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Theses/Dissertations

2013

Cell and Developmental Biology

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Full-Text Articles in Life Sciences

The Effects Of Nesting Environment On Neonatal Hypoxic-Ischemic Injury, Laura Grace Rollins Dec 2013

The Effects Of Nesting Environment On Neonatal Hypoxic-Ischemic Injury, Laura Grace Rollins

Graduate Masters Theses

Term neonates with hypoxic-ischemic (HI) injury are at risk for devastating neurological sequelae. The objective of this study is to determine if altering the early environment for maternal care-taking impacts the immediate and long-term sequelae of HI offspring. The Rice-Vannucci model was used to induce HI in postnatal day (PND) 7 Long-Evans pups. Litters were assigned to a closed nest (CN) or normal standard housing (SH) condition. Neurobehavioral development, cognitive ability, and stress response were assessed to establish any benefits of the CN condition. Finally, postmortem brain tissue was analyzed for morphometric markers of injury.


Prenatal Programming Of Hepatic Glucose And Cholesterol Regulation In Male Rat Offspring By Chronic Intermittent Hypoxia, Waseem Iqbal Dec 2013

Prenatal Programming Of Hepatic Glucose And Cholesterol Regulation In Male Rat Offspring By Chronic Intermittent Hypoxia, Waseem Iqbal

Electronic Thesis and Dissertation Repository

Obstructive sleep apnea (OSA) is a chronic disorder involving repetitive interruptions in breathing during sleep. Sufferers of OSA are exposed to chronic intermittent hypoxia (CIH), characterized by cyclical reductions in oxygen availability. A number of studies have established a link between OSA and various cardiovascular and metabolic comorbidities in adulthood, including hypertension, obesity, and type II diabetes. While the consequences of OSA in adults have been well described, the cross-generational impact of this condition and potential effects on fetal development are not known. Epidemiological and animal studies have demonstrated that physiological insults during pregnancy lead to diminished growth of offspring ...


A Forward Genetics Approach To Identify Molecular Drivers Of Liver Cancer Using Sleeping Beauty Mouse Models, Jesse Daniel Riordan Dec 2013

A Forward Genetics Approach To Identify Molecular Drivers Of Liver Cancer Using Sleeping Beauty Mouse Models, Jesse Daniel Riordan

Theses and Dissertations

Each year liver cancer kills more than half a million people, making it the third

leading cause of cancer-related death worldwide. Annual incidence continues to rise steadily, both domestically and globally, increasing the burden of this disease. Advancements in the ability to obtain detailed molecular profiles of tumors have led to the successful development of targeted therapies for a number of different cancers. Unfortunately, however, the molecular pathogenesis of liver cancer is poorly understood relative to many other types of malignancies. Thus, the identification of factors contributing to the development and progression of liver tumors is a major goal of ...


New Insights Into The Roles Of Human Dna Damage Checkpoint Protein Atr In The Regulation Of Nucleotide Excision Repair And Dna Damage-Induced Cell Death, Zhengke Li Dec 2013

New Insights Into The Roles Of Human Dna Damage Checkpoint Protein Atr In The Regulation Of Nucleotide Excision Repair And Dna Damage-Induced Cell Death, Zhengke Li

Electronic Theses and Dissertations

Integrity of the human genome is frequently threatened by endogenous and exogenous DNA damaging reagents that may lead to genome instability and cancer. Cells have evolved multiple mechanisms to repair DNA damage or to eliminate the damaged cells beyond repair and to prevent diverse diseases. Among these are ataxia telangiectasia and Rad3-related (ATR)-mediated DNA damage checkpoint and nucleotide excision repair (NER) that are the major pathways by which cells handle ultraviolet C (UV-C)- or other exogenous genotoxin-induced bulky DNA damage. However, it is unclear how these 2 pathways may be coordinated. In this study we show that ATR physically ...


