Medicine and Health Sciences Commons^™

Evaluation Of Extracellular Matrix Composition And Rheology As Determinants Of Growth, Invasion, And Response To Photodynamic Therapy In 3d Cell Culture Models Of Pancreatic Ductal Adenocarcinoma, Gwendolyn M. Cramer

Graduate Doctoral Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is a notoriously lethal disease characterized by prominent stromal involvement, which plays complex roles in regulating tumor growth and therapeutic response. The extracellular matrix (ECM)-rich stroma has been implicated as a barrier to drug penetration, although stromal depletion strategies have had mixed clinical success. It remains less clear how biophysical interactions with the ECM regulate invasive progression and susceptibilities to specific therapies. Here, an integrative approach combining 3D cell culture and quantitative imaging techniques is used to evaluate invasive behavior and motility as determinants of response to classical chemotherapy and photodynamic therapy (PDT), in which light …

Possible Breakdown Of Dopamine Receptor Synergism In A Mouse Model Of Huntington's Disease, Samantha F. Kennedy

University of New Orleans Theses and Dissertations

The model of basal ganglia function proposed by Albin, Young and Penney (1989) describes two anatomically independent motor pathways, the direct and indirect. However, under normal conditions striatal dopamine (DA) is required for the expression of motor behavior, and DAergic control of the two pathways (via D1 and D2 receptors, respectively) is dependent on co-activation. We tested for a possible breakdown of D1/D2 synergism using transgenic R6/1 mice bearing the human huntingtin allele (Htt). Motor stereotypy, observed prior to the onset of HD-related symptoms, was rated on a 5-point scale following activation of: A) D1 receptors alone, B) D2 receptors …

Of Rats And Men, Thomas S. Walsh

Capstones

This capstone is a data-driven investigation into New York City's rat problem. By using publicly available government data to map rat activity in NYC, I identified several socio-economic variables that correlate with rat populations at the community district, borough, and city-scale. I used these findings (mainly that rat problems are linked to lower incomes) as the basis of an investigation, which includes interviews with residents, experts, and city officials. Prof. Bobby Corrigan, urban rodentologist and formerly with the NYC Department of Health criticizes the city's efforts for the first time on the record.

https://thomasseiyawalsh.wixsite.com/ratstone

Understanding Huntington's Disease Using Machine Learning Approaches, Sonali Lokhande

KGI Theses and Dissertations

Huntington’s disease (HD) is a debilitating neurodegenerative disorder with a complex pathophysiology. Despite extensive studies to study the disease, the sequence of events through which mutant Huntingtin (mHtt) protein executes its action still remains elusive. The phenotype of HD is an outcome of numerous processes initiated by the mHtt protein along with other proteins that act as either suppressors or enhancers of the effects of mHtt protein and PolyQ aggregates. Utilizing an integrative systems biology approach, I construct and analyze a Huntington’s disease integrome using human orthologs of protein interactors of wild type and mHtt protein. Analysis of this integrome …

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 …

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 …

Lost In Translation, Daniel Pena

Master's Projects and Capstones

At the conclusion of a patient’s hospitalization the Registered Nurse (RN) will review all discharge instructions in the patients room in their preferred language. Plan time for the discharge and facilitate a calm quiet environment, such as the patient’s room with the door closed, if possible. Get the discharge instructions printed out in their preferred language and a set for yourself in English would be best so you are able to review the instructions line by line with them. When the patients medical team, such as but not limited to, medical doctors, pharmacists, physical therapists, and social work have completed …

Identification Of Prognostic Cancer Biomarkers Through The Application Of Rna-Seq Technologies And Bioinformatics, Nathan Wong

McKelvey School of Engineering Theses & Dissertations

MicroRNAs (miRNAs) are short single-stranded RNAs that function as the guide sequence of the post-transcriptional regulatory process known as the RNA-induced silencing complex (RISC), which targets mRNA sequences for degradation through complementary binding to the guide miRNA. Changes in miRNA expression have been reported as correlated with numerous biological processes, including embryonic development, cellular differentiation, and disease manifestation. In the latter case, dysregulation has been observed in response to infection by human papillomavirus (HPV), which has also been established as both oncogenic in cervical cancers and oropharyngeal cancers and favorable for overall patient survival after tumor formation. The identification of …

