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Electronic Theses and Dissertations

2016

Articles 1 - 19 of 19

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Pharmacokinetics, Tissue Distribution, Synergistic Activity, And Antitumor Activity Of Two Isomeric Flavones, Crystal L. Whitted Dec 2016

Pharmacokinetics, Tissue Distribution, Synergistic Activity, And Antitumor Activity Of Two Isomeric Flavones, Crystal L. Whitted

Electronic Theses and Dissertations

Flavonoids are polyphenolic secondary metabolites found in plants that have bioactive properties including antiviral, antioxidant, and anticancer. Two isomeric flavone were extracted from Gnaphalium elegans and Achyrocline bogotensis, plants used by the people from the Andean region of South America as remedies for cancer. 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5, 7–dihydroxy- 3, 6, 8 trimethoxy flavone/ flavone A) and 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3, 5–dihydroxy-6, 7, 8–trimethoxy flavone/ flavone B) have shown antineoplastic activity against colon cancer cell lines dependent upon their differentiation status. Pharmacokinetic studies reported herein were used to determine dosing for antitumor assays, as well as determine target tissue concentration. These included the …

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Tnf-Like Weak Inducer Of Apoptosis (Tweak) : Not So Weak After All., Joseph Dekward Mcmillan Iv Dec 2016

Tnf-Like Weak Inducer Of Apoptosis (Tweak) : Not So Weak After All., Joseph Dekward Mcmillan Iv

Electronic Theses and Dissertations

Background: Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a proinflammatory cytokine belonging to the TNF super family. TWEAK produces a variety of cellular responses through the binding to fibroblast growth factor inducible 14 (Fn14), a member of TNF receptor superfamily. Although Fn14 lacks a death domain, TWEAK has been found to induce apoptosis in some cell types by perturbing the activity of certain pathways such as TNF-receptor signaling. TWEAK is also known to regulate proliferation and differentiation of myogenic cells. We have previously reported that the TWEAK-Fn14 system causes skeletal muscle wasting both in vitro and in …

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A Novel Role Of Human Dna Damage Checkpoint Protein Atr In Suppressing Ca2+ Overload-Induced Parp1-Mediated Necrosis, Hui Wang-Heaton Dec 2016

A Novel Role Of Human Dna Damage Checkpoint Protein Atr In Suppressing Ca2+ Overload-Induced Parp1-Mediated Necrosis, Hui Wang-Heaton

Electronic Theses and Dissertations

Ataxia telangiectasia and Rad3-related (ATR) is well known for its regulatory role in DNA damage responses (DDR) as a checkpoint kinase that phosphorylates hundreds of protein substrates. However, its role in cellular non-DNA damage stress responses (NDDR) is unknown. Necrosis is one form of cell death and traditionally has been regarded as a passive and uncontrolled cell death. Recently, evidence has emerged to support the concept that necrosis also may occur in a programmed manner and that PARP1 can be a mediator. Active poly (ADP-ribose) polymerase 1 (PARP1) hydrolyzes nicotinamide adenine dinucleotide (NAD+) to produce poly (ADP-ribose) (PAR) …

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Dynamic Host-Pathogen Interactions Result In Fungal Epitope Unmasking, Alex Hopke Aug 2016

Dynamic Host-Pathogen Interactions Result In Fungal Epitope Unmasking, Alex Hopke

Electronic Theses and Dissertations

Molecular camouflage is used by a diverse set of pathogens to disguise their identity and avoid recognition by protective host receptors. The opportunistic fungal pathogen Candida albicans is a good example, as it masks the inflammatory component β-glucan in its cell wall to evade detection by the immune receptor Dectin-1. Interestingly, it has been seen that β-glucan becomes unmasked during infection in vivo, though the underlying mechanisms remained unclear. Exposure levels of this epitope may be important, as Dectin-1 mediates protection from some strains of C. albicans and alterations in the organization and composition of the Candida cell wall …

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Characterization Of Sip470, A Family 1 Lipid Transfer Protein And Its Role In Plant Stress Signaling, Timothy Ndagi Audam Aug 2016

Characterization Of Sip470, A Family 1 Lipid Transfer Protein And Its Role In Plant Stress Signaling, Timothy Ndagi Audam

