Medicine and Health Sciences Commons^™

The Effect Of Hearing Impairment On Word Processing Of Infant- And Adult-Directed Speech, Velma Sue Robertson

Theses and Dissertations (ETD)

Objective. Little is known about how children with hearing loss (CHL) process words. The Emergent Coalition Model (ECM) of early word learning proposes that multiple cues (e.g., perceptual, social, linguistic) are used to facilitate word learning. Because hearing loss influences speech perception, different word learning patterns may emerge in CHL relative to children with normal hearing (CNH). One perceptual cue used by young children to access word learning is infant-directed-speech (IDS). Specifically, twenty-one month-olds can learn words in IDS but not in adult directed speech (ADS); however, by 27 months children can learn words in ADS. Currently, it is unknown …

Synthesis And Characterization Of Methacrylated Hyaluronan-Based Hydrogels For Tissue Engineering, Keegan Bradley Compton

Theses and Dissertations (ETD)

Polymers have revolutionized the field of tissue engineering due to the countless possibilities of scaffolds that can be constructed from such a material. Through conjugation of other functional groups onto a polymer backbone, the mechanical properties of polymers can be controlled and has the ability to span a wide range of strengths, allowing for application in multiple tissue environments. One such polymer, hyaluronic acid (HA), is a natural polysaccharide found most abundantly in the extracellular matrix (ECM) of connective tissues with structural, lubricating, and wound healing functions in the human body; for this reason, HA has great potential for utilization …

Mapping The Spatial And Temporal Dynamics Of Sensorimotor Integration During The Perception And Performance Of Wallowing, Megan E. Cuellar

Theses and Dissertations (ETD)

Similar to other complex sequences of muscle activity, swallowing relies heavily upon ‘sensorimotor integration.’ It is well known that the premotor cortex and primary sensorimotor cortices provide critical sensorimotor contributions that help control the strength and timing of swallowing muscle effectors. However, the temporal dynamics of sensorimotor integration remains unclear, even when performed normally without neurological compromise. Recent advances in EEG analysis blind source separation techniques via independent component analysis offer a novel and exciting opportunity to measure cortical sensorimotor activity in realtime during swallowing, concurrently with muscle activity during swallow initiation. In the current study, mu components were identified, …

An Examination Of Factors That Influence Health Behaviors Among Low Income African American Women With Type 2 Diabetes In Memphis, Tn: A Qualitative Inquiry Using Mixed Methods, Adole Muruako

Theses and Dissertations (ETD)

Obesity and type 2 diabetes are increasing health concerns in the United States, particularly among women and minorities. Generally, research has highlighted the health disparities that exist among African American women, especially as these disparities relate to obesity and type 2 diabetes. In Memphis, TN, the ZIP codes of 38106 and 38109 have the highest rates of diabetes hospitalizations in the city. Further, African American women in Memphis, TN have been identified as being most vulnerable to experiencing a potentially avoidable hospitalization due to chronic disease. The purpose of study was to identify factors that may impact African American overweight/obese …

Development Of A Mobility-Enabling Spinal Orthosis And Methods For Evaluating And Developing Spinal Orthoses On A Robotic Platform, John C. Simmons

Theses and Dissertations (ETD)

Introduction: A number of decompressing spinal braces (typically pneumatic) have been introduced that attempt to mechanically emulate the “buoyancy” of water therapy by offloading upper torso load to the pelvic girdle as a treatment for lower back pain (LBP). Unfortunately, the beneficial upward force they apply on the upper torso typically makes it difficult or impossible for the patient to bend. For those cases where stabilization is not indicated, this undesirably hinders therapeutic exercise, independent living, and return to work. The cosmetic stigma of wearing an external pneumatic assembly large enough to provide significant offloading may provide additional disincentives to …

Downregulation Of Prdm16 Is Critical For Hoxb4-Mediated Benign Hsc Expansion In Vivo, Hui Yu

Theses and Dissertations (ETD)

Overexpression of HOXB4 in hematopoietic stem cells (HSCs) leads to increased self-renewal without causing hematopoietic malignancies in transplanted mice. The molecular basis of HOXB4-mediated benign HSC expansion in vivo is not well understood. To gain further insight into the molecular events underlying HOXB4-mediated HSC expansion, we analyzed gene expression changes at multiple time points in Lin-Sca1+c-kit+ (LSK) cells from mice transplanted with bone marrow (BM) cells transduced with a MSCV-HOXB4-ires-YFP vector. A distinct HOXB4 transcriptional program was reproducibly induced and stabilized by 12 weeks after transplant. Dynamic expression changes were observed in genes critical for HSC self- renewal as well …

