Life Sciences Commons^™

A Novel Exo-Proteomic Approach To The Study Of Traumatic Brain Injury, Ron B. Moyron

Loma Linda University Electronic Theses, Dissertations & Projects

Concussions and Traumatic Brain Injuries (TBI) are significant health concerns and affect a wide cross section of society. Current diagnostic criteria and modalities, such as brain imaging and subjective measures of consciousness such as the Glasgow Coma Scale (GCS) score, are insufficient to properly diagnose the full spectrum of head injuries. Assessment of injury severity and outcome are further complicated by the vast array of symptoms, many of which mimic those displayed by other disorders. It is important to possess a better diagnostic tool for head injury triage and outcome prediction. One current line of inquiry seeks to discover a …

Rna-Seq Reveals Transcriptomic Program Associated With Stemness In Taxane Resistant Prostate Cancer, Christina K. Cajigas-Du Ross

Loma Linda University Electronic Theses, Dissertations & Projects

There is no cure for advanced prostate cancer (PCa), and taxane chemotherapy is the only treatment option once other therapies have failed. However, this is problematic since all patients eventually develop chemoresistance. Emerging treatments for advanced PCa have shown promise at the benchside, but clinical trials have not resulted in newly approved drugs due in part to redundant survival pathways utilized by prostate tumor cells to maintain therapy-resistance. Using RNAsequencing—an innovative approach for quantifying gene expression changes—this dissertation sought to elucidate chemoresistance-associated molecular pathways as a catalyst to develop new therapeutic targets. Results revealed a differential upregulation of stemness-associated genes …

The Design Of Complex Weapons Systems In Scorpions: Sexual, Ontogenetic, And Interspecific Variation, Gerard A. A. Fox

Loma Linda University Electronic Theses, Dissertations & Projects

Scorpions possess two integrated multifunctional weapons systems. Anteriorly, they maintain a grasping system comprised of a pair of pedipalps ending in chelae that seize and manipulate prey, ward off predators, and secure mates. Posteriorly, they wield a venom delivery system consisting of a tail-like metasoma with a stinger at the tip of the terminal segment (telson) that can be thrust into prey, predators, or mates to inject venom. Given the complexity of these systems, I hypothesized that weaponry design is subject to selective forces arising from differences in usage between the sexes, during ontogeny, and among closely-related species occupying different …

Effects Of Omega-3s And Vitamin E Prophylactic Diets And The Implications Of Lipid Transport In Spinal Cord Injury, Kathia Cordero-Caban

Loma Linda University Electronic Theses, Dissertations & Projects

Traumatic injury to the central nervous system (CNS) presents a devastating problem to our society. Although current interventions are promising, no effective treatments are available. The neural membrane fatty acid composition is markedly altered during the first few days after spinal cord injury (SCI). SCI results in autonomic dysfunction, paralysis, spasticity, and significant chronic neuropathic pain. The trauma leads to significantly increased levels of free radical and oxidative stress that contribute to obstructing tissue healing and recovery. A growing body of evidence shows that administration of hydrophobic molecules such as Vitamin E and long-chain omega-3 polyunsaturated fatty acids (ω3PUFAs) are …

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 …

Effect Of Extracellular Survivin And Lymphoma Exosomes On Natural Killer Cells, Heather R. Ferguson Bennit

Loma Linda University Electronic Theses, Dissertations & Projects

Tumors alter their microenvironment to promote survival using methods such as angiogenesis promotion, growth signals, and immune suppression. The immune system becomes unresponsive to transformed neoplastic cells through a variety of methods including T cell suppression, increased myeloid-derived suppressor cells (MDSCs), and reduced natural killer (NK) cell activity. NK cells have inherent killing capabilities and thus are among the first responders in recognizing and destroying abnormal cells. However, many types of cancers inhibit the surveillance and cytotoxic abilities of NK cells by releasing exosomes, vesicles that can modulate the tumor microenvironment (TME) and intercellular communication for the purpose of enhancing …

