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Loss Of Gprc5a Enhances Survival In Normal And Malignant Lung Epithelial Cells By Eliciting Persistent Stat3 Activation Induced By Autocrine Lif, Yulong Chen 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Loss Of Gprc5a Enhances Survival In Normal And Malignant Lung Epithelial Cells By Eliciting Persistent Stat3 Activation Induced By Autocrine Lif, Yulong Chen

UT GSBS Dissertations and Theses (Open Access)

Signal transduction and activator of transcription 3 (Stat3) is activated by cytokines and growth factors in many cancers. Persistent activation of Stat3 plays important role in cell growth, survival, and transformation through regulating its targeted genes.

Previously, we found that mice with a deletion of the G protein-coupled receptor, family C, group 5, member a (Gprc5a) gene develop lung tumors indicating that Gprc5a is a tumor suppressor. In the present study, we examined he mechanism of Gprc5a-mediated tumor suppression. We found that epithelial cells from Gprc5a knockout mouse lung (Gprc5a-/- cells) survive better in vitro in medium deprived of exogenous ...


Characterization Of Alpha-Galactosylceramide As A Mucosal Adjuvant, Amy N. Courtney 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Characterization Of Alpha-Galactosylceramide As A Mucosal Adjuvant, Amy N. Courtney

UT GSBS Dissertations and Theses (Open Access)

Adjuvants are essential components of vaccine formulations that enhance adaptive immune responses to antigens, particularly for immunizations targeting the tolerogenic mucosal tissues, which are more biologically relevant for protective immunity against pathogens transmitted by the mucosal routes. Adjuvants possess the inherent capacity to bridge innate and adaptive immune responses through activating innate immune mediators. Here evidence is presented in support of the effectiveness of a synthetic glycolipid, alpha-Galactosylceramide (-GalCer), as an adjuvant for mucosal immunization with peptide and protein antigens, by oral and intranasal routes, to prime antigen-specific immune responses in multiple systemic and mucosal compartments. The adjuvant activity of ...


Understanding Acquired Resistance To Lapatinib In Breast Cancer Cells, Jen-Te Tseng 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Understanding Acquired Resistance To Lapatinib In Breast Cancer Cells, Jen-Te Tseng

UT GSBS Dissertations and Theses (Open Access)

Signaling through epidermal growth factor receptor (EGFR/ErbB) family members plays a very important role in regulating proliferation, development, and malignant transformation of mammary epithelial cells. ErbB family members are often over-expressed in human breast carcinomas. Lapatinib is an ErbB1 and ErbB2 tyrosine kinase inhibitor that has been shown to have anti-proliferative effects in breast and lung cancer cells. Cells treated with Lapatinib undergo G1 phase arrest, followed by apoptosis. Lapatinib has been approved for clinical use, though patients have developed resistance to the drug, as seen previously with other EGFR inhibitors. Moreover, the therapeutic efficacy varies significantly within the ...


Nherf1 – New Modifier Of Colorectal Cancer Progression, Yuho Hayashi 2010 University of Texas Health Science Center at Houston

Nherf1 – New Modifier Of Colorectal Cancer Progression, Yuho Hayashi

UT GSBS Dissertations and Theses (Open Access)

Colorectal cancer (CRC) develops from multiple progressive modifications of normal intestinal epithelium into adenocarcinoma. Loss of cell polarity has been implicated as an early event in this process, but the molecular players involved are not well known. NHERF1 (Na+/H+ Exchanger Regulatory Factor 1) is an adaptor protein with apical membrane localization in polarized epithelia. In this study, we tested our hypothesis that NHERF1 plays a role in CRC. We examined surgical CRC resection specimens for changes in NHERF1 expression, and modeled these changes in two- and three-dimensional (2D and 3D) Caco-2 CRC cell systems. NHERF1 had significant alterations from ...


