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Full-Text Articles in Life Sciences
Contribution Of Specific Amino Acids To Calcium-Dependent Dimerization Of Epithelial Cadherin, Xiaoyun Z. Howard
Contribution Of Specific Amino Acids To Calcium-Dependent Dimerization Of Epithelial Cadherin, Xiaoyun Z. Howard
Electronic Theses and Dissertations
Cadherins are calcium-dependent molecules that play essential roles in embryonic development, tissue morphogenesis, and cancer progression. Epithelial (E-) cadherin is present at adherens junctions, structures that are important for maintaining tissue integrity. At adherens junctions, cell–cell adhesion complexes are formed as clusters of cadherin dimers through strand-swapped dimerization between two interacting protomers from adherent cells. Recently, a number of studies of dimer formation of E-cadherin supported a two-step adhesive binding model. First, an inter-molecular initial encounter complex (X-dimer) forms at the linker region of the first two extracellular domains, EC1 and EC2. Next, strand-swap dimerization occurs via exchange or ''swap'' …
Nucleic Acid Clamp-Mediated Transcriptional And Translational Modulation Of Oncogenes Via The Stabilization Of G-Quadruplexes, Taisen Hao
Electronic Theses and Dissertations
G-quadruplexes (G4s) are non-canonical secondary nucleic acid structures that exit in various biologically important regions within a cell, such as the promoters of DNA, 5’-Untranslated regions (UTR) of mRNA and telomeres. These secondary structures tend to cluster around 1 kb from transcriptional start sites across all human chromosomes in addition to at telomeric regions. Extensive efforts from many research groups have been dedicated to targeting G4s in oncogenic promoters, telomeres, and 5’-UTRs with traditional small molecules. However, most small molecules recognizing multiple G4s raising potential issues in terms of utilizing these small molecules clinically. Therefore, we developed a novel nucleic …
Biochemical And Molecular Assessment Of Toxicity Of Primaquine Metabolites On Erythrocytes, Jagrati Jain
Biochemical And Molecular Assessment Of Toxicity Of Primaquine Metabolites On Erythrocytes, Jagrati Jain
Electronic Theses and Dissertations
The 8-aminoquinoline (8AQ) antimalarial drug primaquine (PQ) is the only drug for prevention of malaria relapse. Moreover, PQ also has gametocytocidal activity against Plasmodium falciparum. However, clinical use of PQ has been limited due to its hemolytic toxicity, especially in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals. Phenolic and quinone metabolites generated via cytochrome P450-dependent pathways appear to be responsible for hemolytic effects of PQ. However, the mechanism for the hemolytic toxicity of PQ is still poorly understood. To explore the mechanism, targets, and pathways for toxicity of PQ, normal and G6PDd human erythrocytes were treated with the potential hemotoxic metabolites of …
Regulation Of The Kras Promoter In Pancreatic Cancer By Proteins And Small Molecules, Harshul Batra
Regulation Of The Kras Promoter In Pancreatic Cancer By Proteins And Small Molecules, Harshul Batra
Electronic Theses and Dissertations
DNA-binding proteins play a pivotal role in cell biology. The major class of DNA-binding proteins are transcription factors (TFs). TFs are central to almost every fundamental cellular process such as cell development, differentiation, cell growth, and gene expression. They account for 10% of the genes in eukaryotes. In mammals, more than 700 TFs are identified to be DNA-binding TFs. They bind to the TF binding sites (TFBSs) in the genome and regulate the expression of their target genes. kRAS is a proto-oncogene with intrinsic GTPase activity, that contributes to cell proliferation, division, and apoptosis. kRAS mutations are observed in >95% …
Nickel Reduces Calcium Dependent Dimerization In Neural Cadherin, Matthew Paul Dukes
Nickel Reduces Calcium Dependent Dimerization In Neural Cadherin, Matthew Paul Dukes
Electronic Theses and Dissertations
Cadherins are the primary transmembrane component in adherens junctions, structures that link the actin cytoskeleton in adjacent cells within solid tissues including neurological synapses, epithelium and endothelium. Cell-cell adhesion by cadherins requires the binding of calcium ions to specific sites in the extracellular region. Given the complexity of the cell adhesion microenvironment, we are investigating whether other divalent cations might affect calciumdependent dimerization of neural-(N-) cadherin. The first chapter focuses on studies to characterize the impact of binding physiological magnesium (II) or neurotoxic nickel (II) on calcium-dependent N-cadherin function. Physiological levels of magnesium have only a small effect on the …