Life Sciences Commons^™

Regulatory Mechanisms In Borrelia Burgdorferi-Induced Arthritis, Emily Siebers Hansen

Theses and Dissertations

Lyme arthritis is a common symptom of Lyme borreliosis that involves inflammation of the synovial joints. Elucidating the immune events involved in Lyme arthritis is complicated by the fact that not all individuals infected with B. burgdorferi develop arthritis. Additionally, Lyme arthritis manifests in different severities between affected individuals. It is known that an inflammatory response is initiated by B. burgdorferi infection and that inflammatory T cells contribute to the development of arthritis. However, the anti-inflammatory mechanisms that regulate the pathogenic T cells’ response are not entirely understood. Here, the hypothesis that a dysregulated immune response results in an excessive …

Synthetic And Biological Exploration Of (+)-Boldine - Identification Of Potential Cns Receptor Ligands, Sujay Joseph

Theses and Dissertations

(+)-Boldine, an aporphine alkaloid, is reported to be biologically active at various Central Nervous System(CNS) receptors. However, only a few Structure Activity Relationship(SAR) studies have been conducted using boldine’s aporphine scaffold. A library of novel analogs was synthesized from boldine to understand the effect of bisbenzylation at C2 and C9 positions on the affinity and selectivity at the serotonin receptors.

Point Of Use Biosand Filters Of The Rural Dominican Republic, Kurtis Quamme

Theses and Dissertations

The point of use biosand filter (BSF) is used globally as a drinking water treatment solution. In this research, point of use BSFs were inoculated with active biosand from the Linnwood Drinking Water Treatment plant slow sand filter beds (Milwaukee, Wisconsin) and with sands collected from point of use filters operating in the Dominican Republic. These filters were maintained with varying source waters (surface water, groundwater, or tap water to simulate chlorination encountered in the field). The microbial community of filters with varied influents and biosand inoculum were analyzed quantitatively by sequencing and qPCR. Filter efficacy and microbial community were …

A Mechanical Study Of Cancer Drug-Receptor Interactions, Specifically In G-Quadruplex Dna And Topoisomerase I Enzymes, Kelly Ann Mulholland

Theses and Dissertations

Computational methods are becoming essential in drug discovery as they provide information that traditional drug development methods lack. Using these methods to understand drug-receptor interactions in detail, researchers are able to efficiently design promising drug candidates. In this study, extra precision Glide docking, molecular dynamics simulations and MMGBSA binding energy calculations provided information about the binding behavior of small molecules to two specific targets for current cancer therapeutics: G-quadruplex DNA and Topoisomerase I enzyme. The first study focuses on the compound Telomestatin, which induces apoptosis of various cancer cells with a relatively low effect on somatic cells due to its …

Unaffected Women’S Decisions To Have Prophylactic Risk-Reducing Mastectomies, Stephanie N. Galloway

Theses and Dissertations

When a woman is at an increased risk of developing breast cancer due to a pathogenic mutation or a significant family history of the disease, she will be faced with choosing from among multiple management options, including risk-reducing mastectomy (RRM). The relative rate of RRM for both diagnosed and unaffected high-risk women has increased in recent years. Previous research has investigated the factors that influence women diagnosed with the disease to undergo RRM, but has not fully addressed how unaffected women make their decisions to choose RRM as an option when they are still healthy. This study was designed to …

Re-Contacting Cancer Genetic Counseling Patients: Expectations Of Patients And Physicians, Zoe Elizabeth Siegel

Theses and Dissertations

The landscape of cancer genetic counseling and testing is rapidly evolving. Genetic testing technology is improving, management guidelines are evolving, and genetic testing options are expanding. These frequent updates to the components of cancer genetics have increased the complexity of managing patient care over time. In particular, this raises questions on the duty to re-contact patients as new information becomes available. This study explored healthcare providers’ duty to re-contact through the interests and expectations of patients, including which circumstances warrant re-contacting, which healthcare provider is responsible for re-contacting the patient, and the preferred method of re-contacting. Physicians’ opinions on whether …

Range Of Motion And Plantar Foot Pressures In Those With And Without A Lateral Hip Shift During An Overhead Squat, Erin M. Lally

