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Articles 1 - 17 of 17
Full-Text Articles in Life Sciences
Towards The Total Synthesis Of Thioviridamide: Thiyl Radical Approach To The Beta-Thioenamide Linkage Formation, Jung-Hoon Kang
Towards The Total Synthesis Of Thioviridamide: Thiyl Radical Approach To The Beta-Thioenamide Linkage Formation, Jung-Hoon Kang
Theses and Dissertations
We developed an approach to the β-thioenamide linkage contained in the S-(2-aminovinyl)cysteine (avCys) residue of thioviridamide.1,2 Kinetic and thermodynamic control of radical additions of thiols to ynamides were studied for the formation of β-thioenamide linkage. Thiyl radicals are electrophilic and ynamides are electron-rich alkynes. This complementary polarity of the radical and acceptor increases the likelihood of a successful radical addition reaction. Because little is known about these types of compounds (β-thioenamides), we were unsure what kinds of yields and stereoselectivities (cis vs. trans) to expect. The adduct stability is another issue to consider. Fortunately, under typical radical addition conditions, the …
Molecular Mechanisms Involved In Oligodendrocyte Development, Rochelle Coelho
Molecular Mechanisms Involved In Oligodendrocyte Development, Rochelle Coelho
Theses and Dissertations
Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by demyelination and loss of oligodendrocytes (OLGs), the CNS myelin-producing cells. Thus, understanding the mechanisms that control OLG development can provide valuable knowledge regarding remyelination therapies for MS. This disease is thought to result from an autoimmune attack towards myelin. FTY720, an immunomodulator under evaluation for MS treatment is a sphingosine-1-phosphate (S1P) analog. We found before that S1P plays a crucial role in the NT-3-mediated survival of OLGs, an observation that led us to investigate whether FTY720 could have any effect on these cells. Our studies …
Regulation Of Mdm2 Mediated Nfκb2 Pathway In Human Lung Cancer, Lathika Mohanraj
Regulation Of Mdm2 Mediated Nfκb2 Pathway In Human Lung Cancer, Lathika Mohanraj
Theses and Dissertations
Overexpression of oncoprotein MDM2 and mutations of tumor suppressor p53 are frequently observed in human cancers. The NFκB pathway is one of the deregulated pathways in oncogenesis. The overall goal of the project was to study the regulation of NFκB pathway by MDM2 in lung cancer. Our first effort was to determine the frequency of MDM2 overexpression in human lung tumor samples and to identify co-occurring abnormal gene expression by studying the levels of MDM2 and members of NFκB pathway with respect to p53 status. Higher than normal levels of MDM2 were found in approximately 30% of the cancer samples …
Crosstalk Between Mdm2 And Akt Signaling Pathway In Oncogenesis., Mahesh Ramamoorthy
Crosstalk Between Mdm2 And Akt Signaling Pathway In Oncogenesis., Mahesh Ramamoorthy
Theses and Dissertations
MDM2, the human homologue of the Mouse Double Minute 2 gene product, has been shown to be over-expressed in many cancers and to induce tumorigenesis. The role of MDM2 in oncogenesis was thought to be p53 dependent. However recent years have shown MDM2 to be a key player in a complex network of interactions that affect cell cycle, apoptosis, and tumorigenesis in a p53 independent manner. Here we report a novel p53 independent role for the multidimensional protein MDM2; its ability to induce phosphorylation of Akt at serine 473 residue. Transient and stable over-expression of MDM2 in cultured cell lines …
Ceramide Kinase And Ceramide-1-Phosphate, Dayanjan Wijesinghe
Ceramide Kinase And Ceramide-1-Phosphate, Dayanjan Wijesinghe
Theses and Dissertations
Ceramide-1-phosphate (C1P) is a bioactive lipid that has been implicated in many biological processes. Our laboratory has conclusively demonstrated its role in inflammation via activation of cPLA2α. The only known enzyme to date responsible for direct synthesis of C1P is ceramide kinase. Very little was known about this enzyme in terms of its enzyme kinetics and substrate specificity. As CERK is an enzyme that acts on membrane lipids, its kinetics cannot be studied using standard bulk dilutions methods. Thus we developed a surface dilution approach using Triton X 100 mixed micelles for studying the kinetics of CERK. We discovered that …
Photocycloaddition Of Allenes, Crystal Ward
Photocycloaddition Of Allenes, Crystal Ward
Theses and Dissertations
For the past ten years the Fleming research group has been involved in the research of allene compounds. We have explored the synthesis of allenes as well as several reactions involving allenes, such as oxidation and nitrene addition. Recently, we have explored the synthesis and photochemistry of allenic alcohols tethered to silicon. There are literature examples using allenes in synthesis, but very few examples exist using allenes in photochemical cycloaddition reactions. We have found that a diisopropylallenyloxy(cinnamyloxy)silane derivative undergoes [2+2] photochemical cycloaddition to produce a cyclobutylsilane product when irradiated for 60-75 minutes.
