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2002

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Articles 1 - 30 of 127

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

Evidence For An Epigenetic Mechanism By Which Hsp90 Acts As A Capacitor For Morphological Evolution, Vincent E. Sollars, Xiangyi Lu, Li Xiao, Xiaoyan Wang, Mark D. Garfinkel, Douglas M. Ruden Dec 2002

Evidence For An Epigenetic Mechanism By Which Hsp90 Acts As A Capacitor For Morphological Evolution, Vincent E. Sollars, Xiangyi Lu, Li Xiao, Xiaoyan Wang, Mark D. Garfinkel, Douglas M. Ruden

Biochemistry and Microbiology

Morphological alterations have been shown to occur in Drosophila melanogaster when function of Hsp90 (heat shock 0-kDa protein 1α, encoded by Hsp83) is compromised during development1. Genetic selection maintains the altered phenotypes in subsequent generations1. Recent experiments have shown, however, that phenotypic variation still occurs in nearly isogenic recombinant inbred strains of Arabidopsis thaliana2. Using a sensitized isogenic D. melanogaster strain, iso-KrIf-1, we confirm this finding and present evidence supporting an epigenetic mechanism for Hsp90’s capacitor function, whereby reduced activity of Hsp90 induces a heritably altered chromatin state. The altered chromatin state is evidenced by ectopic expression ...


The Insulation Of Genes From External Enhancers And Silencing Chromatin, Bonnie Burgess-Beusse, Catherine Farrell, Miklos Gaszner, Michael Litt, Vesco Mutskov, Felix Recillas - Targa, Melanie Simpson, Adam West, Gary Felsenfeld Dec 2002

The Insulation Of Genes From External Enhancers And Silencing Chromatin, Bonnie Burgess-Beusse, Catherine Farrell, Miklos Gaszner, Michael Litt, Vesco Mutskov, Felix Recillas - Targa, Melanie Simpson, Adam West, Gary Felsenfeld

Biochemistry -- Faculty Publications

Insulators are DNA sequence elements that can serve in some cases as barriers to protect a gene against the encroachment of adjacent inactive condensed chromatin. Some insulators also can act as blocking elements to protect against the activating influence of distal enhancers associated with other genes. Although most of the insulators identified so far derive from Drosophila, they also are found in vertebrates. An insulator at the 5′ end of the chicken β -globin locus marks a boundary between an open chromatin domain and a region of constitutively condensed chromatin. Detailed analysis of this element shows that it possesses both ...


Ccr4-Bearing T Cells Participate In Autoimmune Diabetes., Soon H. Kim, Mary M. Cleary, Howard S. Fox, Icos Coporation, Nora Sarvetnick Dec 2002

Ccr4-Bearing T Cells Participate In Autoimmune Diabetes., Soon H. Kim, Mary M. Cleary, Howard S. Fox, Icos Coporation, Nora Sarvetnick

Journal Articles: Regenerative Medicine

Chemokine receptor expression is exquisitely regulated on T cell subsets during the course of their migration to inflammatory sites. In the present study we demonstrate that CCR4 expression marks a pathogenic population of autoimmune T cells. CCR4 was found exclusively on memory CD4(+) T cells during the progression of disease in NOD mice. Cells expressing the CCR4 ligand TARC (thymus- and activation-regulated chemokine) were detected within infiltrated islets from prediabetic mice. Interestingly, neutralization of macrophage-derived chemokine (MDC) with Ab caused a significant reduction of CCR4-positive T cells within the pancreatic infiltrates and inhibited the development of insulitis and diabetes. Furthermore ...


Critical Amino Acids Of The Gα2 Subunit Helical Domain In Dictyostelium Discoideum, Steven Martin Rauch Dec 2002

Critical Amino Acids Of The Gα2 Subunit Helical Domain In Dictyostelium Discoideum, Steven Martin Rauch

Electronic Theses and Dissertations

In Dictyostelium discoideum organism, the Gα2 subunit of the heterotrimeric G-protein signaling complex plays a pivotal role during the aggregation stage in the Dictyostelium life cycle. The biochemical functions of the G-protein complex include separation of the G-protein coupled receptor from the G-protein subunits, GDP displacement by GTP in the Gα subunit, separation of the Gα monomer from the βγ complex, GTP hydrolysis to GDP, activation of adenylyl cyclase as a downstream effector, and activation of guanylyl cyclase as a separate downstream effector. Upon release from the heterotrimer, the βγ subunits lead to downstream activation of the membrane bound adenylyl ...


