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Syk Promotes Tgf-Beta-Induced P-Body Clearance In Breast Cancer Cells Through The Enhancement Of Autophagy, Shana D. Hardy
Syk Promotes Tgf-Beta-Induced P-Body Clearance In Breast Cancer Cells Through The Enhancement Of Autophagy, Shana D. Hardy
Open Access Dissertations
SYK is a protein tyrosine kinase that plays an essential role in the development and activation of immune cells. Its expression, however, is not limited to immune cells. SYK is expressed in a variety of epithelial cell types and epithelial-derived tumors. Reports regarding the role of SYK expression in these diverse cell types and tumors have been opposing. In breast cancer, SYK expression has been overwhelmingly associated with tumor suppression. The loss of Syk expression is observed in invasive breast carcinoma tissue and cell lines and the reintroduction of Syk into metastatic breast cancer cells suppresses tumor growth and metastasis. …
Investigating The Effects Of Ph On Alphaviral E3-E2 Glycoprotein Association, Organization, And Cellular Tropism, Jason Michael Sequra
Investigating The Effects Of Ph On Alphaviral E3-E2 Glycoprotein Association, Organization, And Cellular Tropism, Jason Michael Sequra
Open Access Dissertations
In alphaviruses the role of E3 is required in protecting the fusion peptide region of E1 during intracellular transport. Throughout viral processing, the association of E2 and E3 is required for the successful trafficking and incorporation of E1 into the mature virion. This E3-E2 association has been observed to extend to mature virions in the solved structure for the envelope of Semliki Forest virus (SFV) and supported by the solved structure for the entire Venezuelan equine encephalitis virion (VEEV) with exclusive contacts being made between E3-E2. Immunization with monoclonal antibodies against VEEV E3 provided protection for mice challenged by lethal …
Recombinant Listeria Adhesion Protein Expressing Probiotics Protect Against Listeria Monocytogenes Infection In Animal Models, Valerie E. Ryan
Recombinant Listeria Adhesion Protein Expressing Probiotics Protect Against Listeria Monocytogenes Infection In Animal Models, Valerie E. Ryan
Open Access Theses
Listeria monocytogenes (Lm) is a foodborne pathogen, found ubiquitously in nature, and has a high morbidity rate among immunocompromised individuals, the elderly, and especially pregnant women and their fetuses resulting in abortion, stillbirth, and neonatal infection. There are currently no preventative medical interventions against Lm infection. The Listeria adhesion protein (LAP) is present in both pathogenic and non-pathogenic Listeria (i.e., L. innocua) and has shown to interact with host epithelial proteins causing tight junction dysregulation aiding in pathogen attachment and paracellular translocation across the host intestinal epithelium. Our lab has demonstrated that recombinant probiotics, Lactobacillus casei (LbcWT) expressing LAP …
Intestinal Cytoplasmic Lipid Droplets, Associated Proteins, And The Regulation Of Dietary Fat Absorption, Theresa M. D'Aquila
Intestinal Cytoplasmic Lipid Droplets, Associated Proteins, And The Regulation Of Dietary Fat Absorption, Theresa M. D'Aquila
Open Access Dissertations
Dietary fat provides essential nutrients, contributes to energy balance, and regulates blood lipid concentrations. These functions are important to health, but can also become dysregulated and contribute to diseases such as obesity, diabetes, and cardiovascular disease. The small intestine absorbs dietary fat through an efficient multi step process of digestion, uptake, metabolism, and secretion or storage. When dietary fat is taken up by the absorptive cells of the small intestine, enterocytes, it can be secreted into circulation where it contributes to blood lipid levels or temporarily stored in cytoplasmic lipid droplets (CLDs). The objective of this dissertation is to investigate …
Physiological Bases And A Novel Genetic Determinant Of Water-Use Efficiency (Wue), Jie Yin
Physiological Bases And A Novel Genetic Determinant Of Water-Use Efficiency (Wue), Jie Yin
Open Access Dissertations
Water-use efficiency (WUE), the ratio of biomass to water loss, is a heritable but complex trait, the genetic basis of which is largely unknown. We utilized diverse accessions of the halophyte Eutrema salsugineum to ultimately identify a novel genetic determinant of WUE. E. salsugineum accessions from locations with low water availability, temperature, and radiation have lower transpirational water loss and greater biomass, resulting in higher WUE. High-WUE accessions also have lower stomatal density and index and larger thinner leaves than low-WUE accessions. We identified 14,808 single nucleotide polymorphisms (SNPs) between two accessions of E. salsugineum,Shandong (SH) and Yukon (YK), …
