Digital Commons Network^™

Glial Fibrillary Acidic Protein And Gliosis: Is Gfap More Than A Marker?, Heather Renee Minkel

All ETDs from UAB

Alexander Disease (AxD) is a `gliopathy' caused by toxic, dominant gain-of-function mutations in the gene encoding glial fibrillary acidic protein (GFAP). Two distinct types of AxD exist. Type I AxD affected individuals develop cerebral symptoms by four years of age and generally suffer from macrocephaly, seizures, and physical and mental delays. As detection and diagnosis have improved, a larger portion, now about half of all AxD patients diagnosed, have onset >4 years and brainstem/spinal cord involvement. These type II AxD patients typically experience ataxia, palatal myoclonus, dysphagia and dysphonia. To date no study has examined a mechanistic link between the …

The Role Of Ih In 4-Aminopyridine Induced Epileptiform Activity, Steven Patrick Palladino

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significantly different from sex ratios of control groups produced at constant incubation

3-Dimensional Comparison Of Hard And Soft Tissue Asymmetry In, Philip H. Pan

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Class III malocclusions are particularly prevalent in the Asian population. Threedimensional imaging has improved the ability to portray the three-dimensional characteristics of soft tissue face and underlying skeletal hard tissue. While soft tissue reflects the underlying hard tissue structures, soft tissue may either provide a compensation for hard tissue asymmetry or potentially exacerbate the asymmetry. The current study is novel in that the hard tissue and soft tissue asymmetries are both analyzed relative to the same reference point, and using 3D imaging, we have attempted to elucidate a compensation tendency between the hard and soft tissues. The sample was comprised …

Altered Dna Methylation Contributes To Temporal Lobe Epilepsy And Associated Memory Deficits, Robert Ryley Parrish

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Status epilepticus (SE) triggers molecular mechanisms that underlie the cellular and network changes that occur during the development of temporal lobe epilepsy (TLE). Additionally, gene expression alterations occur during epileptogenesis and in the epileptic brain that contribute to the persistence of the phenotype. However, the underlying epigenetic mechanisms responsible for aberrant gene expression that occur with epilepsy require further investigation. This dissertation investigates how DNA methylation in the hippocampus affects epilepsy and contributes to the memory impairments associated with the disorder. We found that DNA methylation was altered in a hippocampal subregion specific manner in the epileptic brain, displaying altered …

Bio-Hybrid Tubular Electrospun Scaffold For Vascular Tissue Engineering Application, Harsh Narendrakumar Patel

All ETDs from UAB

Atherosclerosis is an asymmetric thickening of the intima (innermost layer) of the artery due to plaque (a combination of lipids, debris, connective tissue elements and cells) build up causing the artery to become narrower and stiffer, resulting in a major hemodynamic disturbance[1, 2]. When atherosclerosis affects coronary arteries and prevents blood flow to the heart muscles posing a threat of, or a actual myocardial infarction, that condition is identified as coronary artery disease (CAD). To treat severely blocked coronary arteries,coronary artery bypass grafts (CABG) have became the gold standard for when angioplasty and stent placement has failed to unclog the …

Akhuwat Issue No. 92, Aga Khan University

AKHUWAT Newsletters

• AKU Pakistan Convocation Held
• University Awards of Distinction - Convocation 2013
• Post Graduate Medical Education-Convocation 2013
• University’s Expansion into Liberal Arts
• Awards Night 2013
• Face to Face with Dr Mughis Sherani Associate Dean PGME
• JCIA Library of Measures -Dashboard
• Service Excellence 2013
• New teleconsultation link connects Gilgit
• Medical Centre and AKU Karachi
• Happenings and Achievements

Biology, Ecology, And Conservation Of Hatchling And Post-Hatchling Diamondback Terrapin (Malaclemys Terrapin Pileata), Tandy Dolin Petrov

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The diamondback terrapin has been considered a keystone species along its range in the coastal, brackish estuaries bordering the Atlantic Coast and Gulf of Mexico. Historically, diamondback terrapin populations have been numerous; however, in Alabama; the population has dramatically declined over the past century due to a variety of threats. The threats in Alabama include predation by raccoons, incidental drowning in crab traps, as well as road mitigated mortality. Because of these threats, collaboration efforts between UAB, USA, DISL, and the Alabama Department of Conservation and Natural Resources, a head-start program has been initiated to mitigate the predation of hatchlings. …