Analysis Of Protistan Grazing On Bioremediative Bacteria Using In Wvo Fluorescent Protein Expression And Flow Cytometry, Yutao Fu Dec 2002

Analysis Of Protistan Grazing On Bioremediative Bacteria Using In Wvo Fluorescent Protein Expression And Flow Cytometry, Yutao Fu

Electronic Theses and Dissertations

Protistan bacterivory can influence the size distribution, cell structure and composition of natural bacterial communities and is of significant concern for design of bioremediation efforts, yet adequate methods for observation and modeling are lacking. In this investigation, fluorescent protein expression and flow cytometry were used to study protistan grazing on genetically modified strains of several bacterial species that have been considered for use in bioremediation. Broad-host-range plasmids were constructed and used to introduce genes encoding GFP (green fluorescent protein) or RFP (red fluorescent protein) to prey species. A heterotrophic flagellate Paraphysomonas imperforata (Hflag) served as a model predator. Predator-prey interactions ...


Bioorganic Studies In Aids: Synthetic Antifungals Against Pneumocystis Carinii Based On The Multivalency Concept, Langu Peng, Cunxiang Chen, Christian R. Gonzalez, Valeria Balogh-Nair Nov 2002

Bioorganic Studies In Aids: Synthetic Antifungals Against Pneumocystis Carinii Based On The Multivalency Concept, Langu Peng, Cunxiang Chen, Christian R. Gonzalez, Valeria Balogh-Nair

Publications and Research

We report the syntheses of antifungals containing the novel pharmacophores: oxaziridines, sulfonyloxaziridines, nitrones and nitronyl nitroxides. We hypothesized that multiple copies of the pharmacophore per molecule might be a prerequisite to enhance efficacy against the opportunistic pathogen, Pneumocystis carinii. Therefore structural optimization of the leads was based on this new “multivalency” approach. All bisoxaziridines were inactive, but a trisoxaziridine caused ca. 50% reduction of the number of P. carinii tropozoites, compared to TMP-SMX, and a hexaoxaziridine at 1 µg/ml showed activity comparable to the currently used drug, TMP-SMX. Insertion of three units of the nitronyl nitroxide pharmacophore per molecule ...


Signal Recognition Particle Rna Localization Within The Nucleolus Differs From The Classical Sites Of Ribosome Synthesis, Joan C. Ritland Politz, Laura B. Lewandowski, Thoru Pederson Nov 2002

Signal Recognition Particle Rna Localization Within The Nucleolus Differs From The Classical Sites Of Ribosome Synthesis, Joan C. Ritland Politz, Laura B. Lewandowski, Thoru Pederson

Open Access Articles

The nucleolus is the site of ribosome biosynthesis, but is now known to have other functions as well. In the present study we have investigated how the distribution of signal recognition particle (SRP) RNA within the nucleolus relates to the known sites of ribosomal RNA synthesis, processing, and nascent ribosome assembly (i.e., the fibrillar centers, the dense fibrillar component (DFC), and the granular component). Very little SRP RNA was detected in fibrillar centers or the DFC of the nucleolus, as defined by the RNA polymerase I-specific upstream binding factor and the protein fibrillarin, respectively. Some SRP RNA was present ...


Calcium Binding To Calmodulin Mutants Monitored By Domain-Specific Intrinsic Phenylalanine And Tyrosine Fluorescence, W. S. Vanscyoc, B. R. Sorensen, E. Rusinova, William Laws, J. B. A. Ross, M. A. Shea Nov 2002

Calcium Binding To Calmodulin Mutants Monitored By Domain-Specific Intrinsic Phenylalanine And Tyrosine Fluorescence, W. S. Vanscyoc, B. R. Sorensen, E. Rusinova, William Laws, J. B. A. Ross, M. A. Shea

Chemistry and Biochemistry Faculty Publications

Cooperative calcium binding to the two homologous domains of calmodulin (CaM) induces conformational changes that regulate its association with and activation of numerous cellular target proteins. Calcium binding to the pair of high-affinity sites (III and IV in the C-domain) can be monitored by observing calcium-dependent changes in intrinsic tyrosine fluorescence intensity (lambda(ex)/lambda(em) of 277/320 nm). However, calcium binding to the low-affinity sites (I and II in the N-domain) is more difficult to measure with optical spectroscopy because that domain of CaM does not contain tryptophan or tyrosine. We recently demonstrated that calcium-dependent changes in intrinsic ...