The Molecular Mechanisms Of Pitx2 In Tooth Development And Enamel Defects In Axenfeld-Rieger Syndrome, Xiao Li Dec 2013

The Molecular Mechanisms Of Pitx2 In Tooth Development And Enamel Defects In Axenfeld-Rieger Syndrome, Xiao Li

Theses and Dissertations

Patients with Axenfeld-Rieger Syndrome (ARS) present various dental abnormalities. ARS is genetically associated with mutations in the PITX2 gene, which encodes one of the earliest transcription factors to initiate tooth development. Thus, Pitx2 has long been considered as an upstream regulator of the transcriptional hierarchy in tooth development. However, it is unclear how its mutant forms cause ARS dental anomalies. In this report, we outline the transcriptional mechanism that is defective in ARS. We demonstrate that during normal tooth development Pitx2 activates Amelogenin (Amel) expression, whose product is required for enamel formation, and that this regulation is perturbed by missense ...


Ezh2 T416 Phosphorylation Enhances Breast Cancer Tumorigenesis, Adam M. Labaff, Adam M. Labaff Dec 2013

Ezh2 T416 Phosphorylation Enhances Breast Cancer Tumorigenesis, Adam M. Labaff, Adam M. Labaff

UT GSBS Dissertations and Theses (Open Access)

Enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and catalyzes the trimethylation of histone H3 on lysine 27 (H3K27Me3), to repress gene transcription. Many types of cancer stem and progenitor cells, including breast, have demonstrated EZH2 to be fundamental in the biology and promoting the expansion of their cellular populations. How EZH2 regulates each of these respective tumor initiating cells (TICs) populations has been studied, but the signaling transduction mechanisms that regulate EZH2 in these TIC populations is yet to be elucidated. Phosphorylation of EZH2 by cyclin dependent kinases (CDK) has been ...


Developmental And Molecular Functions Of Plakophilin-3, William A. Munoz Dec 2013

Developmental And Molecular Functions Of Plakophilin-3, William A. Munoz

UT GSBS Dissertations and Theses (Open Access)

Plakophilin-3, the less studied member of the plakophilin-catenin subfamily, and the larger catenin family, binds directly to desmosomal cadherin cytoplasmic domains and enhances desmosome formation and stability. In mammals, plakophilin-3 is expressed at the highest levels in desmosome-enriched tissues such as epithelia, with the knock-out in mice producing corresponding reductions in ectodermal integrity. In tissue, cellular and intracellular contexts where plakophilin-3 is not at the desmosomal plaque, little is known about its functions in the cytoplasm or nucleus, where it also localizes.

My work employed embryos of the amphibian, Xenopus laevis, to examine plakophilin-3’s developmental roles. I first evaluated ...


Investigating Apoptosis Pathway In Chronic Lymphocytic Leukemia: Stromal Influence And Therapeutic Activation, Viralkumar M. Patel Dec 2013

Investigating Apoptosis Pathway In Chronic Lymphocytic Leukemia: Stromal Influence And Therapeutic Activation, Viralkumar M. Patel

UT GSBS Dissertations and Theses (Open Access)

Chronic lymphocytic leukemia (CLL) is a B-cell malignancy. High levels of Bcl-2 and IAP family proteins are responsible for apoptotic-resistance and accumulation of mature CLL lymphocytes in bone-marrow, lymph nodes and peripheral blood. Besides pro-survival proteins, supporting stromal cells as well as soluble factors in the microenvironment of bone-marrow and lymph nodes provide survival advantage to CLL leukemic cells.

Though the stromal – leukemia cell interactions has been studied extensively, in-depth-knowledge on the regulation of apoptotic pathway proteins in the context of microenvironment is still limited. To address this, the first part of our study focused on comprehensive analysis of 93 ...


