Life Sciences Commons^™

Autonomic And Behavioral Reactivity To An Acute Laboratory Stressor, Jeremy C. Peres

University of New Orleans Theses and Dissertations

Stress has been widely shown to directly influence people’s emotional and behavioral processing as well as their underlying biological systems. This project examined physiological and behavioral responses as indicators of stress and coping in the context of a psychosocial stressor in a controlled laboratory setting. We examined the association between indicators of behavioral coping and underlying physiological reactivity within participants while experiencing stress. Participants included 68 emerging adults. Physiological measures include autonomic biomarkers (e.g., heart-rate, skin conductance) at rest and during the stressor while behavioral indicators that were coded include acute verbal and non-verbal actions exhibited by participants during the …

Involvement Of Interleukin-33/St2 In Myocardial Dysfunction In Murine Model Of Sepsis, Yoonmi Choe

Electronic Thesis and Dissertation Repository

The disruption of myocardial extracellular matrix (ECM) has been implicated in myocardial dysfunction during sepsis. However, the underlying mechanism(s) are not clear. Interleukin-33 (IL-33) is a cytokine which regulates collagen synthesis in various cardiac pathologies. The purpose of the present study is to test whether IL-33 contributes to sepsis-induced myocardial dysfunction through regulation of matrix metalloproteinase-9 (MMP-9). The in vivo, feces-induced peritonitis (FIP) in mice and in vitro lipopolysaccharide (LPS) treatments to isolated cardiomyocytes were used. In FIP mice, myocardial IL-33 and MMP-9 expression were increased and myocardial contractility was decreased. Myocardial function in FIP mice was improved when treated …

Health Care Informatics Support Of A Simulated Study, Zeinab Salari Far

Theses and Dissertations

The objective of this project is to assess the value of REDCap (Harris, 2009) by conducting a simulated breast cancer clinical trial and demonstration. REDCap is a free, secure, web-based application designed to support data capture for research studies. To assess REDCap's value, we conducted a simulation of a clinical trial study designed to compare the use of two new technologies for breast cancer diagnosis and treatment with current best practice breast cancer diagnosis and treatment. We call the trial, "Real-Time Operating Room BC Diagnostic Treatment (RORBCDT)". The RORBCDT clinical trial is designed to assess the value of a new …

A Systematic Framework For Radio Frequency Identification (Rfid) Hazard Mitigation In The Blood Transfusion Supply Chain From Donation To Distribution, Natalie Simone Rahming

Theses and Dissertations

The RFID Consortium is developing what will be the first FDA-approved use of radio frequency identification (RFID) technology to identify, track, manage, and monitor blood throughout the entire blood transfusion supply chain. The iTraceTM is an innovative technological system designed to optimize the procedures currently employed when tracing blood from the donor to the recipient. With all novel technologies it is essential to consider not only the advantages, but also the potential harms that may come about from using the system. The deployment of the iTraceTM consists of two phases: 1) Phase One - application of the iTraceTM from the …

Characterization Of Beryllium As A Novel Agent To Study Cell Cycle Arrest And Cellular Senescence, Priyatham Gorjala

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cancer cells evade senescence, apoptosis, and other constraints on proliferation, often via mutation of the p53 tumor suppressor gene (TP53). Normal human lung fibroblasts have been shown to enter premature senescence upon exposure to beryllium. In these cells, BeSO₄ stabilizes p53 protein, increases p21 gene expression, induces senescence-associated β-galactosidase activity and causes cell proliferation arrest. In the present study, we have investigated whether BeSO₄ is able to induce similar effects in cancer cells that have wildtype p53. We have demonstrated that beryllium salt at low concentration can induce molecular changes in the p53 signaling pathway leading to cell …

Trim24-Regulated Estrogen Response Is Dependent On Specific Histone Modifications In Breast Cancer Cells, Teresa T. Yiu

Dissertations & Theses (Open Access)

In this dissertation, I discovered that function of TRIM24 as a co-activator

of ERα-mediated transcriptional activation is dependent on specific histone

modifications in tumorigenic human breast cancer-derived MCF7 cells. In the first

part, I proved that TRIM24-PHD finger domain, which recognizes unmethylated

histone H3 lysine K4 (H3K4me0), is critical for ERα-regulated transcription.