Theses and Dissertations

Context: Asymmetrical loading between lower limbs can theoretically be explained as an inequality of strength, neuromuscular control, or subconscious reliance on one leg more than the other. Asymmetries are often identified utilizing costly equipment such as force plates and 3D motion analysis cameras. It is important to establish less costly ways of identifying movement and loading asymmetries for clinicians to utilize. One qualitative assessment that may identify asymmetries is a ‘lateral hip shift’ during an overhead squat. Objective: To identify differences in lower extremity range of motion (ROM) and plantar foot pressures in individuals with and without a lateral hip …

Identification Of Xpa And Xpc Gene Mutations In Patients With Xeroderma Pigmentosum, Eman Abdelalim Sidky Rabie

Theses and Dissertations

The human body employs different DNA repair pathways to protect itself against cancers induced by DNA damage. The nucleotide excision repair (NER) pathway comprises different synchronously working DNA repair proteins; two of which are XPA and XPC. Mutations of any of the genes encoding the NER proteins cause an autosomal recessive genetic disorder called Xeroderma Pigmentosum (XP). XP patients present with characteristic dry atrophic freckle-like pigmentation of the skin, photosensitivity and photophobia. Some patients develop neurodegenerative symptoms early in life, including mental retardation. Patients have a 10,000-fold increased risk for UV-induced skin cancers, moreover, a higher risk for ocular, oral …

Age-Associated B Cell And T Helper Cell Dysfunction In Rhesus Macaques, Evan Knox Stalvig

Theses and Dissertations

The immune system undergoes drastic changes as we age, known as immunosenescence. An example of this is the dysfunction and subpopulation distribution changes of immune cells. Due to immunosenescence, the elderly have a higher risk of complications and rapid progression of new challenges to the immune system, including human immunodeficiency virus (HIV). In an effort to determine the mechanism of dysfunction of humoral immunity due to age, I compared B cell and T cell responses to non-specific, mitogenic stimuli between aged and young adult rhesus macaque peripheral blood mononuclear cells (PBMCs). Analysis by flow cytometry revealed several differences in B …

Effects Of Drift, Selection And Gene Flow On Immune Genes In Prairie Grouse, Zachary Bateson

Theses and Dissertations

Fragmentation of natural habitats is related to population decline in many species. The resulting small and isolated populations are expected to lose genetic variation at a rapid rate, which reduces the ability to adapt to environmental change. One concern is that small populations are more susceptible to emerging pathogens due to the loss of variation at immune genes. My dissertation examined the relative effects of gene flow, genetic drift and selection on immune genes in prairie-chickens (Tympanuchus cupido), a species that has undergone drastic population declines across their range. In the first chapter, I examined how artificial gene flow through …

Elementary Educators' Perspective Of Physical Education And The Physical Education Teacher, Jennifer M. Garcia

Theses and Dissertations

Physical education continues to have the reputation it has had for years of being a subject of marginalization and of least importance in the school curriculum. The purpose of this study is to gain a better understanding of the perceptions of educators of physical education and the physical education teacher in the Rio Grande Valley. The researcher attempts to find, understand, and describe the perceptions of the educator’s view of this subject matter. Statistical significance was set at the .05 level for both tests of analyses. The researcher offers the null hypothesis of no difference between educator’s perception of PE …

The Effects Of Two Different Resistance Training Protocols With Similar Volume On Muscular Strength, Muscle Thickness, And Fat-Free Mass, Cory Worthey

Theses and Dissertations

The manipulation of exercise volume, intensity, and order is associated with producing different musculoskeletal changes. These resistance training program variables affect mechanical tension and metabolic stress associated with resistance training, therefore affecting strength and hypertrophic outcomes. PURPOSE: The purpose of this study was to examine the effects of two different volume-equated total body exercise protocols over 9 weeks using compound exercises on muscular strength, muscle thickness, and fat-free mass. METHODS: Eight well-trained men were randomly assigned to a hypertrophy-style protocol (HG) performing 3 sets of 10 repetitions with 90 seconds rest between sets (n = 4) or a strength-style protocol …

The Effects Of Caffeine On Reaction Time Of Two Neurocognitive Tests, Kyle Petit

Theses and Dissertations

Context: A concussion is defined as a traumatically induced transient disturbance of the brain caused by a biomechanical force. These problematic injuries can prevent athletes from participating in physical activity for a number of days, weeks, or even months. Caffeine is known for improving mental alertness in everyday tasks and is found in many popular drinks such as, coffee, tea, energy shots, and even soda. Due to its increase in memory, mental alertness, and concentration, caffeine could potentially be utilized to improve the outcomes of post-concussion neurocognitive testing. This improvement would allow athletes to return to play before they have …

