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1

Reactions of guanine with methyl chloride and methyl bromide: O6-methylation versus charge transfer complex formation  

NASA Astrophysics Data System (ADS)

Density functional theory (DFT) at the B3LYP/6-31+G* and B3LYP/AUG-cc-pVDZ levels was employed to study O6-methylation of guanine due to its reactions with methyl chloride and methyl bromide and to obtain explanation as to why the methyl halides cause genotoxicity and possess mutagenic and carcinogenic properties. Geometries of the various isolated species involved in the reactions, reactant complexes (RCs), and product complexes (PCs) were optimized in gas phase. Transition states connecting the reactant complexes with the product complexes were also optimized in gas phase at the same levels of theory. The reactant complexes, product complexes, and transition states were solvated in aqueous media using the polarizable continuum model (PCM) of the self-consistent reaction field theory. Zero-point energy (ZPE) correction to total energy and the corresponding thermal energy correction to enthalpy were made in each case. The reactant complexes of the keto form of guanine with methyl chloride and methyl bromide in water are appreciably more stable than the corresponding complexes involving the enol form of guanine. The nature of binding in the product complexes was found to be of the charge transfer type (O6mG+ · X-, X dbond Cl, Br). Binding of HCl, HBr, and H2O molecules to the PCs obtained with the keto form of guanine did not alter the positions of the halide anions in the PCs, and the charge transfer character of the PCs was also not modified due to this binding. Further, the complexes obtained due to the binding of HCl, HBr, and H2O molecules to the PCs had greater stability than the isolated PCs. The reaction barriers involved in the formation of PCs were found to be quite high (?50 kcal/mol). Mechanisms of genotoxicity, mutagenesis and carcinogenesis caused by the methyl halides appear to involve charge transfer-type complex formation. Thus the mechanisms of these processes involving the methyl halides appear to be quite different from those that involve the other strongly carcinogenic methylating agents.

Shukla, P. K.; Mishra, P. C.; Suhai, S.

2

The MeCP1 complex represses transcription through preferential binding, remodeling, and deacetylating methylated nucleosomes.  

PubMed

Histone deacetylation plays an important role in methylated DNA silencing. Recent studies indicated that the methyl-CpG-binding protein, MBD2, is a component of the MeCP1 histone deacetylase complex. Interestingly, MBD2 is able to recruit the nucleosome remodeling and histone deacetylase, NuRD, to methylated DNA in vitro. To understand the relationship between the MeCP1 complex and the NuRD complex, we purified the MeCP1 complex to homogeneity and found that it contains 10 major polypeptides including MBD2 and all of the known NuRD components. Functional analysis of the purified MeCP1 complex revealed that it preferentially binds, remodels, and deacetylates methylated nucleosomes. Thus, our study defines the MeCP1 complex, and provides biochemical evidence linking nucleosome remodeling and histone deacetylation to methylated gene silencing. PMID:11297506

Feng, Q; Zhang, Y

2001-04-01

3

Complexity in charge transport for multiwalled carbon nanotube and poly(methyl methacrylate) composites  

E-print Network

) composites Heon Mo Kim, Mahn-Soo Choi, and Jinsoo Joo* Department of Physics and Institute for Nano Science of the charge transport mechanism of the composites of multiwalled carbon nanotubes MWCNTs and poly methylComplexity in charge transport for multiwalled carbon nanotube and poly(methyl methacrylate

Choi, Mahn-Soo

4

Complex Reaction Dynamics in the Cerium-Bromate-2-Methyl-1,4-hydroquinone Photoreaction.  

PubMed

Spontaneous oscillations with a long induction time were observed in the bromate-2-methyl-1,4-hydroquinone photoreaction in a batch reactor, where removal of illumination effectively quenched any reactivity. A substantial lengthening of the oscillatory window and a dramatic increase in the complexity of the reaction behavior arose upon the addition of cerium ions, in which separate bifurcation regions and mixed mode oscillations were present. The complexity has a strong dependence on the intensity of illumination supplied to the system and on the initial concentrations of the reactants. (1)H NMR spectroscopy measurements show that the photoreduction of 2-methyl-1,4-benzoquinone leads to the formation of 2-methyl-1,4-hydroquinone and the compound 2-hydroxy-3-methyl-1,4-benzoquinone. Spectroscopic investigation also indicates that the presence of methyl group hinders the bromination of the studied organic substrate 2-methyl-1,4-hydroquinone, resulting in the formation of 2-methyl-1,4-benzoquinone. PMID:25279948

Bell, Jeffrey G; Green, James R; Wang, Jichang

2014-10-23

5

Partial hydrogenation of methyl esters of sunflower oil catalyzed by highly active rhodium sulfonated triphenylphosphite complexes  

Microsoft Academic Search

The partial hydrogenation of polyunsaturated methyl esters of sunflower oil to monounsaturated methyl esters catalyzed by highly active rhodium sulfonated phosphite (Rh\\/STPP) complexes was studied in order to improve the quality of biodiesel in terms of increased oxidative stability and higher cetane numbers. The hydrogenation reaction proceeds under mild conditions and high catalytic activities (TOF=38,000h?1) were achieved employing Rh\\/STPP catalysts

Nikolaos Nikolaou; Christos E. Papadopoulos; Anastasia Lazaridou; Asimina Koutsoumba; Achilleas Bouriazos; Georgios Papadogianakis

2009-01-01

6

INVOLVED IN DE NOVO 2-containing complex involved in RNA-directed DNA methylation in Arabidopsis  

SciTech Connect

At least three pathways control maintenance of DNA cytosine methylation in Arabidopsis thaliana. However, the RNA-directed DNA methylation (RdDM) pathway is solely responsible for establishment of this silencing mark. We previously described INVOLVED IN DE NOVO 2 (IDN2) as being an RNA-binding RdDM component that is required for DNA methylation establishment. In this study, we describe the discovery of two partially redundant proteins that are paralogous to IDN2 and that form a stable complex with IDN2 in vivo. Null mutations in both genes, termed IDN2-LIKE 1 and IDN2-LIKE 2 (IDNL1 and IDNL2), result in a phenotype that mirrors, but does not further enhance, the idn2 mutant phenotype. Genetic analysis suggests that this complex acts in a step in the downstream portion of the RdDM pathway. We also have performed structural analysis showing that the IDN2 XS domain adopts an RNA recognition motif (RRM) fold. Finally, genome-wide DNA methylation and expression analysis confirms the placement of the IDN proteins in an RdDM pathway that affects DNA methylation and transcriptional control at many sites in the genome. Results from this study identify and describe two unique components of the RdDM machinery, adding to our understanding of DNA methylation control in the Arabidopsis genome.

Ausin, Israel; Greenberg, Maxim V.C.; Simanshu, Dhirendra K.; Hale, Christopher J.; Vashisht, Ajay A.; Simon, Stacey A.; Lee, Tzuu-fen; Feng, Suhua; Española, Sophia D.; Meyers, Blake C.; Wohlschlegel, James A.; Patel, Dinshaw J.; Jacobsen, Steven E. (UCLA); (MSKCC); (Delaware)

2012-10-23

7

Methylation of secondary amines with dialkyl carbonates and hydrosilanes catalysed by iron complexes.  

PubMed

Methylation of secondary amines was achieved using dimethyl carbonate or diethyl carbonate as the C1 source under the catalysis of well-defined half-sandwich iron complexes bearing an N-heterocyclic carbene ligand. The reaction proceeded under mild conditions in the presence of hydrosilanes as the reductants, and the amines were obtained with good to excellent isolated yields. PMID:25285339

Zheng, Jianxia; Darcel, Christophe; Sortais, Jean-Baptiste

2014-10-21

8

New lanthanide complexes of 4-methyl-7-hydroxycoumarin and their pharmacological activity.  

PubMed

Complexes of cerium(III), lanthanum(III) and neodymium(III) with 4-methyl-7-hydroxycoumarin (Mendiaxon, Hymecromone) were synthesized by the mixing of equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin sodium salt in water. The complexes were characterized and identified by elemental analysis, conductivities, IR, (1)H and (13)C NMR spectroscopies and mass spectral data. DTA and TGA have been applied to study the compositions of the compounds. The newly synthesized compounds were assayed for acute intraperitoneal and per oral toxicity, influence on blood clotting time and the most active complex was investigated for spasmolytic activity. The complexes of cerium(III) and neodymium(III) showed marginal cytotoxic activity against transformed leukemic cell lines (P3HR1 and THP-1) as compared to the inorganic salts. PMID:11461759

Kostova, I; Manolov, I; Nicolova, I; Konstantinov, S; Karaivanova, M

2001-04-01

9

A novel structural motif for calix[4]arene dihydrophosphonic acid in its complex with di-methyl ammonium and tetra-methyl ammonium cations  

NASA Astrophysics Data System (ADS)

The structure of calix[4]arene dihydrophosphonic acid in its complex with di-methyl ammonium and tetra-methyl ammonium cations shows a novel dimeric structural motifs for the calixarene assembly, with one calixarene unit showing distal aromatic rings inclined into the cavity and then both of the rings partially included into the cavity of a second molecule present in the flattened cone conformation.

Danylyuk, Oksana; Lazar, Adina N.; Coleman, Anthony W.; Suwinska, Kinga

2008-11-01

10

On the complexation of Trolox with methyl-?-cyclodextrin: characterization, molecular modelling and photostabilizing properties  

Microsoft Academic Search

Exposure to UV radiations could reduce the efficiency of some antioxidants like Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic\\u000a acid), a water-soluble vitamin E analogue largely employed in cosmetic products. Accordingly, in this paper we examined the\\u000a possibility of increasing the stability of Trolox towards UVB irradiation by its complexation with methyl-?-cyclodextrin.\\u000a Formation of the inclusion complex was confirmed by solubility diagrams, differential scanning calorimetry

S. Sapino; M. Trotta; G. Ermondi; G. Caron; R. Cavalli; M. E. Carlotti

2008-01-01

11

Directional DNA Methylation Changes and Complex Intermediate States Accompany Lineage Specificity in the Adult Hematopoietic Compartment  

PubMed Central

SUMMARY DNA methylation has been implicated as an epigenetic component of mechanisms that stabilize cell-fate decisions. Here, we have characterized the methylomes of human female hematopoietic stem/progenitor cells (HSPCs) and mature cells from the myeloid and lymphoid lineages. Hypomethylated regions (HMRs) associated with lineage-specific genes were often methylated in the opposing lineage. In HSPCs, these sites tended to show intermediate, complex patterns that resolve to uniformity upon differentiation, by increased or decreased methylation. Promoter HMRs shared across diverse cell types typically display a constitutive core that expands and contracts in a lineage-specific manner to fine-tune the expression of associated genes. Many newly identified intergenic HMRs, both constitutive and lineage specific, were enriched for factor binding sites with an implied role in genome organization and regulation of gene expression, respectively. Overall, our studies represent an important reference data set and provide insights into directional changes in DNA methylation as cells adopt terminal fates. PMID:21924933

Hodges, Emily; Molaro, Antoine; Dos Santos, Camila O.; Thekkat, Pramod; Song, Qiang; Uren, Philip J.; Park, Jin; Butler, Jason; Rafii, Shahin; McCombie, W. Richard; Smith, Andrew D.; Hannon, Gregory J.

2012-01-01

12

DNA Methylation Profiling of the Human Major Histocompatibility Complex: A Pilot Study for the Human Epigenome Project  

PubMed Central

The Human Epigenome Project aims to identify, catalogue, and interpret genome-wide DNA methylation phenomena. Occurring naturally on cytosine bases at cytosine–guanine dinucleotides, DNA methylation is intimately involved in diverse biological processes and the aetiology of many diseases. Differentially methylated cytosines give rise to distinct profiles, thought to be specific for gene activity, tissue type, and disease state. The identification of such methylation variable positions will significantly improve our understanding of genome biology and our ability to diagnose disease. Here, we report the results of the pilot study for the Human Epigenome Project entailing the methylation analysis of the human major histocompatibility complex. This study involved the development of an integrated pipeline for high-throughput methylation analysis using bisulphite DNA sequencing, discovery of methylation variable positions, epigenotyping by matrix-assisted laser desorption/ionisation mass spectrometry, and development of an integrated public database available at http://www.epigenome.org. Our analysis of DNA methylation levels within the major histocompatibility complex, including regulatory exonic and intronic regions associated with 90 genes in multiple tissues and individuals, reveals a bimodal distribution of methylation profiles (i.e., the vast majority of the analysed regions were either hypo- or hypermethylated), tissue specificity, inter-individual variation, and correlation with independent gene expression data. PMID:15550986

2004-01-01

13

Synthesis and structural characterization of heavier group 1 methyl tetrazolate complexes: New bridging coordination modes of the tetrazolate ligand  

Microsoft Academic Search

A series of sodium, potassium, rubidium, and cesium complexes of methyl tetrazolate was prepared and structurally characterized. Treatment of methyl tetrazole (MetetzH) with the group 1 hydroxides in water at ambient temperature afforded Na(Metetz)(H2O)2 (92%), K(Metetz) (92%), Rb(Metetz) (97%), and Cs(Metetz) (97%) as colorless solids after workup. These complexes were characterized by spectral and analytical methods, thermogravimetric analysis, and by

Selma Poturovic; Dongmei Lu; Mary Jane Heeg; Charles H. Winter

2008-01-01

14

Complexes of polyadenylic acid and the methyl esters of amino acids  

NASA Technical Reports Server (NTRS)

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.

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

1983-01-01

15

Decoding of Methylated Histone H3 Tail by the Pygo-BCL9 Wnt Signaling Complex  

PubMed Central

Summary Pygo and BCL9/Legless transduce the Wnt signal by promoting the transcriptional activity of ?-catenin/Armadillo in normal and malignant cells. We show that human and Drosophila Pygo PHD fingers associate with their cognate HD1 domains from BCL9/Legless to bind specifically to the histone H3 tail methylated at lysine 4 (H3K4me). The crystal structures of ternary complexes between PHD, HD1, and two different H3K4me peptides reveal a unique mode of histone tail recognition: efficient histone binding requires HD1 association, and the PHD-HD1 complex binds preferentially to H3K4me2 while displaying insensitivity to methylation of H3R2. Therefore, this is a prime example of histone tail binding by a PHD finger (of Pygo) being modulated by a cofactor (BCL9/Legless). Rescue experiments in Drosophila indicate that Wnt signaling outputs depend on histone decoding. The specificity of this process provided by the Pygo-BCL9/Legless complex suggests that this complex facilitates an early step in the transition from gene silence to Wnt-induced transcription. PMID:18498752

Fiedler, Marc; Sánchez-Barrena, María José; Nekrasov, Maxim; Mieszczanek, Juliusz; Rybin, Vladimir; Müller, Jürg; Evans, Phil; Bienz, Mariann

2008-01-01

16

Synthesis and phosphorescent properties of the copolymers of N-vinylcarbazole, methyl methacrylate and iridium complex  

NASA Astrophysics Data System (ADS)

The copolymers containing carbazole unit and iridium complexes, such as (Ir(bpy)2Cl, Ir(mbpy)2Cl and Ir(Brbpy)2Cl, were synthesized via radical copolymerization of N-vinylcarbazole, methyl methacrylate and iridium complex. The synthesized copolymers were characterized by FT-IR, UV-Vis absorption spectroscopy and photoluminescence (PL) spectroscopy, respectively. According to the results, the copolymers (Ir(Brbpy)2Cl/PVK and Ir(mbpy)2Cl/PVK) exhibit yellow phosphorescence with an emission peak at around 553 nm under UV-visible light in the solid state. The results also reveal almost complete energy transfer from the host carbazole segments to the guest Ir complex in the copolymer film when the Ir content reaches 1.0 wt.%. The synthesized copolymers are good candidates as blue or yellow phosphorescent materials for PLED applications.

Wang, Wen; Zhou, Minglu; Liang, Luying; Lin, Meijuan; Ling, Qidan

2014-06-01

17

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

PubMed Central

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

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

18

Abstraction of methyl from neutral Fischer-type carbene complexes: A new site for nucleophilic attack  

SciTech Connect

Reactions of Fischer-type carbene complexes, M(CO){sub 5}(C(OMe)pH) (M = Cr, W), with metal carbonyl anions (M`{sup -} = CpFe(CO){sub 2}{sup -@}, Re(CO){sub 5}{sup -}, Mn(CO){sub 4}PPh{sub 3}{sup -}, Co(CO){sub 3}PPh{sub 3}{sup -}, Cp{sup *}Cr(CO){sub 3}{sup -}, CpMo(CO){sub 3}{sup -}) result in demethylation of the carbene complexes. The products are M(CO){sub 5}C(O)Ph{sup -} and M`-Me, characterized by infrared and NMR spectroscopy. A slower rate for reaction with W(CO){sub 5}(C(OEt)Ph) in comparison to the methyl analogue is consistent with nucleophilic attack of the metal carbonyl anion on the methyl of the methoxy group of the carbene. This is a new type of nucleophilic attack of a Fischer-type carbene. 22 refs., 1 fig., 1 tab.

Toomey, L.M.; Atwood, J.D. [State Univ. of New York, Buffalo, NY (United States)] [State Univ. of New York, Buffalo, NY (United States)

1997-02-04

19

Dichlorogold(III) complexes of bis(1-methyl-2-imidazolyl)ketone and related ligands: Geometrical and electronic structures  

Microsoft Academic Search

The ligand bis(1-methyl-2-imidazolyl)ketone (bik) was studied by DFT with respect to the energy minimum conformation in the neutral and the anion radical state. The hitherto unknown crystal structure of bik is reported. X-ray diffraction studies of cationic dichlorogold(III) complexes with bik and the related bis(1-methyl-2-imidazolyl)methoxymethane and bis(1-methyl-2-imidazolyl)hydroxymethane ligands showed the DFT-supported N,N?-coordination to form six-membered chelate rings. The LUMO of

Ece Bulak; Orkan Sarper; Akbey Dogan; Falk Lissner; Thomas Schleid; Wolfgang Kaim

2006-01-01

20

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

PubMed Central

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, the extent and distribution of major histone modifications associated with active expression were defined in interferon-? induced epithelial cells, B cells, and B-cell mutants for MHC-II expression. With active transcription, nucleosome density around the proximal regulatory region was diminished and histone acetylation and methylation modifications were distributed throughout the gene in distinct patterns that were dependent on the modification examined. Irrespective of the location, the majority of these modifications were dependent on the binding of either the X-box binding factor RFX or the class II transactivator (CIITA) to the proximal regulatory region. Importantly, once established, the modifications were stable through multiple cell divisions after the activating stimulus was removed, suggesting that activation of this system resulted in an epigenetic state. A dual crosslinking chromatin immunoprecipitation method was used to detect histone modifying protein components that interacted across the gene. Components of the MLL methyltransferase and GCN5 acetyltransferase complexes were identified. Some MLL complex components were found to be CIITA independent, including MLL1, ASH2L and RbBP5. Likewise, GCN5 containing acetyltransferase complex components belonging to the ATAC and STAGA complexes were also identified. These results suggest that multiple complexes are either used or are assembled as the gene is activated for expression. Together the results define and illustrate a complex network of histone modifying proteins and multisubunit complexes participating in MHC-II transcription. PMID:22701520

Choi, Nancy M.; Boss, Jeremy M.

2012-01-01

21

Structure of the concanavalin A-methyl alpha-D-mannopyranoside complex at 6-A resolution.  

PubMed

The carbohydrate binding site of concanavalin A has been identified in crystals of the concanavalin A-methyl alpha-D-mannopyranoside complex and is 35 A from the iodophenol binding site (K. D. Hardman and C. F. Ainsworth (1973), Biochemistry 12,4442), which has been postulated to be adjacent to the carbohydrate-specific binding site (Edelman et al. (1972), Proc. Natl. Acad. Sci. U.S.A. 69, 2580). The crystals are orthorhombic in space group C222(1) and crystal denisty measurements indicate a protein mass of four monomers (molecular weight of 104 000) per asymmetric unit. However, the electron density map contains eight monomers/asymmetric unit, revealing lattice disorder. The electron density map with a nominal resolution of 6 A has been solved using three heavy-atom derivatives and the position and orientation of each monomer established. Atomic coordinates of the native protein which has previously been determined (K. D. Hardman (1973), Adv. Exp. Med. Biol. 40, 103) were transposed into this new space group and the gross conformations of the monomers, dimers, and tetramers were found to be very similar to the previous structure. However, some minor differences were apparent even at this resolution. After crystal growth, the methyl alpha-D-mannopyranoside was replaced by o-iodophenyl beta-D-glucopyranoside or methyl 2-iodoacetimido-2-deoxy-alpha-D-glucopyranoside in separate experiments, and difference electron density maps were calculated. The highest peaks for both iodinated sugar derivatives associated with each monomer agreed within a few angstroms of each other and were found near side chains Tyr-12 and -100 and Asp-16 and -208. This region is 10-14 A from the manganese, in good agreement with nuclear magnetic resonance (NMR) studies in solution (C. F. Brewer et al. (1973), Biochemistry 12, 4448) and with the site predicted from crosslinked 1222 crystal studies (K. D. Hardman (1973), Adv. Exp. Med. Biol. 40, 103). PMID:1252431

Hardman, K D; Ainsworth, C F

1976-03-01

22

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

NASA Astrophysics Data System (ADS)

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.

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

2003-10-01

23

Crystal and molecular structure of a uranium(VI) complex with salicylaldehyde S-methyl-isothiosemicarbazone  

SciTech Connect

The complex formed between uranium(VI) and salicylaldehyde S-methyl-isothiosemicarbazone (H/sub 2/Q), having the composition (UO/sub 2/ x HQ x OCH/sub 3/)/sub 2/, has been synthesized and studied by x-ray structural analysis. The crystals are monoclinic: a = 1.0334(4), b = 1.0484(5), c = 1.2560(4) nm, ..beta.. = 90.61(3)/sup 0/, V = 1.361 nm/sup 3/, Z = 4 calculated for the dimer, rho/sub calc/ = 2.43 g/cm/sup 3/, P2/sub 1//c space group, R = 0.035, R/sub w/ = 0.044 (MoK/sub ..cap alpha../ irradiation, 1636 reflections). The coordination number of uranium in this complex is equal to seven. Each uranium(VI) atom exhibits distorted pentagonal coordination within an equatorial plane of these molecular complexes via coordination to two N and an O donor atoms from HQ/sup -/, and two oxygen atoms from the methoxy groups. In addition, the methoxy groups act as bridging ligands binding two molecules of each complex in a dimer. The shortest intermolecular distance O(2)...N(2') (x, 1/2 - y, 1/2 + z) between the dimers corresponds to a very weak H-bond; the dimers are associated in the crystal lattice via van der Waals attractions.

Chuguryan, D.G.; Dzyubenko, V.I.; Grigor'ev, M.S.; Yanovskii, A.I.; Struchkov, Yu.T.; Gerbeleu, N.V.; Revenko, M.D.

1988-11-01

24

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

Microsoft Academic Search

Complexation of Np(V) with N-methyl-iminodiacetic acid (MIDA) in 1 M NaClO solution was studied with multiple techniques including potentiometry, spectrophotometry, and microcalorimetry. The 1:2 complex, NpO(MIDA)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)

Guoxin Tian; Linfeng Rao

2010-01-01

25

RNA Methylation by the MIS Complex Regulates a Cell Fate Decision in Yeast  

PubMed Central

For the yeast Saccharomyces cerevisiae, nutrient limitation is a key developmental signal causing diploid cells to switch from yeast-form budding to either foraging pseudohyphal (PH) growth or meiosis and sporulation. Prolonged starvation leads to lineage restriction, such that cells exiting meiotic prophase are committed to complete sporulation even if nutrients are restored. Here, we have identified an earlier commitment point in the starvation program. After this point, cells, returned to nutrient-rich medium, entered a form of synchronous PH development that was morphologically and genetically indistinguishable from starvation-induced PH growth. We show that lineage restriction during this time was, in part, dependent on the mRNA methyltransferase activity of Ime4, which played separable roles in meiotic induction and suppression of the PH program. Normal levels of meiotic mRNA methylation required the catalytic domain of Ime4, as well as two meiotic proteins, Mum2 and Slz1, which interacted and co-immunoprecipitated with Ime4. This MIS complex (Mum2, Ime4, and Slz1) functioned in both starvation pathways. Together, our results support the notion that the yeast starvation response is an extended process that progressively restricts cell fate and reveal a broad role of post-transcriptional RNA methylation in these decisions. PMID:22685417

Agarwala, Sudeep D.; Blitzblau, Hannah G.; Hochwagen, Andreas; Fink, Gerald R.

2012-01-01

26

Aberration in DNA Methylation in B-Cell Lymphomas Has a Complex Origin and Increases with Disease Severity  

E-print Network

in normal B-cell populations and subtypes of B-cell non-Hodgkin lymphoma: follicular lymphoma and diffuse to this work. Introduction Follicular lymphomas (FLs) and diffuse large B-cell lymphomas (DLBCLs) are the mAberration in DNA Methylation in B-Cell Lymphomas Has a Complex Origin and Increases with Disease

27

Five Friends of Methylated Chromatin Target of Protein-Arginine-Methyltransferase[Prmt]-1 (Chtop), a Complex Linking Arginine Methylation to Desumoylation*  

PubMed Central

Chromatin target of Prmt1 (Chtop) is a vertebrate-specific chromatin-bound protein that plays an important role in transcriptional regulation. As its mechanism of action remains unclear, we identified Chtop-interacting proteins using a biotinylation-proteomics approach. Here we describe the identification and initial characterization of Five Friends of Methylated Chtop (5FMC). 5FMC is a nuclear complex that can only be recruited by Chtop when the latter is arginine-methylated by Prmt1. It consists of the co-activator Pelp1, the Sumo-specific protease Senp3, Wdr18, Tex10, and Las1L. Pelp1 functions as the core of 5FMC, as the other components become unstable in the absence of Pelp1. We show that recruitment of 5FMC to Zbp-89, a zinc-finger transcription factor, affects its sumoylation status and transactivation potential. Collectively, our data provide a mechanistic link between arginine methylation and (de)sumoylation in the control of transcriptional activity. PMID:22872859

Fanis, Pavlos; Gillemans, Nynke; Aghajanirefah, Ali; Pourfarzad, Farzin; Demmers, Jeroen; Esteghamat, Fatemehsadat; Vadlamudi, Ratna K.; Grosveld, Frank; Philipsen, Sjaak; van Dijk, Thamar B.

2012-01-01

28

DNA methylation and normal chromosome behavior in Neurospora depend on five components of a histone methyltransferase complex, DCDC.  

PubMed

Methylation of DNA and of Lysine 9 on histone H3 (H3K9) is associated with gene silencing in many animals, plants, and fungi. In Neurospora crassa, methylation of H3K9 by DIM-5 directs cytosine methylation by recruiting a complex containing Heterochromatin Protein-1 (HP1) and the DIM-2 DNA methyltransferase. We report genetic, proteomic, and biochemical investigations into how DIM-5 is controlled. These studies revealed DCDC, a previously unknown protein complex including DIM-5, DIM-7, DIM-9, CUL4, and DDB1. Components of DCDC are required for H3K9me3, proper chromosome segregation, and DNA methylation. DCDC-defective strains, but not HP1-defective strains, are hypersensitive to MMS, revealing an HP1-independent function of H3K9 methylation. In addition to DDB1, DIM-7, and the WD40 domain protein DIM-9, other presumptive DCAFs (DDB1/CUL4 associated factors) co-purified with CUL4, suggesting that CUL4/DDB1 forms multiple complexes with distinct functions. This conclusion was supported by results of drug sensitivity tests. CUL4, DDB1, and DIM-9 are not required for localization of DIM-5 to incipient heterochromatin domains, indicating that recruitment of DIM-5 to chromatin is not sufficient to direct H3K9me3. DIM-7 is required for DIM-5 localization and mediates interaction of DIM-5 with DDB1/CUL4 through DIM-9. These data support a two-step mechanism for H3K9 methylation in Neurospora. PMID:21079689

Lewis, Zachary A; Adhvaryu, Keyur K; Honda, Shinji; Shiver, Anthony L; Knip, Marijn; Sack, Ragna; Selker, Eric U

2010-11-01

29

Stability of the complexes of some lanthanides with coumarin derivatives. I. Cerium(III)-4-methyl-7-hydroxycoumarin.  

PubMed

A complex of cerium(III) with 4-methyl-7-hydroxycoumarin was synthesized by mixing water solutions of cerium(III) nitrate and 4-methyl-7-hydroxycoumarin sodium salt in a metal-to-ligand molar ratio of 1:2. The complex was characterized and identified by elemental analysis, conductometry, IR, 1H and 13C NMR-spectroscopy, mass spectral data, DTA and TGA. Thermal analysis of the complex indicated the formation of a compound of the composition CeR2(OH).5H2O, R standing for the ligand. The reaction of cerium(III) with 4-methyl-7-hydroxycoumarin was studied in detail by the spectrophotometric method. The stepwise formation of two complexes, vis., CeR2+ and CeR2+, was established in the pH region studied. The equilibrium constants for 1:1 and 1:2 complexes were determined to be 10.72 and 9.22, respectively. PMID:15050043

Kostova, Irena P; Manolov, Ilia I; Radulova, Maritza K

2004-03-01

30

Synthesis, photophysical and electroluminescent properties of novel iridium (III) complexes based on 5-methyl-2-phenylbenzo[d]oxazole derivatives  

NASA Astrophysics Data System (ADS)

A new series of phosphorescent iridium (III) complexes based on 5-methyl-2-phenylbenzo[d]oxazole derivatives as main ligands, i.e. bis(5-methyl-2- phenylbenzo[d]oxazole-N,C2?)iridium(acetylacetonate) [(mpbo)2Ir(acac)], bis(2-(4-fluorophenyl)-5-methylbenzo[d]oxazole-N,C2?)iridium(acetylacetonate) [(fmbo)2Ir(acac)] and bis(5-methyl-2-p-tolylbenzo[d]oxazole-N,C2?) iridium(acetylacetonate) [(mtbo)2Ir(acac)], were synthesized for organic light-emitting diodes (OLEDs), and their photophysical, electroluminescent properties were investigated. All complexes have high thermal stability and emit intense phosphorescence from green to yellow at room temperature with high quantum efficiencies and relatively short lifetimes. The OLED based on (fmbo)2Ir(acac) as dopant emitter showed very high luminance of 26,004 cd m-2 and luminance efficiency of 18.5 cd A-1. The evidences indicated that this series of iridium (III) complexes were potential candidates for applications in organic electroluminescent devices.

Li, Xiao; Chi, Hai-Jun; Dong, Yan; Xiao, Guo-Yong; Lei, Peng; Zhang, Dong-Yu; Cui, Zheng

2013-12-01

31

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

SciTech Connect

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.

Tian, Guoxin; Rao, Linfeng

2010-10-01

32

Protein interactions within the Set1 complex and their roles in the regulation of histone 3 lysine 4 methylation.  

PubMed

Set1 is the catalytic subunit and the central component of the evolutionarily conserved Set1 complex (Set1C) that methylates histone 3 lysine 4 (H3K4). Here we have determined protein/protein interactions within the complex and related the substructure to function. The loss of individual Set1C subunits differentially affects Set1 stability, complex integrity, global H3K4 methylation, and distribution of H3K4 methylation along active genes. The complex requires Set1, Swd1, and Swd3 for integrity, and Set1 amount is greatly reduced in the absence of the Swd1-Swd3 heterodimer. Bre2 and Sdc1 also form a heteromeric subunit, which requires the SET domain for interaction with the complex, and Sdc1 strongly interacts with itself. Inactivation of either Bre2 or Sdc1 has very similar effects. Neither is required for complex integrity, and their removal results in an increase of H3K4 mono- and dimethylation and a severe decrease of trimethylation at the 5' end of active coding regions but a decrease of H3K4 dimethylation at the 3' end of coding regions. Cells lacking Spp1 have a reduced amount of Set1 and retain a fraction of trimethylated H3K4, whereas cells lacking Shg1 show slightly elevated levels of both di- and trimethylation. Set1C associates with both serine 5- and serine 2-phosphorylated forms of polymerase II, indicating that the association persists to the 3' end of transcribed genes. Taken together, our results suggest that Set1C subunits stimulate Set1 catalytic activity all along active genes. PMID:16921172

Dehé, Pierre-Marie; Dichtl, Bernhard; Schaft, Daniel; Roguev, Assen; Pamblanco, Mercè; Lebrun, Régine; Rodríguez-Gil, Alfonso; Mkandawire, Msau; Landsberg, Katarina; Shevchenko, Anna; Shevchenko, Andrej; Rosaleny, Lorena E; Tordera, Vicente; Chávez, Sebastián; Stewart, A Francis; Géli, Vincent

2006-11-17

33

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

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 ...

Do, Loi H.

34

Structure of DNMT1-DNA Complex Reveals a Role for Autoinhibition in Maintenance DNA Methylation  

SciTech Connect

Maintenance of genomic methylation patterns is mediated primarily by DNA methyltransferase-1 (DNMT1). We have solved structures of mouse and human DNMT1 composed of CXXC, tandem bromo-adjacent homology (BAH1/2), and methyltransferase domains bound to DNA-containing unmethylated CpG sites. The CXXC specifically binds to unmethylated CpG dinucleotide and positions the CXXC-BAH1 linker between the DNA and the active site of DNMT1, preventing de novo methylation. In addition, a loop projecting from BAH2 interacts with the target recognition domain (TRD) of the methyltransferase, stabilizing the TRD in a retracted position and preventing it from inserting into the DNA major groove. Our studies identify an autoinhibitory mechanism, in which unmethylated CpG dinucleotides are occluded from the active site to ensure that only hemimethylated CpG dinucleotides undergo methylation.

Song, Jikui; Rechkoblit, Olga; Bestor, Timothy H.; Patel, Dinshaw J. (MSKCC); (Columbia)

2011-09-06

35

Structure of DNMT1-DNA Complex Reveals a Role for Autoinhibition in Maintenance DNA Methylation  

SciTech Connect

Maintenance of genomic methylation patterns is mediated primarily by DNA methyltransferase-1 (DNMT1). We have solved structures of mouse and human DNMT1 composed of CXXC, tandem bromo-adjacent homology (BAH1/2), and methyltransferase domains bound to DNA-containing unmethylated CpG sites. The CXXC specifically binds to unmethylated CpG dinucleotide and positions the CXXC-BAH1 linker between the DNA and the active site of DNMT1, preventing de novo methylation. In addition, a loop projecting from BAH2 interacts with the target recognition domain (TRD) of the methyltransferase, stabilizing the TRD in a retracted position and preventing it from inserting into the DNA major groove. Our studies identify an autoinhibitory mechanism, in which unmethylated CpG dinucleotides are occluded from the active site to ensure that only hemimethylated CpG dinucleotides undergo methylation.

J Song; O Rechkoblit; T Bestor; D Patel

2011-12-31

36

Regulation of muscle development by DPF3, a novel histone acetylation and methylation reader of the BAF chromatin remodeling complex  

PubMed Central

Chromatin remodeling and histone modifications facilitate access of transcription factors to DNA by promoting the unwinding and destabilization of histone–DNA interactions. We present DPF3, a new epigenetic key factor for heart and muscle development characterized by a double PHD finger. DPF3 is associated with the BAF chromatin remodeling complex and binds methylated and acetylated lysine residues of histone 3 and 4. Thus, DPF3 may represent the first plant homeodomains that bind acetylated lysines, a feature previously only shown for the bromodomain. During development Dpf3 is expressed in the heart and somites of mouse, chicken, and zebrafish. Morpholino knockdown of dpf3 in zebrafish leads to incomplete cardiac looping and severely reduced ventricular contractility, with disassembled muscular fibers caused by transcriptional deregulation of structural and regulatory proteins. Promoter analysis identified Dpf3 as a novel downstream target of Mef2a. Taken together, DPF3 adds a further layer of complexity to the BAF complex by representing a tissue-specific anchor between histone acetylations as well as methylations and chromatin remodeling. Furthermore, this shows that plant homeodomain proteins play a yet unexplored role in recruiting chromatin remodeling complexes to acetylated histones. PMID:18765789

Lange, Martin; Kaynak, Bogac; Forster, Ulrike B.; Tönjes, Martje; Fischer, Jenny J.; Grimm, Christina; Schlesinger, Jenny; Just, Steffen; Dunkel, Ilona; Krueger, Tammo; Mebus, Siegrun; Lehrach, Hans; Lurz, Rudi; Gobom, Johan; Rottbauer, Wolfgang; Abdelilah-Seyfried, Salim; Sperling, Silke

2008-01-01

37

Thermal history effects and methyl tunneling dynamics in a supramolecular complex of calixarene and para-xylene  

NASA Astrophysics Data System (ADS)

The low-temperature structure and dynamics of guest molecules of p-xylene incorporated in the isopropyl-calix[4] arene(2:1) p-xylene complex have been investigated by solid state nuclear magnetic resonance (NMR). Using one-dimensional H1-decoupled C13 cross-polarization magic-angle-spinning (MAS) NMR and two-dimensional H1-C13 correlation spectroscopy, a full assignment of the C13 and H1 chemical shifts has been made. Using H1 NMR relaxometry, the effects of thermal history on the structure of the system have been investigated. Rapidly cooled samples have H1 spin-lattice relaxation times T1, which at low temperature (T<60K) are typically two orders of magnitude faster than those observed in annealed samples which have been cooled slowly over many hours. In both forms, the low-temperature relaxation is driven by the dynamics of the weakly hindered methyl rotors of the p-xylene guest. The substantial difference in T1 is attributed in the rapidly cooled sample to disorder in the structure of the complex leading to a wide distribution of correlation times and methyl barrier heights. A comparison of the linewidths and splittings in the high resolution C13 MAS spectra of the two forms provides structural insight into the nature of the disorder. Using H1 field-cycling NMR relaxometry, the methyl dynamics of the p-xylene guest in the annealed sample have been fully characterized. The B-field dependence of the H1 T1 maps out the spectral density from which the correlation times are directly measured. The methyl barrier heights are determined from an analysis of the temperature dependence.

Panesar, K. S.; Horsewill, A. J.; Cuda, F.; Carravetta, M.; Mamone, S.; Danquigny, A.; Grossel, M. C.; Levitt, M. H.

2008-04-01

38

Complex methyl group and hydrogen-bonded proton motions in terms of the Arrhenius and Schrödinger equations.  

PubMed

Equations for the temperature dependence of the spectral densities J(is)(m)(momega(I) +/-omega(T)), where m=1, 2, omega(I) and omega(T) are the resonance and tunnel splitting angular frequencies, in the presence of a complex motion, have been derived. The spin pairs of the protons or deuterons of the methyl group perform a complex motion consisting of three component motions. Two of them involve mass transportation over the barrier and through the barrier. They are characterized by k((H)) (Arrhenius) and k((T)) (Schrödinger) rate constants, respectively. The third motion causes fluctuations of the frequencies (nomega(I)+/-omega(T)) and it is related to the lifetime of the methyl spin at the energy level influenced by the rotor-bath interactions. These interactions induce rapid transitions, changing the symmetry of the torsional sublevels either from A to E or from E(a) to E(b). The correlation function for this third motion (k((omega)) rate constant) has been proposed by Müller-Warmuth et al. The spectral densities of the methyl group hindered rotation (k((H)), k((T)) and k((omega)) rate constants) differ from the spectral densities of the proton transfer (k((H)) and k((T)) rate constants) because three compound motions contribute to the complex motion of the methyl group. The recently derived equation [Formula: see text] , where [Formula: see text] and [Formula: see text] are the fraction and energy of particles with energies from zero to E(H), is taken into account in the calculations of the spectral densities. This equation follows from Maxwell's distribution of thermal energy. The spectral densities derived are applied to analyse the experimental temperature dependencies of proton and deuteron spin-lattice relaxation rate in solids containing the methyl group. A wide range of temperatures from zero Kelvin up to the melting point is considered. It has been established that the motion characterized by k((omega)) influences the spin-lattice relaxation up to the temperature T(tun) only. This temperature is directly determined by the equation C(p)T=E(H) (thermal energy=activation energy), where C(p) is the molar heat capacity. Probably the cessation of the third motion is a result of the de Broglie wavelength related to this motion becoming too short. As shown recently, the potential barrier can be an obstacle for the de Broglie wave. The theoretical equations derived in this paper are compared to those known in the literature. PMID:18023155

Latanowicz, L

2008-01-01

39

STRUCTURES AND BINDING ENERGIES OF METHYL TERT-BUTYL ETHER-WATER COMPLEXES  

EPA Science Inventory

Methyl tert-butyl ether (MTBE) is a well-known environmental contaminant owing to its high solubility in water. Since the early 1990s, MTBE has been added to gasoline to improve air quality in some metropolitan areas of the United States. Improved air quality was, however, achiev...

40

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

PubMed Central

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

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

2010-01-01

41

Complex Formation Equilibria Between Zinc(II), Nitrilo-tris(Methyl Phosphonic Acid) and Some Bio-relevant Ligands. The Kinetics and Mechanism for Zinc(II) Ion Promoted Hydrolysis of Glycine Methyl Ester  

Microsoft Academic Search

Binary and ternary complexes of zinc(II) involving nitrilo-tris(methyl phosphonic acid (H6A) and amino acids, peptides (HL), or DNA constituents have been investigated. The stoichiometry and stability constants for\\u000a the complexes formed are reported. The results show that ternary complexes are formed in a stepwise manner whereby nitrilo-tris(methylphosphonic\\u000a acid) binds to zinc(II), which is then followed by coordination of an amino

Mahmoud M. A. Mohamed; Ahmed A. El-Sherif

2010-01-01

42

A simple, low-cost, and rapid device for a DNA methylation-specific amplification/detection system using a flexible plastic and silicon complex.  

PubMed

Abnormal DNA methylation has been associated with the development and progression of several human cancers and is a potential target for treatment. Thus, myriad technologies for the analysis of DNA methylation have been developed over the past few decades. However, most of these technologies are still far from ideal because they are time-consuming, labor-intensive, and complex, and there is the risk of contamination of samples. Here, we present an innovative DNA methylation-specific amplification/detection device for analysis of DNA methylation in cancer-related DNA biomarkers. The assay is based on a microfluidic system that is coupled to a flexible plastic-based on-chip endonuclease digestion device with optimized magnetic field effect and a methylation-specific isothermal solid-phase amplification/detection technique to allow a low-cost, simple, and rapid analysis of DNA methylation status in a label-free and real-time manner. This flexible plastic/silicon-based microfluidic device is relatively simple to fabricate with a flexible thin film and a magnet array by using a laser machine that can overcome the limitations of a PDMS-based microfluidic device. We demonstrated the ability of the methylation analysis based on the proposed flexible device to detect the methylated RAR? gene, which is a common DNA methylation biomarker in several human cancers. The simple platform detected the methylated gene in genomic DNA from human cancer cell lines within 65 min, whereas other methods required at least several hours. Therefore, this simple, low-cost, and rapid methylation analysis platform will be useful for the detection of DNA methylation in point-of-care applications. PMID:25184832

Lee, Tae Yoon; Shin, Yong; Park, Mi Kyoung

2014-11-01

43

Four Ni(II) complexes with the new cyclam-methylimidazole ligand 1-[(1-methyl-1H-imidazol-2-yl)methyl]-1,4,8,11-tetraazacyclotetradecane.  

PubMed

Although it has not proved possible to crystallize the newly prepared cyclam-methylimidazole ligand 1-[(1-methyl-1H-imidazol-2-yl)methyl]-1,4,8,11-tetraazacyclotetradecane (L(Im1)), the trans and cis isomers of an Ni(II) complex, namely trans-aqua{1-[(1-methyl-1H-imidazol-2-yl)methyl]-1,4,8,11-tetraazacyclotetradecane}nickel(II) bis(perchlorate) monohydrate, [Ni(C(15)H(30)N(6))(H(2)O)](ClO(4))(2)·H(2)O, (1), and cis-aqua{1-[(1-methyl-1H-imidazol-2-yl)methyl]-1,4,8,11-tetraazacyclotetradecane}nickel(II) bis(perchlorate), [Ni(C(15)H(30)N(6))(H(2)O)](ClO(4))(2), (2), have been prepared and structurally characterized. At different stages of the crystallization and thermal treatment from which (1) and (2) were obtained, a further two compounds were isolated in crystalline form and their structures also analysed, namely trans-{1-[(1-methyl-1H-imidazol-2-yl)methyl]-1,4,8,11-tetraazacyclotetradecane}(perchlorato)nickel(II) perchlorate, [Ni(ClO(4))(C(15)H(30)N(6))]ClO(4), (3), and cis-{1,8-bis[(1-methyl-1H-imidazol-2-yl)methyl]-1,4,8,11-tetraazacyclotetradecane}nickel(II) bis(perchlorate) 0.24-hydrate, [Ni(C(20)H(36)N(6))](ClO(4))(2)·0.24H(2)O, (4); the 1,8-bis[(1-methyl-1H-imidazol-2-yl)methyl]-1,4,8,11-tetraazacyclotetradecane ligand is a minor side product, probably formed in trace amounts in the synthesis of L(Im1). The configurations of the cyclam macrocycles in the complexes have been analysed and the structures are compared with analogues from the literature. PMID:22552303

De Candia, Ariel G; Molnar, Matias; Slep, Leonardo D; Baggio, Ricardo

2012-05-01

44

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

PubMed

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, (1)H 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. PMID:24317267

Rajendiran, N; Thulasidhasan, J; Saravanan, J

2014-03-25

45

Hydrogen-bonding interactions in cinchonidine-2-methyl-2-hexenoic acid complexes: a combined spectroscopic and theoretical study.  