Immune Modulating Functions By Soypeptide Lunasin In Cancer Immunotherapy, Chun-Yu Tung
Immune Modulating Functions By Soypeptide Lunasin In Cancer Immunotherapy, Chun-Yu Tung
Open Access Dissertations
Chemotherapy is currently the mainstay of treatment for most cancer patients. Despite its efficacy in eliminating cancer cells, a high percentage of chemotherapy patients eventually relapse or suffer progression of the disease. Immunosurveillance is capable of recognizing and eliminating continuously arising transformed mutant cells, and thus cancer immunotherapy is one of the emerging therapeutic strategies that harnesses the power of the immune system to eradicate chemotherapy-resistant cancerous cells. However, the adverse side effects of chemotherapy impede the therapeutic effects of immunotherapy. Our previous studies demonstrate that lymphoma patients are refractory to clinical immunotherapy because of chemotherapy-induced immune dysfunction. In addition, …
Affinity Cryo-Electron Microscopy: Methods Development And Applications, Guimei Yu
Affinity Cryo-Electron Microscopy: Methods Development And Applications, Guimei Yu
Open Access Dissertations
Single particle cryo-electron microscopy (cryo-EM) is an emerging powerful tool for structural studies of macromolecular assemblies. Although less concentrated and smaller amounts of samples are required for single particle cryo-EM compared to X-ray crystallography, it remains challenging to study specimens that are low-abundance, low-yield, or short-lived. The recent development of affinity grid techniques holds great promise to tackle these challenging samples by combining the sample purification and freezing on TEM grids steps in cryo-EM grid preparation into a single step, revolutionize the grid preparation of cryo-EM, and extend single particle cryo-EM to a routine structural biology tool to characterize structures …
Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung
Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung
Open Access Dissertations
In neurons, normal distribution and selective removal of mitochondria are essential for preserving compartmentalized cellular function. Parkin, an E3 ubiquitin ligase associated with familial Parkinson’s disease, has been implicated in mitochondrial dynamics and removal. However, it is not clear how Parkin plays a role in mitochondrial turnover in vivo, and whether the mature neurons possess a compartmentalized Parkin-dependent mitochondrial life cycle. Using the live Drosophila nervous system, here, I investigate the involvement of Parkin in mitochondrial dynamics; organelle distribution, morphology and removal. Parkin deficient animals displayed less number of axonal mitochondria without disturbing organelle motility behaviors, morphology and metabolic state. …
Alternative Regulation Of Myc In Lung Cancer, Patrick N. Backman
Alternative Regulation Of Myc In Lung Cancer, Patrick N. Backman
Open Access Theses
Lung cancer is the leading cause of cancer deaths in the United States, accounting for 27% of all cancer induced deaths1. In an attempt to create a effective targeted therapy for the treatment of lung cancer, a strategy used to treat an activated KrasG12D/+;p53 R172H/+ transgenic lung cancer mouse model was to deliver a known tumor suppressive microRNA (miRNA) to stop tumor growth. The tumor suppressive miRNA let-7 was lentivirally delivered in the form of its primary transcript, pri-let-7a-1, and resulted in increased lung size and inflammation compared to lungs exposed to a control lentivirus. It was identified …
Susceptibility Of Parkinson’S Disease Following Mild Blast Traumatic Brain Injury, Glen Howel Galicia Acosta
Susceptibility Of Parkinson’S Disease Following Mild Blast Traumatic Brain Injury, Glen Howel Galicia Acosta
Open Access Theses
Blast injury-induced neurotrauma (BINT) is steadily increasing in prevalence due to escalated terror activity and constitutes the signature injury associated with current military conflicts. BINT produces significant neurological deficiencies and there is a growing concern that the injury may produce long-term consequences that affect the resilience and the performance of soldiers. One of the potential consequences is an increased susceptibility to Parkinson's disease (PD). A vital goal aimed at curtailing the post-deployment long-term consequences of blast injury-induced neurotrauma is to further our knowledge of pathogenic mechanisms responsible for the escalation of post injury diseases. The purpose of this project is …
