to prevent opsonophagocytosis as nonencap-sulated pneumococci are largely avirulent. Currently, 98 antigenically distinct capsule types (serotypes) have been identified, which vary in virulence. O-acetylation, a subtle capsular modification, contributes to pneumococcal capsular diversity and modulates capsular physicochemical properties and interaction with innate or vaccine immunity. Replacement serotypes (and future vaccine types) 33F and 15B have O-acetylated capsules due to membrane-bound O-acetyltransferases (MOATs). We hypothesize that future …

The Role Of Cognitive Reserve In Recovery From Traumatic Brain Injury, Kayla Steward

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Objective: To examine whether cognitive reserve (CR) attenuates the initial impact of TBI on cognitive performance (passive model) and results in faster cognitive recovery rates in the first year post-injury (active model), and whether the advantage of CR differs based on the severity of TBI. Setting: Inpatient/outpatient clinics at academic medical center. Participants: Adults with mild TBI (mTBI; n=28), complicated mild TBI (cmTBI; n=24), and moderate-to-severe TBI (msevTBI; n=57), and demographically-matched controls (n=66). Design: Retrospective; longitudinal cohort assessed at 1-, 6-, and 12-months post-injury. Main Measures: Outcomes were 3 cognitive domains: processing speed/executive function, verbal fluency, and memory. Premorbid IQ, …

An Investigation Of The Neurobiological Heterogeneity In Autism, Adhd, And Typical Development, Melissa Thye

All ETDs from UAB

Standard fMRI studies of healthy as well as clinical populations rely heavily on group-level averages to draw inferences about brain and behavior. This presumes neural and behavioral homogeneity within diagnostic groups resulting in group-level models which may not capture individual variability. This problem is especially relevant for studies of neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) which clinically present with widespread individual differences. The prevalence of comorbidity between these disorders is roughly 28% highlighting the possibility that there may be shared behavioral and neural markers which cut across the diagnostic boundaries delineating the …

Familial Support And Mental Health Service Use: Differences Among First- And Second-Generation Asian American And Latino Older Adults, Jessica Lynn Valles

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While several studies have shown that US-born Asian Americans and Latinos are more likely to use mental health services than their foreign-born counterparts, the effects of generation status and familial support is unclear. Furthermore, little is known about these associations and how they affect older adults. According to the Socioemotional Selectivity Theory (SST), as adults begin transition into advanced age, they begin to withdraw from broader social networks to focus on more intimate relations, such as those with children. In applying modernization theory to the family and aging, this theory would suggest that the status of older adults in families …

Acute And Chronic Regulation Of Skeletal Muscle Mitochondrial Function, Jonathan Lund Warren

All ETDs from UAB

Obesity and type 2 diabetes (T2D) represent a growing global burden on healthcare and financial resources. One hypothesis for the onset and exacerbation of these diseases is related to the role of mitochondria as the end users of products of the metabolism of the nutrients we consume and in mediating the oxidative state of the body through the production of reactive oxygen species (ROS). In order to meet the demands of a metabolic challenge and prevent excessive ROS production, there appear to be adaptations to mitochondrial physiology and morphology that can occur and we hypothesize that the ability of the …

Viscosity And Morphology Modification Of Length Sorted Single Walled Carbon Nanotubes In Pib Matrices, Hanxiao Huang

All ETDs from UAB

ABSTRACT In this work, Single Walled Carbon Nanotubes (SWNT) were separated by length and chirality using an ultracentrifuge technique. The influence of length-separation on the composites’ viscosity and crystallinity behavior was studied. We found that the compo-sites’ viscosity does not increase monotonously with weight fractions. Specifically, in rel-atively small nanotube weight fractions, the dynamic viscosity of the composites was found to be smaller than that of the pure Polyisotublyene (PIB) matrix. The dimension of nanotube bundles and polymer radius of gyration were compared to further study the mechanism of such a viscosity change. It was observed that nanotubes with shorter …