The Impact Of Interleukin-21 On Intestinal Inflammation During Health And Disease, Catherine Poholek

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The intestinal environment is extremely complex due to the dynamic interactions between host cells and luminal contents. The immune cells located in the intestine are responsible for sensing and responding to intestinal pathogens as well as maintaining tolerance to non-pathogenic organisms and environmental antigens. Disruption in this delicate balance results in chronic intestinal inflammation. Particularly important to the maintenance of intestinal homeostasis are CD4 T cells and innate lymphoid cells (ILCs). These cells produce cytokines in an antigen-specific and antigen-independent manner, respectively, and have analogous subsets with similar cytokine profiles. CD4 T cells and ILCs expressing ROR gamma t (Th17 …

Investigation Of Lateral Incisor Crown Root Angulation And Impacted Maxillary Canines, Samuel Philip Purnell

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Objective: The primary aim of this study was to determine if there is a difference in the mesiodistal crown-root angulation of maxillary lateral incisors between patients with impacted maxillary canines and a control population. Secondary aim 1 compared the same angle measured on panoramic radiographs to determine if a difference existed between the CBCT measurement and the panoramic radiograph measurement. Secondary aim 2 looked to determine if there was a correlation between maxillary lateral incisor tooth width and the mesiodistal crown-root angulation. Materials and Methods: CBCT's were reformatted so that the mesiodistal crown-root angulation of maxillary lateral incisors could be …

Power Issues And Internal Pilot Designs For Cluster-Randomized Trials With Unequal Cluster Sizes, Ashutosh Ranjan

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Cluster-randomized trials that randomize groups of individuals, instead of individuals themselves, run the risk of being underpowered when they are designed assuming equal cluster sizes but end up recruiting unequal clusters. The loss in power of the trial is directly related to the amount of variation present among the cluster sizes. To overcome the loss in power, researchers often employ a weighted analysis of the cluster means. Different weighting procedures have been developed that appear to maintain the power of the trial but there have been fewer attempts to describe the impact of different weights on the type I error …

Molecular And Functional Interaction Of Runx2 And Sp7 For Development Of The Osteoblast Phenotype, Harunur Rashid

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Runx2 and Sp7 transcription factors are essential for skeletogenesis. Deletion of either gene in mice results in failure of bone tissue development. However, underlying mechanisms responsible for a surprisingly similar phenotype by two distinctly unrelated proteins remain unknown. Sp7 is a Runx2 downstream target gene and is not expressed in Runx2 null mice. Thus, the Runx2 null model represents a compound phenotype of loss of both proteins. In contrast, normal levels of Runx2 mRNA are noted in Sp7 null mice. The failure of Runx2 to promote bone formation in Sp7 null mice suggests that Sp7 is required for Runx2 function …

Epithelial Sodium Channel Purification And X-Ray Crystallographic Studies, Bharat G. Reddy

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Epithelial sodium channels (ENaC) play a critical role in maintaining Na+ homeostasis in various tissues throughout our body. Understanding of ENaC structure is mediated from studies of the homologous acid sensing ion channel 1 (ASIC1). However, ENaC has sev-eral notable functional differences compared to ASIC1, thereby providing justification for determination of its three-dimensional structure. Unfortunately, this goal remains elu-sive due to several experimental challenges. Of the subunits that comprise a physiological hetero-trimeric ENaC (α, ß, and γ), the α-subunit alone is of significant interest. αENaC is unique in that it is capable of forming a homo-trimeric structure capable of conducting …

Coping With Chronic Illness: Temporal Patterns Of Spiritual Coping And Adjustment Among Adolescents With Chronic Illness, Nina Cole Reynolds

