Medicine and Health Sciences Commons^™

Epigenetic Modifications Of Human Placenta Associated With Preterm Birth, Drissa Toure

Theses & Dissertations

Preterm birth is a complex multifactorial process. Despite the well-known role of the placenta in supporting the fetal development and maternal-fetal tolerance, the placental epigenetic modifications and preterm birth (PTB) remains poorly understood and under investigated. Various maternal and environment factors can influence epigenetic programming during fetal development to affect the functioning and structures of organs, including the placenta, which can lead to adverse pregnancy outcomes, including PTB. The understanding of the placental epigenetic alterations and maternal determinants associated with PTB are apparently indispensable for the development of actual diagnosis and methods of prevention and treatment of premature labor. The …

The Rise And Fall Of The Bovine Corpus Luteum, Heather Talbott

Theses & Dissertations

This dissertation describes a study of the mechanisms regulating the genesis and subsequent involution of the temporary endocrine structure, the corpus luteum (CL), through the use of a bovine model. The CL is essential for maintaining a suitable uterine environment for embryo implantation and early development through secretion of the steroid hormone progesterone. The “Rise and Fall” of the CL occurs within each estrous cycle whereby the CL must form from the ruptured follicle, secrete sufficient progesterone for uterine maturation, and at the end of the cycle (or pregnancy) regress to allow new follicular development. During the rise of the …

Effect Of Postprandial Walking On The Glycemic Effect Of A Meal: Type I Diabetes, Samantha L. Hinojosa

Theses & Dissertations

This study was conducted to determine if 15 minutes of postprandial light walking has an effect on the glycemic response to a Boost® beverage in individuals with type 1 diabetes. Seven participants, 22.3 + 4.3 yrs, with type 1 diabetes completed the two days of data collection. On day 1, participants measured baseline fasting blood glucose (BG) with a glucometer, consumed a Boost® beverage, and sat quietly, repeating BG measurements 15, 30, 60, 90, and 120 minute. On day 2, participants repeated the protocol, but walked 15 minutes at a light pace (50-60% max HR) immediately after beverage consumption. The …

Target Validation And Pharmacological Characterization Of Novel Nmdar Modulators, Kiran Sapkota

Theses & Dissertations

The N-methyl-D aspartate receptors (NMDARs) are ligand-gated ion channels, which play important roles in learning and memory. Excessive activity of NMDARs is implicated in damage due to stroke and neurodegenerative diseases, whereas hypoactivity of NMDARs contributes to schizophrenia. The initial goal of my dissertation is to evaluate the potential role of the GluN2D-containing NMDARs in neuropathological, behavioral and cognitive alterations associated with schizophrenia and characterize the pharmacology and mechanisms of action of NMDAR modulators which could potentially be used to modulate these receptors in schizophrenia.

A subanesthetic dose of the NMDAR antagonist ketamine elicits symptoms of schizophrenia. This property led …

Mutations Affecting Epigenetic Regulators And Their Role In Peripheral T-Cell Lymphomas, Chao Wang

Theses & Dissertations

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of generally aggressive lymphoid malignancies, accounting for 10-15% of all non-Hodgkin lymphomas. Angioimmunoblastic T-cell lymphoma (AITL) represents approximately 20% of all PTCLs and is recognized as a distinct entity. Accurate diagnosis and classification of PTCL remain challenging. With the exception of ALK+ ALCL, patients with PTCL generally have a poor prognosis with standard chemotherapy and even with the availability of many novel drugs, including HDAC inhibitor (romidepsin and belinostat), gemcitabine, and bortezomib. Therefore, deciphering the pathogenesis of this group of diseases is needed to identify novel treatable targets for better therapeutic intervention. …

Mobility Of Individuals With Multiple Sclerosis And The Influence Of Physical Therapy, Brenda L. Davies

Theses & Dissertations

One main purpose was to explore the compensatory gait strategies of individuals with multiple sclerosis (MS). To address this purpose, we quantified the mechanical work generated by the lower extremity joints during walking. The outcomes from this investi­gation suggested that individuals with MS redistribute positive mechanical work during walking to the hip in order to compensate for a reduced ability of the ankle to generate positive mechanical work. Additionally, we also explored the motor control of the ankle as a potential contributing factor to the mobility limitations of individuals with MS. The outcomes from this investigation indicated that individuals with …

Recurrent Mutations Of T-Cell Receptor And Co-Stimulatory Signaling Proteins In Peripheral T-Cell Lymphomas, Joseph Rohr

Theses & Dissertations

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T-cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation, through many signaling molecules including VAV1. This thesis identifies recurrent mutations in CD28 in PTCLs, as well as mutations in VAV1. Two residues of CD28 – D124 and T195 – were recurrently mutated in 11.3% …

Expression And Function Of Inflammation-Associated Micrornas In Traumatic Brain Injury, Emily Harrison

Theses & Dissertations

MicroRNAs (miRNAs) are important regulators of gene expression. Many neurological diseases, including traumatic brain injury alter expression of miRNAs in the brain. However, the function of these molecules in the context of TBI is largely unknown. Here we report multiple potential roles for miRNAs in TBI, some of which extend beyond the traditional model of post-transcriptional regulation, highlighting that these RNA molecules may have broader implications for the neurobiology of disease. We found that miR-155 plays an essential role in interferon expression after CCI and that miR-155 contributes to TBI induced anxiety, potentially through regulation of interferons. Expression of miR-155 …