C-Jun N-Terminal Kinases Regulate Adenovirus-Mediated Autophagy And Antigen Presentation, Sarah R. Klein Dec 2013

C-Jun N-Terminal Kinases Regulate Adenovirus-Mediated Autophagy And Antigen Presentation, Sarah R. Klein

UT GSBS Dissertations and Theses (Open Access)

Targeted immunotherapy with recombinant, oncolytic adenoviruses is under investigation for the treatment of cancer. Evidence indicates adenoviruses induce autophagy that is required for oncolysis, but the molecular regulation of autophagy in infected cells remains under investigation. Our data suggested the canonical pathway regulating starvation-induced autophagy was not implemented in adenovirus-induced autophagy; however, adenovirus infection triggered phosphorylation of c-Jun N-terminal kinases (JNK) that was essential for autophagy. Adenoviral replication within the host cell elicited JNK pathway activation leading to B cell lymphoma-2 (Bcl-2) phosphorylation. JNK-dependent Bcl-2 phosphorylation stimulated the dissociation of Bcl-2/beclin 1 heterodimers, enabling beclin 1 to initiate autophagy ...


Characterization Of Cis-Acting Partners Within The Cytomegalovirus Major Immediate-Early Enhancer That Strengthen Mie Gene Expression And Viral Fitness, Courtney Searcey Galle Dec 2013

Characterization Of Cis-Acting Partners Within The Cytomegalovirus Major Immediate-Early Enhancer That Strengthen Mie Gene Expression And Viral Fitness, Courtney Searcey Galle

Theses and Dissertations

Human cytomegalovirus infects approximately 50% of adults in the United States and in most cases is asymptomatic. However, in the case of immune compromised persons such as AIDS patients, transplant patients, and newborn babies, life threatening CMV disease can occur. The HCMV major immediate-early enhancer functions as a master regulatory switch, whose activation is essential for the expression of the major IE transactivating proteins, IE1 p72 and IE2 p86. While critical to the viral lifecycle, regulation of MIE enhancer activation is very complex and not yet fully understood. I characterized the role of cis-acting partners within the MIE enhancer that ...


Cell Biological Defects In Juvenile Neuronal Ceroid Lipofuscinosis, Mark Schultz Dec 2013

Cell Biological Defects In Juvenile Neuronal Ceroid Lipofuscinosis, Mark Schultz

Theses and Dissertations

Mutations in the CLN3 gene cause Juvenile Neuronal Ceroid Lipofuscinosis (JNCL), a form of Batten disease that is grouped within the broad class of lysosomal storage diseases. JNCL displays a primary central nervous system phenotype characterized by rapid onset blindness, wide spread brain atrophy and reversal of learned abilities with death occurring 10-20 years after symptom onset. The mechanisms underlying these phenotypes are not known. CLN3 encodes CLN3, a protein with no known molecular function. CLN3 is expressed at very low levels natively in most cells, and is highly hydrophobic.

Similar to other lysosomal storage diseases, it is difficult to ...


Development Of Novel Subunit Vaccine Against H5n1 Influenza, Lu Zhang Dec 2013

Development Of Novel Subunit Vaccine Against H5n1 Influenza, Lu Zhang

Theses and Dissertations

Influenza is a common infectious disease resulting from a frequently mutated RNA virus. Vaccination is currently the most effective method to prevent people from seasonal or pandemic influenza. The production of traditional egg-based influenza vaccine is time-consuming and provides limited effect against new strains. Therefore, it is necessary to develop a rapid method to produce influenza vaccines. We proposed a novel influenza vaccine based on the E.coli expression system. Hemagglutinin (HA) is the major target surface protein of influenza virus for vaccine development. In this study, we sub-cloned the HAs encoding gene into an E. coli expression vector; the ...


Investigating Potential Bioactive Compounds From Rhodococcus And Their Effects On Mcf7 Breast Cancer Cells, Megan N. Crabtree Dec 2013

Investigating Potential Bioactive Compounds From Rhodococcus And Their Effects On Mcf7 Breast Cancer Cells, Megan N. Crabtree

Electronic Theses and Dissertations

Many drugs used in the treatment of various cancers are derived from or influenced by compounds from nature. The soil bacterium Rhodococcus is of interest because of its identified secondary metabolic pathways and the production of novel natural antibiotics from several strains. In this study, a solid agar extraction method was used to collect compounds from strains of Rhodococcus. These bacterial compound extracts were then tested using a MTT assay in order to evaluate their effectiveness in augmenting MCF7 breast cancer cell death. The results of two way ANOVA analyses revealed 18 compound extracts from 15 strains of Rhodococcus that ...