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Issues of spirituality rise to the forefront for youth facing serious health conditions. Positive and negative spiritual coping strategies have been linked with better or worse psychological adjustment, respectively, in pediatric patients. With expansion of research in this area, an empirical synthesis and examination of the prospective relationships between spiritual coping and mental- and physical-health is needed. Accordingly, the first manuscript reports on meta-analytic review of the cross-sectional studies of spiritual coping, health, and psychosocial adjustment. Results revealed that greater use of negative spiritual coping is related to more internalizing problems and poorer quality of life across multiple pediatric illness …

Neuropathology Of Dopamine Systems In Schizophrenia: Regional Dopamine Pathologies In The Substantia Nigra/Ventral Tegmental Area Complex, Matthew Warner Rice

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Dopaminergic neurotransmission anomalies are a well-established aspect of schizophrenia, a devastating mental disorder that affects approximately 1% of the world population. The substantia nigra/ventral tegmental area (SN/VTA), which extends from diencephalic to mesencephalic territories, provides the largest dopaminergic input to the brain. The SN/VTA contains subpopulations of dopaminergic neurons that project preferentially through different pathways, providing dopamine input to brain regions where dopaminergic anomalies have been reported in schizophrenia. We hypothesized that anomalies in the synthesis of tyrosine hydroxylase (TH), the rate-limiting enzyme for the production of dopamine, could contribute to the dopaminergic anomalies observed in this disorder. We first …

White Matter Integrity In Adults With Hemiparetic Multiple Sclerosis Given Constraint-Induced Movement Therapy, Tyler Rickards

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In adults with chronic stroke and children with cerebral palsy, structural changes in grey matter correlate with clinical improvements due to an efficacious upper-extremity (UE) rehabilitation therapy, Constraint-Induced Movement (CI) Therapy. Changes in white matter following CI therapy have not been observed, but damage to white matter tracts has not been found to decrease motor improvement resulting from this treatment. The objectives of this project were to: 1) evaluate the efficacy of CI therapy compared to complementary and alternative medicine (CAM) treatments on improving impaired UE function in participants with the progressive form of multiple sclerosis (MS), 2) investigate whether …

A Mixed Methods Study Of Health Literacy And Its Role In Hpv Vaccine Uptake Among College Students, Michelle Sharonda Williams

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Health literacy includes the ability to understand and process written and spoken health information, and numbers and calculations related to health information. Low health literacy is associated with negative health outcomes, and poor patient-provider communication. In order to advance health literacy research, there is a need to assess health literacy comprehensively and to develop an understanding of how health literacy impacts people at various stages of their lives. A sequential explanatory mixed methods study was conducted to assess college students' health literacy. During the quantitative phase, the Short Test of Functional Health Literacy in Adults (S-TOFHLA), the Newest Vital Sign …

Exploring The Impact Of Youth Participation In Community Service On Health Behaviors, Kymber Nigel Williams

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hydric environment on sex ratios using the red-eared slider, Trachemys scripta, as a

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 …

Fifth Graders' Understanding Of Fractions On The Number Line: A Standard Introduced In The Common Core State Standardards For Third Graders, Taajah Felder Witherspoon

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This was a case-study design of the various ways students represented fractions on number lines. Students responded to task-based interview questions based on identifying fractions as a number on the number line as well as equivalency and problem solving. The tasks were administered individually to 26 fifth-grade students over a 15-minute time frame in their respective schools. The two groups of 10-year-old students answered most questions in written form on pencil and paper. The students were often asked to explain how they arrived at an answer. Student performance was highest when instructed to plot ½ on a number line of …

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.

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 …

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 …

Gut Microbiome And Its Role In Obesity And Aging In C57bl/6j Mice, Yongbin Yang

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

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 …

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 …

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 …

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

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 …

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 …

Studies Of The Effect Of Nicotine On Color Vision In Color Deficient Humans, Warren Gwynn

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Previous research showed that oral nicotine use in non-smoking color normal individuals significantly improved color discrimination scores on the F-M 100 and both white and red increment thresholds of the Red Test. Our research sought to determine if similar results could be found when oral nicotine was administered to color deficient individuals. Ten color deficient individuals were first screened with both the HRR and Nagel Anomaloscope. Next, the F-M 100 and Red Test were performed before and after chewing nicotine gum (four mg). Subjects were introduced to testing procedures in one visit; a second visit, at least 24 hours later, …