Hemoglobin A1c And The Diagnosis Of Diabetes And Prediabetes In Children And Adolescents, Jennifer Mcguire Hitt

Theses and Dissertations (ETD)

Although the American Diabetes Association (ADA) adopted the use of the glycated hemoglobin (A1C) test as a method of diabetes and prediabetes diagnosis, the ADA has not developed firm guidelines concerning the use of the A1C test in children and adolescents, as research has not validated thresholds in this group. Diabetes and prediabetes are diseases influenced by multiple factors, including race and ethnicity, age, vitamin D deficiency, and body mass index (BMI). The purpose of this study was to determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the A1C test compared to the gold …

Effect Of Nedd4 Haploinsufficiency On Insulin Sensitivity, Adiposity And Neuronal Behaviors, Jingjing Li

Theses and Dissertations (ETD)

The neural precursor cell expressed developmentally down-regulated gene 4 (NEDD4) is a HECT-type E3 ubiquitin ligase that has received broad attention in recent years. Many of its reported substrates are active players in metabolism, implying a potential role of NEDD4 itself in metabolic regulation. Since homozygous Nedd4 deletion leads to embryonic or perinatal lethality, we investigated the function of NEDD4 in metabolic regulation in vivo, using Nedd4- haploinsufficient mice in a high fat diet-induced obesity (HFDIO) model.

Our studies show that Nedd4-haploinsufficient mice fed a normal diet (ND) exhibited decreased body weight in both genders and proportionally reduced tissue mass …

Novel Insights Into The Role Of The Smoothened Cysteine Rich Domain In Hedgehog Signalling, Rajashree Rana

Theses and Dissertations (ETD)

The Hedgehog (Hh) signal transduction pathway functions as one of the key developmental pathways and deranged Hh signalling is associated with numerous cancer and tumor conditions. The Smoothened (Smo) G protein coupled receptor (GPCR) functions as the signal transducer of the Hh pathway and is the most attractive drug target of the pathway. The structure of the Smo receptor includes seven membrane spanning domains, extracellular and intracellular loops connecting the membranous domains and the extracellular cysteine rich domain (CRD). The extracellular CRD of the Smo receptor is homologous to the Frizzled (FzD) CRD. The FzD CRD interacts with the physiological …

The Role Of Mcl-1 In The Heart: Gateway From Life To Death, Xi Wang

Theses and Dissertations (ETD)

MCL-1 is an essential BCL-2 family member that promotes the survival of multiple cellular lineages, but its role in cardiac muscle has remained unclear. Here, we have demonstrated that cardiac-specific ablation of Mcl-1 results in a rapidly fatal, dilated cardiomyopathy preceded by loss of myofibrils and cardiac contractility, abnormal mitochondria ultrastructure, defective mitochondrial respiration, and impaired autophagy. Genetic ablation of both pro-apoptotic effectors (Bax and Bak) could largely rescue the lethality and impaired cardiac function induced by Mcl-1 deletion. However, Mcl-1-, Bax-, and Bak-deficient hearts still revealed mitochondrial ultrastructural abnormalities and displayed deficient mitochondrial respiration, and are hypersensitive to chronic …

Group Iv Cytosolic Phospholipase A2Α Is Critical For The Development Of Angiotensin Ii-Induced Hypertension And Associated Pathogenesis, Nayaab Shehbaz Khan

Theses and Dissertations (ETD)

Angiotensin II (Ang II) activates cytosolic phospholipase A2α and releases arachidonic acid (AA) from tissue phospholipids. AA metabolites mediate or modulate one or more renocardiovascular effects of this peptide and have been implicated in hypertension. Since AA release is the rate limiting step in eicosanoid production, it is possible that cPLA2α might play a central role in the development of Ang II-induced hypertension. To test this hypothesis, we investigated the effect of Ang II infusion for 13 days by micro-osmotic pumps (700 ng/kg/min), on systolic blood pressure and associated pathophysiological changes in wild type (cPLA2α+/+) and cPLA2α-/- mice. Ang II …

Mrp4-Dependent Regulation Of Fibroblast Migration, Chandrima Sinha

Theses and Dissertations (ETD)