Endothelial Agonists Stimulate Vwf Release In Vitro And Trigger Ttp In Vivo, Gilbert Van Schaeffer Dec 2013

Endothelial Agonists Stimulate Vwf Release In Vitro And Trigger Ttp In Vivo, Gilbert Van Schaeffer

Theses and Dissertations

Von Willebrand factor (VWF) is a plasma glycoprotein that can bind collagen at a wound site as well as circulating platelets. VWF forms high molecular weight multimers (>20,000 kDa). VWF can also form VWF strings that appear to be attached to the endothelial surface and are capable of binding platelets. These strings are only observed in vitro and in vivo in the absence of the VWF-cleaving protease ADAMTS13. Deficiency in ADAMTS13 results in thrombotic thrombocytopenic purpura (TTP), a clotting disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, renal dysfunction, neurological dysfunction and fever. Patients suffering from TTP demonstrate VWF-and platelet-rich ...


A Novel Role For Prolyl-Hydroxylase 3 Gene Silencing In Epithelial-To-Mesenchymal-Like Transition, Trenton Lane Place Dec 2013

A Novel Role For Prolyl-Hydroxylase 3 Gene Silencing In Epithelial-To-Mesenchymal-Like Transition, Trenton Lane Place

Theses and Dissertations

The ability of cells to sense oxygen is a highly evolved process that facilitates adaptations to the local oxygen environment and is critical to energy homeostasis. In vertebrates, this process is largely controlled by three intracellular prolyl-4-hydroxylases (PHD 1-3). These related enzymes share the ability to hydroxylate the hypoxia-inducible transcription factor (HIF), and therefore control the transcription of genes involved in metabolism and vascular recruitment. However, it is becoming increasingly apparent that proline-4-hydroxylation controls much more than HIF signaling, with PHD3 emerging as the most unique and functionally diverse of the PHD isoforms. In fact, PHD3-mediated hydroxylation has recently been ...


Protective Effects Of Sphingomyelin Against Uv Photodamage In Human Keratinocytes, Kathleen De Guzman Dec 2013

Protective Effects Of Sphingomyelin Against Uv Photodamage In Human Keratinocytes, Kathleen De Guzman

Master's Theses and Project Reports

Ultraviolet (UV) radiation has been demonstrated in numerous studies to be a major risk factor for non-melanoma skin cancer development. Despite the emergence of current UV-preventative strategies, such as sunscreens and skin-protective clothing, the incidence of non-melanoma skin cancer has continued to rise. This has encouraged investigations on alternative methods for UV prevention. In particular, bovine milk sphingomyelin has been studied for its potential in protecting human skin against UV photodamage. While the previous studies have suggested that sphingomyelin exhibits UV-protective properties in a human skin equivalent model, the exact mechanisms behind sphingomyelin’s photoprotective effects are yet unknown.

This ...


The Development Of An In Vivo Microdialysis Collection Method Of Cytokines From Brain Tissue, Anthony W. Herbaugh Dec 2013

The Development Of An In Vivo Microdialysis Collection Method Of Cytokines From Brain Tissue, Anthony W. Herbaugh

Theses and Dissertations

In this thesis, different methods to improve the microdialysis collection procedure for cytokines from brain tissue are presented. The first method was based on stopped flow and results indicating that no significant difference in relative recovery between stopped flow and continuous flow are shown. The second method is an antibody bead-based enhancement method. With the antibody bead-based method, a 3.5 fold increase in the collected concentrations of Chemokine (C-C motif) Ligand 2 (CCL2) were observed. However, there was no significant increase in the in vivo collection efficiency of Interleukin-6 (IL-6) using the antibody enhancement. Finally the development of an ...