Cholesterol Regulation Of Pulmonary Endothelial Calcium Entry Following Chronic Hypoxia, Bojun Zhang

Biomedical Sciences ETDs

Chronic hypoxia (CH)-induced pulmonary hypertension (PH) is associated with diminished ATP-induced endothelial Ca2+ entry as well as membrane cholesterol in pulmonary arteries. Store-operated Ca2+ entry (SOCE) and depolarization-induced Ca2+ entry are major components of the response to ATP and are similarly decreased after CH. Because endothelium-dependent vasodilation is closely associated with pulmonary endothelial [Ca2+]i, the blunted agonist-induced Ca2+ influx in pulmonary artery endothelial cells (PAEC) may contribute to the development of CH-induced PH. Interestingly, impaired agonist-induced Ca2+ influx in PAEC following CH can be restored by membrane cholesterol supplementation. In the current studies, we hypothesized that impaired Ca2+ entry in …

Aging, Inflammation, And Gut Microbiota In Mice, Jody Demeo

Honors Projects

Inflammation and gut microbiota are two areas of study that can be linked to aging in the body. As a person ages, systemic inflammation tends to increase, and changes in microbiota in the gastrointestinal system occur as well.

Analysis Of Diagnostic, Preventive, And Disease-Modifying Therapeutic Measures Of Alzheimer’S Disease, Ghazal Habib Havoutis

HCNSO Student Capstones

Alzheimer’s disease (AD) is the most common late-onset neurodegenerative disorder and cause of dementia, characterized by the formation of neurofibrillary tangles and senile plaque deposits. The heterogeneous nature of the disease (both genetically and environmentally) makes it difficult to prevent or cure. Without prevention, the prevalence of AD is expected to triple by 2050. However, because the diagnosis of AD is usually preceded by years of cognitive impairment, early detection may aid in reducing prevalence. Thus, there is a need for validated diagnostic measures for early and improved diagnosis and prevention. In this review, current and ongoing classifiers of early …

Integrative Cancer Immunogenomic Analysis Of Serial Melanoma Biopsies Reveals Correlates Of Response And Resistance To Sequential Ctla-4 And Pd-1 Blockade Treatment, Whijae Roh

Dissertations & Theses (Open Access)

Melanoma is the most malignant form of skin cancer. The five-year survival rate for metastatic melanoma is 19.9%. Although targeted therapy of BRAF and MEK inhibitors were developed for melanoma, resistance to therapy is inevitable. Immune checkpoint blockade, which reverses the suppression of the immune system, on the other hand, has shown a durable response in 20-30% of patients with metastatic melanoma. However, more predictive and robust biomarkers of response to this therapy are still needed, and resistance mechanisms remain incompletely understood. To address this, we examined a cohort of metastatic melanoma patients treated with sequential checkpoint blockade against cytotoxic …

Investigating The Regulation Of Indole-3-Acetic Acid Production By The Plant Associated Microbe Pantoea Sp. Yr343, Kasey Noel Estenson

Doctoral Dissertations

The auxin indole-3-acetic acid (IAA) plays a central role in plant growth and development and many plant-associated microbes produce IAA. Several IAA biosynthetic pathways have been identified in microbes which use the precursor tryptophan. Pantoea sp. YR343, which was isolated from the Populus deltoides rhizosphere, is a robust plant root colonizer that produces IAA. Using genomic and metabolomics analyses, we predicted that the indole-3-pyruvate (IPA) pathway is the major pathway in Pantoea sp. YR343 for IAA production. To better understand IAA biosynthesis and the effects of IAA exposure on cell physiology, we performed proteomics on Pantoea sp. YR343 grown in …

Evaluating The Therapeutic Efficacy Of Restoring Wild-Type P53 Activity In P53-Mutant Tumors, Connie A. Larsson

Dissertations & Theses (Open Access)

The p53 transcription factor is the most frequently altered in human cancers usually via missense mutations that undermine its transcriptional activity. Clinically, TP53 mutations have been shown to be remarkably predictive of refractoriness to treatment, resulting in poor outcome. Consequently, the development of p53 pathway activating agents is rapidly evolving and gaining more attention in cancer therapeutics research, with several small molecule compounds currently in preclinical and clinical trials. However, it remains largely unknown what types or proportions of p53-mutant tumors will respond to p53 restoration-based therapies.

