Sample records for methylated caffeine-silveri complex

  1. Unusually Stable Pyrazolate-Bridged Dialuminum Complexes Containing Bridging Methyl Groups

    E-print Network

    Schlegel, H. Bernhard

    Unusually Stable Pyrazolate-Bridged Dialuminum Complexes Containing Bridging Methyl Groups Zhengkun pyrazoles with excess trimethylaluminum. The bridging methyl groups in these complexes are more stable than

  2. Transition metal complexes with 2-methyl-, 3-methyl-, and 4-methyl-piperidine dithiocarbamate as ligands

    Microsoft Academic Search

    Antonio C. Fabretti; Gian C. Franchini; Carlo Preti; Giuseppe Tosi; Paolo Zannini

    1985-01-01

    A new series of manganese(III), cobalt(II), nickel(II), zinc(II), cadmium(II) and mercury(II) complexes with monomethylsubstituted dithiocarbamates as ligands has been synthesized and studied. Their structures are discussed in relation to their spectroscopic, magnetic and thermal properties. The dithio-ligands exhibit bidentate behaviour acting as S,S'donors in all the complexes. In the far i.r. region particular attention is paid to a comparison of

  3. Complexation of Inorganic Mercury by Cysteine Promotes Bacterial Methylation of Mercury

    Microsoft Academic Search

    J. K. Schaefer; M. J. Walsh; B. A. Ahner; F. M. Morel

    2007-01-01

    One critical factor controlling methylmercury (MeHg) accumulation in the environment is the chemical form of Hg(II) available for methylation by bacteria. Current models suggest that passive diffusion of neutral sulfide complexes may determine the bioavailability and methylation of mercury; however, these hypotheses have never been thoroughly tested. We have investigated how the chemical speciation of Hg(II) affects mercury methylation in

  4. Epigenome-wide association of liver methylation patterns and complex metabolic traits in mice.

    PubMed

    Orozco, Luz D; Morselli, Marco; Rubbi, Liudmilla; Guo, Weilong; Go, James; Shi, Huwenbo; Lopez, David; Furlotte, Nicholas A; Bennett, Brian J; Farber, Charles R; Ghazalpour, Anatole; Zhang, Michael Q; Bahous, Renata; Rozen, Rima; Lusis, Aldons J; Pellegrini, Matteo

    2015-06-01

    Heritable epigenetic factors can contribute to complex disease etiology. Here we examine the contribution of DNA methylation to complex traits that are precursors to heart disease, diabetes, and osteoporosis. We profiled DNA methylation in the liver using bisulfite sequencing in 90 mouse inbred strains, genome-wide expression levels, proteomics, metabolomics, and 68 clinical traits and performed epigenome-wide association studies (EWAS). We found associations with numerous clinical traits including bone density, insulin resistance, expression, and protein and metabolite levels. A large proportion of associations were unique to EWAS and were not identified using GWAS. Methylation levels were regulated by genetics largely in cis, but we also found evidence of trans regulation, and we demonstrate that genetic variation in the methionine synthase reductase gene Mtrr affects methylation of hundreds of CpGs throughout the genome. Our results indicate that natural variation in methylation levels contributes to the etiology of complex clinical traits. PMID:26039453

  5. LSH and G9a/GLP complex are required for developmentally programmed DNA methylation.

    PubMed

    Myant, Kevin; Termanis, Ausma; Sundaram, Arvind Y M; Boe, Tristin; Li, Chao; Merusi, Cara; Burrage, Joe; de Las Heras, Jose I; Stancheva, Irina

    2011-01-01

    LSH, a member of the SNF2 family of chromatin remodeling ATPases encoded by the Hells gene, is essential for normal levels of DNA methylation in the mammalian genome. While the role of LSH in the methylation of repetitive DNA sequences is well characterized, its contribution to the regulation of DNA methylation and the expression of protein-coding genes has not been studied in detail. In this report we investigate genome-wide patterns of DNA methylation at gene promoters in Hells(-/-) mouse embryonic fibroblasts (MEFs). We find that in the absence of LSH, DNA methylation is lost or significantly reduced at ?20% of all normally methylated promoter sequences. As a consequence, a large number of genes are misexpressed in Hells(-/-) MEFs. Comparison of Hells(-/-) MEFs with wild-type MEFs and embryonic stem (ES) cells suggests that LSH is important for de novo DNA methylation events that accompany the establishment and differentiation of embryonic lineage cells. We further show that the generation of normal DNA methylation patterns and stable gene silencing at specific promoters require cooperation between LSH and the G9a/GLP complex of histone methylases. At such loci, G9a recruitment is compromised when LSH is absent or greatly reduced. Taken together, our data suggest a mechanism whereby LSH promotes binding of DNA methyltransferases and the G9a/GLP complex to specific loci and facilitates developmentally programmed DNA methylation and stable gene silencing during lineage commitment and differentiation. PMID:21149390

  6. Antifungal activity of ?-methyl trans cinnamaldehyde, its ligand and metal complexes: promising growth and ergosterol inhibitors.

    PubMed

    Shreaz, Sheikh; Sheikh, Rayees A; Bhatia, Rimple; Neelofar, Khan; Imran, Sheikh; Hashmi, Athar A; Manzoor, Nikhat; Basir, Seemi F; Khan, Luqman A

    2011-10-01

    Antifungal effectivity and utility of cinnamaldehyde is limited because of its high MIC and skin sensitivity. In this study, ?-methyl trans cinnamaldehyde, a less irritating derivative, have been self coupled and complexed with Co(II) and Ni(II) to generate N, N'-Bis (?-methyl trans cinnamadehyde) ethylenediimine [C(22)H(24)N(2)], [Co(C(44)H(48)N(4))Cl(2)] and [Ni(C(44)H(48)N(4))Cl(2)]. Ligand and complexes were characterized on the basis of FTIR, ESI-MS, IR and (1)HNMR techniques. Synthesized ligand [L] and complexes were investigated for their MICs, inhibition of ergosterol biosynthesis and H(+) extrusion against three strains of Candida: C. albicans 44829, C. tropicalis 750 and C. krusei 6258. Average of three species MIC of methyl cinnamaldehyde is 317 ?g/ml (2168 ?M). Compared to methyl cinnamaldehyde ligand [L], Co(II) and Ni(II) complex are found to be 4.48, 17.78 and 21.46 times more effective in liquid medium and 2.73, 8.93 and 10.38 times more effective in solid medium. At their respective MIC(90) average inhibition of ergosterol biosynthesis caused by methyl cinnamaldehyde, ligand [L], Co(II) and Ni(II) complex, respectively was 80, 78, 90 and 93%. H(+) extrusion was also significantly inhibited but did not co-relate well with MIC(90). Results indicate ergosterol biosynthesis as site of action of ?-methyl cinnamaldehyde, synthesized ligand and complexes. ?-methyl cinnamaldehyde and ligand did not show any toxicity against H9c2 rat cardiac myoblast cell, whereas Co(II) and Ni(II) complexes on an average produced 19% cellular toxicity. PMID:21476019

  7. Antifungal activity of ?-methyl trans cinnamaldehyde, its ligand and metal complexes: promising growth and ergosterol inhibitors

    Microsoft Academic Search

    Sheikh Shreaz; Rayees A. Sheikh; Rimple Bhatia; Khan Neelofar; Sheikh Imran; Athar A. Hashmi; Nikhat Manzoor; Seemi F. Basir; Luqman A. Khan

    Antifungal effectivity and utility of cinnamaldehyde is limited because of its high MIC and skin sensitivity. In this study,\\u000a ?-methyl trans cinnamaldehyde, a less irritating derivative, have been self coupled and complexed with Co(II) and Ni(II) to\\u000a generate N, N?–Bis (?-methyl trans cinnamadehyde) ethylenediimine [C22H24N2], [Co(C44H48N4)Cl2] and [Ni(C44H48N4)Cl2]. Ligand and complexes were characterized on the basis of FTIR, ESI–MS, IR

  8. Fixation of atmospheric carbon dioxide by ruthenium complexes bearing an NHC-based pincer ligand: formation of a methylcarbonato complex and its methylation.

    PubMed

    Arikawa, Yasuhiro; Nakamura, Takuo; Ogushi, Shinji; Eguchi, Kazushige; Umakoshi, Keisuke

    2015-03-28

    A methylcarbonato ruthenium complex was prepared by capture of CO2 from air using the (CNC)(bpy)Ru scaffold. The methylcarbonato complex was relatively inert to decarboxylation. Treatments with methylating reagents released dimethylcarbonate. PMID:25711491

  9. Hydrolysis, hydrosulfidolysis, and aminolysis of imido(methyl)rhenium complexes.

    PubMed

    Wang, W D; Guzei, I A; Espenson, J H

    2000-09-01

    The tris(imido)methylrhenium complex CH3Re(NAd)3 (1a, Ad = 1-adamantyl) reacts with H2O to give CH3Re(NAd)2O (2a) and AdNH2. The resulting di(imido)oxo species can further react with another molecule of H2O to generate CH3Re(NAd)O2 (3a). The kinetics of these reactions have been studied by means of 1H NMR and UV-vis spectroscopies. The second-order rate constant for the reaction of 1a with H2O at 298 K in C6H6 is 3.3 L mol-1 s-1, which is much larger than the value 1 x 10(-4) L mol-1 s-1 obtained for the reaction between CH3Re(NAr)3 (1b, Ar = 2,6-diisopropylphenyl) and H2O in CH3CN at 313 K. Both 1a and 1b react with H2S to produce the rhenium(VII) sulfide, (CH3Re(NR)2)2(mu-S)2 (4a, R = Ad; 4b, R = Ar), with second-order rate constants of 17 and 1.6 x 10(-4) L mol-1 s-1 in C6H6 and CH3CN, respectively. Complex 4b has been structurally characterized. The crystal data are as follows: space group C2/c, a = 30.4831 (19) A, b = 10.9766 (7) A, c = 18.1645 (11) A, beta = 108.268(1) degrees, V = 5771.5 (6) A3, Z = 4. The reaction between CH3Re(NAr)2O (2b) and H2S also yields the dinuclear compound 4b. Unlike 1b, 1a reacts with aniline derivatives to give mixed imido rhenium complexes. PMID:11198866

  10. On the complexation of quercetin with methyl-?-cyclodextrin: photostability and antioxidant studies

    Microsoft Academic Search

    M. E. Carlotti; S. Sapino; E. Ugazio; G. Caron

    2011-01-01

    Quercetin, a plant-derived flavonoid, has been extensively investigated for a wide range of potential health benefits linked\\u000a to its antioxidant properties. Unfortunately the topical administration of this molecule is restricted by its fast photodegradation.\\u000a In the attempt to overcome this limitation the inclusion complex between quercetin (Q) and methyl-?-cyclodextrin (Me-?-CD)\\u000a was prepared and previously investigated by a molecular modelling study,

  11. Influence of the preparation method on the physicochemical properties of indomethacin and methyl-?-cyclodextrin complexes.

    PubMed

    Rudrangi, Shashi Ravi Suman; Bhomia, Ruchir; Trivedi, Vivek; Vine, George J; Mitchell, John C; Alexander, Bruce David; Wicks, Stephen Richard

    2015-02-20

    The main objective of this study was to investigate different manufacturing processes claimed to promote inclusion complexation between indomethacin and cyclodextrins in order to enhance the apparent solubility and dissolution properties of indomethacin. Especially, the effectiveness of supercritical carbon dioxide processing for preparing solid drug-cyclodextrin inclusion complexes was investigated and compared to other preparation methods. The complexes were prepared by physical mixing, co-evaporation, freeze drying from aqueous solution, spray drying and supercritical carbon dioxide processing methods. The prepared complexes were then evaluated by scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, solubility and dissolution studies. The method of preparation of the inclusion complexes was shown to influence the physicochemical properties of the formed complexes. Indomethacin exists in a highly crystalline solid form. Physical mixing of indomethacin and methyl-?-cyclodextrin appeared not to reduce the degree of crystallinity of the drug. The co-evaporated and freeze dried complexes had a lower degree of crystallinity than the physical mix; however the lowest degree of crystallinity was achieved in complexes prepared by spray drying and supercritical carbon dioxide processing methods. All systems based on methyl-?-cyclodextrin exhibited better dissolution properties than the drug alone. The greatest improvement in drug dissolution properties was obtained from complexes prepared using supercritical carbon dioxide processing, thereafter by spray drying, freeze drying, co-evaporation and finally by physical mixing. Supercritical carbon dioxide processing is well known as an energy efficient alternative to other pharmaceutical processes and may have application for the preparation of solid-state drug-cyclodextrin inclusion complexes. It is an effective and economic method that allows the formation of solid complexes with a high yield, without the use of organic solvents and problems associated with their residues. PMID:25579867

  12. Complexes of polyadenylic acid and the methyl esters of amino acids

    NASA Technical Reports Server (NTRS)

    Khaled, M. A.; Mulins, D. W., Jr.; Swindle, M.; Lacey, J. C., Jr.

    1983-01-01

    A study of amino acid methyl esters binding to polyadenylic acid supports the theory that the genetic code originated through weak but selective affinities between amino acids and nucleotides. NMR, insoluble complex analysis, and ultraviolet spectroscopy are used to illustrate a correlation between the hydrophybicities of A amino acids and their binding constants, which, beginning with the largest, are in the order of Phe (having nominally a hydrophobic AAA anticodon), Ile, Leu, Val and Gly (having a hydrophilic anticodon with no A). In general, the binding constants are twice the values by Reuben and Polk (1980) for monomeric AMP, which suggests that polymer amino acids are interacting with only one base. No real differences are found betwen poly A binding for free Phe, Phe methyl ester or Phe amide, except that the amide value is slightly lower.

  13. Rare-earth-metal methyl, amide, and imide complexes supported by a superbulky scorpionate ligand.

    PubMed

    Schädle, Dorothea; Maichle-Mössmer, Cäcilia; Schädle, Christoph; Anwander, Reiner

    2015-01-01

    The reaction of monomeric [(Tp(tBu,Me) )LuMe2 ] (Tp(tBu,Me) =tris(3-Me-5-tBu-pyrazolyl)borate) with primary aliphatic amines H2 NR (R=tBu, Ad=adamantyl) led to lutetium methyl primary amide complexes [(Tp(tBu,Me) )LuMe(NHR)], the solid-state structures of which were determined by XRD analyses. The mixed methyl/tetramethylaluminate compounds [(Tp(tBu,Me) )LnMe({?2 -Me}AlMe3 )] (Ln=Y, Ho) reacted selectively and in high yield with H2 NR, according to methane elimination, to afford heterobimetallic complexes: [(Tp(tBu,Me) )Ln({?2 -Me}AlMe2 )(?2 -NR)] (Ln=Y, Ho). X-ray structure analyses revealed that the monomeric alkylaluminum-supported imide complexes were isostructural, featuring bridging methyl and imido ligands. Deeper insight into the fluxional behavior in solution was gained by (1) H and (13) C?NMR spectroscopic studies at variable temperatures and (1) H-(89) Y HSQC NMR spectroscopy. Treatment of [(Tp(tBu,Me) )LnMe(AlMe4 )] with H2 NtBu gave dimethyl compounds [(Tp(tBu,Me) )LnMe2 ] as minor side products for the mid-sized metals yttrium and holmium and in high yield for the smaller lutetium. Preparative-scale amounts of complexes [(Tp(tBu,Me) )LnMe2 ] (Ln=Y, Ho, Lu) were made accessible through aluminate cleavage of [(Tp(tBu,Me) )LnMe(AlMe4 )] with N,N,N',N'-tetramethylethylenediamine (tmeda). The solid-state structures of [(Tp(tBu,Me) )HoMe(AlMe4 )] and [(Tp(tBu,Me) )HoMe2 ] were analyzed by XRD. PMID:25392940

  14. Drug release from drug-polyanion complex tablets: poly(acrylamido-2-methyl-1-propanesulfonate sodium -co- methyl methacrylate)

    Microsoft Academic Search

    Nandini Konar; Cherng-ju Kim

    1999-01-01

    A new erodible, anionic carrier for cationic drugs has been synthesized for oral drug delivery systems. The release properties of tablets prepared from this new material, poly(acrylamido-2-methyl-1-propanesulfonate sodium -co- methyl methacrylate) (PAMPSNa\\/MMA), are discussed. Pseudo-linear release profiles were obtained and the hydrophobicities of both the polymeric carrier and the bound drugs were found to be an important controlling factor in

  15. Allele-Specific Methylation Occurs at Genetic Variants Associated with Complex Disease

    PubMed Central

    Hutchinson, John N.; Raj, Towfique; Fagerness, Jes; Stahl, Eli; Viloria, Fernando T.; Gimelbrant, Alexander; Seddon, Johanna; Daly, Mark; Chess, Andrew; Plenge, Robert

    2014-01-01

    We hypothesize that the phenomenon of allele-specific methylation (ASM) may underlie the phenotypic effects of multiple variants identified by Genome-Wide Association studies (GWAS). We evaluate ASM in a human population and document its genome-wide patterns in an initial screen at up to 380,678 sites within the genome, or up to 5% of the total genomic CpGs. We show that while substantial inter-individual variation exists, 5% of assessed sites show evidence of ASM in at least six samples; the majority of these events (81%) are under genetic influence. Many of these cis-regulated ASM variants are also eQTLs in peripheral blood mononuclear cells and monocytes and/or in high linkage-disequilibrium with variants linked to complex disease. Finally, focusing on autoimmune phenotypes, we extend this initial screen to confirm the association of cis-regulated ASM with multiple complex disease-associated variants in an independent population using next-generation bisulfite sequencing. These four variants are implicated in complex phenotypes such as ulcerative colitis and AIDS progression disease (rs10491434), Celiac disease (rs2762051), Crohn's disease, IgA nephropathy and early-onset inflammatory bowel disease (rs713875) and height (rs6569648). Our results suggest cis-regulated ASM may provide a mechanistic link between the non-coding genetic changes and phenotypic variation observed in these diseases and further suggests a route to integrating DNA methylation status with GWAS results. PMID:24911414

  16. Intermediate-Valence Tautomerism in Decamethylytterbocene Complexes of Methyl-Substituted Bipyridines

    SciTech Connect

    Booth, Corwin H.; Kazhdan, Daniel; Werkema, Evan L.; Walter, Marc D.; Lukens, Wayne W.; Bauer, Eric D.; Hu, Yung-Jin; Maron, Laurent; Eisenstein, Odile; Head-Gordon, Martin; Andersen, Richard A.

    2011-01-25

    Multiconfigurational, intermediate valent ground states are established in several methyl-substituted bipyridine complexes of bispentamethylcyclopentadienylytterbium, Cp*{sub 2} Yb(Me{sub x}-bipy). In contrast to Cp*{sub 2} Yb(bipy) and other substituted-bipy complexes, the nature of both the ground state and the first excited state are altered by changing the position of the methyl or dimethyl substitutions on the bipyridine rings. In particular, certain substitutions result in multiconfigurational, intermediate valent open-shell singlet states in both the ground state and the first excited state. These conclusions are reached after consideration of single-crystal x-ray diffraction (XRD), the temperature dependence of x-ray absorption near-edge structure (XANES), extended x-ray absorption fine-structure (EXAFS), and magnetic susceptibility data, and are supported by CASSCF-MP2 calculations. These results place the various Cp*{sub 2}Yb(bipy) complexes in a new tautomeric class, that is, intermediate-valence tautomers.

  17. Temperature dependent luminescence of a europium complex incorporated in poly(methyl methacrylate)

    NASA Astrophysics Data System (ADS)

    Liang, Hao; Xie, Fang; Ren, Xiaojun; Chen, Yifa; Chen, Biao; Guo, Fuquan

    2013-12-01

    An europium ?-diketonate complex with a dipyrazolyltriazine derivative ligand, Eu(TTA)3DPBT, has been incorporated into poly(methyl methacryate) (PMMA). The influence of temperature on its luminescence properties has been investigated. The fluorescence emission spectra and luminescence lifetimes showed temperature sensitivity. The analysis of the relative intensity ratio (R) of 5D0 ? 7F2 to 5D0 ? 7F1 transition and Judd-Ofelt experimental intensity parameters ?2 indicated that the local structure and asymmetry in the vicinity of europium ions show no obvious change when the temperature is increased.

  18. Mechanistic Study of the Oxidation of a Methyl Platinum(II) Complex with O2 in Water: PtII

    E-print Network

    Goddard III, William A.

    Mechanistic Study of the Oxidation of a Methyl Platinum(II) Complex with O2 in Water: PtII Me of oxidation by O2 of (dpms)- PtII Me(OH2) (1) and (dpms)PtII Me(OH)- (2) [dpms = di(2- pyridyl)methanesulfonate)PtIV Me(OH)2 (8), a good methylating agent. The secondary deuterium kinetic isotope effect in the reaction

  19. Study on inclusion complex of cyclodextrin with methyl xanthine derivatives by fluorimetry

    NASA Astrophysics Data System (ADS)

    Wei, Yan-Li; Ding, Li-Hua; Dong, Chuan; Niu, Wei-Ping; Shuang, Shao-Min

    2003-10-01

    The inclusion complexes of ?-cyclodextrin (?-CD) and HP-?-cyclodextrin (HP-?-CD) with caffeine, theophylline and theobromine were investigated by fluorimetry. Various factors affecting the formation of inclusion complexes were discussed in detail including forming time, pH effect and temperature. The results indicate that inclusion process was affected seriously by laying time and pH. The forming time of ?-CD inclusion complexes is much longer than that of HP-?-CD. The optimum pH range is about 7-12 for caffeine, 8-10 for TP, 10.5-12 for TB. The intensities of their fluorescence increase with the decreasing of temperature. Their maximum excitation wavelengths are all in the range of 280-290 nm. The emission wavelength of caffeine and theophylline are both in the range of 340-360 nm, and that of theobromine is about 325 nm. The fluorescence signals are intensified with the increasing concentration of CD. The stoichiometry of the inclusion complexes of CD with these three methyl xanthine derivatives are all 1:1 and the formation constant are all calculated.

  20. Cobalt(II) and nickel(II) chloride and bromide complexes of 2-(2?-methyl-8?-quinolyl)benzoxazole and 2-(2? or 4?-methyl 8?-quinolyl)benzimidazole

    Microsoft Academic Search

    Marcella Massacesi; Gerolamo Devoto; Giovanni Micera; Liliana Strinna Erre; Piero Savarino

    1986-01-01

    Cobalt(II) and nickel(II) halide complexes of the ligands 2-(2'-methyl-8'-quinolyl)benzoxazole (m'q'bo), 2-(2'-methyl8'quinolyl)benzimidazole (m'q'bi) and 2-(4'-methyl-8'-quinolyl)benzimidazole (mq'bi) were synthesized and characterized by analytical, thermogravimetric, conductivity and magnetic data, and i.r. and electronic spectra.

  1. NDUFAF7 Methylates Arginine 85 in the NDUFS2 Subunit of Human Complex I*

    PubMed Central

    Rhein, Virginie F.; Carroll, Joe; Ding, Shujing; Fearnley, Ian M.; Walker, John E.

    2013-01-01

    Complex I (NADH ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 44 subunits. One arm is embedded in the inner membrane with the other protruding ?100 ? into the matrix of the organelle. The extrinsic arm contains binding sites for NADH and the primary electron acceptor FMN, and it provides a scaffold for seven iron-sulfur clusters that form an electron pathway linking FMN to the terminal electron acceptor, ubiquinone, which is bound in the region of the junction between the arms. The membrane arm contains four antiporter-like domains, probably energetically coupled to the quinone site and involved in pumping protons from the matrix into the intermembrane space contributing to the proton motive force. Complex I is put together from preassembled subcomplexes. Their compositions have been characterized partially, and at least 12 extrinsic assembly factor proteins are required for the assembly of the complex. One such factor, NDUFAF7, is predicted to belong to the family of S-adenosylmethionine-dependent methyltransferases characterized by the presence in their structures of a seven-?-strand protein fold. In the present study, the presence of NDUFAF7 in the mitochondrial matrix has been confirmed, and it has been demonstrated that it is a protein methylase that symmetrically dimethylates the ?-NG,NG? atoms of residue Arg-85 in the NDUFS2 subunit of complex I. This methylation step occurs early in the assembly of complex I and probably stabilizes a 400-kDa subcomplex that forms the initial nucleus of the peripheral arm and its juncture with the membrane arm. PMID:24089531

  2. Whole-genome DNA methylation patterns and complex associations with gene structure and expression during flower development in Arabidopsis.

    PubMed

    Yang, Hongxing; Chang, Fang; You, Chenjiang; Cui, Jie; Zhu, Genfeng; Wang, Lei; Zheng, Yu; Qi, Ji; Ma, Hong

    2015-01-01

    Flower development is a complex process requiring proper spatiotemporal expression of numerous genes. Accumulating evidence indicates that epigenetic mechanisms, including DNA methylation, play essential roles in modulating gene expression. However, few studies have examined the relationship between DNA methylation and floral gene expression on a genomic scale. Here we present detailed analyses of DNA methylomes at single-base resolution for three Arabidopsis floral periods: meristems, early flowers and late flowers. We detected 1.5 million methylcytosines, and estimated the methylation levels for 24 035 genes. We found that many cytosine sites were methylated de novo from the meristem to the early flower stage, and many sites were demethylated from early to late flowers. A comparison of the transcriptome data of the same three periods revealed that the methylation and demethylation processes were correlated with expression changes of >3000 genes, many of which are important for normal flower development. We also found different methylation patterns for three sequence contexts ((m) CG, (m) CHG and (m) CHH) and in different genic regions, potentially with different roles in gene expression. PMID:25404462

  3. Cobalt(II) and nickel(II) chloride complexes with some 2-(4?Methyl2?-pyridyl and 2?- or 8?-quinolyl)benz-X-azoles

    Microsoft Academic Search

    Marcella Massacesi; Rosalba Pinna; Gerolamo Devoto; Ermanno Barni; Piero Savarino; Liliana Strinna Erre

    1984-01-01

    Complexes of general formula MLmCl2 · nH2O, where M=cobalt(II) or nickel(II); L=2-(4'-methyl, 2'-pyridyl)-benzimidazole (mpbi), 2-(4'-methyl, 2'-pyridyl)benzothiazole (mpbt), 2-(4'-methyl, 2'-pyridyl)benzoxazole (mpbo), 2-(4'-methyl, 2'-quinolyl)benzoxazole (mqbo), or 2-(4'-methyl, 8'-quinolyl)benzoxazole (mq'bo); m=1,2; n=0–3, were prepared and characterized by t.g.a., conductance and magnetic measurements, i.r. and diffuse-reflectance electronic spectra.

  4. Beta-Phosphinoethylboranes as Ambiphilic Ligands in Nickel-Methyl Complexes

    SciTech Connect

    Fischbach, Andreas; Bazinet, Patrick R.; Waterman, Rory; Tilley, T. Don

    2007-10-28

    The ambiphilic {beta}-phosphinoethylboranes Ph{sub 2}PCH{sub 2}CH{sub 2}BR{sub 2} (BR{sub 2} = BCy{sub 2} (1a), BBN (1b)), which feature a ethano spacer CH{sub 2}CH{sub 2} between the Lewis acidic boryl and Lewis basic phosphino groups, were synthesized in nearly quantitative yields via the hydroboration of vinyldiphenylphosphine. Compounds 1a and 1b were fully characterized by elemental analysis, and by NMR and IR spectroscopy. X-ray crystallographic studies of compound 1b revealed infinite helical chains of the molecules connected through P{hor_ellipsis}B donor-acceptor interactions. The ability of these ambiphilic ligands to concurrently act as donors and acceptors was highlighted by their reactions with (dmpe)NiMe{sub 2}. Zwitterionic complexes (dmpe)NiMe(Ph{sub 2}PCH{sub 2}CH{sub 2}BCy{sub 2}Me) (2a) and (dmpe)NiMe(Ph{sub 2}PCH{sub 2}CH{sub 2}[BBN]Me) (2b) were generated via the abstraction of one of the methyl groups, forming a borate, and intramolecular coordination of the phosphine moiety to the resulting cationic metal center. Compound 2b was characterized by X-ray crystallography. Furthermore, B(C{sub 6}F{sub 5}){sub 3} abstracts the methyl group of a coordinated borate ligand to generate a free, 3-coordinate borane center in [(dmpe)NiMe(1a)]{sup +}[MeB(C{sub 6}F{sub 5}){sub 3}]{sup -} (3).

  5. Characterization and evaluation of synthetic riluzole with ?-cyclodextrin and 2,6-di-O-methyl-?-cyclodextrin inclusion complexes.

    PubMed

    Wang, Lili; Li, Shanshan; Tang, Peixiao; Yan, Jin; Xu, Kailin; Li, Hui

    2015-09-20

    ?-Cyclodextrin (?-CD) and 2,6-di-O-methyl-?-cyclodextrin (DM-?-CD) inclusion complexes with riluzole (RLZ) were prepared to improve water solubility and broaden potential pharmaceutical applications. CDs/RLZ inclusion complexes were confirmed via phase solubility studies, FT-IR spectroscopy, PXRD, DSC, (1)H NMR, and SEM. Phase solubility studies indicated that ?-CD and DM-?-CD can form 1:1 inclusion complexes with RLZ, and the stability constants were 663.17 and 1609.07M(-1), respectively. Water solubility and dissolution rate of RLZ were significantly improved in complex forms, implying that the inclusion complexes may develop pharmaceutical applications. Preliminary in vitro cytotoxicity assay also showed that RLZ hepatotoxicity was not increased in the inclusion complexes. PMID:26050882

  6. Spectrophotometric determination of benzydamine HCl, levamisole HCl and mebeverine HCl through ion-pair complex formation with methyl orange

    Microsoft Academic Search

    Akram M. El-Didamony

    2008-01-01

    A simple, rapid and sensitive spectrophotometric method has been proposed for the assay of benzydamine HCl (BENZ), levamisole HCl (LEV) and mebeverine HCl (MBV) in bulk and pharmaceutical formulations. The method based on the reaction of the selected drugs with methyl orange (MO) in buffered aqueous solution at pH 3.6. The formed yellow ion-pair complexes were extracted with dichloromethane and

  7. Trans-ethyl methyl ether in space - A new look at a complex molecule in selected hot core regions

    E-print Network

    G. W. Fuchs; U. Fuchs; T. F. Giesen; F. Wyrowski

    2005-08-18

    An extensive search for the complex molecule trans-ethyl methyl ether towards several hot core regions has been performed. Using the IRAM 30m telescope and the SEST 15m we looked at several frequencies where trans-ethyl methyl ether has strong transitions, as well as lines which are particularly sensitive to the physical conditions in which the molecule can be found. We included G34.26, NGC6334(I), Orion KL, and W51e2 which have previously been proven to have a rich chemistry of complex molecules. Our observations cannot confirm the tentative Orion KL detection made by Charnley et al. (2001) within their stated column density limits, but we confirm the existence of the trans-ethyl methyl ether towards W51e2 with a column density of 2x10^14 cm-2. The dimethyl ether/methanol ratio of 0.6 as well as the newly found ethyl methyl ether/ethanol ratio of 0.13 indicate relative high abundances of ethers toward W51e2. Furthermore, the observation of ethyl methyl ether also confirms the importance of ethanol as a grain mantle constituent. We present new upper limits of around 8x10^13 cm-2 for the column densities of the molecule toward Orion KL, G34.26, NGC6334(I) and estimate the column density towards SgrB2(N) to be of the same order. The W51e2 observations are discussed in more detail.

  8. Complexation of NpO2+ with N-methyl-iminodiacetic Acid: in Comparison with Iminodiacetic and Dipicolinic Acids

    SciTech Connect

    Tian, Guoxin; Rao, Linfeng

    2010-10-01

    Complexation of Np(V) with N-methyl-iminodiacetic acid (MIDA) in 1 M NaClO{sub 4} solution was studied with multiple techniques including potentiometry, spectrophotometry, and microcalorimetry. The 1:2 complex, NpO{sub 2}(MIDA){sub 2}{sup 3-} was identified for the first time in aqueous solution. The correlation between its optical absorption properties and symmetry was discussed, in comparison with Np(V) complexes with two structurally related nitrilo-dicarboxylic acids, iminodiacetic acid (IDA) and dipicolinic acid (DPA). The order of the binding strength (DPA > MIDA > IDA) is explained by the difference in the structural and electronic properties of the ligands. In general, the nitrilo-dicarboxylates form stronger complexes with Np(V) than oxy-dicarboxylates due to a much more favorable enthalpy of complexation.

  9. Histone H3 lysine 36 methylation antagonizes silencing in Saccharomyces cerevisiae independently of the Rpd3S histone deacetylase complex.

    PubMed

    Tompa, Rachel; Madhani, Hiten D

    2007-02-01

    In yeast, methylation of histone H3 on lysine 36 (H3-K36) is catalyzed by the NSD1 leukemia oncoprotein homolog Set2. The histone deacetylase complex Rpd3S is recruited to chromatin via binding of the chromodomain protein Eaf3 to methylated H3-K36 to prevent erroneous transcription initiation. Here we identify a distinct function for H3-K36 methylation. We used random mutagenesis of histones H3 and H4 followed by a reporter-based screen to identify residues necessary to prevent the ectopic spread of silencing from the silent mating-type locus HMRa into flanking euchromatin. Mutations in H3-K36 or deletion of SET2 caused ectopic silencing of a heterochromatin-adjacent reporter. Transcriptional profiling revealed that telomere-proximal genes are enriched for those that display decreased expression in a set2Delta strain. Deletion of SIR4 rescued the expression defect of 26 of 37 telomere-proximal genes with reduced expression in set2Delta cells, implying that H3-K36 methylation prevents the spread of telomeric silencing. Indeed, Sir3 spreads from heterochromatin into neighboring euchromatin in set2Delta cells. Furthermore, genetic experiments demonstrated that cells lacking the Rpd3S-specific subunits Eaf3 or Rco1 did not display the anti-silencing phenotype of mutations in SET2 or H3-K36. Thus, antagonism of silencing is independent of the only known effector of this conserved histone modification. PMID:17179083

  10. Histone H3 Lysine 36 Methylation Antagonizes Silencing in Saccharomyces cerevisiae Independently of the Rpd3S Histone Deacetylase Complex

    PubMed Central

    Tompa, Rachel; Madhani, Hiten D.

    2007-01-01

    In yeast, methylation of histone H3 on lysine 36 (H3-K36) is catalyzed by the NSD1 leukemia oncoprotein homolog Set2. The histone deacetylase complex Rpd3S is recruited to chromatin via binding of the chromodomain protein Eaf3 to methylated H3-K36 to prevent erroneous transcription initiation. Here we identify a distinct function for H3-K36 methylation. We used random mutagenesis of histones H3 and H4 followed by a reporter-based screen to identify residues necessary to prevent the ectopic spread of silencing from the silent mating-type locus HMRa into flanking euchromatin. Mutations in H3-K36 or deletion of SET2 caused ectopic silencing of a heterochromatin-adjacent reporter. Transcriptional profiling revealed that telomere-proximal genes are enriched for those that display decreased expression in a set2? strain. Deletion of SIR4 rescued the expression defect of 26 of 37 telomere-proximal genes with reduced expression in set2? cells, implying that H3-K36 methylation prevents the spread of telomeric silencing. Indeed, Sir3 spreads from heterochromatin into neighboring euchromatin in set2? cells. Furthermore, genetic experiments demonstrated that cells lacking the Rpd3S-specific subunits Eaf3 or Rco1 did not display the anti-silencing phenotype of mutations in SET2 or H3-K36. Thus, antagonism of silencing is independent of the only known effector of this conserved histone modification. PMID:17179083

  11. Computational characterisation of the charge-transfer and T-shaped molecular complexes of N-methyl imidazoline-2-thione and N-methyl imidazolidine-2-thione with the dihalogens Br2 and I2

    Microsoft Academic Search

    Agnie Mylona Kosmas; Demetrios K. Papayannis

    2010-01-01

    The computational characterisation of the molecular complexes of N-methyl imidazoline-2-thione (methimazole) and the related saturated analogue N-methyl imidazolidine-2-thione with Br2 and I2 is carried out using quantum mechanical electronic structure methods. Two kinds of molecular connectivity have been examined. The first displays a collinear S–X–X geometry (X = Br, I) and leads to charge-transfer (CT) type adducts, possible in two stereoisomeric conformations

  12. Application of high vacuum fractional distillation to complex mixtures of methyl esters of polyunsaturated fatty acids

    Microsoft Academic Search

    O. S. Privett; J. D. Nadenicek; F. J. Pusch; E. C. Nickell

    1969-01-01

    A technique for the high vacuum fractional distillation, with a spinning band column, of methyl esters of polyunsaturated\\u000a fatty acids employing a carrier of long chain acetates is described. The carrier is used to facilitate the fractionation of\\u000a minor components and minimize artifact formation in mixtures of methyl esters containing up to six double bonds. The technique\\u000a is demonstrated on

  13. Evaluating the Identity and Diiron Core Transformations of a (?-Oxo)diiron(III) Complex Supported by Electron-Rich Tris(pyridyl-2-methyl)amine Ligands

    E-print Network

    Do, Loi H.

    The composition of a (?-oxo)diiron(III) complex coordinated by tris[(3,5-dimethyl-4-methoxy)pyridyl-2-methyl]amine (R[subscript 3]TPA) ligands was investigated. Characterization using a variety of spectroscopic methods and ...

  14. N-methyl-D-aspartate receptor plasticity in kindling: quantitative and qualitative alterations in the N-methyl-D-aspartate receptor-channel complex.

    PubMed Central

    Yeh, G C; Bonhaus, D W; Nadler, J V; McNamara, J O

    1989-01-01

    Kindling is an animal model of epilepsy and neuronal plasticity produced by periodic electrical stimulation of the brain. Electrophysiologic studies indicate that this phenomenon is associated with increased participation of N-methyl-D-aspartate (NMDA) receptors in excitatory synaptic transmission. Biochemical studies suggest that a change intrinsic to the NMDA receptor-channel complex may contribute to the increase in NMDA receptor-mediated synaptic transmission. We tested this idea by measuring the binding of 3-[(+)-2-(carboxypiperazin-4-yl)][1,2-3H]propyl-1-phosphonic acid ([3H]CPP), [3H]glycine, and tritiated N-[(1-thienyl)cyclohexyl]piperidine [( 3H]TCP) to rat hippocampal membranes. In this preparation these ligands are selective for the NMDA receptor, the strychnine-insensitive glycine receptor, and the NMDA receptor-gated ion channel, respectively. Kindling increased the density of CPP, glycine, and TCP binding sites in hippocampal membranes by 47%, 42%, and 25%, respectively. No significant changes were detected in the affinity of these binding sites. Surprisingly, alterations in the glycine binding site were detected in animals sacrificed 1 month but not 1 day after the final kindling stimulation. Thus, delayed upregulation of the NMDA receptor-channel complex may be one molecular mechanism that maintains the long-lasting hyperexcitability of hippocampal neurons in kindled animals. PMID:2479019

  15. Novel square arrangements in tetranuclear and octanuclear iron(III) complexes with asymmetric iron environments created by the unsymmetric bridging ligand N,N,Nâ²-tris((N-methyl)-2-benzimidazolylmethyl)-Nâ²-methyl-1,3-diamino-2-propanol

    Microsoft Academic Search

    J. H. Jr. Satcher; S. R. Parkin; M. M. Olmstead; B. C. Noll; A. L. Balch; M. W. Droege; L. May

    1998-01-01

    The synthesis and characterization of novel tetranuclear and octanuclear iron(III) complexes with structures based on a nearly square arrangement of four iron ions are reported. Reaction of ferric nitrate, sodium acetate, and the unsymmetrical binucleating ligand HBMDP, where HBMDP is N,N,Nâ²-tris((N-methyl)-2-benzimidazolylmethyl)-Nâ²-methyl-1,3-diamino-2-propanol, in acetone\\/water yields the tetranuclear iron complex [Feâ(μ-O)â(μ-BMDP)â-(μ-OAc)â]{sup 4+}, which exhibits coordination number asymmetry. The structure of [Feâ(μ-O)â(μ-BMDP)â(μ-OAc)â](NOâ)â(OH)·12HâO has

  16. Mononuclear and Dinuclear Manganese(II) Complexes from the Use of Methyl(2-pyridyl)ketone Oxime

    PubMed Central

    Efthymiou, Constantinos G.; Nastopoulos, Vassilios; Raptopoulou, Catherine; Tasiopoulos, Anastasios; Perlepes, Spyros P.; Papatriantafyllopoulou, Constantina

    2010-01-01

    The reactions of methyl(2-pyridyl)ketone oxime, (py)C(Me)NOH, with manganese(II) sulfate monohydrate have been investigated. The reaction between equimolar quantities of MnSO4 · H2O and (py)C(Me)NOH in H2O lead to the dinuclear complex [Mn2(SO4)2{(py)C(Me)NOH}4] · (py)C(Me)NOH, 1 · (py)C(Me)NOH, while employment of NaOMe as base affords the compound [Mn(HCO2)2{(py)C(Me)NOH}2] (2). The structures of both compounds have been determined by single crystal X-ray diffraction. In both complexes, the organic ligand chelates through its nitrogen atoms. The IR data are discussed in terms of the nature of bonding and the structures of the two complexes. PMID:20671965

  17. Iron(III) complexes of some thiosemicarbazones derived from 2-acetylpyridine, its 6-methyl derivative and its N -oxide

    Microsoft Academic Search

    Douglas X. West; Patricia M. Ahrweiler; Gözen Ertem; John P. Scovill; Daniel L. Klayman; Judith L. Flippen-Anderson; Richard Gilardi; Clifford George; Lewis K. Pannell

    1985-01-01

    A series of iron(III) complexes of thiosemicarbazones derived from 2-acetylpyridine, 6-methyl-2-acetylpyridine and 2-acetylpyridineN-oxide have been prepared from Fe(ClO4)3 and FeCl3. All of the isolated solids have cations involving two monobasic tridentate ligands, and either perchlorate or tetrachloroferrate(III) anions and are 1:1 electrolytes. Coordinationvia the pyridine nitrogen (or theN-oxide oxygen), the imine nitrogen and the sulphur atom are confirmed by infrared

  18. Structure and tunneling splitting spectra of methyl groups of tetramethylpyrazine in complexes with chloranilic and bromanilic acids.

    PubMed

    Piecha-Bisiorek, A; Bator, G; Sawka-Dobrowolska, W; Sobczyk, L; Rok, M; Medycki, W; Schneider, G J

    2014-08-28

    The crystal and molecular structure of the 2,3,5,6-tetramethylpyrazine (TMP) complex with 2,5-dibromo-3,6-dihydroxy-p-quinone (bromanilic acid, BRA) has been studied and the results are compared with TMP CLA (2,5-dichloro-3,6-dihydroxy-p-quinone (chloranilic acid, CLA) complex. The X-ray structure of TMP BRA complex indicates the formation of dimeric units, in which two BRA(-) anions are connected by two O-H···O (2.646(2) Å) hydrogen bonds, whereas the cations and anions are joined together by strong N(+)-H···O(-) (2.657(2) Å) hydrogen bonds. The results are analyzed in terms of both the methyl group surroundings and the C-H···O and N(+)-H···O(-) (or N···H-O) bridge formations. Both effects, the strength of the N(+)-H···O(-) hydrogen bonds and steric hindrance for the rotations, are responsible for the CH3 group dynamics. For the TMP CLA and TMP BRA complexes, the inelastic neutron backscattering spectra were also investigated. In the case of TMP CLA, four tunneling signals have been observed in the energy range ±30 ?eV, which indicates four inequivalent methyl groups in the crystal structure at the lowest temperature. No tunneling splitting is observed in the case of the TMP BRA complex, most probably due to the overlapping with the elastic peak. The tunneling results are consistent with the (1)H NMR spin-lattice relaxation time investigations in a wide temperature range, which also point to the CH3 group tunneling effect in the case of TMP CLA. PMID:25099129

  19. Application of urea complexes in the purification of fatty acids, esters, and alcohols. II. Oleic acid and methyl oleate from olive oil

    Microsoft Academic Search

    Daniel Swern; Winfred E. Parker

    1952-01-01

    Summary  Oleic acid and methyl oleate of high purity (97–99%) and substantially free (0.2% or less) of polyunsaturated contaminants\\u000a have been isolated in 60–70% yield from the fatty acids or methyl esters of olive oil by procedures which require only one\\u000a precipitation of urea complexes (single dose of urea technique) one low-temperature crystallization, and one fractional distillation.\\u000a The best yields of

  20. Computational modeling of inclusion complexes of beta-cyclodextrin with enantiomers of salsolinol, N-methyl-salsolinol, and 1-benzyl-tetrahydroisoquinoline

    NASA Astrophysics Data System (ADS)

    Huang, Ming-Ju; Quan, Zhe; Liu, Yi-Ming

    Capillary electrophoresis with beta-CD as a chiral selector has successfully separated the two enantiomers of salsolinol, N-methyl-salsolinol, and 1-benzyl-tetrahydroisoquinoline (BTIQ). The migration times of each enantiomer in capillary electrophoresis reflect the stability of their beta-CD inclusion complexes. This paper reports a computational modeling study of the inclusion complexes of beta-cyclodextrin (beta-CD) with salsolinol, N-methyl-salsolinol, and BTIQ by using PM3 (Parametric Method 3) semiempirical molecular orbital calculations and the ONIOM hybrid method. Two types of the inclusion complexes, cis- and trans-orientations, are considered for each enantiomer of the guest molecules, salsolinol, N-methyl-salsolinol, and BTIQ. In the cis-orientation, the nitrogen in the salsolinol, N-methyl-salsolinol, and BTIQ points toward the secondary hydroxyls of the beta-CD, while in the trans-orientation, the nitrogen in salsolinol, N-methyl-salsolinol, and BTIQ points toward the primary hydroxyls of the beta-CD. We found that the stabilization energies of these inclusion complexes from these PM3 and ONIOM different methods correlate very well with the migration order deduced from the study of capillary electrophoretic separation.

  1. Homogeneous solvation controlled photoreduction of cobalt(III) complexes in aqueous 2-methyl-2-propanol solutions

    Microsoft Academic Search

    K. Anbalagan; I. Sharmila Lydia

    2008-01-01

    The effect of solvent participation on the ligand-to-metal charge transfer (LMCT, L?CoIII) reduction of the of CoIII(en)2Br(RC6H4NH2)2+ where R=m-OCH3, p-F, H, m-CH3, p-CH3,p-OC2H5 and p-OCH3 were examined in aqueous 2-methyl-2-propanol (ButOH) solutions. The change in the reduction behavior of CoIII centre was also examined through cyclic voltammetric studies. The observed reduction in quantum yield due to LMCT excitation can mainly

  2. Inclusion complexation of isoprenaline and methyl dopa with ?- and ?-cyclodextrin nanocavities: Spectral and theoretical study

    NASA Astrophysics Data System (ADS)

    Rajendiran, N.; Thulasidhasan, J.; Saravanan, J.

    2014-03-01

    Inclusion complex formation of isoprenaline (ISOP) and methyldopa (MDOP) with ?-CD and ?-CD were investigated. Solid inclusion complex nanomaterials were characterized by SEM, TEM, FTIR, DSC, 1H NMR and XRD methods. Spectral results showed that single emission (monomer) noticed in aqueous solution where as dual emission (excimer) in CD. Both drugs formed 1:2 (CD-drug2) inclusion complexes with CDs. Time-resolved fluorescence studies show that single exponential decay observed in water whereas biexponential decay observed in CD. Nano-sized particles were found in ISOP/CD while vesicles were obtained in MDOP/CD complexes. DSC results revealed that the thermal stability of drugs was improved when it was included in the CD nanocavity. Based on PM3 calculations, the inclusion structure of ISOP/CD and MDOP/CD complexes were proposed. Thermodynamic parameters and binding affinity of complexation of CD were determined by PM3 method.

  3. Synthesis and characterization of Cu(II), Ni(II) and Zn(II) metal complexes of bidentate NS isomeric Schiff bases derived from S-methyldithiocarbazate (SMDTC): bioactivity of the bidentate NS isomeric Schiff bases, some of their Cu(II), Ni(II) and Zn(II) complexes and the X-ray structure of the bis[ S-methyl-?- N-(2-furyl-methyl)methylenedithiocarbazato]zinc(II) complex

    Microsoft Academic Search

    M. T. H Tarafder; Kar-Beng Chew; Karen A Crouse; A. M Ali; B. M Yamin; H.-K Fun

    2002-01-01

    Two new isomeric Schiff bases, S-methyl-?-N-(2-furylmethyl)methylenedithiocarbazate (NS?) and S-methyl-?-N-(5-methyl-2-furyl)methylenedithiocarbazate (NS?) have been prepared. Bis-chelated complexes of these two bidentate ligands, [M(NS)2], [M=Cu(II), Ni(II) and Zn(II)], were synthesized. The Schiff bases and their metal complexes have been characterized by a variety of physico-chemical techniques. X-ray crystallographic analysis shows that the Zn(II) complex, [Zn(NS?)2], is four-coordinate and has a distorted tetrahedral structure

  4. Electronic and optical response of Ru(II) complexes functionalized by methyl, carboxylate groups: joint theoretical and experimental study

    SciTech Connect

    Tretiak, Sergei [Los Alamos National Laboratory

    2008-01-01

    New photovoltaic and photocatalysis applications have been recently proposed based on the hybrid Ru(II)-bipyridine-complex/semiconductor quantum dot systems. In order to attach the complex to the surface of a semiconductor, a linking bridge - a carboxyl group - is added to one or two of the 2,2{prime}-bipyridine ligands. Such changes in the ligand structure, indeed, affect electronic and optical properties and consequently, the charge transfer reactivity of Ru-systems. In this study, we apply both theoretical and experimental approaches to analyze the effects brought by functionalization of bipyridine ligands with the methyl, carboxyl, and carboxilate groups on the electronic structure and optical response of the Ru(II) bipyridine complex. First principle calculations based on density functional theory (DFT) and linear response time dependent density functional theory (TDDFT) are used to simulate the ground and excited-state structures of functionalized Ru-complexes in the gas phase, as well as in acetonitrile solution. In addition, an inelaborate Frenkel exciton model is used to explain the optical activity and splitting patterns of the low-energy excited states. All theoretical results nicely complement experimental absorption spectra of Ru-complexes and contribute to their interpretation. We found that the carboxyl group breaks the degeneracy of two low-energy optically bright excited states and red-shifts the absorption spectrum, while leaves ionization and affinity energies of complexes almost unchanged. Experimental studies show a high probability of deprotonation of the carbboxyl group in the Ru-complexes resulted in a slight blue shift and decrease of intensities of the low energy absorption peaks. Comparison of experimental and theoretical linear response spectra of deprotanated complexes demonstrate strong agreement when acetonitrile solvent is used in simulations. A polar solvent is found to play an important role in calculations of optical spectra: it stabilizes the energy of states localized on the carboxyl or carboxylate groups eliminating artificial charge transport states, which typically appear in TDDFT calculations. Thus, it is validated that the excited-state structure of the functionalized Ru-complexes, specifically in the case of the deprotonated functions, can be accurately modeled by TDDFT with the addition of a dielectric continuum in simulations.

  5. Absorption spectroscopic study of EDA complexes of [70] fullerene with a series of methyl benzenes

    NASA Astrophysics Data System (ADS)

    Bhattacharya, Sumanta; Nayak, Sandip K.; Chattopadhyay, Subrata K.; Banerjee, Manas; Mukherjee, Asok K.

    2001-02-01

    [70]Fullerene has been shown to form 1:1 molecular complexes with toluene, p-xylene, m-xylene, 1,2,4,5-tetramethyl benzene (durene) and pentamethyl benzene (PMB) in CCl 4 medium by absorption spectroscopic method. Isosbestic points have been detected in case of complexes with PMB and durene. Charge transfer absorption band could not be detected but the intensity of the broad absorption band of C 70 in CCl 4 decreases systematically with increase in the concentration of the added methylbenzenes. From this trend the formation constants ( Kc) of the complexes have been determined at three different wavelengths. The constancy of Kc with respect to change in the wavelength of measurement supports the view that complex of a single stoichiometry (1:1) is formed in each case.

  6. A New XRCC1-Containing Complex and Its Role in Cellular Survival of Methyl Methanesulfonate Treatment

    Microsoft Academic Search

    Hao Luo; Doug W. Chan; Tao Yang; Maria Rodriguez; Benjamin Ping-Chi Chen; Mei Leng; Jung-Jung Mu; David Chen; Zhou Songyang; Yi Wang; Jun Qin

    2004-01-01

    DNA single-strand break repair (SSBR) is important for maintaining genome stability and homeostasis. The current SSBR model derived from an in vitro-reconstituted reaction suggests that the SSBR complex mediated by X-ray repair cross-complementing protein 1 (XRCC1) is assembled sequentially at the site of damage. In this study, we provide biochemical data to demonstrate that two preformed XRCC1 protein complexes exist

  7. An intrinsically disordered region of methyl-CpG binding domain protein 2 (MBD2) recruits the histone deacetylase core of the NuRD complex

    PubMed Central

    Desai, Megha A.; Webb, Heather D.; Sinanan, Leander M.; Scarsdale, J. Neel; Walavalkar, Ninad M.; Ginder, Gordon D.; Williams, David C.

    2015-01-01

    The MBD2-NuRD (Nucleosome Remodeling and Deacetylase) complex is an epigenetic reader of DNA methylation that regulates genes involved in normal development and neoplastic diseases. To delineate the architecture and functional interactions of the MBD2-NuRD complex, we previously solved the structures of MBD2 bound to methylated DNA and a coiled-coil interaction between MBD2 and p66? that recruits the CHD4 nucleosome remodeling protein to the complex. The work presented here identifies novel structural and functional features of a previously uncharacterized domain of MBD2 (MBD2IDR). Biophysical analyses show that the MBD2IDR is an intrinsically disordered region (IDR). However, despite this inherent disorder, MBD2IDR increases the overall binding affinity of MBD2 for methylated DNA. MBD2IDR also recruits the histone deacetylase core components (RbAp48, HDAC2 and MTA2) of NuRD through a critical contact region requiring two contiguous amino acid residues, Arg286 and Leu287. Mutating these residues abrogates interaction of MBD2 with the histone deacetylase core and impairs the ability of MBD2 to repress the methylated tumor suppressor gene PRSS8 in MDA-MB-435 breast cancer cells. These findings expand our knowledge of the multi-dimensional interactions of the MBD2-NuRD complex that govern its function. PMID:25753662

  8. (Eta2-alkyne)methyl(dioxo)rhenium complexes as aldehyde-olefination catalysts.

    PubMed

    Santos, Ana M; Romão, Carlos C; Kühn, Fritz E

    2003-03-01

    Complexes CH3ReO2L (L = 2-butyne, 3-hexyne, diphenylacetylene) are catalysts for the olefination of aldehydes, using 4-nitrobenzaldehyde (4-nba) as the standard aldehyde and ethyldiazoacetate (eda) as the diazo compound. Spectroscopic studies including in situ 31P, 17O, 13C, and 1H NMR spectroscopy are used to elucidate the mechanism and the nature of the active species. One of the key steps of the mechanism is the rapid formation of phosphazine at the beginning of the cycle and its subsequent reaction with the metal dioxide complex to form the catalytically active carbene species. PMID:12603128

  9. Spectrophotometric determination of benzydamine HCl, levamisole HCl and mebeverine HCl through ion-pair complex formation with methyl orange

    NASA Astrophysics Data System (ADS)

    El-Didamony, Akram M.

    2008-03-01

    A simple, rapid and sensitive spectrophotometric method has been proposed for the assay of benzydamine HCl (BENZ), levamisole HCl (LEV) and mebeverine HCl (MBV) in bulk and pharmaceutical formulations. The method based on the reaction of the selected drugs with methyl orange (MO) in buffered aqueous solution at pH 3.6. The formed yellow ion-pair complexes were extracted with dichloromethane and measured quantitatively with maximum absorption at 422 nm. The analytical parameters and their effects on the reported systems are investigated. The extracts are intensely colored and very stable at room temperature. The calibration graphs were linear over the concentration range of 2-10 ?g ml -1 for BENZ, 6-24 ?g ml -1 for LEV and 4-14 ?g ml -1 for MBV. The stoichiometry of the reaction was found to be 1:1 in all cases and the conditional stability constant ( Kf) of the complexes have been calculated. The proposed method was successfully extended to pharmaceutical preparations-tablets. Excipients used as additive in commercial formulations did not interfere in the analysis. The proposed method can be recommended for quality control and routine analysis where time, cost effectiveness and high specificity of analytical technique are of great importance.

  10. Spectrophotometric determination of benzydamine HCl, levamisole HCl and mebeverine HCl through ion-pair complex formation with methyl orange.

    PubMed

    El-Didamony, Akram M

    2008-03-01

    A simple, rapid and sensitive spectrophotometric method has been proposed for the assay of benzydamine HCl (BENZ), levamisole HCl (LEV) and mebeverine HCl (MBV) in bulk and pharmaceutical formulations. The method based on the reaction of the selected drugs with methyl orange (MO) in buffered aqueous solution at pH 3.6. The formed yellow ion-pair complexes were extracted with dichloromethane and measured quantitatively with maximum absorption at 422 nm. The analytical parameters and their effects on the reported systems are investigated. The extracts are intensely colored and very stable at room temperature. The calibration graphs were linear over the concentration range of 2-10 microg ml(-1) for BENZ, 6-24 microg ml(-1) for LEV and 4-14 microg ml(-1) for MBV. The stoichiometry of the reaction was found to be 1:1 in all cases and the conditional stability constant (K(f)) of the complexes have been calculated. The proposed method was successfully extended to pharmaceutical preparations-tablets. Excipients used as additive in commercial formulations did not interfere in the analysis. The proposed method can be recommended for quality control and routine analysis where time, cost effectiveness and high specificity of analytical technique are of great importance. PMID:17625955

  11. Hydroxynaphthoquinone Metal Complexes as Antitumor Agents X: Synthesis, Structure, Spectroscopy and In Vitro Antitumor Activity of 3-Methyl-Phenylazo Lawsone Derivatives and Their Metal Complexes Against Human Breast Cancer Cell Line MCF-7

    PubMed Central

    Gokhale, Nikhil; Newton, Chris; Pritchard, Robin

    2000-01-01

    The C-3 substituted phenylazo derivatives of lawsone (2-hydroxy-l,4 p-naphthoquinone, III) were synthesized and characterized. The X-ray crystal structure was determined for the ligand 3-(3?-methyl phenylazo) lawsone. The copper complexes of these derivatives were found to possess 1:2 metal stoichiometry and square planar geometries with intermolecular stackings, resulting in antiferromagnetic exchange interactions. The in vitro activity of all the synthesized compounds was examined against human breast cancer cell-line, MCF-7, which revealed enhanced activities for the metal complexes, the highest activity being observed for the copper compound of 3-(3?-methyl phenylazo) lawsone. PMID:18475934

  12. Hydroxynaphthoquinone metal complexes as antitumor agents x: synthesis, structure, spectroscopy and in vitro antitumor activity of 3-methyl-phenylazo lawsone derivatives and their metal complexes against human breast cancer cell line mcf-7.

    PubMed

    Gokhale, N; Padhye, S; Newton, C; Pritchard, R

    2000-01-01

    The C-3 substituted phenylazo derivatives of lawsone (2-hydroxy-l,4 p-naphthoquinone, III) were synthesized and characterized. The X-ray crystal structure was determined for the ligand 3-(3'-methyl phenylazo) lawsone. The copper complexes of these derivatives were found to possess 1:2 metal stoichiometry and square planar geometries with intermolecular stackings, resulting in antiferromagnetic exchange interactions. The in vitro activity of all the synthesized compounds was examined against human breast cancer cell-line, MCF-7, which revealed enhanced activities for the metal complexes, the highest activity being observed for the copper compound of 3-(3'-methyl phenylazo) lawsone. PMID:18475934

  13. Multiple Histone Methyl and Acetyltransferase Complex Components Bind the HLA-DRA Gene

    Microsoft Academic Search

    Nancy M. Choi; Jeremy M. Boss

    2012-01-01

    Major histocompatibility complex class II (MHC-II) genes are fundamental components that contribute to adaptive immune responses. While characterization of the chromatin features at the core promoter region of these genes has been studied, the scope of histone modifications and the modifying factors responsible for activation of these genes are less well defined. Using the MHC-II gene HLA-DRA as a model,

  14. Zebularine: A Novel DNL Methylation Inhibitor that Forms a Covalent Complex with DNA Methyltransferases

    SciTech Connect

    Zhou, L.; Cheng, X; Connolly, B; Dickman, M; Hurd, P; Hornby, D

    2009-01-01

    Mechanism-based inhibitors of enzymes, which mimic reactive intermediates in the reaction pathway, have been deployed extensively in the analysis of metabolic pathways and as candidate drugs. The inhibition of cytosine-[C5]-specific DNA methyltransferases (C5 MTases) by oligodeoxynucleotides containing 5-azadeoxycytidine (AzadC) and 5-fluorodeoxycytidine (FdC) provides a well-documented example of mechanism-based inhibition of enzymes central to nucleic acid metabolism. Here, we describe the interaction between the C5 MTase from Haemophilus haemolyticus (M.HhaI) and an oligodeoxynucleotide duplex containing 2-H pyrimidinone, an analogue often referred to as zebularine and known to give rise to high-affinity complexes with MTases. X-ray crystallography has demonstrated the formation of a covalent bond between M.HhaI and the 2-H pyrimidinone-containing oligodeoxynucleotide. This observation enables a comparison between the mechanisms of action of 2-H pyrimidinone with other mechanism-based inhibitors such as FdC. This novel complex provides a molecular explanation for the mechanism of action of the anti-cancer drug zebularine.

  15. Divanadium(V) complexes with 4- R-benzoic acid (1-methyl-3-oxo-butylidene)-hydrazides: Syntheses, structures and properties

    Microsoft Academic Search

    Anindita Sarkar; Samudranil Pal

    2009-01-01

    In acetonitrile, reactions of bis(acetylacetonato)oxidovanadium(IV) ([VO(acac)2]) with 4-R-benzoylhydrazine in 1:1 mole ratio provide coordinatively symmetrical complexes (1–5) of the {OV(?-O)VO}4+ motif in 40–47% yields. On the other hand, in methanol the same reactants provide complexes (6–10) containing the {OV(?-OMe)2VO}4+ core in 37–50% yields. In both series of complexes, the ligand is the O,N,O-donor deprotonated Schiff base system 4-R-benzoic acid (1-methyl-3-oxo-butylidene)-hydrazide

  16. The Paf1 Complex Is Required for Histone H3 Methylation by COMPASS and Dot1p: Linking Transcriptional Elongation to Histone Methylation

    Microsoft Academic Search

    Nevan J. Krogan; Jim Dover; Adam Wood; Jessica Schneider; Jonathan Heidt; Marry Ann Boateng; Kimberly Dean; Owen W. Ryan; Ashkan Golshani; Mark Johnston; Jack F. Greenblatt; Ali Shilatifard

    2003-01-01

    complex COMPASS and Dot1p, respectively, is re- is believed to impede RNA polymerase II elongation by quired for silencing of expression of genes located reducing intracellular GTP or UTP levels (by inhibiting near chromosome telomeres in yeast. We report that enzymes that catalyze their biosynthesis), suggests that the Paf1 protein complex, which is associated with the Paf1 complex may also

  17. Polystyrene bound oxidovanadium(IV) and dioxidovanadium(V) complexes of histamine derived ligand for the oxidation of methyl phenyl sulfide, diphenyl sulfide and benzoin.

    PubMed

    Maurya, Mannar R; Arya, Aarti; Kumar, Amit; Pessoa, João Costa

    2009-03-28

    Ligand Hsal-his (I) derived from salicylaldehyde and histamine has been covalently bound to chloromethylated polystyrene cross-linked with 5% divinylbenzene. Upon treatment with [VO(acac)(2)] in DMF, the polystyrene-bound ligand (abbreviated as PS-Hsal-his, II) gave the stable polystyrene-bound oxidovanadium(iv) complex PS-[V(IV)O(sal-his)(acac)] , which upon oxidation yielded the dioxidovanadium(v) PS-[V(V)O(2)(sal-his)] complex. The corresponding non polymer-bound complexes [V(IV)O(sal-his)(acac)] and [V(V)O(2)(sal-his)] have also been obtained. These complexes have been characterised by IR, electronic, (51)V NMR and EPR spectral studies, and thermal as well as scanning electron micrograph studies. Complexes and have been used as a catalyst for the oxidation of methyl phenyl sulfide, diphenyl sulfide and benzoin with 30% H(2)O(2) as oxidant. Under the optimised reaction conditions, a maximum of 93.8% conversion of methyl phenyl sulfide with 63.7% selectivity towards methyl phenyl sulfoxide and 36.3% towards methyl phenyl sulfone has been achieved in 2 h with 2 . Under similar conditions, diphenyl sulfide gave 83.4% conversion where selectivity of reaction products varied in the order: diphenyl sulfoxide (71.8%) > diphenyl sulfone (28.2%). A maximum of 91.2% conversion of benzoin has been achieved within 6 h, and the selectivities of reaction products are: methylbenzoate (37.0%) > benzil (30.5%) > benzaldehyde-dimethylacetal (22.5%) > benzoic acid (8.1%). The PS-bound complex, 1 exhibits very comparable catalytic potential. These polymer-anchored heterogeneous catalysts do not leach during catalytic action, are recyclable and show higher catalytic activity and turnover frequency than the corresponding non polymer-bound complexes. EPR and (51)V NMR spectroscopy was used to characterise methanolic solutions of 3 and 4 and to identify species formed upon addition of H(2)O(2) and/or acid and/or methyl phenyl sulfide. PMID:19274297

  18. Synthesis and characterization of a Cu(II) complex of 2-benzylmercapto-5-methyl-1,3,4-thiadiazole (C10H10N2S2)

    Microsoft Academic Search

    Gerardo E. Camí; Malva Liu González; Francisco Sanz Ruiz; Carmen Ramírez De Arellano; Rodolfo D. Sánchez; José C. Pedregosa

    2008-01-01

    A Cu(II) complex of 2-benzylmercapto-5-methyl-1,3,4-thiadiazole was synthesized and characterized. The crystal structure of the copper complex and the free ligand were determined by single-crystal X-ray diffraction at room temperature: {[Cu(C10H10N2S2)2(Cl)2], P1 triclinic, a = 8.1450(2) Å, b = 8.1690(2) Å, c = 10.8180(3) Å, ? = 97.4040(12)°, ? = 101.6270(11)°, ? = 116.1431(14)°; C10H10N2S2 ligand, Pbca orthorhombic, a = 8.7938(7)

  19. Synthesis, spectroscopic, anticancer, antibacterial and antifungal studies of Ni(II) and Cu(II) complexes with hydrazine carboxamide, 2-[3-methyl-2-thienyl methylene].

    PubMed

    Chandra, Sulekh; Vandana; Kumar, Suresh

    2015-01-25

    Schiff's base ligand(L) hydrazine carboxamide, 2-[3-methyl-2-thienyl methylene] and its metal complexes have been synthesized and characterized by elemental analysis, molar conductance, various spectroscopic techniques such as electronic, IR, (1)H NMR, mass, EPR. Molar conductance of complexes in DMF solution corresponds to non-electrolyte. Complexes have general composition [M(L)2X2], where M=Ni(II) and Cu(II), X=Cl(-), NO3(-), CH3COO(-) and ½SO4(2-). On the basis of above spectral studies, an octahedral geometry has been assigned for Ni(II) complexes and tetragonal geometry for Cu(II) complexes except [Cu(L)2SO4] which possesses five coordinated trigonal bipyramidal geometry. These metal complexes were also tested for their anticancer, antibacterial and antifungal activities to assess their inhibition potential. Anticancer activity of ligand and its metal complexes were evaluated using SRB fluorometric assay and Adriamycin (ADR) was applied as positive control. Schiff's base ligand and its metal complexes were screened for their antibacterial and antifungal activity against Escherichia coli, Bacillus cereus and Aspergillus niger, Aspergillus flavus, respectively. Kirby-Bauer single disk susceptibility test was used for antibacterial activity and well diffusion method for antifungal activity of the compounds on the used fungi. PMID:25087168

  20. Synthesis, characterization, antimicrobial activity and carbonic anhydrase enzyme inhibitor effects of salicilaldehyde-N-methyl p-toluenesulfonylhydrazone and its Palladium(II), Cobalt(II) complexes

    NASA Astrophysics Data System (ADS)

    Alyar, Saliha; Adem, ?evki

    2014-10-01

    We report the synthesis of the ligand, salicilaldehyde-N-methyl p-toluenesulfonylhydrazone (salptsmh) derived from p-toluenesulfonicacid-1-methylhydrazide (ptsmh) and its Pd(II) and Co(II) metal complexes were synthesized for the first time. The structure of the ligand and their complexes were investigated using elemental analysis, magnetic susceptibility, molar conductance and spectral (IR, NMR and LC-MS) measurements. Salptsmh has also been characterized by single crystal X-ray diffraction. 1H and 13C shielding tensors for crystal structure were calculated with GIAO/DFT/B3LYP/6-311++G(d,p) methods in CDCl3. The complexes were found to have general composition [ML2]. The results of elemental analysis showed 1:2 (metal/ligand) stoichiometry for all the complex. Magnetic and spectral data indicate a square planar geometry for Pd(II) complex and a distorted tetrahedral geometry for Co(II) complexes. The ligand and its metal chelates have been screened for their antimicrobial activities using the disk diffusion method against the selected Gram positive bacteria: Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, Enterococcus faecalis, Gram negative bacteria: Eschericha coli, Pseudomonas aeruginosa, Klebsiella pneumonia. The inhibition activities of these compounds on carbonic anhydrase II (CA II) and carbonic anhydrase I (CA I) have been investigated by comparing IC50 and Ki values and it has been found that Pd(II) complex have more enzyme inhibition efficiency than salptsmh and Co(II) complex.

