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The Role Of Yes-Associated Protein 1 In Ovarian Physiology And Pathology, Xiangmin Lv

Theses & Dissertations

Ovarian granulosa cells are the major somatic components of the ovarian follicle. Proper proliferation and differentiation of ovarian granulosa cells are essential for successful follicle development. Accumulating evidence indicates that the Hippo-YAP signaling pathway plays critical roles in both development and tumorigenesis of several organs. The present study aims to investigate the role of Yes-associated protein 1 (YAP) in ovarian granulosa cell proliferation, differentiation, and malignant transformation. At first, we found that nuclear YAP (active) was highly expressed in proliferative granulosa cells, whereas cytoplasmic YAP (inactive) was detected mainly in terminally-differentiated luteal cells. Further studies suggested that endogenous YAP activity …

Novel Therapeutic Approaches For Juvenile Neuronal Ceroid Lipofuscinosis (Cln3), Megan Elizabeth Bosch

Theses & Dissertations

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by autosomal recessive mutations in CLN3. Neuronal loss is thought to occur via glutamate excitotoxicity; however, little is known about neuron-astrocyte glutamate regulation in JNCL. We discovered that Cln3^Δex7/8 astrocytes have significantly lower basal spontaneous Ca²⁺ oscillations and decreased responses to glutamate, indicating a disrupted signaling network. Cln3^Δex7/8 astrocytes also displayed significantly lower basal mitochondrial respiration and ATP production, suggesting impaired metabolic functions. Concurrent with diminished astrocyte metabolism and Ca²⁺ signaling, Cln3^Δex7/8 neurons were hyper-responsive to glutamate stimulation. These studies suggest that CLN3 …

Focus: A Graph Approach For Data-Mining And Domain-Specific Assembly Of Next Generation Sequencing Data, Julia Sommer

Theses & Dissertations

Next Generation Sequencing (NGS) has emerged as a key technology leading to revolutionary breakthroughs in numerous biomedical research areas. These technologies produce millions to billions of short DNA reads that represent a small fraction of the original target DNA sequence. These short reads contain little information individually but are produced at a high coverage of the original sequence such that many reads overlap. Overlap relationships allow for the reads to be linearly ordered and merged by computational programs called assemblers into long stretches of contiguous sequence called contigs that can be used for research applications. Although the assembly of the …

Organizational Effects Of Defeminizing Toxicants: Lessons Learned From An Environmental Sentinel Organism, The Fathead Minnow., Jonathan Ali

Theses & Dissertations

Endocrine disrupting compounds (EDCs) are chemicals that interfere with hormone function and are increasingly detected in aquatic environments, where they elicit adverse effects from exposed organisms. The toxicological effects of EDCs can be described as either activational (reversible) or organizational (irreversible), where the latter are associated with adverse outcomes in reproductive performance of adult fish. However, few studies have investigated the organizational impacts of anti-estrogenic or “defeminizing” EDCs, e.g. agrichemicals or pharmacological agents, in an environmentally-relevant or “sentinel” species. The objective of this study was to investigate the impacts of early-life EDC-initiated changes in estrogenic gene expression on organizational effects …

Comparative Molecular Characterization Of Typical And Exceptional Responders In Glioblastoma, Kristin Wipfler

Theses & Dissertations

Glioblastoma (GBM) is the most common and the deadliest type of primary brain tumor, with a median survival time of only 15 months despite aggressive treatment. Although most patients have an extremely poor prognosis, a small number of patients survive far beyond the median survival time. Investigation of these “exceptional responders” has sparked a great deal of interest and is becoming an important focus in the field of cancer research. To investigate the molecular differences between typical and exceptional responders in GBM, comparative analyses of copy number, methylation, gene expression, miRNA expression, and protein expression data sets from The Cancer …

Maternal Life Course Adversity: The Intersection Of Psychosocial And Biobehavioral Adaptive Response In Pregnancy, Crystal Modde Epstein

Theses & Dissertations

The link between life course adversity and adverse health outcomes is well established, particularly early life adversity (ELA). There is also evidence that the physiologic adaptations associated with stress, depression and ELA can be transmitted intergenerationally via long-term set-point changes within the maternal hypothalamic-pituitary-adrenal axis (HPA). It is unknown how the type and timing of maternal stress and adversity influences HPA regulation during pregnancy and whether maternal coping attenuates this relationship. Manuscript 1 was an integrative review of studies examining the association between maternal ELA and HPA regulation during pregnancy. In manuscripts 2 and 3 the findings of the dissertation …

The Effect Of Mechanical Vibration On Pain And Rate Of Tooth Movement During Initial Orthodontic Alignment, Leslie Ellingson

Theses & Dissertations

Purpose: The purpose of this investigation was to evaluate the effect of mechanical vibration on pain experienced and rate of tooth movement (OTM) during the initial alignment phase of orthodontic treatment.

