Sample records for n-methyl pyrrolidinone nmp

  1. Partial dissolution of ACQ-treated wood in lithium chloride/N-methyl-2-pyrrolidinone: Separation of copper from potential lignocellulosic feedstocks

    Treesearch

    Thomas L. Eberhardt; Stan Lebow; Karen G. Reed

    2012-01-01

    A cellulose solvent system based on lithium chloride (LiCl) in N-methyl-2-pyrrolidinone (NMP) was used to assess the merits of partial dissolutions of coarsely ground wood samples. Alkaline Copper Quaternary (ACQ)-treated pine wood was of particular interest for treatment given the potential to generate a copper- rich stream apart from solid and/or liquid...

  2. Challenges in Catalytic Manufacture of Renewable Pyrrolidinones from Fermentation Derived Succinate

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    White, James F.; Holladay, Johnathan E.; Zacher, Alan H.

    2014-09-05

    Fermentation derived succinic acid ammonium salt is an ideal precursor for manufacture of renewable N-methyl pyrrolidinone (NMP) or 2-pyrrolidinone (2P) via heterogeneous catalysis. However, there are many challenges to making this a practical reality. Chief among the challenges is avoiding catalyst poisoning by fermentation by- and co-products. Battelle / Pacific Northwest National Laboratory (PNNL) have developed an economically effective technology strategy for this purpose. The technology is a combination of purely thermal processing, followed by simple catalytic hydrogenation that together avoids catalyst poisoning from fermentation impurities and provides high selectivity and yields of NMP or 2P.

  3. [Monograph for N-Methyl-pyrrolidone (NMP) and human biomonitoring values for the metabolites 5-Hydroxy-NMP and 2-Hydroxy-N-methylsuccinimide].

    PubMed

    2015-10-01

    1-Methyl-pyrrolidone (NMP) is used as a solvent in many technical applications. The general population may be exposed to NMP from the use as ingredient in paint and graffiti remover, indoors also from use in paints and carpeting. Because of developmental toxic effects, the use of NMP in consumer products in the EU is regulated. The developmental effects accompanied by weak maternally toxic effects in animal experiments are considered as the critical effects by the German HBM Commission. Based on these effects, HBM-I values of 10 mg/l urine for children and of 15 mg/l for adults, respectively, were derived for the metabolites 5-Hydroxy-NMP and 2-Hydroxy-N-methylsuccinimide. HBM-II-values were set to 30 mg/l urine for children and 50 mg/l for adults, respectively. Because of similar effects of the structural analogue 1-ethyl-2-pyrrolidone (NEP), the possible mixed exposure to both compounds has to be taken into account when evaluating the total burden.

  4. Examination of soil contaminated by coal-liquids by size exclusion chromatography in 1-methyl-2-pyrrolidinone solution to evaluate interference from humic and fulvic acids and extracts from peat.

    PubMed

    Morgan, T J; Herod, A A; Brain, S A; Chambers, F M; Kandiyoti, R

    2005-11-18

    Soil from a redundant coke oven site has been examined by extraction of soluble materials using 1-methyl-2-pyrrolidinone (NMP) followed by size exclusion chromatography (SEC) of the extracted material. The extracted material was found to closely resemble a high temperature coal tar pitch. Standard humic and fulvic acids were also examined since these materials are very soluble in NMP and would be extracted with pitch if present in the soil. Humic substances derived from peat samples and NMP-extracts of peats were also examined. The results show that the humic and fulvic substances were not extracted directly by NMP from peats. They were extracted using caustic soda solution and were different from the peat extracts in NMP. These results indicate that humic and fulvic acids were soluble in NMP in the protonated polyelectrolyte form but not in the original native polyelectrolyte form. The extraction of soil using NMP followed by SEC appears to be a promising method for identifying contamination by coal-based industries.

  5. 40 CFR 721.9005 - 2-Pyrrolidinone, 1,1′-(2-methyl-1,5-pentanediyl)bis-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 2-Pyrrolidinone, 1,1â²-(2-methyl-1,5... Specific Chemical Substances § 721.9005 2-Pyrrolidinone, 1,1′-(2-methyl-1,5-pentanediyl)bis-. (a) Chemical...-pyrrolidinone, 1,1′-(2-methyl-1,5-pentanediyl)bis- (PMN P-93-761; CAS No. 146453-62-5) is subject to reporting...

  6. 40 CFR 721.9005 - 2-Pyrrolidinone, 1,1′-(2-methyl-1,5-pentanediyl)bis-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false 2-Pyrrolidinone, 1,1â²-(2-methyl-1,5... Specific Chemical Substances § 721.9005 2-Pyrrolidinone, 1,1′-(2-methyl-1,5-pentanediyl)bis-. (a) Chemical...-pyrrolidinone, 1,1′-(2-methyl-1,5-pentanediyl)bis- (PMN P-93-761; CAS No. 146453-62-5) is subject to reporting...

  7. 40 CFR 721.9005 - 2-Pyrrolidinone, 1,1′-(2-methyl-1,5-pentanediyl)bis-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 2-Pyrrolidinone, 1,1â²-(2-methyl-1,5... Specific Chemical Substances § 721.9005 2-Pyrrolidinone, 1,1′-(2-methyl-1,5-pentanediyl)bis-. (a) Chemical...-pyrrolidinone, 1,1′-(2-methyl-1,5-pentanediyl)bis- (PMN P-93-761; CAS No. 146453-62-5) is subject to reporting...

  8. 40 CFR 721.9005 - 2-Pyrrolidinone, 1,1′-(2-methyl-1,5-pentanediyl)bis-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false 2-Pyrrolidinone, 1,1â²-(2-methyl-1,5... Specific Chemical Substances § 721.9005 2-Pyrrolidinone, 1,1′-(2-methyl-1,5-pentanediyl)bis-. (a) Chemical...-pyrrolidinone, 1,1′-(2-methyl-1,5-pentanediyl)bis- (PMN P-93-761; CAS No. 146453-62-5) is subject to reporting...

  9. 40 CFR 721.9005 - 2-Pyrrolidinone, 1,1′-(2-methyl-1,5-pentanediyl)bis-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false 2-Pyrrolidinone, 1,1â²-(2-methyl-1,5... Specific Chemical Substances § 721.9005 2-Pyrrolidinone, 1,1′-(2-methyl-1,5-pentanediyl)bis-. (a) Chemical...-pyrrolidinone, 1,1′-(2-methyl-1,5-pentanediyl)bis- (PMN P-93-761; CAS No. 146453-62-5) is subject to reporting...

  10. Experimental exposure of male volunteers to N-methyl-2-pyrrolidone (NMP): acute effects and pharmacokinetics of NMP in plasma and urine.

    PubMed Central

    Akesson, B; Paulsson, K

    1997-01-01

    OBJECTIVES: To study the acute effects of exposure to the increasingly used solvent, N-methyl-2-pyrrolidone (NMP) in male volunteers. Further, to determine the NMP concentration in plasma and urine during and after the exposure. METHODS: Six male volunteers were exposed for eight hours on four different days to 0, 10, 25, and 50 mg/m3 NMP. Plasma was collected and urine was sampled during and after the exposure. Changes in nasal volume were measured by acoustic rhinometry and in airway resistance by spirometry. RESULTS: The eight-hour experimental exposure to 10, 25, and 50 mg/m3 did not induce discomfort to eyes or upper airways. Acute changes in nasal volume were not found, and no changes in the spirometric data could be registered. The elimination curves suggested a non-linear pattern and at the end of exposure showed mean (range) half lifes of NMP in plasma of about 4.0 (2.9-5.8) hours and in urine 4.5 (3.5-6.6) hours. The unmetabolised NMP found in urine samples collected during exposure and at the subsequent 44 hours corresponded to about 2% of the calculated absorbed dose. At the end of the exposure there was a close correlation between exposures and the plasma concentration and urinary excretion of NMP. CONCLUSIONS: NMP was absorbed through the respiratory tract and readily eliminated from the body, mainly by biotransformation to other compounds. Exposure to 10, 25, or 50 mg/m3 NMP did not cause nose, eye, or airway irritation. Thus, NMP is a mild irritant. PMID:9166128

  11. Sleep-inducing N-alkyl-5-[m-(trifluoromethyl)phenyl]-5-hydroxy-2-pyrrolidinones and N-alkyl-3-(trifluoromethyl)cinnamamides.

    PubMed

    Houlihan, W J; Gogerty, J H; Ryan, E A; Schmitt, G

    1985-01-01

    A series of N-alkyl-3-[m-(trifluoromethyl)phenyl]-5-hydroxy-2-pyrrolidinones and N-alkyl-3-(trifluoromethyl)-cinnamamides were prepared and screened in a series of tests designed to detect potential sleep inducers. The more active members of the series were evaluated for their ability to induce sleep in Cebus monkeys. The most active compound, N-methyl-5-[m-(trifluoromethyl)phenyl]-5-hydroxy-2-pyrrolidinone, was equal to methaqualone.

  12. Embryotoxic potential of N-methyl-pyrrolidone (NMP) and three of its metabolites using the rat whole embryo culture system

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Flick, Burkhard; Talsness, Chris E.; Jaeckh, Rudolf

    2009-06-01

    N-methyl-2-pyrrolidone (NMP), which undergoes extensive biotransformation, has been shown in vivo to cause developmental toxicity and, especially after oral treatment, malformations in rats and rabbits. Data are lacking as to whether the original compound or one of its main metabolites is responsible for the toxic effects observed. Therefore, the relative embryotoxicity of the parent compound and its metabolites was evaluated using rat whole embryo culture (WEC) and the balb/c 3T3 cytotoxicity test. The resulting data were evaluated using two strategies; namely, one based on using all endpoints determined in the WEC and the other including endpoints from both the WECmore » and the cytotoxicity test. On basis of the first analysis, the substance with the highest embryotoxic potential is NMP, followed by 5-hydroxy-N-methyl-pyrrolidone (5-HNMP), 2-hydroxy-N-methylsuccinimide (2-HMSI) and N-methylsuccinimide (MSI). Specific dysmorphogeneses induced by NMP and 5-HNMP were aberrations in the head region of the embryos, abnormal development of the second visceral arches and open neural pores. The second evaluation strategy used only two endpoints of the WEC, i.e. the no observed adverse effect concentration (NOAEC{sub WEC}) and the lowest concentration leading to dysmorphogenesis in 100% of the cultured embryos (IC{sub MaxWEC}). In addition to these WEC endpoints the IC{sub 503T3} from the cytotoxicity test (balb/c 3T3 fibroblasts) was included in the evaluation scheme. These three endpoints were applied to a prediction model developed during a validation study of the European Centre for the Validation of Alternative Methods (ECVAM) allowing the classification of the embryotoxic potential of each compound into three classes (non-, weakly- and strongly embryotoxic). Consistent results from both evaluation strategies were observed, whereby NMP and its metabolites revealed a direct embryotoxic potential. Hereby, only NMP and 5-HNMP induced specific embryotoxic effects and

  13. A practical and improved synthesis of (3S,5S)-3-[(tert-butyloxycarbonyl)methyl]- 5-[(methanesulfonyloxy)methyl]-2- pyrrolidinone.

    PubMed

    Yee, Nathan K; Dong, Yong; Kapadia, Suresh R; Song, Jinhua J

    2002-11-29

    A practical and improved synthesis of (3S,5S)-3-[(tert-butyloxycarbonyl)methyl]-5-[(methanesulfonyloxy)methyl]-2-pyrrolidinone (1) is described. The key transformations involve a highly efficient reaction sequence consisting of ethoxycarbonylation, alkylation, hydrolysis, and decarboxylation to produce compound 10. The process described herein is practical, robust, and cost-effective, and it has been successfully implemented in a pilot plant to produce a multikilogram quantity of mesylate 1.

  14. RHEOLOGY OF CONCENTRATED SOLUTIONS OF HYPERBRANCHED POLYESTERS

    EPA Science Inventory

    The solution rheology of different generations of hyperbranched polyesters in N-methyl-2- pyrrolidinone (NMP) solvent was examined in this study. The solutions exhibited Newtonian behavior over a wide range of polyester concentrations. Also, the relative viscosities of poly(amido...

  15. Synthesis of a Chloroamide-Hyperbranched Polymer Additive for Self-Decontaminating Surfaces

    DTIC Science & Technology

    2012-04-01

    dissolved in dichloromethane (DCM) (30 mL) and the solution was dried with anhydrous sodium sulfate (Na2SO4) before being used in the next step...infrared spectroscopy N2 nitrogen Na2SO4 anhydrous sodium sulfate NMP 1-methyl-2-pyrrolidinone PFOA perfluorinated octanoic acid PMMA poly(methyl...16 3.6.1 Synthesis and Characterization of Chlorinated 5,5-Dimethylhydantoin Sodium Salt

  16. SPE-GC/FTD determination of N-methyl-2-pyrrolidone and its metabolites in urine.

    PubMed

    Kubota, Ryuichi; Endo, Yoko; Takeuchi, Akito; Inoue, Yoshinori; Ogata, Hiroko; Ogawa, Masanori; Nakagawa, Tomoo; Onda, Nobuhiko; Endo, Ginji

    2007-07-01

    An analytical method using a combination of solid-phase extraction (SPE) and gas chromatography with a flame thermionic detector (GC/FTD) was developed for determination of N-methyl-2-pyrrolidone (NMP), N-methylsuccinimide (MSI), and 2-hydroxy-N-methylsuccinimide (2-HMSI) in human urine. The SPE cartridge of poly(divinylbenzene/hydroxymethacrylate) used was directly loaded with urine sample, followed by elution with methyl isobutyl ketone (MIBK) and subsequent centrifugation, and the supernatant was injected into the capillary GC using a DB1701. This method allowed efficient separation of NMP, MSI, and 2-HMSI, which were nearly free of interference by other GC peaks arising from urine. Recoveries of NMP, MSI, and 2-HMSI from the SPE cartridge were about 98, 101, and 67%, respectively, with limits of detection of 0.04, 0.02, and 0.06 mg/L, respectively, which met the regulatory requirements. The present method was used for assay in biological monitoring of workers exposed to NMP in their occupational environment.

  17. Synthesis of NMP, a Fluoxetine (Prozac) Precursor, in the Introductory Organic Laboratory

    NASA Astrophysics Data System (ADS)

    Perrine, Daniel M.; Sabanayagam, Nathan R.; Reynolds, Kristy J.

    1998-10-01

    A synthesis of the immediate precursor of the widely used antidepressant fluoxetine (Prozac) is described. The procedure is short, safe, and simple enough to serve as a laboratory exercise for undergraduate students in the second semester of introductory organic chemistry and is one which will be particularly interesting to those planning a career in the health sciences. The compound synthesized is (°)-N,N-dimethyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine, or "N-methyl Prozac" (NMP). The synthesis of NMP requires one two-hour period and a second three-hour period. In the first period, a common Mannich base, 3-dimethylaminopropiophenone, is reduced with sodium borohydride to form (°)-3-dimethylamino-1-phenylpropanol. In the second period, potassium t-butoxide is used to couple (°)-3-dimethylamino-1-phenylpropanol with p-chlorotrifluoromethylbenzene to form NMP, which is isolated as its oxalate salt. All processes use equipment and materials that are inexpensive and readily available in most undergraduate laboratories. Detailed physical data are given on NMP, including high-field DEPT 13C NMR.

  18. DMAC and NMP as Electrolyte Additives for Li-Ion Cells

    NASA Technical Reports Server (NTRS)

    Smart, Marshall; Bugga, Ratnakumar; Lucht, Brett

    2008-01-01

    Dimethyl acetamide (DMAC) and N-methyl pyrrolidinone (NMP) have been found to be useful as high-temperature-resilience-enhancing additives to a baseline electrolyte used in rechargeable lithium-ion electrochemical cells. The baseline electrolyte, which was previously formulated to improve low-temperature performance, comprises LiPF6 dissolved at a concentration of 1.0 M in a mixture comprising equal volume proportions of ethylene carbonate, diethyl carbonate, and dimethyl carbonate. This and other electrolytes comprising lithium salts dissolved in mixtures of esters (including alkyl carbonates) have been studied in continuing research directed toward extending the lower limits of operating temperatures and, more recently, enhancing the high-temperature resilience of such cells. This research at earlier stages, and the underlying physical and chemical principles, were reported in numerous previous NASA Tech Briefs articles. Although these electrolytes provide excellent performance at low temperatures (typically as low as -40 C), when the affected Li-ion cells are subjected to high temperatures during storage and cycling, there occur irreversible losses of capacity accompanied by power fade and deterioration of low-temperature performance. The term "high-temperature resilience" signifies, loosely, the ability of a cell to resist such deterioration, retaining as much as possible of its initial charge/discharge capacity during operation or during storage in the fully charged condition at high temperature. For the purposes of the present development, a temperature is considered to be high if it equals or exceeds the upper limit (typically, 30 C) of the operating-temperature range for which the cells in question are generally designed.

  19. Synthesis and First Principles Investigation of HMX/NMP Cocrystal Explosive

    NASA Astrophysics Data System (ADS)

    Lin, He; Zhu, Shun-Guan; Zhang, Lin; Peng, Xin-Hua; LI, Hong-Zhen

    2013-10-01

    1,3,5,7-Tetranitro-l,3,5,7-tetrazocine (HMX)/N-methyl-2-pyrrolidone (NMP) cocrystal explosive was prepared by a solution evaporation method. This cocrystal explosive crystallized in the trigonal system (space group ? ), with cell parameters a = 16.605(8) Å and c = 31.496(4) Å. Theoretical investigations of the formation mechanism of HMX/NMP cocrystal were carried out in Cambridge serial total energy package (CASTEP) based on dispersion-corrected density functional theory (DFT-D) with a plane wave scheme. The exchange-correlation potential was treated with the Perdew-Burke-Ernzerhof function of generalized gradient approximation, and dispersion force was correlated using Grimme's method. The band structure, density of states, projected density of states, and Mulliken populations were calculated at the generalized gradient approximation level. The results showed that the main host-guest interactions in HMX/NMP cocrystal were hydrogen bonds and stacking interactions, which were the same as those analyzed using X-ray diffraction. Theoretical investigations of HMX/NMP cocrystal explosive may provide the basis for the preparation of cocrystal explosive composed of HMX and energetic materials.

  20. Biomonitoring of exposure to N-methyl-2-pyrrolidone in workers of the automobile industry.

    PubMed

    Meier, Swetlana; Schindler, Birgit K; Koslitz, Stephan; Koch, Holger M; Weiss, Tobias; Käfferlein, Heiko U; Brüning, Thomas

    2013-07-01

    N-methyl-2-pyrrolidone (NMP) is an important organic solvent for varnishes in industry. NMP has been previously shown to be a developmental toxicant in rodents. This study reports current exposures to NMP in the spraying department of an automobile plant using biological monitoring. Two specific metabolites, 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methyl-succinimide (2-HMSI), were analyzed in 69 urine samples of 14 workers exposed to NMP and 9 nonexposed controls. Three different working tasks ('loading' and 'cleaning' of the sprayer system and 'wiping/packing' of the sprayed materials) and three sampling times (preshift, postshift, and preshift of the following day) were studied in exposed workers. Median exposures of 5-HNMP and 2-HMSI in postshift urine of exposed workers were 0.91 and 0.52mg g(-1) creatinine, respectively, whereas median levels in controls were below the limit of detection. Decreased levels of 5-HNMP were observed in preshift urine samples on the following day (0.39mg g(-1) creatinine) in exposed workers, while the concentration of 2-HMSI did not change (0.49mg g(-1) creatinine). Highest exposures occurred during sprayer cleaning with a maximum level of 8.31mg g(-1) creatinine of 5-HNMP in postshift urine. In contrast to 'wipers/packers', no decrease in 5-HNMP could be observed in preshift urine samples on day 2 of the 'loaders' and 'cleaners'. Overall, exposure in terms of 5-HNMP postshift and 2-HMSI preshift of the following day were well below the current biological limit values of the European Union (70 and 20mg g(-1) creatinine). Our results provide initial data on NMP exposure in the automobile industry and suggest that the analysis of 5-HNMP in preshift samples also provides essential information, particularly in situations involving direct handling of liquid NMP-containing formulations.

  1. Dermal absorption and urinary elimination of N-methyl-2-pyrrolidone.

    PubMed

    Bader, Michael; Keener, Stephen A; Wrbitzky, Renate

    2005-09-01

    The dermal absorption of the solvent N-methyl-2-pyrrolidone (NMP) and its elimination in urine was investigated in an experimental study. Seven volunteers were exposed to 1045 mg of liquid NMP under occlusive conditions for 2 h. Urine was collected before, during and up to 72 h after the exposure and analysed for NMP by GC/MS after liquid-liquid extraction. Additionally, the remaining NMP in the pads was determined to estimate the total dermal uptake. The concentration of NMP in urine increased rapidly after beginning of the exposure up to 1 h after the exposure was completed. A peak concentration of 1,836+/-863 microg/l was observed, the half-life in urine was 3.2 h. About 0.5% of the absorbed dose was excreted metabolically unchanged. An average dermal absorption of 5.5 mg cm(-2) h(-1) was calculated. The results of this study show that the percutaneous absorption of NMP may contribute significantly to the overall uptake of the solvent, e.g. in the workplace. Therefore, a biological monitoring of NMP exposed workers is essential for occupational-medical surveillance.

  2. Direct determination of N-methyl-2-pyrrolidone metabolites in urine by HPLC-electrospray ionization-MS/MS using deuterium-labeled compounds as internal standard.

    PubMed

    Suzuki, Yoshihiro; Endo, Yoko; Ogawa, Masanori; Yamamoto, Shinobu; Takeuchi, Akito; Nakagawa, Tomoo; Onda, Nobuhiko

    2009-11-01

    N-methyl-2-pyrrolidone (NMP) has been used in many industries and biological monitoring of NMP exposure is preferred to atmospheric monitoring in occupational health. We developed an analytical method that did not include solid phase extraction (SPE) but utilized deuterium-labeled compounds as internal standard for high-performance liquid chromatography-electrospray ionization-mass spectrometry using a C30 column. Urinary concentrations of NMP and its known metabolites 5-hydoxy-N-methyl-2-pyrrolidone (5-HNMP), N-methyl-succinimide (MSI), and 2-hydroxy-N-methylsuccinimide (2-HMSI) were determined in a single run. The method provided baseline separation of these compounds. Their limits of detection in 10-fold diluted urine were 0.0001, 0.006, 0.008, and 0.03 mg/L, respectively. Linear calibration covered a biological exposure index (BEI) for urinary concentration. The within-run and total precisions (CV, %) were 5.6% and 9.2% for NMP, 3.4% and 4.2% for 5-HNMP, 3.7% and 6.0% for MSI, and 6.5% and 6.9% for 2-HMSI. The method was evaluated using international external quality assessment samples, and urine samples from workers exposed to NMP in an occupational area.

  3. Enhanced photodynamic activity of hypericin by penetration enhancer N-methyl pyrrolidone formulations in the chick chorioallantoic membrane model.

    PubMed

    Saw, Constance Lay Lay; Heng, Paul Wan Sia; Chin, William Wei Lim; Soo, Khee Chee; Olivo, Malini

    2006-07-08

    Hypericin (HY) was examined for photodynamic therapy (PDT)-induced vascular damage using the chick chorioallantoic membrane (CAM) model. Clinically, plasma protein was used to solubilize HY. Upon binding to albumin, free HY available to be transported through the membrane may be limited. Hence, formulations containing a biocompatible solvent, N-Methyl pyrrolidone (NMP), have the potential to enhance HY delivery into solid tumors. At suitable concentrations, NMP and/or light irradiation did not produce antivascular damage. Hypericin-PDT effects showed to be HY and NMP concentrations-dependent. These findings indicate that NMP is a promising solvent and penetration enhancer for HY-PDT clinical applications.

  4. The aniracetam metabolite 2-pyrrolidinone induces a long-term enhancement in AMPA receptor responses via a CaMKII pathway.

    PubMed

    Nishizaki, Tomoyuki; Matsumura, Takuro

    2002-01-31

    The present study was conducted to assess the effect of aniracetam and its metabolites, such as 2-pyrrolidinone, p-anisic acid, and anisamide butyrate, on the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, heteromerically formed of GluR1,2 (GluR1 and GluR2), GluR1,3 (GluR1 and GluR3), and GluR1,2,3 (GluR1, GluR2, and GluR3), expressed in Xenopus oocytes. 2-Pyrrolidinone potentiated kainate-evoked currents through GluR1,2,3 channels in a bell-shaped dose-dependent manner at concentrations ranged from 1 nM to 300 microM, with a maximal effect at 100 microM. The potentiation was long-lasting, reaching approximately 180% of basal levels 60 min after 5-min treatment with 2-pyrrolidinone at 100 microM. 2-Pyrrolidinone (100 microM) potentiated GluR1,3 channel currents as observed in GluR1,2,3, but instead it depressed GluR1,2 currents. Aniracetam and p-anisic acid potentiated GluR1,2,3 channel currents, but to a lesser extent, each about 130 and 103% of basal levels 60 min after treatment at 100 microM. In contrast, anisamide butyrate had no potentiating effect on the currents. Potentiation of GluR1,2,3 channel currents obtained with 2-pyrrolidinone was inhibited by KN-93, a selective inhibitor of calcium/calmodulin-dependent protein kinase (CaMKII), while it was not affected by GF109203X, a selective inhibitor of protein kinase C or H-89, a selective inhibitor of cAMP-dependent protein kinase. The results of the present study suggest that 2-pyrrolidinone persistently enhances activity of the Ca2+-permeable AMPA receptors, GluR1,3 and GluR1,2,3, by interacting with CaMKII.

  5. Responses to Comments for N-Methylpyrrolidone (NMP) Work Plan Risk Assessment

    EPA Pesticide Factsheets

    This document summarizes the public and external peer review comments that the EPA’s Office of Pollution Prevention and Toxics (OPPT) received for the draft work plan risk assessment for n-Methylpyrrolidone (NMP).

  6. Rapid Quantification of N-Methyl-2-pyrrolidone in Polymer Matrices by Thermal Desorption-GC/MS.

    PubMed

    Kim, Young-Min; Kim, Jae Woo; Moon, Hye Mi; Lee, Min-Jin; Hosaka, Akihiko; Watanabe, Atsushi; Teramae, Norio; Park, Young-Kwon; Myung, Seung-Woon

    2017-01-01

    Analysis of a residual solvent in polymeric materials has become an important issue due to the increased regulations and standards for its use. N-Methyl-2-pyrrolidone (NMP) is a solvent widely used in many industries and restricted as one of the chemicals under EU REACH regulations due to its potential harmful effects. In this study, thermal desorption-gas chromatography/mass spectrometry (TD-GC/MS) is applied for the quantitative analysis of NMP with the use of a polymer-coated sample cup. By using the polymer-coated sample cup, the vaporization of NMP was prevented during waiting time before TD-GC/MS analysis. The calibration curve for the TD method showed good linearity (correlation coefficient, r 2 = 0.9998) and precision values (below 5.3% RSD). NMP recovery rates in different polymer matrices (PS, PMMA and PVC) were in the range of 98.8 to 106.6% with RSD values below 5.0%. The quantification result (600 mg NMP/kg PVC) for the blind NMP carrying sample in a PVC matrix by TD-GC/MS was higher than that (532 mg NMP/kg PVC) by solvent extraction-GC/MS method.

  7. Quantification of four major metabolites of embryotoxic N-methyl- and N-ethyl-2-pyrrolidone in human urine by cooled-injection gas chromatography and isotope dilution mass spectrometry.

    PubMed

    Schindler, Birgit K; Koslitz, Stephan; Meier, Swetlana; Belov, Vladimir N; Koch, Holger M; Weiss, Tobias; Brüning, Thomas; Käfferlein, Heiko U

    2012-04-17

    N-Methyl- and N-ethyl-2-pyrollidone (NMP and NEP) are frequently used industrial solvents and were shown to be embryotoxic in animal experiments. We developed a sensitive, specific, and robust analytical method based on cooled-injection (CIS) gas chromatography and isotope dilution mass spectrometry to analyze 5-hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI), two newly identified presumed metabolites of NEP, and their corresponding methyl counterparts (5-HNMP, 2-HMSI) in human urine. The urine was spiked with deuterium-labeled analogues of these metabolites. The analytes were separated from urinary matrix by solid-phase extraction and silylated prior to quantification. Validation of this method was carried out by using both, spiked pooled urine samples and urine samples from 56 individuals of the general population with no known occupational exposure to NMP and NEP. Interday and intraday imprecision was better than 8% for all metabolites, while the limits of detection were between 5 and 20 μg/L depending on the analyte. The high sensitivity of the method enables us to quantify NMP and NEP metabolites at current environmental exposures by human biomonitoring.

  8. Aggregate development in C 60/N-methyl-2-pyrrolidone solution and its mixture with water as revealed by extraction and mass spectroscopy

    NASA Astrophysics Data System (ADS)

    Kyzyma, O. A.; Korobov, M. V.; Avdeev, M. V.; Garamus, V. M.; Snegir, S. V.; Petrenko, V. I.; Aksenov, V. L.; Bulavin, L. A.

    2010-06-01

    The aggregate development in C 60/N-methyl-2-pyrrolidone (C 60/NMP) solution with time is studied by the extraction (hexane) and mass spectroscopy. It is shown that only molecular C 60 in NMP is extracted in hexane, which makes it possible to follow a change in the concentration of non-aggregated fullerene in C 60/NMP during the aggregate growth. It is concluded that almost all fullerene dissolved in NMP is in the aggregates after one month. The reorganization of the aggregates is detected when water is added to the aggregated solution C 60/NMP. Both methods prove that in this case individual fullerene molecules are detached from the aggregates, which contradicts somewhat to complete insolubility of C 60 in water.

  9. DEMONSTRATION OF N-METHYL PYRROLIDONE (NMP) AS A POLLUTION PREVENTION ALTERNATIVE TO PAINT STRIPPING WITH METHYLENE CHLORIDE

    EPA Science Inventory

    This objective of this paper is to demonstrate that NMP is a viable pollution prevention alternative to methylene chloride. Maine Corps Logistics Base (MCLB), Albany, GA, USA was the host site for the demonstration. MCLB's primary function is maintenance of military ground supp...

  10. Considerations for spectroscopy of liquid-exfoliated 2D materials: emerging photoluminescence of N-methyl-2-pyrrolidone.

    PubMed

    Ogilvie, Sean P; Large, Matthew J; Fratta, Giuseppe; Meloni, Manuela; Canton-Vitoria, Ruben; Tagmatarchis, Nikos; Massuyeau, Florian; Ewels, Christopher P; King, Alice A K; Dalton, Alan B

    2017-12-01

    N-methyl-2-pyrrolidone (NMP) has been shown to be the most effective solvent for liquid phase exfoliation and dispersion of a range of 2D materials including graphene, molybdenum disulphide (MoS 2 ) and black phosphorus. However, NMP is also known to be susceptible to sonochemical degradation during exfoliation. We report that this degradation gives rise to strong visible photoluminescence of NMP. Sonochemical modification is shown to influence exfoliation of layered materials in NMP and the optical absorbance of the solvent in the dispersion. The emerging optical properties of the degraded solvent present challenges for spectroscopy of nanomaterial dispersions; most notably the possibility of observing solvent photoluminescence in the spectra of 2D materials such as MoS 2 , highlighting the need for stable solvents and exfoliation processes to minimise the influence of solvent degradation on the properties of liquid-exfoliated 2D materials.

  11. Dispersions of TiS2 nanosheets in organic medium

    NASA Astrophysics Data System (ADS)

    Manjunatha, S.; Kumar, A. Sunil; Machappa, T.

    2018-05-01

    Here in this article, we report Li-intercalated titanium disulfide (TiS2) two-dimensional (2D) nanosheets, exfoliated in 1-methyl-2-pyrrolidinone (NMP) forming a quite stable dispersions of pale brownish color. As synthesized TiS2 nanosheets were characterized by transmission electron microscopy (TEM). Selected area electron diffraction (SAED) pattern confirmed the hexagonal lattice structure of the exfoliated nanosheets.

  12. Role of N-methyl-2-pyrrolidone for preparation of Fe3O4@SiO2 controlled the shell thickness

    NASA Astrophysics Data System (ADS)

    Wee, Sung-Bok; Oh, Hyeon-Cheol; Kim, Tae-Gyun; An, Gye-Seok; Choi, Sung-Churl

    2017-04-01

    We developed a simple and novel approach for the synthesis of Fe3O4@SiO2 nanoparticles with controlled shell thickness, and studied the mechanism. The introduction of N-methyl-2-pyrrolidone (NMP) led to trapping of monomer nuclei in single shell and controlled the shell thickness. Fe3O4@SiO2 controlled the shell thickness, showing a high magnetization value (64.47 emu/g). Our results reveal the role and change in the chemical structure of NMP during the core-shell synthesis process. NMP decomposed to 4-aminobutanoic acid in alkaline condition and decreased the hydrolysis rate of the silica coating process.

  13. Enhancement of Mycophenolate Mofetil Permeation for Topical Use by Eucalyptol and N-Methyl-2-pyrrolidone

    PubMed Central

    Songkram, Chalermkiat

    2016-01-01

    Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) which can be metabolized by esterase. MMF has been approved by the United States Food and Drug Administration (USFDA) for treatment of psoriasis patient with skin symptoms. However, it remains unclear whether MMF is efficiently effective to treat skin symptoms developed from psoriasis. The insufficient amount of MMF penetrating through the skin results in the treatment failure due to the difficulty in MMF penetration through the stratum corneum. Skin permeation enhancers such as eucalyptol (EUL) and N-methyl-2-pyrrolidone (NMP) potentially aid in increasing skin penetration. This study aimed to investigate the effects of a concentration ratio (% w/v) between two enhancers (EUL and NMP). The results showed that EUL enhanced MMF permeation with an enhancement ratio (ER) of 3.44 while NMP was not able to promote the penetration of MMF. Interestingly, the synergistic effect of the two enhancers was observed with a suitable ratio given that the ER was 8.21. EUL and NMP are promising enhancers for the development of MMF based skin product. PMID:27069715

  14. Paint Removers: Methylene Chloride and n-Methylpyrrolidone (NMP)

    EPA Pesticide Factsheets

    This webinar described the risks associated with NMP, provided an overview of TSCA section 6, and solicited input on ways EPA should address identified risks, with a particular emphasis on vulnerable populations.

  15. Accuracy Profiles for Analyzing Residual Solvents in Textiles by GC-MS.

    PubMed

    Bao, Qibei; Fu, Kejie; Ren, Qingqing; Zhong, Yingying; Qian, Dan

    2017-10-01

    Excess residual solvents (RSs) in clothes or other textiles could be toxic and pose risks to both humans and the environment. N,N-Dimethylformamide (DMF), N,N-dimethylacetamide (DMAc) and 1-methyl-2-pyrrolidinone (NMP) are important chemicals frequently used as solvents in the textile industry. Several organizations have proposed limiting DMF, DMAc and NMP in textiles, but an appropriate detection method has not been proposed. A sensitive GC-MS method for the quantification of DMF, DMAc and NMP in textiles was developed. After extraction with ethyl acetate, these RSs were separated on a DB-5MS capillary column. The oven temperature was increased from 50°C (held for 0.5 min) at 10°C/min to 120°C (held for 1 min). The method was fully validated according to the accuracy profile procedure, which is based on β-expectation tolerance intervals for the total measurement bias. Linearity was observed in the range of 0.5-10 mg/L for the solvents with limit of quantification values of 4.2, 3.5 and 2.5 mg/kg for DMF, DMAc and NMP, respectively. The repeatability and intermediate precision were <5.34% and 7.95% for DMF, 5.37% and 9.68% for DMAc, and 2.68% and 5.85% for NMP. The recoveries of DMF, DMAc and NMP were 91.2-106.3%, 89.5-97.7% and 85.6-101.3%, respectively. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Graphene-Fiber-Based Supercapacitors Favor N-Methyl-2-pyrrolidone/Ethyl Acetate as the Spinning Solvent/Coagulant Combination.