  1. Polycomb Repressive Complex 2 and H3K27me3 Cooperate with H3K9 Methylation To Maintain Heterochromatin Protein 1? at Chromatin

    PubMed Central

    Boros, Joanna; Arnoult, Nausica; Stroobant, Vincent; Collet, Jean-François

    2014-01-01

    Methylation of histone H3 on lysine 9 or 27 is crucial for heterochromatin formation. Previously considered hallmarks of, respectively, constitutive and facultative heterochromatin, recent evidence has accumulated in favor of coexistence of these two marks and their cooperation in gene silencing maintenance. H3K9me2/3 ensures anchorage at chromatin of heterochromatin protein 1? (HP1?), a main component of heterochromatin. HP1? chromoshadow domain, involved in dimerization and interaction with partners, has additional but still unclear roles in HP1? recruitment to chromatin. Because of previously suggested links between polycomb repressive complex 2 (PRC2), which catalyzes H3K27 methylation, and HP1?, we tested whether PRC2 may regulate HP1? abundance at chromatin. We found that the EZH2 and SUZ12 subunits of PRC2 are required for HP1? stability, as knockdown of either protein led to HP1? degradation. Similar results were obtained upon overexpression of H3K27me2/3 demethylases. We further showed that binding of HP1?/?/? to H3K9me3 peptides is greatly increased in the presence of H3K27me3, and this is dependent on PRC2. These data fit with recent proteomic studies identifying PRC2 as an indirect H3K9me3 binder in mouse tissues and suggest the existence of a cooperative mechanism of HP1? anchorage at chromatin involving H3 methylation on both K9 and K27 residues. PMID:25047840

  2. Structures of Escherichia coli DNA adenine methyltransferase (Dam) in complex with a non-GATC sequence: potential implications for methylation-independent transcriptional repression

    PubMed Central

    Horton, John R.; Zhang, Xing; Blumenthal, Robert M.; Cheng, Xiaodong

    2015-01-01

    DNA adenine methyltransferase (Dam) is widespread and conserved among the ?-proteobacteria. Methylation of the Ade in GATC sequences regulates diverse bacterial cell functions, including gene expression, mismatch repair and chromosome replication. Dam also controls virulence in many pathogenic Gram-negative bacteria. An unexplained and perplexing observation about Escherichia coli Dam (EcoDam) is that there is no obvious relationship between the genes that are transcriptionally responsive to Dam and the promoter-proximal presence of GATC sequences. Here, we demonstrate that EcoDam interacts with a 5-base pair non-cognate sequence distinct from GATC. The crystal structure of a non-cognate complex allowed us to identify a DNA binding element, GTYTA/TARAC (where Y = C/T and R = A/G). This element immediately flanks GATC sites in some Dam-regulated promoters, including the Pap operon which specifies pyelonephritis-associated pili. In addition, Dam interacts with near-cognate GATC sequences (i.e. 3/4-site ATC and GAT). Taken together, these results imply that Dam, in addition to being responsible for GATC methylation, could also function as a methylation-independent transcriptional repressor. PMID:25845600

  3. In vivo formation of sigma-methyl- and sigma-phenyl-ferric complexes of hemoglobin and liver-cytochrome P-450 upon treatment of rats with methyl- and phenylhydrazine.

    PubMed

    Delaforge, M; Battioni, P; Mahy, J P; Mansuy, D

    1986-10-15

    Ferric sigma-phenyl complexes of hemoglobin and liver cytochrome P-450 are formed in vivo upon administration of C6H5NHNH2 to rats. Small amounts of the sigma-methyl complex of hemoglobin were also detected in vivo upon treatment of rats with CH3NHNH2. At the doses used for CH3NHNH2 (25 and 50 mg/kg) the states and levels of hemoglobin in the blood and spleen, and of cytochrome P-450 in the liver were almost unchanged. On the contrary, C6H5NHNH2 (25-100 mg/kg) led to a decrease of the HbO2 blood level (10-50%), together with an increase in the HbFe(III) level and the appearance of the HbFe(III)-C6H5 complex. The concentration of this complex reaches its maximum value (2 mM) 1 h after C6H5NHNH2 administration (20% of total hemoglobin). At the same time large amounts of HbO2, HbFe(III) and HbFe(III)-C6H5 appeared in the spleen, and remained high up to 24 h after treatment. Treatment of rats with C6H5NHNH2 (25-100 mg/kg) led to a significant decrease in the level of liver cytochrome P-450 (a 70% decrease 2 h after treatment with 100 mg/kg C6H5NHNH2). About 15% of the remaining cytochrome P-450 existed as a cyt.-P-450-Fe(III)-C6H5 complex, a new example of cytochrome P-450-Fe-metabolite complex which is stable in vivo. PMID:3779881

  4. Preparation, spectral, thermal, and biological properties of zinc(II) 4-chloro- and 5-chlorosalicylate complexes with methyl 3-pyridylcarbamate and phenazone

    Microsoft Academic Search

    Zuzana Bujdošová; Katarína Györyová; Daniela Hudecová; Jana Ková?ová; Ladislav Halás

    2010-01-01

    New zinc(II) 4-chloro- and 5-chlorosalicylate complex compounds of the general formula ((4- or 5-Cl)C6H3(2-OH)COO)2Zn · L\\u000a n\\u000a (where L = methyl 3-pyridylcarbamate, phenazone; n = 2, 4) were prepared and characterized by elemental analysis, thermal analysis (TG\\/DTG, DTA), and IR spectroscopy. During\\u000a thermal decomposition, mpc, phen, chlorosalicylic acid, chlorophenol, carbon dioxide, and carbon monoxide were released. Volatile\\u000a products of the

  5. Cyclodextrins in polymer synthesis: photocrosslinkable films via free radical copolymerization of methylated ?-cyclodextrin-complexed styrene with sodium 4-(acrylamido)-phenyldiazosulfonate in aqueous medium

    Microsoft Academic Search

    Joachim Storsberg; Patrick Glöckner; Markus Eigner; Ute Schnöller; Helmut Ritter; Brigitte Voit; Oskar Nuyken

    2001-01-01

    The copolymerization of a methylated-?-cyclodextrin (m-?-CD) 1:1 host-guest compound of styrene (1a) with various molar ratios of sodium 4-(acrylamido)-phenyldiazosulfonate (2) is described. The copolymerization of complex 1a with 2 was carried out in water with 2,2?-azobis(N,N?-dimethyleneisobutyramidine)-dihydrochloride as the free radical initiator at 40°C. Depending on the amount of 2 incorporated in the copolymer, water- or DMF-soluble copolymers of high molar

  6. Effect of methyl group on the cooperativity of CH···O blue-shifted hydrogen bond in HCHO–HCHO–HCHO cyclic complex

    Microsoft Academic Search

    Qingzhong Li; Haiping Liu; Xiulin An; Baoan Gong; Jianbo Cheng

    2008-01-01

    The effect of methyl group on the cooperativity of CH···O blue-shifted hydrogen bond in HCHO–HCHO–HCHO cyclic complex has been studied with quantum chemical calculations at the MP2\\/6-31+G(d,p) level. We report herein the optimized geometries of the stable structures, their vibrational frequencies, NMR chemical shifts, stabilization energies, and binding energies. The cooperativity of CH···O blue-shifted hydrogen bond varies from ?0.57kcal\\/mol in

  7. Hydrogen Bonding and Solvent Effects on Complexation of Alkali Metal Cations by Lower Rim Calix[4]arene Tetra( O -[ N -acetyl- D -phenylglycine methyl ester]) Derivative

    Microsoft Academic Search

    VLADISLAV TOMISIC ´; NIVES GALIC ´; Branimir Bertoša; Leo Frkanec; Vladimir Simeon; Mladen Žini?

    2005-01-01

    Complexation of alkali metal cations with 5,11,17,23-tetra-tert-butyl-26,28,25,27-tetrakis(O-methyl-D-?-phenylglycylcarbonylmethoxy)calix[4]arene (L) was studied by means of spectrophotometric, conductometric and potentiometric titrations at 25 °C. The solvent effect on the binding ability of L was examined by using two solvents with different affinities for hydrogen bonding, viz. methanol and acetonitrile. Despite the presence of intramolecular NH···O=C hydrogen bonds in L, which need to be disrupted

  8. Methylation matters

    PubMed Central

    Costello, J.; Plass, C.

    2001-01-01

    DNA methylation is not just for basic scientists any more. There is a growing awareness in the medical field that having the correct pattern of genomic methylation is essential for healthy cells and organs. If methylation patterns are not properly established or maintained, disorders as diverse as mental retardation, immune deficiency, and sporadic or inherited cancers may follow. Through inappropriate silencing of growth regulating genes and simultaneous destabilisation of whole chromosomes, methylation defects help create a chaotic state from which cancer cells evolve. Methylation defects are present in cells before the onset of obvious malignancy and therefore cannot be explained simply as a consequence of a deregulated cancer cell. Researchers are now able to detect with exquisite sensitivity the cells harbouring methylation defects, sometimes months or years before the time when cancer is clinically detectable. Furthermore, aberrant methylation of specific genes has been directly linked with the tumour response to chemotherapy and patient survival. Advances in our ability to observe the methylation status of the entire cancer cell genome have led us to the unmistakable conclusion that methylation abnormalities are far more prevalent than expected. This methylomics approach permits the integration of an ever growing repertoire of methylation defects with the genetic alterations catalogued from tumours over the past two decades. Here we discuss the current knowledge of DNA methylation in normal cells and disease states, and how this relates directly to our current understanding of the mechanisms by which tumours arise.???Keywords: methylation; cancer PMID:11333864

  9. Synthesis, characterization, crystal structure and theoretical approach of Cu(II) complex with 4-{(Z)-[(2-hydroxybenzoyl)hydrazono]methyl}benzoic acid

    NASA Astrophysics Data System (ADS)

    Chen, Shi-Liang; Liu, Zheng; Liu, Jie; Han, Guo-Cheng; Li, Yan-Hong

    2012-04-01

    The metal complex of [CuL2]·2DMF (L = 4-{(Z)-[(2-hydroxybenzoyl)hydrazono]methyl}benzoic acid, DMF = N,N-dimethylformamide) (1) had been synthesized and characterized by spectral method(IR), UV-Vis electronic absorption spectra, fluorescence spectra, elemental analysis, electrochemistry, thermal analysis (TG, DTG) and single crystal X-ray diffraction techniques. In the complex, the ligands act as univalent anion bidentate and coordination takes place in the enol tautomeric form with the enolic oxygen and azomethine nitrogen atoms. Molecular geometry from X-ray experiment of the title compound in the ground-state has been compared using the density functional method (B3LYP) and LANL2DZ basis set. DFT calculations at B3LYP/LANL2DZ level of theory prove that the electronic spectra of CuL2·2DMF is attributed to intra-complex electronic transitions as well as ?-?* electronic transitions. Also, Mulliken charge analysis, natural bond orbitals (NBO), Wiberg bond index and frontier molecular orbitals (FMO) were performed at B3LYP/LANL2DZ level of theory. In addition, complex 1 exhibits strong photoluminescent emission at room temperature. The electrochemical studies reveal that redox of Cu2+/Cu+ in the complex are quasi-reversible processes. The result of TG analysis shows that the title complex was stable under 100.0 °C.

  10. Distinct Contributions of Histone H3 Lysine 9 and 27 Methylation to Locus-Specific Stability of Polycomb Complexes

    Microsoft Academic Search

    Leonie Ringrose; Heidi Ehret; Renato Paro

    2004-01-01

    The Polycomb group of proteins (PcG) maintains stable epigenetic silencing of over 100 genes via PcG response elements (PREs). Here we investigate the relationship between Polycomb binding, transcriptional status, and histone H3 methylation at lysine 9 (H3K9Me) and 27 (H3K27Me) for over 30 PcG targets in Drosophila. We show that H3K9Me and H3K27Me have distinct distributions at different loci. Our

  11. Complex formed in the system hydrophobically modified polyethylene glycol\\/methylated ?-cyclodextrin\\/water. An NMR diffusometry study

    Microsoft Academic Search

    L. Karlson; C. Malmborg; K. Thuresson; O. Söderman

    2003-01-01

    In aqueous solutions hydrophobically modified polyethylene glycol (HM-PEG) forms a transient polymer network held together by intermolecular hydrophobic associations. In the present investigation we have used NMR-diffusometry to study how the addition of methylated ?-cyclodextrin (M-?-CD) influences the polymer network. The addition of M-?-CD resulted in an increased mean self-diffusion of HM-PEG, DHM-PEG, which is referred to a degradation of

  12. Conductivity, Mechanical and Thermal Studies on Poly(methyl methacrylate)-Based Polymer Electrolytes Complexed with Lithium Tetraborate and Propylene Carbonate

    NASA Astrophysics Data System (ADS)

    Ramesh, S.; Bing, Khoo Ne

    2012-01-01

    A series of different composition ratio of polymer electrolytes based on poly(methyl methacrylate) (PMMA) as host polymer, lithium tetraborate (Li2B4O7) as salt, and propylene carbonate (PC) as plasticizer is produced by solution casting method. Fourier transform infrared (FTIR) spectroscopy studies are used to confirm the formation of polymer electrolyte complex. PMMA: Li2B4O7: PC (52.5:22.5:25.0 wt.%) is obtained as the highest conducting polymer electrolyte with a conductivity of 5.14 × 10-6 S/cm at room temperature (23 °C). The temperature-dependent conductivity of the polymer films shows Arrhenius-like behavior which reveals that the charge carriers move in a liquid-like environment. The addition of PC decreases the Young's modulus and stress at peak values of the complexes. Thermogravimetric analysis (TGA) is employed to study the thermal stability of the electrolytes.

  13. Iron(III) complexes of bis (benzimidazol-2-yl) methyl) thiophene-2,5-dicarboxamide: Synthesis, spectral and oxidation of o-phenylenediamine

    NASA Astrophysics Data System (ADS)

    Tyagi, Nidhi; Mathur, Pavan

    2012-10-01

    Iron(III) complexes of a potentially pentadentate ligand N2, N5-bis ((1H-benzo [d] imidazol-2-yl) methyl) thiophene-2,5-dicarboxamide are synthesized with an exogenous anion X = Cl-, NO3-. Mössbauer and EPR spectroscopy indicates axially distorted complexes. These complexes were utilized for the oxidation of o-phenylenediamine to 2,3-diaminophenazine in presence of H2O2. The initial rate of reaction is dependent on the concentration of o-phenylenediamine as well as the iron(III) complex. Rates of reaction were found to be at least five times higher for the Cl- bound complex. The effect of an added anion like acetate, azide and citrate is found to inhibit the rate of reaction. This suggests that one of the factors affecting the rate determining step is the binding of these anions on a vacant site at the iron(III) centre. The oxidation of o-phenylenediamine to 2,3-diaminophenazine is reminiscent of the functioning of horse radish peroxidase.

  14. Rhodium and iridium complexes containing diphenyl-2-(3-methyl)indolylphosphine: synthesis, structure and application in the catalytic transfer hydrogenation of ketones.

    PubMed

    Kuo, Yu-Ying; Haddow, Mairi F; Pérez-Redondo, Adrián; Owen, Gareth R

    2010-07-21

    The synthesis and characterisation of a number of group nine complexes containing the recently reported ligand, diphenyl-2-(3-methyl)indolylphosphine, is presented herein. The complexes [RhCl(COD){PPh(2)(C(9)H(8)N)}] (1), [IrCl(COD){PPh(2)(C(9)H(8)N)}] (2), [RhCl(NBD){PPh(2)(C(9)H(8)N)}] (3) and [Rh(COD)(MeCN){PPh(2)(C(9)H(8)N)}]BF(4) (4) (where COD = 1,5-cyclooctadiene, NBD = 2,5- norbornadiene) have been structurally characterised by X-ray crystallography. The complex [Rh(2)(COD)(2){N(Me)[double bond, length as m-dash]C(H)Ph)}{PPh(2)(C(9)H(8)N)}][BF(4)](2) (8) was also isolated and structurally characterised. Complex 8 contains a '[Rh(COD)]' fragment coordinated to the aromatic ring of the indolyl group, providing the first example of a eta(6) coordination mode for this ligand. The synthesised complexes were investigated for their activity in the catalytic transfer hydrogenation of ketones and found to be moderately active catalysts. PMID:20523959

  15. Synthesis, growth, spectral, and thermal studies of a new organic molecular charge transfer complex crystal: 3-nitroaniline 4-methyl benzene sulfonate.

    PubMed

    Selvakumar, E; Anandha babu, G; Ramasamy, P; Chandramohan, A

    2014-03-25

    A new organic intermolecular charge transfer complex 3-nitroaniline 4-methyl benzene sulfonate (NATS) has been successfully synthesized and good optical quality single crystals grown by slow solvent evaporation solution growth technique at room temperature using methanol as the solvent. The (1)H and (13)C NMR spectra were recorded to establish the molecular structure of the title complex. The crystal structure of NATS has been determined by single crystal XRD analysis and it belongs to orthorhombic crystal system with space group Pbca. Fourier transform infrared (FT-IR) spectral study has been carried out to confirm the presence of various functional groups present in the complex. Electronic absorption spectrum was recorded to find the prevalent charge transfer activity in the complex. The UV-Vis-NIR transmission spectrum was recorded in the range 200-2500 nm, to find the optical transmittance window and lower cut off wavelength of the title crystal. The thermal stability of the title complex crystal was studied by using thermo-gravimetric and differential thermal analyses and found that the compound is stable up to 215 °C. PMID:24322759

  16. Synthesis, growth, spectral, and thermal studies of a new organic molecular charge transfer complex crystal: 3-Nitroaniline 4-methyl benzene sulfonate

    NASA Astrophysics Data System (ADS)

    Selvakumar, E.; Anandha babu, G.; Ramasamy, P.; Chandramohan, A.

    2014-03-01

    A new organic intermolecular charge transfer complex 3-nitroaniline 4-methyl benzene sulfonate (NATS) has been successfully synthesized and good optical quality single crystals grown by slow solvent evaporation solution growth technique at room temperature using methanol as the solvent. The 1H and 13C NMR spectra were recorded to establish the molecular structure of the title complex. The crystal structure of NATS has been determined by single crystal XRD analysis and it belongs to orthorhombic crystal system with space group Pbca. Fourier transform infrared (FT-IR) spectral study has been carried out to confirm the presence of various functional groups present in the complex. Electronic absorption spectrum was recorded to find the prevalent charge transfer activity in the complex. The UV-Vis-NIR transmission spectrum was recorded in the range 200-2500 nm, to find the optical transmittance window and lower cut off wavelength of the title crystal. The thermal stability of the title complex crystal was studied by using thermo-gravimetric and differential thermal analyses and found that the compound is stable up to 215 °C.

  17. Paramagnetic metal effect on the ligand localized S/sub 1/. -->. T/sub 1/ intersystem crossing in the rare-earth-metal complexes and methyl salicylate

    SciTech Connect

    Tobita, S.; Arakawa, M.; Tanaka, I.

    1985-01-01

    The electronic relaxation processes in the chelates of La/sup 3 +/, Gd/sup 3 +/, Tb/sup 3 +/, and Lu/sup 3 +/ with methyl salicylate have been investigated by measurements of picosecond fluorescence, nanosecond transient absorptions, and quantum yields. The quantum yields of the S/sub 1/ ..-->.. T/sub 1/ intersystem crossing are not appreciably altered by a change in the central metal ions. However, the fluorescence lifetimes are decreased dramatically in the paramagnetic Gd/sup 3 +/ (240 ps) and Tb/sup 3 +/ (<10 ps) complexes compared with those in the diamagnetic La/sup 3 +/ (2.2 ns) and Lu/sup 3 +/ (2.4 ns) complexes. The rate constants derived from these results for the S/sub 1/ ..-->.. T/sub 1/ intersystem crossing, k/sub TM/, in ligands are 5.5 x 10/sup 7/, 7.5 x 10/sup 8/, and 7.9 x 10/sup 7/ s/sup -1/ for the La/sup 3 +/, Gd/sup 3 +/, and Lu/sup 3 +/ complexes, respectively. A large increase of k/sub TM/ is observed in the paramagnetic Gd/sup 3 +/ complexes, which can be attributed to the electron exchange mechanism with ligand ..pi.. electrons. 27 references, 8 figures, 3 tables.

  18. Ionic interactions and transport properties in methyl terminated poly(propylene glycol)(4000) complexed with LiCF{sub 3}SO{sub 3}

    SciTech Connect

    Ferry, A. [Umea Univ. (Sweden)] [Umea Univ. (Sweden)

    1997-01-09

    Alternating current (ac) impedance, restricted diffusion, and vibrational spectroscopic (Raman and IR) measurements have been conducted on complexes of methyl capped poly(propylene glycol) of molecular weight 4000 and LiCF{sub 3}SO{sub 3} salt. The relative concentrations of anions in different chemical environments have been calculated from an analysis of the symmetric anion SO{sub 3} stretch (Raman) over a wide concentration range. Comparisons are made to previous studies on hydroxyl capped PPG systems, and we find that polar polymer end groups play an important role in the solvation of the salt. The relative fraction of anions interacting directly with lithium cations is considerably higher over the entire concentration range in the present study, and we infer the existence of negatively charged ionic aggregates in the solutions. We also note that the fraction of spectroscopically `free` anions increases with increasing salt concentration in the ether oxygen to alkali metal cation ratio (O:M) range 502:1 to 12:1, contrary to a decrease reported for the analogue hydroxyl terminated electrolytes. The ionic conductivity has a more pronounced concentration dependency in the methyl capped system; notably, the molar conductivity ({Lambda}) increases dramatically with increasing salt concentration passing through a relatively sharp maximum at O:M = 20:1 at room temperature. 71 refs., 8 figs., 1 tab.

  19. Spectral and thermal characterization of 3-acetyl-5-azophenyl-4-hydroxy-6-methyl-pyran-2-one and its metal complexes

    NASA Astrophysics Data System (ADS)

    Seth, Susannah; Aravindakshan, K. K.

    2013-08-01

    Five chelates of 3-acetyl-5-azophenyl-4-hydroxy-6-methyl-pyran-2-one (phenylazo dehydroacetic acid) with Cr(III), Fe(III), Ni(II), Cu(II) and Zn(II) have been synthesized and characterized by elemental analysis, magnetic susceptibility measurements, electronic, 1H NMR, FAB mass, IR-spectral and thermal (TG/DTG) analytical techniques. In the present work it has been found that oxygen of the deprotonated sbnd OH group and one of the azo-nitrogens of the ligand take part in coordination. The Cr(III), Fe(III) and Ni(II) complexes were found to be having octahedral geometry and the Cu(II) and Zn(II) tetrahedral.

  20. Accurate Computer Simulation of Phase Equilibrium for Complex Fluid Mixtures. Application to Binaries Involving Isobutene, Methanol, Methyl tert-Butyl Ether, and

    E-print Network

    Lisal, Martin

    to Binaries Involving Isobutene, Methanol, Methyl tert-Butyl Ether, and n-Butane Martin Li´sal,*,, William R + methyl tert-butyl ether (MTBE) and the binaries formed by methanol with isobutene, MTBE, and n

  1. Methyl Iodide

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methyl iodide (MeI, iodomethane, CH3I) was reported as a potential alternative to the stratospheric ozone-depleting fumigant methyl bromide (MeBr) in the mid-1990s (Sims et al., 1995; Ohr et al., 1996). It has since received significant research attention to determine its environmental fate and tran...

  2. Methyl chloroform

    SciTech Connect

    Wray, T.K.

    1994-04-01

    Methyl chloroform is identified as a Class 1 ozone-depleting substance under Title VI of the CAA Amendments. On Nov. 30, 1993, EPA ordered the phaseout of Class 1 ozone-depleting substances -- chlorofluorocarbons (CFCs), halons, carbon tetrachloride and methyl chloroform -- by Jan. 1, 1996. Methyl chloroform and other Class 1 substances may be used after the dead-line if sources can be found through recycling or existing inventories. Methyl chloroform is listed as a hazardous air pollutant under CAA. It also is a SARA Title III, Sec. 313 compound with a reportable quantity of 1,000 pounds. OSHA and the American Conference of Government Industrial Hygienists have set 350 ppm as the time-weighted average airborne exposure level for methyl chloroform. NIOSH lists its immediately dangerous to life or health'' concentration as 1,000 parts per million. DOT identifies the substance as a hazardous material, Class 6.1 (poison).

  3. Synthesis and spectroscopy studies of the inclusion complex of 3-amino-5-methyl pyrazole with beta-cyclodextrin

    NASA Astrophysics Data System (ADS)

    Louiz, S.; Labiadh, H.; Abderrahim, R.

    2015-01-01

    Amino pyrazole belongs to anti-inflammatory class, and is characterized by a low solubility in water. (In order to increase its solubility in water, inclusion complex of amino pyrazole with ?-CD was obtained.) The inclusion complex obtained between AMP and ?-cyclodextrin, was characterized by FT-IR, 1H NMR, 1H-1H NOESY, 13C NMR, DEPT, XHCOR, spectra, through TG analysis, DTA, DSC and Scanning Electron Microscopy (SEM). The stoichiometry of inclusion complex is 1:1 (guest-host) and K stability is 1.1 × 104 M-1.

  4. Homogeneous solvation controlled photoreduction of cobalt(III) complexes in aqueous 2-methyl-2-propanol solutions linear solvation energy relationship and cyclic voltammetric analyses.

    PubMed

    Anbalagan, K; Lydia, I Sharmila

    2008-03-01

    The effect of solvent participation on the ligand-to-metal charge transfer (LMCT, L-->Co(III)) reduction of the of Co(III)(en)(2)Br(RC(6)H(4)NH(2))(2+) where R=m-OCH(3), p-F, H, m-CH(3), p-CH(3,)p-OC(2)H(5) and p-OCH(3) were examined in aqueous 2-methyl-2-propanol (Bu(t)OH) solutions. The change in the reduction behavior of Co(III) centre was also examined through cyclic voltammetric studies. The observed reduction in quantum yield due to LMCT excitation can mainly be accounted using linear solvation energy relationship (LSER) comprising model correlation equations. These consist of empirical parameters such as Grunwald-Winstein's solvent ionizing power, Y, Dimroth-Richardt's solvent micro-polarity parameter, E(T)(N), Gutmann's donor number, DN(N), along with Kamlet-Taft's solvatochromic parameters (hydrogen bond acceptor acidity/basicity alpha/beta and solvent dipolarity/polarizability, pi*). The origin of solvent effect is found to be due to microscopic interaction between the solvent donor and the nitrogen-bound hydrogen of the ligand. Cyclic voltammograms show an irreversible reduction of Co(III) in DMF using Glassy Carbon Electrode, GCE, the redox peaks for the aniline complexes appear at -0.20 and 0.525V. Irradiation of the complexes with UV light (lambda=254nm) in binary mixtures produce Co(II)(aq) and the concentration of this species are highly dependent on x(alc) (x(alc)=mole fraction of alcohol). The observed quantum yield (logPhi(Co(II))) is found to be linearly related to mole fraction of organic co-solvent added in the mixture, therefore, logPhi(Co(II))=26.41 x 10(-2) when x(2)=0.0094 and 43.75 x 10(-2) when x(2)=0.076 for a typical complex Co(III)(en)(2)Br(p-OCH(3)C(6)H(4)NH(2))(2+) in aqueous 2-methyl-2-propanol at 300K. Cyclic voltammetry and LSER analyses illustrate the variation of reduction property of Co(III) by the aryl ligand and homogeneous solvation of the excited state of the complex Co(III)(en)(2)Br(RC(6)H(4)NH(2))(2+) in H(2)O/Bu(t)OH mixtures. PMID:17698408

  5. Homogeneous solvation controlled photoreduction of cobalt(III) complexes in aqueous 2-methyl-2-propanol solutions. Linear solvation energy relationship and cyclic voltammetric analyses

    NASA Astrophysics Data System (ADS)

    Anbalagan, K.; Lydia, I. Sharmila

    2008-03-01

    The effect of solvent participation on the ligand-to-metal charge transfer (LMCT, L ? Co III) reduction of the of Co III(en) 2Br(RC 6H 4NH 2) 2+ where R = m-OCH 3, p-F, H, m-CH 3, p-CH 3,p-OC 2H 5 and p-OCH 3 were examined in aqueous 2-methyl-2-propanol (Bu tOH) solutions. The change in the reduction behavior of Co III centre was also examined through cyclic voltammetric studies. The observed reduction in quantum yield due to LMCT excitation can mainly be accounted using linear solvation energy relationship (LSER) comprising model correlation equations. These consist of empirical parameters such as Grunwald-Winstein's solvent ionizing power, Y, Dimroth-Richardt's solvent micro-polarity parameter, ETN, Gutmann's donor number, DN N, along with Kamlet-Taft's solvatochromic parameters (hydrogen bond acceptor acidity/basicity ?/ ? and solvent dipolarity/polarizability, ?*). The origin of solvent effect is found to be due to microscopic interaction between the solvent donor and the nitrogen-bound hydrogen of the ligand. Cyclic voltammograms show an irreversible reduction of Co III in DMF using Glassy Carbon Electrode, GCE, the redox peaks for the aniline complexes appear at -0.20 and 0.525 V. Irradiation of the complexes with UV light ( ? = 254 nm) in binary mixtures produce Co IIaq and the concentration of this species are highly dependent on xalc ( xalc = mole fraction of alcohol). The observed quantum yield (log ?Co(II)) is found to be linearly related to mole fraction of organic co-solvent added in the mixture, therefore, log ?Co(II) = 26.41 × 10 -2 when x2 = 0.0094 and 43.75 × 10 -2 when x2 = 0.076 for a typical complex Co III(en) 2Br( p-OCH 3C 6H 4NH 2) 2+ in aqueous 2-methyl-2-propanol at 300 K. Cyclic voltammetry and LSER analyses illustrate the variation of reduction property of Co(III) by the aryl ligand and homogeneous solvation of the excited state of the complex Co III(en) 2Br(RC 6H 4NH 2) 2+ in H 2O/Bu tOH mixtures.

  6. Tricarbonyltechnetium(I) and tricarbonylrhenium(I) complexed with N-methyl-2-pyridinecarboxyamide as potential radiopharmaceuticals: a computational study

    Microsoft Academic Search

    L. Fuks; E. Gniazdowska; N. Sadlej-Sosnowska

    2010-01-01

    The electronic and thermodynamic properties of the ‘2 + 1’ tricarbonyltechnetium(I) and -rhenium(I) mixed ligand complexes\\u000a with N-methylpyridine-2-carboxyamide (MPCA) as a bidentate ligand and chloride, water, or tert-butyl-3-isocyanopropanoate (BCP), were investigated within the framework of Density Functional Theory. The atomic charges\\u000a of all complexes, polarization of the CO groups, as well as the effect of transfer of ?-electron density between the ligands

  7. IDENTIFICATION OF METHYL FARNESOATE FROM IN VITRO CULTURE OF THE RETROCEREBRAL COMPLEX OF ADULT FEMALES OF THE MOTH, HELIOTHIS VIRESCENS (LEPIDOPTERA: NOCTUIDAE) AND ITS CONVERSION TO JUVENILE HORMONE III

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gas chromatographic-mass spectral analysis of extracts obtained from in vitro culture of isolated retrocerebral complexes obtained from adult females of the moth Heliothis virescens resulted in identification of methyl farnesoate as well as, juvenile hormone III (JH III) but not JH III acid. Inhibit...

  8. Intrathecally administered D-cycloserine produces nociceptive behavior through the activation of N-methyl-D-aspartate receptor ion-channel complex acting on the glycine recognition site.

    PubMed

    Tan-No, Koichi; Esashi, Akihisa; Nakagawasai, Osamu; Niijima, Fukie; Furuta, Seiichi; Sato, Takumi; Satoh, Susumu; Yasuhara, Hajime; Tadano, Takeshi

    2007-05-01

    Intrathecal (i.t.) administration of D-cycloserine (100 and 300 fmol), a partial agonist of the glycine recognition site on the N-methyl-D-aspartate (NMDA) receptor ion-channel complex, produced a behavioral response mainly consisting of biting and/or licking of the hindpaw and the tail along with slight hindlimb scratching directed toward the flank in mice, which peaked at 5 - 10 min and almost disappeared at 15 min after the injection. The behavior induced by D-cycloserine (300 fmol) was dose-dependently inhibited by an intraperitoneal injection of morphine (0.5-2 mg/kg), suggesting that the behavioral response is related to nociception. The nociceptive behavior was also dose-dependently inhibited by i.t. co-administration of 7-chlorokynurenic acid (0.25-4 nmol), a competitive antagonist of the glycine recognition site on the NMDA receptor ion-channel complex; D-(-)-2-amino-5-phosphonovaleric acid (62.5-500 pmol), a competitive NMDA receptor antagonist; MK-801 (62.5-500 pmol), an NMDA ion-channel blocker; ifenprodil (0.5-8 nmol); arcaine (31-125 pmol); and agmatine (0.1-10 pmol), all being antagonists of the polyamine recognition site on the NMDA receptor ion-channel complex. However, [D-Phe7,D-His9]-substance P(6-11), a specific antagonist for substance P (NK1) receptors, and MEN-10,376, a tachykinin NK2-receptor antagonist, had no effect on D-cycloserine-induced nociceptive behavior. These results in the mouse spinal cord suggest that D-cycloserine-induced nociceptive behavior is mediated through the activation of the NMDA receptor ion-channel complex by acting on the glycine recognition site and that it does not involve the tachykinin receptor mechanism. PMID:17452810

  9. Electropolymerization of ruthenium bis(1,10-phenanthroline)(4-methyl-4'-vinyl-2,2'-bipyridine) complexes through direct attack on the ligand ring system

    SciTech Connect

    Guarr, T.F.; Anson, F.C.

    1987-07-16

    Mixed ligand complexes of the general type RuP/sub 2/(4-methyl-4'-vinyl-2,2'-bipyridine)/sup 2 +/ (where P represents phenanthroline or a substituted phenanthroline) undergo rapid electropolymerization following initial two-electron reduction. The polymerization yields redox-conductive electrode coatings and appears to proceed via radical-radical coupling between the vinyl moiety and a phenanthroline carbon, with the 4- and 7-positions of the phenanthroline being the most reactive. When the phenanthroline ligands possess substituents in the 4- and 7-positions, polymerization still proceeds, but an unexpected reversible electrochemical response near -0.2 V vs. SSCE is generated. The response is attributed to an intermediate which can exist in a stable ligand-centered free-radical form. This radical species has been observed by EPR spectroscopy and is stabilized by 4,7-disubstitution and/or the presence of proton donors. The mechanistic pathways involved in the electropolymerization are complex and lead to multiple products. Polymerized films display unusual electrochemistry, including prominent charge-trapping peaks for which a mechanistic system is proposed.

  10. Characterization of Albendazole-Randomly Methylated-?-Cyclodextrin Inclusion Complex and In Vivo Evaluation of Its Antihelmitic Activity in a Murine Model of Trichinellosis

    PubMed Central

    García, Agustina; Leonardi, Darío; Vasconi, María D.; Hinrichsen, Lucila I.; Lamas, María C.

    2014-01-01

    Albendazole is a benzimidazole carbamate extensively used in oral chemotherapy against intestinal parasites, due to its broad spectrum activity, good tolerance and low cost. However, the drug has the disadvantage of poor bioavailability due to its very low solubility in water; as a consequence, a very active area of research focuses on the development of new pharmaceutical formulations to increase its solubility, dissolution rate, and bioavailability. The primary objective of this study was to prepare randomly methylated ?-cyclodextrins inclusion complexes to increase albendazole dissolution rate, in order to enhance its antiparasitic activity. This formulation therapeutic efficacy was contrasted with that of the pure drug by treating Trichinella spiralis infected mice during the intestinal phase of the parasite cycle, on days five and six post-infection. This protocol significantly decreased muscle larval burden measured in the parenteral stage on day 30 post-infection, when compared with the untreated control. Thus, it could be demonstrated that the inclusion complexes improve the in vivo therapeutic activity of albendazole. PMID:25406084

  11. Pd(II) and Pd(IV) complexes with 5-methyl-5-(4-pyridyl)hydantoin: synthesis, physicochemical, theoretical, and pharmacological investigation.

    PubMed

    Sabounchei, Seyyed Javad; Shahriary, Parisa; Salehzadeh, Sadegh; Gholiee, Yasin; Nematollahi, Davood; Chehregani, Abdolkarim; Amani, Ameneh; Afsartala, Zohreh

    2015-01-25

    The reaction of K2[PdCl4] and PdCl2 with 5-methyl-5-(4-pyridyl)-2,4-imidazolidenedione (L) proceeded with the formation of two different Pd complexes, PdL2Cl2 (1) and PdL2Cl4 (2c), corresponded to a substitution reaction and a substitution reaction along with unanticipated oxidation, respectively. The nature of the oxidizing agent is unknown. These compounds have been studied by elemental analysis, IR, (1)H and (13)CNMR, molar conductivity, and cyclic voltammetry. In addition, structural optimization by DFT calculations and simulation of NMR spectra have been performed and compared with the experimental data. NBO analysis, HOMO and LUMO, have been used to elucidate the information regarding charge transfer within the molecules. Theoretical studies confirmed that in 1 and 2c the trans structures are about 41 and 33 kJ mol(-1) more stable than cis ones. Antibacterial activity and in vitro cytotoxicity of these compounds, as respectively assessed in six bacterial strains and two human tumor cell lines, have been investigated. Results showed the title complexes have the capacity of inhibiting the metabolic growth of bacteria and tumor cells to different extents. PMID:25171052

  12. Pd(II) and Pd(IV) complexes with 5-methyl-5-(4-pyridyl)hydantoin: Synthesis, physicochemical, theoretical, and pharmacological investigation

    NASA Astrophysics Data System (ADS)

    Sabounchei, Seyyed Javad; Shahriary, Parisa; Salehzadeh, Sadegh; Gholiee, Yasin; Nematollahi, Davood; Chehregani, Abdolkarim; Amani, Ameneh; Afsartala, Zohreh

    2015-01-01

    The reaction of K2[PdCl4] and PdCl2 with 5-methyl-5-(4-pyridyl)-2,4-imidazolidenedione (L) proceeded with the formation of two different Pd complexes, PdL2Cl2 (1) and PdL2Cl4 (2c), corresponded to a substitution reaction and a substitution reaction along with unanticipated oxidation, respectively. The nature of the oxidizing agent is unknown. These compounds have been studied by elemental analysis, IR, 1H and 13CNMR, molar conductivity, and cyclic voltammetry. In addition, structural optimization by DFT calculations and simulation of NMR spectra have been performed and compared with the experimental data. NBO analysis, HOMO and LUMO, have been used to elucidate the information regarding charge transfer within the molecules. Theoretical studies confirmed that in 1 and 2c the trans structures are about 41 and 33 kJ mol-1 more stable than cis ones. Antibacterial activity and in vitro cytotoxicity of these compounds, as respectively assessed in six bacterial strains and two human tumor cell lines, have been investigated. Results showed the title complexes have the capacity of inhibiting the metabolic growth of bacteria and tumor cells to different extents.

  13. METHYL GREEN

    PubMed Central

    Kurnick, N. B.; Foster, Marilee

    1950-01-01

    1. Methyl green ("ethyl green") C. I. Number 685 was examined and found to behave identically with methyl green C. I. Number 684 (no longer available) in respect to molar extinction coefficient, effect of combination with polymerized DNA, failure to react with depolymerized DNA, and effect of pH. 2. The mass law permits the calculation of P/dye. This is found to be 13 P/dye. The same value is obtained when an excess of methyl green is caused to fade by adjusting the pH to 7.5. 3. The compound formed by methyl green with DNA has the same maximum absorption at 642.5 to 645 mµ in the pH range 3.5–7.8, whereas the free dye fades markedly above pH 5.0. PMID:14824487

  14. The proto-oncoprotein FBI-1 interacts with MBD3 to recruit the Mi-2/NuRD-HDAC complex and BCoR and to silence p21WAF/CDKN1A by DNA methylation

    PubMed Central

    Choi, Won-Il; Jeon, Bu-Nam; Yoon, Jae-Hyeon; Koh, Dong-In; Kim, Myung-Hwa; Yu, Mi-Young; Lee, Kyung-Mi; Kim, Youngsoo; Kim, Kyunggon; Hur, Sujin Susanne; Lee, Choong-Eun; Kim, Kyung-Sup; Hur, Man-Wook

    2013-01-01

    The tumour-suppressor gene CDKN1A (encoding p21Waf/Cip1) is thought to be epigenetically repressed in cancer cells. FBI-1 (ZBTB7A) is a proto-oncogenic transcription factor repressing the alternative reading frame and p21WAF/CDKN1A genes of the p53 pathway. FBI-1 interacts directly with MBD3 (methyl-CpG–binding domain protein 3) in the nucleus. We demonstrated that FBI-1 binds both non-methylated and methylated DNA and that MBD3 is recruited to the CDKN1A promoter through its interaction with FBI-1, where it enhances transcriptional repression by FBI-1. FBI-1 also interacts with the co-repressors nuclear receptor corepressor (NCoR), silencing mediator for retinoid and thyroid receptors (SMRT) and BCL-6 corepressor (BCoR) to repress transcription. MBD3 regulates a molecular interaction between the co-repressor and FBI-1. MBD3 decreases the interaction between FBI-1 and NCoR/SMRT but increases the interaction between FBI-1 and BCoR. Because MBD3 is a subunit of the Mi-2 autoantigen (Mi-2)/nucleosome remodelling and histone deacetylase (NuRD)-HDAC complex, FBI-1 recruits the Mi-2/NuRD-HDAC complex via MBD3. BCoR interacts with the Mi-2/NuRD-HDAC complex, DNMTs and HP1. MBD3 and BCoR play a significant role in the recruitment of the Mi-2/NuRD-HDAC complex– and the NuRD complex–associated proteins, DNMTs and HP. By recruiting DNMTs and HP1, Mi-2/NuRD-HDAC complex appears to play key roles in epigenetic repression of CDKN1A by DNA methylation. PMID:23658227

  15. The proto-oncoprotein FBI-1 interacts with MBD3 to recruit the Mi-2/NuRD-HDAC complex and BCoR and to silence p21WAF/CDKN1A by DNA methylation.

    PubMed

    Choi, Won-Il; Jeon, Bu-Nam; Yoon, Jae-Hyeon; Koh, Dong-In; Kim, Myung-Hwa; Yu, Mi-Young; Lee, Kyung-Mi; Kim, Youngsoo; Kim, Kyunggon; Hur, Sujin Susanne; Lee, Choong-Eun; Kim, Kyung-Sup; Hur, Man-Wook

    2013-07-01

    The tumour-suppressor gene CDKN1A (encoding p21Waf/Cip1) is thought to be epigenetically repressed in cancer cells. FBI-1 (ZBTB7A) is a proto-oncogenic transcription factor repressing the alternative reading frame and p21WAF/CDKN1A genes of the p53 pathway. FBI-1 interacts directly with MBD3 (methyl-CpG-binding domain protein 3) in the nucleus. We demonstrated that FBI-1 binds both non-methylated and methylated DNA and that MBD3 is recruited to the CDKN1A promoter through its interaction with FBI-1, where it enhances transcriptional repression by FBI-1. FBI-1 also interacts with the co-repressors nuclear receptor corepressor (NCoR), silencing mediator for retinoid and thyroid receptors (SMRT) and BCL-6 corepressor (BCoR) to repress transcription. MBD3 regulates a molecular interaction between the co-repressor and FBI-1. MBD3 decreases the interaction between FBI-1 and NCoR/SMRT but increases the interaction between FBI-1 and BCoR. Because MBD3 is a subunit of the Mi-2 autoantigen (Mi-2)/nucleosome remodelling and histone deacetylase (NuRD)-HDAC complex, FBI-1 recruits the Mi-2/NuRD-HDAC complex via MBD3. BCoR interacts with the Mi-2/NuRD-HDAC complex, DNMTs and HP1. MBD3 and BCoR play a significant role in the recruitment of the Mi-2/NuRD-HDAC complex- and the NuRD complex-associated proteins, DNMTs and HP. By recruiting DNMTs and HP1, Mi-2/NuRD-HDAC complex appears to play key roles in epigenetic repression of CDKN1A by DNA methylation. PMID:23658227

  16. DNA Methylation

    PubMed Central

    Marinus, M.G.; Løbner-Olesen, A.

    2014-01-01

    The DNA of E. coli contains 19,120 6-methyladenines and 12,045 5-methylcytosines in addition to the four regular bases and these are formed by the postreplicative action of three DNA methyltransferases. The majority of the methylated bases are formed by the Dam and Dcm methyltransferases encoded by the dam (DNA adenine methyltransferase) and dcm (DNA cytosine methyltransferase) genes. Although not essential, Dam methylation is important for strand discrimination during repair of replication errors, controlling the frequency of initiation of chromosome replication at oriC, and regulation of transcription initiation at promoters containing GATC sequences. In contrast, there is no known function for Dcm methylation although Dcm recognition sites constitute sequence motifs for Very Short Patch repair of T/G base mismatches. In certain bacteria (e.g., Vibrio cholerae, Caulobacter crescentus) adenine methylation is essential and in C. crescentus, it is important for temporal gene expression which, in turn, is required for coordinating chromosome initiation, replication and division. In practical terms, Dam and Dcm methylation can inhibit restriction enzyme cleavage; decrease transformation frequency in certain bacteria; decrease the stability of short direct repeats; are necessary for site-directed mutagenesis; and to probe eukaryotic structure and function. PMID:25405210

  17. The Influence of Linker Geometry on Uranyl Complexation by Rigidly-Linked Bis(3-hydroxy-N-methyl-pyridin-2-one)

    SciTech Connect

    Szigethy, Geza; Raymond, Kenneth

    2010-04-22

    A series of bis(3-hydroxy-N-methyl-pyridin-2-one) ligands was synthesized, and their respective uranyl complexes were characterized by single crystal X-ray diffraction analyses. These structures were inspected for high-energy conformations and evaluated using a series of metrics to measure co-planarity of chelating moieties with each other and the uranyl coordination plane, as well as to measure coordinative crowding about the uranyl dication. Both very short (ethyl, 3,4-thiophene and o-phenylene) and very long ({alpha},{alpha}{prime}-m-xylene and 1,8-fluorene) linkers provide optimal ligand geometries about the uranyl cation, resulting in planar, unstrained molecular arrangements. The planarity of the rigid linkers also suggests there is a degree of pre-organization for a planar coordination mode that is ideal for uranyl-selective ligand design. Comparison of intramolecular N{sub amide}-O{sub phenolate} distances and {sup 1}H NMR chemical shifts of amide protons supports earlier results that short linkers provide the optimal geometry for intramolecular hydrogen bonding.

  18. Activation of Dimethyl Gold Complexes on MgO for CO Oxidation: Removal of Methyl Ligands and Formation of Catalytically Active Gold Clusters

    SciTech Connect

    Hao, Y.; Gates, B

    2009-01-01

    A supported CO oxidation catalyst was synthesized by the reaction of Au(CH{sub 3}){sub 2}(acac) (acac is acetylacetonate) with partially dehydroxylated MgO powder. The as-prepared sample was found by infrared (IR) and extended X-ray absorption fine structure (EXAFS) spectroscopies to incorporate dimethyl gold complexes that were bonded to the support; it lacked measurable catalytic activity for CO oxidation at room temperature. As the temperature was increased to >373 K with the sample in flowing CO + O{sub 2} at atmospheric pressure, removal of methyl ligands from the gold was observed by IR and EXAFS spectroscopies. Simultaneously, the sample became active for CO oxidation catalysis. EXAFS characterization of the sample right after the activation indicated that the gold had aggregated into clusters consisting of approximately 4-6 Au atoms each, on average. These are among the smallest supported gold clusters yet reported, and they are inferred to be the catalytically active species. The XANES data suggest that the gold in the activated catalyst had not been reduced to the metallic state.

  19. Selective electrocatalytic oxidation of a re-methyl complex to methanol by a surface-bound Ru(II) polypyridyl catalyst.

    PubMed

    Coggins, Michael K; Méndez, Manuel A; Concepcion, Javier J; Periana, Roy A; Meyer, Thomas J

    2014-11-12

    The complex [Ru(Mebimpy)(4,4'-((HO)2OPCH2)2bpy)(OH2)](2+) surface bound to tin-doped indium oxide mesoporous nanoparticle film electrodes (nanoITO-Ru(II)(OH2)(2+)) is an electrocatalyst for the selective oxidation of methylrhenium trioxide (MTO) to methanol in acidic aqueous solution. Oxidative activation of the catalyst to nanoITO-Ru(IV)(OH)(3+) induces oxidation of MTO. The reaction is first order in MTO with rate saturation observed at [MTO] > 12 mM with a limiting rate constant of k = 25 s(-1). Methanol is formed selectively in 87% Faradaic yield in controlled potential electrolyses at 1.3 V vs NHE. At higher potentials, oxidation of MTO by nanoITO-Ru(V)(O)(3+) leads to multiple electrolysis products. The results of an electrochemical kinetics study point to a mechanism in which surface oxidation to nanoITO-Ru(IV)(OH)(3+) is followed by direct insertion into the rhenium-methyl bond of MTO with a detectable intermediate. PMID:25325162

  20. [CuCl3(H2O)](-) complexes aggregated to form hydrate columns in methyl-substituted pyridinium or piperidinium salts.

    PubMed

    Nalla, Sowjanya; Bond, Marcus R

    2011-06-01

    1,2,3-Trimethylpyridinium aquatrichloridocuprate(II), (C(8)H(12)N)[CuCl(3)(H(2)O)], (I), 3,4-dimethylpyridinium aquatrichloridocuprate(II), (C(7)H(10)N)[CuCl(3)(H(2)O)], (II), and 2,3-dimethylpyridinium aquatrichloridocuprate(II), (C(7)H(10)N)[CuCl(3)(H(2)O)], (III), exhibit the same fundamental structure, with (I) and (II) isomorphous and with the unit-cell constants of (III) similar to the reduced unit-cell constants of (I) and (II). The distorted square-planar [CuCl(3)(H(2)O)](-) complex [mirror symmetric in (I) and (II)] forms two semicoordinate Cu···Cl bonds to a neighboring complex to produce a dimer with 2/m symmetry [only inversion symmetry in (III)]. The semicoordinate Cu...Cl bond length of the dimer shows significant elongation at 295 K compared with that at 100 K, while the coordinate Cu-Cl bond lengths are slightly contracted at 295 K compared with those at 100 K. The inorganic dimers are linked by eight hydrogen bonds to four neighboring dimers to establish a checkerboard network layer in the ab plane, with voids between the dimers that accommodate, on both sides, inversion-related organic cation pairs. The organic cations are required by mirror-plane symmetry to be disordered in (I) and (II). The organic cations and [CuCl(3)(H(2)O)](-) complexes are nearly coplanar and tilted out of the layer plane to establish a hybrid organic-inorganic layer structure parallel to (202) [(11-2) in (III)], with hydrate columns (defined by water molecules) and hydrophobic columns (defined by methyl groups) parallel to each other [and along the 2(1) axes in (I) and (II)]. In 1,1-dimethylpiperidinium aquatrichloridocuprate(II), (C(7)H(16)N)[CuCl(3)(H(2)O)], (IV), the bulkier organic cation prevents semicoordinate bonding between complexes, which are hydrogen bonded side-to-side in zigzag chains that place water molecules in columns along half of the 2(1) axes. PMID:21633151

  1. The Effect of Methylated Vitamin B Complex on Depressive and Anxiety Symptoms and Quality of Life in Adults with Depression

    PubMed Central

    Lewis, John E.; Tiozzo, Eduard; Melillo, Angelica B.; Leonard, Susanna; Chen, Lawrence; Mendez, Armando; Woolger, Judi M.; Konefal, Janet

    2013-01-01

    Depression, the most common type of mental illness, is the second leading cause of disability and is increasing among Americans. The effect of improved nutrition, particularly with dietary supplements, on depression may provide an alternative to standard medical treatment. Some studies have shown that certain nutrients (e.g., inositol and S-adenosyl methionine) are effective at improving depressed mood, although the results are not unequivocal. The current study was a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a vitamin B complex nutritional supplement (Max Stress B) for improving depressive and anxiety symptoms according to the Beck Depression and Anxiety Inventories (BDI and BAI) in 60 adults diagnosed with major depression or other forms of depressive disorders. Secondary outcomes included quality of life according to the SF-36. Participants were assessed at baseline and 30- and 60-day followups. Max Stress B showed significant and more continuous improvements in depressive and anxiety symptoms, compared to placebo. Additionally, Max Stress B showed significant improvement on the mental health scale of the SF-36 compared to placebo. Thus, we showed modest utility of Max Stress B to improve mood symptoms and mental health quality of life in adults with depression. PMID:23738221

  2. 99mTc(LL) 3 + complexes containing ether analogs of DMPE 1 1 Abbreviations: DEPE, 1,2-bis(diethylphosphino)ethane; DIARS, o-phenylenebis (dimethylarsine); DMPE, 1,2-bis(dimethylphosphino)ethane, (CH 3) 2 PCH 2CH 2 P(CH 3) 2; FAB, fast atom bombardment; FURPE, 1,2-bis(methyl methylenetetrahydrofuranphosphino)ethane, -(CH 2P(CH 3)(CH 2C 4H 7O)) 2; MIBPE, 1,2-bis(methyl methoxyisobutylphosphino)ethane,-(CH 2P(CH 3) (CH 2C(CH 3) 2 OCH 3)) 2; MMPE, 1,2-bis(methyl methoxyethylphosphino)ethane,-(CH 2P(CH 3) (CH 2CH 2OCH 3)) 2; POM-POM, 1,2-bis(dimethoxyphosphino)ethane; PYRPE, 1,2-bis(methyl methylenetetrahydropyranphosphino) ethane, -(CH 2P(CH 3)(CH 2C 5H 9O)) 2

    Microsoft Academic Search

    E. C Lisic; M. J Heeg; Edward Deutsch

    1999-01-01

    Novel 99mTc(L-L)3+ complexes have been investigated for potential use in myocardial perfusion imaging. Bidentate chelators have been prepared that are based on substituent analogs of 1,2-bis(dimethylphosphino)ethane, onto which alkyl ether groups have been incorporated. The new ligands are: (1) MMPE, 1,2-bis(methyl methoxyethyl phosphino)ethane, (2) MIBPE, 1,2-bis(methyl methoxyisobutyl phosphino)ethane, (3) FURPE, 1,2-bis(methyl tetrahydrofuran phosphino)ethane, and (4) PYRPE, 1,2-bis(methyl tetrahydropyran phosphino)ethane. These

  3. A STUDY OF FUNDAMENTAL REACTION PATHWAYS FOR TRANSITION METAL ALKYL COMPLEXES. I. THE REACTION OF A NICKEL METHYL COMPLEX WITH ALKYNES. II. THE MECHANISM OF ALDEHYDE FORMATION IN THE REACTION OF A MOLYBDENUM HYDRIDE WITH MOLYBDENUM ALKYLS

    SciTech Connect

    Huggins, John Mitchell

    1980-06-01

    I. This study reports the rapid reaction under mild conditions of internal or terminal alkynes with methyl (acetyl~ acetonato) (triphenylphosphine) nickel (1) in either aromatic or ether solvents. In all cases vinylnickel products 2 are formed by insertion of the alkyne into the nickel=methyl bond. These complexes may be converted into a variety of organic products (e.g. alkenes, esters, vinyl halides) by treatment with appropriate reagents. Unsymmetrical alkynes give selectively the one regioisomer with the sterically largest substituent next to the nickel atom. In order to investigate the stereochemistry of the initial insertion, a x-ray diffraction study of the reaction of 1 with diphenylacetylene was carried out. This showed that the vinylnickel complex formed by overall trans insertion was the product of the reaction. Furthermore, subsequent slow isomerization of this complex, to a mixture of it and the corresponding cis isomer, demonstrated that this trans addition product is the kinetic product of the reaction. In studies with other alkynes, the product of trans addition was not always exclusively (or even predominantly) formed, but the ratio of the stereoisomers formed kinetically was substantially different from the thermodynamic ratio. Isotope labeling, added phosphine, and other experiments have allowed us to conclude that the mechanism of this reaction does involve initial cis addition. However, a coordinatively unsaturated vinylnickel complex is initially formed which can undergo rapid, phosphine-catalyzed cis-trans isomerization in competition with its conversion to the isolable phosphine-substituted kinetic reaction products. II. The reaction of CpMo(CO){sub 3}H (1a) with CpMo(CO){sub 3}R (2, R= CH{sub 3}, C{sub 2}H{sub 5}) at 50{degrees} C in THF gives the aldehyde RCHO and the dimers [CpMo(CO){sub 3}]{sub 2} (3a) and [CpMo(CO){sub 2}]{sub 2} (4a). Labeling one of the reactants with a methylcyclopentadienyl ligand it was possible to show that the mixed dimers MeCpMo(CO){sub 3}-(CO){sub 3}MoCp (3b) and MeCpMo(CO){sub 2}{triple_bond}(CO){sub 2}MoCp (4b) are the predominant kinetic products of the reaction. Additionally labeling the carbonyl ligands of 1a with {sup 13}CO led to the conclusion that all three of the carbonyl ligands in 1a end up in the tetracarbonyl dimers 4a if the reaction is carried out under a continuous purge of argon Trapping studies failed to find any evidence for the intermediacy of either [CpMo(CO){sub 3}]{sup -} or [CpMo(CO){sub 3}]{sup +} in this reaction. A mechanism is proposed that involves the initial migration of the alkyl ligand in 2 to CO forming an unsaturated acyl complex which reacts with 1a to give a binuclear complex containing a three center-two electron Mo-H-Mo bond. This complex then selectively looses a carbonyl from the acyl molybdenum, migrates the hydride to that same metal, and forms a metal-metal bond. This binuclear complex with the hydride and acyl ligands on one metal reductively eliminates aldehyde, and migrates a carbonyl ligand, to give 4a directly. The other product 3a is formed by addition of two molecules of free CO to 4a.

  4. A new class of corrosion inhibitors for waterborne coatings: 4-methyl- ?-oxo-benzene-butanoic acid complexes 1 This paper is reproduced with permission from the European Coatings Journal, October, 1997 1

    Microsoft Academic Search

    A Braig

    1997-01-01

    Amine and transition metal based complexes with 4-methyl-?-oxo-benzene-butanoic acid represent a new class of corrosion inhibitors specifically designed for long-term corrosion protection in waterborne coatings. Today, corrosion protection in waterborne technology is typically achieved using traditional anticorrosive pigments initially developed for use in solventborne coatings. Regulations concerning heavy metals and limitations regarding the compatibility and performance of such materials in

  5. DNA Methylation and Its Basic Function

    PubMed Central

    Moore, Lisa D; Le, Thuc; Fan, Guoping

    2013-01-01

    In the mammalian genome, DNA methylation is an epigenetic mechanism involving the transfer of a methyl group onto the C5 position of the cytosine to form 5-methylcytosine. DNA methylation regulates gene expression by recruiting proteins involved in gene repression or by inhibiting the binding of transcription factor(s) to DNA. During development, the pattern of DNA methylation in the genome changes as a result of a dynamic process involving both de novo DNA methylation and demethylation. As a consequence, differentiated cells develop a stable and unique DNA methylation pattern that regulates tissue-specific gene transcription. In this chapter, we will review the process of DNA methylation and demethylation in the nervous system. We will describe the DNA (de)methylation machinery and its association with other epigenetic mechanisms such as histone modifications and noncoding RNAs. Intriguingly, postmitotic neurons still express DNA methyltransferases and components involved in DNA demethylation. Moreover, neuronal activity can modulate their pattern of DNA methylation in response to physiological and environmental stimuli. The precise regulation of DNA methylation is essential for normal cognitive function. Indeed, when DNA methylation is altered as a result of developmental mutations or environmental risk factors, such as drug exposure and neural injury, mental impairment is a common side effect. The investigation into DNA methylation continues to show a rich and complex picture about epigenetic gene regulation in the central nervous system and provides possible therapeutic targets for the treatment of neuropsychiatric disorders. PMID:22781841

  6. Copper(II), Nickel(II), Oxovanadium(IV) and Dioxouranium(VI) Complexes of Novel Asymmetric Tetradentate Schiff Base Ligands Derived from 6Methyl3Formyl4Hydroxy2-(1H)-Quinolone. Part V

    Microsoft Academic Search

    Saied M. E. Khalil; Mahmoud M. Mashaly; Adel A. A. Emara

    1995-01-01

    The novel, half-unit ligand obtained by the single condensation of 6-methyl-3-formyl-4-hydroxy-2-(1H)-quinolone and p-phenylenediamine, was condensed with either acetylacetone or salicylaldehyde to yield novel, asymmetric tetradentate Schiff base ligands, H2La and H2Lb, respectively. The reactions of the ligands with Cu, Ni, VO and UO2 salts yielded complexes of the general formula [L2M2 nH2O, except that of the uranyl complex of the

  7. Magnetic property and thermal analysis of a Mn(II) complex with [Mn(CO2)]n chains based on 4,4?-bis(1H-imidazol-1-yl-methyl)biphenyl

    NASA Astrophysics Data System (ADS)

    Zhang, Ming-Dao; Zheng, Bao-Hui; Wang, Zhe; Jiao, Yan; Chen, Min-Dong

    2014-11-01

    Magnetic coordination polymers have attracted considerable interest due to their novel structures and potential applications. In this paper, one new 2D magnetic manganese coordination polymer {[Mn(bimb)(OBA)]}n (1) was synthesized under solvothermal conditions based on 4,4?-bis(1H-imidazol-1-yl-methyl)biphenyl (bimb) and 4,4?-oxybis(benzoate) (H2OBA). Complex 1 contains [Mn(CO2)]n 1D chains and magnetic susceptibility measurements indicate that compound 1 exhibits an antiferromagnetic coupling interaction. In addition, complex 1 exhibits solid-state photoluminescence and high thermal stability.

  8. Methyl eucomate

    PubMed Central

    Li, Linglin; Zhou, Guang-Xiong; Jiang, Ren-Wang

    2008-01-01

    The crystal structure of the title compound [systematic name: methyl 3-carboxy-3-hydr­oxy-3-(4-hydroxy­benz­yl)propanoate], C12H14O6, is stabilized by inter­molecular O—H?O and C—H?O hydrogen bonds. The mol­ecules are arranged in layers, parallel to (001), which are inter­connected by the O—H?O hydrogen bonds. PMID:21202973

  9. Synthesis, characterization and catalytic properties of diorganotin derivatives. Crystal and molecular structure of the first complex of 2-(2-methyl-3-nitroanilino)benzoic acid of 1,2:3,4-di-?2-2-(2-methyl-3-nitroanilino)benzoato- O, O-1,3-bis-2-(2-methyl-3-nitroanilino)benzoato- O-1,2,4:2,3,4-di-?3-oxo-tetrakis[di-methyltin(IV)

    Microsoft Academic Search

    Vaso N. Dokorou; Dimitra Kovala-Demertzi; Maria Louloudi; Anca Silvestru; Mavroudis A. Demertzis

    2008-01-01

    The complexes [Me2(MNAB)SnOSn(MNAB)Me2]2 (2) and [Me2Sn(MNAB)2] (3), where HMNAB is 2-(2-methyl-3-nitroanilino)benzoic acid, (1), have been prepared and structurally characterized by means of vibrational, 1H and 13C NMR spectroscopies. The crystal structure of [Me2(MNAB)SnOSn(MNAB)Me2]2 has been determined by X-ray crystallography. Three distannoxane rings are present to the dimeric tetraorganodistannoxane of planar ladder arrangement. The structure is centro-symmetric and features a central

  10. Synthesis and spectral characterization of mono- and binuclear copper(II) complexes derived from 2-benzoylpyridine-N?-methyl-3-thiosemicarbazone: crystal structure of a novel sulfur bridged copper(II) box-dimer.

    PubMed

    Jayakumar, K; Sithambaresan, M; Aiswarya, N; Kurup, M R Prathapachandra

    2015-03-15

    Mononuclear and binuclear copper(II) complexes of 2-benzoylpyridine-N(4)-methyl thiosemicarbazone (HL) were prepared and characterized by a variety of spectroscopic techniques. Structural evidence for the novel sulfur bridged copper(II) iodo binuclear complex is obtained by single crystal X-ray diffraction analysis. The complex [Cu2L2I2], a non-centrosymmetric box dimer, crystallizes in monoclinic C2/c space group and it was found to have distorted square pyramidal geometry (Addison parameter, ?=0.238) with the square basal plane occupied by the thiosemicarbazone moiety and iodine atom whereas the sulfur atom from the other coordinated thiosemicarbazone moiety occupies the apical position. This is the first crystallographically studied system having non-centrosymmetrical entities bridged via thiolate S atoms with Cu(II)I bond. The tridentate thiosemicarbazone coordinates in mono deprotonated thionic tautomeric form in all complexes except in sulfato complex, [Cu(HL)(SO4)]·H2O (1) where it binds to the metal centre in neutral form. The magnetic moment values and the EPR spectral studies reflect the binuclearity of some of the complexes. The spin Hamiltonian and bonding parameters are calculated based on EPR studies. In all the complexes g||>g?>2.0023 and the g values in frozen DMF are consistent with the d(x2-y2) ground state. The thermal stabilities of some of the complexes were also determined. PMID:25546494

  11. Biological activity of palladium(II) and platinum(II) complexes of the acetone Schiff bases of S-methyl- and S-benzyldithiocarbazate and the X-ray crystal structure of the [Pd(asme) 2] (asme=anionic form of the acetone Schiff base of S-methyldithiocarbazate) complex

    Microsoft Academic Search

    Mohammad Akbar Ali; Aminul Huq Mirza; Raymond J Butcher; M. T. H Tarafder; Tan Boon Keat; A. Manaf Ali

    2002-01-01

    Palladium(II) and platinum(II) complexes of general empirical formula, [M(NS)2] (NS=uninegatively charged acetone Schiff bases of S-methyl- and S-benzyldithiocarbazate; M=PtII and PdII) have been prepared and characterized by a variety of physicochemical techniques. Based on conductance, IR and electronic spectral evidence, a square-planar structure is assigned to these complexes. The crystal and molecular structure of the [Pd(asme)2] complex (asme=anionic form of

  12. Spectral characterization, molecular modeling and antimicrobial studies on hydrazone metal complexes of 5-acetyl-4-hydroxy-2H-1,3-thiazine-2,6(3H)dione and S-methyl dithiocarbazate.

    PubMed

    Taha, Ali; Emara, Adel A A; Mashaly, Mahmoud M; Adly, Omima M I

    2014-09-15

    Metal complexes of copper(II), nickel(II), cobalt(II), oxovanadium(IV), chromium(III) and cadmium(II) with a new bridged ONS dibasic tridentate hydrazone (H2L) derived from 5-acetyl-4-hydroxy-2H-1,3-thiazine-2,6(3H)-dione with S-methyl dithiocarbazate have been synthesized and characterized by elemental analysis, molar conductance, magnetic susceptibility measurements, spectral (infrared, electronic, mass, 1H NMR and ESR) studies as well as thermal gravimetric analysis (TGA). The synthesized complexes have dimeric structures with the general formula [ML(NO3)m(H2O)x]2·nH2O·zMeOH, L=dianion of the hydrazone, m=0-1, x=0-2, n=0-4 and z=0-1. The metal complexes exhibited square planar, tetrahedral and octahedral geometrical arrangements, the molar conductivity data indicates that all complexes are neutral. The Coats-Redfern equation was used to calculate the kinetic and thermodynamic parameters for the different thermal decomposition stages of some complexes. Structural parameters of the ligand and its metal complexes have been theoretically computed on the basis of semiempirical PM3 level and the results were correlated with their experimental data. Antibacterial activities of the free ligand and its metal complexes were screened against various organisms. PMID:24810030

  13. Spectral characterization, molecular modeling and antimicrobial studies on hydrazone metal complexes of 5-acetyl-4-hydroxy-2H-1,3-thiazine-2,6(3H)dione and S-methyl dithiocarbazate

    NASA Astrophysics Data System (ADS)

    Taha, Ali; Emara, Adel A. A.; Mashaly, Mahmoud M.; Adly, Omima M. I.

    2014-09-01

    Metal complexes of copper(II), nickel(II), cobalt(II), oxovanadium(IV), chromium(III) and cadmium(II) with a new bridged ONS dibasic tridentate hydrazone (H2L) derived from 5-acetyl-4-hydroxy-2H-1,3-thiazine-2,6(3H)-dione with S-methyl dithiocarbazate have been synthesized and characterized by elemental analysis, molar conductance, magnetic susceptibility measurements, spectral (infrared, electronic, mass, 1H NMR and ESR) studies as well as thermal gravimetric analysis (TGA). The synthesized complexes have dimeric structures with the general formula [ML(NO3)m(H2O)x]2·nH2O·zMeOH, L = dianion of the hydrazone, m = 0-1, x = 0-2, n = 0-4 and z = 0-1. The metal complexes exhibited square planar, tetrahedral and octahedral geometrical arrangements, the molar conductivity data indicates that all complexes are neutral. The Coats-Redfern equation was used to calculate the kinetic and thermodynamic parameters for the different thermal decomposition stages of some complexes. Structural parameters of the ligand and its metal complexes have been theoretically computed on the basis of semiempirical PM3 level and the results were correlated with their experimental data. Antibacterial activities of the free ligand and its metal complexes were screened against various organisms.

  14. Stereospecific ligands and their complexes. Part XVII. Synthesis and characterization of ethylenediamine-N,N?-di-S,S-2-(3-methyl)butanoic acid and its platinum(IV) complex with bromido ligands. Crystal structure of s-cis-[PtBr2(S,S-eddv)]·H2O

    NASA Astrophysics Data System (ADS)

    Stojkovi?, Danijela Lj.; Jevti?, Verica V.; Radi?, Gordana P.; Poto??ák, Ivan; Trifunovi?, Sre?ko R.