Endocannabinoid-Dependent Long-Term Depression Of Ventral Tegmental Area Gaba Neurons, Jared Mark Weed Dec 2013

Endocannabinoid-Dependent Long-Term Depression Of Ventral Tegmental Area Gaba Neurons, Jared Mark Weed

Theses and Dissertations

GABA neurons in the ventral tegmental area of the midbrain are important components in the brain's reward circuit. Long term changes in this circuit occur through the process of synaptic plasticity. It has been shown that high frequency stimulation, as well as treatment with endocannabinoids, can cause GABA neurons in the ventral tegmental area to undergo long term depression, a form of synaptic plasticity that decreases excitability of cells. The present study elaborates on the mechanism whereby high frequency stimulation can result in long term depression of ventral tegmental area GABA neurons. Using the whole cell patch clamp technique ...


Involvement Of Ampk And Ap-1 Biochemical Pathways In Il-6 Regulation Of Steroidogenic Enzymes In The Adrenal Cortex, Matharage Shenali De Silva Dec 2013

Involvement Of Ampk And Ap-1 Biochemical Pathways In Il-6 Regulation Of Steroidogenic Enzymes In The Adrenal Cortex, Matharage Shenali De Silva

Theses and Dissertations

The adrenal cortex is a crucial endocrine gland in the mammalian stress response. In chronic inflammatory stress, cortisol is elevated whereas adrenal androgens are decreased. Furthermore, ACTH levels have poor correlation with the plasma cortisol in these conditions, thus suggesting that other factors are driving the stress response during chronic inflammatory stress. Interleukin-6 (IL-6), a cytokine which is released during chronic inflammatory stress, is assumed to be one such factor. Thus the biochemical pathways by which IL-6 increases cortisol release from the zona fasciculata (ZF), and decreases adrenal androgen release from the zona reticularis (ZR) were investigated. Since IL-6 activates ...


Fgf4 Induced Wnt5a Gradient In The Limb Bud Mediates Mesenchymal Cell Directed Migration And Division, John C. Allen Dec 2013

Fgf4 Induced Wnt5a Gradient In The Limb Bud Mediates Mesenchymal Cell Directed Migration And Division, John C. Allen

Theses and Dissertations

The AER has a vital role in directing embryonic limb development. Several models have been developed that attempt to explain how the AER directs limb development, but none of them are fully supported by existing data. I provide evidence that FGFs secreted from the AER induce a gradient of Wnt5a. I also demonstrate that limb mesenchyme grows toward increasing concentrations of Wnt5a. We hypothesize that the changing shape of the AER is critical for patterning the limb along the proximal to distal axis. To better understand the pathway through which Wnt5a elicits its effects, we have performed various genetic studies ...


Transforming Growth Factor-Beta Receptor Signalling Is Modulated By Integrin-Linked Kinase, Stellar H. Boo Nov 2013

Transforming Growth Factor-Beta Receptor Signalling Is Modulated By Integrin-Linked Kinase, Stellar H. Boo

Electronic Thesis and Dissertation Repository

Transforming growth factor-beta 1 (TGF-β1) modulates regeneration after injury through induction of fibroblast proliferation, migration, and differentiation into myofibroblasts. Induction of myofibroblast differentiation by TGF-β1 requires expression of integrin-linked kinase (ILK). I now show that ILK interacts with TGF-β receptor type II (TβRII) in primary dermal fibroblasts. Further, colocalization of ILK and TβRII can be observed at the cell membrane and in intracellular vesicles. The association of TβRII and ILK does not require TGF-β1 stimulation, kinase activity of TGF-β1 receptor type I or TβRII, and it does not involve interactions between ILK and focal adhesion-associated proteins. When this interaction is ...