    PubMed

    He, Nanfei; Pan, Qin; Liu, Yixin; Gao, Wei

    2017-07-26

    One-dimensional flexible fiber supercapacitors (FSCs) have attracted great interest as promising energy-storage units that can be seamlessly incorporated into textiles via weaving, knitting, or braiding. The major challenges in this field are to develop tougher and more efficient FSCs with a relatively easy and scalable process. Here, we demonstrate a wet-spinning process to produce graphene oxide (GO) fibers from GO dispersions in N-methyl-2-pyrrolidone (NMP), with ethyl acetate as the coagulant. Upon chemical reduction of GO, the resulting NMP-based reduced GO (rGO) fibers (rGO@NMP-Fs) are twice as high in the surface area and toughness but comparable in tensile strength and conductivity as that of the water-based rGO fibers (rGO@H 2 O-Fs). When assembled into parallel FSCs, rGO@NMP-F-based supercapacitors (rGO@NMP-FSCs) offered a specific capacitance of 196.7 F cm -3 (147.5 mF cm -2 ), five times higher than that of rGO@H 2 O-F-based supercapacitors (rGO@H 2 O-FSCs) and also higher than most existing wet-spun rGO-FSCs, as well as those FSCs built with metal wires, graphene/carbon nanotube (CNT) fibers, or even pseudocapacitive materials. In addition, our rGO@NMP-FSCs can provide good bending and cycling stability. The energy density of our rGO@NMP-FSCs reaches ca. 6.8 mWh cm -3 , comparable to that of a Li thin-film battery (4 V/500 μAh).

  17. High-strength N-methyl-2-pyrrolidone-containing process wastewater treatment using sequencing batch reactor and membrane bioreactor: A feasibility study.

    PubMed

    Loh, Chun Heng; Wu, Bing; Ge, Liya; Pan, Chaozhi; Wang, Rong

    2018-03-01

    N-methyl-2-pyrrolidone (NMP) is widely used as a solvent in polymeric membrane fabrication process, its elimination from the process wastewater (normally at a high concentration > 1000 mg/L) prior to discharge is essential because of environmental concern. This study investigated the feasibility of treating high-strength NMP-containing process wastewater in a sequencing batch reactor (SBR; i.e., batch feeding and intermittent aerobic/anoxic condition) and a membrane bioreactor (MBR; i.e., continuous feeding and aeration), respectively. The results showed that the SBR with the acclimated sludge was capable of removing >90% of dissolved organic carbon (DOC) and almost 98% of NMP within 2 h. In contrast, the MBR with the acclimated sludge showed a decreasing NMP removal efficiency from 100% to 40% over 15-day operation. The HPLC and LC-MS/MS analytical results showed that NMP degradation in SBR and MBR could undergo different pathways. This may be attributed to the dissimilar bacterial community compositions in the SBR and MBR as identified by 16s rRNA gene sequencing analysis. Interestingly, the NMP-degrading capability of the activated sludge derived from MBR could be recovered to >98% after they were operated at the SBR mode (batch feeding mode with intermittent aerobic/anoxic condition). This study reveals that SBR is probably a more feasible process to treat high-strength NMP-containing wastewater, but residual NMP metabolites in the SBR effluent need to be post-treated by an oxidation or adsorption process in order to achieve zero-discharge of toxic chemicals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Determination of 5-hydroxy-N-methyl-2-pyrrolidone and 2-hydroxy-N-methylsuccinimide in human plasma and urine using liquid chromatography-electrospray tandem mass spectrometry.

    PubMed

    Carnerup, M A; Akesson, B; Jönsson, B A

    2001-09-15

    A method for simultaneous determination of 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) was developed. These compounds are metabolites from N-methyl-2-pyrrolidone (NMP), a powerful and widely used organic solvent. 5-HNMP and 2-HMSI were purified from plasma and urine by solid-phase extraction using Isolute ENV+ columns, and analysed by liquid chromatography coupled to a mass spectrometer fitted with an atmospheric pressure turbo ion spray ionisation interface in the positive ion mode. The method was validated for plasma and urine concentrations from 0.12 to 25 microg/ml. The recoveries for 5-HNMP and 2-HMSI in plasma were 99 and 98%, respectively, and in urine 111 and 106%, respectively. For 5-HNMP and 2-HMSI, the within-day precision in plasma was 1-4 and 3-6%, respectively, and in urine 2-12 and 3-10%, respectively. The corresponding data for the between-day precision was 5 and 3-6%, respectively, and 4-6 and 7-8%, respectively. The detection limit for 5-HNMP was 4 ng/ml in plasma and 120 ng/ml in urine. For 2-HMSI, it was 5 ng/ml in plasma and 85 ng/ml in urine. The method is applicable for analysis of plasma and urine samples from workers exposed to NMP.

  19. Determination of N-vinyl-2-pyrrolidone and N-methyl-2-pyrrolidone in drugs using polypyrrole-based headspace solid-phase microextraction and gas chromatography-nitrogen-phosphorous detection.

    PubMed

    Mehdinia, Ali; Ghassempour, Alireza; Rafati, Hasan; Heydari, Rouhollah

    2007-03-21

    A headspace solid-phase microextraction and gas chromatography-nitrogen-phosphorous detection (HS-SPME-GC-NPD) method using polypyrrole (PPy) fibers has been introduced to determine two derivatives of pyrrolidone; N-vinyl-2-pyrrolidone (NVP) and N-methyl-2-pyrrolidone (NMP). Two types of PPy fibers, prepared using organic and aqueous media, were compared in terms of extraction efficiency and thermal stability. It was found that PPy film prepared using organic medium (i.e. acetonitrile) had higher extraction efficiency and more thermal stability compared to the film prepared in aqueous medium. To enhance the sensitivity of HS-SPME, the effects of pH, ionic strength, extraction time, extraction temperature and the headspace volume on the extraction efficiency were optimized. Using the results of this research, high sensitivity and selectivity had been achieved due to the combination of the high extraction efficiency of PPy film prepared in organic medium and the high sensitivity and selectivity of nitrogen-phosphorous detection. Linear range of the analytes was found to be between 1.0 and 1000 microg L(-1) with regression coefficients (R(2)) of 0.998 and 0.997 for NVP and NMP, consequently. Limits of detection (LODs) were 0.074 and 0.081 microg L(-1) for NVP and NMP, respectively. Relative standard deviation (R.S.D.) for five replications of analyses was found to be less than 6.0%. In real samples the mean recoveries were 94.81% and 94.15% for NVP and NMP, respectively. The results demonstrated the suitability of the HS-SPME technique for analyzing NVP and NMP in two different pharmaceutical matrices. In addition, the method was used for simultaneous detection of NVP, 2-pyrrolidone (2-Pyr), gamma-butyrolactone (GBL) and ethanolamine (EA) compounds.

  20. OPPT workplan risk assessment Methylene Chloride (dichloromethane; CASRN 75-09-2) and N-Methylpyrrolidone (NMP; CASRN 872-50-4)

    EPA Science Inventory

    These assessments will focus on the use of DCM and NMP in paint stripping. NMP exposures scenarios for this use result in inhalation and dermal exposure to consumers and workers. The low concern for environmental effects of NMP will be discussed in the assessment. In the case of ...

  1. Bone Regeneration Using N-Methyl-2-pyrrolidone as an Enhancer for Recombinant Human Bone Morphogenetic Protein-2 in a Rabbit Sinus Augmentation Model

    PubMed Central

    Thoma, Daniel S.

    2017-01-01

    The aim of this study was to determine whether N-methyl-2-pyrrolidone (NMP) can decrease the dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) in sinus augmentation of rabbits. In each of 15 rabbits, 2 sinuses were randomly grafted using 1 of 3 treatment modalities: (i) biphasic calcium phosphate (BCP; control), (ii) rhBMP-2-coated BCP (BMP), or (iii) rhBMP-2-coated BCP soaked in NMP solution (BMP/NMP). The rabbits were sacrificed 2 weeks postoperatively. Histologic and histomorphometric analyses were performed. Bone formation in all groups was predominantly located close to the access window and the lateral walls. Newly formed bone within the total augmented area (NBTA) was greatest in BMP/NMP (1.94 ± 0.69 mm2), followed by BMP (1.50 ± 0.72 mm2) and BCP (1.28 ± 0.52 mm2) (P > 0.05). In the center of the augmentation (NBROI_C) and the area close to the sinus membrane (NBROI_M), BMP/NMP produced the largest area of NB (NBROI_C: 0.10 ± 0.11 mm2; NBROI_M: 0.17 ± 0.08 mm2); the corresponding NB values for BCP were 0.05 ± 0.05 mm2 and 0.08 ± 0.09 mm2, respectively (P > 0.05 for all comparisons). The effect of NMP on bone regeneration was inconsistent between the specimens. Adding NMP as an adjunct to rhBMP-2-coated BCP produced inconsistent effects on bone regeneration, resulting in no significant benefit compared to controls. PMID:28680881

  2. Bone Regeneration Using N-Methyl-2-pyrrolidone as an Enhancer for Recombinant Human Bone Morphogenetic Protein-2 in a Rabbit Sinus Augmentation Model.

    PubMed

    Lim, Hyun-Chang; Thoma, Daniel S; Yoon, So-Ra; Cha, Jae-Kook; Lee, Jung-Seok; Jung, Ui-Won

    2017-01-01

    The aim of this study was to determine whether N-methyl-2-pyrrolidone (NMP) can decrease the dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) in sinus augmentation of rabbits. In each of 15 rabbits, 2 sinuses were randomly grafted using 1 of 3 treatment modalities: (i) biphasic calcium phosphate (BCP; control), (ii) rhBMP-2-coated BCP (BMP), or (iii) rhBMP-2-coated BCP soaked in NMP solution (BMP/NMP). The rabbits were sacrificed 2 weeks postoperatively. Histologic and histomorphometric analyses were performed. Bone formation in all groups was predominantly located close to the access window and the lateral walls. Newly formed bone within the total augmented area (NB TA ) was greatest in BMP/NMP (1.94 ± 0.69 mm 2 ), followed by BMP (1.50 ± 0.72 mm 2 ) and BCP (1.28 ± 0.52 mm 2 ) ( P > 0.05). In the center of the augmentation (NB ROI_C ) and the area close to the sinus membrane (NB ROI_M ), BMP/NMP produced the largest area of NB (NB ROI_C : 0.10 ± 0.11 mm 2 ; NB ROI_M : 0.17 ± 0.08 mm 2 ); the corresponding NB values for BCP were 0.05 ± 0.05 mm 2 and 0.08 ± 0.09 mm 2 , respectively ( P > 0.05 for all comparisons). The effect of NMP on bone regeneration was inconsistent between the specimens. Adding NMP as an adjunct to rhBMP-2-coated BCP produced inconsistent effects on bone regeneration, resulting in no significant benefit compared to controls.

  3. High T(g) Polyimides

    NASA Technical Reports Server (NTRS)

    Chuang, Kathy

    2001-01-01

    The use of high temperature polymer matrix composites in aerospace applications has expanded steadily over the past 30 years, due to the increasing demand of replacing metal parts with light weight composite materials for fuel efficiency and bigger payloads in the aircraft and the space transportation vehicles. Polyimide/carbon fiber composites, especially, have been regarded as major high temperature matrix materials, based on their outstanding performance in terms of heat resistance, high strength-to-weight ratio and property retention compared with epoxies (177 C/350 F) and bismaleimides (232 C/450 F). Traditional, then-neoplastic polyimides were prepared from dianhydrides and diamines in N-methyl-2-pyrrolidinone (NMP) at room temperature to form the polyamic acids, which were then imidized at 150 C to yield polyimides. However, the high-boiling solvent (NMP, BP= 202 C) is very difficult to remove, leading to the formation of voids during composite fabrication. In the early 1970's, PMR addition curing polyimides with reactive endcaps were developed at the Lewis Research Center (renamed NASA Glenn) to ensure the easy processing of imide oligomers in methanol during composite fabrication.

  4. Effects of N-methyl pyrrolidone on the uptake of hypericin in human bladder carcinoma and co-staining with DAPI investigated by confocal microscopy.

    PubMed

    Saw, Constance Lay Lay; Olivo, Malini; Wohland, Thorsten; Fu, Chit Yaw; Kho, Kiang Wei; Soo, Khee Chee; Sia Heng, Paul Wan

    2007-10-01

    Photodynamic diagnosis (PDD) using hypericin (HY), a natural photosensitizer, detects bladder cancer significantly better than white light endoscopy. However, the lipophilicity of HY complicates its administration for clinical applications. Currently, pharmaceutical preparations for HY without plasma protein are being developed. Formulations containing a biocompatible solvent, N-methyl pyrrolidone (NMP) have been shown to enhance the photodynamic therapeutic effects of HY. It was recently reported that, NMP formulations of HY were able to produce significantly higher contrast for fluorescence detection of tumors than albumin-containing HY formulations. This present work hypothesizes that NMP acts both as a solvent and penetration enhancer to improve the delivery of HY into cells by increasing the permeability of cell membranes. This paper reports the use of 3-D confocal microscopy to monitor real-time uptake of HY in human carcinoma. 3-D confocal microscopy was used to investigate the possibility of nuclear localization of HY in MGH cells. The fluorescence of HY was confirmed to be emitted from HY containing cells using spectrometry. The localization of a DNA fluorescent probe 4', 6-diamidino-2-phenylindole dihydrochloride (DAPI) was used to confirm the possibility of colocalization of DAPI and HY. The colocalization analysis in the present study suggests that it was very unlikely that HY colocalized in the nucleus that was stained by DAPI. Fluorescein leakage tests showed that 1% NMP changes the permeability of cell membranes, and enhanced the delivery of HY into cells resulting in lower cell survival ratios. Thus, NMP was able to enhance the photodynamic therapeutic effects of HY on cancer cells.

  5. Shear Rheology of Suspensions of Porous Zeolite Particles in Concentrated Polymer Solutions

    NASA Astrophysics Data System (ADS)

    Olanrewaju, Kayode O.; Breedveld, Victor

    2008-07-01

    We present experimental data on the shear rheology of Ultem (polyetherimide)/NMP(l-methyl-2-pyrrolidinone) solutions with and without suspended surface-modified porous/nonporous zeolite (ZSM-5) particles. We found that the porous zeolite suspensions have relative viscosities that significantly exceed the Krieger-Dougherty predictions for hard sphere suspensions. The major origin of this discrepancy is the selective absorption of NMP solvent into the zeolite pores, which raises both the polymer concentration and the particle volume fraction, thus enhancing both the viscosity of the continuous phase Ultem/NMP polymer solution and the particle contribution to the suspension viscosity. Other factors, such as zeolite non-sphericity and specific interactions with Ultem polymer, contribute to the suspension viscosity to a lesser extent. We propose a predictive model for the viscosity of porous zeolite suspensions by incorporating an absorption parameter, α, into the Krieger-Dougherty model. We also propose independent approaches to determine α. The first one is indirect and based on zeolite density/porosity data, assuming that all pores will be filled with solvent. The other method is based on our experimental data, by comparing the viscosity data of porous versus non-porous zeolite suspensions. The different approaches are compared.

  6. Effect of solvents on the electrochemical properties of binder-free sulfur cathode films in lithium–sulfur batteries

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ryu, Ho-Suk; Kim, Byeong-Wook; Park, Jin-Woo

    Highlights: • The binder-free sulfur electrode with high sulfur contents of 75 wt.% was fabricated. • The binder-free sulfur electrode using NMP solvents showed 784 mAh g{sup −1} after 40 cycles. • The solvent affect the electrochemical properties of binder-free sulfur electrode films. - Abstract: The effects of solvents on the preparation of sulfur cathodes were investigated by fabricating binder-free sulfur electrode films using three different solvents: 1-methyl-2-pyrrolidinone (NMP), acetonitrile, and deionized water. These solvents are commonly employed to dissolve binders used to prepare sulfur cathodes for lithium–sulfur batteries. The sulfur electrode fabricated with NMP had a higher discharge capacitymore » and longer cycle life than the ones fabricated with acetonitrile and deionized water. Better adhesion between the current collector and the sulfur electrode accounted for the improved capacity and cycle life of the battery. In addition, the stability of the electrode in the electrolyte was a result of the solubility of sulfur in the solvent. We thus concluded that the solvents used in the fabrication of sulfur electrodes had a positive influence on the electrochemical properties of Li–S batteries.« less

  7. A One-Step, Solvothermal Reduction Method for Producing Reduced Graphene Oxide Dispersions in Organic Solvents

    PubMed Central

    Dubin, Sergey; Gilje, Scott; Wang, Kan; Tung, Vincent C.; Cha, Kitty; Hall, Anthony S.; Farrar, Jabari; Varshneya, Rupal; Yang, Yang; Kaner, Richard B.

    2014-01-01

    Refluxing graphene oxide (GO) in N-methyl-2-pyrrolidinone (NMP) results in deoxygenation and reduction to yield a stable colloidal dispersion. The solvothermal reduction is accompanied by a color change from light brown to black. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) images of the product confirm the presence of single sheets of the solvothermally reduced graphene oxide (SRGO). X-ray photoelectron spectroscopy (XPS) of SRGO indicates a significant increase in intensity of the C=C bond character, while the oxygen content decreases markedly after the reduction is complete. X-ray diffraction analysis of SRGO shows a single broad peak at 26.24° 2θ (3.4 Å), confirming the presence of graphitic stacking of reduced sheets. SRGO sheets are redispersible in a variety of organic solvents, which may hold promise as an acceptor material for bulk heterojunction photovoltaic cells, or electromagnetic interference shielding applications. PMID:20586422

  8. Technical and economic analysis of solvent-based lithium-ion electrode drying with water and NMP

    DOE PAGES

    Wood, David L.; Quass, Jeffrey D.; Li, Jianlin; ...

    2017-05-16

    Processing lithium-ion battery (LIB) electrode dispersions with water as the solvent during primary drying offers many advantages over N-methylpyrrolidone (NMP). An in-depth analysis of the comparative drying costs of LIB electrodes is discussed for both NMP- and water-based dispersion processing in terms of battery pack $/kWh. Electrode coating manufacturing and capital equipment cost savings are compared for water vs. conventional NMP organic solvent processing. A major finding of this work is that the total electrode manufacturing costs, whether water- or NMP-based, contribute about 8–9% of the total pack cost. However, it was found that up to a 2 × reductionmore » in electrode processing (drying and solvent recovery) cost can be expected along with a $3–6 M savings in associated plant capital equipment (for a plant producing 100,000 10-kWh Plug-in Hybrid Electric Vehicle (PHEV) batteries) using water as the electrode solvent. This paper shows a different perspective in that the most important benefits of aqueous electrode processing actually revolve around capital equipment savings and environmental stewardship and not processing cost savings.« less

  9. The nuclear matrix protein NMP-1 is the transcription factor YY1.

    PubMed Central

    Guo, B; Odgren, P R; van Wijnen, A J; Last, T J; Nickerson, J; Penman, S; Lian, J B; Stein, J L; Stein, G S

    1995-01-01

    NMP-1 was initially identified as a nuclear matrix-associated DNA-binding factor that exhibits sequence-specific recognition for the site IV regulatory element of a histone H4 gene. This distal promoter domain is a nuclear matrix interaction site. In the present study, we show that NMP-1 is the multifunctional transcription factor YY1. Gel-shift and Western blot analyses demonstrate that NMP-1 is immunoreactive with YY1 antibody. Furthermore, purified YY1 protein specifically recognizes site IV and reconstitutes the NMP-1 complex. Western blot and gel-shift analyses indicate that YY1 is present within the nuclear matrix. In situ immunofluorescence studies show that a significant fraction of YY1 is localized in the nuclear matrix, principally but not exclusively associated with residual nucleoli. Our results confirm that NMP-1/YY1 is a ubiquitous protein that is present in both human cells and in rat osteosarcoma ROS 17/2.8 cells. The finding that NMP-1 is identical to YY1 suggests that this transcriptional regulator may mediate gene-matrix interactions. Our results are consistent with the concept that the nuclear matrix may functionally compartmentalize the eukaryotic nucleus to support regulation of gene expression. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7479833

  10. Synthesis, crystal structures, quantum chemical studies and corrosion inhibition potentials of 4-(((4-ethylphenyl)imino)methyl)phenol and (E)-4-((naphthalen-2-ylimino) methyl) phenol Schiff bases

    NASA Astrophysics Data System (ADS)

    Elemike, Elias E.; Nwankwo, Henry U.; Onwudiwe, Damian C.; Hosten, Eric C.

    2017-11-01

    Two Schiff base ligands, 4-(((4-ethylphenyl)imino)methyl)phenol (4EMP) and (E)-4-((naphthalen-2-ylimino) methyl) phenol (4NMP) were synthesized by the reaction of 4-hydroxybenzaldehyde with 4-ethylaniline, 4EMP, or naphthalene-2-amine, 4NMP. The compounds were characterized using NMR (1H and 13C), Fourier transform infra-red (FTIR) and mass spectroscopic techniques. The proton NMR identified the OH peaks at 9.73 and 9.77 ppm for 4EMP and 4NMP respectively, while the 13C NMR showed the imine carbons at 172.57 ppm for 4EMP and at 160.89 ppm for 4NMP. The FTIR spectra showed characteristic peaks at 1605 cm-1 (4EMP) and 1600 cm-1 (4NMP) typical of the azomethine group, and the mass spectra results gave molecular ion peaks of 226.12 and 248.10 respectively. The structures of the compounds were further established by single crystal X-ray analysis. The corrosion inhibition potential of the compounds were studied on mild steel surface in a 1 M hydrochloric acid (HCl) solution, and was analysed using potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS). The results of the electrochemical methods showed that the studied molecules imparted high resistance in allowing flow of electrons across the metal-electrolyte platform and behaved as mixed type inhibitors with 4EMP showing better inhibition properties than 4NMP. Scanning electron microscopy (SEM) showed the formation of film on the mild steel surface. Quantum chemical calculations achieved by density functional theory (DFT) was further applied to explain the adsorption as well as inhibition abilities of the molecules on the mild steel surface. Thermodynamics studies showed that the two compounds obeyed the Langmuir isotherm with 4EMP conforming to chemisorption mechanism while 4NMP involved competitive physisorption and chemisorption mechanism.

  11. The novel fluorescent CDP-analogue (Pbeta)MABA-CDP is a specific probe for the NMP binding site of UMP/CMP kinase.

    PubMed

    Rudolph, M G; Veit, T J; Reinstein, J

    1999-12-01

    Direct thermodynamic and kinetic investigations of the binding of nucleotides to the nucleoside monophosphate (NMP) site of NMP kinases have not been possible so far because a spectroscopic probe was not available. By coupling a fluorescent N-methylanthraniloyl- (mant) group to the beta-phosphate of CDP via a butyl linker, a CDP analogue [(Pbeta)MABA-CDP] was obtained that still binds specifically to the NMP site of UmpKdicty, because the base and the ribose moieties, which are involved in specific interactions, are not modified. This allows the direct determination of binding constants for its substrates in competition experiments.

  12. The novel fluorescent CDP-analogue (Pbeta)MABA-CDP is a specific probe for the NMP binding site of UMP/CMP kinase.

    PubMed Central

    Rudolph, M. G.; Veit, T. J.; Reinstein, J.

    1999-01-01

    Direct thermodynamic and kinetic investigations of the binding of nucleotides to the nucleoside monophosphate (NMP) site of NMP kinases have not been possible so far because a spectroscopic probe was not available. By coupling a fluorescent N-methylanthraniloyl- (mant) group to the beta-phosphate of CDP via a butyl linker, a CDP analogue [(Pbeta)MABA-CDP] was obtained that still binds specifically to the NMP site of UmpKdicty, because the base and the ribose moieties, which are involved in specific interactions, are not modified. This allows the direct determination of binding constants for its substrates in competition experiments. PMID:10631985

  13. Preparation of hydrophilic monolithic capillary column by in situ photo-polymerization of N-vinyl-2-pyrrolidinone and acrylamide for highly selective and sensitive enrichment of N-linked glycopeptides.

    PubMed

    Jiang, Hao; Yuan, Huiming; Qu, Yanyan; Liang, Yu; Jiang, Bo; Wu, Qi; Deng, Nan; Liang, Zhen; Zhang, Lihua; Zhang, Yukui

    2016-01-01

    In this study, a novel kind of amide functionalized hydrophilic monolith was synthesized by the in situ photo-polymerization of N-vinyl-2-pyrrolidinone (NVP), acrylamide (AM), and N, N'-methylenebisacrylamide (MBA) in a UV transparent capillary, and successfully applied for hydrophilic interaction chromatography (HILIC) based enrichment of N-linked glycopeptides. With 2 μg of the tryptic digests of IgG as the sample, after enrichment, 18 glycopeptides could be identified by MALDI-TOF/TOF MS analysis. Furthermore, with the mixture of BSA and IgG digests (10,000:1, m/m) as the sample, 6 N-linked glycopeptides were unambiguously identified after enrichment, indicating the high selectivity and good specificity of such material. Moreover, such a monolithic capillary column was also applied for the N-glycosylation sites profiling of 6 μg protein digests from HeLa cells and 1 μL human serum. In total, 530 and 262 unique N-glycosylated peptides were identified, respectively, corresponding to 282 and 124N-glycoproteins, demonstrating its great potential for the large scale glycoproteomics analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Porous Polyimide Membranes Prepared by Wet Phase Inversion for Use in Low Dielectric Applications

    PubMed Central

    Kim, Soohyun; Jang, Keon-Soo; Choi, Hee-Dok; Choi, Seung-Hoon; Kwon, Seong-Ji; Kim, Il-Doo; Lim, Jung Ah; Hong, Jae-Min

    2013-01-01

    A wet phase inversion process of polyamic acid (PAA) allowed fabrication of a porous membrane of polyimide (PI) with the combination of a low dielectric constant (1.7) and reasonable mechanical properties (Tensile strain: 8.04%, toughness: 3.4 MJ/m3, tensile stress: 39.17 MPa, and young modulus: 1.13 GPa), with further thermal imidization process of PAA. PAA was simply synthesized from purified pyromellitic dianhydride (PMDA) and 4,4-oxydianiline (ODA) in two different reaction solvents such as γ-butyrolactone (GBL) and N-methyl-2-pyrrolidinone (NMP), which produce Mw/PDI of 630,000/1.45 and 280,000/2.0, respectively. The porous PAA membrane was fabricated by the wet phase inversion process based on a solvent/non-solvent system via tailored composition between GBL and NMP. The porosity of PI, indicative of a low electric constant, decreased with increasing concentration of GBL, which was caused by sponge-like formation. However, due to interplay between the low electric constant (structural formation) and the mechanical properties, GBL was employed for further exploration, using toluene and acetone vs. DI-water as a coagulation media. Non-solvents influenced determination of the PAA membrane size and porosity. With this approach, insight into the interplay between dielectric properties and mechanical properties will inform a wide range of potential low-k material applications. PMID:23615465

  15. Deposition of functional nanoparticle thin films by resonant infrared laser ablation.

    NASA Astrophysics Data System (ADS)

    Haglund, Richard; Johnson, Stephen; Park, Hee K.; Appavoo, Kannatessen

    2008-03-01

    We have deposited thin films containing functional nanoparticles, using tunable infrared light from a picosecond free-electron laser (FEL). Thin films of the green light-emitting molecule Alq3 were first deposited by resonant infrared laser ablation at 6.68 μm, targeting the C=C ring mode of the Alq3. TiO2 nanoparticles 50-100 nm diameter were then suspended in a water matrix, frozen, and transferred by resonant infrared laser ablation at 2.94 μm through a shadow mask onto the Alq3 film. Photoluminescence was substantially enhanced in the regions of the film covered by the TiO2 nanoparticles. In a second experiment, gold nanoparticles with diameters in the range of 50-100 nm were suspended in the conducting polymer and anti-static coating material PEDOT:PSS, which was diluted by mixing with N-methyl pyrrolidinone (NMP). The gold nanoparticle concentration was 8-10% by weight. The mixture was frozen and then ablated by tuning the FEL to 3.47 μm, the C-H stretch mode of NMP. Optical spectroscopy of the thin film deposited by resonant infrared laser ablation exhibited the surface-plasmon resonance characteristic of the Au nanoparticles. These experiments illustrate the versatility of matrix-assisted resonant infrared laser ablation as a technique for depositing thin films containing functionalized nanoparticles.

  16. Propargylation of Ugi Amide Dianion: An Entry into Pyrrolidinone and Benzoindolizidine Alkaloid Analogues.

    PubMed

    Zidan, Alaa; Cordier, Marie; El-Naggar, Abeer M; Abd El-Sattar, Nour E A; Hassan, Mohamed Ali; Ali, Ali Khalil; El Kaïm, Laurent

    2018-05-04

    Propargylation of Ugi adducts under the addition of excess sodium hydride in DMSO leads to direct formation of pyrrolidinone enamides, which are useful precursors of iminium intermediates and may be trapped by various nucleophiles. This approach has been applied to the formation of benzoindolizidine alkaloids with high diversity via a Ugi/propargylation/Pictet-Spengler cyclization.

  17. Reaction products from N-methyl-N-nitrosourea and deoxyribonucleic acid containing thymidine residues. Synthesis and identification of a new methylation product, O4-methyl-thymidine

    PubMed Central

    Lawley, P. D.; Orr, D. J.; Shah, S. A.; Farmer, P. B.; Jarman, M.

    1973-01-01

    1. DNA was treated with N-methyl-N-nitrosourea at pH7–8, 37°C, degraded to yield 3- and 7-methylpurines and deoxyribonucleosides and the reaction products were separated by chromatography on ion-exchange resins. The following methods for identification and determination of products were used: with unlabelled N-methyl-N-nitrosourea, u.v. absorption; use of methyl-14C-labelled N-methyl-N-nitrosourea and use of [14C]thymine-labelled DNA. 2. The synthesis of O4-methylthymidine and its identification by u.v. and mass spectroscopy are reported. 3. 3-Methylthymidine and O4-methylthymidine were found as methylation products from N-methyl-N-nitrosourea with thymidine and with DNA, in relatively small yields. Unidentified products containing thymine were found in enzymic digests of N-methyl-N-nitrosourea-treated DNA, which may be phosphotriesters. 4. The possible role of formation of methylthymines in mutagenesis by N-methyl-N-nitrosourea is discussed. PMID:4798180

  18. Poly(N-arylenbenzimidazoles) via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Joseph G., Jr. (Inventor)

    1995-01-01

    Novel poly(N-arylenebenzimidazole)s (PNABIs) are prepared by the aromatic nucleophilic displacement reaction of novel di(hydroxyphenyl-N-arylene benzimidazole) monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. The di(hydroxyphenyl N-arylenebenzimidazole) monomers are synthesized by reacting phenyl 4-hydroxybenzoate with bis(2-aminoanilino) arylenes in diphenylsulfone. Moderate molecular weight PNABIs of new chemical structures were prepared that exhibit a favorable combination of physical and mechanical properties. The use of the novel di(hydroxyphenyl N-arylenebenzimidazole)s permits a more economical and easier way to prepare PNABIs than previous routes.

  19. Methylation of ribonucleic acid by the carcinogens dimethyl sulphate, N-methyl-N-nitrosourea and N-methyl-N′-nitro-N-nitrosoguanidine. Comparisons of chemical analyses at the nucleoside and base levels

    PubMed Central

    Lawley, P. D.; Shah, S. A.

    1972-01-01

    1. The following methods for hydrolysis of methyl-14C-labelled RNA, and for chromatographic isolation and determination of the products, were investigated: enzymic digestion to nucleosides at pH6 or 8; alkaline hydrolysis and conversion into nucleosides; hydrolysis by acid to pyrimidine nucleotides and purine bases, or completely to bases; chromatography on Dowex 50 (NH4+ form) at pH6 or 8.9, or on Dowex 50 (H+ form), or on Sephadex G-10. 2. The suitability of the various methods for determination of methylation products was assessed. The principal product, 7-methylguanosine, was unstable under the conditions used for determinations of nucleosides. 3- and 7-Methyladenine and 3- and 7-methylguanine are best determined as bases; 1-methyladenine and 3-methylcytosine can be isolated as either nucleosides or bases; O6-methylguanine is unstable under the acid hydrolysis conditions used and can be determined as the nucleoside; 3-methyluracil was detected, but may be derived from methylation of the ionized form of uracil. 3. Differences between the patterns of methylation of RNA and homopolyribonucleotides by the N-methyl-N-nitroso compounds and dimethyl sulphate were found: the nitroso compounds were able to methylate O-6 of guanine, were relatively more reactive at N-7 of adenine and probably at N-3 of guanine, but less reactive at N-1 of adenine, N-3 of cytosine and probably at N-3 of uridine. They probably reacted more with the ribose–phosphate chain, but no products from this were identified. 4. The possible influences of these differences on biological action of the methylating agents is discussed. Nitroso compounds may differ principally in their ability to induce miscoding in the Watson–Crick sense by reaction at O-6 of guanine. Both types of agent may induce miscoding to a lesser extent through methylation at N-3 of guanine; both can methylate N atoms, presumably preventing Watson–Crick hydrogen-bonding. N-Methyl-N-nitrosourea can degrade RNA, possibly

  20. Poly(N-arylenebenzimidazole)s via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Jr., Joseph G. (Inventor)

    1996-01-01

    Novel poly(N-arylenebenzimidazole)s (PNABls) are prepared by the aromatic nucleophilic displacement reaction of novel di(hydroxyphenyl-N-arylene benzimidazole) monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. The di(hydroxyphenyl-N-arylenebenzimidazole) monomers are synthesized by reacting phenyl-4-hydroxybenzoate with bis(2-aminoanilino)arylenes in diphenylsulfone. Moderate molecular weight PNABIs of new chemical structures were prepared that exhibit a favorable combination of physical and mechanical properties. The use of the novel di(hydroxyphenyI-N-arylenebenzimidazole)s permits a more economical and easier way to prepare PNABIs than previous routes.

  1. 40 CFR 721.4080 - MNNG (N-methyl-N′-nitro-N-nitrosoguanidine).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false MNNG (N-methyl-Nâ²-nitro-N... Specific Chemical Substances § 721.4080 MNNG (N-methyl-N′-nitro-N-nitrosoguanidine). (a) Chemical substance and significant new use subject to reporting. (1) The chemical substance MNNG (N-methyl-N′-nitro-N...

  2. 40 CFR 721.4080 - MNNG (N-methyl-N′-nitro-N-nitrosoguanidine).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false MNNG (N-methyl-Nâ²-nitro-N... Specific Chemical Substances § 721.4080 MNNG (N-methyl-N′-nitro-N-nitrosoguanidine). (a) Chemical substance and significant new use subject to reporting. (1) The chemical substance MNNG (N-methyl-N′-nitro-N...

  3. N-methyl pyrrolidone/bone morphogenetic protein-2 double delivery with in situ forming implants.

    PubMed

    Karfeld-Sulzer, Lindsay S; Ghayor, Chafik; Siegenthaler, Barbara; de Wild, Michael; Leroux, Jean-Christophe; Weber, Franz E

    2015-04-10

    Bone morphogenetic proteins (BMPs) are growth and differentiation factors involved during development in morphogenesis, organogenesis and later mainly in regeneration processes, in particular in bone where they are responsible for osteoinduction. For more than a decade, recombinant human (rh)BMP-2 has been used in the clinic for lumbar spinal fusion at non-physiological high dosages that appear to be causative for side effects, like male sterility. A possible strategy to reduce the effective amount of rhBMP-2 in the clinic is the co-delivery with an enhancer of BMPs' activity. In an earlier study, we showed that N-methylpyrrolidone (NMP) enhances BMP activity in vitro and in vivo. Here we report on the development of a slow and sustained double delivery of rhBMP-2 and NMP via an in situ forming implant based on poly(lactide-co-glycolide). The results showed that the release of NMP can be adjusted by varying the lactide/glycolide ratio and the polymer's molecular weight. The same applied to rhBMP-2, with release rates that could be sustained from two to three weeks. In the in vivo model of a critical size defect in the calvarial bone of rabbits, the implant containing 50mol% lactide performed better than the one having 75mol% lactide in terms of defect bridging and extent of bony regenerated area. In situ forming implants for the double delivery of the BMP enhancer NMP and rhBMP-2 appear to be promising delivery systems in bone regeneration. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. N-METHYL GROUPS IN BACTERIAL LIPIDS

    PubMed Central

    Goldfine, Howard; Ellis, Martha E.

    1964-01-01

    Goldfine, Howard (Harvard Medical School, Boston, Mass.), and Martha E. Ellis. N-methyl groups in bacterial lipids. J. Bacteriol. 87:8–15. 1964.—The ability of bacteria to synthesize lecithin was examined by measuring the incorporation of the methyl group of methionine into the water-soluble moieties obtained on acid hydrolysis of bacterial lipids. Of 21 species examined, mostly of the order Eubacteriales, only 2, Agrobacterium radiobacter and A. rhizogenes, incorporated the methyl group of methionine into lipid-bound choline. Evidence was also obtained for the formation of lipid-bound N-methylethanolamine and N,N′-dimethylethanolamine in these two organisms. Two other species, Clostridium butyricum and Proteus vulgaris, incorporated the methyl group of methionine into lipid-bound N-methylethanolamine, but did not appear to be able to further methylate these lipids to form lecithin. The results of this study lend further strength to the generalization that bacteria, with the exception of the genus Agrobacterium, are unable to synthesize lecithin. PMID:14102879

  5. Inhibition of protein synthesis by N-methyl-N-nitrosourea in vivo

    PubMed Central

    Kleihues, P.; Magee, P. N.