PubMed

Molecular interactions between cinchonidine (CD) and 2-methyl-2-hexenoic acid (MHA) have been studied by means of NMR, ATR-IR MES, DFT, and ab initio molecular dynamics. These interactions are of particular interest due to their pivotal role in the chiral induction occurring in the heterogeneous catalytic asymmetric hydrogenation of alpha,beta-unsaturated acids. The population density of the Open(3) conformer of CD, the most populated one at room temperature in apolar solvents, considerably increased to a maximum by addition of MHA to CD in toluene. The CD-MHA complex showed prominent symmetric and asymmetric carboxylate stretching vibrations in the regions of 1350-1410 and 1520-1580 cm(-1), respectively. DFT calculations revealed that these vibrational frequencies are expected to significantly shift depending on the chemical surrounding of MHA, that is, the hydrogen bond network. Earlier postulated 1:1 binding between CD and MHA was considered unlikely; instead, a dynamic equilibrium involving the MHA monomer and dimer, the 1:3 and possibly 1:2 CD-MHA complexes, were rationalized. Stable CD-MHA structures suggested by DFT calculations are the "1:3, halfN, cyclic" and the "1:3, halfN, cyclic tilted" complexes, where three MHA molecules are connected in wire by hydrogen bonding, two having direct interaction with CD. The confinement of CD's torsional motions in the complexes, leading to a slightly distorted Open(3) conformer via specific hydrogen-bonding interactions, was clearly reproduced by ab initio molecular dynamics, and the stable and flexible nature of the interaction was verified. Theoretical IR spectra of the complexes reproduced the characteristic vibrational frequencies of the complexes observed experimentally, supporting the stability of the 1:3 and implying the possibility of even higher molecular weight CD-MHA complexes. PMID:18557603

Meier, Daniel M; Urakawa, Atsushi; Turrà, Natascia; Rüegger, Heinz; Baiker, Alfons

2008-07-10

46

Biological and cytoselective anticancer properties of copper(II)-polypyridyl complexes modulated by auxiliary methylated glycine ligand.  

PubMed

A series of ternary copper(II)-1,10-phenanthroline complexes with glycine and methylated glycine derivatives, [Cu(phen)(aa)(H(2)O)]NO(3)·xH(2)O 1-4 (amino acid (aa): glycine (gly), 1; DL: -alanine (DL: -ala), 2; 2,2-dimethylglycine (C-dmg), 3; sarcosine (sar), 4), were synthesized and characterized by FTIR, elemental analysis, electrospray ionization-mass spectra (ESI-MS), UV-visible spectroscopy and molar conductivity measurement. The determined X-ray crystallographic structures of 2 and 3 show each to consist of distorted square pyramidal [Cu(phen)(aa)(H(2)O)](+) cation, a nitrate counter anion, and with or without lattice water, similar to previously reported structure of [Cu(phen)(gly)(H(2)O)]NO(3)·1½H(2)O. It is found that 1-4 exist as 1:1 electrolytes in aqueous solution, and the cationic copper(II) complexes are at least stable up to 24 h. Positive-ion ESI-MS spectra show existence of only undissociated [Cu(phen)(aa)](+) species. Electron paramagnetic resonance, gel electrophoresis, fluorescence quenching, and restriction enzyme inhibition assay were used to study the binding interaction, binding affinity and selectivity of these complexes for various types of B-form DNA duplexes and G-quadruplex. All complexes can bind selectively to DNA by intercalation and electrostatic forces, and inhibit topoisomerase I. The effect of the methyl substituents of the coordinated amino acid in the above complexes on these biological properties are presented and discussed. The IC(50) values (24 h) of 1-4 for nasopharyngeal cancer cell line HK1 are in the range 2.2-5.2 ?M while the corresponding values for normal cell line NP69 are greater than 13.0 ?M. All complexes, at 5 ?M, induced 41-60 % apoptotic cell death in HK1 cells but no significant cell death in NP69 cells. PMID:22836829

Seng, Hoi-Ling; Wang, Wai-San; Kong, Siew-Ming; Alan Ong, Han-Kiat; Win, Yip-Foo; Raja Abd Rahman, Raja Noor Zaliha; Chikira, Makoto; Leong, Weng-Kee; Ahmad, Munirah; Khoo, Alan Soo-Beng; Ng, Chew-Hee

2012-10-01

47

Proteomic Analysis of ?-Amino-3-hydroxy-5-methyl-4-isoxazole Propionate Receptor Complexes*  

PubMed Central

The AMPA receptor (AMPA-R) is a major excitatory neurotransmitter receptor in the brain. Identifying and characterizing the neuronal proteins interacting with AMPA-Rs have provided important information about the molecular mechanisms underlying synaptic transmission and plasticity. In this study, to identify more AMPA-R interactors in vivo, we performed proteomic analyses of AMPA-R complexes from the brain. AMPA-R complexes were isolated from the brain through various combinations of biochemical techniques for solubilization, enrichment, and immunoprecipitation. Mass spectrometry analyses of these isolated complexes identified several novel components of the AMPA-R complexes as well as some previously identified components. The identification of these novel components helps to further define the complex mechanisms involved in the regulation of AMPA receptor function and synaptic plasticity. PMID:22753414

Kang, Myoung-Goo; Nuriya, Mutsuo; Guo, Yurong; Martindale, Kevin D.; Lee, Daniel Z.; Huganir, Richard L.

2012-01-01

48

Pd(II) complexes based on quinoline derivative: structural characterization and their role as a catalyst for hydrogenation of (E)-1-methyl-4-(2-nitrovinyl)benzene.  

PubMed

A series of two new Pd(II) complexes with ligand, HL, (z)-2-((quinolin-3-ylimino)methyl)phenol, derived from 3-aminoquinoline and 2-hydroxybenzaldehyde was reported. The structure of ligand, HL was determined by single crystal X-ray diffraction. The ligand, HL crystallizes in the space group P21/n of the monoclinic system with unit cell dimensions a=8.8733(8), b=6.3318(5), c=11.5145(9). The reaction of ligand, HL with PdX2 [X=Cl(-), OAc] in 2:1molar ratio yielded complexes of the type [Pd(HL)2X2] [X=Cl(-), OAc]. The ligand, HL and its Pd(II) complexes were characterized by various physico-chemical techniques; elemental analyses, ionization mass spectrometry (ESI-MS), UV/Vis, FT-IR, (1)H and (13)C NMR spectroscopy. UV/Vis absorption studies showed a square planar geometry around Pd (II) ion. The selective hydrogenation of (E)-1-methyl-4-(2-nitrovinyl)benzene in ethanol using synthesized Pd(II) complexes as catalysts was investigated at room temperature. The Pd(II) complexes catalyzed the hydrogenation of (E)-1-methyl-4-(2-nitrovinyl)benzene to (E)-1-methyl-4-(2-aminovinyl) benzene. Furthermore, the catalytic activity increased with increasing the quantity of Pd(II) complexes as catalysts. PMID:24380892

Azam, Mohammad; Islam, Mohammad Shahidul; Al-Resayes, Saud I; Rafiq Siddiqui, M; Trzesowska-Kruszynska, Agata; Kruszynski, Rafal

2014-04-01

49

A zinc(II) complex with tris(2-(N-methyl)benzimidazlylmethyl)amine and salicylate: Synthesis, crystal structure, and DNA-binding  

Microsoft Academic Search

A five-coordinate zinc complex with tris(2-(N-methyl)benzimidazylmethyl)amine (Mentb) and salicylate, with composition [Zn(Mentb)(salicylate)](NO3), was synthesized and characterized by elemental analysis, IR and UV\\/Vis spectral measurements. The crystal structure of the zinc complex shows that Zn(II) is bonded to tris(2-(N-methyl)benzimidazylmethyl)amine (Mentb) and a salicylate through four nitrogens and one oxygen, and the coordination geometry is best described as distorted trigonal-bipyramid. The DNA-binding

Huilu Wu; Ying Bai; Jingkun Yuan; Hua Wang; Guolong Pan; Xuyang Fan; Jin Kong

2012-01-01

50

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

Microsoft Academic Search

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

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

51

On the enantioselective hydrogenation of isomeric methyl 3-acetamidobutenoates with RhI complexes.  

PubMed

The enantioselective hydrogenation of E- and Z-methyl 3-acetamidobutenoate, key intermediates in the synthesis of a pharmaceutically important chiral beta-amino acid, with RhI catalysts in MeOH as solvent has been investigated in detail. As chiral ligands, Et-DuPHOS, Me4-BASPHOS, DI-PAMP, DIOP, HO-DIOP and Et-Ferro-TANE have been employed. The particular role of oxyfunctionalization in some diphosphine catalysts is addressed in relation to the E/Z geometry of the substrate and the dependency of the ee on the H2 pressure. Kinetic investigations with [Rh(diphosphane)(MeOH)2]-BF4, taking into consideration the special nature of the precatalyst [[Rh-(cod)2]BF4/ligand versus [Rh(cod)ligand)]BF4], NMR spectroscopic measurements and the H2 pressure dependence of the observed enantioselectivity provide evidence that the reaction proceeds via an "unsaturated route" mechanism. This mechanism correlates to catalytic features found in the past for the hydrogenation of related unsaturated alpha-amino acid precursors. The influence of the temperature was similarly investigated. A nonlinear dependency of the enantiomeric ratio as a function of the reciprocal of the temperature has been found. The correlation between temperature and H2 pressure and their effects on the enantioselectivity is discussed. In general, the highest enantioselectivities for the hydrogenation of both isomeric substrates can be achieved at room temperature and below, whereas the fastest conversion takes place at 30-50 degrees C. PMID:12613038

Heller, Detlef; Drexler, Hans-Joachim; You, Jingsong; Baumann, Wolfgang; Drauz, Karlheinz; Krimmer, Hans-Peter; Börner, Armin

2002-11-15

52

DNA Methylation Profiling of the Human Major Histocompatibility Complex: A Pilot Study for the Human Epigenome Project  

Microsoft Academic Search

The Human Epigenome Project aims to identify, catalogue, and interpret genome-wide DNA methylation phenomena. Occurring naturally on cytosine bases at cytosine–guanine dinucleotides, DNA methylation is intimately involved in diverse biological processes and the aetiology of many diseases. Differentially methylated cytosines give rise to distinct profiles, thought to be specific for gene activity, tissue type, and disease state. The identification of

Vardhman K Rakyan; Thomas Hildmann; Karen L Novik; Jörn Lewin; Jörg Tost; Antony V Cox; T. Dan Andrews; Kevin L Howe; Thomas Otto; Alexander Olek; Judith Fischer; Ivo G Gut; Kurt Berlin; Stephan Beck

2004-01-01

53

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

NASA Astrophysics Data System (ADS)

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.

El-Didamony, Akram M.

2008-03-01

54

Structural Basis for the Recognition of Methylated Histone H3K36 by the Eaf3 Subunit of Histone Deacetylase Complex Rpd3S  

PubMed Central

SUMMARY Deacetylation of nucleosomes by the Rpd3S histone deacetylase along the path of transcribing RNA polymerase II regulates access to DNA, contributing to faithful gene transcription. The association of Rpd3S with chromatin requires its Eaf3 subunit, which binds histone H3 methylated at lysine 36 (H3K36). Eaf3 is also part of NuA4 acetyltransferase that recognizes methylated H3K4. Here we show that Eaf3 in Saccharomyces cerevisiae contains a chromo barrel-related domain that binds methylated peptides, including H3K36 and H3K4, with low specificity and millimolar-range affinity. Nuclear magnetic resonance structure determination of Eaf3 bound to methylated H3K36 was accomplished by engineering a linked Eaf3-H3K36 molecule with a chemically incorporated methyllysine analog. Our study uncovers the molecular details of Eaf3-methylated H3K36 complex formation, and suggests that, in the cell, Eaf3 can only function within a framework of combinatorial interactions. This work also provides a general method for structure determination of low-affinity protein complexes implicated in methyllysine recognition. PMID:18818090

Xu, Chao; Cui, Gaofeng; Botuyan, Maria Victoria; Mer, Georges

2008-01-01

55

A DFT based assessment of coordination modes of the bis(1-methyl-2-imidazolyl)glyoxal ligand in mononuclear and dinuclear complexes  

Microsoft Academic Search

The ligand bis(1-methyl-2-imidazolyl)glyoxal (big) was studied by DFT with respect to energy minimum conformations in the neutral, cation and anion radical states. Coordination alternatives involving chelate rings of different size were calculated for the partly experimentally accessible mononuclear complexes of big with [AuCl2]+, [Rh(C5R5)Cl]+ and Re(CO)3Cl. Comparative DFT calculations of various coordination modes for mononuclear, homodinuclear and heterodinuclear complexes of

Orkan Sarper; Ece Bulak; Wolfgang Kaim; Tereza Varnali

2006-01-01

56

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

SciTech Connect

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.

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

2009-01-01

57

Palladium(II) Complexes Containing Mixed Nitrogen-Sulphur Donor Ligands: Interaction of [Pd(Methionine Methyl Ester)(H2O)2]2+ with Biorelevant Ligands  

PubMed Central

Pd(MME)Cl2 complex (MME = methionine methyl ester) was synthesised and characterized by physicochemical measurements. The reaction of [Pd(MME)(H2O)2]2+ with amino acids, peptides, or dicarboxylic acids was investigated at 25°C and 0.1?M ionic strength. Amino acids and dicarboxylic acids form 1?:?1 complexes. Peptides form both 1?:?1 complexes and the corresponding deprotonated amide species. The stability of the complexes formed was determined and the binding centres of the ligands were assigned. Effect of solvent on the stability constant of Pd(MME)-CBDCA complex, taken as a representative example, shows that the complex is more favoured in a medium of low dielectric constant. The concentration distribution diagrams of the complexes were evaluated. PMID:25214826

Shoukry, Mohamed M.; Ezzat, Sameya M. T.

2014-01-01

58

Crystal structures of copper(II) and nickel(II) nitrate and chloride complexes with 4-bromo-2-[(2-hydroxyethylimino)-methyl]phenol  

SciTech Connect

The crystal structures of {l_brace}4-bromo-2-[(2-hydroxyethylimino)-methyl]phenolo{r_brace}aquacopper(II) nitrate hemihydrate (I), chloro-{l_brace}4-bromo-2-[(2-hydroxyethylimino)-methyl]phenolo{r_brace}copper hemihydrate (II), and chloro-{l_brace}4-bromo-2-[(2-hydroxyethylimino)-methyl]phenolo{r_brace}aquanickel (III) are determined using X-ray diffraction. Crystals of compound I are formed by cationic complexes, nitrate ions, and solvate water molecules. In the cation, the copper atom coordinates the singly deprotonated molecule of tridentate azomethine and the water molecule. The copper complexes are joined into centrosymmetric dimers by the O{sub w}-H...O hydrogen bonds. The crystal structure of compound II is composed of binuclear copper complexes and solvate water molecules. The copper atom coordinates the O,N,O ligand molecule and the chlorine ion, which fulfills a bridging function. The coordination polyhedron of the metal atom is a distorted tetragonal bipyramid in which the vertex is occupied by the chlorine atom of the neighboring complex in the dimer. Compound III is a centrosymmetric dimer complex. The coordination polyhedra of two nickel atoms related via the inversion center are distorted octahedra shared by the edge.

Chumakov, Yu. M. [Academy of Sciences of Moldova, Institute of Applied Physics (Moldova, Republic of); Tsapkov, V. I. [State University of Moldova (Moldova, Republic of); Filippova, I. G., E-mail: Irina.Filippova@phys.asm.md [Academy of Sciences of Moldova, Institute of Applied Physics (Moldova, Republic of); Bocelli, G. [National Research Council (IMEM-CNR), Institute of Materials for Electronics and Magnetism (Italy); Gulea, A. P. [State University of Moldova (Moldova, Republic of)

2008-07-15

59

Equilibrium investigation of complex formation reactions involving copper(II), nitrilo-tris(methyl phosphonic acid) and amino acids, peptides or DNA constitutents. The kinetics, mechanism and correlation of rates with complex stability for metal ion promoted hydrolysis of glycine methyl ester  

Microsoft Academic Search

The complex formation reactions of [Cu(NTP)(OH2)] (NTP?=?nitrilo-tris(methyl phosphonic acid)) with some selected bio-relevant ligands containing different functional groups, are investigated. Stoichiometry and stability constants for the complexes formed are reported. The results show that the ternary complexes are formed in a stepwise mechanism whereby NTP binds to copper(II), followed by coordination of amino acid, peptide or DNA. Copper(II) is found

Ahmed A. El-Sherif; Mohamed M. Shoukry

2006-01-01

60

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

Microsoft Academic Search

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

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

61

Syntheses, Crystal Structures, and Fluorescent Properties of Three Complexes Based on 1-((Benzotriazol-1-yl)methyl)-1-H-1,3-imdazole  

Microsoft Academic Search

Three new complexes formulated as [Zn(bmi)2Cl2] (1), [Zn(bmi)2(N3)2](2), and [Hg(bmi)Cl2]2 (3) (bmi = 1-((benzotriazol-1-yl)methyl)-1-H-1,3-imdazole) have been synthesized and characterized by elemental analysis, IR and single crystal X-ray diffraction. Complexes 1 and 2 show mononuclear structures, and complex 3 exhibits binuclear structure. In the solid state, they all possess a three-dimensional network formed by hydrogen bonds and ?-? interactions. Their fluorescent

Likun Duan; Shuangliang Liu; Wan Zhou; Xiangru Meng

2010-01-01

62

Aberration in DNA methylation in B-cell lymphomas has a complex origin and increases with disease severity.  

PubMed

Despite mounting evidence that epigenetic abnormalities play a key role in cancer biology, their contributions to the malignant phenotype remain poorly understood. Here we studied genome-wide DNA methylation in normal B-cell populations and subtypes of B-cell non-Hodgkin lymphoma: follicular lymphoma and diffuse large B-cell lymphomas. These lymphomas display striking and progressive intra-tumor heterogeneity and also inter-patient heterogeneity in their cytosine methylation patterns. Epigenetic heterogeneity is initiated in normal germinal center B-cells, increases markedly with disease aggressiveness, and is associated with unfavorable clinical outcome. Moreover, patterns of abnormal methylation vary depending upon chromosomal regions, gene density and the status of neighboring genes. DNA methylation abnormalities arise via two distinct processes: i) lymphomagenic transcriptional regulators perturb promoter DNA methylation in a target gene-specific manner, and ii) aberrant epigenetic states tend to spread to neighboring promoters in the absence of CTCF insulator binding sites. PMID:23326238

De, Subhajyoti; Shaknovich, Rita; Riester, Markus; Elemento, Olivier; Geng, Huimin; Kormaksson, Matthias; Jiang, Yanwen; Woolcock, Bruce; Johnson, Nathalie; Polo, Jose M; Cerchietti, Leandro; Gascoyne, Randy D; Melnick, Ari; Michor, Franziska

2013-01-01

63

A High Molar Extinction Coefficient Bisterpyridyl Homoleptic Ru(II) Complex with trans-2-Methyl-2-butenoic Acid Functionality: Potential Dye for Dye-Sensitized Solar Cells  

PubMed Central

In our continued efforts in the synthesis of ruthenium(II) polypyridine complexes as potential dyes for use in varied applications, such as the dye-sensitized solar cells (DSSCs), this work particularly describes the synthesis, absorption spectrum, redox behavior and luminescence properties of a new homoleptic ruthenium(II) complex bearing a simple trans-2-methyl-2-butenoic acid functionality as the anchoring ligand on terpyridine moiety. The functionalized terpyridine ligand: 4?-(trans-2-methyl-2-butenoic acid)-terpyridyl (L1) was synthesized by aryl bromide substitution on terpyridine in a basic reaction condition under palladium carbide catalysis. In particular, the photophysical and redox properties of the complex formulated as: bis-4?-(trans-2-methyl-2-butenoic acid)-terpyridyl ruthenium(II) bis-hexafluorophosphate [Ru(L1)2(PF6)2] are significantly better compared to those of [Ru(tpy)2]2+ and compare well with those of the best emitters of Ru(II) polypyridine family containing tridentate ligands. Reasons for the improved photophysical and redox properties of the complex may be attributed partly to the presence of a substituted ?,?-unsaturated carboxylic acid moiety leading to increase in the length of ?-conjugation bond thereby enhancing the MLCT-MC (Metal-to-ligand-charge transfer-metal centred) energy gap, and to the reduced difference between the minima of the excited and ground states potential energy surfaces. PMID:22489165

Adeloye, Adewale O.; Olomola, Temitope O.; Adebayo, Akinbulu I.; Ajibade, Peter A.

2012-01-01

64

Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence  

PubMed Central

Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation of the relative contribution of genetic and shared and nonshared environmental factors to phenotypic variability. Using DNA methylation profiling of ?20,000 CpG sites as a phenotype, we have examined discordance levels in three neonatal tissues from 22 MZ and 12 DZ twin pairs. MZ twins exhibit a wide range of within-pair differences at birth, but show discordance levels generally lower than DZ pairs. Within-pair methylation discordance was lowest in CpG islands in all twins and increased as a function of distance from islands. Variance component decomposition analysis of DNA methylation in MZ and DZ pairs revealed a low mean heritability across all tissues, although a wide range of heritabilities was detected for specific genomic CpG sites. The largest component of variation was attributed to the combined effects of nonshared intrauterine environment and stochastic factors. Regression analysis of methylation on birth weight revealed a general association between methylation of genes involved in metabolism and biosynthesis, providing further support for epigenetic change in the previously described link between low birth weight and increasing risk for cardiovascular, metabolic, and other complex diseases. Finally, comparison of our data with that of several older twins revealed little evidence for genome-wide epigenetic drift with increasing age. This is the first study to analyze DNA methylation on a genome scale in twins at birth, further highlighting the importance of the intrauterine environment on shaping the neonatal epigenome. PMID:22800725

Gordon, Lavinia; Joo, Jihoon E.; Powell, Joseph E.; Ollikainen, Miina; Novakovic, Boris; Li, Xin; Andronikos, Roberta; Cruickshank, Mark N.; Conneely, Karen N.; Smith, Alicia K.; Alisch, Reid S.; Morley, Ruth; Visscher, Peter M.; Craig, Jeffrey M.; Saffery, Richard

2012-01-01

65

Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence.  

PubMed

Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation of the relative contribution of genetic and shared and nonshared environmental factors to phenotypic variability. Using DNA methylation profiling of ?20,000 CpG sites as a phenotype, we have examined discordance levels in three neonatal tissues from 22 MZ and 12 DZ twin pairs. MZ twins exhibit a wide range of within-pair differences at birth, but show discordance levels generally lower than DZ pairs. Within-pair methylation discordance was lowest in CpG islands in all twins and increased as a function of distance from islands. Variance component decomposition analysis of DNA methylation in MZ and DZ pairs revealed a low mean heritability across all tissues, although a wide range of heritabilities was detected for specific genomic CpG sites. The largest component of variation was attributed to the combined effects of nonshared intrauterine environment and stochastic factors. Regression analysis of methylation on birth weight revealed a general association between methylation of genes involved in metabolism and biosynthesis, providing further support for epigenetic change in the previously described link between low birth weight and increasing risk for cardiovascular, metabolic, and other complex diseases. Finally, comparison of our data with that of several older twins revealed little evidence for genome-wide epigenetic drift with increasing age. This is the first study to analyze DNA methylation on a genome scale in twins at birth, further highlighting the importance of the intrauterine environment on shaping the neonatal epigenome. PMID:22800725

Gordon, Lavinia; Joo, Jihoon E; Powell, Joseph E; Ollikainen, Miina; Novakovic, Boris; Li, Xin; Andronikos, Roberta; Cruickshank, Mark N; Conneely, Karen N; Smith, Alicia K; Alisch, Reid S; Morley, Ruth; Visscher, Peter M; Craig, Jeffrey M; Saffery, Richard

2012-08-01

66

Pyrazolonato complexes of lead. Crystal structures of bis(1-phenyl-3-methyl-4-acetyl pyrazolonato)lead(II) and bis(1-phenyl-3-methyl-4-butanoylpyrazolonato)lead(II)  

Microsoft Academic Search

The structures of the complexes [PbL2], L = 1-phenyl-3-methyl-4-acylpyrazolonato, RCOC10H8N2O, R = Me (2) or Pr (3), have been determined by X-ray diffraction studies. Compound 2 is monoclinic, space group P21, a = 11.285(4), b = 14.727(4), c = 20.749(5) A?, ? = 95.83(3)°, R = 0.039 for 4486 reflections, and 3 is monoclinic, space group C2\\/c, a = 27.528(11),

B. Augustus Uzoukwu; P. U. Adiukwu; Salih S. Al-Juaid; Peter B. Hitchcock; J. David Smith

1996-01-01

67

Two nickel(II) bis[(pyridin-2-yl)methyl]amine complexes with homophthalic and benzene-1,2,4,5-tetracarboxylic acids.  

PubMed

Two new Ni(II) complexes involving the ancillary ligand bis[(pyridin-2-yl)methyl]amine (bpma) and two different carboxylate ligands, i.e. homophthalate [hph; systematic name: 2-(2-carboxylatophenyl)acetate] and benzene-1,2,4,5-tetracarboxylate (btc), namely catena-poly[[aqua{bis[(pyridin-2-yl)methyl]amine-?(3)N,N',N''}nickel(II)]-?-2-(2-carboxylatophenyl)aceteto-?(2)O:O'], [Ni(C9H6O4)(C12H13N3)(H2O)]n, and (?-benzene-1,2,4,5-tetracarboxylato-?(4)O(1),O(2):O(4),O(5))bis(aqua{bis[(pyridin-2-yl)methyl]amine-?(3)N,N',N''}nickel(II)) bis(triaqua{bis[(pyridin-2-yl)methyl]amine-?(3)N,N',N''}nickel(II)) benzene-1,2,4,5-tetracarboxylate hexahydrate, [Ni2(C10H2O8)(C12H13N3)2(H2O)2]·[Ni(C12H13N3)(H2O)3]2(C10H2O8)·6H2O, (II), are presented. Compound (I) is a one-dimensional polymer with hph acting as a bridging ligand and with the chains linked by weak C-H···O interactions. The structure of compound (II) is much more complex, with two independent Ni(II) centres having different environments, one of them as part of centrosymmetric [Ni(bpma)(H2O)]2(btc) dinuclear complexes and the other in mononuclear [Ni(bpma)(H2O)3](2+) cations which (in a 2:1 ratio) provide charge balance for btc(4-) anions. A profuse hydrogen-bonding scheme, where both coordinated and crystal water molecules play a crucial role, provides the supramolecular linkage of the different groups. PMID:24898954

Atria, Ana María; Garland, Maria Teresa; Baggio, Ricardo

2014-06-15

68

Stereospecific ligands and their complexes. Part XIX. Synthesis, characterization, circular dichroism and antimicrobial activity of oxalato and malonato-(S,S)-ethylenediamine-N,N?-di-2-(3-methyl)butanoato-chromate(III) complexes  

NASA Astrophysics Data System (ADS)

The s-cis-[Cr(S,S-eddv)L]-complexes (1,2) (S,S-eddv = (S,S)-ethylenediamine-N,N?-di-2-(3-methyl)butanoato ion; L = oxalate or malonate ion) were prepared. The complexes were purified by ion-exchange chromatography. The geometry of the complexes has been supposed on the basis of the infrared and electronic absorption spectra, and the absolute configurations of the isolated s-cis-[Cr(S,S-eddv)L]-complexes have been predicted on the basis of their circular dichroism (CD) spectra. Also, the results of thermal decomposition have been discussed. Antimicrobial activity of the prepared complexes (1-4) was investigated against 28 species of microorganisms. Testing was performed by microdilution method and minimum inhibitory concentrations (MIC) and minimum microbicidal concentration (MMC) have been determined. Complexes demonstrated in generally low antibacterial and antifungal activity.

Ili?, Dragoslav; Jevti?, Verica V.; Radojevi?, Ivana D.; Vasi?, Sava M.; Stefanovi?, Olgica D.; ?omi?, Ljiljana R.; Vasojevi?, Miorad M.; Jeli?, Miodrag Ž.; Koval'chuk, Tatyana V.; Loginova, Natalia V.; Trifunovi?, Sre?ko R.

2013-10-01

69

Influence of chirality on vibrational and relaxational properties of (S)- and (R,S)-ibuprofen/methyl-?-cyclodextrin inclusion complexes: an INS and QENS study.  

PubMed

In this paper, we analyze the internal picosecond dynamics of enantiomeric ((S)-) and racemic ((R,S)-) ibuprofen (IBP), when forming inclusion complexes, in solid state, with methyl-?-cyclodextrin (Me-?-CD), by inelastic and quasi elastic neutron scattering. The study was aimed at understanding, by the analysis of the vibrational and relaxational properties of the inclusion complexes also with respect to the single components, if and how the differences in the structural properties of the hydrogen bond (HB) network of (S)- and (R,S)-IBP can have influence on the complexation process triggered by "host-guest" interactions, whose detailed knowledge is retained as a prerequisite for enantiodiscrimination. From the results, a similar complexation mechanism for (S)- and (R,S)-IBP is argued, with a preferred penetration mode involving the isopropyl group of IBP. PMID:24015824

Crupi, Vincenza; Guella, Graziano; Longeville, Stéphane; Majolino, Domenico; Mancini, Ines; Paciaroni, Alessandro; Rossi, Barbara; Venuti, Valentina

2013-10-01

70

Synthesis, spectroscopic characterization, electrochemical behaviour and antibacterial activity of Ru(III) complexes of 2-[(4-N,N'-dimethylaminophenylimino)-methyl]-4-halophenol  

NASA Astrophysics Data System (ADS)

The reaction of the chelating Schiff base ligands 2-[(4-N,N'-dimethylaminophenylimino)-methyl]-4-X-phenol with [Ru(Cl) 3(EPh 3) 3]; (E = P or As); (X = Cl, Br or I) in the benzene afforded new stable ruthenium complexes of the general formula [Ru(Cl) 2(EPh 3) 2(L)] (L = anion of bidentate Schiff bases). The newly synthesized complexes were characterized using molar conductivity, spectral (UV-vis, FT-IR and EPR) and electrochemical studies. The molar conductance measurements proved that all these complexes are non-electrolytes. All complexes show strong d-d transition in the visible region. The coordination of imine nitrogen and phenolic oxygen of ligands to ruthenium metal was confirmed with the change in the IR stretching frequency values. The EPR spectral data showed that the complexes are paramagnetic with one unpaired electrons. The redox behaviour of the complexes have been investigated by the cyclic voltammetric technique. All the complexes display an irreversible reduction (Ru III/Ru II) in the range of -0.826 to -0.971 V. In view of the biological activity, the ligands and the complexes were observed that all the complexes showed moderate activity. Also the antibacterial activity of the ligand increased on chelation with metal ion.

Puthilibai, G.; Vasudhevan, S.; Kutti Rani, S.; Rajagopal, G.

2009-05-01

71

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)

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.

Alyar, Saliha; Adem, ?evki

2014-10-01

72

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

PubMed

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

Chandra, Sulekh; Vandana; Kumar, Suresh

2015-01-25

73

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

PubMed

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. (1)H and (13)C 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. PMID:24835932

Alyar, Saliha; Adem, ?evki

2014-10-15

74

Fluorimetric properties of a 2-hydroxypropyl-beta-cyclodextrin: 9-methyl-benzo[a]phenothiazine inclusion complex in aqueous media. Analytical usefulness.  

PubMed

The formation of an inclusion complex between 9-methyl-12H-benzo[a]phenothiazine (MeBPHT) and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was investigated in aqueous medium. A 12-fold fluorescence emission intensity enhancement was found for the complexed relative to the free analyte. MeBPHT forms a 1:1 stoichiometry complex with HP-beta-CD. A formation constant of 460 (+/-100) M(-1) was calculated using the Benesi-Hildebrand method and fluorimetric data. The limit of detection was 7 ng ml(-1) for MeBPHT in the presence of HP-beta-CD instead of 60 ng ml(-1) in the absence of HP-beta-CD. PMID:18966968

Maafi, M; Mahedero, M C; Aaron, J J

1997-12-01

75

Mononuclear zinc(II) complexes of 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols: Synthesis, structural characterization, DNA binding and cheminuclease activities  

NASA Astrophysics Data System (ADS)

Four new zinc(II) complexes [Zn(HL1-4)Cl2] (1-4), where HL1-4 = 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols, have been isolated and fully characterized using various spectro-analytical techniques. The X-ray crystal structure of complex 4 shows the distorted trigonal-bipyramidal coordination geometry around zinc(II) ion. The crystal packing is stabilized by intermolecular NH⋯O hydrogen bonding interaction. The complexes display no d-d electronic band in the visible region due to d10 electronic configuration of zinc(II) ion. The electrochemical properties of the synthesized ligands and their complexes exhibit similar voltammogram at reduction potential due to electrochemically innocent Zn(II) ion, which evidenced that the electron transfer is due to the nature of the ligand. Binding interaction of complexes with calf thymus DNA was studied by UV-Vis absorption titration, viscometric titration and cyclic voltammetry. All complexes bind with CT DNA by intercalation, giving the binding affinity in the order of 2 > 1 ? 3 > 4. The prominent cheminuclease activity of complexes on plasmid DNA (pBR322 DNA) was observed in the absence and presence of H2O2. Oxidative pathway reveals that the underlying mechanism involves hydroxyl radical.

Ravichandran, J.; Gurumoorthy, P.; Karthick, C.; Kalilur Rahiman, A.

2014-03-01

76

Antioxidant, DNA binding and nuclease activities of heteroleptic copper(II) complexes derived from 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols and diimines  

NASA Astrophysics Data System (ADS)

A series of heteroleptic copper(II) complexes of the type [CuL1-4(diimine)](ClO4)2 (1-8) [L1-4 = 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols, and diimine = 2,2?-bipyridyl (bpy) or 1,10-phenanthroline (phen)], have been synthesized and characterized by spectroscopic methods. The IR spectra of complexes indicate the presence of uncoordinated perchlorate anions and the electronic spectra revealed the square pyramidal geometry with N4O coordination environment around copper(II) nuclei. Electrochemical studies of the mononuclear complexes evidenced one-electron irreversible reduction wave in the cathodic region. The EPR spectra of complexes with g|| (2.206-2.214) and A|| (154-172 × 10-4 cm-1) values support the square-based CuN3O coordination chromophore and the presence of unpaired electron localized in dx-y ground state. Antioxidant studies against DPPH revealed effective radical scavenging properties of the synthesized complexes. Binding studies suggest that the heteroleptic copper(II) complexes interact with calf thymus DNA (CT-DNA) through minor-groove and electrostatic interaction, and all the complexes display pronounced nuclease activity against supercoiled pBR322 DNA.

Ravichandran, J.; Gurumoorthy, P.; Imran Musthafa, M. A.; Kalilur Rahiman, A.

2014-12-01

77

Antioxidant, DNA binding and nuclease activities of heteroleptic copper(II) complexes derived from 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols and diimines.  

PubMed

A series of heteroleptic copper(II) complexes of the type [CuL(1-4)(diimine)](ClO4)2 (1-8) [L(1-4)=2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols, and diimine=2,2'-bipyridyl (bpy) or 1,10-phenanthroline (phen)], have been synthesized and characterized by spectroscopic methods. The IR spectra of complexes indicate the presence of uncoordinated perchlorate anions and the electronic spectra revealed the square pyramidal geometry with N4O coordination environment around copper(II) nuclei. Electrochemical studies of the mononuclear complexes evidenced one-electron irreversible reduction wave in the cathodic region. The EPR spectra of complexes with g|| (2.206-2.214) and A|| (154-172×10(-)(4)cm(-)(1)) values support the square-based CuN3O coordination chromophore and the presence of unpaired electron localized in [Formula: see text] ground state. Antioxidant studies against DPPH revealed effective radical scavenging properties of the synthesized complexes. Binding studies suggest that the heteroleptic copper(II) complexes interact with calf thymus DNA (CT-DNA) through minor-groove and electrostatic interaction, and all the complexes display pronounced nuclease activity against supercoiled pBR322 DNA. PMID:24998685

Ravichandran, J; Gurumoorthy, P; Imran Musthafa, M A; Kalilur Rahiman, A

2014-12-10

78

Excited state complex formation between methyl glyoxal and some aromatic bio-molecules: a fluorescence quenching study  

Microsoft Academic Search

Fluorescence quenching of some important aromatic bio-molecules (ABM) such as 3-aminophthalhydrazide (luminol), tryptophan (Try), phenylalanine and tyrosine (Tyr) by methyl glyoxal (MG) has been studied employing different spectroscopic techniques. The interaction of MG with ABM in the excited state has been analysed using Stern–Volmer (S–V) mechanism. In the case of MG–luminol system time correlated single photon counting (TCSPC) technique has

D. Banerjee; A Mandal; S Mukherjee

2003-01-01

79

Mixed ligand ruthenium(III) complexes of benzaldehyde 4-methyl-3-thiosemicarbazones with triphenylphosphine/triphenylarsine co-ligands: Synthesis, DNA binding, DNA cleavage, antioxidative and cytotoxic activity  

NASA Astrophysics Data System (ADS)

The new ruthenium(III) complexes with 4-methyl-3-thiosemicarbazone ligands, (E)-2-(2-chlorobenzylidene)-N-methylhydrazinecarbothioamide (HL1) and (E)-2-(2-nitrobenzylidene)-N-methylhydrazinecarbothioamide (HL2), were prepared and characterized by various physico-chemical and spectroscopic methods. The title compounds act as bidentate, monobasic chelating ligands with S and N as the donor sites and are preferably found in the thiol form in all the complexes studied. The molecular structure of HL1 and HL2 were determined by single crystal X-ray diffraction method. DNA binding of the ligands and complexes were investigated by absorption spectroscopy and IR spectroscopy. It reveals that the compounds bind to nitrogenous bases of DNA via intercalation. The oxidative cleavage of the complexes with CT-DNA inferred that the effects of cleavage are dose dependent. Antioxidant study of the ligands and complexes showed the significant antioxidant activity against DPPH radical. In addition, the in vitro cytotoxicity of the ligands and complexes against MCF-7 cell line was assayed which showed higher cytotoxic activity with the lower IC50 values indicating their efficiency in killing the cancer cells even at low concentrations.

Sampath, K.; Sathiyaraj, S.; Raja, G.; Jayabalakrishnan, C.

2013-08-01

80

Synthesis, spectral, electrochemical and biological studies of Co(II), Ni(II) and Cu(II) complexes with Schiff bases of 8-formyl-7-hydroxy-4-methyl coumarin  

Microsoft Academic Search

A series of Co(II), Ni(II) and Cu(II) complexes have been synthesized with Schiff bases derived from 8-formyl-7-hydroxy-4-methyl coumarin and o-chloroaniline\\/o-toluidine. The structures of the complexes have been proposed from analytical, spectral (IR, UV-Vis, ESR and FAB-mass), magnetic, thermal and fluorescence studies. The complexes are soluble in DMF and DMSO and molar conductance values indicate the complexes are non-electrolytes. Elemental analyses

Ajaykumar Kulkarni; Prakash Gouda Avaji; Gangadhar B. Bagihalli; Sangamesh A. Patil; Prema S. Badami

2009-01-01

81

Synthesis, characterization, crystal structure and thermal behavior of 4-Bromo-2-(((5-chloro-2-hydroxyphenyl)imino)methyl)phenol and its oxido-vanadium(V) complexes  

NASA Astrophysics Data System (ADS)

A new Schiff base ligand (ONO), 4-Bromo-2-(((5-chloro-2-hydroxyphenyl)imino)methyl)phenol and its vanadium(V) complexes [VO(L)(MeO)(MeOH)] 1, [VO(L)(EtO)]22, [VO(L)(2-BuO)] 3, were prepared and characterized by elemental analyses, FT-IR, UV-Vis, 1H NMR and TGA techniques. The structures of the free ligand and all complexes have been determined by X-ray diffraction. The ligand exists in a zwitterionic form while 1 has the metal in a distorted octahedral environment. Both 2 and 3 display distorted square pyramidal coordination for the metal with the former existing as a dimer while the latter is monomeric although showing a weak Vsbnd O interaction with a neighboring molecule.

Yousef Ebrahimipour, S.; Mague, Joel T.; Akbari, Alireza; Takjoo, Reza

2012-11-01

82

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)

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.

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

2014-03-01

83

Effect of polymer charge density and ionic strength on the formation of complexes between sodium arylamido-2-methyl-1-propane-sulfonate-co-acrylamide gels and cetylpyridinium chloride.  

PubMed

The effects of sodium chloride on the composition and structure of polyelectrolyte gel-surfactant complexes (PSCs) formed by the sodium salt of acrylamide-2-methyl-1-propane-sulfonic acid-co-acrylamide gels and cetylpyridinium chloride have been studied. At a low ionic strength of the solution, the composition of all the complexes is close to stoichiometric by charge. In the presence of 0.3 M sodium chloride, the composition of the complexes formed by the gel with 99 mol % charged groups is close to stoichiometric, while for the gel with 33 mol % charged monomer units, a nonstoichiometric complex with a high excess of the surfactant is formed. Further decrease of the charge density up to 10 mol % leads to partial or complete dissociation of the PSCs. The study of PSCs by the method of small-angle X-ray scattering (SAXS) shows that the complexes formed by the gels with high and intermediate charge densities are highly ordered. The decrease of the charge density of the swollen networks at first leads to a change in symmetry of the ordered domains in the PSCs and then to their disordering. The formation of nonstoichiometric PSCs at a high enough concentration of salt is explained by the effect of fitting, when the packing of the surfactant and polymer components in the PSCs is improved due to the inclusion of extra surfactant molecules together with their counterions in the ordered domains. PMID:15274561

Starodubtsev, Sergey G; Dembo, Alexander T; Dembo, Kirill A

2004-08-01

84

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)

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.

Tyagi, Nidhi; Mathur, Pavan

2012-10-01

85

Hydrolysis Mechanism of the NAMI-A-type Antitumor Complex (HL)[trans-RuCl4L(dmso-S)] (L=1-methyl-1,2,4-triazole)  

NASA Astrophysics Data System (ADS)

The hydrolysis process of Ru(III) complex (HL)[trans-RuCl4L(dmso-S)] (L=1-methyl-1,2,4-triazole and dmso-S=S-dimethyl sulfoxide) (1), a potential antitumor complex similar to the well-known antitumor agent (Him)[trans-RuCl4(dmso-S)(im)] (NAMI-A, im=imidazole), was investigated using density functional theory combined with the conductor-like polarizable continuum model approach. The structural characteristics and the detailed energy profiles for the hydrolysis processes of this complex were obtained. For the first hydrolysis step, complex 1 has slightly higher barrier energies than the reported anticancer drug NAMI-A, and the result is in accordance with the experimental evidence indicating larger half-life for complex 1. For the second hydrolysis step, the formation of cis-diaqua species is thermodynamic preferred to that of trans isomers. In addition, on the basis of the analysis of electronic characteristics of species in the hydrolysis process, the trend in nucleophilic attack abilities of hydrolysis products by pertinent biomolecules is revealed and predicted.

Chen, Lan-mei; Chen, Jin-can; Liao, Si-yan; Liu, Jiang-qin; Luo, Hui; Zheng, Kang-cheng

2011-08-01

86

Zinc complexes supported by methyl salicylato ligands: synthesis, structure, and application in ring-opening polymerization of L-lactide.  