Prenatal Undernutrition, Metyrapone, And The Cerebrovasculature, Lara Durrant

Loma Linda University Electronic Theses, Dissertations & Projects

The link between intrauterine environmental conditions and adult cardiovascular system is well established. Independent of lifestyle factors such as poor diet and exercise habits, individuals who have been exposed to stressful conditions in utero show an increased risk of health problems such as hypertension, stroke, and type II diabetes. In support of the Fetal Origin of Adult Disease hypothesis, many labs have reported permanent anatomical and physiological changes associated with fetal stress and nutrient deficiency, with a focus on organ systems such as the kidney and heart. One key idea proposed by many of these studies is the glucocorticoid hypothesis, …

Pas Signaling Mechanisms In Aer And Aer2, Darysbel Garcia

Loma Linda University Electronic Theses, Dissertations & Projects

PAS domains are widespread signal sensors that share a conserved three-dimensional αβ fold that consists of a central β-sheet flanked by several α- helices. The aerotaxis receptor Aer from Escherichia coli and the Aer2 chemoreceptor from Pseudomonas aeruginosa both contain PAS domains. Aer senses oxygen (O2) indirectly via an FAD cofactor bound to its PAS domain, while Aer2 directly binds O2 to its PAS b-type heme cofactor. The Aer and Aer2 PAS domains both interact with a signal transduction domain known as a HAMP domain. The PAS-HAMP arrangement differs between Aer and Aer2, with Aer- PAS residing adjacent to its …

A Novel Population Of Cardiovascular Progenitors Persist In Neonates As Mesendodermal Cells, Julia Kim

Loma Linda University Electronic Theses, Dissertations & Projects

The rise in mortality due to cardiovascular disease has increased the need to develop an efficient regenerative therapeutic for heart failure. Numerous cell-based therapies have been investigated for myocardial regeneration; however, an optimal progenitor has yet to be discovered. Identifying a resident cell population with enhanced ability to differentiate into multiple lineages would greatly contribute to the field of stem cell-based regenerative therapy. Evidence suggests that endogenous cardiovascular progenitor cells (CPCs) that have been isolated from the heart itself express ISL1, KDR, and MESP1, and are capable of differentiating into all major cardiac lineages. The earlier developmental stage at which …

Synthesis Of Huacat® Analogues As Novel Organocatalysts For The Formation Of Asymmetric C-C Bonds, Kenneth Laboy

Loma Linda University Electronic Theses, Dissertations & Projects

The synthesis of organic compounds with preferential stereochemistry is ubiquitous in the scientific community. A chemical reaction that asymmetrically induces one stereoisomer over another is achieved through the use of catalysts and various coupling reagents.1 Inorganic catalysts, such as TiCl4 and ZnCl2, have been documented for many decades as effective agents in the synthesis of asymmetric bonds, however, there are environmental limitations to their use. First, the asymmetric reactions involving these metal catalysts require solvents that are not environmentally-friendly, especially when used on an industrial scale and second, the metal catalysts are recycled when possible, however, there is always metal …

Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay

Loma Linda University Electronic Theses, Dissertations & Projects

Touted among the major achievements in the diagnosis and management of Prostate cancer (PCa) in the past few decades has been, the dramatic decline of men with advanced/metastatic PCa at diagnosis coupled with a significant improvement ( >90%) in the five and ten year survival rates of the disease. Non-palpable PCa (potentially clinically treatable disease) now accounts for 70-80% of all newly diagnosed cases of PCa. Preceding these changes by about a decade was the introduction of Prostatic Specific Antigen (PSA) into clinical practice; first as biomarker for monitoring response to therapy and subsequently as a complementary screening tool. It …

Mechanism Of Chimeric Vaccine Mediated Immune Suppression Of Human Dendritic Cells, Jacques Christian Mbongue

Loma Linda University Electronic Theses, Dissertations & Projects

Type 1 diabetes mellitus is a chronic inflammatory disease in which insulin producing β-cells of the pancreatic islets are killed by autoreactive cells of the immune system in response to a loss of tolerance. Dendritic cells (DC) interact predominantly with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this dissertation, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of …

Comparative Studies Of Tslp And Il-7 In Normal Early Human Neonatal And Adult B Cell Development, Terry-Ann Milford

Loma Linda University Electronic Theses, Dissertations & Projects

Defining the role of cytokines in promoting human B cell development is important for understanding B cell leukemia and for developing strategies to restore B cell production that is lost during some therapies. The purpose of this study was to investigate the roles of the IL-7R ligands, thymic stromal lymphopoietin (TSLP) and IL- 7, in the early stages of normal postnatal and adult human B cell development. Using novel in vitro and in vivo model systems, we show that TSLP and IL-7 are able to expand B cell precursors individually and in combination from CB hematopoietic stem cells. In this …