    2014-05-01

    The synthesis of novel platinum(IV) complex of formula [PtBr2(S,S-eddv)]·H2O (S,S-eddv = ethylenediamine-N,N?-di-S,S-2-(3-methyl)butanoate ion) is reported. The complex has been obtained by direct reaction of potassium-hexabromidoplatinate(IV) with neutralized ethylenediamine-N,N?-di-S,S-2-(3-methyl)butanoic acid (H2-S,S-eddv). The ligand and complex were characterized by elemental analysis, infrared, 1H and 13C NMR spectroscopy. The spectroscopically predicted geometrical configuration of the obtained complex was confirmed by X-ray analyses of the crystal structure of the s-cis-[PtBr2(S,S-eddv)]·H2O. The asymmetric unit of the complex contains three crystallographically independent s-cis-[PtBr2(S,S-eddv)] and water molecules. The Pt(IV) atom in each complex molecule exhibits a distorted octahedral coordination geometry, built up by two cis-coordinated bromido ligands and one cis-N,N? and trans-O,O? coordinated S,S-eddv ligand (configuration index: OC-6-33). In the crystal structure, intermolecular N-H⋯O hydrogen bonds are found between the complex and water molecules.

  15. Automethylation Activities within the Mixed Lineage Leukemia-1 (MLL1) Core Complex Reveal Evidence Supporting a “Two-active Site” Model for Multiple Histone H3 Lysine 4 Methylation*

    PubMed Central

    Patel, Anamika; Vought, Valarie E.; Swatkoski, Stephen; Viggiano, Susan; Howard, Benny; Dharmarajan, Venkatasubramanian; Monteith, Kelsey E.; Kupakuwana, Gillian; Namitz, Kevin E.; Shinsky, Stephen A.; Cotter, Robert J.; Cosgrove, Michael S.

    2014-01-01

    The mixed lineage leukemia-1 (MLL1) core complex predominantly catalyzes mono- and dimethylation of histone H3 at lysine 4 (H3K4) and is frequently altered in aggressive acute leukemias. The molecular mechanisms that account for conversion of mono- to dimethyl H3K4 (H3K4me1,2) are not well understood. In this investigation, we report that the suppressor of variegation, enhancer of zeste, trithorax (SET) domains from human MLL1 and Drosophila Trithorax undergo robust intramolecular automethylation reactions at an evolutionarily conserved cysteine residue in the active site, which is inhibited by unmodified histone H3. The location of the automethylation in the SET-I subdomain indicates that the MLL1 SET domain possesses significantly more conformational plasticity in solution than suggested by its crystal structure. We also report that MLL1 methylates Ash2L in the absence of histone H3, but only when assembled within a complex with WDR5 and RbBP5, suggesting a restraint for the architectural arrangement of subunits within the complex. Using MLL1 and Ash2L automethylation reactions as probes for histone binding, we observed that both automethylation reactions are significantly inhibited by stoichiometric amounts of unmethylated histone H3, but not by histones previously mono-, di-, or trimethylated at H3K4. These results suggest that the H3K4me1 intermediate does not significantly bind to the MLL1 SET domain during the dimethylation reaction. Consistent with this hypothesis, we demonstrate that the MLL1 core complex assembled with a catalytically inactive SET domain variant preferentially catalyzes H3K4 dimethylation using the H3K4me1 substrate. Taken together, these results are consistent with a “two-active site” model for multiple H3K4 methylation by the MLL1 core complex. PMID:24235145

  16. Crystal Structure of Silkworm Bombyx mori JHBP in Complex With 2-Methyl-2,4-Pentanediol: Plasticity of JH-Binding Pocket and Ligand-Induced Conformational Change of the Second Cavity in JHBP

    PubMed Central

    Fujimoto, Zui; Suzuki, Rintaro; Shiotsuki, Takahiro; Tsuchiya, Wataru; Tase, Akira; Momma, Mitsuru; Yamazaki, Toshimasa

    2013-01-01

    Juvenile hormones (JHs) control a diversity of crucial life events in insects. In Lepidoptera which major agricultural pests belong to, JH signaling is critically controlled by a species-specific high-affinity, low molecular weight JH-binding protein (JHBP) in hemolymph, which transports JH from the site of its synthesis to target tissues. Hence, JHBP is expected to be an excellent target for the development of novel specific insect growth regulators (IGRs) and insecticides. A better understanding of the structural biology of JHBP should pave the way for the structure-based drug design of such compounds. Here, we report the crystal structure of the silkworm Bombyx mori JHBP in complex with two molecules of 2-methyl-2,4-pentanediol (MPD), one molecule (MPD1) bound in the JH-binding pocket while the other (MPD2) in a second cavity. Detailed comparison with the apo-JHBP and JHBP-JH II complex structures previously reported by us led to a number of intriguing findings. First, the JH-binding pocket changes its size in a ligand-dependent manner due to flexibility of the gate ?1 helix. Second, MPD1 mimics interactions of the epoxide moiety of JH previously observed in the JHBP-JH complex, and MPD can compete with JH in binding to the JH-binding pocket. We also confirmed that methoprene, which has an MPD-like structure, inhibits the complex formation between JHBP and JH while the unepoxydated JH III (methyl farnesoate) does not. These findings may open the door to the development of novel IGRs targeted against JHBP. Third, binding of MPD to the second cavity of JHBP induces significant conformational changes accompanied with a cavity expansion. This finding, together with MPD2-JHBP interaction mechanism identified in the JHBP-MPD complex, should provide important guidance in the search for the natural ligand of the second cavity. PMID:23437107

  17. Synthesis, Characterization and Thermal Studies of Zn(II), Cd(II) and Hg(II) Complexes of N-Methyl-N-Phenyldithiocarbamate: The Single Crystal Structure of [(C6H5)(CH3)NCS2]4Hg2

    PubMed Central

    Onwudiwe, Damian C.; Ajibade, Peter A.

    2011-01-01

    Zn(II), Cd(II) and Hg(II) complexes of N-methyl-N-phenyl dithiocarbamate have been synthesized and characterized by elemental analysis and spectral studies (IR, 1H and 13C-NMR). The single crystal X-ray structure of the mercury complex revealed that the complex contains a Hg centre with a distorted tetrahedral coordination sphere in which the dinuclear Hg complex resides on a crystallographic inversion centre and each Hg atom is coordinated to four S atoms from the dithiocarbamate moiety. One dithiocarbamate ligand acts as chelating ligand while the other acts as chelating bridging ligand between two Hg atoms, resulting in a dinuclear eight-member ring. The course of the thermal degradation of the complexes has been investigated using thermogravimetric and differential thermal analyses techniques. Thermogravimetric analysis of the complexes show a single weight loss to give MS (M = Zn, Cd, Hg) indicating that they might be useful as single source precursors for the synthesis of MS nanoparticles and thin films. PMID:21673933

  18. Mono and BiNuclear Metal Complexes of Schiff-Base Hydrazone (ONN) Derived from o-Hydroxyacetophenone and 2Amino4Hydrazino6Methyl Pyrimidine

    Microsoft Academic Search

    Saied M. E. Khalil; H. S. Seleem; B. A. El-Shetary; M. Shebl

    2002-01-01

    A tridentate ONN donor Schiff-base hydrazone ligand, H2L, was synthesized by the condensation of 2-amino-4-hydrazino-6-methyl pyrimidine with o-hydroxyacetophenone. The structure of the ligand was elucidated by IR and H NMR spectra which indicated the presence of three different coordinating groups, the oxygen atom of the phenolic OH group, the nitrogen atom of the azomethine, C=N, group and one of the

  19. Sorption behavior of bensulfuron-methyl on andisols and ultisols volcanic ash-derived soils: contribution of humic fractions and mineral-organic complexes.

    PubMed

    Espinoza, Jeannette; Fuentes, Edwar; Báez, María E

    2009-12-01

    Bensulfuron-methyl sorption was studied in Andisol and Ultisol soils in view of their characteristic physical and chemical properties, presenting acidic pH and variable charge. Humic and fulvic acids (HA and FA) and humin (HUM) contributions were established. Sorption was studied by using two synthetic sorbents, an aluminum-silicate with iron oxide coverage and the same sorbent coated with humic acid. Freundlich model described Bensulfuron-methyl behavior in all sorbents (R(2) 0.969-0.998). K(f) for soils (8.3-20.7 microg(1-1/n) mL(1/n) g(-1)) were higher than those reported in the literature. Organic matter, halloysite or kaolinite, and specific surface area contributed to the global process. The highest K(f) for HA, FA and HUM were 539.5, 82.9, and 98.7 microg(1-1/n) mL(1/n) g(-1). Model sorbents described the participation of variable charge materials with high adsorption capacity. The constant capacitance model was used to assess effects of Bensulfuron-methyl adsorption on the distribution of SOH, SOH(2)(+) and SO(-) sites of sorbents. PMID:19608318

  20. The crystal structure of 4-methyl-2,6-dibenzoylphenol and its conversion into a mononuclear cobalt(III) complex by treatment with cobalt(II) chloride and propane-1,3-diamine

    Microsoft Academic Search

    Sushil K Gupta; Peter B Hitchcock; Yogendra S Kushwah

    2002-01-01

    The mononuclear cobalt(III) complex [Co(L)2]Cl (1) (where HL is H2N(CH2)3NC(Ph)C6H2(Me)(OH)COPh) has been synthesized by condensation of 4-methyl-2,6-dibenzoylphenol (mdbp) I and propane-1,3-diamine in the presence of CoCl2·6H2O. Compound 1 has been characterized by mass, IR, electronic, 1H and 13C NMR spectroscopy, conductivity measurements, elemental analysis, TGA, cyclic voltammetry and an X-ray structure determination of the solid complex 1·2EtOH·H2NCH2CH2CH2NH2. The cobalt(III) coordination

  1. Analytical Methodologies for Detection of Gamma-Valerolactone, Delta-Valerolactone, Acephate and Azinphos Methyl and Their Associated Metabolites in Complex Biological Matrices

    SciTech Connect

    Zink, E.; Clark, R.; Grant, K.; Campbell, J.; Hoppe, E.

    2005-01-01

    Non-invasive biomonitoring for chemicals of interest in law enforcement and similar monitoring of pesticides, together with their metabolites, can not only save money but can lead to faster medical attention for individuals exposed to these chemicals. This study describes methods developed for the analysis of gamma-valerolactone (GVL), delta-valerolactone (DVL), acephate, and azinphos methyl in saliva and serum. Liquid chromatography/mass spectrometry (LC/MS) operated in the negative and positive ion mode and gas chromatography/mass spectrometry (GC/MS) were used to analyze GVL and DVL. Although both analytical techniques worked well, lower detection limits were obtained with GC/MS. The lactones and their corresponding sodium salts were spiked into both saliva and serum. The lactones were isolated from saliva or serum using newly developed extraction techniques and then subsequently analyzed using GC/MS. The sodium salts of the lactones are nonvolatile and require derivatization prior to analysis by this method. N-methyl-N-(t-butyldimethylsilyl)-trifluoroacetamide (MTBSTFA) was ultimately selected as the reagent for derivatization because the acidic conditions required for reactions with diazomethane caused the salts to undergo intramolecular cyclization to the corresponding lactones. In vitro studies were conducted using rat liver microsomes to determine other metabolites associated with these compounds. Azinphos methyl and acephate are classified as organophosphate pesticides, and are known to be cholinesterase inhibitors in humans and insects, causing neurotoxicity. For this reason they have both exposure and environmental impact implications. These compounds were spiked into serum and saliva and prepared for analysis by GC/MS. Continuation of this research would include analysis by GC/MS under positive ion mode to determine the parent ions of the unknown metabolites. Further research is planned through an in vivo analysis of the lactones and pesticides. These methodologies could be extended for further analysis of other similar compounds.

  2. Control of the DNA Methylation System Component MBD2 by Protein Arginine Methylation

    PubMed Central

    Tan, Choon Ping; Nakielny, Sara

    2006-01-01

    DNA methylation is vital for proper chromatin structure and function in mammalian cells. Genetic removal of the enzymes that catalyze DNA methylation results in defective imprinting, transposon silencing, X chromosome dosage compensation, and genome stability. This epigenetic modification is interpreted by methyl-DNA binding domain (MBD) proteins. MBD proteins respond to methylated DNA by recruiting histone deacetylases (HDAC) and other transcription repression factors to the chromatin. The MBD2 protein is dispensable for animal viability, but it is implicated in the genesis of colon tumors. Here we report that the MBD2 protein is controlled by arginine methylation. We identify the protein arginine methyltransferase enzymes that catalyze this modification and show that arginine methylation inhibits the function of MBD2. Arginine methylation of MBD2 reduces MBD2-methyl-DNA complex formation, reduces MBD2-HDAC repression complex formation, and impairs the transcription repression function of MBD2 in cells. Our report provides a molecular description of a potential regulatory mechanism for an MBD protein family member. It is the first to demonstrate that protein arginine methyltransferases participate in the DNA methylation system of chromatin control. PMID:16980624

  3. Coordination chemistry and bioactivity of Ni 2+, Cu 2+, Cd 2+ and Zn 2+ complexes containing bidentate Schiff bases derived from S-benzyldithiocarbazate and the X-ray crystal structure of bis[ S-benzyl-?- N-(5-methyl-2-furylmethylene)dithiocarbazato]cadmium(II)

    Microsoft Academic Search

    M. T. H Tarafder; Khoo Teng Jin; Karen A Crouse; A. M Ali; B. M Yamin; H.-K Fun

    2002-01-01

    New bidentate isomeric NS and NS? Schiff bases were derived from the condensation of S-benzyldithiocarbazate (SBDTC) with 5-methyl-2-furyldehyde and 2-furyl-methylketone. Reaction of NS ligand with Ni(II), Cu(II), Cd(II) and Zn(II) salts gave solid complexes. Only the Ni(II) complex of the NS? ligand was isolated. All complexes were characterized by a variety of physico-chemical techniques, viz. elemental analyses, molar conductivity, i.r.

  4. Effect of persistence length on binding of DNA to polyions and overcharging of their intermolecular complexes in aqueous and in 1-methyl-3-octyl imidazolium chloride ionic liquid solutions.

    PubMed

    Rawat, Kamla; Pathak, Jyotsana; Bohidar, H B

    2013-08-01

    The effect of persistence length on the intermolecular binding of DNA (200 bp, persistence length l(p) = 50 nm, polyanion) with three proteins, gelatin B (GB) (l(p) = 2 nm, polyampholyte chain), bovine serum albumin (BSA) (l(p) = 7 nm, polyampholyte colloid), gelatin A (GA) (l(p) = 10 nm, polyampholyte chain), and a polysaccharide chitosan (l(p) = 17 nm, polycation), was investigated in aqueous and in 1-methyl-3-octyl imidazolium chloride ionic liquid ([C8mim][Cl]) solutions. In DNA-GB and DNA-BSA solutions complexation primarily arises from surface patch binding whereas DNA-chitosan and DNA-GA binding was predominantly governed by electrostatic forces. These occurred at well defined pH values: (i) at pHc associative interactions ensued and soluble complexes were formed, (ii) at pH? soluble complexes coalesced to give rise to liquid-liquid phase separation (coacervation) and (iii) at pH(prep) formation of large insoluble complexes drove the solution towards liquid-solid phase separation. A universal phase diagram encapsulating the aforesaid interactions can be made using the persistence length of polyion as an independent variable. DNA formed overcharged intermolecular complexes with all these polyions when the polyion concentration was more than the concentration required to produce charge neutralized complexes (disproportionate binding). In IL solutions maximum binding occurred when 0.075 < [IL] < 0.10% (w/v) and the effect of overcharging was substantially screened. The extent of overcharge was a monotonous increasing function of the polyion persistence length. Results clearly revealed that DNA-polyion binding was hierarchical in polyion concentration and persistence length. Overcharging of the DNA-polyion complex was found to be ubiquitous for the polyions used in the present study. PMID:23775068

  5. Structural rearrangement in the formation of jet-cooled complexes of chiral (S)-1,2,3,4-tetrahydro-3-isoquinolinemethanol with methyl lactate: chirality effect in conformer selection.

    PubMed

    Mahjoub, Ahmed; Le Barbu-Debus, Katia; Zehnacker, Anne

    2013-04-11

    The jet-cooled complexes between the two enantiomers of methyl lactate (ML) and (S)-1,2,3,4-tetrahydro-3-isoquinolinemethanol (THIQM) are studied by double resonance spectroscopy combined with ab initio calculations. Both diastereomer complexes exist in different isomers, involving either direct addition of THIQM on ML with no structural rearrangement of the subunits or formation of very stable structures involving multiple intermolecular hydrogen bonds and extensive deformation of the subunits. Competition between these two processes and its dependence upon chirality are discussed. It is shown that the most stable form of the chromophore (THIQMI with an OH···N hydrogen bond) prefers to directly stick to ML to form the addition complex whereas the second conformer (THIQMII with NH···O hydrogen bond) rearranges to form a strongly bound structure. The two structures are formed for the homochiral as well the heterochiral complex, however with different relative abundance. This shows an enantioselective binding preference of ML for one of the conformers of the chromophore. PMID:23496094

  6. The origins of atmospheric methyl mercury

    SciTech Connect

    Prestbo, E.M.; Bloom, N.S. [Frontier Geosciences, Inc., Seattle, WA (United States)

    1995-12-31

    Methyl Hg in precipitation shows strong regional patterns, with highest volume weighted mean values (0.4 ng/L) in the Pacific Northwest and lowest values in Florida (<0.01 ng/l). Over most of the North Central region, average values range from 0.05 to 0.2 ng/L. Several potential sources of methyl Hg to the atmosphere have been investigated, including direct anthropogenic emissions, atmospheric methylation of Hg{sup o} or Hg(II), and emissions of methyl or dimethyl Hg from natural surfaces (oceans, bogs, or forests). Direct measurements of major total Hg sources such as coal and waste combustors, and sewage treatment facilities suggest that direct anthropogenic emissions are an insignificant source of methyl Hg to the atmosphere. The gas phase reaction of methyl halides with Hg{sup o} also appears to be an insignificant source of methyl Hg to the atmosphere. Recent laboratory experiments have provided a likely mechanism for atmospheric Hg methylation via a complex reaction involving acetate, sulfite, and iron. From a series of field measurements, another source appears to be the degradation of dimethyl mercury emitted by the upwelling of deep ocean water.

  7. Synthesis and characterization of the inclusion compound of a ferrocenyldiimine dioxomolybdenum complex with heptakis-2,3,6-tri- O-methyl-?-cyclodextrin

    Microsoft Academic Search

    Željko Petrovski; Susana S. Braga; Ana M. Santos; Sandra S. Rodrigues; Isabel S. Gonçalves; Martyn Pillinger; Fritz E. Kühn; Carlos C. Romão

    2005-01-01

    A dioxomolybdenum(VI) complex bearing the diimine ligand N,N?-bis(ferrocenylmethylene)ethylenediamine (FcNN) has been prepared in good yield by the reaction of FcNN with MoO2Cl2(THF)2. One isomeric form was identified by 1H NMR (including NOE experiments), corresponding to the cis,cis geometry with respect to the CN bonds of the free ligand. The polynuclear complex was immobilized in permethylated ?-cyclodextrin (TRIMEB) by addition of

  8. Strategy to enhance efficacy of doxorubicin in solid tumor cells by methyl-?-cyclodextrin: Involvement of p53 and Fas receptor ligand complex

    PubMed Central

    Mohammad, Naoshad; Vikram Singh, Shivendra; Malvi, Parmanand; Chaube, Balkrishna; Athavale, Dipti; Vanuopadath, Muralidharan; Nair, Sudarslal Sadasivan; Nair, Bipin; Bhat, Manoj Kumar

    2015-01-01

    Doxorubicin (DOX) is one of the preferred drugs for treating breast and liver cancers. However, its clinical application is limited due to severe side effects and the accompanying drug resistance. In this context, we investigated the effect on therapeutic efficacy of DOX by cholesterol depleting agent methyl-?-cyclodextrin (MCD), and explored the involvement of p53. MCD sensitizes MCF-7 and Hepa1–6 cells to DOX, Combination of MCD and marginal dose of DOX reduces the cell viability, and promoted apoptosis through induction of pro-apoptotic protein, Bax, activation of caspase-8 and caspase-7, down regulation of anti-apoptotic protein Bcl-2 and finally promoting PARP cleavage. Mechanistically, sensitization to DOX by MCD was due to the induction of FasR/FasL pathway through p53 activation. Furthermore, inhibition of p53 by pharmacological inhibitor pifithrin-? (PFT-?) or its specific siRNA attenuated p53 function and down-regulated FasR/FasL, thereby preventing cell death. Animal experiments were performed using C57BL/6J mouse isografted with Hepa1–6 cells. Tumor growth was retarded and survival increased in mice administered MCD together with DOX to as compared to either agent alone. Collectively, these results suggest that MCD enhances the sensitivity to DOX for which wild type p53 is an important determinant. PMID:26149967

  9. Structural Basis for Methyl Transfer by a Radical SAM Enzyme

    SciTech Connect

    Boal, Amie K.; Grove, Tyler L.; McLaughlin, Monica I.; Yennawar, Neela H.; Booker, Squire J.; Rosenzweig, Amy C. (NWU); (Penn)

    2014-10-02

    The radical S-adenosyl-l-methionine (SAM) enzymes RlmN and Cfr methylate 23S ribosomal RNA, modifying the C2 or C8 position of adenosine 2503. The methyl groups are installed by a two-step sequence involving initial methylation of a conserved Cys residue (RlmN Cys{sup 355}) by SAM. Methyl transfer to the substrate requires reductive cleavage of a second equivalent of SAM. Crystal structures of RlmN and RlmN with SAM show that a single molecule of SAM coordinates the [4Fe-4S] cluster. Residue Cys{sup 355} is S-methylated and located proximal to the SAM methyl group, suggesting the SAM that is involved in the initial methyl transfer binds at the same site. Thus, RlmN accomplishes its complex reaction with structural economy, harnessing the two most important reactivities of SAM within a single site.

  10. Mechanistic study of the oxidation of a methyl platinum(II) complex with O(2) in water: Pt(II)Me-to-Pt(IV)Me and Pt(II)Me-to-Pt(IV)Me(2) reactivity.

    PubMed

    Sberegaeva, Anna V; Liu, Wei-Guang; Nielsen, Robert J; Goddard, William A; Vedernikov, Andrei N

    2014-03-26

    The mechanism of oxidation by O2 of (dpms)Pt(II)Me(OH2) (1) and (dpms)Pt(II)Me(OH)(-) (2) [dpms = di(2-pyridyl)methanesulfonate] in water in the pH range of 4-14 at 21 °C was explored using kinetic and isotopic labeling experiments. At pH ? 8, the reaction leads to a C1-symmetric monomethyl Pt(IV) complex (dpms)Pt(IV)Me(OH)2 (5) with high selectivity ?97%; the reaction rate is first-order in [Pt(II)Me] and fastest at pH 8.0. This behavior was accounted for by assuming that (i) the O2 activation at the Pt(II) center to form a Pt(IV) hydroperoxo species 4 is the reaction rate-limiting step and (ii) the anionic complex 2 is more reactive toward O2 than neutral complex 1 (pKa = 8.15 ± 0.02). At pH ? 10, the oxidation is inhibited by OH(-) ions; the reaction order in [Pt(II)Me] changes to 2, consistent with a change of the rate-limiting step, which now involves oxidation of complex 2 by Pt(IV) hydroperoxide 4. At pH ? 12, formation of a C1-symmetric dimethyl complex 6, (dpms)Pt(IV)Me2(OH), along with [(dpms)Pt(II)(OH)2](-) (7) becomes the dominant reaction pathway (50-70% selectivity). This change in the product distribution is explained by the formation of a Cs-symmetric intermediate (dpms)Pt(IV)Me(OH)2 (8), a good methylating agent. The secondary deuterium kinetic isotope effect in the reaction leading to complex 6 is negligible; kH/kD = 0.98 ± 0.02. This observation and experiments with a radical scavenger TEMPO do not support a homolytic mechanism. A SN2 mechanism was proposed for the formation of complex 6 that involves complex 2 as a nucleophile and intermediate 8 as an electrophile. PMID:24597998

  11. Synthesis, characterization and biological activities of 2-((E)-(benzo[d][1,3]dioxol-6-ylimino)methyl)-6-ethoxyphenol and its metal complexes

    NASA Astrophysics Data System (ADS)

    Sundararajan, M. L.; Anandakumaran, J.; Jeyakumar, T.

    Metal complexes of Zn(II), Cd(II), Ni(II), Cu(II), and Fe(III) have been synthesized from the Schiff base ligand derived by the condensation of 3,4-(methylenedioxy)aniline and 3-ethoxy salicylaldehyde. The compounds have been characterized by using elemental analysis, molar conductance, IR, UV-Visible, 1H NMR, 13C NMR, mass spectra and thermal analysis (TG/DTA). The elemental analysis suggests the stoichiometry to be 1:1 (metal:ligand). The IR, 1H NMR, 13C NMR and UV-Visible spectral data suggest that the ligand coordinate to the metal atom by imino nitrogen and phenolic oxygen as bidentate manner. The mass spectral data also strengthen the formation of the metal complexes. The thermal behaviors of the complexes prove the presence of lattice as well as coordinated water molecules in the complexes. The in vitro biological screening effects of the synthesized compounds are tested against five bacterial species and three fungal species by well diffusion method. Antioxidant activities have also been performed for all the compounds. Metal complexes show more pronounced biological activity than the free ligand.

  12. Synthesis, characterization and biological activities of 2-((E)-(benzo[d][1,3]dioxol-6-ylimino)methyl)-6-ethoxyphenol and its metal complexes.

    PubMed

    Sundararajan, M L; Anandakumaran, J; Jeyakumar, T

    2014-05-01

    Metal complexes of Zn(II), Cd(II), Ni(II), Cu(II), and Fe(III) have been synthesized from the Schiff base ligand derived by the condensation of 3,4-(methylenedioxy)aniline and 3-ethoxy salicylaldehyde. The compounds have been characterized by using elemental analysis, molar conductance, IR, UV-Visible, (1)H NMR, (13)C NMR, mass spectra and thermal analysis (TG/DTA). The elemental analysis suggests the stoichiometry to be 1:1 (metal:ligand). The IR, (1)H NMR, (13)C NMR and UV-Visible spectral data suggest that the ligand coordinate to the metal atom by imino nitrogen and phenolic oxygen as bidentate manner. The mass spectral data also strengthen the formation of the metal complexes. The thermal behaviors of the complexes prove the presence of lattice as well as coordinated water molecules in the complexes. The in vitro biological screening effects of the synthesized compounds are tested against five bacterial species and three fungal species by well diffusion method. Antioxidant activities have also been performed for all the compounds. Metal complexes show more pronounced biological activity than the free ligand. PMID:24531110

  13. A complex study of 5-amino-3-methyl-4-[2-(5-amino-1,3,4-oxadiazolo)]-isoxazole monohydrate: A new low-molecular-weight immune response modifier

    NASA Astrophysics Data System (ADS)

    Ryng, Stanis?aw; Zimecki, Micha?; Jezierska-Mazzarello, Aneta; Panek, Jaros?aw J.; M?czy?ski, Marcin; G?owiak, Tadeusz; Sawka-Dobrowolska, Wanda; Koll, Aleksander

    2011-07-01

    A new potential lead structure with immunological activity, 5-amino-3-methyl-4-[2-(5-amino-1,3,4-oxadiazolo)]-isoxazole monohydrate, was synthesized. A detailed description of synthesis is presented together with X-ray structural analysis. In vitro assays showed that the compound had a potent immunosuppressive activity. Next, Density Functional Theory (DFT) was employed to shed a light on molecular properties of the investigated isoxazole derivative. The molecular modeling part included geometric as well as electronic structure descriptions: (i) the conformational analysis was performed to localize the most appropriate conformation; (ii) the coordination energy and Basis Set Superposition Error (BSSE) were estimated for the complex of the isoxazole derivative interacting with water molecule; (iii) the potential energy distribution was used to assign molecular vibrations, and NBO population analysis served to describe the electronic structure; (iv) the electrostatic potential map was generated to provide the graphical presentation of regions exposed for intermolecular interactions. The contacts between the water molecule and the nitrogen atom of the isoxazole ring edge were present in the solid phase. On the other hand, the theoretical DFT prediction was that the oxygen atom of the edge should form a more stable complex with the water molecule.

  14. Enhanced catalysis and enantioselective resolution of racemic naproxen methyl ester by lipase encapsulated within iron oxide nanoparticles coated with calix[8]arene valeric acid complexes.

    PubMed

    Sayin, Serkan; Akoz, Enise; Yilmaz, Mustafa

    2014-09-14

    In this study, two types of nanoparticles have been used as additives for the encapsulation of Candida rugosa lipase via the sol-gel method. In one case, the nanoparticles were covalently linked with a new synthesized calix[8]arene octa valeric acid derivative (C[8]-C4-COOH) to produce new calix[8]arene-adorned magnetite nanoparticles (NP-C[8]-C4-COOH), and then NP-C[8]-C4-COOH was used as an additive in the sol-gel encapsulation process. In the other case, iron oxide nanoparticles were directly added into the sol-gel encapsulation process in order to interact electrostatically with both C[8]-C4-COOH and Candida rugosa lipase. The catalytic activities and enantioselectivities of two novel encapsulated lipases (Enc-NP-C[8]-C4-COOH and Enc-C[8]-C4-COOH@Fe3O4) in the hydrolysis reaction of racemic naproxen methyl ester were evaluated. The results showed that the activity and enantioselectivity of the lipase were improved when the lipase was encapsulated in the presence of calixarene-based additives. Indeed, the encapsulated lipases have an excellent rate of enantioselectivity, with E = 371 and 265, respectively, as compared to the free enzyme (E = 137). The lipases encapsulated with C[8]-C4-COOH and iron oxide nanoparticles (Enc-C[8]-C4-COOH@Fe3O4) retained more than 86% of their initial activities after 5 repeated uses and 92% with NP-C[8]-C4-COOH. PMID:25012138

  15. Anti-N-methyl-d-aspartate receptor encephalitis in a patient with a 7-year history of being diagnosed as schizophrenia: complexities in diagnosis and treatment

    PubMed Central

    Huang, Chaohua; Kang, Yukun; Zhang, Bo; Li, Bin; Qiu, Changjian; Liu, Shanming; Ren, Hongyan; Yang, Yanchun; Liu, Xiehe; Li, Tao; Guo, Wanjun

    2015-01-01

    Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a form of autoimmune encephalitis associated with antibodies against the NR1 subunits of NMDARs. Although new-onset acute prominent psychotic syndromes in patients with NMDAR encephalitis have been well documented, there is a lack of case studies on differential diagnosis and treatment of anti-NMDAR encephalitis after a long-term diagnostic history of functional psychotic disorders. The present study reports an unusual case of anti-NMDAR encephalitis. The patient had been diagnosed with schizophrenia 7 years earlier, and was currently hospitalized for acute-onset psychiatric symptoms. The diagnosis became unclear when the initial psychosis was confounded with considerations of other neurotoxicities (such as neuroleptic malignant syndrome). Finally, identification of specific immunoglobulin G NR1 autoantibodies in the cerebrospinal fluid and greater effectiveness of immunotherapy over antipsychotics alone (which has been well documented in anti-NMDAR encephalitis) indicated the diagnosis of anti-NMDAR encephalitis in this case. Based on the available evidence, however, the relationship between the newly diagnosed anti-NMDAR encephalitis and the seemingly clear, long-term history of schizophrenia in the preceding 7 years is uncertain. This case report illustrates that psychiatrists should consider anti-NMDAR encephalitis and order tests for specific immunoglobulin G NR1 autoantibodies in patients presenting with disorientation, disturbance of consciousness, cognitive deficit, dyskinesia, autonomic disturbance, or rapid deterioration, even with a seemingly clear history of a psychiatric disorder and no specific findings on routine neuroimaging, electroencephalography, or cerebrospinal fluid tests in the early stage of the illness.

  16. Methylating agents and DNA repair responses: methylated bases and sources of strand breaks

    PubMed Central

    Wyatt, Michael D.; Pittman, Douglas L.

    2008-01-01

    The chemical methylating agents methylmethane sulfonate (MMS) and N-methyl-N?-nitro-N-nitrosoguanidine (MNNG) have been used for decades as classical DNA damaging agents. These agents have been utilized to uncover and explore pathways of DNA repair, DNA damage response, and mutagenesis. MMS and MNNG modify DNA by adding methyl groups to a number of nucleophilic sites on the DNA bases, although MNNG produces a greater percentage of O-methyl adducts. There has been substantial progress elucidating direct reversal proteins that remove methyl groups and base excision repair (BER), which removes and replaces methylated bases. Direct reversal proteins and BER thus counteract the toxic, mutagenic and clastogenic effects of methylating agents. Despite recent progress, the complexity of DNA damage responses to methylating agents is still being discovered. In particular, there is growing understanding of pathways such as homologous recombination, lesion bypass, and mismatch repair that react when the response of direct reversal proteins and BER is insufficient. Furthermore, the importance of proper balance within the steps in BER has been uncovered with the knowledge that DNA structural intermediates during BER are deleterious. A number of issues complicate elucidating the downstream responses when direct reversal is insufficient or BER is imbalanced. These include inter-species differences, cell-type specific differences within mammals and between cancer cell lines, and the type of methyl damage or BER intermediate encountered. MMS also carries a misleading reputation of being a ‘radiomimetic,’ i.e., capable of directly producing strand breaks. This review focuses on the DNA methyl damage caused by MMS and MNNG for each site of potential methylation to summarize what is known about the repair of such damage and the downstream responses and consequences if not repaired. PMID:17173371

  17. A preference of histone H1 for methylated DNA.

    PubMed Central

    McArthur, M; Thomas, J O

    1996-01-01

    We have identified a clear preference of histone H1 for CpG-methylated DNA, irrespective of DNA sequence. The conditions under which this preference is observed allowed cooperative binding of H1; the H1-DNA complexes formed were shown earlier to be 'tramlines' of two DNA duplexes bridged by an array of H1 molecules, and multiples of these. The preference for methylated DNA is clear in sedimentation assays, which also show that the preference is greater with increased methylation level, and in gel retardation assays with an oligonucleotide containing a single methyl-CpG pair; it is shared by the globular domain which also binds cooperatively to DNA. A small intrinsic preference of H1 for methylated DNA is also apparent in Southwestern assays where the immobilized H1 presumably cannot bind cooperatively. Methylated DNA in H1-DNA complexes was partially protected (relative to unmethylated DNA) against digestion by MspI but not by enzymes whose cutting sites were not methylated, consistent with a direct interaction of H1 with methylated nucleotides; this was also true of GH1-DNA complexes. H1 variants (spH1 and H5) from transcriptionally repressed nuclei have a stronger preference than H1 for methylated DNA, suggesting that this may be relevant to the stabilization of chromatin higher order structure and transcriptional repression. Images PMID:8612595

  18. Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln

    Microsoft Academic Search

    Gunter Meister; Christian Eggert; Dirk Bühler; Hero Brahms; Christian Kambach; Utz Fischer

    2001-01-01

    Seven Sm proteins, termed B\\/B?, D1, D2, D3, E, F, and G, assemble in an ordered manner onto U snRNAs to form the Sm core of the spliceosomal snRNPs U1, U2, U4\\/U6, and U5 [1–4]. The survival of motor neuron (SMN) protein binds to Sm proteins and mediates in the context of a macromolecular (SMN-) complex the assembly of the

  19. Pharmacokinetics and pharmacodynamics of methyl parathion.

    PubMed

    Kramer, Robert E; Ho, Ing K

    2002-05-01

    Methyl parathion and other organophosphorus insecticides are widely used in agriculture. Poisonings to this class of compounds are common and exerted primarily through inhibition of acetylcholinesterase. Methyl parathion became a major health concern when it was illegally sprayed in private homes. Since there are limited data with which to predict the long-term effects resulting from a pattern of exposure to methyl parathion that may have occurred in domestic settings, studies were performed to compare its pharmacokinetics and pharmacodynamics after intravenous, oral or dermal exposure. Methyl parathion was given to adult female rats as a single dose intravenously (2.5 mg/kg) through a femoral catheter, orally (2.5 mg/kg) by gavage, or dermally (< or = 50 mg/kg) by application to shaved skin at the nape of the neck. Blood (200 microl) was collected at increasing times from a separate catheter or from the retro-orbital sinus. Cholinesterase activity was measured in blood and normalized to hemoglobin content, whereas activities in brain and peripheral tissues were normalized to protein. Blood methyl parathion was quantitated by gas chromatography-electron capture. The pharmacokinetics of methyl parathion after intravenous exposure best fit a model in which it was distributed between two compartments and rapidly eliminated. Maximal concentrations of methyl parathion ranged from 200 to 350 ng/ml. The half-life of methyl parathion was 51 minutes, its volume of distribution was 10.1 L/kg, and clearance was 108 ml/min/kg. The kinetics of methyl parathion after single oral exposure contrasted with those after intravenous exposure. Despite a high absorption coefficient, oral bioavailability of methyl parathion was less than 5%, and concentrations in blood were 2% or less of those after intravenous exposure. After single dermal exposure (25 or 50 mg/kg), blood methyl parathion levels increased during the first 6 h and then remained constant for the next 42 h at about 150 ng/ml. Despite differences in its pharmacokinetics, methyl parathion caused similar time-dependent changes in blood and brain cholinesterase activities after intravenous or oral administration. Maximal inhibition of blood cholinesterase occurred within 15-60 min, and activities recovered within 30 - 48 h. In contrast, inhibition of blood cholinesterase caused by single dermal exposure (> or = 25 mg/kg) to methyl parathion developed gradually over 24 h, but was sustained. Cholinesterase inhibited by a lower dose (< or = 12 mg/kg) of methyl parathion required up to 21 days to recover fully. The pharmacokinetics and pharmacodynamics of methyl parathion are complex, and the complexity varies with the route of exposure. A significant 'first pass' effect for methyl parathion is seen with oral administration. Dermal exposure to methyl parathion, as likely occurred with the illegal spraying of private homes and businesses, may exacerbate toxicity and increase the potential for long-term adverse health effects. PMID:12166762

  20. Synthesis, characterization and crystal structures of technetium(V)-oxo complexes useful in nuclear medicine. 1. Complexes of mercaptoacetylglycylglycylglycine (MAG{sub 3}) and its methyl ester derivative (MAG{sub 3}OMe)

    SciTech Connect

    Grummon, G.; Rajagopalan, R.; Palenik, G.J. [Mallinckrodt Medical, Inc., St. Louis, MO (United States)

    1995-03-29

    Mercptoacetylpeptide complexes of {sup 99g}Tc are useful compounds for nuclear medicine. This work describes the synthesis and structural characterization of a mercaptoacetylglyclglycylglycine complex and its esterified analog. Structural characterization is accomplished through NMR, mass spectrometry, and X-ray crystallography.

  1. DNA-gelatin complex coacervation, UCST and first-order phase transition of coacervate to anisotropic ion gel in 1-methyl-3-octylimidazolium chloride ionic liquid solutions.

    PubMed

    Rawat, Kamla; Aswal, V K; Bohidar, H B

    2012-12-27

    Study of kinetics of complex coacervation occurring in aqueous 1-octyl-3-methylimidazolium chloride ionic liquid solution of low charge density polypeptide (gelatin A) and 200 base pair DNA, and thermally activated coacervate into anisotropic gel transition, is reported here. Associative interaction between DNA and gelatin A (GA) having charge ratio (DNA:GA = 16:1) and persistence length ratio (5:1) was studied at fixed DNA (0.005% (w/v)) and varying GA concentration (C(GA) = 0-0.25% (w/v)). The interaction profile was found to be strongly hierarchical and revealed three distinct binding regions: (i) Region I showed DNA-condensation (primary binding) for C(GA) < 0.10% (w/v), the DNA ? potential decrease from -80 to -5 mV (95%) (partial charge neutralization), and a size decrease by ?60%. (ii) Region II (0.10 < C(GA) < 0.15% (w/v)) indicated secondary binding, a 4-fold turbidity increase, a ? potential decrease from -5 to 0 mV (complete charge neutralization), which resulted in the appearance of soluble complexes and initiation of coacervation. (iii) Region III (0.15 < C(GA) < 0.25% (w/v)) revealed growth of insoluble complexes followed by precipitation. The hydration of coacervate was found to be protein concentration specific in Raman studies. The binding profile of DNA-GA complex with IL concentration revealed optimum IL concentration (=0.05% (w/v)) was required to maximize the interactions. Small angle neutron scattering (SANS) data of coacervates gave static structure factor profiles, I(q) versus wave vector q, that were remarkably similar and invariant of protein concentration. This data could be split into two distinct regions: (i) for 0.0173 < q < 0.0353 Å(-1), I(q) ~ q(-?) with ? = 1.35-1.67, and (ii) for 0.0353 < q < 0.35 Å(-1), I(q) = I(0)/(1 + q(2)?(2)). The correlation length found was ? = 2 ± 0.1 nm independent of protein concentration. The viscoelastic length (?8 nm) was found to have value close to the persistence length of the protein (?10 nm). Rheology data indicated that the coacervate phase resided close to the gelation state of the protein. Thus, on a heating-cooling cycle (heating to 50 °C followed by cooling to 20 °C), the heterogeneous coacervate exhibited an irreversible first-order phase transition to an anisotropic ion gel. This established a coacervate-ion gel phase diagram having a well-defined UCST. PMID:23194173

  2. Iron and chromium complexes containing tridentate chelates based on nacnac and imino- and methyl-pyridine components: triggering C-X bond formation.

    PubMed

    Morris, Wesley D; Wolczanski, Peter T; Sutter, Jörg; Meyer, Karsten; Cundari, Thomas R; Lobkovsky, Emil B

    2014-07-21

    Nacnac-based tridentate ligands containing a pyridyl-methyl and a 2,6-dialkyl-phenylamine (i.e., (2,6-R2-C6H3N?C(Me)CH?C(Me)NH(CH2py); R = Et, {Et(nn)PM}H; R = (i)Pr, {(i)Pr(nn)PM}H) were synthesized by condensation routes. Treatment of M{N(TMS)2}THFn (M = Cr, n = 2; M = Fe, Co, n = 1; TMS = trimethylsilane; THF = tetrahydrofuran) with {(i)Pr(nn)PM}H) afforded {(i)Pr(nn)PM}MN(TMS)2 (1-M(iPr); M = Cr, Fe); {Et(nn)PM}MN(TMS)2 (1-M(Et); M = Fe, Co) was similarly obtained. {R(nn)PM}FeBr (R = (i)Pr, Et; 2-Fe(R)) were prepared from FeBr2 and {R(nn)PM}Li, and alkylated to generate {R(nn)PM}Fe(neo)Pe (R = (i)Pr, Et; 3-Fe(R)). Carbonylation of 3-Fe(R) provided {(i)Pr(nn)PM}Fe(CO(neo)Pe)CO (4-Fe(iPr)), and carbonylations of 1-Fe(R) (R = Et, (i)Pr) and 1-Cr(iPr) induced deamination to afford {R(nn)PI}Fe(CO)2 (R = (i)Pr, 5-Fe(iPr); Et, 5-Fe(Et)), where PI is pyridine-imine, and {?(2)-N,N-pyrim-pyr}Cr(CO)4 (6-Cr(iPr)), in which the aryl-amide side of the nacnac attacked the incipient PI group. Carbon-carbon bonds were formed at the imine carbon of the {R(nn)PI} ligand. Addition of [{(i)Pr(nn)PI}(2-)](K(+)(THF)x)2 to FeCl3 generated {(i)Pr(nn)CHpy}2Fe2Cl2 (7-Fe(iPr)), and TMSN3 induced the deamination of 1-Fe(Et), but with disproportionation to provide {[Et(nn)CHpy]2}Fe (8-Fe(Et)). Ph2CN2 induced C-C bond formation with 1-Fe(iPr) via its thermal degradation to ultimately afford {(i)Pr(nn)CHpy}2(FeN?CPh2)2 (9-Fe(iPr)). The compounds were examined by X-ray crystallography (1-M(iPr), M = Cr, Fe; 1-Co(Et); 2-Fe(iPr); 4-Fe(iPr); 5-Fe(iPr); 6-Cr(iPr); 7-Fe(iPr); 8-Fe(Et); 9-Fe(iPr)), Mössbauer spectroscopy, and NMR spectroscopy. Structural parameters assessing redox noninnocence are discussed, as are structural and mechanistic consequences of the various electronic environments. PMID:25010819

  3. DNA methylation: bisulphite modification and analysis.

    PubMed

    Patterson, Kate; Molloy, Laura; Qu, Wenjia; Clark, Susan

    2011-01-01

    Epigenetics describes the heritable changes in gene function that occur independently to the DNA sequence. The molecular basis of epigenetic gene regulation is complex, but essentially involves modifications to the DNA itself or the proteins with which DNA associates. The predominant epigenetic modification of DNA in mammalian genomes is methylation of cytosine nucleotides (5-MeC). DNA methylation provides instruction to gene expression machinery as to where and when the gene should be expressed. The primary target sequence for DNA methylation in mammals is 5'-CpG-3' dinucleotides (Figure 1). CpG dinucleotides are not uniformly distributed throughout the genome, but are concentrated in regions of repetitive genomic sequences and CpG "islands" commonly associated with gene promoters (Figure 1). DNA methylation patterns are established early in development, modulated during tissue specific differentiation and disrupted in many disease states including cancer. To understand the biological role of DNA methylation and its role in human disease, precise, efficient and reproducible methods are required to detect and quantify individual 5-MeCs. This protocol for bisulphite conversion is the "gold standard" for DNA methylation analysis and facilitates identification and quantification of DNA methylation at single nucleotide resolution. The chemistry of cytosine deamination by sodium bisulphite involves three steps (Figure 2). (1) Sulphonation: The addition of bisulphite to the 5-6 double bond of cytosine (2) Hydrolic Deamination: hydrolytic deamination of the resulting cytosine-bisulphite derivative to give a uracil-bisulphite derivative (3) Alkali Desulphonation: Removal of the sulphonate group by an alkali treatment, to give uracil. Bisulphite preferentially deaminates cytosine to uracil in single stranded DNA, whereas 5-MeC, is refractory to bisulphite-mediated deamination. Upon PCR amplification, uracil is amplified as thymine while 5-MeC residues remain as cytosines, allowing methylated CpGs to be distinguished from unmethylated CpGs by presence of a cytosine "C" versus thymine "T" residue during sequencing. DNA modification by bisulphite conversion is a well-established protocol that can be exploited for many methods of DNA methylation analysis. Since the detection of 5-MeC by bisulphite conversion was first demonstrated by Frommer et al. and Clark et al., methods based around bisulphite conversion of genomic DNA account for the majority of new data on DNA methylation. Different methods of post PCR analysis may be utilized, depending on the degree of specificity and resolution of methylation required. Cloning and sequencing is still the most readily available method that can give single nucleotide resolution for methylation across the DNA molecule. PMID:22042230

  4. Synthesis and Characterization of Bioactive Acylpyrazolone Sulfanilamides and Their Transition Metal Complexes: Single Crystal Structure of 4-Benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one Sulfanilamide

    PubMed Central

    Idemudia, Omoruyi G.; Sadimenko, Alexander P.; Afolayan, Anthony J.; Hosten, Eric C.

    2015-01-01

    Two Schiff base ligands Ampp-Sn 1 and Bmpp-Sn 2, afforded by a condensation reaction between sulfanilamide and the respective acylpyrazolone carbonyl precursors, their Mn(II), Co(II), Ni(II), and Cu(II) complexes prepared by the reaction of ligands and corresponding metal salts in aqueous solutions, were synthesized and then characterized by both analytical and spectroscopic methods, in a view to developing new improved bioactive materials with novel properties. On the basis of elemental analysis, spectroscopic and TGA results, transition metal complexes, with octahedral geometry having two molecules of the bidentate keto-imine ligand each, have been proposed. The single crystal structure of Bmpp-Sn according to X-ray crystallography showed a keto-imine tautomer type of Schiff base, having three intramolecular bonds, one short N2?H2?O3 hydrogen bond of 1.90?Å and two long C13?H13?O2 and C32?H32?O3 hydrogen bonds of 2.48?Å. A moderate to low biological activities have been exhibited by synthesized compounds when compared with standard antimicrobial agents on screening the synthesized compounds against Staphylococcus aureus, Bacillus pumilus, Proteus vulgaris, and Aeromonas hydrophila for antibacterial activity and against free radical 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) for antioxidant activity.

  5. Identification of functionally methylated regions based on discriminant analysis through integrating methylation and gene expression data.

    PubMed

    Zhang, Yuanyuan; Zhang, Junying

    2015-06-16

    DNA methylation is essential not only in cellular differentiation but also in diseases. Identification of differentially methylated patterns between case and control groups is important in understanding the mechanism and possible functionality of complex diseases. We propose a method to find possible functionally methylated regions which not only are differentially methylated but also have an effect on gene expression. It integrates methylation and gene expression data and is based on distance discriminant analysis (DDA). In the procedure of identifying differentially methylated regions (DMRs), we do not need to cluster methylation sites or partition the genome in advance. Therefore, the identified DMRs have a larger coverage than those of bump hunting and Ong's methods. Furthermore, through incorporating gene expression data as a complementary source, whether these DMRs are functional is determined through estimating the difference of the corresponding genes. Through a comparison of our approach with bump hunting and Ong's methods for simulation data, it is shown that our method is more powerful in identifying DMRs which have a larger distance in the genome, or only consist of a few sites and have higher sensitivity and specificity. Also, our method is more robust to heterogeneity of data. Applied to different real datasets, we find that most of the functional DMRs are hyper-methylated and located at CpG rich regions (e.g. islands, TSS200 and TSS1500), consistent with the fact that the methylation levels of CpG islands are higher in tumors than normal. Through comparing and analyzing the results of different datasets, we find that the change of methylation in some regions may be related to diseases through changing expression of the corresponding genes, and show the effectiveness of our method. PMID:25865601

  6. DNA Methylation Biomarkers: Cancer and Beyond

    PubMed Central

    Mikeska, Thomas; Craig, Jeffrey M.

    2014-01-01

    Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease. PMID:25229548

  7. Genome-scale DNA methylation analysis

    PubMed Central

    Fouse, Shaun D; Nagarajan, Raman P; Costello, Joseph F

    2010-01-01

    The haploid human genome contains approximately 29 million CpGs that exist in a methylated, hydroxymethylated or unmethylated state, collectively referred to as the DNA methylome. The methylation status of cytosines in CpGs and occasionally in non-CpG cytosines influences protein–DNA interactions, gene expression, and chromatin structure and stability. The degree of DNA methylation at particular loci may be heritable transgenerationally and may be altered by environmental exposures and diet, potentially contributing to the development of human diseases. For the vast majority of normal and disease methylomes however, less than 1% of the CpGs have been assessed, revealing the formative stage of methylation mapping techniques. Thus, there is significant discovery potential in new genome-scale platforms applied to methylome mapping, particularly oligonucleotide arrays and the transformative technology of next-generation sequencing. Here, we outline the currently used methylation detection reagents and their application to microarray and sequencing platforms. A comparison of the emerging methods is presented, highlighting their degrees of technical complexity, methylome coverage and precision in resolving methylation. Because there are hundreds of unique methylomes to map within one individual and interindividual variation is likely to be significant, international coordination is essential to standardize methylome platforms and to create a full repository of methylome maps from tissues and unique cell types. PMID:20657796

  8. 5-Hydroxytryptamine 5HT2C Receptors Form a Protein Complex with N-Methyl-d-aspartate GluN2A Subunits and Activate Phosphorylation of Src Protein to Modulate Motoneuronal Depolarization*

    PubMed Central

    Bigford, Gregory E.; Chaudhry, Nauman S.; Keane, Robert W.; Holohean, Alice M.

    2012-01-01

    N-Methyl-d-aspartate (NMDA)-gated ion channels are known to play a critical role in motoneuron depolarization, but the molecular mechanisms modulating NMDA activation in the spinal cord are not well understood. This study demonstrates that activated 5HT2C receptors enhance NMDA depolarizations recorded electrophysiologically from motoneurons. Pharmacological studies indicate involvement of Src tyrosine kinase mediates 5HT2C facilitation of NMDA. RT-PCR analysis revealed edited forms of 5HT2C were present in mammalian spinal cord, indicating the availability of G-protein-independent isoforms. Spinal cord neurons treated with the 5HT2C agonist MK 212 showed increased SrcTyr-416 phosphorylation in a dose-dependent manner thus verifying that Src is activated after treatment. In addition, 5HT2C antagonists and tyrosine kinase inhibitors blocked 5HT2C-mediated SrcTyr-416 phosphorylation and also enhanced NMDA-induced motoneuron depolarization. Co-immunoprecipitation of synaptosomal fractions showed that GluN2A, 5HT2C receptors, and Src tyrosine kinase form protein associations in synaptosomes. Moreover, immunohistochemical analysis demonstrated GluN2A and 5HT2C receptors co-localize on the processes of spinal neurons. These findings reveal that a distinct multiprotein complex links 5-hydroxytryptamine-activated intracellular signaling events with NMDA-mediated functional activity. PMID:22291020

  9. 5-Hydroxytryptamine 5HT2C receptors form a protein complex with N-methyl-D-aspartate GluN2A subunits and activate phosphorylation of Src protein to modulate motoneuronal depolarization.

    PubMed

    Bigford, Gregory E; Chaudhry, Nauman S; Keane, Robert W; Holohean, Alice M

    2012-03-30

    N-Methyl-D-aspartate (NMDA)-gated ion channels are known to play a critical role in motoneuron depolarization, but the molecular mechanisms modulating NMDA activation in the spinal cord are not well understood. This study demonstrates that activated 5HT2C receptors enhance NMDA depolarizations recorded electrophysiologically from motoneurons. Pharmacological studies indicate involvement of Src tyrosine kinase mediates 5HT2C facilitation of NMDA. RT-PCR analysis revealed edited forms of 5HT2C were present in mammalian spinal cord, indicating the availability of G-protein-independent isoforms. Spinal cord neurons treated with the 5HT2C agonist MK 212 showed increased Src(Tyr-416) phosphorylation in a dose-dependent manner thus verifying that Src is activated after treatment. In addition, 5HT2C antagonists and tyrosine kinase inhibitors blocked 5HT2C-mediated Src(Tyr-416) phosphorylation and also enhanced NMDA-induced motoneuron depolarization. Co-immunoprecipitation of synaptosomal fractions showed that GluN2A, 5HT2C receptors, and Src tyrosine kinase form protein associations in synaptosomes. Moreover, immunohistochemical analysis demonstrated GluN2A and 5HT2C receptors co-localize on the processes of spinal neurons. These findings reveal that a distinct multiprotein complex links 5-hydroxytryptamine-activated intracellular signaling events with NMDA-mediated functional activity. PMID:22291020

  10. The Stem Cell Population of the Human Colon Crypt: Analysis via Methylation Patterns

    Microsoft Academic Search

    Pierre Nicolas; Kyoung-Mee Kim; Darryl Shibata; Simon Tavaré

    2007-01-01

    The analysis of methylation patterns is a promising approach to investigate the genealogy of cell populations in an organism. In a stem cell–niche scenario, sampled methylation patterns are the stochastic outcome of a complex interplay between niche structural features such as the number of stem cells within a niche and the niche succession time, the methylation\\/demethylation process, and the randomness

  11. The Stem Cell Population of the Human Colon Crypt: Analysis via Methylation Patterns

    Microsoft Academic Search

    Pierre Nicolas; Kyoung-Mee Kim; Darryl Shibata; Simon Tavare

    2005-01-01

    The analysis of methylation patterns is a promising approach to investigate the genealogy of cell populations in an organism. In a stem cell-niche scenario, sampled methylation patterns are the stochastic outcome of a complex interplay between niche structural features such as the number of stem cells within a niche and the niche succession time, the methylation\\/demethylation process, and the randomness

  12. High definition profiling of mammalian DNA methylation by array capture and single molecule bisulfite sequencing

    Microsoft Academic Search

    Emily Hodges; Andrew D. Smith; Jude Kendall; Zhenyu Xuan; Kandasamy Ravi; Michelle Rooks; Michael Q. Zhang; Kenny Ye; Arindam Bhattacharjee; Leonardo Brizuela; W. Richard McCombie; Michael Wigler; Gregory J. Hannon; James B. Hicks

    2009-01-01

    DNA methylation stabilizes developmentally programmed gene expression states. Aberrant methylation is associated with disease progression and is a common feature of cancer genomes. Presently, few methods enable quantitative, large- scale, single-base resolution mapping of DNA methylation states in desired regions of a complex mammalian genome. Here, we present an approach that combines array-based hybrid selection and massively parallel bisulfite sequencing

  13. Profile analysis and prediction of tissue-specific CpG island methylation classes

    Microsoft Academic Search

    Christopher Previti; Oscar Harari; Igor Zwir; Coral Del Val

    2009-01-01

    BACKGROUND: The computational prediction of DNA methylation has become an important topic in the recent years due to its role in the epigenetic control of normal and cancer-related processes. While previous prediction approaches focused merely on differences between methylated and unmethylated DNA sequences, recent experimental results have shown the presence of much more complex patterns of methylation across tissues and

  14. ENZYMOLOGY OF ARSENIC METHYLATION

    EPA Science Inventory

    Enzymology of Arsenic Methylation David J. Thomas, Pharmacokinetics Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park...

  15. DNA methylation and differentiation.

    PubMed Central

    Michalowsky, L A; Jones, P A

    1989-01-01

    The methylation of specific cytosine residues in DNA has been implicated in regulating gene expression and facilitating functional specialization of cellular phenotypes. Generally, the demethylation of certain CpG sites correlates with transcriptional activation of genes. 5-Azacytidine is an inhibitor of DNA methylation and has been widely used as a potent activator of suppressed genetic information. Treatment of cells with 5-azacytidine results in profound phenotypic alterations. The drug-induced hypomethylation of DNA apparently perturbs DNA-protein interactions that may consequently alter transcriptional activity and cell determination. The inhibitory effect of cytosine methylation may be exerted via altered DNA-protein interactions specifically or may be transduced by a change in the conformation of chromatin. Recent studies have demonstrated that cytosine methylation also plays a central role in parental imprinting, which in turn determines the differential expression of maternal and paternal genomes during embryogenesis. In other words, methylation is the mechanism whereby the embryo retains memory of the gametic origin of each component of genetic information. A memory of this type would probably persist during DNA replication and cell division as methylation patterns are stable and heritable. PMID:2466640

  16. DNA methylation and differentiation

    SciTech Connect

    Michalowky, L.A.; Jones, P.A. (USC Cancer Center, Los Angeles, CA (USA))

    1989-03-01

    The methylation of specific cytosine residues in DNA has been implicated in regulating gene expression and facilitating functional specialization of cellular phenotypes. Generally, the demethylation of certain CpG sites correlates with transcriptional activation of genes. 5-Azacytidine is an inhibitor of DNA methylation and has been widely used as a potent activator of suppressed genetic information. Treatment of cells with 5-azacytidine results in profound phenotypic alterations. The drug-induced hypomethylation of DNA apparently perturbs DNA-protein interactions that may consequently alter transcriptional activity and cell determination. The inhibitory effect of cytosine methylation may be exerted via altered DNA-protein interactions specifically or may be transduced by a change in the conformation of chromatin. Recent studies have demonstrated that cytosine methylation also plays a central role in parental imprinting, which in turn determines the differential expression of maternal and paternal genomes during embryogenesis. In other words, methylation is the mechanism whereby the embryo retains memory of the gametic origin of each component of genetic information. A memory of this type would probably persist during DNA replication and cell division as methylation patterns are stable and heritable.

  17. Simultaneous chiral separation of leucovorin and its major metabolite 5-methyl-tetrahydrofolate by capillary electrophoresis using cyclodextrins as chiral selectors: Estimation of the formation constant and mobility of the solute-cyclodextrin complexes

    Microsoft Academic Search

    A. Shibukawa; D. K. Lloyd; I. W. Wainer

    1993-01-01

    Capillary electrophoresis with an electrolyte containing cyclodextrin was investigated for the simultaneous separation of the diastereoisomers of 6R,S-leucovorin and its active metabolite 6R,S-5-methyl-tetrahydrofolate. ?, ? and ?-cyclodextrin separated the diastereoisomers of 5-methyl-tetrahydrofolate, while only ?-cyclodextrin was found to be effective for the chiral separation of leucovorin. The effect of ?-cyclodextrin concentration was investigated, and subsequently a curve-fitting analysis for the

  18. Biological activity of palladium(II) and platinum(II) complexes of the acetone Schiff bases of S-methyl- and S-benzyldithiocarbazate and the X-ray crystal structure of the [Pd(asme)2] (asme=anionic form of the acetone Schiff base of S-methyldithiocarbazate) complex.

    PubMed

    Akbar Ali, Mohammad; Mirza, Aminul Huq; Butcher, Raymond J; Tarafder, M T H; Keat, Tan Boon; Ali, A Manaf

    2002-11-25

    Palladium(II) and platinum(II) complexes of general empirical formula, [M(NS)(2)] (NS=uninegatively charged acetone Schiff bases of S-methyl- and S-benzyldithiocarbazate; M=Pt(II) and Pd(II)) have been prepared and characterized by a variety of physicochemical techniques. Based on conductance, IR and electronic spectral evidence, a square-planar structure is assigned to these complexes. The crystal and molecular structure of the [Pd(asme)(2)] complex (asme=anionic form of the acetone Schiff base of S-methyldithiocarbazate) has been determined by X-ray diffraction. The complex has a distorted cis-square planar structure with the ligands coordinated to the palladium(II) ions as uninegatively charged bidentate NS chelating agents via the azomethine nitrogen and the mercaptide sulfur atoms. The distortion from a regular square-planar geometry is attributed to the restricted bite angles of the ligands. Antimicrobial tests indicate that the Schiff bases exhibit strong activities against the pathogenic bacteria, Bacillus subtilis (mutant defective DNA repair), methicillin-resistant Staphylococcus aureus, B. subtilis (wild type) and Pseudomonas aeruginosa and the fungi, Candida albicans (CA), Candida lypotica (2075), Saccharomyces cerevisiae (20341) and Aspergillus ochraceous (398)-the activities exhibited by these compounds being greater than that of the standard antibacterial and antifungal drugs, streptomycin and nystatin, respectively. The palladium(II) and platinum(II) complexes are inactive against most of these organisms but, the microbe, Pseudomonas aeruginosa shows strong sensitivity to the platinum(II) complexes. Screening of the compounds for their cytotoxicities against T-lymphoblastic leukemia cancer cells has shown that the acetone Schiff base of S-methyldithiocarbazate (Hasme) exhibits a very weak activity, whereas the S-benzyl derivative (Hasbz) is inactive. However, the palladium(II) complexes exhibit strong cytotoxicities against this cancer; their activities being more than that of the standard anticancer drug, tamoxifen. The [Pt(asme)(2)] complex exhibits a very weak cytotoxicity, whereas [Pt(asbz)(2)] is inactive against leukemic cells. PMID:12433421

  19. Coagulation of methylated arsenic from drinking water: Influence of methyl substitution.

    PubMed

    Hu, Chengzhi; Chen, Qingxin; Liu, Huijuan; Qu, Jiuhui

    2015-08-15

    Methylated arsenic can be found in virtually all earth surface environments. So far, however, little information has been collected regarding their removal by coagulation. In this study, the removal of monomethylarsenate (MMA) and dimethylarsenate (DMA) from drinking water by coagulation was investigated from the viewpoint of methyl substitution. Results indicated that FeCl3 was more efficient than AlCl3 and polyaluminum chloride (PACl) in methylated As removal. For the initial arsenic concentration of 200?g/L, an FeCl3 dosage of 0.2mmol Fe/L was sufficient to attain about 95% removal of MMA, while a dosage of 0.6mmol Fe/L achieved about 57% removal of DMA. Arsenic removal efficiency was negatively correlated with the degree of methyl substitution. With the increase in methyl group number, the quantity of negatively charged arsenic species decreased and molecular size increased, leading to the decrease of methylated As removal by coagulation. Adsorption on preformed hydroxide flocs was the major mechanism during coagulation. Both FTIR and XPS results indicated that the AsO group of As might substitute the OH group of Fe/Al hydroxide to form a Fe/AlOAs complex. Furthermore, the use of traditional oxidants and coagulation aids exhibited limited help for improving coagulation removal of DMA. PMID:25855566

  20. Is There a Relationship between DNA Methylation and Phenotypic Plasticity in Invertebrates?

    PubMed Central

    Roberts, Steven B.; Gavery, Mackenzie R.