Electronic Theses and Dissertations

SIP470, a putative tobacco lipid transfer protein, was identified in a yeast two-hybrid screen to interact with SABP2. SABP2 is a critical role in SA-mediated signaling in tobacco and other plants. In vitro studies using purified recombinant SIP470 confirmed that it is a lipid binding protein. In an attempt to determine its role in mediating stress responses, Arabidopsis T-DNA insertion knockout lines lacking SIP470 homolog were used for the analysis. These mutant plants were defective in basal resistance against microbial pathogens. Expression of defense gene PR-1 was also delayed in these mutant plants. Interestingly, these mutant plants were not defective …

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A Systems Biology Approach Identifies A Gene Regulatory Network In Parotid Acinar Cell Differentiation., Melissa Ann Metzler Aug 2016

A Systems Biology Approach Identifies A Gene Regulatory Network In Parotid Acinar Cell Differentiation., Melissa Ann Metzler

Electronic Theses and Dissertations

Objective: This project sought to understand the gene regulatory networks that drive parotid salivary gland acinar cells to terminally differentiate, and drive expression of terminal differentiation genes in dedifferentiated ParC5 cells. Methodology: Laser capture microdissection was used to isolate acinar cells at multiple time points during differentiation. This important step allowed us to measure gene expression in a single and important cell type. A systems biology approach was taken to measure global mRNA and microRNA expression across acinar cell terminal differentiation in the rat parotid salivary gland. In ParC5 cells, the ER stress activator tunicamycin was used to stimulate Xbp1 …

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Exploring The Relationship Between Behaviour And Neurochemistry In The Polyphenic Spider, Anelosimus Studiosus (Araneae: Theridiidae), Jennifer B. Price Aug 2016

Exploring The Relationship Between Behaviour And Neurochemistry In The Polyphenic Spider, Anelosimus Studiosus (Araneae: Theridiidae), Jennifer B. Price

Electronic Theses and Dissertations

The importance of social behaviour is evident in human society, but there are both costs and benefits associated with cooperation and sociality throughout the animal kingdom. At what point do the benefits outweigh the costs, and when do selective pressures favour sociality and colonization over solitude and independence? To investigate these questions, we have focused on an anomalous species of spider, Anelosimus studiosus, also known now as the northern social spider. Throughout its broad range, A. studiosus is solitary and aggressive, but recently, colonies of cooperative and social individuals have been observed at northern latitudes. This leads to two …

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Investigation Of Novel Functions For Dna Damage Response And Repair Proteins In Escherichia Coli And Humans, Benjamin A. Hilton May 2016

Investigation Of Novel Functions For Dna Damage Response And Repair Proteins In Escherichia Coli And Humans, Benjamin A. Hilton

Electronic Theses and Dissertations

Endogenous and exogenous agents that can damage DNA are a constant threat to genome stability in all living cells. In response, cells have evolved an array of mechanisms to repair DNA damage or to eliminate the cells damaged beyond repair. One of these mechanisms is nucleotide excision repair (NER) which is the major repair pathway responsible for removing a wide variety of bulky DNA lesions. Deficiency, or mutation, in one or several of the NER repair proteins is responsible for many diseases, including cancer. Prokaryotic NER involves only three proteins to recognize and incise a damaged site, while eukaryotic NER …

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Role Of Microrna-21 In Atherogenesis., Rihab Hamed-Berair May 2016

Role Of Microrna-21 In Atherogenesis., Rihab Hamed-Berair

Electronic Theses and Dissertations

MicroRNA-21 (miR-21) is an evolutionarily conserved microRNA, abundant in most cardiovascular tissues. It has been implicated in the pathogenesis of several cardiovascular diseases including restenosis, myocardial infarction, and heart failure. However, little is known about the contribution of miR-21 in atherosclerosis. My data show that expression of miR-21 is increased by >1.5-fold in murine atherosclerotic lesions and by 1.5-2.0-fold in the macrophages of Western diet (WD)-fed LDLR-KO mice (for 12-20 weeks). In vitro, LDL, oxidized LDL, acetylated LDL and LPS induced miR-21 by 2-4-fold and down-regulated its target protein, PDCD4, in bone marrow-derived macrophages. Basally, macrophages isolated from miR-21-KO …

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Modulation Of Cell Death Signaling And Cell Proliferation By The Interaction Of Homoserine Lactones And Paraoxonase 2., Aaron Mackallan Neely May 2016