Crotalus Snake Venom Preconditioning To Prevent Surgical Brain Injury, Cherine Hee-Sun Kim

Loma Linda University Electronic Theses, Dissertations & Projects

Preventive measures are increasingly relevant to medical practice. Preconditioning, a preemptive therapy that administers mildly harmful stimuli to induce endogenous protective mechanisms before major injury, has been shown to minimize injury in many animal models. Given the elective nature of most neurosurgical procedures, the surgical brain injury (SBI) rodent model provides an ideal platform for preconditioning. Our work shows that preconditioning with Crotalus rattlesnake venom, known for its hemorrhagic and inflammatory effects, mitigates some harmful effects of SBI. We have identified two proteins of interest in Crotalus venom: snake venom metalloproteinase (SVMP), an enzyme with hemorrhagic effects, and phospholipase A2 …

Curcumin: A Multi-Dimensional Approach To Pancreatic Cancer Targeting Cell Death And Exosomes, Carlos J. Diaz Osterman

Loma Linda University Electronic Theses, Dissertations & Projects

Pancreatic cancer is currently one of the most difficult diseases to treat due to difficulty of detection and the aggressive nature of the disease. In addition, pancreatic cancer has the highest mortality rates compared to other cancer types. These mortality rates are attributable in part to increasing resistance to cancer therapy. Cancer therapy resistance is caused by adaptations that favor survival within cancer cells and their environment, termed the tumor microenvironment. Intracellular adaptations include the overexpression of resistance-linked genes, such as the inhibitor of apoptosis (IAP) family of proteins and overall resistance to cell death. Adaptations in the tumor microenvironment …

Modulation Of T Lymphocytes By Tumor-Released Survivin, Jessica Marie Jutzy

Loma Linda University Electronic Theses, Dissertations & Projects

The tumor microenvironment is an area of intense interaction between normal and malignant cells. Factors and cell types within this environment can play a crucial role in the progression or regression of the tumor. Of primary interest are tumor-infiltrating T lymphocytes, which have been shown to have a key role in modifying the dynamics of the tumor microenvironment to promote or prevent tumor growth. While there is much in vitro and in vivo evidence for a modification of the tumor infiltrating T cell population toward a pro-tumor environment, what induces these changes within the tumor microenvironment has remained elusive. Our …

Cd21 And Cd24 Co-Expression: A Translational Model Between Mouse And Human, Abigail Benitez

Loma Linda University Electronic Theses, Dissertations & Projects

Systemic Lupus Erythematosus and Rheumatoid Arthritis are B cell-mediated autoimmune diseases that afflict millions of people worldwide. B cell-targeted therapies for these diseases result in variable clinical outcomes. Thus, a need exists to better understand the dynamics of human B cell production and function. The mouse model has provided a foundation for understanding the mechanisms involved in human B cell development and autoimmune disease. However, differences in mouse and human B cells are not fully understood. Our work shows that the co-expression of CD21 and CD24, determined by 7-color flow cytometry, can be used to demarcate developmental subsets of B …

Quantitative Characterization Of Conserved Noncoding Regions By Flow Cytometry, Amber Brown

Loma Linda University Electronic Theses, Dissertations & Projects

Spatial and temporal regulation of developmental gene transcription often involves regulatory sequences found in noncoding DNA separate from the gene’s promoter. Conservation of a noncoding region (CNR) across divergent species may indicate a regulatory region critical to basic morphogenesis. CNR-green fluorescent protein (GFP) constructs can demonstrate spatial and temporal CNR activity by microscopy visualization. However, characterization of regulatory modules within a CNR requires quantitative, in addition to qualitative, analysis. The study presented here describes the development and implementation of a novel application of flow cytometry in the quantitative characterization of CNRs. The technique couples fluorescent microscopy localization with flow cytometry …

Exosomal Survivin-T34a: A Novel, Potential Cancer Therapeutic, Jonathan Richard Aspe