    2011-01-01

    There is a significant amount of variation in DNA methylation characteristics across organisms. Likewise, the biological role of DNA methylation varies across taxonomic lineages. The complexity of DNA methylation patterns in invertebrates has only recently begun to be characterized in-depth. In some invertebrate species that have been examined to date, methylated DNA is found primarily within coding regions and patterning is closely associated with gene function. Here we provide a perspective on the potential role of DNA methylation in these invertebrates with a focus on how limited methylation may contribute to increased phenotypic plasticity in highly fluctuating environments. Specifically, limited methylation could facilitate a variety of transcriptional opportunities including access to alternative transcription start sites, increasing sequence mutations, exon skipping, and transient methylation. PMID:22232607

  1. Evolution of DNA Methylation Is Linked to Genetic Aberrations in Chronic Lymphocytic Leukemia

    PubMed Central

    Oakes, Christopher C.; Claus, Rainer; Gu, Lei; Assenov, Yassen; Hüllein, Jennifer; Zucknick, Manuela; Bieg, Matthias; Brocks, David; Bogatyrova, Olga; Schmidt, Christopher R.; Rassenti, Laura; Kipps, Thomas J.; Mertens, Daniel; Lichter, Peter; Döhner, Hartmut; Stilgenbauer, Stephan; Byrd, John C.; Zenz, Thorsten; Plass, Christoph

    2014-01-01

    Although clonal selection by genetic driver aberrations in cancer is well documented, the ability of epigenetic alterations to promote tumor evolution is undefined. We used 450k arrays and next-generation sequencing to evaluate intratumor heterogeneity and evolution of DNA methylation and genetic aberrations in chronic lymphocytic leukemia (CLL). CLL cases exhibit vast interpatient differences in intratumor methylation heterogeneity, with genetically clonal cases maintaining low methylation heterogeneity and up to 10% of total CpGs in a monoallelically methylated state. Increasing methylation heterogeneity correlates with advanced genetic subclonal complexity. Selection of novel DNA methylation patterns is observed only in cases that undergo genetic evolution, and independent genetic evolution is uncommon and is restricted to low-risk alterations. These results reveal that although evolution of DNA methylation occurs in high-risk, clinically progressive cases, positive selection of novel methylation patterns entails coevolution of genetic alteration(s) in CLL. PMID:24356097

  2. Evolution of DNA methylation is linked to genetic aberrations in chronic lymphocytic leukemia.

    PubMed

    Oakes, Christopher C; Claus, Rainer; Gu, Lei; Assenov, Yassen; Hüllein, Jennifer; Zucknick, Manuela; Bieg, Matthias; Brocks, David; Bogatyrova, Olga; Schmidt, Christopher R; Rassenti, Laura; Kipps, Thomas J; Mertens, Daniel; Lichter, Peter; Döhner, Hartmut; Stilgenbauer, Stephan; Byrd, John C; Zenz, Thorsten; Plass, Christoph

    2014-03-01

    Although clonal selection by genetic driver aberrations in cancer is well documented, the ability of epigenetic alterations to promote tumor evolution is undefined. We used 450k arrays and next-generation sequencing to evaluate intratumor heterogeneity and evolution of DNA methylation and genetic aberrations in chronic lymphocytic leukemia (CLL). CLL cases exhibit vast interpatient differences in intratumor methylation heterogeneity, with genetically clonal cases maintaining low methylation heterogeneity and up to 10% of total CpGs in a monoallelically methylated state. Increasing methylation heterogeneity correlates with advanced genetic subclonal complexity. Selection of novel DNA methylation patterns is observed only in cases that undergo genetic evolution, and independent genetic evolution is uncommon and is restricted to low-risk alterations. These results reveal that although evolution of DNA methylation occurs in high-risk, clinically progressive cases, positive selection of novel methylation patterns entails coevolution of genetic alteration(s) in CLL. PMID:24356097

  3. Selective targeting of histone methylation.

    PubMed

    Islam, Abul B M M K; Richter, William F; Lopez-Bigas, Nuria; Benevolenskaya, Elizaveta V

    2011-02-01

    Histones are post-translationally modified by multiple histone-modifying enzymes, which in turn influences gene expression. Much of the work in the field to date has focused on genetic, biochemical and structural characterization of these enzymes. The most recent genome-wide methods provide insights into specific recruitment of histone-modifying enzymes in vivo and, therefore, onto mechanisms of establishing a differential expression pattern. Here we focus on the recruitment mechanisms of the enzymes involved in the placement of two contrasting histone marks, histone H3 lysine 4 (H3K4) methylation and histone H3 lysine 27 (H3K27) methylation. We describe distribution of their binding sites and show that recruitment of different histone-modifying proteins can be coordinated, opposed, or alternating. Specifically, genomic sites of the H3K4 histone demethylase KDM5A become accessible to its homolog KDM5B in cells with a lowered KDM5A level. The currently available data on recruitment of H3K4/H3K27 modifying enzymes suggests that the formed protein complexes are targeted in a sequential and temporal manner, but that additional, still unknown, interactions contribute to targeting specificity. PMID:21270517

  4. CpG methylation in the Fhit regulatory region: relation to Fhit expression in murine tumors.

    PubMed

    Han, Shuang-Yin; Iliopoulos, Dimitrios; Druck, Teresa; Guler, Gulnur; Grubbs, Clinton J; Pereira, Michael; Zhang, Zhongqiu; You, Ming; Lubet, Ronald A; Fong, Louise Y Y; Huebner, Kay

    2004-05-13

    To determine if: (1) 5' CpG island methylation is related to Fhit inactivation; (2) there are tumor or carcinogen-specific methylation patterns, we examined 35 CpG sites in the promoter, exon and intron 1 of the mouse Fhit gene. In primary tumors of lung, urinary bladder and tongue, induced by different carcinogens, 15-35% of sites were methylated, with specific methylation patterns associated with each cancer type, suggesting cancer- or tissue-specific methylation patterns. The methylation patterns were associated with reduced Fhit expression, as determined by immunohistochemical analyses. Methylation of rat Fhit 5' CpGs in mammary adenocarcinomas, detected by methylation specific PCR amplification, also correlated with reduced gene expression. Thus, there was an overall association between promoter/exon 1 methylation and decreased Fhit expression. In contrast, in cancer-derived cell lines 70-95% of the CpG sites were methylated. This is the first detailed study of the relationship between Fhit 5' CpG island methylation and Fhit expression in murine tumors, our main models for preclinical cancer studies, and provides evidence that loss of Fhit expression and methylation are correlated in these mouse models and these models will be useful to examine the complex relationships among gene expression, methylation patterns and organ specificity. PMID:15007387

  5. Aberrant methylation patterns in cancer: a clinical view

    PubMed Central

    Paska, Alja Videtic; Hudler, Petra

    2015-01-01

    Epigenetic mechanisms, such as DNA methylation, DNA hydroxymethylation, post-translational modifications (PTMs) of histone proteins affecting nucleosome remodelling, and regulation by small and large non-coding RNAs (ncRNAs) work in concert with cis and trans acting elements to drive appropriate gene expression. Advances in detection methods and development of dedicated platforms and methylation arrays resulted in an explosion of information on aberrantly methylated sequences linking deviations in epigenetic landscape with the initiation and progression of complex diseases. Here, we consider how DNA methylation changes in malignancies, such as breast, pancreatic, colorectal, and gastric cancer could be exploited for the purpose of developing specific diagnostic tools. DNA methylation changes can be applicable as biomarkers for detection of malignant disease in easily accessible tissues. Methylation signatures are already proving to be an important marker for determination of drug sensitivity. Even more, promoter methylation patterns of some genes, such as MGMT, SHOX2, and SEPT9, have already been translated into commercial clinical assays aiding in patient assessment as adjunct diagnostic tools. In conclusion, the changes in DNA methylation patterns in tumour cells are slowly gaining entrance into routine diagnostic tests as promising biomarkers and as potential therapeutic targets. PMID:26110029

  6. Human body epigenome maps reveal noncanonical DNA methylation variation.

    PubMed

    Schultz, Matthew D; He, Yupeng; Whitaker, John W; Hariharan, Manoj; Mukamel, Eran A; Leung, Danny; Rajagopal, Nisha; Nery, Joseph R; Urich, Mark A; Chen, Huaming; Lin, Shin; Lin, Yiing; Jung, Inkyung; Schmitt, Anthony D; Selvaraj, Siddarth; Ren, Bing; Sejnowski, Terrence J; Wang, Wei; Ecker, Joseph R

    2015-07-01

    Understanding the diversity of human tissues is fundamental to disease and requires linking genetic information, which is identical in most of an individual's cells, with epigenetic mechanisms that could have tissue-specific roles. Surveys of DNA methylation in human tissues have established a complex landscape including both tissue-specific and invariant methylation patterns. Here we report high coverage methylomes that catalogue cytosine methylation in all contexts for the major human organ systems, integrated with matched transcriptomes and genomic sequence. By combining these diverse data types with each individuals' phased genome, we identified widespread tissue-specific differential CG methylation (mCG), partially methylated domains, allele-specific methylation and transcription, and the unexpected presence of non-CG methylation (mCH) in almost all human tissues. mCH correlated with tissue-specific functions, and using this mark, we made novel predictions of genes that escape X-chromosome inactivation in specific tissues. Overall, DNA methylation in several genomic contexts varies substantially among human tissues. PMID:26030523

  7. In vitro methylation assay to study protein arginine methylation.

    PubMed

    Bikkavilli, Rama Kamesh; Avasarala, Sreedevi; Van Scoyk, Michelle; Karuppusamy Rathinam, Manoj Kumar; Tauler, Jordi; Borowicz, Stanley; Winn, Robert A

    2014-01-01

    Protein arginine methylation is one of the most abundant post-translational modifications in the nucleus. Protein arginine methylation can be identified and/or determined via proteomic approaches, and/or immunoblotting with methyl-arginine specific antibodies. However, these techniques sometimes can be misleading and often provide false positive results. Most importantly, these techniques cannot provide direct evidence in support of the PRMT substrate specificity. In vitro methylation assays, on the other hand, are useful biochemical assays, which are sensitive, and consistently reveal if the identified proteins are indeed PRMT substrates. A typical in vitro methylation assay includes purified, active PRMTs, purified substrate and a radioisotope labeled methyl donor (S-adenosyl-L-[methyl-(3)H] methionine). Here we describe a step-by-step protocol to isolate catalytically active PRMT1, a ubiquitously expressed PRMT family member. The methyl transferase activities of the purified PRMT1 were later tested on Ras-GTPase activating protein binding protein 1 (G3BP1), a known PRMT substrate, in the presence of S-adenosyl-L-[methyl-(3)H] methionine as the methyl donor. This protocol can be employed not only for establishing the methylation status of novel physiological PRMT1 substrates, but also for understanding the basic mechanism of protein arginine methylation. PMID:25350748

  8. Methyl Bromide and Methyl Chloride Degradation in the Southern Ocean

    Microsoft Academic Search

    R. Tokarczyk; K. Goodwin; E. S. Saltzman

    2002-01-01

    The oceans are both a source and sink for atmospheric methyl bromide and methyl chloride and play a significant role in the atmospheric budgets of these ozone-active gases. We have carried out a series of shipboard studies designed to characterize the loss rate of methyl halides in the surface ocean, using a 13C stable isotope incubation technique. Here we present

  9. DNA Methylation and Cancer Diagnosis

    PubMed Central

    Delpu, Yannick; Cordelier, Pierre; Cho, William C.; Torrisani, Jérôme

    2013-01-01

    DNA methylation is a major epigenetic modification that is strongly involved in the physiological control of genome expression. DNA methylation patterns are largely modified in cancer cells and can therefore be used to distinguish cancer cells from normal tissues. This review describes the main technologies available for the detection and the discovery of aberrantly methylated DNA patterns. It also presents the different sources of biological samples suitable for DNA methylation studies. We discuss the interest and perspectives on the use of DNA methylation measurements for cancer diagnosis through examples of methylated genes commonly documented in the literature. The discussion leads to our consideration for why DNA methylation is not commonly used in clinical practice through an examination of the main requirements that constitute a reliable biomarker. Finally, we describe the main DNA methylation inhibitors currently used in clinical trials and those that exhibit promising results. PMID:23873296

  10. Boryl-assisted hydrogenolysis of a nickel-methyl bond.

    PubMed

    Curado, Natalia; Maya, Celia; López-Serrano, Joaquín; Rodríguez, Amor

    2014-12-25

    A stable nickel(II) methyl complex containing a diphosphino-boryl (PBP) pincer ligand is described. Mechanistic studies on the hydrogenolysis of the Ni-Me bond suggest a metal ligand cooperation mechanism that involves the intermediacy of a ?-B-H Ni(0) species that further undergoes B-H oxidative addition to form a Ni(II) hydride complex. PMID:25364792

  11. Kapok oil methyl esters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The increased need for biodiesel feedstocks has caused various vegetable oils to be examined for this purpose. In the present work, the methyl esters of kapok (Ceiba pentandra) oil were prepared. The essential fuel properties were comprehensively determined and evaluated in comparison to specificati...

  12. Kenaf methyl esters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Additional or alternative feedstocks are one of the major areas of interest regarding biodiesel. In this paper, for the first time, the fuel properties of kenaf (Hibiscus cannabinus L.) seed oil methyl esters are comprehensively reported. This biodiesel is also relatively unique by containing small ...

  13. Understanding the relationship between DNA methylation and histone lysine methylation?

    PubMed Central

    Rose, Nathan R.; Klose, Robert J.

    2014-01-01

    DNA methylation acts as an epigenetic modification in vertebrate DNA. Recently it has become clear that the DNA and histone lysine methylation systems are highly interrelated and rely mechanistically on each other for normal chromatin function in vivo. Here we examine some of the functional links between these systems, with a particular focus on several recent discoveries suggesting how lysine methylation may help to target DNA methylation during development, and vice versa. In addition, the emerging role of non-methylated DNA found in CpG islands in defining histone lysine methylation profiles at gene regulatory elements will be discussed in the context of gene regulation. This article is part of a Special Issue entitled: Methylation: A Multifaceted Modification — looking at transcription and beyond. PMID:24560929

  14. The first structural determination of a Copper (II) complex containing the ligand [1-(4-((1H-benzo[d][1,2,3]triazol-2(3H)-yl)methyl)benzyl)-1H-benzo[d][1,2,3]triazole

    Microsoft Academic Search

    George E. Kostakis; Pantelis Xydias; Ebbe Nordlander; John C. Plakatouras

    The reaction of the ligand [1-(4-((1H-benzo[d][1,2,3]triazol-2(3H)-yl)methyl)benzyl)-1H-benzo[d][1,2,3]triazole] (L) with CuCl2 in acetonitrile yields a dinuclear copper (II) complex [Cu2Cl4L2] · 2CH3CN (1 ·2CH3CN), which has been characterized by elemental analysis, powder and single crystal X-ray diffraction, thermal gravimetric analysis as well as IR, UV-Vis and EPR spectroscopy The crystal structure reveals that the metal coordination geometry is best described as square

  15. Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni

    PubMed Central

    Geyer, Kathrin K.; Rodríguez López, Carlos M.; Chalmers, Iain W.; Munshi, Sabrina E.; Truscott, Martha; Heald, James; Wilkinson, Mike J.; Hoffmann, Karl F.

    2011-01-01

    Similar to other metazoan pathogens, Schistosoma mansoni undergoes transcriptional and developmental regulation during its complex lifecycle and host interactions. DNA methylation as a mechanism to control these processes has, to date, been discounted in this parasite. Here we show the first evidence for cytosine methylation in the S. mansoni genome. Transcriptional coregulation of novel DNA methyltransferase (SmDnmt2) and methyl-CpG-binding domain proteins mirrors the detection of cytosine methylation abundance and implicates the presence of a functional DNA methylation machinery. Genome losses in cytosine methylation upon SmDnmt2 silencing and the identification of a hypermethylated, repetitive intron within a predicted forkhead gene confirm this assertion. Importantly, disruption of egg production and egg maturation by 5-azacytidine establishes an essential role for 5-methylcytosine in this parasite. These findings provide the first functional confirmation for this epigenetic modification in any worm species and link the cytosine methylation machinery to platyhelminth oviposition processes. PMID:21829186

  16. Spectroscopic and biological studies of new binuclear metal complexes of a tridentate ONS hydrazone ligand derived from 4-amino-6-methyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one and 4,6-diacetylresorcinol

    NASA Astrophysics Data System (ADS)

    Adly, Omima M. I.; Emara, Adel A. A.

    2014-11-01

    The binuclear hydrazone, H2L, ligand derived from 4-amino-6-methyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one and 4,6-diacetylresorcinol, in the molar ratio 2:1, and its copper(II), nickel(II), cobalt(II), zinc(II), cadmium(II), cerium(III), iron(III), oxovanadium(IV) and dioxouranium(VI) complexes have been synthesized. Structures of the ligand and its metal complexes were characterized by elemental analyses, spectral (infrared, electronic, mass, 1H NMR and ESR) data, magnetic susceptibility, molar conductivity measurements and thermal gravimetric analysis (TGA). The ligand acts as dibasic with two ONS tridentate sites. The bonding sites are the azomethine nitrogen, phenolate oxygen and sulfur atoms. The metal complexes exhibit different geometrical arrangements such as square planer, tetrahedral and octahedral. The Coats-Redfern equation was used to calculate the kinetic and thermodynamic parameters for the different thermal decomposition steps of some complexes. The ligand and its metal complexes showed antimicrobial activity towards Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram-negative bacteria (Salmonella typhimurium and Escherichia coli), yeast (Candida albicans) and fungus (Aspergillus fumigatus). Structural parameters of the ligand and its metal complexes were theoretically computed on the basis of semiempirical PM3 level, and the results were correlated with their experimental data.

  17. Spectroscopic and biological studies of new binuclear metal complexes of a tridentate ONS hydrazone ligand derived from 4-amino-6-methyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one and 4,6-diacetylresorcinol.

    PubMed

    Adly, Omima M I; Emara, Adel A A

    2014-11-11

    The binuclear hydrazone, H2L, ligand derived from 4-amino-6-methyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one and 4,6-diacetylresorcinol, in the molar ratio 2:1, and its copper(II), nickel(II), cobalt(II), zinc(II), cadmium(II), cerium(III), iron(III), oxovanadium(IV) and dioxouranium(VI) complexes have been synthesized. Structures of the ligand and its metal complexes were characterized by elemental analyses, spectral (infrared, electronic, mass, 1H NMR and ESR) data, magnetic susceptibility, molar conductivity measurements and thermal gravimetric analysis (TGA). The ligand acts as dibasic with two ONS tridentate sites. The bonding sites are the azomethine nitrogen, phenolate oxygen and sulfur atoms. The metal complexes exhibit different geometrical arrangements such as square planer, tetrahedral and octahedral. The Coats-Redfern equation was used to calculate the kinetic and thermodynamic parameters for the different thermal decomposition steps of some complexes. The ligand and its metal complexes showed antimicrobial activity towards Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram-negative bacteria (Salmonella typhimurium and Escherichia coli), yeast (Candida albicans) and fungus (Aspergillus fumigatus). Structural parameters of the ligand and its metal complexes were theoretically computed on the basis of semiempirical PM3 level, and the results were correlated with their experimental data. PMID:24858350

  18. Differential methylation of the TRPA1 promoter in pain sensitivity.

    PubMed

    Bell, J T; Loomis, A K; Butcher, L M; Gao, F; Zhang, B; Hyde, C L; Sun, J; Wu, H; Ward, K; Harris, J; Scollen, S; Davies, M N; Schalkwyk, L C; Mill, J; Williams, F M K; Li, N; Deloukas, P; Beck, S; McMahon, S B; Wang, J; John, S L; Spector, T D

    2014-01-01

    Chronic pain is a global public health problem, but the underlying molecular mechanisms are not fully understood. Here we examine genome-wide DNA methylation, first in 50 identical twins discordant for heat pain sensitivity and then in 50 further unrelated individuals. Whole-blood DNA methylation was characterized at 5.2 million loci by MeDIP sequencing and assessed longitudinally to identify differentially methylated regions associated with high or low pain sensitivity (pain DMRs). Nine meta-analysis pain DMRs show robust evidence for association (false discovery rate 5%) with the strongest signal in the pain gene TRPA1 (P=1.2 × 10(-13)). Several pain DMRs show longitudinal stability consistent with susceptibility effects, have similar methylation levels in the brain and altered expression in the skin. Our approach identifies epigenetic changes in both novel and established candidate genes that provide molecular insights into pain and may generalize to other complex traits. PMID:24496475

  19. Differential methylation of the TRPA1 promoter in pain sensitivity

    PubMed Central

    Bell, J.T.; Loomis, A.K.; Butcher, L.M.; Gao, F.; Zhang, B.; Hyde, C.L.; Sun, J.; Wu, H.; Ward, K.; Harris, J.; Scollen, S.; Davies, M.N.; Schalkwyk, L.C.; Mill, J.; Ahmadi, Kourosh R.; Ainali, Chrysanthi; Barrett, Amy; Bataille, Veronique; Bell, Jordana T.; Buil, Alfonso; Deloukas, Panos; Dermitzakis, Emmanoil T.; Dimas, Antigone S.; Durbin, Richard; Glass, Daniel; Grundberg, Elin; Hassanali, Neelam; Hedman, Asa K.; Ingle, Catherine; Knowles, David; Krestyaninova, Maria; Lindgren, Cecilia M.; Lowe, Christopher E.; McCarthy, Mark I.; Meduri, Eshwar; di Meglio, Paola; Min, Josine L.; Montgomery, Stephen B.; Nestle, Frank O.; Nica, Alexandra C.; Nisbet, James; O’Rahilly, Stephen; Parts, Leopold; Potter, Simon; Sekowska, Magdalena; Shin, So-Youn; Small, Kerrin S.; Soranzo, Nicole; Spector, Tim D.; Surdulescu, Gabriela; Travers, Mary E.; Tsaprouni, Loukia; Tsoka, Sophia; Wilk, Alicja; Yang, Tsun-Po; Zondervan, Krina T.; Williams, F.M.K.; Li, N.; Deloukas, P.; Beck, S.; McMahon, S.B.; Wang, J.; John, S.L.; Spector, T.D.

    2014-01-01

    Chronic pain is a global public health problem, but the underlying molecular mechanisms are not fully understood. Here we examine genome-wide DNA methylation, first in 50 identical twins discordant for heat pain sensitivity and then in 50 further unrelated individuals. Whole-blood DNA methylation was characterized at 5.2 million loci by MeDIP sequencing and assessed longitudinally to identify differentially methylated regions associated with high or low pain sensitivity (pain DMRs). Nine meta-analysis pain DMRs show robust evidence for association (false discovery rate 5%) with the strongest signal in the pain gene TRPA1 (P=1.2 × 10?13). Several pain DMRs show longitudinal stability consistent with susceptibility effects, have similar methylation levels in the brain and altered expression in the skin. Our approach identifies epigenetic changes in both novel and established candidate genes that provide molecular insights into pain and may generalize to other complex traits. PMID:24496475

  20. Antagonism between DNA and H3K27 Methylation at the Imprinted Rasgrf1 Locus

    PubMed Central

    McLean, Chelsea M.; Dokshin, Gregoriy A.; Persson, Jenna M.; Herman, Herry; Pasini, Diego; Miró, Xavier; Donohoe, Mary E.; Lee, Jeannie T.; Helin, Kristian; Soloway, Paul D.

    2008-01-01

    At the imprinted Rasgrf1 locus in mouse, a cis-acting sequence controls DNA methylation at a differentially methylated domain (DMD). While characterizing epigenetic marks over the DMD, we observed that DNA and H3K27 trimethylation are mutually exclusive, with DNA and H3K27 methylation limited to the paternal and maternal sequences, respectively. The mutual exclusion arises because one mark prevents placement of the other. We demonstrated this in five ways: using 5-azacytidine treatments and mutations at the endogenous locus that disrupt DNA methylation; using a transgenic model in which the maternal DMD inappropriately acquired DNA methylation; and by analyzing materials from cells and embryos lacking SUZ12 and YY1. SUZ12 is part of the PRC2 complex, which is needed for placing H3K27me3, and YY1 recruits PRC2 to sites of action. Results from each experimental system consistently demonstrated antagonism between H3K27me3 and DNA methylation. When DNA methylation was lost, H3K27me3 encroached into sites where it had not been before; inappropriate acquisition of DNA methylation excluded normal placement of H3K27me3, and loss of factors needed for H3K27 methylation enabled DNA methylation to appear where it had been excluded. These data reveal the previously unknown antagonism between H3K27 and DNA methylation and identify a means by which epigenetic states may change during disease and development. PMID:18670629

  1. Quantitative reconstruction of leukocyte subsets using DNA methylation

    PubMed Central

    2014-01-01

    Background Cell lineage-specific DNA methylation patterns distinguish normal human leukocyte subsets and can be used to detect and quantify these subsets in peripheral blood. We have developed an approach that uses DNA methylation to simultaneously quantify multiple leukocyte subsets, enabling investigation of immune modulations in virtually any blood sample including archived samples previously precluded from such analysis. Here we assess the performance characteristics and validity of this approach. Results Using Illumina Infinium HumanMethylation27 and VeraCode GoldenGate Methylation Assay microarrays, we measure DNA methylation in leukocyte subsets purified from human whole blood and identify cell lineage-specific DNA methylation signatures that distinguish human T cells, B cells, NK cells, monocytes, eosinophils, basophils and neutrophils. We employ a bioinformatics-based approach to quantify these cell types in complex mixtures, including whole blood, using DNA methylation at as few as 20 CpG loci. A reconstruction experiment confirms that the approach could accurately measure the composition of mixtures of human blood leukocyte subsets. Applying the DNA methylation-based approach to quantify the cellular components of human whole blood, we verify its accuracy by direct comparison to gold standard immune quantification methods that utilize physical, optical and proteomic characteristics of the cells. We also demonstrate that the approach is not affected by storage of blood samples, even under conditions prohibiting the use of gold standard methods. Conclusions Cell mixture distributions within peripheral blood can be assessed accurately and reliably using DNA methylation. Thus, precise immune cell differential estimates can be reconstructed using only DNA rather than whole cells. PMID:24598480

  2. Methylation signature of lymph node metastases in breast cancer patients

    PubMed Central

    2012-01-01

    Background Invasion and metastasis are two important hallmarks of malignant tumors caused by complex genetic and epigenetic alterations. The present study investigated the contribution of aberrant methylation profiles of cancer related genes, APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P14 (ARF), P16 (CDKN2A), P21 (CDKN1A), PTEN, and TIMP3, in the matched axillary lymph node metastasis in comparison to the primary tumor tissue and the adjacent normal tissue from the same breast cancer patients to identify the potential of candidate genes methylation as metastatic markers. Methods The quantitative methylation analysis was performed using the SEQUENOM’s EpiTYPER™ assay which relies on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Results The quantitative DNA methylation analysis of the candidate genes showed higher methylation proportion in the primary tumor tissue than that of the matched normal tissue and the differences were significant for the APC, BIN1, BMP6, BRCA1, CST6, ESR-b, P16, PTEN and TIMP3 promoter regions (P<0.05). Among those candidate methylated genes, APC, BMP6, BRCA1 and P16 displayed higher methylation proportion in the matched lymph node metastasis than that found in the normal tissue (P<0.05). The pathway analysis revealed that BMP6, BRCA1 and P16 have a role in prevention of neoplasm metastasis. Conclusions The results of the present study showed methylation heterogeneity between primary tumors and metastatic lesion. The contribution of aberrant methylation alterations of BMP6, BRCA1 and P16 genes in lymph node metastasis might provide a further clue to establish useful biomarkers for screening metastasis. PMID:22695536

  3. Differentially Methylated Regions of Imprinted Genes in Prenatal, Perinatal and Postnatal Human Tissues

    Microsoft Academic Search

    Susan K. Murphy; Zhiqing Huang; Cathrine Hoyo

    2012-01-01

    Epigenetic plasticity in relation to in utero exposures may mechanistically explain observed differences in the likelihood of developing common complex diseases including hypertension, diabetes and cardiovascular disease through the cumulative effects of subtle alterations in gene expression. Imprinted genes are essential mediators of growth and development and are characterized by differentially methylated regulatory regions (DMRs) that carry parental allele-specific methylation

  4. Phencyclidine-induced discriminative stimulus is mediated via phencyclidine binding sites on the N-methyl- d-aspartate receptor-ion channel complex, not via sigma 1 receptors

    Microsoft Academic Search

    Akitomo Mori; Yukihiro Noda; Takayoshi Mamiya; Yoshiaki Miyamoto; Akira Nakajima; Hiroshi Furukawa; Toshitaka Nabeshima

    2001-01-01

    The effects of several N-methyl-d-aspartate (NMDA) receptor- and sigma receptor-related compounds on the discriminative stimulus effects of phencyclidine (PCP) were examined in rats trained to discriminate PCP (1.5 mg\\/kg, i.p.) from saline under a two-lever fixed ratio 20 schedule of food reinforcement. PCP produced a dose-dependent increase in PCP-appropriate responding. A non-competitive NMDA receptor antagonist, dizocilpine (0.2 mg\\/kg, i.p.) and

  5. Differentially Methylated Regions of Imprinted Genes in Prenatal, Perinatal and Postnatal Human Tissues

    PubMed Central

    Murphy, Susan K.; Huang, Zhiqing; Hoyo, Cathrine

    2012-01-01

    Epigenetic plasticity in relation to in utero exposures may mechanistically explain observed differences in the likelihood of developing common complex diseases including hypertension, diabetes and cardiovascular disease through the cumulative effects of subtle alterations in gene expression. Imprinted genes are essential mediators of growth and development and are characterized by differentially methylated regulatory regions (DMRs) that carry parental allele-specific methylation profiles. This theoretical 50% level of methylation provides a baseline from which endogenously- or exogenously-induced deviations in methylation can be detected. We quantified DNA methylation at imprinted gene DMRs in a large panel of human conceptal tissues, in matched buccal cell specimens collected at birth and at one year of age, and in the major cell fractions of umbilical cord blood to assess the stability of methylation at these regions. DNA methylation was measured using validated pyrosequencing assays at seven DMRs regulating the IGF2/H19, DLK1/MEG3, MEST, NNAT and SGCE/PEG10 imprinted domains. DMR methylation did not significantly differ for the H19, MEST and SGCE/PEG10 DMRs across all conceptal tissues analyzed (ANOVA p>0.10). Methylation differences at several DMRs were observed in tissues from brain (IGF2 and MEG3-IG DMRs), liver (IGF2 and MEG3 DMRs) and placenta (both DLK1/MEG3 DMRs and NNAT DMR). In most infants, methylation profiles in buccal cells at birth and at one year of age were comparable, as was methylation in the major cell fractions of umbilical cord blood. Several infants showed temporal deviations in methylation at multiple DMRs. Similarity of inter-individual and intra-individual methylation at some, but not all of the DMRs analyzed supports the possibility that methylation of these regions can serve as useful biosensors of exposure. PMID:22808284

  6. Genomic DNA methylation in various developmental stages of two plant pathogenic fungi

    E-print Network

    Schliesing, Laura Jo

    1990-01-01

    -adenosylmethionine (SAM) as a source of the methyl group, and have specific target sites for modification. Cytosines followed on the 3'-side by a guanosine (CpG) are targets for methylation in mam- mals, while bacterial and bacteriophage methylases all have more... complex sequence requirements. In plants, there is extensive methylation of both CpG and CpNpG sequences (Gruenbaum et al. , 1981). No complete methylation of all methylatable This thesis follows the format of Cell sequences has been found...

  7. Neural tube defects, folic acid and methylation.

    PubMed

    Imbard, Apolline; Benoist, Jean-François; Blom, Henk J

    2013-09-01

    Neural tube defects (NTDs) are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s) underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects. PMID:24048206

  8. Neural Tube Defects, Folic Acid and Methylation

    PubMed Central

    Imbard, Apolline; Benoist, Jean-François; Blom, Henk J.

    2013-01-01

    Neural tube defects (NTDs) are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s) underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects. PMID:24048206

  9. DNA methylation and human disease

    Microsoft Academic Search

    Keith D. Robertson

    2005-01-01

    DNA methylation is a crucial epigenetic modification of the genome that is involved in regulating many cellular processes. These include embryonic development, transcription, chromatin structure, X chromosome inactivation, genomic imprinting and chromosome stability. Consistent with these important roles, a growing number of human diseases have been found to be associated with aberrant DNA methylation. The study of these diseases has

  10. The Potential Role of DNA Methylation in Abdominal Aortic Aneurysms

    PubMed Central

    Ryer, Evan J.; Ronning, Kaitryn E.; Erdman, Robert; Schworer, Charles M.; Elmore, James R.; Peeler, Thomas C.; Nevius, Christopher D.; Lillvis, John H.; Garvin, Robert P.; Franklin, David P.; Kuivaniemi, Helena; Tromp, Gerard

    2015-01-01

    Abdominal aortic aneurysm (AAA) is a complex disorder that has a significant impact on the aging population. While both genetic and environmental risk factors have been implicated in AAA formation, the precise genetic markers involved and the factors influencing their expression remain an area of ongoing investigation. DNA methylation has been previously used to study gene silencing in other inflammatory disorders and since AAA has an extensive inflammatory component, we sought to examine the genome-wide DNA methylation profiles in mononuclear blood cells of AAA cases and matched non-AAA controls. To this end, we collected blood samples and isolated mononuclear cells for DNA and RNA extraction from four all male groups: AAA smokers (n = 11), AAA non-smokers (n = 9), control smokers (n = 10) and control non-smokers (n = 11). Methylation data were obtained using the Illumina 450k Human Methylation Bead Chip and analyzed using the R language and multiple Bioconductor packages. Principal component analysis and linear analysis of CpG island subsets identified four regions with significant differences in methylation with respect to AAA: kelch-like family member 35 (KLHL35), calponin 2 (CNN2), serpin peptidase inhibitor clade B (ovalbumin) member 9 (SERPINB9), and adenylate cyclase 10 pseudogene 1 (ADCY10P1). Follow-up studies included RT-PCR and immunostaining for CNN2 and SERPINB9. These findings are novel and suggest DNA methylation may play a role in AAA pathobiology. PMID:25993294

  11. COMPARATIVE IN VITRO METHYLATION OF TRIVALENT AND PENTAVALENT ARSENIC SPECIES

    EPA Science Inventory

    The time course and extent of methylation of 1 uM arsenite (iAsIII), arsenate (iAsV), methylarsenite (MeAsV), methylarsenate (MeAsV) and MeAsIII - diglutathione complex (MAsIII(GS)2) were examined in an in vitro assay system that contained rat liver cytosol. recursor arsenicals a...

  12. Methyl Halide Production by Fungi

    NASA Astrophysics Data System (ADS)

    Dailey, G. D.; Varner, R. K.; Blanchard, R. O.; Sive, B. C.; Crill, P. M.

    2005-12-01

    Methyl chloride (CH3Cl), methyl bromide (CH3Br) and methyl iodide (CH3I) are methyl halide gases that contribute significant amounts of halogen radicals to the atmosphere. In an effort to better understand the global budget of methyl halides and their impact on the atmosphere, we need to identify the natural sources in addition to the known anthropogenic sources of these compounds. We are investigating the role of fungi in the production of methyl halides in the soils and wetlands in southern New Hampshire, USA. Previous research has shown that wood decay fungi and ectomycorrhizal fungi, which are within a group of fungi called basidiomycetes, emit methyl halides. In our study, measurements of headspace gas extracted from flasks containing fungi grown in culture demonstrate that a variety of fungi, including basidiomycetes and non-basidiomycetes, emit methyl halides. Our research sites include four ecosystems: an agricultural field, a temperate forest, a fresh water wetland, and coastal salt marshes. We have collected and isolated fungi at each site by culturing tissue samples of fruiting bodies and plant material, by using wood baits, and from the direct culture of soil. We compared the rates of methyl halide emissions from the fungi in the four ecosystems. In addition, we measured emissions from previously assayed fungal isolates after reintroducing them to sterilized soils that were collected from their original environments. Fungal biomass was determined by substrate-induced respiration (SIR). The emission rate by the fungus was determined by a linear regression of the concentration of methyl halide in the sample headspace over time divided by the fungal biomass.

  13. Accounting for Population Stratification in DNA Methylation Studies

    PubMed Central

    Barfield, Richard T.; Almli, Lynn M.; Kilaru, Varun; Smith, Alicia K.; Mercer, Kristina B.; Duncan, Richard; Klengel, Torsten; Mehta, Divya; Binder, Elisabeth B.; Epstein, Michael P.; Ressler, Kerry J.; Conneely, Karen N.

    2014-01-01

    DNA methylation is an important epigenetic mechanism that has been linked to complex disease and is of great interest to researchers as a potential link between genome, environment, and disease. As the scale of DNA methylation association studies approaches that of genome-wide association studies (GWAS), issues such as population stratification will need to be addressed. It is well-documented that failure to adjust for population stratification can lead to false positives in genetic association studies, but population stratification is often unaccounted for in DNA methylation studies. Here, we propose several approaches to correct for population stratification using principal components from different subsets of genome-wide methylation data. We first illustrate the potential for confounding due to population stratification by demonstrating widespread associations between DNA methylation and race in 388 individuals (365 African American and 23 Caucasian). We subsequently evaluate the performance of our principal-components approaches and other methods in adjusting for confounding due to population stratification. Our simulations show that 1) all of the methods considered are effective at removing inflation due to population stratification, and 2) maximum power can be obtained with SNP-based principal components, followed by methylation-based principal components, which out-perform both surrogate variable analysis and genomic control. Among our different approaches to computing methylation-based principal components, we find that principal components based on CpG sites chosen for their potential to proxy nearby SNPs can provide a powerful and computationally efficient approach to adjustment for population stratification in DNA methylation studies when genome-wide SNP data are unavailable. PMID:24478250

  14. Selectivity in metal-carbon bond protonolysis in p-tolyl- (or methyl)-cycloplatinated(II) complexes: kinetics and mechanism of the uncatalyzed isomerization of the resulting Pt(II) products.

    PubMed

    Haghighi, Mohsen Golbon; Nabavizadeh, S Masoud; Rashidi, Mehdi; Kubicki, Maciej

    2013-10-01

    Reaction of each of the known starting complexes [PtR(C^N)(SMe2)], 1, in which R = Me or p-MeC6H4 and C^N is either ppy (deprotonated 2-phenylpyridine) or bhq (deprotonated benzo[h]quinoline), with one equivalent of CF3CO2H, gave the complexes [Pt(C^N)(CF3CO2)(SMe2)], 3 (C^N = ppy, 3a; bhq, 3b). The bis-chelate complexes [Pt(C^N)(P^P)](CF3CO2), 4, were obtained by reaction of complexes 3 with one equivalent of either of the P^P bisphosphine reagents, dppf = 1,1'-bis(diphenylphosphino)ferrocene or dppe = bis(diphenylphosphino)ethane. Complexes 4 were alternatively made by reaction of the complexes [PtMe(?(1)C-C^N)(P^P)], 2, with one equivalent of CF3CO2H. When the complex 3b was reacted with 0.5 equivalents of dppe, 0.5 equivalents of the related bis-chelate product, 4d, formed along with 0.5 equivalents of the unreacted starting complex 3b. In contrast, when the complex 3b was reacted with 0.5 equivalents of dppf, then the dimeric complex [Pt2(bhq)2(CF3CO2)2(?-dppf)], 5, formed in pure form. In all the above-mentioned acid reactions, the M-R bond rather than the M-C bond of the cycloplatinated complex is cleaved. When the PPh3 analogues of complexes 1, i.e. the complexes [PtR(C^N)(PPh3)], 6, in which C^N is ppy or tpy = deprotonated 2-p-tolylpyridine, were reacted with one equivalent of CF3CO2H, the course of the reaction reversed and the M-C bonds of the cycloplatinated complexes are cleaved rather than the M-R bonds. The latter reaction gave [PtR(?(1)N-HC^N)(PPh3)(CF3CO2)], as an equilibrium mixture of two isomers 7 and 8. Crystal structures of the typical complexes show a variety of extensive intermolecular hydrogen bonding involving C-H bonds from the different ligands and electronegative atoms (O or F) from the CF3CO2 moiety. On the basis of data obtained from kinetic studies (using (1)H NMR spectroscopy), a dissociative mechanism is proposed for the case of the 7c/8c isomerization process, involving dissociation of the ?(1)N-Htpy neutral ligand, rather than the alternative route of PPh3 or CF3CO2 ligand dissociation. PMID:23887622

  15. Molecular Structure of Methyl mercaptan

    NSDL National Science Digital Library

    2003-06-03

    Methyl mercaptan is a colorless, flammable and volatile sulfur compound that is responsible for the rotten cabbage or burnt rubber aroma. This substance can be found in the blood, brain, and other tissues of humans and other animals, it is released from animal feces and occurs naturally in foods such as nuts and cheeses. The formation of methyl mercaptan is commonly noted as a problem in the process of the post-fermentation of wine. Despite the repulsive smell methyl mercaptan is used as a gas odorant, as an intermediate in the production of fungicides, as jet fuel additives, flavoring agents, plastics, as well as in the synthesis of methionines, and as catalysts.

  16. Formation of methyl methacrylate from methyl propionate and methanol

    Microsoft Academic Search

    Mamoru Ai

    2006-01-01

    The formation of methyl methacrylate (MMA) was studied in a vapor-phase reaction between methyl propionate (MP) and methanol without using any sources of formaldehyde. Silica-supported CsOH doped with a small amount of silver Ag was found to be the best catalyst. The optimum Ag\\/Cs\\/Si atomic ratio was 4–10\\/20–25\\/1000. When the reaction was performed in the absence of oxygen in the

  17. Rice Allelopathy Induced by Methyl Jasmonate and Methyl Salicylate

    Microsoft Academic Search

    Hai Hong Bi; Ren Sen Zeng; Li Ming Su; Min An; Shi Ming Luo

    2007-01-01

    Methyl jasmonate (MeJA) and methyl salicylate (MeSA) are important signaling molecules that induce plant defense against insect\\u000a herbivores and microbial pathogens. We tested the hypothesis that allelopathy is an inducible defense mechanism, and that\\u000a the JA and SA signaling pathways may activate allelochemicals release. Exogenous application of MeJA and MeSA to rice (Oryza sativa L.) enhanced rice allelopathic potential and

  18. Methyl chloride and methyl bromide degradation in the Southern Ocean

    Microsoft Academic Search

    Ryszard Tokarczyk; Kelly D. Goodwin; Eric S. Saltzman

    2003-01-01

    This study presents shipboard measurements of the loss rate constants of methyl bromide and methyl chloride in surface seawater in the Southern Ocean, using a 13C stable isotope incubation technique. The measurements were made during October-December, 2001, on a cruise track extending from Hobart, Tasmania to Buchanan Bay (Mertz Glacier) at the coast of Antarctica (46-67°S, 138-145°E). Significant loss rates

  19. Methyl chloride and methyl bromide degradation in the Southern Ocean

    Microsoft Academic Search

    Ryszard Tokarczyk; Kelly D. Goodwin; Eric S. Saltzman

    2003-01-01

    This study presents shipboard measurements of the loss rate constants of methyl bromide and methyl chloride in surface seawater in the Southern Ocean, using a 13C stable isotope incubation technique. The measurements were made during October–December, 2001, on a cruise track extending from Hobart, Tasmania to Buchanan Bay (Mertz Glacier) at the coast of Antarctica (46–67°S, 138–145°E). Significant loss rates

  20. Hydridomethyl iridium complex

    DOEpatents

    Bergman, Robert G. (P.O. Box 7141, San Francisco, CA 94120-7141); Buchanan, J. Michael (P.O. Box 7141, San Francisco, CA 94120-7141); Stryker, Jeffrey M. (P.O. Box 7141, San Francisco, CA 94120-7141); Wax, Michael J. (P.O. Box 7141, San Francisco, CA 94120-7141)

    1989-01-01

    A process for functionalizing methane comprising: (a) reacting methane with a hydridoalkyl metal complex of the formula: CpIr[P(R.sub.1).sub.3 ]H(R.sub.2) wherein Cp represents a cyclopentadienyl or alkylcyclopentadienyl radical having from 1 to 5 carbon atoms; Ir represents an iridium atom; P represents a phosphorus atom; R.sub.1 represents an alkyl group; R.sub.2 represents an alkyl group having at least two carbon atoms; and H represents a hydrogen atom, in the presence of a liquid alkane R.sub.3 H having at least three carbon atoms to form a hydridomethyl complex of the formula: CpIr[P(R.sub.1).sub.3 ]HMe where Me represents a methyl radical. (b) reacting said hydridomethyl complex with an organic halogenating agent such as a tetrahalomethane or a haloform of the formulas: CX'X"X'"X"" or CHX'X"X'"; wherein X', X", X"', and X"" represent halogens selected from bromine, iodine and chlorine, to halomethyl complex of step (a) having the formula: CpIr[P(R.sub.1).sub.3 ]MeX: (c) reacting said halomethyl complex with a mercuric halide of the formula HgX.sub.2 to form a methyl mercuric halide of the formula HgMeX; and (d) reacting said methyl mercuric halide with a molecular halogen of the formula X.sub.2 to form methyl halide.

  1. Methylation of cysteine in hemoglobin following exposure to methylating agents

    SciTech Connect

    Bailey, E.; Connors, T.A.; Farmer, P.B.; Gorf, S.M.; Rickard, J.

    1981-06-01

    In addition to reacting with biologically important nucleophilic sites in DNA, alkylating agents also interact with amino acids in proteins. Measurements of the extent of formation of these alkyl amino acids may be used as a means of determining exposure to these compounds. The degree of S-methylation of cysteine in hemoglobin was studied following in vivo exposure of rats to methyl methanesulfonate, dimethylnitrosamine, and 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide. A linear dose-response curve was observed for methyl methanesulfonate over a 100-fold dose range. For dimethylnitrosamine, there was a threshold of doses where no methylation could be detected, and a curved dose-response curve was obtained. At high doses, the degree of methylation of hemoglobin cysteine was 7-fold lower than that with methyl methanesulfonate. In vivo, no alkylation could be observed with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide; however, the existence of naturally occurring S-methylcysteine in the rat hemoglobin may have overshadowed small increases in alkylation arising from exposure to this compound. The natural occurrence of S-methylcysteine was studied in 13 species, and amounts ranging from 5.6 nmol/g globin (hamster) to 481 nmol/g globin (partridge) were observed. The reason for its occurrence is unknown but is under investigation.

  2. DNA methylation in breast and colorectal cancers

    Microsoft Academic Search

    Anshu Agrawal; Richard F Murphy; Devendra K Agrawal

    2007-01-01

    DNA methylation is one of several epigenetic changes observed in cells. Aberrant methylation of tumor suppressor genes, proto-oncogenes, and vital cell cycle genes has led many scientists to investigate the underlying cellular mechanisms of DNA methylation under normal and pathological conditions. Although DNA methylation is necessary for normal mammalian embryogenesis, both hypo- and hypermethylation of DNA are frequently observed in

  3. Naturally occurring methyl salicylate glycosides.

    PubMed

    Mao, Ping; Liu, Zizhen; Xie, Meng; Jiang, Rui; Liu, Weirui; Wang, Xiaohong; Meng, Shen; She, Gaimei

    2014-01-01

    As an important part of non steroids anti-inflammation drug (NSAIDs), salicylate has developed from natural substance salicylic acid to natrium salicylicum, to aspirin. Now, methyl salicylate glycoside, a new derivative of salicylic acid, is modified with a -COOH group integrated one methyl radical into formic ether, and a -OH linked with a monosaccharide, a disaccharide or a trisaccharide unit by glycosidic linkage. It has the similar pharmacological activities, anti-inflammatory, analgesic, antipyretic and antithrombotic as the previous salicylates' without resulting in serious side effects, particularly the gastrointestinal toxicity. Owing to the superiority of those significant bioactivities, methyl salicylate glycosides have became a hot research area in NSAIDs for several years. This paper compiles all 9 naturally occurring methyl salicylate glycosides, their distribution of the resource and pharmacological mechanism, which could contribute to the new drug discovery. PMID:24329991

  4. Adenine Methylation in Eukaryotic DNA

    Microsoft Academic Search

    B. F. Vanyushin

    2005-01-01

    N6-Methyladenine (m6A) has been found in DNAs of various eukaryotes (algae, fungi, protozoa, and higher plants). Like bacterial DNA, DNAs of these organisms are subject to enzymatic modification (methylation) not only at cytosine, but also at adenine bases. There is indirect evidence that adenine methylation of the genome occurs in animals as well. In plants, m6A was detected in total,

  5. Synthesis, spectral, antitumor, antioxidant and antimicrobial studies on Cu(II), Ni(II) and Co(II) complexes of 4-[(1H-Benzoimidazol-2-ylimino)-methyl]-benzene-1,3-diol.

    PubMed

    El-Wakiel, Nadia; El-Keiy, Mai; Gaber, Mohamed

    2015-08-01

    A new Schiff base of 2-aminobenzimidazole with 2,4-dihydroybezaldehyde (H3L), and its Cu(II), Ni(II) and Co(II) complexes have been synthesized and characterized by elemental analyses, molar conductance, thermal analysis (TGA), inductive coupled plasma (ICP), magnetic moment measurements, IR, EI-mass, UV-Vis. and ESR spectral studies. On the basis of spectral studies and analytical data, it is evident that the Schiff base acts as dibasic tridentate ligand coordinating via deprotonated OH, NH and azomethine nitrogen atom. The results showed that Co(II) and Ni(II) complexes have tetrahedral structure while Cu(II) complexes has octahedral geometry. The kinetic and thermodynamic parameters of the thermal decomposition stages have been evaluated. The studied complexes were tested for their in vitro antimicrobial activities against some bacterial strains. The anticancer activity of the ligand and its metal complexes is evaluated against human liver Carcinoma (HEPG2) cell. These compounds exhibited a moderate and weak activity against the tested HEPG2 cell lines with IC50 of 9.08, 18.2 and 19.7?g/ml for ligand, Cu(II) and Ni(II) complexes, respectively. In vitro antioxidant activity of the newly synthesized compounds has also been evaluated. PMID:25827773

  6. Genome-wide conserved consensus transcription factor binding motifs are hyper-methylated

    PubMed Central

    2010-01-01

    Background DNA methylation can regulate gene expression by modulating the interaction between DNA and proteins or protein complexes. Conserved consensus motifs exist across the human genome ("predicted transcription factor binding sites": "predicted TFBS") but the large majority of these are proven by chromatin immunoprecipitation and high throughput sequencing (ChIP-seq) not to be biological transcription factor binding sites ("empirical TFBS"). We hypothesize that DNA methylation at conserved consensus motifs prevents promiscuous or disorderly transcription factor binding. Results Using genome-wide methylation maps of the human heart and sperm, we found that all conserved consensus motifs as well as the subset of those that reside outside CpG islands have an aggregate profile of hyper-methylation. In contrast, empirical TFBS with conserved consensus motifs have a profile of hypo-methylation. 40% of empirical TFBS with conserved consensus motifs resided in CpG islands whereas only 7% of all conserved consensus motifs were in CpG islands. Finally we further identified a minority subset of TF whose profiles are either hypo-methylated or neutral at their respective conserved consensus motifs implicating that these TF may be responsible for establishing or maintaining an un-methylated DNA state, or whose binding is not regulated by DNA methylation. Conclusions Our analysis supports the hypothesis that at least for a subset of TF, empirical binding to conserved consensus motifs genome-wide may be controlled by DNA methylation. PMID:20875111

  7. DNA methylation increases nucleosome compaction and rigidity.

    PubMed

    Choy, John S; Wei, Sijie; Lee, Ju Yeon; Tan, Song; Chu, Steven; Lee, Tae-Hee

    2010-02-17

    Cytosine methylation on CpG dinucleotides is an essential epigenetic modification in eukaryotes. How DNA methylation modulates nucleosome structure and dynamics has been a long-standing question. We implemented a single-molecule method to monitor the effects of DNA methylation on the structure and dynamics of mononucleosomes. Our studies show that DNA methylation induces a more compact and rigid nucleosome structure, providing a physical basis for how DNA methylation might contribute to regulating chromatin structure. PMID:20095602

  8. ROS-mediated DNA methylation pattern alterations in carcinogenesis.

    PubMed

    Wu, Qihan; Ni, Xiaohua

    2015-01-01

    Elevated levels of both reactive oxygen species (ROS) and DNA methylation are characteristic of various types of cancer cells. However, the relation between these two is not well understood. Here we will discuss the cause-consequence relationship between ROS and DNA methylation. Cancer research reveals that disregulation of DNA methylation results in regional CpG island hypermethylation and generalized genomic hypomethylation. ROS-induced oxidative stress is associated with both aberrant hypermethylation of tumor suppressor gene (TSG) promoter regions and global hypomethylation. The DNA oxidation structure, 8-hydroxy-2'-deoxyguanosine (8-OHdG), can induce DNA hypomethylation by inhibiting DNA methylation at nearby cytosine bases, while another DNA oxidation structure, 5-hydroxymethylcytosine (5hmC), may achieve active DNA demethylation processes, thus, causing DNA hypomethylation. Recently, it has been found that ROS can function as catalysts of DNA methylation, further accounting for TSG promoter hypermethylation. Moreover, ROS may induce site-specific hypermethylation via either the up-regulation of expression of DNA methyltransferases (DNMTs) or the formation of a new DNMT containing complex. In addition, these ROS-induced DNA methylation pattern alterations have been implicated with not only malignant transformation, but also the progression of numerous tumors. In conclusion, ROS can influence both aspects of DNA methylation changes through different mechanisms, which play an important role of epigenetic regulation in cancer cells. Therefore, the comprehension of mechanisms leading to epigenetic modifications associated with ROS may help better understand the carcinogenesis and progression, as well as aid in the development of potential biomarkers for better cancer diagnostics and novel therapeutic strategies. PMID:25585126

  9. The Search for a Complex Molecule in a Selected Hot Core Region: A Rigorous Attempt to Confirm trans-Ethyl Methyl Ether toward W51 e1/e2

    E-print Network

    Carroll, P Brandon; Blake, Geoffrey A; Apponi, A J; Ziuyrs, L M; Remijan, Anthony

    2014-01-01

    An extensive search has been conducted to confirm transitions of \\textit{trans}-ethyl methyl ether (tEME, C$_2$H$_5$OCH$_3$), toward the high mass star forming region W51 e1/e2 using the 12 m Telescope of the Arizona Radio Observatory (ARO) at wavelengths from 2 mm and 3 mm. In short, we cannot confirm the detection of tEME toward W51 e1/e2 and our results call into question the initial identification of this species by \\citet{FuchsSpace}. Additionally, reevaluation of the data from the original detection indicates that tEME is not present toward W51 e1/e2 in the abundance reported by Fuchs and colleagues. Typical peak-to-peak noise levels for the present observations of W51 e1/e2 were between 10 - 30 mK, yielding an upper limit of the tEME column density of $\\leq$ 1.5 $\\times$ 10$^{15}$ cm$^{-2}$. This would make tEME at least a factor 2 times less abundant than dimethyl ether (CH$_3$OCH$_3$) toward W51 e1/e2. We also performed an extensive search for this species toward the high mass star forming region Sgr...

  10. Tissue-specific dysregulation of DNA methylation in aging

    PubMed Central

    Thompson, Reid F.; Atzmon, Gil; Gheorghe, Ciprian; Liang, Hong Qian; Lowes, Christina; Greally, John M.; Barzilai, Nir

    2010-01-01

    SUMMARY The normal aging process is a complex phenomenon associated with physiological alterations in the function of cells and organs over time. Although an attractive candidate for mediating transcriptional dysregulation, the contribution of epigenetic dysregulation to these progressive changes in cellular physiology remains unclear. In this study, we employed the genome-wide HELP assay to define patterns of cytosine methylation throughout the rat genome, and the LUMA assay to measure global levels of DNA methylation in the same samples. We studied both liver and visceral adipose tissue, and demonstrated significant differences in DNA methylation with age at >5% of sites analyzed. Furthermore, we showed that epigenetic dysregulation with age is a highly tissue-dependent phenomenon. The most distinctive loci were located at intergenic sequences and conserved non-coding elements, and not at promoters nor at CG-dinucleotide dense loci. Despite this, we found that there was a subset of genes at which cytosine methylation and gene expression changes were concordant. Finally, we demonstrated that changes in methylation occur consistently near genes that are involved in metabolism and metabolic regulation, implicating their potential role in the pathogenesis of age-related diseases. We conclude that different patterns of epigenetic dysregulation occur in each tissue over time and may cause some of the physiological changes associated with normal aging. PMID:20497131

  11. Genome-wide methylation study on depression: differential methylation and variable methylation in monozygotic twins

    PubMed Central

    Córdova-Palomera, A; Fatjó-Vilas, M; Gastó, C; Navarro, V; Krebs, M-O; Fañanás, L

    2015-01-01

    Depressive disorders have been shown to be highly influenced by environmental pathogenic factors, some of which are believed to exert stress on human brain functioning via epigenetic modifications. Previous genome-wide methylomic studies on depression have suggested that, along with differential DNA methylation, affected co-twins of monozygotic (MZ) pairs have increased DNA methylation variability, probably in line with theories of epigenetic stochasticity. Nevertheless, the potential biological roots of this variability remain largely unexplored. The current study aimed to evaluate whether DNA methylation differences within MZ twin pairs were related to differences in their psychopathological status. Data from the Illumina Infinium HumanMethylation450 Beadchip was used to evaluate peripheral blood DNA methylation of 34 twins (17 MZ pairs). Two analytical strategies were used to identify (a) differentially methylated probes (DMPs) and (b) variably methylated probes (VMPs). Most DMPs were located in genes previously related to neuropsychiatric phenotypes. Remarkably, one of these DMPs (cg01122889) was located in the WDR26 gene, the DNA sequence of which has been implicated in major depressive disorder from genome-wide association studies. Expression of WDR26 has also been proposed as a biomarker of depression in human blood. Complementarily, VMPs were located in genes such as CACNA1C, IGF2 and the p38 MAP kinase MAPK11, showing enrichment for biological processes such as glucocorticoid signaling. These results expand on previous research to indicate that both differential methylation and differential variability have a role in the etiology and clinical manifestation of depression, and provide clues on specific genomic loci of potential interest in the epigenetics of depression. PMID:25918994

  12. Identification of HN-methyl NOEs in large proteins using simultaneous amide-methyl TROSY-based detection.

    PubMed

    Guo, Chenyun; Tugarinov, Vitali

    2009-01-01

    A pair of HN-methyl NOESY experiments that are based on simultaneous TROSY-type detection of amide and methyl groups is described. The preservation of cross-peak symmetry in the simultaneous (1)H-(15)N/(13)CH(3) NOE spectra enables straightforward assignments of HN-methyl NOE cross-peaks in large and complex protein structures. The pulse schemes are designed to preserve the slowly decaying components of both (1)H-(15)N and methyl (13)CH(3) spin-systems in the course of indirect evolution (t (2)) and acquisition period (t (3)) of 3D NOESY experiments. The methodology has been tested on {U-[(15)N,(2)H]; Iledelta1-[(13)CH(3)]; Leu,Val-[(13)CH(3),(12)CD(3)]}-labeled 82-kDa enzyme Malate Synthase G (MSG). A straightforward procedure that utilizes the symmetry of NOE cross-peaks in the time-shared 3D NOE data sets allows unambiguous assignments of more than 300 HN-methyl interactions in MSG from a single 3D data set providing important structural restraints for derivation of the backbone global fold. PMID:19002386

  13. 4,4'-, 5,5'-, and 6,6'-dimethyl-2,2'-bipyridyls: the structures, phase transitions, vibrations, and methyl group tunneling of their complexes with chloranilic acid.

    PubMed

    Bator, G; Sawka-Dobrowolska, W; Sobczyk, L; Grech, E; Nowicka-Scheibe, J; Pawlukoj?, A; Wuttke, J; Baran, J; Owczarek, M

    2011-07-28

    The crystal and molecular structures of 4,4(')- and 6,6(')-dimethyl-2,2(')-bipyridyl complexes with 2,5-dichloro-3,6-dihydroxy-p-benzoquinone (chloranilic acid, CLA) have been determined and compared with those of the complex with the 5,5(')-derivative, which is known to possess interesting antiferroelectric properties. In the crystalline state, all three compounds form hydrogen bonded chains with N(+)-H···O(-) and O-H···N bridges on both sides of the bipyridyl constituent. The comparison of three derivatives indicates that the N(+)-H···O(-) hydrogen bonds are shortest for the 5,5(')-dimethyl complex. The 4,4(')- and 6,6(')-derivatives do not show any ferroelectric feature. The 6,6(')-one is, however, characterized by a continuous phase transition, revealed in the differential scanning calorimetry, dilatometric, and dielectric characteristics. The tunneling splitting measured by neutron backscattering in the energy range ±30 ?eV for the neat dimethyl bipyridyls and their complexes with CLA indicates that the different splittings are primarily due to the crystal packing effect and that charge transfer between interacting compounds plays only a minor role. PMID:21806140

  14. Methyl-beta-cyclodextrins: the role of number and types of substituents in solubilizing power.

    PubMed

    Fenyvesi, Éva; Szemán, Julianna; Csabai, Katalin; Malanga, Milo; Szente, Lajos

    2014-05-01

    Methylated cyclodextrins (CDs) are effective solubilizers of poorly soluble organic compounds. In this work, we compared various methylated ?-CDs concerning their structure characterized by nuclear magnetic resonance spectroscopy, composition analyzed by HPLC and solubilizing capability by using model compounds such as cholesterol, fatty acids, furosemide, tamoxifen, and amiodarone. All the commercially available methylated ?-CDs are mixtures of various isomers and homologues except trimethyl ?-CD. The effects of the degree of methylation, the composition, as well as the influence of further derivatization with ionic groups were studied. The number of methyl groups in a CD ring should be around 14 to get the highest solubility for the included guest molecules. Although the distribution of isomers and related compounds has hardly any effect at constant degree of substitution, the introduction of amino and succinyl moieties on the CD ring adds ionic interactions to the hydrophobic interactions of the inclusion complex formation, which might result in synergic effect in solubilization. PMID:24590624

  15. Exploring genome wide bisulfite sequencing for DNA methylation analysis in livestock: a technical assessment

    PubMed Central

    Doherty, Rachael; Couldrey, Christine

    2014-01-01

    Recent advances made in “omics” technologies are contributing to a revolution in livestock selection and breeding practices. Epigenetic mechanisms, including DNA methylation are important determinants for the control of gene expression in mammals. DNA methylation research will help our understanding of how environmental factors contribute to phenotypic variation of complex production and health traits. High-throughput sequencing is a vital tool for the comprehensive analysis of DNA methylation, and bisulfite-based strategies coupled with DNA sequencing allows for quantitative, site-specific methylation analysis at the genome level or genome wide. Reduced representation bisulfite sequencing (RRBS) and more recently whole genome bisulfite sequencing (WGBS) have proven to be effective techniques for studying DNA methylation in both humans and mice. Here we report the development of RRBS and WGBS for use in sheep, the first application of this technology in livestock species. Important technical issues associated with these methodologies including fragment size selection and sequence depth are examined and discussed. PMID:24860595

  16. Synthesis of 3-Methyl-4-(4-methylbenzoyl)-1-phenyl-pyrazol-5-One: How to Avoid O-Acylation

    ERIC Educational Resources Information Center

    Kurteva, Vanya B.; Petrova, Maria A.

    2015-01-01

    In this laboratory experiment, students synthesize 3-methyl-4-(4-methylbenzoyl)-1-phenyl-pyrazol-5-one by selective C-acylation of 3-methyl-1-phenyl-1H-pyrazol-5-one. Calcium hydroxide is used to push the tautomeric equilibrium toward the enol form, to protect the hydroxyl functionality as a complex, to trap the liberated hydrogen chloride, and to…

  17. 40 CFR 721.10121 - Poly[oxy(methyl-1,2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched...2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched...2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-,...

  18. 40 CFR 721.10121 - Poly[oxy(methyl-1,2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched...2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched...2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-,...

  19. 40 CFR 721.10121 - Poly[oxy(methyl-1,2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched...2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched...2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-,...

  20. 40 CFR 721.10121 - Poly[oxy(methyl-1,2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched...2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched...2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-,...

  1. 40 CFR 721.10121 - Poly[oxy(methyl-1,2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched...2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched...2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-,...

  2. SYNTHESIS AND STRUCTURAL FEATURES OF COPPER(II) COMPLEXES OF BENZOIC ACID AND METHYL SUBSTITUTED BENZOIC ACID HYDRAZIDES AND X-RAY STRUCTURE OF Cu[C6H5CONHNH2]2(NO3)2

    Microsoft Academic Search

    Olusegun A. Odunola; Idowu O. Adeoye; Joseph A. O. Woods

    2002-01-01

    The synthesis, spectroscopic, magnetic and biological activities of copper(II) complexes of benzoic acid hydrazides (BAH) and o, m, and p-substituted methylbenzoic acid hydrazides (MBAH) and the single crystal X-ray structure for bis(benzoic acid hydrazide)copper(II) nitrate {Cu[BAH]2-(NO3)2} (BAH=Benzoic acid hydrazide) are reported. The composition of the ligands was established by elemental analyses, H NMR, and GC-MS. Magnetic susceptibility, electronic and infrared

  3. Genome-wide DNA methylation profiling of non-small cell lung carcinomas

    PubMed Central

    2012-01-01

    Background Non-small cell lung carcinoma (NSCLC) is a complex malignancy that owing to its heterogeneity and poor prognosis poses many challenges to diagnosis, prognosis and patient treatment. DNA methylation is an important mechanism of epigenetic regulation involved in normal development and cancer. It is a very stable and specific modification and therefore in principle a very suitable marker for epigenetic phenotyping of tumors. Here we present a genome-wide DNA methylation analysis of NSCLC samples and paired lung tissues, where we combine MethylCap and next generation sequencing (MethylCap-seq) to provide comprehensive DNA methylation maps of the tumor and paired lung samples. The MethylCap-seq data were validated by bisulfite sequencing and methyl-specific polymerase chain reaction of selected regions. Results Analysis of the MethylCap-seq data revealed a strong positive correlation between replicate experiments and between paired tumor/lung samples. We identified 57 differentially methylated regions (DMRs) present in all NSCLC tumors analyzed by MethylCap-seq. While hypomethylated DMRs did not correlate to any particular functional category of genes, the hypermethylated DMRs were strongly associated with genes encoding transcriptional regulators. Furthermore, subtelomeric regions and satellite repeats were hypomethylated in the NSCLC samples. We also identified DMRs that were specific to two of the major subtypes of NSCLC, adenocarcinomas and squamous cell carcinomas. Conclusions Collectively, we provide a resource containing genome-wide DNA methylation maps of NSCLC and their paired lung tissues, and comprehensive lists of known and novel DMRs and associated genes in NSCLC. PMID:22726460

  4. Vibrational spectroscopy of Methyl benzoate.

    PubMed

    Maiti, Kiran Sankar

    2015-08-14

    Methyl benzoate is studied as a model compound for the development of new IR pulse schemes with possible applicability to biomolecules. Anharmonic vibrational modes of Methyl benzoate are calculated on different level (MP2, SCS, CCSD(T) with varying basis sets) ab initio PESs using the vibrational self-consistent field (VSCF) method and its correlation corrected extensions. Dual level schemes, combining different quantum chemical methods for diagonal and coupling potentials, are systematically studied and applied successfully to reduce the computational cost. Isotopic substitution of ?-hydrogen by deuterium is studied to obtain a better understanding of the molecular vibrational coupling topology. PMID:26050760

  5. Methylation of cysteine in hemoglobin following exposure to methylating agents

    Microsoft Academic Search

    Eric Bailey; Thomas A. Connors; Peter B. Farmer; Susan M. Gorf; Janet Rickard

    1981-01-01

    In addition to reacting with biologically important nucleophilic sites in DNA, alkylating agents also interact with amino acids in proteins. Measurements of the extent of formation of these alkyl amino acids may be used as a means of determining exposure to these compounds. The degree of S-methylation of cysteine in hemoglobin was studied following in vivo exposure of rats to

  6. Selenium reduces the retention of methyl mercury in the brown shrimp Crangon crangon.

    PubMed

    Bjerregaard, Poul; Christensen, Alan

    2012-06-01

    Methyl mercury accumulated at the top of aquatic food chains constitutes a toxicological risk to humans and other top predators. Because the methyl mercury enters the aquatic food chains at the lower trophic levels, uptake and elimination processes at these levels affect the methyl mercury content at the higher levels. Selenium modulates the biokinetics of mercury in aquatic organisms in fairly complex ways, increasing mercury retention in some aquatic mammals, but decreasing methyl mercury retention in fish. However, it is not known if selenium modulates methyl mercury accumulation at lower trophic levels in aquatic food chains. Here, we show that selenium administered via the food augments the elimination of methyl mercury from marine shrimp and that the effect is dose-dependent, demonstrable down to natural selenium concentrations in aquatic food items. Selenite, seleno-cystine, and seleno-methionine exert this effect but selenate does not. Our results suggest that the selenium naturally present at the lower trophic levels in marine food chains may play an essential role as a modifier of methyl mercury accumulation at these levels, thereby potentially also affecting biomagnification of methyl mercury toward the higher trophic levels in the aquatic food chains. PMID:22550937

  7. The functions of DNA methylation by CcrM in Caulobacter crescentus: a global approach

    PubMed Central

    Gonzalez, Diego; Kozdon, Jennifer B.; McAdams, Harley H.; Shapiro, Lucy; Collier, Justine

    2014-01-01

    DNA methylation is involved in a diversity of processes in bacteria, including maintenance of genome integrity and regulation of gene expression. Here, using Caulobacter crescentus as a model, we exploit genome-wide experimental methods to uncover the functions of CcrM, a DNA methyltransferase conserved in most Alphaproteobacteria. Using single molecule sequencing, we provide evidence that most CcrM target motifs (GANTC) switch from a fully methylated to a hemi-methylated state when they are replicated, and back to a fully methylated state at the onset of cell division. We show that DNA methylation by CcrM is not required for the control of the initiation of chromosome replication or for DNA mismatch repair. By contrast, our transcriptome analysis shows that >10% of the genes are misexpressed in cells lacking or constitutively over-expressing CcrM. Strikingly, GANTC methylation is needed for the efficient transcription of dozens of genes that are essential for cell cycle progression, in particular for DNA metabolism and cell division. Many of them are controlled by promoters methylated by CcrM and co-regulated by other global cell cycle regulators, demonstrating an extensive cross talk between DNA methylation and the complex regulatory network that controls the cell cycle of C. crescentus and, presumably, of many other Alphaproteobacteria. PMID:24398711

  8. Experimental and quantum-chemical studies of 1H, 13C and 15N NMR coordination shifts in Pd(II) and Pt(II) chloride complexes with methyl and phenyl derivatives of 2,2'-bipyridine and 1,10-phenanthroline.

    PubMed

    Pazderski, Leszek; Tousek, Jaromír; Sitkowski, Jerzy; Kozerski, Lech; Sz?yk, Edward

    2007-12-01

    1H, 13C and 15N NMR studies of platinide(II) (M=Pd, Pt) chloride complexes with methyl and phenyl derivatives of 2,2'-bipyridine and 1,10-phenanthroline [LL=4,4'-dimethyl-2,2'-bipyridine (dmbpy); 4,4'-diphenyl-2,2'-bipyridine (dpbpy); 4,7-dimethyl-1,10-phenanthroline (dmphen); 4,7-diphenyl-1,10-phenanthroline (dpphen)] having a general [M(LL)Cl2] formula were performed and the respective chemical shifts (delta1H, delta13C, delta15N) reported. 1H high-frequency coordination shifts (Delta1Hcoord=delta1Hcomplex-delta1Hligand) were discussed in relation to the changes of diamagnetic contribution in the relevant 1H shielding constants. The comparison to literature data for similar [M(LL)(XX)], [M(LL)X2] and [M(LL)XY] coordination or organometallic compounds containing various auxiliary ligands revealed a large dependence of delta1H parameters on inductive and anisotropic effects. 15N low-frequency coordination shifts (Delta15Ncoord=delta 15Ncomplex-delta15Nligand) of ca 88-96 ppm for M=Pd and ca 103-111 ppm for M=Pt were attributed to both the decrease of the absolute value of paramagnetic contribution and the increase of the diamagnetic term in the expression for 15N shielding constants. The absolute magnitude of Delta15Ncoord parameter increased by ca 15 ppm upon Pd(II)-->Pt(II) transition and by ca 6-7 ppm following dmbpy-->dmphen or dpbpy-->dpphen ligand replacement; variations between analogous complexes containing methyl and phenyl ligands (dmbpy vs dpbpy; dmphen vs dpphen) did not exceed+/-1.5 ppm. Experimental 1H, 13C, 15N NMR chemical shifts were compared to those quantum-chemically calculated by B3LYP/LanL2DZ+6-31G**//B3LYP/LanL2DZ+6-31G*, both in vacuo and in DMSO or DMF solution. PMID:18044804

  9. Protein methylation is required to maintain optimal HIV-1 infectivity

    PubMed Central

    Willemsen, Nicole M; Hitchen, Eleanor M; Bodetti, Tracey J; Apolloni, Ann; Warrilow, David; Piller, Sabine C; Harrich, David

    2006-01-01

    Background: Protein methylation is recognized as a major protein modification pathway regulating diverse cellular events such as protein trafficking, transcription, and signal transduction. More recently, protein arginine methyltransferase activity has been shown to regulate HIV-1 transcription via Tat. In this study, adenosine periodate (AdOx) was used to globally inhibit protein methyltransferase activity so that the effect of protein methylation on HIV-1 infectivity could be assessed. Results: Two cell culture models were used: HIV-1-infected CEM T-cells and HEK293T cells transfected with a proviral DNA plasmid. In both models, AdOx treatment of cells increased the levels of virion in culture supernatant. However, these viruses had increased levels of unprocessed or partially processed Gag-Pol, significantly increased diameter, and displayed reduced infectivity in a MAGI X4 assay. AdOx reduced infectivity equally in both dividing and non-dividing cells. However, infectivity was further reduced if Vpr was deleted suggesting virion proteins, other than Vpr, were affected by protein methylation. Endogenous reverse transcription was not inhibited in AdOx-treated HIV-1, and infectivity could be restored by pseudotyping HIV with VSV-G envelope protein. These experiments suggest that AdOx affects an early event between receptor binding and uncoating, but not reverse transcription. Conclusion: Overall, we have shown for the first time that protein methylation contributes towards maximal virus infectivity. Furthermore, our results also indicate that protein methylation regulates HIV-1 infectivity in a complex manner most likely involving the methylation of multiple viral or cellular proteins and/or multiple steps of replication. PMID:17169163

  10. Decrease in net mercury methylation rates following iron amendment to anoxic wetland sediment slurries.

    PubMed

    Mehrotra, Anna S; Sedlak, David L

    2005-04-15

    The rate of mercury methylation in anoxic wetland sediments is affected by the concentration of bioavailable complexes between Hg and sulfide. Previous research with pure bacterial cultures has shown that addition of ferrous iron reduces the net rate of mercury methylation by decreasing the concentration of dissolved sulfide. To assess the possibility of using this approach to decrease net mercury methylation in restored and constructed wetlands, laboratory experiments were conducted by adding Hg(II) and Fe(II) to sediments collected from six sites in five estuarine wetlands. Addition of 30 mM (0.07 mmol g(-1) or 3.9 mg g(-1)) Fe(II) decreased net mercury methylation relative to that of unamended controls by a factor of 2.1-6.6. In all cases, the observed decrease in net mercury methylation was accompanied by a decrease in the concentrations of sulfide and filterable mercury in the water overlying the sediments. When iron was added to one of the sediment samples at doses that were small relative to the concentration of sulfide present, net mercury methylation either increased slightly or was unaffected. Comparison of the results to speciation model predictions suggests that dissolved reduced sulfur-containing species play a role in the formation of uncharged, bioavailable Hg complexes. Although further research is needed to determine the long-term effect of iron amendment, these results suggest that iron addition decreases mercury methylation in authentic wetland sediments. PMID:15884350

  11. Conformational properties of Methyl ?-maltoside and Methyl ?- and ?-cellobioside disaccharides

    PubMed Central

    Hatcher, Elizabeth; Säwén, Elin; Widmalm, Göran; MacKerell, Alexander D.