Using a mouse model of Li Fraumeni syndrome, we genetically restored wild-type …

Exercise, Cognition, And The Aging Process Among Active, Competitive, And Sedentary Middle-Aged And Older Adults, Katherine Adams

Health, Human Performance and Recreation Undergraduate Honors Theses

Purpose This study aimed to compare the cognitive measures of reaction time and dual-task performance among recreationally active, master athletes, and sedentary older adults aged 50 years or older. Methods 59 late middle-aged and older adults between the ages of 50 to 88 years old participated in reaction time and dual-task tests of which consisted of multiple trials on the same day. Subjects were placed either into the recreationally active, masters athlete, or sedentary activity level group based on the Rapid Assessment of Physical Activity (RAPA) form. For the gait speed with associated dual-task component, subjects walked 10-meters at two …

Dopamine Levels In The Brain Of Rat Models Of Human Rheumatoid Arthritis, Amelia Stinson

Theses & Dissertations

Research Focus. Rheumatoid arthritis (RA) is a chronic, debilitating, autoimmune disease that causes the destruction of bone tissue and the articular structures of joints. At least 30% of RA patient populations have cognitive impairment. Acidic dopamine (DA) is the principal neuroimmunotransmitter that links the central nervous system and peripheral nervous system together. The aim of the present study was to determine the levels of DA and its two acidic metabolites: 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in arthritic induced rats, and whether their levels vary across four different parts of the brain: amygdala (AMG), front cerebral cortex (CX), hippocampus …

An Investigation Of The Levels Of Pro-Inflammation Cytokines In The Brain Of Autoimmune Lewis Rats, Han Yang

Theses & Dissertations

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which can cause cartilage and bone damage, as well as disability. A reported symptom of RA includes tissue inflammation disease and cognitive dysfunction. This study aimed to compare the concentration of selected cytokines in the cerebral cortex, hippocampus, hypothalamus, amygdala, and cerebellum of Lewis rats. Age and sex-matched Lewis rats were separated into two groups: control and adjuvant-induced RA. Twenty-eight days after the adjuvant injection, groups were sacrificed and brains dissected using the stereotaxic atlas of Paximos and Watson as a guide. Pro-inflammatory cytokines IL-1β, IL-6, and IL-23, plus the anti-inflammatory …

Association Of Childhood Blood Lead Levels With Firearm Violence Perpetration And Victimization, Lindsay Rae Emer

Theses and Dissertations

Over 10,000 Americans are killed in firearm homicides each year, and an additional 40,000 are injured in nonfatal shootings. There is a significant public health need to identify risk factors that can be modified to prevent firearm violence. Environmental lead exposure is a demonstrated neurotoxicant which causes behavior changes that are known to be criminogenic. More recent research has demonstrated that homicides and nonfatal shootings differ by the circumstances that lead to the shootings (i.e. gang, domestic violence, arguments) and aggregating them could lead to biased results. Although studies have found a relationship between childhood lead exposure and criminal behaviors, …

Exercise, Learning And Emotional Health: Interdisciplinary Approaches To Translational Action, Tessa L. Koschel

UNLV Theses, Dissertations, Professional Papers, and Capstones

Exercise positively effects physical, psychological and neurological wellbeing. Though the population at large is becoming increasingly aware of the multi-faceted benefits of exercise, the majority of people fail to meet daily exercise recommendations. Largely, demands of everyday life such as work, school and family take priority over fitness. The issue therefore becomes a matter of time. In a world of media multi-tasking and immediate gratification, the challenge to health professionals becomes incorporation and manipulation of these consistencies to improve exercise uptake and adherence. Focus must shift from the idea of making additional time for exercise, to adding exercise to time …