    1973-01-01

    1. The intraperitoneal injection of N-methyl-N-nitrosourea (100mg/kg) caused a partial inhibition of protein synthesis in several organs of the rat, the maximum effect occurring after 2–3h. 2. In the liver the inhibition of protein synthesis was paralleled by a marked disaggregation of polyribosomes and an increase in ribosome monomers and ribosomal subunits. No significant breakdown of polyribosomes was found in adult rat brains although N-methyl-N-nitrosourea inhibited cerebral and hepatic protein synthesis to a similar extent. In weanling rats N-methyl-N-nitrosourea caused a shift in the cerebral polyribosome profile similar to but less marked than that in rat liver. 3. Reaction of polyribosomal RNA with N-[14C]methyl-N-nitrosourea in vitro did not lead to a disaggregation of polyribosomes although the amounts of 7-methylguanine produced were up to twenty times higher than those found after administration of sublethal doses in vivo. 4. It was concluded that changes in the polyribosome profile induced by N-methyl-N-nitrosourea may reflect the mechanism of inhibition of protein synthesis rather than being a direct consequence of the methylation of polyribosomal mRNA. PMID:4774397

  6. Effects of carbonization and solvent-extraction on change in fuel characteristics of sewage sludge.

    PubMed

    Park, Sang-Woo; Jang, Cheol-Hyeon

    2011-09-01

    Urban sewage sludge was carbonized at 300-500°C for 1h, and combustible components were extracted through the solvent-extraction process. N-methyl-2-pyrrolidinone (NMP) was used as the solvent for extraction, and the extraction temperature was fixed at 360°C. The atomic ratios of the solvent-extracted sludge of CS300 (ECS300) were shown to be 1.04 for H/C and 0.11 for O/C, which represented the characteristics of its coal band. Thus, its coal band was similar to that of a high-rank fuel such as bituminous coal. FT-IR analysis showed that the absorbance band of ECS300 was considerably different from that of dried sludge (RS) or the carbonized sludge at 300°C (CS300) but similar to that of coal, although the ash content absorbance band of 800-1200 cm(-1) was of very low intensity. The combustion profile showed that combustion of ESC300 occurred at a temperature higher than the ignition temperature (T(i)) or maximum weight loss rate (DTG(max)) of coal. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Vapor Pressure of Methyl Salicylate and n-Hexadecane

    DTIC Science & Technology

    2014-01-01

    VAPOR PRESSURE OF METHYL SALICYLATE AND N-HEXADECANE ECBC-TR-1184 David E. Tevault Leonard C. Buettner...REPORT TYPE Final 3. DATES COVERED (From - To) Mar 2000-Dec 2001 4. TITLE AND SUBTITLE Vapor Pressure of Methyl Salicylate and n-Hexadecane 5a...ABSTRACT Vapor pressure data are reported for O-hydroxybenzoic acid, methyl ester, more commonly known as methyl salicylate (MeS), and n-hexadecane in

  8. 40 CFR 721.4925 - Methyl n-butyl ketone.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Methyl n-butyl ketone. 721.4925... Substances § 721.4925 Methyl n-butyl ketone. (a) Chemical substance and significant new use subject to reporting. (1) The chemical substance methyl n-butyl ketone, CAS Number 591-78-6, is subject to reporting...

  9. 40 CFR 721.4925 - Methyl n-butyl ketone.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Methyl n-butyl ketone. 721.4925... Substances § 721.4925 Methyl n-butyl ketone. (a) Chemical substance and significant new use subject to reporting. (1) The chemical substance methyl n-butyl ketone, CAS Number 591-78-6, is subject to reporting...

  10. Decision curve analysis assessing the clinical benefit of NMP22 in the detection of bladder cancer: secondary analysis of a prospective trial.

    PubMed

    Barbieri, Christopher E; Cha, Eugene K; Chromecki, Thomas F; Dunning, Allison; Lotan, Yair; Svatek, Robert S; Scherr, Douglas S; Karakiewicz, Pierre I; Sun, Maxine; Mazumdar, Madhu; Shariat, Shahrokh F

    2012-03-01

    • To employ decision curve analysis to determine the impact of nuclear matrix protein 22 (NMP22) on clinical decision making in the detection of bladder cancer using data from a prospective trial. • The study included 1303 patients at risk for bladder cancer who underwent cystoscopy, urine cytology and measurement of urinary NMP22 levels. • We constructed several prediction models to estimate risk of bladder cancer. The base model was generated using patient characteristics (age, gender, race, smoking and haematuria); cytology and NMP22 were added to the base model to determine effects on predictive accuracy. • Clinical net benefit was calculated by summing the benefits and subtracting the harms and weighting these by the threshold probability at which a patient or clinician would opt for cystoscopy. • In all, 72 patients were found to have bladder cancer (5.5%). In univariate analyses, NMP22 was the strongest predictor of bladder cancer presence (predictive accuracy 71.3%), followed by age (67.5%) and cytology (64.3%). • In multivariable prediction models, NMP22 improved the predictive accuracy of the base model by 8.2% (area under the curve 70.2-78.4%) and of the base model plus cytology by 4.2% (area under the curve 75.9-80.1%). • Decision curve analysis revealed that adding NMP22 to other models increased clinical benefit, particularly at higher threshold probabilities. • NMP22 is a strong, independent predictor of bladder cancer. • Addition of NMP22 improves the accuracy of standard predictors by a statistically and clinically significant margin. • Decision curve analysis suggests that integration of NMP22 into clinical decision making helps avoid unnecessary cystoscopies, with minimal increased risk of missing a cancer. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

  11. Phenylethylamine N-methylation by human brain preparations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mosnaim, A.D.; Callaghan, O.H.; Wolf, M.E.

    Alterations in the brain metabolism of biogenic amines has been postulated to play a role in the pathophysiology of several psychiatric disorders. There is some evidence suggesting schizogenic properties for some abnormal neuroamine methylated derivatives. The authors now report that postmortem human brain preparations, obtained from the putamen and thalamus, convert phenylethylamine (PEA) to its behaviorally active derivative N-methyl PEA, a reaction which is carried out by the 100,000 xg supernatant (in presence of 1 x 10 /sup -5/M pargyline) and enhanced by the addition of NADPH. PEA N-methylation occurred in schizophrenics as well as in sex and age matchedmore » controls. The formation of increased amounts of (/sup 3/H-) or (/sup 14/C-) N-methyl PEA when incubating either cold amine and /sup 3/H-SAM or 1-/sup 14/C PEA and cold SAM, respectively, indicates that SAM is a methyl group donor in this reaction. They will discuss the physiological and pharmacological implications of these results.« less

  12. Adaptation of the Nomophobia Questionnaire (NMP-Q) to Spanish in a sample of adolescents.

    PubMed

    González-Cabrera, Joaquín; León-Mejía, Ana; Pérez-Sancho, Carlota; Calvete, Esther

    2017-07-01

    Nomophobia is the fear of being out of mobile phone contact. People suffering from this anxiety disorder have feelings of stress and nervousness when access to their mobiles or computers is not possible. This work is an adaptation and validation study of the Spanish version of the Nomophobia Questionnaire (NMP-Q). The study included 306 students (46.1% males and 53.9% females) with ages ranging 13 to 19 years (Md=15.41±1.22). Exploratory factor analysis revealed four dimensions that accounted for 64.4% of total variance. The ordinal α-value was 0.95, ranging from 0.75 to 0.92 across factors. Measure of stability was calculated by the testretest method (r=0.823). Indicators of convergence with the Spanish versions of the “Mobile Phone Problem Use Scale” (r=0.654) and the “Generalized Problematic Internet Use Scale” (r=0.531) were identified. Problematic mobile phone use patterns were examined taking the 15P, 80P and 95P percentiles as cut-off points. Scores of 39, 87 and 116 on NMP-Q corresponded to occasional, at-risk and problematic users, respectively. Psychometric analysis shows that the Spanish version of the NMP-Q is a valid and reliable tool for the study of nomophobia.

  13. 40 CFR 721.225 - 2-Chloro-N-methyl-N-substituted acetamide (generic name).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 2-Chloro-N-methyl-N-substituted... Specific Chemical Substances § 721.225 2-Chloro-N-methyl-N-substituted acetamide (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance 2-chloro-N...

  14. 40 CFR 721.225 - 2-Chloro-N-methyl-N-substituted acetamide (generic name).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 2-Chloro-N-methyl-N-substituted... Specific Chemical Substances § 721.225 2-Chloro-N-methyl-N-substituted acetamide (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance 2-chloro-N...

  15. Protein chemical synthesis by α-ketoacid-hydroxylamine ligation.

    PubMed

    Harmand, Thibault J; Murar, Claudia E; Bode, Jeffrey W

    2016-06-01

    Total chemical synthesis of proteins allows researchers to custom design proteins without the complex molecular biology that is required to insert non-natural amino acids or the biocontamination that arises from methods relying on overexpression in cells. We describe a detailed procedure for the chemical synthesis of proteins with the α-ketoacid-hydroxylamine (KAHA ligation), using (S)-5-oxaproline (Opr) as a key building block. This protocol comprises two main parts: (i) the synthesis of peptide fragments by standard fluorenylmethoxycarbonyl (Fmoc) chemistry and (ii) the KAHA ligation between fragments containing Opr and a C-terminal peptide α-ketoacid. This procedure provides an alternative to native chemical ligation (NCL) that could be valuable for the synthesis of proteins, particularly targets that do not contain cysteine residues. The ligation conditions-acidic DMSO/H2O or N-methyl-2-pyrrolidinone (NMP)/H2O-are ideally suited for solubilizing peptide segments, including many hydrophobic examples. The utility and efficiency of the protocol is demonstrated by the total chemical synthesis of the mature betatrophin (also called ANGPTL8), a 177-residue protein that contains no cysteine residues. With this protocol, the total synthesis of the betatrophin protein has been achieved in around 35 working days on a multimilligram scale.

  16. 40 CFR 721.1085 - Benzenamine,4,4′-methylenebis[N-ethyl-N-methyl-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Benzenamine,4,4â²-methylenebis[N-ethyl-N-methyl-. 721.1085 Section 721.1085 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.1085 Benzenamine,4,4′-methylenebis[N-ethyl-N-methyl-. (a) Chemical...

  17. 40 CFR 721.1085 - Benzenamine,4,4′-methylenebis[N-ethyl-N-methyl-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Benzenamine,4,4â²-methylenebis[N-ethyl-N-methyl-. 721.1085 Section 721.1085 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.1085 Benzenamine,4,4′-methylenebis[N-ethyl-N-methyl-. (a) Chemical...

  18. INTERLABORATORY STUDY OF A THERMOSPRAY-LIQUID CHROMATOGRAPHIC/MASS SPECTROMETRIC METHOD FOR SELECTED N-METHYL CARBAMATES, N-METHYL CARBAMOYLOXIMES, AND SUBSTITUTED UREA PESTICIDES

    EPA Science Inventory

    A thermospray-liquid chromatographic/mass spectrometric (TS-LC/MS) method was evaluated in an interlaboratory study for determining 3 N-methyl carbamates (bendiocarb, carbaryl, and carbofuran), 3-N-methyl carbamoyloximes (aldicarb, methomyl, and oxamyl), 2 substituted urea pestic...

  19. N-(3-azidophenyl)-N-methyl-N'-([4-1H]- and [4-3H]-1-naphthyl)guanidine. A potent and selective ligand designed as a photoaffinity label for the phencyclidine site of the N-methyl-D-aspartate receptor.

    PubMed

    Gee, K R; Durant, G J; Holmes, D L; Magar, S S; Weber, E; Wong, S T; Keana, J F

    1993-01-01

    A novel radiolabeled photoaffinity ligand has been synthesized for the phencyclidine (PCP) site of the N-methyl-D-aspartate (NMDA) receptor. N-(3-Azidophenyl)-N-methyl-N'-([4-3H]-1-naphthyl)guanidine (13) was prepared with a specific activity of 25 Ci/mmol by diazotization of N-(3-aminophenyl)-N-methyl-N'-([4-3H]-1-naphthyl)guanidine (12) followed by treatment with sodium azide. Guanidine 12 was obtained by catalytic tritiation of N-(4-bromo-1-naphthyl)-N'-methyl-N'-(3-nitrophenyl)guanidine (11). The nontritiated analog 5 of 13 was prepared beginning with N-methyl-N'-1-naphthyl-N-(3-nitrophenyl)guanidine (9). The guanidines 9 and 11 were prepared in moderate yield by the aluminum chloride-catalyzed reaction of N-methyl-3-nitroaniline hydrochloride with 1-naphthylcyanamide and 4-bromo-1-naphthylcyanamide, respectively. Azide 5 showed high selectivity and affinity (IC50 = 100 nM vs [3H]MK801; 3000 nM vs [3H]ditolylguanidine) for the PCP site of the NMDA receptor in guinea pig brain homogenate. Photolabeling experiments with 13, however, failed to radiolabel a significant amount of receptor polypeptide.

  20. Protective effects of folic acid on DNA damage and DNA methylation levels induced by N-methyl- N'-nitro- N-nitrosoguanidine in Kazakh esophageal epithelial cells.

    PubMed

    Chen, Y; Feng, H; Chen, D; Abuduwaili, K; Li, X; Zhang, H

    2018-01-01

    The protective effects of folic acid on DNA damage and DNA methylation induced by N-methyl- N'-nitro- N-nitrosoguanidine (MNNG) in Kazakh esophageal epithelial cells were investigated using a 3 × 3 factorial design trial. The cells were cultured in vitro and exposed to media containing different concentrations of folic acid and MNNG, after which growth indices were detected. DNA damage levels were measured using comet assays, and genome-wide DNA methylation levels (MLs) were measured using high-performance liquid chromatography. The DNA methylation of methylenetetrahydrofolate reductase (MTHFR) and folate receptor- α (FR α) genes was detected by bisulfite sequencing polymerase chain reaction (PCR). The results showed significant increases in tail DNA concentration, tail length, and Olive tail moment ( p < 0.01); a significant reduction of genome-wide DNA MLs ( p < 0.01); and an increase in the methylation frequencies of MTHFR and FR α genes. In particular, significant differences were observed in the promoter regions of both genes ( p < 0.01). Our study indicated that a reduction in folic acid concentration promotes DNA damage and DNA methylation in Kazakh esophageal epithelial cells upon MNNG exposure. Thus, sufficient folic acid levels could play a protective role against the damage induced by this compound.

  1. 27 CFR 21.118 - Methyl n-butyl ketone.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Methyl n-butyl ketone. 21.118 Section 21.118 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU....118 Methyl n-butyl ketone. (a) Acidity (as acetic acid). 0.02 percent by weight, maximum. (b) Color...

  2. 21 CFR 500.1410 - N-methyl-2-pyrrolidone.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false N-methyl-2-pyrrolidone. 500.1410 Section 500.1410 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Used in Food-Producing Animals § 500.1410 N-methyl-2-pyrrolidone. (a) Standard for residues. No...

  3. 21 CFR 500.1410 - N-methyl-2-pyrrolidone.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false N-methyl-2-pyrrolidone. 500.1410 Section 500.1410 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Used in Food-Producing Animals § 500.1410 N-methyl-2-pyrrolidone. (a) Standard for residues. No...

  4. 27 CFR 21.118 - Methyl n-butyl ketone.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Methyl n-butyl ketone. 21.118 Section 21.118 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU....118 Methyl n-butyl ketone. (a) Acidity (as acetic acid). 0.02 percent by weight, maximum. (b) Color...

  5. Structural and spectroscopic characterization of methyl isocyanate, methyl cyanate, methyl fulminate, and acetonitrile N-oxide using highly correlated ab initio methods.

    PubMed

    Dalbouha, S; Senent, M L; Komiha, N; Domínguez-Gómez, R

    2016-09-28

    Various astrophysical relevant molecules obeying the empirical formula C 2 H 3 NO are characterized using explicitly correlated coupled cluster methods (CCSD(T)-F12). Rotational and rovibrational parameters are provided for four isomers: methyl isocyanate (CH 3 NCO), methyl cyanate (CH 3 OCN), methyl fulminate (CH 3 ONC), and acetonitrile N-oxide (CH 3 CNO). A CH 3 CON transition state is inspected. A variational procedure is employed to explore the far infrared region because some species present non-rigidity. Second order perturbation theory is used for the determination of anharmonic frequencies, rovibrational constants, and to predict Fermi resonances. Three species, methyl cyanate, methyl fulminate, and CH 3 CON, show a unique methyl torsion hindered by energy barriers. In methyl isocyanate, the methyl group barrier is so low that the internal top can be considered a free rotor. On the other hand, acetonitrile N-oxide presents a linear skeleton, C 3v symmetry, and free internal rotation. Its equilibrium geometry depends strongly on electron correlation. The remaining isomers present a bend skeleton. Divergences between theoretical rotational constants and previous parameters fitted from observed lines for methyl isocyanate are discussed on the basis of the relevant rovibrational interaction and the quasi-linearity of the molecular skeleton.

  6. Structural and spectroscopic characterization of methyl isocyanate, methyl cyanate, methyl fulminate, and acetonitrile N-oxide using highly correlated ab initio methods

    NASA Astrophysics Data System (ADS)

    Dalbouha, S.; Senent, M. L.; Komiha, N.; Domínguez-Gómez, R.

    2016-09-01

    Various astrophysical relevant molecules obeying the empirical formula C2H3NO are characterized using explicitly correlated coupled cluster methods (CCSD(T)-F12). Rotational and rovibrational parameters are provided for four isomers: methyl isocyanate (CH3NCO), methyl cyanate (CH3OCN), methyl fulminate (CH3ONC), and acetonitrile N-oxide (CH3CNO). A CH3CON transition state is inspected. A variational procedure is employed to explore the far infrared region because some species present non-rigidity. Second order perturbation theory is used for the determination of anharmonic frequencies, rovibrational constants, and to predict Fermi resonances. Three species, methyl cyanate, methyl fulminate, and CH3CON, show a unique methyl torsion hindered by energy barriers. In methyl isocyanate, the methyl group barrier is so low that the internal top can be considered a free rotor. On the other hand, acetonitrile N-oxide presents a linear skeleton, C3v symmetry, and free internal rotation. Its equilibrium geometry depends strongly on electron correlation. The remaining isomers present a bend skeleton. Divergences between theoretical rotational constants and previous parameters fitted from observed lines for methyl isocyanate are discussed on the basis of the relevant rovibrational interaction and the quasi-linearity of the molecular skeleton.

  7. DOE Office of Scientific and Technical Information (OSTI.GOV)

    S. Dong; N. Paterson; S.G. Kazarian

    A suite of tuyere-level coke samples have been withdrawn from a working blast furnace during coal injection, using the core-drilling technique. The samples have been characterized by size exclusion chromatography (SEC), Fourier transform Raman spectroscopy (FT-RS), and X-ray powder diffraction (XRD) spectroscopy. The 1-methyl-2-pyrrolidinone (NMP) extracts of the cokes sampled from the 'bosh', the rear of the 'bird's nest', and the 'dead man' zones were found by SEC to contain heavy soot-like materials (ca. 10{sup 7}-10{sup 8} apparent mass units). In contrast, NMP extracts of cokes taken from the raceway and the front of the 'bird's nest' only contained amore » small amount of material of relatively lower apparent molecular mass (up to ca. 10{sup 5} u). Since the feed coke contained no materials extractable by the present method, the soot-like materials are thought to have formed during the reactions of volatile matter released from the injectant coal, probably via dehydrogenation and repolymerization of the tars. The Raman spectra of the NMP-extracted core-drilled coke samples showed variations reflecting their temperature histories. Area ratios of D-band to G-band decreased as the exposure temperature increased, while intensity ratios of D to G band and those of 2D to G bands increased with temperature. The graphitic (G), defect (D), and random (R) fractions of the carbon structure of the cokes were also derived from the Raman spectra. The R fractions decreased with increasing temperature, whereas G fractions increased, while the D fractions showed a more complex variation with temperature. These data appear to give clues regarding the graphitization mechanism of tuyere-level cokes in the blast furnace. 41 refs., 9 figs., 6 tabs.« less

  8. Surface Fluorination of Reactive Battery Anode Materials for Enhanced Stability

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhao, Jie; Liao, Lei; Shi, Feifei

    Significant increases in the energy density of batteries must be achieved by exploring new materials and cell configurations. Lithium metal and lithiated silicon are two promising high-capacity anode materials. Unfortunately, both of these anodes require a reliable passivating layer to survive the serious environmental corrosion during handling and cycling. Here we developed a surface fluorination process to form a homogeneous and dense LiF coating on reactive anode materials, with in situ generated fluorine gas, by using a fluoropolymer, CYTOP, as the precursor. The process is effectively a “reaction in the beaker”, avoiding direct handling of highly toxic fluorine gas. Formore » lithium metal, this LiF coating serves as a chemically stable and mechanically strong interphase, which minimizes the corrosion reaction with carbonate electrolytes and suppresses dendrite formation, enabling dendrite-free and stable cycling over 300 cycles with current densities up to 5 mA/cm 2. Lithiated silicon can serve as either a pre-lithiation additive for existing lithium-ion batteries or a replacement for lithium metal in Li–O 2 and Li–S batteries. However, lithiated silicon reacts vigorously with the standard slurry solvent N-methyl-2-pyrrolidinone (NMP), indicating it is not compatible with the real battery fabrication process. With the protection of crystalline and dense LiF coating, Li xSi can be processed in anhydrous NMP with a high capacity of 2504 mAh/g. With low solubility of LiF in water, this protection layer also allows Li xSi to be stable in humid air (~40% relative humidity). Furthermore, this facile surface fluorination process brings huge benefit to both the existing lithium-ion batteries and next-generation lithium metal batteries.« less

  9. Surface Fluorination of Reactive Battery Anode Materials for Enhanced Stability

    DOE PAGES

    Zhao, Jie; Liao, Lei; Shi, Feifei; ...

    2017-07-26

    Significant increases in the energy density of batteries must be achieved by exploring new materials and cell configurations. Lithium metal and lithiated silicon are two promising high-capacity anode materials. Unfortunately, both of these anodes require a reliable passivating layer to survive the serious environmental corrosion during handling and cycling. Here we developed a surface fluorination process to form a homogeneous and dense LiF coating on reactive anode materials, with in situ generated fluorine gas, by using a fluoropolymer, CYTOP, as the precursor. The process is effectively a “reaction in the beaker”, avoiding direct handling of highly toxic fluorine gas. Formore » lithium metal, this LiF coating serves as a chemically stable and mechanically strong interphase, which minimizes the corrosion reaction with carbonate electrolytes and suppresses dendrite formation, enabling dendrite-free and stable cycling over 300 cycles with current densities up to 5 mA/cm 2. Lithiated silicon can serve as either a pre-lithiation additive for existing lithium-ion batteries or a replacement for lithium metal in Li–O 2 and Li–S batteries. However, lithiated silicon reacts vigorously with the standard slurry solvent N-methyl-2-pyrrolidinone (NMP), indicating it is not compatible with the real battery fabrication process. With the protection of crystalline and dense LiF coating, Li xSi can be processed in anhydrous NMP with a high capacity of 2504 mAh/g. With low solubility of LiF in water, this protection layer also allows Li xSi to be stable in humid air (~40% relative humidity). Furthermore, this facile surface fluorination process brings huge benefit to both the existing lithium-ion batteries and next-generation lithium metal batteries.« less

  10. Determination of N-methylsuccinimide and 2-hydroxy-N-methylsuccinimide in human urine and plasma.

    PubMed

    Jönsson, B A; Akesson, B

    1997-12-19

    A method for determination of N-methylsuccinimide (MSI) and 2-hydroxy-N-methylsuccinimide (2-HMSI) in human urine and of MSI in human plasma was developed. MSI and 2-HMSI are metabolites of the widely used organic solvent N-methyl-2-pyrrolidone (NMP). MSI and 2-HMSI were purified from urine and plasma by C8 solid-phase extraction and analysed by gas chromatography-mass spectrometry in the negative-ion chemical ionisation mode. The intra-day precisions in urine were 2-6% for MSI (50 and 400 ng/ml) and 3-5% for 2-HMSI (1000 and 8000 ng/ml). For MSI in plasma it was 2% (60 and 1200 ng/ml). The between-day precisions in urine were 3-4% for MSI (100 and 1000 ng/ml) and 2-4% for 2-HMSI (10,000 and 18,000 ng/ml) and 3-4% for MSI in plasma (100 and 900 ng/ml). The recoveries from urine were 109-117% for MSI (50 and 400 ng/ml) and 81-89% for 2-HMSI (1000 and 8000 ng/ml). The recovery of MSI from plasma was 91-101% (50 and 500 ng/ml). The detection limits for MSI were 3 ng/ml in urine and 1 ng/ml in plasma and that of 2-HMSI in urine was 200 ng/ml. The method is applicable for analysis of urine and plasma samples from workers exposed to NMP.

  11. Low cost environmental sensors for Spaceflight : NMP Space Environmental Monitor (SEM) requirements

    NASA Technical Reports Server (NTRS)

    Garrett, Henry B.; Buelher, Martin G.; Brinza, D.; Patel, J. U.

    2005-01-01

    An outstanding problem in spaceflight is the lack of adequate sensors for monitoring the space environment and its effects on engineering systems. By adequate, we mean low cost in terms of mission impact (e.g., low price, low mass/size, low power, low data rate, and low design impact). The New Millennium Program (NMP) is investigating the development of such a low-cost Space Environmental Monitor (SEM) package for inclusion on its technology validation flights. This effort follows from the need by NMP to characterize the space environment during testing so that potential users can extrapolate the test results to end-use conditions. The immediate objective of this effort is to develop a small diagnostic sensor package that could be obtained from commercial sources. Environments being considered are: contamination, atomic oxygen, ionizing radiation, cosmic radiation, EMI, and temperature. This talk describes the requirements and rational for selecting these environments and reviews a preliminary design that includes a micro-controller data logger with data storage and interfaces to the sensors and spacecraft. If successful, such a sensor package could be the basis of a unique, long term program for monitoring the effects of the space environment on spacecraft systems.

  12. Low Cost Environmental Sensors for Spaceflight: NMP Space Environmental Monitor (SEM) Requirements

    NASA Technical Reports Server (NTRS)

    Garrett, Henry B.; Buehler, Martin G.; Brinza, D.; Patel, J. U.

    2005-01-01

    An outstanding problem in spaceflight is the lack of adequate sensors for monitoring the space environment and its effects on engineering systems. By adequate, we mean low cost in terms of mission impact (e.g., low price, low mass/size, low power, low data rate, and low design impact). The New Millennium Program (NMP) is investigating the development of such a low-cost Space Environmental Monitor (SEM) package for inclusion on its technology validation flights. This effort follows from the need by NMP to characterize the space environment during testing so that potential users can extrapolate the test results to end-use conditions. The immediate objective of this effort is to develop a small diagnostic sensor package that could be obtained from commercial sources. Environments being considered are: contamination, atomic oxygen, ionizing radiation, cosmic radiation, EMI, and temperature. This talk describes the requirements and rational for selecting these environments and reviews a preliminary design that includes a micro-controller data logger with data storage and interfaces to the sensors and spacecraft. If successful, such a sensor package could be the basis of a unique, long term program for monitoring the effects of the space environment on spacecraft systems.

  13. 78 FR 52525 - Dichloromethane and N-Methylpyrrolidone TSCA Chemical Risk Assessment; Notice of Public Meetings...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-23

    ... Dichloromethane and N-Methylpyrrolidone.'' Dichloromethane and N-Methylpyrrolidone (DCM and NMP) (CASRN 75-09-2... represent and should not be construed to represent any Agency determination or policy. The draft DCM and NMP..., to assemble a panel of experts to evaluate the draft DCM and NMP TSCA risk assessment report for...

  14. Determination of the radius of comet 19P/Borrelly in support of the NMP DS1 Flyby

    NASA Astrophysics Data System (ADS)

    Festou, Michel

    1999-07-01

    Comet 19P/Borrelly is the ultimate target of the New Mellinium Program {NMP} Deep Space 1 asteroid-comet flyby mission. The size of this comet's nucleus is a critical parameter needed for flyby planning activities. However, as we describe below, P/Borrelly's radius is not well established. We, the NMP DS1 Science Team, request 1 orbit of HST/STIS time in Cycle 8 to refine the nuclear size estimate. This program cannot wait until Cycle 9 because of mission planning constraints and the fact that the comet is likely to be producing a weak but nonetheless enhanced coma by the time of Cycle 9. We therefore propose to observe comet P/Borrelly in Cycle 8 when the activity level of its nucleus is near its minimum, and quite possibly negligible. From a clear separation of the contributions of the coma and the nucleus in the inner part of STIS images, we will extract the cross section of Borrelly's nucleus. In addition to its immediate value for NMP DS1 mission planning, when c oupled to existing data sets, the STIS data will then enable us to model the coma morphology to better infer the effect of the nucleus outgassing on the comet's motion.

  15. Assessment of the best N(3-) donors in preparation of [M(N)(PNP)]-based (M=(99m)Tc-; (188)Re) target-specific radiopharmaceuticals: Comparison among succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG600-DTCZ).

    PubMed

    Carta, Davide; Jentschel, Christian; Thieme, Stefan; Salvarese, Nicola; Morellato, Nicolò; Refosco, Fiorenzo; Ruzza, Paolo; Bergmann, Ralf; Pietzsch, Hans-Jurgen; Bolzati, Cristina

    2014-08-01

    Succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG600-DTCZ) are nitrido nitrogen atom donors employed for the preparation of nitride [M(N)]-complexes (M=(99m)Tc and (188)Re). This study aims to compare the capability and the efficiency of these three N(3-) group donors, in the preparation of [M(N)PNP]-based target-specific compounds (M=(99m)Tc, (188)Re; PNP=aminodiphosphine). For this purpose, three different kit formulations (SDH kit; HO2C-PEG600-DTCZ kit; HDTCZ kit) were assembled and used in the preparation of [M(N)(cys~)(PNP3)](0/+) complexes (cys~=cysteine derivate ligands). For each formulation, the radiochemical yield (RCY) of the [M(N)(~cys)(PNP3)] compounds, was determined by HPLC. The deviation of the percentage of RCY, due to changes in concentration of the N(3-) donors and of the exchanging ligand, was determined. For (99m)Tc, data clearly show that HDTCZ is the most efficient donor of N(3-); however, SDH is the most suitable nitrido nitrogen atom donor for the preparation of [(99m)Tc(N)(PNP)]-based target-specific agents with high specific activity. When HO2C-PEG600-DTCZ or HDTCZ are used in N(3-) donation, high amounts of the exchanging ligand (10(-4)M) were required for the formation of the final complex in acceptable yield. The possibility to use microgram amounts of HDTCZ also in [(188)Re(N)] preparation (0.050mg) reduces its ability to compete in ligand exchange reactions, minimizing the quantity of chelators required to obtain the final complex in high yield. This finding can be exploit for increasing the radiolabeling efficiency in [(188)Re(N)]-radiopharmaceutical preparations compared to the previously reported HDTCZ-based procedure, notwithstanding a purification process could be necessary to improve the specific activity of the complexes. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. 40 CFR 721.1070 - Benzenamine, 4-methoxy-2-methyl-N-(3-methylphenyl).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... as benzenamine, 4-methoxy-2-methyl-N-(3-methylphenyl) (PMN P-01-152; CAS No. 93072-06-1) is subject... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Benzenamine, 4-methoxy-2-methyl-N-(3... Specific Chemical Substances § 721.1070 Benzenamine, 4-methoxy-2-methyl-N-(3-methylphenyl). (a) Chemical...

  17. [Preparation of 1-(2-naphthyl) -3-methyl-5-pyrazolone as pre-column derivatization reagent for the determination of saccharides using high performance liquid chromatography-mass spectrometry].

    PubMed

    Sun, Zhiwei; Liu, Lingjun; Hu, Baojun; Sheng, Xiao; Wang, Xiaoyan; Suo, Yourui; You, Jinmao

    2008-03-01

    Eight saccharides were derivatized using 1-(2-naphthyl)-3-methyl-5-pyrazolone (NMP) as pre-column derivatizing reagent, and separated on a reversed-phase Hypersil ODS 2 column (4.6 mm x 200 mm, 5 microm), by high performance liquid chromatography (HPLC) in conjunction with a gradient elution, detected by a diode array detector (DAD), and identified by electrospray ionization-mass spectrometry (ESI-MS) in positive ion mode. NMP reacted with reductive saccharides easily in the presence of 17% ammonia water at 70 degrees C. All linear correlation coefficients for saccharide derivatives were over 0.998 5. The detection limits (at signal-to-noise of 3:1) were 0.58 - 1.1 pmol for saccharide derivatives. The characteristic fragment ions, especially m/z 473, from the cleavage of NMP-labeled saccharides exhibited high regularity for the identification of the composition of saccharide mixture. The established method is sensitive and repeatable for the determination of saccharides.

  18. N-methylated tryptamine derivatives in citrus genus plants: identification of N,N,N-trimethyltryptamine in bergamot.

    PubMed

    Servillo, Luigi; Giovane, Alfonso; Balestrieri, Maria Luisa; Cautela, Domenico; Castaldo, Domenico

    2012-09-19

    The occurrence of N-methylated tryptamine derivatives in bergamot plant (Citrus bergamia Risso et Poit) is reported for the first time. Interestingly, the most abundant of these substances is N,N,N-trimethyltryptamine, which has not been previously identified in any citrus plant. The N-methylated tryptamine derivatives were identified and quantitated in leaves, peel, juice, and seeds by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. N,N,N-Trimethyltryptamine was confirmed by MS(3) and comparison with the synthesized authentic standard. In addition, the study of the distribution of tryptophan, tryptamine, N-methyltryptamine, N,N-dimethyltryptamine, and N,N,N-trimethyltryptamine indicated that these compounds are differently expressed in the various tissues of the bergamot plant. Intriguingly, chemically synthesized N,N,N-trimethyltryptamine was reported to possess nicotine-like activity being a stimulant of parasympathetic ganglia by exerting its action on acetylcholine receptors. On this basis, the identification of N,N,N-trimethyltryptamine at a relatively high level in leaves suggests a possible role in a physiological mechanism of plant defense.

  19. N.m.r. studies of the conformation of analogues of methyl beta-lactoside in methyl sulfoxide-d6.

    PubMed

    Rivera-Sagredo, A; Jiménez-Barbero, J; Martín-Lomas, M

    1991-12-16

    The 1H- and 13C-n.m.r. spectra of solutions of methyl beta-lactoside (1), all of its monodeoxy derivatives (2, 3, 6-10), the 3-O-methyl derivative (4), and methyl 4-O-beta-D-galactopyranosyl-D-xylopyranoside (5) in methyl sulfoxide-d6 have been analysed. The n.O.e.'s and specific desheildings indicate similar distributions of low-energy conformers, comparable to those in aqueous solution. The major conformer has torsion angles phi H and psi H of 49 degrees and 5 degrees, respectively, with contributions of conformers with phi/psi 24 degrees/-59 degrees, 22 degrees/32 degrees, and 6 degrees/44 degrees.

  20. Folding Properties of Cytosine Monophosphate Kinase from E. coli Indicate Stabilization through an Additional Insert in the NMP Binding Domain

    PubMed Central

    Beitlich, Thorsten; Lorenz, Thorsten; Reinstein, Jochen

    2013-01-01

    The globular 25 kDa protein cytosine monophosphate kinase (CMPK, EC ID: 2.7.4.14) from E. coli belongs to the family of nucleoside monophosphate (NMP) kinases (NMPK). Many proteins of this family share medium to high sequence and high structure similarity including the frequently found α/β topology. A unique feature of CMPK in the family of NMPKs is the positioning of a single cis-proline residue in the CORE-domain (cis-Pro124) in conjunction with a large insert in the NMP binding domain. This insert is not found in other well studied NMPKs such as AMPK or UMP/CMPK. We have analyzed the folding pathway of CMPK using time resolved tryptophan and FRET fluorescence as well as CD. Our results indicate that unfolding at high urea concentrations is governed by a single process, whereas refolding in low urea concentrations follows at least a three step process which we interpret as follows: Pro124 in the CORE-domain is in cis in the native state (Nc) and equilibrates with its trans-isomer in the unfolded state (Uc - Ut). Under refolding conditions, at least the Ut species and possibly also the Uc species undergo a fast initial collapse to form intermediates with significant amount of secondary structure, from which the trans-Pro124 fraction folds to the native state with a 100-fold lower rate constant than the cis-Pro124 species. CMPK thus differs from homologous NMP kinases like UMP/CMP kinase or AMP kinase, where folding intermediates show much lower content of secondary structure. Importantly also unfolding is up to 100-fold faster compared to CMPK. We therefore propose that the stabilizing effect of the long NMP-domain insert in conjunction with a subtle twist in the positioning of a single cis-Pro residue allows for substantial stabilization compared to other NMP kinases with α/β topology. PMID:24205218

  1. Methacrylate derivatives incorporating pyroglutamic acid.

    PubMed

    Smith, Tara J; Mathias, Lon J

    2002-01-01

    Methacrylates containing pyroglutamic acid were synthesized in good yields. Methyl alpha-pyroglutamyl methylacrylate (PyMM) and methyl alpha-pyroglutamidoundecanoyl methylacrylate (PyUM) give very fast photopolymerization rates both in homopolymerizations and with widely used commercial monomers N-vinyl pyrrolidinone (NVP) and hydroxyethyl methacrylate (HEMA). Soluble or cross-linked homopolymers can be obtained depending upon polymerization temperature. Pyroglutamic methacrylates polymerize without added initiator in the melt. Solution cast, photocured, and thermally cured coatings gave good to excellent adhesion to poly(ethylene terephthalate) and glass surfaces.