Roles of cyclic nucleotides and cyclic nucleotide-dependent signaling molecules in regulating several signaling pathways including cell migration have long been known. However, the new and revolutionary concept is that it is not just the absence or presence of cyclic nucleotides, but a highly coordinated balance between these molecules regulates cell migration. Multi-drug resistance protein 4 (MRP4), is a member of the large family of ATP binding cassette (ABC) transporter proteins, that localizes to the plasma membrane and functions as a nucleotide efflux transporter and thus plays a pivotal role in the regulation of intracellular cyclic nucleotide dynamics. In our study …

Autoimmune Susceptibility Imposed By Public Tcrβ Chains, Yunqian Zhao

Theses and Dissertations (ETD)

The major histocompatibility complex (MHC) is the strongest genetic risk factor for autoimmunity. It acts together with a corresponding TCR repertoire, yet, considering the extent of the repertoire's diversity, how this imposes disease susceptibility on a population is not well understood. We address the hypothesis that shared or public TCR, those present in most individuals, modulate autoimmune risk. High resolution analyses of autoimmune encephalomyelitis-associated T-cell receptor β chain (TCRβ) showed preferential utilization of public TCR sequences, implicating them in pathogenesis. Disease-associated public TCRβ, when transgenically expressed in association with endogenously rearranged T-cell receptor α chain (TCRα), could further endow unprimed …

Genetic And Chemical Dissection Of Bloodbrain Barrier Development In Zebrafish, Robyn Anne Umans

Theses and Dissertations (ETD)

The blood-brain barrier (BBB) maintains a homeostatic environment as well as prohibits the entrance of xenobiotics into the brain. Because of these qualities, drug delivery is a fundamental challenge for the treatment of many diseases of the central nervous system (CNS). Along with limiting the access of therapeutics into the brain, the BBB is also impaired in CNS pathologies. Understanding the molecular cues that are essential for healthy BBB development and integrity may reveal targets for drug delivery leading to decreased progression or possible treatment of many detrimental CNS diseases. While the central features of the BBB have been accepted, …

Computer-Aided Drug Design And Discovery, Screening And Synthesis Of Small Molecule Inhibitors Of Nucleoside Transporters, Hilaire Colleen Playa

Theses and Dissertations (ETD)

Using prior biological data, pharmacophore models were made for hCNT1, hCNT3, hENT1, and hENT4. The hCNT3 and hCNT1 pharmacophore were used to select compounds for biological testing. The NBMPR analogue and dipyridamole analogue hENT1 pharmacophores were compared to each other and to a combined pharmacophore for hENT1. The dipyridamole analogue pharmacophore better predicted non-nucleoside small molecule inhibitors, and as such appears to be the better tool for aiding in the design of new small molecule inhibitors. The hCNT3 pharmacophore failed to select active compounds and as such must be redesigned. The hCNT1 pharmacophore succeeded in identifying two moderately active compounds …

Strengths And Weaknesses Of Hybrid Tpr Technology For Obtaining Structural And Mechanistic Insights Into Tpr Proteins, Shanshan Yu

Theses and Dissertations (ETD)

Tetratricopeptide (TPR) repeats are a 34-residue helix-turn-helix motif that when repeated pack into a superhelical structure. TPR domains are frequently found mediating protein-protein interactions, often through a central groove. One protein complex bearing numerous TPR repeats is the Anaphase Promoting Complex (APC). The anaphase-promoting complex (APC) is a multi-subunit complex, which orchestrates mitotic cell cycles. APC is an E3 ligase in the ubiquitin cascade, and directs the 26S proteosome degradation of cell-cycle regulators. Throughout mitotic progression, proteins that are key regulators of the cell cycle are assembled with polyubiquitin chains by APC.

One domain of the human APC is comprised …

Functional And Genetic Analysis Of Choroid Plexus Development In Zebrafish, Hannah Elizabeth Henson

Theses and Dissertations (ETD)

The choroid plexus (CP) is an epithelial based structure localized within the brain ventricles and functions as the blood-cerebrospinal fluid barrier (BCSFB). Under normal conditions, the CP is responsible for generating the cerebrospinal fluid (CSF) and regulating its components. Abnormal CP function has been associated with neurodegenerative diseases, tumor formation in CP epithelia (CPe), and hydrocephalus. Despite the significant role of the CP in these disorders, little research has been done to characterize its functional properties and genetically dissect the pathways involved in normal CP development and disease. For this study, we have utilized zebrafish, (Danio rerio), as a model …

Determination Of The Functional Relationship Between Lumbar Lordosis And Pelvic Tilt, Casey Tyler Hebert

Theses and Dissertations (ETD)

