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Theses/Dissertations

2013

Cell Biology

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Full-Text Articles in Life Sciences

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 ...


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 ...


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 ...


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 ...


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 ...


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 ...


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 ...


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 ...


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 ...


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 ...


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 ...


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 ...


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 ...


Analysis Of Subcellular Localization Patterns Suggest Non-Enzymatic Roles For Select Arogenate Dehydratases, Travis R. Howes Aug 2013

Analysis Of Subcellular Localization Patterns Suggest Non-Enzymatic Roles For Select Arogenate Dehydratases, Travis R. Howes

Electronic Thesis and Dissertation Repository

The final step of phenylalanine biosynthesis in planta is catalyzed by arogenate dehydratases (ADTs). Previously cloned ADT-CFP fusion genes were used to provide an in depth study of the subcellular localization of all six ADTs from Arabidopsis thaliana. Through co-localization of ADT-CFPs with a stroma-marker it is shown that most ADTs localize to stroma-filled projections from chloroplasts called stromules. The localization of ADT5 and ADT2 provide evidence for additional, non-enzymatic roles. In the case of ADT5, it is found to localize to the nucleus, suggestive of an uncharacterized nuclear role. The localization patterns of ADT2 are suggestive of a role ...


Metformin-Induced Pedf Expression Regulates Cell Proliferation And Lipid Metabolism In Prostate Cancer Cells, Miguel Angel Tolentino Aug 2013

Metformin-Induced Pedf Expression Regulates Cell Proliferation And Lipid Metabolism In Prostate Cancer Cells, Miguel Angel Tolentino

Theses and Dissertations

Prostate cancer (PCa) is one of the most common cancers in American males. A high fat diet and obesity accelerate PCa progression and increase the 1risk of death from disease. Epidemiological studies have indicated that PCa patients with type 2 diabetes have higher mortality rates than PCa patients without diabetes. Type 2 diabetics who are on metformin, a drug to control blood sugar levels, show a delay in PCa progression in comparison with PCa patients with type 2 diabetes who are not on metformin. It has been proposed that metformin inhibits proliferation via activation of AMP-activated protein kinase (AMPK) or ...


Chromatin Insulators: Master Regulators Of The Eukaryotic Genome, Todd Andrew Schoborg Aug 2013

Chromatin Insulators: Master Regulators Of The Eukaryotic Genome, Todd Andrew Schoborg

Doctoral Dissertations

Proper organization of the chromatin fiber within the three dimensional space of the eukaryotic nucleus relies on a number of DNA elements and their interacting proteins whose structural and functional consequences exert significant influence on genome behavior. Chromatin insulators are one such example, where it is thought that these elements assist in the formation of higher order chromatin loop structures by mediating long-range contacts between distant sites scattered throughout the genome. Such looping serves a dual role, helping to satisfy both the physical constraints needed to package the linear DNA polymer within the small volume of the nucleus while simultaneously ...


Characterization Of Jak, Stat, And Src Interactions In Head And Neck Squamous Cell Carcinoma, Reshma Jaseja, Reshma Jaseja Aug 2013

Characterization Of Jak, Stat, And Src Interactions In Head And Neck Squamous Cell Carcinoma, Reshma Jaseja, Reshma Jaseja

UT GSBS Dissertations and Theses (Open Access)

Recurrence of Head and Neck Squamous Cell Carcinoma (HNSCC) is common; thus, it is essential to improve the effectiveness and reduce toxicity of current treatments. Proteins in the Src/Jak/STAT pathway represent potential therapeutic targets, as this pathway is hyperactive in HNSCC and it has roles in cell migration, metastasis, proliferation, survival, and angiogenesis. During short-term Src inhibition, Janus kinase (Jak) 2, and signal transducer and activator of transcription (STAT) 3 and STAT5 are dephosphorylated and inactivated. Following sustained Src inhibition, STAT5 remains inactive, but Jak2 and STAT3 are reactivated following their early inhibition. To further characterize the mechanism ...


Mechanism Of Lpa-Induced Lipid Uptake In Macrophages, Kan Xu Aug 2013

Mechanism Of Lpa-Induced Lipid Uptake In Macrophages, Kan Xu

Masters Theses

Cardiovascular disease, currently the leading cause of mortality throughout the developed countries, is mainly caused by atherosclerosis, which is recognized as a chronic inflammatory disease. Atherosclerotic plaques are characterized by accumulations of lipid in arterial walls together with infiltration of macrophages. These macrophages differentiate from monocytes which transform into foam cells through phagocytizing various forms of lipid, are believed to be the main component of early atherosclerotic lesions.

Lysophosphatidic acid (LPA), a potent bioactive lipid, regulates a broad range of cellular functions in various cell types. In our findings, LPA-induced macrophages may enhance the lipid uptake effect in both J774A ...


The Role Of K63-Linked Ubiquitination Cycles In Akt Kinase Activation, Wei-Lei Yang Aug 2013

The Role Of K63-Linked Ubiquitination Cycles In Akt Kinase Activation, Wei-Lei Yang

UT GSBS Dissertations and Theses (Open Access)

Akt (also known as protein kinase B) serves a central regulator in PI3K/Akt signaling pathways to regulate numerous physiological functions including cell proliferation, survival and metabolism. Akt activation requires the binding of Akt to phospholipid PIP3 on the plasma membrane and subsequent phosphorylation of Akt by its kinases. Growth factor-mediated membrane recruitment of Akt is a crucial step for Akt activation. However, the mechanism of Akt membrane translocation is unclear. Protein ubiquitination is a significant posttranslational modification that controls many biological functions such as protein trafficking and signaling activation. Therefore, we hypothesize that ubiquitination may be involved in Akt ...