  2. 5-Bromo-N-methyl­pyrimidin-2-amine

    PubMed Central

    Yang, Qi; Xu, Ning; Zhu, Kai; Lv, Xiaoping; Han, Ping-fang

    2012-01-01

    In the title mol­ecule, C5H6BrN3, the pyrimidine ring is essentially planar, with an r.m.s. deviation of 0.007 Å. The Br and N atoms substituted to the pyrimidine ring are coplanar with the ring [displacements = 0.032 (1) and 0.009 (5) Å, respectively], while the methyl C atom lies 0.100 (15) Å from this plane with a dihedral angle between the pyrimidine ring and the methyl­amine group of 4.5 (3)°. In the crystal, C—H⋯N, C—H⋯Br and N—H⋯N hydrogen bonds link the mol­ecules into a two-dimensional network in the (011) plane. PMID:22259398

  3. Concomitant monitoring of implant formation and drug release of in situ forming poly (lactide-co-glycolide acid) implants in a hydrogel matrix mimicking the subcutis using UV-vis imaging.

    PubMed

    Sun, Yu; Jensen, Henrik; Petersen, Nickolaj J; Larsen, Susan W; Østergaard, Jesper

    2018-02-20

    For poly (lactide-co-glycolide acid) (PLGA)-based in situ forming implants, the rate of implant formation plays an important role in determining the overall drug release kinetics. Currently, in vitro techniques capable of characterizing the processes of drug release and implant formation at the same time are not available. A hydrogel-based in vitro experimental setup was recently developed requiring only microliter of formulation and forming a closed system potentially suitable for interfacing with various spectroscopic techniques. The aim of the present proof-of-concept study was to investigate the feasibility of concomitant UV imaging, Vis imaging and light microscopy for detailed characterization of the behavior of in situ forming PLGA implants in the hydrogel matrix mimicking the subcutis. The model compounds, piroxicam and α-lactalbumin were added to PLGA-1-methyl-2-pyrrolidinone and PLGA-triacetin solutions. Upon bringing the PLGA-solvent-compound pre-formulation in contact with the hydrogel, Vis imaging and light microscopy were applied to visualize the depot formation and UV imaging was used to quantify drug transport in the hydrogel. As compared to piroxicam, the α-lactalbumin invoked an acceleration of phase separation and an increase of implant size. α-Lactalbumin was released faster from the PLGA-1-methyl-2-pyrrolidinone system than the PLGA-triacetin system opposite to the piroxicam release pattern. A linear relationship between the rate of implant formation and initial compound release within the first 4h was established for the PLGA-NMP systems. This implies that phase separation may be one of the controlling factors in drug release. The rate of implant formation may be an important parameter for predicting and tailoring drug release. The approach combining UV imaging, Vis imaging and light microscopy may facilitate understanding of release processes and holds potential for becoming a useful tool in formulation development of in situ forming

  4. C60 Cheese Sticks: Supramolecular Architecture of an Amphiphilic Fullerene Pentapod.

    PubMed

    Samal, Monica; Acharya, Sandhyarani; Yi, Dong Kee; Lee, Jae-Suk; Samal, Shashadhar

    2015-09-01

    An amphiphillic fullerene pentaphenol derivative, C60(4-HOC6H4)5H, in an aprotic solvent N-methyl-2-pyrrolidone (NMP), spontaneously self-assembles to a hitherto unknown cheese stick-like (CS) structure. This fascinating structure is observed only for C60(4-HOC6H4)5H and only in dry NMP solvent. The reason for such unique self-assembly behavior is ascribed to solvating power typical of NMP. The CS structure is observed in a narrow concentration range of the solution. This indicates that there exists between the solute and the solvent an optimal interaction condition for CS to remain stable.

  5. Crystal structure of 2-bromo-3-di­methyl­amino-N,N,N′,N′,4-penta­methyl-4-(tri­methyl­sil­yloxy)pent-2-eneamidinium bromide

    PubMed Central

    Tiritiris, Ioannis; Kress, Ralf; Kantlehner, Willi

    2015-01-01

    The reaction of the ortho­amide 1,1,1-tris­(di­methyl­amino)-4-methyl-4-(tri­methyl­sil­yloxy)pent-2-yne with bromine in benzene, yields the title salt, C15H33BrN3OSi+·Br−. The C—N bond lengths in the amidinium unit are 1.319 (6) and 1.333 (6) Å, indicating double-bond character, pointing towards charge delocalization within the NCN plane. The C—Br bond length of 1.926 (5) Å is characteristic for a C—Br single bond. Additionally, there is a bromine–bromine inter­action [3.229 (3) Å] present involving the anion and cation. In the crystal, weak C—H⋯Br inter­actions between the methyl H atoms of the cation and the bromide ions are present. PMID:26870498

  6. Reevaluation of the effect of ellagic acid on N-methyl-N-nitrosourea DNA alkylation and mutagenicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lord, H.L.; Josephy, P.D.; Snieckus, V.A.

    N-Methyl-N-nitrosourea (MNU) is a reactive, mutagenic methylating agent. MNU methylates DNA at various sites, including guanine N{sup 7}, guanine O{sup 6}, and adenine N{sup 3}. Dixit and Gold ((1986) Proc. Natl, Acad. Sci. U.S.A. 83, 8039-8043) reported that ellagic acid, a phenolic natural product, inhibited the mutagenicity of MNU in Salmonella typhimurium strain TA 100, inhibited salmon sperm DNA alkylation by ({sup 3}H)MNU, and also greatly reduced the ratio of guanine O{sup 6} to guanine N{sup 7} alkylation. We have examined the MNU-induced alkylation of calf thymus DNA and evaluated the effect of ellagic acid on this binding. Ellagic acidmore » had only a slight effect on total alkylation and did not alter the ratio of methylation at guanine-O{sup 6} and -N{sup 7} positions. In further experiments, ellagic acid did not significantly inhibit MNU mutagenicity. These findings do not support the potential use of ellagic acid as an inhibitor of biological damage induced by nitrosoureas.« less

  7. Immortalization and characterization of osteoblast cell lines generated from wild-type and Nmp4-null mouse bone marrow stromal cells using murine telomerase reverse transcriptase (mTERT).

    PubMed

    Alvarez, Marta B; Childress, Paul; Philip, Binu K; Gerard-O'Riley, Rita; Hanlon, Michael; Herbert, Brittney-Shea; Robling, Alexander G; Pavalko, Fredrick M; Bidwell, Joseph P

    2012-05-01

    Intermittent parathyroid hormone (PTH) adds new bone to the osteoporotic skeleton; the transcription factor Nmp4/CIZ represses PTH-induced bone formation in mice and as a consequence is a potential drug target for improving hormone clinical efficacy. To explore the impact of Nmp4/CIZ on osteoblast phenotype, we immortalized bone marrow stromal cells from wildtype (WT) and Nmp4-knockout (KO) mice using murine telomerase reverse transcriptase. Clonal lines were initially chosen based on their positive staining for alkaline phosphatase and capacity for mineralization. Disabling Nmp4/CIZ had no gross impact on osteoblast phenotype development. WT and KO clones exhibited identical sustained growth, reduced population doubling times, extended maintenance of the mature osteoblast phenotype, and competency for differentiating toward the osteoblast and adipocyte lineages. Additional screening of the immortalized cells for PTH-responsiveness permitted further studies with single WT and KO clones. We recently demonstrated that PTH-induced c-fos femoral mRNA expression is enhanced in Nmp4-KO mice and in the present study we observed that hormone stimulated either an equivalent or modestly enhanced increase in c-fos mRNA expression in both primary null and KO clone cells depending on PTH concentration. The null primary osteoblasts and KO clone cells exhibited a transiently enhanced response to bone morphogenetic protein 2 (BMP2). The clones exhibited lower and higher expressions of the PTH receptor (Pthr1) and the BMP2 receptor (Bmpr1a, Alk3), respectively, as compared to primary cells. These immortalized cell lines will provide a valuable tool for disentangling the complex functional roles underlying Nmp4/CIZ regulation of bone anabolism. Copyright © 2011 Wiley Periodicals, Inc.

  8. 40 CFR 721.2275 - N,N,N′,N′-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false N,N,Nâ²,Nâ²-Tetrakis(oxi-ranyl- methyl... Significant New Uses for Specific Chemical Substances § 721.2275 N,N,N′,N′-Tetrakis(oxi-ranyl- methyl)-1,3... chemical substance identified as N,N,N′,N′-tetrakis(oxiranylmethyl)-1,3-cyclohexanedimethanamine (P-84-7...

  9. 40 CFR 721.2275 - N,N,N′,N′-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false N,N,Nâ²,Nâ²-Tetrakis(oxi-ranyl- methyl... Significant New Uses for Specific Chemical Substances § 721.2275 N,N,N′,N′-Tetrakis(oxi-ranyl- methyl)-1,3... chemical substance identified as N,N,N′,N′-tetrakis(oxiranylmethyl)-1,3-cyclohexanedimethanamine (P-84-7...

  10. NMP22 BladderChek Test: point-of-care technology with life- and money-saving potential.

    PubMed

    Tomera, Kevin M

    2004-11-01

    A new, relatively obscure tumor marker assay, the NMP22 BladderChek Test (Matritech, Inc.), represents a paradigm shift in the diagnosis and management of urinary bladder cancer (transitional cell carcinoma). Specifically, BladderChek should be employed every time a cystoscopy is performed, with corresponding changes in the diagnostic protocol and the guidelines of the American Urological Association for the diagnosis and management of bladder cancer. Currently, cystoscopy is the reference standard and NMP22 BladderChek Test in combination with cystoscopy improves the performance of cystoscopy. At every stage of disease, BladderChek provides a higher sensitivity for the detection of bladder cancer than cytology, which now represents the adjunctive standard of care. Moreover, BladderChek is four-times more sensitive than cytology and is available at half the cost. Early detection of bladder cancer improves prognosis, quality of life and survival. BladderChek may be analogous to the prostate-specific antigen test and eventually expand beyond the urologic setting into the primary care setting for the testing of high-risk patients characterized by smoking history, occupational exposures or age.

  11. Dynamic coupling between the LID and NMP domain motions in the catalytic conversion of ATP and AMP to ADP by adenylate kinase

    NASA Astrophysics Data System (ADS)

    Jana, Biman; Adkar, Bharat V.; Biswas, Rajib; Bagchi, Biman

    2011-01-01

    The catalytic conversion of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) to adenosine diphosphate (ADP) by adenylate kinase (ADK) involves large amplitude, ligand induced domain motions, involving the opening and the closing of ATP binding domain (LID) and AMP binding domain (NMP) domains, during the repeated catalytic cycle. We discover and analyze an interesting dynamical coupling between the motion of the two domains during the opening, using large scale atomistic molecular dynamics trajectory analysis, covariance analysis, and multidimensional free energy calculations with explicit water. Initially, the LID domain must open by a certain amount before the NMP domain can begin to open. Dynamical correlation map shows interesting cross-peak between LID and NMP domain which suggests the presence of correlated motion between them. This is also reflected in our calculated two-dimensional free energy surface contour diagram which has an interesting elliptic shape, revealing a strong correlation between the opening of the LID domain and that of the NMP domain. Our free energy surface of the LID domain motion is rugged due to interaction with water and the signature of ruggedness is evident in the observed root mean square deviation variation and its fluctuation time correlation functions. We develop a correlated dynamical disorder-type theoretical model to explain the observed dynamic coupling between the motion of the two domains in ADK. Our model correctly reproduces several features of the cross-correlation observed in simulations.

  12. Methyl N-phenyl carbamate synthesis from aniline and methyl formate: carbon recycling to chemical products.

    PubMed

    Yalfani, Mohammad S; Lolli, Giulio; Müller, Thomas E; Wolf, Aurel; Mleczko, Leslaw

    2015-02-01

    Methyl N-phenyl carbamate was synthesized from aniline by using methyl formate as a green and efficient carbonylating agent. High yields were obtained at milder reaction conditions compared to the conventional CO/CH3 OH route. Studies on the reaction sequence led to suggest an alternative and more efficient route to the carbamate via formanilide as intermediate. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. 4-Methyl-N-(1-methyl-1H-indazol-5-yl)benzene-sulfonamide.

    PubMed

    Chicha, Hakima; Oulemda, Bassou; Rakib, El Mostapha; Saadi, Mohamed; El Ammari, Lahcen

    2013-01-01

    In the title compound, C15H15N3O2S, the fused ring system is close to planar, the largest deviation from the mean plane being 0.030 (2) Å, and makes a dihedral angle of 48.84 (9)° with the benzene ring belonging to the methyl-benzene-sulfonamide moiety. In the crystal, mol-ecules are -connected through N-H⋯N hydrogen bonds and weak C-H⋯O contacts, forming a two-dimensional network parallel to (001).

  14. Two-step iron(0)-mediated N-demethylation of N-methyl alkaloids.

    PubMed

    Kok, Gaik B; Pye, Cory C; Singer, Robert D; Scammells, Peter J

    2010-07-16

    A mild and simple two-step Fe(0)-mediated N-demethylation of a number of tertiary N-methyl alkaloids is described. The tertiary N-methylamine is first oxidized to the corresponding N-oxide, which is isolated as the hydrochloride salt. Subsequent treatment of the N-oxide hydrochloride with iron powder readily provides the N-demethylated amine. Representative substrates include a number of opiate and tropane alkaloids. Key intermediates in the synthesis of semisynthetic 14-hydroxy pharmaceutical opiates such as oxycodone and oxymorphone are also readily N-demethylated using this method.

  15. Formation of silicon carbide by laser ablation in graphene oxide-N-methyl-2-pyrrolidone suspension on silicon surface

    NASA Astrophysics Data System (ADS)

    Jaleh, Babak; Ghasemi, Samaneh; Torkamany, Mohammad Javad; Salehzadeh, Sadegh; Maleki, Farahnaz

    2018-01-01

    Laser ablation of a silicon wafer in graphene oxide-N-methyl-2-pyrrolidone (GO-NMP) suspension was carried out with a pulsed Nd:YAG laser (pulse duration = 250 ns, wavelength = 1064 nm). The surface of silicon wafer before and after laser ablation was studied using optical microscopy, scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX). The results showed that the ablation of silicon surface in liquid by pulsed laser was done by the process of melt expulsion under the influence of the confined plasma-induced pressure or shock wave trapped between the silicon wafer and the liquid. The X-ray diffraction‌ (XRD) pattern of Si wafer after laser ablation showed that 4H-SiC layer is formed on its surface. The formation of the above layer was also confirmed by Raman spectroscopy, and X-ray photoelectron spectroscopy‌ (XPS), as well as EDX was utilized. The reflectance of samples decreased with increasing pulse energy. Therefore, the morphological alteration and the formation of SiC layer at high energy increase absorption intensity in the UV‌-vis regions. Theoretical calculations confirm that the formation of silicon carbide from graphene oxide and silicon wafer is considerably endothermic. Development of new methods for increasing the reflectance without causing harmful effects is still an important issue for crystalline Si solar cells. By using the method described in this paper, the optical properties of solar cells can be improved.

  16. A new NASA LaRC Multi-Purpose Prepregging Unit

    NASA Technical Reports Server (NTRS)

    Wilkinson, S. P.; Marchello, J. M.; Dixon, D.; Johnston, N. J.

    1993-01-01

    A multi-purpose prepregging machine has been designed and built for NASA Langley Research Center. The machine has numerous advantages over existing units due to its various modular components. Each of these can be used individually or simultaneously depending on the required prepregging method. A reverse roll coater provides the ability to prepare thin films from typical hot-melt thermoset formulations. Also, if necessary, the design allows direct fiber impregnation within the reverse roll coater gap. Included in the impregnation module is a solution dip tank allowing the fabrication of thermoplastic prepregs from solution. The proceeding modules within the unit consist of four nip stations, two hot-plates, a hot-sled option and a high temperature oven. This paper describes the advantages of such a modular construction and discusses the various processing combinations available to the prepregger. A variety of high performance prepreg material systems were produced on IM7 (Hercules) carbon fiber. These included LaRC RP46, a PMR-type resin processed from methanol and two polyamide acids, LaRC IA and LaRC ITPI, prpregged from N-methyl pyrrolidinone (NMP). Parameters involved in the production of these prepreg materials are presented as are the mechanical properties of the resulting good quality laminates. A brief introduction into the existing prepregging science is presented. Topics relating to solution prepregging are identified with a focus on the current research effort and its future development.

  17. N-substituted methyl maleamates as larvicidal compounds against Aedes aegypti (Diptera: Culicidae).

    PubMed

    Harburguer, Laura; Gonzalez, Paula V; Gonzalez Audino, Paola; Zerba, Eduardo; Masuh, Héctor

    2018-02-01

    Severe human arboviral diseases can be transmitted by the mosquito Aedes aegypti (L.), including dengue, chikungunya, zika, and yellow fever. The use of larvicides in containers that can result as potential breeding places and cannot be eliminated is the main alternative in control programs. However, their continuous and widespread use caused an increase in insecticide-resistant populations of this mosquito. The aim of this study was to evaluate the effect of three N-substituted methyl maleamates as larvicides on Ae. aegypti, the N-propyl methyl maleamate (PMM), N-butyl methyl maleamate (BMM), and N-hexyl methyl maleamate (HMM). These compounds could have a different mode of action from those larvicides known so far. We evaluated the larva mortality after 1 and 24 h of exposure and we found that mortality was fast and occurs within the first 60 min. HMM was slightly more effective with LC 50 values of 0.7 and 0.3 ppm for 1 and 24 h of exposure and LC 95 of 11 and 3 ppm. Our results demonstrate that N-substituted methyl maleamates have insecticidal properties for the control of Ae. aegypti larvae. These compounds could become useful alternatives to traditional larvicides after studying their insecticidal mechanism as well as their toxicity towards non target organisms.

  18. The Enzymatic Release of O6-methylguanine and 3-methyladenine from DNA Reacted with the Carcinogen N-methyl-N-nitrosourea

    PubMed Central

    Kirtikar, D. M.; Goldthwait, D. A.

    1974-01-01

    Endonuclease II (deoxyribonucleate oligonucleotidohydrolase, EC 3.1.4.30) of Escherichia coli has been shown to break phosphodiester bonds in alkylated DNA and depurinated DNA. The hypothesis that depurination is a step in the mechanism of the reaction with alkylated DNA is supported by in vitro experiments with DNA reacted with N-methyl-N-nitrosourea. Endonuclease II releases O6-methylguanine and 3-methyladenine, but not 7-methylguanine, from DNA that has been methylated by the carcinogen N-methyl-N-nitrosourea. PMID:4600266

  19. Control of box C/D snoRNP assembly by N6-methylation of adenine.

    PubMed

    Huang, Lin; Ashraf, Saira; Wang, Jia; Lilley, David Mj

    2017-09-01

    N 6 -methyladenine is the most widespread mRNA modification. A subset of human box C/D snoRNA species have target GAC sequences that lead to formation of N 6 -methyladenine at a key trans Hoogsteen-sugar A·G base pair, of which half are methylated in vivo The GAC target is conserved only in those that are methylated. Methylation prevents binding of the 15.5-kDa protein and the induced folding of the RNA Thus, the assembly of the box C/D snoRNP could in principle be regulated by RNA methylation at its critical first stage. Crystallography reveals that N 6 -methylation of adenine prevents the formation of trans Hoogsteen-sugar A·G base pairs, explaining why the box C/D RNA cannot adopt its kinked conformation. More generally, our data indicate that sheared A·G base pairs (but not Watson-Crick base pairs) are more susceptible to disruption by N 6 mA methylation and are therefore possible regulatory sites. The human signal recognition particle RNA and many related Alu retrotransposon RNA species are also methylated at N6 of an adenine that forms a sheared base pair with guanine and mediates a key tertiary interaction. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  20. Microwave-assisted extraction of polycyclic aromatic compounds from coal.

    PubMed

    Kerst, M; Andersson, J T

    2001-08-01

    Microwave-assisted extraction (MAE) of polycyclic aromatic compounds (PACs) from coal is shown to give the same pattern of compounds as Soxhlet extraction. MAE requires only 10 mL solvent and 10 min extraction time whereas Soxhlet uses 200 mL and takes 24 h. Although the yields were lower, dichloromethane (DCM) was preferred to pyridine, N-methyl-2-pyrrolidone (NMP), and NMP with CS2 because the pattern of the PACs is shown to be independent of solvent and DCM is a much more convenient solvent to work with.

  1. Inhibition of Osteoclast Differentiation and Bone Resorption by N-Methylpyrrolidone*

    PubMed Central

    Ghayor, Chafik; Correro, Rita M.; Lange, Katrin; Karfeld-Sulzer, Lindsay S.; Grätz, Klaus W.; Weber, Franz E.

    2011-01-01

    Regulation of RANKL (receptor activator of nuclear factor κB ligand)-induced osteoclast differentiation is of current interest in the development of antiresorptive agents. Osteoclasts are multinucleated cells that play a crucial role in bone resorption. In this study, we investigated the effects of N-methylpyrrolidone (NMP) on the regulation of RANKL-induced osteoclastogenesis. NMP inhibited RANKL-induced tartrate-resistant acid phosphatase activity and the formation of tartrate-resistant acid phosphatase-positive multinucleated cells. The RANKL-induced expression of NFATc1 (nuclear factor of activated T cells, cytoplasmic 1) and c-Fos, which are key transcription factors for osteoclastogenesis, was also reduced by treatment with NMP. Furthermore, NMP induced disruption of the actin rings and decreased the mRNAs of cathepsin K and MMP-9 (matrix metalloproteinase-9), both involved in bone resorption. Taken together, these results suggest that NMP inhibits osteoclast differentiation and attenuates bone resorption. Therefore, NMP could prove useful for the treatment of osteoporosis or other bone diseases associated with excessive bone resorption. PMID:21613210

  2. Kinetic and analytic investigations on the formation of N-nitroso-N-methyl-N-cyclohexylamine from bromhexine and nitrite.

    PubMed

    Schmid, J; Daneck, K; Koss, F W; Eisenbrand, G; Schlemmer, K H

    1988-09-01

    Bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammoniumhydr ochloride) forms N-nitroso-N-methyl-N-cyclohexylamine (NMCA) under the conditions of the WHO Nitrosation Assay Procedure (NAP-test). The formation kinetics of this compound was investigated. The formation of NMCA depends on the square of the nitrite concentration. The reaction has a narrow pH-optimum at pH 3. The reaction is quick: After 1 h about 70% of the maximum amount of NMCA is formed. To study this reaction kinetics sensitive assays with a detection limit up to 0.5 ng/ml NMCA were developed. The stability of the components of the system, especially that of NMCA and nitrite, were further studied. The latter is rather instable under conditions found in an acidic stomach.

  3. Mutation in a locus linked to penB-nmp causes suppression of the Mtr phenotype of Neisseria gonorrhoeae.

    PubMed Central

    Shinners, E N; Catlin, B W

    1988-01-01

    The chromosomal locus mtr, which encodes low-level resistance to multiple antibacterial agents in Neisseria gonorrhoeae, is subject to phenotypic suppression by env mutations that increase the permeability of the envelope. We have identified a new locus, mom (for modifier of Mtr), which is located on the chromosome very close to penB and nmp, loci known to be linked to each other and to spc. Phenotypic suppression of Mtr was recognized by reductions of resistance to benzylpenicillin and also to oxacillin and the hydrophobic agents novobiocin and erythromycin. The resistance to each of these antibiotics returned to the Mtr levels in mom+ transformants isolated by selection for increased resistance to either novobiocin or erythromycin; the accompanying change of the outer membrane protein I seroreactions confirmed the proximity of nmp and mom. Thus, some mutant gonococci display wild-type antibiotic susceptibilities but can express multiple resistance following a mom+ mutation that releases the suppressed Mtr phenotype. PMID:3142343

  4. Formation of O2-methylthymine in poly(dA-dT) on methylation with N-methyl-N-nitrosourea and dimethyl sulphate. Evidence that O2-methylthymine does not miscode during DNA synthesis.

    PubMed Central

    Saffhill, R; Abbott, P J

    1978-01-01

    The alternating co-polymer has been methylated with either N methyl-N-nitrosourea (MNU) or dimethyl sulphate (DMS) and the levels of the various methylated thymidines (O2-methylthymidine, 3-methylthymidine and O4-methylthymidine) measured. MNU produced all three compounds whereas DMS only produced 3-methylthymidine and O2-methylthymidine at detectable levels. These results have been combined with our earlier results concerning the misincorporation of dGMP with E. coli DNA polymerase using MNU-methylated poly(dA-dT). These results indicate that O2-methylthymidine does not miscode during DNA synthesis. PMID:353735

  5. Microscale Alloy Type Lithium Ion Battery Anodes

    DTIC Science & Technology

    2015-09-01

    hexamethyldisilazane Li lithium Ni nickel NMP n-methyl-2-pyrolidone RMS root mean square SEI solid electrolyte interphase SEM scanning electron microscopy...process also leads to an unstable solid electrolyte interphase (SEI) and further capacity loss. An extraordinary amount of work has been done in an...

  6. New Poly(amide-imide)/Nanocomposites Reinforced Silicate Nanoparticles Based on N-pyromellitimido-L-phenyl Alanine Containing Ether Moieties

    NASA Astrophysics Data System (ADS)

    Faghihi, Khalil; Shabanian, Meisam; Dadfar, Ehsan

    2012-02-01

    A series of Poly(amide-imide)/montmorillonite nanocomposites containing N-pyromellitimido-L-phenyl alanine moiety in the main chain were synthesized by a convenient solution intercalation technique. Poly(amide-imide) (PAI) 5 as a source of polymer matrix was synthesized by the direct polycondensation reaction of N-pyromellitimido-L-phenyl alanine 3 with 4,4'-diamino diphenyl ether 4 in the presence of triphenyl phosphite (TPP), CaCl2, pyridine and N-methyl-2-pyrrolidone (NMP). The resulting nanocomposite films were characterized by Fourier transform infrared spectra (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The results showed that organo-modified clay was dispersed homogeneously in PAI matrix. TGA indicated an enhancement of thermal stability of new nanocomposites compared with the pure polymer.

  7. Biofuel and chemical production by recombinant microorganisms via fermentation of proteinaceous biomass

    DOEpatents

    Liao, James C.; Cho, Kwang Myung; Yan, Yajun; Huo, Yixin

    2016-03-15

    Provided herein are metabolically modified microorganisms characterized by having an increased keto-acid flux when compared with the wild-type organism and comprising at least one polynucleotide encoding an enzyme that when expressed results in the production of a greater quantity of a chemical product when compared with the wild-type organism. The recombinant microorganisms are useful for producing a large number of chemical compositions from various nitrogen containing biomass compositions and other carbon sources. More specifically, provided herein are methods of producing alcohols, acetaldehyde, acetate, isobutyraldehyde, isobutyric acid, n-butyraldehyde, n-butyric acid, 2-methyl-1-butyraldehyde, 2-methyl-1-butyric acid, 3-methyl-1-butyraldehyde, 3-methyl-1-butyric acid, ammonia, ammonium, amino acids, 2,3-butanediol, 1,4-butanediol, 2-methyl-1,4-butanediol, 2-methyl-1,4-butanediamine, isobutene, itaconate, acetoin, acetone, isobutene, 1,5-diaminopentane, L-lactic acid, D-lactic acid, shikimic acid, mevalonate, polyhydroxybutyrate (PHB), isoprenoids, fatty acids, homoalanine, 4-aminobutyric acid (GABA), succinic acid, malic acid, citric acid, adipic acid, p-hydroxy-cinnamic acid, tetrahydrofuran, 3-methyl-tetrahydrofuran, gamma-butyrolactone, pyrrolidinone, n-methylpyrrolidone, aspartic acid, lysine, cadeverine, 2-ketoadipic acid, and/or S-adenosyl-methionine (SAM) from a suitable nitrogen rich biomass.

  8. Tungsten carbide nanorods with zirconium dioxide composite for low cost with high efficiency Pt-free counter electrode in dye sensitized solar cell

    NASA Astrophysics Data System (ADS)

    Vijayakumar, P.; Senthil Pandian, M.; Ramasamy, P.

    2018-04-01

    Tungsten carbide nanorods/Zirconium dioxide (WC-NRs/ZrO2) composite material was used as a counter electrode (CE) for efficient dye-sensitized solar cell (DSSC) fabrication. The prepared WC-NRs/ZrO2 (N-Methyl-2-pyrrolidone (NMP)/2-Propanol) gel is drop casted on the FTO substrate for CE. The morphological analysis was confirmed by FESEM and TEM. Nyquist plot clearly indicates that the NMP based WC-NRs/ZrO2 CE possesses high electrocatalytic activity and faster charge-transfer ability for the reduction of I3- due to the lower charge transfer resistance. The fabricated WC-NRs/ZrO2 (NMP) composite CE is demonstrated with high power conversion efficiency (PCE) of 6.63% in comparison to the WC-NRs/ZrO2 (2-propanol) CE of 2.29% under same conditions.

  9. 4-Methyl-N-(1-methyl-1H-indazol-5-yl)benzene­sulfonamide

    PubMed Central

    Chicha, Hakima; Oulemda, Bassou; Rakib, El Mostapha; Saadi, Mohamed; El Ammari, Lahcen

    2013-01-01

    In the title compound, C15H15N3O2S, the fused ring system is close to planar, the largest deviation from the mean plane being 0.030 (2) Å, and makes a dihedral angle of 48.84 (9)° with the benzene ring belonging to the methyl­benzene­sulfonamide moiety. In the crystal, mol­ecules are ­connected through N—H⋯N hydrogen bonds and weak C—H⋯O contacts, forming a two-dimensional network parallel to (001). PMID:24427093

  10. N-Methyl Inversion in Pseudo-Pelletierine

    NASA Astrophysics Data System (ADS)

    Vallejo-López, Montserrat; Ecija, Patricia; Cocinero, Emilio J.; Lesarri, Alberto; Basterretxea, Francisco J.; Fernández, José A.

    2016-06-01

    We have previously conducted rotational studies of several tropanes, since this bicyclic structural motif forms the core of different alkaloids of pharmaceutical interest. Now we report on the conformational properties and molecular structure of pseudo-pelletierine (9-methyl-9-azabicyclo[3.3.1]nonan-3-one), probed in a jet expansion with Fourier-transform microwave spectroscopy. Pseudo-pelletierine is an azabicycle with two fused six-membered rings, where the N-methyl group can produce inverting axial o equatorial conformations. The two conformations were detected in the rotational spectrum, recorded in the region 6-18 GHz. Unlike tropinone and N-methylpiperidone, where the most stable conformer is equatorial, the axial species was found dominant for pseudo-pelletierine. All monosubstituted isotopic species (13C, 15N and 18O) were identified for the axial conformer, leading to an accurate determination of the effective and substitution structures. An estimation of conformational populations was derived from relative intensities. The experimental results will be compared with ab initio (MP2) and DFT (M06-2X, B3LYP) calculations. E. J. Cocinero, A. Lesarri, P. Écija, J.-U. Grabow, J. A. Fernández, F. Castaño, Phys. Chem. Chem. Phys. 2010, 49, 4503 P. Écija, E. J. Cocinero, A. Lesarri, F. J. Basterretxea, J. A. Fernández, F. Castaño, Chem. Phys. Chem. 2013, 14, 1830 P. Écija, M. Vallejo-Lopez, I. Uriarte, F. J. Basterretxea, A. Lesarri, J. A. Fernández, E. J. Cocinero, submitted 2016

  11. Bioconversion of 6-(N-methyl-N-phenyl)aminomethyl androstane steroids by Nocardioides simplex.

    PubMed

    Sukhodolskaya, Galina; Fokina, Victoria; Shutov, Andrei; Nikolayeva, Vera; Savinova, Tatiana; Grishin, Yuri; Kazantsev, Alexey; Lukashev, Nikolay; Donova, Marina

    2017-02-01

    The newly synthesized (α/β)-diastereomers of 6-(N-methyl-N-phenyl)aminomethylandrost-4-ene-3,17-dione (5) and 6-(N-methyl-N-phenyl)aminomethylandrost-4-en-17β-ol-3-one (6) were firstly investigated as substrates for the whole cells of Nocardioides simplex VKM Ac-2033D in comparison with their unsubstituted analogs, - androst-4-ene-3,17-dione (1) and androst-4-en-17β-ol-3-one (2). 1(2)-Dehydroderivatives were identified as the major bioconversion products from all the substrates tested. When using the mixtures of (α/β)-stereoisomers of 5 and 6 as the substrates, only β-stereoisomers of the corresponding 1,4-diene-steroids were formed. Along with 1(2)-dehydrogenation, N. simplex VKM Ac-2033D promoted oxidation of the hydroxyl group at C-17 position of 6: both 6(α) and 6(β) were transformed to the corresponding 17-keto derivatives. No steroid core destruction was observed during the conversion of the 6-substituted androstanes 5 and 6, while it was significant when 1 or 2 was used as the substrate. The results suggested high potentials of N. simplex VKM Ac-2033D for the generation of novel 1(2)-dehydroanalogs. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. DNA precursor pool: a significant target for N-methyl-N-nitrosourea in C3H/10T1/2 clone 8 cells.

    PubMed Central

    Topal, M D; Baker, M S

    1982-01-01

    Synchronized C3H/10T1/2 clone 8 cells were treated in vitro with a nontoxic dose of N-methyl-N-nitrosourea during their S phase. Chromatographic isolation of the deoxyribonucleotide DNA precursor pool and measurement of the precursor content per cell showed that a nucleic acid residue in the precursor pool is 190-13,000 times more susceptible to methylation than a residue in the DNA duplex, depending on the site of methylation. This conclusion comes from measurements indicating that, for example, the N-1 position of adenine in dATP is 6.3 times more methylated than the same position in the DNA, even though the adenine content of the pool is only a fraction (0.0005) of the adenine content of the DNA helix. The comparative susceptibility between pool and DNA was found to vary with the site of methylation in the order the N-1 position of adenine greater than phosphate greater than the N-3 position of adenine greater than the O6 position of guanine greater than the N-7 position of guanine. The significance of these results for chemical mutagenesis and carcinogenesis is discussed. PMID:6954535

  13. Synthesis and characterization of 3-acetoxy-2-methyl-N-(phenyl)benzamide and 3-acetoxy-2-methyl-N-(4- methylphenyl)benzamide

    NASA Astrophysics Data System (ADS)

    Kırca, Başak Koşar; Çakmak, Şükriye; Kütük, Halil; Odabaşoğlu, Mustafa; Büyükgüngör, Orhan

    2018-01-01

    This study treats about two successfully synthesized secondary amide compounds 3-Acetoxy-2-methyl-N-(phenyl)benzamide, I and 3-Acetoxy-2-methyl-N-(4-methylphenyl)benzamide, II. Compounds were characterized by FTIR, 1H NMR, 13C NMR and X-ray single crystal diffraction analysis techniques. Single crystal X-ray diffraction analyses show that while I crystallized in the orthorhombic system with space group Pbca, II crystallized in the triclinic system with space group P-1 and the asymmetric unit of II consists of two crystallographically independent molecules. Lattice constants are a = 7.9713 (3) Å, b = 9.5059 (3) Å, c = 37.1762 (2) Å, Z = 8 for I and a = 7.5579 (8) Å, b = 8.8601 (8) Å, c = 23.363 (3) Å, α = 97.011 (9) °, β = 96.932 (9)°, γ = 90.051 (8)°, Z = 4 for II. Crystallographic studies also show that the supramolecular structures were stabilized by intramolecular, intermolecular hydrogen bonds and Csbnd H … π interactions for both compounds. Characteristic amide bonds were observed in IR and NMR spectra.

  14. Induction of glandular stomach cancers in Helicobacter pylori-sensitive Mongolian gerbils treated with N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine in drinking water.