Analysis Of Chd Remodelers During Development: A Tale In Two Organisms, Brett Bishop
Analysis Of Chd Remodelers During Development: A Tale In Two Organisms, Brett Bishop
Open Access Dissertations
The correct development of different organisms requires the precise timing of genes important for development transitions. Organisms have recruited ATP-dependent chromatin remodelers to ensure the correct timing of gene expression during developmental transitions. Here I show how different CHD ATP-dependent chromatin remodelers regulate developmental transitions of different organisms. I show that PICKLE not only promotes H3K27me3 during development to repress developmental genes but also is targeted to these genes. The association of PICKLE to these genes suggests that both repression and H3K27me3 levels is a direct action of PICKLE on these loci. Using zebrafish as a model system, I show …
Characterization Of Hessian Fly From Israel, Alisha J Johnson
Characterization Of Hessian Fly From Israel, Alisha J Johnson
Open Access Dissertations
Mayetiola destructor Say, the Hessian fly, is a gall midge and a member of the Dipteran family Cecidomyiidae. It is a common pest of wheat found throughout all of the major wheat growing areas of the world and poses a serious economic threat to the United States (US), particularly in the Southeast winter wheat region. Damage to wheat is done solely by feeding first and second in-star larvae. Hessian fly (Hf) infestations result in a loss in grain yield by the stunting and/or killing of seedling wheat plants in the winter and by causing breakage at the nodes of the …
Biochemical Investigation Of The Ubiquitin Carboxyl-Terminal Hydrolase Family, Joseph Rashon Chaney
Biochemical Investigation Of The Ubiquitin Carboxyl-Terminal Hydrolase Family, Joseph Rashon Chaney
Open Access Dissertations
The proteasome is the machinery in eukaryotic cells that degrades protein and recycles the amino acids. Protein degradation is a highly regulated process which starts by the attachment of chains of ubiquitin, which serves as a tag that marks a protein for degradation. This function involves the work of several proteins at the proteasome that work either as ubiquitin chaperones, ubiquitin binders or cleave ubiquitin from the protein that is to be degraded. As this is a highly regulated process, various irregularities can have deleterious effects including the onset of disease, including cardiovascular, cancer, and neurological. ^ The focus of …
Transcriptional Stress Response In Foodborne Pathogens, Aaron M. Pleitner
Transcriptional Stress Response In Foodborne Pathogens, Aaron M. Pleitner
Open Access Dissertations
Novel molecular method use is leading to better identification and understanding of microbial presence in food and food processing environments. The application of molecular methods targeting foodborne pathogens provides genetic profiling and targeted intervention methods. Whole-genome sequencing (WGS) provides information on the genomic uniqueness of specific pathogens and is being implemented in epidemiological investigations. Transcriptomic profiling allows for tracking the differential expression of genes and elucidating stress responses. Effective methods and treatments require an understanding of intervention (e.g. sanitizers) and treatment (e.g. antibiotics) mechanisms and efficacies. Accurate novel molecular method use requires proper learning of theory and data management. ^ …
Mach: A Model For Explaining Molecular And Cellular Mechanisms, Caleb M. Trujillo
Mach: A Model For Explaining Molecular And Cellular Mechanisms, Caleb M. Trujillo
Open Access Dissertations
Biologists use mechanistic explanations to understand behaviors of the immense complexity of molecular and cellular systems. In undergraduate biology courses, students are expected to explain molecular and cellular mechanisms, but teaching this skill presents many challenges due to the highly abstract, intangible nature of the cellular world, the influence of everyday language, and the tendency of students to overestimate how much they can explain. Therefore, across three studies this dissertation addresses these obstacles to teach undergraduate biology students to explain molecular and cellular mechanisms. ^ The first step was to model how biology experts explain molecular and cellular mechanisms, and …