PubMed

Two novel zinc alkoxides supported by chelating methyl salicylato (MesalO; MesalOH = methyl salicylate) ligands were successfully synthesized and characterized. Reaction of MesalOH with ZnEt2 (2:1) gives a tetranuclear cluster [Zn(MesalO)2]4 (1), which by addition of pyridine is transformed to the mononuclear compound [Zn(MesalO)2(py)2] (2). Compounds 1 and 2 were characterized by elemental analysis, NMR, IR, and single crystal X-ray diffraction. The catalytic activity of both compounds was tested for the ring-opening polymerization (ROP) of L-lactide (L-LA). It was found that compounds 1 and 2 are efficient initiators of the ROP of L-LA, yielding cyclic PLLA with weight average molecular weights up to 100 kDa for 2. The treatment of 2 with 1 equiv. of BnOH in toluene afforded a dimeric compound [Zn(OBn)(MesalO)(py)]2 (3). The addition of L-LA to a combination of 1 and 4 equiv. of BnOH in THF or 2 and 1 equiv. of BnOH in toluene led to the rapid and efficient generation of PLLA with end-capped BnO groups. PMID:23811782

Petrus, Rafa?; Sobota, Piotr

2013-10-14

87

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

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.

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

1985-01-01

88

Methylation matters  

PubMed Central

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

Costello, J.; Plass, C.

2001-01-01

89

Excited state complex formation between methyl glyoxal and some aromatic bio-molecules: a fluorescence quenching study  

NASA Astrophysics Data System (ADS)

Fluorescence quenching of some important aromatic bio-molecules (ABM) such as 3-aminophthalhydrazide (luminol), tryptophan (Try), phenylalanine and tyrosine (Tyr) by methyl glyoxal (MG) has been studied employing different spectroscopic techniques. The interaction of MG with ABM in the excited state has been analysed using Stern-Volmer (S-V) mechanism. In the case of MG-luminol system time correlated single photon counting (TCSPC) technique has also been applied to explain the S-V mechanism. The bimolecular rate constants obtained are found to be higher than the rate constant for diffusion controlled process. A plausible explanation of the quenching mechanism has been discussed on the basis of hydrogen bonding, charge transfer and energy transfer interaction between the colliding species.

Banerjee, D.; Mandal, A.; Mukherjee, S.

2003-01-01

90

Assignment of heme methyl 1H-NMR resonances of high-spin and low-spin ferric complexes of cytochrome p450cam using one-dimensional and two-dimensional paramagnetic signals enhancement (PASE) magnetization transfer experiments.  

PubMed

An 1H-NMR study of ferric cytochrome P450cam in different paramagnetic states was performed. Assignment of three heme methyl resonances of the isocyanide adduct of cytochrome P450 in the ferric low-spin state was recently performed using electron exchange in the presence of putidaredoxin [Mouro, C., Bondon, A., Jung, C., Hui Bon Hoa, G., De Certaines, J.D., Spencer, R.G.S. & Simonneaux, G. (1999) FEBS Lett. 455, 302-306]. In this study, heme methyl protons of cytochrome P450 in the native high-spin and low-spin states were assigned through one-dimensional and two-dimensional magnetization transfer spectroscopy using the paramagnetic signals enhancement (PASE) method. The order of the methyl proton chemical shifts is inverted between high-spin and low-spin states. The methyl order observed in the ferric low-spin isocyanide complexes is related to the orientation of the cysteinate ligand. PMID:10601869

Mouro, C; Bondon, A; Jung, C; De Certaines, J D; Simonneaux, G

2000-01-01

91

Methyl thiophanate as a DNA minor groove binder produces MT-Cu(II)-DNA ternary complex preferably with AT rich region for initiation of DNA damage.  

PubMed

Interaction of a genotoxic fungicide methyl thiophanate (MT) has been studied in vitro with calf thymus DNA. Fluorescence quenching data revealed the binding constant (K(a)=3.23 x 10(4)M(-1)) and binding capacity (n=1.1) of MT with ctDNA. Ligand displacement studies using specific probes suggested the MT binding at DNA minor groove. The docking analysis further substantiated MT interaction with at least three AT base pairs within the DNA groove. A discernable change in E(0)' value with decreased peak currents in cyclic voltammogram, and peak shifts in CD spectra reflected the formation of MT-ctDNA and MT-ctDNA-Cu(II) complexes. The results elucidate the significance of specific MT-DNA interactions as an initiating event in MT-induced DNA damage. PMID:20371372

Saquib, Quaiser; Al-Khedhairy, Abdulaziz A; Alarifi, Saud A; Dutta, Sansa; Dasgupta, Swagata; Musarrat, Javed

2010-07-01

92

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)

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.

Seth, Susannah; Aravindakshan, K. K.

2013-08-01

93

Inorganic iron complexes derived from the nitric oxide donor nitroprusside: competitive N-methyl-D-aspartate receptor antagonists with nanomolar affinity.  

PubMed

Aquopentacyanoferrate(II), [Fe(II)H2O(CN)5]3-, is one of the photodegradation products of the vasodilator and nitric oxide donor nitroprusside. Earlier observations concerning the light dependence of N-methyl-D-aspartate (NMDA) receptor blockade by nitroprusside prompted us to examine the effects of this iron complex on the NMDA receptor. [Fe(II)H2O(CN)5]3- and two other related species, aminopentacyanoferrate(II) and aminopentacyanoferrate(III), were found to be highly potent, competitive, and selective NMDA receptor antagonists. In a binding assay for the transmitter recognition site on the NMDA receptor, these iron complexes displaced the radioligand [3H]CGP 39653 with nanomolar affinities. They did not displace radioligands labeling the channel ([3H]MK-801) or the glycine co-agonist ([3H]glycine) sites of the NMDA receptor, nor did they have any relevant affinities for a number of other neurotransmitter (alpha-adrenergic, 5-hydroxytryptamine, dopamine, opiate) receptors. The iron complexes blocked NMDA-induced depolarizations in rat cortical slices at submicromolar concentrations, whereas responses to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate were not affected. In another functional receptor assay (potentiation of [3H]MK-801 binding by glutamate under non-equilibrium conditions), Schild analysis demonstrated the competitive nature of the NMDA receptor antagonism. The pA2 values obtained from these experiments were similar to the pK(i) values derived from radioligand ([3H]CGP 39653) binding assays. To explain the high affinity and selectivity of these compounds for the NMDA receptor, a novel mechanism of antagonist-receptor interaction is proposed, involving a ligand exchange process in which a loosely bound species (here H2O or NH3) in the coordination sphere of the iron complex is replaced by a functional group of an amino acid side chain placed at the glutamate recognition site of the NMDA receptor, thereby hindering agonist binding. PMID:11172739

Neijt, H; Koller, M; Urwyler, S

2001-02-01

94

Enzyme inhibitor studies reveal complex control of methyl-D-erythritol 4-phosphate (MEP) pathway enzyme expression in Catharanthus roseus.  

PubMed

In Catharanthus roseus, the monoterpene moiety exerts a strong flux control for monoterpene indole alkaloid (MIA) formation. Monoterpene synthesis depends on the methyl-D-erythritol 4-phosphate (MEP) pathway. Here, we have explored the regulation of this pathway in response to developmental and environmental cues and in response to specific enzyme inhibitors. For the MEP pathway entry enzyme 1-deoxy-D-xylulose 5-phosphate synthase (DXS), a new (type I) DXS isoform, CrDXS1, has been cloned, which, in contrast to previous reports on type II CrDXS, was not transcriptionally activated by the transcription factor ORCA3. Regulation of the MEP pathway in response to metabolic perturbations has been explored using the enzyme inhibitors clomazone (precursor of 5-ketochlomazone, inhibitor of DXS) and fosmidomycin (inhibitor of deoxyxylulose 5-phosphate reductoisomerase (DXR)), respectively. Young leaves of non-flowering plants were exposed to both inhibitors, adopting a non-invasive in vivo technique. Transcripts and proteins of DXS (3 isoforms), DXR, and hydroxymethylbutenyl diphosphate synthase (HDS) were monitored, and protein stability was followed in isolated chloroplasts. Transcripts for DXS1 were repressed by both inhibitors, whereas transcripts for DXS2A&B, DXR and HDS increased after clomazone treatment but were barely affected by fosmidomycin treatment. DXS protein accumulated in response to both inhibitors, whereas DXR and HDS proteins were less affected. Fosmidomycin-induced accumulation of DXS protein indicated substantial posttranscriptional regulation. Furthermore, fosmidomycin effectively protected DXR against degradation in planta and in isolated chloroplasts. Thus our results suggest that DXR protein stability may be affected by substrate binding. In summary, the present results provide novel insight into the regulation of DXS expression in C. roseus in response to MEP-pathway perturbation. PMID:23650515

Han, Mei; Heppel, Simon C; Su, Tao; Bogs, Jochen; Zu, Yuangang; An, Zhigang; Rausch, Thomas

2013-01-01

95

Enzyme Inhibitor Studies Reveal Complex Control of Methyl-D-Erythritol 4-Phosphate (MEP) Pathway Enzyme Expression in Catharanthus roseus  

PubMed Central

In Catharanthus roseus, the monoterpene moiety exerts a strong flux control for monoterpene indole alkaloid (MIA) formation. Monoterpene synthesis depends on the methyl-D-erythritol 4-phosphate (MEP) pathway. Here, we have explored the regulation of this pathway in response to developmental and environmental cues and in response to specific enzyme inhibitors. For the MEP pathway entry enzyme 1-deoxy-D-xylulose 5-phosphate synthase (DXS), a new (type I) DXS isoform, CrDXS1, has been cloned, which, in contrast to previous reports on type II CrDXS, was not transcriptionally activated by the transcription factor ORCA3. Regulation of the MEP pathway in response to metabolic perturbations has been explored using the enzyme inhibitors clomazone (precursor of 5-ketochlomazone, inhibitor of DXS) and fosmidomycin (inhibitor of deoxyxylulose 5-phosphate reductoisomerase (DXR)), respectively. Young leaves of non-flowering plants were exposed to both inhibitors, adopting a non-invasive in vivo technique. Transcripts and proteins of DXS (3 isoforms), DXR, and hydroxymethylbutenyl diphosphate synthase (HDS) were monitored, and protein stability was followed in isolated chloroplasts. Transcripts for DXS1 were repressed by both inhibitors, whereas transcripts for DXS2A&B, DXR and HDS increased after clomazone treatment but were barely affected by fosmidomycin treatment. DXS protein accumulated in response to both inhibitors, whereas DXR and HDS proteins were less affected. Fosmidomycin-induced accumulation of DXS protein indicated substantial posttranscriptional regulation. Furthermore, fosmidomycin effectively protected DXR against degradation in planta and in isolated chloroplasts. Thus our results suggest that DXR protein stability may be affected by substrate binding. In summary, the present results provide novel insight into the regulation of DXS expression in C. roseus in response to MEP-pathway perturbation. PMID:23650515

Han, Mei; Heppel, Simon C.; Su, Tao; Bogs, Jochen; Zu, Yuangang; An, Zhigang; Rausch, Thomas

2013-01-01

96

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

E-print Network

scavenger TEMPO do not support a homolytic mechanism. A SN2 mechanism was proposed for the formation. At pH 8, the reaction leads to a C1-symmetric monomethyl PtIV complex (dpms)PtIV Me(OH)2 (5) with high selectivity 97%; the reaction rate is first-order in [PtII Me] and fastest at pH 8.0. This behavior

Goddard III, William A.

97

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

PubMed

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 33kJmol(-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

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

2015-01-25

98

Structural, spectroscopic and theoretical studies of short OHO hydrogen bonds in 2:1 complexes of 1-methyl-6-oxyquinolinium betaine with mineral acids  

NASA Astrophysics Data System (ADS)

Bis(1-methyl-6-oxyquinolinium) hydroiodide, (6QB) 2HI ( 1), has been characterized by X-ray diffraction, B3LYP calculations, FTIR and NMR spectroscopy. The complex crystallizes in triclinic P1¯ space group. A pair of 6QB molecules is bridged by the O·H·O hydrogen bond of 2.450(2) Å. The anion I - electrostatically interacts with both positively charged nitrogen atoms of the neighboring 6QB molecules. The isolated entities of the complex were analyzed at the B3LYP/6-311G(d,p) level of theory in order to determine the influence of counter ions (X - = I -, Br -, Cl - and ClO4-) on the hydrogen bond in (6QB) 2HX ( 2- 5). The FTIR spectra of (6QB) 2HI and (6QB) 2HClO 4 show a broad and intense absorption in the 1500-400 cm -1 region, typical for short hydrogen bonds. Both 1H and 13C chemical shifts depend on the acid-base stoichiometry and counter ions.

Barczy?ski, P.; Komasa, A.; Ratajczak-Sitarz, M.; Katrusiak, A.; Dega-Szafran, Z.; Szafran, M.

2010-12-01

99

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

PubMed Central

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

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

2014-01-01

100

An H3K36 methylation-engaging Tudor motif of polycomb-like proteins mediates PRC2 complex targeting.  

PubMed

Polycomb repressive complex 2 (PRC2) regulates pluripotency, differentiation, and tumorigenesis through catalysis of histone H3 lysine 27 trimethylation (H3K27me3) on chromatin. However, the mechanisms that underlie PRC2 recruitment and spreading on chromatin remain unclear. Here we report that histone H3 lysine 36 trimethylation (H3K36me3) binding activity is harbored in the Tudor motifs of PRC2-associated polycomb-like (PCL) proteins PHF1/PCL1 and PHF19/PCL3. Ectopically expressed PHF1 induced Tudor-dependent stabilization of PRC2 complexes on bulk chromatin and mediated spreading of PRC2 and H3K27me3 into H3K36me3-containing chromatin regions. In murine pluripotent stem cells, we identified coexistence of H3K36me3, H3K27me3, and PHF19/PCL3 at a subset of poised developmental genes and demonstrated that PHF19/PCL3 Tudor function is required for optimal H3K27me3 and repression of these loci. Collectively, our data suggest that PCL recognition of H3K36me3 promotes intrusion of PRC2 complexes into active chromatin regions to promote gene silencing and modulate the chromatin landscape during development. PMID:23273982

Cai, Ling; Rothbart, Scott B; Lu, Rui; Xu, Bowen; Chen, Wei-Yi; Tripathy, Ashutosh; Rockowitz, Shira; Zheng, Deyou; Patel, Dinshaw J; Allis, C David; Strahl, Brian D; Song, Jikui; Wang, Gang Greg

2013-02-01

101

An H3K36 methylation engaging Tudor motif of polycomb-like proteins mediates PRC2 complex targeting  

PubMed Central

SUMMARY Polycomb repressive complex 2 (PRC2) regulates pluripotency, differentiation and tumorigenesis through catalysis of histone H3 lysine 27 trimethylation (H3K27me3) on chromatin. However, the mechanisms that underlie PRC2 recruitment and spreading on chromatin remain unclear. Here we report that histone H3 lysine 36 trimethylation (H3K36me3)-binding activity is harbored in the Tudor motifs of PRC2-associated polycomblike (PCL) proteins PHF1/PCL1 and PHF19/PCL3. Ectopically expressed PHF1 induced Tudor-dependent stabilization of PRC2 complexes on bulk chromatin and mediated spreading of PRC2 and H3K27me3 into H3K36me3-containing chromatin regions. In murine pluripotent stem cells, we identified coexistence of H3K36me3, H3K27me3, and PHF19/PCL3 at a subset of ‘poised’ developmental genes, and demonstrated that PHF19/PCL3 Tudor function is required for optimal H3K27me3 and repression of these loci. Collectively, our data suggest that PCL recognition of H3K36me3 promotes intrusion of PRC2 complexes into active chromatin regions to promote gene silencing and modulate the chromatin landscape during development. PMID:23273982

Cai, Ling; Rothbart, Scott B.; Lu, Rui; Xu, Bowen; Chen, Wei-Yi; Tripathy, Ashutosh; Rockowitz, Shira; Zheng, Deyou; Patel, Dinshaw J; Allis, C. David; Strahl, Brian D.; Song, Jikui; Wang, Gang Greg

2012-01-01

102

Self-assembly of three Cd(II) complexes: From 0-D to 1-D and 2-D structures based on 1-((benzotriazol-1-yl)methyl)-1- H-1,3-imidazole ligand and different anions  

Microsoft Academic Search

Three new complexes with the formulas [Cd(bmi)2I2] (1), [Cd(bmi)2(Cl)2]n (2) and [Cd(bmi)2(SCN)2]n (3) have been obtained through the self-assembly of an unsymmetrical ligand 1-((benzotriazol-1-yl)methyl)-1-H-1,3-imidazole (bmi) with Cd(II) salts at room temperature. Single crystal X-ray diffraction determination shows that complex 1 possesses mononuclear structure, complex 2 displays 1-D chain structure constructed by chloride bridging Cd(II) ions, and complex 3 exhibits 2-D

Likun Duan; Yanan Ding; Xiangru Meng; Weiqiang Li; Hongwei Hou; Yaoting Fan

2010-01-01

103

Synthesis and luminescence of lanthanide complexes of a branched macrocyclic ligand containing 2,2[prime]-bipyridine and 9-methyl-1,10-phenanthroline subunits  

SciTech Connect

The synthesis of the branched-macrocyclic ligand 1 incorporating two 2,2[prime]-bipyridine units in the macrocycle and two 9-methyl-1,10-phenanthroline units in the branches is described as well as the synthesis and the photophysical properties of its Eu[sup 3+], Tb[sup 3+], and Gd[sup 3+] complexes. These complexes do not decompose in water in contrast to those of the related ligand containing 2,2[prime]-bipyridine instead of 1,10-phenanthroline. They show intense absorption bands in the UV region due to absorption in the ligand. The emission spectra of the [Eu[contained in]1][sup 3+] and [Tb[contained in]1][sup 3+] complexes obtained upon ligand excitation show the usual Eu[sup 3+] and Tb[sup 3+] transitions. The pattern of the emission spectrum of the [Eu[contained in]1][sup 3+] complex allows one to assess a low (presumably C[sub 2]) symmetry as the probable site symmetry of the metal ion in the complex. For [Eu[contained in]1][sup 3+] and [Tb[contained in]1][sup 3+], the metal luminescence excitation spectra in water match the ligand absorption spectra while in methanol the absorption due to the phenanthroline is missing. This suggests that in water the efficiency of the ligand-to-metal energy transfer is similar for the two chromophores while in methanol phenanthroline transfers energy to the metal ion less efficiently than bipyridine. The luminescence quantum yield values in water and methanol confirm this interpretation. The lifetimes of the Eu[sup 3+] and Tb[sup 3+] emitting state indicate that the shielding of the metal ion from solvent molecules is rather inefficient. For the [Tb[contained in]1][sup 3+] complex the lifetimes are temperature dependent which is attributed to the presence of an equilibrium between the metal emitting state and triplet excited states of the ligand; this process is most likely responsible for the low luminescence quantum yields and the oxygen effect on the Tb[sup 3+] luminescence.

Sabbatini, N.; Guardigli, M.; Manet, I.; Bolletta, F. (Universita di Bologna (Italy)); Ziessel, R. (IPCMS, Groupe des Materiaux Inorganiques, Strasbourg (France))

1994-03-02

104

Photobehaviour of methyl-pyridinium and quinolinium iodide derivatives, free and complexed with DNA. A case of bisintercalation.  

PubMed

Excited state dynamics of four azinium salts were studied in buffered water and in the presence of salmon testes DNA. Complexation with DNA changes the photobehaviour of the free ligands lowering the photoreactivity and emission in favor of internal conversion. The interaction of these four dyes with DNA was studied with different techniques with the aim to establish the affinity and the type of binding between the ligands and DNA. The results from spectrophotometric and fluorimetric titrations provided evidence of a strong interaction between the azinium salts and the polynucleotide, with a binding constant of about 10(6) M(-1), making them interesting for therapeutical applications. Dichroic measurements allowed us to determine the possible modes of binding for each complex. Short living excited states of the free dyes were detected and characterized by ultrafast absorption spectroscopy. A further decrease of transient lifetimes was observed upon interaction with DNA. The bicationic pyridinium iodide was found to act as a bisintercalative agent, potentially increasing the cytotoxicity with low dose and less collateral effects. PMID:24740459

Mazzoli, Alessandra; Carlotti, Benedetta; Consiglio, Giuseppe; Fortuna, Cosimo G; Miolo, Giorgia; Spalletti, Anna

2014-06-01

105

Multifaceted Genome Control by Set1 Dependent and Independent of H3K4 Methylation and the Set1C/COMPASS Complex  

PubMed Central

Histone modifiers are critical regulators of chromatin-based processes in eukaryotes. The histone methyltransferase Set1, a component of the Set1C/COMPASS complex, catalyzes the methylation at lysine 4 of histone H3 (H3K4me), a hallmark of euchromatin. Here, we show that the fission yeast Schizosaccharomyces pombe Set1 utilizes distinct domain modules to regulate disparate classes of repetitive elements associated with euchromatin and heterochromatin via H3K4me-dependent and -independent pathways. Set1 employs its RNA-binding RRM2 and catalytic SET domains to repress Tf2 retrotransposons and pericentromeric repeats while relying on its H3K4me function to maintain transcriptional repression at the silent mating type (mat) locus and subtelomeric regions. These repressive functions of Set1 correlate with the requirement of Set1C components to maintain repression at the mat locus and subtelomeres while dispensing Set1C in repressing Tf2s and pericentromeric repeats. We show that the contributions of several Set1C subunits to the states of H3K4me diverge considerably from those of Saccharomyces cerevisiae orthologs. Moreover, unlike S. cerevisiae, the regulation of Set1 protein level is not coupled to the status of H3K4me or histone H2B ubiquitination by the HULC complex. Intriguingly, we uncover a genome organization role for Set1C and H3K4me in mediating the clustering of Tf2s into Tf bodies by antagonizing the acetyltransferase Mst1-mediated H3K4 acetylation. Our study provides unexpected insights into the regulatory intricacies of a highly conserved chromatin-modifying complex with diverse roles in genome control. PMID:25356590

Lorenz, David R.; Cam, Hugh P.

2014-01-01

106

Coordination and fluorescence of the intracellular Zn2+ probe [2-methyl-8-(4-toluenesulfonamido)-6-quinolyloxy]acetic acid (Zinquin A) in ternary Zn2+ complexes.  

PubMed

A potentiometric study of the coordination of the fluorophore, 2-methyl-8-(4-toluenesulfonamido)-6-quinolyloxyacetic acid, (1)LH(2) (the intracellular Zn(2+) probe, Zinquin A) in its deprotonated form, (1)L(2)(-), in Zn(2+) ternary complexes, [Zn(n)L(1)L](n) (where n is the charge of (n)L) at 298.2 K in 50% aqueous ethanol (v/v) and I = 0.10 (NaClO(4)), shows that the formation of [Zn(n)L(1)L](n) from [Zn(n)L]((2+)(n)(+) is characterized by log(K(5)/dm(3) mol(-1)) = 8.23 +/- 0.05, 4.36 +/- 0.18, 8.45 +/- 0.10, 10.00 +/- 0.06, 11.53 +/- 0.06 and 5.92 +/- 0.15, respectively, where (n)L = (2)L - (6)L and (7)L(3-) are 1,4,7,10-tetraazacyclododecane, 1,4,8,11-tetraazacyclotetradecane, 1,4,7-triazacyclononane, 1,5,9-triazacyclododecane, tris(2-aminoethyl)amine and nitrilotriacetate, respectively, and K(5) is the stepwise complexation constant. Dissociation of a hydroxo proton from triethanolamine, (8)L, occurs in the formation of [Zn(8)LH(-1)](+) that subsequently forms [Zn(8)LH(-1)(1)L](-) for which log(K(5)/dm(3) mol(-1)) = 9.87 +/- 0.08. The variation of K(5) and the 5-fold variation of quantum yield of (1)L(2)(-) as its coordination environment changes in Zn(2+) ternary complexes are discussed with reference to the use of (1)L(2-) in the detection of intracellular Zn(2+). PMID:12656623

Hendrickson, Kym M; Geue, Jason P; Wyness, Oska; Lincoln, Stephen F; Ward, A David

2003-04-01

107

DNA methylation program during development  

PubMed Central

DNA methylation is a key epigenetic mark when occurring in the promoter and enhancer regions regulates the accessibility of the binding protein and gene transcription. DNA methylation is inheritable and can be de novo-synthesized, erased and reinstated, making it arguably one of the most dynamic upstream regulators for gene expression and the most influential pacer for development. Recent progress has demonstrated that two forms of cytosine methylation and two pathways for demethylation constitute ample complexity for an instructional program for orchestrated gene expression and development. The forum of the current discussion and review are whether there is such a program, if so what the DNA methylation program entails, and what environment can change the DNA methylation program. The translational implication of the DNA methylation program is also proposed. PMID:23687512

ZHOU, Feng C.

2013-01-01

108

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

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

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

109

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

SciTech Connect

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.

Hao, Y.; Gates, B

2009-01-01

110

Reporter molecules as probes of DNA conformation: structure of a crystalline complex containing 2-methyl-4-nitro-aniline ethylene dimethylammonium hydrobromide - 5-iodocytidylyl(3'-5')guanosine  

SciTech Connect

2-Methyl-4-nitroaniline ethylene dimethylammonium hydrobromide forms a crystalline complex with the self-complementary dinucleoside monophosphate, 5-iodocytidylyl(3'-5')guanosine. The crystals are tetragonal, with a = b = 32.192 A and c = 23.964 A, space group P4/sub 3/2/sub 1/2. The structure has been solved to atomic resolution by Patterson and Fourier methods, and refined by full matrix least squares. 5-Iodocytidylyl(3'-5')guanosine molecules are held together in pairs through Watson-Crick base-pairing, forming an antiparallel duplex structure. Nitroaniline molecules stack above and below guanine-cytosine pairs in this duplex structure. In addition, a third nitroaniline molecule stacks on one of the other two nitroaniline molecules. The asymmetric unit contains two 5-iodocytidylyl(3'-5')guanosine molecules, three nitroaniline molecules, one bromide ion and thirty-one water molecules, at total of 160 atoms. Details of the structure are described. 15 references, 4 figures, 2 tables.

Vyas, N.K.; Nyas, M.N.; Jain, S.C.; Sobell, H.M.

1984-05-31

111

Selective Electrocatalytic Oxidation of a Re-Methyl Complex to Methanol by a Surface-Bound Ru(II) Polypyridyl Catalyst.  

PubMed

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

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

2014-11-12

112

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

SciTech Connect

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.

Szigethy, Geza; Raymond, Kenneth

2010-04-22

113

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

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.

Huggins, John Mitchell

1980-06-01

114

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

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

A Braig

1997-01-01

115

7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex.  

PubMed Central

Glycine markedly potentiates N-methyl-D-aspartate (N-Me-D-Asp) responses in mammalian neurons by an action at a modulatory site on the N-Me-D-Asp receptor-ionophore complex. Here we present evidence that 7-chlorokynurenic acid (7-Cl KYNA) inhibits N-Me-D-Asp responses by a selective antagonism of glycine at this modulatory site. In rat cortical slices 7-Cl KYNA (10-100 microM) noncompetitively inhibited N-Me-D-Asp responses, and this effect could be reversed by the addition of glycine (100 microM) or D-serine (100 microM). Radioligand binding experiments showed that 7-Cl KYNA had a much higher affinity for the strychnine-insensitive [3H]glycine binding site (IC50 = 0.56 microM) than for the N-Me-D-Asp (IC50 169 microM), quisqualate (IC50 = 153 microM), or kainate (IC50 greater than 1000 microM) recognition sites. In whole-cell patch-clamp recordings from rat cortical neurones in culture, the inhibitory effects of 7-Cl KYNA on N-Me-D-Asp-induced currents could not be overcome by increasing the N-Me-D-Asp concentration but could be reversed by increasing the glycine concentration. 7-Cl KYNA could completely abolish N-Me-D-Asp responses, including basal responses in the absence of added glycine, suggesting that it may possess negative modulatory effects at the glycine site. These findings indicate that the glycine modulatory site is functional in intact adult tissue and that 7-Cl KYNA should prove to be a selective tool for elucidating the involvement of this site in physiological and pathological events mediated by N-Me-D-Asp receptors. PMID:2842779

Kemp, J A; Foster, A C; Leeson, P D; Priestley, T; Tridgett, R; Iversen, L L; Woodruff, G N

1988-01-01

116

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)

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.

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

2014-11-01

117

DNA methylation and evolution of duplicate genes  

PubMed Central

The evolutionary mechanisms underlying duplicate gene maintenance and divergence remain highly debated. Epigenetic modifications, such as DNA methylation, may contribute to duplicate gene evolution by facilitating tissue-specific regulation. However, the role of epigenetic divergence on duplicate gene evolution remains little understood. Here we show, using comprehensive data across 10 diverse human tissues, that DNA methylation plays critical roles in several aspects of duplicate gene evolution. We first demonstrate that duplicate genes are initially heavily methylated, before gradually losing DNA methylation as they age. Within each pair, DNA methylation divergence between duplicate partners increases with evolutionary age. Importantly, tissue-specific DNA methylation of duplicates correlates with tissue-specific expression, implicating DNA methylation as a causative factor for functional divergence of duplicate genes. These patterns are apparent in promoters but not in gene bodies, in accord with the complex relationship between gene-body DNA methylation and transcription. Remarkably, many duplicate gene pairs exhibit consistent division of DNA methylation across multiple, divergent tissues: For the majority (73%) of duplicate gene pairs, one partner is always hypermethylated compared with the other. This is indicative of a common underlying determinant of DNA methylation. The division of DNA methylation is also consistent with their chromatin accessibility profiles. Moreover, at least two sequence motifs known to interact with the Sp1 transcription factor mark promoters of more hypomethylated duplicate partners. These results demonstrate critical roles of DNA methylation, as well as complex interaction between genome and epigenome, on duplicate gene evolution. PMID:24711408

Keller, Thomas E.; Yi, Soojin V.

2014-01-01

118

Synthesis, spectroscopic characterization, DNA interaction and biological activities of Mn(II), Co(II), Ni(II) and Cu(II) complexes with [(1H-1,2,4-triazole-3-ylimino)methyl]naphthalene-2-ol  

NASA Astrophysics Data System (ADS)

Manganese(II), cobalt(II), nickel(II) and copper(II) complexes of [(1H-1,2,4-triazole-3-ylimino)methyl]naphthalene-2-ol have been synthesized. The structure of complexes have been characterized by elemental analysis, molar conductance, magnetic moment measurements and spectral (IR, 1H NMR, EI-mass, UV-Vis and ESR), and thermal studies. The results showed that the chloro and nitrato Cu(II) complexes have octahedral geometry while Ni(II), Co(II) and Mn(II) complexes in addition to acetato Cu(II) complex have tetrahedral geometry. The possible structures of the metal complexes have been computed using the molecular mechanic calculations using the hyper chem. 8.03 molecular modeling program to confirm the proposed structures. The kinetic and thermodynamic parameters of the thermal decomposition steps were calculated from the TG curves. The binding modes of the complexes with DNA have been investigated by UV-Vis absorption titration. The results showed that the mode of binding of the complexes to DNA is intercalative or non-intercalative binding modes. Schiff base and its metal complexes have been screened for their in vitro antimicrobial activities against Gram positive bacteria (Staphylococcus aureus), Gram negative bacteria (Escherichia coli and Pesudomonas aeruginosa), fungi (Asperigllus flavus and Mucer) and yeast (Candida albicans and Malassezia furfur).

Gaber, Mohamed; El-Wakiel, Nadia A.; El-Ghamry, Hoda; Fathalla, Shaimaa K.

2014-11-01

119

DNA Methylation and Its Basic Function  

PubMed Central

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

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

2013-01-01

120

DNA methylation and its basic function.  

PubMed

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

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

2013-01-01

121

Synthesis of a polyrotaxane-based macroporous polymer as stationary phase for capillary electrochromatography via host-guest complexation of N,N '-ethylenedianilinediacrylamide with statistically methylated beta-cyclodextrin.  

PubMed

A synthetic route to acrylamide-based monolithic stationary phases for CEC with rotaxane-type immobilized derivatized beta-CD was explored. N,N'-Ethylenedianilinediacrylamide was synthesized as the water-insoluble crosslinker forming water-soluble inclusion complexes with statistically methylated beta-CD. Mixed-mode stationary phases were synthesized by free radical copolymerization of the bisacrylamide-CD host-guest complex with water-soluble monomers and an additional water-soluble crosslinker in aqueous solution. Complex formation in solution and inclusion of the pseudorotaxane into the polymeric network (formation of a polyrotaxane architecture) were studied by means of (1)H-NMR chemical shift analysis, CD modified micellar EKC (CD-MEKC), 2D-NOESY spectroscopy, and solid state( 13)C-NMR spectroscopy. The presence of a mixed-mode selectivity of the stationary phase based on hydrophobic and hydrophilic interaction was confirmed by CEC with neutral polar and nonpolar solutes. PMID:18428178

Wahl, Annika; Al-Rimawi, Fuad; Schnell, Ingo; Kornysova, Olga; Maruska, Audrius; Pyell, Ute

2008-05-01

122

Synthesis, Characterization, and Biological Activity of N?-[(Z)-(3-Methyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)(phenyl)methyl]benzohydrazide and Its Co(II), Ni(II), and Cu(II) Complexes  

PubMed Central

Reaction of 1-phenyl-3-methyl-4-benzoyl-pyrazol-5-one and benzoyl hydrazide in refluxing ethanol gave N?-[(Z)-(3-methyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)(phenyl)methyl]benzohydrazide (HL1), which was characterized by NMR spectroscopy and single-crystal X-ray structure study. X-ray diffraction analyses of the crystals revealed a nonplanar molecule, existing in the keto-amine form, with intermolecular hydrogen bonding forming a seven-membered ring system. The reaction of HL1 with Co(II), Ni(II), and Cu(II) halides gave the corresponding complexes, which were characterized by elemental analysis, molar conductance, magnetic measurements, and infrared and electronic spectral studies. The compounds were screened for their in vitro cytotoxic activity against HL-60 human promyelocytic leukemia cells and antimicrobial activity against some bacteria and yeasts. Results showed that the compounds are potent against HL-60 cells with the IC50 value ?5??M, while some of the compounds were active against few studied Gram-positive bacteria. PMID:25332694

Asegbeloyin, Jonnie N.; Ujam, Oguejiofo T.; Okafor, Emmanuel C.; Babahan, Ilknur; Coban, Esin Poyrazoglu; Özmen, Ali; Biyik, Halil

2014-01-01

123

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)

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.

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

2014-09-01

124

The solution structure of the first PHD finger of autoimmune regulator in complex with non-modified histone H3 tail reveals the antagonistic role of H3R2 methylation  

PubMed Central

Plant homeodomain (PHD) fingers are often present in chromatin-binding proteins and have been shown to bind histone H3 N-terminal tails. Mutations in the autoimmune regulator (AIRE) protein, which harbours two PHD fingers, cause a rare monogenic disease, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). AIRE activates the expression of tissue-specific antigens by directly binding through its first PHD finger (AIRE-PHD1) to histone H3 tails non-methylated at K4 (H3K4me0). Here, we present the solution structure of AIRE-PHD1 in complex with H3K4me0 peptide and show that AIRE-PHD1 is a highly specialized non-modified histone H3 tail reader, as post-translational modifications of the first 10 histone H3 residues reduce binding affinity. In particular, H3R2 dimethylation abrogates AIRE-PHD1 binding in vitro and reduces the in vivo activation of AIRE target genes in HEK293 cells. The observed antagonism by R2 methylation on AIRE-PHD1 binding is unique among the H3K4me0 histone readers and represents the first case of epigenetic negative cross-talk between non-methylated H3K4 and methylated H3R2. Collectively, our results point to a very specific histone code responsible for non-modified H3 tail recognition by AIRE-PHD1 and describe at atomic level one crucial step in the molecular mechanism responsible for antigen expression in the thymus. PMID:19293276

Chignola, Francesca; Gaetani, Massimiliano; Rebane, Ana; Org, Tonis; Mollica, Luca; Zucchelli, Chiara; Spitaleri, Andrea; Mannella, Valeria; Peterson, Part; Musco, Giovanna

2009-01-01

125

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

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

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

2013-01-01

126

New rhodium(III) and ruthenium(II) water-soluble complexes with 3,5-diaza-1-methyl-1-azonia-7-phosphatricyclo[3.3.1.1(3,7)]decane.  

PubMed

The new water-soluble phosphine complexes of rhodium(III), [RhI(4)(mtpa)(2)]I (1), and ruthenium(II), [RuI(4)(mtpa)(2)].2H(2)O (2) and [RuI(2)(mtpa)(3)(H(2)O)]I(3).2H(2)O (3) (mtpa = 3,5-diaza-1-methyl-1-azonia-7-phosphatricyclo[3.3.1.1(3,7)]decane cation), have been prepared in the reactions of RhCl(3).3H(2)O and RuCl(3).3H(2)O in water in the presence of phosphine and potassium iodide. Properties and reactivity of the complexes have been investigated using (1)H and (31)P NMR and IR spectroscopies. The complexes have also been structurally characterized by single crystal X-ray diffraction studies. The compounds [RhI(4)(mtpa)(2)]I and [RuI(4)(mtpa)(2)].2H(2)O are zwitterionic octahedral complexes. The compounds were tested as catalysts for two-phase hydroformylation of 1-hexene and hydrogenation of cinnamaldehyde. Complex 1 is a selective catalyst for reduction of the C=C bond while complexes 2 and 3 selectively hydrogenate the C=O bond. PMID:12739973

Smole?ski, Piotr; Pruchnik, Florian P; Ciunik, Zbigniew; Lis, Tadeusz

2003-05-19

127

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

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

Onwudiwe, Damian C.; Ajibade, Peter A.

2011-01-01

128

The complexes between Schiff base of gossypol with L-phenylalanine methyl ester and some monovalent cations studied by 1H NMR, ESI MS, FT-IR as well as PM5 semi-empirical methods  

NASA Astrophysics Data System (ADS)

The Schiff base of racemic gossypol with L-phenylalanine methyl ester and its complexes with H + and monovalent metal cations was synthesized and studied by FT-IR, 1H NMR spectroscopy and Electrospray Ionization mass spectrometry as well as by the PM5 semi-empirical method. The studied Schiff base exists in acetonitrile solution in the enamine-enamine tautomeric form. After the protonation, the tautomeric form changes into the imine-imine one. For this form of the Schiff base the existence of diastereoisomers was very well visible in the 1H NMR spectra. The structures of the protonated Schiff base and its 1:1 complex with K + cation as well as the respective hydrogen bonds within these structures are discussed.

Przybylski, Piotr; Brzezinski, Bogumil

2003-06-01

129

Flavivirus RNA methylation.  

PubMed

The 5' end of eukaryotic mRNA contains the type-1 (m7GpppNm) or type-2 (m7GpppNmNm) cap structure. Many viruses have evolved various mechanisms to develop their own capping enzymes (e.g. flavivirus and coronavirus) or to 'steal' caps from host mRNAs (e.g. influenza virus). Other viruses have developed 'cap-mimicking' mechanisms by attaching a peptide to the 5' end of viral RNA (e.g. picornavirus and calicivirus) or by having a complex 5' RNA structure (internal ribosome entry site) for translation initiation (e.g. picornavirus, pestivirus and hepacivirus). Here we review the diverse viral RNA capping mechanisms. Using flavivirus as a model, we summarize how a single methyltransferase catalyses two distinct N-7 and 2'-O methylations of viral RNA cap in a sequential manner. For antiviral development, a structural feature unique to the flavivirus methyltransferase was successfully used to design selective inhibitors that block viral methyltransferase without affecting host methyltransferases. Functionally, capping is essential for prevention of triphosphate-triggered innate immune activation; N-7 methylation is critical for enhancement of viral translation; and 2'-O methylation is important for subversion of innate immune response during viral infection. Flaviviruses defective in 2'-O methyltransferase are replicative, but their viral RNAs lack 2'-O methylation and are recognized and eliminated by the host immune response. Such mutant viruses could be rationally designed as live attenuated vaccines. This concept has recently been proved with Japanese encephalitis virus and dengue virus. The findings obtained with flavivirus should be applicable to other RNA viruses. PMID:24486628

Dong, Hongping; Fink, Katja; Züst, Roland; Lim, Siew Pheng; Qin, Cheng-Feng; Shi, Pei-Yong

2014-04-01

130

Cigarette smoking and DNA methylation  

PubMed Central

DNA methylation is the most studied epigenetic modification, capable of controlling gene expression in the contexts of normal traits or diseases. It is highly dynamic during early embryogenesis and remains relatively stable throughout life, and such patterns are intricately related to human development. DNA methylation is a quantitative trait determined by a complex interplay of genetic and environmental factors. Genetic variants at a specific locus can influence both regional and distant DNA methylation. The environment can have varying effects on DNA methylation depending on when the exposure occurs, such as during prenatal life or during adulthood. In particular, cigarette smoking in the context of both current smoking and prenatal exposure is a strong modifier of DNA methylation. Epigenome-wide association studies have uncovered candidate genes associated with cigarette smoking that have biologically relevant functions in the etiology of smoking-related diseases. As such, DNA methylation is a potential mechanistic link between current smoking and cancer, as well as prenatal cigarette-smoke exposure and the development of adult chronic diseases. PMID:23882278

Lee, Ken W. K.; Pausova, Zdenka

2013-01-01

131

The influence of counter ion and ligand methyl substitution on the solid-state structures and photophysical properties of mercury(II) complexes with (E)-N-(pyridin-2-ylmethylidene)arylamines.  

PubMed

Ten neutral monomeric, dimeric and polymeric mercury(II) complexes of compositions HgX(2)L (3, 8), [HgX(2)L](2) (1, 2, 4-6 and 7), [Hg(NO(3))(2)L](n) (9) and {[Hg(N(3))(2)L](2)}(n) (10) where X = chloride, bromide, iodide, nitrate and azide, and L = (E)-N-(pyridin-2-ylmethylidene)arylamine, are described. Compounds 1-10 were characterized by elemental analyses, and IR and (1)H NMR spectroscopic studies. The solution-state photophysical properties of the complexes are highly dependent on the anions as seen in the fluorescence emission features. Single-crystal X-ray crystallography showed that the molecular complexes can aggregate into larger entities depending upon the anion coordinated to the metal centre. Iodide gives discrete monomeric complexes, chloride and bromide generate binuclear complexes formed through Hg-X-Hg bridges, while nitrate and azide lead to 1D coordination polymers. The significant differences in the observed aggregation patterns of the compounds indicate that the anions exert a substantial influence on the formation of the compounds. A further influence upon supramolecular aggregation is the presence of methyl substituents in L(3) and L(4), which generally enhances the probability of forming supramolecular ?? interactions involving the five-membered C(2)N(2)Hg chelate rings in their crystal structures. PMID:23172550

Basu Baul, Tushar S; Kundu, Sajal; Mitra, Sivaprasad; Höpfl, Herbert; Tiekink, Edward R T; Linden, Anthony

2013-02-01

132

Characterization and partial purification of mRNA N6-adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex.  

PubMed

N6-Methyladenosine is found at internal positions of mRNA in higher eukaryotes. This post-transcriptional modification occurs at a frequency of one to three methylation/average mRNA molecule in mammalian cell lines and is sequence-specific. A highly conserved consensus recognition site for the methyltransferase has been determined from both viral and cellular messages, consisting of the sequence Pu(G/A)AC(U/A) (with A being methylated). Despite the ubiquity and the specificity of this modification, little is known about the mechanism of formation of N6-methyladenosine. Utilizing an in vitro methylation system from HeLa cell nuclear extracts, and a substrate RNA derived from the mRNA coding for bovine prolactin, the mRNA N6-adenosine methyltransferase has been characterized and partially purified. Unique among other characterized nucleic acid methyltransferases, the enzyme is composed of three components which are separable under non-denaturing conditions. The molecular masses of the components are 30, 200, and 875 kDa as determined by gel filtration and glycerol gradient sedimentation. The 200-kDa component appears to contain the S-adenosylmethionine-binding site on a 70-kDa subunit. The 875-kDa component has affinity for single-stranded DNA-agarose, suggesting that it may contain the mRNA-binding site. N6-Adenosine methyltransferase is not sensitive to treatment with micrococcal nuclease, nor to immunodepletion using an anti-trimethylguanosine antibody, suggesting that it does not contain an essential RNA component. PMID:8021282

Bokar, J A; Rath-Shambaugh, M E; Ludwiczak, R; Narayan, P; Rottman, F

1994-07-01

133

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

SciTech Connect

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.

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

2005-01-01

134

Aerobic oxidation of methyl p-tolyl sulfide catalyzed by a remarkably labile heteroscorpionate RuII-aqua complex, fac-[RuII(H2O)(dpp)(tppm)]2+.  