A Bulged Stem Tethers Est1p To Telomerase Rna In Budding Yeast, Anita G. Seto, April J. Livengood, Yehuda Tzfati, Elizabeth H. Blackburn, Thomas R. Cech Nov 2002

A Bulged Stem Tethers Est1p To Telomerase Rna In Budding Yeast, Anita G. Seto, April J. Livengood, Yehuda Tzfati, Elizabeth H. Blackburn, Thomas R. Cech

Chemistry & Biochemistry Faculty Contributions (1986-2018)

It is well established that the template for telomeric DNA synthesis is provided by the RNA subunit of telomerase; however, the additional functions provided by most of the rest of the RNA (>1000 nucleotides in budding yeast) are largely unknown. By alignment of telomerase RNAs of Saccharomyces cerevisiae and sixKluyveromycesspecies followed by mutagenesis of the S. cerevisiae RNA, we found a conserved region that is essential for telomere maintenance. Phylogenetic analysis and computer folding revealed that this region is conserved not only in primary nucleotide sequence but also in secondary structure. A common bulged-stem structure was predicted in ...


Human Pot1 (Protection Of Telomeres) Protein: Cytolocalization Gene Structure, And Alternative Splicing, Peter Baumann, Elaine Podell, Thomas R. Cech Nov 2002

Human Pot1 (Protection Of Telomeres) Protein: Cytolocalization Gene Structure, And Alternative Splicing, Peter Baumann, Elaine Podell, Thomas R. Cech

Chemistry & Biochemistry Faculty Contributions (1986-2018)

Fission yeast Pot1 (protection of telomeres) is a single-stranded telomeric DNA binding protein with a critical role in ensuring chromosome stability. A putative human homolog (hPot1) was previously identified, based on moderate sequence similarity with fission yeast Pot1 and telomere end-binding proteins from ciliated protozoa. Using indirect immunofluorescence, we show here that epitope-tagged hPot1 localizes to telomeres in interphase nuclei of human cells, consistent with a direct role in telomere end protection. The hPOT1 gene contains 22 exons, most of which are present in all cDNAs examined. However, four exons are subject to exon skipping in some transcripts, giving rise ...


Anisomycin Activates Jnk And Sensitises Du 145 Prostate Carcinoma Cells To Fas Mediated Apoptosis, James Curtin, Thomas Cotter Nov 2002

Anisomycin Activates Jnk And Sensitises Du 145 Prostate Carcinoma Cells To Fas Mediated Apoptosis, James Curtin, Thomas Cotter

Articles

Treatment of the hormone refractory prostate cancer cell line DU 145 with sublethal concentrations of chemotherapeutic drugs has been reported to sensitise these cells to Fas mediated apoptosis. However, the mechanism by which this occurs has not been determined. Our group has shown that inhibition of JNK activity completely abrogates the effects of chemotherapeutic drugs. Using anisomycin, a potent JNK agonist, we have demonstrated a role for JNK in Fas mediated apoptosis in DU 145 cells. Inhibition of Caspase 8 and Caspase 9 completely inhibits this process which suggests that DU 145 cells require mitochondrial amplification of the Fas apoptotic ...