Therefore, when LSD1-mediated demethylation of H3K4 is inhibited, activation of

TRIM24-regulated ERα target genes is greatly impaired. Importantly, I

demonstrated that TRIM24 and LSD1 are cyclically recruited to estrogen

responsive elements (EREs) in a time-dependent manner upon estrogen

induction, and depletion of their expression exert corresponding time-dependent

effect …

Regulation Of The Heat Shock Response By Thiol-Reactive Compounds In The Yeast Saccharomyces Cerevisiae, Yanyu Wang

Dissertations & Theses (Open Access)

Cells govern their activities and modulate their interactions with the environment to achieve homeostasis. The heat shock response (HSR) is one of the most well studied fundamental cellular responses to environmental and physiological challenges, resulting in rapid synthesis of heat shock proteins (HSPs), which serve to protect cellular constituents from the deleterious effects of stress. In addition to its role in cytoprotection, the HSR also influences lifespan and is associated with a variety of human diseases including cancer, aging and neurodegenerative disorders. In most eukaryotes, the HSR is primarily mediated by the highly conserved transcription factor HSF1, which recognizes target …

Anti-Tumor Effects Of The Notch Pathway In Gastrointestinal Stromal Tumors, Amaury G. Dumont

Dissertations & Theses (Open Access)

Gastrointestinal Stromal Tumors (GIST) are sarcomas driven by gain-of-function mutations of KIT or PDGFRA. Although, the introduction of tyrosine kinase inhibitors has dramatically changed the history of this disease, evidences emerge that inhibition of KIT or PDGFRA are not sufficient to cure patients. The developmental pathway Notch has a critical role in the cell fate, regulating cell proliferation and differentiation. Dysregulation of Notch pathway has been implicated in a wide variety of cancers functioning as a tumor promoter or a tumor suppressor in a cell context dependent manner.

Given that Notch activation deregulates the morphogenesis of mesenchymal cells in …

The Role Of The Arched Helicases In Exosome-Mediated Function, A. Alejandra Klauer

Dissertations & Theses (Open Access)

RNA processing and degradation are two important functions that control gene expression and promote RNA fidelity in the cell. A major ribonuclease complex, called the exosome, is involved in both of these processes. The exosome is composed of ten essential proteins with only one catalytically active subunit, called Rrp44. While the same ten essential subunits make up both the nuclear and cytoplasmic exosome, there are nuclear and cytoplasmic exosome cofactors that promote specific exosome functions in each of the cell compartments. To date, it is unclear how the exosome distinguishes between RNA substrates. We hypothesize that compartment specific cofactors may …

Functional Analysis Of Drosophila Integrator Complex In Snrna 3' End Processing, Jiandong Chen

Dissertations & Theses (Open Access)

Uridine-rich small nuclear RNAs (U snRNAs) play essential roles in eukaryotic gene expression by facilitating the removal of introns from mRNA precursors and the processing of the replication-dependent histone pre-mRNAs. Formation of the 3’ end of these snRNAs is carried out by a poorly characterized, twelve-membered protein complex named Integrator Complex.

In the effort to understand Integrator Complex function in the formation of the snRNA 3’ end, we performed a functional RNAi screen in Drosophila S2 cells to identify protein factors required for snRNA 3’ end formation. This screen was conducted by using a fluorescence-based reporter that elicits GFP expression …

Immunological Mechanisms Of Extracorporeal Photopheresis In Cutaneous T Cell Lymphoma And Graft Versus Host Disease, Lisa Shiue

Dissertations & Theses (Open Access)

IMMUNOLOGICAL MECHANISMS OF EXTRACORPOREAL PHOTOPHERESIS IN CUTANEOUS T CELL LYMPHOMA AND GRAFT VERSUS HOST DISEASE

Publication No.___________

Lisa Harn-Ging Shiue, B.S.

Supervisory Professor: Madeleine Duvic, M.D.

Extracorporeal photopheresis (ECP) is an effective, low-risk immunomodulating therapy for leukemic cutaneous T cell lymphoma (L-CTCL) and graft versus host disease (GVHD), but whether the mechanism(s) of action in these two diseases is (are) identical or different is unclear. To determine the effects of ECP in vivo, we studied regulatory T cells (T-regs), cytotoxic T lymphocytes (CTLs), and dendritic cells (DCs) by immunofluorescence flow cytometry in 18 L-CTCL and 11 GVHD patients before …

Effects Of Obesity On Thermoregulation And Cardiovascular Function During Exercise In Females, Jon David Adams

Graduate Theses and Dissertations

Previous research has shown that obese individuals are at greater risk for heat illnesses because of impaired thermoregulation. However, laboratory studies investigating cardiovascular and thermoregulatory function in obese individuals are difficult to interpret because of low sample sizes and methodological concerns. The purpose of this study was to determine if there are differences in thermoregulatory and cardiovascular function between obese and non-obese females. Twenty-four females, 13 obese (43.3 ± 4 .3 % fat, 77.2 ± 13.7 kg) and 11 non-obese (27.8 ± 6.0 % fat, 55.7±6.7 kg), cycled for 60 min in a warm environment (~40°C, 30% humidity) at a …