Americans are undergoing spinal fusion surgery (SFS) at an ever increasing rate; in 2008 over 400,000 Americans underwent SFS with a national cost of approximately $33.9 billion. During SFS it is difficult for the surgeon to properly align the spine’s s-shape, as viewed from the patient’s side. Abnormal alignment of the spine then alters the position of the pelvis and hip joints, which may impact the function and hip contact patterns. Several studies have shown that patients with spinal pathology, such as arthritis, often have a coexisting hip pathology or subsequently develop hip pathology, and it is estimated that 18% …

Glioma: A Tale Of Corticosteroids, Thiopurines And Proposed Novel Antiglioma Small Molecules, Amira Ahmed

Theses and Dissertations (ETD)

Glioma is a brain tumor that arises from glial cells or glial progenitor cells, and represents 80% of malignant brain tumor incidence in the United States. Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor malignancy with fewer than 8% of patients with GBM surviving for 3 years. Over the past 10 years, despite improvement in diagnosis and therapies for cancer, the survival rate for high-grade glioma patients remains unchanged. The main focus of this dissertation is to investigate two therapeutic agents that are related to increase tumor resistance or increase secondary tumor incidence, which might play a role …

Racial Disparities In Adherence To Cardiovascular Medications Among The Elderly In Medicare: Three Empirical Essays, Mustafa Hussein Muhammad Hussein

Theses and Dissertations (ETD)

This dissertation sought to explore the relatively understudied area of racial disparities in adherence to cardiovascular medication regimens among the elderly. Black and Hispanic seniors are well documented to have lower rates of adherence to their prescribed cardiovascular medications, relative to their white counterparts. This disproportionately lower adherence places these minority groups at higher risk for worse cardiovascular prognosis and premature cardiovascular death. The Medicare Program, which covers healthcare predominantly for elderly Americans, offers an interesting laboratory to study these disparities and their response to policy changes. Using nationally representative data from the Medical Expenditure Panel Survey on white, black, …

Language Skills, Oral Narrative Production, And Executive Functions Of Children Who Are Deaf Or Hard Of Hearing, Hyejin Park

Theses and Dissertations (ETD)

This study assessed the language skills, oral narrative abilities, and executive functions (EFs) of children who are deaf or hard of hearing (DHH) and normal hearing (NH), and examined the differences between two groups as well as the relationships between oral narrative production and EFs.

Eleven children who are DHH and ten who are NH, between 9 and 11 years of age, participated in the study. All of the children in the DHH group had bilateral hearing losses ranging from moderate through profound, and had no other diagnosed social, emotional or intellectual problems. All had more than 4 years 10 …

Dopaminergic Genetic Contributions To Obesity In Kidney Transplant Recipients, Ashley Grimes Stanfill

Theses and Dissertations (ETD)

Background: Kidney transplant recipients are a population who experience a high likelihood of gaining a significant amount of weight (between 6 and 13 kilograms) during the first year after transplantation. However, not all kidney transplant recipients gain weight. Studies have found little difference in physical activity and nutritional intake among those who do and do not gain weight. Immunosuppressant medications have also not been shown to play a substantive role in post-transplant weight gain. Additionally, although some studies have shown that age, gender, and race can influence weight gain, this information does not fully capture the observed variance. These observations …

Total Knee Arthroplasty Wear Is Caused By Malrotation And Excessive Laxity, Erik Woodard

Theses and Dissertations (ETD)

Total knee arthroplasty is a proven technique which combines specially designed components and surgical processes to treat cartilage degeneration and alleviate pain in arthritic knees. However, this technique is limited by component design and surgical precision. Due to these limitations, knee arthroplasty components will eventually wear out, causing rejection and necessitating the need for a replacement. For this reason, it would be beneficial to experts if the primary causes of this wear could be identified in order to minimize the number of replacements.

This study aims to determine if a correlation exists between instability of a knee joint and the …

Predictors And Mediators Of Long-Term Functional Limitations In The Older Adult Population, Teresa Maria Bell

Theses and Dissertations (ETD)

With nearly 40 million Americans being treated for nonfatal injuries in emergency departments annually, the burden of nonfatal injury in the United States is extensive. The longterm functional consequences of these injuries can be enduring and far-reaching, especially for older adults. Although studies have reported that persistent functional deficits exist after injury, less information is known about long-term recovery patterns and the factors that influence functional outcomes.