Materials and Methods: Participants were randomly allocated to control, low frequency or high frequency. An electric toothbrush was modified to provide high frequency vibration. A low frequency vibration device was acquired from a commercial vendor. Experimental groups applied vibration to the dentition for 20 minutes daily. All participants completed questionnaires using visual analog scales at five time points. Pain experience was measured in millimeters (mm) with the scale measuring …

Public Health Perspectives On Sexual Health And Family Planning, Molly Mccarthy

Theses & Dissertations

Large bodies of evidence document the importance of sexual and reproductive health (SRH) in the lives of individuals and among populations. Of particular interest are sexually transmitted diseases (STDs), due to their potential for long-term health consequences, and unintended pregnancy because of its association with social and economic outcomes for women and families.

This dissertation addressed three distinct but related areas of reproductive health and family planning: counseling for condom use following an STD test, counseling for contraception following a pregnancy test in a clinical setting, and the effect of abortion on having and achieving long-term plans. These topics are …

Perturbing Anti-Apoptotic Proteins To Develop Novel Cancer Therapies, Jacob Contreras

Theses & Dissertations

The apoptotic pathway involves a tightly regulated network of proteins which respond to various stimuli. Previous studies have indicated Mcl-1 and Bcl-xL are intimately involved in determining cell fate, and if both are concurrently neutralized, it activates the apoptotic pathway. The inactivation of Bcl-xL and Mcl-1 as a mechanism to trigger the intrinsic apoptotic response can be used as a platform to develop therapeutic strategies to target cancer cells. The apoptotic pathway is largely dysregulated and often leads to therapy resistance in cancer cells. Although direct inhibitors of Bcl-xL have been developed and have advanced to clinical trials, development of …

A Role For Δ-Catenin In Synaptic Regulation, Li Yuan

Theses & Dissertations

The cadherin-catenin complex regulates cell-cell adhesion and signal transduction in epithelial cells. It is becoming increasingly evident that components of the complex regulate various aspects of neuronal architecture and function. δ-catenin is a cytosolic component of the cadherin-catenin complex and is predominantly expressed in the central nervous system. Loss of CTNND2, which encodes δ-catenin, is associated with intellectual disability and mutations in CTNND2 have been identified in autism, suggesting that δ-catenin is a critical component of the molecular machinery underlying neural circuit function. We have previously demonstrated that δ-catenin regulates multiple aspects of synaptic and dendritic development, including dendritic …

Evaluation Of Immune-Modulating Therapies For Parkinson's Disease, Katherine E. Olson

Theses & Dissertations

Parkinson’s disease (PD) is the second most common neurodegenerative

disorder, second only to Alzheimer’s disease (AD). It is characterized by a

progressive loss of dopaminergic neurons along the nigrostriatal axis and the

formation of proteinaceous inclusions of alpha-synuclein (α-syn). Secondary to

the loss of dopaminergic neurons is a progression in motor and non-motor

symptoms. Motor symptoms are characterized by slowness in movement,

stiffness and tremor. Non-motor symptoms include depression, constipation,

sleep abnormalities and loss of sense of smell. The cause of disease remains

incompletely understood. However, age, genetics, environment, viral infection,

and interplay between the innate and adaptive immune system …

In-Vitro And In-Vivo Models Of Bile Acid Metabolism And Transport, Rhishikesh Thakare

Theses & Dissertations

All biomedical research is conducted in animal models first. In addition, the Food and Drug Administration requires extrapolation from animal data to predict human responses. There are ongoing scientific and regulatory challenges translating interspecies comparisons and predictions. Metabolic pathways are a cornerstone to understanding drug metabolism and toxicities and the liver is a key organ in this process. Bile acids (BAs) play a central role in the hepatobiliary toxicities of chemicals, toxins, and biological reagents. BAs have many physiological functions including regulation of genes involved in cholesterol and glucose metabolism and BA homeostasis. However, BAs also have several pathological effects …