I. Thermodynamics And Magnetism Of Cu2ocl2 Ii. Repairs To Microcalorimeter The "2"S Are Subscripts, And The Second 2 Is Preceded By A Lower Case L, Not A One, Thomas J. Parry
Theses and Dissertations
Adiabatic calorimetry provides accurate and precise specific heat (Cp) data. From this data, thermodynamic functions may be calculated. Cu2OCl2, melanothallite, became of interest as part of a study of a particular thermochemical cycle. The experimental specific heat data and the calculated thermodynamic functions are reported here. Free energies of formation, calculated from the thermodynamic functions, suggest the particular cycle of interest with this compound as an intermediate is not feasible; uncertainty as to the accuracy of CuO and CuCl2 data used in the calculations indicate further study may be necessary. Upon collection of the specific heat data, an antiferromagnetic transition …
A Radical Conjugate Addition Approach To The Total Synthesis Of Celogentin C, Steven G. Capps
A Radical Conjugate Addition Approach To The Total Synthesis Of Celogentin C, Steven G. Capps
Theses and Dissertations
The synthesis of five chiral DBFOX (dibenzofuran-oxazoline) ligands with either aryl or benzyl substituents will be presented. The requisite amino alcohols were obtained with high enantioselectivity either commercially (DBFOX/Bn), via Sharpless asymmetric aminohydroxylation (DBFOX/Nap, DBFOX/t-BuPh, DBFOX/Pip), or via phase-transfer catalyzed asymmetric alkylation (DBFOX/MeNap). These ligands, complexed with Mg(NTf2)2, were used as Lewis acid promoters of enantioselective radical conjugate additions to α/β-unsaturated nitro-amides/esters. A summary of these results is presented and discussed. These findings led us to believe that our initial binding model between metal, ligand, and substrate was flawed. Thus, we figured that if we started with a functionality known …
Regulators Of G-Protein Signaling, Rgs13 And Rgs16, Are Associated With Cxcl12-Mediated Cd4+ T Cell Migration, Lijin Xia
Theses and Dissertations
Chemokines are important chemical signals that guide lymphocyte movement within the immune system and promote the organization and functions of germinal centers (GCs) in the secondary lymphoid tissues. Previous studies have shown that GC T cells exhibit high expression of chemokine receptor 4, CXCR4, but that these cells are unable to migrate to the ligand for this receptor, the chemokine CXCL12. This “migratory paralysis” to CXCL12 was found to be correlated with the expression of two Regulators of G-protein Signaling, RGS13 and RGS16 in the GC T cells. The objective of my research was to determine whether RGS13 and RGS16 …
Spectroscopic Study Of Compressible Mobile Phase And Stationary Phase Behavior In Chromatography, Lawrence R. Baker
Spectroscopic Study Of Compressible Mobile Phase And Stationary Phase Behavior In Chromatography, Lawrence R. Baker
Theses and Dissertations
Raman spectroscopy, laser-induced fluorescence, and sum-frequency generation (SFG) spectroscopy are used to investigate the behavior of compressible mobile phases and stationary phases under a variety of chromatographic conditions. Efforts to understand and optimize separations employing compressible mobile phases have been limited by a lack of understanding of the mobile phase density gradient. Mobile phase compressibility leads to gradients in linear velocity and solute retention and affects separation speed and efficiency, especially in packed columns. This work describes on-column density measurement of CO2, a common carrier fluid for SFC and SGC, in packed capillary columns using Raman microspectroscopy. On-column detection by …
Genetic Analysis Of The Role Of Smpb In Establishing The Reading Frame On Tmrna, Talina Christensen Watts
Genetic Analysis Of The Role Of Smpb In Establishing The Reading Frame On Tmrna, Talina Christensen Watts
Theses and Dissertations
Ribosomes translate the genetic information encoded by mRNA into proteins. Defective mRNAs can cause stalling of translating ribosomes. The molecule tmRNA (transfer-messenger RNA) rescues stalled ribosomes in eubacteria. Together with its protein partner SmpB, tmRNA mimics a tRNA by entering the ribosomal A site and linking an alanine residue to the growing polypeptide chain. The ribosome then abandons the defective mRNA template and resumes translation on tmRNA, adding ten more amino acids to the nascent polypeptide. As a result of tmRNA action, stalled ribosomes are released and recycled, the defective mRNA is destroyed, and the aborted protein product is tagged …
Ion Permeation Through Membrane Channels: Molecular Dynamics Simulations Studies, Morad Mustafa
Ion Permeation Through Membrane Channels: Molecular Dynamics Simulations Studies, Morad Mustafa
Theses and Dissertations
Molecular dynamics simulation was used to study ion permeation through different membrane proteins embedded in a lipid bilayer (DMPC) with different saline solutions. The potential of mean force (PMF) for ion transport was obtained by umbrella sampling simulations. A revised MacKerell force field for tryptophan residues was studied using gramicidin A (gA) channel as a test model. The revised force field contribution to the Na+ PMF was consonant with the prediction from the experimental results, but in stark contrast to the prediction of the CHARMM force field, version 22, for the tryptophan side-chain. A new grid-based correction map algorithm by …