Characterizing A Novel Genetic Locus Associated With Familial Co-Occurrence Of Thoracic Aortic Aneurysms And Intracranial Aneurysms, Alexander H. Li 2010 University Of Texas Graduate School of Biomedical Sciences at Houston

Characterizing A Novel Genetic Locus Associated With Familial Co-Occurrence Of Thoracic Aortic Aneurysms And Intracranial Aneurysms, Alexander H. Li

UT GSBS Dissertations and Theses (Open Access)

The Mendelian inheritance of genetic mutations can lead to adult-onset cardiovascular disease. Several genetic loci have been mapped for the familial form of Thoracic Aortic Aneurysms (TAA), and many causal mutations have been identified for this disease. Intracranial Aneurysms (ICA) also show linkage heterogeneity, but no mutations have been identified causing familial ICA alone.

Here, we characterized a large family (TAA288) with an autosomal dominant pattern of inherited aneurysms. It is intriguing that female patients predominantly present with ICA and male patients predominantly with TAA in this family. To identify a causal mutation in this family, a genome-wide linkage analysis ...


The Role Of Tyrosine Phosphorylation In The Functions Of The Tumor Suppressor Gprc5a, xiaofeng lin 2010 University of Texas Graduate School of Biomedical Sciences at Houston

The Role Of Tyrosine Phosphorylation In The Functions Of The Tumor Suppressor Gprc5a, Xiaofeng Lin

UT GSBS Dissertations and Theses (Open Access)

The retinoic acid inducible G protein coupled receptor family C group 5 type A (GPRC5A) is expressed preferentially in normal lung tissue but its expression is suppressed in the majority of human non-small cell lung cancer cell lines and tissues. This differential expression has led to the idea that GPRC5A is a potential tumor suppressor. This notion was supported by the finding that mice with a deletion of the Gprc5a gene develop spontaneous lung tumors. However, there are various tumor cell lines and tissue samples, including lung, that exhibit higher GPRC5A expression than normal tissues and some reports by other ...


Double-Strand Break Repair Pathways In Dna Structure-Induced Genetic Instability, Diem T. Kha 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Double-Strand Break Repair Pathways In Dna Structure-Induced Genetic Instability, Diem T. Kha

UT GSBS Dissertations and Theses (Open Access)

Genetic instability in mammalian cells can occur by many different mechanisms. In the absence of exogenous sources of DNA damage, the DNA structure itself has been implicated in genetic instability. When the canonical B-DNA helix is naturally altered to form a non-canonical DNA structure such as a Z-DNA or H-DNA, this can lead to genetic instability in the form of DNA double-strand breaks (DSBs) (1, 2). Our laboratory found that the stability of these non-B DNA structures was different in mammals versus Escherichia coli (E.coli) bacteria (1, 2). One explanation for the difference between these species may be a ...


Direct Inputs To Off Α And G9 Ganglion Cells From Aii Amacrine Cells In Rabbit Retina, Wei-Li Liu 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Direct Inputs To Off Α And G9 Ganglion Cells From Aii Amacrine Cells In Rabbit Retina, Wei-Li Liu

UT GSBS Dissertations and Theses (Open Access)

In the mammalian retina, AII amacrine cells are essential in the rod pathway for dark-adapted vision. But they also have a “day job”, to provide inhibitory inputs to certain OFF ganglion cells in photopic conditions. This is known as crossover inhibition. Physiological evidence from several different labs implies that AII amacrine cells provide direct input to certain OFF ganglion cells. However, previous EM analysis of the rabbit retina suggests that the dominant output of the AII amacrine cell in sublamina a goes to OFF cone bipolar cells (Strettoi et al., 1992).

Two OFF ganglion cell types in the rabbit retina ...