Modulation Of Cell Death Signaling And Cell Proliferation By The Interaction Of Homoserine Lactones And Paraoxonase 2., Aaron Mackallan Neely

Electronic Theses and Dissertations

Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule that functions to facilitate bacteria-bacteria communication. C12 has also been reported to affect many aspects of human host cell physiology, including evoking cell death in various types of cells. However, the signaling pathway(s) leading to C12-triggerred cell death remains unclear. To clarify cell death signaling induced by C12, we examined mouse embryonic fibroblasts (MEFs) deficient in one or more caspases. Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in cells, probably through the direct induction of mitochondrial membrane permeabilization. Previous studies indicate that …

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Regulation Of Acute And Chronic Immune Responses By Β-Arrestin2, Hui Yan May 2016

Regulation Of Acute And Chronic Immune Responses By Β-Arrestin2, Hui Yan

Electronic Theses and Dissertations

β-arrestin2, previously recognized as a facilitator for G-protein associated 7 TMR desensitization/ internalization, has now been appreciated as an independent signal transducer that regulates multiple cellular responses including inflammation. Cecal ligation and puncture procedure (CLP) induced septic shock is an acute inflammatory response characterized by uncontrolled systemic inflammation. Myocardial ischemia/reperfusion is a chronic sterilize inflammation that requires the reaction of macrophages, fibroblasts and cardiac stem cells for regeneration and remodeling of the infarcted myocardium. Restrained chronic stress is an immune suppression model in which the inactivation of macrophages may be involved. Here we showed β-arrestin2 overexpression inhibited CLP-induced heart dysfunction …

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Chlamydia Trachomatis Transformants Show A Significant Reduction In Rates Of Invasion Upon Removal Of Key Tarp Domains, Christopher Parrett Jan 2016

Chlamydia Trachomatis Transformants Show A Significant Reduction In Rates Of Invasion Upon Removal Of Key Tarp Domains, Christopher Parrett

Electronic Theses and Dissertations

Chlamydia trachomatis is an obligate, intracellular bacterium which is known to cause multiple human infections including nongonococcal urethritis (serovars D-K), lymphogranuloma venereum (serovars L1, L2, L3) and trachoma (serovars A-C). The infectious form of the bacterium, called the elementary body (EB), harbors a type III secreted effector known as Tarp (translocated actin recruiting phosphoprotein) which is a candidate virulence factor and is hypothesized to play a role in C. trachomatis' ability to invade and grow within epithelial cells in a human host. C. trachomatis L2 Tarp harbors five unique protein domains which include the Phosphorylation Domain, the Proline Rich Domain, …

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Towards Structural Determination Of Human Α1-Glycine Receptor Allostery, Rathna Jyothi Veeramachaneni Jan 2016

Towards Structural Determination Of Human Α1-Glycine Receptor Allostery, Rathna Jyothi Veeramachaneni

Electronic Theses and Dissertations

Recent advances in technology have led to the determination of numerous notable structures of membrane proteins. While they provide valuable information about the structure of membrane proteins these studies often provide static images with potentially limited dynamics, and structural determination often requires truncation of flexible regions, and often utilizes bacterial homologs given the need for stable, heterologous overexpression. In order to better understand allostery at a molecular level, state-dependent crosslinking studies coupled with multidimensional mass spectrometry (MS) were conducted on glycine receptor (GlyR) stabilized in different allosteric states. Predominant allosteric states were stabilized using wild type or mutated receptor in …

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Source Apportionment Of Atmospheric Particulate Matter In Developing Countries Using Trace Elements And Stable Metal Isotope Ratios, Nitika Dewan Jan 2016

Source Apportionment Of Atmospheric Particulate Matter In Developing Countries Using Trace Elements And Stable Metal Isotope Ratios, Nitika Dewan

Electronic Theses and Dissertations

The work presented herein details the source apportionment of atmospheric particulate matter in developing countries (Kyrgyzstan in Central Asia, metropolitan cities in Northern India, and Shenzhen in China) using trace elements and stable metal isotope ratios. The first study focused on the development of a novel method for the concomitant separation of rare-earth elements in environmental samples of any geological origin. The separation procedure is based on three extraction chromatographic materials, referred to as Sr.Spec, TRU.Spec, and Ln.Spec. This triple column arrangement enables the simultaneous isolation of pure Sr and Nd fractions in less than one day and with great …