PubMed

fac-[RuII(Cl)(dpp)(L3)]+ (L3 = tris(pyrid-2-yl)methoxymethane (tpmm) = [1A]+ and tris(pyrid-2-yl)pentoxymethane (tppm) = [1B]+ and dpp = di(pyrazol-1-yl)propane) rapidly undergo ligand substitution with water to form fac-[RuII(H2O)(dpp)(L3)]2+ (L3 = tpmm = [2A]2+ and tppm = [2B]2+). In the structure of [2A]2+, the distorted octahedral arrangement of ligands around Ru is evident by a long Ru(1)-O(40) of 2.172(3) A and a large angle O(40)-Ru(1)-N(51) of 96.95(14) degrees . The remarkably short distance between O(40) of H2O and H(45a) of dpp confirms the heteroscorpionate ligand effect of dpp on H2O. [2B]2+ aerobically catalyzes methyl p-tolyl sulfide to methyl p-tolyl sulfoxide in 1,2-dichlorobenzene at 25.0 +/- 0.1 degrees C under 11.4 psi of O2. Experimental facts in support of this aerobic sulfide oxidation are the absence of H2O2 and the oxidative reactivity of the putative Ru(IV)-oxo intermediate toward methyl p-tolyl sulfide, 2-propanol, and allyl alcohol. This study provides the first documented example of aerobic-sulfide oxidation catalyzed by the remarkably labile heteroscorpionate Ru(II)-aqua complex without the formation of a highly reactive peroxide as an intermediate. PMID:12517123

Huynh, My Hang V; Witham, Laura M; Lasker, Joanne M; Wetzler, Modi; Mort, Brendan; Jameson, Donald L; White, Peter S; Takeuchi, Kenneth J

2003-01-15

135

Synthesis, Characterization, and Biological Activity of N1-Methyl-2-(1H-1,2,3-Benzotriazol-1-y1)-3-Oxobutan- ethioamide Complexes with Some Divalent Metal (II) Ions  

PubMed Central

A new series of Zn2+, Cu2+, Ni2+, and Co2+ complexes of N1-methyl-2-(1H-1,2,3-benzotriazol-1-yl)-3-oxobutanethioamide (MBOBT), HL, has been synthesized and characterized by different spectral and magnetic measurements and elemental analysis. IR spectral data indicates that (MBOBT) exists only in the thione form in the solid state while 13C NMR spectrum indicates its existence in thione and thiole tautomeric forms. The IR spectra of all complexes indicate that (MBOBT) acts as a monobasic bidentate ligand coordinating to the metal(II) ions via the keto-oxygen and thiolato-sulphur atoms. The electronic spectral studies showed that (MBOBT) bonded to all metal ions through sulphur and nitrogen atoms based on the positions and intensity of their charge transfer bands. Furthermore, the spectra reflect four coordinate tetrahedral zinc(II), tetragonally distorted copper(II), square planar nickel(II), and cobalt(II) complexes. Thermal decomposition study of the complexes was monitored by TG and DTG analyses under N2 atmosphere. The decomposition course and steps were analyzed and the activation parameters of the nonisothermal decomposition are determined. The isolated metal chelates have been screened for their antimicrobial activities and the findings have been reported and discussed in relation to their structures. PMID:18364993

Al-Awadi, Nouria A.; Shuaib, Nadia M.; Abbas, Alaa; El-Sherif, Ahmed A.; El-Dissouky, Ali; Al-Saleh, Esmaeil

2008-01-01

136

Equilibrium and 1 H NMR Kinetic Study of the Reactions of Dichlorido [S-Methyl-L-Cysteine(N,S)]Platinum(II) Complex with Some Relevant Biomolecules  

Microsoft Academic Search

The formation equilibria of the [Pt(SMC)(H2O)2]+ complex with some biologically relevant ligands such as L-methionine (L-met) and glutathione (GSH) were studied. The stoichiometry\\u000a and stability constants of the formed complexes are reported, and the concentration distribution of the various complex species\\u000a has been evaluated as a function of pH. The reaction between [PtCl2(SMC)] and guanosine-5?-monophosphate (5?-GMP) was studied by 1H

Tanja Soldatovi?; Predrag ?anovi?; Radivoje Nikoli?; Ratomir Jeli?; Živadin D. Bugar?i?

2009-01-01

137

The RING Finger Protein MSL2 in the MOF Complex is an E3 Ubiquitin Ligase for H2B K34 and is Involved in Crosstalk with H3 K4 and K79 Methylation  

PubMed Central

SUMMARY We demonstrate that RING finger protein MSL2 in the MOF-MSL complex is a histone ubiquitin E3 ligase. MSL2, together with MSL1, has robust histone ubiquitylation activity that mainly targets nucleosomal H2B on lysine 34 (H2B K34ub), a site within a conserved basic patch on H2B tail. H2B K34ub by MSL1/2 directly regulates H3 K4 and K79 methylation through trans-tail crosstalk both in vitro and in cells. The significance of MSL1/2 mediated histone H2B ubiquitylation is underscored by facts that MSL1/2 activity is important for transcription activation at HOXA9 and MEIS1 loci and that this activity is evolutionarily conserved in the Drosophila dosage compensation complex. Altogether, these results establish that the MOF-MSL complex possesses two distinct chromatin-modifying activities (i.e. H4 K16 acetylation and H2B K34 ubiquitylation) through MOF and MSL2 subunits. They also shed new lights on how intricate network of chromatin modifying enzymes functions coordinately in gene activation. PMID:21726816

Wu, Lipeng; Zee, Barry M.; Wang, Yanming; Garcia, Benjamin A.; Dou, Yali

2014-01-01

138

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

PubMed

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

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

2014-05-01

139

Synthesis, spectroscopic studies and structures of square-planar nickel(II) and copper(II) complexes derived from 2-{(Z)-[furan-2-ylmethyl]imino]methyl}-6-methoxyphenol.  

PubMed

Two new nickel(II) [Ni(L)(2)] and copper(II) [Cu(L)(2)] complexes have been synthesized with bidentate NO donor Schiff base ligand (2-{(Z)-[furan-2-ylmethyl]imino]methyl}-6-methoxyphenol) (HL) and both complexes Ni(L)(2) and Cu(L)(2) have been characterized by elemental analyses, IR, UV-vis, (1)H, (13)C NMR, mass spectroscopy and room temperature magnetic susceptibility measurement. The tautomeric equilibria (phenol-imine, O-H...N and keto-amine, O...H-N forms) have been systemetically studied by using UV-vis absorption spectra for the ligand HL. The UV-vis spectra of this ligand HL were recorded and commented in polar, non-polar, acidic and basic media. The crystal structures of these complexes have also been determined by using X-ray crystallographic techniques. The complexes Ni(L)(2) and Cu(L)(2) crystallize in the monoclinic space group P2(1)/n and P2(1)/c with unit cell parameters: a=10.4552(3)A and 12.1667(4)A, b=8.0121(3)A and 10.4792(3)A, c=13.9625(4)A and 129.6616(3)A, V=1155.22(6)A(3) and 1155.22(6)A(3), D(x)=1.493 and 1.476 g cm(-3) and Z=2 and 2, respectively. The crystal structures were solved by direct methods and refined by full-matrix least squares to a find R=0.0377 and 0.0336 of for 2340 and 2402 observed reflections, respectively. PMID:20047854

Unver, Hüseyin; Hayvali, Zeliha

2010-02-01

140

Methyl salicylate overdose  

MedlinePLUS

Methyl salicylate is a wintergreen-scented chemical found in many over-the-counter products, including muscle ache creams. Methyl salicylate overdose occurs when someone accidentally or intentionally takes ...

141

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

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.

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

1995-03-29

142

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

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

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

2012-12-27

143

Steric and electronic effects on arylthiolate coordination in the pseudotetrahedral complexes [(Tp(Ph,Me))Ni-SAr] (Tp(Ph,Me) = hydrotris{3-phenyl-5-methyl-1-pyrazolyl}borate).  

PubMed

Synthesis and characterization of several new pseudotetrahedral arylthiolate complexes [(Tp(Ph,Me))Ni-SAr] (Tp(Ph,Me) = hydrotris{3-phenyl-5-methyl-1-pyrazolyl}borate; Ar = Ph, 2,4,6-(i)Pr3C6H2, C6H4-4-Cl, C6H4-4-Me, C6H4-4-OMe) are reported, including X-ray crystal structures of the first two complexes. With prior results, two series of complexes are spanned, [(Tp(Ph,Me))Ni-S-2,4,6-RC6H2] (R'' = H, Me, (i)Pr) plus the xylyl analogue [(Tp(Ph,Me))Ni-S-2,6-Me2C6H3], as well as [(Tp(Ph,Me))Ni-S-C6H4-4-Y] (Y = Cl, H, Me, OMe), intended to elucidate steric and/or electronic effects on arylthiolate coordination. In contrast to [(Tp(Me,Me))Ni-SAr] analogues that adopt a sawhorse conformation, the ortho-disubstituted complexes show enhanced trigonal and Ni-S-Ar bending, reflecting the size of the 3-pyrazole substituents. Moreover, weakened scorpionate ligation is implied by spectroscopic data. Little spectroscopic effect is observed in the series of para-substituted complexes, suggesting the observed effects are primarily steric in origin. The relatively electron-rich and encumbered complex [(Tp(Ph,Me))Ni-S-2,4,6-(i)Pr3C6H2] behaves uniquely when dissolved in CH3CN, forming a square planar solvent adduct with a bidentate scorpionate ligand, [(?(2)-Tp(Ph,Me))Ni(NCMe)(S-2,4,6-(i)Pr3C6H2)]. This adduct was isolated and characterized by X-ray crystallography. Single-point DFT and TD-DFT calculations on a simplified [(?(2)-Tp)Ni(NCMe)(SPh)] model were used to clarify the electronic spectrum of the adduct, and to elucidate differences between Ni-SAr bonding and spectroscopy between pseudotetrahedral and square planar geometries. PMID:25341014

Deb, Tapash; Anderson, Caitlin M; Chattopadhyay, Swarup; Ma, Huaibo; Young, Victor G; Jensen, Michael P

2014-11-01

144

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

PubMed

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

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

2014-07-21

145

Isomer Dependence in the Assembly and Lability of Silver(I) Trifluoromethanesulfonate Complexes of the Heteroditopic Ligands, 2-, 3-, and 4-[Di(1H-pyrazolyl)methyl]phenyl(di-p-tolyl)phosphine.  

PubMed

Three isomers of a new heteroditopic ligand that contains a di(1H-pyrazolyl)methyl (-CHpz2) moiety connected to a di(p-tolyl)phosphine group via a para-, meta-, or ortho-phenylene spacer (pL, mL, and oL, respectively) have been synthesized by using a palladium(0)-catalyzed coupling reaction between HP(p-tolyl)2 and the appropriate isomer of (IC6H4)CHpz2. The 1:1 complexes of silver(I) trifluoromethanesulfonate, Ag(OTf), were prepared to examine the nature of ligand coordination and the type of supramolecular isomer (monomeric, cyclic oligomeric, or polymeric) that would be obtained. The single crystal X-ray diffraction studies showed that [Ag(pL)](OTf), 1, and [Ag(mL)](OTf), 2, possessed cyclic dimeric dications, whereas [Ag(oL)](OTf), 3, was a coordination polymer. The polymeric chain in 3 could be disrupted by reaction with triphenylphosphine, and the resulting complex, [Ag(oL)(PPh3)](OTf), 4, possessed a monometallic cation where the ligand was bound to silver in a chelating ?(2)P,N- coordination mode. The solution structures of 1-4 were probed via a combination of IR, variable-temperature multinuclear ((1)H, (13)C, (31)P) NMR spectroscopy, as well as by electron spray ionization (ESI)(+) mass spectrometry. A related complex [Ag(m-IC6H4CHpz2)2](OTf), 5, was also prepared, and its solid-state and solution spectroscopic properties were studied for comparison purposes. These studies suggest that the cyclic structures of 1 and 2 are likely preserved but are dynamic in solution at room temperature. Moreover, both 3 and 4 have dynamic solution structures where 3 is likely extensively dissociated in CH3CN or acetone rather than being polymeric as in the solid state. PMID:25375040

Gardinier, James R; Hewage, Jeewantha S; Lindeman, Sergey V

2014-11-17

146

Structural basis for Klf4 recognition of methylated DNA  

PubMed Central

Transcription factor Krüppel-like factor 4 (Klf4), one of the factors directing cellular reprogramming, recognizes the CpG dinucleotide (whether methylated or unmodified) within a specific G/C-rich sequence. The binding affinity of the mouse Klf4 DNA-binding domain for methylated DNA is only slightly stronger than that for an unmodified oligonucleotide. The structure of the C-terminal three Krüppel-like zinc fingers (ZnFs) of mouse Klf4, in complex with fully methylated DNA, was determined at 1.85 Å resolution. An arginine and a glutamate interact with the methyl group. By comparison with two other recently characterized structures of ZnF protein complexes with methylated DNA, we propose a common principle of recognition of methylated CpG by C2H2 ZnF proteins, which involves a spatially conserved Arg–Glu pair. PMID:24520114

Liu, Yiwei; Olanrewaju, Yusuf Olatunde; Zheng, Yu; Hashimoto, Hideharu; Blumenthal, Robert M.; Zhang, Xing; Cheng, Xiaodong

2014-01-01

147

Methyl rotors in flavoproteins.  

PubMed

In this contribution we present the study of the thermal dependence of the ENDOR spectra of flavodoxin at low temperatures which reveals the dynamics of the methyl groups bound to the flavin moiety in flavoproteins. The methyl groups behave as quantum rotors locked by a deep rotational well and undergoing a tunneling process. At room temperature, methyl rotors are locked and the hopping motion is slow. This picture of the dynamics of the methyl groups of the flavin ring is quite different from the one usually accepted and has relevant consequences on the understanding of the mechanisms of flavoproteins. PMID:25363087

Martínez, Jesús I; Alonso, Pablo J; García-Rubio, Inés; Medina, Milagros

2014-12-21

148

H3K36 Methylation Antagonizes PRC2-mediated H3K27 Methylation*  

PubMed Central

H3K27 methylation mediated by the histone methyltransferase complex PRC2 is critical for transcriptional regulation, Polycomb silencing, Drosophila segmentation, mammalian X chromosome inactivation, and cancer. PRC2-mediated H3K27 methylation can spread along the chromatin and propagate the repressive chromatin environment; thus, chromatin components that antagonize the activity of PRC2 are important for restraining Polycomb silencing. Here we report that in HeLa cells, H3 histones unmethylated at Lys-36 are mostly methylated at Lys-27, with the exception of newly synthesized H3. In addition, K27me3 rarely co-exists with K36me2 or K36me3 on the same histone H3 polypeptide. Moreover, PRC2 activity is greatly inhibited on nucleosomal substrates with preinstalled H3K36 methylation. These findings collectively identify H3K36 methylation as a chromatin component that restricts the PRC2-mediated spread of H3K27 methylation. Finally, we provide evidence that the controversial histone lysine methyltransferase Ash1, a known Trithorax group protein that antagonizes Polycomb silencing in vivo, is an H3K36-specific dimethylase, not an H3K4 methylase, further supporting the role of H3K36 methylation in antagonizing PRC2-mediated H3K27 methylation. PMID:21239496

Yuan, Wen; Xu, Mo; Huang, Chang; Liu, Nan; Chen, She; Zhu, Bing

2011-01-01

149

DNA Methylation Biomarkers: Cancer and Beyond  

PubMed Central

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

Mikeska, Thomas; Craig, Jeffrey M.

2014-01-01

150

Asymmetric Synthesis of P-Chiral Diphosphines. Steric Effects on the Palladium-Complex-Promoted Asymmetric Diels-Alder Reaction between a Dimethylphenylphosphole and (E/Z)-Methyl-Substituted Diphenylvinylphosphines.  

PubMed

The organopalladium complex containing ortho-metalated (S)-(1-(dimethylamino)ethyl)naphthalene as the chiral auxiliary has been used successfully to promote the asymmetric [4+2] Diels-Alder reactions between 1-phenyl-3,4-dimethylphosphole and the following coordinated dienophiles: (a) diphenylvinylphosphine; (b) (E)-diphenyl-1-propenylphosphine; (c) (Z)-diphenyl-1-propenylphosphine. Reaction a generates three carbon and one phosphorus stereogenic centers while reactions b and c each produce four carbon and one phosphorus chiral centers. In dichloromethane, all three reactions proceeded smoothly at room temperature giving the corresponding rigid diphosphines in high yields. Under similar reaction conditions, the reaction times observed for reactions a-c are 2, 3, and 50 h, respectively. Two-dimensional ROESY NMR studies confirmed that the prolonged reaction time required for reaction c is due to several major repulsive interactions between the chiral naphthylamine auxiliary and the (Z)-methyl-substituted vinylphosphine in the transition state. Nevertheless, all three reactions gave the corresponding rigid diphosphine in high yields. The absolute stereochemistries of the three bidentate phosphine ligands that were produced from the cycloaddition reactions have been assigned by 2D ROESY NMR spectroscopy. These diphosphines are powerful sequesterers of group 8 metals although they are highly air-sensitive in the free ligand form. The coordination chemistry and the absolute stereochemistry of the optically active complex [1alpha,4alpha,5alpha(S),6alpha(S),7R]-dichloro[5-(diphenylphosphino)-2,3,6-trimethy-7-phenyl-7-phosphabicyclo[2.2.1]-hept-2-ene-P(5)(),P(7)()]palladium(II) has been studied by single-crystal X-ray analysis. Crystal structure data: C(27)H(28)Cl(2)P(2)Pd, M(r) = 591.7; triclinic; space group P1; a = 8.643(3), b = 9.044(6), c = 9.058(4) Å; alpha = 102.75(4) degrees, beta = 108.59(2) degrees, gamma = 97.82(3) degrees; V = 638.0(5) Å(3); Z = 1; R(1) = 0.036. PMID:11669835

Aw, Beng-Hwee; Hor, T. S. Andy; Selvaratnam, S.; Mok, K. F.; White, Andrew J. P.; Williams, David J.; Rees, Nicholas H.; McFarlane, William; Leung, Pak-Hing

1997-05-01

151

Inter-individual variation of DNA methylation and its implications for large-scale epigenome mapping  

Microsoft Academic Search

Genomic DNA methylation profiles exhibit substan- tial variation within the human population, with important functional implications for gene regula- tion. So far little is known about the characteristics and determinants of DNA methylation variation among healthy individuals. We performed bioinfor- matic analysis of high-resolution methylation pro- files from multiple individuals, uncovering complex patterns of inter-individual variation that are strongly correlated

Christoph Bock; Jörn Walter; Martina Paulsen; Thomas Lengauer

2008-01-01

152

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...

153

DNA methylation and differentiation.  

PubMed Central

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

Michalowsky, L A; Jones, P A

1989-01-01

154

DNA methylation changes in inflammatory bowel disease  

PubMed Central

The cause of inflammatory bowel disease, encompassing Crohn’s disease and ulcerative colitis, remains a mystery but evidence is accumulating that complex interactions between the genetic background and the gut microbiota of the host and environmental factors associated with rapid industrialization and westernized life styles may underlie its pathogenesis. Recent epigenetic studies have suggested that interactions between environment and host DNA may play a leading role in the phenotypical expression of both diseases, explaining amongst others the differences in disease expression in monozygotic twins. DNA methylation is the most studied epigenetic modification and during the last decade its correlation to IBD pathogenesis has been well established. Genes from different molecular pathways have been studied but till now there is no standardized database of methylated genes in IBD. Thus, a thorough and in depth study of DNA methylation, its potential relation to IBD and its interaction with the available pharmaceutical armamentarium is of great interest. PMID:24733658

Karatzas, Pantelis S.; Gazouli, Maria; Safioleas, Michael; Mantzaris, Gerasimos J.

2014-01-01

155

Abiotic Formation of Methyl Halides in the Terrestrial Environment  

NASA Astrophysics Data System (ADS)

Methyl chloride and methyl bromide are the most abundant chlorine and bromine containing organic compounds in the atmosphere. Since both compounds have relatively long tropospheric lifetimes they can effectively transport halogen atoms from the Earth's surface, where they are released, to the stratosphere and following photolytic oxidation form reactive halogen gases that lead to the chemical destruction of ozone. Methyl chloride and methyl bromide account for more than 20% of the ozone-depleting halogens delivered to the stratosphere and are predicted to grow in importance as the chlorine contribution to the stratosphere from anthropogenic CFCs decline. Today methyl chloride and methyl bromide originate mainly from natural sources with only a minor fraction considered to be of anthropogenic origin. However, until as recently as 2000 most of the methyl chloride and methyl bromide input to the atmosphere was considered to originate from the oceans, but investigations in recent years have clearly demonstrated that terrestrial sources such as biomass burning, wood-rotting fungi, coastal salt marshes, tropical vegetation and organic matter degradation must dominate the atmospheric budgets of these trace gases. However, many uncertainties still exist regarding strengths of both sources and sinks, as well as the mechanisms of formation of these naturally occurring halogenated gases. A better understanding of the atmospheric budget of both methyl chloride and methyl bromide is therefore required for reliable prediction of future ozone depletion. Biotic and abiotic methylation processes of chloride and bromide ion are considered to be the dominant pathways of formation of these methyl halides in nature. In this presentation I will focus on abiotic formation processes in the terrestrial environment and the potential parameters that control their emissions. Recent advances in our understanding of the abiotic formation pathway of methyl halides will be discussed. This will include a consideration on how stable isotope studies assisted advancements in this subject area. For example, it has been shown that the methoxyl groups of lignin and pectin which together constitute the bulk of the C1 plant pool have a carbon isotope signature significantly depleted in 13C. Plant-derived C1 volatile organic compounds (VOCs) are also highly depleted in 13C compared with Cn+1 VOCs. These observations suggest that the plant methoxyl pool is the predominant source of methyl halides released from senescent and dead plant litter. The distinct 13C depletion of plant methoxyl groups and naturally produced methyl halides may provide a helpful tool in constraining complex environmental processes and therefore improve our understanding of the global cycles of atmospheric methyl halides.

Keppler, F.

2011-12-01

156

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

PubMed Central

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

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

2014-01-01

157

Predicting DNA methylation level across human tissues  

PubMed Central

Differences in methylation across tissues are critical to cell differentiation and are key to understanding the role of epigenetics in complex diseases. In this investigation, we found that locus-specific methylation differences between tissues are highly consistent across individuals. We developed a novel statistical model to predict locus-specific methylation in target tissue based on methylation in surrogate tissue. The method was evaluated in publicly available data and in two studies using the latest IlluminaBeadChips: a childhood asthma study with methylation measured in both peripheral blood leukocytes (PBL) and lymphoblastoid cell lines; and a study of postoperative atrial fibrillation with methylation in PBL, atrium and artery. We found that our method can greatly improve accuracy of cross-tissue prediction at CpG sites that are variable in the target tissue [R2 increases from 0.38 (original R2 between tissues) to 0.89 for PBL-to-artery prediction; from 0.39 to 0.95 for PBL-to-atrium; and from 0.81 to 0.98 for lymphoblastoid cell line-to-PBL based on cross-validation, and confirmed using cross-study prediction]. An extended model with multiple CpGs further improved performance. Our results suggest that large-scale epidemiology studies using easy-to-access surrogate tissues (e.g. blood) could be recalibrated to improve understanding of epigenetics in hard-to-access tissues (e.g. atrium) and might enable non-invasive disease screening using epigenetic profiles. PMID:24445802

Ma, Baoshan; Wilker, Elissa H.; Willis-Owen, Saffron A. G.; Byun, Hyang-Min; Wong, Kenny C. C.; Motta, Valeria; Baccarelli, Andrea A.; Schwartz, Joel; Cookson, William O. C. M.; Khabbaz, Kamal; Mittleman, Murray A.; Moffatt, Miriam F.; Liang, Liming

2014-01-01

158

4-(Di-methyl-amino)-pyridinium trichlorido[4-(di-methyl-amino)-pyridine-?N]cobaltate(II)  

PubMed Central

In the anion of the title compound, (C7H11N2)[CoCl3(C7H10N2)], the CoII ion is coordinated by one N atom from a 4-(di­methyl­amino)­pyridine (DMAP) ligand and three Cl atoms, forming a CoNCl3 polyhedron with a distorted tetra­hedral geometry. In the crystal, cations and anions are linked via weak N—H?Cl and C—H?Cl hydrogen bonds. Double layers of complex anions stack along the b- axis direction, which alternate with double layers of 4-(di­methyl­amino)-pyridinium cations. PMID:24046560

Guenifa, Fatiha; Hadjadj, Nasreddine; Zeghouan, Ouahida; Bendjeddou, Lamia; Merazig, Hocine

2013-01-01

159

Long non-coding RNAs as targets for cytosine methylation  

PubMed Central

Post-synthetic modifications of nucleic acids have long been known to affect their functional and structural properties. For instance, numerous different chemical modifications modulate the structural organization, stability or translation efficiency of tRNAs and rRNAs. In contrast, little is known about modifications of poly(A)RNAs. Here, we demonstrate for the first time that the two well-studied regulatory long non-coding RNAs HOTAIR and XIST are targets of site-specific cytosine methylation. In both XIST and HOTAIR, we found methylated cytosines located within or near functionally important regions that are known to mediate interaction with chromatin-associated protein complexes. We show that cytosine methylation in the XIST A structure strongly affects binding to the chromatin-modifying complex PRC2 in vitro. These results suggest that cytosine methylation may serve as a general strategy to regulate the function of long non-coding RNAs. PMID:23595112

Amort, Thomas; Souliere, Marie F.; Wille, Alexandra; Jia, Xi-Yu; Fiegl, Heidi; Worle, Hildegard; Micura, Ronald; Lusser, Alexandra

2013-01-01

160

Histone methylation in higher plants.  

PubMed

Histone methylation plays a fundamental role in regulating diverse developmental processes and is also involved in silencing repetitive sequences in order to maintain genome stability. The methylation marks are written on lysine or arginine by distinct enzymes, namely, histone lysine methyltransferases (HKMTs) or protein arginine methyltransferases (PRMTs). Once established, the methylation marks are specifically recognized by the proteins that act as readers and are interpreted into specific biological outcomes. Histone methylation status is dynamic; methylation marks can be removed by eraser enzymes, the histone demethylases (HDMs). The proteins responsible for writing, reading, and erasing the methylation marks are known mostly in animals. During the past several years, a growing body of literature has demonstrated the impact of histone methylation on genome management, transcriptional regulation, and development in plants. The aim of this review is to summarize the biochemical, genetic, and molecular action of histone methylation in two plants, the dicot Arabidopsis and the monocot rice. PMID:20192747

Liu, Chunyan; Lu, Falong; Cui, Xia; Cao, Xiaofeng

2010-01-01

161

DNA Methylation and Cancer Diagnosis  

PubMed Central

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

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

2013-01-01

162

Electron paramagnetic resonance spectroscopy with N-methyl-D-glucamine dithiocarbamate iron complexes distinguishes nitric oxide and nitroxyl anion in a redox-dependent manner: applications in identifying nitrogen monoxide products from nitric oxide synthase  

Microsoft Academic Search

Though a large number of studies indicate that nitric oxide synthase (NOS) is responsible for NO production in biological systems, controversy still remains concerning whether NOS directly produces NO. Schmidt et al. (PNAS 93:144492, 1996) proposed that NOS first synthesizes nitroxyl anion (NO?), which is then converted to NO by superoxide dismutase (SOD). With electron paramagnetic resonance spectroscopy using N-methyl-D-glucamine

Yong Xia; A. J Cardounel; Anatoly F Vanin; Jay L Zweier

2000-01-01

163

Epigenetic biomarkers of colorectal cancer: Focus on DNA methylation.  

PubMed

The original theory of the multi-step process of colorectal cancer (CRC), suggesting that the disease resulted from the accumulation of mutations in oncogenes and tumor suppressor genes in colonic mucosa cells, has been largely revised following the observation that epigenetic modifications of several genes occur in the average CRC genome. Therefore, the current opinion is that CRCs are the consequence of the accumulation of both mutations and epigenetic modifications of several genes. This mini-review article focuses on DNA methylation biomarkers in CRC. Recent large-scale DNA methylation studies suggest that CRCs can be divided into at least three-four subtypes according to the frequency of DNA methylation and those of mutations in key CRC genes. Despite hundreds of genes might be epigenetically modified in CRC cells, there is interest in the identification of DNA methylation biomarkers to be used for CRC diagnosis, progression, tendency to tissue invasion and metastasis, prognosis, and response to chemotherapeutic agents. Moreover, DNA methylation largely depends on one-carbon metabolism, the metabolic pathway required for the production of S-adenosylmethionine, the major intracellular methylating agent. Complex interactions are emerging among dietary one-carbon nutrients (folates, vitamin B6, vitamin B12, methionine, and others), their metabolic genes, CRC risk, and DNA methylation profiles in CRC. Moreover, active research is also focused on the possible contribution of folic acid dietary fortification during pregnancy and the possible methylation of CRC-related genes in the offspring. PMID:22202641

Coppedè, Fabio

2014-01-28

164

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)

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.

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

2014-11-01

165

What difference does a methyl group make: pentamethylbenzene?  

PubMed

The crystal structure of pentamethylbenzene has been obtained for the first time with the use of synchrotron radiation, whilst the low-energy spectrum of lattice dynamics, dominated by the methyl group torsions, was obtained using inelastic neutron scattering. The effect of symmetry lowering by the removal of a single methyl group relative to hexamethylbenzene has been investigated, including the role that this plays in the charge-transfer characteristics of complexes formed with tetracyanoethylene. PMID:25212729

Mudge, Matthew; Ng, Boon K; Onie, Catherine Jessica; Bhadbhade, Mohan; Mole, Richard A; Rule, Kirrily C; Stampfl, Anton P J; Stride, John A

2014-12-01

166

Lung cancer: From single-gene methylation to methylome profiling  

Microsoft Academic Search

DNA methylation as part of the epigenetic gene-silencing complex is a universal occurring change in lung cancer. Numerous\\u000a studies investigated methylation of specific genes in primary tumors, in serum or plasma samples, and in specimens from the\\u000a aerodigestive tract epithelium of lung cancer patients. In most studies, single genes or small numbers of genes were analyzed.\\u000a Moreover, it has been

Gerwin Heller; Christoph C. Zielinski; Sabine Zöchbauer-Müller

2010-01-01

167

Synthesis of carbohydrate methyl phosphoramidates.  

PubMed

A two-step route for introducing methyl phosphoramidate moieties onto carbohydrates is reported. The approach uses methyl pivolyl H-phosphonate as the phosphorylating reagent to produce an isolable carbohydrate H-phosphonate intermediate that is then oxidized by a Todd-Atherton reaction. The stability of the product methyl phosphoramidates was subsequently evaluated using various deprotection strategies. PMID:24783964

Ashmus, Roger A; Lowary, Todd L

2014-05-01

168

DIMETHYL METHYLPHOSPHONATE AS METHYLATING REAGENT  

Microsoft Academic Search

The methylating properties of dimethyl methylphosphonate have been investigated. Aromatic mono- and polycarboxylic acids were converted into their methyl esters by heating with dimethyl methylphosphonate. Similarly phenols or amines gave their respective O- or N-methyl derivatives. The sodium salts of sulfinic acids also reacted yielding sulfones in high yield.

Peter Sutter; Claus D. Weis

1978-01-01

169

fullRecord:"sulfo OR methylate" OR "sulfo OR methylated" OR "sulfo OR methylates" OR "sulfo OR methylating" OR "sulfo OR methylation" OR sulfomethylate OR sulfomethylated OR sulfomethylates OR sulfomethylating OR sulfomethylation  

EPA Pesticide Factsheets

Search instead for fullRecord:"sulfo OR methylate" OR "sulfo OR methylated" OR "sulfo OR methylates" OR "sulfo OR methylating" OR "sulfo OR methylation" OR sulfomethylate OR sulfomethylated OR sulfomethylates OR sulfomethylating OR sulfomethylation ?

170

DNA Methylation Screening and Analysis  

PubMed Central

DNA methylation is an epigenetic form of gene regulation that is universally important throughout the life course, especially during in utero and postnatal development. DNA methylation aids in cell cycle regulation and cellular differentiation processes. Previous studies have demonstrated that DNA methylation profiles may be altered by diet and the environment, and that these profiles are especially vulnerable during development. Thus, it is important to understand the role of DNA methylation in developmental governance and subsequent disease progression. A variety of molecular methods exist to assay for global, gene-specific, and epigenome-wide methylation. Here we describe these methods and discuss their relative strengths and limitations. PMID:22669678

Sant, Karilyn E.; Nahar, Muna S.; Dolinoy, Dana C.

2013-01-01

171

Mercury Methylation by Desulfovibrio desulfuricans ND132 in the Presence of Polysulfides  

PubMed Central

The extracellular speciation of mercury may control bacterial uptake and methylation. Mercury-polysulfide complexes have recently been shown to be prevalent in sulfidic waters containing zero-valent sulfur. Despite substantial increases in total dissolved mercury concentration, methylation rates in cultures of Desulfovibrio desulfuricans ND132 equilibrated with cinnabar did not increase in the presence of polysulfides, as expected due to the large size and charged nature of most of the complexes. In natural waters not at saturation with cinnabar, mercury-polysulfide complexes would be expected to shift the speciation of mercury from HgS0(aq) toward charged complexes, thereby decreasing methylation rates. PMID:12406773

Jay, Jenny Ayla; Murray, Karen J.; Gilmour, Cynthia C.; Mason, Robert P.; Morel, Francois M. M.; Roberts, A. Lynn; Hemond, Harold F.

2002-01-01

172

Dynamic DNA methylation across diverse human cell lines and tissues.  

PubMed

As studies of DNA methylation increase in scope, it has become evident that methylation has a complex relationship with gene expression, plays an important role in defining cell types, and is disrupted in many diseases. We describe large-scale single-base resolution DNA methylation profiling on a diverse collection of 82 human cell lines and tissues using reduced representation bisulfite sequencing (RRBS). Analysis integrating RNA-seq and ChIP-seq data illuminates the functional role of this dynamic mark. Loci that are hypermethylated across cancer types are enriched for sites bound by NANOG in embryonic stem cells, which supports and expands the model of a stem/progenitor cell signature in cancer. CpGs that are hypomethylated across cancer types are concentrated in megabase-scale domains that occur near the telomeres and centromeres of chromosomes, are depleted of genes, and are enriched for cancer-specific EZH2 binding and H3K27me3 (repressive chromatin). In noncancer samples, there are cell-type specific methylation signatures preserved in primary cell lines and tissues as well as methylation differences induced by cell culture. The relationship between methylation and expression is context-dependent, and we find that CpG-rich enhancers bound by EP300 in the bodies of expressed genes are unmethylated despite the dense gene-body methylation surrounding them. Non-CpG cytosine methylation occurs in human somatic tissue, is particularly prevalent in brain tissue, and is reproducible across many individuals. This study provides an atlas of DNA methylation across diverse and well-characterized samples and enables new discoveries about DNA methylation and its role in gene regulation and disease. PMID:23325432

Varley, Katherine E; Gertz, Jason; Bowling, Kevin M; Parker, Stephanie L; Reddy, Timothy E; Pauli-Behn, Florencia; Cross, Marie K; Williams, Brian A; Stamatoyannopoulos, John A; Crawford, Gregory E; Absher, Devin M; Wold, Barbara J; Myers, Richard M

2013-03-01

173

Copper(II)- and iron(II)-complexes of methyl 2-(2-aminoethyl)-aminomethyl-pyridine-6-carboxyl-histidinate (AMPHIS), a peptide mimicking the metal-chelating moiety of bleomycin. An ESR investigation.  

PubMed

Methyl 2-(2-aminoethyl)-aminomethyl-pyridine-6-carboxyl-histidinate (AMPHIS), a synthetic analogue of the chelating part of bleomycin (BLM), has been studied for its metal binding properties. Electron spin resonance parameters of AMPHIS-Cu(II) and BLM-Cu(II) have been found to be closely similar likewise spectra of oxygen radicals spin-adducts induced by AMPHIS-Fe(II)-O2 and BLM-Fe(II)-O2 systems. Thus, AMPHIS could constitute a very useful tool for the study of BLM mode of action. PMID:2579645

Hénichart, J P; Bernier, J L; Houssin, R; Lohez, M; Kenani, A; Catteau, J P

1985-02-15

174

Event extraction for DNA methylation  

PubMed Central

Background We consider the task of automatically extracting DNA methylation events from the biomedical domain literature. DNA methylation is a key mechanism of epigenetic control of gene expression and implicated in many cancers, but there has been little study of automatic information extraction for DNA methylation. Results We present an annotation scheme for DNA methylation following the representation of the BioNLP shared task on event extraction, select a set of 200 abstracts including a representative sample of all PubMed citations relevant to DNA methylation, and introduce manual annotation for this corpus marking nearly 3000 gene/protein mentions and 1500 DNA methylation and demethylation events. We retrain a state-of-the-art event extraction system on the corpus and find that automatic extraction of DNA methylation events, the methylated genes, and their methylation sites can be performed at 78% precision and 76% recall. Conclusions Our results demonstrate that reliable extraction methods for DNA methylation events can be created through corpus annotation and straightforward retraining of a general event extraction system. The introduced resources are freely available for use in research from the GENIA project homepage http://www-tsujii.is.s.u-tokyo.ac.jp/GENIA. PMID:22166595

2011-01-01

175

Differential methylation of the TRPA1 promoter in pain sensitivity  

PubMed Central

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

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

176

Hydridomethyl iridium complex  

DOEpatents

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.

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

177

Synthesis and crystal structures of silver(I) complexes of 3(5)-methyl-5(3)-phenyl-1 H -1,2,4-triazole: two isomeric infinite chains coexisting in the same crystal  

Microsoft Academic Search

Reactions of 3(5)-methyl-5(3)-phenyl-1H-1,2,4-triazole (3-Me-5-Ph-tzH) with AgNO3 in the absence\\/presence of NH3 yield a mononuclear [Ag(3-Me-5-Ph-tzH)2]NO3·3H2O (1) and a polymeric [Ag(3-Me-5-Ph-tz)]n (2), respectively. Two structurally different infinite chains, however, with the same formula of AgC9H8N3—one is double-decked and the other single zigzag—coexist in 1:1 ratio in the crystal of 2. As far as we know, 2 is the first binary silver(I)

Wen-Hua Zhang; Xiu-Bao Wei; Ping-Ning Jin; Jun-Feng Kou; Guang Yang

2011-01-01

178

Quantitative reconstruction of leukocyte subsets using DNA methylation  

PubMed Central

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

2014-01-01

179

Methylation signature of lymph node metastases in breast cancer patients  

PubMed Central

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

2012-01-01

180

Electrochemical strategy for sensing DNA methylation and DNA methyltransferase activity.  

PubMed

The present work demonstrates a novel signal-off electrochemical method for the determination of DNA methylation and the assay of methyltransferase activity using the electroactive complex [Ru(NH3)6](3+) (RuHex) as a signal transducer. The assay exploits the electrostatic interactions between RuHex and DNA strands. Thiolated single strand DNA1 was firstly self-assembled on a gold electrode via Au-S bonding, followed by hybridization with single strand DNA2 to form double strand DNA containing specific recognition sequence of DNA adenine methylation MTase and methylation-responsive restriction endonuclease Dpn I. The double strand DNA may adsorb lots of electrochemical species ([Ru(NH3)6](3+)) via the electrostatic interaction, thus resulting in a high electrochemical signal. In the presence of DNA adenine methylation methyltransferase and S-adenosyl-l-methionine, the formed double strand DNA was methylated by DNA adenine methylation methyltransferase, then the double strand DNA can be cleaved by methylation-responsive restriction endonuclease Dpn I, leading to the dissociation of a large amount of signaling probes from the electrode. As a result, the adsorption amount of RuHex reduced, resulting in a decrease in electrochemical signal. Thus, a sensitive electrochemical method for detection of DNA methylation is proposed. The proposed method yielded a linear response to concentration of Dam MTase ranging from 0.25 to 10UmL(-1) with a detection limit of 0.18UmL(-1) (S/N=3), which might promise this method as a good candidate for monitoring DNA methylation in the future. PMID:23473252

Wang, Gang Lin; Zhou, Long Yin; Luo, Hong Qun; Li, Nian Bing

2013-03-20

181

Genomics of CpG methylation in developing and developed zebrafish.  

PubMed

DNA methylation is a dynamic process through which specific chromatin modifications can be stably transmitted from parent to daughter cells. A large body of work has suggested that DNA methylation influences gene expression by silencing gene promoters. However, these conclusions were drawn from data focused mostly on promoter regions. Regarding the entire genome, it is unclear how methylation and gene transcription patterns are related during vertebrate development. To identify the genome-wide distribution of CpG methylation, we created series of high-resolution methylome maps of Danio rerio embryos during development and in mature, differentiated tissues. We found that embryonic and terminal tissues have unique methylation signatures in CpG islands and repetitive sequences. Fully differentiated tissues have increased CpG and LTR methylation and decreased SINE methylation relative to embryonic tissues. Unsupervised clustering analyses reveal that the embryonic and terminal tissues can be classified solely by their methylation patterning. Novel analyses also identify a previously undescribed genome-wide exon methylation signature. We also compared whole genome methylation with genome-wide mRNA expression levels using publicly available RNA-seq datasets. These comparisons revealed previously unrecognized relationships between gene expression, alternative splicing, and exon methylation. Surprisingly, we found that exonic methylation is a better predictor of mRNA expression level than promoter methylation. We also found that transcriptionally skipped exons have significantly less methylation than retained exons. Our integrative analyses reveal highly complex interplay between gene expression, alternative splicing, development, and methylation patterning in zebrafish. PMID:24657902

McGaughey, David M; Abaan, Hatice Ozel; Miller, Ryan M; Kropp, Peter A; Brody, Lawrence C

2014-05-01

182

Different measures of "genome-wide" DNA methylation exhibit unique properties in placental and somatic tissues  

PubMed Central

DNA methylation of CpGs located in two types of repetitive elements—LINE1 (L1) and Alu—is used to assess “global” changes in DNA methylation in studies of human disease and environmental exposure. L1 and Alu contribute close to 30% of all base pairs in the human genome and transposition of repetitive elements is repressed through DNA methylation. Few studies have investigated whether repetitive element DNA methylation is associated with DNA methylation at other genomic regions, or the biological and technical factors that influence potential associations. Here, we assess L1 and Alu DNA methylation by Pyrosequencing of consensus sequences and using subsets of probes included in the Illumina Infinium HumanMethylation27 BeadChip array. We show that evolutionary age and assay method affect the assessment of repetitive element DNA methylation. Additionally, we compare Pyrosequencing results for repetitive elements to average DNA methylation of CpG islands, as assessed by array probes classified into strong, weak and non-islands. We demonstrate that each of these dispersed sequences exhibits different patterns of tissue-specific DNA methylation. Correlation of DNA methylation suggests an association between L1 and weak CpG island DNA methylation in some of the tissues examined. We caution, however, that L1, Alu and CpG island DNA methylation are distinct measures of dispersed DNA methylation and one should not be used in lieu of another. Analysis of DNA methylation data is complex and assays may be influenced by environment and pathology in different or complementary ways. PMID:22531475

Price, E. Magda; Cotton, Allison M.; Penaherrera, Maria S.; McFadden, Deborah E.; Kobor, Michael S.; Robinson, Wendy

2012-01-01

183

Protective Actions of Aspirin-Triggered (17R) Resolvin D1 and Its Analogue, 17R-Hydroxy-19-Para-Fluorophenoxy-Resolvin D1 Methyl Ester, in C5a-Dependent IgG Immune Complex-Induced Inflammation and Lung Injury.  