Hox Gene Regulation And Function During Zebrafish Embryogenesis: A Dissertation, Steven E. Weicksel Oct 2013

Hox Gene Regulation And Function During Zebrafish Embryogenesis: A Dissertation, Steven E. Weicksel

GSBS Dissertations and Theses

Hox genes encode a conserved family of homeodomain containing transcription factors essential for metazoan development. The establishment of overlapping Hox expression domains specifies tissue identities along the anterior-posterior axis during early embryogenesis and is regulated by chromatin architecture and retinoic acid (RA). Here we present the role nucleosome positioning plays in hox activation during embryogenesis. Using four stages of early embryo development, we map nucleosome positions at 37 zebrafish hox promoters. We find nucleosome arrangement to be progressive, taking place over several stages independent of RA. This progressive change in nucleosome arrangement on invariant sequence suggests that trans-factors play an ...


The Mechanism Of The Gastric Epithelial Stem Cell Response To Metaplastic Injury, Shradha Sachin Khurana Oct 2013

The Mechanism Of The Gastric Epithelial Stem Cell Response To Metaplastic Injury, Shradha Sachin Khurana

All Theses and Dissertations (ETDs)

Almost nothing is known about the identity of the epithelial stem cell of the gastric corpus, either during normal turnover or in response to injury. Our lab has shown that injection of the selective estrogen receptor modulator tamoxifen leads to near complete atrophy of parietal cells by 3 days and induces expansion of an undifferentiated cell population within the normal stem cell niche in the isthmus of the gastric unit. Here we show that CD44 labels the membranes of such undifferentiated isthmal cells, both in the normal gastric epithelium and when those cells expand fourfold upon injury with tamoxifen. Loss ...


Establishing The Role Of The Pancreatic Transcription Factor Mist1 In Xbp1-Mediated Maintenance Of Pancreatic Acinar Cell Homeostasis, David Alan Hess Oct 2013

Establishing The Role Of The Pancreatic Transcription Factor Mist1 In Xbp1-Mediated Maintenance Of Pancreatic Acinar Cell Homeostasis, David Alan Hess

Open Access Dissertations

Pancreatic acinar cells (PACs) continuously produce more protein than any other cell type in the human body. As a result, PACs and other specialized secretory cells have a constant demand placed on their protein synthetic and packaging machinery. When demand for secreted products exceeds the capacity of the cell's basal protein production facilities, dangerous accumulations of misfolded proteins can build up, resulting in a condition known as ER stress. To ameliorate this stress, secretory cells activate a coordinated, three-part compensatory network collectively known as the unfolded protein response (UPR) to both expand the capacity of the ER and directly ...


Measuring And Modeling The Response Characteristics Of The Environmental Phosphate Transducer In Escherichia Coli, Chetan Sood Oct 2013

Measuring And Modeling The Response Characteristics Of The Environmental Phosphate Transducer In Escherichia Coli, Chetan Sood

Open Access Dissertations

The PhoR/PhoB two-component system in Escherichia coli is a biological transducer that senses the limitation of environmental inorganic orthophosphate, the bacteria's preferred source of the essential nutrient phosphate, and transmits that information to the interior of the cell initiating a response that mitigates phosphate starvation. In the first part of this study, we present and apply a fluorescence microscopy technique to measure, in vivo, the dynamic response characteristics of the transducer with single-cell resolution. We report that the transience in the PhoR/PhoB TCS response is consistent with the transducer having a threshold sensitivity to the concentration of ...


A Novel Autophagy Regulatory Mechanism That Functions During Programmed Cell Death: A Dissertation, Tsun-Kai Chang Sep 2013

A Novel Autophagy Regulatory Mechanism That Functions During Programmed Cell Death: A Dissertation, Tsun-Kai Chang

GSBS Dissertations and Theses

Autophagy is a cellular process that delivers cytoplasmic materials for degradation by the lysosomes. Autophagy-related (Atg) genes were identified in yeast genetic screens for vehicle formation under stress conditions, and Atg genes are conserved from yeast to human. When cells or animals are under stress, autophagy is induced and Atg8 (LC3 in mammal) is activated by E1 activating enzyme Atg7. Atg8-containing membranes form and surround cargos, close and mature to become the autophagosomes. Autophagosomes fuse with lysosomes, and cargos are degraded by lysosomal enzymes to sustain cell viability. Therefore, autophagy is most frequently considered to function in cell survival. Whether ...