Comparing The Effectiveness Of Alternative And Prescription Antibiotics Against Gram-Positive Bacteria, Rachel Jenkins, Roan Dickenson, Sam Turnbull, Marcela Torres

Senior Theses

The rapid emergence of antibiotic-resistant bacteria is a global public health concern that threatens the efficacy of antibiotic drugs. We found that natural remedies, specifically coconut oil, honey and cinnamon essential oil, have the potential to be used as a clinical alternative to treat antibiotic-resistant infections. In this experiment, we performed a disk diffusion test and measured the area of inhibition of each treatment to compare the effectiveness of natural and prescription antibiotics. Cinnamon essential oil showed significantly greater antibiotic activity compared to a prescription treatment, amoxicillin. With bacterial resistance continuously expanding, more work needs to be done to determine …

Behavioral Ecology And Associated Virology Of Mosquito-Host Interactions In Southern California, Oliver Eshun

Loma Linda University Electronic Theses, Dissertations & Projects

Elucidating characteristics of mosquito-host interactions are critical for understanding the ecology and epidemiology of mosquito-borne diseases. In this dissertation, I conducted three studies to explore potential mosquito-host interactions and associated virus infection rates. I first demonstrated that mosquito captures at CO2-baited traps decreased most markedly with height above ground, and also decreased with distance from water at a riparian area but not at an open water source lacking a vegetated border. Birds might therefore prefer elevated nests or roosts to avoid mosquitoes. The second study examined the anti-mosquito behaviors of budgerigars (Melopsittacus undulatus) in a laboratory study. The birds defended …

Impact Of Terminology Mapping On Population Health Cohorts Impact, Barbara A. Berkovich

Dissertations & Theses (Open Access)

Background and Objectives: The population health care delivery model uses phenotype algorithms in the electronic health record (EHR) system to identify patient cohorts targeted for clinical interventions such as laboratory tests, and procedures. The standard terminology used to identify disease cohorts may contribute to significant variation in error rates for patient inclusion or exclusion. The United States requires EHR systems to support two diagnosis terminologies, the International Classification of Disease (ICD) and the Systematized Nomenclature of Medicine (SNOMED). Terminology mapping enables the retrieval of diagnosis data using either terminology. There are no standards of practice by which to evaluate and …

Brain Energy Homeostasis And The Regulation Of N-Acetyl-Aspartate Metabolism In Development And Disease, Samantha Zaroff

Graduate School of Biomedical Sciences Theses and Dissertations

N-acetylaspartate (NAA) is a non-invasive clinical marker of neuronal metabolic integrity because of its strong proton magnetic resonance spectroscopy (H-MRS) peak and direct correlation with energetic integrity. Specifically, NAA is used to track the progression of neurodegenerative diseases due to the characteristic reduction of whole brain levels of NAA which occur simultaneously with reduced glucose utilization and mitochondrial dysfunction, but prior to the onset of disease specific pathology. However, NAA will also significantly increase simultaneously with energetic integrity during periods of recovery or remission in applicable disorders, such as traumatic brain injuries. Unfortunately, it remains enigmatic exactly why NAA is …

Developing Algorithms For Quantifying The Super Resolution Microscopic Data: Applications To The Quantification Of Protein-Reorganization In Bacteria Responding To Treatment By Silver Ions, Sai Divya Challapalli

Graduate Theses and Dissertations

Histone-like nucleoid structuring proteins (HNS) play significant roles in shaping the chromosomal DNA, regulation of transcriptional networks in microbes, as well as bacterial responses to environmental changes such as temperature fluctuations. In this work, the intracellular organization of HNS proteins in E. coli bacteria was investigated utilizing super-resolution fluorescence microscopy, which surpasses conventional microscopy by 10–20 fold in spatial resolution. More importantly, the changes of the spatial distribution of HNS proteins in E. coli, by addition of silver ions into the growth medium were explored. To quantify the spatial distribution of HNS in bacteria and its changes, an automatic method …