Prostate Cancer Stem Cells: Drug Tolerance, Experimental Reconstitution And Castration Resistance, Xin Chen

Dissertations & Theses (Open Access)

Prostate cancer (PCa) is one of the leading malignancies affecting men in the Western world. Although tremendous effort has been made towards understanding PCa development and developing clinical treatments in the past decades, the exact mechanisms of PCa are still not clearly understood. Emerging evidence has postulated that a population of stem cell-like cells inside a tumor, termed ‘cancer stem cells (CSCs)’, may be the cells responsible for tumor initiation, progression, recurrence, metastasis and therapy resistance. Like CSC studies in other cancer types, it has been reported that PCa also contains CSCs. However, there remain several unresolved questions that need …

Cellular Uptake Of Neutrohpil Elastase Links Inflammation To Adaptive Immunity, Elizabeth A. Mittendorf

Dissertations & Theses (Open Access)

Many tumors arise from sites of inflammation providing evidence that innate immunity is a critical component in the development and progression of cancer. Neutrophils are primary mediators of the innate immune response. Upon activation, an important function of neutrophils is release of an assortment of proteins from their granules including the serine protease neutrophil elastase (NE). The effect of NE on cancer has been attributed primarily to its ability to degrade the extracellular matrix thereby promoting invasion and metastasis. Recently, it was shown that NE could be taken up by lung cancer cells leading to degradation of insulin receptor substrate-1 …

Dreissena Rostiformis Bugensis: Desiccation Of Adult Quagga Mussels Found In Lake Mead As A Preventive Measure Against Overland Dispersal In The Western United States, Matthew Kappel

UNLV Theses, Dissertations, Professional Papers, and Capstones

The expansion of civilization across all borders of the world has proven to affect major components of ecosystems. Since the introduction and establishment of the aquatic invasive species (AIS),Dreissena rostiformis bugensis, commonly known as the quagga mussel, into the United States there has been an extensive amount of time and money spent on controlling and preventing their expansion across the United States. The quagga mussel is of major concern because of its ability to disrupt the ecological communities in previously non-infested bodies of water, which may cause a loss in biodiversity and effect environmental health. The quagga mussel has spread …

Complexity And Uncertainty In Human And Ecological Risk Assessment, Matthew Jordan Dellinger

Theses and Dissertations

Multiple interacting stressors in the environment present increasingly complex risks to human health. Too often, however, the data required for traditional risk assessment are either lacking or unavailable at the necessary spatial or temporal scale. In addition, assessment practices and management policies need to move away from single factor approaches in order to accommodate the reality of complex chemical mixtures and environmental stressors. Recent literature suggests that a paradigm shift is under way. This points to a need for the development of new techniques both for rapid data collection and flexible risk assessment strategies that can adapt to make use …

Genetic Analysis Of The Hippo Pathway In Mouse Liver, Li Lu

Dissertations & Theses (Open Access)

Cancer therapy and tumor treatment remain unsolved puzzles. Genetic screening for tumor suppressor genes in Drosophila revealed the Hippo-signaling pathway as a kinase cascade consisting of five core components. Disrupting the pathway by deleting the main component genes breaks the balance of cell proliferation and apoptosis and results in epithelial tissue tumorigenesis. The pathway is therefore believed to be a tumor suppressor pathway. However, a corresponding role in mammals is yet to be determined. Our lab began to investigate the tumor suppression function of the potent mammalian Hippo pathway by putting floxed alleles into the mouse genome flanking the functional-domain-expressing …

Biochemical Characterization Of Binding Partners Of Two Hsp70 Co-Chaperones In Saccharomyces Cerevisiae, Jacob Verghese

Dissertations & Theses (Open Access)

Cells are exposed to a variety of environmental and physiological changes including temperature, pH and nutrient availability. These changes cause stress to cells, which results in protein misfolding and altered cellular protein homeostasis. How proteins fold into their three-dimensional functional structure is a fundamental biological process with important relevance to human health. Misfolded and aggregated proteins are linked to multiple neurodegenerative diseases, cardiovascular disease and cystic fibrosis. To combat proteotoxic stress, cells deploy an array of molecular chaperones that assist in the repair or removal of misfolded proteins.