Alternative Methodological Approaches For Quantifying Dental Caries And Non-Water Beverage Consumptions For The Improvement Of Caries Risk Analyses In Children, Kelsey Harris Jordan

All ETDs from UAB

Researchers assume caries progress constantly, all crowned/extracted tooth surfaces are carious, and non-water beverage consumption (NWBC) habits are similar by relying on increments, dmfs scoring, and consumption frequencies, respectively. These assumptions are likely inaccurate. The purpose of this research was to evaluate and modify the use of 1) longitudinal caries disease assessment, 2) the dmfs score and 3) NWBC variables to more accurately estimate disease and identify risk factors. To investigate, young (8-18 months at baseline), healthy, poor, rural, African American, Alabamian children were observed annually for five years. Three calibrated dentists performed oral examinations (without radiographs), calculating the number …

Bioactive Materials: Ion Release, Flexural Strength, Secondary Caries Depth And Elemental Analysis Of Surrounding Tooth Structure, Prajakta Shreeram Kulkarni

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ABSTRACT Objectives: Bioactive materials release calcium, phosphate, and fluoride which may increase tooth remineralization. But limited data is available demonstrating the superiority of bioactive or ion releasing materials compared to fluoride or no ion releasing materials. The aims of the present study are to measure and compare the calcium, fluoride, and phosphate ion release at different pH, flexural strength and caries protecting ability of the materials including the ion uptake of surrounding tooth structure. Methods: Activa, Cention N, Fuji LC II and Filtek Supreme Ultra were the restorative materials tested. Firstly, the fluoride and calcium release of these materials was …

Fpga Implementation And Study Of Hardware Trojan In A Closed Loop Control System, Ranveer Kumar

All ETDs from UAB

A closed-loop system is a primary technology used to automate our critical infrastructure and major industries to improve their efficiency. Their dependability is challenged by probable vulnerabilities in the core computing system. These vulnerabilities can appear on both front (software) and back (hardware) ends of the computing system. While the software vulnerabilities are well researched and documented, the hardware ones are normally overlooked. However, with hardware-inclusive technological evolutions like Cyber-Physical Systems and Internet-of-Things, hardware vulnerabilities should be addressed appropriately. In this work, we present a study of one such vulnerability, called hardware Trojan (HT), on a closed-loop control system. Since …

The Role Of Klotho In Adult Neurogenesis, Ann Laszczyk

All ETDs from UAB

Klotho is an anti-aging protein that when upregulated, extends lifespan and enhances cognition. Klotho knockout mice age prematurely and die by ~8 weeks of life after developing cognitive impairment. Klotho function outside of the brain is well established but the protein’s action within the brain remains unknown. As klotho regulates peripheral stem cell populations, I sought to determine whether klotho contributes to cognition through a role in the maintenance of the adult hippocampal neurogenic niche. I examined adult mouse neurogenesis using global klotho-deficiency or global klotho overexpression models. Klotho knockout brains show reduced progenitor proliferation and granule cell production while …

Polymeric Stimuli-Sensitive Self-Assembled Micro- And Nano-Particles For Controlled Drug Delivery, Fei Liu

All ETDs from UAB

The research presented in this thesis is focused on the design and development of stimuli-responsive polymeric particles for drug delivery, including tannic acid-based layer-by-layer capsules with pH- and ionic strength-dependent permeability as well as size- and structure-tunable poly-(N-vinylcaprolactam)-based temperature-responsive polymersomes and micelles. Polymer-based particles play essential roles in controlled drug delivery due to their tunable sizes and nanostructures, and can be further advanced through functionalization, allowing pH-, ionic strength- and temperature-sensitivities to alter the therapeutics’ pharmacokinetics and bio-distribution. Two typical pathways for engineering polymeric drug delivery vehicles are introduced in this thesis, layer-by-layer self-assembly at inter-faces and self-assembly from block …