Role Of Transforming Growth Factor (Tgf) – Β Signaling In Craniofacial Development, Malignancies And Regeneration, Jingpeng Liu

Theses & Dissertations

The transforming growth factor (TGF) – β signaling pathway regulates a diversity of fundamental cellular processes such as cell growth and proliferation, cell differentiation, migration, apoptosis and other biological functions, both during embryogenesis and in adult tissue homeostasis. TGF-β is known to play a critical role in palatal development as in TGF-β knockout murine models, TGF-β deficiency causes cleft palate, a common craniofacial deformity in humans due to the abnormality of growth, elevation or fusion of the two palatal shelves. In order to investigate the mechanisms of how TGF-β regulates palatogenesis, we generated TGF-β3 knockout (-/-) murine models, performed systematic …

Self-Efficacy For Symptom Management In Adult Hematopoietic Stem Cell Transplant Patients, Lynn White

Theses & Dissertations

Hematopoietic stem cell transplant (HSCT) is a treatment for hematologic cancers and other hematologic conditions that causes severe treatment-related symptoms. The first 30 days after HSCT, or the acute phase, is when symptoms are most intense. During this time, the ability of patients to manage their symptoms, in collaboration with their health care providers, is crucial to reduce the distress caused by the symptoms. Self-efficacy is the person’s confidence in their ability to perform a behavior, such as symptom management. This body of work describes the concept of self-efficacy for symptom management (SESM), presents an integrated literature review on self-efficacy …

Novel Therapeutic Strategies For Treatment Of Castration-Resistant Prostate Cancer, Matthew A. Ingersoll

Theses & Dissertations

Prostate cancer (PCa) remains the most commonly diagnosed solid tumor and is the third leading cause of cancer-related death in United States men. While androgen deprivation therapy is the current standard-of-care treatment for metastatic PCa, most patients eventually relapse and develop castration-resistant (CR) tumors, for which there is currently no effective treatment. Therefore, synthesis of novel therapeutic agents and identification of alternative target proteins are necessary to improve treatment. Herein, I investigate the efficacy of novel imidazopyridine and statin derivatives as alternative therapeutic compounds. These molecules not only inhibit androgen receptor signaling, but also block activation of the AKT axis, …

Risk Of Post-Ercp Pancreatitis In Liver Transplant Patients: Single Center Experience, Shailender Singh

Theses & Dissertations

Introduction: Acute pancreatitis remains the most common severe complication of endoscopic retrograde cholangiopancreatography (ERCP). The exact cause of post-ERCP pancreatitis (PEP) is unclear. Regardless of the mechanism that initiates PEP, the pathways of inflammation are similar to other forms of acute pancreatitis and include the activation of various inflammatory cytokines, released from the acinar cells and subsequently from helper T lymphocytes and macrophages. Liver transplants (LTx) patients on immunosuppressive medications have impaired T-cell response and hence decreased ability to generate these cytokines. The aim of this study was to review incidence rates and risk factors of PEP in this …

Relationships Between Complex Pediatric Health Conditions And The Built, Physical And Social Environments, Brittany Corley

Theses & Dissertations

The relationship between human health and the environment is complex and overall poorly understood. The environment has a lasting impact on health, and the processes appear to start at conception. Thus, this dissertation examines the potential relationship between pediatric health and the environment.

The first relationship examined was between the built environment and comorbid Attention Deficient Hyperactivity Disorder and Autism Spectrum Disorder. Many publications have reported the relationship between socioeconomic disadvantage, Attention Deficient Hyperactivity Disorder, and Autism Spectrum Disorder. However, the link between the built environment and Attention Deficient Hyperactivity Disorder and Autism Spectrum Disorder symptom severity is poorly understood. …

Identifying The Role Of Janus Kinase 1 In Mammary Gland Development And Breast Cancer, Barbara Swenson

Theses & Dissertations

The development of the postnatal mammary gland is tightly controlled by peptide hormones and cytokines. The signaling of these extracellular ligands through their corresponding receptors rely on Janus Kinases (JAKs) that activate downstream Signal Transducers and Activators of Transcription (STATs). The JAK/STAT signaling pathway is crucial for processes such as growth, proliferation, and cell survival of the epithelial tissue, but also for the breakdown and remodeling of the mammary gland via IL-6 class inflammatory cytokines (e.g. LIF and OSM). JAK1 and JAK2, which are expressed in the mammary gland, are thought to have redundant functions. However, our previous studies demonstrated …

Evaluation Of Aminopyrazole Analogs As Cyclin-Dependent Kinase Inhibitors For Colorectal Cancer Therapy, Caroline Robb

Theses & Dissertations

Colorectal cancer (CRC) remains one of the leading causes of cancer related deaths in the United States. Currently, there are limited therapeutic options for CRC patients, none of which focus on the cell signaling mechanisms controlled by members of the cyclin dependent kinase (CDK) family. CDK5 has been implicated in a variety of cancers, and most recently as a tumor promoter in CRC.