Plant Rac-Like Gtpases Are Activated By Auxin And Mediate Auxin-Responsive Gene Expression, L. Z. Tao, Alice Cheung, H. M. Wu Oct 2002

Plant Rac-Like Gtpases Are Activated By Auxin And Mediate Auxin-Responsive Gene Expression, L. Z. Tao, Alice Cheung, H. M. Wu

Alice Cheung

The auxin indole-3-acetic acid is a key plant hormone essential for a broad range of growth and developmental processes. Here, we show that auxin activates Rac-like GTPases (referred to as Rac/Rop GTPases), and they in turn stimulate auxin-responsive gene expression. In particular, we show that overexpressing a wild-type tobacco Rac/Rop GTPase, NtRac1, and its constitutively active mutant form activates auxin-responsive gene expression. On the other hand, overexpressing dominant-negative NtRac1 and Rac-negative regulators, or reducing the endogenous NtRac1 level, suppresses auxin-induced gene expression. Furthermore, overexpression of NtRac1 activity or suppression of its expression in transgenic seedlings induces phenotypes that ...


Molecular Dynamics Simulations Of Sodium Dodecyl Sulfate Micelle In Water: The Behavior Of Water, Chrystal Bruce, Sanjib Senapati, Max Berkowitz, L. Perera, M. Forbes Oct 2002

Molecular Dynamics Simulations Of Sodium Dodecyl Sulfate Micelle In Water: The Behavior Of Water, Chrystal Bruce, Sanjib Senapati, Max Berkowitz, L. Perera, M. Forbes

Chrystal D. Bruce

Using a 5 ns explicit atom molecular dynamics simulation of a 60 monomer sodium dodecyl sulfate micellar system containing 7579 TIP3P water molecules, the behavior of water in different electrostatic environments was examined. Structural evaluation of the system revealed that penetration of water molecules into the micelle was restricted to the headgroup region, leaving a 12 Å water-free hydrocarbon core. Water molecules near the headgroup exhibit a distortion of the water−water hydrogen bonding network due to headgroup oxygen−water hydrogen bond formation. The dynamic implications of this distortion are manifested in the decay of the dipole autocorrelation function, Φ ...


Reaction Mechanism, Evolutionary Analysis, And Role Of Zinc In Drosophila Methionine-R-Sulfoxide Reductase, R. Abhilash Kumar, Ahmet Koc, Ronald Cerny, Vadim N. Gladyshev Oct 2002

Reaction Mechanism, Evolutionary Analysis, And Role Of Zinc In Drosophila Methionine-R-Sulfoxide Reductase, R. Abhilash Kumar, Ahmet Koc, Ronald Cerny, Vadim N. Gladyshev

Vadim Gladyshev Publications

Methionine residues in proteins are susceptible to oxidation, and the resulting methionine sulfoxides can be reduced back to methionines by methionine- S-sulfoxide reductase (MsrA) and methionine-R-sulfoxide reductase (MsrB). Herein, we have identified two MsrB families that differ by the presence of zinc. Evolutionary analyses suggested that the zinc-containing MsrB proteins are prototype enzymes and that the metal was lost in certain MsrB proteins later in evolution. Zinc-containing Drosophila MsrB was further characterized. The enzyme was found to employ a catalytic Cys124 thiolate, which directly interacted with methionine sulfoxide, resulting in methionine and a Cys124 sulfenic ...


Guanine And 7,8-Dihydro-8-Oxo-Guanine-Specific Oxidation In Dna By Chromium(V), Kent D. Sugden, Brooke Martin Oct 2002

Guanine And 7,8-Dihydro-8-Oxo-Guanine-Specific Oxidation In Dna By Chromium(V), Kent D. Sugden, Brooke Martin

Chemistry and Biochemistry Faculty Publications

The hexavalent oxidation state of chromium [Cr(VI)] is a well-established human carcinogen, although the mechanism of cancer induction is currently unknown. Intracellular reduction of Cr(VI) forms Cr(V), which is thought to play a fundamental role in the mechanism of DNA damage by this carcinogen. Two separate pathways of DNA damage, an oxidative pathway and a metal-binding pathway, have been proposed to account for the lesions observed in cell systems. We have used a model Cr(V) complex, N,N´-ethylenebis(salicylidene-animato)oxochromium(V) [Cr(V)-Salen], to investigate the oxidative pathway of DNA damage and to elucidate ...


