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Development And Application Of Mass Spectrometry-Based Proteomics To Generate And Navigate The Proteomes Of The Genus Populus, Paul Edward Abraham

Doctoral Dissertations

Historically, there has been tremendous synergy between biology and analytical technology, such that one drives the development of the other. Over the past two decades, their interrelatedness has catalyzed entirely new experimental approaches and unlocked new types of biological questions, as exemplified by the advancements of the field of mass spectrometry (MS)-based proteomics. MS-based proteomics, which provides a more complete measurement of all the proteins in a cell, has revolutionized a variety of scientific fields, ranging from characterizing proteins expressed by a microorganism to tracking cancer-related biomarkers. Though MS technology has advanced significantly, the analysis of complicated proteomes, such as …

Suppression Of Chronically Induced Breast Carcinogenesis And Role Of Mesenchymal Stem-Like Cells, Kusum Rathore

Doctoral Dissertations

Sporadic breast cancers are mainly attributable to long-term exposure to environmental factors, via a multi-year, multi-step, and multi-path process of tumorigenesis involving cumulative genetic and epigenetic alterations in the chronic carcinogenesis of breast cells from a non-cancerous stage to precancerous and cancerous stages. Epidemiologic and experimental studies have suggested that various dietary compounds like green tea and grape seed may be used as preventive agents for breast cancer control. In this research, I have developed a cellular model that mimics breast cell carcinogenesis chronically induced by cumulative exposures to low doses of environmental carcinogens. I used the chronic carcinogenesis model …

A Time-And-Space Parallelized Algorithm For The Cable Equation, Chuan Li

Doctoral Dissertations

Electrical propagation in excitable tissue, such as nerve fibers and heart muscle, is described by a nonlinear diffusion-reaction parabolic partial differential equation for the transmembrane voltage $V(x,t)$, known as the cable equation. This equation involves a highly nonlinear source term, representing the total ionic current across the membrane, governed by a Hodgkin-Huxley type ionic model, and requires the solution of a system of ordinary differential equations. Thus, the model consists of a PDE (in 1-, 2- or 3-dimensions) coupled to a system of ODEs, and it is very expensive to solve, especially in 2 and 3 dimensions.

In order to …

Protein Engineering For The Enhanced Photo-Production Of Hydrogen By Cyanobacterial Photosystem I, Ifeyinwa Jane Iwuchukwu

Doctoral Dissertations

Photosystem I (PSI) from plants, algae, and cyanobacteria can mediate H2 evolution in vivo and in vitro. A simple, self-platinization procedure that permits stable PSI-mediated H2 evolution in vitro has been developed. The H2 evolution capabilities of PSI from Thermosynechococcus elongatus have been characterized. This organism utilizes cytochrome c6 (cyt c6) as the e- donor to P700. Using a solution-based, self-organized platinization of the PSI nanoparticles, this study demonstrates a sodium ascorbate-cyt-PSI-Pt-H2 electron transport and proton reduction system that yields light-dependent H2. The system was thermostable with H2 evolution increasing up to 55°C. In addition, stability studies have shown the …

Novel Constitutively Active Point Mutations In The Nh2 Domain Of Cxcr2 Capture The Receptor In Different Activation States, Giljun Park

Doctoral Dissertations

Chemokines are structurally and functionally related 8-10 kDa proteins defined by four conserved cysteine residues. They consist of a superfamily of proinflammatory mediators that promote the recruitment of various kinds of leukocytes and other cell types through binding to their respective chemokine receptor, a member of the GPCR family. Abnormal control of this system results in various diseases including tumorigenesis and cancer metastasis. Deregulation can occur when constitutively active mutant (CAM) chemokine receptors are locked in the “on” position. This can lead to cellular transformation/tumorigenesis. A viral CAM receptor, ORF74, that can cause tumors in humans, also has homology to …

Human Decomposition Ecology At The University Of Tennessee Anthropology Research Facility, Franklin Edward Damann

Doctoral Dissertations

The University of Tennessee Anthropology Research Facility (ARF) is well known for its unique history as a site of human decomposition research in a natural environment. It has been integral to our understanding of the processes of human decomposition. Over the last 30 years 1,089 bodies have decomposed at this 1.28 acre facility, producing a density of 850 corpses per acre of land. This project evaluated the abiotic and biotic characteristics of the soil exposed to various levels of human decomposition in order to determine the effect on the physicochemical properties and the indigenous bacterial communities.