Epacs: Epigenetic Regulators That Affect Cell Survival In Cancer., Catherine Murari

Theses & Dissertations

Cyclic adenosine monophosphate (cAMP) is a second messenger responsive to many external stimuli, playing an important role in cellular gene expression, metabolism, migration, differentiation, hypertrophy, apoptosis and secretion. All of these cellular functions are important in many diseases including cancer. Most of its effects were initially attributed to the classical protein kinase A (PKA) protein, but cellular functions such as proliferation and migration were found to be PKA independent and dependent on the newly discovered exchange proteins directly activated by cAMP (EPACs). EPACs are single polypeptides that primarily function as guanine exchange factors (GEFs) for Rap proteins that allow the …

The Effect Of Body Mass Index On Graft Function And Kidney Transplant Outcomes, Morgan Galle

Theses & Dissertations

Background: When determining eligibility for kidney transplantation, body mass index (BMI) is often a debatable criterion for transplant due to the clinical indication, an elevated BMI has adverse effects on kidney transplant outcomes. There is a current gap in research on the effect BMI has on kidney transplant outcomes.

Purpose: The purpose of this study was to determine the role BMI plays in post-kidney transplant clinical outcomes including delayed graft function, new onset diabetes after transplant, wound complications, hospital length of stay, albumin, and readmissions to the hospital from initial hospitalization and at six months following kidney transplantation. The primary …

The Feedforward And Feedback Controls On Gait In Adults With Diabetes, Chun-Kai Huang

Theses & Dissertations

There are nearly 26 million people with diabetes mellitus (DM) in the US, and half of chronic DMs develop somatosensory deficits due to diabetic polyneuropathy or diabetic peripheral neuropathy (DPN). The absence or impaired somatosensory feedback (e.g. touch sensation or joint proprioception) resulted from the damage of large nerve fiber, and motor deficits such as attenuated muscle strength and abnormal plantar pressure of lower extremity have been identified in DPN, and these sensorimotor impairments lead to an increased number of falls. To reduce the risk of falling, a well-coordinated and adapted limb movement driven by the feedforward (anticipatory) and feedback …

Interaction Between Angiotensin Ii And Bdnf In Modulating Sympathetic Nerve Activity, Bryan K. Becker

Theses & Dissertations

Over activation of the sympathetic nervous system is prevalent in many forms of cardiovascular disease such as chronic heart failure (CHF) and hypertension. Although increased neuronal renin-angiotensin system activity in presympathetic neurons has been well implicated in mediating this sympatho-excitation, many of the neuronal effects of angiotensin II (Ang II) signaling remain poorly understood. One particular mechanism of Ang II-mediated increases in presympathetic neuronal activity is through reductions in voltage-gated K⁺ currents. Another pathway that has profound effects on neuronal K⁺ currents and that has been previously implicated in Ang II-signaling is brain-derived neurotrophic factor (BDNF) activity through …

Role Of Macrophages In Muscle Transfection With Pdna/Pluronic Formulation, Vivek Mahajan

Theses & Dissertations

Non-ionic amphiphilic block copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), Pluronics, arranged in a tri-block structure PEO-PPO-PEO, have raised a considerable interest in skeletal muscle Gene Therapy. Previous studies have demonstrated that co-administration of Pluronics with naked plasmid DNA (pDNA) by direct i.m. injection enhanced transgene expression not only in muscle but also in distal lymphoid organs (spleen and lymph nodes) and this response was strain-dependent; not observed in athymic (BALB/c nu/nu) mouse; suggesting a role of immune cells in gene transfer to skeletal muscles. Therefore, we first evaluated the role of inflammation and inflammatory cells, on muscle …

Investigation Of Behavioral And Cellular Changes In The Maternal Immune Activation Model Of Autism Spectrum Disorders, Shreya Roy

Theses & Dissertations

Maternal infection during pregnancy, which leads to maternal immune activation (MIA), is an environmental risk factor for autism spectrum disorders (ASD). MIA can be induced in mice and their offspring exhibit behaviors that model the core symptoms of ASD. One of the core behavioral symptoms in ASD patients is presence of increased repetitive behavior, which is modeled by an increase in marble burying in MIA mice. It has been shown that the deficits seen in MIA mice are associated with the dysregulation of cytokine levels in the developing brain, specifically an increase in pro-inflammatory cytokines. In this thesis, I tested …

The Effects Of Atropine On The Growth And Respiration Of Two Species Of Bacteria Normally Inhabiting The Human Gastro-Intestinal System, Mary M. Ramos

Theses & Dissertations

It is the purpose of this study to determine whether the drug atropine has an effect on bacteria found normally inhabiting the human body, most specifically the gastrointestinal system. Atropine is one of the oldest drugs in medicine. It is derived from the roots and leaves of solanaceous plants such as henbane and Jimson weed. Atropine is often termed a belladonna alkaloid because it can also be found in the deadly nightshade plant, Atropa belladonna. Atropine is a highly competitive antagonist of acetylcholine at receptor sites in smooth muscles, cardiac muscle, and various glandular cells (5). Therefore, its effects are …