Resolution Of Inflammation Rescues Axon Initial Segment Disruption, Nicholas M. George

Theses and Dissertations

Axonal domains are required for proper neuron function. These domains are unstable and degenerate concurrent with the inflammation in multiple sclerosis (MS) and the inflammatory disease models experimental autoimmune encephalomyelitis (EAE) and lipopolysaccharide (LPS) induced inflammation. Previous studies from our laboratory have shown that the axon initial segment (AIS) is maintained independently of the presence of myelin, but that AIS disruption is seen in MS as well as EAE and LPS-mediated inflammation. AIS loss can be interrupted in the early stage of EAE using the anti-inflammatory drug Didox. However, the potential for Didox directed repair of the AIS in later …

Stains Induce Apoptosis And Autophagy In Primary And Transformed Mast Cells, Patrick A. Paez

Theses and Dissertations

Statin drugs are widely employed in the clinic to reduce serum low density lipoproteins (LDLs) in patients with hypocholesteremia. In addition to their cholesterol-lowering effects through HMG CoA reductase antagonism, isoprenyl lipids necessary for membrane anchorage and signaling of small G-proteins are abrogated. We previously found that statins suppress mast cell activation in murine and human cells, suggesting these drugs might be useful in treating allergic disease. While mast cell function is critical to allergic inflammation, mast cell hyperplasia and survival also impact these diseases, and were not studied in our previous work. In this study, we describe Fluvastatin-mediated apoptosis …

Role Of Vav2 In Podocyte Inflammasome Activation And Glomerular Injury During Hyperhomocysteinemia, Sabena Conley

Theses and Dissertations

Hyperhomocysteinemia (hHcys) is a widely known pathogenic factor in the progression of end-stage renal disease (ESRD) and it is also associated with an increased risk for injurious cardiovascular pathologies during ESRD. HHcys is linked to the formation and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, characterized as a critical early mechanism initiating the inflammatory response. NADPH oxidase (NOX)-derived reactive oxygen species (ROS) mediate the activation of the NLRP3 inflammasome in podocytes in response to elevated levels of homocysteine (Hcys) in vitro and in vivo. However, it remains unknown how NLRP3 inflammasome activation is triggered by NOX. The …

A Mechanistic Study Of An Ipsc Model For Leigh’S Disease Caused By Mtdna Mutataion (8993 T>G), John P. Galdun

Theses and Dissertations

Mitochondrial diseases encompass a broad range of devastating disorders that typically affect tissues with high-energy requirements. These disorders have been difficult to diagnose and research because of the complexity of mitochondrial genetics, and the large variability seen among patient populations. We have devised and carried out a mechanistic study to generate a cell based model for Leigh’s disease caused by mitochondrial DNA mutation 8993 T>G. Leigh’s disease is a multi-organ system disorder that depends heavily on the mutation burden seen within various tissues. Using new reprogramming and sequencing technologies, we were able to show that Leigh’s disease patient fibroblasts …

Introducing Novel Combinatorial Targeted Therapies In Multiple Types Of Cancer, Mehrad Tavallai

Theses and Dissertations

The cancers of liver, colon and breast are amongst the top five most prevalent and most fatal worldwide. As the Raf/MEK/ERK pathway is frequently deregulated in hepatocellular carcinoma (HCC), sorafenib, a Raf kinase inhibitor, became the first systemic therapy approved for the treatment of patients with HCC. However, sorafenib only produced modest effects with low response rates in the clinic. Similarly, regorafenib, which was approved for the treatment of metastatic colorectal cancer (CRC), has had a poor response rate in the clinic. Since phosphodiesterase type 5 has been reported to be overexpressed in HCC and CRC, we hypothesized that sildenafil, …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

The Informational And Emotional Support Needs Of Grandparents Of Children With Pompe Disease, Natasha Lousie Rudy

Theses and Dissertations

The complex roles and experiences of grandparents of children with various diagnoses have been described, but previous studies have not investigated the roles and experiences of grandparents of children with treatable, Mendelian conditions such as Pompe disease. The availability of treatment and heritable nature of Pompe introduce the possibility for unique grandparent roles, experiences and needs. This is a particularly timely investigation given the advent of newborn screening for Pompe. This study aimed to characterize grandparents’ roles and involvement, identify grandparents’ information and emotional support needs, and explore the psychosocial impact felt by grandparents of children with Pompe. An online …