    2010-01-01

    An investigation of the conformational properties of methyl ?-maltoside, methyl ?-cellobioside and methyl ?-cellobioside disaccharides, using NMR spectroscopy and molecular dynamics (MD) techniques, is presented. Emphasis is placed on validation of a recently presented force field for hexopyranose disaccharides followed by elucidation of the conformational properties of two different types of glycosidic linkages, ?-(1?4) and ?-(1?4). Both gas-phase and aqueous-phase simulations are performed to gain insight into the effect of solvent on the conformational properties. A number of transglycosidic J-coupling constants and proton-proton distances are calculated from the simulations and are used to identify the percent sampling of the three glycosidic conformations, syn, anti-? and anti-?, and, in turn, describe the flexibility around the glycosidic linkage. The results show the force field to be in overall good agreement with experiment, though some very small limitations are evident. Subsequently, a thorough hydrogen bonding analysis is performed to obtain insights into the conformational properties of the disaccharides. In methyl ?-maltoside competition between HO2?-O3 intramolecular hydrogen bonding and intermolecular hydrogen bonding of those groups with solvent lead to increased sampling of syn ?,? conformations and better agreement with NMR J-coupling constants. In methyl ? and ?-cellobioside, O5?-HO6 and HO2?-O3 hydrogen bonding interactions are in competition with intermolecular hydrogen bonding involving the solvent molecules. This competition leads to retention of the O5?-HO3 hydrogen bond and increased sampling of the syn region of the ?/? map. Moreover, glycosidic torsions are correlated to the intramolecular hydrogen bonding occurring in the molecules. The present results verify that in the ?-(1?4)-linkage intramolecular hydrogen bonding in the aqueous phase is due to the decreased ability of water to successfully compete for the O5? and HO3 hydrogen bonding moieties in contrast to that occurring between the O5? and HO6 atoms in this ?-(1?4)-linkage. PMID:21158455

  12. METHYLATION OF MERCURY IN AGRICULTURAL SOILS

    EPA Science Inventory

    Methylation of applied divalent mercury ion was found to occur in agricultural soils. The production of methylmercury was affected by soil texture, soil moisture content, soil temperature, concentration of the ionic mercury amendment, and time. Methylation was directly proportion...

  13. Antimicrobial activity of Fe III , Cu II , Ag I , Zn II and Hg II complexes of 2-(2-hydroxy-5-bromo\\/nitro-phenyl)-1 H - and 2-(2-hydroxyphenyl)-5-methyl\\/chloro\\/nitro-1 H -benzimidazoles

    Microsoft Academic Search

    B. Ülküseven; A. Tavman; G. Ötük; S. Birteksöz

    2002-01-01

    Antimicrobial activity of 2-(2-hydroxyphenyl)-5-R5-1H-benzimidazoles, 2-(2-hydroxy-5-R5?-phenyl)-1H-benzimidazoles and their FeIII, CuII, AgI, ZnII and HgII nitrate complexes was tested towardStaphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella\\u000a typhi, Shigella flexneri, andProteus mirabilis. Antifungal activity was tested againstCandida albicans. Benzimidazole benzene ring substituents increase the antimicrobial activity, phenol ring substituents decrease it. The ligands\\u000a show an antibacterial effect against onlyS.

  14. Hydrogen-bonded network structures in dipyridinium, bis­(2-methyl­pyridinium), bis­(3-methyl­pyridinium) and bis­(4-methyl­pyridinium) dioxidobis(oxydiacetato)uranate(VI)

    PubMed Central

    Lennartson, Anders; Håkansson, Mikael

    2010-01-01

    Four complexes containing the [UO2(oda)2]2? anion (oda is oxy­diacetate) are reported, namely dipyridinium dioxidobis(oxydiacetato)uranate(VI), (C5H6N)2[U(C4H4O5)2O2], (I), bis(2-methyl­pyridinium) dioxidobis(oxydiacetato)uranate(VI), (C8H8N)2[U(C4H4O5)2O2], (II), bis­(3-methyl­pyridinium) di­oxido­bis(oxydiacetato)uranate(VI), (C8H8N)2[U(C4H4O5)2O2], (III), and bis­(4-methyl­pyridinium) dioxidobis(oxydiacetato)uranate(VI), (C8H8N)2[U(C4H4O5)2O2], (IV). The anions are achiral and are located on a mirror plane in (I) and on inversion centres in (II)–(IV). The four complexes are assembled into three-dimensional structures via N—H?O and C—H?O inter­actions. Compounds (III) and (IV) are isomorphous; the [UO2(oda)2]2? anions form a porous matrix which is nearly identical in the two structures, and the cations are located in channels formed in this matrix. Compounds (I) and (II) are very different from (III) and (IV): (I) forms a layered structure, while (II) forms ribbons. PMID:20203398

  15. Flocculation of diatomite by methylated egg albumin

    Microsoft Academic Search

    Hideshi Seki; Akira Suzuki

    2003-01-01

    A common and inexpensive protein, egg albumin, was applied to the solid–liquid separation or flocculation of diatomite. Egg albumin was methylated in a 0.05 M HCl methyl alcohol solution at room temperature. About 90% of the carboxylic groups of egg albumin could be methylated within 24 h. The adsorption of egg albumin onto diatomite at pH 6.8 was remarkably enhanced by methylation. The adsorption

  16. [(Methyl­carbamothio­yl)disulfan­yl]methyl N-methyl­carbamodithio­ate

    PubMed Central

    Khan, Hizbullah; Aziz, Muhammad; Neuhausen, Christine; Murtaza, Ghulam; Shaheen, Farkhanda

    2010-01-01

    The title compound, C5H10N2S5, was unintentionally obtained as the product of an attempted synthesis of a methyl­carbamodithioic acid using methyl­amine and carbon disulfide. In the mol­ecule, two dithio­carbamate groups are bridged by a –CH2S– unit. The C—S—S—C torsion angle is ?90.13?(11)°. The crystal structure is stabilized by N—H?S inter­actions between neighbouring mol­ecules. An intra­molecular N—H?S hydrogen bond also occurs. PMID:21587641

  17. The structure, methyl rotation reflected in inelastic and quasielastic neutron scattering and vibrational spectra of 1,2,3,5-tetramethoxybenzene and its 2:1 complex with 1,2,4,5-tetracyanobenzene.

    PubMed

    Pawlukoj?, Andrzej; Prager, Michael; Dobrowolska, Wanda Sawka; Bator, Grazyna; Sobczyk, Lucjan; Ivanov, Alexander; Rols, Stéphane; Grech, Eugeniusz; Nowicka-Scheibe, Joanna; Unruh, Tobias

    2008-10-21

    X-ray diffraction studies show that molecules of the 1,2,3,5-tetramethoxybenzene (TMOB)(2) x 1,2,4,5-tetracyanobenzene complex form ...CCDCCDCC... columns with the short distances between molecular planes of C and D molecules equal to 3.186 A. The vibrational spectra recorded by using the inelastic neutron scattering, Raman, IR, and quasielastic neutron scattering (QENS) techniques aided by density functional theory calculations for the isolated molecules and the crystalline state enabled all four inequivalent librational modes, ascribed to the methoxy groups, to be analyzed. A rather good consistency was found between the experimental frequencies and those calculated for the crystal. The consistency was also achieved between the experimental structure of molecules and the theoretically reproduced one. A close similarity of the structures of the TMOB molecule isolated and in the complex is taken as a sign of dominating intramolecular interaction. The QENS spectra contain three Lorentzians of relative intensities of 1:1:2. Thus the two most strongly hindered of the four inequivalent methoxy groups in the crystalline lattice are characterized by rather similar barrier heights in good agreement with the packing analysis. PMID:19045208

  18. Water Column Methylation in Estuaries

    NASA Astrophysics Data System (ADS)

    Schartup, A. T.; Calder, R.; Soerensen, A. L.; Mason, R. P.; Balcom, P. H.; Sunderland, E. M.

    2014-12-01

    Methylmercury (MeHg) is a neurotoxin that bioaccumulates in aquatic food webs and affects humans and wildlife through fish consumption. Many studies have measured active methylation/demethylation in ocean margin sediments but few have reported similar rates for the marine water column. This presentation will review available evidence for water column methylation in estuaries, including new experimental measurements of methylation/demethylation rates from a deep subarctic fjord in Labrador Canada collected in Spring and Fall of 2012-2013. We used these and other data to construct a mass budget for MeHg in the estuary and show that water column methylation (with rates ranging from 1.5 to 2.8 % day-1), is the largest contributor, followed by inputs from rivers (4.9 mol year-1), to the in situ pool of MeHg available for uptake by biota. By contrast, the sediment in this system is a net sink for MeHg (-1.5 mol year-1). We discuss the relationship between observed MeHg and other ancillary environmental factors (organic carbon, sulfur and nutrients) as well as implications for the response time of fish to future changes in mercury inputs.

  19. Modeling of the oxidation of methyl esters--Validation for methyl hexanoate, methyl heptanoate, and methyl decanoate in a

    E-print Network

    Paris-Sud XI, Université de

    sources (e.g., rapeseed oil in Europe, soybean oil in the United States, and palm oil in Asia%), with small amounts of mono- and di-glycerides. The fatty acid composition of rapeseed oil is 64.4% oleic acid data, this detailed mechanism has only been tested for reproducing the oxidation of rapeseed oil methyl

  20. Gene methylation in gastric cancer.

    PubMed

    Qu, Yiping; Dang, Siwen; Hou, Peng

    2013-09-23

    Gastric cancer is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. Over 70% of new cases and deaths occur in developing countries. In the early years of the molecular biology revolution, cancer research mainly focuses on genetic alterations, including gastric cancer. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer, including DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs, and microRNAs. Aberrant DNA methylation in the promoter regions of gene, which leads to inactivation of tumor suppressor and other cancer-related genes in cancer cells, is the most well-defined epigenetic hallmark in gastric cancer. The advantages of gene methylation as a target for detection and diagnosis of cancer in biopsy specimens and non-invasive body fluids such as serum and gastric washes have led to many studies of application in gastric cancer. This review focuses on the most common and important phenomenon of epigenetics, DNA methylation, in gastric cancer and illustrates the impact epigenetics has had on this field. PMID:23669186

  1. ELUCIDATING THE PATHWAY FOR ARSENIC METHYLATION

    EPA Science Inventory

    Enzymatically-catalyzed methylation of arsenic is part of a metabolic pathway that converts inorganic arsenic into methylated products. Hence, in humans chronically exposed to inorganic arsenic, methyl and dimethyl arsenic account for most of the arsenic that is excreted in the ...

  2. 5, 13611378, 2008 Methyl arsenic and

    E-print Network

    Paris-Sud XI, Université de

    BGD 5, 1361­1378, 2008 Methyl arsenic and antimony species in suspended matter L. Duester et al of Biogeosciences Methylated arsenic and antimony species in suspended matter of the river Ruhr, Germany L. Duester1 of the European Geosciences Union. 1361 #12;BGD 5, 1361­1378, 2008 Methyl arsenic and antimony species

  3. Pancancer analysis of DNA methylation-driven genes using MethylMix | Office of Cancer Genomics

    Cancer.gov

    Aberrant DNA methylation is an important mechanism that contributes to oncogenesis. Yet, few algorithms exist that exploit this vast dataset to identify hypo- and hyper-methylated genes in cancer. We developed a novel computational algorithm called MethylMix to identify differentially methylated genes that are also predictive of transcription. We apply MethylMix to twelve individual cancer sites, and additionally combine all cancer sites in a pancancer analysis. We discover pancancer hypo- and hyper-methylated genes and identify novel methylation-driven subgroups with clinical implications.

  4. Pancancer analysis of DNA methylation-driven genes using MethylMix

    Cancer.gov

    Aberrant DNA methylation is an important mechanism that contributes to oncogenesis. Yet, few algorithms exist that exploit this vast dataset to identify hypo- and hyper-methylated genes in cancer. We developed a novel computational algorithm called MethylMix to identify differentially methylated genes that are also predictive of transcription. We apply MethylMix to twelve individual cancer sites, and additionally combine all cancer sites in a pancancer analysis. We discover pancancer hypo- and hyper-methylated genes and identify novel methylation-driven subgroups with clinical implications.

  5. Identification of Differentially Methylated Sequences in Colorectal Cancer by Methylated CpG Island Amplification1

    Microsoft Academic Search

    Minoru Toyota; Coty Ho; Nita Ahuja; Kam-Wing Jair; Qing Li; Mutsumi Ohe-Toyota; Stephen B. Baylin; Jean-Pierre J. Issa

    1999-01-01

    CpG island methylation has been linked to tumor suppressor gene inactivation in neoplasia and may serve as a useful marker to clone novel cancer-related genes. We have developed a novel PCR-based method, methylated CpG island amplification (MCA), which is useful for both methylation analysis and cloning differentially methylated genes. Using restriction enzymes that have differential sensitivity to 5-methyl-cytosine, followed by

  6. How to interpret Methylation Sensitive Amplified Polymorphism (MSAP) profiles?

    PubMed Central

    2014-01-01

    Background DNA methylation plays a key role in development, contributes to genome stability, and may also respond to external factors supporting adaptation and evolution. To connect different types of stimuli with particular biological processes, identifying genome regions with altered 5-methylcytosine distribution at a genome-wide scale is important. Many researchers are using the simple, reliable, and relatively inexpensive Methylation Sensitive Amplified Polymorphism (MSAP) method that is particularly useful in studies of epigenetic variation. However, electrophoretic patterns produced by the method are rather difficult to interpret, particularly when MspI and HpaII isoschizomers are used because these enzymes are methylation-sensitive, and any C within the CCGG recognition motif can be methylated in plant DNA. Results Here, we evaluate MSAP patterns with respect to current knowledge of the enzyme activities and the level and distribution of 5-methylcytosine in plant and vertebrate genomes. We discuss potential caveats related to complex MSAP patterns and provide clues regarding how to interpret them. We further show that addition of combined HpaII?+?MspI digestion would assist in the interpretation of the most controversial MSAP pattern represented by the signal in the HpaII but not in the MspI profile. Conclusions We recommend modification of the MSAP protocol that definitely discerns between putative hemimethylated mCCGG and internal CmCGG sites. We believe that our view and the simple improvement will assist in correct MSAP data interpretation. PMID:24393618

  7. Toxicological profile for methyl parathion. Final report

    SciTech Connect

    Not Available

    1992-09-01

    The Statement was prepared to give information about methyl parathion and to emphasize the human health effects that may result from exposure to it. The Environmental Protection Agency (EPA) has identified 1,177 sites on its National Priorities List (NPL). Methyl parathion has been found at 3 of these sites. As EPA evaluates more sites, the number of sites at which methyl parathion is found may change. The information is important because methyl parathion may cause harmful health effects and because these sites are potential or actual sources of human exposure to methyl parathion.

  8. Structural consequences of two methyl additions in the E. coli trp repressor L-tryptophan binding pocket

    SciTech Connect

    Lawson, C.L.

    1995-12-01

    The flexibility and specificity of the L-tryptophan corepressor binding pocket of E coli trp repressor are being investigated by high-resolution crystallographic examination of aporepressor/corepressor analog complexes. While addition of a methyl group on the corepressor indole (5-methyl-tryptophan) results in a small but measurable shift in the position of that functional group introduction of a methyl group on a nearby residue in the binding pocket (Val 58 {yields} Ile) leaves the indole position of L-tryptophan essentially unchanged. Careful alignment of these structures with aporepressor/L-tryptophan/operator-DNA complexes reveal why 5-methyltryptophan is a better corepressor than L-tryptophan.

  9. The reaction mechanism of methyl-coenzyme M reductase: how an enzyme enforces strict binding order.

    PubMed

    Wongnate, Thanyaporn; Ragsdale, Stephen W

    2015-04-10

    Methyl-coenzyme M reductase (MCR) is a nickel tetrahydrocorphinoid (coenzyme F430) containing enzyme involved in the biological synthesis and anaerobic oxidation of methane. MCR catalyzes the conversion of methyl-2-mercaptoethanesulfonate (methyl-SCoM) and N-7-mercaptoheptanoylthreonine phosphate (CoB7SH) to CH4 and the mixed disulfide CoBS-SCoM. In this study, the reaction of MCR from Methanothermobacter marburgensis, with its native substrates was investigated using static binding, chemical quench, and stopped-flow techniques. Rate constants were measured for each step in this strictly ordered ternary complex catalytic mechanism. Surprisingly, in the absence of the other substrate, MCR can bind either substrate; however, only one binary complex (MCR·methyl-SCoM) is productive whereas the other (MCR·CoB7SH) is inhibitory. Moreover, the kinetic data demonstrate that binding of methyl-SCoM to the inhibitory MCR·CoB7SH complex is highly disfavored (Kd = 56 mM). However, binding of CoB7SH to the productive MCR·methyl-SCoM complex to form the active ternary complex (CoB7SH·MCR(Ni(I))·CH3SCoM) is highly favored (Kd = 79 ?M). Only then can the chemical reaction occur (kobs = 20 s(-1) at 25 °C), leading to rapid formation and dissociation of CH4 leaving the binary product complex (MCR(Ni(II))·CoB7S(-)·SCoM), which undergoes electron transfer to regenerate Ni(I) and the final product CoBS-SCoM. This first rapid kinetics study of MCR with its natural substrates describes how an enzyme can enforce a strictly ordered ternary complex mechanism and serves as a template for identification of the reaction intermediates. PMID:25691570

  10. Altered DNA methylation in PAH deficient phenylketonuria.

    PubMed

    Dobrowolski, Steven F; Lyons-Weiler, James; Spridik, Kayla; Biery, Amy; Breck, Jane; Vockley, Jerry; Yatsenko, Svetlana; Sultana, Tamanna

    2015-01-01

    While phenylalanine (PHE) is the toxic insult in phenylketonuria (PKU), mechanisms underlying PHE toxicity remain ill-defined. Altered DNA methylation in response to toxic exposures is well-recognized. DNA methylation patterns were assessed in blood and brain from PKU patients to determine if PHE toxicity impacts methylation. Methylome assessment, utilizing methylated DNA immunoprecipitation and paired-end sequencing, was performed in DNA obtained from brain tissue of classical PKU patients, leukocytes from poorly controlled PKU patients, leukocytes from well controlled PKU patients, and appropriate control tissues. In PKU brain tissue, expression analysis determined the impact of methylation on gene function. Differential methylation was observed in brain tissue of PKU patients and expression studies identified downstream impact on gene expression. Altered patterns of methylation were observed in leukocytes of well controlled and poorly controlled patients with more extensive methylation in patients with high PHE exposure. Differential methylation of noncoding RNA genes was extensive in patients with high PHE exposure but minimal in well controlled patients. Methylome repatterning leading to altered gene expression was present in brain tissue of PKU patients, suggesting a role in neuropathology. Aberrant methylation is observed in leukocytes of PKU patients and is influenced by PHE exposure. DNA methylation may provide a biomarker relating to historic PHE exposure. PMID:25990862

  11. MethylMix: an R package for identifying DNA methylation-driven genes

    PubMed Central

    2015-01-01

    Summary: DNA methylation is an important mechanism regulating gene transcription, and its role in carcinogenesis has been extensively studied. Hyper and hypomethylation of genes is an alternative mechanism to deregulate gene expression in a wide range of diseases. At the same time, high-throughput DNA methylation assays have been developed generating vast amounts of genome wide DNA methylation measurements. Yet, few tools exist that can formally identify hypo and hypermethylated genes that are predictive of transcription and thus functionally relevant for a particular disease. To accommodate this lack of tools, we developed MethylMix, an algorithm implemented in R to identify disease specific hyper and hypomethylated genes. MethylMix is based on a beta mixture model to identify methylation states and compares them with the normal DNA methylation state. MethylMix introduces a novel metric, the ‘Differential Methylation value’ or DM-value defined as the difference of a methylation state with the normal methylation state. Finally, matched gene expression data are used to identify, besides differential, transcriptionally predictive methylation states by focusing on methylation changes that effect gene expression. Availability and implementation: MethylMix was implemented as an R package and is available in bioconductor. Contact: olivier.gevaert@stanford.edu PMID:25609794

  12. DNA Methylation in Colorectal Cancer

    Microsoft Academic Search

    Jeremy R. Jass; Vicki L. J. Whitehall; Joanne Young; Barbara A. Leggett

    In this chapter, it is pointed out that colorectal cancer is a heterogeneous disease. The case is made for a ‘serrated pathway’\\u000a of neoplasia that would evolve relatively rapidly through the early acquisition of DNA instability. DNA hypermethylation is\\u000a likely to be of critical importance in driving this pathway. Inhibition of apoptosis is conceived as the first step. Thereafter,\\u000a methylation

  13. Methyl rotational tunneling dynamics of p-xylene confined in a crystalline zeolite host

    NASA Astrophysics Data System (ADS)

    Nair, Sankar; Dimeo, Robert M.; Neumann, Dan A.; Horsewill, Anthony J.; Tsapatsis, Michael

    2004-09-01

    The methyl rotational tunneling spectrum of p-xylene confined in nanoporous zeolite crystals has been measured by inelastic neutron scattering (INS) and proton nuclear magnetic resonance (NMR), and analyzed to extract the rotational potential energy surfaces characteristic of the methyl groups in the host-guest complex. The number and relative intensities of the tunneling peaks observed by INS indicate the presence of methyl-methyl coupling interactions in addition to the methyl-zeolite interactions. The INS tunneling spectra from the crystals (space group P212121 with four crystallographically inequivalent methyl rotors) are quantitatively interpreted as a combination of transitions involving two coupled methyl rotors as well as a transition involving single-particle tunneling of a third inequivalent rotor, in a manner consistent with the observed tunneling energies and relative intensities. Together, the crystal structure and the absence of additional peaks in the INS spectra suggest that the tunneling of the fourth inequivalent rotor is strongly hindered and inaccessible to INS measurements. This is verified by proton NMR measurements of the spin-lattice relaxation time which reveal the tunneling characteristics of the fourth inequivalent rotor.

  14. Comprehensive and quantitative multilocus methylation analysis reveals the susceptibility of specific imprinted differentially methylated regions to aberrant methylation in Beckwith–Wiedemann syndrome with epimutations

    PubMed Central

    Maeda, Toshiyuki; Higashimoto, Ken; Jozaki, Kosuke; Yatsuki, Hitomi; Nakabayashi, Kazuhiko; Makita, Yoshio; Tonoki, Hidefumi; Okamoto, Nobuhiko; Takada, Fumio; Ohashi, Hirofumi; Migita, Makoto; Kosaki, Rika; Matsubara, Keiko; Ogata, Tsutomu; Matsuo, Muneaki; Hamasaki, Yuhei; Ohtsuka, Yasufumi; Nishioka, Kenichi; Joh, Keiichiro; Mukai, Tsunehiro; Hata, Kenichiro; Soejima, Hidenobu

    2014-01-01

    Purpose: Expression of imprinted genes is regulated by DNA methylation of differentially methylated regions (DMRs). Beckwith–Wiedemann syndrome is an imprinting disorder caused by epimutations of DMRs at 11p15.5. To date, multiple methylation defects have been reported in Beckwith–Wiedemann syndrome patients with epimutations; however, limited numbers of DMRs have been analyzed. The susceptibility of DMRs to aberrant methylation, alteration of gene expression due to aberrant methylation, and causative factors for multiple methylation defects remain undetermined. Methods: Comprehensive methylation analysis with two quantitative methods, matrix-assisted laser desorption/ionization mass spectrometry and bisulfite pyrosequencing, was conducted across 29 DMRs in 54 Beckwith–Wiedemann syndrome patients with epimutations. Allelic expressions of three genes with aberrant methylation were analyzed. All DMRs with aberrant methylation were sequenced. Results: Thirty-four percent of KvDMR1–loss of methylation patients and 30% of H19DMR–gain of methylation patients showed multiple methylation defects. Maternally methylated DMRs were susceptible to aberrant hypomethylation in KvDMR1–loss of methylation patients. Biallelic expression of the genes was associated with aberrant methylation. Cis-acting pathological variations were not found in any aberrantly methylated DMR. Conclusion: Maternally methylated DMRs may be vulnerable to DNA demethylation during the preimplantation stage, when hypomethylation of KvDMR1 occurs, and aberrant methylation of DMRs affects imprinted gene expression. Cis-acting variations of the DMRs are not involved in the multiple methylation defects. PMID:24810686

  15. The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders

    PubMed Central

    Grayson, Dennis R; Guidotti, Alessandro

    2013-01-01

    Major psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BP) with psychosis (BP+) express a complex symptomatology characterized by positive symptoms, negative symptoms, and cognitive impairment. Postmortem studies of human SZ and BP+ brains show considerable alterations in the transcriptome of a variety of cortical structures, including multiple mRNAs that are downregulated in both inhibitory GABAergic and excitatory pyramidal neurons compared with non-psychiatric subjects (NPS). Several reports show increased expression of DNA methyltransferases in telencephalic GABAergic neurons. Accumulating evidence suggests a critical role for altered DNA methylation processes in the pathogenesis of SZ and related psychiatric disorders. The establishment and maintenance of CpG site methylation is essential during central nervous system differentiation and this methylation has been implicated in synaptic plasticity, learning, and memory. Atypical hypermethylation of candidate gene promoters expressed in GABAergic neurons is associated with transcriptional downregulation of the corresponding mRNAs, including glutamic acid decarboxylase 67 (GAD67) and reelin (RELN). Recent reports indicate that the methylation status of promoter proximal CpG dinucleotides is in a dynamic balance between DNA methylation and DNA hydroxymethylation. Hydroxymethylation and subsequent DNA demethylation is more complex and involves additional proteins downstream of 5-hydroxymethylcytosine, including members of the base excision repair (BER) pathway. Recent advances in our understanding of altered CpG methylation, hydroxymethylation, and active DNA demethylation provide a framework for the identification of new targets, which may be exploited for the pharmacological intervention of the psychosis associated with SZ and possibly BP+. PMID:22948975

  16. N6-Adenosine Methylation in MiRNAs

    PubMed Central

    Berulava, Tea; Rahmann, Sven; Rademacher, Katrin; Klein-Hitpass, Ludgar; Horsthemke, Bernhard

    2015-01-01

    Methylation of N6-adenosine (m6A) has been observed in many different classes of RNA, but its prevalence in microRNAs (miRNAs) has not yet been studied. Here we show that a knockdown of the m6A demethylase FTO affects the steady-state levels of several miRNAs. Moreover, RNA immunoprecipitation with an anti-m6A-antibody followed by RNA-seq revealed that a significant fraction of miRNAs contains m6A. By motif searches we have discovered consensus sequences discriminating between methylated and unmethylated miRNAs. The epigenetic modification of an epigenetic modifier as described here adds a new layer to the complexity of the posttranscriptional regulation of gene expression. PMID:25723394

  17. Methylation patterns of immunoglobulin genes in lymphoid cells: correlation of expression and differentiation with undermethylation.

    PubMed Central

    Storb, U; Arp, B

    1983-01-01

    Different states of eukaryotic gene expression are often correlated with different levels of methylation of DNA sequences containing structural genes and their flanking regions. To assess the potential role of DNA methylation in the expression of immunoglobulin genes, which require complex rearrangements prior to expression, methylation patterns were examined in cell lines representing different stages of lymphocyte maturation. Methylation of the second cytosine in the sequence 5' C-C-G-G 3' was determined by using Hpa II/Msp I endonuclease digestion. Four CH genes (C mu, C delta, C gamma 2b, and C alpha), C kappa, V kappa, C lambda, and V lambda genes were analyzed. The results lead to the following conclusions: (i) transcribed immunoglobulin genes are undermethylated; (ii) the C gene allelic to an expressed C gene is always also undermethylated; and (iii) all immunoglobulin loci tend to become increasingly undermethylated as B cells mature. Images PMID:6314334

  18. A novel methyl-binding domain protein enrichment method for identifying genome-wide tissue-specific DNA methylation from nanogram DNA samples

    PubMed Central

    2013-01-01

    Background Growing evidence suggests that DNA methylation plays a role in tissue-specific differentiation. Current approaches to methylome analysis using enrichment with the methyl-binding domain protein (MBD) are restricted to large (?1 ?g) DNA samples, limiting the analysis of small tissue samples. Here we present a technique that enables characterization of genome-wide tissue-specific methylation patterns from nanogram quantities of DNA. Results We have developed a methodology utilizing MBD2b/MBD3L1 enrichment for methylated DNA, kinase pre-treated ligation-mediated PCR amplification (MeKL) and hybridization to the comprehensive high-throughput array for relative methylation (CHARM) customized tiling arrays, which we termed MeKL-chip. Kinase modification in combination with the addition of PEG has increased ligation-mediated PCR amplification over 20-fold, enabling >400-fold amplification of starting DNA. We have shown that MeKL-chip can be applied to as little as 20 ng of DNA, enabling comprehensive analysis of small DNA samples. Applying MeKL-chip to the mouse retina (a limited tissue source) and brain, 2,498 tissue-specific differentially methylated regions (T-DMRs) were characterized. The top five T-DMRs (Rgs20, Hes2, Nfic, Cckbr and Six3os1) were validated by pyrosequencing. Conclusions MeKL-chip enables genome-wide methylation analysis of nanogram quantities of DNA with a wide range of observed-to-expected CpG ratios due to the binding properties of the MBD2b/MBD3L1 protein complex. This methodology enabled the first analysis of genome-wide methylation in the mouse retina, characterizing novel T-DMRs. PMID:23759032

  19. An integrated workflow for DNA methylation analysis.

    PubMed

    Li, Pingchuan; Demirci, Feray; Mahalingam, Gayathri; Demirci, Caghan; Nakano, Mayumi; Meyers, Blake C

    2013-05-20

    The analysis of cytosine methylation provides a new way to assess and describe epigenetic regulation at a whole-genome level in many eukaryotes. DNA methylation has a demonstrated role in the genome stability and protection, regulation of gene expression and many other aspects of genome function and maintenance. BS-seq is a relatively unbiased method for profiling the DNA methylation, with a resolution capable of measuring methylation at individual cytosines. Here we describe, as an example, a workflow to handle DNA methylation analysis, from BS-seq library preparation to the data visualization. We describe some applications for the analysis and interpretation of these data. Our laboratory provides public access to plant DNA methylation data via visualization tools available at our "Next-Gen Sequence" websites (http://mpss.udel.edu), along with small RNA, RNA-seq and other data types. PMID:23706300

  20. Methyl parathion: a review of health effects.

    PubMed

    Garcia, Stephanie J; Abu-Qare, Aqel W; Meeker-O'Connell, Winifred A; Borton, Anita J; Abou-Donia, Mohamed B

    2003-01-01

    Methyl parathion is an organophosphorus (OP) insecticide with insecticidal properties derived from acetylcholinesterase (AChE) inhibition; this same property is also the root of its toxicity in humans. Poisoning with methyl parathion leads to cholinergic overstimulation with signs of toxicity including sweating, dizziness, vomiting, diarrhea, convulsions, cardiac arrest, respiratory arrest, and, in extreme cases, death. Reports of methyl parathion intoxication, usually seen only in field pesticide applicators, have increased throughout the United States as a result of unauthorized application of methyl parathion inside homes. The health concerns of the use of methyl parathion have resulted in cancellation of its use in most food crops in the United States. This review examines the well-documented neurotoxicity of methyl parathion as well as effects on other organ systems. PMID:12554434

  1. Genomic distribution of H3K9me2 and DNA methylation in a maize genome.

    PubMed

    West, Patrick T; Li, Qing; Ji, Lexiang; Eichten, Steven R; Song, Jawon; Vaughn, Matthew W; Schmitz, Robert J; Springer, Nathan M

    2014-01-01

    DNA methylation and dimethylation of lysine 9 of histone H3 (H3K9me2) are two chromatin modifications that can be associated with gene expression or recombination rate. The maize genome provides a complex landscape of interspersed genes and transposons. The genome-wide distribution of DNA methylation and H3K9me2 were investigated in seedling tissue for the maize inbred B73 and compared to patterns of these modifications observed in Arabidopsis thaliana. Most maize transposons are highly enriched for DNA methylation in CG and CHG contexts and for H3K9me2. In contrast to findings in Arabidopsis, maize CHH levels in transposons are generally low but some sub-families of transposons are enriched for CHH methylation and these families exhibit low levels of H3K9me2. The profile of modifications over genes reveals that DNA methylation and H3K9me2 is quite low near the beginning and end of genes. Although elevated CG and CHG methylation are found within gene bodies, CHH and H3K9me2 remain low. Maize has much higher levels of CHG methylation within gene bodies than observed in Arabidopsis and this is partially attributable to the presence of transposons within introns for some maize genes. These transposons are associated with high levels of CHG methylation and H3K9me2 but do not appear to prevent transcriptional elongation. Although the general trend is for a strong depletion of H3K9me2 and CHG near the transcription start site there are some putative genes that have high levels of these chromatin modifications. This study provides a clear view of the relationship between DNA methylation and H3K9me2 in the maize genome and how the distribution of these modifications is shaped by the interplay of genes and transposons. PMID:25122127

  2. Genetic mechanisms underlying the methylation level of anthocyanins in grape (Vitis vinifera L.)

    PubMed Central

    2011-01-01

    Background Plant color variation is due not only to the global pigment concentration but also to the proportion of different types of pigment. Variation in the color spectrum may arise from secondary modifications, such as hydroxylation and methylation, affecting the chromatic properties of pigments. In grapes (Vitis vinifera L.), the level of methylation modifies the stability and reactivity of anthocyanin, which directly influence the color of the berry. Anthocyanin methylation, as a complex trait, is controlled by multiple molecular factors likely to involve multiple regulatory steps. Results In a Syrah × Grenache progeny, two QTLs were detected for variation in level of anthocyanin methylation. The first one, explaining up to 27% of variance, colocalized with a cluster of Myb-type transcription factor genes. The second one, explaining up to 20% of variance, colocalized with a cluster of O-methyltransferase coding genes (AOMT). In a collection of 32 unrelated cultivars, MybA and AOMT expression profiles correlated with the level of methylated anthocyanin. In addition, the newly characterized AOMT2 gene presented two SNPs associated with methylation level. These mutations, probably leading to a structural change of the AOMT2 protein significantly affected the enzyme specific catalytic efficiency for the 3'-O-methylation of delphinidin 3-glucoside. Conclusion We demonstrated that variation in methylated anthocyanin accumulation is susceptible to involve both transcriptional regulation and structural variation. We report here the identification of novel AOMT variants likely to cause methylated anthocyanin variation. The integration of QTL mapping and molecular approaches enabled a better understanding of how variation in gene expression and catalytic efficiency of the resulting enzyme may influence the grape anthocyanin profile. PMID:22171701

  3. Hierarchical Clustering of Breast Cancer Methylomes Revealed Differentially Methylated and Expressed Breast Cancer Genes

    PubMed Central

    Lin, I-Hsuan; Chen, Dow-Tien; Chang, Yi-Feng; Lee, Yu-Ling; Su, Chia-Hsin; Cheng, Ching; Tsai, Yi-Chien; Ng, Swee-Chuan; Chen, Hsiao-Tan; Lee, Mei-Chen; Chen, Hong-Wei; Suen, Shih-Hui; Chen, Yu-Cheng; Liu, Tze-Tze; Chang, Chuan-Hsiung; Hsu, Ming-Ta

    2015-01-01

    Oncogenic transformation of normal cells often involves epigenetic alterations, including histone modification and DNA methylation. We conducted whole-genome bisulfite sequencing to determine the DNA methylomes of normal breast, fibroadenoma, invasive ductal carcinomas and MCF7. The emergence, disappearance, expansion and contraction of kilobase-sized hypomethylated regions (HMRs) and the hypomethylation of the megabase-sized partially methylated domains (PMDs) are the major forms of methylation changes observed in breast tumor samples. Hierarchical clustering of HMR revealed tumor-specific hypermethylated clusters and differential methylated enhancers specific to normal or breast cancer cell lines. Joint analysis of gene expression and DNA methylation data of normal breast and breast cancer cells identified differentially methylated and expressed genes associated with breast and/or ovarian cancers in cancer-specific HMR clusters. Furthermore, aberrant patterns of X-chromosome inactivation (XCI) was found in breast cancer cell lines as well as breast tumor samples in the TCGA BRCA (breast invasive carcinoma) dataset. They were characterized with differentially hypermethylated XIST promoter, reduced expression of XIST, and over-expression of hypomethylated X-linked genes. High expressions of these genes were significantly associated with lower survival rates in breast cancer patients. Comprehensive analysis of the normal and breast tumor methylomes suggests selective targeting of DNA methylation changes during breast cancer progression. The weak causal relationship between DNA methylation and gene expression observed in this study is evident of more complex role of DNA methylation in the regulation of gene expression in human epigenetics that deserves further investigation. PMID:25706888

  4. Effect of Body Mass Index on Global DNA Methylation in Healthy Korean Women

    PubMed Central

    Na, Yeon Kyung; Hong, Hae Sook; Lee, Duk Hee; Lee, Won Kee; Kim, Dong Sun

    2014-01-01

    Obesity is known to be strongly associated with cardiovascular disease and cancer, the leading causes of mortality worldwide, and develops owing to interactions between genes and the environment. DNA methylation can act as a downstream effector of environmental signals, and analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. Global DNA methylation of peripheral blood cells has recently been proposed as a potential biomarker for disease risk. Repetitive element DNA methylation has been shown to be associated with prominent obesity-related chronic diseases, but little is known about its relationship with weight status. In this study, we quantified the methylation of Alu elements in the peripheral blood DNA of 244 healthy women with a range of body mass indexes (BMIs) using pyrosequencing technology. Among the study participants, certain clinical laboratory parameters, including hemoglobin, serum glutamic oxaloacetic transaminase, serum glutamic-pyruvic transaminase, total cholesterol, and triglyceride levels were found to be strongly associated with BMI. Moreover, a U-shaped association between BMI and Alu methylation was observed, with the lowest methylation levels occurring at BMIs of between 23 and 30 kg/m2. However, there was no significant association between Alu methylation and age, smoking status, or alcohol consumption. Overall, we identified a differential influence of BMI on global DNA methylation in healthy Korean women, indicating that BMI-related changes in Alu methylation might play a complex role in the etiology and pathogenesis of obesity. Further studies are required to elucidate the mechanisms underlying this relationship. PMID:24938226

  5. Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the Mycobacterium tuberculosis complex. Evidence that all strains synthesize glycosylated p-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene.

    PubMed

    Constant, Patricia; Perez, Esther; Malaga, Wladimir; Lanéelle, Marie-Antoinette; Saurel, Olivier; Daffé, Mamadou; Guilhot, Christophe

    2002-10-11

    Diesters of phthiocerol and phenolphthiocerol are important virulence factors of Mycobacterium tuberculosis and Mycobacterium leprae, the two main mycobacterial pathogens in humans. They are both long-chain beta-diols, and their biosynthetic pathway is beginning to be elucidated. Although the two classes of molecules share a common lipid core, phthiocerol diesters have been found in all the strains of the M. tuberculosis complex examined although phenolphthiocerol diesters are produced by only a few groups of strains. To address the question of the origin of this diversity 8 reference strains and 10 clinical isolates of M. tuberculosis were analyzed. We report the presence of glycosylated p-hydroxybenzoic acid methyl esters, structurally related to the type-specific phenolphthiocerol glycolipids, in the culture media of all reference strains of M. tuberculosis, suggesting that the strains devoid of phenolphthiocerol derivatives are unable to elongate the putative p-hydroxybenzoic acid precursor. We also show that all the strains of M. tuberculosis examined and deficient in the production of phenolphthiocerol derivatives are natural mutants with a frameshift mutation in pks15/1 whereas a single open reading frame for pks15/1 is found in Mycobacterium bovis BCG, M. leprae, and strains of M. tuberculosis that produce phenolphthiocerol derivatives. Complementation of the H37Rv strain of M. tuberculosis, which is devoid of phenolphthiocerol derivatives, with the fused pks15/1 gene from M. bovis BCG restored phenolphthiocerol glycolipids production. Conversely, disruption of the pks15/1 gene in M. bovis BCG led to the abolition of the synthesis of type-specific phenolphthiocerol glycolipid. These data indicate that Pks15/1 is involved in the elongation of p-hydroxybenzoic acid to give p-hydroxyphenylalkanoates, which in turn are converted, presumably by the PpsA-E synthase, to phenolphthiocerol derivatives. PMID:12138124

  6. Methyl esters in the fatty acid industry

    Microsoft Academic Search

    R. D. Farris

    1979-01-01

    Methyl esters, derived from natural fats or oils, can be used as alternatives to fatty acids in the production of a number\\u000a of derivatives. The derivatives that can be made from methyl esters include fatty alkanolamides, fatty alcohols, isopropyl\\u000a esters, and sucrose polyesters. By using methyl esters as the raw materials, several benefits may be realized, such as, the\\u000a ability

  7. Enzymatic methylation of canola oil deodorizer distillate

    Microsoft Academic Search

    Suresh Ramamurthi; Prakash R. Bhirud; Alan R. McCurdy

    1991-01-01

    Methylation of canola oil deodorizer distillate catalyzed by a nonspecific lipase was investigated. The conversion of fatty\\u000a acids to methyl esters has been optimized by using a statistical design. Up to 96.5% conversion of fatty acids to their methyl\\u000a esters has been achieved without the aid of vacuum or any water-removing agent. The effects of temperature, ratio of the reactants

  8. Combustion characterization of methylal in reciprocating engines

    Microsoft Academic Search

    L. Dodge; D. Naegeli

    1994-01-01

    Methylal, CHâOCHâOCHâ, also known as dimethoxy-methane, is unique among oxygenates in that it has a low autoignition temperature, no carbon-carbon bonds, and is soluble in middle distillate fuels. Because of these properties, methylal has been shown to be a favorable fuel additive for reducing smoke in diesel engines. Recent measurements of ignition delay times indicate that methylal has a cetane

  9. Detailed Chemical Kinetic Reaction Mechanism for Biodiesel Components Methyl Stearate and Methyl Oleate

    SciTech Connect

    Naik, C; Westbrook, C K; Herbinet, O; Pitz, W J; Mehl, M

    2010-01-22

    New chemical kinetic reaction mechanisms are developed for two of the five major components of biodiesel fuel, methyl stearate and methyl oleate. The mechanisms are produced using existing reaction classes and rules for reaction rates, with additional reaction classes to describe other reactions unique to methyl ester species. Mechanism capabilities were examined by computing fuel/air autoignition delay times and comparing the results with more conventional hydrocarbon fuels for which experimental results are available. Additional comparisons were carried out with measured results taken from jet-stirred reactor experiments for rapeseed methyl ester fuels. In both sets of computational tests, methyl oleate was found to be slightly less reactive than methyl stearate, and an explanation of this observation is made showing that the double bond in methyl oleate inhibits certain low temperature chain branching reaction pathways important in methyl stearate. The resulting detailed chemical kinetic reaction mechanism includes more approximately 3500 chemical species and more than 17,000 chemical reactions.

  10. RNA-directed DNA methylation in Arabidopsis

    PubMed Central

    Aufsatz, Werner; Mette, M. Florian; van der Winden, Johannes; Matzke, Antonius J. M.; Matzke, Marjori

    2002-01-01

    In plants, double-stranded RNA that is processed to short RNAs ?21–24 nt in length can trigger two types of epigenetic gene silencing. Posttranscriptional gene silencing, which is related to RNA interference in animals and quelling in fungi, involves targeted elimination of homologous mRNA in the cytoplasm. RNA-directed DNA methylation involves de novo methylation of almost all cytosine residues within a region of RNA–DNA sequence identity. RNA-directed DNA methylation is presumed to be responsible for the methylation observed in protein coding regions of posttranscriptionally silenced genes. Moreover, a type of transcriptional gene silencing and de novo methylation of homologous promoters in trans can occur if a double-stranded RNA contains promoter sequences. Although RNA-directed DNA methylation has been described so far only in plants, there is increasing evidence that RNA can also target genome modifications in other organisms. To understand how RNA directs methylation to identical DNA sequences and how changes in chromatin configuration contribute to initiating or maintaining DNA methylation induced by RNA, a promoter double-stranded RNA-mediated transcriptional gene silencing system has been established in Arabidopsis. A genetic analysis of this system is helping to unravel the relationships among RNA signals, DNA methylation, and chromatin structure. PMID:12169664

  11. Microbial methylation of mercury in estuarine sediments

    SciTech Connect

    Compeau, G.C.

    1985-01-01

    Mercury is a common and potentially hazardous pollutant. Although all forms of the element are toxic, alkylated mercurials are particularly toxic and accumulate in living tissues. Factors affecting the availability of mercury and the microorganisms responsible for methylation are described. The methylation of mercuric ions (Hg/sup + +/) was investigated in pure culture, in estuarine sediments, and as a function of the anionic constituents of seawater. Studies on abiotic methylation of Hg/sup + +/ by methylcobalamin in the presence of sea salts showed that only the sulfide (formed in sulfate reduction) and bicarbonate components interfere with Hg/sup + +/ methylation. Other sea salt anions have no significant influence on the methylation of Hg/sup + +/. Methylation, demethylation, and volatilization of Hg/sup + +/ were studied in estuarine sediments maintained at present values of pH, redox, and salinity. Volatilization of Hg/sup 0/ and CH/sub 3/HgCH/sub 3/ were found to be minimal. Methylation was favored at low redox potential (-220 mW) and low salinity (0.4%) conditions. High salinity (2.5%) decreased methylation at -220 mV, but not at (+110 mV). Demethylation of CH/sub 3/HgCl was favored at +110 mV regardless of the salinity level. Low redox potential under low salinity conditions inhibited demethylation, but high salinity reversed this inhibition. The sulfate-reducing bacteria were identified as the principal Hg/sup + +/ methylating population in anaerobic estuarine sediments.

  12. Methylation – an uncommon modification of glycans*

    PubMed Central

    Staudacher, Erika

    2013-01-01

    A methyl group on a sugar residue is a rarely reported event. Until now this kind of modification has been found in the kingdom of animals only in worms and molluscs, whereas it is more frequently present in some species of bacteria, fungi, algae and plants, but not in mammals. The monosaccharides involved as well as the positions of the methyl groups on the sugar vary with the species. Methylation seems to play a role in some recognition events but details are still unknown. This review summarises the current knowledge on methylation of sugars in all kinds of organism. PMID:22944672

  13. Large-scale synthesis of methyl cis -9, trans -11-octadecadienoate from methyl ricinoleate

    Microsoft Academic Search

    O. Berdeaux; W. W. Christie; F. D. Gunstone; J.-L. Sebedio

    1997-01-01

    The conjugated linoleic acid methyl cis-9,trans-11-octadecadienoate has been prepared on a large scale from methyl ricinoleate. Methyl ricinoleate was purified from castor\\u000a esters by a partition method. It was converted to the mesylate, which was reacted with a base (1,8-diazabicyclo[5,4,0]-undec-7-ene)\\u000a to give a product that contained 66% of the desired ester. Two urea crystallizations produced a product containing 83% methyl

  14. Methylation-dependent silencing at the H19 imprinting control region by MeCP2

    PubMed Central

    Drewell, Robert A.; Goddard, Carolyn J.; Thomas, Jean O.; Surani, M. Azim

    2002-01-01

    Methylation of CpG dinucleotides is correlated with transcriptional repression of genes, including imprinted genes. In the case of the imprinted H19 gene, a 2 kb imprinting control region (ICR) is subject to differential methylation, as it is methylated only on the silenced paternal allele. This region has previously been shown to act as a silencer element at the endogenous locus. The proteins that bind at the H19 differentially methylated domain (DMD) and mediate transcriptional silencing have yet to be identified, although a family of proteins containing a methyl-CpG-binding domain (MBD), of which MeCP2 is the best characterised, are obvious candidates. MeCP2 can bind to a single methylated CpG dinucleotide through its MBD and also contains a transcriptional repression domain (TRD). The TRD interacts with Sin3a and histone deacetylases (HDACs) in vivo, forming a repressive complex. Here we show that MeCP2 is recruited to the H19 DMD in vivo and can silence a reporter gene regulated by the H19 DMD in a methylation-dependent manner. This repression can be alleviated by deletion of the TRD from MeCP2 or by inhibition of HDAC activity. These data indicate that transcriptional silencing from the H19 ICR involves recruitment of MeCP2 and presumably an associated protein complex with deacetylase activity. This complex may also be recruited to the ICR in vivo, resulting in a compact, repressive chromatin structure capable of silencing the paternal H19 allele. PMID:11861904

  15. Enzymatic synthesis of [3'-O-methyl-(3)H]malvidin-3-glucoside from petunidin-3-glucoside.

    PubMed

    Zimman, Alejandro; Waterhouse, Andrew L

    2002-04-10

    Malvidin-3-glucoside has been labeled by enzymatic synthesis in a single-step experiment. Catechol-O-methyl transferase catalyzed the B-ring methylation of petunidin-3-glucoside, and S-Adenosyl-L-[methyl-(3)H] methionine was the methyl donor. Solid phase extraction and preparative high-performance liquid chromatography were necessary to separate [3'-O-methyl-(3)H]malvidin-3-glucoside from an isomer and the starting material. The specific activity was 2.2 Ci mmol(-1), and the yield of incorporation was 1.1%. A possible application of the labeled material is the study of anthocyanin reactions in complex mixtures such as red wine where products are difficult to isolate and analyze. PMID:11929308

  16. Molecular Structure of Methyl Cyanide

    NSDL National Science Digital Library

    2003-06-03

    Methyl Cyanide is a toxic, colorless liquid with an aromatic (ether like) odor and forms explosive mixtures with air. It is a critical solvent for several important processes e.g., it is widely used as a mobile phase solvent in chromatography applications, as a wash solvent and in preparing reagent solutions for oligonucleotide synthesis. It is employed in the manufacturing of acrylic fibers, pharmaceuticals, perfumes, nitrile rubber, batteries, pesticides, and inorganic salts. It can be utilized to remove tars, phenols, and coloring matter from petroleum hydrocarbons, to extract fatty acids from fish liver, animal, and vegetable oils, and to recrystallize steroids.

  17. MethylMix: an R package for identifying DNA methylation driven genes | Office of Cancer Genomics

    Cancer.gov

    DNA methylation is an important mechanism regulating gene transcription, and its role in carcinogenesis has been extensively studied. Hyper and hypomethylation of genes is an alternative mechanism to deregulate gene expression in a wide range of diseases. At the same time high throughput DNA methylation assays have been developed generating vast amounts of genome wide DNA methylation measurements.

  18. MethylMix: an R package for identifying DNA methylation driven genes

    Cancer.gov

    DNA methylation is an important mechanism regulating gene transcription, and its role in carcinogenesis has been extensively studied. Hyper and hypomethylation of genes is an alternative mechanism to deregulate gene expression in a wide range of diseases. At the same time high throughput DNA methylation assays have been developed generating vast amounts of genome wide DNA methylation measurements.

  19. Genome-Wide Binding of MBD2 Reveals Strong Preference for Highly Methylated Loci

    PubMed Central

    Menafra, Roberta; Brinkman, Arie B.; Matarese, Filomena; Franci, Gianluigi; Bartels, Stefanie J. J.; Nguyen, Luan; Shimbo, Takashi; Wade, Paul A.; Hubner, Nina C.; Stunnenberg, Hendrik G.

    2014-01-01

    MBD2 is a subunit of the NuRD complex that is postulated to mediate gene repression via recruitment of the complex to methylated DNA. In this study we adopted an MBD2 tagging-approach to study its genome wide binding characteristics. We show that in vivo MBD2 is mainly recruited to CpG island promoters that are highly methylated. Interestingly, MBD2 binds around 1 kb downstream of the transcription start site of a subset of ?400 CpG island promoters that are characterized by the presence of active histone marks, RNA polymerase II (Pol2) and low to medium gene expression levels and H3K36me3 deposition. These tagged-MBD2 binding sites in MCF-7 show increased methylation in a cohort of primary breast cancers but not in normal breast samples, suggesting a putative role for MBD2 in breast cancer. PMID:24927503

  20. Crystal structure of bis-(1-methyl-1H-imidazole-?N (3))(5,10,15,20-tetra-phenyl-porphyrinato-?(4) N)iron(II)-1-methyl-1H-imidazole (1/2).

    PubMed

    Guan, Ye; Powell, Douglas R; Richter-Addo, George B

    2015-03-01

    The title compound, [Fe(C44H28N4)(C4H6N2)2]·2C4H6N2, is a six-coordinate Fe(II)-porphyrinate complex with the metal located on a center of inversion and coordinated by two axial 1-methyl-imidazole ligands; the complex crystallizes as a 1-methyl-imidazole disolvate. The 1-methyl-imidazole group bonded to the Fe(II) atom [occupancy ratio 0.789?(4):0.211?(4)] and the unbound 1-methyl-imidazole mol-ecule [0.519?(4):0.481?(4)] were disordered. The average Fe-N(porphyrinate) bond length is 1.998?(3)?Å and the axial Fe-N(imidazole) bond length is 1.9970?(12)?Å. In the crystal, mol-ecules are linked into a three-mol-ecule aggregate by two weak C-H?N inter-actions. PMID:25844207

  1. Chiral methyl-branched pheromones.

    PubMed

    Ando, Tetsu; Yamakawa, Rei

    2015-06-26

    Covering: up to October 2014Insect pheromones are some of the most interesting natural products because they are utilized for interspecific communication between various insects, such as beetles, moths, ants, and cockroaches. A large number of compounds of many kinds have been identified as pheromone components, reflecting the diversity of insect species. While this review deals only with chiral methyl-branched pheromones, the chemical structures of more than one hundred non-terpene compounds have been determined by applying excellent analytical techniques. Furthermore, their stereoselective syntheses have been achieved by employing trustworthy chiral sources and ingenious enantioselective reactions. The information has been reviewed here not only to make them available for new research but also to understand the characteristic chemical structures of the chiral pheromones. Since biosynthetic studies are still limited, it might be meaningful to examine whether the structures, particularly the positions and configurations of the branched methyl groups, are correlated with the taxonomy of the pheromone producers and also with the function of the pheromones in communication systems. PMID:25849023

  2. Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility.

    PubMed

    Reinius, Lovisa E; Acevedo, Nathalie; Joerink, Maaike; Pershagen, Göran; Dahlén, Sven-Erik; Greco, Dario; Söderhäll, Cilla; Scheynius, Annika; Kere, Juha

    2012-01-01

    Methylation of cytosines at CpG sites is a common epigenetic DNA modification that can be measured by a large number of methods, now even in a genome-wide manner for hundreds of thousands of sites. The application of DNA methylation analysis is becoming widely popular in complex disorders, for example, to understand part of the "missing heritability". The DNA samples most readily available for methylation studies are derived from whole blood. However, blood consists of many functionally and developmentally distinct cell populations in varying proportions. We studied whether such variation might affect the interpretation of methylation studies based on whole blood DNA. We found in healthy male blood donors there is important variation in the methylation profiles of whole blood, mononuclear cells, granulocytes, and cells from seven selected purified lineages. CpG methylation between mononuclear cells and granulocytes differed for 22% of the 8252 probes covering the selected 343 genes implicated in immune-related disorders by genome-wide association studies, and at least one probe was differentially methylated for 85% of the genes, indicating that whole blood methylation results might be unintelligible. For individual genes, even if the overall methylation patterns might appear similar, a few CpG sites in the regulatory regions may have opposite methylation patterns (i.e., hypo/hyper) in the main blood cell types. We conclude that interpretation of whole blood methylation profiles should be performed with great caution and for any differences implicated in a disorder, the differences resulting from varying proportions of white blood cell types should be considered. PMID:22848472

  3. Arginine methylation initiates BMP-induced Smad signaling

    PubMed Central

    Xu, Jian; Wang, A. Hongjun; Oses-Prieto, Juan; Makhijani, Kalpana; Katsuno, Yoko; Pei, Ming; Yan, Leilei; Zheng, Y. George; Burlingame, Alma; Brückner, Katja; Derynck, Rik

    2014-01-01

    Summary Kinase activation and substrate phosphorylation commonly form the backbone of signaling cascades. Bone morphogenetic proteins (BMPs), a subclass of TGF-? family ligands, induce activation of their signaling effectors, the Smads, through C-terminal phosphorylation by transmembrane receptor kinases. However, the slow kinetics of Smad activation in response to BMP suggests a preceding step in the initiation of BMP signaling. We now show that arginine methylation, which is known to regulate gene expression, yet also modifies some signaling mediators, initiates BMP-induced Smad signaling. BMP-induced receptor complex formation promotes interaction of the methyltransferase PRMT1 with the inhibitory Smad6, resulting in Smad6 methylation and relocalization at the receptor, leading to activation of effector Smads through phosphorylation. PRMT1 is required for BMP-induced biological responses across species, as evidenced by the role of its ortholog Dart1 in BMP signaling during Drosophila wing development. Activation of signaling by arginine methylation may also apply to other signaling pathways. PMID:23747011

  4. Control of mercury methylation in wetlands through iron addition

    E-print Network

    Sedlak, David L; Ulrich, Patrick D

    2009-01-01

    to methylating bacteria in sediment pore waters.bacteria - principle methylators of mercury in anoxic estuarine sediment.sediments by limiting the bioavailability of inorganic Hg(II) to the methylating bacteria.

  5. Synthesis, potentiometric and antimicrobial studies on metal complexes of isoxazole Schiff bases

    Microsoft Academic Search

    Y. Prashanthi; K. Kiranmai; N. J. P. Subhashini; Shivaraj

    2008-01-01

    The metal complexes of Cu(II), Ni(II) and Co(II) with Schiff bases of 3-(2-hydroxy-3-ethoxybenzylideneamino)-5-methyl isoxazole [HEBMI] and 3-(2-hydroxy-5-nitrobenzylidene amino)-5-methyl isoxazole [HNBMI] which were obtained by the condensation of 3-amino-5-methyl isoxazole with substituted salicylaldehydes have been synthesized. Schiff bases and their complexes have been characterized on the basis of elemental analysis, magnetic moments, molar conductivity, thermal analysis and spectral (IR, UV, NMR

  6. The Synthesis of Methyl Salicylate: Amine Diazotization.

    ERIC Educational Resources Information Center

    Zanger, Murray; McKee, James R.

    1988-01-01

    Notes that this experiment takes safety and noncarcinogenic reactants into account. Demonstrates the use of diazonium salts for the replacement of an aromatic amine group by a phenolic hydroxyl. Involves two pleasant-smelling organic compounds, methyl anthranilate (grape) and methyl salicylate (oil of wintergreen). (MVL)

  7. DNA methylation landscapes: provocative insights from epigenomics

    Microsoft Academic Search

    Adrian Bird; Miho M. Suzuki

    2008-01-01

    The genomes of many animals, plants and fungi are tagged by methylation of DNA cytosine. To understand the biological significance of this epigenetic mark it is essential to know where in the genome it is located. New techniques are making it easier to map DNA methylation patterns on a large scale and the results have already provided surprises. In particular,

  8. Effects of DNA methylation on nucleosome stability

    PubMed Central

    Collings, Clayton K.; Waddell, Peter J.; Anderson, John N.

    2013-01-01

    Methylation of DNA at CpG dinucleotides represents one of the most important epigenetic mechanisms involved in the control of gene expression in vertebrate cells. In this report, we conducted nucleosome reconstitution experiments in conjunction with high-throughput sequencing on 572 KB of human DNA and 668 KB of mouse DNA that was unmethylated or methylated in order to investigate the effects of this epigenetic modification on the positioning and stability of nucleosomes. The results demonstrated that a subset of nucleosomes positioned by nucleotide sequence was sensitive to methylation where the modification increased the affinity of these sequences for the histone octamer. The features that distinguished these nucleosomes from the bulk of the methylation-insensitive nucleosomes were an increase in the frequency of CpG dinucleotides and a unique rotational orientation of CpGs such that their minor grooves tended to face toward the histones in the nucleosome rather than away. These methylation-sensitive nucleosomes were preferentially associated with exons as compared to introns while unmethylated CpG islands near transcription start sites became enriched in nucleosomes upon methylation. The results of this study suggest that the effects of DNA methylation on nucleosome stability in vitro can recapitulate what has been observed in the cell and provide a direct link between DNA methylation and the structure and function of chromatin. PMID:23355616

  9. Microbial methylation of mercury in estuarine sediments

    Microsoft Academic Search

    Compeau

    1985-01-01

    Mercury is a common and potentially hazardous pollutant. Although all forms of the element are toxic, alkylated mercurials are particularly toxic and accumulate in living tissues. Factors affecting the availability of mercury and the microorganisms responsible for methylation are described. The methylation of mercuric ions (Hg\\/sup + +\\/) was investigated in pure culture, in estuarine sediments, and as a function

  10. Enzymatic synthesis of methyl-galactoaldehyde

    NASA Astrophysics Data System (ADS)

    Qun, Wang; Guangli, Yu

    2002-10-01

    Methyl-galactosides were oxidized at room temperature by galactose oxidase in a one-step reaction and afforded methyl-galactoaldehyde in excellent yield and high purity. The resulting galactoaldehyde as a useful intermediate can be directly used in glycopeptide synthesis.

  11. DNA methylation in health and disease

    Microsoft Academic Search

    Keith D. Robertson; Alan P. Wolffe

    2000-01-01

    DNA methylation has recently moved to centre stage in the aetiology of human neurodevelopmental syndromes such as the fragile X, ICF and Rett syndromes. These diseases result from the misregulation of genes that occurs with the loss of appropriate epigenetic controls during neuronal development. Recent advances have connected DNA methylation to chromatin-remodelling enzymes, and understanding this link will be central

  12. Emission Characteristics of Sunflower Oil Methyl Ester

    Microsoft Academic Search

    Y. Ulusoy; R. Arslan; C. Kaplan

    2009-01-01

    In this study, use of sunflower oil methyl ester as an alternative fuel in a 4 stroke turbo diesel engine with 4 cylinders, direct injection, and 55 kW power was analyzed. The engine has been fueled by diesel fuel and biodiesel (B100) obtained from methyl ester of sunflower oil and by running the test engine with 14 different speeds and

  13. Interindividual concordance of methylation profiles in human genes for tumor necrosis factors. alpha. and. beta

    SciTech Connect

    Kochanek, S.; Toth, M.; Dehmel, A.; Renz, D.; Doerfler, W. (Univ. of Cologne (West Germany))

    1990-11-01

    The DNA in mammalian genomes is characterized by complex patterns of DNA methylation that reflect the states of all genetic activities of that genome. The modified nucleotide 5-methyldeoxycytidine ({sup 5}mdC) can affect the interactions of specific proteins with DNA sequence motifs. The most extensively studied effect of sequence-specific methylations is that of the long-term silencing of eukaryotic (mammalian) promoters. The authors have initiated studies on the methylation status of parts of the human genome to view patterns of DNA methylation as indicators for genetic activities. In this report, analyses using both restriction enzyme-Southern blotting and the very precise genomic sequencing technique have been done. The results are characterized by a remarkable interindividual concordance of DNA methylation in specific human cell types. The patterns are identical in the DNA from one cell type for different individuals even of different genetic origins but different in the DNA from different cell types. The TNF-{beta} promoter is methylated in granulocytes from 9 different individuals, and TNF-{beta} is not expressed. In human lymphocytes, the main source of TNF-{beta}, the TNF-{beta} promoter is free of {sup 5}mdC residues.

  14. A novel method for detecting association between DNA methylation and diseases using spatial information.

    PubMed

    Yip, Wai-Ki; Fier, Heide; DeMeo, Dawn L; Aryee, Martin; Laird, Nan; Lange, Christoph

    2014-12-01

    DNA methylation may represent an important contributor to the missing heritability described in complex trait genetics. However, technology to measure DNA methylation has outpaced statistical methods for analysis. Taking advantage of the recent finding that methylated sites cluster together, we propose a Spatial Clustering Method (SCM) to detect differentially methylated regions (DMRs) in the genome in case and control studies using spatial location information. This new method compares the distribution of distances in cases and controls between DNA methylation marks in the genomic region of interest. A statistic is computed based on these distances. Proper type I error rate is maintained and statistical significance is evaluated using permutation test. The effectiveness of the SCM we propose is evaluated by a simulation study. By simulating a simple disease model, we demonstrate that SCM has good power to detect DMRs associated with the disease. Finally, we applied the SCM to an exploratory analysis of chromosome 14 from a colorectal cancer data set and identified statistically significant genomic regions. Identification of these regions should lead to a better understanding of methylated sites and their contribution to disease. The SCM can be used as a reliable statistical method for the identification of DMRs associated with disease states in exploratory epigenetic analyses. PMID:25250875

  15. DNA Methylation Profiling Identifies Global Methylation Differences and Markers of Adrenocortical Tumors

    PubMed Central

    Rechache, Nesrin S.; Wang, Yonghong; Stevenson, Holly S.; Killian, J. Keith; Edelman, Daniel C.; Merino, Maria; Zhang, Lisa; Nilubol, Naris; Stratakis, Constantine A.; Meltzer, Paul S.

    2012-01-01

    Context: It is not known whether there are any DNA methylation alterations in adrenocortical tumors. Objective: The objective of the study was to determine the methylation profile of normal adrenal cortex and benign and malignant adrenocortical tumors. Methods: Genome-wide methylation status of CpG regions were determined in normal (n = 19), benign (n = 48), primary malignant (n = 8), and metastatic malignant (n = 12) adrenocortical tissue samples. An integrated analysis of genome-wide methylation and mRNA expression in benign vs. malignant adrenocortical tissue samples was also performed. Results: Methylation profiling revealed the following: 1) that methylation patterns were distinctly different and could distinguish normal, benign, primary malignant, and metastatic tissue samples; 2) that malignant samples have global hypomethylation; and 3) that the methylation of CpG regions are different in benign adrenocortical tumors by functional status. Normal compared with benign samples had the least amount of methylation differences, whereas normal compared with primary and metastatic adrenocortical carcinoma samples had the greatest variability in methylation (adjusted P ? 0.01). Of 215 down-regulated genes (?2-fold, adjusted P ? 0.05) in malignant primary adrenocortical tumor samples, 52 of these genes were also hypermethylated. Conclusions: Malignant adrenocortical tumors are globally hypomethylated as compared with normal and benign tumors. Methylation profile differences may accurately distinguish between primary benign and malignant adrenocortical tumors. Several differentially methylated sites are associated with genes known to be dysregulated in malignant adrenocortical tumors. PMID:22472567

  16. CEBPA methylation and mutation in myelodysplastic syndrome.

    PubMed

    Wen, Xiang-mei; Hu, Jia-bo; Yang, Jing; Qian, Wei; Yao, Dong-ming; Deng, Zhao-qun; Zhang, Ying-ying; Zhu, Xiao-wen; Guo, Hong; Lin, Jiang; Qian, Jun

    2015-07-01

    Aberrant methylation of CCAAT/enhancer-binding protein alpha (CEBPA) promoter has been observed in acute myeloid leukemia. However, little is known about CEBPA promoter in myelodysplastic syndrome (MDS). The purpose of this study was to investigate the alteration of CEBPA promoter in MDS patients and further determine the association with CEBPA expression and mutation. CEBPA promoter was significantly methylated in 105 MDS patients compared to 22 controls (median 0.016 vs. 0.000) (P < 0.0001). Receiver operating characteristic curve analysis discriminated all patients or cytogenetically normal patients from normal controls. Three cases (3 %) were identified with single-mutated CEBPA and one (1 %) with double-mutated CEBPA. CEBPA methylation and mutation occurred mutually exclusive. No significant correlation was found between CEBPA expression and methylation (P = 0.586). Our findings indicate that CEBPA methylation is a common event in MDS, but could not act as a prognostic biomarker for MDS patients. PMID:26025484

  17. Targeting histone lysine methylation in cancer.

    PubMed

    McGrath, John; Trojer, Patrick

    2015-06-01

    Within the vast landscape of histone modifications lysine methylation has gained increasing attention because of its profound regulatory potential. The methylation of lysine residues on histone proteins modulates chromatin structure and thereby contributes to the regulation of DNA-based nuclear processes such as transcription, replication and repair. Protein families with opposing catalytic activities, lysine methyltransferases (KMTs) and demethylases (KDMs), dynamically control levels of histone lysine methylation and individual enzymes within these families have become candidate oncology targets in recent years. A number of high quality small molecule inhibitors of these enzymes have been identified. Several of these compounds elicit selective cancer cell killing in vitro and robust efficacy in vivo, suggesting that targeting 'histone lysine methylation pathways' may be a relevant, emerging cancer therapeutic strategy. Here, we discuss individual histone lysine methylation pathway targets, the properties of currently available small molecule inhibitors and their application in the context of cancer. PMID:25578037

  18. Dissolved organic matter enhances microbial mercury methylation under sulfidic conditions.

    PubMed

    Graham, Andrew M; Aiken, George R; Gilmour, Cynthia C

    2012-03-01

    Dissolved organic matter (DOM) is generally thought to lower metal bioavailability in aquatic systems due to the formation of metal-DOM complexes that reduce free metal ion concentrations. However, this model may not be pertinent for metal nanoparticles, which are now understood to be ubiquitous, sometimes dominant, metal species in the environment. The influence of DOM on Hg bioavailability to microorganisms was examined under conditions (0.5-5.0 nM Hg and 2-10 ?M sulfide) that favor the formation of ?-HgS(s) (metacinnabar) nanoparticles. We used the methylation of stable-isotope enriched (201)HgCl(2) by Desulfovibrio desulfuricans ND132 in short-term washed cell assays as a sensitive, environmentally significant proxy for Hg uptake. Suwannee River humic acid (SRHA) and Williams Lake hydrophobic acid (WLHPoA) substantially enhanced (2- to 38-fold) the bioavailability of Hg to ND132 over a wide range of Hg/DOM ratios (9.4 pmol/mg DOM to 9.4 nmol/mg DOM), including environmentally relevant ratios. Methylmercury (MeHg) production by ND132 increased linearly with either SRHA or WLHPoA concentration, but SRHA, a terrestrially derived DOM, was far more effective at enhancing Hg-methylation than WLHPoA, an aquatic DOM dominated by autochthonous sources. No DOM-dependent enhancement in Hg methylation was observed in Hg-DOM-sulfide solutions amended with sufficient l-cysteine to prevent ?-HgS(s) formation. We hypothesize that small HgS particles, stabilized against aggregation by DOM, are bioavailable to Hg-methylating bacteria. Our laboratory experiments provide a mechanism for the positive correlations between DOC and MeHg production observed in many aquatic sediments and wetland soils. PMID:22309093

  19. Chemical incorporation of thioxanthone into ?-cyclodextrin and its use in aqueous photopolymerization of methyl methacrylate

    Microsoft Academic Search

    Demet Karaca Balta; Emine Bagdatli; Nergis Arsu; Nuket Ocal; Yusuf Yagci

    2008-01-01

    Photoinitiated free radical polymerization of methyl methacrylate (MMA) in aqueous solution via hydrogen abstraction mechanism was described. For this purpose, thioxanthone (TX) chromophoric group was chemically incorporated into ?-cyclodextrin (?-CD) by a simple esterification process. The resulting thioxanthone photoinitiator (TX–?-CD) exhibited similar spectral characteristics and photoactivity to that of the parent TX molecule. Host guest complexes of MMA with TX–?-CD

  20. Palladium-catalyzed, pyrrolidine-mediated arylmethylation of ketones and aldehydes with coumarinyl(methyl) acetates†

    PubMed Central

    Cattopadhyay, Kalicharan; Recio, Antonio; Tunge, Jon A.