Molecular And Biochemical Characterization Of Cellular Stress Sensing Proteins Gcn2 And Ire1 In Arabidopsis Thaliana Immune Responses, Xiaoyu Liu

All ETDs from UAB

Plants are capable of recognizing conserved molecular structures from pathogens and precisely regulates gene expression to establish effective and efficient immune responses. Transcriptional regulation has been extensively characterized in plant immunity, while relatively less is understood on the translational level. Moreover, switching cellular energy from growth- to defense-related activity may result in the buildup of misfolded or unfolded proteins within the endoplasmic reticulum (ER), and activating the unfolded protein response (UPR) is critical for restoringllular homeostasis. My dissertation is set out to understand the function of translational regulatory mechanism and UPR in plant immune responses. As a key transcriptional regulator …

Intraocular Pressure Measurement In Eye By Using Disposable Solid State Pressure Sensor, Anvesh Loka Loka

All ETDs from UAB

There are many eye infections and eye diseases like Diabetic Retinopathy, Glaucoma, Age-related Macular Degeneration, Cataract, etc., which cause eye blindness. Glaucoma is one of the major eye diseases that can cause complete blindness. According to National Eye Institute (NIH), there are 2.72 million people are suffering from Glaucoma in the U.S. The primary cause for Glaucoma is higher Intraocular Pressure (IOP), so detecting IOP in the early stages is a vital aspect in the assessment of patients at hazard from glaucoma. The instrument used to measure IOP is called Tonometer and usually used for clinical purposes. However, some part …

Circulating Mirnas And Human Insulin Resistance, Elizabeth Ma

All ETDs from UAB

Insulin resistance (IR) is central to the pathophysiology of Type 2 diabetes (T2DM), and is a risk factor for cardiovascular disease. The mechanisms behind IR are not clear, but microRNA (miR; short, non-coding RNA strands that base-pair with mRNA to modify gene expression) have garnered interest as potential contributors. miRs have recently been shown to be detectable in the circulation, and can be taken up and regulate target genes within recipient cells. Our primary objective was to identify circulating miRs (c-miRs) that play a role in regulating systemic metabolism and participate in the pathophysiology of IR and cardiometabolic disease. Three …

A Multi-Modal Approach To Sulforaphane-Mediated Chemoprevention Using The Epigenetic Network, Samantha Martin

All ETDs from UAB

Colon cancer is the third most common diagnosed cancer in both women and men in the United States. It is reported that dietary factors are responsible for 70-90% of colon cancer cases. While some investigators have observed a direct correlation in high fat diets and cancer initiation, other studies have observed opposite effects mediated by fruit and vegetable consumption. Recently, studies have highlighted the importance of Epigenetics as it modifies gene expression without changing the DNA sequence. Notably, several nutritive compounds have been reported to alter epigenetic profiles in many cancer forms. SFN, an isothiocyanate found in cruciferous vegetables such …

Formaldehyde Emissions From Laminate Flooring, Stephanie Latisha Marzette

All ETDs from UAB

In recent years, several incidents have caused public concern about the levels of formaldehyde present in residential homes. It is one of the most prevalent and regularly detected pollutants in an indoor environment. This is due to the presence of formalde-hyde in many common products, such as household cleaners and paints, as well as build-ing materials. Formaldehyde exposure can lead to sore throat, coughing, eye and airway irritation, and increased occurrences of asthma symptoms. Due to the public health con-cerns, this research was designed to investigate the distinctive nature of formaldehyde emissions from laminate flooring and test the reliability of …

The Ecology And Evolution Of Invertebrate-Cyanobacterial Symbioses, Kenan Matterson

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Intimate partnerships between marine invertebrates and microbial symbionts have garnered renewed interest, as advances in next generation sequencing have revealed substantial microbial diversity in tropical sponges and ascidians. These datasets have generated a suite of new questions concerning the evolutionary and ecological mechanisms that structure these microbial partnerships. The research presented herein addresses such questions by integrating in situ ecological manipulations with modern molecular techniques to characterize the interactions between the host invertebrate and microbiome and its potential role in structuring marine communities. Implementing in situ manipulative shading experiments alongside replicated bacterial clone libraries, I documented significant variation in host …