Loma Linda University Electronic Theses, Dissertations & Projects

Pancreatic cancer is the fourth most common cause of cancer fatality in American men and women with a less than 5% survival rate. Currently, if diagnosed early, surgical resection remains the only viable cure. However, only 20% of pancreatic cancer patients meet these criteria. It is therefore necessary to discover new therapies or therapeutic combinations in order to impact significantly this deadly disease. The anti-metabolite agent Gemcitabine is currently being employed to treat pancreatic cancer. While Gem-citabine has shown significant benefit in clinical applications, its ability to more than modestly impact pancreatic cancer is limited. It has been speculated that …

Effect Of Maternal Hypoxia On Fetal Development: Programming Of Hie Phenotype In Neonatal Rat Brain, Pablo J. Gonzalez-Rodriguez

Loma Linda University Electronic Theses, Dissertations & Projects

Developmental programming of health and disease correlates the adverse intrauterine environment and the risk of disease later in life as cardiovascular disease, metabolic diseases, renal dysfunction or neurobehavioral disorders among others. Maternal hypoxia is one of the most common intrauterine growth restricted environment during pregnancy. Perinatal hypoxic-ischemic encephalopathy is an important cause of brain injury in the newborn due to a systematic asphyxia. Our study aims to test the hypothesis that maternal hypoxia affect the organogenesis of the kidney by affecting the kidney structure and focusing on the roles of AT1R and AT2R, while the brain development will also be …

Benefits And Barriers To Hiv Testing In A Population Of Federal Detention Inmates, Nicole A. Knight

Loma Linda University Electronic Theses, Dissertations & Projects

Voluntary HIV testing in combination with early medical intervention has been shown to be effective in reducing the rate of new infections and improving the health and life expectancy of those living with HIV. There are however several high-risk populations in the US that remain largely unreached by HIV testing efforts, some of which could be reached while they spend time in prison or jail. Per current Bureau of Prisons (BOP) policy, HIV testing is routinely offered only to “high risk” pretrial and sentenced inmates. We conducted a cross-sectional study with 721 pretrial and sentenced inmates who entered a large …

Survivin: Regulation By Yy1 And Role In Pancreatic Cancer Combination Therapy, Nicholas R. Galloway

Loma Linda University Electronic Theses, Dissertations & Projects

Despite significant clinical and basic science advancements, cancer remains a devastating disease that affects people of all ages, races, and background. Survivin, the fourth most common transcript found in cancer cells, is a protein that is thought to be involved in the enhanced proliferation, survival, and metastasis of cancer cells. Therefore understanding how this gene is regulated is potentially of vital importance to improving cancer management and therapy. Our work has identified a novel transcriptional regulator of survivin called Yin Yang 1 (YY1). YY1 is a transcription factor that has been observed to activate some gene promoters and repress others, …

Retinoic Acid Regulation Of Thyroid Hormone Action In Bone Cells, Anjali Babbar

Loma Linda University Electronic Theses, Dissertations & Projects

Retinoic acid and thyroid hormone are known to play key roles in the regulation of endochondral ossification. However, the issue of whether these two hormones interact with each other to regulate bone functions remains to be established. We investigated how thyroid hormone and retinoic acid interact to regulate cells involved in endochondral bone formation. We demonstrate that thyroid hormone treatment stimulates differentiation of ATDC5 chondrocytes and promotes formation of mineralized nodules while retinoic acid treatment at high dose inhibits chondrocyte differentiation and formation of mineralized nodules. Furthermore, thyroid hormone induced mineralized nodule formation is inhibited by co-treatment with retinoic acid …

Caveolins And Njks Influence Brain Endothelial Permeability After Juvenile Tbi, David Olufemi Ajao

Loma Linda University Electronic Theses, Dissertations & Projects

Disruption of blood-brain barrier (BBB) is a key secondary event that exacerbates brain damage following traumatic brain injury (TBI). BBB disruption is particularly damaging to the developing brain – which is highly vulnerable to various stress stimuli, resulting in increased brain swelling, disrupted cerebral blood flow (CBF) autoregulation, long-term disabilities and death following TBI in young demographic. Unsurprisingly, BBB disruption and the resultant cerebral edema have emerged as therapeutic targets in juvenile TBI. It is therefore important to understand the molecular players and mechanisms involved in TBI-induced BBB disruption in the juvenile brain. To this end, the endothelial caveolins and …

Expression And Function Of Ca2+-Activated K+ Channels In Uterine Arteries, Ronghui Zhu