E2f1 And Tumor Suppression: The Role Of P21, Mirnas, And The Dna Damage Response, Regina L. Weaks 2010 University of Texas Graduate School of Biomedical Sciences at Houston

E2f1 And Tumor Suppression: The Role Of P21, Mirnas, And The Dna Damage Response, Regina L. Weaks

UT GSBS Dissertations and Theses (Open Access)

E2F1 is a multi-faceted protein that has roles in a number of important cellular processes including cell cycle regulation, apoptosis, proliferation, and the DNA damage response (DDR). Moreover, E2F1 has opposing roles in tumor development, acting as either a tumor suppressor or an oncogene depending on the context. In human cancer, E2F1 is often deregulated through aberrations in the Rb-p16INK4a-cyclin D1 pathway. In these studies we examined three mechanisms by which E2F1 might mediate its tumor suppressive properties: p21-induced senescence, miRNAs, and the DNA damage response. We found that E2F1 acts as a tumor suppressor in response to ras activation ...


Modeling Sporadic Tumor Formation Driven By Telomere Dysfunction In The Gastrointestinal Tract, Suzanne S. Chan 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Modeling Sporadic Tumor Formation Driven By Telomere Dysfunction In The Gastrointestinal Tract, Suzanne S. Chan

UT GSBS Dissertations and Theses (Open Access)

Colorectal cancer is a complex disease that is thought to arise when cells accumulate mutations that allow for uncontrolled growth. There are several recognized mechanisms for generating such mutations in sporadic colon cancer; one of which is chromosomal instability (CIN). One hypothesized driver of CIN in cancer is the improper repair of dysfunctional telomeres. Telomeres comprise the linear ends of chromosomes and play a dual role in cancer. Its length is maintained by the ribonucleoprotein, telomerase, which is not a normally expressed in somatic cells and as cells divide, telomeres continuously shorten. Critically shortened telomeres are considered dysfunctional as they ...


A Metagenomic Study Of The Tick Midgut, Daniel T. Yuan 2010 University of Texas Graduate School of Biomedical Sciences at Houston

A Metagenomic Study Of The Tick Midgut, Daniel T. Yuan

UT GSBS Dissertations and Theses (Open Access)

A Metagenomic Study of the Tick Midgut
Daniel Yuan, B.S.
Supervisory Professor : Steven J. Norris, Ph.D.
Southern tick–associated rash illness (STARI) or Master’s disease is a Lyme-like illness that occurs following bites by Amblyomma americanum, the lone-star tick. Clinical symptoms include a bull’s eye rash similar to the erythema migrans lesions of Lyme disease, as well as fever and joint pains. Lyme disease is caused by Borrelia burgdorferi and related spirochetes. However, B. burgdorferi has not been detected in STARI patients, or in ticks in the South Central U.S. The causative agent of STARI ...


Role And Regulation Of Epha2 In Pancreatic Cancer, Pavel A. Levin 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Role And Regulation Of Epha2 In Pancreatic Cancer, Pavel A. Levin

UT GSBS Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cancer cause of death in the US. Gemcitabine is the first-line therapy for this disease, but unfortunately it shows only very modest benefit. The focus of the current study was to investigate the role and regulation of EphA2, a receptor tyrosine kinase expressed in PDAC, to further understand this disease and identify new therapeutic targets.

The role of EphA2 was determined in PDAC by siRNA mediated silencing. In combination with gemcitabine, silencing of EphA2 caused a dramatic increase in apoptosis even in highly resistant cells in vitro. Furthermore, EphA2 silencing was found ...


Specific, Reversible Cytostatic Protection Of Normal Cells Against Negative Effects Of Chemotherapy, Benjamin B. Mull 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Specific, Reversible Cytostatic Protection Of Normal Cells Against Negative Effects Of Chemotherapy, Benjamin B. Mull

UT GSBS Dissertations and Theses (Open Access)

Chemotherapy is a common and effective method to treat many forms of cancer. However, treatment of cancer with chemotherapy has severe side effects which often limit the doses of therapy administered. Because some cancer chemotherapeutics target proliferating cells and tissues, all dividing cells, whether normal or tumor, are affected. Cell culture studies have demonstrated that UCN-01 is able to reversibly and selectively arrest normal dividing cells; tumor cells lines do not undergo this temporary arrest. Following UCN-01 treatment, normal cells displayed a 50-fold increase in IC50 for camptothecin; tumor cells showed no such increased tolerance.