    2012-01-01

    We report the palladium-catalyzed, pyrrolidine-mediated ?-benzylation of enamines generated from aldehydes and ketones. The method allows for direct coupling of medicinally relevant coumarin moieties with aldehydes and ketones in good yield under mild conditions. The reaction is believed to proceed via a Pd-?-benzyl complex generated from (coumarinyl)methyl acetates. PMID:22832549

  1. Monozygotic twins affected with major depressive disorder have greater variance in methylation than

    E-print Network

    Cai, Long

    Monozygotic twins affected with major depressive disorder have greater variance in methylation than Martin2 , GW Montgomery2 , L Krause2,5 and NR Wray1,5 Our understanding of major depressive disorder (MDD depressive disorder (MDD) is a complex disorder with a considerable impact on the quality of patient's lives1

  2. The Role of Methyl Salicylate in Prey Searching Behavior of the Predatory Mite Phytoseiulus persimilis

    Microsoft Academic Search

    Jetske G. De Boer; Marcel Dicke

    2004-01-01

    Many carnivorous arthropods use herbivore-induced plant volatiles to locate their prey. These plant volatiles are blends of up to hundreds of compounds. It is often unknown which compounds in such a complex volatile blend represent the signal to the foraging carnivore. We studied the role of methyl salicylate (MeSA) as part of the volatile blend in the foraging behavior of

  3. DNA Methylation: An Introduction to the Biology and the Disease-Associated Changes of a Promising Biomarker

    Microsoft Academic Search

    Jörg Tost

    2010-01-01

    DNA methylation occurring on the 5 position of the pyrimidine ring of cytosines in the context of the dinucleotide sequence\\u000a CpG forms one of the multiple layers of epigenetic mechanisms controlling and modulating gene expression through chromatin\\u000a structure. It closely interacts with histone modifications and chromatin remodeling complexes to form the genomic chromatin\\u000a landscape. DNA methylation is essential for proper

  4. Is the Fungus Magnaporthe Losing DNA Methylation?

    PubMed Central

    Ikeda, Ken-ichi; Van Vu, Ba; Kadotani, Naoki; Tanaka, Masaki; Murata, Toshiki; Shiina, Kohta; Chuma, Izumi; Tosa, Yukio; Nakayashiki, Hitoshi

    2013-01-01

    The long terminal repeat retrotransposon, Magnaporthe gypsy-like element (MAGGY), has been shown to be targeted for cytosine methylation in a subset of Magnaporthe oryzae field isolates. Analysis of the F1 progeny from a genetic cross between methylation-proficient (Br48) and methylation-deficient (GFSI1-7-2) isolates revealed that methylation of the MAGGY element was governed by a single dominant gene. Positional cloning followed by gene disruption and complementation experiments revealed that the responsible gene was the DNA methyltransferase, MoDMT1, an ortholog of Neurospora crassa Dim-2. A survey of MAGGY methylation in 60 Magnaporthe field isolates revealed that 42 isolates from rice, common millet, wheat, finger millet, and buffelgrass were methylation proficient while 18 isolates from foxtail millet, green bristlegrass, Japanese panicgrass, torpedo grass, Guinea grass, and crabgrass were methylation deficient. Phenotypic analyses showed that MoDMT1 plays no major role in development and pathogenicity of the fungus. Quantitative polymerase chain reaction analysis showed that the average copy number of genomic MAGGY elements was not significantly different between methylation-deficient and -proficient field isolates even though the levels of MAGGY transcript were generally higher in the former group. MoDMT1 gene sequences in the methylation-deficient isolates suggested that at least three independent mutations were responsible for the loss of MoDMT1 function. Overall, our data suggest that MoDMT1 is not essential for the natural life cycle of the fungus and raise the possibility that the genus Magnaporthe may be losing the mechanism of DNA methylation on the evolutionary time scale. PMID:23979580

  5. 7 CFR 305.6 - Methyl bromide fumigation treatment schedules.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...false Methyl bromide fumigation treatment schedules.305.6 Section 305...DEPARTMENT OF AGRICULTURE PHYTOSANITARY TREATMENTSChemical Treatments § 305.6Methyl bromide fumigation treatment schedules. (a) Standard...

  6. Pharmacokinetics of methyl parathion: a comparison following single intravenous, oral or dermal administration.

    PubMed

    Kramer, Robert E; Wellman, Susan E; Rockhold, Robin W; Baker, Rodney C

    2002-01-01

    Assessment of the risks posed by the residential use of methyl parathion requires an understanding of its pharmacokinetics after different routes of exposure. Thus, studies were performed using adult female rats to define the pharmacokinetic parameters for methyl parathion after intravenous injection and to apply the described model to an examination of its pharmacokinetics after single oral or dermal exposure. The pharmacokinetics of methyl parathion after intravenous administration (1.5 mg/kg) were best described by a three-compartment model; the apparent volume of the central compartment was 1.45 liters/kg, clearance was 1.85 liters/h/kg and the terminal half-life was 6.6 h with an elimination constant of 0.50 h(-1). The apparent oral absorption coefficient for methyl parathion (1.5 mg/kg) was 1.24 h(-1), and its oral bioavailability was approximately 20%. The latter likely includes a significant first pass effect. Concentrations of methyl parathion increased during the initial 10-60 min and then declined during the next 15-36 h. After dermal administration (6.25-25 mg/kg), methyl parathion concentrations peaked within 12-26 h and then declined dose dependently. The apparent dermal absorption coefficient was approximately 0.41 h(-1), and only two pharmacokinetic compartments could be distinguished. In conclusion, the pharmacokinetics of methyl parathion are complex and route dependent. Also, dermal exposure, because of sustained methyl parathion concentrations, may pose the greatest risk. PMID:12145528

  7. Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma.

    PubMed

    Dai, Wei; Cheung, Arthur Kwok Leung; Ko, Josephine Mun Yee; Cheng, Yue; Zheng, Hong; Ngan, Roger Kai Cheong; Ng, Wai Tong; Lee, Anne Wing Mui; Yau, Chun Chung; Lee, Victor Ho Fu; Lung, Maria Li

    2015-07-01

    Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10(-9) ), but was less obvious in other types of solid tumors except for prostate and Epstein-Barr virus (EBV)-positive gastric cancer (FDR<10(-3) ). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection. PMID:25924914

  8. DNA methylation changes in the postmortem dorsolateral prefrontal cortex of patients with schizophrenia

    PubMed Central

    Numata, Shusuke; Ye, Tianzhang; Herman, Mary; Lipska, Barbara K.

    2014-01-01

    Background: Schizophrenia is a complex psychiatric disorder with a lifetime morbidity rate of 0.5–1.0%. The pathophysiology of schizophrenia still remains obscure. Accumulating evidence indicates that DNA methylation, which is the addition of a methyl group to the cytosine in a CpG dinucleotide, might play an important role in the pathogenesis of schizophrenia. Methods: To gain further insight into the molecular mechanisms underlying schizophrenia, a genome-wide DNA methylation profiling (27,578 CpG dinucleotides spanning 14,495 genes) of the human dorsolateral prefrontal cortex (DLPFC) was conducted in a large cohort (n = 216) of well characterized specimens from individuals with schizophrenia and non-psychiatric controls, combined with an analysis of genetic variance at ~880,000 SNPs. Results: Aberrant DNA methylation in schizophrenia was identified at 107 CpG sites at 5% Bonferroni correction (p < 1.99 × 10?6). Of these significantly altered sites, hyper-DNA methylation was observed at 79 sites (73.8%), mostly in the CpG islands (CGIs) and in the regions flanking CGIs (CGI: 31 sites; CGI shore: 35 sites; CGI shelf: 3 sites). Furthermore, a large number of cis-methylation quantitative trait loci (mQTL) were identified, including associations with risk SNPs implicated in schizophrenia. Conclusions: These results suggest that altered DNA methylation might be involved in the pathophysiology and/or treatment of schizophrenia, and that a combination of epigenetic and genetic approaches will be useful to understanding the molecular mechanism of this complex disorder. PMID:25206360

  9. Effect of Methylation on the Properties of the H-Bridges in DNA. A Systematic Theoretical Study on the Couples of Base Pairs.

    PubMed

    Villani, Giovanni

    2015-06-25

    The effects of the addition of one (hemimethylation) or two (methylation) methyl groups on the 10 different couples of base pairs of DNA (three dimers of A-T, three of C-G, and four mixed A-T and C-G complexes) has been studied. Changes in the main static properties (energy, structure, atomic charges) and dynamics (movement of hydrogen atoms from one base to the other) have been considered and analyzed. The results of this study support the idea that the quantitative effects of the methylation of these complexes depend on the specific system under consideration and on the H-bridge studied. In any case, some general behavior can be highlighted. In particular, the relationship between the transfer of hydrogen atoms between the bases (with the possible generation of mutation points) and the methylation can be schematized in the two most important methylated bases: adenine and cytosine. A different behavior has been found in these two cases, and we suggest that this could be related to the different amounts of these methylated systems in prokaryotes and eukaryotes. In particular, this different behavior could explain why adenine methylation is present mainly in the bacteria and cytosine methylation is present in more complex organisms. PMID:26051549

  10. Characterization of methyl mercury in dental wastewater and correlation with sulfate-reducing bacterial DNA.

    PubMed

    Zhao, Xiuhong; Rockne, Karl J; Drummond, James L; Hurley, Ryan K; Shade, Christopher W; Hudson, Robert J M

    2008-04-15

    Dental wastewater (DWW) was collected over two months from a 12-chair clinic and a single-chair office to identify conditions that may affect Hg methylation. DWW was settled for 24 h and samples were collected from the top and bottom of the supernatant to simulate a range of particles that may escape in-line traps. Total Hg spanned 5 orders of magnitude (0.02-5000 microM), following a log-normal distribution with p10, p50, and p90 concentration values of 0.24, 31 and 4000 microM, respectively; typically well in excess of free aqueous Hg solubility. Methyl Hg was present in high levels (2-270 nM), also following a log-normal distribution with p10, p50, and p90 concentration values of 2.8, 17, and 100 nM, respectively. There were no statistically significant differences (90% CI) in p50 methyl Hg or total Hg between the clinic and office. Methyl Hg was predicted from total Hg data by (+/- 95% CI): Log (Me-Hg) = 0.33 (+/- 0.06) x Log (T-Hg) - 2.27 (+/- 0.13). Total methyl Hg from DWW to U.S. wastewater collection systems is estimated to be 2-5 kg yr(-1). Equilibrium speciation modeling predicted that DWW Hg was primarily in sulfide-Hg complexes, except at high total Hg levels where organo-Hg complexes become significant. DNA extracts amplified by quantitative polymerase chain reaction with primers for total eubacteria and sulfate-reducing bacteria (SRB) indicated that the total eubacterial DNA was composed primarily of SRB, and highly significant correlations were found between methyl Hg and both amplified Desulfobacteraceae (p < 0.0001) and Desulfovibrionacaea DNA (p < 0.00001). Both are known Hg methylators. In marked contrast, there was no significant correlation between methyl Hg and amplified Desulfobulbus DNA, a genus generally not known to methylate Hg at high rates. These results strongly suggest that SRB are implicated in DWW Hg methylation. PMID:18497123

  11. Direct Interaction between DNA Methyltransferase DIM-2 and HP1 Is Required for DNA Methylation in Neurospora crassa? †

    PubMed Central

    Honda, Shinji; Selker, Eric U.

    2008-01-01

    DNA methylation is involved in gene silencing and genomic stability in mammals, plants, and fungi. Genetics studies of Neurospora crassa have revealed that a DNA methyltransferase (DIM-2), a histone H3K9 methyltransferase (DIM-5), and heterochromatin protein 1 (HP1) are required for DNA methylation. We explored the interrelationships of these components of the methylation machinery. A yeast two-hybrid screen revealed that HP1 interacts with DIM-2. We confirmed the interaction in vivo and demonstrated that it involves a pair of PXVXL-related motifs in the N-terminal region of DIM-2 and the chromo shadow domain of HP1. Both regions are essential for proper DNA methylation. We also determined that DIM-2 and HP1 form a stable complex independently of the trimethylation of histone H3K9, although the association of DIM-2 with its substrate sequences depends on trimethyl-H3K9. The DIM-2/HP1 complex does not include DIM-5. We conclude that DNA methylation in Neurospora is largely or exclusively the result of a unidirectional pathway in which DIM-5 methylates histone H3K9 and then the DIM-2/HP1 complex recognizes the resulting trimethyl-H3K9 mark via the chromo domain of HP1. PMID:18678653

  12. Formation of methyl formate after cosmic ion irradiation of icy grain mantles

    NASA Astrophysics Data System (ADS)

    Modica, P.; Palumbo, M. E.

    2010-09-01

    Context. Methyl formate (HCOOCH3) is a complex organic molecule detected in hot cores and hot corinos. Gas-phase chemistry fails to reproduce its observed abundance, which usually varies between 10-7 and 10-9 with respect to H2. Aims: Laboratory experiments were performed in order to investigate a solid-state route of methyl formate formation, to obtain an estimate of the amount that can be formed, and to verify whether it can account for the observed abundances. Methods: Several solid samples (16 K) of astrophysical interest were analyzed by infrared spectroscopy in the 4400-400 cm-1 range. The infrared spectral characteristics of frozen methyl formate were studied by deriving their band strength values. The effects produced upon warm-up of the samples were analyzed comparing the spectra taken at different temperatures. In order to study the formation and destruction mechanism of methyl formate in the interstellar ices, a binary mixture of methanol (CH3OH) and carbon monoxide (CO) ice and a sample of pure methanol were irradiated at 16 K with 200 keV protons. Methyl formate was identified through its fundamental mode (CH3 rocking) at about 1160 cm-1. Results: We present the mid-infrared methyl formate ice spectrum showing both the amorphous (16 K) and the crystalline (110 K) structure. We report novel measurements of the band strength values of the six main methyl formate bands. We prove the formation and the destruction of methyl formate after irradiation of CH3OH and a CO:CH3OH mixture. Extrapolating our results to the interstellar medium conditions we found that the production timescale of methyl formate agrees well with the evolutionary time of molecular clouds. The comparison with the observational data indicates that the amount of methyl formate formed after irradiation can account for the observed abundances. Conclusions: The present results allow us to suggest that gas phase methyl formate observed in dense molecular clouds is formed in the solid state after cosmic ion irradiation of icy grain mantles containing CO and CH3OH and released to the gas phase after desorption of icy mantles.

  13. Regulation of DNA transposition by CpG methylation and chromatin structure in human cells

    PubMed Central

    2013-01-01

    Background The activity of transposable elements can be regulated by different means. DNA CpG methylation is known to decrease or inhibit transpositional activity of diverse transposons. However, very surprisingly, it was previously shown that CpG methylation of the Sleeping Beauty (SB) transposon significantly enhanced transposition in mouse embryonic stem cells. Results In order to investigate the unexpected response of SB transposition to CpG methylation, related transposons from the Tc1/mariner superfamily, that is, Tc1, Himar1, Hsmar1, Frog Prince (FP) and Minos were tested to see how transposition was affected by CpG methylation. A significant increase of >20-fold in transposition of SB, FP and Minos was seen, whereas Tc1, Himar1 and Hsmar1 showed no difference in transposition upon CpG-methylation. The terminal inverted repeats (TIRs) of the SB, FP and Minos elements share a common structure, in which each TIR contains two functionally important binding sites for the transposase (termed the IR/DR structure). The group of IR/DR elements showed increased excision after CpG methylation compared to untreated transposon donor plasmids. We found that de novo CpG methylation is not required for transposition. A mutated FP donor plasmid with depleted CpG sites in both TIRs was as efficient in transposition as the wild-type transposon, indicating that CpG sites inside the TIRs are not responsible for altered binding of factors potentially modulating transposition. By using an in vivo one-hybrid DNA-binding assay in cultured human cells we found that CpG methylation had no appreciable effect on the affinity of SB transposase to its binding sites. However, chromatin immunoprecipitation indicated that CpG-methylated transposon donor plasmids are associated with a condensed chromatin structure characterized by trimethylated histone H3K9. Finally, DNA compaction by protamine was found to enhance SB transposition. Conclusions We have shown that DNA CpG methylation upregulates transposition of IR/DR elements in the Tc1/mariner superfamily. CpG methylation provokes the formation of a tight chromatin structure at the transposon DNA, likely aiding the formation of a catalytically active complex by facilitating synapsis of sites bound by the transposase. PMID:23676100

  14. DNA methylation in white blood cells

    PubMed Central

    Delgado-Cruzata, Lissette; Vin-Raviv, Neomi; Wu, Hui Chen; Santella, Regina M

    2011-01-01

    Alterations in DNA methylation patterns, both at specific loci and overall in the genome, have been associated with many different health outcomes. In cancer and other diseases, most of these changes have been observed at the tissue level. Data on whether DNA methylation changes in white blood cells (WBC) can serve as a useful biomarker for different health outcomes are much more limited, but rapidly emerging. Epidemiologic studies have reported associations between global WBC methylation and several different cancers including cancers of the colon, bladder, stomach, breast, and head and neck, as well as schizophrenia and myelodysplastic syndrome. Evidence for WBC methylation at specific loci and disease risk is more limited, but increasing. Differences in WBC DNA methylation by selected risk factors including demographic (age, gender, race), environmental exposures (benzene, persistent organic pollutants, lead, arsenic and air pollution), and other risk factors (cigarette smoke, alcohol drinking, body size, physical activity and diet) have been observed in epidemiologic studies though the patterns are far from consistent. Challenges in inferences from the existing data are primarily due to the cross-sectional fashion and small size of most studies performed to date, as well as to the differences in results across assay type and source of DNA. Large, prospective studies will be needed to understand whether changes in risk factors are associated with changes in DNA methylation patterns, and if changes in DNA methylation patterns are associated with changes in disease endpoints. PMID:21636973

  15. Mercury methylation by the methanogen Methanospirillum hungatei.

    PubMed

    Yu, Ri-Qing; Reinfelder, John R; Hines, Mark E; Barkay, Tamar

    2013-10-01

    Methylmercury (MeHg), a neurotoxic substance that accumulates in aquatic food chains and poses a risk to human health, is synthesized by anaerobic microorganisms in the environment. To date, mercury (Hg) methylation has been attributed to sulfate- and iron-reducing bacteria (SRB and IRB, respectively). Here we report that a methanogen, Methanospirillum hungatei JF-1, methylated Hg in a sulfide-free medium at comparable rates, but with higher yields, than those observed for some SRB and IRB. Phylogenetic analyses showed that the concatenated orthologs of the Hg methylation proteins HgcA and HgcB from M. hungatei are closely related to those from known SRB and IRB methylators and that they cluster together with proteins from eight other methanogens, suggesting that these methanogens may also methylate Hg. Because all nine methanogens with HgcA and HgcB orthologs belong to the class Methanomicrobia, constituting the late-evolving methanogenic lineage, methanogenic Hg methylation could not be considered an ancient metabolic trait. Our results identify methanogens as a new guild of Hg-methylating microbes with a potentially important role in mineral-poor (sulfate- and iron-limited) anoxic freshwater environments. PMID:23934484

  16. Rice allelopathy induced by methyl jasmonate and methyl salicylate.

    PubMed

    Bi, Hai Hong; Zeng, Ren Sen; Su, Li Ming; An, Min; Luo, Shi Ming

    2007-05-01

    Methyl jasmonate (MeJA) and methyl salicylate (MeSA) are important signaling molecules that induce plant defense against insect herbivores and microbial pathogens. We tested the hypothesis that allelopathy is an inducible defense mechanism, and that the JA and SA signaling pathways may activate allelochemicals release. Exogenous application of MeJA and MeSA to rice (Oryza sativa L.) enhanced rice allelopathic potential and led to accumulation of phenolics, an increase in enzymatic activities, and gene transcription of phenylalanine ammonia-lyase (PAL) and cinnamate 4-hydroxylase (C4H), two key enzymes in the phenylpropanoid pathway. Aqueous extracts of the leaves of rice IAC165, a putative allelopathic variety, treated with MeSA (5 mM) or MeJA (0.05 mM), showed increased inhibitory effects (25 and 21%, respectively) on root growth of barnyardgrass (Echinochloa crus-galli L.), and increased inhibitory effects (18 and 23%, respectively) on shoot growth. Aqueous extracts from leaves of Huajingxian 1 rice, a putative nonallelopathic variety treated with MeJA and MeSA, caused 63 and 24% inhibition of root growth in barnyardgrass seedlings. The root exudates of both IAC165 and Huajingxian 1 plants treated with MeJA and MeSA for 48 hr also showed significant increases in their inhibitory effects on root growth of barnyardgrass seedlings. At the four-leaf stage, levels of 3,4-hydroxybenzoic acid, vanillic acid, coumaric acid, and ferulic acid that accumulated in the leaves were 5.3-, 31.3-, 2.2-, and 1.7-fold higher in response to MeJA exposure, and 3.3-, 13.1-, 2.0-, and 2.2-fold higher in response to MeSA. Treatments of MeSA and MeJA enhanced the PAL activity in the rice leaves up to 52.3 and 80.1%, respectively, whereas C4H activity was increased by 40.2 and 67%. Gene transcription of PAL and C4H in rice leaves significantly increased after the plants were subjected to treatment with MeJA and MeSA. These results suggest that allelopathy may be an active defense mechanism, and that plant signaling compounds are potentially valuable in its regulation. PMID:17415624

  17. Effects of Sulforaphane and 3,3?-Diindolylmethane on Genome-Wide Promoter Methylation in Normal Prostate Epithelial Cells and Prostate Cancer Cells

    PubMed Central

    Wong, Carmen P.; Hsu, Anna; Buchanan, Alex; Palomera-Sanchez, Zoraya; Beaver, Laura M.; Houseman, E. Andres; Williams, David E.; Dashwood, Roderick H.; Ho, Emily

    2014-01-01

    Epigenetic changes, including aberrant DNA methylation, result in altered gene expression and play an important role in carcinogenesis. Phytochemicals such as sulforaphane (SFN) and 3,3?-diindolylmethane (DIM) are promising chemopreventive agents for the treatment of prostate cancer. Both have been shown to induce re-expression of genes, including tumor suppressor genes silenced in cancer cells, via modulation of epigenetic marks including DNA methylation. However, it remained unclear the effects SFN and DIM on DNA methylation at a genomic scale. The goal of this study was to determine the genome-wide effects of SFN and DIM on promoter methylation in normal prostate epithelial cells and prostate cancer cells. Both SFN and DIM treatment decreased DNA methyltransferase expression in normal prostate epithelial cells (PrEC), and androgen-dependent (LnCAP) and androgen-independent (PC3) prostate cancer cells. The effects of SFN and DIM on promoter methylation profiles in normal PrEC, LnCAP and PC3 prostate cancer cells were determined using methyl-DNA immunoprecipitation followed by genome-wide DNA methylation array. We showed widespread changes in promoter methylation patterns, including both increased and decreased methylation, in all three prostate cell lines in response to SFN or DIM treatments. In particular, SFN and DIM altered promoter methylation in distinct sets of genes in PrEC, LnCAP, and PC3 cells, but shared similar gene targets within a single cell line. We further showed that SFN and DIM reversed many of the cancer-associated methylation alterations, including aberrantly methylated genes that are dysregulated or are highly involved in cancer progression. Overall, our data suggested that both SFN and DIM are epigenetic modulators that have broad and complex effects on DNA methylation profiles in both normal and cancerous prostate epithelial cells. Results from our study may provide new insights into the epigenetic mechanisms by which SFN and DIM exert their cancer chemopreventive effects. PMID:24466240

  18. Effects of sulforaphane and 3,3'-diindolylmethane on genome-wide promoter methylation in normal prostate epithelial cells and prostate cancer cells.

    PubMed

    Wong, Carmen P; Hsu, Anna; Buchanan, Alex; Palomera-Sanchez, Zoraya; Beaver, Laura M; Houseman, E Andres; Williams, David E; Dashwood, Roderick H; Ho, Emily

    2014-01-01

    Epigenetic changes, including aberrant DNA methylation, result in altered gene expression and play an important role in carcinogenesis. Phytochemicals such as sulforaphane (SFN) and 3,3'-diindolylmethane (DIM) are promising chemopreventive agents for the treatment of prostate cancer. Both have been shown to induce re-expression of genes, including tumor suppressor genes silenced in cancer cells, via modulation of epigenetic marks including DNA methylation. However, it remained unclear the effects SFN and DIM on DNA methylation at a genomic scale. The goal of this study was to determine the genome-wide effects of SFN and DIM on promoter methylation in normal prostate epithelial cells and prostate cancer cells. Both SFN and DIM treatment decreased DNA methyltransferase expression in normal prostate epithelial cells (PrEC), and androgen-dependent (LnCAP) and androgen-independent (PC3) prostate cancer cells. The effects of SFN and DIM on promoter methylation profiles in normal PrEC, LnCAP and PC3 prostate cancer cells were determined using methyl-DNA immunoprecipitation followed by genome-wide DNA methylation array. We showed widespread changes in promoter methylation patterns, including both increased and decreased methylation, in all three prostate cell lines in response to SFN or DIM treatments. In particular, SFN and DIM altered promoter methylation in distinct sets of genes in PrEC, LnCAP, and PC3 cells, but shared similar gene targets within a single cell line. We further showed that SFN and DIM reversed many of the cancer-associated methylation alterations, including aberrantly methylated genes that are dysregulated or are highly involved in cancer progression. Overall, our data suggested that both SFN and DIM are epigenetic modulators that have broad and complex effects on DNA methylation profiles in both normal and cancerous prostate epithelial cells. Results from our study may provide new insights into the epigenetic mechanisms by which SFN and DIM exert their cancer chemopreventive effects. PMID:24466240

  19. Integrated Genetic and Epigenetic Analysis Identifies Haplotype-Specific Methylation in the FTO Type 2 Diabetes and Obesity Susceptibility Locus

    PubMed Central

    Wilson, Gareth A.; Rakyan, Vardhman K.; Teschendorff, Andrew E.; Akan, Pelin; Stupka, Elia; Down, Thomas A.; Prokopenko, Inga; Morison, Ian M.; Mill, Jonathan; Pidsley, Ruth; Deloukas, Panos; Frayling, Timothy M.; Hattersley, Andrew T.; McCarthy, Mark I.; Beck, Stephan; Hitman, Graham A.

    2010-01-01

    Recent multi-dimensional approaches to the study of complex disease have revealed powerful insights into how genetic and epigenetic factors may underlie their aetiopathogenesis. We examined genotype-epigenotype interactions in the context of Type 2 Diabetes (T2D), focussing on known regions of genomic susceptibility. We assayed DNA methylation in 60 females, stratified according to disease susceptibility haplotype using previously identified association loci. CpG methylation was assessed using methylated DNA immunoprecipitation on a targeted array (MeDIP-chip) and absolute methylation values were estimated using a Bayesian algorithm (BATMAN). Absolute methylation levels were quantified across LD blocks, and we identified increased DNA methylation on the FTO obesity susceptibility haplotype, tagged by the rs8050136 risk allele A (p?=?9.40×10?4, permutation p?=?1.0×10?3). Further analysis across the 46 kb LD block using sliding windows localised the most significant difference to be within a 7.7 kb region (p?=?1.13×10?7). Sequence level analysis, followed by pyrosequencing validation, revealed that the methylation difference was driven by the co-ordinated phase of CpG-creating SNPs across the risk haplotype. This 7.7 kb region of haplotype-specific methylation (HSM), encapsulates a Highly Conserved Non-Coding Element (HCNE) that has previously been validated as a long-range enhancer, supported by the histone H3K4me1 enhancer signature. This study demonstrates that integration of Genome-Wide Association (GWA) SNP and epigenomic DNA methylation data can identify potential novel genotype-epigenotype interactions within disease-associated loci, thus providing a novel route to aid unravelling common complex diseases. PMID:21124985

  20. Dietary and lifestyle factors of DNA methylation.

    PubMed

    Lim, Unhee; Song, Min-Ae

    2012-01-01

    Lifestyle factors, such as diet, smoking, physical activity, and body weight management, are known to constitute the majority of cancer causes. Epigenetics has been widely proposed as a main mechanism that mediates the reversible effects of dietary and lifestyle factors on carcinogenesis. This chapter reviews human studies on potential dietary and lifestyle determinants of DNA methylation. Apart from a few prospective investigations and interventions of limited size and duration, evidence mostly comes from cross-sectional observational studies and supports some associations. Studies to date suggest that certain dietary components may alter genomic and gene-specific DNA methylation levels in systemic and target tissues, affecting genomic stability and transcription of tumor suppressors and oncogenes. Most data and supportive evidence exist for folate, a key nutritional factor in one-carbon metabolism that supplies the methyl units for DNA methylation. Other candidate bioactive food components include alcohol and other key nutritional factors of one-carbon metabolism, polyphenols and flavonoids in green tea, phytoestrogen, and lycopene. Some data also support a link of DNA methylation with physical activity and energy balance. Effects of dietary and lifestyle exposures on DNA methylation may be additionally modified by common genetic variants, environmental carcinogens, and infectious agents, an aspect that remains largely unexplored. In addition, growing literature supports that the environmental conditions during critical developmental stages may influence later risk of metabolic disorders in part through persistent programming of DNA methylation. Further research of these modifiable determinants of DNA methylation will improve our understanding of cancer etiology and may present certain DNA methylation markers as attractive surrogate endpoints for prevention research. Considering the plasticity of epigenetic marks and correlated nature of lifestyle factors, more longitudinal studies of healthy individuals of varying age, sex, and ethnic groups are warranted, ideally with comprehensive data collection on various lifestyle factors. PMID:22359306

  1. A genetic sensor for strong methylating compounds

    PubMed Central

    Moser, Felix; Horwitz, Andrew; Chen, Jacinto; Lim, Wendell A.; Voigt, Christopher A.

    2013-01-01

    Methylating chemicals are common in industry and agriculture and are often toxic, partly due to their propensity to methylate DNA. The Escherichia coli Ada protein detects methylating compounds by sensing aberrant methyl adducts on the phosphoester backbone of DNA. We characterize this system as a genetic sensor and engineer it to lower the detection threshold. By overexpressing Ada from a plasmid, we improve the sensor’s dynamic range to 350-fold induction and lower its detection threshold to 40 µM for methyl iodide. In eukaryotes, there is no known sensor of methyl adducts on the phosphoester backbone of DNA. By fusing the N-terminal domain of Ada to the Gal4 transcriptional activation domain, we built a functional sensor for methyl phosphotriester adducts in Saccharomyces cerevisiae. This sensor can be tuned to variable specifications by altering the expression level of the chimeric sensor and changing the number of Ada operators upstream of the Gal4-sensitive reporter promoter. These changes result in a detection threshold of 28 µM and 5.2-fold induction in response to methyl iodide. When the yeast sensor is exposed to different SN1 and SN2 alkylating compounds, its response profile is similar to that observed for the native Ada protein in E. coli, indicating that its native function is retained in yeast. Finally, we demonstrate that the specifications achieved for the yeast sensor are suitable for detecting methylating compounds at relevant concentrations in environmental samples. This work demonstrates the movement of a sensor from a prokaryotic to eukaryotic system and its rational tuning to achieve desired specifications. PMID:24032656

  2. Synthesis and characterization of a pentadentate Schiff base N[sub 3]O[sub 2] ligand and its neutral technetium(V) complex. X-ray structure of (N,N[prime]-3-azapentane-1,5-diylbis(3-(1-iminoethyl)-6-methyl-2H-pyran-2,4(3H)-dionato)(3-)-O,O[prime],N,N[prime],N[double prime])oxotechnetium(V)

    SciTech Connect

    Shuang Liu; Rettig, S.J.; Orvig, C. (Univ. of British Columbia, Vancouver (Canada))

    1991-12-25

    Preparations of a potentially pentadentate ligand, N,N[prime]-3-azapentane-1,5-diylbis(3-(1-iminoethyl)-6-methyl-2H-pyran-2,4-(3H)-dione) (H[sub 3]apa), and its neutral technetium(V) complex, [TcO(apa)], are described. The [sup 13]C and [sup 1]H NMR, infrared, optical, and mass spectra of the pentadentate ligand and its technetium(V) complex are reported. The X-ray structure of [TcO(apa)] has been determined. Crystals are orthorhombic, space group Pbca, with a = 12.833 (2) [angstrom], b = 33.320 (5) [angstrom], c = 9.942(4) [angstrom], V = 4251 (2) [angstrom], and Z = 8. The structure was solved by Patterson and Fourier methods and was refined by full-matrix least-squares procedures to R = 0.028 and R[sub W] = 0.032 for 4054 reflections with I [ge] 3[sigma](I). The technetium(V) complex has a highly distorted octahedral coordination geometry comprising a [TcO][sup 3+] core and the triply deprotonated pentadentate ligand wrapping around the metal center. One of the two oxygen donor atoms of the pentadentate ligand is located trans to the Tc[double bond]O bond while the remaining four donor atoms, N[sub 3]O, occupy the equatorial sites. The distance between the deprotonated N(1) atom to the Tc center is significantly shorter than a normal Tc-N single bond length of 2.10 angstroms, but longer than that for a Tc-N triple bond. [sup 1]H NMR spectral data reveal a rigid solution structure for the complex, which undergoes no conformational and configurational exchange at temperatures up to 50C.

  3. INFLUENCE OF DISSOLVED ORGANIC MATTER ON THE COMPLEXATION OF MERCURY UNDER SULFIDIC CONDITIONS

    Microsoft Academic Search

    Carrie L. Miller; Robert P. Mason; Cynthia C. Gilmour; Andrew Heyes

    2007-01-01

    The complexation of Hg under sulfidic conditions influences its bioavailability for microbial methylation. Neutral dissolved Hg-sulfide complexes are readily available to Hg-methylating bacteria in culture, and thermodynamic models predict that inorganic Hg-sulfide complexes dominate dissolved Hg speciation under natural sulfidic conditions. However, these models have not been validated in the field. To examine the complexation of Hg in natural sulfidic

  4. Prenatal Exposure to Polycyclic Aromatic Hydrocarbons, Benzo[a]pyrene–DNA Adducts, and Genomic DNA Methylation in Cord Blood

    PubMed Central

    Tang, Deliang; Zhu, Deguang; Qu, Lirong; Sjödin, Andreas; Li, Zheng; Camann, David; Perera, Frederica P.

    2012-01-01

    Background: Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic environmental pollutants generated during incomplete combustion. After exposure and during metabolism, PAHs can form reactive epoxides that can covalently bind to DNA. These PAH–DNA adducts are established markers of cancer risk. PAH exposure has been associated with epigenetic alterations, including genomic cytosine methylation. Both global hypomethylation and hypermethylation of specific genes have been associated with cancer and other diseases in humans. Experimental evidence suggests that PAH–DNA adduct formation may preferentially target methylated genomic regions. Early embryonic development may be a particularly susceptible period for PAH exposure, resulting in both increased PAH–DNA adducts and altered DNA methylation. Objective: We explored whether prenatal exposure to PAHs is associated with genomic DNA methylation in cord blood and whether methylation levels are associated with the presence of detectable PAH–DNA adducts. Methods: In a longitudinal cohort study of nonsmoking women in New York City, we measured PAH exposure during pregnancy using personal air monitors, assessed PAH internal dose using prenatal urinary metabolites (in a subset), and quantified benzo[a]pyrene–DNA adducts and genomic DNA methylation in cord blood DNA among 164 participants. Results: Prenatal PAH exposure was associated with lower global methylation in umbilical cord white blood cells (p = 0.05), but global methylation levels were positively associated with the presence of detectable adducts in cord blood (p = 0.01). Conclusions: These observations suggest that PAH exposure was adequate to alter global methylation in our study population. Additional epidemiologic studies that can measure site-specific cytosine methylation and adduct formation will improve our ability to understand this complex molecular pathway in vivo. PMID:22256332

  5. Infrared spectra and chemical abundance of methyl propionate in icy astrochemical conditions

    NASA Astrophysics Data System (ADS)

    Sivaraman, B.; Radhika, N.; Das, A.; Gopakumar, G.; Majumdar, L.; Chakrabarti, S. K.; Subramanian, K. P.; Raja Sekhar, B. N.; Hada, M.

    2015-04-01

    We carried out an experiment in order to obtain the infrared (IR) spectra of methyl propionate (CH3CH2COOCH3) in astrochemical conditions and present the IR spectra for future identification of this molecule in the interstellar medium (ISM). The experimental IR spectrum is compared with the theoretical spectrum, and an attempt was made to assign the observed peak positions to their corresponding molecular vibrations in condensed phase. Moreover, our calculations suggest that methyl propionate must be synthesized efficiently within the complex chemical network of the ISM and therefore be present in cold dust grains, awaiting identification.

  6. Studies on in vitro S-methylation of naturally occurring thiol compounds with N-methyl-N-nitrosourea and methyl methanesulfonate

    SciTech Connect

    Trezl, L.; Park, K.S.; Kim, S.; Paik, W.K.

    1987-08-01

    N-Methyl-N-nitrosourea (MNU) and methyl methanesulfonate (MMS) were found to rapidly methylate glutathione (GSH) in vitro yielding S-methyl glutathione, as verified and quantitated by high-performance liquid chromatography and thin-layer chromatography. Formation of S-methylcysteine in the acid-hydrolyzate of the methylated GSH further confirmed the formation of S-methyl glutathione. Other naturally occurring thiol compounds such as cystein and homocysteine were also methylated by MNU. The observed pH dependency of GSH methylation by MNU suggests that the sulfide anion form of the thiol may represent the favored methyl acceptor. The high reactivity of GSH toward MNU and MMS may be of biological significance in that it could compete with macromolecular cellular components as a target for alkylation.

  7. Hydrogen bonding NH/? interactions between betacarboline and methyl benzene derivatives

    NASA Astrophysics Data System (ADS)

    Muñoz, María. A.; Sama, Octavio; Galán, Manuel; Guardado, Pilar; Carmona, Carmen; Balón, Manuel

    2001-04-01

    In the presence of benzene, toluene, m-xylene, mesitylene and durene, the pyrrolic NH stretching band of betacarboline, 9H-pyrido[3,4-b]indole, and its 1-methyl derivative, harmane, in tetrachloroethane diminishes in intensity while a new red-shifted band grows up. The shifts of the associated bands increase linearly with the ?-electron density of the substrates. These spectral changes are attributed to the formation of 1:1 molecular association complexes between the betacarbolines and the benzenoid substrates. The complexes are stabilized by the hydrogen-bonding interaction between the pyrrolic NH group of betacarboline and the ?-delocalized electrons of the benzene derivatives. The influence of these NH/? hydrogen-bonding interactions in the fluorescence spectra of betacarboline is discussed.

  8. Methyl parathion interaction with human and bovine serum albumin.

    PubMed

    Silva, Dílson; Cortez, Célia M; Cunha-Bastos, Jayme; Louro, Sônia R W

    2004-02-28

    Methyl parathion (MP; O,O-dimethyl O-p-nitrophenyl phosphorothioate) is an organophosphorous compound still largely used in agriculture and fish hatcheries. This pesticide is not quite selective and is potentially toxic for both vertebrates and invertebrates. Its mechanism of acute toxicity is the inhibition of the enzyme acetylcholinesterase in nervous tissue. Binding of pesticides to plasma proteins is one of many factors that influence their distribution and elimination. The free concentration available for toxic action can be effectively reduced for pesticides with high binding to plasma proteins, although the affinity of pesticides to plasma proteins is often lower than for the enzyme targets. Several different transport proteins exist in blood plasma, but albumin only is able to bind a wide diversity of xenobiotics reversibly with high affinity. It was already known that parathion (ethyl parathion) exhibits a high affinity to human and bovine serum albumins. We studied interactions of methyl parathion with these albumins by using fluorescence quenching techniques. We selectively excited the fluorescence of tryptophan residues with a 290 nm wavelength light, and observed quenching by titrating human and bovine serum albumin solutions with methyl parathion. Stern-Volmer graphs were plotted and quenching constants were estimated. Our results pointed to the formation of complexes of methyl parathion with albumins. Association constants at 25 degrees C were 3.07 x 10(4) (1.2 x 10(3))M(-1) for human serum albumin, and 1.96 x 10(4) (+/- 4.5 x 10(2))M(-1) for bovine serum albumin. At 37 degrees C, they were 1.08 x 10(4) (+/- 2.0 x 10(2))M(-1) for human serum albumin, and 8.16 x 10(3) (+/- 1.9 x 10(2))M(-1) for bovine serum albumin. Results also suggest that the primary binding site for methyl parathion on albumin is close to tryptophan residues 214 of human serum albumin and 212 of bovine serum albumin. PMID:14700528

  9. Aberrant Methylation in Gastric Cancer Associated with the CpG Island Methylator Phenotype1

    Microsoft Academic Search

    Minoru Toyota; Nita Ahuja; Hiromu Suzuki; Fumio Itoh; Mutsumi Ohe-Toyota; Kohzoh Imai; Stephen B. Baylin; Jean-Pierre J. Issa

    1999-01-01

    Aberrant methylation of 5* CpG islands is thought to play an important role in the inactivation of tumor suppressor genes in cancer. In colorectal cancer, a group of tumors is characterized by a hypermethylator pheno- type termed CpG island methylator phenotype (CIMP), which includes methylation of such genes as p16 and hMLH1. To study whether CIMP is present in gastric

  10. Conversion of methyl ricinoleate to methyl 12ketostearate with Raney nickel

    Microsoft Academic Search

    Bernard Freedman; Jane S. Nelson; R. G. Binder; T. H. Applewhite

    1965-01-01

    A convenient laboratory preparation of methyl 12-ketostearate is described. Methyl ricinoleate is converted to methyl 12-ketostearate\\u000a in 70–75% yield by Raney nickel. The type and quantity of Raney nickel have a marked influence on the yield as well as on\\u000a the time and temp required for the conversion. The reaction is not a direct isomerization as previously assumed but appears

  11. Seasonality, Sinks and Sources of Methyl Chloride and Methyl Bromide From the Tallgrass Prairie

    Microsoft Academic Search

    T. Abel; R. C. Rhew

    2008-01-01

    Net and gross fluxes of methyl chloride (CH3Cl) and methyl bromide (CH3Br) were measured between 2006 and 2008 from a variety of vegetation types and climatic conditions at a tallgrass prairie (Konza Prairie, Manhattan, KS). Gross consumption and production rates were calculated using a stable isotope tracer technique that entailed a small addition of 13C labeled methyl halides, and an

  12. Are one or two dangerous? Methyl salicylate exposure in toddlers

    Microsoft Academic Search

    Jonathan E. Davis

    2007-01-01

    Serious toxicity can result from exposure to small amounts of methyl salicylate. Methyl salicylate is widely available as a component in many over-the-counter brands of creams, ointments, lotions, liniments and medicated oils intended for topical application to relieve musculoskeletal aches and pains. Among the most potent forms of methyl salicylate is oil of wintergreen (98% methyl salicylate). Other products with

  13. Emission of methyl bromide from biomass burning

    SciTech Connect

    Manoe, S.; Andreae, M.O. (Max Planck Institute for Chemistry, Mainz (Germany))

    1994-03-04

    Bromine is, per atom, far more efficient than chlorine in destroying stratospheric ozone, and methyl bromide is the single largest source of stratospheric bromine. The two main previously known sources of this compound are emissions from the ocean and from the compound's use as an agricultural pesticide. Laboratory biomass combustion experiments showed that methyl bromide was emitted in the smoke from various fuels tested. Methyl bromide was also found in smoke plumes from wildfires in savannas, chaparral, and boreal forest. Global emissions of methyl bromide from biomass burning are estimated to be in the range of 10 to 50 gigagrams per year, which is comparable to the amount produced by ocean emission and pesticide use and represents a major contribution ([approximately]30 percent) to the stratospheric bromine budget.

  14. METHYLATED TRIVALENT ARSENIC SPECIES ARE GENOTOXIC

    EPA Science Inventory

    ABSTRACT The genotoxic effects of arsenic compounds are generally believed to result from other than direct interacton with DNA. The reactivties of methyloxarsine (MAsIII) and iododimethylarsine (DMAsIII), two methylated trivalent arsenicals, toward supercoiled X174 RFI ...

  15. Degradation of methyl bromide in anaerobic sediments

    USGS Publications Warehouse

    Oremland, R.S.; Miller, L.G.; Strohmaler, F.E.

    1994-01-01

    Methyl bromide (MeBr) was anaerobically degraded in saltmarsh sediments after reaction with sulfide. The product of this nucleophilic substitution reaction was methanethiol, which underwent further chemical and bacterial reactions to form dimethyl sulfide. These two gases appeared transiently during sediment incubations because they were metabolized by methanogenic and sulfate-reducing bacteria. A second, less significant reaction of MeBr was the exchange with chloride, forming methyl chloride, which was also susceptible to attack by sulfide. Incubation of 14C-labeled methyl iodide as an analogue of MeBr resulted in the formation of 14CH4 and 14CO2 and also indicated that sulfate-reducing bacteria as well as methanogens metabolized the methylated sulfur intermediates. These results suggest that exposed sediments with abundant free sulfide, such as coastal salt-marshes, may constitute a sink for atmospheric MeBr.

  16. Aberrant DNA Methylation in ES Cells

    PubMed Central

    Hecht, Merav; Orlanski, Shari; Abu-Remaileh, Monther; Yanuka, Ofra; Sandler, Oded; Marx, Amichai; Roberts, Douglas; Benvenisty, Nissim; Bergman, Yehudit; Mendelsohn, Monica; Cedar, Howard

    2014-01-01

    Both mouse and human embryonic stem cells can be differentiated in vitro to produce a variety of somatic cell types. Using a new developmental tracing approach, we show that these cells are subject to massive aberrant CpG island de novo methylation that is exacerbated by differentiation in vitro. Bioinformatics analysis indicates that there are two distinct forms of abnormal de novo methylation, global as opposed to targeted, and in each case the resulting pattern is determined by molecular rules correlated with local pre-existing histone modification profiles. Since much of the abnormal methylation generated in vitro appears to be stably maintained, this modification may inhibit normal differentiation and could predispose to cancer if cells are used for replacement therapy. Excess CpG island methylation is also observed in normal placenta, suggesting that this process may be governed by an inherent program. PMID:24852222

  17. Heterochromatin Dynamics during the Differentiation Process Revealed by the DNA Methylation Reporter Mouse, MethylRO

    PubMed Central

    Ueda, Jun; Maehara, Kazumitsu; Mashiko, Daisuke; Ichinose, Takako; Yao, Tatsuma; Hori, Mayuko; Sato, Yuko; Kimura, Hiroshi; Ohkawa, Yasuyuki; Yamagata, Kazuo

    2014-01-01

    Summary In mammals, DNA is methylated at CpG sites, which play pivotal roles in gene silencing and chromatin organization. Furthermore, DNA methylation undergoes dynamic changes during development, differentiation, and in pathological processes. The conventional methods represent snapshots; therefore, the dynamics of this marker within living organisms remains unclear. To track this dynamics, we made a knockin mouse that expresses a red fluorescent protein (RFP)-fused methyl-CpG-binding domain (MBD) protein from the ROSA26 locus ubiquitously; we named it MethylRO (methylation probe in ROSA26 locus). Using this mouse, we performed RFP-mediated methylated DNA immunoprecipitation sequencing (MeDIP-seq), whole-body section analysis, and live-cell imaging. We discovered that mobility and pattern of heterochromatin as well as DNA methylation signal intensity inside the nuclei can be markers for cellular differentiation status. Thus, the MethylRO mouse represents a powerful bioresource and technique for DNA methylation dynamics studies in developmental biology, stem cell biology, as well as in disease states. PMID:24936475

  18. Heterochromatin dynamics during the differentiation process revealed by the DNA methylation reporter mouse, MethylRO.

    PubMed

    Ueda, Jun; Maehara, Kazumitsu; Mashiko, Daisuke; Ichinose, Takako; Yao, Tatsuma; Hori, Mayuko; Sato, Yuko; Kimura, Hiroshi; Ohkawa, Yasuyuki; Yamagata, Kazuo

    2014-06-01

    In mammals, DNA is methylated at CpG sites, which play pivotal roles in gene silencing and chromatin organization. Furthermore, DNA methylation undergoes dynamic changes during development, differentiation, and in pathological processes. The conventional methods represent snapshots; therefore, the dynamics of this marker within living organisms remains unclear. To track this dynamics, we made a knockin mouse that expresses a red fluorescent protein (RFP)-fused methyl-CpG-binding domain (MBD) protein from the ROSA26 locus ubiquitously; we named it MethylRO (methylation probe in ROSA26 locus). Using this mouse, we performed RFP-mediated methylated DNA immunoprecipitation sequencing (MeDIP-seq), whole-body section analysis, and live-cell imaging. We discovered that mobility and pattern of heterochromatin as well as DNA methylation signal intensity inside the nuclei can be markers for cellular differentiation status. Thus, the MethylRO mouse represents a powerful bioresource and technique for DNA methylation dynamics studies in developmental biology, stem cell biology, as well as in disease states. PMID:24936475

  19. Histone methylation marks play important roles in predicting the methylation status of CpG islands.

    PubMed

    Fan, Shicai; Zhang, Michael Q; Zhang, Xuegong

    2008-09-26

    The methylation status of CpG islands is highly correlated with gene expression. Current methods for computational prediction of DNA methylation only utilize DNA sequence features. In this study, besides 35 DNA sequence features, we added four histone methylation marks to predict the methylation status of CpG islands, and improved the accuracy to 89.94%. Also we applied our model to predict the methylation pattern of all the CpG islands in the human genome, and the results are consistent with the previous reports. Our results imply the important roles of histone methylation marks in affecting the methylation status of CpG islands. H3K4me enriched in the methylation-resistant CpG islands could disrupt the contacts between nucleosomes, unravel chromatin and make DNA sequences accessible. And the established open environment may be a prerequisite for or a consequence of the function implementation of zinc finger proteins that could protect CpG islands from DNA methylation. PMID:18656446

  20. Oligodeoxynucleotides containing N1-methyl-2'-deoxyadenosine and N6-methyl-2'-deoxyadenosine.

    PubMed

    Mikhailov, Sergey N; Timofeev, Edward N; Drenichev, Mikhail S; Efimtseva, Ekaterina V; Herdewijn, Piet; Roesch, Eric B; Lemaitre, Marc M

    2009-09-01

    This unit describes a simple and efficient synthesis of the phosphoramidite derivative of N(1)-methyl-2'-deoxyadenosine from 2'-deoxyadenosine. The synthesis starts with the monomethoxytritylation of 2'-deoxyadenosine followed by methylation of 5'-O-protected nucleoside at N-1. Subsequent N-chloroacetylation leads to N(6)-chloroacetyl-N(1)-methyl-5'-O-(p-anisyldiphenylmethyl)-2'-deoxyadenosine, which is finally converted to its 3' phosphoramidite derivative. This phosphoramidite is used to incorporate N(1)-methyl-2'-deoxyadenosine into synthetic oligonucleotides. N-Chloroacetyl protection and controlled anhydrous deprotection conditions are used to avoid the Dimroth rearrangement. PMID:19746356

  1. Bacterial DNA Methylation: a Cell Cycle Regulator?

    Microsoft Academic Search

    ANN REISENAUER; LYN SUE KAHNG; SUSAN MCCOLLUM; LUCY SHAPIRO

    1999-01-01

    Although bacterial DNA methyltransferases are generally associated with restriction-modification systems, DNA methyl- ation also regulates chromosome replication, transcription, re- pair, and most likely other fundamental processes. The two best-studied DNA methyltransferases without apparent cog- nate restriction enzymes are the Escherichia coli Dam and Caulobacter crescentus CcrM enzymes. Dam methylation is re- quired for the control of chromosome replication (5, 18),

  2. Hidden among the crowd: differential DNA methylation-expression correlations in cancer occur at important oncogenic pathways

    PubMed Central

    Mosquera Orgueira, Adrián

    2015-01-01

    DNA methylation is a frequent epigenetic mechanism that participates in transcriptional repression. Variations in DNA methylation with respect to gene expression are constant, and, for unknown reasons, some genes with highly methylated promoters are sometimes overexpressed. In this study we have analyzed the expression and methylation patterns of thousands of genes in five groups of cancer and normal tissue samples in order to determine local and genome-wide differences. We observed significant changes in global methylation-expression correlation in all the neoplasms, which suggests that differential correlation events are frequent in cancer. A focused analysis in the breast cancer cohort identified 1662 genes whose correlation varies significantly between normal and cancerous breast, but whose DNA methylation and gene expression patterns do not change substantially. These genes were enriched in cancer-related pathways and repressive chromatin features across various model cell lines, such as PRC2 binding and H3K27me3 marks. Substantial changes in methylation-expression correlation indicate that these genes are subject to epigenetic remodeling, where the differential activity of other factors break the expected relationship between both variables. Our findings suggest a complex regulatory landscape where a redistribution of local and large-scale chromatin repressive domains at differentially correlated genes (DCGs) creates epigenetic hotspots that modulate cancer-specific gene expression.

  3. A study of the autoxidation of some unsaturated fatty acid methyl esters using Fourier transform Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Agbenyega, J. K.; Claybourn, M.; Ellis, G.

    Near-infrared Fourier transform Raman and Fourier transform infrared spectroscopy have been used to investigate the chemical changes taking place during the curing reaction of several fatty acid methyl esters, which are used for modelling processes in the autoxidation of alkyd resin coatings. We have studied methyl oleate, methyl linoleate, and methyl linolenate in an attempt to monitor the degree of unsaturation within the fatty acid methyl esters (FAMES) during the complex autoxidation/polymerisation reaction that takes place once the paint system is coated onto a substrate and exposed to the atmosphere. The peaks around 1655 cm -1 have been assigned as follows: to the trans isomer at 1670 cm -1, the cis isomer at 1655 cm -1 and the conjugated structure at 1640 cm -1 [B. Schrader, Raman/Infrared Atlas of Organic Compounds (2nd Edn), VCH, Weinheim (1989); J. K. Abenyega, M. Claybourn and G. Ellis, in preparations]. Raman spectra for the cure of methyl linoleate after 24 h show several interesting features, suggesting the formation of a highly conjugated cyclic structure. Current theories about the mechanism for the autoxidation of methyl linoleate make no mention of this aromatic product.

  4. Ni/sup II/(dioxo(16)aneN/sub 5/)-induced methane formation from methyl coenzyme M

    SciTech Connect

    Drain, C.M.; Sable, D.B.; Corden, B.B.

    1988-07-13

    A mechanism has been previously proposed for methyl-coenzyme M (H/sub 3/CSCH/sub 2/CH/sub 2/SO/sub 3//sup /minus//) reductase where Ni/sup II/F/sub 430/ is first reduced to NiF/sub 430/, which homolytically cleaves the methyl-coenzyme M to produce methyl-Ni/sup I/F/sub 430/ followed by the protonation of methyl-Ni/sup I/F/sub 430/ to yield CH/sub 4/ and Ni/sup II/F/sub 430/. The role of the nickel ion oxidation state in methyl-coenzyme M catalysis has been examined. It was found that both the mono- and divalent oxidation states of the water soluble Ni (dioxo(16)-aneN/sub 5/), NiL, complex catalyze the methyl-coenzyme M to methane and coenzyme M. Some aqueous solutions of other nickel compounds, e.g. nickel (II) acetate, nickel(II) tetraethylenepentamine, or nickel(II) 1,4,8,11-tetraazacyclotetradecane-5,7-dione, do not convert methyl-coenzyme M to methane under argon or hydrogen. 30 references, 1 figure.

  5. DNA methylation profiling reveals a predominant immune component in breast cancers.

    PubMed

    Dedeurwaerder, Sarah; Desmedt, Christine; Calonne, Emilie; Singhal, Sandeep K; Haibe-Kains, Benjamin; Defrance, Matthieu; Michiels, Stefan; Volkmar, Michael; Deplus, Rachel; Luciani, Judith; Lallemand, Françoise; Larsimont, Denis; Toussaint, Jérôme; Haussy, Sandy; Rothé, Françoise; Rouas, Ghizlane; Metzger, Otto; Majjaj, Samira; Saini, Kamal; Putmans, Pascale; Hames, Gérald; van Baren, Nicolas; Coulie, Pierre G; Piccart, Martine; Sotiriou, Christos; Fuks, François

    2011-12-01

    Breast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimizing treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but the involvement of the epigenome in breast cancer and its contribution to the complexity of the disease are still poorly understood. By means of DNA methylation profiling of 248 breast tissues, we have highlighted the existence of previously unrecognized breast cancer groups that go beyond the currently known 'expression subtypes'. Interestingly, we showed that DNA methylation profiling can reflect the cell type composition of the tumour microenvironment, and in particular a T lymphocyte infiltration of the tumours. Further, we highlighted a set of immune genes having high prognostic value in specific tumour categories. The immune component uncovered here by DNA methylation profiles provides a new perspective for the importance of the microenvironment in breast cancer, holding implications for better management of breast cancer patients. PMID:21910250

  6. Biodegradation-inspired bioproduction of methylacetoin and 2-methyl-2,3-butanediol.

    PubMed

    Jiang, Xinglin; Zhang, Haibo; Yang, Jianming; Zheng, Yanning; Feng, Dexin; Liu, Wei; Xu, Xin; Cao, Yujin; Zou, Huibin; Zhang, Rubin; Cheng, Tao; Jiao, Fengjiao; Xian, Mo

    2013-01-01

    Methylacetoin (3-hydroxy-3-methylbutan-2-one) and 2-methyl-2,3-butanediol are currently obtained exclusively via chemical synthesis. Here, we report, to the best of our knowledge, the first alternative route, using engineered Escherichia coli. The biological synthesis of methylacetoin was first accomplished by reversing its biodegradation, which involved modifying the enzyme complex involved, switching the reaction substrate, and coupling the process to an exothermic reaction. 2-Methyl-2,3-butanediol was then obtained by reducing methylacetoin by exploiting the substrate promiscuity of acetoin reductase. A complete biosynthetic pathway from renewable glucose and acetone was then established and optimized via in vivo enzyme screening and host metabolic engineering, which led to titers of 3.4 and 3.2 g l(-1) for methylacetoin and 2-methyl-2,3-butanediol, respectively. This work presents a biodegradation-inspired approach to creating new biosynthetic pathways for small molecules with no available natural biosynthetic pathway. PMID:23945710

  7. Native DNA repeats and methylation in Ascobolus.

    PubMed Central

    Goyon, C; Rossignol, J L; Faugeron, G

    1996-01-01

    We identified two classes of native dispersed DNA repeats in the Ascobolus genome. The first class consisted of several kilobase long, methylated repeats. These repeats, named Mars (methylated Ascobolus repeated sequences), fell in one family of LINE-like elements and in three families of LTR-containing retrotransposable elements. The methylation features of Mars elements were those expected if they were natural targets for the MIP (methylation induced premeiotically) previously discovered in Ascobolus. The second class consisted of short repeats, approximately 100 bp long, corresponding to 5S rRNA and tRNA genes. As expected from their size, which was too small to allow MIP to occur, they were unmethylated, as were 26 kb of unique sequences tested. These observations are consistent with the hypothesis that MIP is targeted at natural DNA repeats and constitutes a defensive process against the detrimental consequences of the spreading of mobile elements throughout the genome. The 9 kb tandem repeats harbouring the 28S, 18S and 5.8S rRNA genes displayed methylation features suggesting that rDNA methylation proceeds through a process other than MIP. PMID:8811089

  8. DNA methylation and application in forensic sciences.

    PubMed

    Kader, Farzeen; Ghai, Meenu

    2015-04-01

    DNA methylation of cytosine residues is a stable epigenetic alteration, beginning as early as foetal development in the uterus and continuously evolving throughout life. DNA methylation as well as other epigenetic modifications such as chromatin remodelling and histone modifications are indispensable in mammalian development. Methylation is to a large extent influenced by the ageing process, diets and lifestyle choices. Our understanding of this crucial modification may even contribute to the treatment and prevention of age-related illnesses in the very near future. Genome-wide methylation analysis using high throughput DNA technologies has discovered numerous differentially methylated regions (tDMRs) which differ in levels of methylation in various cell types and tissues. TDMRs have been useful in various applications, particularly medicine and forensic sciences. Forensic scientists are constantly seeking exciting and novel methods to aid in the reconstruction of crime scenes, and the analysis of tDMRs represents a new and reliable technique to identify biological fluids and tissues found at the scene of a violent act. Not only has research been able to unequivocally identify various fluids and tissues, but methods to determine the sex, age and phenotype of donors has been developed. New tDMRs in genes are being searched for consistently to serve as novel markers in forensic DNA analysis. PMID:25732744

  9. Efficient acquisition of high-resolution 4-D diagonal-suppressed methyl-methyl NOESY for large proteins

    NASA Astrophysics Data System (ADS)

    Wen, Jie; Zhou, Pei; Wu, Jihui

    2012-05-01

    The methyl-methyl NOESY experiment plays an important role in determining the global folds of large proteins. Despite the high sensitivity of this experiment, the analysis of methyl-methyl NOEs is frequently hindered by the limited chemical shift dispersion of methyl groups, particularly methyl protons. This makes it difficult to unambiguously assign all of the methyl-methyl NOE crosspeaks using 3-D spectroscopy. The recent development of sparse sampling methods enables highly efficient acquisition of high-resolution 4-D spectra, which provides an excellent solution to resolving the degeneracy of methyl signals. However, many reconstruction algorithms for processing sparsely-sampled NMR data do not provide adequate suppression of aliasing artifacts in the presence of strong NOE diagonal signals. In order to overcome this limitation, we present a 4-D diagonal-suppressed methyl-methyl NOESY experiment specifically optimized for ultrasparse sampling and evaluate it using a deuterated, ILV methyl-protonated sample of the 42 kDa Escherichia coli maltose binding protein (MBP). Suppression of diagonal signals removes the dynamic range barrier of the methyl-methyl NOESY experiment such that residual aliasing artifacts in the CLEAN-reconstructed high-resolution 4-D spectrum can be further reduced. At an ultrasparse sampling rate of less than 1%, we were able to identify and unambiguously assign the vast majority of expected NOE crosspeaks between methyl groups separated by less than 5 Å and to detect very weak NOE crosspeaks from methyl groups that are over 7 Å apart.

  10. A Prototypic Lysine Methyltransferase 4 from Archaea with Degenerate Sequence Specificity Methylates Chromatin Proteins Sul7d and Cren7 in Different Patterns*

    PubMed Central

    Niu, Yanling; Xia, Yisui; Wang, Sishuo; Li, Jiani; Niu, Caoyuan; Li, Xiao; Zhao, Yuehui; Xiong, Huiyang; Li, Zhen; Lou, Huiqiang; Cao, Qinhong

    2013-01-01

    Histone methylation is one of the major epigenetic modifications even in early diverging unicellular eukaryotes. We show that a widespread lysine methyltransferase from Archaea (aKMT4), bears striking structural and functional resemblance to the core of distantly related eukaryotic KMT4/Dot1. aKMT4 methylates a set of various proteins, including the chromatin proteins Sul7d and Cren7, and RNA exosome components. Csl4- and Rrp4-exosome complexes are methylated in different patterns. aKMT4 can self-methylate intramolecularly and compete with other proteins for the methyl group. Automethylation is inhibited by suitable substrates or DNA in a concentration-dependent manner. The automethylated enzyme shows relatively compromised activity. aKMT4-8A mutant with abrogated automethylation shows a more than 150% increase in methylation of substrates, suggesting a possible mechanism to regulate methyltransferase activity. More interestingly, methylation of Sul7d, but not Cren7, by aKMT4 is significantly enhanced by DNA. MS/MS and kinetic analysis further suggest that aKMT4 methylates Sul7d in the chromatin context. These data provide a clue to the possible regulation of aKMT4 activity by the local chromatin environment, albeit as a promiscuous enzyme required for extensive and variegated lysine methylation in Sulfolobus. This study supports the prokaryotic origin model of eukaryotic histone modification enzymes and sheds light on regulation of archaeal chromatin. PMID:23530048

  11. CpG Island Methylator Phenotype in Colorectal Cancer

    Microsoft Academic Search

    Minoru Toyota; Nita Ahuja; Mutsumi Ohe-Toyota; James G. Herman; Stephen B. Baylin; Jean-Pierre J. Issa

    1999-01-01

    Aberrant methylation of promoter region CpG islands is associated with transcriptional inactivation of tumor-suppressor genes in neoplasia. To understand global patterns of CpG island methylation in colorectal cancer, we have used a recently developed technique called methylated CpG island amplication to examine 30 newly cloned differentially methylated DNA sequences. Of these 30 clones, 19 (63%) were progressively methylated in an

  12. Methyl halide emissions from savanna fires in southern Africa

    Microsoft Academic Search

    M. O. Andreae; E. Atlas; G. W. Harris; G. Helas; A. de Kock; R. Koppmann; W. Maenhaut; S. Manø; W. H. Pollock; J. Rudolph; D. Scharffe; G. Schebeske; M. Welling

    1996-01-01

    The methyl halides, methyl chloride (CH3Cl), methyl bromide (CH3Br), and methyl iodide (CH3I), were measured in regional air samples and smoke from savanna fires in southern Africa during the Southern Africa Fire-Atmosphere Research Initiative-92 (SAFARI-92) experiment (August-October 1992). All three species were significantly enhanced in the smoke plumes relative to the regional background. Good correlations were found between the methyl

  13. Increased methylation of interleukin 6 gene is associated with obesity in korean women.

    PubMed

    Na, Yeon Kyung; Hong, Hae Sook; Lee, Won Kee; Kim, Young Hun; Kim, Dong Sun

    2015-05-31

    Obesity is the fifth leading risk for death globally, and a significant challenge to global health. It is a common, complex, non-malignant disease and develops due to interactions between the genes and the environment. DNA methylation can act as a downstream effector of environmental signals; analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. To assess the effects of excessive weight and obesity on gene-specific methylation levels of promoter regions, we determined the methylation status of four genes involved in inflammation and oxidative stress [interleukin 6 (IL6), tumor necrosis factor ? (TNF?), mitochondrial transcription factor A (TFAM), and glucose transport 4 (GLUT4)] in blood cell-derived DNA from healthy women volunteers with a range of body mass indices (BMIs) by methylation-specific PCR. Interestingly, the samples from obese individuals (BMI ? 30 kg/m(2)) showed significantly increased hypermethylation for IL6 gene compared to normal weight (BMI < 23 kg/m(2)) and overweight samples (23 kg/m(2) ? BMI < 30 kg/m(2)) (P = 0.034 and P = 0.026). However, there was no statistically significant difference in promoter methylation of the other 3 genes between each group. These findings suggest that aberrant DNA methylation of IL6 gene promoter may play an important role in the etiology and pathogenesis of obesity and IL6 methylation could be used as molecular biomarker for obesity risk assessment. Further studies are required to elucidate the potential mechanisms underlying this relationship. PMID:25921605

  14. Notes on the role of dynamic DNA methylation in mammalian development.

    PubMed

    Bestor, Timothy H; Edwards, John R; Boulard, Mathieu

    2015-06-01

    It has been nearly 40 y since it was suggested that genomic methylation patterns could be transmitted via maintenance methylation during S phase and might play a role in the dynamic regulation of gene expression during development [Holliday R, Pugh JE (1975) Science 187(4173):226-232; Riggs AD (1975) Cytogenet Cell Genet 14(1):9-25]. This revolutionary proposal was justified by "... our almost complete ignorance of the mechanism for the unfolding of the genetic program during development" that prevailed at the time. Many correlations between transcriptional activation and demethylation have since been reported, but causation has not been demonstrated and to date there is no reasonable proof of the existence of a complex biochemical system that activates and represses genes via reversible DNA methylation. Such a system would supplement or replace the conserved web of transcription factors that regulate cellular differentiation in organisms that have unmethylated genomes (such as Caenorhaditis elegans and the Dipteran insects) and those that methylate their genomes. DNA methylation does have essential roles in irreversible promoter silencing, as in the monoallelic expression of imprinted genes, in the silencing of transposons, and in X chromosome inactivation in female mammals. Rather than reinforcing or replacing regulatory pathways that are conserved between organisms that have either methylated or unmethylated genomes, DNA methylation endows genomes with the ability to subject specific sequences to irreversible transcriptional silencing even in the presence of all of the factors required for their expression, an ability that is generally unavailable to organisms that have unmethylated genomes. PMID:25368180

  15. DNA methylation analysis of murine hematopoietic side population cells during aging.

    PubMed

    Taiwo, Oluwatosin; Wilson, Gareth A; Emmett, Warren; Morris, Tiffany; Bonnet, Dominique; Schuster, Eugene; Adejumo, Tomas; Beck, Stephan; Pearce, Daniel J

    2013-10-01

    Stem cells have been found in most tissues/organs. These somatic stem cells produce replacements for lost and damaged cells, and it is not completely understood how this regenerative capacity becomes diminished during aging. To study the possible involvement of epigenetic changes in somatic stem cell aging, we used murine hematopoiesis as a model system. Hematopoietic stem cells (HSCs) were enriched for via Hoechst exclusion activity (SP-HSC) from young, medium-aged and old mice and subjected to comprehensive, global methylome (MeDIP-seq) analysis. With age, we observed a global loss of DNA methylation of approximately 5%, but an increase in methylation at some CpG islands. Just over 100 significant (FDR<0.2) aging-specific differentially methylated regions (aDMRs) were identified, which are surprisingly few considering the profound age-based changes that occur in HSC biology. Interestingly, the polycomb repressive complex -2 (PCRC2) target genes Kiss1r, Nav2 and Hsf4 were hypermethylated with age. The promoter for the Sdpr gene was determined to be progressively hypomethylated with age. This occurred concurrently with an increase in gene expression with age. To explore this relationship further, we cultured isolated SP-HSC in the presence of 5-aza-deoxycytdine and demonstrated a negative correlation between Sdpr promoter methylation and gene expression. We report that DNA methylation patterns are well preserved during hematopoietic stem cell aging, confirm that PCRC2 targets are increasingly methylated with age, and suggest that SDPR expression changes with age in HSCs may be regulated via age-based alterations in DNA methylation. PMID:23949429

  16. Importance of sulfate reducing bacteria in mercury methylation and demethylation in periphyton from Bolivian Amazon region.