Electrically Mediated Delivery Of Vector Plasmid Dna Elicits An Antitumor Effect, L. Heller, D. Coppola Oct 2002

Electrically Mediated Delivery Of Vector Plasmid Dna Elicits An Antitumor Effect, L. Heller, D. Coppola

Bioelectrics Publications

In vivo electroporation is an efficient means of increasing plasmid DNA delivery to normal tissues, such as skin and muscle, as well as directly to tumors. In the experiments described here, plasmid DNA was delivered by in vivo electroporation to B16 mouse melanomas using two very different pulsing protocols. Reporter expression increased 21- or 42-fold, respectively with electroporation over injection alone. The growth of experimental melanomas with an approximate diameter of 4 mm on the day of treatment was monitored after electroporation delivery of reporter plasmid DNA. Remarkably, short-term complete regressions using one of these pulsing protocols occurred in up ...


A Comparison Of The Low Mode And Monte Carlo Conformational Search Methods, Carol A. Parish, Rosina Lombardi, Kent Sinclair, Emelyn Smith, Alla Goldberg, Melissa Rappleye, Myrianne Dure Oct 2002

A Comparison Of The Low Mode And Monte Carlo Conformational Search Methods, Carol A. Parish, Rosina Lombardi, Kent Sinclair, Emelyn Smith, Alla Goldberg, Melissa Rappleye, Myrianne Dure

Chemistry Faculty Publications

The Low Mode (LM) and Monte Carlo (MC) conformational search methods were compared on three diverse molecular systems; (4R, 5S, 6S, 7R)-hexahydro-5,6-dihydroxy-1,3,4,7-tetrakis(phenylmethyl)-2H-1,3-diazapin-2-one (1), 2-methoxy-2-phenyl-2-triflouromethyl-N-α-methyl benzyl propanamide (2) and a trimeric 39-membered polyazamacrolide (3). We find that either method, or a combination of the methods, is equally efficient at searching the conformational space of the smaller molecular systems while a 50:50 hybrid of Low Mode and Monte Carlo is most efficient at searching the space of the larger molecular system.


Meiotic Cohesion Requires Accumulation Of Ord On Chromosomes Before Condensation, Eric M. Balicky, Matthew W. Endres, Cary Lai, Sharon E. Bickel Sep 2002

Meiotic Cohesion Requires Accumulation Of Ord On Chromosomes Before Condensation, Eric M. Balicky, Matthew W. Endres, Cary Lai, Sharon E. Bickel

Open Dartmouth: Faculty Open Access Scholarship

Cohesion between sister chromatids is a prerequisite for accurate chromosome segregation during mitosis and meiosis. To allow chromosome condensation during prophase, the connections that hold sister chromatids together must be maintained but still permit extensive chromatin compaction. In Drosophila, null mutations in the orientation disruptor (ord) gene lead to meiotic nondisjunction in males and females because cohesion is absent by the time that sister kinetochores make stable microtubule attachments. We provide evidence that ORD is concentrated within the extrachromosomal domains of the nuclei ofDrosophila primary spermatocytes during early G2, but accumulates on the meiotic chromosomes by mid to late ...


Monte Carlo Simulation On The Indirect Exchange Interactions Of Co-Doped Zno Film, Abraham F. Jalbout, Hanning Chen, Scott L. Whittenburg Sep 2002

Monte Carlo Simulation On The Indirect Exchange Interactions Of Co-Doped Zno Film, Abraham F. Jalbout, Hanning Chen, Scott L. Whittenburg

Chemistry and Biochemistry Faculty Publications

Monte Carlo simulations using a three-dimensional lattice model studied the Ruderman–Kittel–Kasuya–Yosida (RKKY) indirect exchange interaction of doped magnetic Co ions in ZnOfilms. The results of the calculations show that the RKKY interaction in Co-doped ZnO is long ranged and its magnitude is proportional to (inverse of the distance from a central ion). The sign oscillates with a frequency that depends on the concentration of the carrier. The long-distance sum of the RKKY indirect exchange energies is positive indicating that these materials are ferromagnetic, in direct correlation with previously reported results.