    PubMed

    Tatematsu, M; Yamamoto, M; Shimizu, N; Yoshikawa, A; Fukami, H; Kaminishi, M; Oohara, T; Sugiyama, A; Ikeno, T

    1998-02-01

    An animal model of stomach carcinogenesis was established using Mongolian gerbils with N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as the carcinogens. In addition, the sensitivity of these gerbils to Helicobacter pylori (H. pylori) was confirmed. One hundred and sixty specific pathogen-free male MGS/Sea animals, 7 weeks old, were treated with MNU in the drinking water (30 ppm for alternate weeks to give 10 weeks exposure, or 10 ppm or 3 ppm for 20 weeks continuous exposure), or given MNNG in the drinking water at 400 ppm or 200 ppm for 20 weeks, or orally inoculated with ATCC43504 H. pylori (1.7 x 10(8) CFUs/animal). Adenocarcinomas in the glandular stomach were found in 2 out of 12 effective animals (2/ 12) treated with 30 ppm MNU at week 20, although all were dead or moribund by week 30 due to MNU toxicity. At week 50, the incidences of gastric adenocarcinomas in groups treated with 10 ppm MNU, 3 ppm MNU, 400 ppm MNNG, and 200 ppm MNNG were 2/21 (9.5%), 1/23 (4.3%), 7/ 11 (63.6%), and 1/10 (10.0%). The lesions were generally well differentiated, although poorly differentiated adenocarcinoma was also found in a single gerbil in each of the 10 ppm MNU and 400 ppm MNNG groups. In control animals no tumors were found. In the infection study, the animals were killed at week 20, and H. pylori was detected in all cases, causing multiple erosions with marked inflammatory cell infiltration in the lamina propria and submucosa, and frequent formation of lymphoid follicles. Thus, MNU and MNNG in the drinking water induced neoplastic lesions in the glandular stomach epithelium of H. pylori-sensitive gerbils.

  15. Mössbauer and NMR study of novel Tin(IV)-lactames

    NASA Astrophysics Data System (ADS)

    Kuzmann, Erno; Szalay, Roland; Homonnay, Zoltan; Nagy, Sandor

    2012-03-01

    N-tributylstannylated 2-pyrrolidinone was reacted with tributyltin triflate in different molar ratios and the complex formation monitored using 1H-NMR, 13C-NMR and 119Sn Mössbauer spectroscopy. Comparing the carbon NMR and tin Mössbauer results, a reaction scheme is suggested for the complexation which assumes the formation of a simultaneously O- and N-tributylstannylated pyrrolidinone cation. The formation of the only O-stannylated pyrrolidinone is also assumed to account for the non-constant Mössbauer parameters of the two tin environments in the distannylated pyrrolidinone cation when the ratio of tributyltin triflate is increased in the reaction.

  16. N-Methyl Inversion and Accurate Equilibrium Structures in Alkaloids: Pseudopelletierine.

    PubMed

    Vallejo-López, Montserrat; Écija, Patricia; Vogt, Natalja; Demaison, Jean; Lesarri, Alberto; Basterretxea, Francisco J; Cocinero, Emilio J

    2017-11-21

    A rotational spectroscopy investigation has resolved the conformational equilibrium and structural properties of the alkaloid pseudopelletierine. Two different conformers, which originate from inversion of the N-methyl group from an axial to an equatorial position, have been unambiguously identified in the gas phase, and nine independent isotopologues have been recorded by Fourier-transform microwave spectroscopy in a jet expansion. Both conformers share a chair-chair configuration of the two bridged six-membered rings. The conformational equilibrium is displaced towards the axial form, with a relative population in the supersonic jet of N axial /N equatorial ≈2/1. An accurate equilibrium structure has been determined by using the semiexperimental mixed-estimation method and alternatively computed by quantum-chemical methods up to the coupled-cluster level of theory. A comparison with the N-methyl inversion equilibria in related tropanes is also presented. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Novel pyrrolinones as N-methyl-D-aspartate receptor antagonists.

    PubMed

    Poschenrieder, Hermann; Stachel, Hans-Dietrich; Höfner, Georg; Mayer, Peter

    2005-04-01

    A series of oximes, deriving from 2-arylidene-pyrroline-3,4-diones (7, 8, 22, 23) has been prepared. The presence of tautomers in their solutions has been established by spectroscopic means. The compounds reacted with diazomethane chiefly by N-methylation forming nitrones (10, 11). The analogously prepared 2-arylidene-4-nitropyrrolin-3-ones (12, 13, 24, 25), formally derived from nitrotetramic acids, yielded nitronic acid esters (14, 15, 26) upon reaction with diazomethane. The structures were elucidated by spectral evidence and-in the case of compounds 10 and 20b-by X-ray diffraction analysis. The binding affinity of some of the new compounds toward the N-methyl-d-aspartate (NMDA) (glycine site) receptor has been measured thus providing the basis for further structure-activity relationship studies. Oxime 8b showed the highest binding potency (Ki= 9.2 microM).

  18. Insight into the theoretical and experimental studies of 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone N(4)-methyl-N(4)- phenylthiosemicarbazone - A potential NLO material

    NASA Astrophysics Data System (ADS)

    Sangeetha, K. G.; Aravindakshan, K. K.; Safna Hussan, K. P.

    2017-12-01

    The synthesis, geometrical parameters, spectroscopic studies, optimised molecular structure, vibrational analysis, Mullikan population analysis, MEP, NBO, frontier molecular orbitals and NLO effects of 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone N-(4)-methyl-N-(4)-phenylthiosemicarbazone, C25H23N5OS (L1) have been communicated in this paper. A combined experimental and theoretical approach was used to explore the structure and properties of the compound. For computational studies, Gaussian 09 program was used. Starting geometry of molecule was taken from X-ray refinement data and has been optimized by using DFT (B3LYP) method with the 6-31+G (d, p) basis sets. NBO analysis gave insight into the strongly delocalized structure, responsible for the nonlinearity and hence the stability of the molecule. Frontier molecular orbitals have been defined to forecast the global reactivity descriptors of L1. The computed first-order hyperpolarizability (β) of the compound is 2 times higher than that of urea and this account for its nonlinear optical property. Simultaneously, a molecular docking study of the compound was performed using GLIDE Program. For this, three biological enzymes, histone deacetylase, ribonucleotide reductase and DNA methyl transferase, were selected as receptor molecules.

  19. TOXICITY OF TETRYL (N-METHYL-N,2,4,6-TETRANITROANILINE) IN F344 RATS

    EPA Science Inventory

    The toxicity of tetryl (N-methyl-N,2,4,6-tetranitroaniline) in male and female F344 rats was evaluated after adminstration in the diet for 14 or 90 days. The 14-day study diet concentrations used were 0, 500, 1250, 2000, 2500, and 5000 ppm; the 90-day study diet concentrations we...

  20. DNA methylation of ESR-1 and N-33 in colorectal mucosa of patients with ulcerative colitis (UC).

    PubMed

    Arasaradnam, Ramesh P; Khoo, Kevin; Bradburn, Mike; Mathers, John C; Kelly, Seamus B

    2010-07-01

    Epigenetic marking such as DNA methylation influence gene transcription and chromosomal stability and may also be affected by environmental exposures. Few studies exist on alteration in DNA methylation profiles (genomic and gene specific methylation) in patients with Ulcerative Colitis (UC) and no studies exist that assess its relationship with lifestyle exposures. The methylation level of both ESR-1 and N-33 genes were significantly higher in UC subjects compared with controls (7.9% vs. 5.9%; p = 0.015 and 66% vs. 9.3%; p < 0.001 respectively). There was no detectable difference in global DNA methylation between patients with UC and age and sex matched controls. No associations between indices of DNA methylation and anthropometric measures or smoking patterns were detected. To assess genomic methylation and promoter methylation of the ESR-1 (oestrogen receptor-1) and N-33 (tumor suppressor candidate-3) genes in the macroscopically normal mucosa of UC patients as well as to investigate effects of anthropometric and lifestyle exposures on DNA methylation. Sixty eight subjects were recruited (24 UC and 44 age and sex matched controls). Colorectal mucosal biopsies were obtained and DNA was extracted. Genomic DNA methylation was quantified using the tritium-labelled cytosine extension assay (3[H] dCTP) while gene specific methylation was quantified using the COBRA method. For the first time, we have shown increased methylation in the promoter regions of the putative tumor suppressor gene N-33 in macroscopically normal mucosa of patients with UC. In addition, we have confirmed that methylation of ESR-1 promoter is higher in UC patients compared with age and sex matched controls. These findings suggest that inactivation through methylation of the putative tumor suppressor genes N-33 and ESR-1 may not be associated with colorectal carcinogenesis in UC.

  1. MeDIP-seq and nCpG analyses illuminate sexually dimorphic methylation of gonadal development genes with high historic methylation in turtle hatchlings with temperature-dependent sex determination.

    PubMed

    Radhakrishnan, Srihari; Literman, Robert; Mizoguchi, Beatriz; Valenzuela, Nicole

    2017-01-01

    DNA methylation alters gene expression but not DNA sequence and mediates some cases of phenotypic plasticity. Temperature-dependent sex determination (TSD) epitomizes phenotypic plasticity where environmental temperature drives embryonic sexual fate, as occurs commonly in turtles. Importantly, the temperature-specific transcription of two genes underlying gonadal differentiation is known to be induced by differential methylation in TSD fish, turtle and alligator. Yet, how extensive is the link between DNA methylation and TSD remains unclear. Here we test for broad differences in genome-wide DNA methylation between male and female hatchling gonads of the TSD painted turtle Chrysemys picta using methyl DNA immunoprecipitation sequencing, to identify differentially methylated candidates for future study. We also examine the genome-wide nCpG distribution (which affects DNA methylation) in painted turtles and test for historic methylation in genes regulating vertebrate gonadogenesis. Turtle global methylation was consistent with other vertebrates (57% of the genome, 78% of all CpG dinucleotides). Numerous genes predicted to regulate turtle gonadogenesis exhibited sex-specific methylation and were proximal to methylated repeats. nCpG distribution predicted actual turtle DNA methylation and was bimodal in gene promoters (as other vertebrates) and introns (unlike other vertebrates). Differentially methylated genes, including regulators of sexual development, had lower nCpG content indicative of higher historic methylation. Ours is the first evidence suggesting that sexually dimorphic DNA methylation is pervasive in turtle gonads (perhaps mediated by repeat methylation) and that it targets numerous regulators of gonadal development, consistent with the hypothesis that it may regulate thermosensitive transcription in TSD vertebrates. However, further research during embryogenesis will help test this hypothesis and the alternative that instead, most differential methylation

  2. Morphology and kinetics of the formation of polyamide benzimidazole in N-methylpyrrolidone

    NASA Astrophysics Data System (ADS)

    Khanchich, O. A.; Larionov, V. B.; Biryukov, A. L.

    2018-02-01

    Polymerization-optical methods were used to study the supermolecular structure in the gelation of systems based on polyamidobenzimidazole (PABI) in N-methylpyrrolidone (N-MP) and the kinetics of phase transformations during polymer coagulation from a the solution. It was found that the use of N-MP leads to the appearance in the PABI-N-MP-H2O system of spherulites having a structure characteristic of LC structures. It is shown that the alternation of metastable structures upon gelation of the PABY - N-MP-H2O system is consistent with the appearance of the LC phase of the cholesteric type.

  3. Reduced DNA repair in mouse satellite DNA after treatment with methylmethanesulfonate, and N-methyl-N-nitrosourea.

    PubMed Central

    Bodell, W J; Banerjee, M R

    1976-01-01

    We have measured DNA repair in mouse satellite and main band DNA as resolved by Ag+-Cs2SO4 centrifugation in response to treatment with the alkylating agents, methyl methanesulfonate, and N-methyl-N-nitrosourea. We find that there is a statistically significant lower incorporation of 3H-Tdr into the satellite DNA as compared to the main band at varying periods after treatment with the alkylating agents. This suggests a reduced repair activity in the satellite DNA. We have measured the extent of binding of 14C-methyl methanesulfonate to the satellite, and main band DNA, and no difference in binding was observed, indicating that the reduced repair activity of satellite DNA is not due to a difference in binding of alkylating agents. We believe that the reduced incorporation of 3H-Tdr into satellite DNA may be due to its location in the condensed chromatin fraction. PMID:184436

  4. 21 CFR 177.1560 - Polyarylsulfone resins.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... reduced viscosity of 0.40 deciliter per gram in 1-methyl-2-pyrrolidinone in accordance with ASTM method D2857-70 (Reapproved 1977), “Standard Test Method for Dilute Solution Viscosity of Polymers,” which is...

  5. N-mustard analogs of S-adenosyl-L-methionine as biochemical probes of protein arginine methylation.

    PubMed

    Hymbaugh Bergman, Sarah J; Comstock, Lindsay R

    2015-08-01

    Nucleosomes, the fundamental building blocks of eukaryotic chromatin, undergo post-synthetic modifications and play a major role in the regulation of transcriptional processes. Combinations of these modifications, including methylation, regulate chromatin structure, determining its different functional states and playing a central role in differentiation. The biological significance of cellular methylation, particularly on chromatin, is widely recognized, yet we know little about the mechanisms that link biological methylation events. To characterize and fully understand protein methylation, we describe here novel N-mustard analogs of S-adenosyl-l-methionine (SAM) as biochemical tools to better understand protein arginine methylation events using protein arginine methyltransferase 1 (PRMT1). Specifically, azide- and alkyne-functionalized N-mustard analogs serve as cofactor mimics of SAM and are enzymatically transferred to a model peptide substrate in a PRMT1-dependent fashion. Once incorporated, the resulting alkynes and azides can be modified through chemoselective ligations, including click chemistry and the Staudinger ligation. These results readily demonstrate the feasibility of utilizing N-mustard analogs as biochemical tools to site-specifically label substrates of PRMT1 and serve as an alternative approach to study protein methylation events. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. SOLUTION RHEOLOGY OF HYPERBRANCHED POLYESTERS AND THEIR BLENDS WITH LINEAR POLYMERS

    EPA Science Inventory

    In this study, the rheological properties of different generations of hyperbranched polyesters in 1-methyl-2-pyrrolidinone solvent and their blends with poly(2-hydroxyethyl methacrylate) have ben investigated. All the hyperbranched polyester solutions exhibited Newtonian behavior...

  7. 4-(Di­methyl­amino)­pyridinium trichlorido[4-(di­methyl­amino)­pyridine-κN]cobaltate(II)

    PubMed Central

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

    2013-01-01

    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

  8. Enhancing the Liquid-Phase Exfoliation of Graphene in Organic Solvents upon Addition of n-Octylbenzene

    PubMed Central

    Haar, Sébastien; El Gemayel, Mirella; Shin, Yuyoung; Melinte, Georgian; Squillaci, Marco A.; Ersen, Ovidiu; Casiraghi, Cinzia; Ciesielski, Artur; Samorì, Paolo

    2015-01-01

    Due to a unique combination of electrical and thermal conductivity, mechanical stiffness, strength and elasticity, graphene became a rising star on the horizon of materials science. This two-dimensional material has found applications in many areas of science ranging from electronics to composites. Making use of different approaches, unfunctionalized and non-oxidized graphene sheets can be produced; among them an inexpensive and scalable method based on liquid-phase exfoliation of graphite (LPE) holds potential for applications in opto-electronics and nanocomposites. Here we have used n-octylbenzene molecules as graphene dispersion-stabilizing agents during the graphite LPE process. We have demonstrated that by tuning the ratio between organic solvents such as N-methyl-2-pyrrolidinone or ortho-dichlorobenzene, and n-octylbenzene molecules, the concentration of exfoliated graphene can be enhanced by 230% as a result of the high affinity of the latter molecules for the basal plane of graphene. The LPE processed graphene dispersions were further deposited onto solid substrates by exploiting a new deposition technique called spin-controlled drop casting, which was shown to produce uniform highly conductive and transparent graphene films. PMID:26573383

  9. Preparation, electrochemical and spectral properties of free-base and manganese N-methyl-pyridylethynyl porphyrins.

    PubMed

    Lin, Ching-Yao; Chen, Yen-Chuan; Yao, Chi-Wen; Huang, Sung-Chou; Cheng, Yi-Hui

    2008-02-14

    Two series of free-base and manganese N-methyl-pyridylethynyl-5,15-biphenyl porphyrins were synthesized, and their UV-Visible, electrochemical and spectro-electrochemical properties were studied. Cyclic voltammetry experiments showed positive shifts in the reduction potentials and the UV-Visible spectra showed significant red-shifts in the absorption wavelengths of these porphyrins, indicating the effects of N-methyl-pyridylethynyl substituents.

  10. An Ultrastable Europium(III)-Organic Framework with the Capacity of Discriminating Fe2+/Fe3+ Ions in Various Solutions.

    PubMed

    Wen, Guo-Xuan; Wu, Ya-Pan; Dong, Wen-Wen; Zhao, Jun; Li, Dong-Sheng; Zhang, Jian

    2016-10-05

    An ultrastable luminescent europium-organic framework, {[Eu(L)(H 2 O) 2 ]·NMP·H 2 O} n (CTGU-2; NMP = N-methyl-2-pyrrolidone), can first detect Fe 2+ /Fe 3+ cations in different medium systems with high selectivity and sensitivity, and it also exhibits high sensitivity for Cr 2 O 7 2- anion and acetone with a wide linear range and a low detection limit.

  11. Genetic locus (nmp-1) affecting the principal outer membrane protein of Neisseria gonorrhoeae.

    PubMed Central

    Cannon, J G; Klapper, D G; Blackman, E Y; Sparling, P F

    1980-01-01

    An increase in the apparent molecular weight of the principal outer membrane protein (POMP) of Neisseria gonorrhoeae is associated with introduction of the penB2 genetic marker, which results in low-level, relatively nonspecific antibiotic resistance. Limited proteolysis of the two forms of POMP showed that they had few if any peptides in common. The nonspecific antibiotic resistance of penB2 was separated from the change in POMP by genetic transformation and by isolation of spontaneous penB mutants that showed no change in POMP. The genetic locus involved in the change from one POMP to another, which we have designated nmp-1, is closely linked to, but not identical with, penB2. Images PMID:6782080

  12. Graphene-conducting polymer nanocomposite as novel electrode for supercapacitors

    NASA Astrophysics Data System (ADS)

    Gómez, Humberto; Ram, Manoj K.; Alvi, Farah.; Villalba, P.; Stefanakos, Elias (Lee); Kumar, Ashok

    A novel graphene-polyaniline nanocomposite material synthesized using chemical precipitation technique is reported as an electrode for supercapacitors. The graphene (G)-polyaniline (PANI) nanocomposite film was dissolved in N-Methyl-2-pyrrolidone (NMP) and characterized using Raman, FTIR, Scanning Electron Microscopy, Transmission Electron Microscopy, and cyclic voltammetry (CV) techniques. The interesting composite structure could be observed using different ratios of graphene and aniline monomer. The supercapacitor is fabricated using G-PANI in N-Methyl-2-pyrrolidone (NMP) and G-PANI-Nafion films on graphite electrodes. A specific capacitance of 300-500 F g -1 at a current density of 0.1 A g -1 is observed over graphene-PANI nanocomposite materials. The aim of this study is to tailor the properties of the capacitors through the optimization of their components, and packaging towards a qualification for portable systems applications. Based on experimental data shown in this work, conducting polymer nanocomposite capacitor technology could be viable, and could also surpass existing technologies when such a novel approach is used.

  13. Steric control of the asymmetric synthesis of N-substituted 2-methyl-4-piperidones

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Grishina, G.V.; Potapov, V.M.; Abdulganeeva, S.A.

    Transmission of the iodomethylate of 1,2-dimethyl-4-piperidone by (S)-sec-butylamine gives 1-(S-sec-butyl)-2S-methyl-4-piperidone in 33% optical yield while transamination by (S)-1-methyl-2-phenylethylamine gives a 1:1 diastereomeric mixture of 1-(1-methyl-2-phenylethyl)-2-methyl-4-piperidone. The decrease in the optical yield is related to the facile opening of the piperidone ring at the C-N bond with subsequent recyclization. The /sup 13/C NMR data indicate that all the diastereomers of the 4-piperidones obtained are in the chain conformation with predominantly equatorial orientation of the methyl group at C/sub (2)/. The chiral optical properties were studied and the absolution configurations of the 4-piperidones obtained were established.

  14. Methods of Functionalization of Carbon Nanotubes by Photooxidation

    NASA Technical Reports Server (NTRS)

    Lebron-Colon, Marisabel (Inventor); Meador, Michael A. (Inventor)

    2016-01-01

    A method of photooxidizing carbon nanotubes, such as single-walled and multi-walled carbon nanotubes. The nanotubes are purified and dispersed in a solvent, such as n-methyl pyrrolidinone or dimethylformamide. A singlet oxygen sensitizer like Rose Bengal is added to the solution. Oxygen gas is continuously supplied while irradiating the solution while irradiating the solution with ultraviolet light to produce singlet oxygen to oxidize the single-walled carbon nanotubes. Advantageously, the method significantly increases the level of oxidation compared with prior art methods.

  15. Polybenzimidazoles Via Aromatic Nucleophilic Displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergerrother, Paul M. (Inventor); Smith, Joseph G., Jr. (Inventor)

    1997-01-01

    Novel molecular weight controlled and endcapped polybenzimidazoles (PBI) are prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenylbenzimidazole) monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The PBI are endcapped with mono(hydroxyphenyl)benzimidazoles. The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. Mono(hydroxyphenyl)benzimidazoles are synthesized by reacting phenyl-4-hydroxybenzoate with aromatic (o-diamine)s in diphenylsulfone. Molecular weight controlled and endcapped PBI of new chemical structures are prepared that exhibit a favorable combination of physical and mechanical properties.

  16. Polybenzimidazoles via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Joseph G., Jr. (Inventor)

    1995-01-01

    Novel molecular weight controlled and endcapped polybenzimidazoles (PBI) are prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl benzimidazole) monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The PBI are endcapped with mono(hydroxyphenyl) benzimidazoles. The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. Mono(hydroxyphenyl) benzimidazoles are synthesizedby reacting phenyl-4-hydroxybenzoate with aromatic (o-diamine)s in diphenylsulfone. Molecular weight controlled and endcapped PBI of new chemical structures are prepared that exhibit a favorable combination of physical and mechanical properties.

  17. 40 CFR 721.1000 - Benzenamine, 3-chloro-2,6-dinitro-N,N-dipropyl-4-(tri-fluoro-methyl)-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Benzenamine, 3-chloro-2,6-dinitro-N,N-dipropyl-4-(tri-fluoro-methyl)-. 721.1000 Section 721.1000 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.1000 Benzenamine, 3-chloro-2,6-dinitro-N,N...

  18. DOSE-RESPONSE MODELING FOR THE ASSESSMENT OF CUMULATIVE RISK DUE TO EXPOSURE TO N-METHYL CARBAMATE PESTICIDES

    EPA Science Inventory

    The US EPAs N-Methyl Carbamate Cumulative Risk Assessment (NMCRA) assesses the effect on acetylcholine esterase (AChE) activity of exposure to 10 N-methyl carbamate (NMC) pesticides through dietary, drinking water, and residential exposures.

  19. Cyclic mu-opioid receptor ligands containing multiple N-methylated amino acid residues.

    PubMed

    Adamska-Bartłomiejczyk, Anna; Janecka, Anna; Szabó, Márton Richárd; Cerlesi, Maria Camilla; Calo, Girolamo; Kluczyk, Alicja; Tömböly, Csaba; Borics, Attila

    2017-04-15

    In this study we report the in vitro activities of four cyclic opioid peptides with various sequence length/macrocycle size and N-methylamino acid residue content. N-Methylated amino acids were incorporated and cyclization was employed to enhance conformational rigidity to various extent. The effect of such modifications on ligand structure and binding properties were studied. The pentapeptide containing one endocyclic and one exocyclic N-methylated amino acid displayed the highest affinity to the mu-opioid receptor. This peptide was also shown to be a full agonist, while the other analogs failed to activate the mu opioid receptor. Results of molecular docking studies provided rationale for the explanation of binding properties on a structural basis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Formation, expansion, and interconversion of metallarings in a sulfur-bridged Au(I) Co(III) coordination system.

    PubMed

    Oji, Katsuya; Igashira-Kamiyama, Asako; Yoshinari, Nobuto; Konno, Takumi

    2014-02-10

    A novel Au(I) Co(III) coordination system that is derived from the newly prepared [Co(D-nmp)2 ](-) (1(-) ; D-nmp=N-methyl-D-penicillaminate) and a gold(I) precursor Au(I) is reported. Complex 1(-) acts as a sulfur-donating metallaligand and reacts with the gold(I) precursor to give [Au2 Co2 (D-nmp)4 ] (2), which has an eight-membered Au(I) 2 Co(III) 2 metallaring. Treatment of 2 with [Au2 (dppe)2 ](2+) (dppe=1,2-bis(diphenylphosphino)ethane) leads to the formation of [Au4 Co2 (dppe)2 (D-nmp)4 ](2+) (3(2+) ), which consists of an 18-membered Au(I) 4 Co(III) 2 metallaring that accommodates a tetrahedral anion (BF4 (-) , ClO4 (-) , ReO4 (-) ). In solution, the metallaring structure of 3(2+) is readily interconvertible with the nine-membered Au(I) 2 Co(III) metallaring structure of [Au2 Co(dppe)(D-nmp)2 ](+) (4(+) ); this process depends on external factors, such as solvent, concentration, and nature of the counteranion. These results reveal the lability of the AuS and AuP bonds, which is essential for metallaring expansion and contraction. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. COMPARISON OF ACUTE NEUROBEHAVIORAL EFFECTS OF N-METHYL CARBAMATE INSECTICIDES.

    EPA Science Inventory

    The acute neurobehavioral and cholinesterase (ChE)-inhibiting effects of N-methyl carbamate insecticides have not been systematically compared. We evaluated five carbamates - carbaryl (CB), propoxur (PP), oxamyl (OM), methomyl (MM), and methiocarb (MC). Adult male Long-Evans ra...

  2. Radiosynthesis and radiopharmacological evaluation of [N-methyl-11C]Org 34850 as a glucocorticoid receptor (GR)-binding radiotracer.

    PubMed

    Wuest, Frank; Kniess, Torsten; Henry, Brian; Peeters, Bernardus W M M; Wiegerinck, Peter H G; Pietzsch, Jens; Bergmann, Ralf

    2009-02-01

    The radiosynthesis of [N-methyl-(11)C]Org 34850 as a potential brain glucocorticoid receptor (GR)-binding radiotracer is described. The radiosynthesis was accomplished via N-methylation of the corresponding desmethyl precursor with [(11)C]methyl triflate in a remotely controlled synthesis module to give the desired compound in a radiochemical yield of 23+/-5% (decay-corrected, based upon [(11)C]CO(2)) at a specific activity of 47+/-12 GBq/micromol (n=15) at the end-of-synthesis (EOS). The radiochemical purity after semi-preparative HPLC purification exceeded 95%. The total synthesis time was 35-40 min after end-of-bombardment (EOB). The radiotracer is rapidly metabolized in rat plasma leading to the formation of two more hydrophilic metabolites as the major metabolites. Radiopharmacological evaluation involving biodistribution and small animal PET imaging in normal Wistar rats showed that the compound [N-methyl-(11)C]Org 34850 is not able to sufficiently penetrate the blood-brain barrier. Therefore, compound [N-methyl-(11)C]Org 34850 seems not to be a suitable PET radiotracer for imaging rat brain GRs. However, involvement of Pgp or species differences requires further clarification to establish whether the radiotracer [N-methyl-(11)C]Org 34850 may still represent a suitable candidate for imaging GRs in humans.

  3. DNA methylation profiling identifies global methylation differences and markers of adrenocortical tumors.

    PubMed

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

    2012-06-01

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

  4. Efficient and Selective N-Methylation of Nitroarenes under Mild Reaction Conditions.

    PubMed

    Pedrajas, Elena; Sorribes, Iván; Guillamón, Eva; Junge, Kathrin; Beller, Matthias; Llusar, Rosa

    2017-09-21

    Herein, we report a straightforward protocol for the preparation of N,N-dimethylated amines from readily available nitro starting materials using formic acid as a renewable C 1 source and silanes as reducing agents. This tandem process is efficiently accomplished in the presence of a cubane-type Mo 3 PtS 4 catalyst. For the preparation of the novel [Mo 3 Pt(PPh 3 )S 4 Cl 3 (dmen) 3 ] + (3 + ) (dmen: N,N'-dimethylethylenediamine) compound we have followed a [3+1] building block strategy starting from the trinuclear [Mo 3 S 4 Cl 3 (dmen) 3 ] + (1 + ) and Pt(PPh 3 ) 4 (2) complexes. The heterobimetallic 3 + cation preserves the main structural features of its 1 + cluster precursor. Interestingly, this catalytic protocol operates at room temperature with high chemoselectivity when the 3 + catalyst co-exists with its trinuclear 1 + precursor. N-heterocyclic arenes, double bonds, ketones, cyanides and ester functional groups are well retained after N-methylation of the corresponding functionalized nitroarenes. In addition, benzylic-type as well as aliphatic nitro compounds can also be methylated following this protocol. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Formation, Structure and Properties of Boron Nitride Fibers from Polymer Precursors

    DTIC Science & Technology

    1992-02-25

    conversion, have been demonstrated in this study. Poly(ethylene oxide) (PEO), poly(N-vinyl-2-pyrrolidinone) ( PVP ), and poly(methyl methacrylate) (PMMA) were...vinylpyrrolidinone ( PVP , Mw = 360,000). A 100 ml reaction flask with teflon boiling chips and a 100 ml receiving flask were used on a high boiling distilling...CH 3 OBO) 3 : B(OH)3 Predicted 2 Experiment Experiment, 1 wt% PVP 2:1 47.8 mole% CH 3 OH 39.6 mole% CH 3OH 35.2 mole% CH3 OH 3:1 47.8 - 35.5 4:1 47.8

  6. In vitro cytotoxicity and differential cellular sensitivity of derivatives of diamino acids. II. N1-methyl, N1-allyl, N1-(2-chloroethyl) and N1-propargyl nitrosoureas.

    PubMed

    Dulude, H; Salvador, R; Gallant, G

    1995-01-01

    The in vitro cytotoxicity and differential cellular sensitivity of a series of new N1-methyl, N1-allyl, N1-2-chloroethyl and N1-propargyl nitrosourea derivatives of diamino acids were determined in the National Cancer Institute's primary antitumor drug screen. The compounds tested showed an in vitro anticancer activity similar to commercialized nitrosoureas such as CCNU, BCNU, MeCCNU, chlorozotocin, streptozotocin and PCNU. The alkylating moiety of the nitrosoureas seems to play a role in the general selectivity of our compounds. The N1-methyl and N1-2-chloroethyl nitrosourea derivatives are more selective for central nervous system cell lines, the N1-allyl nitrosourea derivatives are more selective for lung cancer cell lines and the N1-propargyl nitrosoureas are more selective for leukemia cell lines.

  7. N-(1-Allyl-1H-indazol-5-yl)-4-methyl-benzene-sulfonamide.

    PubMed

    Chicha, Hakima; Rakib, El Mostapha; Abderrafia, Hafid; Saadi, Mohamed; El Ammari, Lahcen

    2013-11-30

    The asymmetric unit of the title compound, C17H17N3O2S, contains two independent mol-ecules linked by an N-H⋯O hydrogen bond. The mol-ecules show different conformations. In the first mol-ecule, the fused five- and six-membered ring system is almost perpendicular to the plane through the atoms forming the allyl group, as indicated by the dihedral angle of 85.1 (4)°. The dihedral angle with the methyl-benzene-sulfonamide group is 78.8 (1)°. On the other hand, in the second mol-ecule, the dihedral angles between the indazole plane and the allyl and methyl-benzene-sulfonamide groups are 80.3 (3) and 41.5 (1)°, respectively. In the crystal, mol-ecules are further linked by N-H⋯N and C-H⋯O hydrogen bonds, forming a three-dimensional network.

  8. Crystal structures of isomeric 3,5-di-chloro-N-(2,3-di-methyl-phen-yl)benzene-sulfonamide, 3,5-di-chloro-N-(2,6-di-methyl-phen-yl)benzene-sulfonamide and 3,5-di-chloro-N-(3,5-di-methyl-phen-yl)benzene-sulfonamide.

    PubMed

    Shakuntala, K; Naveen, S; Lokanath, N K; Suchetan, P A

    2017-05-01

    The crystal structures of three isomeric compounds of formula C 14 H 13 Cl 2 NO 2 S, namely 3,5-di-chloro- N -(2,3-di-methyl-phen-yl)-benzene-sulfonamide (I), 3,5-di-chloro- N -(2,6-di-methyl-phen-yl)benzene-sulfonamide (II) and 3,5-di-chloro- N -(3,5-di-methyl-phen-yl)benzene-sulfonamide (III) are described. The mol-ecules of all the three compounds are U-shaped with the two aromatic rings inclined at 41.3 (6)° in (I), 42.1 (2)° in (II) and 54.4 (3)° in (III). The mol-ecular conformation of (II) is stabilized by intra-molecular C-H⋯O hydrogen bonds and C-H⋯π inter-actions. The crystal structure of (I) features N-H⋯O hydrogen-bonded R 2 2 (8) loops inter-connected via C (7) chains of C-H⋯O inter-actions, forming a three-dimensional architecture. The structure also features π-π inter-actions [ Cg ⋯ Cg = 3.6970 (14) Å]. In (II), N-H⋯O hydrogen-bonded R 2 2 (8) loops are inter-connected via π-π inter-actions [inter-centroid distance = 3.606 (3) Å] to form a one-dimensional architecture running parallel to the a axis. In (III), adjacent C (4) chains of N-H⋯O hydrogen-bonded mol-ecules running parallel to [010] are connected via C-H⋯π inter-actions, forming sheets parallel to the ab plane. Neighbouring sheets are linked via offset π-π inter-actions [inter-centroid distance = 3.8303 (16) Å] to form a three-dimensional architecture.

  9. Stimulation of Methanogenesis by Aldicarb and Several Other N-Methyl Carbamate Pesticides †

    PubMed Central

    Kiene, Ronald P.; Capone, Douglas G.

    1986-01-01

    Aldicarb and several other N-methyl carbamate pesticides stimulated methane production in anaerobic salt marsh soils and organic-rich aquifer soils. Stimulation was biological and linearly related to the amount of carbamate added. Of the four carbamates studied, methomyl gave the greatest stimulation followed by carbaryl, aldicarb, and baygon. The percent conversions [(moles of CH4 in excess of control/mole of carbamate added) × 100] for methomyl, carbaryl, aldicarb, and baygon were 88, 57, 40, and 11, respectively. Using aldicarb as a model carbamate, we found that monomethylamine (MA) accumulated in sediments as a result of aldicarb addition. MA arises from the N-methyl carbamoyl portion of the carbamates as a result of presumptive biological hydrolysis. MA levels decreased as CH4 production was stimulated, and 2-bromoethane sulfonic acid (a specific inhibitor of mathanogenesis) partially inhibited the loss of MA. These findings suggest that N-methyl carbamates are readily hydrolyzed to MA in the presence of an active microbial population under anaerobic conditions and that methanogenesis is stimulated as a result of the consumption of MA by methanogenic bacteria. PMID:16347082

  10. Preparation and Characterization of Polyimide/Organoclay Nanocomposites

    NASA Technical Reports Server (NTRS)

    Delozier, D. M.; Orwoll, R. A.; Cahoon, J. F.; Johnston, N. J.; Smith, J. G., Jr.; Connell, J. W.

    2002-01-01

    Organically modified montmorrrillonite clay, containing a long chain aliphatic quarternary ammonium cation, was used to prepare polyimide/organoclay hybrids. Several approaches were examined in an attempt to achieve fully exfoliated nanocomposites. These included simple mixing of the clay in a pre-made high molecular weight poly(amide acid) solution; simple mixing followed by sonication of the organoclay/poly(amide acid) solutions; and the preparation of high molecular weight poly(amide acid)s in the presence of the organoclay dispersed in N-methyl-2-pyrrolidinone (NMP). The best results were obtained using the in-situ polymerization approach. The resulting nanocomposite films (both amide acid and imide), containing 3-8% by weight of organoclay, were characterized by differential scanning calorimetry (DSC), dynamic thermogravimetric analysis (TGA), transmission electron microscopy (TEM), X-ray diffraction (XRD), and thin film tensile properties. A significant degree of dispersion was observed in the nanocomposite films of the amide acid and the imide. After thermal treatment of amide acid films to effect imidization, in both air and nitrogen, the films were visually darker than control films without clay and the level of clay dispersion appeared to have decreased. In the latter case, the separation between the layers of the clay decreased to a spacing less than that present in the original organoclay. These observations suggest that thermal degradation of the aliphatic quarternary ammonium cation occurred likely during thermal treatment to effect imidization and solvent removal. These thermal degradation effects were less pronounced when thermal treatment was performed under nitrogen. The polyimide/organoclay hybrid films exhibited higher room temperature tensile moduli and lower strength and elongation to break than the control films.