Computational Identification Of Noncoding Driver Mutations Based On Impact On Rna Processing, Kevin Zhu

Dissertations & Theses (Open Access)

Despite the prevalence of mutations in the noncoding regions of the DNA, their effects on cancer development remain largely uninvestigated. This is especially evident when compared to coding mutations, which have been relatively well-studied and, in certain cases, been identified as driver mutations for cancer. Recent studies, however, have identified noncoding mutations that frequently appear in certain types of cancer, which may be evidence that those mutations are important to cancer development. Nonetheless, the role of noncoding mutations in cancer remains unclear. A potential vector for understanding this mechanism is through observing the relation between noncoding mutations and functional RNA …

Circulating Autoantibodies In Human Traumatic Spinal Cord Injury Subjects And Their Relationship To The Development Of Neuropathic Pain, Georgene Hergenroeder

Dissertations & Theses (Open Access)

Background:

Approximately 17,500 spinal cord injuries (SCI) occur yearly in the U.S. causing considerable morbidity and mortality. Neuropathic pain (NP) ensues in 40-70% of SCI. An autoimmune response resulting from disruption of the blood-spinal cord-barrier may be a contributor to NP. However, the relationship between autoantibodies and NP after SCI in humans has not been thoroughly characterized nor have autoantigens been identified. Glial fibrillary acidic protein (GFAP) and collapsin response mediator protein2 (CRMP2) were identified as candidate autoantigens. The hypothesis is that proteins from the injured spinal cord released by SCI trigger autoantibody production which can lead to the development …

Mechanism Of Candida Albicans Biofilm And Virulence Inhibition By A Bacterial Secreted Factor, Carrie Graham

Dissertations & Theses (Open Access)

The human microbiome is a diverse polymicrobial population comprised of both fungi and bacteria. Perturbations of the normal microbiome can have a profound impact on health, including the development of infections. Exploitation of these polymicrobial interactions has the potential to provide novel treatment and prevention strategies for infectious diseases. Enterococcus faecalis, a Gram-positive bacterium, and Candida albicans, a polymorphic fungus, occupy overlapping niches as ubiquitous constituents of the gastrointestinal and oral microbiome. Both species are also amongst the most important and problematic, opportunistic nosocomial pathogens and are often co-isolated during infection. Surprisingly, these two species antagonize each other’s …

Effect Of Endophyte-Infected Tall Fescue Toxins On Growth Performance And The Microbial Community In The Rumen And Feces In Pregnant Ewes, Saleh Alrashedi

Graduate Theses and Dissertations

Fifty pregnant Katahdin ewes grazed pastures with high (HE) and moderate (MI) levels of Neotyphodium coenophialum-infected tall fescue between February 1 and May 24 to determine the impacts of tall fescue toxins on body weight (BW), body condition scores, FAMACHA scores, fecal egg counts (FEC), and serum Cu, Zn, prolactin, and non-esterified fatty acids (NEFA). Within those 50 ewes, 15 were selected randomly for fecal and rumen sampling to assess the impacts of HE and MI on the microbiome community. Total bacterial DNA was extracted from rumen and fecal samples, and alpha and beta diversities were used to relate microbiome …

The Effects Of Continuous Insulin Pump Therapy On Glycemic Control In Pregnant Type 1 Diabetics, Kimberly Kelsey

Senior Theses

Type 1 Diabetics have various ways of managing their diabetes that have been studied for their effectiveness. Pregnancy in the Type 1 Diabetic has been understudied. It is known that Diabetics in general have poorer pregnancy outcomes because of poor glycemic control. This coupled with the fact that the body needs 3-4 times more insulin as pregnancy comes to an end makes managing blood glucose levels challenging for diabetics (Lowdermilk, 2016, p. 689). For the Type 1 Diabetic, there are two main ways to control diabetes: multiple daily injections using at least two type of insulin and continuous subcutaneous insulin …