The Association Between Cancer And Risk Of Sepsis Among Whites And Blacks In The Regards Cohort, Justin Xavier Moore

All ETDs from UAB

Cancer is the second leading cause of morbidity and death in the United States corresponding to more than 1.7 million incident cases and responsible for more than 550,000 deaths annually. In addition, hospitalized cancer patients are nearly 10 times more likely to develop sepsis when compared to participants with no cancer history. As treatments and therapies for cancer continue to improve, the average 5-year survival is approaching 70% overall among the US population; however, to date there is very limited research that has examined the association between patients with a history of cancer and future risk of sepsis among a …

Alterations In Ubc9 Substrate Specificity Affect The Cellular Response To Dna Damage, Joshua Enyeribe Onuiri

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This dissertation seeks to uncover the impact of a post-translational modification, the small ubiquitin-related modifier (SUMO), on the cell response to DNA damage. Covalent modification of cellular proteins by SUMO occurs through an enzymatic cascade involving an E1 activating enzyme, an E2 conjugating enzyme, and a ligase (E3). Eukaryotic cells possess a single E1 and a single E2 for SUMO conjugation. The E2 for SUMO, Ubc9, is able to recognize and modify substrates on its own, although substrate recognition and modification are enhanced in the presence of the E3. Two independent genetic screens carried out in the budding yeast Saccharomyces …

The Role Of Macrophages In Pressure-Overload Induced Cardiac Remodeling, Bindiya Dinesh Patel

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Cardiac pressure-overload is a state of increased hemodynamic load and is initially characterized by concentric left ventricular (LV) hypertrophy, but can transition to eccentric hypertrophy and adverse LV remodeling leading to heart failure (HF). Cardiac remodeling during pressure-overload is accompanied by dysregulated collagen deposition, cardiomyocyte hypertrophy, and increased inflammatory signaling. Both clinical and preclinical studies have documented increased expression of inflammatory cytokines and leukocyte infiltration in the pressure-overloaded heart, indicating inflammatory mechanisms are active during cardiac remodeling. Despite the well-known link between leukocyte infiltration and exacerbated tissue injury, the role of innate immune cells, particularly monocytes, macrophages and dendritic cells, …

High Achievers Awards 2017 - Celebrating The Leaders Of Tomorrow, Aga Khan University Examination Board

The Aga Khan University Examination Board Archives

• About the Aga Khan University Examination Board
• Director’s Message
• Secondary School Certificate 201 7 High Achievers
• Secondary School Certificate 20 1 7 Results
• SSC Group and Subject-wise High Achievers
• Higher Secondary School Certificate 20 1 7 High Achievers
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• HSSC Group and Subject-wise High Achievers
• Bridge to a Better Future
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Investigating Phenotypic Severity Associated With Sister Chromatid Cohesion Defects In Human Disease, Stefanie Marie Percival

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INVESTIGATING PHENOTYPIC SEVERITY ASSOCIATED WITH SISTER CHROMATID COHESION DEFECTS IN HUMAN DISEASE STEFANIE M. PERCIVAL GRADUATE BIOMEDICAL SCIENCES ABSTRACT Sister chromatid cohesion (SCC) is a process that utilizes a proteinaceous ring, cohesin, for accurate chromosome segregation. An essential process in S phase termed cohesion establishment is necessary to stabilize cohesin rings around sister chromatids. Mutations in establishment of cohesion homolog 2 (ESCO2), a protein essential for cohesion establishment, cause a developmental disorder called Roberts Syndrome (RBS). Cytogenetic analysis in patients reveals heterochromatic repulsion (HR), a centromeric puffing, indicative of cohesion defects. The severity of phenotypes varies from preterm lethal to …