  11. Oxygenated N-Acyl Alanine Methyl Esters (NAMEs) from the Marine Bacterium Roseovarius tolerans EL-164.

    PubMed

    Bruns, Hilke; Herrmann, Jennifer; Müller, Rolf; Wang, Hui; Wagner Döbler, Irene; Schulz, Stefan

    2018-01-26

    The marine bacterium Roseovarius tolerans EL-164 (Rhodobacteraceae) can produce unique N-acylalanine methyl esters (NAMEs) besides strucutrally related N-acylhomoserine lactones (AHLs), bacterial signaling compounds widespread in the Rhodobacteraceae. The structures of two unprecedented NAMEs carrying a rare terminally oxidized acyl chain are reported here. The compounds (Z)-N-16-hydroxyhexadec-9-enoyl-l-alanine methyl ester (Z9-16-OH-C16:1-NAME, 3) and (Z)-N-15-carboxypentadec-9-enoyl-l-alanine methyl ester (16COOH-C16:1-NAME, 4) were isolated, and the structures were determined by NMR and MS experiments. Both compounds were synthesized to prove assignments and to test their biological activity. Finally, non-natural, structurally related Z9-3-OH-C16:1-NAME (18) was synthesized to investigate the mass spectroscopy of structurally related NAMEs. Compound 3 showed moderate antibacterial activity against microorganisms such as Bacillus, Streptococcus, Micrococcus, or Mucor strains. In contrast to AHLs, quorum-sensing or quorum-quenching activity was not observed.

  12. Rotationally inelastic scattering of methyl radicals with Ar and N{sub 2}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tkáč, Ondřej; Orr-Ewing, Andrew J., E-mail: a.orr-ewing@bristol.ac.uk; Ma, Qianli

    2015-01-07

    The rotationally inelastic scattering of methyl radical with Ar and N{sub 2} is examined at collision energies of 330 ± 25 cm{sup −1} and 425 ± 50 cm{sup −1}, respectively. Differential cross sections (DCSs) were measured for different final n′ rotational levels (up to n′ = 5) of the methyl radicals, averaged over k′ sub-levels, using a crossed molecular beam machine with velocity map imaging. For Ar as a collision partner, we present a newly constructed ab initio potential energy surface and quantum mechanical scattering calculations of state-resolved DCSs. These computed DCSs agree well with the measurements. The DCSs formore » both Ar and N{sub 2} collision partners are strongly forward peaked for all spectroscopic lines measured. For scattering angles below 60°, the theoretical CD{sub 3}–Ar DCSs show diffraction oscillations that become less pronounced as n′ increases, but these oscillations are not resolved experimentally. Comparisons are drawn with our recently reported DCSs for scattering of methyl radicals with He atoms.« less

  13. Synthesis and characterization of a thermo-sensitive poly( N-methyl acryloylglycine methyl ester) used as a drug release carrier

    NASA Astrophysics Data System (ADS)

    Deng, Kui-Lin; Zhong, Hai-Bin; Jiao, Yi-Suo; Fan, Ting; Qiao, Xiao; Zhang, Peng-Fei; Ren, Xiao-Bo

    2010-06-01

    In this article, poly( N-methyl acryloylglycine methyl ester) (PNMAME) was prepared as a novel thermosensitive material with a lower critical solution temperature (LCST) at around 49.5°C. The chemical structures of the monomer NMAME and PNMAME were characterized by 1H NMR and IR measurements. The LCST was investigated systematically as a function of PNMAME concentration, inorganic salt solution and pH value. The results indicated that LCST of PNMAME was obviously dependent on PNMAME concentration and pH. The LCST was increased with a decrease in pH value and PNMAME concentration. To obtain a thermo-sensitive hydrogel with the phase transition temperature close to human body temperature, the copolymerization was conducted between NMAME and N-acryloylglycine ethyl ester (NAGEE). The release behavior of caffeine was evaluated at different temperatures and contents of cross-linkers ( N, N-methylenebis(acrylamide) (NMBA)). The increase of cross-linker content led to a decrease in the release rate of caffeine due to higher crossing density in the hydrogel network. In addition, a faster release of caffeine from the hydrogel with 3% NMBA at 37°C was found in contrast to that at 18°C.

  14. Crystal structure of {2,6-bis-[(di-methyl-amino)-meth-yl]phenyl-κ3N,C1,N'}(bromido/chlorido)-mercury(II).

    PubMed

    Gupta, Anand; Singh, Harkesh B; Butcher, Ray J

    2017-11-01

    In the mol-ecular structure of the title compound, {2,6-bis-[(di-methyl-amino)-meth-yl]phenyl-κ 3 N , C 1 , N '}[bromido/chlorido-(0.30/0.70)]mercury(II)-{2,6-bis-[(di-methyl-amino)-meth-yl]phenyl-κ 3 N , C 1 , N '}[bromido/chlorido-(0.24/0.76)]mer-cury(II) (1/1), [HgBr 0.30 Cl 0.70 (C 12 H 19 N 2 )]·[HgBr 0.24 Cl 0.76 (C 12 H 19 N 2 )], there are two mol-ecules in the asymmetric unit of formula L Hg X { L = 2,6-bis-[(di-methyl-amino)-meth-yl]phenyl and X = Cl/Br}. In each mol-ecule, the halide site is mixed Cl/Br, with occupancies of 0.699 (7):0.301 (7) and 0.763 (7):0.237 (7), respectively. The two mol-ecules are linked into dimers by a combination of Hg⋯Hg [Hg⋯Hg = 3.6153 (3) Å] and C-H⋯Cl and C-H⋯π inter-actions.

  15. [Mammary gland tumor induction in rats by N-nitroso-N-methylurea and N-methyl-N1-nitro-N-nitrosoguanidine].

    PubMed

    Eliseev, V V; Vlasov, N N

    1980-01-01

    Cancer of the mammary gland was induced in female non-inbred rats under the local effect of N-nitroso-N-methylurea (NMU) and N-methyl-N-nitro-N-nitrosoguanidine (MNNG). During 10 weeks 2.5 mg of the substance in 0.2 ml of saline was injected in the region of the third mammary gland once a week. Under NMU exposure a primary tumor arose 3 months following the initiation of the experiment, the average latent period being 5.8 months, the incidence rate--76.7%. All tumors of this series were adenocarcinomas, in 5 cases there were noted sites of fibroadenomatosis with malignification along the tumor node margins. MNNG produced a primary tumor at the 7th month of the experiment, an average latent period--8.3 months, the incidence rate--56.7%. Tumors were mostly adenocarcinomas.

  16. Oxidation and formation of deposit precursors in hydrocarbon fuels

    NASA Technical Reports Server (NTRS)

    Mayo, F. R.; Lan, B.; Cotts, D. B.; Buttrill, S. E., Jr.; St.john, G. A.

    1983-01-01

    The oxidation of two jet turbine fuels and some pure hydrocarbons was studied at 130 C with and without the presence of small amounts of N-methyl pyrrole (NMP) or indene. Tendency to form solid-deposit precursors was studied by measuring soluble gum formation as well as dimer and trimer formation using field ionization mass spectrometry. Pure n-dodecane oxidized fastest and gave the smallest amount of procursors. An unstable fuel oil oxidized much slower but formed large amounts of precursors. Stable Jet A fuel oxidized slowest and gave little precursors. Indene either retarded or accelerated the oxidation of n-dodecane, depending on its concentration, but always caused more gum formation. The NMP greatly retarded n-dodecane oxidation but accelerated Jet A oxidation and greatly increased the latter's gum formation. In general, the additive reacted faster and formed most of the gum. Results are interpreted in terms of classical cooxidation theory. The effect of oxygen pressure on gum formation is also reported.

  17. N-Methyl-D-Aspartate Receptor Activation May Contribute to Glufosinate Neurotoxicity

    EPA Science Inventory

    N-Methyl-D-aspartate Receptor Activation May Contribute to Glufosinate Neurotoxicity Glufosinate (GLF) at high levels in mammals causes convulsions through a mechanism that is not completely understood. The structural similarity of GLF to glutamate (GLU) implicates the glutamate...

  18. Nonparaneoplastic anti-N-methyl-D-aspartate receptor encephalitis: a case series of four children.

    PubMed

    Raha, Sarbani; Gadgil, Pradnya; Sankhla, Charulata; Udani, Vrajesh

    2012-04-01

    A rare, severe form of immune-mediated encephalitis recently has been described, associated with antibodies against N-methyl-D-aspartate receptors. It is reported mostly in women with ovarian tumors. Nonparaneoplastic presentations are less common. We describe four children with a neuropsychiatric and extrapyramidal syndrome associated with the presence of anti-N-methyl-D-aspartate receptor antibodies in cerebrospinal fluid and serum, without evidence of neoplasia. Three children recovered completely after immunomodulatory therapy, i.e., intravenous immunoglobulin and/or steroids, methylprednisolone, and/or adrenocorticotrophic hormone. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. The cocrystal rac-1-[(N,4-dimethylbenzenesulfonamido)methyl]-2-(diphenylphosphoryl)ferrocene-rac-1-[(N,4-dimethylbenzenesulfonamido)methyl]-2-(diphenylphosphanyl)ferrocene (0.45/0.55).

    PubMed

    Wei, Muh Mei; Audin, Catherine; Manoury, Eric; Deydier, Eric; Daran, Jean Claude

    2014-03-01

    As part of our interest in the synthesis and catalytic applications of chiral (diphenylphosphanyl)ferrocene ligands, we designed a number of P,N-containing ligands for use in asymmetric transfer hydrogenation (ATH). During the synthetic procedure to obtain rac-1-[(N,4-dimethylbenzenesulfonamido)methyl]-2-(diphenylphosphanyl)ferrocene, the title compound, [Fe(C5H5)(C26H25NO2PS)]0.55 · [Fe(C5H5)(C26H25NO3PS)]0.45, was obtained as a by-product. It is composed of a ferrocene group disubstituted by a partially oxidized diphenylphosphanyl group, as confirmed by (31)P NMR analysis, and an (N,4-dimethylbenzenesulfonamido)methyl substituent. Owing to the partially oxidized diphenylphosphanyl group, it is best to view the crystal as being composed of a mixture of non-oxidized and oxidized phosphane, so it can be regarded as a cocrystal. It is also a racemate. To the best of our knowledge, the P=O distance [1.344 (4) Å] is the shortest observed for related (diphenylphosphoryl)ferrocene compounds. The packing is stabilized by weak C-H...O interactions, forming R2(2)(10) hydrogen-bonding motifs, which build up a chain along the c axis.

  20. Design synthesis and structure-activity relationship of 5-substituted (tetrahydronaphthalen-2yl)methyl with N-phenyl-N-(piperidin-2-yl)propionamide derivatives as opioid ligands.

    PubMed

    Deekonda, Srinivas; Rankin, David; Davis, Peg; Lai, Josephine; Vanderah, Todd W; Porecca, Frank; Hruby, Victor J

    2016-01-15

    Here, we report the design, synthesis and structure activity relationship of novel small molecule opioid ligands based on 5-amino substituted (tetrahydronaphthalen-2-yl)methyl moiety with N-phenyl-N-(piperidin-2-yl)propionamide derivatives. We synthesized various molecules including amino, amide and hydroxy substitution on the 5th position of the (tetrahydronaphthalen-2-yl)methyl moiety. In our further designs we replaced the (tetrahydronaphthalen-2-yl)methyl moiety with benzyl and phenethyl moiety. These N-phenyl-N-(piperidin-2-yl)propionamide analogues showed moderate to good binding affinities (850-4 nM) and were selective towards the μ opioid receptor over the δ opioid receptors. From the structure activity relationship studies, we found that a hydroxyl substitution at the 5th position of (tetrahydronapthalen-2yl)methyl group, ligands 19 and 20, showed excellent binding affinities 4 and 5 nM, respectively, and 1000 fold selectivity towards the μ opioid relative to the delta opioid receptor. The ligand 19 showed potent agonist activities 75±21 nM, and 190±42 nM in the GPI and MVD assays. Surprisingly the fluoro analogue 20 showed good agonist activities in MVD assays 170±42 nM, in contrast to its binding affinity results. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. N-hexane inhalation during pregnancy alters DNA promoter methylation in the ovarian granulosa cells of rat offspring.

    PubMed

    Li, Hong; Liu, Jin; Sun, Yan; Wang, Wenxiang; Weng, Shaozheng; Xiao, Shihua; Huang, Huiling; Zhang, Wenchang

    2014-08-01

    The N-hexane-induced impact on the reproductive system of the offspring of animals exposed to n-hexane has caused great concern. Pregnant Wistar rats inhaled 500, 2 500 or 12 500 ppm n-hexane during gestational days 1-20. Clinical characteristics and developmental indices were observed. Ovarian granulosa cells were extracted from F1 rats, the number of follicles was determined in ovarian slices and promoter methylation was assessed using MeDIP-Chip. Several methods were used to analyze the scanned genes, including the Gene Ontology Consortium tools, the DAVID Functional Annotation Clustering Tool, hierarchical clustering and KEGG pathway analysis. The results indicated that the live pups/litter ratio was significantly lowest in the 12 500 ppm group. A significant decrease in secondary follicles and an increase in atresic follicles were observed in the 12 500 ppm group. The number of shared demethylated genes was higher than that of the methylated genes, and the differentially methylated genes were enriched in cell death and apoptosis, cell growth and hormone regulation. The methylation profiles of the offspring from the 500 ppm and control groups were different from those of the 2500 and 12 500 ppm groups. Furthermore, the methylation status of genes in the PI3K-Akt and NF-kappa B signaling pathways was changed after n-hexane exposure. The Cyp11a1, Cyp17a1, Hsd3b1, Cyp1a1 and Srd5a1 promoters were hypermethylated in the n-hexane-exposed groups. These results indicate that the developmental toxicity of n-hexane in F1 ovaries is accompanied by the altered methylation of promoters of genes associated with apoptotic processes and steroid hormone biosynthesis. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Guided bone regeneration with a synthetic biodegradable membrane: a comparative study in dogs.

    PubMed

    Jung, Ronald E; Kokovic, Vladimir; Jurisic, Milan; Yaman, Duygu; Subramani, Karthikeyan; Weber, Franz E

    2011-08-01

    The aim of the present study was to compare a newly developed biodegradable polylactide/polyglycolide/N-methyl-2-pyrrolidone (PLGA/NMP) membrane with a standard resorbable collagen membrane (RCM) in combination with and without the use of a bone substitute material (deproteinized bovine bone mineral [DBBM]) looking at the proposed tenting effect and bone regeneration. In five adult German sheepdogs, the mandibular premolars P2, P3, P4, and the molar M1 were bilaterally extracted creating two bony defects on each site. A total of 20 dental implants were inserted and allocated to four different treatment modalities within each dog: PLGA/NMP membrane only (Test 1), PLGA/NMP membrane with DBBM (Test 2), RCM only (negative control), and RCM with DBBM (positive control). A histomorphometric analysis was performed 12 weeks after implantation. For statistical analysis, a Friedman test and subsequently a Wilcoxon signed ranks test were applied. In four out of five PLGA/NMP membrane-treated defects, the membranes had broken into pieces without the support of DBBM. This led to a worse outcome than in the RCM group. In combination with DBBM, both membranes revealed similar amounts of area of bone regeneration and bone-to-implant contact without significant differences. On the level of the third implant thread, the PLGA/NMP membrane induced more horizontal bone formation beyond the graft than the RCM. The newly developed PLGA/NMP membrane performs equally well as the RCM when applied in combination with DBBM. Without bone substitute material, the PLGA/NMP membrane performed worse than the RCM in challenging defects, and therefore, a combination with a bone substitute material is recommended. © 2010 John Wiley & Sons A/S.

  3. The Effects of Alkali and Temperature on the Hydrolysis Rate of N-methylpyrrolidone

    NASA Astrophysics Data System (ADS)

    Ou, Yu Jing; Wang, Xiao Mei; Lei Li, Chun; Zhu, Ya Long; Li, Xiao Long

    2017-12-01

    By studying the hydrolysis of N-methylpyrrolidone, it was found that the effects of NaOH concentration and temperature on N-methylpyrrolidone's hydrolysis were remarkable. Fourier transform infrared (FTIR) and Gel Permeation Chromatography (GPC) detected that the mainly hydrolyzate was 4-(methylamino)butyric acid, and the hydrolyzate can generate polymers, which of molecular weight increases with temperature rising. The results of Gas Chromatography (GC) and moisture meter test showed that adding alkaline and raising temperature can aggravate hydrolysis of NMP. This study provide theoretical basis for recycling solvent (NMP) in the production of polyphenylene sulfide (PPS).

  4. Radiosynthesis of N-¹¹C-Methyl-Taurine-Conjugated Bile Acids and Biodistribution Studies in Pigs by PET/CT.

    PubMed

    Schacht, Anna Christina; Sørensen, Michael; Munk, Ole Lajord; Frisch, Kim

    2016-04-01

    During cholestasis, accumulation of conjugated bile acids may occur in the liver and lead to hepatocellular damage. Inspired by our recent development of N-(11)C-methyl-glycocholic acid-that is, (11)C-cholylsarcosine-a tracer for PET of the endogenous glycine conjugate of cholic acid, we report here a radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids and biodistribution studies in pigs by PET/CT. A radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids was developed and used to prepare N-(11)C-methyl-taurine conjugates derived from cholic, chenodeoxycholic, deoxycholic, ursodeoxycholic, and lithocholic acid. The lipophilicity of these new tracers was determined by reversed-phase thin-layer chromatography. The effect of lipophilicity and structure on the biodistribution was investigated in pigs by PET/CT using the tracers derived from cholic acid (3α-OH, 7α-OH, 12α-OH), ursodeoxycholic acid (3α-OH, 7β-OH), and lithocholic acid (3α-OH). The radiosyntheses of the N-(11)C-methyl-taurine-conjugated bile acids proceeded with radiochemical yields of 61% (decay-corrected) or greater and radiochemical purities greater than 99%. PET/CT in pigs revealed that the tracers were rapidly taken up by the liver and secreted into bile. There was no detectable radioactivity in urine. Significant reflux of N-(11)C-methyl-taurolithocholic acid into the stomach was observed. We have successfully developed a radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids. These tracers behave in a manner similar to endogenous taurine-conjugated bile acids in vivo and are thus promising for functional PET of patients with cholestatic diseases. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  5. Resistance of Salmonella typhimurium TA 1535 to O6-guanine methylation and mutagenesis induced by low doses of N-methyl-N'-nitro-N-nitrosoguanidine: an apparent constitutive repair activity.

    PubMed

    Guttenplan, J B; Milstein, S

    1982-01-01

    Salmonella tester strains which are reverted by base-pair substitution mutagens are relatively insensitive to the mutagenic effects of N-methyl-N-nitroso compounds. One reason for this insensitivity is the ability of these strains to withstand low doses of these compounds before they become sensitive to their mutagenic effects. In this report it is shown that mutagenesis induced by treatment of Salmonella typhimurium TA 1535 with N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) in buffer is biphasic with a low sensitivity range at low doses where little mutagenesis occurs, followed by a high sensitivity range whose onset begins after an apparent threshold dose has been exceeded. levels of O6-methylguanine (O6-MeG) in the DNA extracted from the bacteria follow a similar dose-response curve suggesting a dependency of mutagenesis on O6-MeG. In contrast, levels of 7-methylguanine (7-MeG) in the DNA increase linearly with dose. O6-MeG was undetectable at the lowest dose of MNNG whereas 7-MeG was readily detectable. Although such resistance to O6-alkylation has been demonstrated in MNNG- pretreated (adapted) E. coli, it has not been reported in unpretreated cells. Then isolated DNA was treated with MNNG a linear dose-response in the generation of O6-MeG was observed. The lack of O6-MeG in DNA isolated from MNNG treated cells after low doses is attributed to a saturable, constitutive repair activity in the bacteria. An attempt to observe the removal of O6-MeG from the bacteria after exposure to a short challenge dose of N-nitroso-N-methylurea (NMU) followed by a subsequent incubation in buffer was unsuccessful, probably because all the repair occurred within the time necessary to treat and lyse the cells.

  6. Computational Study of Environmental Effects on Torsional Free Energy Surface of N-Acetyl-N'-methyl-L-alanylamide Dipeptide

    ERIC Educational Resources Information Center

    Carlotto, Silvia; Zerbetto, Mirco

    2014-01-01

    We propose an articulated computational experiment in which both quantum mechanics (QM) and molecular mechanics (MM) methods are employed to investigate environment effects on the free energy surface for the backbone dihedral angles rotation of the small dipeptide N-Acetyl-N'-methyl-L-alanylamide. This computation exercise is appropriate for an…

  7. Crystal structure of N-[3-(di­methyl­aza­nium­yl)prop­yl]-N′,N′,N′′,N′′-tetra­methyl-N-(N,N,N′,N′-tetra­methyl­form­am­id­in­ium­yl)­guanidinium dibromide hydroxide monohydrate

    PubMed Central

    Tiritiris, Ioannis; Kantlehner, Willi

    2015-01-01

    The asymmetric unit of the title hydrated salt, C15H37N6 3+·2Br−·OH−·H2O, contains one cation, three partial-occupancy bromide ions, one hydroxide ion and one water mol­ecule. Refinement of the site-occupancy factors of the three disordered bromide ions converges with occupancies 0.701 (2), 0.831 (2) and 0.456 (2) summing to approximately two bromide ions per formula unit. The structure was refined as a two-component inversion twin with volume fractions 0.109 (8):0.891 (8) for the two domains. The central C3N unit of the bis­amidinium ion is linked to the aliphatic propyl chain by a C—N single bond. The other two bonds in this unit have double-bond character as have the four C—N bonds to the outer NMe2 groups. In contrast, the three C—N bonds to the central N atom of the (di­methyl­aza­nium­yl)propyl group have single-bond character. Delocalization of the two positive charges occurs in the N/C/N and C/N/C planes, while the third positive charge is localized on the di­methyl­ammonium group. The crystal structure is stabilized by O—H⋯O, N—H⋯Br, O—H⋯Br and C—H⋯Br hydrogen bonds, forming a three-dimensional network. PMID:26870507

  8. Dibromidobis(N,N,N′,N′-tetra­methyl­thio­urea-κS)cadmium(II)

    PubMed Central

    Nawaz, Sidra; Sadaf, Sana; Fettouhi, Mohammed; Fazal, Atif; Ahmad, Saeed

    2010-01-01

    In the title compound, [CdBr2(C5H12N2S)2], the CdII atom lies on a twofold rotation axis. It exhibits a distorted tetra­hedral coordination environment defined by two S atoms of two tetra­methyl­thio­urea (tmtu) ligands and two bromide ions. The crystal structure is consolidated by C—H⋯N and C—H⋯S hydrogen bonds. PMID:21588180

  9. 40 CFR 180.296 - Dimethyl phosphate of 3-hydroxy-N-methyl-cis-crotonamide; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-methyl-cis-crotonamide; tolerances for residues. 180.296 Section 180.296 Protection of Environment... RESIDUES IN FOOD Specific Tolerances § 180.296 Dimethyl phosphate of 3-hydroxy-N-methyl-cis-crotonamide; tolerances for residues. (a) General. Tolerances are established for residues of the insecticide Dimethyl...

  10. 40 CFR 721.2275 - N,N,N′,N′-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false N,N,Nâ²,Nâ²-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine. 721.2275 Section 721.2275 Protection of Environment ENVIRONMENTAL...-cyclohexane di-meth-anamine. (a) Chemical substances and significant new uses subject to reporting. (1) The...

  11. 40 CFR 721.2275 - N,N,N′,N′-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false N,N,Nâ²,Nâ²-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine. 721.2275 Section 721.2275 Protection of Environment ENVIRONMENTAL...-cyclohexane di-meth-anamine. (a) Chemical substances and significant new uses subject to reporting. (1) The...

  12. 40 CFR 721.2275 - N,N,N′,N′-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false N,N,Nâ²,Nâ²-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine. 721.2275 Section 721.2275 Protection of Environment ENVIRONMENTAL...-cyclohexane di-meth-anamine. (a) Chemical substances and significant new uses subject to reporting. (1) The...

  13. Enzymatic hydrolysis of cellulose pretreated with ionic liquids and N-methyl Morpholine N-Oxide

    NASA Astrophysics Data System (ADS)

    Yau Li, Elizabeth

    The effect of N-methyl Morpholine N-Oxide (NMMO), 1-ethyl-3-methyl-imidazolium acetate ([Emim]Ac) and 1-ethyl-3-methyl-imidazolium diethyl phosphate ([Emim]DEP) on pretreatment and enzymatic hydrolysis of dissolving pulp was studied. X-ray diffraction measurements of regenerated cellulose from these solvents showed that solvent pretreatment reduces the crystallinity of cellulose. However, crystallinity might not be a major factor affecting the in-situ enzymatic hydrolysis of cellulose in these solvents. Although regenerated cellulose from [Emim]DEP showed the lowest crystallinity index (˜15%), in-situ enzymatic hydrolysis of cellulose dissolved in NMMO showed the highest cellulose conversion (68% compared to 65% for [Emim]Ac and 37% for [Emim]DEP at enzyme loading of 122 FPU/g). Moreover, results showed that enzymes could tolerate up to NMMO concentration of 100 g/L and still yield full conversion of cellulose. Since it is not necessary to remove all the NMMO, less amount of water will be required for the washing step and thus the process will be more economical. The HCH-1 model was used in an attempt to model the enzymatic hydrolysis of cellulose in NMMO. With the incorporation of NMMO inhibition and a factor to account for unreacted cellulose, the model was able to correlate the experimental data of the enzymatic hydrolysis of cellulose (6.68 g/L) at various NMMO concentrations (0, 50, 100, 150 and 250 g/L). However, the experimental results also suggest that NMMO might be deactivating the enzymes rather than inhibiting them. More studies need to be done at varying cellulose, NMMO and enzyme concentrations to find the exact nature of this deactivation of NMMO.

  14. Density and viscosity of aqueous blends of N-methyldiethanolamine and 2-amino-2-methyl-1-propanol

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Welsh, L.M.; Davis, R.A.

    Aqueous solutions of alkanolamines such as N-methyldiethanolamine (MDEA) and 2-amino-2-methyl-1-propanol (AMP) have application in acid gas treatment for the removal of acid gases such as carbon dioxide and hydrogen sulfide. The density and kinematic viscosity of aqueous blends of N-methyldiethanolamine and 2-amino-2-methyl-1-propanol were determined from experiments within the temperature range 10--60 C. The composition of the alkanolamines in water ranged from 5% to 50% by mass.

  15. Tyramine Pathways in Citrus Plant Defense: Glycoconjugates of Tyramine and Its N-Methylated Derivatives.

    PubMed

    Servillo, Luigi; Castaldo, Domenico; Giovane, Alfonso; Casale, Rosario; D'Onofrio, Nunzia; Cautela, Domenico; Balestrieri, Maria Luisa

    2017-02-01

    Glucosylated forms of tyramine and some of its N-methylated derivatives are here reported for the first time to occur in Citrus genus plants. The compounds tyramine-O-β-d-glucoside, N-methyltyramine-O-β-d-glucoside, and N,N-dimethyltyramine-O-β-d-glucoside were detected in juice and leaves of sweet orange, bitter orange, bergamot, citron, lemon, mandarin, and pomelo. The compounds were identified by mass spectrometric analysis, enzymatic synthesis, and comparison with extracts of Stapelia hirsuta L., a plant belonging to the Apocynaceae family in which N,N-dimethyltyramine-O-β-d-glucoside was identified by others. Interestingly, in Stapelia hirsuta we discovered also tyramine-O-β-d-glucoside, N-methyltyramine-O-β-d-glucoside, and the tyramine metabolite, N,N,N-trimethyltyramine-O-β-glucoside. However, the latter tyramine metabolite, never described before, was not detected in any of the Citrus plants included in this study. The presence of N-methylated tyramine derivatives and their glucosylated forms in Citrus plants, together with octopamine and synephrine, also deriving from tyramine, supports the hypothesis of specific biosynthetic pathways of adrenergic compounds aimed to defend against biotic stress.

  16. A DOSE-RESPONSE STUDY OF THE TOXICITY OF A MIXTURE OF 7N-METHYL CARBAMATE PESTICIDES IN ADULT, MALE RATS.

    EPA Science Inventory

    There is scarce knowledge regarding the toxicity of pesticide mixtures, especially mixtures of the anticholinesterase N-methyl carbamates. A mixture study was conducted using 7 N-methyl carbamates (carbaryl, carbofuran, formetanate HCl, methiocarb, methomyl, oxamyl, and propoxur...

  17. N,N,N′,N′-Tetra­methyl­guanidinium tetra­phenyl­borate

    PubMed Central

    Tiritiris, Ioannis

    2012-01-01

    In the title salt, C5H14N3 +·C24H20B−, the C—N bond lengths in the central CN3 unit are 1.3322 (11), 1.3385 (12) and 1.3422 (12) Å, indicating partial double-bond character. The central C atom is bonded to the three N atoms in a nearly ideal trigonal-planar geometry [N—C—N angles = 119.51 (8), 119.81 (9) and 120.69 (8)°] and the positive charge is delocalized in the CN3 plane. The bond lengths between the N atoms and the terminal methyl groups all have values close to a typical single bond [1.4597 (12)–1.4695 (13) Å]. The crystal packing is caused by electrostatic inter­actions between cations and anions. PMID:23476307

  18. Effect of pressure on bilayer phase behavior of N-methylated di-O-hexadecylphosphatidylethanolamines: relevance of head-group modification on the bilayer interdigitation.

    PubMed

    Goto, Masaki; Aoki, Yuya; Tamai, Nobutake; Matsuki, Hitoshi

    2017-12-01

    The phase transitions of N-methylated di-O-hexadecylphosphatidylethanolamines (DHPE, DH-N-methyl-PE (DHMePE) and DH-N,N-dimethyl-PE (DHMe 2 PE)) were observed by differential scanning calorimetry (DSC) and fluorometry under atmospheric pressure and by light-transmittance measurements under high pressure. The DSC thermograms showed that the N-methylated DHPE bilayers underwent the phase transition from the gel phase to the liquid crystalline (L α ) phase under atmospheric pressure. The gel phase was identified by fluorometry as the lamellar gel (L β ) phase, and not interdigitated gel (L β I) phase. The gel/L α transition temperature increased with pressure while decreased stepwise with increasing polar head-group size. This stepwise depression of the transition temperature may be caused by the inverse-proportional hydrogen-bonding capabilities of the head-group to the head-group size. The thermodynamic quantities of the gel/L α transition were comparable for the N-methylated DHPE bilayers. The pressure-induced L β I phase was not found in these bilayers although the bilayer of di-O-hexadecylphosphatidylcholine (DHPC), which is a kind of N-methylated DHPEs, forms the L β I phase only by hydration under atmospheric pressure. Taking into account that the bilayers of diacyl-homologs of N-methylated DHPEs, N-methylated dipalmitoyl-PEs except for dipalmitoylphosphatidylcholine (DPPC), do not form the L β I phase in the whole pressure range investigated but the DPPC bilayer forms the L β I phase under high pressure, we can say that the interdigitation requires weaker interaction between large-sized head groups like the bulky choline group. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Synthesis, structural, optical and thermal properties of N-methyl-N-aryl benzamide organic single crystals grown by a slow evaporation technique

    NASA Astrophysics Data System (ADS)

    Prabukanthan, P.; Lakshmi, R.; Harichandran, G.; Kumar, C. Sudarsana

    2018-03-01

    The organic materials, N-methyl-N-aryl benzamides were synthesized from benzoylation of N-methyl-4-nitrobenzenamine (MNBA) using suitably substituted benzoyl chlorides. The products were purified by recrystallization and their single crystal were grown by a slow evaporation technique. The crystals were characterized by FTIR, UV-Vis-NIR, 1H &13C NMR, and single & powder X-ray diffraction. Thermal stability of the crystals was studied by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Dielectric and NLO properties of MNPB, FMNPB and MMNPB crystals were studied. The second harmonic generation (SHG) has been confirmed by the Kurtz powder test for all these crystals and the SHG efficiency of MMNPB crystal was found to be 2.25 times higher than that of KDP crystal.

  20. Aberrant TET1 Methylation Closely Associated with CpG Island Methylator Phenotype in Colorectal Cancer.

    PubMed

    Ichimura, Norihisa; Shinjo, Keiko; An, Byonggu; Shimizu, Yasuhiro; Yamao, Kenji; Ohka, Fumiharu; Katsushima, Keisuke; Hatanaka, Akira; Tojo, Masayuki; Yamamoto, Eiichiro; Suzuki, Hiromu; Ueda, Minoru; Kondo, Yutaka

    2015-08-01

    Inactivation of methylcytosine dioxygenase, ten-eleven translocation (TET) is known to be associated with aberrant DNA methylation in cancers. Tumors with a CpG island methylator phenotype (CIMP), a distinct subgroup with extensive DNA methylation, show characteristic features in the case of colorectal cancer. The relationship between TET inactivation and CIMP in colorectal cancers is not well understood. The expression level of TET family genes was compared between CIMP-positive (CIMP-P) and CIMP-negative (CIMP-N) colorectal cancers. Furthermore, DNA methylation profiling, including assessment of the TET1 gene, was assessed in colorectal cancers, as well as colon polyps. The TET1 was silenced by DNA methylation in a subset of colorectal cancers as well as cell lines, expression of which was reactivated by demethylating agent. TET1 methylation was more frequent in CIMP-P (23/55, 42%) than CIMP-N (2/113, 2%, P < 0.0001) colorectal cancers. This trend was also observed in colon polyps (CIMP-P, 16/40, 40%; CIMP-N, 2/24, 8%; P = 0.002), suggesting that TET1 methylation is an early event in CIMP tumorigenesis. TET1 methylation was significantly associated with BRAF mutation but not with hMLH1 methylation in the CIMP-P colorectal cancers. Colorectal cancers with TET1 methylation have a significantly greater number of DNA methylated genes and less pathological metastasis compared to those without TET1 methylation (P = 0.007 and 0.045, respectively). Our data suggest that TET1 methylation may contribute to the establishment of a unique pathway in respect to CIMP-mediated tumorigenesis, which may be incidental to hMLH1 methylation. In addition, our findings provide evidence that TET1 methylation may be a good biomarker for the prediction of metastasis in colorectal cancer. ©2015 American Association for Cancer Research.

  1. The use of J-coupling as a sole criterion to assign the total absolute stereochemistry of new pyrrolidinone class synthetic analogs, derived from S-pyroglutamic acid

    NASA Astrophysics Data System (ADS)

    Kellici, Tahsin F.; Ntountaniotis, Dimitrios; Vanioti, Marianna; Golic Grdadolnik, Simona; Simcic, Mihael; Michas, Georgios; Moutevelis-Minakakis, Panagiota; Mavromoustakos, Thomas

    2017-02-01

    During the synthesis of new pyrrolidinone analogs possessing biological activity it is intriguing to assign their absolute stereochemistry as it is well known that drug potency is influenced by the stereochemistry. The combination of J-coupling information with theoretical results was used in order to establish their total stereochemistry when the chiral center of the starting material has known absolute stereochemistry. The J-coupling can be used as a sole criterion for novel synthetic analogs to identify the right stereochemistry. This approach is extremely useful especially in the case of analogs whose 2D NOESY spectra cannot provide this information. Few synthetic examples are given to prove the significance of this approach.

  2. Crystal structure and electrochemical properties of [Ni(bztmpen)(CH3CN)](BF4)2 {bztmpen is N-benzyl-N,N',N'-tris-[(6-methyl-pyridin-2-yl)meth-yl]ethane-1,2-di-amine}.

    PubMed

    Chen, Lin; Ren, Gan; Guo, Yakun; Sang, Ge

    2017-06-01

    The mononuclear nickel title complex (acetonitrile-κ N ){ N -benzyl- N , N ', N '-tris-[(6-methyl-pyridin-2-yl)meth-yl]ethane-1,2-di-amine}-nickel(II) bis-(tetra-fluor-ido-borate), [Ni(C 30 H 35 N 5 )(CH 3 CN)](BF 4 ) 2 , was prepared from the reaction of Ni(BF 4 ) 2 ·6H 2 O with N -benzyl- N , N ', N '-tris-[(6-methyl-pyridin-2-yl)meth-yl]ethane-1,2-di-amine ( bztmpen ) in aceto-nitrile at room temperature. With an open site occupied by the aceto-nitrile mol-ecule, the nickel(II) atom is chelated by five N-atom sites from the ligand and one N atom from the ligand, showing an overall octa-hedral coordination environment. Compared with analogues where the 6-methyl substituent is absent, the bond length around the Ni 2+ cation are evidently longer. Upon reductive dissociation of the acetro-nitrile mol-ecule, the title complex has an open site for a catalytic reaction. The title complex has two redox couples at -1.50 and -1.80 V ( versus F c +/0 ) based on nickel. The F atoms of the two BF 4 - counter-anions are split into two groups and the occupancy ratios refined to 0.611 (18):0.389 (18) and 0.71 (2):0.29 (2).