The primary aims of this study are to (1) classify differences in long-term, longitudinal changes in functional limitations within the injured population, (2) identify individual characteristics that predict recovery after injury and (3) …

Characterization Of Cre Mouse Models To Target Cns Barriers For Generating Conditional Knockouts Of Abc Transporters, Rachel L. Scheib

Theses and Dissertations (ETD)

The central nervous system (CNS) includes the brain and spinal cord, where both possess a blood to brain and a blood to cerebrospinal fluid (CSF) barrier. The blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) regulate the passage of many molecules to maintain and protect these sensitive organs from harmful xenobiotics (i.e. drugs, pollutants, etc.) or physiologic changes (i.e. glucose, ion, or water composition). These barriers also express ABC transporters, including P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP), which are known to contribute to efflux of endogenous toxins and therapeutics from the CNS. Pgp and BCRP expression and activity are …

Preliminary Study On How Tumor Suppressor Nf2 Inhibits Transcriptional Coactivators Yap/Taz In The Developing Mouse Brain, Yu He

Theses and Dissertations (ETD)

Normal brain development requires precise coordination of neural progenitor proliferation and differentiation, the mechanism of which is not well known. Recently the tumor suppressor neurofibromatosis 2 (Nf2) was shown to regulate the balance of neural progenitor proliferation and differentiation in the developing mouse brain through the Hippo pathway effectors, transcriptional coactivators Yap/Taz. The molecular mechanism of how Nf2 regulates Yap/Taz is not understood. Here I showed that Nf2 regulated the Yap/Taz activity by decreasing the stability of Yap/Taz. The regulation was independent of Yap-S366 phosphorylation, which is required for Yap degradation. I also showed that Nf2 did not regulate Lats1/2 …

Persistant Gata2 Expression Promotes Self-Renewal Of Myeloid Progenitors And Blocks Lymphoid Differentiation., Satish Kumar Nandakumar

Theses and Dissertations (ETD)

The transcription factor GATA2 is highly expressed in hematopoietic stem cells (HSCs) and is downregulated during differentiation. Overexpression of GATA2 is frequently observed in acute myeloid leukemia. In previous studies, enforced expression of GATA2 using a MSCV GATA2 retroviral vector blocked differentiation of HSC and progenitors without inducing leukemia. We hypothesized that a lower dose of GATA2 can relieve the HSC block and eventually transform myeloid progenitors into leukemia stem cells. To test this hypothesis we generated a MSCV GATA2-ERT vector in which nuclear concentration of GATA2 can be regulated by Tamoxifen (TAM). The GATA2-ERT protein was confirmed to leak …

The Mi-2 Homolog Mit1 Actively Positions Nucleosomes Within Heterochromatin To Suppress Transcription, Kevin M. Creamer

Theses and Dissertations (ETD)

Eukaryotic DNA is packaged into the nucleus in complex with proteins that regulate access and utilization of the genetic material. These DNA and protein complexes form a dynamic structure known as chromatin. Nucleosomes are the repeating unit of chromatin, and consist of DNA wrapped around an octamer of histone proteins. Nucleosomes can then be modified and spatially arranged to facilitate processes such as transcription, DNA replication, and repair. A special transcriptionally repressive chromatin structure assembles onto gene-poor, repetitive regions of the genome known as constitutive heterochromatin. Mit1 is the putative chromatin remodeling subunit of the fission yeast Snf2/HDAC repressor complex …

Adenosine Production Is Essential For Closing The Critical Period Of Cortical Plasticity, Rachel A. Chassan

Theses and Dissertations (ETD)

Sensory inputs from the external world are represented as highly organized systems in the adult brain for effective adaptation to the environment. At the cortical level, this organization is referred to as cortical maps. The establishment of cortical maps begins with early life experiences during the critical period, a brief period during development of heightened sensitivity to sensory stimuli. During this time, organization of cortical maps is plastic and highly subject to change through passive sensory experience. As an animal matures, the critical period closes and changes to cortical maps occur less freely. The cellular mechanisms of cortical map plasticity …

The Health-Related Quality Of Life Of Adults With Down Syndrome, Rebecca Jermyn Graves

Theses and Dissertations (ETD)

Purpose. The purpose of this study was to examine the health-related quality of life (HRQOL) and factors associated with the HRQOL of adults with Down syndrome (DS) as reported by adults with DS and their caregivers. The study was designed to compare measures of HRQOL, health problems, health risks, and health-care utilization of adults with DS based on self-report with those from caregiver-report and to explore associations between HRQOL and health problems, health risks, health-care utilization, adaptive behavior, and demographic characteristics. Background. The life expectancy of individuals with DS has lengthened from approximately 30 years around 1960 to over 50 …