Identification, Description, And Activity Of Proteins In The Tergal Glands Of The German Cockroach, Blattella Germanica (L.), Aaron Myers
Open Access Theses
German cockroaches are important urban pests that have been linked to asthma and serious allergic reactions in sensitized individuals. In this research project I, (i) identified different proteins expressed in the tergal glands of male German cockroaches, (ii) determined the expression levels of these proteins in different cockroach life stages and tissues, and (iii) investigated the role of the tergal gland alpha-amylase (BGTG-1) protein. ^ Four major tergal gland proteins were separated on denaturing polyacrylamide gels. With peptide sequencing two of these proteins were identified as alpha-amylase (BGTG-1) and Blattella germanica allergen 2 (Bla g 2). Both of these proteins …
Host Cell Death In Legionella Pneumophila Pathogenesis And Immunity, Wenhan Zhu
Host Cell Death In Legionella Pneumophila Pathogenesis And Immunity, Wenhan Zhu
Open Access Dissertations
Legionella pneumophila is an intracellular pathogen that causes a severe, atypical pneumonia termed Legionnaires' disease. Upon entering the host cell, L. pneumophila resides in a membrane-bound vacuole, in which the bacterium evades lysosomal fusion and replicates. The establishment of the vacuole requires the Dot/Icm (Defect in organelle trafficking/ intracellular multiplication) transport system, which translocates a large number of substrates into host cells to re-orchestrate various cellular processes, such as intracellular trafficking, protein synthesis and host cell death pathways. Therefore, a key step in understanding the biology of Legionella is to dissect the mechanisms of action of the Dot/Icm substrates. By …
Associated Behavioral, Genetic, And Gene Expression Variation With Alternative Life History Tactics In Salmonid Fishes, Ashley Chin-Baarstad
Associated Behavioral, Genetic, And Gene Expression Variation With Alternative Life History Tactics In Salmonid Fishes, Ashley Chin-Baarstad
Open Access Dissertations
Individual differences in behavior can have potential fitness consequences and often reflect underlying genetic variation. My research focuses on three objectives related to individual level variation: 1) evaluating the innate behavioral variation within and between individuals, families, and progeny of different life-history types across time; 2) testing for differences in gene expression within the brain associated with this behavioral variation; and 3) using genetic polymorphisms to test for associations with ecotype, as well as population structure, in polymorphic populations. First, we evaluated the variation in a suite of ecologically relevant behaviors across time in juvenile progeny produced from crosses within …
Dietary Carbohydrates Influence The Structure And Function Of The Intestinal Alpha-Glucosidases, Mohammad Chegeni
Dietary Carbohydrates Influence The Structure And Function Of The Intestinal Alpha-Glucosidases, Mohammad Chegeni
Open Access Dissertations
As the primary products of starch digestion by pancreatic α-amylase, maltooligosaccharides (including maltose) are the main substrates for the α-glucosidases at the intestinal brush border. Here, maltose was shown to induce the formation of a higher molecular weight (HMW) sucrase-isomaltase (SI) species in Caco-2 cells that sorts more quickly to the enterocyte surface to act as a digestive enzyme. As this finding suggested a maltose sensing ability of small intestinal enterocytes, molecular mechanisms associated with the maturation and trafficking of HMW SI were further investigated. A pulse-chase experiment using [ 35S]-methionine revealed a higher rate of early trafficking and …
New Strategies To Reveal Protein Candidates In Protein-Protein Interactome Study, Meng-Chieh Chen
New Strategies To Reveal Protein Candidates In Protein-Protein Interactome Study, Meng-Chieh Chen
Open Access Theses
Comprehensive protein-protein interaction network analysis can help reveal protein functions in a system-wide manner. A reliable knowledgebase of interaction networks is not only important for selecting the candidates for drug therapies, but also for evaluating the disease risk. In current interaction databases, 322579 interactions comprised of 56460 proteins have been reported (statistical analysis from APID: Agile Protein Interaction DataAnalyzer; http://bioinfow.dep.usal.es/apid/index.htm). The huge datasets are contributed mainly by yeast -two -hybrid (Y2H) screening and affinity-purification followed by mass spectrometry (AP-MS). High false positive rates and failing to cover certain interaction categories are the limitations of these two methods. Here, we developed …