Proteomic And Biochemical Studies Of Estrogen-Mediated Signaling And Novel Estrogen Receptor-Interacting Proteins In Breast Cancer Cells, Zhenqi Zhou Aug 2013

Proteomic And Biochemical Studies Of Estrogen-Mediated Signaling And Novel Estrogen Receptor-Interacting Proteins In Breast Cancer Cells, Zhenqi Zhou

Theses and Dissertations

Estrogen plays essential roles in the growth, development, and homeostasis of a number of tissues, and can also be linked to the growth of breast cancer. The biological activities of estrogen are mediated by estrogen receptors (ERs) ERá and ERâ, and also orphan G-protein-coupled receptor 30 (GPR30). In order to identify novel proteins that are involved in ER-mediated actions of estrogen, we used mass spectrometry-based quantitative proteomic methods to systematically profile global protein expression in responses to E2 (17â-estradiol) stimulation in human breast cancer cell, and identify and characterize cellular novel proteins that are associated with ERs in breast cancer ...


P2x7 Nucleotide Receptor Signaling In Osteoblasts, Matthew W. Grol Jul 2013

P2x7 Nucleotide Receptor Signaling In Osteoblasts, Matthew W. Grol

Electronic Thesis and Dissertation Repository

Nucleotides are released from cells of the osteoblast lineage in response to mechanical stimulation, and signal through two families of P2 nucleotide receptors – G protein-coupled P2Y receptors and ligand-gated P2X cation channels. Nearly every cell-type expresses multiple P2 receptor subtypes. However, the significance of these networks of receptors in any system is unclear. In this thesis, we demonstrate that the endogenous network of P2 receptors expressed by osteoblasts permits graded increases in Ca2+ signaling over a million-fold range of ATP concentrations. P2Y receptors mediate transient activation of the Ca2+/NFATc1 pathway, whereas stimulation of P2X7 causes sustained Ca ...


Morphogenetic Requirements For Embryo Patterning And The Generation Of Stem Cell-Derived Mice: A Dissertation, Yeonsoo Yoon Jul 2013

Morphogenetic Requirements For Embryo Patterning And The Generation Of Stem Cell-Derived Mice: A Dissertation, Yeonsoo Yoon

GSBS Dissertations and Theses

Cell proliferation and differentiation are tightly regulated processes required for the proper development of multi-cellular organisms. To understand the effects of cell proliferation on embryo patterning in mice, we inactivated Aurora A, a gene essential for completion of the cell cycle. We discovered that inhibiting cell proliferation leads to different outcomes depending on the tissue affected. If the epiblast, the embryonic component, is compromised, it leads to gastrulation failure. However, when Aurora A is inactivated in extra-embryonic tissues, mutant embryos fail to properly establish the anteroposterior axis. Ablation of Aurora A in the epiblast eventually leads to abnormal embryos composed ...


Studies Of Proliferating Cell Nuclear Antigen Mutant Proteins Defective In Translesion Synthesis And Mismatch Repair, Lynne Margaret Dieckman Jul 2013

Studies Of Proliferating Cell Nuclear Antigen Mutant Proteins Defective In Translesion Synthesis And Mismatch Repair, Lynne Margaret Dieckman

Theses and Dissertations

Proliferating cell nuclear antigen (PCNA) is a versatile protein involved in all pathways of DNA metabolism. It is best known as a processivity factor for classical polymerases, which synthesize DNA on non-damaged templates during DNA replication (ex: pol δ). Non-classical polymerases, on the other hand, are those that synthesize DNA on damaged templates (ex: pol η). PCNA also functions in repair, recombination, and most other DNA-dependent cellular processes. A number of separation of function mutant PCNA proteins have been identified, suggesting that PCNA could be a valuable target to manipulate DNA metabolism. This thesis focuses on the study of PCNA ...


New Types Of Morpho-Physiological Changes In Cells Exposed To Nanosecond Pulsed Electric Field, Mikhail A. Rassokhin Jul 2013

New Types Of Morpho-Physiological Changes In Cells Exposed To Nanosecond Pulsed Electric Field, Mikhail A. Rassokhin

Theses and Dissertations in Biomedical Sciences

Exposure of cells to a pulsed electric field (PEF) is the basis of multiple techniques and treatments. Nanosecond pulsed electric field (nsPEF) poses unique characteristics to induce subtle cellular effects while preserving cell integrity. Improving understanding of the mechanisms triggered by nsPEF in cells inspires new applications for the nanosecond pulse technology. Although many effects of nsPEF remain unknown, they can be inferred from morpho-physiologic changes, or cell reshaping, that accompany nsPEF exposure. During the exposure cells undergo reshaping that is manifested in swelling and diffuse blebbing. Recently we identified two new distinct forms of reshaping, pseudopod-like blebbing and microvesiculation ...


Understanding The Contribution Of Individual Zinc Fingers To A Multi-Functional, Polydactyl Transcription Factor, Ryan M. Baxley Jul 2013

Understanding The Contribution Of Individual Zinc Fingers To A Multi-Functional, Polydactyl Transcription Factor, Ryan M. Baxley

Theses and Dissertations

Suppressor of Hairy-wing [Su(Hw)] is a twelve zinc-finger (ZF), DNA binding transcription factor. Su(Hw) has been well characterized as critical component of the gypsy insulator complex, required for the enhancer blocking and the barrier activity of the insulator. In addition to gypsy, Su(Hw) localizes to ~3,000 binding sites in the Drosophila genome, with association to a subset of sites required for female germline development. Loss of Su(Hw) results in activation of a developmental checkpoint and apoptosis at mid- oogenesis, with a critical role during oogenesis in down-regulation of neural genes. Studies of Su(Hw) function ...