    PubMed

    Achá, Darío; Hintelmann, Holger; Yee, Janet

    2011-02-01

    Sulfate reducing bacteria (SRB) are important mercury methylators in sediments, but information on mercury methylators in other compartments is ambiguous. To investigate SRB involvement in methylation in Amazonian periphyton, the relationship between Hg methylation potential and SRB (Desulfobacteraceae, Desulfobulbaceae and Desulfovibrionaceae) abundance in Eichhornia crassipes and Polygonum densiflorum root associated periphyton was examined. Periphyton subsamples of each macrophyte were amended with electron donors (lactate, acetate and propionate) or inhibitors (molybdate) of sulfate reduction to create differences in SRB subgroup abundance, which was measured by quantitative real-time PCR with primers specific for the 16S rRNA gene. Mercury methylation and demethylation potentials were determined by a stable isotope tracer technique using 200HgCl and CH3(202)HgCl, respectively. Relative abundance of Desulfobacteraceae (<0.01-12.5%) and Desulfovibrionaceae (0.01-6.8%) were both highly variable among samples and subsamples, but a significant linear relationship (p<0.05) was found between Desulfobacteraceae abundance and net methylmercury formation among treatments of the same macrophyte periphyton and among all P. densiflorum samples, suggesting that Desulfobacteraceae bacteria are the most important mercury methylators among SRB families. Yet, molybdate only partially inhibited mercury methylation potentials, suggesting the involvement of other microorganisms as well. The response of net methylmercury production to the different electron donors and molybdate was highly variable (3-1104 pg g(-1) in 12 h) among samples, as was the net formation in control samples (17-164 pg g(-1) in 12 h). This demonstrates the importance of community variability and complexity of microbial interactions for the overall methylmercury production in periphyton and their response to external stimulus. PMID:21074243

  17. RlmN and Cfr are Radical SAM Enzymes Involved in Methylation of Ribosomal RNA

    PubMed Central

    Yan, Feng; LaMarre, Jacqueline M.; Röhrich, Rene; Wiesner, Jochen; Jomaa, Hassan; Mankin, Alexander S.; Fujimori, Danica Galoni?

    2010-01-01

    Posttranscriptional modifications of ribosomal RNA (rRNA) nucleotides are a common mechanism of modulating the ribosome’s function and conferring bacterial resistance to ribosome-targeting antibiotics. One such modification is methylation of an adenosine nucleotide within the peptidyl transferase center of the ribosome mediated by the indigenous methyltransferase RlmN and its evolutionary-related resistance enzyme Cfr. These methyltransferases catalyze methyl transfer to aromatic carbon atoms of the adenosine within a complex 23S rRNA substrate to form the 2,8-dimethylated product. RlmN and Cfr are members of the Radical SAM superfamily, and contain the characteristic cysteine rich CX3CX2C motif. We demonstrate that both enzymes are capable of accommodating the requisite [4Fe-4S] cluster. S-adenosylmethionine (SAM) is both the methyl donor and the source of a 5?-deoxyadenosyl radical, which activates the substrate for methylation. Detailed analyses of the rRNA requirements show that the enzymes can utilize protein-free 23S rRNA as a substrate, but not the fully-assembled large ribosomal subunit, suggesting that the methylations take place during the assembly of the ribosome. The key recognition elements in the 23S rRNA are helices 90–92 and the adjacent single stranded RNA that encompasses A2503. To our knowledge, this study represents the first in vitro description of a methyl transfer catalyzed by a member of Radical SAM superfamily, and it expands the catalytic repertoire of this diverse enzyme class. Furthermore, by providing information on both the timing of methylation and its substrate requirements, our findings have important implications for the functional consequences of Cfr-mediated modification of rRNA in acquisition of antibiotic resistance. PMID:20184321

  18. A Genome-Wide Methylation Study on Essential Hypertension in Young African American Males

    PubMed Central

    Wang, Xiaoling; Falkner, Bonita; Zhu, Haidong; Shi, Huidong; Su, Shaoyong; Xu, Xiaojing; Sharma, Ashok Kumar; Dong, Yanbin; Treiber, Frank; Gutin, Bernard; Harshfield, Gregory; Snieder, Harold

    2013-01-01

    Objective There is emerging evidence from animal studies suggesting a key role for methylation in the pathogenesis of essential hypertension. However, to date, very few studies have investigated the role of methylation in the development of human hypertension, and none has taken a genome-wide approach. Based on the recent studies that highlight the involvement of inflammation in the development of hypertension, we hypothesize that changes in DNA methylation of leukocytes are involved in the pathogenesis of hypertension. Method & Results We conducted a genome-wide methylation analysis on 8 hypertensive cases and 8 normotensive age-matched controls aged 14–23 years and performed validation of the most significant CpG sites in 2 genes in an independent sample of 36 hypertensive cases and 60 normotensive controls aged 14–30 years. Validation of the CpG sites in the SULF1 gene was further conducted in a second replication sample of 36 hypertensive cases and 34 controls aged 15.8–40 years. A CpG site in the SULF1 gene showed higher methylation levels in cases than in healthy controls in the genome-wide step (p?=?6.2×10?5), which was confirmed in the validation step (p?=?0.011) for subjects ?30 years old but was not significant for subjects of all ages combined (p?=?0.095). Conclusion The identification of a difference in a blood leukocyte DNA methylation site between hypertensive cases and normotensive controls suggests that changes in DNA methylation may play an important role in the pathogenesis of hypertension. The age dependency of the effect further suggests complexity of epigenetic regulation in this age-related disease. PMID:23325143

  19. Increased Methylation of Interleukin 6 Gene Is Associated with Obesity in Korean Women

    PubMed Central

    Na, Yeon Kyung; Hong, Hae Sook; Lee, Won Kee; Kim, Young Hun; Kim, Dong Sun

    2015-01-01

    Obesity is the fifth leading risk for death globally, and a significant challenge to global health. It is a common, complex, non-malignant disease and develops due to interactions between the genes and the environment. DNA methylation can act as a downstream effector of environmental signals; analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. To assess the effects of excessive weight and obesity on gene-specific methylation levels of promoter regions, we determined the methylation status of four genes involved in inflammation and oxidative stress [interleukin 6 (IL6), tumor necrosis factor ? (TNF?), mitochondrial transcription factor A (TFAM), and glucose transport 4 (GLUT4)] in blood cell-derived DNA from healthy women volunteers with a range of body mass indices (BMIs) by methylation-specific PCR. Interestingly, the samples from obese individuals (BMI ? 30 kg/m2) showed significantly increased hypermethylation for IL6 gene compared to normal weight (BMI < 23 kg/m2) and overweight samples (23 kg/m2 ? BMI < 30 kg/m2) (P = 0.034 and P = 0.026). However, there was no statistically significant difference in promoter methylation of the other 3 genes between each group. These findings suggest that aberrant DNA methylation of IL6 gene promoter may play an important role in the etiology and pathogenesis of obesity and IL6 methylation could be used as molecular biomarker for obesity risk assessment. Further studies are required to elucidate the potential mechanisms underlying this relationship. PMID:25921605

  20. Synergistic Function of DNA Methyltransferases Dnmt3a and Dnmt3b in the Methylation of Oct4 and Nanog?

    PubMed Central

    Li, Jing-Yu; Pu, Min-Tie; Hirasawa, Ryutaro; Li, Bin-Zhong; Huang, Yan-Nv; Zeng, Rong; Jing, Nai-He; Chen, Taiping; Li, En; Sasaki, Hiroyuki; Xu, Guo-Liang

    2007-01-01

    DNA methylation plays an important role in gene silencing in mammals. Two de novo methyltransferases, Dnmt3a and Dnmt3b, are required for the establishment of genomic methylation patterns in development. However, little is known about their coordinate function in the silencing of genes critical for embryonic development and how their activity is regulated. Here we show that Dnmt3a and Dnmt3b are the major components of a native complex purified from embryonic stem cells. The two enzymes directly interact and mutually stimulate each other both in vitro and in vivo. The stimulatory effect is independent of the catalytic activity of the enzyme. In differentiating embryonic carcinoma or embryonic stem cells and mouse postimplantation embryos, they function synergistically to methylate the promoters of the Oct4 and Nanog genes. Inadequate methylation caused by ablating Dnmt3a and Dnmt3b is associated with dysregulated expression of Oct4 and Nanog during the differentiation of pluripotent cells and mouse embryonic development. These results suggest that Dnmt3a and Dnmt3b form a complex through direct contact in living cells and cooperate in the methylation of the promoters of Oct4 and Nanog during cell differentiation. The physical and functional interaction between Dnmt3a and Dnmt3b represents a novel regulatory mechanism to ensure the proper establishment of genomic methylation patterns for gene silencing in development. PMID:17938196

  1. Genome-wide analysis of DNA methylation in bovine placentas

    PubMed Central

    2014-01-01

    Background DNA methylation is an important epigenetic modification that is essential for epigenetic gene regulation in development and disease. To date, the genome-wide DNA methylation maps of many organisms have been reported, but the methylation pattern of cattle remains unknown. Results We showed the genome-wide DNA methylation map in placental tissues using methylated DNA immunoprecipitation combined with high-throughput sequencing (MeDIP-seq). In cattle, the methylation levels in the gene body are relatively high, whereas the promoter remains hypomethylated. We obtained thousands of highly methylated regions (HMRs), methylated CpG islands, and methylated genes from bovine placenta. DNA methylation levels around the transcription start sites of genes are negatively correlated with the gene expression level. However, the relationship between gene-body DNA methylation and gene expression is non-monotonic. Moderately expressed genes generally have the highest levels of gene-body DNA methylation, whereas the highly, and lowly expressed genes, as well as silent genes, show moderate DNA methylation levels. Genes with the highest expression show the lowest DNA methylation levels. Conclusions We have generated the genome-wide mapping of DNA methylation in cattle for the first time, and our results can be used for future studies on epigenetic gene regulation in cattle. This study contributes to the knowledge on epigenetics in cattle. PMID:24397284

  2. Non-reversible solvatochromism in N-methyl-2-pyrrolidone/toluene mixed solutions of fullerene C60

    NASA Astrophysics Data System (ADS)

    Kyzyma, O. A.; Kyrey, T. ?.; Avdeev, M. V.; Korobov, M. V.; Bulavin, L. A.; Aksenov, V. L.

    2013-01-01

    Non-reversible changes in the UV-Vis spectra (solvatochromism) of C60 fullerene in the binary solvent N-methyl-2-pyrrolidone/toluene are observed when varying the mixture composition. The solvatochromism strongly depends on the order of the mixture preparation. We attribute the effect to a great difference in the polarity of the liquid components, which determines different solvent-solute interaction with respect to the formation of charge-transfer complexes and, thus, provides conditions for selective solvation. The effect is also dependent on the temporal changes in the complexes C60-N-methyl-2-pyrrolidone and C60 cluster formation.

  3. Lysine methylation-dependent binding of 53BP1 to the pRb tumor suppressor

    PubMed Central

    Carr, Simon M.; Munro, Shonagh; Zalmas, Lykourgos-Panagiotis; Fedorov, Oleg; Johansson, Catrine; Krojer, Tobias; Sagum, Cari A.; Bedford, Mark T.; Oppermann, Udo; La Thangue, Nicholas B.

    2014-01-01

    The retinoblastoma tumor suppressor protein pRb is a key regulator of cell cycle progression and mediator of the DNA damage response. Lysine methylation at K810, which occurs within a critical Cdk phosphorylation motif, holds pRb in the hypophosphorylated growth-suppressing state. We show here that methyl K810 is read by the tandem tudor domain containing tumor protein p53 binding protein 1 (53BP1). Structural elucidation of 53BP1 in complex with a methylated K810 pRb peptide emphasized the role of the 53BP1 tandem tudor domain in recognition of the methylated lysine and surrounding residues. Significantly, binding of 53BP1 to methyl K810 occurs on E2 promoter binding factor target genes and allows pRb activity to be effectively integrated with the DNA damage response. Our results widen the repertoire of cellular targets for 53BP1 and suggest a previously unidentified role for 53BP1 in regulating pRb tumor suppressor activity. PMID:25049398

  4. Arginine methylation of DRBD18 differentially impacts its opposing effects on the trypanosome transcriptome

    PubMed Central

    Lott, Kaylen; Mukhopadhyay, Shreya; Li, Jun; Wang, Jie; Yao, Jin; Sun, Yijun; Qu, Jun; Read, Laurie K.

    2015-01-01

    Arginine methylation is a posttranslational modification that impacts wide-ranging cellular functions, including transcription, mRNA splicing and translation. RNA binding proteins (RBPs) represent one of the largest classes of arginine methylated proteins in both mammals and the early diverging parasitic protozoan, Trypanosoma brucei. Here, we report the effects of arginine methylation on the functions of the essential and previously uncharacterized T. brucei RBP, DRBD18. RNAseq analysis shows that DRBD18 depletion causes extensive rearrangement of the T. brucei transcriptome, with increases and decreases in hundreds of mRNAs. DRBD18 contains three methylated arginines, and we used complementation of DRBD18 knockdown cells with methylmimic or hypomethylated DRBD18 to assess the functions of these methylmarks. Methylmimic and hypomethylated DRBD18 associate with different ribonucleoprotein complexes. These altered macromolecular interactions translate into differential impacts on the T. brucei transcriptome. Methylmimic DRBD18 preferentially stabilizes target RNAs, while hypomethylated DRBD18 is more efficient at destabilizing RNA. The protein arginine methyltransferase, TbPRMT1, interacts with DRBD18 and knockdown of TbPRMT1 recapitulates the effects of hypomethylated DRBD18 on mRNA levels. Together, these data support a model in which arginine methylation acts as a switch that regulates T. brucei gene expression. PMID:25940618

  5. Abnormalities of the DNA methylation mark and its machinery: an emerging cause of neurologic dysfunction.

    PubMed

    Weissman, Jacqueline; Naidu, Sakkubai; Bjornsson, Hans T

    2014-07-01

    Recently, Mendelian disorders of the DNA methylation machinery have been described which demonstrate the complex roles of epigenetics in neurodevelopment and disease. For example, defects of DNMT1, the maintenance methyltransferase, lead to adult-onset progressive neurologic disorders, whereas defects of the de novo methyltransferases DNMT3A and DNMT3B lead to nonprogressive neurodevelopmental conditions. Furthermore, patients with DNMT3A deficiency demonstrate overgrowth, a feature common to disorders of histone machinery and imprinting disorders, highlighting the interconnectedness of the many epigenetic layers. Disorders of the DNA methylation machinery include both the aforementioned "writers" and also the "readers" of the methyl mark, such as MeCP2, the cause of Rett syndrome. Any dosage disruption, either haploinsufficiency or overexpression of DNA methylation machinery leads to widespread gene expression changes in trans, disrupting expression of a subset of target genes that contribute to individual disease phenotypes. In contrast, classical imprinting disorders such as Angelman syndrome have been thought generally to cause epigenetic dysregulation in cis. However, the recent description of multilocus methylation disorders challenges this generalization. Here, in addition to summarizing recent developments in identifying the pathogenesis of these diseases, we highlight clinical considerations and some unexpected therapeutic opportunities, such as topoisomerase inhibitors for classical imprinting disorders. PMID:25192503

  6. Mercury methylation by HgcA: theory supports carbanion transfer to Hg(II).

    PubMed

    Zhou, Jing; Riccardi, Demian; Beste, Ariana; Smith, Jeremy C; Parks, Jerry M

    2014-01-21

    Many proteins use corrinoid cofactors to facilitate methyl transfer reactions. Recently, a corrinoid protein, HgcA, has been shown to be required for the production of the neurotoxin methylmercury by anaerobic bacteria. A strictly conserved Cys residue in HgcA was predicted to be a lower-axial ligand to Co(III), which has never been observed in a corrinoid protein. Here, we use density functional theory to study homolytic and heterolytic Co-C bond dissociation and methyl transfer to Hg(II) substrates with model methylcobalamin complexes containing a lower-axial Cys or His ligand to cobalt, the latter of which is commonly found in other corrinoid proteins. We find that Cys thiolate coordination to Co facilitates both methyl radical and methyl carbanion transfer to Hg(II) substrates, but carbanion transfer is more favorable overall in the condensed phase. Thus, our findings are consistent with HgcA representing a new class of corrinoid protein capable of transferring methyl groups to electrophilic substrates. PMID:24377658

  7. Role of morphological growth state and gene expression in Desulfovibrio africanus strain Walvis Bay mercury methylation.

    PubMed

    Moberly, James G; Miller, Carrie L; Brown, Steven D; Biswas, Abir; Brandt, Craig C; Palumbo, Anthony V; Elias, Dwayne A

    2012-05-01

    The biogeochemical transformations of mercury are a complex process, with the production of methylmercury, a potent human neurotoxin, repeatedly demonstrated in sulfate- and Fe(III)-reducing as well as methanogenic bacteria. However, little is known regarding the morphology, genes, or proteins involved in methylmercury generation. Desulfovibrio africanus strain Walvis Bay is a Hg-methylating ?-proteobacterium with a sequenced genome and has unusual pleomorphic forms. In this study, a relationship between the pleomorphism and Hg methylation was investigated. Proportional increases in the sigmoidal (regular) cell form corresponded with increased net MeHg production but decreased when the pinched cocci (persister) form became the major morphotype. D. africanus microarrays indicated that the ferrous iron transport genes (feoAB), as well as ribosomal genes and several genes whose products are predicted to have metal binding domains (CxxC), were up-regulated during exposure to Hg in the exponential phase. Whereas no specific methylation pathways were identified, the finding that Hg may interfere with iron transport and the correlation of growth-phase-dependent morphology with MeHg production are notable. The identification of these relationships between differential gene expression, morphology, and the growth-phase dependence of Hg transformations suggests that actively growing cells are primarily responsible for methylation, and so areas with ample carbon and electron-acceptor concentrations may also generate a higher proportion of methylmercury than more oligotrophic environments. The observation of increased iron transporter expression also suggests that Hg methylation may interfere with iron biogeochemical cycles. PMID:22500779

  8. Arginine methylation of DRBD18 differentially impacts its opposing effects on the trypanosome transcriptome.

    PubMed

    Lott, Kaylen; Mukhopadhyay, Shreya; Li, Jun; Wang, Jie; Yao, Jin; Sun, Yijun; Qu, Jun; Read, Laurie K

    2015-06-23

    Arginine methylation is a posttranslational modification that impacts wide-ranging cellular functions, including transcription, mRNA splicing and translation. RNA binding proteins (RBPs) represent one of the largest classes of arginine methylated proteins in both mammals and the early diverging parasitic protozoan, Trypanosoma brucei. Here, we report the effects of arginine methylation on the functions of the essential and previously uncharacterized T. brucei RBP, DRBD18. RNAseq analysis shows that DRBD18 depletion causes extensive rearrangement of the T. brucei transcriptome, with increases and decreases in hundreds of mRNAs. DRBD18 contains three methylated arginines, and we used complementation of DRBD18 knockdown cells with methylmimic or hypomethylated DRBD18 to assess the functions of these methylmarks. Methylmimic and hypomethylated DRBD18 associate with different ribonucleoprotein complexes. These altered macromolecular interactions translate into differential impacts on the T. brucei transcriptome. Methylmimic DRBD18 preferentially stabilizes target RNAs, while hypomethylated DRBD18 is more efficient at destabilizing RNA. The protein arginine methyltransferase, TbPRMT1, interacts with DRBD18 and knockdown of TbPRMT1 recapitulates the effects of hypomethylated DRBD18 on mRNA levels. Together, these data support a model in which arginine methylation acts as a switch that regulates T. brucei gene expression. PMID:25940618

  9. SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer

    PubMed Central

    Mazur, Pawel K.; Reynoird, Nicolas; Khatri, Purvesh; Jansen, Pascal W.T.C.; Wilkinson, Alex; Liu, Shichong; Barbash, Olena; Van Aller, Glenn S.; Huddleston, Michael; Dhanak, Dashyant; Tummino, Peter J.; Kruger, Ryan G.; Garcia, Benjamin; Butte, Atul J.; Vermeulen, Michiel; Sage, Julien; Gozani, Or

    2014-01-01

    Deregulation in lysine methylation signaling has emerged as a common etiologic factor in cancer pathogenesis, with inhibitors of several histone lysine methyltransferases (KMTs) being developed as chemotherapeutics1. The largely cytoplasmic KMT SMYD3 (SET and MYND domain containing protein 3) is overexpressed in numerous human tumors2-4. However, the molecular mechanism by which SMYD3 regulates cancer pathways and its relationship to tumorigenesis in vivo are largely unknown. Here we show that methylation of MAP3K2 by SMYD3 increases MAP Kinase signaling and promotes the formation of Ras-driven carcinomas. Using mouse models for pancreatic ductal adenocarcinoma (PDAC) and lung adenocarcinoma (LAC), we found that abrogating SMYD3 catalytic activity inhibits tumor development in response to oncogenic Ras. We employed protein array technology to identify the MAP3K2 kinase as a target of SMYD3. In cancer cell lines, SMYD3-mediated methylation of MAP3K2 at lysine 260 potentiates activation of the Ras/Raf/MEK/ERK signaling module. Finally, the PP2A phosphatase complex, a key negative regulator of the MAP Kinase pathway, binds to MAP3K2 and this interaction is blocked by methylation. Together, our results elucidate a new role for lysine methylation in integrating cytoplasmic kinase-signaling cascades and establish a pivotal role for SMYD3 in the regulation of oncogenic Ras signaling. PMID:24847881

  10. Enhanced Reduced Representation Bisulfite Sequencing for Assessment of DNA Methylation at Base Pair Resolution

    PubMed Central

    Kacmarczyk, Thadeous J.; Ishii, Jennifer; Betel, Doron; Alonso, Alicia; Mason, Christopher E.; Figueroa, Maria E.; Melnick, Ari M.

    2015-01-01

    DNA methylation pattern mapping is heavily studied in normal and diseased tissues. A variety of methods have been established to interrogate the cytosine methylation patterns in cells. Reduced representation of whole genome bisulfite sequencing was developed to detect quantitative base pair resolution cytosine methylation patterns at GC-rich genomic loci. This is accomplished by combining the use of a restriction enzyme followed by bisulfite conversion. Enhanced Reduced Representation Bisulfite Sequencing (ERRBS) increases the biologically relevant genomic loci covered and has been used to profile cytosine methylation in DNA from human, mouse and other organisms. ERRBS initiates with restriction enzyme digestion of DNA to generate low molecular weight fragments for use in library preparation. These fragments are subjected to standard library construction for next generation sequencing. Bisulfite conversion of unmethylated cytosines prior to the final amplification step allows for quantitative base resolution of cytosine methylation levels in covered genomic loci. The protocol can be completed within four days. Despite low complexity in the first three bases sequenced, ERRBS libraries yield high quality data when using a designated sequencing control lane. Mapping and bioinformatics analysis is then performed and yields data that can be easily integrated with a variety of genome-wide platforms. ERRBS can utilize small input material quantities making it feasible to process human clinical samples and applicable in a range of research applications. The video produced demonstrates critical steps of the ERRBS protocol. PMID:25742437

  11. Lysine methylation-dependent binding of 53BP1 to the pRb tumor suppressor.

    PubMed

    Carr, Simon M; Munro, Shonagh; Zalmas, Lykourgos-Panagiotis; Fedorov, Oleg; Johansson, Catrine; Krojer, Tobias; Sagum, Cari A; Bedford, Mark T; Oppermann, Udo; La Thangue, Nicholas B

    2014-08-01

    The retinoblastoma tumor suppressor protein pRb is a key regulator of cell cycle progression and mediator of the DNA damage response. Lysine methylation at K810, which occurs within a critical Cdk phosphorylation motif, holds pRb in the hypophosphorylated growth-suppressing state. We show here that methyl K810 is read by the tandem tudor domain containing tumor protein p53 binding protein 1 (53BP1). Structural elucidation of 53BP1 in complex with a methylated K810 pRb peptide emphasized the role of the 53BP1 tandem tudor domain in recognition of the methylated lysine and surrounding residues. Significantly, binding of 53BP1 to methyl K810 occurs on E2 promoter binding factor target genes and allows pRb activity to be effectively integrated with the DNA damage response. Our results widen the repertoire of cellular targets for 53BP1 and suggest a previously unidentified role for 53BP1 in regulating pRb tumor suppressor activity. PMID:25049398

  12. Solubility of anthracene in binary alcohol + 2-methyl-1-propanol and alcohol + 3-methyl-1-butanol solvent mixtures

    Microsoft Academic Search

    Anita I. Zvaigzne; William E. Acree

    1995-01-01

    Solid-liquid equilibrium data of organic nonelectrolyte systems are becoming increasingly important in the petroleum industry, particularly in light of present rends toward heavier feedstocks and known carcinogenicity\\/mutagenicity of many of the larger polycyclic aromatic compounds. Experimental solubilities are reported for anthracene dissolved in binary 2-propanol + 3-methyl-1-butanol, 2-propanol + 2-methyl-1-propanol, 1-propanol + 2-methyl-1-propanol, 1-octanol + 2-methyl-1-propanol, 1-butanol + 3-methyl-1-butanol, 2-butanol

  13. DNA methylation in the Neuropeptide S Receptor 1 (NPSR1) promoter in relation to asthma and environmental factors.

    PubMed

    Reinius, Lovisa E; Gref, Anna; Sääf, Annika; Acevedo, Nathalie; Joerink, Maaike; Kupczyk, Maciej; D'Amato, Mauro; Bergström, Anna; Melén, Erik; Scheynius, Annika; Dahlén, Sven-Erik; Pershagen, Göran; Söderhäll, Cilla; Kere, Juha

    2013-01-01

    Asthma and allergy are complex disorders influenced by both inheritance and environment, a relationship that might be further clarified by epigenetics. Neuropeptide S Receptor 1 (NPSR1) has been associated with asthma and allergy and a study suggested modulation of the genetic risk by environmental factors. We aimed to study DNA methylation in the promoter region of NPSR1 in relation to asthma and environmental exposures. Electrophoretic Mobility Shift Assay (EMSA) was used to investigate potential functional roles of both genotypes and methylation status in the NPSR1 promoter. DNA methylation was analysed using EpiTYPER in blood samples from two well-characterized cohorts; the BIOAIR study of severe asthma in adults and the Swedish birth cohort BAMSE. We observed that DNA methylation and genetic variants in the promoter influenced the binding of nuclear proteins to DNA, suggesting functional relevance. Significant, although small, differences in methylation were related to both adult severe asthma (p?=?0.0001) and childhood allergic asthma (p?=?0.01). Furthermore, DNA methylation was associated with exposures such as current smoking in adults for two CpG sites (p?=?0.005 and 0.04), parental smoking during infancy in the children (p?=?0.02) and in which month the sample was taken (p?=?0.01). In summary, DNA methylation levels in the promoter of NPSR1 showed small but significant associations with asthma, both in adults and in children, and to related traits such as allergy and certain environmental exposures. Both genetic variation and the methylated state of CpG sites seem to have an effect on the binding of nuclear proteins in the regulatory region of NPSR1 suggesting complex regulation of this gene in asthma and allergy. PMID:23372674

  14. Growing season methyl bromide and methyl chloride fluxes at a sub-arctic wetland in Sweden 

    E-print Network

    Hardacre, Catherine J.; Blei, Emanuel; Heal, Mathew R

    2009-01-01

    Methyl bromide and methyl chloride fluxes were measured at several sites in a sub-arctic wetland near Abisko, Sweden (68°28?N 18°49?E) throughout the 2008 growing season. Averaged over 92 flux measurements the sub-arctic wetland was found to be a...

  15. DNA methylation at hepatitis B viral integrants is associated with methylation at flanking human genomic sequences.

    PubMed

    Watanabe, Yoshiyuki; Yamamoto, Hiroyuki; Oikawa, Ritsuko; Toyota, Minoru; Yamamoto, Masakazu; Kokudo, Norihiro; Tanaka, Shinji; Arii, Shigeki; Yotsuyanagi, Hiroshi; Koike, Kazuhiko; Itoh, Fumio

    2015-03-01

    Integration of DNA viruses into the human genome plays an important role in various types of tumors, including hepatitis B virus (HBV)-related hepatocellular carcinoma. However, the molecular details and clinical impact of HBV integration on either human or HBV epigenomes are unknown. Here, we show that methylation of the integrated HBV DNA is related to the methylation status of the flanking human genome. We developed a next-generation sequencing-based method for structural methylation analysis of integrated viral genomes (denoted G-NaVI). This method is a novel approach that enables enrichment of viral fragments for sequencing using unique baits based on the sequence of the HBV genome. We detected integrated HBV sequences in the genome of the PLC/PRF/5 cell line and found variable levels of methylation within the integrated HBV genomes. Allele-specific methylation analysis revealed that the HBV genome often became significantly methylated when integrated into highly methylated host sites. After integration into unmethylated human genome regions such as promoters, however, the HBV DNA remains unmethylated and may eventually play an important role in tumorigenesis. The observed dynamic changes in DNA methylation of the host and viral genomes may functionally affect the biological behavior of HBV. These findings may impact public health given that millions of people worldwide are carriers of HBV. We also believe our assay will be a powerful tool to increase our understanding of the various types of DNA virus-associated tumorigenesis. PMID:25653310

  16. DMRforPairs: identifying Differentially Methylated Regions between unique samples using array based methylation profiles

    PubMed Central

    2014-01-01

    Background Array based methylation profiling is a cost-effective solution to study the association between genome methylation and human disease & development. Available tools to analyze the Illumina Infinium HumanMethylation450 BeadChip focus on comparing methylation levels per locus. Other tools combine multiple probes into a range, identifying differential methylated regions (DMRs). These tools all require groups of samples to compare. However, comparison of unique, individual samples is essential in situations where larger sample sizes are not possible. Results DMRforPairs was designed to compare regional methylation status between unique samples. It identifies probe dense genomic regions and quantifies/tests their (difference in) methylation level between the samples. As a proof of concept, DMRforPairs is applied to public data from four human cell lines: two lymphoblastoid cell lines from healthy individuals and the cancer cell lines A431 and MCF7 (including 2 technical replicates each). DMRforPairs identified an increasing number of DMRs related to the sample phenotype when biological similarity of the samples decreased. DMRs identified by DMRforPairs were related to the biological origin of the cell lines. Conclusion To our knowledge, DMRforPairs is the first tool to identify and visualize relevant and significant differentially methylated regions between unique samples. PMID:24884391

  17. Methyl esters from vegetable oils with hydroxy fatty acids: Comparison of lesquerella and castor methyl esters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The search for alternative feedstocks for biodiesel as partial replacement for petrodiesel has recently extended to castor oil. In this work, the castor oil methyl esters were prepared and their properties determined in comparison to the methyl esters of lesquerella oil, which in turn is seen as alt...

  18. Molecular structure of poly(methyl methacrylate) surface II: Effect of stereoregularity examined through all-atom molecular dynamics.

    PubMed

    Jha, Kshitij C; Zhu, He; Dhinojwala, Ali; Tsige, Mesfin

    2014-11-01

    Utilizing all-atom molecular dynamics (MD), we have analyzed the effect of tacticity and temperature on the surface structure of poly(methyl methacrylate) (PMMA) at the polymer-vacuum interface. We quantify these effects primarily through orientation, measured as the tilt with respect to the surface normal, and the surface number densities of the ?-methyl, ester-methyl, carbonyl, and backbone methylene groups. Molecular structure on the surface is a complex interplay between orientation and number densities and is challenging to capture through sum frequency generation (SFG) spectroscopy alone. Independent quantification of the number density and orientation of chemical groups through all-atom MD presents a comprehensive model of stereoregular PMMA on the surface. SFG analysis presented in part I of this joint publication measures the orientation of molecules that are in agreement with MD results. We observe the ester-methyl groups as preferentially oriented, irrespective of tacticity, followed by the ?-methyl and carbonyl groups. SFG spectroscopy also points to ester-methyl being dominant on the surface. The backbone methylene groups show a very broad angular distribution, centered along the surface plane. The surface number density ratios of ester-methyl to ?-methyl groups show syndiotactic PMMA having the lowest value. Isotactic PMMA has the highest ratios of ester- to ?-methyl. These subtle trends in the relative angular orientation and number densities that influence the variation of surface structure with tacticity are highlighted in this article. A more planar conformation of the syndiotactic PMMA along the surface (x-y plane) can be visualized through the trajectories from all-atom MD. Results from conformation tensor calculations for chains with any of their segments contributing to the surface validate the visual observation. PMID:25310276

  19. Active transport, substrate specificity, and methylation of Hg(II) in anaerobic bacteria.

    PubMed

    Schaefer, Jeffra K; Rocks, Sara S; Zheng, Wang; Liang, Liyuan; Gu, Baohua; Morel, François M M

    2011-05-24

    The formation of methylmercury (MeHg), which is biomagnified in aquatic food chains and poses a risk to human health, is effected by some iron- and sulfate-reducing bacteria (FeRB and SRB) in anaerobic environments. However, very little is known regarding the mechanism of uptake of inorganic Hg by these organisms, in part because of the inherent difficulty in measuring the intracellular Hg concentration. By using the FeRB Geobacter sulfurreducens and the SRB Desulfovibrio desulfuricans ND132 as model organisms, we demonstrate that Hg(II) uptake occurs by active transport. We also establish that Hg(II) uptake by G. sulfurreducens is highly dependent on the characteristics of the thiols that bind Hg(II) in the external medium, with some thiols promoting uptake and methylation and others inhibiting both. The Hg(II) uptake system of D. desulfuricans has a higher affinity than that of G. sulfurreducens and promotes Hg methylation in the presence of stronger complexing thiols. We observed a tight coupling between Hg methylation and MeHg export from the cell, suggesting that these two processes may serve to avoid the build up and toxicity of cellular Hg. Our results bring up the question of whether cellular Hg uptake is specific for Hg(II) or accidental, occurring via some essential metal importer. Our data also point at Hg(II) complexation by thiols as an important factor controlling Hg methylation in anaerobic environments. PMID:21555571

  20. Molecular basis for recognition of methylated and specific DNA sequences by the zinc finger protein Kaiso

    PubMed Central

    Buck-Koehntop, Bethany A.; Stanfield, Robyn L.; Ekiert, Damian C.; Martinez-Yamout, Maria A.; Dyson, H. Jane; Wilson, Ian A.; Wright, Peter E.

    2012-01-01

    Methylation of CpG dinucleotides in DNA is a common epigenetic modification in eukaryotes that plays a central role in maintenance of genome stability, gene silencing, genomic imprinting, development, and disease. Kaiso, a bifunctional Cys2His2 zinc finger protein implicated in tumor-cell proliferation, binds to both methylated CpG (mCpG) sites and a specific nonmethylated DNA motif (TCCTGCNA) and represses transcription by recruiting chromatin remodeling corepression machinery to target genes. Here we report structures of the Kaiso zinc finger DNA-binding domain in complex with its nonmethylated, sequence-specific DNA target (KBS) and with a symmetrically methylated DNA sequence derived from the promoter region of E-cadherin. Recognition of specific bases in the major groove of the core KBS and mCpG sites is accomplished through both classical and methyl CH···O hydrogen-bonding interactions with residues in the first two zinc fingers, whereas residues in the C-terminal extension following the third zinc finger bind in the opposing minor groove and are required for high-affinity binding. The C-terminal region is disordered in the free protein and adopts an ordered structure upon binding to DNA. The structures of these Kaiso complexes provide insights into the mechanism by which a zinc finger protein can recognize mCpG sites as well as a specific, nonmethylated regulatory DNA sequence. PMID:22949637

  1. Molecular basis for recognition of methylated and specific DNA sequences by the zinc finger protein Kaiso.

    PubMed

    Buck-Koehntop, Bethany A; Stanfield, Robyn L; Ekiert, Damian C; Martinez-Yamout, Maria A; Dyson, H Jane; Wilson, Ian A; Wright, Peter E

    2012-09-18

    Methylation of CpG dinucleotides in DNA is a common epigenetic modification in eukaryotes that plays a central role in maintenance of genome stability, gene silencing, genomic imprinting, development, and disease. Kaiso, a bifunctional Cys(2)His(2) zinc finger protein implicated in tumor-cell proliferation, binds to both methylated CpG (mCpG) sites and a specific nonmethylated DNA motif (TCCTGCNA) and represses transcription by recruiting chromatin remodeling corepression machinery to target genes. Here we report structures of the Kaiso zinc finger DNA-binding domain in complex with its nonmethylated, sequence-specific DNA target (KBS) and with a symmetrically methylated DNA sequence derived from the promoter region of E-cadherin. Recognition of specific bases in the major groove of the core KBS and mCpG sites is accomplished through both classical and methyl CH···O hydrogen-bonding interactions with residues in the first two zinc fingers, whereas residues in the C-terminal extension following the third zinc finger bind in the opposing minor groove and are required for high-affinity binding. The C-terminal region is disordered in the free protein and adopts an ordered structure upon binding to DNA. The structures of these Kaiso complexes provide insights into the mechanism by which a zinc finger protein can recognize mCpG sites as well as a specific, nonmethylated regulatory DNA sequence. PMID:22949637

  2. Glutamine methylation in Histone H2A is an RNA Polymerase I dedicated modification

    PubMed Central

    Tessarz, Peter; Santos-Rosa, Helena; Robson, Sam C.; Sylvestersen, Kathrine B.; Nelson, Christopher J; Nielsen, Michael L.; Kouzarides, Tony

    2013-01-01

    Nucleosomes are decorated with numerous post-translational modifications capable of influencing many DNA processes1. Here, we describe a new class of histone modification, methylation of glutamine, occurring on yeast histone H2A at position 105 (Q105) and human H2A at Q104. We identify Nop1 as the methyltransferase in yeast and demonstrate that Fibrillarin is the ortholog enzyme in human cells. Glutamine methylation of H2A is restricted to the nucleolus. Global analysis in yeast, using an H2AQ105me specific antibody, show that this modification is exclusively enriched over the 35S rDNA transcriptional unit. We show that the Q105 residue is part of the binding site for the histone chaperone FACT (Facilitator of Transcription) complex2. Methylation of Q105 or its substitution to alanine disrupts binding to FACT in vitro. A yeast strain mutated at Q105 exhibits reduced histone incorporation and increased transcription at the rDNA locus. These features are phenocopied by mutations in FACT complex components. Together these data identify glutamine methylation of H2A as the first histone epigenetic mark dedicated to a specific RNA polymerase and define its function as a regulator of FACT interaction with nucleosomes. PMID:24352239

  3. The Chirped-Pulse and Cavity Based Ftmw Spectroscopy of the Methyl Lactate-Water and Methyl Lactate-Deuterium Oxide Dimers

    NASA Astrophysics Data System (ADS)

    Thomas, Javix; Sukhorukov, Oleksandr; Jäger, Wolfgang; Xu, Yunjie

    2011-06-01

    The delicate competition between the inter- and intramolecular hydrogen-bonding in the complex consisting of a chiral alpha-hydroxy ester, methyl lactate, and water, has been studied using rotational spectroscopy and high level ab initio calculations. Extensive ab initio calculations have been performed to locate all possible low energy conformers of the methyl lactate-water contact pair and five lowest energy conformers have been identified. The most stable conformer forms a seven membered ring with two intermolecular hydrogen bonds: one between the alcoholic hydroxy group of methyl lactate and the oxygen of the water molecule and the other between the hydrogen of water and the oxygen of the carbonyl group. Broadband scans for the rotational spectra of these conformers have been carried out using a newly built chirped-pulse FTMW instrument and the final frequency measurements with a cavity based FTMW instrument. Spectral assignments have been made for the lowest energy conformer of methyl lactate-H2O and D2O. The hyperfine splitting and the source of the splitting will be discussed.

  4. Immunoaffinity Enrichment and Mass Spectrometry Analysis of Protein Methylation

    PubMed Central

    Guo, Ailan; Gu, Hongbo; Zhou, Jing; Mulhern, Daniel; Wang, Yi; Lee, Kimberly A.; Yang, Vicky; Aguiar, Mike; Kornhauser, Jon; Jia, Xiaoying; Ren, Jianmin; Beausoleil, Sean A.; Silva, Jeffrey C.; Vemulapalli, Vidyasiri; Bedford, Mark T.; Comb, Michael J.

    2014-01-01

    Protein methylation is a common posttranslational modification that mostly occurs on arginine and lysine residues. Arginine methylation has been reported to regulate RNA processing, gene transcription, DNA damage repair, protein translocation, and signal transduction. Lysine methylation is best known to regulate histone function and is involved in epigenetic regulation of gene transcription. To better study protein methylation, we have developed highly specific antibodies against monomethyl arginine; asymmetric dimethyl arginine; and monomethyl, dimethyl, and trimethyl lysine motifs. These antibodies were used to perform immunoaffinity purification of methyl peptides followed by LC-MS/MS analysis to identify and quantify arginine and lysine methylation sites in several model studies. Overall, we identified over 1000 arginine methylation sites in human cell line and mouse tissues, and ?160 lysine methylation sites in human cell line HCT116. The number of methylation sites identified in this study exceeds those found in the literature to date. Detailed analysis of arginine-methylated proteins observed in mouse brain compared with those found in mouse embryo shows a tissue-specific distribution of arginine methylation, and extends the types of proteins that are known to be arginine methylated to include many new protein types. Many arginine-methylated proteins that we identified from the brain, including receptors, ion channels, transporters, and vesicle proteins, are involved in synaptic transmission, whereas the most abundant methylated proteins identified from mouse embryo are transcriptional regulators and RNA processing proteins. PMID:24129315

  5. DNA methylation array analyses identified breast cancer-associated HYAL2 methylation in peripheral blood.

    PubMed

    Yang, Rongxi; Pfütze, Katrin; Zucknick, Manuela; Sutter, Christian; Wappenschmidt, Barbara; Marme, Frederik; Qu, Bin; Cuk, Katarina; Engel, Christoph; Schott, Sarah; Schneeweiss, Andreas; Brenner, Hermann; Claus, Rainer; Plass, Christoph; Bugert, Peter; Hoth, Markus; Sohn, Christof; Schmutzler, Rita; Bartram, Claus R; Burwinkel, Barbara

    2015-04-15

    Breast cancer (BC) is the leading cause of cancer-related mortality in women worldwide. Changes in DNA methylation in peripheral blood could be associated with malignancy at early stage. However, the BC-associated DNA methylation signatures in peripheral blood were largely unknown. Here, we performed a genome-wide methylation screening and identified a BC-associated differentially methylated CpG site cg27091787 in the hyaluronoglucosaminidase 2 gene (HYAL2) (discovery round with 72 BC case and 24 controls: p = 2.61 × 10(-9) adjusted for cell-type proportions). The substantially decreased methylation of cg27091787 in BC cases was confirmed in two validation rounds (first validation round with 338 BC case and 507 controls: p < 0.0001; second validation round with 189 BC case and 189 controls: p < 0.0001). In addition to cg27091787, the decreased methylation of a 650-bp CpG island shore of HYAL2 was also associated with increased risk of BC. Moreover, the expression and methylation of HYAL2 were inversely correlated with a p-value of 0.006. To note, the BC-associated decreased HYAL2 methylation was replicated in the T-cell fraction (p = 0.034). The cg27091787 methylation level enabled a powerful discrimination of early-stage BC cases (stages 0 and I) from healthy controls [area under curve (AUC) = 0.89], and was robust for the detection of BC in younger women as well (age < 50, AUC = 0.87). Our study reveals a strong association between decreased HYAL2 methylation in peripheral blood and BC, and provides a promising blood-based marker for the detection of early BC. PMID:25213452

  6. Methylation plotter: a web tool for dynamic visualization of DNA methylation data.

    PubMed

    Mallona, Izaskun; Díez-Villanueva, Anna; Peinado, Miguel A

    2014-01-01

    Methylation plotter is a Web tool that allows the visualization of methylation data in a user-friendly manner and with publication-ready quality. The user is asked to introduce a file containing the methylation status of a genomic region. This file can contain up to 100 samples and 100 CpGs. Optionally, the user can assign a group for each sample (i.e. whether a sample is a tumoral or normal tissue). After the data upload, the tool produces different graphical representations of the results following the most commonly used styles to display this type of data. They include an interactive plot that summarizes the status of every CpG site and for every sample in lollipop or grid styles. Methylation values ranging from 0 (unmethylated) to 1 (fully methylated) are represented using a gray color gradient. A practical feature of the tool allows the user to choose from different types of arrangement of the samples in the display: for instance, sorting by overall methylation level, by group, by unsupervised clustering or just following the order in which data were entered. In addition to the detailed plot, Methylation plotter produces a methylation profile plot that summarizes the status of the scrutinized region, a boxplot that sums up the differences between groups (if any) and a dendrogram that classifies the data by unsupervised clustering. Coupled with this analysis, descriptive statistics and testing for differences at both CpG and group levels are provided. The implementation is based in R/shiny, providing a highly dynamic user interface that generates quality graphics without the need of writing R code. Methylation plotter is freely available at http://gattaca.imppc.org:3838/methylation_plotter/. PMID:25260021

  7. Prognostic DNA Methylation Markers for Prostate Cancer

    PubMed Central

    Strand, Siri H.; Orntoft, Torben F.; Sorensen, Karina D.

    2014-01-01

    Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC. PMID:25238417

  8. DNA methylation and demethylation: a pathway to gametogenesis and development.

    PubMed

    Dean, Wendy

    2014-02-01

    The generation of gametes falls between two reprogramming phases. These phases are characterised by profound periods of transcriptional activity, which define and reinforce lineage decisions. The control of these transcriptional programs and the interpretation of the underlying genetic instruction is the task of the epigenome. As such, dynamic processes during reprogramming are critical for the development of the germ line and its resetting, which propels that developmental process forward and provides the transfer of genetic and epigenetic information between generations. Central in this reprogramming is the addition and subtraction of DNA methylation and its oxidative products, coupled to the mechanisms at play to achieve this goal. The activities competent to add DNA methylation, and identification of those enzymes able to modify it, have heralded a new chapter in our understanding of the complexities that dictate and direct cellular fates. How the early embryos makes use of these marks and how they are modulated will give us insight into cellular differentiation and reprogramming critical for health and into the process of aging. This review details some of these processes and the activities essential to achieve the immortality of the mammalian germ line. PMID:24214338

  9. Matrix Isolation Vibrational Spectroscopy of Methyl Pernitrite

    NASA Astrophysics Data System (ADS)

    Flowers, B. A.; Zhang, X.; Ellison, G. B.

    2006-12-01

    Reactions between organic peroxyl radicals (ROO·) and NO are important sources of NO2 in the atmosphere. Methyl pernitrite is the reactive intermediate in CH3OO· + NO ? [CH3OONO] ? CH3O· + NO2. However, the CH3OONO intermediate can also isomerize to methyl nitrate (CH3ONO2). The subsequent decomposition of CH3OONO determines the branching ratio between organic nitrate and NO2 formation. Methyl pernitrite and its deuterated analogue CD3OONO have been synthesized and isolated in a low temperature Ar matrix. Harmonic and anharmonic CCSD(T) vibrational frequencies are used to aid the spectral assignments. Atmospheric implications for in situ organic nitrate production as well as branching ratios in higher order organic peroxyl reactions will be discussed.

  10. Aromatase inhibition by bioavailable methylated flavones.

    PubMed

    Ta, Nga; Walle, Thomas

    2007-10-01

    Previous studies have shown chrysin, 7-hydroxyflavone and 7,4'-dihydroxyflavone to be the most potent flavonoid inhibitors of aromatase. However, very poor oral bioavailability is a major limitation for the successful use of dietary flavonoids as chemopreventive agents. We have recently shown that methylated flavones, including 5,7-dimethoxyflavone, 7-methoxyflavone and 7,4'-dimethoxyflavone, are much more resistant to metabolism than their unmethylated analogs and have much higher intestinal absorption. In this study, we examined these fully methylated flavones as potential aromatase inhibitors for the prevention and/or treatment of hormone-dependent cancers. Whereas 5,7-dimethoxyflavone had poor effect compared to its unmethylated analog chrysin, 7-methoxyflavone and 7,4'-dimethoxyflavone were almost equipotent to their unmethylated analogs with IC(50) values of 2-9 microM. Thus, some fully methylated flavones appear to have great potential as cancer chemopreventive/chemotherapeutic agents. PMID:17624765

  11. Aromatase inhibition by bioavailable methylated flavones

    PubMed Central

    Ta, Nga; Walle, Thomas

    2007-01-01

    Previous studies have shown chrysin, 7-hydroxyflavone and 7,4?-dihydroxyflavone to be the most potent flavonoid inhibitors of aromatase. However, very poor oral bioavailability is a major limitation for the successful use of dietary flavonoids as chemopreventive agents. We have recently shown that methylated flavones, including 5,7-dimethoxyflavone, 7-methoxyflavone and 7,4?-dimethoxyflavone, are much more resistant to metabolism than their unmethylated analogs and have much higher intestinal absorption. In this study, we examined these fully methylated flavones as potential aromatase inhibitors for the prevention and/or treatment of hormone-dependent cancers. Whereas 5,7-dimethoxyflavone had poor effect compared to its unmethylated analog chrysin, 7-methoxyflavone and 7,4?-dimethoxyflavone were almost equipotent to their unmethylated analogs with IC50 values of 2 to 9 ?M. Thus, some fully methylated flavones appear to have great potential as cancer chemopreventive/chemotherapeutic agents. PMID:17624765

  12. MGMT promoter methylation status in clival chordoma.

    PubMed

    Marucci, Gianluca; Morandi, Luca; Mazzatenta, Diego; Frank, Giorgio; Pasquini, Ernesto; Foschini, Maria Pia

    2014-06-01

    Chordomas are rare, slow-growing neoplasms, characterized by locally aggressive growth patterns and high local recurrence rates. To the best of our knowledge, the MGMT promoter methylation status has not been studied in a population of patients with chordomas to determine if a biologic rationale exists to support the use of temozolomide. We here show for the first time that methylation of MGMT promoter is present in a significant portion or recurring clival chordomas; on the contrary in clival chordomas without recurrence MGMT promoter was always unmethylated (p = 0.0317). Although these observations need to be confirmed in a larger study population, our results (1) indicate that methylation of MGMT promoter is present in a significant portion of recurring chordomas, and (2) prompt further investigation into the potential role of temozolomide as an adjuvant treatment of these tumors. PMID:24771251

  13. N-methylation underlying Parkinson's disease.

    PubMed

    Matsubara, Kazuo; Aoyama, Koji; Suno, Manabu; Awaya, Toshio

    2002-01-01

    The discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) leads to the hypothesis that Parkinson's disease (PD) is maybe initiated or precipitated by environmental or endogenous toxins by the mechanism similar to that of MPTP in genetically-predisposed individuals. Endogenous analogs of MPTP, such as beta-carbolines (betaCs) and tetrahydroisoquinolines, have been proposed as possible causative candidates causing PD and are bioactivated into potential neurotoxins by N-methylation enzyme(s). These N-methylated betaCs and tetrahydroisoquinoline have been higher cerebrospinal levels in parkinsonian patients than age-matched controls. Thus, there is a hypotheses to influence the pathogenesis of PD, that is, the excess enzyme activity to activate neurotoxins, such as N-methyltransferase, might be higher in PDs. Indeed, simple betaCs, via N-methylation steps, induced bradykinesia with the decreased dopamine contents in the striatum and midbrain in C57/BL mice. In younger (65 years old) PD patients, the excretion amount of N(1)-methyl-nicotinamaide was significantly higher than that in younger controls. The protein amount of nicotinamide N-methyltransferase (NNMT) was also significantly higher in younger PD patients than that in younger controls. These findings described here would indicate that the excess N-methylation ability for azaheterocyclic amines, such as betaCs, before the onset had been implicated in PD pathogenesis. On the other hand, the contribution of aberrant cytochrome P450 or aldehyde oxidase activity acting on the pyridine ring, that could act as detoxification routes of endogenous neurotoxins, would be small in the etiology of PD. PMID:12200190

  14. Selenophene transition metal complexes

    SciTech Connect

    White, C.J.

    1994-07-27

    This research shows that selenophene transition metal complexes have a chemistry that is similar to their thiophene analogs. Selenophene coordination has been demonstrated and confirmed by molecular structure in both the {eta}{sup 5}- and the {eta}{sup 1}(Se)-coordination modes. The reaction chemistry of selenophene complexes closely resembles that of the analogous thiophene complexes. One major difference, however, is that selenophene is a better donor ligand than thiophene making the selenophene complexes more stable than the corresponding thiophene complexes. The {sup 77}Se NMR chemical shift values for selenophene complexes fall within distinct regions primarily depending on the coordination mode of the selenophene ligand. In the final paper, the C-H bond activation of {eta}{sup 1}(S)-bound thiophenes, {eta}{sup 1}(S)-benzothiophene and {eta}{sup 1}(Se)-bound selenophenes has been demonstrated. The deprotonation and rearrangement of the {eta}{sup 1}(E)-bound ligand to the carbon bound L-yl complex readily occurs in the presence of base. Reprotonation with a strong acid gives a carbene complex that is unreactive towards nucleophilic attack at the carbene carbon and is stable towards exposure to air. The molecular structure of [Cp(NO)(PPh{sub 3})Re(2-benzothioenylcarbene)]O{sub 3}SCF{sub 3} was determined and contains a Re-C bond with substantial double bond character. Methyl substitution for the thienylcarbene or selenylcarbene gives a carbene that rearranges thermally to give back the {eta}{sup 1}(E)-bound complex. Based on these model reactions, a new mechanism for the H/D exchange of thiophene over the hydrodesulfurization catalyst has been proposed.

  15. Vibration and DFT analysis of 2-methyl-3-nitrophenyl isocyanate and 4-methyl-2-nitrophenyl isocyanate

    NASA Astrophysics Data System (ADS)

    Tonannavar, J.; Prasannakumar, Sushanti; Savanur, J.; Yenagi, Jayashree

    2012-09-01

    Vibrational spectra of 2-methyl-3-nitrophenyl isocyanate and 4-methyl-2-nitrophenyl isocyanate, in the spectral region 4000-100 cm-1, have been measured and assigned. Conformational and harmonic frequency analyses have been performed at B3LYP/6-311G? level of calculations. The two stable conformers, cis and trans, have been computed for each of the molecules. It has been determined that the trans conformer has lower energy than the cis by 3.954 kJ/mol for 2-methyl-3-nitrophenyl isocyanate; whereas the cis conformer has lower energy than the trans by 10.230 kJ/mol for 4-methyl-2-nitrophenyl isocyanate. The vibration structure of 2-methyl-3-nitrophenyl isocyanate conforms to the combined behavior of its both conformers from which the deviation is shown by the structure of 4-methyl-2-nitrophenyl isocyanate which follows only the trans conformer. The occurrence of symmetric mode of the methyl group at higher frequency near 2944-20 cm-1 is attributed to the phenyl ring strain caused by the substituents. As for the other stretching and bending modes, mutually exclusive pattern appears to work for the molecules: The nitro group's non-coplanarity with the phenyl ring is more evident in 4-methyl-2-nitrophenyl isocyanate where the asymmetric mode was assigned to the band at 1569 cm-1, whereas the symmetric mode at lower frequency 1339 cm-1. Occasional doublet appearance of the strong asymmetric absorption near 2282 cm-1 due to isocyanate moiety has been observed in the present study and is assumed to arise from the torsional vibration motion of the moiety rendered by the small energy gap between the conformers of 2-methyl-3-nitrophenyl isocyanate.

  16. Crystal structure of 3-methyl-5-tri­methyl­silyl-1H-pyrazole

    PubMed Central

    Ferrence, Gregory M.; Kocher, Joshua L.

    2015-01-01

    The title compound, C7H14N2Si, crystallizes in a tetra­gonal space group and exists as an N—H?N hydrogen-bonded tetra­mer, formed around the crystallographic fourfold rotoinversion axis. The mol­ecular identity is clearly the 5-tri­methyl­silyl-3-methyl-1H-pyrazole tautomer and the structure is isomorphous with that of 5-tert-butyl-3-methyl-1H-pyrazole [Foces-Foces & Trofimenko (2001 ?). Acta Cryst. E57, o32–o34].

  17. Thermal reactions of methyl linoleate. II. The structure of aromatic C18 methyl esters.

    PubMed

    Michael, W R

    1966-09-01

    This second report describes the characterization of C(18) aromatic esters from the heated linoleate and the independent synthesis of two of them. The esters were isolated by a combination of molecular distillation, urea adduction, column chromatography, and gas chromatography. They were characterized by infrared, ultraviolet, NMR, and mass spectroscopy. The analytical data for the isolated esters were compared with the data for the synthetic esters, methyl 11-(2'-methylphenyl) undecanoate, methyl 7-(2'-pentylphenyl) heptanoate, and methyl 8-(2'-butylphenyl) octanoate. The latter two compounds were found to be components of the aromatic fraction isolated from heated linoleate, and their synthesis is deseribed in detail. PMID:17805602

  18. A cis-acting element that directs the activity of the murine methylation modifier locus Ssm1

    PubMed Central

    Engler, Peter; Doglio, Lynn T.; Bozek, Grazyna; Storb, Ursula

    1998-01-01

    Silencing of chromosomal domains has been described in diverse systems such as position effect variegation in insects, silencing near yeast telomeres, and mammalian X chromosome inactivation. In mammals, silencing is associated with methylation at CpG dinucleotides, but little is known about how methylation patterns are established or altered during development. We previously described a strain-specific modifier locus, Ssm1, that controls the methylation of a complex transgene. In this study we address the questions of the nature of Ssm1’s targets and whether its effect extends into adjacent sequences. By examining the inheritance of methylation patterns in a series of mice harboring deletion derivatives of the original transgene, we have identified a discrete segment, derived from the gpt gene of Escherichia coli, that is a major determinant for Ssm1-mediated methylation. Methylation analysis of sequences adjacent to a transgenic target indicates that the influence of this modifier extends into the surrounding chromosome in a strain-dependent fashion. Implications for the mechanism of Ssm1 action are discussed. PMID:9724778

  19. Role of Morphological Growth State and Gene Expression in Desulfovibrio africanus strain Walvis Bay Mercury Methylation

    Microsoft Academic Search

    James G Moberly; Carrie L Miller; Steven D Brown; Abir Biswas; Craig C Brandt; Anthony Vito Palumbo; Dwayne A Elias

    2012-01-01

    The biogeochemical transformations of mercury are a complex process, with the production of methylmercury, a potent human neurotoxin, repeatedly demonstrated in sulfate- and Fe(III)-reducing as well as methanogenic bacteria. However, little is known regarding the morphology, genes or proteins involved in methylmercury generation. Desulfovibrio africanus strain Walvis Bay is a Hg-methylating-proteobacterium with a sequenced genome and has unusual pleomorphic forms.

  20. Preparation of fatty acid methyl esters for gas-chromatographic analysis of lipids in biological materials

    Microsoft Academic Search

    Ke-Shun Liu

    1994-01-01

    Theoretically, preparation of fatty acid methyl esters (FAMEs) deals with reversible chemical reactions in a complex system.\\u000a Methodologically, there are numerous ways, generally characterized by the type of catalysts used and steps involved. Although\\u000a there are more than a half dozen common catalysts, the majority fall into either acidic (HCl, H2SO4 and BF3) or alkaline types (NaOCH3, KOH and NaOH),

  1. 40 CFR 180.451 - Tribenuron methyl; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...General . Tolerances are established for residues of the herbicide tribenuron methyl and its metabolites and degradates...defined in § 180.1(l) are established for residues of the herbicide tribenuron methyl...

  2. 40 CFR 180.451 - Tribenuron methyl; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...General. Tolerances are established for residues of the herbicide tribenuron methyl and its metabolites and degradates...defined in § 180.1(l) are established for residues of the herbicide tribenuron methyl...

  3. 40 CFR 180.451 - Tribenuron methyl; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...General . Tolerances are established for residues of the herbicide tribenuron methyl and its metabolites and degradates...defined in § 180.1(l) are established for residues of the herbicide tribenuron methyl...

  4. 40 CFR 180.451 - Tribenuron methyl; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...General . Tolerances are established for residues of the herbicide tribenuron methyl and its metabolites and degradates...defined in § 180.1(l) are established for residues of the herbicide tribenuron methyl...

  5. DNA methylation as a molecular biomarker in gastric cancer.

    PubMed

    Tahara, Tomomitsu; Arisawa, Tomiyasu

    2015-06-01

    DNA methylation plays a significant role in gastric carcinogenesis. The CpG island methylator phenotype (CIMP) characterizes distinct subtypes of gastric cancer (GC) and the relationship between specific methylation patterns and clinicopathological features has been evaluated. Altered DNA methylation is also observed in Helicobacter pylori-infected gastric mucosa, and its potential utility for GC risk estimation has been suggested. The ability to detect small amounts of methylated DNA among tissues allows us to use DNA methylation as a molecular biomarker in GC in a variety of samples, including serum, plasma and gastric washes. The DNA methylation status of nontargeted tissue, particularly blood, has been associated with predisposition to GC. We focus on the recent development of DNA methylation-based biomarkers in GC. PMID:26077432

  6. 29 CFR 1910.1006 - Methyl chloromethyl ether.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...2012-07-01 2012-07-01 false Methyl chloromethyl ether. 1910.1006 Section 1910.1006 Labor Regulations...and Hazardous Substances § 1910.1006 Methyl chloromethyl ether. See § 1910.1003, 13 carcinogens. [61 FR 9245,...

  7. 29 CFR 1926.1106 - Methyl chloromethyl ether.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...2014-07-01 2014-07-01 false Methyl chloromethyl ether. 1926.1106 Section 1926.1106 Labor Regulations...and Hazardous Substances § 1926.1106 Methyl chloromethyl ether. Note: The requirements applicable to construction...

  8. 29 CFR 1926.1106 - Methyl chloromethyl ether.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...2012-07-01 2012-07-01 false Methyl chloromethyl ether. 1926.1106 Section 1926.1106 Labor Regulations...and Hazardous Substances § 1926.1106 Methyl chloromethyl ether. Note: The requirements applicable to construction...

  9. 29 CFR 1910.1006 - Methyl chloromethyl ether.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...2014-07-01 2013-07-01 true Methyl chloromethyl ether. 1910.1006 Section 1910.1006 Labor Regulations...and Hazardous Substances § 1910.1006 Methyl chloromethyl ether. See § 1910.1003, 13 carcinogens. [61 FR 9245,...

  10. 29 CFR 1926.1106 - Methyl chloromethyl ether.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...2011-07-01 2011-07-01 false Methyl chloromethyl ether. 1926.1106 Section 1926.1106 Labor Regulations...and Hazardous Substances § 1926.1106 Methyl chloromethyl ether. Note: The requirements applicable to construction...

  11. 29 CFR 1926.1106 - Methyl chloromethyl ether.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2013-07-01 2013-07-01 false Methyl chloromethyl ether. 1926.1106 Section 1926.1106 Labor Regulations...and Hazardous Substances § 1926.1106 Methyl chloromethyl ether. Note: The requirements applicable to construction...

  12. 29 CFR 1910.1006 - Methyl chloromethyl ether.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2013-07-01 2013-07-01 false Methyl chloromethyl ether. 1910.1006 Section 1910.1006 Labor Regulations...and Hazardous Substances § 1910.1006 Methyl chloromethyl ether. See § 1910.1003, 13 carcinogens. [61 FR 9245,...

  13. 29 CFR 1910.1006 - Methyl chloromethyl ether.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...2011-07-01 2011-07-01 false Methyl chloromethyl ether. 1910.1006 Section 1910.1006 Labor Regulations...and Hazardous Substances § 1910.1006 Methyl chloromethyl ether. See § 1910.1003, 13 carcinogens. [61 FR 9245,...

  14. Conservation and divergence of methylation patterning in plants and animals

    E-print Network

    Jacobsen, Steve

    types according to the sequence context of the cytosines, namely CG, CHG, and CHH (H = A, C, or T). CG methylation is maintained by conserved Dnmt1 DNA methyltransferase enzymes. CHH methylation, and, to some

  15. 29 CFR 1926.1106 - Methyl chloromethyl ether.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...2010-07-01 2010-07-01 false Methyl chloromethyl ether. 1926.1106 Section 1926.1106 Labor Regulations...and Hazardous Substances § 1926.1106 Methyl chloromethyl ether. Note: The requirements applicable to construction...

  16. 29 CFR 1915.1006 - Methyl chloromethyl ether.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...2010-07-01 2010-07-01 false Methyl chloromethyl ether. 1915.1006 Section 1915.1006 Labor Regulations...and Hazardous Substances § 1915.1006 Methyl chloromethyl ether. Note: The requirements applicable to shipyard...

  17. 29 CFR 1910.1006 - Methyl chloromethyl ether.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...2010-07-01 2010-07-01 false Methyl chloromethyl ether. 1910.1006 Section 1910.1006 Labor Regulations...and Hazardous Substances § 1910.1006 Methyl chloromethyl ether. See § 1910.1003, 13 carcinogens. [61 FR 9245,...

  18. Intermediate DNA methylation is a conserved signature of genome regulation.

    PubMed

    Elliott, GiNell; Hong, Chibo; Xing, Xiaoyun; Zhou, Xin; Li, Daofeng; Coarfa, Cristian; Bell, Robert J A; Maire, Cecile L; Ligon, Keith L; Sigaroudinia, Mahvash; Gascard, Philippe; Tlsty, Thea D; Harris, R Alan; Schalkwyk, Leonard C; Bilenky, Misha; Mill, Jonathan; Farnham, Peggy J; Kellis, Manolis; Marra, Marco A; Milosavljevic, Aleksandar; Hirst, Martin; Stormo, Gary D; Wang, Ting; Costello, Joseph F

    2015-01-01

    The role of intermediate methylation states in DNA is unclear. Here, to comprehensively identify regions of intermediate methylation and their quantitative relationship with gene activity, we apply integrative and comparative epigenomics to 25 human primary cell and tissue samples. We report 18,452 intermediate methylation regions located near 36% of genes and enriched at enhancers, exons and DNase I hypersensitivity sites. Intermediate methylation regions average 57% methylation, are predominantly allele-independent and are conserved across individuals and between mouse and human, suggesting a conserved function. These regions have an intermediate level of active chromatin marks and their associated genes have intermediate transcriptional activity. Exonic intermediate methylation correlates with exon inclusion at a level between that of fully methylated and unmethylated exons, highlighting gene context-dependent functions. We conclude that intermediate DNA methylation is a conserved signature of gene regulation and exon usage. PMID:25691127

  19. Intermediate DNA methylation is a conserved signature of genome regulation

    PubMed Central

    Elliott, GiNell; Hong, Chibo; Xing, Xiaoyun; Zhou, Xin; Li, Daofeng; Coarfa, Cristian; Bell, Robert J.A.; Maire, Cecile L.; Ligon, Keith L.; Sigaroudinia, Mahvash; Gascard, Philippe; Tlsty, Thea D.; Harris, R. Alan; Schalkwyk, Leonard C.; Bilenky, Misha; Mill, Jonathan; Farnham, Peggy J.; Kellis, Manolis; Marra, Marco A.; Milosavljevic, Aleksandar; Hirst, Martin; Stormo, Gary D.; Wang, Ting; Costello, Joseph F.