We have examined the response ...


The Glycoproteins Of Porcine Reproductive And Respiratory Syndrome Virus And Their Role In Infection And Immunity, Phani B. Das 2010 University of Nebraska-Lincoln

The Glycoproteins Of Porcine Reproductive And Respiratory Syndrome Virus And Their Role In Infection And Immunity, Phani B. Das

Dissertations & Theses in Veterinary and Biomedical Science

The porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen of swine and is known to cause abortion and infertility in pregnant sows and respiratory distress in piglets. PRRSV contains a major glycoprotein (GP5) and three minor glycoproteins (GP2a, GP3, and GP4) on the virion envelope, all of which are required for infectious virus production. To study their interactions amongst each other and with a cellular receptor for PRRSV, CD163, I cloned each of the viral glycoproteins and CD163 in various expression vectors. My studies have shown that while the GP2a, GP3, and GP4 are co-translationally glycosylated ...


Mutations In Bone Marrow-Derived Stromal Stem Cells Unmask Latent Malignancy, JeanMarie Houghton, Hanchen Li, Xueli Fan, Yingwang Liu, Jian Hua Liu, Varada P. Rao, Theofilos Poutahidis, Christine L. Taylor, Erin A. Jackson, Christine Hewes, Stephen Lyle, Anna M. Cerny, Glennice N. Bowen, Jan Cerny, Nathan F. Moore, Evelyn A. Kurt-Jones, Susan E. Erdman 2010 University of Massachusetts Medical School

Mutations In Bone Marrow-Derived Stromal Stem Cells Unmask Latent Malignancy, Jeanmarie Houghton, Hanchen Li, Xueli Fan, Yingwang Liu, Jian Hua Liu, Varada P. Rao, Theofilos Poutahidis, Christine L. Taylor, Erin A. Jackson, Christine Hewes, Stephen Lyle, Anna M. Cerny, Glennice N. Bowen, Jan Cerny, Nathan F. Moore, Evelyn A. Kurt-Jones, Susan E. Erdman

GSBS Student Publications

Neoplastic epithelia may remain dormant and clinically unapparent in human patients for decades. Multiple risk factors including mutations in tumor cells or the stromal cells may affect the switch from dormancy to malignancy. Gene mutations, including p53 mutations, within the stroma of tumors are associated with a worse clinical prognosis; however, it is not known if these stromal mutations can promote tumors in genetically at-risk tissue. To address this question, Apc(Min/+) and Apc(Min/+) Rag2(-/-) mice, which have a predilection to mammary carcinoma (as well as wild-type (wt) mice), received mesenchymal stem cells (MSC) with mutant p53 (p53MSC) transferred ...


Meta-Analysis Of Fertilization Experiments Indicates Multiple Limiting Nutrients In Northeastern Deciduous Forests, Matthew A. Vadeboncoeur 2010 University of New Hampshire - Main Campus

Meta-Analysis Of Fertilization Experiments Indicates Multiple Limiting Nutrients In Northeastern Deciduous Forests, Matthew A. Vadeboncoeur

Earth Systems Research Center

It is widely accepted that nitrogen limits primary production in temperate forests, although co-limitation by N and P has also been suggested, and on some soils Ca and base cations are in short supply. I conducted a meta-analysis to assess the strength of existing experimental evidence for limitation of primary production by N, P, and Ca in hardwood forests of the northeastern United States and southeastern Canada, using data from 35 fertilization experiments in deciduous forests on glaciated soils across the region.

There is strong evidence for N limitation (formal meta-analysis weighted mean response ratio = 1.51, p < 0.01; simple mean = 1.42, p < 0.001). Forest productivity also tends to increase with additions of P (simple mean = 1.15, p = 0.05) and Ca (simple mean = 1.36 p < 0.001). Across all treatments, 85% of response ratios were positive. Multiple-element additions had larger effects than single elements, but factorial experiments showed little evidence of synergistic effects between nutrient additions. Production responses correlated positively with the rate of N fertilization, but this effect was reduced at high rates of ambient N deposition.