Loma Linda University Electronic Theses, Dissertations & Projects

Chronic hypoxia during pregnancy is one of the most common insults to the maternal cardiovascular system and fetal development, and is associated with increased uterine vascular tone and heightened risk of preeclampsia and fetal intrauterine growth restriction (IUGR). The present study tested the hypothesis that calcium-activated potassium (KCa) channels play an essential role in uterine vascular adaptation to pregnancy, which is inhibited by chronic hypoxia during gestation. Uterine arteries (UAs) were isolated from nonpregnant ewes (NPUAs) and near-term pregnant ewes (PUAs) that had been maintained at sea level (~300 m) or exposed to high altitude (3,801 m) for 110 days. …

Fetal Programming And Later Obesity In A Predominantly Latino Wic Population, Eric George Walsh

Loma Linda University Electronic Theses, Dissertations & Projects

Background: In utero stressors may work to program the metabolism of the developing fetus in such a way that predisposes him/her to obesity later on. Studies have shown that breastfeeding is protective against childhood obesity and suggest that after six months the weight gain in breastfed babies slows opposed to formula fed babies who continue with rapid weight gain. This slowing of weight gain has been shown to be protective against adiposity and later life weight gain.

Purpose: This study looks to further explore these findings in a low income Latino population adding mother’s feelings about the pregnancy and the …

Ontogeny Of Venom Use And Venom Composition In The Western Widow Spider Latrodectus Hesperus, David Roger Nelsen

Loma Linda University Electronic Theses, Dissertations & Projects

I investigated the behavioral ecology of venom and venom use by the western widow spider (Latrodectus hesperus), emphasizing the role of ontogeny. In an introductory paper, I reviewed existing definitions of venom and poison, and refined these by adding a third category of toxic biological secretions: toxungen. These three can be distinguished by mode of toxin delivery and presence of a wound. In the first of four empirical studies, I investigated venom use by adult females in the context of threat assessment. A single brief poke at the lowest threat level elicited primarily avoidance responses ("move" and "retract"), repeated prodding …

Small Molecule Inhibitors Of Hpv16 E6, Chung-Hsiang Yuan

Loma Linda University Electronic Theses, Dissertations & Projects

High-risk human papillomaviruses (HR-HPVs) cause nearly all cases of cervical cancer. HPV 16 E6, one of two viral oncogenes, protects cells from apoptosis by binding to and accelerating the degradation of several apoptotic proteins, including caspase 8 and p53. We proposed that blocking the interactions between HPV E6 and its partners using small molecules had the potential to re-sensitize HPV+ cells to apoptosis. To test this prediction, we screened libraries of small molecules for candidates that could block E6/caspase 8 binding, and identified several candidates from different chemical classes. Testing hits for dose-dependency and specificity in vitro and for toxicity …

Relationship Between Nut Consumption And Memory Domains Of Cognitive Function Among Elderly Seventh-Day Adventists, Angeline B. David

Loma Linda University Electronic Theses, Dissertations & Projects

Objective. To determine the relationship between consumption of all types of nuts, tree nuts, and peanut and peanut butter and specific memory domains of cognitive function in a community-dwelling elderly population.

Design. Cross-sectional analysis using clinic data from the Biopsychosocial Religion and Health Study and dietary intake data from the Adventist Health Study-2.

Subjects/Methods. Adults aged 50 and older were administered the California Verbal Learning Test-II (CVLT) Short Form and provided self-report frequency and portion sizes of nut consumption, anthropometric measures, and other demographic, lifestyle, and clinic data. CVLT scores were age- and gender-strata specific z-scores normed to a …

Effects Of Consuming Beans Before Or With A Meal On Satiety And Gastrointestinal Hormones Concentration In Obese Men And Women, Lisa Delia Griffith

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Consuming beans and staggering meals may control energy intake. We examined the effect of consuming 0.5 cup of beans 15 minutes before a meal on gastrointestinal (GI) peptides concentrations in obese men and women.

Methods: A randomized crossover design was used to measure GI peptides response to two test meals in 28 healthy obese adults. Subjects consumed a standardized breakfast meal on each test day followed by one of two test meals: a meal incorporating 0.5 cup of beans (control bean meal), and an isocaloric meal (staggered bean meal) in which 0.5 cup of beans was consumed 15 minutes …