    2015-01-01

    The role of intermediate methylation states in DNA is unclear. Here, to comprehensively identify regions of intermediate methylation and their quantitative relationship with gene activity, we apply integrative and comparative epigenomics to 25 human primary cell and tissue samples. We report 18,452 intermediate methylation regions located near 36% of genes and enriched at enhancers, exons and DNase I hypersensitivity sites. Intermediate methylation regions average 57% methylation, are predominantly allele-independent and are conserved across individuals and between mouse and human, suggesting a conserved function. These regions have an intermediate level of active chromatin marks and their associated genes have intermediate transcriptional activity. Exonic intermediate methylation correlates with exon inclusion at a level between that of fully methylated and unmethylated exons, highlighting gene context-dependent functions. We conclude that intermediate DNA methylation is a conserved signature of gene regulation and exon usage. PMID:25691127

  20. 40 CFR 180.479 - Halosulfuron-methyl; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...General . (1) Tolerances are established for residues of the herbicide halosulfuron-methyl, methyl 5-[(4,6-dimethoxy-2-pyrimidiny...1 (2) Tolerances are established for residues of the herbicide halosulfuron-methyl, methyl...

  1. 40 CFR 180.479 - Halosulfuron-methyl; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...General . (1) Tolerances are established for residues of the herbicide halosulfuron-methyl, methyl 5-[(4,6-dimethoxy-2-pyrimidiny...0 (2) Tolerances are established for residues of the herbicide halosulfuron-methyl, methyl...

  2. 40 CFR 180.580 - Iodosulfuron-Methyl-Sodium; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...Iodosulfuron-Methyl-Sodium; tolerances for residues. (a) General. Tolerances are established for residues of the herbicide Iodosulfuron-Methyl-Sodium (methyl 4-iodo-2-[3-(4-methoxy-6-methyl-1,3,5...

  3. 40 CFR 180.479 - Halosulfuron-methyl; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...General. (1) Tolerances are established for residues of the herbicide halosulfuron-methyl, methyl 5-[(4,6-dimethoxy-2-pyrimidiny...0 (2) Tolerances are established for residues of the herbicide halosulfuron-methyl, methyl...

  4. 40 CFR 180.479 - Halosulfuron-methyl; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...General . (1) Tolerances are established for residues of the herbicide halosulfuron-methyl, methyl 5-[(4,6-dimethoxy-2-pyrimidiny...1 (2) Tolerances are established for residues of the herbicide halosulfuron-methyl, methyl...

  5. Chemical Speciation and Mobilization of Mercury and Methyl Mercury at Sub-anoxic Conditions in Wetlands and Sediments with Special Emphasis on Organic Thiols

    Microsoft Academic Search

    U. Skyllberg

    2007-01-01

    A correct description of the chemical speciation of Hg and MeHg is a prerequisite for understanding biogeochemical processes like retention-mobilization, methylation-demethylation and bioaccumulation. Binding affinity experiments and spectroscopic studies have clearly established that both inorganic Hg and methyl mercury (MeHg) are strongly complexed by reduced organic functional groups (thiols, RSH) in natural organic matter (NOM). Stability constants for Hg and

  6. In Vitro Reconstitution of SARS-Coronavirus mRNA Cap Methylation

    PubMed Central

    Bouvet, Mickaël; Debarnot, Claire; Imbert, Isabelle; Selisko, Barbara; Snijder, Eric J.; Canard, Bruno; Decroly, Etienne

    2010-01-01

    SARS-coronavirus (SARS-CoV) genome expression depends on the synthesis of a set of mRNAs, which presumably are capped at their 5? end and direct the synthesis of all viral proteins in the infected cell. Sixteen viral non-structural proteins (nsp1 to nsp16) constitute an unusually large replicase complex, which includes two methyltransferases putatively involved in viral mRNA cap formation. The S-adenosyl-L-methionine (AdoMet)-dependent (guanine-N7)-methyltransferase (N7-MTase) activity was recently attributed to nsp14, whereas nsp16 has been predicted to be the AdoMet-dependent (nucleoside-2?O)-methyltransferase. Here, we have reconstituted complete SARS-CoV mRNA cap methylation in vitro. We show that mRNA cap methylation requires a third viral protein, nsp10, which acts as an essential trigger to complete RNA cap-1 formation. The obligate sequence of methylation events is initiated by nsp14, which first methylates capped RNA transcripts to generate cap-0 7MeGpppA-RNAs. The latter are then selectively 2?O-methylated by the 2?O-MTase nsp16 in complex with its activator nsp10 to give rise to cap-1 7MeGpppA2?OMe-RNAs. Furthermore, sensitive in vitro inhibition assays of both activities show that aurintricarboxylic acid, active in SARS-CoV infected cells, targets both MTases with IC50 values in the micromolar range, providing a validated basis for anti-coronavirus drug design. PMID:20421945

  7. Dissolved humic substances initiate DNA-methylation in cladocerans.

    PubMed

    Menzel, Stefanie; Bouchnak, Rihab; Menzel, Ralph; Steinberg, Christian E W

    2011-10-01

    DNA-methylation is one pathway of epigenetic programming of gene expression and can be responsive to environmental challenges such as methylating agents in the food. Here we report on the DNA-methylation in the cladocerans Daphnia magna and Moina macrocopa exposed to humic substances, ubiquitous biogeochemicals. The methylation of DNA can alter the stress response, presumably including exposure to synthetic xenobiotic chemicals. PMID:21963594

  8. Induction of xylanase in Aspergillus tamarii by methyl ?- d -xyloside

    Microsoft Academic Search

    R. C. Simão; C. G. M. Souza; R. M. Peralta

    1997-01-01

    Aspergillus tamarii produced extracellular xylanase and intracellular ?-xylosidase inductively in washed glucose-grown mycelia incubated with\\u000a xylan and methyl ?-d-xyloside, a synthetic glycoside. Methyl ?-d-xyloside was a more effective inducer than xylan at the same concentration for both enzymes. Glucose and cycloheximide were\\u000a found to inhibit xylanase production by methyl ?-d-xyloside. Methyl ?-d-xyloside was hydrolyzed to xylose by mycelial extract in

  9. Flocculation of diatomite by methylated milk casein in seawater

    Microsoft Academic Search

    Hideshi Seki; Akira Suzuki; Masahiro Shinguh; Hideo Maruyama

    2004-01-01

    A new biodegradable flocculant was prepared from a common and inexpensive protein. Milk casein was methylated in a 0.05 M HCl methyl alcohol solution at room temperature. The methylated milk casein (MeCS), having a methylation degree of 81%, was applied to the separation or flocculation of diatomite in seawater (pH 8.1±0.1) at room temperature (18–23°C). The flocculating ability of MeCS

  10. Arginine Methylation of STAT1 Modulates IFN?\\/?-Induced Transcription

    Microsoft Academic Search

    Kerri A. Mowen; Jie Tang; Wei Zhu; Brandon T. Schurter; Ke Shuai; Harvey R. Herschman; Michael David

    2001-01-01

    Transcriptional induction by interferons requires the tyrosine and serine phosphorylation of STAT transcription factors. The N-terminal region is highly homologous among the STAT proteins and surrounds a completely conserved arginine residue. Here we demonstrate arginine methylation of STAT1 by the protein arginine methyl-transferase PRMT1 as a novel requirement for IFN?\\/?-induced transcription. Methyl-thioadenosine, a methyl-transferase inhibitor that accumulates in many transformed

  11. Isomorphous methyl-and chloro-substituted small heterocyclic

    E-print Network

    Müller, Peter

    isomorphous structures [3-methyl-4-(4-methyl- phenyl)-1-phenyl-6-trifluoromethyl-1H-pyrazolo[3,4-b]pyri- din-5-yl](thiophen-2-yl)methanone, C26H18F3N3OS, (I), and [4-(4-chlorophenyl)-3-methyl-1-phenyl-6. The crystal structures analysed in the present study, namely [3-methyl-4-(4-methylphenyl)-1-phenyl-6

  12. Insensitivity of chloroplast gene expression to DNA methylation

    Microsoft Academic Search

    Daniela Ahlert; Sandra Stegemann; Sabine Kahlau; Stephanie Ruf; Ralph Bock

    2009-01-01

    Presence and possible functions of DNA methylation in plastid genomes of higher plants have been highly controversial. While\\u000a a number of studies presented evidence for the occurrence of both cytosine and adenine methylation in plastid genomes and\\u000a proposed a role of cytosine methylation in the transcriptional regulation of plastid genes, several recent studies suggested\\u000a that at least cytosine methylation may

  13. Dynamic viscosities of the binary mixtures (methyl acetate or methanol + 2-methyl-2-butanol) and the ternary mixtures (methyl acetate + methanol + 2-propanol, or 2-butanol, or 2-methyl-2-butanol) at T = 298.15 K

    Microsoft Academic Search

    J. Canosa; A. Rodr??guez; J. Tojo

    2000-01-01

    Dynamic viscosities at T= 298.15 K and atmospheric pressure have been measured over the whole composition range for (methyl acetate + methanol + 2-propanol, or 2-butanol, or 2-methyl-2-butanol) and (methyl acetate or methanol + 2-methyl-2-butanol). Viscosity deviations for binary and ternary systems were calculated and fitted to Redlich–Kister and Cibulka equations, respectively, in order to estimate the parameters and the

  14. Advanced oxidation and reduction process chemistry of methyl tert-butyl ether (MTBE) reaction intermediates in aqueous solution: 2Methoxy2-methyl-propanal, 2-methoxy-2-methyl-propanol, and 2-methoxy-2-methyl-propanoic acid

    Microsoft Academic Search

    Stephen P. Mezyk; D. Rance Hardison; Weihua Song; Kevin E. O’Shea; David M. Bartels; William J. Cooper

    2009-01-01

    Absolute rate constants for the reaction of three important degradation products of methyl-tert-butyl ether (MTBE) with the hydroxyl radical, hydrated electron and hydrogen atom were determined in aqueous solution at room temperature. These three intermediate species; 2-methoxy-2-methyl propanal (MMP), 2-methoxy-2-methyl-propanol (MMP-OH) and 2-methoxy-2-methyl-propionic acid (MMP-acid), are formed in the degradation of MTBE under advanced oxidation and reduction process conditions. The

  15. Epigenetic regulation: methylation of histone and non-histone proteins

    Microsoft Academic Search

    Fei Lan; Yang Shi

    2009-01-01

    Histone methylation is believed to play important roles in epigenetic memory in various biological processes. However, questions\\u000a like whether the methylation marks themselves are faithfully transmitted into daughter cells and through what mechanisms are\\u000a currently under active investigation. Previously, methylation was considered to be irreversible, but the recent discovery\\u000a of histone lysine demethylases revealed a dynamic nature of histone methylation

  16. Reducing the crystallization temperature of biodiesel by winterizing methyl soyate

    Microsoft Academic Search

    Inmok Lee; Lawrence A. Johnson; Earl G. Hammond

    1996-01-01

    Methyl soyate, made from typical soybean varieties, has a crystallization onset temperature (T\\u000a co) of 3.7°C and, as a biodiesel fuel, is prone to crystallization of its high-melting saturated methyl esters at cold operating\\u000a temperatures. Removal of saturated esters by winterization was assessed as a means of reducing theT\\u000a co of methyl soyate. Winterizing neat methyl esters of typical soybean

  17. Effect of divalent metals on Hg(II) uptake and methylation by bacteria.

    PubMed

    Schaefer, Jeffra K; Szczuka, Aleksandra; Morel, François M M

    2014-03-01

    The production of methylmercury by some bacteria is a key first step in the accumulation and biomagnification of this toxic substance in aquatic food webs, a major human health concern. By direct measurement of cellular Hg(II) uptake in model iron and sulfate reducing bacteria, we have observed that specific trace metals, such as Zn(II) and Cd(II), inhibit uptake and methylation in these organisms, whereas other metals, such as Ni(II), Co(II), or Fe(II), do not. The inhibition of Hg(II) methylation by Zn(II) was competitive in nature and related to the concentration of inorganically complexed Zn(II) (Zn'). The inhibition of Hg(II) methylation was alleviated by decreasing the free Zn' concentration through complexation with nitrilotriacetic acid without altering the speciation of Hg(II). The inhibitory effect by Zn(II) was observed when either Hg-cysteine complexes or neutral HgCl2 dominated the speciation of Hg(II), demonstrating that both charged and neutral species are transported into the cytosol by an active rather than passive process. We propose that Hg(II) uptake is the result of its accidental uptake by metal transporter(s), possibly one effecting the transport of Zn(II). PMID:24512453

  18. Synthesis and Electrical Conductivity Studies of Poly (methyl methacrylate) in Presence of Transition Metal Ions

    NASA Astrophysics Data System (ADS)

    Ramesan, M. T.; Pradyumnan, P. P.

    2011-10-01

    Metal complexes of polymer based on poly methyl methacrylate (PMMA) were prepared by the in situ bulk polymerization of methyl methacrylate with different molar concentrations of salts of iron II chloride and cobalt II nitrate. These complexes were characterized by FTIR and UV spectroscopic studies revealed that the metal is coordinated to carbonyl oxygen and methoxy oxygen of methacrylate moiety. The surface morphology of these composite was studied with scanning electron microscope (SEM), indicated that metal incorporated polymer exhibit well dispersed structures. The basic decomposition pattern and thermal stability of the samples were carried out using TGA. The incorporation of metal in main chain of PMMA enhances excellent thermal resistance. Lower concentration of metal incorporated PMMA has superior thermal stability than higher dosage of metals. The a.c. conductivity behavior was investigated in the frequency range of 102-106 at room temperature. The molar concentrations of metal particle in the polymer matrix have greater influence on the observed conductivity values. Nickel (II) complexes of poly (methyl methacrylate) have better conductivity, dielectric constant and loss factor than that of iron (II) introduced polymer matrix.

  19. Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation

    PubMed Central

    Jia, Da; Jurkowska, Renata Z.; Zhang, Xing; Jeltsch, Albert; Cheng, Xiaodong

    2009-01-01

    Genetic imprinting, found in flowering plants and placental mammals, uses DNA methylation to yield gene expression that is dependent on the parent of origin1. DNA methyltransferase 3a (Dnmt3a) and its regulatory factor, DNA methyltransferase 3-like protein (Dnmt3L), are both required for the de novo DNA methylation of imprinted genes in mammalian germ cells. Dnmt3L interacts specifically with unmethylated lysine 4 of histone H3 through its amino-terminal PHD (plant homeodomain)-like domain2. Here we show, with the use of crystallography, that the carboxy-terminal domain of human Dnmt3L interacts with the catalytic domain of Dnmt3a, demonstrating that Dnmt3L has dual functions of binding the unmethylated histone tail and activating DNA methyltransferase. The complexed C-terminal domains of Dnmt3a and Dnmt3L showed further dimerization through Dnmt3a–Dnmt3a interaction, forming a tetrameric complex with two active sites. Substitution of key non-catalytic residues at the Dnmt3a–Dnmt3L interface or the Dnmt3a–Dnmt3a interface eliminated enzymatic activity. Molecular modelling of a DNA–Dnmt3a dimer indicated that the two active sites are separated by about one DNA helical turn. The C-terminal domain of Dnmt3a oligomerizes on DNA to form a nucleoprotein filament. A periodicity in the activity of Dnmt3a on long DNA revealed a correlation of methylated CpG sites at distances of eight to ten base pairs, indicating that oligomerization leads Dnmt3a to methylate DNA in a periodic pattern. A similar periodicity is observed for the frequency of CpG sites in the differentially methylated regions of 12 maternally imprinted mouse genes. These results suggest a basis for the recognition and methylation of differentially methylated regions in imprinted genes, involving the detection of both nucleosome modification and CpG spacing. PMID:17713477

  20. Methyl bromide alternatives for raspberry nurseries

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Raspberry nurseries must produce plants free from disease to meet marketplace and export requirements. Minor disease infestations in nurseries can cause severe epidemics in production fields. Raspberry nurseries presently qualify for critical use and quarantine/preshipment exemptions to use Methyl B...

  1. DNA methylation in health, disease, and cancer.

    PubMed

    Shames, David S; Minna, John D; Gazdar, Adi F

    2007-02-01

    The spatial arrangement and three-dimensional structure of DNA in the nucleus is controlled through the interdigitation of DNA binding proteins such as histones and their modifiers, the Polycomb-Trithorax proteins, and the DNA methyltransferase enzymes. DNA methylation forms the foundation of chromatin and is crucial to epigenetic gene regulation in mammals. Disease pathogenesis mediated through infectious agents, inflammation, aging, or genetic damage often involves changes in gene expression. In particular, cellular transformation coincides with multiple changes in chromatin architecture, many of which appear to affect genome integrity and gene expression. Infectious agents, such as viruses directly affect genome structure and induce methylation of particular sequences to suppress host immune responses. Hyperproliferative tissues such as those in the gastrointestinal tract and colon have been shown to gradually acquire aberrant promoter hypermethylation. Here we review recent findings on altered DNA methylation in human disease, with particular focus on cancer and the increasingly large number of genes subject to tumor-specific promoter hypermethylation and the possible role of aberrant methylation in tumor development. PMID:17311535

  2. 67 FR 51088 - Metsulfuron Methyl; Pesticide Tolerance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2002-08-07

    ...mammalian is not a clastogen chromosome under the aberrations-CHO...mammalian Metsulfuron methyl chromosome did not induce a aberrations-rat...significant bone marrow increase in chromosome aberrations in bone marrow...estimate risk which represents a probability of occurrence of...

  3. Occupational allergic contact dermatitis from methyl aminolevulinate.

    PubMed

    Antonia Pastor-Nieto, María; Olivares, Mercedes; Sánchez-Herreros, Consuelo; Belmar, Paulina; De Eusebio, Esther

    2011-01-01

    Photodynamic therapy (PDT) is used to treat certain types of nonmelanoma skin cancer. Metvix cream applied topically in PDT is composed of the active substance methyl aminolevulinate and 14 excipients composing the vehicle. One case of occupational allergic contact dermatitis from methyl aminolevulinate is reported. A 49-year-old nurse's aide working in a PDT unit in the dermatology department developed a dermatitis involving the eyelids and fingers. The lesions began a few months after she started working in that unit. Patch tests were performed with the standard series (Spanish Group for Research into Dermatitis and Skin Allergies [GEIDAC]), cosmetics series, Metvix cream "as is," the Metvix vehicle supplied by the manufacturer, and some of the excipients separately (methyl para-hydroxybenzoate [Nipagin M], propyl para-hydroxybenzoate [Nipasol M], isopropyl myristate, cetostearyl alcohol [Lanette N], and disodium edetate). After day-2, day-4, and day-7 readings, positive results were achieved only with Metvix cream "as is." Tests performed on a control group of 15 individuals were negative. Literature on cases of allergic contact dermatitis from methyl aminolevulinate is reviewed. It should be emphasized that the present case is the first occupational case reported so far. PMID:21781638

  4. METHYL MERCURY IN LAKE MICHIGAN SURFICIAL SEDIMENTS

    EPA Science Inventory

    Sediment samples were collected from Lake Michigan between 1994 and 1996. One purpose of the sampling was to define the horizontal distribution of methyl mercury in the surficial 1 cm of sediment. Samples were collected from 51 stations using a box core from which subcores for ...

  5. Pharmacodynamic Measurements of Methyl Nicotinate Percutaneous Absorption

    Microsoft Academic Search

    Richard H. Guy; Ethel Tur; Barry Bugatto; Caroline Gaebel; Lewis B. Sheiner; Howard I. Maibach

    1984-01-01

    The local kinetics of percutaneous absorption provide information of relevance to the treatment of skin diseases and to the potential efficacy of transdermally delivered chemotherapy for systemic effect. This paper describes two non-invasive procedures (laser Doppler velocimetry and photopulse plethysmography) which permit pharmacodynamic measurements of methyl nicotinate skin penetration to be made in vivo in man. The methods are sensitive

  6. Mobility and molecular ions of dimethyl methyl phosphonate, methyl salicylate and acetone

    NASA Astrophysics Data System (ADS)

    Nowak, D. M.

    1983-06-01

    The mobilities of positive and negative reactant ions are reported for (H2O)nH(+); (H2O)2O2 and (H2O)2CO3(-) ion clusters. The formation of positive DMMP monomer and dimer is reported, and equilbria molecular reactions are reported. Acetone is reported as forming a dimer at 81 ppb with a reduced mobility (K sub o) of 1.82, Methyl salicylate is shown to form a protonated and hydrated positive monomer. Mixtures of DMMP and methyl salicylate with acetone showed a substantial change in DMMP ion clustering and little or no change in the methyl salicylate mobility spectra. Negative ions were not observed for DMMP, methyl salicylate, acetone and the mixtures under the conditions reported.

  7. Effect of oxygen, methyl mercaptan, and methyl chloride on friction behavior of copper-iron contacts

    NASA Technical Reports Server (NTRS)

    Buckley, D. H.

    1978-01-01

    Sliding friction experiments were conducted with an iron rider on a copper disk and a copper rider on an iron disk. The sputter cleaned iron and copper disk surfaces were saturated with oxygen, methyl mercaptan, and methyl chloride at atmospheric pressure. Auger emission spectroscopy was used to monitor the surfaces. Lower friction was obtained in all experiments with the copper rider sliding on the iron disk than when the couple was reversed. For both iron and copper disks, methyl mercaptan gave the best surface coverage and was most effective in reducing friction. For both iron and copper disks, methyl chloride was the least effective in reducing friction. With sliding, copper transferred to iron and iron to copper.

  8. SINE transcription by RNA polymerase III is suppressed by histone methylation but not by DNA methylation

    PubMed Central

    Varshney, Dhaval; Vavrova-Anderson, Jana; Oler, Andrew J.; Cowling, Victoria H.; Cairns, Bradley R.; White, Robert J.

    2015-01-01

    Short interspersed nuclear elements (SINEs), such as Alu, spread by retrotransposition, which requires their transcripts to be copied into DNA and then inserted into new chromosomal sites. This can lead to genetic damage through insertional mutagenesis and chromosomal rearrangements between non-allelic SINEs at distinct loci. SINE DNA is heavily methylated and this was thought to suppress its accessibility and transcription, thereby protecting against retrotransposition. Here we provide several lines of evidence that methylated SINE DNA is occupied by RNA polymerase III, including the use of high-throughput bisulphite sequencing of ChIP DNA. We find that loss of DNA methylation has little effect on accessibility of SINEs to transcription machinery or their expression in vivo. In contrast, a histone methyltransferase inhibitor selectively promotes SINE expression and occupancy by RNA polymerase III. The data suggest that methylation of histones rather than DNA plays a dominant role in suppressing SINE transcription. PMID:25798578

  9. Synthesis and properties of phosphono-derivatives of methyl stearate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A series of phosphono-derivatives of methyl stearate (PhDMS) were synthesized from methyl oleate and dialkyl H-phosphonates (dialkyl-phosphites). The alkyl groups in the phosphonates were methyl, ethyl, and butyl. The reaction can be carried to 98+% completion with a radical initiator. It is possibl...

  10. WEED CONTROL IN THE LIFE AFTER METHYL BROMIDE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vegetable growers are losing the soil fumigant methyl bromide. Efforts are on-going to extend the deadline for using methyl bromide until suitable alternatives are developed. Regardless of whether the deadline is extended or not, growers need to begin to study alternatives to methyl bromide and be...

  11. Rapeseed oil methyl esters preparation using heterogeneous catalysts

    Microsoft Academic Search

    S. Gryglewicz

    1999-01-01

    The classical method of fatty acids methyl esters (FAME) production is based on triglyceride transesterification to methyl esters. Sodium hydroxide dissolved in methanol is used as a catalyst. The purpose of this work was to examine a heterogeneous catalyst, in particular calcium compounds, to produce methyl esters of rapeseed oil. This research showed that the transesterification of rapeseed oil by

  12. DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction

    Microsoft Academic Search

    Ann-Marie Bröske; Lena Vockentanz; Shabnam Kharazi; Matthew R Huska; Elena Mancini; Marina Scheller; Christiane Kuhl; Andreas Enns; Marco Prinz; Rudolf Jaenisch; Claus Nerlov; Achim Leutz; Miguel A Andrade-Navarro; Sten Eirik W Jacobsen; Frank Rosenbauer

    2009-01-01

    DNA methylation is a dynamic epigenetic mark that undergoes extensive changes during differentiation of self-renewing stem cells. However, whether these changes are the cause or consequence of stem cell fate remains unknown. Here, we show that alternative functional programs of hematopoietic stem cells (HSCs) are governed by gradual differences in methylation levels. Constitutive methylation is essential for HSC self-renewal but

  13. New process for the preparation of methyl carbonates.

    PubMed

    Wuts, Peter G M; Ashford, Scott W; Anderson, Andrew M; Atkins, Joseph R

    2003-05-01

    The methyl carbonate of HOBt was developed for the conversion of alcohols to carbonates. This method is superior to the use of methyl chloroformate or methyl pyrocarbonate, especially with more hindered alcohols. The reagent is a stable solid that is easily prepared on a multigram scale. [reaction: see text] PMID:12713304

  14. Mercury Methylation in the Epilithon of Boreal Shield Aquatic Ecosystems

    E-print Network

    Long, Bernard

    's shore for 1-2 years. At temperatures above 20 °C, epilithon Hg methylation rates were fast and reached and that the integrity of the epilithic biofilm is important for its ability to methylate Hg. Introduction In the boreal methylation is very slow in forested soils (6, 7), and Hg delivered to aquatic systems from the watersheds

  15. Cobalt Limitation of Growth and Mercury Methylation in

    E-print Network

    Morel, François M. M.

    Cobalt Limitation of Growth and Mercury Methylation in Sulfate-Reducing Bacteria E I L E E N B . E is known of the physiologyandbiochemistryofmercury(Hg)methylation.Corrinoid compounds have been implicated in enzymatic Hg methylation, although recent experiments with a vitamin B12 inhibitor indicated that incomplete

  16. DNA methylation and the analysis of CpG Islands

    E-print Network

    Czygrinow, Andrzej

    DNA methylation and the analysis of CpG Islands in genomes M. F. Wojciechowski MAT 351 25 March 2005 #12;#12;Nucleotides #12;Base pairing * * #12;DNA methylation In mammalian genomes, methylation residues represent a target for covalent modification of DNA Cytosine is one of two bases found commonly

  17. Neutron scattering investigations on methyl group dynamics in polymers

    Microsoft Academic Search

    Juan Colmenero; Angel J. Moreno; Angel Alegria

    2005-01-01

    Among the different dynamical processes that take place in polymers, methyl group rotation is perhaps the simplest one, since all the relevant interactions on the methyl group can be condensed in an effective mean-field one-dimensional potential. Recent experimental neutron scattering results have stimulated a new revival of the interest on methyl group dynamics in glasses and polymer systems. The existence

  18. Methyl substituted polyimides containing carbonyl and ether connecting groups

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M. (inventor); Havens, Stephen J. (inventor)

    1992-01-01

    Polyimides were prepared from the reaction of aromatic dianhydrides with novel aromatic diamines having carbonyl and ether groups connecting aromatic rings containing pendant methyl groups. The methyl substituent polyimides exhibit good solubility and form tough, strong films. Upon exposure to ultraviolet irradiation and/or heat, the methyl substituted polyimides crosslink to become insoluble.

  19. Heterogeneity of DNA methylation in multifocal prostate cancer.

    PubMed

    Serenaite, Inga; Daniunaite, Kristina; Jankevicius, Feliksas; Laurinavicius, Arvydas; Petroska, Donatas; Lazutka, Juozas R; Jarmalaite, Sonata

    2015-01-01

    Most prostate cancer (PCa) cases are multifocal, and separate foci display histological and molecular heterogeneity. DNA hypermethylation is a frequent alteration in PCa, but interfocal heterogeneity of these changes has not been extensively investigated. Ten pairs of foci from multifocal PCa and 15 benign prostatic hyperplasia (BPH) samples were obtained from prostatectomy specimens, resulting altogether in 35 samples. Methylation-specific PCR (MSP) was used to evaluate methylation status of nine tumor suppressor genes (TSGs), and a set of selected TSGs was quantitatively analyzed for methylation intensity by pyrosequencing. Promoter sequences of the RASSF1 and ESR1 genes were methylated in all paired PCa foci, and frequent (?75 %) DNA methylation was detected in RARB, GSTP1, and ABCB1 genes. MSP revealed different methylation status of at least one gene in separate foci in 8 out of 10 multifocal tumors. The mean methylation level of ESR1, GSTP1, RASSF1, and RARB differed between the paired foci of all PCa cases. The intensity of DNA methylation in these TSGs was significantly higher in PCa cases than in BPH (p < 0.001). Hierarchical cluster analysis revealed a divergent methylation profile of paired PCa foci, while the foci from separate cases with biochemical recurrence showed similar methylation profile and the highest mean levels of DNA methylation. Our findings suggest that PCa tissue is heterogeneous, as between paired foci differences in DNA methylation status were found. Common epigenetic profile of recurrent tumors can be inferred from our data. PMID:25369892

  20. Oceanic Uptake of Methyl Bromide: Implications for Oceanic Production

    Microsoft Academic Search

    S. A. Yvon-Lewis; J. H. Butler; D. B. King; E. S. Saltzman; R. Tokarczyk

    2002-01-01

    Methyl bromide (CH3Br) is a source of inorganic bromine (Br) in the stratosphere, where it contributes to the depletion of stratospheric ozone. Unlike the chlorofluorocarbons, which are entirely anthropogenic, methyl bromide has both natural and anthropogenic sources. At ~10 parts per trillion in the troposphere, methyl bromide is believed to be the single largest contributor of stratospheric Br. Once in

  1. Reading the unique DNA methylation landscape of the brain: Non-CpG methylation, hydroxymethylation, and MeCP2

    PubMed Central

    Kinde, Benyam; Gabel, Harrison W.; Gilbert, Caitlin S.; Griffith, Eric C.; Greenberg, Michael E.

    2015-01-01

    DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system. PMID:25739960

  2. Reading the unique DNA methylation landscape of the brain: Non-CpG methylation, hydroxymethylation, and MeCP2.

    PubMed

    Kinde, Benyam; Gabel, Harrison W; Gilbert, Caitlin S; Griffith, Eric C; Greenberg, Michael E

    2015-06-01

    DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system. PMID:25739960

  3. A change of phenolic acids content in poplar leaves induced by methyl salicylate and methyl jasmonate

    Microsoft Academic Search

    Yu An; Ying-bai Shen; Li-juan Wu; Zhi-xiang Zhang

    2006-01-01

    The contents of seven different phenolic acids such as gallic acid, catechinic acid, pyrocatechol, caffeic acid, coumaric\\u000a acid, ferulic acid and benzoic acid in the poplar leaves (Populus Simonii × Populus Pyramibalis c. v and Populus deltoids) suffocated by Methyl jasmonate (MeJA) and Methyl salicylate (MeSA) were monitored for analyzing their functions in interplant\\u000a communications by using high-pressure liquid chromatography

  4. Determination of azinphos-methyl and parathion-methyl in honey by stripping voltammetry

    Microsoft Academic Search

    Constantinos G. Tsiafoulis; Christos G. Nanos

    2010-01-01

    An electrochemical method for the determination of azinphos-methyl and parathion-methyl in honey is presented. The determination is established by adsorptive stripping differential pulse voltammetry at hanging mercury working electrode.In contrast to the chromatographic methods for the determination of pesticide residues, the sample preparation of the proposed method is minimal; analytes were extracted from honey samples with a mixture of (acetone):(Britton–Robinson

  5. Global fits of methyl-methyl recombinational data to Prezhdo`s new interpolation formula

    Microsoft Academic Search

    Jan P. Hessler

    1996-01-01

    Prezhdo has suggested a new interpolation formula for the pressure-dependent behavior of dissociative and recombinational reactions. This formula, k(P{sub r}) = k[P{sub r}\\/[1+P{sub r}+(P{sub r}\\/B){sup A}] TBC], introduces two phenomenological parameters, A and B. Fits to isothermal methyl-methyl recombinational data are used to determine their temperature dependence. Global fits to an extensive set of data give high-pressure rates coefficients which

  6. Confirmation of the Carbon Chemical Shifts of Ethylenic Carbon Atoms in Methyl Ricinoleate and Methyl Ricinelaidate

    Microsoft Academic Search

    A. K. L. Cheng

    1993-01-01

    The carbon chemical shifts of the ethylenic carbon atoms of methyl ricinoleate (12-hydroxy-9-cis-octadecenoate) are 133.32, C-9; 125.28, C-10 and those of methyl ricinelaidate (12-hydroxy-9-trans-octadecenoate) are 134.56, C-9 and 125.97, C-10. The shift values were confirmed by double irradiation (spin decoupling) and H-C COSY nuclear magnetic resonance techique.

  7. Methylal and Methylal-Diesel Blended Fuels from Use In Compression-Ignition Engines

    Microsoft Academic Search

    Keith D. Vertin; James M. Ohi; David W. Naegeli; Kenneth H. Childress; Gary P. Hagen; Chris I. McCarthy; Adelbert S. Cheng; Robert W. Dibble

    1999-01-01

    Gas-to-liquids catalytic conversion technologies show promise for liberating stranded natural gas reserves and for achieving energy diversity worldwide. Some gas-to-liquids products are used as transportation fuels and as blendstocks for upgrading crude derived fuels. Methylal (CHâ-O-CHâ-O-CHâ) also known as dimethoxymethane or DMM, is a gas-to-liquid chemical that has been evaluated for use as a diesel fuel component. Methylal contains 42%

  8. Natural methyl bromide and methyl chloride emissions from coastal salt marshes

    Microsoft Academic Search

    Robert C. Rhew; Benjamin R. Miller; Ray F. Weiss

    2000-01-01

    Atmospheric methyl bromide (CH3Br) and methyl chloride (CH 3Cl), compounds that are involved in stratospheric ozone depletion, originate from both natural and anthropogenic sources. Current estimates of CH3Br and CH3Cl emissions from oceanic sources, terrestrial plants and fungi, biomass burning and anthropogenic inputs do not balance their losses owing to oxidation by hydroxyl radicals, oceanic degradation, and consumption in soils,

  9. DNA Methylation as a Biomarker for Preeclampsia

    SciTech Connect

    Anderson, Cindy M.; Ralph, Jody L.; Wright, Michelle L.; Linggi, Bryan E.; Ohm, Joyce E.

    2014-10-01

    Background: Preeclampsia contributes significantly to pregnancy-associated morbidity and mortality as well as future risk of cardiovascular disease in mother and offspring, and preeclampsia in offspring. The lack of reliable methods for early detection limits the opportunities for prevention, diagnosis, and timely treatment. Purpose: The purpose of this study was to explore distinct DNA methylation patterns associated with preeclampsia in both maternal cells and fetal-derived tissue that represent potential biomarkers to predict future preeclampsia and inheritance in children. Method: A convenience sample of nulliparous women (N = 55) in the first trimester of pregnancy was recruited for this prospective study. Genome-wide DNA methylation was quantified in first-trimester maternal peripheral white blood cells and placental chorionic tissue from normotensive women and those with preeclampsia (n = 6/group). Results: Late-onset preeclampsia developed in 12.7% of women. Significant differences in DNA methylation were identified in 207 individual linked cytosine and guanine (CpG) sites in maternal white blood cells collected in the first trimester (132 sites with gain and 75 sites with loss of methylation), which were common to approximately 75% of the differentially methylated CpG sites identified in chorionic tissue of fetal origin. Conclusion: This study is the first to identify maternal epigenetic targets and common targets in fetal-derived tissue that represent putative biomarkers for early detection and heritable risk of preeclampsia. Findings may pave the way for diagnosis of preeclampsia prior to its clinical presentation and acute damaging effects, and the potential for prevention of the detrimental long-term sequelae.

  10. Temperature dependence of surface tension of 2-methyl-1-propanol and 2-methyl-2-propanol+n-hexane mixtures

    Microsoft Academic Search

    Beatriz Giner; Isabel Bandrés; Ignacio Giner; Diego F. Montaño; M. Carmen López

    2008-01-01

    Surface tensions of binary mixtures of 2-methyl-1-propanol or 2-methyl-2-propanol with n-hexane have been measured in the temperature range 283.15 K–313.15 K for mixtures containing 2-methyl-1-propanol and from 298.15 K to 313.15 K for mixtures formed by 2-methyl-2-propanol, with a drop volume tensiometer. The corresponding surface tension deviations have been calculated and correlated. Using the temperature dependence of surface tensions, the

  11. Tissue specific differentially methylated regions (TDMR): Changes in DNA methylation during development

    PubMed Central

    Song, Fei; Mahmood, Saleh; Ghosh, Srimoyee; Liang, Ping; Smiraglia, Domminic J.; Nagase, Hiroki

    2009-01-01

    Tissue specific differentially methylated regions (TDMRs) were identified and localized in the mouse genome using second generation virtual RLGS (vRLGS). Sequenom MassARRAY quantitative methylation analysis was used to confirm and determine the fine structure of tissue specific differences in DNA methylation. TDMRs have a broad distribution of locations to intragenic and intergenic regions including both CpG islands, and non-CpG islands regions. Somewhat surprising, there is a strong bias for TDMR location in non-promoter intragenic regions. Although some TDMRs are within or close to repeat sequences, overall they are less frequently associated with repetitive elements than expected from a random distribution. Many TDMRs are methylated at early developmental stages, but unmethylated later, suggesting active or passive demethylation, or expansions of populations of cells with unmethylated TDMRs. This is notable during postnatal testis differentiation where many testis-specific TDMRs become progressively “demethylated”. These results suggest that methylation changes during development are dynamic, involve demethylation and methylation, and may occur at late stages of embryonic development or even postnatally. PMID:18952162

  12. A novel method for detecting 7-methyl guanine reveals aberrant methylation levels in Huntington disease

    PubMed Central

    Thomas, Beena; Matson, Samantha; Chopra, Vanita; Sun, Liping; Sharma, Swati; Hersch, Steven; Rosas, H. Diana; Scherzer, Clemens; Ferrante, Robert; Matson, Wayne

    2014-01-01

    Guanine methylation is a ubiquitous process affecting DNA and various RNA species. N-7 guanine methylation (7-MG), though relatively less studied, could have a significant role in normal transcriptional regulation as well as in the onset and development of pathological conditions. The lack of a sensitive method to accurately quantify trace amounts of altered bases like 7-MG, has been a major deterrent in delineating its biological function(s). Here we report the development of methods to detect trace amounts of 7-MG in biological samples using electrochemical detection combined with HPLC separation of compounds. We further sought to assess global alterations in DNA methylation in Huntington's disease (HD) in which transcriptional dysregulation, is a major factor in pathogenesis. The developed method was used to study guanine methylation in cytoplasmic and nuclear nucleic acids from human and transgenic mouse HD brain and controls. Significant differences were observed in the guanine methylation levels in mouse and human samples, consistent with the known transcriptional pathology of HD. The sensitivity of the method makes it capable of detecting subtle aberrations. Identification of changes in methylation pattern will provide insights into the molecular mechanisms changes that translate into onset and/or development of symptoms in diseases like HD. PMID:23416183

  13. Principles of nucleation of H3K27 methylation during embryonic development.

    PubMed

    van Heeringen, Simon J; Akkers, Robert C; van Kruijsbergen, Ila; Arif, M Asif; Hanssen, Lars L P; Sharifi, Nilofar; Veenstra, Gert Jan C

    2014-03-01

    During embryonic development, maintenance of cell identity and lineage commitment requires the Polycomb-group PRC2 complex, which catalyzes histone H3 lysine 27 trimethylation (H3K27me3). However, the developmental origins of this regulation are unknown. Here we show that H3K27me3 enrichment increases from blastula stages onward in embryos of the Western clawed frog (Xenopus tropicalis) within constrained domains strictly defined by sequence. Strikingly, although PRC2 also binds widely to active enhancers, H3K27me3 is only deposited at a small subset of these sites. Using a Support Vector Machine algorithm, these sequences can be predicted accurately on the basis of DNA sequence alone, with a sequence signature conserved between humans, frogs, and fish. These regions correspond to the subset of blastula-stage DNA methylation-free domains that are depleted for activating promoter motifs, and enriched for motifs of developmental factors. These results imply a genetic-default model in which a preexisting absence of DNA methylation is the major determinant of H3K27 methylation when not opposed by transcriptional activation. The sequence and motif signatures reveal the hierarchical and genetically inheritable features of epigenetic cross-talk that impose constraints on Polycomb regulation and guide H3K27 methylation during the exit of pluripotency. PMID:24336765

  14. Principles of nucleation of H3K27 methylation during embryonic development

    PubMed Central

    van Heeringen, Simon J.; Akkers, Robert C.; van Kruijsbergen, Ila; Arif, M. Asif; Hanssen, Lars L.P.; Sharifi, Nilofar; Veenstra, Gert Jan C.

    2014-01-01

    During embryonic development, maintenance of cell identity and lineage commitment requires the Polycomb-group PRC2 complex, which catalyzes histone H3 lysine 27 trimethylation (H3K27me3). However, the developmental origins of this regulation are unknown. Here we show that H3K27me3 enrichment increases from blastula stages onward in embryos of the Western clawed frog (Xenopus tropicalis) within constrained domains strictly defined by sequence. Strikingly, although PRC2 also binds widely to active enhancers, H3K27me3 is only deposited at a small subset of these sites. Using a Support Vector Machine algorithm, these sequences can be predicted accurately on the basis of DNA sequence alone, with a sequence signature conserved between humans, frogs, and fish. These regions correspond to the subset of blastula-stage DNA methylation-free domains that are depleted for activating promoter motifs, and enriched for motifs of developmental factors. These results imply a genetic-default model in which a preexisting absence of DNA methylation is the major determinant of H3K27 methylation when not opposed by transcriptional activation. The sequence and motif signatures reveal the hierarchical and genetically inheritable features of epigenetic cross-talk that impose constraints on Polycomb regulation and guide H3K27 methylation during the exit of pluripotency. PMID:24336765

  15. Human papilloma virus, DNA methylation and microRNA expression in cervical cancer (Review)

    PubMed Central

    JIMÉNEZ-WENCES, HILDA; PERALTA-ZARAGOZA, OSCAR; FERNÁNDEZ-TILAPA, GLORIA

    2014-01-01

    Cancer is a complex disease caused by genetic and epigenetic abnormalities that affect gene expression. The progression from precursor lesions to invasive cervical cancer is influenced by persistent human papilloma virus (HPV) infection, which induces changes in the host genome and epigenome. Epigenetic alterations, such as aberrant miRNA expression and changes in DNA methylation status, favor the expression of oncogenes and the silencing of tumor-suppressor genes. Given that some miRNA genes can be regulated through epigenetic mechanisms, it has been proposed that alterations in the methylation status of miRNA promoters could be the driving mechanism behind their aberrant expression in cervical cancer. For these reasons, we assessed the relationship among HPV infection, cellular DNA methylation and miRNA expression. We conclude that alterations in the methylation status of protein-coding genes and various miRNA genes are influenced by HPV infection, the viral genotype, the physical state of the viral DNA, and viral oncogenic risk. Furthermore, HPV induces deregulation of miRNA expression, particularly at loci near fragile sites. This deregulation occurs through the E6 and E7 proteins, which target miRNA transcription factors such as p53. PMID:24737381

  16. Evaluation of Methyl-Binding Domain Based Enrichment Approaches Revisited

    PubMed Central

    Aberg, Karolina A.; Xie, Linying; Chan, Robin F.; Zhao, Min; Pandey, Ashutosh K.; Kumar, Gaurav; Clark, Shaunna L.; van den Oord, Edwin J. C. G.

    2015-01-01

    Methyl-binding domain (MBD) enrichment followed by deep sequencing (MBD-seq), is a robust and cost efficient approach for methylome-wide association studies (MWAS). MBD-seq has been demonstrated to be capable of identifying differentially methylated regions, detecting previously reported robust associations and producing findings that replicate with other technologies such as targeted pyrosequencing of bisulfite converted DNA. There are several kits commercially available that can be used for MBD enrichment. Our previous work has involved MethylMiner (Life Technologies, Foster City, CA, USA) that we chose after careful investigation of its properties. However, in a recent evaluation of five commercially available MBD-enrichment kits the performance of the MethylMiner was deemed poor. Given our positive experience with MethylMiner, we were surprised by this report. In an attempt to reproduce these findings we here have performed a direct comparison of MethylMiner with MethylCap (Diagenode Inc, Denville, NJ, USA), the best performing kit in that study. We find that both MethylMiner and MethylCap are two well performing MBD-enrichment kits. However, MethylMiner shows somewhat better enrichment efficiency and lower levels of background “noise”. In addition, for the purpose of MWAS where we want to investigate the majority of CpGs, we find MethylMiner to be superior as it allows tailoring the enrichment to the regions where most CpGs are located. Using targeted bisulfite sequencing we confirmed that sites where methylation was detected by either MethylMiner or by MethylCap indeed were methylated. PMID:26177298

  17. Protein and nucleic acid methylating enzymes: mechanisms and regulation

    PubMed Central

    Le, Daniel D; Fujimori, Danica Galoni?

    2012-01-01

    Protein and nucleic acid methylating enzymes are implicated in myriad cellular processes. These enzymes utilize diverse chemical mechanisms ranging from nucleophilic substitution-displacement to a novel radical-based reaction found in bacterial iron–sulfur cluster proteins. Within the cell, methylation activity is governed by interactions with endogenous molecular machinery. Of particular interest are the observations that methylating enzyme activity can be allosterically controlled by regulatory binding partners. Recent advances and emerging trends in the study of methylating enzyme mechanisms and regulation highlight the importance of protein and nucleic acid methylation in cellular physiology and disease. PMID:23085277

  18. Colorimetric determination of methyl parathion and oxygen analog.

    PubMed

    Nanda Kumar, N V; Ramasundari, M

    1980-05-01

    A simple, sensitive, and rapid colorimetric method is described for determining methyl parathion (O,O-dimethyl-O-p-nitrophenyl phosphorothioate) and methyl paraoxon (O,O-dimethyl-O-p-nitrophenyl phosphate), using p-nitrobenzene diazonium fluoroborate as the chromogenic salt. This colorimetric method is more sensitive than are other colorimetric methods based on non-enzymatic reactions. Pig liver acetone powder cholinesterase was found to be sensitive to methyl parathion. Inhibition can be detected at picogram levels, and 50-80 ng methyl paraoxon and 1-9 micrograms methyl parathion can be estimated. PMID:7430041

  19. Structure-guided design of a methyl donor cofactor that controls a viral histone H3 lysine 27 methyltransferase activity.

    PubMed

    Li, Jiaojie; Wei, Hua; Zhou, Ming-Ming

    2011-11-10

    vSET (a viral SET domain protein) is an attractive polycomb repressive complex 2 (PRC2) surrogate to study the effect of histone H3 lysine 27 (H3K27) methylation on gene transcription, as both catalyze histone H3K27 trimethylation. To control the enzymatic activity of vSET in vivo with an engineered S-adenosyl-l-methionine (SAM) analogue as methyl donor cofactor, we have carried out structure-guided design, synthesis, and characterization of orthogonal vSET methyltransferase mutant/SAM analogue pairs using a "bump-and-hole" strategy. PMID:21958314

  20. Regulation and function of DNA methylation in plants and animals

    PubMed Central

    He, Xin-Jian; Chen, Taiping; Zhu, Jian-Kang

    2011-01-01

    DNA methylation is an important epigenetic mark involved in diverse biological processes. In plants, DNA methylation can be established through the RNA-directed DNA methylation pathway, an RNA interference pathway for transcriptional gene silencing (TGS), which requires 24-nt small interfering RNAs. In mammals, de novo DNA methylation occurs primarily at two developmental stages: during early embryogenesis and during gametogenesis. While it is not clear whether establishment of DNA methylation patterns in mammals involves RNA interference in general, de novo DNA methylation and suppression of transposons in germ cells require 24-32-nt piwi-interacting small RNAs. DNA methylation status is dynamically regulated by DNA methylation and demethylation reactions. In plants, active DNA demethylation relies on the repressor of silencing 1 family of bifunctional DNA glycosylases, which remove the 5-methylcytosine base and then cleave the DNA backbone at the abasic site, initiating a base excision repair (BER) pathway. In animals, multiple mechanisms of active DNA demethylation have been proposed, including a deaminase- and DNA glycosylase-initiated BER pathway. New information concerning the effects of various histone modifications on the establishment and maintenance of DNA methylation has broadened our understanding of the regulation of DNA methylation. The function of DNA methylation in plants and animals is also discussed in this review. PMID:21321601

  1. Sarcolemmal phospholipid N-methylation in genetically determined hamster cardiomyopathy

    SciTech Connect

    Okumura, K.; Panagia, V.; Jasmin, G.; Dhalla, N.S.

    1987-02-27

    The heart sarcolemmal phosphatidylethanolamine N-methylation in UM-X7.1 strain of cardiomyopathic hamsters was examined by using 0.055, 10 and 150 microM S-adenosyl-L-(methyl-/sup 3/H) methionine as methyl donor for sites I, II and III, respectively. In comparison with control values, methylation activities at site I was increased in 40, 120 and 250 days old cardiomyopathic hamsters. On the other hand, methylation activities at sites II and III in 120 and 250 days old cardiomyopathic animals were depressed without any change in the 40 days old group. The alterations in N-methylation activities were associated with kinetic changes in apparent Vmax values without any changes in the apparent Km. These results indicate a defect in the phospholipid N-methylation process in heart sarcolemma during the development of genetically determined cardiomyopathy.

  2. Dynamic Changes in DNA Methylation in Ischemic Tolerance

    PubMed Central

    Meller, Robert; Pearson, Andrea; Simon, Roger P.

    2015-01-01

    Epigenetic mediators of gene expression are hypothesized to regulate transcriptomic responses to preconditioning ischemia and ischemic tolerance. Here, we utilized a methyl-DNA enrichment protocol and sequencing (ChIP-seq) to identify patterns of DNA methylation in an established model of ischemic tolerance in neuronal cultures (oxygen and glucose deprivation: OGD). We observed an overall decrease in global DNA methylation at 4?h following preconditioning ischemia (30?min OGD), harmful ischemia (120?min OGD), and in ischemic tolerant neuronal cultures (30?min OGD, 24?h recovery, 120?min OGD). We detected a smaller cohort of hypermethylated regions following ischemic conditions, which were further analyzed revealing differential chromosomal localization of methylation, and a differential concentration of methylation on genomic regions. Together, these data show that the temporal profiles of DNA methylation with respect to chromatin hyper- and hypo-methylation following various ischemic conditions are highly dynamic, and may reveal novel targets for neuroprotection. PMID:26029158

  3. Protein Interfaces in Signaling Regulated by Arginine Methylation

    NSDL National Science Digital Library

    Francois-Michel Boisvert (McGill University; Departments of Oncology and Medicine REV)

    2005-02-15

    Posttranslational covalent modifications of proteins provide a major mechanism for cellular signal transduction. Arginine methylation is a covalent modification that results in the addition of methyl groups on the arginine side chains catalyzed by members of the protein arginine methyltransferase (PRMT) family. Identification of several arginine-methylated proteins indicates that arginine methylation influences several signaling pathways. Involvement of PRMT1, the major arginine methyltransferase, in T cell signaling, in response to lipopolysaccharides, in the stabilization of tumor necrosis factor–? mRNA, and in cytokine responses implicates this posttranslational modification in regulation of cell proliferation and antiviral responses. Arginine methylation can regulate protein-protein interactions. SH3 domains that normally associate with polyproline-rich ligands fail to do so when the neighboring arginine is dimethylated. Many other examples have now been documented, including protein interactions that are positively regulated by arginine methylation. This review focuses on how arginine methylation is implicated in protein-protein interactions that influence cell signaling.

  4. Target recognition, RNA methylation activity and transcriptional regulation of the Dictyostelium discoideum Dnmt2-homologue (DnmA).

    PubMed

    Müller, Sara; Windhof, Indra M; Maximov, Vladimir; Jurkowski, Tomasz; Jeltsch, Albert; Förstner, Konrad U; Sharma, Cynthia M; Gräf, Ralph; Nellen, Wolfgang

    2013-10-01

    Although the DNA methyltransferase 2 family is highly conserved during evolution and recent reports suggested a dual specificity with stronger activity on transfer RNA (tRNA) than DNA substrates, the biological function is still obscure. We show that the Dictyostelium discoideum Dnmt2-homologue DnmA is an active tRNA methyltransferase that modifies C38 in tRNA(Asp(GUC)) in vitro and in vivo. By an ultraviolet-crosslinking and immunoprecipitation approach, we identified further DnmA targets. This revealed specific tRNA fragments bound by the enzyme and identified tRNA(Glu(CUC/UUC)) and tRNA(Gly(GCC)) as new but weaker substrates for both human Dnmt2 and DnmA in vitro but apparently not in vivo. Dnmt2 enzymes form transient covalent complexes with their substrates. The dynamics of complex formation and complex resolution reflect methylation efficiency in vitro. Quantitative PCR analyses revealed alterations in dnmA expression during development, cell cycle and in response to temperature stress. However, dnmA expression only partially correlated with tRNA methylation in vivo. Strikingly, dnmA expression in the laboratory strain AX2 was significantly lower than in the NC4 parent strain. As expression levels and binding of DnmA to a target in vivo are apparently not necessarily accompanied by methylation, we propose an additional biological function of DnmA apart from methylation. PMID:23877245

  5. Quantitative DNA methylation analysis of candidate genes in cervical cancer.

    PubMed

    Siegel, Erin M; Riggs, Bridget M; Delmas, Amber L; Koch, Abby; Hakam, Ardeshir; Brown, Kevin D

    2015-01-01

    Aberrant DNA methylation has been observed in cervical cancer; however, most studies have used non-quantitative approaches to measure DNA methylation. The objective of this study was to quantify methylation within a select panel of genes previously identified as targets for epigenetic silencing in cervical cancer and to identify genes with elevated methylation that can distinguish cancer from normal cervical tissues. We identified 49 women with invasive squamous cell cancer of the cervix and 22 women with normal cytology specimens. Bisulfite-modified genomic DNA was amplified and quantitative pyrosequencing completed for 10 genes (APC, CCNA, CDH1, CDH13, WIF1, TIMP3, DAPK1, RARB, FHIT, and SLIT2). A Methylation Index was calculated as the mean percent methylation across all CpG sites analyzed per gene (~4-9 CpG site) per sequence. A binary cut-point was defined at >15% methylation. Sensitivity, specificity and area under ROC curve (AUC) of methylation in individual genes or a panel was examined. The median methylation index was significantly higher in cases compared to controls in 8 genes, whereas there was no difference in median methylation for 2 genes. Compared to HPV and age, the combination of DNA methylation level of DAPK1, SLIT2, WIF1 and RARB with HPV and age significantly improved the AUC from 0.79 to 0.99 (95% CI: 0.97-1.00, p-value = 0.003). Pyrosequencing analysis confirmed that several genes are common targets for aberrant methylation in cervical cancer and DNA methylation level of four genes appears to increase specificity to identify cancer compared to HPV detection alone. Alterations in DNA methylation of specific genes in cervical cancers, such as DAPK1, RARB, WIF1, and SLIT2, may also occur early in cervical carcinogenesis and should be evaluated. PMID:25826459

  6. EPR study of ?-irradiated cholesteryl methyl carbonate

    NASA Astrophysics Data System (ADS)

    Aras, Erdal; I?lek, Yasemin; Karata?, Ozgul; Abbass, Hind Kh; Birey, Mehmet; Kiliç, Ahmet

    2014-11-01

    The electron paramagnetic resonance (EPR) of ?-irradiated single crystals of cholesteryl methyl carbonate (C29H48O3) has been studied for different orientations of the crystals in a magnetic field. EPR spectra of cholesteryl methyl carbonate (C29H48O3irradiated by 60Co-? were recorded between 125 K and 300 K for different orientations of the crystal in the magnetic field. The spectra were found to be temperature independent. In C29H48O3 single crystal, the radiation damage centers caused by a 60Co-? source were determined as CH?3CH2CH radical. For CH?3CH2CH radical, a value of spectroscopic splitting factor g was calculated and experimentally results were supported by simulation program (WinEPR).

  7. Metsulfuron-methyl-based herbicidal ionic liquids.

    PubMed

    Pernak, Juliusz; Niemczak, Micha?; Shamshina, Julia L; Gurau, Gabriela; G?owacki, Grzegorz; Praczyk, Tadeusz; Marcinkowska, Katarzyna; Rogers, Robin D

    2015-04-01

    Ten sulfonylurea-based herbicidal ionic liquids (HILs) were prepared by combining the metsulfuron-methyl anion with various cation types including quaternary ammonium ([bis(2-hydroxyethyl)methyloleylammonium](+), [2-hydroxyethyltrimethylammonium](+)), pyridinium ([1-dodecylpyridinium](+)), piperidinium ([1-methyl-1-propylpiperidinium](+)), imidazolium ([1-allyl-3-methylimidazolium](+), [1-butyl-3-methylimidazolium](+)), pyrrolidinium ([1-butyl-1-methylpyrrolidinium](+)), morpholinium ([4-decyl-4-methylmorpholinium](+)), and phosphonium ([trihexyltetradecylphosphonium](+) and [tetrabutylphosphonium](+)). Their herbicidal efficacy was studied in both greenhouse tests and field trials. Preliminary results for the greenhouse tests showed at least twice the activity for all HILs when compared to the activity of commercial Galmet 20 SG, with HILs with phosphonium cations being the most effective. The results of two-year field studies showed significantly less enhancement of activity than observed in the greenhouse; nonetheless, it was found that the herbicidal efficacy was higher than that of the commercial analog, and efficacy varied depending on the plant species. PMID:25734891

  8. Protein Arginine Methylation Is More Prone to Inhibition by S-Adenosylhomocysteine than DNA Methylation in Vascular Endothelial Cells

    PubMed Central

    Esse, Ruben; Rocha, Monica S.; Barroso, Madalena; Florindo, Cristina; Teerlink, Tom; Kok, Robert M.; Smulders, Yvo M.; Rivera, Isabel; Leandro, Paula; Koolwijk, Pieter; Castro, Rita; Blom, Henk J.; de Almeida, Isabel Tavares

    2013-01-01

    Methyltransferases use S-adenosylmethionine (AdoMet) as methyl group donor, forming S-adenosylhomocysteine (AdoHcy) and methylated substrates, including DNA and proteins. AdoHcy inhibits most methyltransferases. Accumulation of intracellular AdoHcy secondary to Hcy elevation elicits global DNA hypomethylation. We aimed at determining the extent at which protein arginine methylation status is affected by accumulation of intracellular AdoHcy. AdoHcy accumulation in human umbilical vein endothelial cells was induced by inhibition of AdoHcy hydrolase by adenosine-2,3-dialdehyde (AdOx). As a measure of protein arginine methylation status, the levels of monomethylarginine (MMA) and asymmetric and symmetric dimethylated arginine residues (ADMA and SDMA, respectively) in cell protein hydrolysates were measured by HPLC. A 10% decrease was observed at a 2.5-fold increase of intracellular AdoHcy. Western blotting revealed that the translational levels of the main enzymes catalyzing protein arginine methylation, protein arginine methyl transferases (PRMTs) 1 and 5, were not affected by AdoHcy accumulation. Global DNA methylation status was evaluated by measuring 5-methylcytosine and total cytosine concentrations in DNA hydrolysates by LC-MS/MS. DNA methylation decreased by 10% only when intracellular AdoHcy concentration accumulated to 6-fold of its basal value. In conclusion, our results indicate that protein arginine methylation is more sensitive to AdoHcy accumulation than DNA methylation, pinpointing a possible new player in methylation-related pathology. PMID:23408989

  9. Genomic methylation patterns in archaeological barley show de-methylation as a time-dependent diagenetic process.

    PubMed

    Smith, Oliver; Clapham, Alan J; Rose, Pam; Liu, Yuan; Wang, Jun; Allaby, Robin G

    2014-01-01

    Genomic methylation is variable under biotic and abiotic stresses in plants. In particular, viral infection is thought to significantly increase genomic methylation with particularly high activity around transposable elements. Here we present the genomic methylation profiles of grains of archaeological barley (Hordeum vulgare) from several strata from a site in southern Egypt, from the Napatan to the Islamic periods (800 BCE - 1812 CE). One sample tested positive for viral infection and exhibits an unusually high degree of genomic methylation compared to the rest. A decreasing trend in global methylation levels according to deposition date shows in-situ de-methylation of 5-methylcytosine, which can be described as a diagenetic process. This is most likely a deamination mediated de-methylation process and is expected to lead to 5?mC > T base modifications in addition to the C > U modifications due to cytosine deamination, so represents a time-dependent process of DNA diagenesis in ancient DNA. PMID:24993353

  10. Tribenuron-Methyl Resistant Flixweed ( Descurainia sophia)

    Microsoft Academic Search

    Hai-lan CUI; Chao-xian ZHANG; Hong-jun ZHANG; Hong-juan HUANG; Shou-hui WEI; Xue LIU; Gui-qi WANG; Yan LIU

    2009-01-01

    Flixweed seeds were collected from suspected winter wheat fields and remote hillside in Shaanxi Province, China, their sensitivities to tribenuron-methyl were evaluated in the greenhouse. Results revealed that biotype S was susceptible to tribenuron, and its GR50 was 0.23 g a.i. ha?1, whereas biotypes R1, R2, R3, and R4 were resistant to the tribenuron, and their GR50 were 161.99, 79.70,

  11. Dual Methylation Pathways in Lignin Biosynthesis

    Microsoft Academic Search

    Ruiqin Zhong; W. Herbert Morrison; Jonathan Negrel; Zheng-Hua Ye

    1998-01-01

    Caffeoyl-coenzyme A (CoA) O -methyltransferase (CCoAOMT) has been proposed to be involved in an alternative meth- ylation pathway of lignin biosynthesis. However, no direct evidence has been available to confirm that CCoAOMT is es- sential for lignin biosynthesis. To understand further the methylation steps in lignin biosynthesis, we used an antisense approach to alter O -methyltransferase ( OMT ) gene

  12. Collisional excitation of interstellar methyl cyanide

    NASA Technical Reports Server (NTRS)

    Green, Sheldon

    1986-01-01

    Theoretical calculations are used to determine the collisional excitation rates of methyl cyanide under interstellar molecular cloud conditions. The required Q(L,M) as a function of kinetic temperature were determined by averaging fixed energy IOS (infinite order sudden) results over appropriate Boltzmann distributions of collision energies. At a kinetic temperature of 40 K, rates within a K ladder were found to be accurate to generally better than about 30 percent.

  13. Collisional excitation of interstellar methyl cyanide

    SciTech Connect

    Green, S.

    1986-10-01

    Theoretical calculations are used to determine the collisional excitation rates of methyl cyanide under interstellar molecular cloud conditions. The required Q(L,M) as a function of kinetic temperature were determined by averaging fixed energy IOS (infinite order sudden) results over appropriate Boltzmann distributions of collision energies. At a kinetic temperature of 40 K, rates within a K ladder were found to be accurate to generally better than about 30 percent. 11 references.

  14. Aromatase inhibition by bioavailable methylated flavones

    Microsoft Academic Search

    Nga Ta; Thomas Walle

    2007-01-01

    Previous studies have shown chrysin, 7-hydroxyflavone and 7,4?-dihydroxyflavone to be the most potent flavonoid inhibitors of aromatase. However, very poor oral bioavailability is a major limitation for the successful use of dietary flavonoids as chemopreventive agents. We have recently shown that methylated flavones, including 5,7-dimethoxyflavone, 7-methoxyflavone and 7,4?-dimethoxyflavone, are much more resistant to metabolism than their unmethylated analogs and have

  15. High-yield preparation of methyl stearolate

    Microsoft Academic Search

    R. O. Butterfield; H. J. Dutton

    1968-01-01

    A simplified laboratory procedure for preparing methyl stearolate consists of three steps—bromination, dehydrobromination,\\u000a and purification. A variety of starting materials was investigated, including oleic acid, olive fatty acids, and triglycerides.\\u000a Brominations of both fatty acids and triglycerides were conducted in diethyl ether. Dehydrobrominations were carried out in\\u000a boiling 30% KOH-ethylene glycol solutions or in 30% KOH-water solutions under pressure. Saponification

  16. Molecular basis for the recognition of methylated adenines in RNA by the eukaryotic YTH domain

    PubMed Central

    Luo, Shukun; Tong, Liang

    2014-01-01

    Methylation of the N6 position of selected internal adenines (m6A) in mRNAs and noncoding RNAs is widespread in eukaryotes, and the YTH domain in a collection of proteins recognizes this modification. We report the crystal structure of the splicing factor YT521-B homology (YTH) domain of Zygosaccharomyces rouxii MRB1 in complex with a heptaribonucleotide with an m6A residue in the center. The m6A modification is recognized by an aromatic cage, being sandwiched between a Trp and Tyr residue and with the methyl group pointed toward another Trp residue. Mutations of YTH domain residues in the RNA binding site can abolish the formation of the complex, confirming the structural observations. These residues are conserved in the human YTH proteins that also bind m6A RNA, suggesting a conserved mode of recognition. Overall, our structural and biochemical studies have defined the molecular basis for how the YTH domain functions as a reader of methylated adenines. PMID:25201973

  17. Inactivation of ultraviolet repair in normal and xeroderma pigmentosum cells by methyl methanesulfonate

    SciTech Connect

    Cleaver, J.E.

    1982-03-01

    Excision repair of ultraviolet damage in the DNA of normal and xeroderma pigmentosum (Groups C, D, and variant) cells was inactivated by exposure of cells to methyl methanesulfonate immediately before irradiation independent of the presence of 0 to 10% fetal calf serum. The inactivation could be represented by a semilog relationship between the amount of repair and methyl methanesulfonate concentration up to approximately 5 mM. The inactivation can be considered to occur as the result of alkylation of a large (about 10(6) daltons) repair enzyme complex, and the dose required to reduce repair to 37% for most cells types was between 4 and 7 mM. No consistent, large difference in sensitivity to methyl methanesulfonate was found in any xeroderma pigmentosum complementation group compared to normal cells, implying that reduced repair in these groups may be caused by small inherited changes in the amino acid composition (i.e., point mutations or small deletions) rather than by losses of major components of the repair enzyme complex.

  18. Cytosine methylation does not affect binding of transcription factor Sp1

    SciTech Connect

    Harrington, M.A.; Jones, P.A. (Univ. of Southern California School of Medicine, Los Angeles (USA)); Imagawa, M.; Karin, M. (Univ. of California, San Diego, La Jolla (USA))

    1988-04-01

    DNA methylation may be a component of a multilevel control mechanism that regulates eukaryotic gene expression. The authors used synthetic oligonucleotides to investigate the effect of cytosine methylation on the binding of the transcription factor Sp1 to its target sequence (a G+C-rich sequence known as a GC box). Concatemers of double-stranded 14-mers containing a GC box successfully competed with the human metallothionein IIA promoter for binding to Sp1 in DNase I protection experiments. The presence of 5-methylcytosine in the CpG sequence of the GC box did not influence Sp1 binding. The result was confirmed using double-stranded 20-mers containing 16 base pairs of complementary sequence. Electrophoretic gel retardation analysis of annealed 28-mers containing a GC box incubated with an Sp1-containing HeLa cell nuclear extract demonstrated the formation of DNA-protein complexes; formation of these complexes was not inhibited when an oligomer without a GC box was used as a competitor. Once again, the presence of a 5-methylcytosine residue in the GC box did not influence the binding of the protein to DNA. The results therefore preclude a direct effect of cytosine methylation on Sp1-DNA interactions.

  19. Coordination of methyl coenzyme M and coenzyme M at divalent and trivalent nickel cyclams: model studies of methyl coenzyme M reductase active site.

    PubMed

    Nishigaki, Jun-ichi; Matsumoto, Tsuyoshi; Tatsumi, Kazuyuki

    2012-03-19

    Divalent and trivalent nickel complexes of 1,4,8,11-tetraazacyclotetradecane, denoted as cyclam hereafter, coordinated by methyl coenzyme M (MeSCoM(-)) and coenzyme M (HSCoM(-)) have been synthesized in the course our model studies of methyl coenzyme M reductase (MCR). The divalent nickel complexes Ni(cyclam)(RSCoM)(2) (R = Me, H) have two trans-disposed RSCoM(-) ligands at the nickel(II) center as sulfonates, and thus, the nickels have an octahedral coordination. The SCoM(2-) adduct Ni(cyclam)(SCoM) was also synthesized, in which the SCoM(2-) ligand chelates the nickel via the thiolate sulfur and a sulfonate oxygen. The trivalent MeSCoM adduct [Ni(cyclam)(MeSCoM)(2)](OTf) was synthesized by treatment of [Ni(cyclam)(NCCH(3))(2)](OTf)(3) with ((n)Bu(4)N)[MeSCoM]. A similar reaction with ((n)Bu(4)N)[HSCoM] did not afford the corresponding trivalent HSCoM(-) adduct, but rather the divalent nickel complex polymer [-Ni(II)(cyclam)(CoMSSCoM)-](n) was obtained, in which the terminal thiol of HSCoM(-) was oxidized to the disulfide (CoMSSCoM)(2-) by the Ni(III) center. PMID:22400908

  20. Mechanism of plasma polymerization of methyl methacrylate

    SciTech Connect

    Denes, F.; Sarmadi, A.M.; Hop, C.E.C.A.; Young, R.A. [Univ. of Wisconsin, Madison, WI (United States)

    1993-12-31

    Molecular fragments from radio-frequency plasma polymerization of methylmethacrylate (MMA) were cold-trapped and characterized by gas chromatography-mass spectroscopy (GC/MS). The gas phase and the liquid phase products from the cold trap were analyzed separately. The gas phase contained a predominance of the saturated aliphatic compounds butane, pentane, and isopentane and unsaturated l-butene, in addition to saturated MMA monomer (methyl isobutyrate); the liquid phase contained mainly isopropenyl alcohol, saturated MMA and a methylated form of the saturated MMA. Calculations of the predominant plasma-generated molecular clusters using the CG/MS data for both the gas and liquid phases indicated that saturated and unsaturated propyl radicals (molecular weight 41-43) were by far the predominant radical species in the plasma reactions and would lead to a hydrocarbon-type polymer with considerable unsaturation and crosslinking. The occurrence of other radical species containing methyl ester and hydroxyl groups accounts for the presence of these functional groups in the final polymer. Infrared and ultraviolet spectra confirmed the participation of the predominant aliphatic radicals in the formation of PPMMA. Clearly PPMA is a distinctly different polymer when compared to conventional PMMA.