Effects Of Altered Expression Of The Sumo Conjugating Enzyme, Ubc9 On Mitosis, Meiosis And Conjugation In Tetrahymena Thermophila, Qianyi Yang
Open Access Dissertations
SUMOylation is a critical posttranslational modification in eukaryotic species. Ubc9p is the E2-conjugating enzyme for SUMOylation and consequently it influences multiple cellular pathways. Nuclear proteins are common targets of SUMOylation and regulate nuclear events such as transcription, DNA repair and mitosis. The segregation of the Tetrahymena thermophila genome into two different nuclear compartments provides an unusual context for the analysis of SUMOylation. Each cell contains a transcriptionally silent, diploid germ line micronucleus (MIC) that divides by mitosis and a polyploid transcriptionally active somatic macronucleus (MAC) that divides by an amitotic mechanism. With the long-term goal to exploit these opportunities we …
1,25-Dihydroxyvitamin D Alters Lipid Metabolism And Epithelialto- Mesenchymal Transition In Metastatic Epithelial Breast Cancer Cells, Alle Nicole Barnard
1,25-Dihydroxyvitamin D Alters Lipid Metabolism And Epithelialto- Mesenchymal Transition In Metastatic Epithelial Breast Cancer Cells, Alle Nicole Barnard
Open Access Theses
Evidence suggests that high vitamin D status (marked by serum 25-hydroxyvitamin D, 25(OH)2 D) is associated with a decreased risk of breast cancer. It has been established that 1,25-dihydroxyvitamin D (1,25(OH) 2 D) can alter glycolysis and the Krebs cycle of breast cancer cells (Jiang et al., 2010; Zheng et al., 2013) but little information is available on 1,25(OH) 2 D's alterations of lipid metabolism in breast cancer cells. Thus, the current research investigates if there was an effect of 1,25(OH) 2 D on proteins that regulate lipid metabolism in MCF10A, MCF10A-ras, MCF10CA1h, and MCF10CA1a epithelial breast cancer cells. While …
Key Residues Of Human Cytoplasmic Protein Tyrosine Phosphatase-A And -B For Substrate Binding And Specificity, Byunghyun Park
Key Residues Of Human Cytoplasmic Protein Tyrosine Phosphatase-A And -B For Substrate Binding And Specificity, Byunghyun Park
Open Access Theses
Reversible tyrosine phosphorylation plays an important role in signaling pathways that are essential for regulating cellular growth, differentiation and metabolism. Moreover, several human diseases such as diabetes, obesity and cancers are associated with the deregulation of protein tyrosine phosphatases (PTPs). Several studies provide evidence that PTPs not only contribute to cellular differentiation, but over-expression of these molecules also leads to transformation of non-transfomed cells as well. Based on these results, designing specific PTP inhibitors may ultimately function as potential therapeutic agents to treat various diseases including cancer, diabetes, and autoimmune diseases. EphA2 is a receptor tyrosine kinase which is hypo-phosphorylated …
Neurotrophins And Their Effects On Breast Cancer Cell Proliferation And Migration, Kayla Elise Minser
Neurotrophins And Their Effects On Breast Cancer Cell Proliferation And Migration, Kayla Elise Minser
Open Access Theses
Cancer is a large health issue in all parts of the world. In the United States alone, approximately 1 in 4 deaths are cancer related. Breast cancer is a particularly prevalent form, accounting for a little over 14 percent of all cancer incidence. The largest obstacle to overcome for breast cancer morbidity is metastasis. Over 90 percent of all breast cancer related deaths are due to metastasis. Because metastasis is a complex, multi-step process, it is difficult to treat. A recent observation in the Kirshner lab has revealed a type of phenotypic plasticity, where migratory cancer cells have a neuronal-like …
Pharmaceuticals And Personal Care Products: Emerging Contaminants In Aquatic Ecosystems, Jenny E. Zenobio
Pharmaceuticals And Personal Care Products: Emerging Contaminants In Aquatic Ecosystems, Jenny E. Zenobio
Open Access Theses
In recent years, the presence of pharmaceuticals and personal care products (PPCPs) in aquatic systems has led to research on their fate and effects. PPCPs have been found in mixture in wastewater effluents, surface, ground, and drinking water at low concentrations from areas of intense urbanization. Although adverse effects to human health from the current environmental concentrations are unlikely, the impacts to ecological receptors are not clear. We performed field and laboratory studies to quantify and evaluate effects of PPCPs on fish. First, a field study was conducted at the Baca National Wildlife Refuge, Colorado (2010-2012) because a portion of …