Hsp70, an evolutionarily conserved molecular chaperone, promotes protein folding and helps maintain …

Differential Activity Of The Kras Oncogene By Method Of Activation: Implications For Signaling And Therapeutic Intervention, Nathan Ihle

Dissertations & Theses (Open Access)

Despite having been identified over thirty years ago and definitively established as having a critical role in driving tumor growth and predicting for resistance to therapy, the KRAS oncogene remains a target in cancer for which there is no effective treatment. KRas is activated b y mutations at a few sites, primarily amino acid substitutions at codon 12 which promote a constitutively active state. I have found that different amino acid substitutions at codon 12 can activate different KRas downstream signaling pathways, determine clonogenic growth potential and determine patient response to molecularly targeted therapies. Computer modeling of the KRas structure …

Identifying Genetic Variants And Characterizing Their Role In Clubfoot, Katelyn S. Weymouth

Dissertations & Theses (Open Access)

Clubfoot is a common, complex birth defect affecting 4,000 newborns in the United States and 135,000 world-wide each year. The clubfoot deformity is characterized by inward and rigid downward displacement of one or both feet, along with persistent calf muscle hypoplasia. Despite strong evidence for a genetic liability, there is a limited understanding of the genetic and environmental factors contributing to the etiology of clubfoot. The studies described in this dissertation were performed to identify variants and/or genes associated with clubfoot. Genome-wide linkage scan performed on ten multiplex clubfoot families identified seven new chromosomal regions that provide new areas to …

Characterization Of A Novel Role For The Tousled- Like Kinase In Kinetochore Assembly And Function In Caenorhabditis Elegans, Jessica M. De Orbeta

Dissertations & Theses (Open Access)

Chromosome segregation is a critical step during cell division to avoid aneuploidy and promote proper organismal development. Correct sister chromatid positioning and separation during mitosis helps to achieve faithful transmission of genetic material to daughter cells. This prevents improper chromosome partitioning that can potentially result in extrachromosomal fragments, increasing the tumorigenic potential of the cells. The kinetochore is a protenaicious structure responsible for the initiation and orchestration of chromosome movement during mitosis. This highly conserved structure among eukaryotes is required for chromosome attachment to the mitotic spindle and failure to assemble the kinetochore results in aberrant chromosome segregation. Thus elucidating …

Stress-Adaptation And Stress-Induced Changes In Campylobacter Jejuni, Geetha Sanal Kumar-Phillips

Graduate Theses and Dissertations

The foodborne pathogen Campylobacter jejuni is one of the leading causes of human gastroenteritis. This bacterium is not a robust organism compared with many other foodborne pathogens and requires special conditions in the laboratory for its growth. In nature, however, this organism is able to survive in very diverse and hostile environments and produce disease in humans. The different mechanisms by which C. jejuni survives stressful conditions in the environment remain unclear. Adhesion and invasion are thought to be important factors for the colonization of C. jejuni in the intestinal tracts of hosts. Previous research in our laboratory showed that …

Frictional Forces Of A Fixed, Esthetic Orthodontic Appliance System, Brady Michael Nance

UNLV Theses, Dissertations, Professional Papers, and Capstones

Purpose: The demands of an all esthetic fixed orthodontic appliance system are ever increasing in today's world. Frictional values of an esthetic, fixed orthodontic appliance system are needed to evaluate their clinical effectiveness for orthodontic treatment. The aim of this study is to evaluate the frictional values of various esthetic orthodontic archwires ligated to an esthetic orthodontic bracket.

Methods: Three types of stainless steel and nickel titanium alloy (niti) esthetic orthodontic archwires (epoxy, poly, plastic) in four sizes (.016, .018, .017 x .025, .019 x .025 inches) were ligated to both a stainless steel bracket system and a ceramic (esthetic) …

A Study On The Function Of 14-3-3sigma In Regulating Cancer Energy Metabolism, Liem M. Phan, Liem M. Phan

Dissertations & Theses (Open Access)

Metabolic reprogramming has been shown to be a major cancer hallmark providing tumor cells with significant advantages for survival, proliferation, growth, metastasis and resistance against anti-cancer therapies. Glycolysis, glutaminolysis and mitochondrial biogenesis are among the most essential cancer metabolic alterations because these pathways provide cancer cells with not only energy but also crucial metabolites to support large-scale biosynthesis, rapid proliferation and tumorigenesis. In this study, we find that 14-3-3σ suppresses all these three metabolic processes by promoting the degradation of their main driver, c-Myc. In fact, 14-3-3s significantly enhances c-Myc poly-ubiquitination and subsequent degradation, reduces c-Myc transcriptional activity, and down-regulates …

The Impact Of Bovine Spongiform Encephalopathy (Bse) On World Protein Supply, Jarrod Kersey