The Response Of Hn4 Cells To Porphyromonas Gingivalis Dna, Cheyanne Warren
The Response Of Hn4 Cells To Porphyromonas Gingivalis Dna, Cheyanne Warren
Theses and Dissertations
Periodontal disease is one of the most common human diseases. Bacteria trigger the onset and progression of the disease and among them Porphyromonas gingivalis has been demonstrated to be a major etiologic agent. Although the interaction of the bacterium with the host is of major importance for the understanding of the disease mechanisms, both the host as well as the pathogen components involved in the interaction remain poorly understood. One of the bacterial components capable of eliciting a host response is unmethylated CpG DNA motifs found in bacteria. Thus, the first aim was to determine the response of oral epithelial …
Biological Functions Of The Novel Lysophosphatidic Acid (Lpa) Receptor, Lpa4/P2y9/Gpr23, Peilun Lee
Biological Functions Of The Novel Lysophosphatidic Acid (Lpa) Receptor, Lpa4/P2y9/Gpr23, Peilun Lee
Theses and Dissertations
Lysophosphatidic acid (LPA), a naturally occurring phospholipid present in serum and malignant effusions, elicits diverse biological functions through binding and activating specific cell surface G-protein coupled receptors. In addition to the conventional LPA1/Edg2, LPA2/Edg4 and LPA3/Edg7 receptors of the endothelial differentiation gene (Edg) family, LPA4/p2y9/GPR23 of the purinergic receptor family and the related LPA5/GPR92 and LPA6/p2y5 have been identified as novel LPA receptors. These newly identified LPA receptors are structurally distant from the Edg LPA1-3 receptors and couple to Gq, G12/13 and probably Gs subunits. However, the roles of the LPA4-6 receptors in LPA signal transduction and physiology are poorly …
Regulation Of Platelet-Activating Factor Acetylhydrolase By Oxidized Phospholipids And Proinflammatory Cytokines, Muralikrishna Mukkamala
Regulation Of Platelet-Activating Factor Acetylhydrolase By Oxidized Phospholipids And Proinflammatory Cytokines, Muralikrishna Mukkamala
Theses and Dissertations
Platelet-Activating Factor Acetylhydrolase (PAFAH) is a monocyte-derived phospholipase A2 that catalyzes the hydrolysis of platelet-activating factor (PAF) and has been implicated in atherosclerosis. Although PAF and other proinflammatory stimuli are postulated to induce the enzyme, mechanisms controlling PAFAH expression are largely unknown at present. We have shown that PAFAH induction in monocytes is increased in response to oxidized phospholipids. The PAFAH 5' flanking region has at least 10 putative Stat elements, and IL-6 has been shown to be downstream from the prostaglandin receptor, EP2, which has been shown to bind oxidized phospholipids, prompting the hypothesis that Stat proteins might regulate …
Inflammation-Associated Gene Regulation In Primary Astrocytes, Glial Tumors And Cellular Differentiation, Katarzyna Marta Wilczynska
Inflammation-Associated Gene Regulation In Primary Astrocytes, Glial Tumors And Cellular Differentiation, Katarzyna Marta Wilczynska
Theses and Dissertations
This dissertation elucidates several independent molecular mechanisms that function in astrocytes and glial tumor cells, and suggest that developmental and inflammatory signals may contribute to the development of brain tumors. First, we analyzed the mechanism of TIMP-1 activation in astrocytes and glioblastoma cells. TIMP-1 expression is activated by IL-1, which is the major neuroinflammatory cytokine, via simultaneous activation of IKK/NF-kB and MEK3/6/p38/ATF-2 pathways in primary human astrocytes. In contrast to astrocytes, TIMP-1 is expressed at lower levels in glioblastomas, and is not regulated by IL-1 due to either dysfunctional IKK/NF-kB or MEK3/6/p38/ATF-2 activation. Thus, we propose a novel mechanism of …
Fibronectin-Dependent Activation Of Camk-Ii Promotes Focal Adhesion Turnover By Inducing Tyrosine Dephosphorylation Of Fak And Paxillin, Charles Easley Iv
Fibronectin-Dependent Activation Of Camk-Ii Promotes Focal Adhesion Turnover By Inducing Tyrosine Dephosphorylation Of Fak And Paxillin, Charles Easley Iv
Theses and Dissertations
Transient elevations in Ca2+ have previously been shown to promote focal adhesion disassembly and cell motility. Yet the targets of these Ca2+ transients have not been fully examined. In this study, we demonstrate that CaMK-II, a Ca2+/calmodulin dependent protein kinase, is activated in response to β1 integrin engagement with fibronectin to influence fibroblast adhesion and motility. We also show that CaMK-II is dynamically localized to the cell surface using Total Internal Reflection Fluorescence microscopy (TIRFm) and that inhibition of CaMK-II with two mechanistically distinct, membrane permeant inhibitors accelerates spreading on fibronectin, enlarges paxillin-containing focal adhesions and …