PubMed

Increasing evidence suggests that the novel anti-inflammatory and proresolving mediators such as the resolvins play an important role during inflammation. However, the functions of these lipid mediators in immune complex-induced lung injury remain unknown. In this study, we determined the role of aspirin-triggered resolvin D1 (AT-RvD1) and its metabolically stable analog, 17R-hydroxy-19-para-fluorophenoxy-resolvin D1 methyl ester (p-RvD1), in IgG immune complex-induced inflammatory responses in myeloid cells and injury in the lung. We show that lung vascular permeability in the AT-RvD1- or p-RvD1-treated mice was significantly reduced when compared with values in mice receiving control vesicle during the injury. Furthermore, i.v. administration of either AT-RvD1 or p-RvD1 caused significant decreases in the bronchoalveolar lavage fluid contents of neutrophils, inflammatory cytokines, and chemokines. Of interest, AT-RvD1 or p-RvD1 significantly reduced bronchoalveolar lavage fluid complement C5a level. By EMSA, we demonstrate that IgG immune complex-induced activation of NF-?B and C/EBP? transcription factors in the lung was significantly inhibited by AT-RvD1 and p-RvD1. Moreover, AT-RvD1 dramatically mitigates IgG immune complex-induced NF-?B and C/EBP activity in alveolar macrophages. Also, secretion of TNF-?, IL-6, keratinocyte cell-derived chemokine, and MIP-1? from IgG immune complex-stimulated alveolar macrophages or neutrophils was significantly decreased by AT-RvD1. These results suggest a new approach to the blocking of immune complex-induced inflammation. PMID:25172497

Tang, Huifang; Liu, Yanlan; Yan, Chunguang; Petasis, Nicos A; Serhan, Charles N; Gao, Hongwei

2014-10-01

184

Cyclopentadienyl ring methylation and its effect on Si-H bond activation in (. eta. sup 5 -C sub 5 H sub 5 minus n (CH sub f3 ) sub n )Mn(CO) sub 2 HSiH(C sub 6 H sub 5 ) sub 2 (n = 0,1,5) complexes  

SciTech Connect

The He I photoelectron spectra of ({eta}{sup 5}-C{sub 5}H{sub 5})Mn(CO){sub 2}HSiHPh{sub 2}, ({eta}{sup 5}-C{sub 5}H{sub 4}CH{sub 3})Mn(CO){sub 2}HSiHPh{sub 2} and ({eta}{sup 5}-C{sub 5}(CH{sub 3}){sub 5})Mn(CO){sub 2}HSiHPh{sub 2} (Ph is C{sub 6}H{sub 5}) are compared to observe the effect of cyclopentadienyl ring methylation on the extent of Si-H bond interaction with the transition metal in these complexes.

Lichtenberger, D.L.; Rai-Chaudhuri, A. (Univ. of Arizona, Tucson (USA))

1990-05-01

185

Histone methylation marks play important roles in predicting the methylation status of CpG islands  

E-print Network

Histone methylation marks play important roles in predicting the methylation status of CpG islands CpG island Histone methylation Epigenetics a b s t r a c t The methylation status of CpG islands histone methylation marks to predict the methylation status of CpG islands, and improved the accuracy

186

Genetic analysis of DNA methylation and gene expression levels in whole blood of healthy human subjects  

PubMed Central

Background The predominant model for regulation of gene expression through DNA methylation is an inverse association in which increased methylation results in decreased gene expression levels. However, recent studies suggest that the relationship between genetic variation, DNA methylation and expression is more complex. Results Systems genetic approaches for examining relationships between gene expression and methylation array data were used to find both negative and positive associations between these levels. A weighted correlation network analysis revealed that i) both transcriptome and methylome are organized in modules, ii) co-expression modules are generally not preserved in the methylation data and vice-versa, and iii) highly significant correlations exist between co-expression and co-methylation modules, suggesting the existence of factors that affect expression and methylation of different modules (i.e., trans effects at the level of modules). We observed that methylation probes associated with expression in cis were more likely to be located outside CpG islands, whereas specificity for CpG island shores was present when methylation, associated with expression, was under local genetic control. A structural equation model based analysis found strong support in particular for a traditional causal model in which gene expression is regulated by genetic variation via DNA methylation instead of gene expression affecting DNA methylation levels. Conclusions Our results provide new insights into the complex mechanisms between genetic markers, epigenetic mechanisms and gene expression. We find strong support for the classical model of genetic variants regulating methylation, which in turn regulates gene expression. Moreover we show that, although the methylation and expression modules differ, they are highly correlated. PMID:23157493

2012-01-01

187

Neural tube defects, folic acid and methylation.  

PubMed

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

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

2013-09-01

188

DNA methylation and human disease  

Microsoft Academic Search

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

Keith D. Robertson

2005-01-01

189

Molecular Structure of Methyl benzoate  

NSDL National Science Digital Library

Methyl benzoate is used mainly as a perfume; it has a very pleasant smell and mixes well with scents of ylang ylang, musk, rose, and geranium. Methyl benzoate also acts as a solvent for cellulose esters, as a dying carrier, disinfectant additive, penetrating agent, and as a pesticide.

2002-10-11

190

Hydridomethyl iridium complex  

SciTech Connect

This patent describes a hydridomethyl complex of the formula: CpIr(P(R{sub 1}){sub 3})HMe. Cp represents a cyclopentadienyl or alkyl cyclopentadienyl radical; Ir represents an iridium atom; P represents a phosphorus atom; R{sub 1} represents an alkyl group; and Me represents a methyl group.

Bergman, R.G; Buchanan, J.M.; Stryker, J.M.; Wax, M.J.

1989-07-18

191

Novel mixed ligand complexes of bioactive Schiff base (E)-4-(phenyl (phenylimino) methyl) benzene-1,3-diol and 2-aminophenol/2-aminobenzoic acid: synthesis, spectral characterization, antimicrobial and nuclease studies.  

PubMed

A novel bidentate Schiff base ligand has been synthesized using 2,4-dihydroxybenzophenone and aniline. Its mixed ligand complexes of MAB type [M=Mn(II), Co(II), Ni(II), Cu(II) and Zn(II); HA=Schiff base and B=2-aminophenol/2-aminobenzoic acid] have been synthesized and characterized on the basis of spectral data UV-Vis, IR, (1)H NMR, FAB-Mass, EPR, SEM and magnetic studies. All the complexes were soluble in DMF and DMSO. Elemental analysis and molar conductance values indicate that the complexes are non-electrolytes. HA binds with M(II) ions through azomethine and deprotonated phenolic group and B binds through the primary amine group and deprotonated phenolic/carboxylic groups. Using FAB-Mass the cleavage pattern of the ligand (HA) has been established. All the complexes adopt octahedral geometry around the metal ions. It has been confirmed with the help of UV-Vis, IR, (1)H NMR and FAB-Mass spectral data. DNA binding activities of the complexes 1d and 2d are studied by UV-Vis spectroscopy and cleavage studies of Schiff base ligand and its complexes 1d and 2d have been by agarose gel electrophoresis method. In vitro biological activities of the free ligand (HA) and their metal complexes (1a-1e and 2a-2e) were screened against few bacteria, Escherichia coli, Staphylococcus saphyphiticus, Staphylococcus aureus, Pseudomonas aeruginosa and fungi Aspergillus niger, Enterobacter species, Candida albicans by well diffusion technique. PMID:23981416

Subbaraj, P; Ramu, A; Raman, N; Dharmaraja, J

2014-01-01

192

Methods of DNA methylation detection  

NASA Technical Reports Server (NTRS)

The present invention provides for methods of DNA methylation detection. The present invention provides for methods of generating and detecting specific electronic signals that report the methylation status of targeted DNA molecules in biological samples.Two methods are described, direct and indirect detection of methylated DNA molecules in a nano transistor based device. In the direct detection, methylated target DNA molecules are captured on the sensing surface resulting in changes in the electrical properties of a nano transistor. These changes generate detectable electronic signals. In the indirect detection, antibody-DNA conjugates are used to identify methylated DNA molecules. RNA signal molecules are generated through an in vitro transcription process. These RNA molecules are captured on the sensing surface change the electrical properties of nano transistor thereby generating detectable electronic signals.

Maki, Wusi Chen (Inventor); Filanoski, Brian John (Inventor); Mishra, Nirankar (Inventor); Rastogi, Shiva (Inventor)

2010-01-01

193

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

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...

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

2014-01-01

194

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...

195

Factors underlying variable DNA methylation in a human community cohort.  

PubMed

Epigenetics is emerging as an attractive mechanism to explain the persistent genomic embedding of early-life experiences. Tightly linked to chromatin, which packages DNA into chromosomes, epigenetic marks primarily serve to regulate the activity of genes. DNA methylation is the most accessible and characterized component of the many chromatin marks that constitute the epigenome, making it an ideal target for epigenetic studies in human populations. Here, using peripheral blood mononuclear cells collected from a community-based cohort stratified for early-life socioeconomic status, we measured DNA methylation in the promoter regions of more than 14,000 human genes. Using this approach, we broadly assessed and characterized epigenetic variation, identified some of the factors that sculpt the epigenome, and determined its functional relation to gene expression. We found that the leukocyte composition of peripheral blood covaried with patterns of DNA methylation at many sites, as did demographic factors, such as sex, age, and ethnicity. Furthermore, psychosocial factors, such as perceived stress, and cortisol output were associated with DNA methylation, as was early-life socioeconomic status. Interestingly, we determined that DNA methylation was strongly correlated to the ex vivo inflammatory response of peripheral blood mononuclear cells to stimulation with microbial products that engage Toll-like receptors. In contrast, our work found limited effects of DNA methylation marks on the expression of associated genes across individuals, suggesting a more complex relationship than anticipated. PMID:23045638

Lam, Lucia L; Emberly, Eldon; Fraser, Hunter B; Neumann, Sarah M; Chen, Edith; Miller, Gregory E; Kobor, Michael S

2012-10-16

196

Synthesis, structure and catalase-like activity of dimanganese(III) complexes of 1,5-bis(X-salicylidenamino)pentan-3-ol (X = 3- and 5-methyl). Influence of phenyl-ring substituents on catalytic activity.  

PubMed

The diMn(III) complexes [Mn2(5-Me-salpentO)(mu-MeO)(mu-AcO)(H2O)Br] (1) and [Mn2(3-Me-salpentO)(mu-MeO)(mu-AcO)(MeOH)2]Br (2), where salpentOH = 1,5-bis(salicylidenamino)pentan-3-ol, were synthesised and structurally characterized. The two complexes include a bis(micro-alkoxo)(micro-acetato) triply-bridged diMn(III) core with an Mn...Mn separation of 2.93-2.94 A, the structure of which is retained upon dissolution. Complexes 1 and 2 show catalytic activity toward disproportionation of H2O2, with first-order dependence on the catalyst, and saturation kinetics on [H2O2], in methanol and DMF. In DMF, the two complexes are able to disproportionate at least 1500 eq. of H2O2 without significant decomposition, while in methanol, they rapidly lose activity with formation of a non-coupled Mn(II) species. Electrospray ionisation mass spectrometry, EPR and UV/vis spectroscopy used to monitor the reaction suggest that the major active form of the catalyst occurs in the Mn2(III) oxidation state during cycling. The correlation between log(k(cat)) and the redox potentials of 1, 2 and analogous complexes of other X-salpentOH derivatives indicates that, in this series, the oxidation of the catalyst is probably the rate-limiting step in the catalytic cycle. It is also noted that formation of the catalyst-peroxide adduct is more sensitive to steric effects in DMF than in methanol. Overall, kinetics and spectroscopic studies of H2O2 dismutation by these complexes converge at a catalytic cycle that involves the Mn2(III) and Mn2(IV) oxidation states. PMID:17077889

Moreno, Diego; Palopoli, Claudia; Daier, Verónica; Shova, Sergiu; Vendier, Laure; Sierra, Manuel González; Tuchagues, Jean-Pierre; Signorella, Sandra

2006-11-21

197

Accounting for Population Stratification in DNA Methylation Studies  

PubMed Central

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

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

198

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles  

E-print Network

The palladium-catalyzed nucleophilic substitution of (coumarinyl)methyl acetates is described. The reaction proceeds though a palladium ?-benzyl-like complex and allows for many different types of C-, N-, and S-nucleophiles to be regioselectively...

Chattopadhyay, Kalicharan; Fenster, Erik; Grenning, Alexander James; Tunge, Jon A.

2012-07-27

199

Methyl-CpG binding proteins: specialized transcriptional repressors or structural components of chromatin?  

PubMed Central

DNA methylation is an epigenetic modification that is implicated in transcriptional silencing. It is becoming increasingly clear that both correct levels and proper interpretation of DNA methylation are important for normal development and function of many organisms, including humans. In this review we focus on recent advances in understanding of how proteins that bind to methylated DNA recognize their binding sites and translate the DNA methylation signal into functional states of chromatin. Although the function of methyl-CpG binding proteins in transcriptional repression has been attributed to their cooperation with corepressor complexes, additional roles for these proteins in chromatin compaction and spatial organization of nuclear domains have also been proposed. Finally, we provide a brief overview of how methyl-CpG proteins contribute to human disease processes such as Rett Syndrome and cancer. PMID:18322651

Clouaire, Thomas; Stancheva, Irina

2009-01-01

200

Epigenome-wide inheritance of cytosine methylation variants in a recombinant inbred population  

PubMed Central

Cytosine DNA methylation is one avenue for passing information through cell divisions. Here, we present epigenomic analyses of soybean recombinant inbred lines (RILs) and their parents. Identification of differentially methylated regions (DMRs) revealed that DMRs mostly cosegregated with the genotype from which they were derived, but examples of the uncoupling of genotype and epigenotype were identified. Linkage mapping of methylation states assessed from whole-genome bisulfite sequencing of 83 RILs uncovered widespread evidence for local methylQTL. This epigenomics approach provides a comprehensive study of the patterns and heritability of methylation variants in a complex genetic population over multiple generations, paving the way for understanding how methylation variants contribute to phenotypic variation. PMID:23739894

Schmitz, Robert J.; He, Yupeng; Valdes-Lopez, Oswaldo; Khan, Saad M.; Joshi, Trupti; Urich, Mark A.; Nery, Joseph R.; Diers, Brian; Xu, Dong; Stacey, Gary; Ecker, Joseph R.

2013-01-01

201

DNA methylation and gene expression.  

PubMed Central

A large body of evidence demonstrates that DNA methylation plays a role in gene regulation in animal cells. Not only is there a correlation between gene transcription and undermethylation, but also transfection experiments clearly show that the presence of methyl moieties inhibits gene expression in vivo. Furthermore, gene activation can be induced by treatment of cells with 5-azacytidine, a potent demethylating agent. Methylation appears to influence gene expression by affecting the interactions with DNA of both chromatin proteins and specific transcription factors. Although methylation patterns are very stable in somatic cells, the early embryo is characterized by large alterations in DNA modification. New methodologies are now becoming available for studying methylation at this stage and in the germ line. During development, tissue-specific genes undergo demethylation in their tissue of expression. In tissue culture cells this process is highly specific and appears to involve an active mechanism which takes place in the absence of DNA replication. The X chromosome undergoes inactivation during development; this is accompanied by de novo methylation, which appears necessary to stably maintain its silent state. As opposed to the programmed changes in DNA methylation which occur in vivo, immortalized tissue culture cells demonstrate alterations in DNA modification which take place over a long time scale and which appear to be the result of selective pressures present during the growth of these cells in culture. PMID:1943996

Razin, A; Cedar, H

1991-01-01

202

Molecular Structure of Methyl mercaptan  

NSDL National Science Digital Library

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.

2003-06-03

203

Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing  

Microsoft Academic Search

Polycomb group (PcG) proteins play important roles in maintaining the silent state of HOX genes. Recent studies have implicated histone methylation in long-term gene silencing. However, a connection between PcG-mediated gene silencing and histone methylation has not been established. Here we report the purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex. We demonstrate

Ru Cao; Liangjun Wang; Hengbin Wang; Li Xia; Hediye Erdjument-Bromage; Paul Tempst; Richard S. Jones; Yi Zhang

2002-01-01

204

Rice Allelopathy Induced by Methyl Jasmonate and Methyl Salicylate  

Microsoft Academic Search

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

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

2007-01-01

205

Density functional theory study of oxygen-atom insertion into metal-methyl bonds of iron(II), ruthenium(II), and osmium(II) complexes: study of metal-mediated C-O bond formation.  

PubMed

Metal-mediated C-O bond formation is a key step in hydrocarbon oxygenation catalytic cycles; however, few examples of this reaction have been reported for low-oxidation-state complexes. Oxygen insertion into a metal-carbon bond of Cp*M(CO)(OPy)R (Cp* = ?(5)-pentamethylcyclopentadienyl; R = Me, Ph; OPy = pyridine-N-oxide; M = Fe, Ru, Os) was analyzed via density functional theory calculations. Oxygen-atom insertions through a concerted single-step organometallic Baeyer-Villiger pathway and a two-step pathway via a metal-oxo intermediate were studied; calculations predict that the former pathway was lower in energy. The results indicated that functionalization of M-R to M-OR (R = Me, Ph) is plausible using iron(II) complexes. Starting from Cp*Fe(CO)(OPy)Ph, the intermediate Fe-oxo showed oxyl character and, thus, is best considered an Fe(III)O(•-) complex. Oxidation of the ?-acid ancillary ligand CO was facile. Substitutions of CO with dimethylamide and NH3 were calculated to lower the activation barrier by ?1-2 kcal/mol for formation of the Fe(III)O(•-) intermediate, whereas a chloride ligand raised the activation barrier to 26 kcal/mol from 22.9 kcal/mol. PMID:24571202

Pardue, Daniel B; Mei, Jiajun; Cundari, Thomas R; Gunnoe, T Brent

2014-03-17

206

Study of the inclusion processes of styrene and ?-methyl-styrene in ?-cyclodextrin  

NASA Astrophysics Data System (ADS)

The inclusion complexes of styrene and ?-methyl-styrene with ?-cyclodextrin (?-CD) were investigated by using [ 1H] NMR titration in solution and X-ray diffraction (XRD) analysis, thermo-gravimetric analysis (TGA), elemental analysis (EA) in the solid state. The inclusion process has been studied by using PM3 quantum-mechanical semi-empirical method. The calculated results are in agreed with the experimental data. All results show that ?-methyl-styrene has stronger interaction with ?-cyclodextrin than styrene does, so the complex of ?-CD-?-methyl-styrene is more stable.

Cao, Yujuan; Xiao, Xiaohua; Ji, Shengfu; Lu, Runhua; Guo, Qingxiang

2004-03-01

207

Phototransformation of herbicide metsulfuron methyl.  

PubMed

Phototransformation of the herbicide metsulfuron methyl was investigated on glass surface under sunlight and ultraviolet (UV) light and compared with dark condition. The half-lives of metsulfuron methyl under UV light and sunlight were found to be 0.5 and 7.8 days respectively. Rate of phototransformation followed first order kinetics with significant correlation coefficient. The major photoproducts were identified as methyl-2-sulfonyl-amino-benzoate, 2-amino-6-methoxy-4-methyltriazine and saccharin (O-sulfobenzoimide). Various metabolites from this study were identified by high performance liquid chromatography (HPLC). Authentic samples required for HPLC comparison were prepared in laboratory and characterized on the basis of nuclear magnetic resonance (NMR) and infra red (IR) spectral data. These metabolites were also identified from metsulfuron methyl treated wheat field soil. PMID:18665987

Paul, Rupak; Singh, Shashi B

2008-08-01

208

Naturally occurring methyl salicylate glycosides.  

PubMed

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

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

2014-01-01

209

Nickel-Catalyzed Reductive Methylation of Alkyl Halides and Acid Chlorides with Methyl p-Tosylate.  

PubMed

Methylation of unactivated alkyl halides and acid chlorides under Ni-catalyzed reductive coupling conditions led to efficient formation of methylated alkanes and ketones using methyl p-methyl tosylate as the methylation reagent. Moderate to excellent coupling yields as well as excellent functional group tolerance were observed under the present mild and easy-to-operate reaction conditions. PMID:25333482

Liang, Zhuye; Xue, Weichao; Lin, Kunhua; Gong, Hegui

2014-11-01

210

Global Methylation in Exposure Biology and Translational Medical Science  

PubMed Central

Background: Many groups are actively investigating how the epigenetic state relates to environmental exposures and development of disease, including cancer. There are myriad choices for capturing and measuring the epigenetic state of a tissue, ranging from assessing the total methyl-CpG content to array-based platforms that simultaneously probe hundreds of thousands of CpG loci. There is an emerging literature that uses CpG methylation at repetitive sequences, including LINE-1 (long interspersed nuclear element-1) elements, to capture the epigenomic state. Objectives: We explored the complexity of using CpG methylation at repetitive sequences in epidemiology and translational medical research and suggest needed avenues of research to clarify its meaning and utility. Conclusions: Among the most urgent avenues of research is the need for prospective studies to eliminate the possibilities of reverse causality, and development of new LINE-1 assays that capture both class of LINE-1 element and copy number. PMID:21669556

Marsit, Carmen J.; Kelsey, Karl T.

2011-01-01

211

DNA methylation in inflammatory bowel disease and beyond  

PubMed Central

Inflammatory bowel disease (IBD) is a consequence of the complex, dysregulated interplay between genetic predisposition, environmental factors, and microbial composition in the intestine. Despite a great advancement in identifying host-susceptibility genes using genome-wide association studies (GWAS), the majority of IBD cases are still underrepresented. The immediate challenge in post-GWAS era is to identify other causative genetic factors of IBD. DNA methylation has received increasing attention for its mechanistical role in IBD pathogenesis. This stable, yet dynamic DNA modification, can directly affect gene expression that have important implications in IBD development. The alterations in DNA methylation associated with IBD are likely to outset as early as embryogenesis all the way until old-age. In this review, we will discuss the recent advancement in understanding how DNA methylation alterations can contribute to the development of IBD. PMID:23983426

Low, Daren; Mizoguchi, Atsushi; Mizoguchi, Emiko

2013-01-01

212

Insight into the amplification by methylated urea of the anion specificity of macromolecules.  

PubMed

Methylated urea and sugar are chaotropic and kosmotropic osmolytes, respectively. In the present work, we have investigated the specific anion effect on the lower critical solution temperature (LCST) behavior of poly(N-isopropylacrylamide) (PNIPAM) in the presence of methylated urea or sugars. Differential scanning calorimetry studies revealed that tetramethylurea can adsorb onto the PNIPAM surface, but glucose is excluded from the PNIPAM surface. The specific anion effect on the LCST behavior of PNIPAM is amplified by methylated urea but not by sugars. The amplification of the anion specificity by methylated urea is attributed to an increased difference in the anion-specific polarization of hydrogen bonds, induced by the formation of PNIPAM/methylated urea complexes via hydrophobic interactions. As the number of methyl groups on the methylated urea increases, the extent of amplification of the anion specificity increases due to increasing hydrophobic interactions between the PNIPAM and methylated urea. Additionally, no amplification of the anion specificity is observed in the presence of urea because a PNIPAM/urea complex cannot be formed via hydrophobic interactions. PMID:24667999

Liu, Lvdan; Shi, Yang; Liu, Chang; Wang, Tao; Liu, Guangming; Zhang, Guangzhao

2014-04-28

213

Genome-wide DNA methylation analysis in cohesin mutant human cell lines  

PubMed Central

The cohesin complex has recently been shown to be a key regulator of eukaryotic gene expression, although the mechanisms by which it exerts its effects are poorly understood. We have undertaken a genome-wide analysis of DNA methylation in cohesin-deficient cell lines from probands with Cornelia de Lange syndrome (CdLS). Heterozygous mutations in NIPBL, SMC1A and SMC3 genes account for ?65% of individuals with CdLS. SMC1A and SMC3 are subunits of the cohesin complex that controls sister chromatid cohesion, whereas NIPBL facilitates cohesin loading and unloading. We have examined the methylation status of 27 578 CpG dinucleotides in 72 CdLS and control samples. We have documented the DNA methylation pattern in human lymphoblastoid cell lines (LCLs) as well as identified specific differential DNA methylation in CdLS. Subgroups of CdLS probands and controls can be classified using selected CpG loci. The X chromosome was also found to have a unique DNA methylation pattern in CdLS. Cohesin preferentially binds to hypo-methylated DNA in control LCLs, whereas the differential DNA methylation alters cohesin binding in CdLS. Our results suggest that in addition to DNA methylation multiple mechanisms may be involved in transcriptional regulation in human cells and in the resultant gene misexpression in CdLS. PMID:20448023

Liu, Jinglan; Zhang, Zhe; Bando, Masashige; Itoh, Takehiko; Deardorff, Matthew A.; Li, Jennifer R.; Clark, Dinah; Kaur, Maninder; Tatsuro, Kondo; Kline, Antonie D.; Chang, Celia; Vega, Hugo; Jackson, Laird G.; Spinner, Nancy B.; Shirahige, Katsuhiko; Krantz, Ian D.

2010-01-01

214

Anticancer Activity of Methyl-Substituted Oxaliplatin Analogs†  

PubMed Central

Oxaliplatin is successfully used in systemic cancer therapy. However, resistance development and severe adverse effects are limiting factors for curative cancer treatment with oxaliplatin. The purpose of this study was to comparatively investigate in vitro and in vivo anticancer properties as well as the adverse effects of two methyl-substituted enantiomerically pure oxaliplatin analogs [[(1R,2R,4R)-4-methyl-1,2-cyclohexanediamine] oxalatoplatinum(II) (KP1537), and [(1R,2R,4S)-4-methyl-1,2-cyclohexanediamine]oxalatoplatinum(II) (KP1691)] and to evaluate the impact of stereoisomerism. Although the novel oxaliplatin analogs demonstrated in multiple aspects activities comparable with those of the parental compound, several key differences were discovered. The analogs were characterized by reduced vulnerability to resistance mechanisms such as p53 mutations, reduced dependence on immunogenic cell death induction, and distinctly attenuated adverse effects including weight loss and cold hyperalgesia. Stereoisomerism of the substituted methyl group had a complex and in some aspects even contradictory impact on drug accumulation and anticancer activity both in vitro and in vivo. To summarize, methyl-substituted oxaliplatin analogs harbor improved therapeutic characteristics including significantly reduced adverse effects. Hence, they might be promising metal-based anticancer drug candidates for further (pre)clinical evaluation. PMID:22331606

Jungwirth, Ute; Xanthos, Dimitris N.; Gojo, Johannes; Bytzek, Anna K.; Korner, Wilfried; Heffeter, Petra; Abramkin, Sergey A.; Jakupec, Michael A.; Hartinger, Christian G.; Windberger, Ursula; Galanski, Markus; Keppler, Bernhard K.; Berger, Walter

2012-01-01

215

DNA Methylation Modifications Associated with Chronic Fatigue Syndrome  

PubMed Central

Chronic Fatigue Syndrome (CFS), also known as myalgic encephalomyelitis, is a complex multifactorial disease that is characterized by the persistent presence of fatigue and other particular symptoms for a minimum of 6 months. Symptoms fail to dissipate after sufficient rest and have major effects on the daily functioning of CFS sufferers. CFS is a multi-system disease with a heterogeneous patient population showing a wide variety of functional disabilities and its biological basis remains poorly understood. Stable alterations in gene function in the immune system have been reported in several studies of CFS. Epigenetic modifications have been implicated in long-term effects on gene function, however, to our knowledge, genome-wide epigenetic modifications associated with CFS have not been explored. We examined the DNA methylome in peripheral blood mononuclear cells isolated from CFS patients and healthy controls using the Illumina HumanMethylation450 BeadChip array, controlling for invariant probes and probes overlapping polymorphic sequences. Gene ontology (GO) and network analysis of differentially methylated genes was performed to determine potential biological pathways showing changes in DNA methylation in CFS. We found an increased abundance of differentially methylated genes related to the immune response, cellular metabolism, and kinase activity. Genes associated with immune cell regulation, the largest coordinated enrichment of differentially methylated pathways, showed hypomethylation within promoters and other gene regulatory elements in CFS. These data are consistent with evidence of multisystem dysregulation in CFS and implicate the involvement of DNA modifications in CFS pathology. PMID:25111603

de Vega, Wilfred C.; Vernon, Suzanne D.; McGowan, Patrick O.

2014-01-01

216

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

PubMed Central

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

2010-01-01

217

Corruption of the Intra-Gene DNA Methylation Architecture Is a Hallmark of Cancer  

PubMed Central

Epigenetic processes - including DNA methylation - are increasingly seen as having a fundamental role in chronic diseases like cancer. It is well known that methylation levels at particular genes or loci differ between normal and diseased tissue. Here we investigate whether the intra-gene methylation architecture is corrupted in cancer and whether the variability of levels of methylation of individual CpGs within a defined gene is able to discriminate cancerous from normal tissue, and is associated with heterogeneous tumour phenotype, as defined by gene expression. We analysed 270985 CpGs annotated to 18272 genes, in 3284 cancerous and 681 normal samples, corresponding to 14 different cancer types. In doing so, we found novel differences in intra-gene methylation pattern across phenotypes, particularly in those genes which are crucial for stem cell biology; our measures of intra-gene methylation architecture are a better determinant of phenotype than measures based on mean methylation level alone (K-S test in all 14 diseases tested). These per-gene methylation measures also represent a considerable reduction in complexity, compared to conventional per-CpG beta-values. Our findings strongly support the view that intra-gene methylation architecture has great clinical potential for the development of DNA-based cancer biomarkers. PMID:23874574

Bartlett, Thomas E.; Zaikin, Alexey; Olhede, Sofia C.; West, James; Teschendorff, Andrew E.; Widschwendter, Martin

2013-01-01

218

Corruption of the intra-gene DNA methylation architecture is a hallmark of cancer.  

PubMed

Epigenetic processes--including DNA methylation--are increasingly seen as having a fundamental role in chronic diseases like cancer. It is well known that methylation levels at particular genes or loci differ between normal and diseased tissue. Here we investigate whether the intra-gene methylation architecture is corrupted in cancer and whether the variability of levels of methylation of individual CpGs within a defined gene is able to discriminate cancerous from normal tissue, and is associated with heterogeneous tumour phenotype, as defined by gene expression. We analysed 270985 CpGs annotated to 18272 genes, in 3284 cancerous and 681 normal samples, corresponding to 14 different cancer types. In doing so, we found novel differences in intra-gene methylation pattern across phenotypes, particularly in those genes which are crucial for stem cell biology; our measures of intra-gene methylation architecture are a better determinant of phenotype than measures based on mean methylation level alone (K-S test [Formula: see text] in all 14 diseases tested). These per-gene methylation measures also represent a considerable reduction in complexity, compared to conventional per-CpG beta-values. Our findings strongly support the view that intra-gene methylation architecture has great clinical potential for the development of DNA-based cancer biomarkers. PMID:23874574

Bartlett, Thomas E; Zaikin, Alexey; Olhede, Sofia C; West, James; Teschendorff, Andrew E; Widschwendter, Martin

2013-01-01

219

Doubly pyrazolate-bridged dinuclear complexes of a highly constrained bis-terdentate ligand: observation of a [high spin-low spin] state for [Fe(II)2(PMAP)2][SbF6]2.2.25(C3H8O) (PMAP = 3,5-bis{[N-(2-pyridylmethyl)amino]-methyl}-1H-pyrazolate).  

PubMed

The bis-terdentate pyrazole-based ligand 3,5-bis{[N-(2-pyridylmethyl)amino]methyl}-1H-pyrazole (PMAPH) was synthesized from 3,5-(1H)-pyrazoledicarbaldehyde and 2 equiv of 2-(aminomethyl)pyridine, using sodium borohydride to reduce the imine intermediate. A family of dinuclear complexes [M(II/III)(2)(PMAP)(2)](X)(2/4) was prepared by 2:2:2 reactions of MX(2)/PMAPH/base, where M = Zn(II) and X = BF(4)(-); M = Cu(II) and X = ClO(4)(-), BF(4)(-), OAc(-), NO(3)(-); M = Ni(II), Fe(III) and X = ClO(4)(-), BF(4)(-); M = Fe(II) and X = SbF(6)(-). Single crystal X-ray structure determinations on four complexes: [Fe(III)(2)(PMAP)(2)](BF(4))(4).2MeCN, [Ni(II)(2)(PMAP)(2)](ClO(4))(2).2MeCN, [Cu(II)(2)(PMAP)(2)](BF(4))(2).2MeCN, and [Zn(II)(2)(PMAP)(2)](BF(4))(2).2MeCN confirmed a dinuclear doubly pyrazolate-bridged structure for each. The two metal centers in these complexes have similar N(6) distorted octahedral coordination spheres, with all donors provided by the two deprotonated PMAP(-) ligands. Magnetic measurements reveal intra-dinuclear antiferromagnetic interactions for both the M = Cu(II) and Ni(II) [M(2)(PMAP)(2)](BF(4))(4) complexes, with J/k(B) = -252(2) K and J/k(B) = -24.7(2) K (H = -2JS(M)S(M)), respectively. Interestingly magnetic measurements show that the complex [Fe(2)(II)(PMAP)(2)](SbF(6))(2).2.25(C(3)H(8)O) is in a mixed high spin (HS)-low spin (LS) spin state, [HS-LS], from 300 to 1.8 K, with no sign of spin crossover to a fully low spin form [LS-LS] even at 1.8 K. PMID:20394410

Noble, Andy; Olguín, Juan; Clérac, Rodolphe; Brooker, Sally

2010-05-17

220

Alcohol, DNA Methylation, and Cancer  

PubMed Central

Cancer is one of the most significant diseases associated with chronic alcohol consumption, and chronic drinking is a strong risk factor for cancer, particularly of the upper aerodigestive tract, liver, colorectum, and breast. Several factors contribute to alcohol-induced cancer development (i.e., carcinogenesis), including the actions of acetaldehyde, the first and primary metabolite of ethanol, and oxidative stress. However, increasing evidence suggests that aberrant patterns of DNA methylation, an important epigenetic mechanism of transcriptional control, also could be part of the pathogenetic mechanisms that lead to alcohol-induced cancer development. The effects of alcohol on global and local DNA methylation patterns likely are mediated by its ability to interfere with the availability of the principal biological methyl donor, S-adenosylmethionine (SAMe), as well as pathways related to it. Several mechanisms may mediate the effects of alcohol on DNA methylation, including reduced folate levels and inhibition of key enzymes in one-carbon metabolism that ultimately lead to lower SAMe levels, as well as inhibition of activity and expression of enzymes involved in DNA methylation (i.e., DNA methyltransferases). Finally, variations (i.e., polymorphisms) of several genes involved in one-carbon metabolism also modulate the risk of alcohol-associated carcinogenesis. PMID:24313162

Varela-Rey, Marta; Woodhoo, Ashwin; Martinez-Chantar, Maria-Luz; Mato, Jose M.; Lu, Shelly C.

2013-01-01

221

Space Complexity Algorithms & Complexity  

E-print Network

Space Complexity Algorithms & Complexity Space Complexity Nicolas Stroppa Patrik Lambert - plambert@computing.dcu.ie CA313@Dublin City University. 2008-2009. December 4, 2008 #12;Space Complexity Hierarchy of problems #12;Space Complexity NP-intermediate Languages If P = NP, then are there languages which neither in P

Way, Andy

222

Water Mediated Ligand Functional Group Cooperativity: The Contribution of a Methyl Group to Binding Affinity is Enhanced by a COO? Group Through Changes in the Structure and Thermo dynamics of the Hydration Waters of Ligand-Thermolysin Complexes  

PubMed Central

Ligand functional groups can modulate the contributions of one another to the ligand-protein binding thermodynamics, producing either positive or negative cooperativity. Data presented for four thermolysin phosphonamidate inhibitors demonstrate that the differential binding free energy and enthalpy caused by replacement of a H with a Me group, which binds in the well-hydrated S2? pocket, are more favorable in presence of a ligand carboxylate. The differential entropy is however less favorable. Dissection of these differential thermodynamic parameters, X-ray crystallography, and density-functional theory calculations suggest that these cooperativities are caused by variations in the thermodynamics of the complex hydration shell changes accompanying the H?Me replacement. Specifically, the COO? reduces both the enthalpic penalty and the entropic advantage of displacing water molecules from the S2? pocket, and causes a subsequent acquisition of a more enthalpically, less entropically, favorable water network. This study contributes to understanding the important role water plays in ligand-protein binding. PMID:22894131

Nasief, Nader N; Tan, Hongwei; Kong, Jing; Hangauer, David

2012-01-01

223

Low Density Lipoprotein Receptor-related Protein 1 (LRP1) Modulates N-Methyl-d-aspartate (NMDA) Receptor-dependent Intracellular Signaling and NMDA-induced Regulation of Postsynaptic Protein Complexes*  

PubMed Central

The lipoprotein receptor LRP1 is essential in neurons of the central nervous system, as was revealed by the analysis of conditional Lrp1-deficient mouse models. The molecular basis of its neuronal functions, however, is still incompletely understood. Here we show by immunocytochemistry, electron microscopy, and postsynaptic density preparation that LRP1 is located postsynaptically. Basal and NMDA-induced phosphorylation of the transcription factor cAMP-response element-binding protein (CREB) as well as NMDA target gene transcription are reduced in LRP1-deficient neurons. In control neurons, NMDA promotes ?-secretase-dependent release of the LRP1 intracellular domain (LRP1-ICD). However, pull-down and chromatin immunoprecipitation (ChIP) assays showed no direct interaction between the LRP1-ICD and either CREB or target gene promoters. On the other hand, NMDA-induced degradation of the postsynaptic scaffold protein PSD-95 was impaired in the absence of LRP1, whereas its ubiquitination was increased, indicating that LRP1 influences the composition of postsynaptic protein complexes. Accordingly, NMDA-induced internalization of the AMPA receptor subunit GluA1 was impaired in LRP1-deficient neurons. These results show a role of LRP1 in the regulation and turnover of synaptic proteins, which may contribute to the reduced dendritic branching and to the neurological phenotype observed in the absence of LRP1. PMID:23760271

Nakajima, Chikako; Kulik, Akos; Frotscher, Michael; Herz, Joachim; Schafer, Michael; Bock, Hans H.; May, Petra

2013-01-01

224

Methylation of ribosomal proteins in Bacillus subtilis.  

PubMed Central

We measured the methylation of ribosomal proteins from the 30S and 50S subunits of Bacillus subtilis after growing the cells in the presence of [1-14C]methionine and [methyl-3H]methionine. Two-dimensional polyacrylamide gel electrophoretic analysis revealed a preferential methylation of the 50S ribosomal proteins. Proteins L11 and L16, and possibly L9, L10, L18, and L20, were methylated. On the other hand, only two possibly methylated proteins were found on the 30S subunit. A comparison of these results with those for Escherichia coli suggests a common methylation pattern for the bacterial ribosomal proteins. Images PMID:6768716

Mardones, E; Amaro, A M; Jerez, C A

1980-01-01

225

Comparisons of Non-Gaussian Statistical Models in DNA Methylation Analysis  

PubMed Central

As a key regulatory mechanism of gene expression, DNA methylation patterns are widely altered in many complex genetic diseases, including cancer. DNA methylation is naturally quantified by bounded support data; therefore, it is non-Gaussian distributed. In order to capture such properties, we introduce some non-Gaussian statistical models to perform dimension reduction on DNA methylation data. Afterwards, non-Gaussian statistical model-based unsupervised clustering strategies are applied to cluster the data. Comparisons and analysis of different dimension reduction strategies and unsupervised clustering methods are presented. Experimental results show that the non-Gaussian statistical model-based methods are superior to the conventional Gaussian distribution-based method. They are meaningful tools for DNA methylation analysis. Moreover, among several non-Gaussian methods, the one that captures the bounded nature of DNA methylation data reveals the best clustering performance. PMID:24937687

Ma, Zhanyu; Teschendorff, Andrew E.; Yu, Hong; Taghia, Jalil; Guo, Jun

2014-01-01

226

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

PubMed

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

Doherty, Rachael; Couldrey, Christine

2014-01-01

227

Effect of anionic surfactants on the process of Fenton degradation of methyl orange.  

PubMed

Fenton process has been shown to be very successful to remove dyes from water. However, the influence of other constituents in dyeing industry wastewater, such as Sodium Dodecyl Sulphate (SDS) surfactants, has not been investigated. In this study, the effect of SDS surfactant on the kinetics of Methyl Orange degradation undergoing Fenton process was investigated. Results show that Methyl Orange degradation rate decreased as SDS concentration increased, which was attributed to the consumption of hydroxyl radicals (OH) by surfactants and the formation of Methyl Orange-SDS complex. No evidence was found that the Methyl Orange degradation pathway was affected by the presence of SDS. The kinetics modelling indicates the reaction was the first-order reaction to Methyl Orange. PMID:19934501

Yang, C W; Wang, D

2009-01-01

228

Linking DNA methylation to the onset of human tubal ectopic pregnancy  

PubMed Central

Ectopic pregnancy is a common reproductive disorder of unknown etiology and is a leading cause of maternal and fetal mortality. Because of the asymptomatic nature of early tubal ectopic pregnancy and the lack of specific biomarkers for early diagnosis, a better understanding of the complex cellular and molecular interactions that contribute to tubal ectopic pregnancy is required. DNA methylation is the most studied epigenetic process in various tissues and cells, and the goal of this article is to provide a brief review of recent work describing the potential mechanisms of DNA methylation and the biological function of such methylation in normal intrauterine pregnancy. Further, novel findings from our laboratory highlight the possible role of DNA methylation in human Fallopian tube dysfunction and suggest a possible correlation between methylation of estrogen receptor ? in women and the occurrence of tubal ectopic pregnancies. PMID:23573357

Wang, Lei; Feng, Yi; Zou, Shien; Brännström, Mats; He, Lin; Billig, Håkan; Shao, Ruijin

2013-01-01

229

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

PubMed Central

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

Doherty, Rachael; Couldrey, Christine

2014-01-01

230

Conformational properties of methyl ?-maltoside and methyl ?- and ?-cellobioside disaccharides.  

PubMed

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, although 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 leads to increased sampling of syn, anti-?, and anti-? 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

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

2011-01-27

231

Molecular Structure of Methyl Corylone  

NSDL National Science Digital Library

Methyl Corylone produces a taste and fragrance similar to Cyclotene. It is naturally found in coffee, tobacco and tobacco substitute cigarettes. This substance has a maple and caramel taste and as a flavor additive, it is recommended for caramel, maple, coffee and raisin.

2006-10-04

232

Gene methylation in gastric cancer.  

PubMed

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

Qu, Yiping; Dang, Siwen; Hou, Peng

2013-09-23

233

DNA Methylation of Cancer Genome  

PubMed Central

DNA methylation plays an important role in regulating normal development and carcinogenesis. Current understanding of the biological roles of DNA methylation is limited to its role in the regulation of gene transcription, genomic imprinting, genomic stability, and X chromosome inactivation. In the past 2 decades, a large number of changes have been identified in cancer epigenomes when compared with normals. These alterations fall into two main categories, namely, hypermethylation of tumor suppressor genes and hypomethylation of oncogenes or heterochromatin, respectively. Aberrant methylation of genes controlling the cell cycle, proliferation, apoptosis, metastasis, drug resistance, and intracellular signaling has been identified in multiple cancer types. Recent advancements in whole-genome analysis of methylome have yielded numerous differentially methylated regions, the functions of which are largely unknown. With the development of high resolution tiling microarrays and high throughput DNA sequencing, more cancer methylomes will be profiled, facilitating the identification of new candidate genes or ncRNAs that are related to oncogenesis, new prognostic markers, and the discovery of new target genes for cancer therapy.† PMID:19960550

Cheung, Hoi-Hung; Lee, Tin-Lap; Rennert, Owen M.; Chan, Wai-Yee

2010-01-01

234

Hydrogen-bonded network structures in dipyridinium, bis-(2-methyl-pyridinium), bis-(3-methyl-pyridinium) and bis-(4-methyl-pyridinium) dioxidobis(oxydiacetato)uranate(VI)  

PubMed Central

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

Lennartson, Anders; Hakansson, Mikael

2010-01-01

235

Comparative study on the nonadditivity of methyl group in lithium bonding and hydrogen bonding  

NASA Astrophysics Data System (ADS)

Quantum chemical calculations at the second-order Moeller-Plesset (MP2) level with 6-311++G(d,p) basis set have been performed on the lithium-bonded and hydrogen-bonded systems. The interaction energy, binding distance, bond length, and stretch frequency in these systems have been analyzed to study the nonadditivity of methyl group in the lithium bonding and hydrogen bonding. In the complexes involving with NH3, the introduction of one methyl group into NH3 molecule results in an increase of the strength of lithium bonding and hydrogen bonding. The insertion of two methyl groups into NH3 molecule also leads to an increase of the hydrogen bonding strength but a decrease of the lithium bonding strength relative to that of the first methyl group. The addition of three methyl groups into NH3 molecule causes the strongest hydrogen bonding and the weakest lithium bonding. Although the presence of methyl group has a different influence on the lithium bonding and hydrogen bonding, a negative nonadditivity of methyl group is found in both interactions. The effect of methyl group on the lithium bonding and hydrogen bonding has also been investigated with the natural bond orbital and atoms in molecule analyses.