Inhibition Of Prostate Tumor Cell Hyaluronan Synthesis Impairs Subcutaneous Growth And Vascularization In Immunocompromised Mice, Melanie A. Simpson, Christopher M. Wilson, James B. Mccarthy Sep 2002

Inhibition Of Prostate Tumor Cell Hyaluronan Synthesis Impairs Subcutaneous Growth And Vascularization In Immunocompromised Mice, Melanie A. Simpson, Christopher M. Wilson, James B. Mccarthy

Biochemistry -- Faculty Publications

Hyaluronan (HA), a secreted glycosaminoglycan component of extracellular matrices, is critical for cellular proliferation and motility during development. However, elevated circulating and cell-associated levels correlate with various types of cancer, including prostate. We have previously shown that aggressive PC3M-LN4 prostate tumor cells synthesize excessive HA relative to less aggressive cells, and express correspondingly higher levels of the HA biosynthetic enzymes HAS2 and HAS3. Inhibition of these enzymes by stable transfection of PC3M-LN4 cells with anti-sense HAS2 or HAS3 expression constructs diminishes HA synthesis and surface retention. In this report, we used these HA-deficient cell lines to examine the role of ...


Solution And Micelle-Bound Structures Of Tachyplesin I And Its Active Aromatic Linear Derivatives, Alain Laederach, Amy H. Andreotti, D. Bruce Fulton Sep 2002

Solution And Micelle-Bound Structures Of Tachyplesin I And Its Active Aromatic Linear Derivatives, Alain Laederach, Amy H. Andreotti, D. Bruce Fulton

Biochemistry, Biophysics and Molecular Biology Publications

Tachyplesin I is a 17-residue peptide isolated from the horseshoe crab, Tachyplesus tridentatus. It has high antimicrobial activity and adopts a β-hairpin conformation in solution stabilized by two cross-strand disulfide bonds. We report an NMR structural investigation of wild-type tachyplesin I and three linear derivatives (denoted TPY4, TPF4, and TPA4 in which the bridging cysteine residues are uniformly replaced with tyrosine, phenylalanine, and alanine, respectively). The three-dimensional aqueous solution structures of the wild type and the active variant TPY4 reveal very similar β-hairpin conformations. In contrast, the inactive variant TPA4 is unstructured in solution. The arrangement of the tyrosine side ...


The Regulation Of Actin Organization By Actin-Depolymerizing Factor In Elongating Pollen Tubes, C. Y. Chen, E. I. Wong, L. Vidali, A. Estavillo, P. K. Hepler, H. M. Wu, Alice Cheung Aug 2002

The Regulation Of Actin Organization By Actin-Depolymerizing Factor In Elongating Pollen Tubes, C. Y. Chen, E. I. Wong, L. Vidali, A. Estavillo, P. K. Hepler, H. M. Wu, Alice Cheung

Alice Cheung

Pollen tube elongation is a polarized cell growth process that transports the male gametes from the stigma to the ovary for fertilization inside the ovules. Actomyosin-driven intracellular trafficking and active actin remodeling in the apical and subapical regions of pollen tubes are both important aspects of this rapid tip growth process. Actin-depolymerizing factor (ADF) and cofilin are actin binding proteins that enhance the depolymerization of microfilaments at their minus, or slow-growing, ends. A pollen-specific ADF from tobacco, NtADF1, was used to dissect the role of ADF in pollen tube growth. Overexpression of NtADF1 resulted in the reduction of fine, axially ...


Kalirin Dbl-Homology Guanine Nucleotide Exchange Factor 1 Domain Initiates New Axon Outgrowths Via Rhog-Mediated Mechanisms, Victor May, Martin R. Schiller, Betty A. Eipper, Richard E. Mains Aug 2002

Kalirin Dbl-Homology Guanine Nucleotide Exchange Factor 1 Domain Initiates New Axon Outgrowths Via Rhog-Mediated Mechanisms, Victor May, Martin R. Schiller, Betty A. Eipper, Richard E. Mains

Life Sciences Faculty Publications

The large multidomain Kalirin and Trio proteins containing dual Rho GTPase guanine nucleotide exchange factor (GEF) domains have been implicated in the regulation of neuronal fiber extension and pathfinding during evelopment. In mammals, Kalirin is expressed predominantly in the nervous system, whereas Trio, broadly expressed throughout the body, is expressed at a lower level in the nervous system. To evaluate the role of Kalirin in fiber initiation and outgrowth, we microinjected cultured sympathetic neurons with vectors encoding Kalirin or with Kalirin antisense oligonucleotides, and we assessed neuronal fiber growth in a serum-free, satellite cell-free environment. Kalirin antisense oligonucleotides blocked the ...