  3. Self-assembly of a tetrahedral 58-nuclear barium vanadium oxide cluster.

    PubMed

    Kastner, Katharina; Puscher, Bianka; Streb, Carsten

    2013-01-07

    We report the synthesis and characterization of a molecular barium vanadium oxide cluster featuring high nuclearity and high symmetry. The tetrameric, 2.3 nm cluster H(5)[Ba(10)(NMP)(14)(H(2)O)(8)[V(12)O(33)](4)Br] is based on a bromide-centred, octahedral barium scaffold which is capped by four previously unknown [V(12)O(33)](6-) clusters in a tetrahedral fashion. The compound represents the largest polyoxovanadate-based heterometallic cluster known to date. The cluster is formed in organic solution and it is suggested that the bulky N-methyl-2-pyrrolidone (NMP) solvent ligands allow the isolation of this giant molecule and prevent further condensation to a solid-state metal oxide. The cluster is fully characterized using single-crystal XRD, elemental analysis, ESI mass spectrometry and other spectroscopic techniques.

  4. Selenium quantum dots: Preparation, structure, and properties

    NASA Astrophysics Data System (ADS)

    Qian, Fuli; Li, Xueming; Tang, Libin; Lai, Sin Ki; Lu, Chaoyu; Lau, Shu Ping

    2017-01-01

    An interesting class of low-dimensional nanomaterials, namely, selenium quantum dots (SeQDs), which are composed of nano-sized selenium particles, is reported in this study. The SeQDs possess a hexagonal crystal structure. They can be synthesized in large quantity by ultrasound liquid-phase exfoliation using NbSe2 powders as the source material and N-Methyl-2-pyrrolidone (NMP) as the dispersant. During sonication, the Nb-Se bonds dissociate; the SeQDs are formed, while niobium is separated by centrifugation. The SeQDs have a narrow diameter distribution from 1.9 to 4.6 nm and can be dispersed with high stability in NMP without the need for passivating agents. They exhibit photoluminescence properties that are expected to find useful applications in bioimaging, optoelectronics, as well as nanocomposites.

  5. mRNA N6-methyladenosine methylation of postnatal liver development in pig.

    PubMed

    He, Shen; Wang, Hong; Liu, Rui; He, Mengnan; Che, Tiandong; Jin, Long; Deng, Lamei; Tian, Shilin; Li, Yan; Lu, Hongfeng; Li, Xuewei; Jiang, Zhi; Li, Diyan; Li, Mingzhou

    2017-01-01

    N6-methyladenosine (m6A) is a ubiquitous reversible epigenetic RNA modification that plays an important role in the regulation of post-transcriptional protein coding gene expression. Liver is a vital organ and plays a major role in metabolism with numerous functions. Information concerning the dynamic patterns of mRNA m6A methylation during postnatal development of liver has been long overdue and elucidation of this information will benefit for further deciphering a multitude of functional outcomes of mRNA m6A methylation. Here, we profile transcriptome-wide m6A in porcine liver at three developmental stages: newborn (0 day), suckling (21 days) and adult (2 years). About 33% of transcribed genes were modified by m6A, with 1.33 to 1.42 m6A peaks per modified gene. m6A was distributed predominantly around stop codons. The consensus motif sequence RRm6ACH was observed in 78.90% of m6A peaks. A negative correlation (average Pearson's r = -0.45, P < 10-16) was found between levels of m6A methylation and gene expression. Functional enrichment analysis of genes consistently modified by m6A methylation at all three stages showed genes relevant to important functions, including regulation of growth and development, regulation of metabolic processes and protein catabolic processes. Genes with higher m6A methylation and lower expression levels at any particular stage were associated with the biological processes required for or unique to that stage. We suggest that differential m6A methylation may be important for the regulation of nutrient metabolism in porcine liver.

  6. DHA-rich n-3 fatty acid supplementation decreases DNA methylation in blood leukocytes: the OmegAD study.

    PubMed

    Karimi, Mohsen; Vedin, Inger; Freund Levi, Yvonne; Basun, Hans; Faxén Irving, Gerd; Eriksdotter, Maria; Wahlund, Lars-Olof; Schultzberg, Marianne; Hjorth, Erik; Cederholm, Tommy; Palmblad, Jan

    2017-10-01

    Background: Dietary fish oils, rich in long-chain n-3 (ω-3) fatty acids (FAs) [e.g., docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3)], modulate inflammatory reactions through various mechanisms, including gene expression, which is measured as messenger RNA concentration. However, the effects of long-term treatment of humans with DHA and EPA on various epigenetic factors-such as DNA methylation, which controls messenger RNA generation-are poorly described. Objective: We wanted to determine the effects of 6 mo of dietary supplementation with an n-3 FA preparation rich in DHA on global DNA methylation of peripheral blood leukocytes (PBLs) and the relation to plasma EPA and DHA concentrations in Alzheimer disease (AD) patients. Design: In the present study, DNA methylation in four 5'-cytosine-phosphate-guanine-3' (CpG) sites of long interspersed nuclear element-1 repetitive sequences was assessed in a group of 63 patients (30 given the n-3 FA preparation and 33 given placebo) as an estimation of the global DNA methylation in blood cells. Patients originated from the randomized, double-blind, placebo-controlled OmegAD study, in which 174 AD patients received either 1.7 g DHA and 0.6 g EPA (the n-3 FA group) or placebo daily for 6 mo. Results: At 6 mo, the n-3 FA group displayed marked increases in DHA and EPA plasma concentrations (2.6- and 3.5-fold), as well as decreased methylation in 2 out of 4 CpG sites ( P < 0.05 for all), respectively. This hypomethylation in CpG2 and CpG4 sites showed a reverse correlation to changes in plasma EPA concentration ( r = -0.25, P = 0.045; and r = -0.26, P = 0.041, respectively), but not to changes in plasma DHA concentration, and were not related to apolipoprotein E-4 allele frequency. Conclusion: Supplementation with n-3 FA for 6 mo was associated with global DNA hypomethylation in PBLs. Our data may be of importance in measuring various effects of marine oils, including gene expression, in patients

  7. Structure of human IFIT1 with capped RNA reveals adaptable mRNA binding and mechanisms for sensing N1 and N2 ribose 2′-O methylations

    PubMed Central

    Laudenbach, Beatrice Theres; Martínez-Montero, Saúl; Cencic, Regina; Habjan, Matthias; Pichlmair, Andreas; Damha, Masad J.; Pelletier, Jerry; Nagar, Bhushan

    2017-01-01

    IFIT1 (IFN-induced protein with tetratricopeptide repeats-1) is an effector of the host innate immune antiviral response that prevents propagation of virus infection by selectively inhibiting translation of viral mRNA. It relies on its ability to compete with the translation initiation factor eIF4F to specifically recognize foreign capped mRNAs, while remaining inactive against host mRNAs marked by ribose 2′-O methylation at the first cap-proximal nucleotide (N1). We report here several crystal structures of RNA-bound human IFIT1, including a 1.6-Å complex with capped RNA. IFIT1 forms a water-filled, positively charged RNA-binding tunnel with a separate hydrophobic extension that unexpectedly engages the cap in multiple conformations (syn and anti) giving rise to a relatively plastic and nonspecific mode of binding, in stark contrast to eIF4E. Cap-proximal nucleotides encircled by the tunnel provide affinity to compete with eIF4F while allowing IFIT1 to select against N1 methylated mRNA. Gel-shift binding assays confirm that N1 methylation interferes with IFIT1 binding, but in an RNA-dependent manner, whereas translation assays reveal that N1 methylation alone is not sufficient to prevent mRNA recognition at high IFIT1 concentrations. Structural and functional analysis show that 2′-O methylation at N2, another abundant mRNA modification, is also detrimental for RNA binding, thus revealing a potentially synergistic role for it in self- versus nonself-mRNA discernment. Finally, structure-guided mutational analysis confirms the importance of RNA binding for IFIT1 restriction of a human coronavirus mutant lacking viral N1 methylation. Our structural and biochemical analysis sheds new light on the molecular basis for IFIT1 translational inhibition of capped viral RNA. PMID:28251928

  8. Chemical carcinogenesis in the nervous system. Preferential accumulation of O6-methylguanine in rat brain deoxyribonucleic acid during repetitive administration of N-methyl-N-nitrosourea.

    PubMed Central

    Margison, G P; Kleihues, P

    1975-01-01

    The alkylation of purine bases in DNA of several rat tissues was determined during weekly injections (10 mg/kg) of N-[3H]methyl-N-nitrosourea, a dose schedule known to selectively induce tumours of the nervous system. Each group of animals was killed 1 week after the final injection, and the DNA hydrolysates were analysed by chromatography on Sephadex G-10. After five weekly applications, O6-methylguanine had accumulated in brain DNA to an extent which greatly exceeded that in kidney, spleen and intestine. In the liver, the final O6-methylguanine concentration was less than 1% of that in brain. Between the first and the fifth injection, the O6-methylguanine/7-methylguanine ratio in cerebral DNA increased from 0.28 to 0.68. In addition, 3-methylguanine was found to accumulate in brain DNA whereas in the other organs no significant quantities of this base were detectable. The results are compatible with the hypothesis that O6-alkylation of guanine in DNA plays a major role in the induction of tumours by N-methyl-N-nitrosourea and related carcinogens. The kinetics of the increase of O6-methylguanine in cerebral DNA suggest that there is no major cell fraction in the brain which is capable of excising chemically methylated bases from DNA. This repair deficiency could be a determining factor in the selective induction of nervous-system tumours by N-methyl-N-nitrosourea and other neuro-oncogenic compounds. PMID:1200992

  9. Fatty acid methyl ester from Neurospora intermedia N-1 isolated from Indonesian red peanut cake (oncom merah).

    PubMed

    Priatni, S; Hartati, S; Dewi, P; Kardono, L B S; Singgih, M; Gusdinar, T

    2010-08-01

    The objective of this study was to identify the Fatty Acid Methyl Ester (FAME) from Neurospora intermedia N-1 that isolated from Indonesian red peanut cake (oncom). FAME profiles have been used as biochemical characters to study many different groups of organisms, such as bacteria and yeasts. FAME from N. intermedia N-1 was obtained by some stages of extraction the orange spores and fractination using a chromatotron. The pure compound (1) was characterized by 500 mHz NMR (1H and 13C), FTIR and LC-MS. Summarized data's of 1H and 13C NMR spectra of compound 1 contained 19 Carbon, 34 Hydrogen and 2 Oxygen (C19H34O2). The position of the double bonds at carbon number 8 and 12 were indicated in the HMBC spectrum (2D-NMR). LC-MS spectrum indicates molecular weight of the compound 1 as 294 which is visible by the presence of protonated molecular ion [M+H] at m/z 295. Methyl esters of long chain fatty acids was presented by a 3 band pattern of IR spectrum with bands near 1249, 1199 and 1172 cm(-1). We suggested that the structure of the pure compound 1 is methyl octadeca-8,12-dienoate. The presence methyl octadeca-8,12-dienoate in N. intermedia is the first report.

  10. Bis[μ-N-(tert-butyl­dimethyl­silyl)-N-(pyridin-2-ylmeth­yl)amido]­bis­[methyl­cobalt(II)

    PubMed Central

    Malassa, Astrid; Agthe, Christine; Görls, Helmar; Westerhausen, Matthias

    2012-01-01

    The green title complex, [Co2(CH3)2(C12H21N2Si)2], was obtained from bis­{[μ-N-tert-butyl­dimethyl­silyl-N-(pyridin-2-ylmeth­yl)amido]­chloridocobalt(II)} and methyl­lithium in diethyl ether at 195 K via a metathesis reaction. The dimeric cobalt(II) complex exhibits a crystallographic center of inversion in the middle of the Co2N2 ring (average Co—N = 2.050 Å). The CoII atom shows a distorted tetra­hedral coordination sphere. The exocyclic Co—N bond length to the pyridyl group shows a similar value of 2.045 (4) Å. The exocyclic methyl group has a rather long Co—C bond length of 2.019 (5) Å. PMID:22969464

  11. Fact Sheet: N-Methylpyrrolidone (NMP)

    EPA Pesticide Factsheets

    EPA's existing chemicals programs address pollution prevention, risk assessment, hazard and exposure assessment and/or characterization, and risk management for chemicals substances in commercial use.

  12. Gestational intake of methyl donors and global LINE-1 DNA methylation in maternal and cord blood

    PubMed Central

    Baccarelli, Andrea; Kleinman, Ken P; Burris, Heather H; Litonjua, Augusto A; Rifas-Shiman, Sheryl L; Tarantini, Letizia; Gillman, Matthew W

    2012-01-01

    Maternal diet affects offspring DNA methylation in animal models, but evidence from humans is limited. We investigated the extent to which gestational intake of methyl donor nutrients affects global DNA methylation in maternal and umbilical cord blood. Among mother-infant pairs in Project Viva, a folate-replete US population, we estimated maternal intakes of vitamin B12, betaine, choline, folate, cadmium, zinc and iron periconceptionally and during the second trimester. We examined associations of these nutrients with DNA methylation, measured as %5-methyl cytosines (%5mC) in Long Interspersed Nuclear Element-1 (LINE-1), in first trimester (n = 830) and second trimester (n = 671) maternal blood and in cord blood at delivery (n = 516). Cord blood methylation was higher for male than female infants {mean [standard deviation (SD)] 84.8 [0.6] vs. 84.4 [0.7]%}. In the multivariable-adjusted model, maternal intake of methyl donor nutrients periconceptionally and during the second trimester of pregnancy was not positively associated with first trimester, second trimester or cord blood LINE-1 methylation. Periconceptional betaine intake was inversely associated with cord blood methylation [regression coefficient = −0.08% (95% confidence interval (CI): −0.14, −0.01)] but this association was attenuated after adjustment for dietary cadmium, which itself was directly associated with first trimester methylation and inversely associated with cord blood methylation. We also found an inverse association between periconceptional choline [−0.10%, 95% CI: −0.17, −0.03 for each SD (∼63 mg/day)] and cord blood methylation in males only. In this folate-replete population, we did not find positive associations between intake of methyl donor nutrients during pregnancy and DNA methylation overall, but among males, higher early pregnancy intakes of choline were associated with lower cord blood methylation. PMID:22430801

  13. Solubility and diffusivity of N{sub 2}O and CO{sub 2} in (diethanolamine + N-methyldiethanolamine + water) and in (diethanolamine + 2-amino-2-methyl-1-propanol + water)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, M.H.; Lee, W.C.

    1996-05-01

    Acid gases such as CO{sub 2} and H{sub 2}S are frequently removed from natural gas, synthetic natural gas, and other process gas streams by means of absorption into aqueous alkanol-amine solutions. The solubility and diffusivity of N{sub 2}O in (diethanolamine + N-methyldiethanolamine + water) and in (diethanolamine + 2-amino-2-methyl-1-propanol + water) were measured at (30, 35, and 40)C and at atmospheric pressure. Five (diethanolamine + N-methyldiethanolamine + water) and four (diethanolamine + 2-amino-2-methyl-1-propanol + water) systems were studied. The total amine mass percent in all cases was 30. A solubility apparatus was used to measure the solubility of N{sub 2}Omore » in amine solutions. The diffusivity was measured by a wetted wall column absorber. The N{sub 2}O analogy was used to estimate the solubility and diffusivity of CO{sub 2} in (diethanolamine + N-methyldiethanolamine + water) and in (diethanolamine + 2-amino-2-methyl-1-propanol + water).« less

  14. Are in situ formulations the keys for the therapeutic future of S-nitrosothiols?

    PubMed

    Parent, Marianne; Boudier, Ariane; Dupuis, François; Nouvel, Cécile; Sapin, Anne; Lartaud, Isabelle; Six, Jean-Luc; Leroy, Pierre; Maincent, Philippe

    2013-11-01

    S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP) were formulated into in situ forming implants (ISI) and microparticles (ISM) using PLGA and either N-methyl-2-pyrrolidone (NMP) or triacetin. Physicochemical characterization was carried out, including the study of matrix structure and degradation. A strong correlation between drug hydrophobicity and the in vitro release profiles was observed: whatever the formulation, GSNO and SNAP were completely released after ca. 1 day and 1 week, respectively. Then, selected formulations (i.e., SNAP-loaded NMP formulations) demonstrated the ability to sustain the vasodilation effect of SNAP, as shown by monitoring the arterial pressure (telemetry) of Wistar rats after subcutaneous injection. Both ISI and ISM injections resulted in a 3-fold extended decrease in pulse arterial pressure compared with the unloaded drug, without significant decrease in the mean arterial pressure. Hence, the results emphasize the suitability of these formulations as drug delivery systems for S-nitrosothiols, widening their therapeutic potential. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Crystal structure of N,N,N′,N′,N′′,N′′-hexa­methyl­guanidinium cyanate 1.5-hydrate

    PubMed Central

    Tiritiris, Ioannis; Kantlehner, Willi

    2015-01-01

    The title hydrated salt, C7H18N3 +·OCN−.1.5H2O, was synthesized starting from N,N,N′,N′,N′′,N′′-hexa­methyl­guanidinium chloride by a twofold anion-exchange reaction. The asymmetric unit contains two cations, two cyanate anions and three water mol­ecules. One cation shows orientational disorder and two sets of N-atom positions were found related by a 60° rotation, with an occupancy ratio of 0.852 (6):0.148 (6). The C—N bond lengths in both guanidin­ium ions range from 1.329 (2) to 1.358 (10) Å, indicating double-bond character, pointing towards charge delocalization within the NCN planes. Strong O—H⋯N hydrogen bonds between the crystal water mol­ecules and the cyanate ions and strong O—H⋯O hydrogen bonds between the water mol­ecules are present, resulting in a two-dimensional hydrogen bonded network running parallel to the (001) plane. The hexa­methyl­guanidinium ions are packed in between the layers built up by water mol­ecules and cyanate ions. PMID:26870506

  16. TIME-COURSE OF ACUTE NEUROTOXICITY PRODUCED BY N-METHYL CARBAMATES IN PREWEANLING RATS.

    EPA Science Inventory

    N-methyl carbamate insecticides are reversible inhibitors of central and peripheral acetylcholinesterease (ChE). Despite their widespread and long-term use, we could find no studies of a systematic comparison of neurotoxicity in young animals across this group of chemicals. To ...

  17. Modification of N6-methyladenosine RNA methylation on heat shock protein expression.

    PubMed

    Yu, Jiayao; Li, Yi; Wang, Tian; Zhong, Xiang

    2018-01-01

    This study was conducted to investigate effect of N6-methyladenosine (m6A) RNA methylation on Heat shock proteins (HSPs) and dissect the profile of HSP RNA methylation. The results showed that m6A methyltransferases METTL3 mRNA was decreased in responses to heat shock stress in HepG2 cells, but m6A-specific binding protein YTHDF2 mRNA was upregulated in a manner similar to HSP70 induction. Immunofluorescence staining showed that the majority of YTHDF2 was present in the cytosol, however, nearly all YTHDF2 translocated from the cytosol into the nucleus after heat shock. METTL3 knockdown significantly changed HSP70, HSP60, and HSP27 mRNA expression in HepG2 cells using siRNA, however, mRNA lifetime was not impacted. Silence of YTHDF2 using siRNA did not change expression of HSP70, but significantly increased HSP90, HSP60, and HSPB1 mRNA expression. In addition, m6A-seq revealed that HSP m6A methylation peaks are mainly enriched on exons and around stop codons, and shows a unique distribution profile in the 5'UTR and 3'UTR. Knockdown of METTL3 changed the methylation patterns of HSPs transcript. In conclusion, m6A RNA methylation regulates HSP gene expression. Differential expression of HSPs modulated by m6A may depend on the m6A site and abundance of the target gene. This finding provides insights into new regulatory mechanisms of HSPs in normal and stress situations.

  18. Direct detection of methylation in genomic DNA

    PubMed Central

    Bart, A.; van Passel, M. W. J.; van Amsterdam, K.; van der Ende, A.

    2005-01-01

    The identification of methylated sites on bacterial genomic DNA would be a useful tool to study the major roles of DNA methylation in prokaryotes: distinction of self and nonself DNA, direction of post-replicative mismatch repair, control of DNA replication and cell cycle, and regulation of gene expression. Three types of methylated nucleobases are known: N6-methyladenine, 5-methylcytosine and N4-methylcytosine. The aim of this study was to develop a method to detect all three types of DNA methylation in complete genomic DNA. It was previously shown that N6-methyladenine and 5-methylcytosine in plasmid and viral DNA can be detected by intersequence trace comparison of methylated and unmethylated DNA. We extended this method to include N4-methylcytosine detection in both in vitro and in vivo methylated DNA. Furthermore, application of intersequence trace comparison was extended to bacterial genomic DNA. Finally, we present evidence that intrasequence comparison suffices to detect methylated sites in genomic DNA. In conclusion, we present a method to detect all three natural types of DNA methylation in bacterial genomic DNA. This provides the possibility to define the complete methylome of any prokaryote. PMID:16091626

  19. EPR study of gamma-irradiated N-methyl-L-alanine, DL-2-methyl glutamic acid hemihydrate and Di-leucine hydrochloride in solid state

    NASA Astrophysics Data System (ADS)

    Sütçü, Kerem; Osmanoğlu, Y. Emre

    2017-12-01

    In this study, it was aimed to investigate ɣ-irradiated powders of N-methyl-L-alanine (NMLA), DL-2-methyl glutamic acid hemihydrate (DL2MGAH), and Di-leucine hydrochloride (DLHCl) at room temperature by electron paramagnetic resonance spectroscopy. After the γ-irradiation the samples indicated the existence of the CH3ĊNHCH3COOH, HOOCCH3NH2CĊHCH2COOH·1/2H2O and (CH3)2ĊCH2CH NHCOOHCOCH (NH2HCl) CH2CH (CH3)2 radicals, respectively. The spectral parameters of the radicals were determined. The results were compared with the earlier studies and discussed accordingly.

  20. Data-derived uncertainty factor approach in the revised N-methyl carbamate risk assessment.

    EPA Science Inventory

    EPA completed its Revised Cumulative Risk Assessment (CRA) of the N-methyl Carbamate (NMC) Pesticides in 2007. This assessment evaluated the joint risk to 10 pesticides from food, water, and residential exposure. NMCs share the ability to inhibit acetylcholinesterase (AChE) via c...

  1. Study on CO2/ N2 separation: the effect of rubbery polymer coating on PVDF membrane

    NASA Astrophysics Data System (ADS)

    Zuwairi, M. Z.; Rahman, S. A.

    2017-06-01

    The emission of harmful gases such as carbon dioxide (CO2) via gas processing plant and daily human activities gave negative impacts to the environment and global inhabitant. Flat sheet asymmetric membranes were produced from homogenous solution of Poly(vinylideneflouride) (PVDF) via phase inversion method using N-methyl-2-pyrrolidone (NMP) as the solvent. While the poly ether b-amide (PEBAX) was dissolve by using of (70 ethanol and 30 water) as a solvent and and lithium chloride as a additives. The morphology and cross section of the produced membranes were observed by Scanning Electron Microscope (SEM). Then, the membranes were tested for chemical analysis to define the presence of PEBAX in the membrane by using Fourier Transform Infrared (FTIR) spectroscopy. The permeation performances of the membranes were evaluated in terms of permeability and selectivity of the membranes by using gas permeation test. Increasing the PEBAX content significantly increased the selectivity of the PVDF membrane to separate the CO2/N2 gases but decreased the amount of the gases that passed through the membrane.

  2. Antimutagenic components in Glycyrrhiza against N-methyl-N-nitrosourea in the Ames assay.

    PubMed

    Inami, Keiko; Mine, Yusuke; Kojo, Yukiko; Tanaka, Satomi; Ishikawa, Satoko; Mochizuki, Masataka

    2017-03-01

    Antimutagenesis against N-nitroso compounds contribute to prevention of human cancer. We have found that Glycyrrhiza aspera ethanolic extract exhibits antimutagenic activity against N-methyl-N-nitrosourea (MNU) using the Ames assay with Salmonella typhimurium TA1535. In the present study, eight purified components from Glycyrrhiza, namely glabridin, glycyrrhetinic acid, glycyrrhizin, licochalcone A, licoricesaponin H2, licoricesaponin G2, liquiritigenin and liquiritin were evaluated for their antimutagenicity against MNU in the Ames assay with S. typhimurium TA1535. Glycyrrhetinic acid, glycyrrhizin, licoricesaponin G2, licoricesaponin H2 and liquiritin did not show the antimutagenicity against MNU in S. typhimurium TA1535. Glabridin, licochalcone A and liquiritigenin reduced revertant colonies derived from MNU in S. typhimurium TA1535 without showing cytotoxic effects, indicating that these compounds possess antimutagenic activity against MNU. The inhibitory activity of glabridin and licochalcone A was more effective than that of liquiritigenin. Thus, Glycyrrhiza contains antimutagenic components against DNA alkylating, direct-acting carcinogens.

  3. Glycerol as a Building Block for Prochiral Aminoketone, N-Formamide, and N-Methyl Amine Synthesis.

    PubMed

    Dai, Xingchao; Rabeah, Jabor; Yuan, Hangkong; Brückner, Angelika; Cui, Xinjiang; Shi, Feng

    2016-11-23

    Prochiral aminoketones are key intermediates for the synthesis of optically active amino alcohols, and glycerol is one of the main biomass-based alcohols available in industry. In this work, glycerol was catalytically activated and purposefully converted with amines to generate highly valuable prochiral aminoketones, as well as N-formamides and N-methyl amines, over CuNiAlO x catalyst. The catalyst structure can be anticipated as nano-Ni species on or in CuAlO x via the formation of nano- Cu-Ni alloy particles. This concept may present a novel and valuable methodology for glycerol utilization. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Alkylation of deoxyribonucleic acid by carcinogens dimethyl sulphate, ethyl methanesulphonate, N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea. Relative reactivity of the phosphodiester site thymidylyl(3'-5')thymidine.

    PubMed Central

    Swenson, D H; Lawley, P D

    1978-01-01

    1. The ethyl phosphotriester of thymidylyl(3'-5')thymidine, dTp(Et)dT, was identified as a product from reaction of DNA with N-ethyl-N-nitrosourea, by procedures parallel to those reported previously for the methyl homologue produced by N-methyl-N-nitrosourea. 2. Enzymic degradation to yield alkyl phosphotriesters from DNA alkylated by these carcinogens and by dimethyl sulphate and ethyl methanesulphonate was studied quantitatively, and the relative yields of the triesters dTp(Alk)dT were determined. The relative reactivity of the phosphodiester group dTpdT to each of the four carcinogens was thus obtained, and compared with that of DNA overall, or with that of the N-7 atom of guanine in DNA. Relative reactivity of the phosphodiester group was lowest towards dimethyl sulphate, the least electrophilic of the reagents used, and was highest towards N-ethyl-N-nitrosourea, the most electrophilic reagent. 3. The nature of the alkyl group transferred also influenced reactivity of the phosphodiester site, since this site was relatively more reactive towards ethylation than would be predicted simply from the known Swain-Scott s values of the alkylating agents. It was therefore suggested that the steric accessibility of the weakly nucleophilic phosphodiester group on the outside of the DNA macromolecule favours its reaction with ethylating, as opposed to methylating, reagents. 4. Taking a value of the Swain-Scott nucleophilicity (n) of 2.5 for an average DNA nucleotide unit [Walles & Ehrenberg (1969) Acta Chem. Scand. 23, 1080-1084], a value of n of about 1 for the phosphodiester group was deduced, and this value was found to be 2-3 units less than that for the N-7 atom of guanine in DNA. 5. The reactivity of DNA overall was markedly high towards the alkylnitrosoureas, despite their relatively low s values. This was ascribed to an electrostatic factor that favoured reaction of the negatively charged polymer with alkyldiazonium cation intermediates. PMID:208508

  5. Synthesis of asymmetric polyetherimide membrane for CO2/N2 separation

    NASA Astrophysics Data System (ADS)

    Ahmad, A. L.; Salaudeen, Y. O.; Jawad, Z. A.

    2017-06-01

    Large emission of carbon dioxide (CO2) to the environment requires mitigation to avoid unbearable consequences on global climate change. The CO2 emissions generated by fossil fuel combustion within the power and industrial sectors need to be quickly curbed. The gas emission can be abated using membrane technology; this is one of the most promising approaches for selective separation of CO2/N2. The purpose of the study is to synthesis an asymmetric polyetherimide (PEI) membrane and to establish its morphological characteristics for CO2/N2 separation. The PEI flat-sheet asymmetric membrane was fabricated using phase inversion with N-methyl-2-pyrrolidone (NMP) as solvent and water-isopropanol as a coagulant. Particularly, polymer concentration of 20, 25, and 30 wt. % were studied. In addition, the structure and morphology of the produced membrane were observed using scanning electron microscopy (SEM). Importantly, results showed that the membrane with high PEI concentration of 30 wt. % yield an optimal selectivity of 10.7 for CO2/Nitrogen (N2) separation at 1 bar and 25 ºC for pure gas, aided by the membrane surface morphology. The dense skin present was as a result of non-solvent (water) while isopropanol generates a porous sponge structure. This appreciable separation performance makes the PEI asymmetric membrane an attractive alternative for CO2/N2 separation.

  6. Distribution and elimination of the glycosidase inhibitors 1-deoxymannojirimycin and N-methyl-1-deoxynojirimycin in the rat in vivo.

    PubMed

    Faber, E D; Oosting, R; Neefjes, J J; Ploegh, H L; Meijer, D K

    1992-11-01

    We studied the pharmacokinetics of two synthetic derivatives of 1-deoxynojirimycin in the rat after intravenous administration. The mannosidase IA/B inhibitor 1-deoxymannojirimycin and the glucosidase inhibitor N-methyl-1-deoxynojirimycin exhibited minimal plasma protein binding and showed a rapid biphasic plasma disappearance, with an initial t1/2 of 3.0 and 4.5 min, respectively, and a terminal t1/2 of 51 and 32 min, respectively. For both compounds renal excretion is the major route of elimination. After 120 min, 52% of the dose of 1-deoxymannojirimycin and 80% of the dose of N-methyl-1-deoxymannojirimycin was recovered unchanged from the urine, whereas only 4.9 and 0.2%, respectively, of the dose was excreted in bile. Urinary clearance of 1-deoxymannojirimycin was similar to the glomerular filtration rate. In contrast, urinary clearance of N-methyl-1-deoxynojirimycin was two to three times higher than the glomerular filtration rate, indicating active tubular secretion. Ligation of the renal vessels decreased the total-body clearance of 1-deoxymannojirimycin and N-methyl-1-deoxynojirimycin 18- and 24-fold, respectively. Neither alkalinization of the urine by infusion of bicarbonate solutions nor forced diuresis altered the renal excretion rate of these compounds, implying the absence of tubular reabsorption. At 120 min, the amounts of 1-deoxymannojirimycin in liver and kidney were 2.1 and 1.1% of the dose, respectively, while small intestine, stomach, and heart contained only 0.9, 0.6 and 0.1%. Less than 1% of the dose of N-methyl-1-deoxynojirimycin was found in the collected organs 2 hr after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Biotransformation and pharmacokinetics of the nitrate trans-2-amino-2-methyl-N-(4-nitroxycyclohexyl)-propionamide in dogs.

    PubMed

    Pressmar, F; Neidlein, R; Strein, K

    1992-11-01

    The biotransformation and the pharmacokinetic behavior of the organic nitrate trans-2-Amino-2-methyl-N-(4-nitroxycyclohexyl)-propionamide (BM 12.1179, CAS 129795-96-6) were examined in dogs. BM 12.1179 was predominantly eliminated by urinary excretion, and the unchanged molecule prevailed in urine as well as in plasma. By means of various mass spectroscopic methods, the chemical structures of the metabolites were elucidated. As metabolites trans-2-amino-2-methyl-N-(4-hydroxycyclohexyl)-propionamide and trans-2-amino-2-methyl-N-(4-oxocyclohexyl)-propionamide were formed. Urine levels of the main metabolite were determined by high-pressure liquid chromatography; plasma and urine levels of BM 12.1179 were determined by capillary gas chromatography. The absolute bioavailability of BM 12.1179 was 80-100%. The plasma protein binding was about 34% which is high in comparison to other organic nitrates. BM 12.1179 represents a long-acting organic nitrate in that it shows a slow reductive denitration, and a long elimination half-life of about 10 h.

  8. Time-course, dose-response, and age comparative sensitivity of N-methyl carbamates in rats

    EPA Science Inventory

    N-Methyl carbamate insecticides are reversible inhibitors of central and peripheral acetylcholinesterease (ChE). Despite their widespread use, there are few studies of neurotoxicity in young animals. To study potential age-related differences, we evaluated seven carbamates (carba...

  9. TSCA Work Plan Chemical Risk Assessment N-Methylpyrrolidone: Paint Stripper Use

    EPA Pesticide Factsheets

    This final assessment for N-Methylpyrrolidone identified acute and chronic health risks to people, particularly pregnant women and women of childbearing age, who who are exposed to paint and coating removal products containing high concentrations of NMP.

  10. Energy impact of cathode drying and solvent recovery during lithium-ion battery manufacturing

    NASA Astrophysics Data System (ADS)

    Ahmed, Shabbir; Nelson, Paul A.; Gallagher, Kevin G.; Dees, Dennis W.

    2016-08-01

    Successful deployment of electric vehicles requires maturity of the manufacturing process to reduce the cost of the lithium ion battery (LIB) pack. Drying the coated cathode layer and subsequent recovery of the solvent for recycle is a vital step in the lithium ion battery manufacturing plant and offers significant potential for cost reduction. A spreadsheet model of the drying and recovery of the solvent, is used to study the energy demand of this step and its contribution towards the cost of the battery pack. The base case scenario indicates that the drying and recovery process imposes an energy demand of ∼10 kWh per kg of the solvent n-methyl pyrrolidone (NMP), and is almost 45 times the heat needed to vaporize the NMP. For a plant producing 100 K battery packs per year for 10 kWh plug-in hybrid vehicles (PHEV), the energy demand is ∼5900 kW and the process contributes 107 or 3.4% to the cost of the battery pack. The cost of drying and recovery is equivalent to 1.12 per kg of NMP recovered, saving 2.08 per kg in replacement purchase.

  11. Propofol effectively inhibits lithium-pilocarpine- induced status epilepticus in rats via downregulation of N-methyl-D-aspartate receptor 2B subunit expression

    PubMed Central

    Wang, Henglin; Wang, Zhuoqiang; Mi, Weidong; Zhao, Cong; Liu, Yanqin; Wang, Yongan; Sun, Haipeng

    2012-01-01

    Status epilepticus was induced via intraperitoneal injection of lithium-pilocarpine. The inhibitory effects of propofol on status epilepticus in rats were judged based on observation of behavior, electroencephalography and 24-hour survival rate. Propofol (12.5–100 mg/kg) improved status epilepticus in a dose-dependent manner, and significantly reduced the number of deaths within 24 hours of lithium-pilocarpine injection. Western blot results showed that, 24 hours after induction of status epilepticus, the levels of N-methyl-D-aspartate receptor 2A and 2B subunits were significantly increased in rat cerebral cortex and hippocampus. Propofol at 50 mg/kg significantly suppressed the increase in N-methyl-D-aspartate receptor 2B subunit levels, but not the increase in N-methyl-D-aspartate receptor 2A subunit levels. The results suggest that propofol can effectively inhibit status epilepticus induced by lithium-pilocarpine. This effect may be associated with downregulation of N-methyl-D-aspartate receptor 2B subunit expression after seizures. PMID:25737709

  12. From N-triisopropylsilylpyrrole to an optically active C-4 substituted pyroglutamic acid: total synthesis of penmacric acid.

    PubMed

    Berini, Christophe; Pelloux-Léon, Nadia; Minassian, Frédéric; Denis, Jean-Noël

    2009-11-07

    The stereoselective synthesis of penmacric acid, an optically active C-4 substituted pyroglutamic acid, has been efficiently achieved through an unusual 11-step sequence starting from simple N-triisopropylsilylpyrrole. The key-steps are the initial addition of the pyrrole nucleus onto a chiral nitrone and the obtention of the pyroglutamic acid moiety by reductive hydrogenation of the pyrrole followed by oxidation of the corresponding pyrrolidine into pyrrolidinone.