Li, Qingzhong; Cheng, Jianbo; Li, Wenzuo; Gong, Baoan; Sun, Jiazhong

236

Genome-Wide DNA Methylation Patterns and Transcription Analysis in Sheep Muscle  

PubMed Central

DNA methylation plays a central role in regulating many aspects of growth and development in mammals through regulating gene expression. The development of next generation sequencing technologies have paved the way for genome-wide, high resolution analysis of DNA methylation landscapes using methodology known as reduced representation bisulfite sequencing (RRBS). While RRBS has proven to be effective in understanding DNA methylation landscapes in humans, mice, and rats, to date, few studies have utilised this powerful method for investigating DNA methylation in agricultural animals. Here we describe the utilisation of RRBS to investigate DNA methylation in sheep Longissimus dorsi muscles. RRBS analysis of ?1% of the genome from Longissimus dorsi muscles provided data of suitably high precision and accuracy for DNA methylation analysis, at all levels of resolution from genome-wide to individual nucleotides. Combining RRBS data with mRNAseq data allowed the sheep Longissimus dorsi muscle methylome to be compared with methylomes from other species. While some species differences were identified, many similarities were observed between DNA methylation patterns in sheep and other more commonly studied species. The RRBS data presented here highlights the complexity of epigenetic regulation of genes. However, the similarities observed across species are promising, in that knowledge gained from epigenetic studies in human and mice may be applied, with caution, to agricultural species. The ability to accurately measure DNA methylation in agricultural animals will contribute an additional layer of information to the genetic analyses currently being used to maximise production gains in these species. PMID:25010796

Couldrey, Christine; Brauning, Rudiger; Bracegirdle, Jeremy; Maclean, Paul; Henderson, Harold V.; McEwan, John C.

2014-01-01

237

Recovery of nickel from aqueous samples with water-soluble carboxyl methyl cellulose–acetone system  

Microsoft Academic Search

A simple and efficient method, which involves carboxyl methyl cellulose (CMC) and acetone, was developed for recovery of trace nickel from aqueous solutions. This method was based on the fact that Ni2+ could react with CMC and form water-soluble complexes, which would solidify in excess acetone. After centrifugation, the solid mass consisting of the nickel complex and free CMC was

Zhike Wang; Zheng Fu; Cunling Ye

2009-01-01

238

Detailed chemical kinetic reaction mechanism for biodiesel components methyl stearate and methyl oleate  

E-print Network

Detailed chemical kinetic reaction mechanism for biodiesel components methyl stearate and methyl are developed for two of the five major components of biodiesel fuel, methyl stearate and methyl oleate renewable sources, can reduce net emissions of greenhouse gases. An important class of biodiesel fuels

Paris-Sud XI, Université de

239

Enzymological properties of sterol-C4-methyl-oxidase of yeast sterol biosynthesis  

Microsoft Academic Search

Despite genes of the sterol methyl-oxidase component (SMO) of the sterol-C4-demethylation multienzymatic complex have been identified in a variety of organisms and the key role played by SMO in yeast sterol biosynthesis, the enzymological properties of yeast SMO have not been investigated. An enzymatic assay for measuring specifically sterol 4?-methyl-oxidase activity in Saccharomyces cerevisiae has been developed for the first

Sylvain Darnet; Alain Rahier

2003-01-01

240

40 CFR 180.428 - Metsulfuron methyl; tolerances for residues.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Metsulfuron methyl; tolerances for residues...Tolerances § 180.428 Metsulfuron methyl; tolerances for residues...the combined residues of the herbicide metsulfuron methyl (methyl...

2010-07-01

241

40 CFR 180.428 - Metsulfuron methyl; tolerances for residues.  

Code of Federal Regulations, 2011 CFR

...Metsulfuron methyl; tolerances for residues. (a) General. (1) Tolerances are established for the combined residues of the herbicide metsulfuron methyl (methyl 2-[[[[(4-methoxy-6-methyl-1,3,5- triazin-...

2011-07-01

242

Protein methylation in pea chloroplasts. [Pisum sativum  

SciTech Connect

The methylation of chloroplast proteins has been investigated by incubating intact pea (Pisum sativum) chloroplasts with ({sup 3}H-methyl)-S-adenosylmethionine. Incubation in the light increases the amount of methylation in both the thylakoid and stromal fractions. Numerous thylakoid proteins serve as substrates for the methyltransfer reactions. Three of these thylakoid proteins are methylated to a significantly greater extent in the light than in the dark. The primary stromal polypeptide methylated is the large subunit of ribulose bisphosphate carboxylase/oxygenase. One other stromal polypeptide is also methylated much more in the light than in the dark. Two distinct types of protein methylation occur. One methylinkage is stable to basic conditions whereas a second type is base labile. The base-stable linkage is indicative of N-methylation of amino acid residues while base-lability is suggestive of carboxymethylation of amino acid residues. Labeling in the light increases the percentage of methylation that is base labile in the thylakoid fraction while no difference is observed in the amount of base-labile methylations in light-labeled and dark-labeled stromal proteins. Also suggestive of carboxymethylation is the detection of volatile ({sup 3}H)methyl radioactivity which increases during the labeling period and is greater in chloroplasts labeled in the light as opposed to being labeled in the dark; this implies in vivo turnover of the ({sup 3}H)methyl group.

Niemi, K.J.; Adler, J.; Selman, B.R. (Univ. of Wisconsin, Madison (USA))

1990-07-01

243

5, 13611378, 2008 Methyl arsenic and  

E-print Network

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

Paris-Sud XI, Université de

244

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 ...

245

Radical SAM-mediated methylation reactions.  

PubMed

A subset of enzymes that belong to the radical S-adenosylmethionine (SAM) superfamily is able to catalyze methylation reactions. Substrates of these enzymes are distinct from the nucleophilic substrates that undergo methylation by a polar mechanism. Recently, activities of several radical SAM methylating enzymes have been reconstituted in vitro and their mechanisms of catalysis investigated. The RNA modifying enzymes RlmN and Cfr catalyze methylation via a methyl synthase mechanism. These enzymes use SAM in two distinct roles: as a source of a methyl group transferred to a conserved cysteine and as a source of 5'-deoxyadenosyl radical (5'-dA). Hydrogen atom abstraction by this species generates a thiomethylene radical which adds into the RNA substrate, forming an enzyme-substrate covalent adduct. In another recent study, methylation of the indole moiety of tryptophan by the radical SAM and cobalamin-binding domain enzyme TsrM has been reconstituted. Methylcobalamin serves as an intermediate methyl donor in TsrM, and is proposed to transfer the methyl group as a methyl radical. Interestingly, despite the presence of the radical SAM motif, no reductive cleavage of SAM has been observed in this methylation. These important reconstitutions set the stage for further studies on mechanisms of radical methylation. PMID:23835516

Fujimori, Danica Galoni?

2013-08-01

246

Radical SAM-Mediated Methylation Reactions  

PubMed Central

A subset of enzymes that belong to the radical S-adenosylmethionine (SAM) superfamily are able to catalyze methylation reactions. Substrates of these enzymes are distinct from the nucleophilic substrates that undergo methylation by a polar mechanism. Recently, activities of several radical SAM methylating enzymes have been reconstituted in vitro and their mechanisms of catalysis investigated. The RNA modifying enzymes RlmN and Cfr catalyze methylation via a methyl synthase mechanism. These enzymes use SAM in two distinct roles: as a source of a methyl group transferred to a conserved cysteine and as a source of 5?-deoxyadenosyl radical (5?-dA•). Hydrogen atom abstraction by this species generates a thiomethylene radical which adds into the RNA substrate, forming an enzyme-substrate covalent adduct. In another recent study, methylation of the indole moiety of tryptophan by the radical SAM and cobalamin-binding domain enzyme TsrM has been reconstituted. Methylcobalamin serves as an intermediate methyl donor in TsrM, and is proposed to transfer the methyl group as a methyl radical. Interestingly, despite the presence of the radical SAM motif, no reductive cleavage of SAM has been observed in this methylation. These important reconstitutions set the stage for further studies on mechanisms of radical methylation. PMID:23835516

Fujimori, Danica Galonic

2013-01-01

247

Structural Studies of Methyl-Accepting Chemotaxis Proteins of Escherichia coli: Evidence for Multiple Methylation Sites  

Microsoft Academic Search

Two-dimensional analysis of tryptic peptides from [35S]methionine-labeled methyl-accepting chemotaxis proteins, MCP I and MCP II, demonstrates a high degree of homology between the two proteins. After the methylation sites were labeled with S-adenosyl-L-[methyl-3H]methionine, peptides of three distinct migrations in each protein were found to carry a methyl group. These multiple methylations appear to be responsible in part for the observed

Daniel Chelsky; F. W. Dahlquist

1980-01-01

248

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

PubMed Central

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

2014-01-01

249

Persistence of the sulfonylurea herbicides thifensulfuron-methyl, ethametsulfuron-methyl, and metsulfuron-methyl in farm dugouts (ponds).  

PubMed

Sulfonylurea herbicides are applied at relatively low rates (3 to 40 g ha(-1)) to control weeds in a variety of crops across the Canadian prairies. Because of their high phytotoxicity and the likelihood of their transport in surface runoff, there is concern about their possible impact to aquatic ecosystems. Little is known, however, about their persistence and behavior in aquatic ecosystems. To assess persistence in aquatic ecosystems, three prairie farm dugouts (ponds) were fortified with either thifensulfuron-methyl {methyl 3-[[[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)amino]carbonyl]amino]sulfonyl]-2-thiophenecarboxylate}, ethametsulfuron-methyl {methyl 2-[[[[[4-ethoxy-6-(methylamino)-1,3,5-triazin-2-yl]amino]carbonyl]amino]sulfonyl]benzoate} or metsulfuron-methyl {methyl 2-[[[[(4-methoxy-6-methyl-1,3,5-triazinyl)amino]carbonyl]amino]sulfonyl]benzoate}. The decreasing order of persistence of environmentally relevant concentrations (1 to 4.6 microg L(-1)) of these herbicides in dugout water over the June to October period was metsulfuron-methyl>ethametsulfuron-methyl>thifensulfuron-methyl. The corresponding dissipation half-lives (DT(50)) of 84, 30, and 16 d, respectively, are in the same relative order as the recropping intervals for these herbicides. Thifensulfuron-methyl showed a biphasic dissipation with slower dissipation during the winter months. In contrast, the dissipation of metsulfuron-methyl, the sulfonylurea herbicide with the longest DT(50), was somewhat enhanced under winter conditions. One of the major routes of sulfonylurea herbicide dissipation was removal from the water column when dugout water was lost during hydrological discharge. The relatively long persistence of these herbicides in water indicates that partitioning into sediments was minimal, the sulfonylurea and methyl ester linkages in these compounds were resistant to hydrolysis in weakly alkaline waters, and that microbial and photolytic degradation in dugout waters were slow. PMID:17071910

Cessna, Allan J; Donald, David B; Bailey, Jonathan; Waiser, Marley; Headley, J V

2006-01-01

250

Modification of yeast ribosomal proteins. Methylation.  

PubMed Central

Two-dimensional polyacrylamide-gel electrophoretic analysis of yeast ribosomal proteins uniformly labelled in vivo with [methyl-3H]methionine and [1-14C]methionine revealed that four ribosomal proteins are methylated, i.e. proteins S31, S32, L15 and L41. Lysine and arginine appear to be the predominant acceptors of the methyl groups. The degree of methylation ranges from 0.09 to 0.20 methyl group per modified ribosomal protein species. PMID:367366

Kruiswijk, T; Kunst, A; Planta, R J; Mager, W H

1978-01-01

251

Enzymatic methyl esterification of pituitary polypeptides.  

PubMed

Methyl esterification of pituitary polypeptides by protein methylase II (S-adenosylmethionine:protein-carboxyl O-methyltransferase, EC. 2.1.1.24) has been investigated. Ovine lutropin and adrenocorticotropin (alpha1-39-ACTH) were found to be good methyl acceptor substrates, followed by beta-lipotropin. While the alpha-subunit of lutropin had nearly equal the methyl accepting activity of lutropin, the beta-subunit was devoid of accepting activity. The maximum amount of esterification occurred between 15 and 30 min at 37 degrees C) depending on the methyl acceptor molecule. The rate of the methyl esterification of adrenocorticotropin fragments was also studied. While alpha7-38-ACTH had less than half of alpha1-37-ACTH methyl accepting capacity, alpha1-17-ACTH did not serve as methyl acceptor. However, when a mixture of the two fragments was preincubated, the resulting mixture had full alpha1-39-ACTH activity. PMID:218889

Kim, S; Li, C H

1979-03-01

252

Increased DNA methylation in the suicide brain  

PubMed Central

Clinical studies find that childhood adversity and stress-ful life events in adulthood increase the risk for major depression and for suicide. The predispositions to either major depression or suicide are thought to depend on genetic risk factors or epigenetic effects. We investigated DNA methylation signatures postmortem in brains of suicides with diagnosis of major depressive disorder. DNA methylation levels were determined at single C-phosphate-G (CpG) resolution sites within ventral prefrontal cortex of 53 suicides and nonpsychiatric controls, aged 16 to 89 years. We found that DNA methylation increases throughout the lifespan. Suicides showed an 8-fold greater number of methylated CpG sites relative to controls (P<2.2x10-16), with greater DNA methylation changes over and above the increased methylation observed in normal aging. This increased DNA methylation may be a significant contributor to the neuropathology and psychopathology underlying the risk of suicide in depression. PMID:25364291

Haghighi, Fatemeh; Xin, Yurong; Chanrion, Benjamin; O'Donnell, Anne H.; Ge, Yongchao; Dwork, Andrew J.; Arango, Victoria; Mann, J. John

2014-01-01

253

Molecular Structure of Methyl Acrylate  

NSDL National Science Digital Library

Commercially available since 1944, methyl acrylate is a clear, colorless liquid with a sweet, fruity odor. This lachrymator often found in tobacco smoke, is used in the manufacturing of polymers, leather finishing, resins, textile, paper coatings, and plastic films. It is highly flammable and polymerizes explosively with exposure to light or heat. Inhibition by hydroquinone monomethyl ether, MEHQ, helps to prevent this problem. Because MEHQ functionality is reliant on oxygen, methyl acrylate must never be stored in an inert environment. Contact with skin will lead to severe deep burns, while ingestion or inhalation could lead to nausea, cough and abdominal pain. The liver, lungs, and kidneys are target organs for this compound, and medical attention should be sought immediately upon exposure.

2002-10-01

254

PAF1-complex-mediated histone methylation of FLOWERING  

E-print Network

are involved in multiple flowering pathways that account for the broad effects of elf7 and elf8 mutations in response to increased ambient temperature (Blazquez et al. 2003). The autonomous pathway and a gibberellin

Raines, Ronald T.

255

Requirement of rRNA Methylation for 80S Ribosome Assembly on a Cohort of Cellular Internal Ribosome Entry Sites?  

PubMed Central

Protein syntheses mediated by cellular and viral internal ribosome entry sites (IRESs) are believed to have many features in common. Distinct mechanisms for ribosome recruitment and preinitiation complex assembly between the two processes have not been identified thus far. Here we show that the methylation status of rRNA differentially influenced the mechanism of 80S complex formation on IRES elements from the cellular sodium-coupled neutral amino acid transporter 2 (SNAT2) versus the hepatitis C virus mRNA. Translation initiation involves the assembly of the 48S preinitiation complex, followed by joining of the 60S ribosomal subunit and formation of the 80S complex. Abrogation of rRNA methylation did not affect the 48S complex but resulted in impairment of 80S complex assembly on the cellular, but not the viral, IRESs tested. Impairment of 80S complex assembly on the amino acid transporter SNAT2 IRES was rescued by purified 60S subunits containing fully methylated rRNA. We found that rRNA methylation did not affect the activity of any of the viral IRESs tested but affected the activity of numerous cellular IRESs. This work reveals a novel mechanism operating on a cohort of cellular IRESs that involves rRNA methylation for proper 80S complex assembly and efficient translation initiation. PMID:21930789

Basu, Abhijit; Das, Priyanka; Chaudhuri, Sujan; Bevilacqua, Elena; Andrews, Joel; Barik, Sailen; Hatzoglou, Maria; Komar, Anton A.; Mazumder, Barsanjit

2011-01-01

256

Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27  

Microsoft Academic Search

Polycomb group (PcG) complexes 2 and 3 are involved in transcriptional silencing. These complexes contain a histone lysine methyltransferase (HKMT) activity that targets different lysine residues on histones H1 or H3 in vitro. However, it is not known if these histones are methylation targets in vivo because the human PRC2\\/3 complexes have not been studied in the context of a

Antonis Kirmizis; Stephanie M. Bartley; Andrei Kuzmichev; Raphael Margueron; Danny Reinberg; Roland Green; Peggy J. Farnham

2004-01-01

257

Combustion characterization of methylal in reciprocating engines  

SciTech Connect

Methylal, CH{sub 3}OCH{sub 2}OCH{sub 3}, 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 number in the range of 45-50, which is compatible with diesel fuels. Engine tests have shown that adding methylal to diesel fuel significantly reduces smoke emissions. Gaseous emissions and combustion efficiencies obtained with methylal/diesel fuel blends remain essentially the same as those measured using neat diesel fuel. Lubricity measurements of methylal/diesel fuel blends with a ball on cylinder lubrication evaluator (BOCLE) show that methylal improves the lubricity of diesel fuel. Even though additions of methylal lower the fuel viscosity, the results of the BOCLE tests indicate that the methylal/diesel fuel blends cause less pump wear than neat diesel fuel. The one drawback is that methylal has a low boiling point (42{degrees}C) and a relatively high vapor pressure. As a result, it lowers the flash point of diesel fuel and causes a potential fuel tank flammability hazard. One solution to this increased volatility is to make polyoxymethylenes with the general formula of CH{sub 3}O(CH{sub 2}O){sub x}CH{sub 3} where x > 2. The molecules are similar to methylal, but have higher molecular weights and thus higher viscosities and substantially lower vapor pressures. Therefore, their flash points will be compatible with regular diesel fuel. The polyoxymethylenes are expected to have combustion properties similar to methylal. It is theorized that by analogy with hydrocarbons, the ignition quality (i.e., cetane number) of the polyoxymethylenes will be better than that of methylal.

Dodge, L.; Naegeli, D. [Southwest Research Institute, San Antonio, TX (United States)

1994-06-01

258

High-resolution mapping reveals a conserved, widespread, dynamic meiotically regulated mRNA methylation program  

PubMed Central

N6-methyladenosine (m6A) is the most ubiquitous mRNA base modification, but little is known about its precise location, temporal dynamics, and regulation. Here, we generated genomic maps of m6A sites in meiotic yeast transcripts at nearly single-nucleotide resolution, identifying 1,308 putatively methylated sites within 1,183 transcripts. We validated 8/8 methylation sites in different genes with direct genetic analysis, demonstrated that methylated sites are significantly conserved in a related species, and built a model that predicts methylated sites directly from sequence. Sites vary in their methylation profiles along a dense meiotic time-course, and are regulated both locally, via predictable methylatability of each site, and globally, through the core meiotic circuitry. The methyltransferase complex components localize to the yeast nucleolus, and this localization is essential for mRNA methylation. Our data illuminates a conserved, dynamically regulated methylation program in yeast meiosis, and provides an important resource for studying the function of this epitranscriptomic modification. PMID:24269006

Schwartz, Schraga; Agarwala, Sudeep D.; Mumbach, Maxwell R.; Jovanovic, Marko; Mertins, Philipp; Shishkin, Alexander; Tabach, Yuval; Mikkelsen, Tarjei S; Satija, Rahul; Ruvkun, Gary; Carr, Steven A.; Lander, Eric S.; Fink, Gerald R.; Regev, Aviv

2014-01-01

259

Dynamics of DNA Methylation in Recent Human and Great Ape Evolution  

PubMed Central

DNA methylation is an epigenetic modification involved in regulatory processes such as cell differentiation during development, X-chromosome inactivation, genomic imprinting and susceptibility to complex disease. However, the dynamics of DNA methylation changes between humans and their closest relatives are still poorly understood. We performed a comparative analysis of CpG methylation patterns between 9 humans and 23 primate samples including all species of great apes (chimpanzee, bonobo, gorilla and orangutan) using Illumina Methylation450 bead arrays. Our analysis identified ?800 genes with significantly altered methylation patterns among the great apes, including ?170 genes with a methylation pattern unique to human. Some of these are known to be involved in developmental and neurological features, suggesting that epigenetic changes have been frequent during recent human and primate evolution. We identified a significant positive relationship between the rate of coding variation and alterations of methylation at the promoter level, indicative of co-occurrence between evolution of protein sequence and gene regulation. In contrast, and supporting the idea that many phenotypic differences between humans and great apes are not due to amino acid differences, our analysis also identified 184 genes that are perfectly conserved at protein level between human and chimpanzee, yet show significant epigenetic differences between these two species. We conclude that epigenetic alterations are an important force during primate evolution and have been under-explored in evolutionary comparative genomics. PMID:24039605

Hernando-Herraez, Irene; Prado-Martinez, Javier; Garg, Paras; Fernandez-Callejo, Marcos; Heyn, Holger; Hvilsom, Christina; Navarro, Arcadi; Esteller, Manel

2013-01-01

260

Methylation-dependent and -independent genomic targeting principles of the MBD protein family.  

PubMed

To gain insight into the cellular readout of DNA methylation, we established a strategy for systematically profiling the genome-wide distribution of chromatin-interacting factors. This enabled us to create genomic maps for the methyl-CpG-binding domain (MBD) family of proteins, including disease-relevant mutants, deletions, and isoforms. In vivo binding of MBD proteins occurs predominantly as a linear function of local methylation density, requiring functional MBD domains and methyl-CPGs. This interaction directs specificity of MBD proteins to methylated, CpG-dense, and inactive regulatory regions. In contrast, binding to unmethylated sites varies between MBD proteins and is mediated via alternative domains or protein-protein interactions. Such targeting is exemplified by NuRD-complex-mediated tethering of MBD2 to a subset of unmethylated, active regulatory regions. Interestingly, MBD3 also occupies these sites, but like MBD2, binding is independent of the presence of hydroxymethylation. These functional binding maps reveal methylation-dependent and -independent binding modes and revise current models of DNA methylation readout through MBD proteins. PMID:23582333

Baubec, Tuncay; Ivánek, Robert; Lienert, Florian; Schübeler, Dirk

2013-04-11

261

Aberrant Methylation of Gene Associated CpG Sites Occurs in Borderline Personality Disorder  

PubMed Central

Borderline personality disorder (BPD) is a complex psychiatric disease with an increased impact in the last years. While the diagnosis and therapy are well established, little is known on the pathogenesis of borderline personality disorder. Previously, a significant increase in DNA methylation of relevant neuropsychiatric genes in BPD patients has been reported. In our study we performed genome wide methylation analysis and revealed specific CpG sites that exhibited increased methylation in 24 female BPD patients compared to 11 female healthy controls. Bead chip technology and quantitative bisulfite pyrosequencing showed a significantly increased methylation at CpG sites of APBA2 (1.1 fold) and APBA3 (1.1 fold), KCNQ1 (1.5 fold), MCF2 (1.1 fold) and NINJ2 (1.2 fold) in BPD patients. For the CpG sites of GATA4 and HLCS an increase in DNA methylation was observed, but was only significant in the bead chip assay. Moreover genome wide methylation levels of blood samples of BPD patients and control samples are similar. In summary, our results show a significant 1.26 fold average increase in methylation at the analyzed gene associated CpG sites in the blood of BPD patients compared to controls samples (p<0.001). This data may provide new insights into epigenetic mechanisms underlying the pathogenesis of BPD. PMID:24367640

Kunzel, Natascha; Schmidt, Christian; Kiehl, Steffen; Dammann, Gerhard; Dammann, Reinhard

2013-01-01

262

DNA methylation in gastric cancer, related to Helicobacter pylori and Epstein-Barr virus  

PubMed Central

Gastric cancer is a leading cause of cancer death worldwide, and significant effort has been focused on clarifying the pathology of gastric cancer. In particular, the development of genome-wide analysis tools has enabled the detection of genetic and epigenetic alterations in gastric cancer; for example, aberrant DNA methylation in gene promoter regions is thought to play a crucial role in gastric carcinogenesis. The etiological viewpoint is also essential for the study of gastric cancers, and two distinct pathogens, Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV), are known to participate in gastric carcinogenesis. Chronic inflammation of the gastric epithelium due to H. pylori infection induces aberrant polyclonal methylation that may lead to an increased risk of gastric cancer. In addition, EBV infection is known to cause extensive methylation, and EBV-positive gastric cancers display a high methylation epigenotype, in which aberrant methylation extends to not only Polycomb repressive complex (PRC)-target genes in embryonic stem cells but also non-PRC-target genes. Here, we review aberrant DNA methylation in gastric cancer and the association between methylation and infection with H. pylori and EBV. PMID:24744581

Matsusaka, Keisuke; Funata, Sayaka; Fukayama, Masashi; Kaneda, Atsushi

2014-01-01

263

Structural basis of substrate methylation and inhibition of SMYD2.  

PubMed

Protein lysine methyltransferases are important regulators of epigenetic signaling. These enzymes catalyze the transfer of donor methyl groups from S-adenosylmethionine to specific acceptor lysines on histones, leading to changes in chromatin structure and transcriptional regulation. These enzymes also methylate nonhistone protein substrates, revealing an additional mechanism to regulate cellular physiology. The oncogenic protein SMYD2 represses the functional activities of the tumor suppressor proteins p53 and Rb, making it an attractive drug target. Here we report the discovery of AZ505, a potent and selective inhibitor of SMYD2 that was identified from a high throughput chemical screen. We also present the crystal structures of SMYD2 with p53 substrate and product peptides, and notably, in complex with AZ505. This substrate competitive inhibitor is bound in the peptide binding groove of SMYD2. These results have implications for the development of SMYD2 inhibitors, and indicate the potential for developing novel therapies targeting this target class. PMID:21782458

Ferguson, Andrew D; Larsen, Nicholas A; Howard, Tina; Pollard, Hannah; Green, Isabelle; Grande, Christie; Cheung, Tony; Garcia-Arenas, Renee; Cowen, Scott; Wu, Jiaquan; Godin, Robert; Chen, Huawei; Keen, Nicholas

2011-09-01

264

The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders  

PubMed Central

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

Grayson, Dennis R; Guidotti, Alessandro

2013-01-01

265

Nitric Oxide Modifies Global Histone Methylation by Inhibiting Jumonji C Domain-containing Demethylases*?  

PubMed Central

Methylation of lysine residues on histone tails is an important epigenetic modification that is dynamically regulated through the combined effects of methyltransferases and demethylases. The Jumonji C domain Fe(II) ?-ketoglutarate family of proteins performs the majority of histone demethylation. We demonstrate that nitric oxide (•NO) directly inhibits the activity of the demethylase KDM3A by forming a nitrosyliron complex in the catalytic pocket. Exposing cells to either chemical or cellular sources of •NO resulted in a significant increase in dimethyl Lys-9 on histone 3 (H3K9me2), the preferred substrate for KDM3A. G9a, the primary methyltransferase acting on H3K9me2, was down-regulated in response to •NO, and changes in methylation state could not be accounted for by methylation in general. Furthermore, cellular iron sequestration via dinitrosyliron complex formation correlated with increased methylation. The mRNA of several histone demethylases and methyltransferases was also differentially regulated in response to •NO. Taken together, these data reveal three novel and distinct mechanisms whereby •NO can affect histone methylation as follows: direct inhibition of Jumonji C demethylase activity, reduction in iron cofactor availability, and regulation of expression of methyl-modifying enzymes. This model of •NO as an epigenetic modulator provides a novel explanation for nonclassical gene regulation by •NO. PMID:23546878

Hickok, Jason R.; Vasudevan, Divya; Antholine, William E.; Thomas, Douglas D.

2013-01-01

266

DNA methylation: old dog, new tricks?  

PubMed

DNA methylation is an epigenetic modification that is generally associated with repression of transcription initiation at CpG-island promoters. Here we argue that, on the basis of recent high-throughput genomic and proteomic screenings, DNA methylation can also have different outcomes, including activation of transcription. This is evidenced by the fact that transcription factors can interact with methylated DNA sequences. Furthermore, in certain cellular contexts, genes containing methylated promoters are highly transcribed. Interestingly, this uncoupling between methylated DNA and repression of transcription seems to be particularly evident in germ cells and pluripotent cells. Thus, contrary to previous assumptions, DNA methylation is not exclusively associated with repression of transcription initiation. PMID:25372310

Spruijt, Cornelia G; Vermeulen, Michiel

2014-11-01

267

Dichlorido(9-methyl-adenine-?N 7)(?5-penta-methyl-cyclo-penta-dien-yl)iridium(III) dichloromethane solvate  

PubMed Central

In the title complex, [Ir(C10H15)Cl2(C6H7N5)]·CH2Cl2 or [Ir(?5-C5Me5)Cl2(9-MeAde-?N 7)]·CH2Cl2 (9-MeAde = 9-methyl­adenine), the coordination geometry of the IrIII atom approximates to a three-legged piano stool. The 9-methyl­adenine ligand is coordinated in a monodentate fashion to the Ir centre through its N-7 atom. The crystal structure contains centrosymmetric pairs of mol­ecules, inter­acting through two N—H?N hydrogen bonds. An intra­molecular N—H?Cl hydrogen bond is formed between the H atom of an NH2 group and a chlorido ligand. Further short intra- and inter­molecular C—H?Cl contacts are observed. PMID:21201851

Bruhn, Clemens; Kuger, Thomas; Steinborn, Dirk

2008-01-01

268

Glycerolysis of fats and methyl esters  

Microsoft Academic Search

The glycerolysis of methyl esters and triglycerides with crude glycerol, a coproduct from the transesterification of triglycerides,\\u000a was studied. Three procedures were followed for this conversion. The first procedure was a one-step glycerolysis with methyl\\u000a esters. The second procedure was a two-step process. This procedure involved an initial partial glycerolysis with methyl esters,\\u000a followed by fat glycerolysis. The third procedure

H. Noureddini; V. Medikonduru

1997-01-01

269

Preprocessing differential methylation hybridization microarray data  

Microsoft Academic Search

Background  DNA methylation plays a very important role in the silencing of tumor suppressor genes in various tumor types. In order to\\u000a gain a genome-wide understanding of how changes in methylation affect tumor growth, the differential methylation hybridization\\u000a (DMH) protocol has been developed and large amounts of DMH microarray data have been generated. However, it is still unclear\\u000a how to preprocess

Shuying Sun; Yi-Wen Huang; Pearlly S Yan; Tim HM Huang; Shili Lin

2011-01-01

270

Dimethylcarbonate for eco-friendly methylation reactions  

Microsoft Academic Search

Dimethylcarbonate (DMC), an environmentally friendly substitute for dimethylsulfate and methyl halides in methylation reactions, is a very selective reagent. Both under gas–liquid phase transfer catalysis (GL-PTC) and under batch conditions, with potassium carbonate as the catalyst, the reactions of DMC with methylene-active compounds (arylacetonitriles and arylacetoesters, aroxyacetonitriles and methyl aroxyacetates, benzylaryl- and alkylarylsulphones) produce monomethylated derivatives, with a selectivity not

S. Memoli; M. Selva; P. Tundo

2001-01-01

271

RNA-directed DNA methylation in Arabidopsis  

PubMed Central

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

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

2002-01-01

272

Methylation - an uncommon modification of glycans*  

PubMed Central

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

Staudacher, Erika

2013-01-01

273

Seasonality Modifies Methylation Profiles in Healthy People  

PubMed Central

DNA methylation is a well-characterized epigenetic modification that plays an important role in the regulation of gene expression. There is growing evidence on the involvement of epigenetic mechanisms in disease onset, including cancer. Environmental factors seem to induce changes in DNA methylation affecting human health. However, little is known about basal methylation levels in healthy people and about the correlation between environmental factors and different methylation profiles. We investigated the effect of seasonality on basal methylation by testing methylation levels in the long interspersed nucleotide element-1 (LINE-1) and in two cancer-related genes (RASSF1A and MGMT) of 88 healthy male heavy smokers involved in an Italian randomized study; at enrolment the subjects donated a blood sample collected in different months. Methylation analyses were performed by pyrosequencing. Mean methylation percentage was higher in spring and summer for the LINE1, RASSF1A and MGMT genes (68.26%, 2.35%, and 9.52% respectively) compared with autumn and winter (67.43%, 2.17%, and 8.60% respectively). In particular, LINE-1 was significantly hypomethylated (p?=?0.04 or 0.05 depending on the CpG island involved) in autumn and winter compared with spring and summer. Seasonality seems to be a modifier of methylation levels and this observation should be taken into account in future analyses. PMID:25210735

Ricceri, Fulvio; Trevisan, Morena; Fiano, Valentina; Grasso, Chiara; Fasanelli, Francesca; Scoccianti, Chiara; De Marco, Laura; Tos, Anna Gillio; Vineis, Paolo; Sacerdote, Carlotta

2014-01-01

274

Synthesis and solution properties of lanthanum(III), europium(III), and lutetium(III) THP complexes and an X-ray diffraction study of a crystal containing four stereoisomers of a europium(III) THP complex (THP = 1,4,7,10-tetrakis(2-hydroxypropryl)-1,4,7,10-tetraazacyclododecane). Methyl groups impart rigidity to S,S,S,S-THP macrocyclic complexes  

SciTech Connect

The macrocycle 1,4,7,10-tetrakis(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane (THP) prepared from racemic propylene oxide and cyclen (1,4,7,10-tetraazacyclododecane) consists of a mixture of stereoisomers that arise from the chiral {alpha}-carbons of the hydroxypropyl groups. {sup 13}C NMR studies suggest that five different diastereomers are formed. Lanthanum(III), europium(III), and lutetium(III) THP complexes are synthesized from the mixture of THP stereoisomers. Europium(III) THP complexes containing R,R,R,S and S,S,S,R configurations at the {alpha}-carbons of the hydroxypropyl groups cocrystallize from solution. The complex [Eu(THP)(H{sub 2}O)]{sub 2}(CF{sub 3}SO{sub 3}){sub 6}{center_dot}2EtOH{center_dot}H{sub 2}O crystallizes in the centrosymetric monoclinic space group P2{sub 1}/c (No. 14). Four stereoisomers (two enantiomeric pairs) of the complex appear in the crystal. Each asymmetric unit consists of two different diastereomers of the europium(III) cation, six triflate anions, two ethanol molecules, and one water molecule of solvation. The structure was solved and refined to R = 5.54% and R{sub w} = 5.72% for those 3351 reflections with {vert_bar}F{sub o}{vert_bar} > 6{sigma}{vert_bar}F{sub o}{vert_bar}. In addition, synthesis of the THP stereoisomer with all hydroxypropyl groups containing the S-configuration (S-THP) is accomplished by use of S-propylene oxide. The synthesis of lanthanum(III), europium(III), and lutetium(III) complexes of S-THP is reported; {sup 1}H and {sup 13}C NMR spectra of the lanthanum and lutetium complexes indicate that only one diastereomer is present in solution.

Chin, K.O.A.; Morrow, J.R.; Lake, C.H.; Churchill, M.R. [State Univ. of New York, Buffalo, NY (United States)

1994-02-16

275

A Genome-wide screen identifies frequently methylated genes in haematological and epithelial cancers  

PubMed Central

Background Genetic as well as epigenetic alterations are a hallmark of both epithelial and haematological malignancies. High throughput screens are required to identify epigenetic markers that can be useful for diagnostic and prognostic purposes across malignancies. Results Here we report for the first time the use of the MIRA assay (methylated CpG island recovery assay) in combination with genome-wide CpG island arrays to identify epigenetic molecular markers in childhood acute lymphoblastic leukemia (ALL) on a genome-wide scale. We identified 30 genes demonstrating methylation frequencies of ?25% in childhood ALL, nine genes showed significantly different methylation frequencies in B vs T-ALL. For majority of the genes expression could be restored in methylated leukemia lines after treatment with 5-azaDC. Forty-four percent of the genes represent targets of the polycomb complex. In chronic myeloid leukemia (CML) two of the genes, (TFAP2A and EBF2), demonstrated increased methylation in blast crisis compared to chronic phase (P < 0.05). Furthermore hypermethylation of an autophagy related gene ATG16L2 was associated with poorer prognosis in terms of molecular response to Imatinib treatment. Lastly we demonstrated that ten of these genes were also frequently methylated in common epithelial cancers. Conclusion In summary we have identified a large number of genes showing frequent methylation in childhood ALL, methylation status of two of these genes is associated with advanced disease in CML and methylation status of another gene is associated with prognosis. In addition a subset of these genes may act as epigenetic markers across hematological malignancies as well as common epithelial cancers. PMID:20184741

2010-01-01

276

Catechol-O-methyltransferase gene methylation and substance use in adolescents: the TRAILS study.  

PubMed

Substance use often starts in adolescence and poses a major problem for society and individual health. The dopamine system plays a role in substance use, and catechol-O-methyltransferase (COMT) is an important enzyme that degrades dopamine. The Val(108/158) Met polymorphism modulates COMT activity and thus dopamine levels, and has been linked to substance use. COMT gene methylation, on the other hand, may affect expression and thus indirectly COMT activity. We investigated whether methylation of the COMT gene was associated with adolescents' substance use. Furthermore, we explored whether the COMT Val(108/158) Met polymorphism interacts with COMT gene methylation in association with substance use. In 463 adolescents (mean age=16, 50.8% girls), substance use (cigarette smoking, alcohol and cannabis use) was assessed with self-report questionnaires. From blood samples, COMT Val(108/158) Met genotype and methylation rates of membrane bound (MB) and soluble (S) COMT promoters were assessed. MB-COMT promoter methylation was associated with non-daily smoking [odds ratio (OR)=1.82, P=0.03], but not with daily smoking (OR=1.20, P=0.34), MB-COMT promoter methylation was not associated with alcohol use. Adolescents with the Met/Met genotype and high rates of MB-COMT promoter methylation were less likely to be high-frequent cannabis users than adolescents with the Val/Val or Val/Met genotype. S-COMT promoter methylation was not associated with substance use. These results indicate that there is an association between substance use and COMT gene methylation. Although this association is complex, combining genetic and epigenetic variation of the COMT gene may be helpful in further elucidating the influence of the dopamine system on substance use in adolescence. PMID:24902721

van der Knaap, L J; Schaefer, J M; Franken, I H A; Verhulst, F C; van Oort, F V A; Riese, H

2014-09-01

277

Genomic Distribution of H3K9me2 and DNA Methylation in a Maize Genome  

PubMed Central

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

Ji, Lexiang; Eichten, Steven R.; Song, Jawon; Vaughn, Matthew W.; Schmitz, Robert J.; Springer, Nathan M.

2014-01-01

278

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

PubMed Central

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

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

2014-01-01

279

Effect of body mass index on global DNA methylation in healthy Korean women.  

PubMed

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/m(2). 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

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

2014-06-01

280

A combined HM-PCR/SNuPE method for high sensitive detection of rare DNA methylation  

PubMed Central

Background DNA methylation changes are widely used as early molecular markers in cancer detection. Sensitive detection and classification of rare methylation changes in DNA extracted from circulating body fluids or complex tissue samples is crucial for the understanding of tumor etiology, clinical diagnosis and treatment. In this paper, we describe a combined method to monitor the presence of methylated tumor DNA in an excess of unmethylated background DNA of non-tumorous cells. The method combines heavy methyl-PCR, which favors preferential amplification of methylated marker sequence from bisulfite-treated DNA with a methylation-specific single nucleotide primer extension monitored by ion-pair, reversed-phase, high-performance liquid chromatography separation. Results This combined method allows detection of 14 pg (that is, four to five genomic copies) of methylated chromosomal DNA in a 2000-fold excess (that is, 50 ng) of unmethylated chromosomal background, with an analytical sensitivity of > 90%. We outline a detailed protocol for the combined assay on two examples of known cancer markers (SEPT9 and TMEFF2) and discuss general aspects of assay design and data interpretation. Finally, we provide an application example for rapid testing on tumor methylation in plasma DNA derived from a small cohort of patients with colorectal cancer. Conclusion The method allows unambiguous detection of rare DNA methylation, for example in body fluid or DNA isolates from cells or tissues, with very high sensitivity and accuracy. The application combines standard technologies and can easily be adapted to any target region of interest. It does not require costly reagents and can be used for routine screening of many samples. PMID:20525169

2010-01-01

281

Infrared anisotropy and structure of crystalline methyl stearate and methyl octadecyl sulfonate  

Microsoft Academic Search

Infrared spectra of highly oriented crystalline films of methyl stearate and methyl 1-octadecyl sulfonate have been obtained\\u000a using polarized radiation with the electric vector parallel and at 45 to crystallographic axes. The anisotropy of methyl\\u000a stearate is in good agreement with the known structure and with vibrational assignments. The results obtained on the methyl\\u000a ester of octadecyl sulfonic acid suggest

H. Susi; Anne S. Jahn

1966-01-01

282

Carbonyl oxides reactions from geraniol-trans-(3,7-dimethylocta-2,6-dien-1-ol), 6-methyl-5-hepten-2-one, and 6-hydroxy-4-methyl-4-hexenal ozonolysis: kinetics and mechanisms.  

PubMed

A density functional theory (DFT) study of the mechanisms of carbonyl oxide reactions from geraniol-trans, 6-methyl-5-hepten-2-one, and 6-hydroxy-4-methyl-4-hexenal ozonolysis is presented. The geometries, energies, and harmonic vibrational frequencies of each stationary point were determined by B3LYP/6-31(d,p) and BH&HLYP/cc-pVDZ methods. According to the calculations, the ozonolysis reactions are initiated by the formation of van der Waals (VDW) complexes to yield primary ozonides, which rapidly open to carbonyl oxide compounds. These carbonyl oxide compounds react to form dioxanes and hydroperoxides. The hydroperoxides react by isomerization to form stable products. Glyoxal and methyl-glyoxal have been identified as the final product from geraniol-trans, 6-methyl-5-hepten-2-one, and 6-hydroxy-4-methyl-4-hexenal ozonolysis. Our results are in good agreement with the experimental studies. PMID:21609020

Leonardo, Tadeu; Baptista, Leonardo; da Silva, Edilson Clemente; Arbilla, Graciela

2011-07-01

283

Capacitive integration to produce high precision isotope ratio measurements on methyl chloride and methyl bromide  

Microsoft Academic Search

A capacitive integration circuit for the measurement of ion current ratios in an isotope ratio mass spectrometer is described. Sources of error and their effect on measurement precision are discussed. Results from the isotopic analysis of methyl chloride and of methyl bromide gases are presented. The relative standard deviation of measured ratios for methyl chloride was 13 parts in 10⁶

John F. Willey; James W. Taylor

1978-01-01

284

Pathodiagnostic parameters and evaluation of O?- methyl guanine methyl transferase gene promoter methylation in meningiomas.  

PubMed

Histopathological evaluation and grading of meningioma give important prognostic information. We evaluated retrospectively monotonous sheeting, necrosis, hypercellularity, nuclear pleomorphism, small cell changes, brain invasion, mitosis, mast cells, psammoma bodies, MIB-1 labeling index (MIB-1 LI) and histological grade of 230 primary meningioma tumors according to the latest World Health Organization (WHO) classification. To reveal any possible association between clinical features and promoter hypermethylation of O(6)-methylguanine-DNA methyltransferase (MGMT) as an important epigenetic modification in many human cancers, we also evaluated the methylation status of MGMT in meningiomas by a SYBR-green-based real-time PCR method. There was a female predominance (2.38 to 1) in the meningiomas. The mean age of the patients was 49.9 ± 12.6 years (range 16 to 78 years). Transitional meningiomas were the most common subtype of the meningiomas (35.21%, n=81). Most of the meningiomas were located in the falx and parasagital area. There was a significant correlation between histopathological features of malignancy. These features were observed more frequently and with statistical relation to grade II rather than grade I. Mast cells, psammoma bodies and nuclear pleomorphism had poor associations (P>0.05). When we re-evaluated the tumor grading, 31 patients with grade I meningiomas were upgraded to grade II. None of the meningiomas tested by MSQP were methylated in MGMT promoter sequence. High MIB-1 LI could be indicative for higher grade of meningioma. Continuous revision of the classification system is needed to improve the accuracy of prognostic judgments in meningioma. The data confirm that there is no rationale to test meningiomas for MGMT methylation status. PMID:24398011

Jabini, Raheleh; Moradi, Afshin; Afsharnezhad, Sima; Ayatollahi, Hossein; Behravan, Javad; Raziee, Hamid Reza; Mosaffa, Fatemeh

2014-04-01

285

Magnetic Properties of a Series of Trinuclear Complexes (CuL)(2)Mn.xB (L Representing the Deprotonated Form of N-(4-Methyl-6-oxo-3-azahept-4-enyl)oxamic Acid and B Representing Respectively H(2)O (x = 5, 4.5, 3, 1), (CH(3))(2)SO (x = 2), and C(5)H(5)N (x = 4)). Crystal and Molecular Structure of (CuL)(2)Mn.2(CH(3))(2)SO.  