Specifically, 75 soil samples …

The Role Of The Suppressor Of Hairy-Wing Insulator Protein In Chromatin Organization And Expression Of Transposable Elements In Drosophila Melanogaster, Heather Anne Wallace

Doctoral Dissertations

ABSTRACT Chromatin insulators are required for proper temporal and spatial expression of genes in metazoans. Insulators are thought to play an important role in the regulation of gene expression through the formation of higher-order chromatin structures. One of the best characterized insulators is the Drosophila gypsy insulator, which is located in the gypsy retrovirus. Several proteins are required for gypsy insulator function, including Su(Hw), Mod(mdg4), and CP190. In addition to the gypsy insulator, these proteins are located throughout the genome at sites which are thought to correspond to endogenous insulators. Analysis of the distribution of insulator proteins across a region …

Characterizing The Role Of Dna Repair Proteins In Telomere Length Regulation And Maintenance: Fanconi Anemia Complementation Group C Protein And 8-Oxoguanine Dna Glycosylase, David Beomjin Rhee

Doctoral Dissertations

Telomeres are the chromosome end structures consisting of telomere-associated proteins and short tandem repeat sequences, TTAGGG, in humans and mice. Telomeres prevent chromosome termini from being recognized as broken DNA ends. The structural integrity of DNA including telomeres is constantly threatened by a variety of DNA damaging agents on a daily basis. To counteract the constant threats from DNA damage, organisms have developed a number of DNA repair pathways to ensure that the integrity of genome remains intact. A number of DNA repair proteins localize to telomeres and contribute to telomere maintenance; however, it is still unclear as to what …

Dynamics Of The Toc Gtpases: Modulation By Nucleotides And Transit Peptides Reveal A Mechanism For Chloroplast Protein Import, Lovett Evan Reddick

Doctoral Dissertations

The chloroplast is the green organelle in the plant cell responsible for harvesting energy from sunlight and converting it into sugars and ATP. Origins of this organelle can be traced back to an endosymbiotic event in which a primitive eukaryotic cell capable of oxidative phosphorylation engulfed a free-living cyanobacterium capable of photosynthetic respiration (1). Immediately following this event the details are not clear, however what is known is that over the course of evolution, the engulfed cyanobacteria relinquished approximately 97% of its protein coding sequences to the host cell nucleus, thus making the newly formed chloroplast reliant on its host …

Functional Analysis Of Chromodomain Helicase Dna Binding Protein 2(Chd2) Mediated Genomic Stability, Sangeetha Rajagopalan

Doctoral Dissertations

Histone modifying enzymes and chromatin remodeling complexes play an important regulatory role in chromatin dynamics that dictate the interaction of regulatory factors involved in processes such as DNA replication, recombination, repair and transcription, with DNA template. The CHD (Chromodomain Helicase DNA Binding Protein) family of proteins is known to be involved in the regulation of gene expression, recombination and chromatin remodeling via their chromatin specific interactions and activities. Phenotypic analysis of the Chd2 mutant mouse model developed by our laboratory indicates that the Chd2 protein plays a critical role in tumor suppression as the heterozygous mutant mice develop spontaneous lymphomas. …

Reverse Genetic And Cell Biological Approaches To The Study Of Developmental Functions Of Class Xi Myosin In Arabidopsis Thaliana, Eunsook Park

Doctoral Dissertations

Myosin proteins function as molecular motors that drive the ATP-dependent movement of cellular components along actin filaments. Vascular plants encode two different types of myosin, referred to as class VIII and class XI. Although class XI myosins have been suggested to function in organelle movement and cytoplasmic streaming, little is known about their cellular function in detail.

The Arabidopsis genome encodes 13 class XI myosin genes. The reasons for the relatively large number of myosin XI isoforms present within a single plant species are unknown. To investigate the function of these gene products in the cell, we determined the spatial …

High Resolution X-Ray And Neutron Crystallographic Studies Of Escherichia Coli Dihydrofolate Reductase, Brad C. Bennett

Doctoral Dissertations

Dihydrofolate Reductases (DHFRs) have been identified in nearly every proteome and are essential for most biosynthetic pathways involving one-carbon transfer reactions due to their recycling of tetrahydrofolate (THF). They catalyze the NADPH-dependent reduction of dihydrofolate (DHF), producing THF. Inhibition of DHFR ultimately depletes cellular pools of THF; causing a reduced supply of thymine nucleotides for DNA synthesis, resulting in genomic instability and cell death. Therefore, DHFRs remain important drug targets in antimicrobial and chemotherapeutic treatments. Despite exhaustive investigation of E. coli chromosomal DHFR, controversy persists over the dynamics of regulatory loops (the Met20, the βF-βG, and the βG-βH) and the …