Graduate Theses and Dissertations

As world population, per capita income and urbanization increase, consumption of meat, poultry, milk and eggs will continue to rise to meet the needs of approximately nine billion people in 2050. Global beef, pig and chicken production and per capita consumption increased between 2000 and 2010, with growth in broiler production and consumption outpacing both beef and swine. The increased production and consumption requires readily available feed ingredients in regions where animal production is rapidly developing. Animal-based protein feed ingredients are often difficult to move from country to country due to real or perceived risk of animal disease. Zoosanitary standards …

Evaluating The Impact Of Two Different Methods Of Diabetes Self-Management Education On Knowledge, Attitude, And Behaviours Of Patients With Type 2 Diabetes Mellitus, Laura B. Briden

Electronic Thesis and Dissertation Repository

This study compared the effectiveness of diabetes self-management education (DSME) methods by examining changes in knowledge, attitude, and behaviour (KAB) after receiving education. Participants from a convenience sample were randomized into two groups, one receiving education through conversation maps and the other through traditional group education. Participants’ knowledge and attitude changes were measured by using a repeated measures pre-test/post-test design and changes in Hb A1c were observed. Focus groups were conducted after education was received to obtain perceptions and self-reported behaviour changes. Significant knowledge and attitude score changes were observed in the conversation map group after education. When comparing the …

Characterization Of Cardiomyopathy In A Mouse Model Of Duchenne Muscular Dystrophy (Dmd) Using Echocardiography, Dce-Ct, And Pet-Fdg, Seyed Hamed Moazami

Electronic Thesis and Dissertation Repository

Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disease that is the result of a loss of functional dystrophin, which causes cardiomyocyte fibrosis and death, leading to cardiomyopathy. In this thesis, I have utilized dynamic contrast-enhanced computed tomography (DCE-CT), positron emission tomography-fluorodeoxyglucose (PET-FDG), echocardiography, and traditional histology to longitudinally assess disease progression and degree of cardiomyopathy in a murine model of DMD (mdx:utrn-/-). No significant changes were observed in the blood flow, blood volume, or cardiac volume measured via DCE-CT, nor in standard uptake value (SUV) of glucose as measured by PET-FDG in the left myocardium between and within …

An Investigation Into The Combined Effects Of Β-Amyloid Toxicity And Cerebral Ischemia On The Pathological Expression Of Gangliosides., Jeffrey D. Hepburn

Electronic Thesis and Dissertation Repository

Identifying mechanisms underlying the synergistic pathological interaction between stroke and Alzheimer’s disease (AD) can effectively guide future therapeutic strategies for these highly co-morbid conditions. Aberrant ganglioside expression marked by the pathological accumulation of ganglioside GM3 is common to stroke and AD, yet it is unclear whether GM3 is synergistically enhanced in a comorbid model, or if GM3 is a viable therapeutic target. Adult male Wistar rats received a unilateral ischemic striatal infarct via endothelin-1 (ET-1) injection alone or in combination with bilateral intracerebroventricular injection of the β-Amyloid 25-35 peptide (Aβ) to induce generalized Aβ toxicity (Aβ/ET-1). Animals were sacrificed after …

Sexual Reward And Depression, Andrea R. Di Sebastiano

Electronic Thesis and Dissertation Repository

Sexual behavior in male rats is a complex rewarding behavior and many neurotransmitters and neuropeptides play an important role in mediation of sexual performance, motivation and reward. The hypothalamic neuropeptide orexin has been shown play a key role in reward associated with food and drugs of abuse, but the role of this neuropeptide in control of sexual performance, motivation and reward is currently unclear. First, it was shown that orexin neurons in the hypothalamus are activated during sexual performance and reward. Next, using cell specific lesions of orexin neurons it was demonstrated that orexin is involved in arousal and anxiety, …

Real-Time Analysis Of Brain Tumor Cell Dynamics: Novel Thermoelectric Detection Of L-Glutamate And Cell Metabolism Using Microfluidics, Siva Mahesh Tangutooru

Doctoral Dissertations

This study describes the design, fabrication and applications of a novel thermoelectric microfluidic bio-sensor. The bio-sensor is used for real time detection of the L-glutamate (L-glu) dynamics and metabolism for brain tumor cells immobilized in a microfluidic device. The microfluidic device is fabricated using a polymer/glass laminating technique (Xurography). An antimony-bismuth thin-film thermopile (primary sensing element) is integrated to the microfluidic device. The brain tumor cells are immobilized over the thermopile covering measuring and reference junctions of the thermopile using a poly-l-lysine coating layer. L-glutamate oxidase (L-GLOD) is immobilized over the measuring junctions of the thermopile prior to the immobilization …