The Termite Digestome: Understanding The Digestive Physiology Involved In Lignocellulosic Biomass Degradation, Zachary John Karl
The Termite Digestome: Understanding The Digestive Physiology Involved In Lignocellulosic Biomass Degradation, Zachary John Karl
Open Access Dissertations
The purpose of this research was to advance the understanding of lower termite digestive physiology and discover potential biocatalysts that can aid in the degradation of lignocellulosic biomass. Various protein characterization and gene expression methods were used throughout this research in order to accomplish these objectives. The results of this dissertation indicate that: 1) termites and their symbionts act in a synergistic manner to degrade biomass in vitro, 2) the host fraction of the gut (i.e., foregut and midgut) is the likely site of glucose absorption, 3) the termite and its symbionts contribute specific enzymes to the digestive process, 4) …
Genetic Engineering Of Black Cherry (Prunus Serotina) For Reproductive Sterility And Insect Pest Resistance, Ying Wang
Open Access Dissertations
Black cherry (Prunus serotina Ehrh.) is one of the most valuable hardwoods for high- end cabinetry, furniture, architectural millwork, paneling, and veneer. However, the damage caused by cambial-mining insect pests triggers gummosis in black cherry, a non-specific defense response in which resinous gum is deposited at the site of injury. The gum defects dramatically decrease the yield of high-quality black cherry lumber, and the value can be reduced by as much as 90%. The goal of this project was to optimize the transformation and in vitro rooting system, and to develop transgenic black cherry for reproductive sterility and insect pest …
Characterization Of Caxck31, A Bacterial Calcium/Proton Antiporter, Marc Robert Ridilla
Characterization Of Caxck31, A Bacterial Calcium/Proton Antiporter, Marc Robert Ridilla
Open Access Dissertations
To better understand a class of transporters known as Calcium/Cation Antiporters (CaCAs), the bacterial calcium/proton antiporter CAXCK31 was purified and characterized. New methods were developed for its heterologous overexpression and purification. These methods help to define stress responses to toxic membrane overproduction in E. coli and may be broadly applicable to studies of membrane proteins. The results from a variety of biochemical and biophysical experiments demonstrated that CAXCK31 exists as a dimer in the membrane and can be purified in the dimeric state. The methods used include chemical cross-linking, FRET, and SEC-MALS. In addition, various transport properties of CAXCK31, including …
Structural Studies On The Rubella Virus Capsid Protein And Its Organization In The Virion, Vidya Mangala Prasad
Structural Studies On The Rubella Virus Capsid Protein And Its Organization In The Virion, Vidya Mangala Prasad
Open Access Dissertations
Rubella virus is a leading cause of birth defects due to infectious agents. When contracted during pregnancy, rubella infection leads to severe damage in fetuses. Despite its medical importance, very little is known about the structure of the pleomorphic rubella virus as compared to its alphavirus relatives. The rubella capsid protein is a critical structural component of virions as well as a key factor in virus-host interactions. Three crystal structures of the structural domain of the rubella capsid protein have been described here. The polypeptide fold of the capsid protomer has not been observed previously. The capsid protein structure, along …
Generation And Statistical Modeling Of Active Protein Chimeras: A Sequence Based Approach, Nicholas Fico
Generation And Statistical Modeling Of Active Protein Chimeras: A Sequence Based Approach, Nicholas Fico
Open Access Dissertations
Generation of active protein chimeras is a valuable tool to probe the functional space of proteins. Statistical modeling is the next logical step, allowing us to build a model of gene fragment replaceability between species. In this thesis I begin to develop the statistical tools that are needed to systematically describe combinatorial protein libraries. I present three sets of diverse chimeric protein libraries developed using sequence information. The statistical model of the human N-Ras and human K-Ras-4B genes reveal a set previously unidetifed surface residues on the N-Ras G-Domain that may be involved in cellular localization. Statistical modeling of a …