Glutathione Levels And Bax Activation During Apoptosis Due To Oxidative Stress In Cells Expressing Wild-Type And Mutant Cystic Fibrosis Transmembrane Conductance Regulator, Thomas Jungas, Iris Motta, Francis Duffieux, Pascale Fanen, Veronique Stoven, David M. Ojcius Aug 2002

Glutathione Levels And Bax Activation During Apoptosis Due To Oxidative Stress In Cells Expressing Wild-Type And Mutant Cystic Fibrosis Transmembrane Conductance Regulator, Thomas Jungas, Iris Motta, Francis Duffieux, Pascale Fanen, Veronique Stoven, David M. Ojcius

Dugoni School of Dentistry Faculty Articles

Cystic fibrosis is characterized by chronic inflammation and an imbalance in the concentrations of alveolar and lung oxidants and antioxidants, which result in cell damage. Modifications in lung glutathione concentrations are recognized as a salient feature of inflammatory lung diseases such as cystic fibrosis, and glutathione plays a major role in protection against oxidative stress and is important in modulation of apoptosis. The cystic fibrosis transmembrane conductance regulator (CFTR) is permeable to Cl−, larger organic ions, and reduced and oxidized forms of glutathione, and the ΔF508 CFTR mutation found in cystic fibrosis patients has been correlated with impaired glutathione transport ...


Investigation Of Biochemical Mechanisms Associated With Insulin Resistance In The Non-Insulin-Dependent Diabetes Mellitus, To-Yu Huang Aug 2002

Investigation Of Biochemical Mechanisms Associated With Insulin Resistance In The Non-Insulin-Dependent Diabetes Mellitus, To-Yu Huang

Doctoral Dissertations

Non-insulin dependent diabetes mellitus (NIDDM) is a heterogeneous disease arising from metabolic defects in insulin secretion and insulin action. The inability of insulin to trigger full metabolic responses results in impaired glucose transport, which elicits compensatory hyperinsulinemia with increased lipogenesis. In order to identify the molecular defects responsible for insulin resistance, we have investigated three different model systems: the ability of sulfonylurea receptor (SUR) ligands to modify insulin regulated events in cultured rodent adipocytes; the ability of agouti and/or agouti related polypeptide (AGRP) to modify insulin regulated events; and the regulation of the activity and amount of the HNF-1a ...


Jun Dimerization Protein 2 Functions As A Progesterone Receptor N-Terminal Domain Coactivator, James S. Adelman, Suzanne E. Wardell, Viroj Boonyaratanakornkit, Ami Aronheim Aug 2002

Jun Dimerization Protein 2 Functions As A Progesterone Receptor N-Terminal Domain Coactivator, James S. Adelman, Suzanne E. Wardell, Viroj Boonyaratanakornkit, Ami Aronheim

James S. Adelman

The progesterone receptor (PR) contains two transcription activation function (AF) domains, constitutive AF-1 in the N terminus and AF-2 in the C terminus. AF-2 activity is mediated by a hormone-dependent interaction with a family of steroid receptor coactivators (SRCs). SRC-1 can also stimulate AF-1 activity through a secondary domain that interacts simultaneously with the primary AF-2 interaction site. Other protein interactions and mechanisms that mediate AF-1 activity are not well defined. By interaction cloning, we identified an AP-1 family member, Jun dimerization protein 2 (JDP-2), as a novel PR-interacting protein. JDP-2 was first defined as a c-Jun interacting protein that ...