PubMed

A series of (Cu, Mn, Cu) complexes have been prepared and characterized. They may be described by the overall formula (CuL)(2)Mn.xB where L stands for the deprotonated form of N-(4-methyl-6-oxo-3-azahept-4-enyl)oxamic acid and B for respectively H(2)O (with x = 5, 4.5, 3, 1), (CH(3))(2)SO (with x = 2), and C(5)H(5)N (with x = 4). The crystal and molecular structures of (CuL)(2)Mn.2(CH(3))(2)SO have been solved. The crystals are monoclinic, space group P2(1)/n with cell constants a = 8.362(2) Å, b = 14.426(3) Å, c = 24.442(6) Å, and Z = 4. In each (Cu, Mn, Cu) molecular unit the central Mn(II) ion is bridged to two copper(II) ions through two oxamato groups. Short intermolecular Cu.Cu distances lead to the formation of a chain-like packing pattern running parallel to the c-axis. Magnetic susceptibility measurements have been performed for the six complexes. Five complexes display the same behavior which corresponds to the occurrence of antiferromagnetic Cu-Mn interactions within isolated trinuclear units. The J values are between -29.4(2) and -33.8(5) cm(-)(1). Surprisingly the field and temperature dependence of the magnetization for (CuL)(2)Mn.4.5H(2)O confirms that a magnetic phase transition occurs at low temperature and that, below T(c) = 37 K, the complex displays weak ferromagnetism. PMID:11670139

Costes, Jean-Pierre; Laurent, Jean-Pierre; Sanchez, Jose Maria Moreno; Varela, Jose Suarez; Ahlgren, Markku; Sundberg, Markku

1997-10-01

286

Determination of total and methyl mercury in human permanent healthy teeth by electrothermal atomic absorption spectrometry after extraction in organic phase  

Microsoft Academic Search

A simple and sensitive method has been developed for determination of inorganic and methyl mercury in biological samples by ETAAS. For determination of methyl mercury; it was transferred to toluene phase by acid leaching extraction method. For total mercury after digestion of samples; it was extracted to toluene phase by means of the chelating agent diethyldithiocarbamate. Formation of complex between

M. Saber-Tehrani; M. H. Givianrad; H. Hashemi-Moghaddam

2007-01-01

287

Methylated DNA-binding protein is present in various mammalian cell types  

SciTech Connect

A DNA-binding protein from human placenta, methylated DNA-binding protein (MDBP), binds to certain DNA sequences only when they contain 5-methylcytosine (m{sup 5}C) residues at specific positions. The authors found a very similar DNA-binding activity in nuclear extracts of rat tissues, calf thymus, human embryonal carcinoma cells, HeLa cells, and mouse LTK cells. Like human placental MDBP, the analogous DNA-binding proteins from the above mammalian cell lines formed a number of different low-electrophoretic-mobility complexes with a 14-bp MDBP-specific oligonucleotide duplex. All of these complexes exhibited the same DNA methylation specificity and DNA sequence specificity. Although MDBP activity was found in various mammalian cell types, it was not detected in extracts of cultured mosquito cells and so may be associated only with cells with vertebrate-type DNA methylation.

Supakar, P.C.; Weist, D.; Zhang, D.; Inamdar, N.; Zhang, Xianyang; Khan, R.; Ehrlich, M. (Tulane Medical School, New Orleans, LA (USA)); Ehrlich, K.C. (Department of Agriculture, New Orleans, LA (USA))

1988-08-25

288

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

PubMed Central

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

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

289

Arginine methylation initiates BMP-induced Smad signaling  

PubMed Central

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

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

2014-01-01

290

DNA methylation contributes to natural human variation  

PubMed Central

DNA methylation patterns are important for establishing cell, tissue, and organism phenotypes, but little is known about their contribution to natural human variation. To determine their contribution to variability, we have generated genome-scale DNA methylation profiles of three human populations (Caucasian-American, African-American, and Han Chinese-American) and examined the differentially methylated CpG sites. The distinctly methylated genes identified suggest an influence of DNA methylation on phenotype differences, such as susceptibility to certain diseases and pathogens, and response to drugs and environmental agents. DNA methylation differences can be partially traced back to genetic variation, suggesting that differentially methylated CpG sites serve as evolutionarily established mediators between the genetic code and phenotypic variability. Notably, one-third of the DNA methylation differences were not associated with any genetic variation, suggesting that variation in population-specific sites takes place at the genetic and epigenetic levels, highlighting the contribution of epigenetic modification to natural human variation. PMID:23908385

Heyn, Holger; Moran, Sebastian; Hernando-Herraez, Irene; Sayols, Sergi; Gomez, Antonio; Sandoval, Juan; Monk, Dave; Hata, Kenichiro; Marques-Bonet, Tomas; Wang, Liewei; Esteller, Manel

2013-01-01

291

Infraspecific DNA Methylation Polymorphism in Cotton (Gossypium  

E-print Network

Infraspecific DNA Methylation Polymorphism in Cotton (Gossypium hirsutum L.) ANNA L. KEYTE, RYAN in plants and has been implicated in silencing duplicate genes after polyploid formation in several plant-polymorphism diversity at CCGG sites within allotetraploid cotton, Gossypium hirsutum, using a methylation

Wendel, Jonathan F.

292

Methyl Glyoxal as an Intermediary in Fermentation  

Microsoft Academic Search

WHILST the earlier work on fermentation, especially Prof. Neuberg's investigation of the second form of fermentation, rendered the participation of methyl glyoxal as an intermediary stage probable, proof that methyl glyoxal is formed by systems capable of fermenting or glycolysing sugar has been obtained by the recent work of Toeniessen and Fischer (Zeits. physiol. Chem., 161, 254), Ariyama (Jour. Biol.

J. O. Girsavicius

1930-01-01

293

Adsorption kinetics of methyl violet onto perlite  

Microsoft Academic Search

This study examines adsorption kinetics and activation parameters of methyl violet on perlite. The effect of process parameters like contact time, concentration of dye, temperature and pH on the extent of methyl violet adsorption from solution has been investigated. Results of the kinetic studies show that the adsorption reaction is first order with respect to dye solution concentration with activation

Mehmet Do?an; Mahir Alkan

2003-01-01

294

ABIOLOGICAL METHYLATION OF MERCURY IN SOIL  

EPA Science Inventory

This work defines several factors influencing the methylation of mercuric ion in soil. Two of the most important findings were that it is possible to extract the mercury methylating factor from soil with a solution of 0.5N sodium hydroxide and that this factor is responsible for ...

295

Emission Characteristics of Sunflower Oil Methyl Ester  

Microsoft Academic Search

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

Y. Ulusoy; R. Arslan; C. Kaplan

2009-01-01

296

Methylated Cell-Free DNA In Vitro and In Vivo  

Microsoft Academic Search

\\u000a We have investigated the stability, circulation and generation of methylated DNA (methDNA) in vivo and in vitro. In serum,\\u000a the methDNA (free and as nucleoprotein complexes circulating in human blood) was shown to degraded more slowly then unmethylated\\u000a DNA (unmethDNA). Residual free methDNA circulates in blood for longer than unmethDNA although it is eliminated faster from\\u000a blood immediately after injection.

Tatyana E. Skvortsova; Olga E. Bryzgunova; Alena O. Lebedeva; Viktoria V. Mak; Valentin V. Vlassov; Pavel P. Laktionov

297

Protein methylation reactions in intact pea chloroplasts  

SciTech Connect

Post-translational protein methylation was investigated in Pisum sativum chloroplasts. Intact pea chloroplasts were incubated with ({sup 3}H-methyl)-S-adenosylmethionine under various conditions. The chloroplasts were then separated into stromal and thylakoid fractions and analyzed for radioactivity transferred to protein. Light enhanced the magnitude of labeling in both fractions. One thylakoid polypeptide with an apparent molecular mass of 43 kDa was labeled only in the light. Several other thylakoid and stromal proteins were labeled in both light and dark-labeling conditions. Both base-labile methylation, carboxy-methylesters and base-stable groups, N-methylations were found. Further characterization of the methyl-transfer reactions will be presented.

Niemi, K.J. (Univ. of Wisconsin, Madison (USA))

1989-04-01

298

DNA methylation: roles in rheumatoid arthritis.  

PubMed

Rheumatoid arthritis (RA) is an immune-mediated disease of unknown cause that primarily affects the joints and ultimately leads to joint destruction. In recent years, the potential role of DNA methylation in the development of RA is raising great expectations among clinicians and researchers. DNA methylation influences diverse aspects of the disease and regulates epigenetic silencing of genes and behavior of several cell types, especially fibroblast-like synoviocytes (FLS), the most resident cells in joints. The activation of FLS is generally regarded as a key process in the development of RA that actively results in the promotion of ongoing inflammation and joint damage. It has also been shown that aberrant DNA methylation occurs in the pathogenesis of RA and contributes to the development of the disease. Recently, there has been an impressive increase in studies involving DNA methylation in RA. In this paper, we consider the role of DNA methylation in the development of RA. PMID:24652004

Yuan, Feng-Lai; Li, Xia; Xu, Rui-Sheng; Jiang, Dong-Lin; Zhou, Xiao-Gang

2014-09-01

299

Differential DNA Methylation in Purified Human Blood Cells: Implications for Cell Lineage and Studies on Disease Susceptibility  

PubMed Central

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

Reinius, Lovisa E.; Acevedo, Nathalie; Joerink, Maaike; Pershagen, Goran; Dahlen, Sven-Erik; Greco, Dario; Soderhall, Cilla; Scheynius, Annika; Kere, Juha

2012-01-01

300

Dissolved organic matter enhances microbial mercury methylation under sulfidic conditions.  

PubMed

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

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

2012-03-01

301

Mouse Oocyte Methylomes at Base Resolution Reveal Genome-Wide Accumulation of Non-CpG Methylation and Role of DNA Methyltransferases  

PubMed Central

DNA methylation is an epigenetic modification that plays a crucial role in normal mammalian development, retrotransposon silencing, and cellular reprogramming. Although methylation mainly occurs on the cytosine in a CG site, non-CG methylation is prevalent in pluripotent stem cells, brain, and oocytes. We previously identified non-CG methylation in several CG-rich regions in mouse germinal vesicle oocytes (GVOs), but the overall distribution of non-CG methylation and the enzymes responsible for this modification are unknown. Using amplification-free whole-genome bisulfite sequencing, which can be used with minute amounts of DNA, we constructed the base-resolution methylome maps of GVOs, non-growing oocytes (NGOs), and mutant GVOs lacking the DNA methyltransferase Dnmt1, Dnmt3a, Dnmt3b, or Dnmt3L. We found that nearly two-thirds of all methylcytosines occur in a non-CG context in GVOs. The distribution of non-CG methylation closely resembled that of CG methylation throughout the genome and showed clear enrichment in gene bodies. Compared to NGOs, GVOs were over four times more methylated at non-CG sites, indicating that non-CG methylation accumulates during oocyte growth. Lack of Dnmt3a or Dnmt3L resulted in a global reduction in both CG and non-CG methylation, showing that non-CG methylation depends on the Dnmt3a-Dnmt3L complex. Dnmt3b was dispensable. Of note, lack of Dnmt1 resulted in a slight decrease in CG methylation, suggesting that this maintenance enzyme plays a role in non-dividing oocytes. Dnmt1 may act on CG sites that remain hemimethylated in the de novo methylation process. Our results provide a basis for understanding the mechanisms and significance of non-CG methylation in mammalian oocytes. PMID:23637617

Shirane, Kenjiro; Toh, Hidehiro; Kobayashi, Hisato; Miura, Fumihito; Chiba, Hatsune; Ito, Takashi; Kono, Tomohiro; Sasaki, Hiroyuki

2013-01-01

302

DETERMINATION OF NEPTUNIUM IN URANIUM--FISSION PRODUCT MIXTURES. INITIAL EXTRACTION WITH METHYL ISOBUTYL KETONE  

Microsoft Academic Search

A method for the separation and determination of neptunium in uranium--; fission product mixtures uses a twocycle extraction system. Neptunium is ; oxidized to 6+ with permanganate and quantitatively extracted as a nitrate ; complex into methyl isobutyl ketone from an acid-deficient aluminum nitrate ; salting solution containing tetrapropylammonium nitrate. Neptunium is stripped ; from the ketone phase and simultaneously

W. J. Maeck; G. L. Booman; M. C. Elliott; J. E. Rein

1960-01-01

303

Interaction between methyl glyoxal and ascorbic acid: experimental and theoretical aspects  

Microsoft Academic Search

The absorption spectral change of methyl glyoxal (MG) due to the interaction with ascorbic acid (AA or Vitamin C) has been investigated using steady-state spectroscopic technique. A plausible explanation for the spectral change has been discussed on the basis of hydrogen bonding interaction between the two interacting species. The equilibrium constant for the complex formation due to hydrogen bonding interaction

D. Banerjee; A. Koll; A. Filarowski; S. P. Bhattacharyya; S. Mukherjee

2004-01-01

304

LABORATORY ECOSYSTEMS FOR STUDYING CHEMICAL FATE: AN EVALUATION USING METHYL PARATHION  

EPA Science Inventory

The use of complex microcosms as tools for testing mathematical models of pollutant fate was evaluated by determining the transport and transformation of methyl parathion in two-8-compartment, continuous flow microcosms designed to enhance the effects of different degradation pro...

305

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

Microsoft Academic Search

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

Jetske G. De Boer; Marcel Dicke

2004-01-01

306

Split -Lactamase Sensor for the Sequence-Specific Detection of DNA Methylation  

E-print Network

of epigenetic regulation of genetic information. Toward this end, we have recently reported the first design the recruitment of chromatin modification complexes.4-6 Though CpG methylation is distributed throughout the genome, this chemical modification is normally excluded from promoter-associated CpG-rich regions of a se

Ghosh, Indraneel

307

A Gas-phase Formation Route to Interstellar Trans-methyl Formate  

NASA Astrophysics Data System (ADS)

The abundance of methyl formate in the interstellar medium has previously been underpredicted by chemical models. Additionally, grain surface chemistry cannot account for the relative abundance of the cis- and trans-conformers of methyl formate, and the trans-conformer is not even formed at detectable abundance on these surfaces. This highlights the importance of studying formation pathways to methyl formate in the gas phase. The rate constant and branching fractions are reported for the gas-phase reaction between protonated methanol and formic acid to form protonated trans-methyl formate and water as well as adduct ion: Rate constants were experimentally determined using a flowing afterglow-selected ion flow tube apparatus at 300 K and a pressure of 530 mTorr helium. The results indicate a moderate overall rate constant of (3.19 ± 0.39) × 10-10 cm3 s-1 (± 1?) and an average branching fraction of 0.05 ± 0.04 for protonated trans-methyl formate and 0.95 ± 0.04 for the adduct ion. These experimental results are reinforced by ab initio calculations at the MP2(full)/aug-cc-pVTZ level of theory to examine the reaction coordinate and complement previous density functional theory calculations. This study underscores the need for continued observational studies of trans-methyl formate and for the exploration of other gas-phase formation routes to complex organic molecules.

Cole, Callie A.; Wehres, Nadine; Yang, Zhibo; Thomsen, Ditte L.; Snow, Theodore P.; Bierbaum, Veronica M.

2012-07-01

308

Leisingera methylohalidivorans gen. nov., sp. nov., a marine methylotroph that grows on methyl bromide  

USGS Publications Warehouse

A marine methylotroph, designated strain MB2T, was isolated for its ability to grow on methyl bromide as a sole carbon and energy source. Methyl chloride and methyl iodide also supported growth, as did methionine and glycine betaine. A limited amount of growth was observed with dimethyl sulfide. Growth was also noted with unidentified components of the complex media marine broth 2216, yeast extract and Casamino acids. No growth was observed on methylated amines, methanol, formate, acetate, glucose or a variety of other substrates. Growth on methyl bromide and methyl iodide resulted in their oxidation to CO2 with stoichiometric release of bromide and iodide, respectively. Strain MB2T exhibited growth optima at NaCl and Mg2+ concentrations similar to that of seawater. Phylogenetic analysis of the 16S rDNA sequence placed this strain in the ??-Proteobacteria in proximity to the genera Ruegeria and Roseobacter. It is proposed that strain MB2T (= ATCC BAA-92T = DSM 14336T) be designated Leisingera methylohalidivorans gen. nov., sp. nov.

Schaefer, J. K.; Goodwin, K. D.; McDonald, I. R.; Murrell, J. C.; Oremland, R. S.

2002-01-01

309

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

PubMed

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

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

2014-12-01

310

Effective, homogeneous and transient interference with cytosine methylation in plant genomic DNA by zebularine  

PubMed Central

Covalent modification by methylation of cytosine residues represents an important epigenetic hallmark. While sequence analysis after bisulphite conversion allows correlative analyses with single-base resolution, functional analysis by interference with DNA methylation is less precise, due to the complexity of methylation enzymes and their targets. A cytidine analogue, 5-azacytidine, is frequently used as an inhibitor of DNA methyltransferases, but its rapid degradation in aqueous solution is problematic for culture periods of longer than a few hours. Application of zebularine, a more stable cytidine analogue with a similar mode of action that is successfully used as a methylation inhibitor in Neurospora and mammalian tumour cell lines, can significantly reduce DNA methylation in plants in a dose-dependent and transient manner independent of sequence context. Demethylation is connected with transcriptional reactivation and partial decondensation of heterochromatin. Zebularine represents a promising new and versatile tool for investigating the role of DNA methylation in plants with regard to transcriptional control, maintenance and formation of (hetero-) chromatin. PMID:18826433

Baubec, Tuncay; Pecinka, Ales; Rozhon, Wilfried; Mittelsten Scheid, Ortrun

2009-01-01

311

Selective editing of Val and Leu methyl groups in high molecular weight protein NMR  

PubMed Central

The development of methyl-TROSY approaches and specific 13C–1H labeling of Ile, Leu and Val methyl groups in highly deuterated proteins has made it possible to study high molecular weight proteins, either alone or in complexes, using solution nuclear magnetic resonance (NMR) spectroscopy. Here we present 2-dimensional (2D) and 3-dimensional (3D) NMR experiments designed to achieve complete separation of the methyl resonances of Val and Leu, labeled using the same precursor, ?-ketoisovalerate or acetolactate. The 2D experiment can further select the methyl resonances of Val or Leu based on the C? or C? chemical shift values of Val or Leu, respectively. In the 3D spectrum, the methyl cross peaks of Val and Leu residues have opposite signs; thus, not only can the residue types be easily distinguished, but the methyl pairs from the same residue can also be identified. The feasibility of this approach, implemented in both 2D and 3D experiments, has been demonstrated on an 82 kDa protein, malate synthase G. The methods developed in this study will reduce resonance overlaps and also facilitate structure-guided resonance assignments. PMID:22532128

Hu, Weidong; Namanja, Andrew T.; Wong, Steven

2013-01-01

312

High-frequency aberrantly methylated targets in pancreatic adenocarcinoma identified via global DNA methylation analysis using methylCap-seq  

PubMed Central

Background Extensive reprogramming and dysregulation of DNA methylation is an important characteristic of pancreatic cancer (PC). Our study aimed to characterize the genomic methylation patterns in various genomic contexts of PC. The methyl capture sequencing (methylCap-seq) method was used to map differently methylated regions (DMRs) in pooled samples from ten PC tissues and ten adjacent non-tumor (PN) tissues. A selection of DMRs was validated in an independent set of PC and PN samples using methylation-specific PCR (MSP), bisulfite sequencing PCR (BSP), and methylation sensitive restriction enzyme-based qPCR (MSRE-qPCR). The mRNA and expressed sequence tag (EST) expression of the corresponding genes was investigated using RT-qPCR. Results A total of 1,131 PC-specific and 727 PN-specific hypermethylated DMRs were identified in association with CpG islands (CGIs), including gene-associated CGIs and orphan CGIs; 2,955 PC-specific and 2,386 PN-specific hypermethylated DMRs were associated with gene promoters, including promoters containing or lacking CGIs. Moreover, 1,744 PC-specific and 1,488 PN-specific hypermethylated DMRs were found to be associated with CGIs or CGI shores. These results suggested that aberrant hypermethylation in PC typically occurs in regions surrounding the transcription start site (TSS). The BSP, MSP, MSRE-qPCR, and RT-qPCR data indicated that the aberrant DNA methylation in PC tissue and in PC cell lines was associated with gene (or corresponding EST) expression. Conclusions Our study characterized the genome-wide DNA methylation patterns in PC and identified DMRs that were distributed among various genomic contexts that might influence the expression of corresponding genes or transcripts to promote PC. These DMRs might serve as diagnostic biomarkers or therapeutic targets for PC.

2014-01-01

313

Fabrication of duplex DNA microarrays incorporating methyl-5-cytosine  

PubMed Central

We synthesized customized double-stranded DNA microarrays including methyl-5-cytosine at CpG dinucleotides and produced all 163,555 possible 8-mers (un-, hemi-, and di-methylated) to gain insight into how methylation affects transcription factor binding. An antibody to methyl-5-cytidine showed greater binding to the methylated DNA, demonstrating efficient incorporation of methyl-5-cytosine into the synthesized DNA. In contrast, binding of the transcription factor CREB was inhibited by CpG methylation. This platform represents a powerful new technology to evaluate the effect of DNA methylation on protein binding in any sequence context. PMID:22139143

Warren, Christopher L.; Zhao, Jianfei; Glass, Kimberly; Rishi, Vikas; Ansari, Aseem Z.; Vinson, Charles

2014-01-01

314

Methylation of Histone H3 by Set2 in Saccharomyces cerevisiae Is Linked to Transcriptional Elongation by RNA Polymerase II  

Microsoft Academic Search

Set2 methylates Lys36 of histone H3. We show here that yeast Set2 copurifies with RNA polymerase II (RNAPII). Chromatin immunoprecipitation analyses demonstrated that Set2 and histone H3 Lys36 methyl- ation are associated with the coding regions of several genes that were tested and correlate with active transcription. Both depend, as well, on the Paf1 elongation factor complex. The C terminus

Nevan J. Krogan; Minkyu Kim; Amy Tong; Ashkan Golshani; Gerard Cagney; Veronica Canadien; Dawn P. Richards; Bryan K. Beattie; Andrew Emili; Charles Boone; Ali Shilatifard; Stephen Buratowski; Jack Greenblatt

2003-01-01

315

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

Microsoft Academic Search

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

Jörg Tost

2010-01-01

316

Decreased global methylation in patients with bipolar disorder who respond to lithium.  

PubMed

Mitochondrial dysfunction, oxidative stress, and alterations in DNA methylation, are all associated with the pathophysiology of bipolar disorder (BD). We therefore studied the relationship between oxidative stress and DNA methylation in patients with BD with an excellent response to lithium treatment, their affected and unaffected relatives and healthy controls. Transformed lymphoblasts were cultured in the presence or absence of lithium chloride (0.75 mM). DNA and proteins were extracted from the cells to determine levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), 5-methylcytosine (5-mc), mitochondrial complex I and glutathione peroxidase (GPx) activities. Methylation was decreased in BD subjects and their relatives compared to controls and remained so after lithium treatment in BD subjects but not in their relatives. 8-OHdG levels and complex I activity did not differ between groups before and after lithium treatment. Finally, relatives of patients showed increased GPx activity before and after lithium treatment, which negatively correlated with 5-mc levels. Changes in global methylation may be specific for BD and lithium may be involved in glutathione regulation. The present study supports the importance of DNA methylation to the pathophysiology of BD and the therapeutic potential of antioxidants in this illness. PMID:24345589

Huzayyin, Aya A; Andreazza, Ana C; Turecki, Gustavo; Cruceanu, Cristiana; Rouleau, Guy A; Alda, Martin; Young, L Trevor

2014-04-01

317

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

PubMed Central

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.

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

2014-01-01

318

Factors affecting the selectivity of the oxidation of methyl p-toluate by cobalt(III).  

PubMed

The anaerobic oxidation of methyl p-toluate by cobalt(III) in acetic acid was investigated. Observed products were 4-carbomethoxybenzaldehyde (2), 4-carbomethoxybenzoic acid (3), 4-carbomethoxybenzyl acetate (1), 4,4'-dicarbomethoxybibenzyl (6), methyl 2,4-dimethylbenzoate (8), and methyl 3,4-dimethylbenzoate (9). Deuterium isotope labeling showed that 2 was not formed from 1, but appeared to be formed directly from methyl p-toluate via 4-carbomethoxybenzyl alcohol (5). The ratio of (2 + 3) to 1 was 0.5 with [py3Co3O(OAc)5OH[PF6] and 1.0 with cobaltic acetate. Cobaltic acetate was generated in situ by the reaction of cobaltous acetate and peracetic acid. When the oxidation was carried out in the presence of chromium (0.05 equiv based on cobalt), the ratio increased dramatically and no 6 was observed. Other transition metals such as vanadium, molybdenum, and manganese had a similar effect, but were not as effective as chromium. Chromium was observed to form a mixed-metal cluster complex with cobalt. Treatment of an acetic acid solution of cobaltous acetate and methyl isonicotinate with K2CrO4 produced a solid tentatively identified as [(MIN)3Co2CrO(OAc)6][CrO4H] (MIN = methyl isonicotinate). The selectivity for the oxidation of methyl p-toluate exhibited by the mixed-metal cluster complex was similar to that observed by the addition of chromium to oxidations using [py3Co3O(OAc)5OH[PF6]. PMID:18225893

Sumner, Charles E; Morrill, Kent A; Howell, Jeff S; Little, James

2008-03-17

319

Preparation and Characterization of Pioglitazone Cyclodextrin Inclusion Complexes  

PubMed Central

Pioglitazone, a class II Biopharmaceutical Classification System drug having poor water solubility and slow dissolution rate may have a negative impact on its subtherapeutic plasma drug levels leading to therapeutic failure. In order to improve its water solubility and thus dissolution, cyclodextrin complexation technique was followed. The phase solubility studies were carried using three different types of cyclodextrins viz., ?, methyl-? and ?-cyclodextrins. The Gibbs free energy was calculated in order to determine ease of the complexation. Binary systems of pioglitazone with cyclodextrins were prepared by kneading method and spray drying method. The phase solubility profiles with all the three cyclodextrins were classified as AL-type, indicating the formation of 1:1 stoichiometric inclusion complexes. The complexation capability of cyclodextrins with pioglitazone increased in the order of methyl-? > ? > ?-cyclodextrin. The Gibbs free energy was found to be in the order ? > methyl-? > ? cyclodextrin. Characterization of inclusion complexes was done by solubility studies, in vitro dissolution studies, Fourier transformation-infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry and X-ray powder diffractometry studies. Inclusion complexes exhibited higher rates of dissolution than the corresponding physical mixtures and pure drug. Greater solubility was observed with spray-dried methyl-? cyclodextrin complexes (2.29 ± 0.001 mg/ml) in comparison to the kneaded methyl-? cyclodextrin complexes (1.584 ± 0.053 mg/ml) and pure drug (0.0714 ± 0.0018 mg/ml). PMID:22224032

Pandit, V; Gorantla, R; Devi, K; Pai, RS; Sarasija, S

2011-01-01

320

Selenophene transition metal complexes  

SciTech Connect

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.

White, C.J.

1994-07-27

321

Mercury Methylation by the Methanogen Methanospirillum hungatei  

PubMed Central

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

Reinfelder, John R.; Hines, Mark E.

2013-01-01

322

Methyl bromide and methyl chloride fluxes from temperate forest litter  

NASA Astrophysics Data System (ADS)

Methyl halide fluxes were measured from fine (nonwoody) litter samples at a temperate deciduous forest site in Scotland on 16 occasions over more than a year and at a coniferous forest site. The resulting mean (±1 sd) CH 3Br and CH 3Cl fluxes were 4.1 ± 3.7 ng kg -1 h -1 and 0.98 ± 0.62 ?g kg -1 h -1, respectively, for dry mass leaf litter and 5.7 ± 6.3 ng kg -1 h -1 and 0.47 ± 0.14 ?g kg -1 h -1 for dry mass needle litter. Temporal variations of net fluxes from leaf litter were significantly greater than spatial variations suggesting seasonality in the fluxes. The mean CH 3Cl/CH 3Br mass ratio of fluxes was ˜200 (to 1 sig. fig.), an order of magnitude larger than the ratio of their estimated global turnovers. Temperate forest litter may be a moderate net source of CH 3Cl globally but a negligible source of CH 3Br. These statements refer to the nonwoody litter component only.

Blei, Emanuel; Heal, Mathew R.

2011-03-01

323

Global DNA methylation analysis using methyl-sensitive amplification polymorphism (MSAP).  

PubMed

DNA methylation is a crucial epigenetic process which helps control gene transcription activity in eukaryotes. Information regarding the methylation status of a regulatory sequence of a particular gene provides important knowledge of this transcriptional control. DNA methylation can be detected using several methods, including sodium bisulfite sequencing and restriction digestion using methylation-sensitive endonucleases. Methyl-Sensitive Amplification Polymorphism (MSAP) is a technique used to study the global DNA methylation status of an organism and hence to distinguish between two individuals based on the DNA methylation status determined by the differential digestion pattern. Therefore, this technique is a useful method for DNA methylation mapping and positional cloning of differentially methylated genes. In this technique, genomic DNA is first digested with a methylation-sensitive restriction enzyme such as HpaII, and then the DNA fragments are ligated to adaptors in order to facilitate their amplification. Digestion using a methylation-insensitive isoschizomer of HpaII, MspI is used in a parallel digestion reaction as a loading control in the experiment. Subsequently, these fragments are selectively amplified by fluorescently labeled primers. PCR products from different individuals are compared, and once an interesting polymorphic locus is recognized, the desired DNA fragment can be isolated from a denaturing polyacrylamide gel, sequenced and identified based on DNA sequence similarity to other sequences available in the database. We will use analysis of met1, ddm1, and atmbd9 mutants and wild-type plants treated with a cytidine analogue, 5-azaC, or zebularine to demonstrate how to assess the genetic modulation of DNA methylation in Arabidopsis. It should be noted that despite the fact that MSAP is a reliable technique used to fish for polymorphic methylated loci, its power is limited to the restriction recognition sites of the enzymes used in the genomic DNA digestion. PMID:24057373

Yaish, Mahmoud W; Peng, Mingsheng; Rothstein, Steven J

2014-01-01

324

DNA methylation analysis reveals distinct methylation signatures in pediatric germ cell tumors  

PubMed Central

Background Aberrant DNA methylation is a prominent feature of many cancers, and may be especially relevant in germ cell tumors (GCTs) due to the extensive epigenetic reprogramming that occurs in the germ line during normal development. Methods We used the Illumina GoldenGate Cancer Methylation Panel to compare DNA methylation in the three main histologic subtypes of pediatric GCTs (germinoma, teratoma and yolk sac tumor (YST); N?=?51) and used recursively partitioned mixture models (RPMM) to test associations between methylation pattern and tumor and demographic characteristics. We identified genes and pathways that were differentially methylated using generalized linear models and Ingenuity Pathway Analysis. We also measured global DNA methylation at LINE1 elements and evaluated methylation at selected imprinted loci using pyrosequencing. Results Methylation patterns differed by tumor histology, with 18/19 YSTs forming a distinct methylation class. Four pathways showed significant enrichment for YSTs, including a human embryonic stem cell pluripotency pathway. We identified 190 CpG loci with significant methylation differences in mature and immature teratomas (q?methylation at LINE1 elements compared with normal adjacent tissue while there was no difference between teratoma (mature and immature) and normal tissue. DNA methylation at imprinted loci differed significantly by tumor histology and location. Conclusion Understanding methylation patterns may identify the developmental stage at which the GCT arose and the at-risk period when environmental exposures could be most harmful. Further, identification of relevant genetic pathways could lead to the development of new targets for therapy. PMID:23806198

2013-01-01

325

Methyl chloride via oxhydrochlorination of methane  

SciTech Connect

Dow Corning is developing a route from methane to methyl chloride via oxyhydrochlorination (OHC) chemistry with joint support from the Gas Research Institute and the Department of Energy Federal Energy Technology Center. Dow Corning is the world`s largest producer of methyl chloride and uses it as an intermediate in the production of silicone materials. Other uses include production of higher hydrocarbons, methyl cellulose, quaternary ammonium salts and herbicides. The objective of this project is to demonstrate and develop a route to methyl chloride with reduced variable cost by using methane instead of methanol raw materials. Methyl chloride is currently produced from methanol, but U.S. demand is typically higher than available domestic supply, resulting in fluctuating prices. OHC technology utilizes domestic natural gas as a feedstock, which allows a lower-cost source of methyl chloride which is independent of methanol. In addition to other uses of methyl chloride, OHC could be a key step in a gas-to-liquid fuels process. These uses could divert significant methanol demand to methane. A stable and selective catalyst has been developed in the laboratory and evaluated in a purpose-built demonstration unit. Materials of construction issues have been resolved and the unit has been run under a range of conditions to evaluate catalyst performance and stability. Many technological advances have been made, especially in the areas of catalyst development, online FTIR analysis of the product stream, and recovery of methyl chloride product via an absorber/stripper system. Significant technological hurdles still remain including heat transfer, catalysts scaleup, orthogonality in modeling, and scaleable absorption data. Economics of the oxyhydrochlorination process have been evaluated an found to be unfavorable due to high capital and utility costs. Future efforts will focus on improved methane conversion at high methyl chloride selectivity.

Jarvis, R.F. Jr.

1997-12-31

326

A genetic sensor for strong methylating compounds  

PubMed Central

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

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

2013-01-01

327

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

PubMed Central

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

2013-01-01

328

Diiodidobis{4-[2-(2-methyl-phen-yl)ethen-yl]pyridine-?N}cadmium  

PubMed Central

In the title complex, [CdI2(C14H13N)2], the Cd atom lies on a twofold rotation axis that relates the I atom and the 4-(2-methyl­styr­yl)pyridine ligand to their counterparts. Therefore the asymmetric unit contains one crystallographically independent half-mol­ecule. The Cd atom adopts a tetra­hedral coordination geometry, coordinated by two I atoms and two N atoms from the symmetry-related 4-(2-methyl­styr­yl)pyridine ligands. PMID:22058706

Liu, Dong

2011-01-01

329

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

PubMed

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

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

330

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

PubMed Central

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

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

331

Two Arabidopsis methylation-deficiency mutations confer only partial effects on a methylated endogenous gene family  

Microsoft Academic Search

In Arabidopsis a SWI2\\/SNF2 chromatin remodeling factor-related protein DDM1 and a cytosine methyl- transferase MET1 are required for maintenance of genomic cytosine methylation. Mutations in either gene cause global demethylation. In this work we have assessed the effects of these mutations on the PAI tryptophan biosynthetic gene family, which consists of four densely methylated genes arranged as a tail-to-tail inverted

Lisa Bartee; Judith Bender

2001-01-01

332

A systematic comparison of quantitative high-resolution DNA methylation analysis and methylation-specific PCR  

PubMed Central

Assessment of DNA methylation has become a critical factor for the identification, development and application of methylation based biomarkers. Here we describe a systematic comparison of a quantitative high-resolution mass spectrometry-based approach (MassARRAY), pyrosequencing and the broadly used methylation-specific PCR (MSP) technique analyzing clinically relevant epigenetically silenced genes in acute myeloid leukemia (AML). By MassARRAY and pyrosequencing, we identified significant DNA methylation differences at the ID4 gene promoter and in the 5? region of members of the SFRP gene family in 62 AML patients compared with healthy controls. We found a good correlation between data obtained by MassARRAY and pyrosequencing (correlation coefficient R2 = 0.88). MSP-based assessment of the identical samples showed less pronounced differences between AML patients and controls. By direct comparison of MSP-derived and MassARRAY-based methylation data as well as pyrosequencing, we could determine overestimation of DNA methylation data by MSP. We found sequence-context dependent highly variable cut-off values of quantitative DNA methylation values serving as discriminator for the two MSP methylation categories. Moreover, good agreements between quantitative methods and MSP could not be achieved for all investigated loci. Significant correlation of the quantitative assessment but not of MSP-derived methylation data with clinically important characteristics in our patient cohort demonstrated clinical relevance of quantitative DNA methylation assessment. Taken together, while MSP is still the most commonly applied technique for DNA methylation assessment, our data highlight advantages of quantitative approaches for precise characterization and reliable biomarker use of aberrant DNA methylation in primary patient samples, particularly. PMID:22647397

Claus, Rainer; Wilop, Stefan; Hielscher, Thomas; Sonnet, Miriam; Dahl, Edgar; Galm, Oliver; Jost, Edgar; Plass, Christoph

2012-01-01

333

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

Microsoft Academic Search

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

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

1999-01-01

334

Methylation of cytosines in nonconventional methylation acceptor sites can contribute to reduced gene expression  

Microsoft Academic Search

Epigenetic silencing of gene expression is often correlated with extensive DNA methylation at cytosine residues in the promoter\\u000a and the coding region of silenced genes. Increasing evidence indicates that, in such cases, DNA methylation can also occur\\u000a in sequence contexts other than CG and CNG, resulting in genomic regions with almost complete modification of cytosines. Whether\\u000a this nonconventional methylation at

M. J. Diéguez; M. Bellotto; K. Afsar; O. Mittelsten Scheid; J. Paszkowski

1997-01-01

335

DNA methylation in development and human disease  

PubMed Central

DNA methylation is a heritable and stable epigenetic mark associated with transcriptional repression. Changes in the patterns and levels of global and regional DNA methylation regulate development and contribute directly to disease states such as cancer. Recent findings provide intriguing insights into the epigenetic crosstalk between DNA methylation, histone modifications, and small interfering RNAs in the control of cell development and carcinogenesis. In this review, we summarize the recent studies in DNA methylation primarily focusing on the interplay between different epigenetic modifications and their potential role in gene silencing in development and disease. Although the molecular mechanisms involved in the epigenetic crosstalk are not fully understood, unraveling their precise regulation is important not only for understanding the underpinnings of cellular development and cancer, but also for the design of clinically relevant and efficient therapeutics using stem cells and anticancer drugs that target tumor initiating cells. PMID:18778722

Gopalakrishnan, Suhasni; Emburgh, Beth O. Van; Robertson, Keith D

2008-01-01

336

27 CFR 21.116 - Methyl alcohol.  

27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Methyl alcohol. 21.116 Section 21.116 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF...

2014-04-01

337

Prognostic Significance of DNA and Histone Methylation  

Cancer.gov

Nutritional Science Research Group Recently Funded Projects Prognostic Significance of DNA and Histone Methylation Principal Investigator: Piyathilake, Chandrika J Institution: University of Alabama at Birmingham   NCI/DCP Program Director: Ross, Sharon

338

Targeting DNA Methylation for Epigenetic Therapy  

PubMed Central

DNA methylation patterns are established during embryonic development and faithfully copied through somatic cell divisions. Based on our understanding of DNA methylation and other interrelated epigenetic modifications, a comprehensive view of the epigenetic landscape and cancer epigenome is evolving. The cancer methylome is highly disrupted, making DNA methylation an excellent target for anti-cancer therapies. During the last few decades, an increasing number of drugs targeting DNA methylation have been developed in an effort to increase efficacy, stability and to decrease toxicity. The earliest and the most successful epigenetic drug to date, 5-Azacytidine, is currently recommended as the first-line treatment for high risk myelodysplastic syndromes (MDS) patients. Encouraging results from clinical trials have prompted further efforts to elucidate epigenetic alterations in cancer and subsequently develop new epigenetic therapies. This review delineates the latest cancer epigenetic models, recent discovery of hypomethylation agents and their application in the clinic. PMID:20846732

Yang, Xiaojing; Lay, Fides; Han, Han; Jones, Peter A.

2010-01-01

339

Emission of methyl bromide from biomass burning  

SciTech Connect

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.

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

1994-03-04

340

75 FR 19272 - Thifensulfuron methyl; Pesticide Tolerances  

Federal Register 2010, 2011, 2012, 2013

...of a different factor. 2. Prenatal and postnatal sensitivity. The prenatal and postnatal toxicology database...methyl includes rat and rabbit prenatal developmental toxicity studies...and subchronic neurotoxicity testing. Recent changes to 40...

2010-04-14

341

Function and Evolution of DNA Methylation in Nasonia vitripennis  

PubMed Central

The parasitoid wasp Nasonia vitripennis is an emerging genetic model for functional analysis of DNA methylation. Here, we characterize genome-wide methylation at a base-pair resolution, and compare these results to gene expression across five developmental stages and to methylation patterns reported in other insects. An accurate assessment of DNA methylation across the genome is accomplished using bisulfite sequencing of adult females from a highly inbred line. One-third of genes show extensive methylation over the gene body, yet methylated DNA is not found in non-coding regions and rarely in transposons. Methylated genes occur in small clusters across the genome. Methylation demarcates exon-intron boundaries, with elevated levels over exons, primarily in the 5? regions of genes. It is also elevated near the sites of translational initiation and termination, with reduced levels in 5? and 3? UTRs. Methylated genes have higher median expression levels and lower expression variation across development stages than non-methylated genes. There is no difference in frequency of differential splicing between methylated and non-methylated genes, and as yet no established role for methylation in regulating alternative splicing in Nasonia. Phylogenetic comparisons indicate that many genes maintain methylation status across long evolutionary time scales. Nasonia methylated genes are more likely to be conserved in insects, but even those that are not conserved show broader expression across development than comparable non-methylated genes. Finally, examination of duplicated genes shows that those paralogs that have lost methylation in the Nasonia lineage following gene duplication evolve more rapidly, show decreased median expression levels, and increased specialization in expression across development. Methylation of Nasonia genes signals constitutive transcription across developmental stages, whereas non-methylated genes show more dynamic developmental expression patterns. We speculate that loss of methylation may result in increased developmental specialization in evolution and acquisition of methylation may lead to broader constitutive expression. PMID:24130511

Wang, Xu; Wheeler, David; Avery, Amanda; Rago, Alfredo; Choi, Jeong-Hyeon; Colbourne, John K.; Clark, Andrew G.; Werren, John H.

2013-01-01

342

Isothermal vapor-liquid equilibria for 2-methyl-2-butanol + 2-methyl-1-butanol + 1-pentanol  

SciTech Connect

Vapor-liquid equilibria (VLE) for 2-methyl-2-butanol + 2-methyl-1-butanol and 2-methyl-2-butanol + 2-methyl-1-butanol + 1-pentanol have been measured at 373.15 K. The binary VLE results have been correlated by different liquid-phase activity coefficient models. The binary interaction parameters obtained from Wilson, NRTL, and UNIQUAC models in this and a previously study are used to predict the VLE data for the ternary system. Vapor-liquid equilibrium (VLE) data are necessary for the design of distillation processes.

Aucejo, A.; Burguet, M.C.; Monton, J.B.; Munoz, R.; Sanchotello, M.; Vazquez, M.I. (Univ. of Valencia (Spain). Dept. de Ingenieria Quimica)

1994-07-01

343

Structural Dynamics of Protein Lysine Methylation and De-Methylation - 2006  

PubMed Central

Lysine methylation plays a central role in the “histone code” that regulates chromatin structure, impacts transcription, and responds to DNA damage. A single lysine can be mono-, di-, trimethylated, or unmethylated, with different functional consequences for each of the four forms. This review describes structural aspects of methylation of histone lysine residues by two enzyme families with entirely different structural scaffolding (the SET proteins and Dot1p), and the protein motifs that recognize (decode) these methyl-lysine signals. We also discuss the recently discovered protein lysine de-methylating enzymes (LSD1 and JmjC domains). PMID:17374386

Cheng, Xiaodong; Zhang, Xing

2007-01-01

344

AFLP-Based detection of DNA methylation  

Microsoft Academic Search

By using the isoschizomersHpa II andMsp I which display differential sensitivity to cytosine methylation, a modified amplified fragment length polymorphism (AFLP)\\u000a technique has been developed to investigate DNA methylation profiles in eukaryotic organims. Genomic DNA was digested with\\u000a a mixture ofEcoR I and one of the isoschizomers, and ligated to oligonucleotide adapters. After two rounds of selective PCR amplification,\\u000a followed

Mingliang Xu; Xiangqian Li; Schuyler S. Korban

2000-01-01

345

Performance of sulfoxylated fatty acid methyl esters  

Microsoft Academic Search

Sulfoxidation of fatty acid methyl esters with SO2, O2, and ultraviolet light of appropriate wavelength has led to the synthesis of methyl esters sulfonates or sulfoxylates known\\u000a as ?-MES because of the possible random position of SO3 group in the alkyl chain. This work describes experimental measurements of physical properties such as solubility and viscosity\\u000a of sodium ?-MES water solutions.