Examining Genetic And Environmental Influences On Alcohol Use And Externalizing Behaviors In African American Adolescents, Neeru Goyal

Theses and Dissertations

The aim of this thesis is to expand our understanding of the etiology of alcohol misuse and related disorders in African Americans using genetically informative study designs. Specifically, we take advantage of the candidate-gene approach and polygenic score analysis to extend the literature specific to African American populations. Chapter 2 explores gene x environment (GxE) interactions through the candidate gene approach to explore the relationship between two genes chosen on their potential relevance to stress response and adolescent alcohol use and misuse, among African American youth living in highly impoverished neighborhoods, as moderated by stressful life events. Chapter 3 implements …

Power Analysis In Applied Linear Regression For Cell Type-Specific Differential Expression Detection, Edmund Glass

Theses and Dissertations

The goal of many human disease-oriented studies is to detect molecular mechanisms different between healthy controls and patients. Yet, commonly used gene expression measurements from any tissues suffer from variability of cell composition. This variability hinders the detection of differentially expressed genes and is often ignored. However, this variability may actually be advantageous, as heterogeneous gene expression measurements coupled with cell counts may provide deeper insights into the gene expression differences on the cell type-specific level. Published computational methods use linear regression to estimate cell type-specific differential expression. Yet, they do not consider many artifacts hidden in high-dimensional gene expression …

Investigating The Molecular Etiologies Of Sporadic Als (Sals) Using Rna-Sequencing, David G. Brohawn

Theses and Dissertations

ALS is an often lethal disease involving degeneration of motor neurons in the brain and spinal cord. Current treatments only extend life by several months, and novel therapies are needed. We combined RNA-Sequencing, systems biology analyses, and molecular biology assays to elucidate sporadic ALS group-specific differences in postmortem cervical spinal sections (7 sALS and 8 control samples) that may be relevant to disease pathology. >55 million 2X150 RNA-sequencing reads per sample were generated and processed.

In Chapter 2, we used bioinformatics tools to identify nuclear differentially expressed genes (DEGs) between our two groups. Further, we used Weighted Gene Co-Expression Network …

The Effect Of Pre-Deployment Physiology As A Predictor Of Post-Traumatic Stress Disorder Among A Sample Of United States Army National Guard And Reserve Soldiers, David J. Rothman

Theses and Dissertations

Potential risk factors for development of Post-Traumatic Stress Disorder (PTSD) are still unclear. One potential risk factor for the development of PTSD is an individual’s cardiovascular reactivity and recovery in response to stressor tasks. The current study was conducted with 763 Army National Guard and Army Reserve soldiers. Participants completed a stressful induction along with self-report measures prior to deployment. Post-deployment, self-report measures were completed to assess PTSD symptomatology and experiences related to deployment and combat. Multiple regression was used to determine the ability of blood pressure response to stress to predict PTSD symptoms immediately and one-year after return from …

Predictors Of Caffeine-Related Withdrawal Symptoms In College Freshmen, David J. Pomm

Theses and Dissertations

While caffeine withdrawal has been well-characterized, research on caffeine intake and factors associated with withdrawal has been limited. The present study examined prevalence rates of caffeine use and identified psychosocial factors associated with having caffeine withdrawal headaches (CWH). Participants were N = 1,989 college freshmen who participated in the 2011 Spit for Science project. Caffeine use was reported by 80% of the sample. Females were more likely than males to consume caffeine, and soda was the primary source of caffeine for both genders. As hypothesized, daily caffeine users were more likely to report CWH than non-daily users. When multivariable analyses …

The Study Of The Regulon Of Oxyr In Escherichia Coli And Porphyromonas Gingivalis, Christopher K. Pham

Theses and Dissertations

The facultative anaerobe, Escherichia coli and the obligate anaerobe, Porphyromonas gingivalis are two bacteria that reside in our body. Although they reside in separate environments, they are both subject to hydrogen peroxide stress and have mechanisms to regulate the stress. OxyR is the primary transcriptional regulator/sensor of oxidative stress response caused by hydrogen peroxide. OxyR in P. gingivalis is not well-characterized compared to OxyR in E. coli. We sought to characterize and compare the two forms of OxyR in order to gain a better understanding of the protein. We determined the oligomeric state of both proteins: primarily a tetramer for …