As such, we evaluated a compound developed by Pfizer, CP-668863 (a.k.a. 20-223), that inhibits CDK5 in neurodegenerative disorders. In our CRC xenograft model, 20-223 reduced tumor growth and tumor weight, indicating its value as a potential anti-CRC …

Defining The Role Of Neuropilin-2 In Macrophages: Implications In Tumor Associated Macrophages In Pancreatic Cancer, Sohini Roy

Theses & Dissertations

Macrophages are extremely heterogeneous and highly plastic hematopoietic cells that reside in all tissues and act as a bridge between the innate and adaptive arms of the immune responses. Besides, they undertake a wide array of housekeeping functions like, clearance of cellular debris that arise due to regular turnover in tissues, iron homeostasis, immune surveillance as well as tissue repair processes post inflammation. They are also causally associated with several clinical conditions, including cancer where the infiltration of macrophages contribute to disease progression, metastasis and therapy resistance, and thereby poor clinical outcome.

Neuropilins (NRPs) are non-tyrosine kinase cell surface glycoproteins …

Exploring Perceptions And Experiences With Resources Among Rural Alzheimer's Dementia Family Caregivers In The Midwest, Rita M. Million

Theses & Dissertations

Exploring PERCEPTIONS AND EXPERIENCES WITH RESOURCES AMONG RURAL Alzheimer’s Dementia Family Caregivers in the Midwest

Rita M. Million

University of Nebraska, 2017

Supervisor: Karen Schumacher, Ph.D., RN

Background. Despite vast amounts of research on informal caregiving in the Alzheimer’s dementia (AD) population, research on the experience and perceptions of rural caregivers is limited. A better understanding of rural caregivers’ knowledge, use, and nonuse of resources is essential to offset the impact of caregiving. Purpose. This study explored Alzheimer’s dementia family caregivers’ experiences and perceptions with resources in rural Midwest communities. Design. A descriptive qualitative approach with one-time semi-structured interviews was …

Metabolic Reprogramming Of Pancreatic Ductal Adenocarcinoma Cells In Response To Chronic Low Ph Stress, Jaime Abrego

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of all cancers with a 5-year survival rate of only 8.2%. This is because PDAC is diagnosed in its advanced stages and is characterized by radio and chemotherapy resistance. Aggressiveness of PDAC tumors is attributed to its high metabolic phenotype, which is characterized by increased glycolysis rate and lactate secretion, while oxidative metabolism is reduced. These metabolic features are required to fulfill the biosynthetic demands of proliferating PDAC cells. However, this increase in metabolic activity results in acidification of the extracellular space because the dense fibrotic stroma of PDAC tumors limits …

Effects Of Gm-Csf On Dendritic Cells And Regulatory T Cells In Parkinson’S Disease Patients And Models Of Parkinson’S Disease, Charles Schutt

Theses & Dissertations

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder. Pathologically, loss of nigrostriatal neurons and dopamine released by these neurons are responsible for PD motor symptoms. During PD, activation of resident microglia and infiltrating lymphocytes leads to progressive neuroinflammation and reduction in the number and function of regulatory immune cells. Neuroinflammation contributes to progressive neurodegeneration and declining motor function. Reducing neuroinflammation is the target for novel PD therapeutics. Our goal is to increase the number and function of regulatory T cells (Tregs) in PD patients to decrease neuroinflammation and reduce PD symptoms. One potential therapy is granulocyte-macrophage colony stimulating …

Transcriptome Profiling Of Cleft Palate Intgf-Beta3 Knockout Mice Alleles: Rna-Seq Analysis Of Tgf-Beta3 Mice, Kelsey White

Theses & Dissertations

Background: Orofacial clefts are the most common craniofacial birth defect with a complex, combinatorial etiology. Tgf-b3 regulates palatal fusion in mice; Tgf-b3 knockout mice have cleft palate (CP) lacking other major deformities. The genes downstream of Tgf-b3 during palatogenesis remain largely unexplored. Our objective was to analyze the global transcriptome changes and their contribution to CP and identify novel Tgf-b3 associated genes involved in formation of CP. We used RNA-sequencing to analyze and compare the whole transcriptome of Tgf-b3 alleles during palatal growth and fusion in mice.