Developmental Characterization Of Tissue Inhibitor Of Metalloproteinase Domain Functions In Xenopus Laevis, Michelle A. Nieuwesteeg Sep 2013

Developmental Characterization Of Tissue Inhibitor Of Metalloproteinase Domain Functions In Xenopus Laevis, Michelle A. Nieuwesteeg

Electronic Thesis and Dissertation Repository

During development the extracellular matrix is cleaved and remodeled to facilitate the large-scale cell rearrangements that are necessary for processes like gastrulation, neurulation, angiogenesis and organogenesis. ECM remodeling occurs primarily through secreted enzymes called matrix metalloproteinases (MMPs). Regulation of MMP activity is achieved through the tissue inhibitor of metalloproteinases (TIMPs), a small family of secreted proteins that bind MMPs in a 1:1 manner to inhibit their activity. Although TIMPs were originally characterized based on their MMP-inhibitory activities, in vitro studies have revealed that TIMPs are multifunctional proteins, with structurally and functionally distinct N- and C-terminal domains. TIMP N-terminal domains ...


The Role Of Ykl-40 In The Progression Of Glioblastoma, Ralph Anthony Francescone Sep 2013

The Role Of Ykl-40 In The Progression Of Glioblastoma, Ralph Anthony Francescone

Open Access Dissertations

Glioblastoma Multiforme (GBM) is the most common brain cancer and one of the most fatal forms of cancer overall. The average survival time is 10-14 months, and less than 10% of patients survive more than 5 years after diagnosis. It is characterized by extreme vasculature, chemo/radioresistance, and invasiveness into the normal brain. The current standard of care, which includes surgical removal of tumor, radiation, and the chemotherapeutic agent temozolomide, initially stunt tumor growth. Nevertheless, the tumor invariably rebounds and the patient succumbs to the disease. Therefore, there is an urgent need to develop new therapies for this devastating disease ...


Effects Of Phytochemicals From Rhodiola Crenulata On Highly Invasive Breast Cancer Cell Lines And Embryonic Models Of Migration, Adaris Rodriguez-Cortes Sep 2013

Effects Of Phytochemicals From Rhodiola Crenulata On Highly Invasive Breast Cancer Cell Lines And Embryonic Models Of Migration, Adaris Rodriguez-Cortes

Open Access Dissertations

The root of the Tibetan plant Rhodiola crenulata is part of eastern traditional medicine. Studies have suggested that members of the Rhodiola genus display anticancer properties. In this study we examine the effect of R. crenulata in a cellular model of invasive breast cancer, this disease being the second cause of cancer death among women in the US. Deregulation of the Wnt/β-catenin pathway has been frequently observed in breast cancers and appears to have a key role in the transformation of benign cells to a malignant form. Although mutations of the Wnt growth factor are rarely observed in cancer ...


Hiv-1 And The Nucleolus: A Role For Nucleophosmin/Npm1 In Viral Replication: A Dissertation, Tracy E. Schmidt Aug 2013

Hiv-1 And The Nucleolus: A Role For Nucleophosmin/Npm1 In Viral Replication: A Dissertation, Tracy E. Schmidt

GSBS Dissertations and Theses

The nucleolus is a plurifunctional organelle with dynamic protein exchange involved in diverse aspects of cell biology. Additionally, the nucleolus has been shown to have a role in the replication of numerous viruses, which includes HIV-1. Several groups have reported HIV-1 vRNA localization within the nucleolus. Moreover, it has been demonstrated the HIV-1 Rev protein localizes to the nucleolus and interacts with nucleolar proteins, including NPM1. Despite evidence for a nucleolar involvement during replication, a functional link has not been demonstrated. I investigated whether introncontaining vRNAs have a Rev-mediated nucleolar localization step prior to export. Furthermore, I examined whether NPM1 ...