Variability Of Placental Expression Of Cyclin E Low Molecular Weight Variants, A Bukovsky, Maria Cekanova, Mr Caudle, J Wimalasena, Js Foster, Ja Keenan, Rf Elder Jul 2002

Variability Of Placental Expression Of Cyclin E Low Molecular Weight Variants, A Bukovsky, Maria Cekanova, Mr Caudle, J Wimalasena, Js Foster, Ja Keenan, Rf Elder

Maria Cekanova MS, RNDr, PhD

Cyclin E, a G(1) cyclin serving to activate cyclin-dependent kinase 2, is the only cyclin gene for which alternative splicing leading to structurally different proteins has been described. Different cyclin E proteins are present in tumor tissues but absent from normal (steady) tissues. Cyclin E contributes to the regulation of cell proliferation and ongoing differentiation and aging. Because trophoblast has invasive properties and differentiates into syncytium and placental aging may develop at term, we examined cyclin E protein variants in human placenta. Placental samples were collected from 27 deliveries between 33 and 41 wk and were compared with ovarian ...


Selenoproteins And Selenocysteine Insertion System In The Model Plant Cell System, Chlamydomonas Reinhardtii, Sergey V. Novoselov, Mahadev Rao, Natalia V. Onoshko, Huijun Zhi, Gregory V. Kryukov, Youbin Xiang, Donald P. Weeks, Dolph A. Hatfield, Vadim Gladyshev Jul 2002

Selenoproteins And Selenocysteine Insertion System In The Model Plant Cell System, Chlamydomonas Reinhardtii, Sergey V. Novoselov, Mahadev Rao, Natalia V. Onoshko, Huijun Zhi, Gregory V. Kryukov, Youbin Xiang, Donald P. Weeks, Dolph A. Hatfield, Vadim Gladyshev

Vadim Gladyshev Publications

Known eukaryotic selenocysteine (Sec)-containing proteins are animal proteins, whereas selenoproteins have not been found in yeast and plants. Surprisingly, we detected selenoproteins in a member of the plant kingdom, Chlumydomonas reinhardtii, and directly identified two of them as phospholipid hydroperoxide glutathione peroxidase and selenoprotein W homologs. Moreover, a selenocysteyl-tRNA was isolated that recognized specifically the Sec codon UGA. Subsequent gene cloning and bioinformatics analyses identified eight additional selenoproteins, including methionine-Ssulfoxide reductase, a selenoprotein specific to Chlumydomonas. Chlumydomonas selenoprotein genes contained selenocysteine insertion sequence (SECIS) elements that were similar, but not identical, to those of animals. These SECIS elements could ...


Comparison Of Water Quality, Zooplankton Density, And Cover In Razorback Sucker (Xyrauchen Texanus [Abbott]) Spawning Areas Of Lake Mead And Lake Mohave, Michael E. Golden, Paul B. Holden, Southern Nevada Water Authority Jul 2002

Comparison Of Water Quality, Zooplankton Density, And Cover In Razorback Sucker (Xyrauchen Texanus [Abbott]) Spawning Areas Of Lake Mead And Lake Mohave, Michael E. Golden, Paul B. Holden, Southern Nevada Water Authority

Publications (WR)

Las Vegas Bay and Echo Bay in Lake Mead have small, self-sustaining populations of razorback sucker (Xyrauchen texanus [Abbot]). Increased productivity and cover have been hypothesized as reasons for successful recruitment of razorback sucker in Lake Mead. Conversely, reproduction has been documented on Lake Mohave, another lower Colorado River reservoir, but no recruitment has been observed. In 2000, BIO-WEST, Inc. was contracted by the Southern Nevada Water Authority to design and implement a study to examine nutrient levels, zooplankton density, and cover in areas with and without razorback sucker recruitment success. We sampled Echo Bay, Las Vegas Bay, and Trail ...


Regulation And Measurement Of Oxidative Stress In Apoptosis, James Curtin, Maryanne Donovan, Thomas Cotter Jul 2002

Regulation And Measurement Of Oxidative Stress In Apoptosis, James Curtin, Maryanne Donovan, Thomas Cotter

Articles

Cells are constantly generating reactive oxygen species (ROS) during aerobic metabolism. As a consequence, each cell is equipped with an extensive antioxidant defence system to combat excessive production of ROS. Oxidative stress occurs in cells when the generation of ROS overwhelms the cell's natural antioxidant defences. There is a growing consensus that oxidative stress and the redox state of a cell plays a pivotal role in regulating apoptosis, a tightly controlled form of cell death in which a cell partakes in its own demise. More recently, a role for reactive nitrogen species (RNI) as both positive and negative regulators ...