Leon Cohen; Francisco Trujillo

1999-01-01

346

Aberrant DNA Methylation and Prostate Cancer  

PubMed Central

Prostate cancer (PCa) is the most prevalent cancer, a significant contributor to morbidity and a leading cause of cancer-related death in men in Western industrialized countries. In contrast to genetic changes that vary among individual cases, somatic epigenetic alterations are early and highly consistent events. Epigenetics encompasses several different phenomena, such as DNA methylation, histone modifications, RNA interference, and genomic imprinting. Epigenetic processes regulate gene expression and can change malignancy-associated phenotypes such as growth, migration, invasion, or angiogenesis. Methylations of certain genes are associated with PCa progression. Compared to normal prostate tissues, several hypermethylated genes have also been identified in benign prostate hyperplasia, which suggests a role for aberrant methylation in this growth dysfunction. Global and gene-specific DNA methylation could be affected by environmental and dietary factors. Among other epigenetic changes, aberrant DNA methylation might have a great potential as diagnostic or prognostic marker for PCa and could be tested in tumor tissues and various body fluids (e.g., serum, urine). The DNA methylation markers are simple in nature, have high sensitivity, and could be detected either quantitatively or qualitatively. Availability of genome-wide screening methodologies also allows the identification of epigenetic signatures in high throughput population studies. Unlike irreversible genetic changes, epigenetic alterations are reversible and could be used for PCa targeted therapies. PMID:22547956

Majumdar, Sunipa; Buckles, Eric; Estrada, John; Koochekpour, Shahriar

2011-01-01

347

Methyl halide emissions from savanna fires in southern Africa  

Microsoft Academic Search

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

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

348

Altered Breast Methylation after Low/Hi Dose Isoflavones  

Cancer.gov

DNA methylation is a vital process in normal development and in cancer. Most cancers demonstrate whole genomic hypomethylation and promoter hypermethylation in certain critical tumor suppressor and growth regulatory genes, which leads to genetic instability. There is growing evidence that nutraceuticals can influence gene expression through DNA methylation. Dietary methyl donors such as folic acid are known to affect DNA methylation, and numerous studies indicate that a diet deficient in methyl donors is associated with an increased breast cancer risk.

349

A fluorescence method for detection of DNA and DNA methylation based on graphene oxide and restriction endonuclease HpaII.  

PubMed

DNA methylation plays an important role in many biological events and is associated with various diseases. Most traditional methods for detection of DNA methylation are based on the complex and expensive bisulfite method. In this paper, we report a novel fluorescence method to detect DNA and DNA methylation based on graphene oxide (GO) and restriction endonuclease HpaII. The skillfully designed probe DNA labeled with 5-carboxyfluorescein (FAM) and optimized GO concentration keep the probe/target DNA still adsorbed on the GO. After the cleavage action of HpaII the labeled FAM is released from the GO surface and its fluorescence recovers, which could be used to detect DNA in the linear range of 50pM-50nM with a detection limit of 43pM. DNA methylation induced by transmethylase (Mtase) or other chemical reagents prevents HpaII from recognizing and cleaving the specific site; as a result, fluorescence cannot recover. The fluorescence recovery efficiency is closely related to the DNA methylation level, which can be used to detect DNA methylation by comparing it with the fluorescence in the presence of intact target DNA. The method for detection of DNA and DNA methylation is simple, reliable and accurate. PMID:25281112

Wei, Wei; Gao, Chunyan; Xiong, Yanxiang; Zhang, Yuanjian; Liu, Songqin; Pu, Yuepu

2015-01-01

350

A 5' differentially methylated sequence and the 3'-flanking region are necessary for H19 transgene imprinting.  

PubMed Central

The mouse H19 gene is expressed exclusively from the maternal allele. The imprinted expression of the endogenous gene can be recapitulated in mice by using a 14-kb transgene encompassing 4 kb of 5'-flanking sequence, 8 kb of 3'-flanking sequence, which includes the two endoderm-specific enhancers, and an internally deleted structural gene. We have generated multiple transgenic lines with this 14-kb transgene and found that high-copy-number transgenes most closely follow the imprinted expression of the endogenous gene. To determine which sequences are important for imprinted expression, deletions were introduced into the transgene. Deletion of the 5' region, where a differentially methylated sequence proposed to be important in determining parental-specific expression is located, resulted in transgenes that were expressed and hypomethylated, regardless of parental origin. A 6-kb transgene, which contains most of the differentially methylated sequence but lacks the 8-kb 3' region, was not expressed and also not methylated. These results indicate that expression of either the H19 transgene or a 3' DNA sequence is key to establishing the differential methylation pattern observed at the endogenous locus. Finally, methylation analysis of transgenic sperm DNA from the lines that are not imprinted reveals that the transgenes are not capable of establishing and maintaining the paternal methylation pattern observed for imprinted transgenes and the endogenous paternal allele. Thus, the imprinting of the H19 gene requires a complex set of elements including the region of differential methylation and the 3'-flanking sequence. PMID:8972211

Elson, D A; Bartolomei, M S

1997-01-01

351

High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis.  

PubMed

N(6)-methyladenosine (m(6)A) is the most ubiquitous mRNA base modification, but little is known about its precise location, temporal dynamics, and regulation. Here, we generated genomic maps of m(6)A sites in meiotic yeast transcripts at nearly single-nucleotide resolution, identifying 1,308 putatively methylated sites within 1,183 transcripts. We validated eight out of eight methylation sites in different genes with direct genetic analysis, demonstrated that methylated sites are significantly conserved in a related species, and built a model that predicts methylated sites directly from sequence. Sites vary in their methylation profiles along a dense meiotic time course and are regulated both locally, via predictable methylatability of each site, and globally, through the core meiotic circuitry. The methyltransferase complex components localize to the yeast nucleolus, and this localization is essential for mRNA methylation. Our data illuminate a conserved, dynamically regulated methylation program in yeast meiosis and provide an important resource for studying the function of this epitranscriptomic modification. PMID:24269006

Schwartz, Schraga; Agarwala, Sudeep D; Mumbach, Maxwell R; Jovanovic, Marko; Mertins, Philipp; Shishkin, Alexander; Tabach, Yuval; Mikkelsen, Tarjei S; Satija, Rahul; Ruvkun, Gary; Carr, Steven A; Lander, Eric S; Fink, Gerald R; Regev, Aviv

2013-12-01

352

Importance of sulfate reducing bacteria in mercury methylation and demethylation in periphyton from Bolivian Amazon region.  

PubMed

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

Achá, Darío; Hintelmann, Holger; Yee, Janet

2011-02-01

353

Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas  

PubMed Central

Background High-grade soft tissue sarcomas are a heterogeneous, complex group of aggressive malignant tumors showing mesenchymal differentiation. Recently, soft tissue sarcomas have increasingly been classified on the basis of underlying genetic alterations; however, the role of aberrant DNA methylation in these tumors is not well understood and, consequently, the usefulness of methylation-based classification is unclear. Results We used the Infinium HumanMethylation27 platform to profile DNA methylation in 80 primary, untreated high-grade soft tissue sarcomas, representing eight relevant subtypes, two non-neoplastic fat samples and 14 representative sarcoma cell lines. The primary samples were partitioned into seven stable clusters. A classification algorithm identified 216 CpG sites, mapping to 246 genes, showing different degrees of DNA methylation between these seven groups. The differences between the clusters were best represented by a set of eight CpG sites located in the genes SPEG, NNAT, FBLN2, PYROXD2, ZNF217, COL14A1, DMRT2 and CDKN2A. By integrating DNA methylation and mRNA expression data, we identified 27 genes showing negative and three genes showing positive correlation. Compared with non-neoplastic fat, NNAT showed DNA hypomethylation and inverse gene expression in myxoid liposarcomas, and DNA hypermethylation and inverse gene expression in dedifferentiated and pleomorphic liposarcomas. Recovery of NNAT in a hypermethylated myxoid liposarcoma cell line decreased cell migration and viability. Conclusions Our analysis represents the first comprehensive integration of DNA methylation and transcriptional data in primary high-grade soft tissue sarcomas. We propose novel biomarkers and genes relevant for pathogenesis, including NNAT as a potential tumor suppressor in myxoid liposarcomas. PMID:24345474

2013-01-01

354

Subtype-dependence of N-methyl-D-aspartate receptor modulation by pregnenolone sulfate.  

PubMed

N-methyl-D-aspartate receptors play a critical role in synaptogenesis, synaptic plasticity, and excitotoxicity. They are heteromeric complexes of NR1 combined with NR2A-D and/or NR3A-B subunits. The subunit composition determines the biophysical and pharmacological properties of the N-methyl-D-aspartate receptor channel complex. In this study, we report that responses mediated by recombinant rat N-methyl-D-aspartate receptors expressed in human embryonic kidney HEK293 cells are differentially affected by naturally occurring neurosteroid pregnenolone sulfate. We show that responses induced by 1mM glutamate in NR1-1a/NR2A and NR1-1a/NR2B receptors are potentiated five- to eight-fold more by pregnenolone sulfate than responses of NR1-1a/NR2C and NR1-1a/NR2D receptors with no differences in the concentration of pregnenolone sulfate that produced 50% potentiation. In addition to potentiation, pregnenolone sulfate also has an inhibitory effect at recombinant N-methyl-D-aspartate receptors, with values of the concentration of pregnenolone sulfate that produces 50% inhibition of NR1/NR2D=NR1/NR2Cmethyl-D-aspartate receptor. These data provide insight into the mechanisms by which pregnenolone sulfate and related sulfated neurosteroids modulate activity of N-methyl-D-aspartate receptor channels. PMID:16257494

Horak, M; Vlcek, K; Chodounska, H; Vyklicky, L

2006-01-01

355

DNA methylation. The effect of minor bases on DNA-protein interactions.  

PubMed Central

DNA methylation is found almost ubiquitously in nature and the methyltransferases show evidence of a common evolutionary origin. It will be a fascinating study in protein evolution to follow the ways in which the structures of the various enzymes have developed. Although methylation may have a direct effect on DNA structure the evidence for the importance of this in vivo is accumulating only slowly. In contrast, there is now abundant evidence that methylation of DNA affects DNA-protein interactions and so may have a function in all processes in which such interactions occur. The binding of nucleases is affected in the processes of mismatch repair, DNA restriction and possibly demethylation during differentiation in vertebrates. The binding of transcription factors is affected by DNA methylation and the association of DNA with packaging and segregation proteins may play a part in the control of transcription and replication. The interplay of these effects makes DNA methylation a complex but rewarding area for study. Perhaps we should no longer refer to methylcytosine and methyladenine as minor bases, but rather as key bases which help regulate the functions of DNA. PMID:2405840

Adams, R L

1990-01-01

356

Regulation of histone H3K4 methylation in brain development and disease.  

PubMed

The growing list of mutations implicated in monogenic disorders of the developing brain includes at least seven genes (ARX, CUL4B, KDM5A, KDM5C, KMT2A, KMT2C, KMT2D) with loss-of-function mutations affecting proper regulation of histone H3 lysine 4 methylation, a chromatin mark which on a genome-wide scale is broadly associated with active gene expression, with its mono-, di- and trimethylated forms differentially enriched at promoter and enhancer and other regulatory sequences. In addition to these rare genetic syndromes, dysregulated H3K4 methylation could also play a role in the pathophysiology of some cases diagnosed with autism or schizophrenia, two conditions which on a genome-wide scale are associated with H3K4 methylation changes at hundreds of loci in a subject-specific manner. Importantly, the reported alterations for some of the diseased brain specimens included a widespread broadening of H3K4 methylation profiles at gene promoters, a process that could be regulated by the UpSET(KMT2E/MLL5)-histone deacetylase complex. Furthermore, preclinical studies identified maternal immune activation, parental care and monoaminergic drugs as environmental determinants for brain-specific H3K4 methylation. These novel insights into the epigenetic risk architectures of neurodevelopmental disease will be highly relevant for efforts aimed at improved prevention and treatment of autism and psychosis spectrum disorders. PMID:25135975

Shen, Erica; Shulha, Hennady; Weng, Zhiping; Akbarian, Schahram

2014-09-26

357

Role of Morphological Growth State and Gene Expression in Desulfovibrio africanus strain Walvis Bay Mercury Methylation  

SciTech Connect

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. While 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.

Moberly, James G [ORNL; Miller, Carrie L [ORNL; Brown, Steven D [ORNL; Biswas, Abir [ORNL; Brandt, Craig C [ORNL; Palumbo, Anthony Vito [ORNL; Elias, Dwayne A [ORNL

2012-01-01

358

Developmental regulation of N-terminal H2B methylation in Drosophila melanogaster  

PubMed Central

Histone post-translational modifications play an important role in regulating chromatin structure and gene expression in vivo. Extensive studies investigated the post-translational modifications of the core histones H3 and H4 or the linker histone H1. Much less is known on the regulation of H2A and H2B modifications. Here, we show that a major modification of H2B in Drosophila melanogaster is the methylation of the N-terminal proline, which increases during fly development. Experiments performed in cultured cells revealed higher levels of H2B methylation when cells are dense, regardless of their cell cycle distribution. We identified dNTMT (CG1675) as the enzyme responsible for H2B methylation. We also found that the level of N-terminal methylation is regulated by dART8, an arginine methyltransferase that physically interacts with dNTMT and asymmetrically methylates H3R2. Our results demonstrate the existence of a complex containing two methyltransferases enzymes, which negatively influence each other’s activity. PMID:22053083

Villar-Garea, Ana; Forne, Ignasi; Vetter, Irene; Kremmer, Elisabeth; Thomae, Andreas; Imhof, Axel

2012-01-01

359

Mercury methylation by HgcA: theory supports carbanion transfer to Hg(II).  

PubMed

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

Zhou, Jing; Riccardi, Demian; Beste, Ariana; Smith, Jeremy C; Parks, Jerry M

2014-01-21

360

Conceptual links between DNA methylation reprogramming in the early embryo and primordial germ cells.  

PubMed

DNA methylation is a carrier of important regulatory information that undergoes global reprogramming in the mammalian germ line, including pre-implantation embryos and primordial germ cells (PGCs). A flurry of recent studies have employed technical advances to generate global profiles of methylation and hydroxymethylation in these cells, unravelling the dynamics of methylation erasure at single locus resolution. Active demethylation in the zygote, involving extensive oxidation, is followed by passive loss over early cell divisions. Certain gamete-contributed methylation marks appear to have evolved non-canonical mechanisms for targeted maintenance of methylation in the face of these processes. These protected sequences include the imprinting control regions (ICRs) required for parental imprinting but also a surprising number of other regions. Such targeted maintenance mechanisms may also operate at certain sequences during early PGC migration when global passive demethylation occurs. In later gonadal PGCs, imprints must be reset and this may be achieved through the targeting of active mechanisms including oxidation. Thus, emerging evidence paints a complex picture whereby active and passive demethylation pathways operate synergistically and in parallel to ensure robust erasure in the early embryo and PGCs. PMID:23510682

Seisenberger, Stefanie; Peat, Julian R; Reik, Wolf

2013-06-01

361

Extracting coordinated patterns of DNA methylation and gene expression in ovarian cancer  

PubMed Central

Objective DNA methylation, a regulator of gene expression, plays an important role in diverse biological processes including developmental process, carcinogenesis and aging. In particular, aberrant DNA methylation has been largely observed in several types of cancers. Currently, it is important to extract disease-specific gene sets associated with the regulation of DNA methylation. Materials and methods Here we propose a novel approach to find the minimum regulatory units of genes, co-methylated and co-expressed gene pairs (MEGP) that are highly correlated gene pairs between DNA methylation and gene expression showing the co-regulatory relationship. To evaluate whether our method is applicable to extract disease-associated genes, we applied our method to a large-scale dataset from the Cancer Genome Atlas extracting significantly associated MEGP and analyzed their functional correlation. Results We observed that many MEGP physically interacted with each other and showed high semantic similarity with gene ontology terms. Furthermore, we performed gene set enrichment tests to identify how they are correlated in a complex biological process. Our MEGP were highly enriched in the biological pathway associated with ovarian cancers. Conclusions Our approach is useful for discovering coordinated epigenetic markers associated with specific diseases. PMID:23599224

Joung, Je-Gun; Kim, Dokyoon; Kim, Kyung Hwa; Kim, Ju Han

2013-01-01

362

A Study on the Environmental Degradation of Pesticides Azinphos Methyl and Parathion Methyl  

Microsoft Academic Search

The effect of environmental parameters (temperature and relative humidity) on the degradation rate of azinphos methyl and parathion methyl was studied. Proprietary emulsifiable concentrates were diluted and added to each of 90 glass Petri dishes for each pesticide and were left overnight to dry. Petri dishes were placed in 18 air-tight containers (9 for each pesticide) in which were created

Panagiotis E. Athanasopoulos; Nikolaos V. Kyriakidis; Panagiotis Stavropoulos

2004-01-01

363

Cytosine methylation is the most common covalent modification of DNA in eukaryotes. DNA methylation has an  

E-print Network

- throughput sequencing has made the mapping of DNA methylation feasible on a genome-wide scale. Here we 0.1% of the human genome has been analyzed in detail (Schumacher et al., 2006). A number of recent discuss recent developments and future directions for identifying and mapping methylation, in an effort

364

Pharmacokinetic study of methyl glyoxal-bis-guanylhydrazone (methyl-GAG)  

Microsoft Academic Search

Using a paired ion exchange high pressure liquid Chromatographic assay, pharmacokinetic evaluation of methyl glyoxal bis guanylhydrazone (methyl-GAG) was performed in nine male New Zealand albino rabbits following administration of a single intravenous bolus dose of 50 mg\\/kg B.W (550 mg\\/m2 BSA).

Milan Slavik; Thomas Clouse; Alan Wood; Oscar Blanc; Robert C. Eschbach

1983-01-01

365

Methylal and Methylal-Diesel Blended Fuels from Use In Compression-Ignition Engines  

SciTech Connect

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 (CH{sub 3}-O-CH{sub 2}-O-CH{sub 3}) 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% oxygen by weight and is soluble in diesel fuel. The physical and chemical properties of neat methylal and for blends of methylal in conventional diesel fuel are presented. Methylal was found to be more volatile than diesel fuel, and special precautions for distribution and fuel tank storage are discussed. Steady state engine tests were also performed using an unmodified Cummins 85.9 turbocharged diesel engine to examine the effect of methylal blend concentration on performance and emissions. Substantial reductions of particulate matter emissions h ave been demonstrated 3r IO to 30% blends of methylal in diesel fuel. This research indicates that methylal may be an effective blendstock for diesel fuel provided design changes are made to vehicle fuel handling systems.

Keith D. Vertin; James M. Ohi; David W. Naegeli; Kenneth H. Childress; Gary P. Hagen; Chris I. McCarthy; Adelbert S. Cheng; Robert W. Dibble

1999-05-05

366

DMRforPairs: identifying Differentially Methylated Regions between unique samples using array based methylation profiles  

PubMed Central

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

2014-01-01

367

Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype.  

PubMed

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 phenotype termed CpG island methylator phenotype (CIMP), which includes methylation of such genes as p16 and hMLH1. To study whether CIMP is present in gastric cancer, the methylation status of five newly cloned CpG islands was examined in 56 gastric cancers using bisulfite-PCR. Simultaneous methylation of three loci or more was observed in 23 (41%) of 56 cancers, which suggests that these tumors have the hypermethylator phenotype CIMP. There was a significant concordance between CIMP and the methylation of known genes including p16, and hMLH1; methylation of p16 was detected in 16 (70%) of 23 CIMP+ tumors, 1 (8%) of 12 CIMP intermediate tumors, and 1 (5%) of 21 CIMP- tumors (P<0.0001). Methylation of the hMLH1 gene was detected in three of five tumors that showed microsatellite instability, and all three of the cases were CIMP+. The CIMP phenotype is an early event in gastric cancer, being present in the normal tissue adjacent to cancer in 5 of 56 cases. These results suggest that CIMP may be one of the major pathways that contribute to tumorigenesis in gastric cancers. PMID:10554013

Toyota, M; Ahuja, N; Suzuki, H; Itoh, F; Ohe-Toyota, M; Imai, K; Baylin, S B; Issa, J P

1999-11-01

368

shinyMethyl: interactive quality control of Illumina 450k DNA methylation arrays in R  

PubMed Central

We present shinyMethyl, a Bioconductor package for interactive quality control of DNA methylation data from Illumina 450k arrays. The package summarizes 450k experiments into small exportable R objects from which an interactive interface is launched. Reactive plots allow fast and intuitive quality control assessment of the samples. In addition, exploration of the phenotypic associations is possible through coloring and principal component analysis. Altogether, the package makes it easy to perform quality assessment of large-scale methylation datasets, such as epigenome-wide association studies or the datasets available through The Cancer Genome Atlas portal. The shinyMethyl package is implemented in R and available via Bioconductor. Its development repository is at https://github.com/jfortin1/shinyMethyl. PMID:25285208

Fortin, Jean-Philippe; Fertig, Elana; Hansen, Kasper

2014-01-01

369

The Behavior of Methyl Esters Sulphonate at the Water–Oil Interface: Straight-Chained Methyl Ester from Lauryl to Stearyl as an Oil Phase  

Microsoft Academic Search

The interfacial behavior of four sodium salt of alpha-sulphonated methyl ester derived from palm oil (C12MES, methyl laurate sulphonate; C14MES, methyl myristate sulphonate; C16MES, methyl palmitate sulphonate; and C16\\/18MES, mixtures of palmitate and methyl stearate sulphonate) was determined at the water–oil interface. Five linear hydrocarbon chained methyl esters from methyl laurate (C12ME) to methyl stearate (C16ME) were used as an

Wen Huei Lim; Rafa Azhana Ramle

2009-01-01

370

DNA Methylation in the Neuropeptide S Receptor 1 (NPSR1) Promoter in Relation to Asthma and Environmental Factors  

PubMed Central

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

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

371

Methylation plotter: a web tool for dynamic visualization of DNA methylation data.  

PubMed

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

Mallona, Izaskun; Díez-Villanueva, Anna; Peinado, Miguel A

2014-01-01

372

Histone Lysine Methylation in Diabetic Nephropathy  

PubMed Central

Diabetic nephropathy (DN) belongs to debilitating microvascular complications of diabetes and is the leading cause of end-stage renal diseases worldwide. Furthermore, outcomes from the DCCT/EDIC study showed that DN often persists and progresses despite intensive glucose control in many diabetes patients, possibly as a result of prior episode of hyperglycemia, which is called “metabolic memory.” The underlying mechanisms responsible for the development and progression of DN remain poorly understood. Activation of multiple signaling pathways and key transcription factors can lead to aberrant expression of DN-related pathologic genes in target renal cells. Increasing evidence suggests that epigenetic mechanisms in chromatin such as DNA methylation, histone acetylation, and methylation can influence the pathophysiology of DN and metabolic memory. Exciting researches from cell culture and experimental animals have shown that key histone methylation patterns and the related histone methyltransferases and histone demethylases can play important roles in the regulation of inflammatory and profibrotic genes in renal cells under diabetic conditions. Because histone methylation is dynamic and potentially reversible, it can provide a window of opportunity for the development of much-needed novel therapeutic potential for DN in the future. In this minireview, we discuss recent advances in the field of histone methylation and its roles in the pathogenesis and progression of DN.

Sun, Guang-dong; Cui, Wen-peng; Guo, Qiao-yan; Miao, Li-ning

2014-01-01

373

Modeling of the oxidation of methyl esters - Validation for methyl hexanoate, methyl heptanoate, and methyl decanoate in a jet-stirred reactor  

SciTech Connect

The modeling of the oxidation of methyl esters was investigated and the specific chemistry, which is due to the presence of the ester group in this class of molecules, is described. New reactions and rate parameters were defined and included in the software EXGAS for the automatic generation of kinetic mechanisms. Models generated with EXGAS were successfully validated against data from the literature (oxidation of methyl hexanoate and methyl heptanoate in a jet-stirred reactor) and a new set of experimental results for methyl decanoate. The oxidation of this last species was investigated in a jet-stirred reactor at temperatures from 500 to 1100 K, including the negative temperature coefficient region, under stoichiometric conditions, at a pressure of 1.06 bar and for a residence time of 1.5 s: more than 30 reaction products, including olefins, unsaturated esters, and cyclic ethers, were quantified and successfully simulated. Flow rate analysis showed that reactions pathways for the oxidation of methyl esters in the low-temperature range are similar to that of alkanes. (author)

Glaude, Pierre Alexandre; Herbinet, Olivier; Bax, Sarah; Biet, Joffrey; Warth, Valerie; Battin-Leclerc, Frederique [Laboratoire Reactions et Genie des Procedes, CNRS UPR 3349, Nancy-Universite, ENSIC, 1 rue Grandville, BP 20451, 54001 Nancy Cedex (France)

2010-11-15

374

Autism: A Redox/Methylation Disorder  

PubMed Central

While autism is still a mysterious developmental disorder, expansion of research efforts over the past 10 to 15 years has yielded a number of important clues implicating both genetic and environmental factors. We can now assert with a measure of confidence that contemporary autism reflects the combined impact of multiple environmental factors on the processes that regulate development in genetically vulnerable individuals. Since epigenetic regulation of gene expression is acknowledged as the most critical factor in development and DNA methylation (the addition of a carbon atom at discrete locations) is the fundamental event for epigenetic regulation, dysfunctional methylation can be considered as a likely cause of autism. Since methylation activity is highly sensitive to oxidative stress (an abnormal redox state) and many environmental factors promote oxidative stress, we have proposed a redox/methylation hypothesis for autism causation. The narrative herein describes the evolution of this hypothesis, which is essentially a series of linked discoveries about how the brain uniquely relies on oxidation and methylation to guide its development and to carry out its cognitive functions. PMID:24416710

2013-01-01

375

Formation of Methyl Mercury by Bacteria  

PubMed Central

Twenty-three Hg2+ resistant cultures were isolated from sediment of the Savannah River in Georgia; of these, 14 were gram-negative short rods belonging to the genera Escherichia and Enterobacter, six were gram-positive cocci (three Staphylococcus sp. and three Streptococcus sp.) and three were Bacillus sp. All the Escherichia, Enterobacter, and the Bacillus strain were more resistant to Hg2+ than the strains of staphylococci and streptococci. Adaptation using serial dilutions and concentration gradient agar plate techniques showed that it was possible to select a Hg2+-resistant strain from a parent culture identified as Enterobacter aerogenes. This culture resisted 1,200 ?g of Hg2+ per ml of medium and produced methyl mercury from HgCl2, but was unable to convert Hg2+ to volatile elemental mercury (Hg0). Under constant aeration (i.e., submerged culture), slightly more methyl mercury was formed than in the absence of aeration. Production of methyl mercury was cyclic in nature and slightly decreased if DL-homocysteine was present in media, but increased with methyl-cobalamine. It is concluded that the bacterial production of methyl mercury may be a means of resistance and detoxification against mercurials in which inorganic Hg2+ is converted to organic form and secreted into the environment. PMID:1180551

Hamdy, M. K.; Noyes, O. R.

1975-01-01

376

DNA methylation, a hand behind neurodegenerative diseases  

PubMed Central

Epigenetic alterations represent a sort of functional modifications related to the genome that are not responsible for changes in the nucleotide sequence. DNA methylation is one of such epigenetic modifications that have been studied intensively for the past several decades. The transfer of a methyl group to the 5 position of a cytosine is the key feature of DNA methylation. A simple change as such can be caused by a variety of factors, which can be the cause of many serious diseases including several neurodegenerative diseases. In this review, we have reviewed and summarized recent progress regarding DNA methylation in four major neurodegenerative diseases: Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). The studies of these four major neurodegenerative diseases conclude the strong suggestion of the important role DNA methylation plays in these diseases. However, each of these diseases has not yet been understood completely as details in some areas remain unclear, and will be investigated in future studies. We hope this review can provide new insights into the understanding of neurodegenerative diseases from the epigenetic perspective. PMID:24367332

Lu, Haoyang; Liu, Xinzhou; Deng, Yulin; Qing, Hong

2013-01-01

377

Prognostic DNA Methylation Markers for Prostate Cancer  

PubMed Central

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

Strand, Siri H.; Orntoft, Torben F.; Sorensen, Karina D.

2014-01-01

378

Developmental differences in posttranslational calmodulin methylation in pea plants  

SciTech Connect

A calmodulin-N-methyltransferase was used to analyze the degree of lysine-115 methylation of pea calmodulin. Calmodulin was isolated from segments of developing roots of young etiolated and green pea plants and was tested for its ability to be methylated by the calmodulin methyltransferase in the presence of {sup 3}H-methyl-S-adenosylmethionine. Calmodulin methylation levels were lower in apical root segments and in the young lateral roots compared with the mature, differentiated root tissues. The methylation of these calmodulin samples occurs specifically at lysine 115 since site-directed mutants of calmodulin with substitutions at this position were not methylated and competitively inhibited methylation. The present findings, combined with previous data showing differences in NAD kinase activation by methylated and unmethylated calmodulins, raise the possibility that posttranslational methylation could affect calmodulin action.

Oh, Sukheung; Roberts, D.M. (Univ. of Tennessee, Knoxville (USA))

1990-05-01

379

Dynamic Alu Methylation during Normal Development, Aging, and Tumorigenesis  

PubMed Central

DNA methylation primarily occurs on CpG dinucleotides and plays an important role in transcriptional regulations during tissue development and cell differentiation. Over 25% of CpG dinucleotides in the human genome reside within Alu elements, the most abundant human repeats. The methylation of Alu elements is an important mechanism to suppress Alu transcription and subsequent retrotransposition. Decades of studies revealed that Alu methylation is highly dynamic during early development and aging. Recently, many environmental factors were shown to have a great impact on Alu methylation. In addition, aberrant Alu methylation has been documented to be an early event in many tumors and Alu methylation levels have been associated with tumor aggressiveness. The assessment of the Alu methylation has become an important approach for early diagnosis and/or prognosis of cancer. This review focuses on the dynamic Alu methylation during development, aging, and tumor genesis. The cause and consequence of Alu methylation changes will be discussed.

Lu, Xuemei

2014-01-01

380

Glutamine methylation in Histone H2A is an RNA Polymerase I dedicated modification  

PubMed Central

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

Tessarz, Peter; Santos-Rosa, Helena; Robson, Sam C.; Sylvestersen, Kathrine B.; Nelson, Christopher J; Nielsen, Michael L.; Kouzarides, Tony

2013-01-01

381

Active transport, substrate specificity, and methylation of Hg(II) in anaerobic bacteria  

PubMed Central

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

Schaefer, Jeffra K.; Rocks, Sara S.; Zheng, Wang; Liang, Liyuan; Gu, Baohua; Morel, Francois M. M.

2011-01-01

382

Position-specific isotope analysis of the methyl group carbon in methylcobalamin for the investigation of biomethylation processes.  

PubMed

In the environment, the methylation of metal(loid)s is a widespread phenomenon, which enhances both biomobility as well as mostly the toxicity of the precursory metal(loid)s. Different reaction mechanisms have been proposed for arsenic, but not really proven yet. Here, carbon isotope analysis can foster our understanding of these processes, as the extent of the isotopic fractionation allows to differentiate between different types of reaction, such as concerted (SN2) or stepwise nucleophilic substitution (SN1) as well as to determine the origin of the methyl group. However, for the determination of the kinetic isotope effect the initial isotopic value of the transferred methyl group has to be determined. To that end, we used hydroiodic acid for abstraction of the methyl group from methylcobalamin (CH3Cob) or S-adenosyl methionine (SAM) and subsequent analysis of the formed methyl iodide by gas chromatography (GC) isotope ratio mass spectrometry (IRMS). In addition, three further independent methods have been investigated to determine the position-specific ? (13)C value of CH3Cob involving photolytic cleavage with different additives or thermolytic cleavage of the methyl-cobalt bonding and subsequent measurement of the formed methane by GC-IRMS. The thermolytic cleavage gave comparable results as the abstraction using HI. In contrast, photolysis led to an isotopic fractionation of about 7 to 9 ‰. Furthermore, we extended a recently developed method for the determination of carbon isotope ratios of organometal(loid)s in complex matrices using hydride generation for volatilization and matrix separation before heart-cut GC and IRMS to the analysis of the low boiling partly methylated arsenicals, which are formed in the course of arsenic methylation. Finally, we demonstrated the applicability of this methodology by investigation of carbon fractionation due to the methyl transfer from CH3Cob to arsenic induced by glutathione. PMID:23325400

Wuerfel, Oliver; Greule, Markus; Keppler, Frank; Jochmann, Maik A; Schmidt, Torsten C

2013-03-01

383

Ion-pair charge transfer complex with near-IR absorption: Synthesis, crystal structure and properties of [Hb] 2[Cu(mnt) 2] (Hb = 1-(4-((1H-imidazol-1-yl)methyl)benzyl)-1H-imidazol-3-ium)  

NASA Astrophysics Data System (ADS)

The compound [Hb] 2[Cu(mnt) 2] ( 1) [Hb = 1-(4-((1H-imidazol-1-yl)methyl)benzyl)-1H-imidazol-3-ium] has been synthesized, starting from 1,4-bis((1H-imidazol-1-yl)methyl)benzene, cupric chloride, and Na 2mnt in methanol. Compound 1 crystallizes in monoclinic system with C2/ c space group. In the crystal structure, the interactions between cations and anions via bifurcated C sbnd H···(NC-mnt) 2 hydrogen bonds give rise to a two dimensional supramolecular network. It has also been observed that two cation moieties (Hb) are attached together by a very short C sbnd H···N hydrogen bonding interaction with H···N distance of 1.74 Å, ?CHN bond angle of 174.9°. Compound 1 is additionally characterized by cyclic voltammetry, UV-Vis, IR, 1H NMR and EPR spectroscopy. The ion-pair compound 1 shows an intense absorption in the near-IR region at ˜1214 nm which has been described as a charge transfer band from HOMO of the copper dithiolate anion [Cu(mnt) 2] 2-, to LUMO of the [Hb] + cation. The title compound exhibits an oxidative response at +0.46 V vs. Ag/AgCl and a reductive event at -0.67 V vs. Ag/AgCl.

Kishore, Ravada; Tripuramallu, Bharat Kumar; Durgaprasad, Gummadi; Das, Samar K.

2011-03-01

384

First evidence of DNA methylation in insect Tribolium castaneum  

PubMed Central

DNA methylation has been studied in many eukaryotic organisms, in particular vertebrates, and was implicated in developmental and phenotypic variations. Little is known about the role of DNA methylation in invertebrates, although insects are considered as excellent models for studying the evolution of DNA methylation. In the red flour beetle, Tribolium castaneum (Tenebrionidae, Coleoptera), no evidence of DNA methylation has been found till now. In this paper, a cytosine methylation in Tribolium castaneum embryos was detected by methylation sensitive restriction endonucleases and immuno-dot blot assay. DNA methylation in embryos is followed by a global demethylation in larvae, pupae and adults. DNA demethylation seems to proceed actively through 5-hydroxymethylcytosine, most probably by the action of TET enzyme. Bisulfite sequencing of a highly abundant satellite DNA located in pericentromeric heterochromatin revealed similar profile of cytosine methylation in adults and embryos. Cytosine methylation was not only restricted to CpG sites but was found at CpA, CpT and CpC sites. In addition, complete cytosine demethylation of heterochromatic satellite DNA was induced by heat stress. The results reveal existence of DNA methylation cycling in T. castaneum ranging from strong overall cytosine methylation in embryos to a weak DNA methylation in other developmental stages. Nevertheless, DNA methylation is preserved within heterochromatin during development, indicating its role in heterochromatin formation and maintenance. It is, however, strongly affected by heat stress, suggesting a role for DNA methylation in heterochromatin structure modulation during heat stress response. PMID:23644818

Feliciello, Isidoro; Parazajder, Josip; Akrap, Ivana; Ugarkovic, ?ur?ica

2013-01-01

385

[Selenium methylation and toxicity mechanism of selenocystine].  

PubMed

Selenium is an essential trace element and a toxicant for animals. Selenocystine, a selenium-containing amino acid, is one of the chemical forms in which selenium exists in food. This review summarized recent studies on the toxicity mechanism of selenocystine in experimental animals. Hepatotoxicity is caused by repeated oral administration of selenocystine. Selenocystine is metabolized by reduced glutathione and/or glutathione reductase to hydrogen selenide via selenocysteine-glutathione selenenyl sulfide. The hydrogen selenide is a key intermediate in the selenium methylation metabolism of inorganic and organic selenium compounds. Accumulation of the hydrogen selenide resulting from inhibition of the selenium methylation metabolism, detoxification metabolic pathway of selenium, is found in animals following repeated administration of a toxic dose of selenocystine. The excess of the hydrogen selenide produced by inhibition of the selenium methylation metabolism contributes to the hepatotoxicity caused by selenocystine. PMID:9414580

Sayato, Y; Nakamuro, K; Hasegawa, T

1997-11-01

386

Influence of Sequential Guanidinium Methylation on the Energetics of the Guanidinium...Guanine Dimer and Guanidinium...Guanine...Cytosine Trimer: Implications For the Control of Protein...DNA Interactions By Arginine Methyltransferases  

PubMed Central

Arginine methylation is a post-translational protein modification that is catalyzed by proteins known as arginine methyl transferases (RMTs). Recently, arginine methylation was postulated as an important modification in modulating biomolecular interactions. RMTs largely target nuclear proteins, so it is highly likely that they aid in modulating protein...DNA interactions. In this study we probe the influence that sequential guanidinium methylation has on the energetics of the guanidinium...guanine and guanidinium...guanine...cytosine complex using ab initio and doublehybrid DFT methods. Structures of guanidinium...guanine complexes derived at the MP2/6-31+G** level of theory show that mono-methylated, symmetrically dimethylated, and unsymmetrical dimethylated guanidiniums are all capable of forming guanidinium...guanine complexes. However, when cytosine is involved in a base pair to guanine only the mono-methylated and symmetrically dimethylated guanidinium groups are capable of forming hydrogen-bond complexes with guanine. At the B2-PLYP/6-311++G** level of theory we found that methylation of the guanidinium group stabilizes the formation of the guanidinium...guanine complex relative to the unmethylated guanidinium...guanine complex by ~2.5 kcal mol–1. The biological implication of these findings are discussed. PMID:19368013

Shearer, Jason

2010-01-01

387

LnOs H LnOs Synthesis and reactivity of the osmium methylidene complex  

E-print Network

LnOs H LnOs H CH3 LnOs CH2 + CH3 + ­H2 (1) + Synthesis and reactivity of the osmium methylidene, or by abstraction of a proton from a cationic methyl compound.13 We now describe the synthesis of an osmium methylidene complex from the reaction of an osmium hydride with methyl trifluoromethanesulfonate (Me

Girolami, Gregory S.

388

Fluorometric determination of phosphatidylcholine as a measure of phospholipid methylation.  

PubMed

The successive methylation of phosphatidylethanolamine to phosphatidylcholine (phospholipid methylation) has been measured by the incorporation of S-[methyl-3H]adenosylmethionine or colorimetric assay of phosphatidylcholine extracted from adipocyte plasma membranes. A fluorometric assay for phosphatidylcholine was developed to measure phospholipid methylation. This assay is 10 times more sensitive than the colorimetric assay and demonstrates no significant interference with other methylated phospholipids. The fluorometric assay was used to determine a biphasic insulin dose response in adipocyte plasma membranes. This fluorometric assay for phosphatidylcholine represents an alternative method for monitoring phospholipid methylation, especially when increased sensitivity is required. PMID:1776685

Dandurand, D M; Kiechle, F L; Strandbergh, D R; Zak, B; Artiss, J D

1991-08-01

389

Microplate-based platform for combined chromatin and DNA methylation immunoprecipitation assays  

PubMed Central

Background The processes that compose expression of a given gene are far more complex than previously thought presenting unprecedented conceptual and mechanistic challenges that require development of new tools. Chromatin structure, which is regulated by DNA methylation and histone modification, is at the center of gene regulation. Immunoprecipitations of chromatin (ChIP) and methylated DNA (MeDIP) represent a major achievement in this area that allow researchers to probe chromatin modifications as well as specific protein-DNA interactions in vivo and to estimate the density of proteins at specific sites genome-wide. Although a critical component of chromatin structure, DNA methylation has often been studied independently of other chromatin events and transcription. Results To allow simultaneous measurements of DNA methylation with other genomic processes, we developed and validated a simple and easy-to-use high throughput microplate-based platform for analysis of DNA methylation. Compared to the traditional beads-based MeDIP the microplate MeDIP was more sensitive and had lower non-specific binding. We integrated the MeDIP method with a microplate ChIP assay which allows measurements of both DNA methylation and histone marks at the same time, Matrix ChIP-MeDIP platform. We illustrated several applications of this platform to relate DNA methylation, with chromatin and transcription events at selected genes in cultured cells, human cancer and in a model of diabetic kidney disease. Conclusion The high throughput capacity of Matrix ChIP-MeDIP to profile tens and potentially hundreds of different genomic events at the same time as DNA methylation represents a powerful platform to explore complex genomic mechanism at selected genes in cultured cells and in whole tissues. In this regard, Matrix ChIP-MeDIP should be useful to complement genome-wide studies where the rich chromatin and transcription database resources provide fruitful foundation to pursue mechanistic, functional and diagnostic information at genes of interest in health and disease. PMID:22098709

2011-01-01

390

40 CFR 721.10409 - Poly(oxyalkylenediyl), .alpha. - [ [ [methyl - 3 - [ [ [ (polyfluoroalkyl)oxy]carbonyl ] amino...  

Code of Federal Regulations, 2013 CFR

...methyl - 3 - [ [ [ (polyfluoroalkyl...amino]carbonyl] - .omega. - methoxy - (generic...methyl - 3 - [ [ [ (polyfluoroalkyl...amino]carbonyl] - .omega. - methoxy - (generic...methyl-3-[[[(polyfluoroalkyl...amino]...

2013-07-01

391

Azido-tetrazolo tautomers of methylated azolopyridazines  

NASA Astrophysics Data System (ADS)

Azido-tetrazolo tautomeric conversions have been investigated by NMR, X-ray and semiempirical calculations in a series of new 7(8)-methylated azolopyridazines. The transannular effects of the triazole- and tetrazole-ring fusion with pyridazine have been compared, and the thermodynamic equilibrium of the 7- to 8-methyl conversions of the 6-azido-7(8)-methyltetrazolopyridazines monitored in the function of temperature by 1H NMR shifts of the pyridazine hydrogens. General rules governing the azido-tetrazolo conversions in azolopyridazines have been formulated and based on the molecular structure and strains induced in the pyridazine ring by its substituents.

Katrusiak, Anna; Skierska, Urszula; Katrusiak, Andrzej

2005-09-01

392

Fumigant methyl iodide can methylate inorganic mercury species in natural waters.  

PubMed

Methyl iodide or iodomethane (CH3I) has recently been registered as a fumigant in many countries, although its environmental impacts are not well understood. Here we report the results of a study on the methylation of mercury by CH3I in natural water by incubation experiments using both Hg ((199)HgCl2 and CH3(201)Hg(+))- and hydrogen (CD3I)-stable isotope addition techniques. We find that methylation of Hg(0), Hg2(2+) and Hg(2+) by CH3I can occur in natural water under sunlight, while only Hg(0) and Hg2(2+) can be methylated in deionized water. We propose that the methylation of Hg by CH3I in natural waters is mediated by sunlight and involves two steps, the reduction of Hg(2+) to Hg(0)/Hg2(2+) and the subsequent methylation of Hg(0)/Hg2(2+) by CH3I. Further quantitative assessment suggests that CH3I-involved methylation of inorganic Hg could be an important source of CH3Hg(+) in an environment where CH3I has been used in large amounts as a fumigant. PMID:25137238

Yin, Yongguang; Li, Yanbin; Tai, Chao; Cai, Yong; Jiang, Guibin

2014-01-01

393

C-H bond activation with actinides: The first example of intramolecular ring bite of a pentamethylcyclopentadienyl methyl group  

SciTech Connect

Thermolysis of (C{sub 5}Me{sub 5}){sub 2}U({double_bond}NAd){sub 2}, 1 (Ad = 1-adamantyl), in benzene or hexane results in the intramolecular C-H bond activation of a methyl group on a pentamethylcyclopentadienyl ligand across the two imido functional groups. The product of this reaction has been spectroscopically and structurally characterized. The activation product is a reduced U(IV) metallocene bis(amide) complex with an N-bound methylene unit derived from the met