Temporal And Spatial Assessment Of Evaporation, Transpiration, And Soil Moisture Redistribution, Brian M. Bird 2010 University of Nevada, Las Vegas

Temporal And Spatial Assessment Of Evaporation, Transpiration, And Soil Moisture Redistribution, Brian M. Bird

UNLV Theses, Dissertations, Professional Papers, and Capstones

At a native stand of creosote bush (Larrea tridentata) in North Las Vegas, a rainfall simulation study was conducted over a 12 month period from October 2005 to October 2006. Simulated rainfall occurred during the winter, spring, summer, and fall periods. Rainfall simulation systems were positioned on each of 12 plots, each containing a single creosote bush. Simulated rainfall events occurred at night with multiple short pulses designed to maximize infiltration while minimizing ponding. Yearly simulated rainfall amounts were set at 0, 15, 30 and 60 cm (replicated three times) and were approximately 0, 1.5, 3.0 and 6 ...


The Larval Salivary Gland Of Drosophila Melangogaster: A Model System For Temporal And Spatial Steroid Hormone Regulation, Benjamin Constantino 2010 University of Nevada, Las Vegas

The Larval Salivary Gland Of Drosophila Melangogaster: A Model System For Temporal And Spatial Steroid Hormone Regulation, Benjamin Constantino

UNLV Theses, Dissertations, Professional Papers, and Capstones

Drosophila melanogaster provides an ideal model organism to test genetic and molecular biological mechanisms within the context of a living animal. For over one hundred years Drosophila continues to produce a boundless extent of informative and important scientific data providing crucial insight into development, disease progression and genetic interactions. A century as a model organism allowed for the development of an abundance of unique genetic and molecular tools allowing researchers to tease apart cellular mechanisms with very little limitation. From the whole adult body to tissue function to molecular networks, if a biological question arises it most likely can be ...


Presenilin Is Necessary For The Function Of Cbp In The Adult Drosophila Cns, Randy S. Boyles 2010 University of Nevada, Las Vegas

Presenilin Is Necessary For The Function Of Cbp In The Adult Drosophila Cns, Randy S. Boyles

UNLV Theses, Dissertations, Professional Papers, and Capstones

Dominant mutations in Presenilin (Psn) have been correlated with the formation of Aß- containing plaques in patients with inherited forms of Alzheimer's disease (AD). However, a clear mechanism directly linking amyloid plaques to the pathology of familial or sporadic forms of AD has remained elusive. Thus, recent discoveries of several new substrates for Psn protease activity have sparked alternative hypotheses to explain the preclinical symptoms of AD. CBP (CREB-binding protein) is a haplo- insufficient transcriptional co-activator with histone acetyltransferase (HAT) activity that has been proposed to be a downstream target for Psn signaling. Individuals with reduced CBP levels have ...


The Effect Of Self-Efficacy Manipulation On The Efficiency, Rate Of Perceived Exertion, And Affective State Of Runners, Isabelle Stoate 2010 University of Nevada, Las Vegas

The Effect Of Self-Efficacy Manipulation On The Efficiency, Rate Of Perceived Exertion, And Affective State Of Runners, Isabelle Stoate

UNLV Theses, Dissertations, Professional Papers, and Capstones

Objectives: To determine the effect of self-efficacy manipulation on the movement efficiency, rate of perceived exertion (RPE), and affective state of runners while running on the treadmill at a constant submaximal pace.

Methods: 20 trained male and female runners were randomly assigned to experimental (self-efficacy manipulation) and control groups. Participants first filled out a pre self-efficacy questionnaire and the positive affect negative affect schedule (PANAS), and then completed a 20 minute run on the treadmill running at 75% of their peak treadmill running speed. After 10 minutes, their oxygen consumption (VO2), heart rate (HR), and RPE was recorded. Participants (n ...


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