Results: …

Role Of Ezrin In Colorectal Cancer Cell Survival Regulation, Premila Leiphrakpam

Theses & Dissertations

Colorectal cancer (CRC) is the second most common cause of cancer related deaths in the United States, mainly due to metastasis to the distant organ sites. However, the molecular basis of CRC metastasis is poorly understood. Therefore, identification and characterization of novel potential anti-cancer therapeutic targets CRC is of urgent need. Utilizing a 2D-DIGE proteomics approach ezrin was identified as a protein that is differentially expressed between primary colon tumors xenografts, orthotopically implanted in athymic nude mice, and corresponding and liver metastatic deposits. Ezrin, a cytoskeletal protein belonging to the ezrin–radixin–moesin (ERM) family plays important roles in cell motility, invasion …

A Translational Evaluation Of Renewal Of Inappropriate Mealtime Behavior, Vivian Ibañez, Cathleen C. Piazza, Kathryn M. Peterson

Theses & Dissertations

The term renewal describes the recurrence of previously extinguished behavior that occurs when the intervention context changes. Renewal has important clinical relevance as a paradigm for studying treatment relapse because context changes are necessary for generalization and maintenance of most intervention outcomes (Podlesnik, Kelley, Jimenez-Gomez, & Bouton, 2017). The effect of context changes are particularly important during intervention for children with feeding disorders because children eat in a variety of contexts, and extinction is an empirically supported and often necessary intervention. Therefore, we used an ABA arrangement to test for renewal during intervention with 3 children diagnosed with a feeding …

Cpap-Mad Combination Therapy For Cpap Intolerant Patients With Moderate To Severe Osa, Jacob Stadiem

Theses & Dissertations

The treatment of obstructive sleep apnea (OSA) allows for a multidisciplinary approach between dentistry and medicine. Continuous positive airway pressure (CPAP) is the gold standard for OSA treatment, but the non-adherence rates are high. The mandibular advancement device (MAD) has a higher acceptance rate than the CPAP, however the efficacy is much lower in cases of moderate to severe OSA. This thesis attempted to evaluate if there was a change in compliance when a MAD was added as a combination therapy to moderate to severe OSA subjects that were currently non-compliant with their CPAP. In addition, the change in air …

Analysis Of Food Security, Snap Benefit Duration, Income Level And The Relationship With Depression In Households With Children In Omaha., Tatiana Tchouankam

Capstone Experience

Food insecurity is defined as a lack of access to “sufficient, safe, and nutritious food that meets individuals’ dietary needs and preferences for an active and healthy life.” From 2015 to 2016, the number of people undernourished increased from 777 million to 815 million worldwide. Food insecurity affected 12.3 % of Nebraskans and 13.8% of the residents in Douglas County during the same year. There is evidence of associations between food insecurity, income level, and several adverse health outcomes, specifically with regards to mental health. The objective of this study was to examine food security, SNAP benefit duration (i.e., how …

Examination Of Collaborative Efforts Of Central District To Achieve Success Of The Community Health Improvement Plan, Liene Topko

Capstone Experience

This was a quality improvement project that helped Central District Health Department (CDHD) work more closely with their community partners to identify the activities and programs that are currently in place to address priority health needs that were included in the 2016 Comprehensive Community Health Needs Assessment (CHNA). The purpose of this project is to identify the specific activities and programs that are being implemented by the health department and community partners in relation to the priority needs. These activities and programs were identified by conducting a survey of the major community partners. The findings from the survey helped to …

Hpv Vaccination Of Children Among Motherse Of Mexican Origin, Bibiana M. Carvajal-Suarez

Capstone Experience

Background. The Human Papillomavirus (HPV) is a causative agent for the development of cancer which is a public health concern worldwide. In the United States (US), the highest incidence of cervical cancer is among Hispanics/Latinos. Although Hispanics/Latinos show the highest utilization rate of HPV vaccine, in general, the vaccination rates are still behind the Healthy People 2020 goal of 80%. The knowledge about this virus has been found low or nonexistent among most populations in the US, especially among minorities and populations with lower education and socioeconomic status. The knowledge and beliefs of Hispanic/Latin mothers about HPV and HPV …