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C-Reactive Protein Interactions With Cellular Membranes And Supported Lipid Bilayers, Aml Abd Alhamed Alnaas Jan 2016

C-Reactive Protein Interactions With Cellular Membranes And Supported Lipid Bilayers, Aml Abd Alhamed Alnaas

Electronic Theses and Dissertations

C-reactive protein (CRP) is a serum protein that binds to damaged membranes and initiates the complement immune response. Different forms of CRP are thought to alter how the body responds to inflammation and the degradation of foreign material. Despite knowing that a modified form of CRP(mCRP) binds to downstream protein binding partners better than the native pentameric form, the role of CRP conformation on lipid binding is yet unknown. In this work, three main assays were performed to characterize how conformation affects CRP-membrane interactions. The first assay utilized supported lipid bilayers that mimic the plasma membrane of apoptotic cells. The …

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Akap150 Dynamics In Anterior Pituitary Cells, Kristen E. Dew Jan 2016

Akap150 Dynamics In Anterior Pituitary Cells, Kristen E. Dew

Electronic Theses and Dissertations

Cellular communication occurs as a result of changes in signaling pathways. A well-studied signaling pathway is through G protein coupled receptors (GPCRs). In gonadotropes, GPCR stimulation by GnRH leads to the activation of protein kinase A (PKA). Activated PKA can phosphorylate ion channels, potentially causing an influx of calcium, depolarization and secretion of hormones. A scaffolding protein known as AKAP150 anchors PKA near L-type calcium channels. In addition, AKAP150 anchors phosphatases, which provides temporal control during signaling events. It was recently shown that AKAP150 is mobile in neuronal dendrites, providing regulation to where the signaling cascade occurs in the cell. …

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Functional Effects Of Calcium Regulation Of Thin Filaments At Single Particle Resolution, Christopher Solis-Ocampo Jan 2016

Functional Effects Of Calcium Regulation Of Thin Filaments At Single Particle Resolution, Christopher Solis-Ocampo

Electronic Theses and Dissertations

Heart disease is the leading cause of death in the United States. Understanding heart function at the molecular level is critical for developing of more effective treatments. In the cardiac muscle, the thin filament is composed by troponin (Tn), tropomyosin (Tm), and F-actin. It provides Ca2+-dependent regulation of contraction by modulating myosin attachment and force generation in a cooperative scheme. However, this mechanism remains unclear. To understand thin filament activation, we studied the binding and functional properties of Tn and Tm to F-actin at single particle resolution by employing fluorescence image colocalization, in vitro motility assays, and Förster resonance energy …

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A Fret Investigation Into Molecular Mechanisms Of Cardiac Troponin Activation In Reconstituted Thin Filaments, Maria Eleni Moutsoglou Jan 2016

A Fret Investigation Into Molecular Mechanisms Of Cardiac Troponin Activation In Reconstituted Thin Filaments, Maria Eleni Moutsoglou

Electronic Theses and Dissertations

Cardiomyopathies (CM) are the leading cause of death in America, and can develop from mutations in sarcomeric proteins, leading to altered protein structure and function. Current therapies target upstream signaling pathways to treat the symptoms of heart failure, but are associated with increased mortality by affecting downstream signaling pathways and other muscle types. Rational drug design can develop therapies to treat CM at the protein level. However, a detailed knowledge of how sarcomeric proteins regulate muscle contraction is required. Muscle contraction occurs through a cyclic interaction between actin thin and myosin thick filaments, regulated by intracellular Ca2+ concentration. Troponin (Tn), …

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Small Molecule Disruption Of Ros-Regulating Pathways In Human Carcinoma, Rebecca E. Mccall Jan 2016

Small Molecule Disruption Of Ros-Regulating Pathways In Human Carcinoma, Rebecca E. Mccall

Electronic Theses and Dissertations

Gold (I) coordinated N-heterocyclic carbenes containing appended redox cycling moieties were designed and analyzed for their ability to target the antioxidant network via multiple mechanisms in various human cancer cell models. Complexes containing either ferrocene or naphthoquinone redox cycling moieties were screened for inhibition of cell growth, inhibition of thioredoxin reductase (TrxR), and accentuation of exogenous ROS. The cell death pathway employed was determined by flow cytometry via detection of Annexin-V FITC. Furthermore, differential gene expression between treated cells and untreated cells revealed the induction of endoplasmic reticulum stress and unfolded protein response pathways.

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