  13. Top-Contact Pentacene-Based Organic Thin Film Transistor (OTFT) with N, N'-Bis(3-Methyl Phenyl)- N, N'-Diphenyl Benzidine (TPD)/Au Bilayer Source-Drain Electrode

    NASA Astrophysics Data System (ADS)

    Borthakur, Tribeni; Sarma, Ranjit

    2018-01-01

    A top-contact Pentacene-based organic thin film transistor (OTFT) with N, N'-Bis (3-methyl phenyl)- N, N'-diphenyl benzidine (TPD)/Au bilayer source-drain electrode is reported. The devices with TPD/Au bilayer source-drain (S-D) electrodes show better performance than the single layer S-D electrode OTFT devices. The field-effect mobility of 4.13 cm2 v-1 s-1, the on-off ratio of 1.86 × 107, the threshold voltage of -4 v and the subthreshold slope of .27 v/decade, respectively, are obtained from the device with a TPD/Au bilayer source-drain electrode.

  14. The preference of tryptophan for membrane interfaces: insights from N-methylation of tryptophans in gramicidin channels.

    PubMed

    Sun, Haiyan; Greathouse, Denise V; Andersen, Olaf S; Koeppe, Roger E

    2008-08-08

    To better understand the structural and functional roles of tryptophan at the membrane/water interface in membrane proteins, we examined the structural and functional consequences of Trp --> 1-methyl-tryptophan substitutions in membrane-spanning gramicidin A channels. Gramicidin A channels are miniproteins that are anchored to the interface by four Trps near the C terminus of each subunit in a membrane-spanning dimer. We masked the hydrogen bonding ability of individual or multiple Trps by 1-methylation of the indole ring and examined the structural and functional changes using circular dichroism spectroscopy, size exclusion chromatography, solid state (2)H NMR spectroscopy, and single channel analysis. N-Methylation causes distinct changes in the subunit conformational preference, channel-forming propensity, single channel conductance and lifetime, and average indole ring orientations within the membrane-spanning channels. The extent of the local ring dynamic wobble does not increase, and may decrease slightly, when the indole NH is replaced by the non-hydrogen-bonding and more bulky and hydrophobic N-CH(3) group. The changes in conformational preference, which are associated with a shift in the distribution of the aromatic residues across the bilayer, are similar to those observed previously with Trp --> Phe substitutions. We conclude that indole N-H hydrogen bonding is of major importance for the folding of gramicidin channels. The changes in ion permeability, however, are quite different for Trp --> Phe and Trp --> 1-methyl-tryptophan substitutions, indicating that the indole dipole moment and perhaps also ring size and are important for ion permeation through these channels.

  15. Development of ferret as a human lung cancer model by injecting4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

    USDA-ARS?s Scientific Manuscript database

    Development of new animal lung cancer models that are relevant to human lung carcinogenesis is important for lung cancer research. Previously we have shown the induction of lung tumor in ferrets (Mustela putorius furo) exposed to both tobacco smoke and a tobacco carcinogen (4-(N-methyl-N-nitrosamino...

  16. Progesterone up-regulates vasodilator effects of calcitonin gene-related peptide in N(G)-nitro-L-arginine methyl ester-induced hypertension.

    PubMed

    Gangula, P R; Wimalawansa, S J; Yallampalli, C

    1997-04-01

    We recently reported that calcitonin gene-related peptide can reverse the hypertension produced by N(G)-nitro-L-arginine methyl ester in pregnant rats. In the current study we investigated whether these vasodilator effects of calcitonin gene-related peptide were progesterone dependent. Calcitonin gene-related peptide or N(G)-nitro-L-arginine methyl ester was infused through osmotic minipumps, either separately or in combination, to groups of five pregnant rats from day 17 of gestation until day 8 post partum or to nonpregnant ovariectomized rats for 8 days. Progesterone was injected during days 1 to 6 post partum and for 6 days after ovariectomy. Systolic blood pressure was measured daily. Animals receiving N(G)-nitro-L-arginine methyl ester exhibited significant elevations of blood pressure during pregnancy and post partum. Coadministration of calcitonin gene-related peptide to these rats reversed the hypertension during pregnancy but not during the postpartum period. At the dose used in this study calcitonin gene-related peptide administered alone was without significant effects on blood pressure. However, it reduced both the mortality and growth restriction of the fetus associated with N(G)-nitro-L-arginine methyl ester in these animals. Calcitonin gene-related peptide reversed the hypertension in N(G)-nitro-L-arginine methyl ester-infused postpartum rats during the periods of progesterone treatment only, and these effects were lost when progesterone treatment was stopped. Neither progesterone nor calcitonin gene-related peptide alone were effective. To further confirm these observations, progesterone effects were tested in ovariectomized adult rats. Similar to the findings in postpartum rats, calcitonin gene-related peptide completely reversed the elevation in blood pressure in N(G)-nitro-L-arginine methyl ester-treated rats receiving progesterone injections. The effects of calcitonin gene-related peptide were apparent only during the progesterone treatment

  17. Abundant Lysine Methylation and N-Terminal Acetylation in Sulfolobus islandicus Revealed by Bottom-Up and Top-Down Proteomics*

    PubMed Central

    Vorontsov, Egor A.; Rensen, Elena; Prangishvili, David; Krupovic, Mart; Chamot-Rooke, Julia

    2016-01-01

    Protein post-translational methylation has been reported to occur in archaea, including members of the genus Sulfolobus, but has never been characterized on a proteome-wide scale. Among important Sulfolobus proteins carrying such modification are the chromatin proteins that have been described to be methylated on lysine side chains, resembling eukaryotic histones in that aspect. To get more insight into the extent of this modification and its dynamics during the different growth steps of the thermoacidophylic archaeon S. islandicus LAL14/1, we performed a global and deep proteomic analysis using a combination of high-throughput bottom-up and top-down approaches on a single high-resolution mass spectrometer. 1,931 methylation sites on 751 proteins were found by the bottom-up analysis, with methylation sites on 526 proteins monitored throughout three cell culture growth stages: early-exponential, mid-exponential, and stationary. The top-down analysis revealed 3,978 proteoforms arising from 681 proteins, including 292 methylated proteoforms, 85 of which were comprehensively characterized. Methylated proteoforms of the five chromatin proteins (Alba1, Alba2, Cren7, Sul7d1, Sul7d2) were fully characterized by a combination of bottom-up and top-down data. The top-down analysis also revealed an increase of methylation during cell growth for two chromatin proteins, which had not been evidenced by bottom-up. These results shed new light on the ubiquitous lysine methylation throughout the S. islandicus proteome. Furthermore, we found that S. islandicus proteins are frequently acetylated at the N terminus, following the removal of the N-terminal methionine. This study highlights the great value of combining bottom-up and top-down proteomics for obtaining an unprecedented level of accuracy in detecting differentially modified intact proteoforms. The data have been deposited to the ProteomeXchange with identifiers PXD003074 and PXD004179. PMID:27555370

  18. A pivotal role for reductive methylation in the de novo crystallization of a ternary complex composed of Yersinia pestis virulence factors YopN, SycN and YscB.

    PubMed

    Schubot, Florian D; Waugh, David S

    2004-11-01

    Structural studies of a ternary complex composed of the Yersina pestis virulence factors YopN, SycN and YscB were initially hampered by poor solubility of the individual proteins. Co-expression of all three proteins in Escherichia coli yielded a well behaved complex, but this sample proved to be recalcitrant to crystallization. As crystallization efforts remained fruitless, even after the proteolysis-guided engineering of a truncated YopN polypeptide, reductive methylation of lysine residues was employed to alter the surface properties of the complex. The methylated complex yielded crystals that diffracted X-rays to a maximal resolution of 1.8 A. The potential utility of reductive methylation as a remedial strategy for high-throughput structural biology was further underscored by the successful modification of a selenomethionine-substituted sample.

  19. Methylation profiling identified novel differentially methylated markers including OPCML and FLRT2 in prostate cancer.

    PubMed

    Wu, Yu; Davison, Jerry; Qu, Xiaoyu; Morrissey, Colm; Storer, Barry; Brown, Lisha; Vessella, Robert; Nelson, Peter; Fang, Min

    2016-04-02

    To develop new methods to distinguish indolent from aggressive prostate cancers (PCa), we utilized comprehensive high-throughput array-based relative methylation (CHARM) assay to identify differentially methylated regions (DMRs) throughout the genome, including both CpG island (CGI) and non-CGI regions in PCa patients based on Gleason grade. Initially, 26 samples, including 8 each of low [Gleason score (GS) 6] and high (GS ≥7) grade PCa samples and 10 matched normal prostate tissues, were analyzed as a discovery cohort. We identified 3,567 DMRs between normal and cancer tissues, and 913 DMRs distinguishing low from high-grade cancers. Most of these DMRs were located at CGI shores. The top 5 candidate DMRs from the low vs. high Gleason comparison, including OPCML, ELAVL2, EXT1, IRX5, and FLRT2, were validated by pyrosequencing using the discovery cohort. OPCML and FLRT2 were further validated in an independent cohort consisting of 20 low-Gleason and 33 high-Gleason tissues. We then compared patients with biochemical recurrence (n=70) vs. those without (n=86) in a third cohort, and they showed no difference in methylation at these DMR loci. When GS 3+4 cases and GS 4+3 cases were compared, OPCML-DMR methylation showed a trend of lower methylation in the recurrence group (n=30) than in the no-recurrence (n=52) group. We conclude that whole-genome methylation profiling with CHARM revealed distinct patterns of differential DNA methylation between normal prostate and PCa tissues, as well as between different risk groups of PCa as defined by Gleason scores. A panel of selected DMRs may serve as novel surrogate biomarkers for Gleason score in PCa.

  20. COMPARISON OF ACUTE NEUROBEHAVIORAL AND CHOLINESTERASE INHIBITORY EFFECTS OF N-METHYL CARBAMATES IN RAT

    EPA Science Inventory

    There are few studies evaluating direct functional and biochemical consequences of exposure. In the present study of the acute toxicity of seven N-methyl carbamate pesticides, we evaluated the dose-response profiles of cholinesterase (ChE) inhibition in brain and erythrocytes (R...

  1. Efficient and scalable synthesis of bardoxolone methyl (cddo-methyl ester).

    PubMed

    Fu, Liangfeng; Gribble, Gordon W

    2013-04-05

    Bardoxolone methyl (2-cyano-3,12-dioxooleane-1,9(11)-dien-28-oic acid methyl ester; CDDO-Me) (1), a synthetic oleanane triterpenoid with highly potent anti-inflammatory activity (levels below 1 nM), has completed a successful phase I clinical trial for the treatment of cancer and a successful phase II trial for the treatment of chronic kidney disease in type 2 diabetes patients. Our synthesis of bardoxolone methyl (1) proceeds in ∼50% overall yield in five steps from oleanolic acid (2), requires only one to two chromatographic purifications, and can provide gram quantities of 1.

  2. Study of the n-methyl-d-aspartate antagonistic properties of anticholinergic drugs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McDonough, J.H.; Shih, T.M.

    1995-12-31

    A study of the N-methyl-D-aspartate antagonistic properties of anticholinergic drugs. PHARMACOL BIOCHEM BEHAV. 51(2/3) 249-253, 1995. Drugs that act at the N-methyl-D-aspartate (NMDA) receptor complex have the ability to terminate nerve agent-induced seizures and modulate the neuropathologic consequences of agent exposure. Drugs with mixed anticholinergic and anti-NMDA properties potentially provide an ideal class of compounds for development as anticonvulsant treatments for nerve agent casualties. The present experiment evaluated the potential NMDA antagonist activity of 11 anticholinergic drugs by determining whether pretreatment with the compound was capable of protecting mice from the lethal effects of NMDA. The following anticholinergic drugs antagonizedmore » NMDA lethality and are ranked according to their potency: mecamylamine > procyclidine = benactyzine > biperiden > tribexyphenidyl. The anticholinergics atropine, aprophen, azaprophen, benztropine, 3-quinudidinyl benzilate (QNB), and scopolamine failed to show NMDA antagonist properties. In addition, and unexpectedly, diazepam, ethanol, and pentobarbital were also shown to be capable of antagonizing NMDA lethality over a certain range of doses. The advantages and limitations of using antagonism of NMDA lethality in mice as a bioassay for determining the NMDA antagonist properties of drugs are also discussed.« less

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Boal, Amie K.; Grove, Tyler L.; McLaughlin, Monica I.

    2014-10-02

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

  4. Solubility and diffusivity of N{sub 2}O and CO{sub 2} in (monoethanolamine + N-methyldiethanolamine + water) and in (monoethanolamine + 2-amino-2-methyl-1-propanol + water)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, M.H.; Lai, M.D.

    1995-03-01

    Solutions of amines are frequently used in gas-treating processes to remove acid gases, such as CO{sub 2} and H{sub 2}S, from gas streams in the natural gas and synthetic ammonia industries and petroleum chemical plants. The solubility and diffusivity of N{sub 2}O in (monoethanolamine + N-methyldiethanolamine + water) and in (monoethanolamine + 2-amino-2-methyl-l-propanol + water) were measured at 30, 35, and 40 C and at atmospheric pressure. Six (monoethanolamine + N-methyldiethanolamine + water) and five (monoethanolamine + 2-amino-2-methyl-l-propanol + water) systems were studied. The total amine mass percent in all cases was 30. The solubilities were measured by a solubilitymore » apparatus similar to that of Haimour and Sandall (1984). A wetted wall column absorber was used to obtain the diffusivity of N{sub 2}O in amines. The N{sub 2}O solubilities in amine solutions have been correlated on the basis of the excess Henry constant correlation of Wang et al. (1992). The N{sub 2}O analogy was used to estimate the solubility and diffusivity of CO{sub 2} in (monoethanolamine + N-methyldiethanolamine + water) and in (monoethanolamine + 2-amino-2-methyl-l-propanol + water).« less

  5. Proline derivatives in fruits of bergamot (Citrus bergamia Risso et Poit): presence of N-methyl-L-proline and 4-hydroxy-L-prolinebetaine.

    PubMed

    Servillo, Luigi; Giovane, Alfonso; Balestrieri, Maria Luisa; Cautela, Domenico; Castaldo, Domenico

    2011-01-12

    The content of proline and various compounds deriving from its metabolism (4-hydroxy-L-proline, N-methyl-L-proline, N,N-dimethylproline, and 4-hydroxy-L-prolinebetaine) was determined in fruits and seeds of Bergamot (Citrus bergamia Risso et Poit), growing in the Calabria region (South Italy). A HPLC-ESI-tandem mass spectrometry method, which allowed rapid determination of L-proline, 4-hydroxy-L-proline, N-methyl-L-proline, N,N-dimethylproline, and 4-hydroxy-L-prolinebetaine in juice and extracts of bergamot fruit with minimum sample preparation and short analysis time (about 10 min), is presented. Proline and 4-hydroxy-L-proline levels in the samples were also determined by HPLC analysis with fluorescence detection and the results compared to those obtained with HPLC-ESI-tandem mass spectrometry. For the first time, the presence of N-methyl-L-proline and 4-hydroxy-L-prolinebetaine in the fruits of a plant of the Citrus genus is reported.

  6. Methylated spirit burns: an ongoing problem.

    PubMed

    Jansbeken, J R H; Vloemans, A F P M; Tempelman, F R H; Breederveld, R S

    2012-09-01

    Despite many educational campaigns we still see burns caused by methylated spirit every year. We undertook a retrospective study to analyse the impact of this problem. We retrospectively collected data of all patients with burns caused by methylated spirit over twelve years from 1996 to 2008. Our main endpoints were: incidence, age, mechanism of injury, total body surface area (TBSA) burned, burn depth, need for surgery and length of hospital stay. Ninety-seven patients with methylated spirit burns were included. During the study period there was no decrease in the number of patients annually admitted to the burn unit with methylated spirit burns. 28% of the patients (n=27) were younger than eighteen years old, 15% (n=15) were ten years old or younger. The most common cause of burns was carelessness in activities involving barbecues, campfires and fondues. Mean TBSA burned was 16% (SD 12.4). 70% (n=68) had full thickness burns. 66% (n=64) needed grafting. Mean length of hospital stay was 23 days (SD 24.7). The use of methylated spirit is an ongoing problem, which continues to cause severe burns in adults and children. Therefore methylated spirit should be banned in households. We suggest sale only in specialised shops, clear labelling and mandatory warnings. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  7. Maternal intake of methyl-group donors affects DNA methylation of metabolic genes in infants.

    PubMed

    Pauwels, Sara; Ghosh, Manosij; Duca, Radu Corneliu; Bekaert, Bram; Freson, Kathleen; Huybrechts, Inge; Langie, Sabine A S; Koppen, Gudrun; Devlieger, Roland; Godderis, Lode

    2017-01-01

    Maternal nutrition during pregnancy and infant nutrition in the early postnatal period (lactation) are critically involved in the development and health of the newborn infant. The Maternal Nutrition and Offspring's Epigenome (MANOE) study was set up to assess the effect of maternal methyl-group donor intake (choline, betaine, folate, methionine) on infant DNA methylation. Maternal intake of dietary methyl-group donors was assessed using a food-frequency questionnaire (FFQ). Before and during pregnancy, we evaluated maternal methyl-group donor intake through diet and supplementation (folic acid) in relation to gene-specific ( IGF2 DMR, DNMT1 , LEP , RXRA ) buccal epithelial cell DNA methylation in 6 months old infants ( n  = 114) via pyrosequencing. In the early postnatal period, we determined the effect of maternal choline intake during lactation (in mothers who breast-fed for at least 3 months) on gene-specific buccal DNA methylation ( n  = 65). Maternal dietary and supplemental intake of methyl-group donors (folate, betaine, folic acid), only in the periconception period, was associated with buccal cell DNA methylation in genes related to growth ( IGF2 DMR), metabolism ( RXRA ), and appetite control ( LEP ). A negative association was found between maternal folate and folic acid intake before pregnancy and infant LEP (slope = -1.233, 95% CI -2.342; -0.125, p  = 0.0298) and IGF2 DMR methylation (slope = -0.706, 95% CI -1.242; -0.107, p  = 0.0101), respectively. Positive associations were observed for maternal betaine (slope = 0.875, 95% CI 0.118; 1.633, p  = 0.0241) and folate (slope = 0.685, 95% CI 0.245; 1.125, p  = 0.0027) intake before pregnancy and RXRA methylation. Buccal DNMT1 methylation in the infant was negatively associated with maternal methyl-group donor intake in the first and second trimester of pregnancy and negatively in the third trimester. We found no clear association between maternal choline intake

  8. Solvent engineering for high-quality perovskite solar cell with an efficiency approaching 20%

    NASA Astrophysics Data System (ADS)

    Wu, Tongyue; Wu, Jihuai; Tu, Yongguang; He, Xin; Lan, Zhang; Huang, Miaoliang; Lin, Jianming

    2017-10-01

    The perovskite layer is the most crucial factor for the high performance perovskite solar cells. Based on solvent engineering, we develop a ternary-mixed-solvent method for the growth of high-quality [Cs0.05(MA0.17FA0.83)0.95Pb(I0.83Br0.17)3] cation-anion-mixed perovskite films by introducing N-methyl-2-pyrrolidone (NMP) into the precursor mixed solution. By controlling rapid nucleation and retarding crystal growth via intermediate phase PbI2-NMP (Lewis acid-base adduct), a dense, large grain, pinhole-free and long charge carrier lifetime perovskite film is obtained. By optimizing the precursor solvent composition, the perovskite solar cell achieves an impressive power conversion efficiency of 19.61% under one-sun illumination. The research presented here provides a facile, low-cost and highly efficient way for the preparation of perovskite solar cells.

  9. N-(1-Allyl-1H-indazol-5-yl)-4-methyl­benzene­sulfonamide

    PubMed Central

    Chicha, Hakima; Rakib, El Mostapha; Abderrafia, Hafid; Saadi, Mohamed; El Ammari, Lahcen

    2013-01-01

    The asymmetric unit of the title compound, C17H17N3O2S, contains two independent mol­ecules linked by an N—H⋯O hydrogen bond. The mol­ecules show different conformations. In the first mol­ecule, the fused five- and six-membered ring system is almost perpendicular to the plane through the atoms forming the allyl group, as indicated by the dihedral angle of 85.1 (4)°. The dihedral angle with the methyl­benzene­sulfonamide group is 78.8 (1)°. On the other hand, in the second mol­ecule, the dihedral angles between the indazole plane and the allyl and methyl­benzene­sulfonamide groups are 80.3 (3) and 41.5 (1)°, respectively. In the crystal, mol­ecules are further linked by N—H⋯N and C—H⋯O hydrogen bonds, forming a three-dimensional network. PMID:24454264

  10. [N-methyl-D-aspartate receptor antibody encephalitis: value of immunomodulatory therapy].

    PubMed

    Le Moigno, L; Ternant, D; Paintaud, G; Thibault, G; Cloarec, S; Tardieu, M; Lagrue, E; Castelnau, P

    2014-06-01

    Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is little known to pediatricians and likely underdiagnosed. The child's vital and cognitive prognosis is at stake. The use of immunomodulatory drugs, such as rituximab has led to spectacular results, but many questions remain about its mode of action in this type of pathology. We report the case of a 6-year-old girl with no medical history, admitted for status epilepticus preceded by behavior symptoms and sleep disorders. Gradually, the child became bedridden, mute, and animated by predominantly orofacial dyskinesia. Examinations were normal (cerebrospinal fluid [CSF] analysis, brain MRI). The diagnosis was established by the presence of NMDA-R antibodies in the CSF. After exclusion of a tumor-associated syndrome, treatment was started initially by intravenous immunoglobulins, then by plasma exchange, and finally rituximab. The patient was cured with rituximab despite an unusually early recovery of the B-cell pool. Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a severe but potentially reversible neurologic disorder only recently described, even in childhood. It may be reversible without sequelae if diagnosed and treated early. The use of immunomodulatory therapy, such as rituximab seemingly improves the outcome. Immunological monitoring is needed to better understand its mechanism of action in autoimmune diseases of the nervous system in childhood. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  11. Improving oral bioavailability of cyclic peptides by N-methylation.

    PubMed

    Räder, Andreas F B; Reichart, Florian; Weinmüller, Michael; Kessler, Horst

    2018-06-01

    The renaissance of peptides in pharmaceutical industry results from their importance in many biological functions. However, low metabolic stability and the lack of oral availability of most peptides is a certain limitation. Whereas metabolic instability may be often overcome by development of small cyclic peptides containing d-amino acids, the very low oral availability of most peptides is a serious limitation for some medicinal applications. The situation is complicated because a twofold optimization - biological activity and oral availability - is required to overcome this problem. Moreover, most simple "rules" for achieving oral availability are not general and are applicable only to limited cases. Many structural modifications for increasing biological activities and metabolic stabilities of cyclic peptides have been described, of which N-alkylation is probably the most common. This mini-review focuses on the effects of N-methylation of cyclic peptides in strategies to optimize bioavailabilities. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Intricate Effects of α-Amino and Lysine Modifications on Arginine Methylation of the N-Terminal Tail of Histone H4.

    PubMed

    Fulton, Melody D; Zhang, Jing; He, Maomao; Ho, Meng-Chiao; Zheng, Y George

    2017-07-18

    Chemical modifications of the DNA and nucleosomal histones tightly control the gene transcription program in eukaryotic cells. The "histone code" hypothesis proposes that the frequency, combination, and location of post-translational modifications (PTMs) of the core histones compose a complex network of epigenetic regulation. Currently, there are at least 23 different types and >450 histone PTMs that have been discovered, and the PTMs of lysine and arginine residues account for a crucial part of the histone code. Although significant progress has been achieved in recent years, the molecular basis for the histone code is far from being fully understood. In this study, we investigated how naturally occurring N-terminal acetylation and PTMs of histone H4 lysine-5 (H4K5) affect arginine-3 methylation catalyzed by both type I and type II PRMTs at the biochemical level. Our studies found that acylations of H4K5 resulted in decreased levels of arginine methylation by PRMT1, PRMT3, and PRMT8. In contrast, PRMT5 exhibits an increased rate of arginine methylation upon H4K5 acetylation, propionylation, and crotonylation, but not upon H4K5 methylation, butyrylation, or 2-hydroxyisobutyrylation. Methylation of H4K5 did not affect arginine methylation by PRMT1 or PRMT5. There was a small increase in the rate of arginine methylation by PRMT8. Strikingly, a marked increase in the rate of arginine methylation was observed for PRMT3. Finally, N-terminal acetylation reduced the rate of arginine methylation by PRMT3 but had little influence on PRMT1, -5, and -8 activity. These results together highlight the underlying mechanistic differences in substrate recognition among different PRMTs and pave the way for the elucidation of the complex interplay of histone modifications.

  13. Causes and Consequences of Flavivirus RNA Methylation.

    PubMed

    Bradrick, Shelton S

    2017-01-01

    Mosquito-borne flaviviruses are important human pathogens that represent global threats to human health. The genomes of these positive-strand RNA viruses have been shown to be substrates of both viral and cellular methyltransferases. N 7 -methylation of the 5' cap structure is essential for infection whereas 2'- O -methylation of the penultimate nucleotide is required for evasion of host innate immunity. N 6 -methylation of internal adenosine nucleotides has also been shown to impact flavivirus infection. Here, I summarize recent progress made in understanding roles for methylation in the flavivirus life-cycle and discuss relevant emerging hypotheses.

  14. N-methyl-D-aspartate receptors and large conductance calcium-sensitive potassium channels inhibit the release of opioid peptides that induce mu-opioid receptor internalization in the rat spinal cord.

    PubMed

    Song, B; Marvizón, J C G

    2005-01-01

    Endogenous opioids in the spinal cord play an important role in nociception, but the mechanisms that control their release are poorly understood. To simultaneously detect all opioids able to activate the mu-opioid receptor, we measured mu-opioid receptor internalization in rat spinal cord slices stimulated electrically or chemically to evoke opioid release. Electrical stimulation of the dorsal horn in the presence of peptidase inhibitors produced mu-opioid receptor internalization in half of the mu-opioid receptor neurons. This internalization was rapidly abolished by N-methyl-D-aspartate (IC50=2 microM), and N-methyl-D-aspartate antagonists prevented this effect. mu-Opioid receptor internalization evoked by high K+ or veratridine was also inhibited by N-methyl-D-aspartate receptor activation. N-methyl-D-aspartate did not affect mu-opioid receptor internalization induced by exogenous endomorphins, confirming that the effect of N-methyl-D-aspartate was on opioid release. We hypothesized that this inhibition was mediated by large conductance Ca2+-sensitive K+ channels BK(Ca2+). Indeed, inhibition by N-methyl-D-aspartate was prevented by tetraethylammonium and by the selective BK(Ca2+) blockers paxilline, penitrem A and verruculogen. Paxilline did not increase mu-opioid receptor internalization in the absence of N-methyl-D-aspartate, indicating that it does not produce an increase in opioid release unrelated to the inhibition by N-methyl-d-aspartate. The BK(Ca2+) involved appears to be a subtype with slow association kinetics for iberiotoxin, which was effective only with long incubations. The BK(Ca2+) opener NS-1619 also inhibited the evoked mu-opioid receptor internalization, and iberiotoxin prevented this effect. We concluded that Ca2+ influx through N-methyl-D-aspartate receptors causes the opening of BK(Ca2+) and hyperpolarization in opioid-containing dorsal horn neurons, resulting in the inhibition of opioid release. Since mu-opioid receptors in the dorsal horn

  15. N-METHYL-d-ASPARTATE RECEPTORS AND LARGE CONDUCTANCE CALCIUM-SENSITIVE POTASSIUM CHANNELS INHIBIT THE RELEASE OF OPIOID PEPTIDES THAT INDUCE μ-OPIOID RECEPTOR INTERNALIZATION IN THE RAT SPINAL CORD

    PubMed Central

    SONG, B.; MARVIZÓN, J. C. G.

    2006-01-01

    Endogenous opioids in the spinal cord play an important role in nociception, but the mechanisms that control their release are poorly understood. To simultaneously detect all opioids able to activate the μ-opioid receptor, we measured μ-opioid receptor internalization in rat spinal cord slices stimulated electrically or chemically to evoke opioid release. Electrical stimulation of the dorsal horn in the presence of peptidase inhibitors produced μ-opioid receptor internalization in half of the μ-opioid receptor neurons. This internalization was rapidly abolished by N-methyl-d-aspartate (IC50=2 μM), and N-methyl-d-aspartate antagonists prevented this effect. μ-Opioid receptor internalization evoked by high K+ or veratridine was also inhibited by N-methyl-d-aspartate receptor activation. N-methyl-d-aspartate did not affect μ-opioid receptor internalization induced by exogenous endomorphins, confirming that the effect of N-methyl-d-aspartate was on opioid release. We hypothesized that this inhibition was mediated by large conductance Ca2+-sensitive K+ channels BK(Ca2+). Indeed, inhibition by N-methyl-d-aspartate was prevented by tetraethylammonium and by the selective BK(Ca2+) blockers paxilline, penitrem A and verruculogen. Paxilline did not increase μ-opioid receptor internalization in the absence of N-methyl-d-aspartate, indicating that it does not produce an increase in opioid release unrelated to the inhibition by N-methyl-d-aspartate. The BK(Ca2+) involved appears to be a subtype with slow association kinetics for iberiotoxin, which was effective only with long incubations. The BK(Ca2+) opener NS-1619 also inhibited the evoked μ-opioid receptor internalization, and iberiotoxin prevented this effect. We concluded that Ca2+ influx through N-methyl-d-aspartate receptors causes the opening of BK(Ca2+) and hyperpolarization in opioid-containing dorsal horn neurons, resulting in the inhibition of opioid release. Since μ-opioid receptors in the dorsal horn

  16. The pharmacokinetics of pyridostigmine and 3-hydroxy-N-methylpyridinium in the rat: dose-dependent effects after portal vein administration.

    PubMed Central

    Barber, H E; Bourne, G R; Calvey, T N; Muir, K T

    1975-01-01

    1 The elimination kinectis of [14C]-pyridostigmine iodine and [14-C-methyl]-3-hydroxypyridinium bromide (3-OH NMP) have been studied in the rat. 2 For pyridostigmine, at a given dose level, the fraction of the dose eliminated unchanged was reduced and the metabolite fraction was increased after portal vein administration when compared to jugular vein administration. This indicates that pyridostigmine is subject to metabolism during the first passage through the liver. 3 When doses of pyridostigmine 1.25 mumol/kg and higher were injected via the portal vein, the proportion excreted in urine as unchanged drug remained constant; in contrast, the percentage of the dose eliminated as the metabolite was significantly reduced. This indicates that a dose-dependent process is involved in the urinary excretion of 3-OH NMP. 4 This conclusion was supported by studies involving the portal and systemic venous injection of 3-OH NMP at different dose levels. After 4 h, approximately85% of the lowest dose was eliminated unchanged in ug this period. The proportion of the dose eliminated in urine was not related to the route of administration. 5 After the injection of pyridostigmine into the jugular vein, the initial rate of drug excretion fell rapidly for approximately 10 min; in contrast, after injection into the portal vein, the rate of excretion of the drug rose to a maximum at 30 minutes. This suggests that the hepatoportal system behaves as a distinct region during the distribution of this drug. PMID:173444

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

    PubMed Central

    Chattopadhyay, Kalicharan; Fenster, Erik; Grenning, Alexander J

    2012-01-01

    Summary The palladium-catalyzed nucleophilic substitution of (coumarinyl)methyl acetates is described. The reaction proceeds though a palladium π-benzyl-like complex and allows for many different types of C-, N-, and S-nucleophiles to be regioselectively added to the biologically active coumarin motif. This new method was utilized to prepare a 128-membered library of aminated coumarins for biological screening. PMID:23019448

  18. Clinically significant response to zolpidem in disorders of consciousness secondary to anti-N-methyl-D-aspartate receptor encephalitis in a teenager: a case report.

    PubMed

    Appu, Merveen; Noetzel, Michael

    2014-03-01

    Anti-N-methyl-d-aspartate receptor encephalitis has been associated with a prolonged neuropsychiatric phase that may last for months to years. We report the case of a 16-year-old girl who was diagnosed with anti-N-methyl-d-aspartate receptor encephalitis resulting from left ovarian mature teratoma 2 weeks after presentation with psychosis. Following tumor removal and immunotherapy, recovery from a minimally conscious state was accelerated significantly by zolpidem that was used for her sleep disturbance. Our patient was discharged home 8 weeks after admission with marked improvement in her neurological function. Zolpidem has been reported to improve arousal in disorders of consciousness but there are no previous reports of its benefit among patients with anti-N-methyl-d-aspartate receptor encephalitis. Zolpidem would be a reasonable consideration as an adjunctive treatment in anti-N-methyl-d-aspartate receptor encephalitis after tumor removal and immunotherapy to accelerate recovery and rehabilitation. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. DNA methylation on N6-adenine in mammalian embryonic stem cells

    PubMed Central

    Wu, Tao P.; Wang, Tao; Seetin, Matthew G.; Lai, Yongquan; Zhu, Shijia; Lin, Kaixuan; Liu, Yifei; Byrum, Stephanie D.; Mackintosh, Samuel G.; Zhong, Mei; Tackett, Alan; Wang, Guilin; Hon, Lawrence S.; Fang, Gang; Swenberg, James A.; Xiao, Andrew Z.

    2016-01-01

    It has been widely accepted that 5-methylcytosine is the only form of DNA methylation in mammalian genomes. Here we identify N6-methyladenine as another form of DNA modification in mouse embryonic stem cells. Alkbh1 encodes a demethylase for N6-methyladenine. An increase of N6-methyladenine levels in Alkbh1-deficient cells leads to transcriptional silencing. N6-methyladenine deposition is inversely correlated with the evolutionary age of LINE-1 transposons; its deposition is strongly enriched at young (<1.5 million years old) but not old (>6 million years old) L1 elements. The deposition of N6-methyladenine correlates with epigenetic silencing of such LINE-1 transposons, together with their neighbouring enhancers and genes, thereby resisting the gene activation signals during embryonic stem cell differentiation. As young full-length LINE-1 transposons are strongly enriched on the X chromosome, genes located on the X chromosome are also silenced. Thus, N6-methyladenine developed a new role in epigenetic silencing in mammalian evolution distinct from its role in gene activation in other organisms. Our results demonstrate that N6-methyladenine constitutes a crucial component of the epigenetic regulation repertoire in mammalian genomes. PMID:27027282

  20. Methyl-N-methylanthranilate, a pungent compound from Citrus reticulata Blanco leaves.

    PubMed

    Correa, Edwin; Quiñones, Winston; Echeverri, Fernando

    2016-01-01

    More analgesic compounds are needed in medicine against pain since the available drugs displayed secondary effects. Natural products are a source of molecules to develop new analgesics, using the information of plants, applied against pain, with effects such as pungency, tingling, and needle, due to their possible role in the central nervous system (NCS). Citrus reticulata Blanco (Rutaceae) leaves are usually bitten to flavor the mouth and possess this type effect in lips and tongues; due to this fact the structure of the bioctive compound could be the source of other types of analgesics. The objective of this study is to determine the causal agent of the pungent effect in mandarin essential oil. Mandarin essential oil was obtained and then purified by column chromatography. Each fraction was tested and pungency was detected only in the first fraction which was pure. The compound responsible for the pungency in the essential oils of leaves from Citrus reticulata (mandarin) was purified and the structure was assigned as methyl-N-methylanthranilate, on the basis of NMR 1D and 2D and MS. This substance corresponds to another type of molecule involving an antinociceptive effect. Terpenes are compounds found in essential oils. The compound responsible for the pungency of mandarin and other citrus leaves was isolated, and surprisingly it was identified as a methyl-N-methylanthranilate. This kind of molecules with this activity could be used to discover new analgesics in human therapy against pain.

  1. (BOSC) DOSE-RESPONSE MODELING FOR THE ASSESSMENT OF CUMULATIVE RISK DUE TO EXPOSURE TO N-METHYL CARBAMATE PRESTICIDES

    EPA Science Inventory

    THE US EPA'S N-METHYL CARBAMATE CUMULATIVE RISK ASSESSMENT (NMCRA) ASSESSES THE EFFECT ON ACETYLCHOLINE ESTERASE (AChE) ACTIVITY OF EXPOSURE TO 10 N-METHLY CARBAMATE (NMC)PESTICIDES THROUGH DIETARY, DRINKING WATER, AND RESIDENTIAL EXPOSURES. THESE DATA THUS INFORM, BUT DO NOT COM...

  2. Altered Levels of Zinc and N-methyl-D-aspartic Acid Receptor Underlying Multiple Organ Dysfunctions After Severe Trauma

    PubMed Central

    Wang, Guanghuan; Yu, Xiaojun; Wang, Dian; Xu, Xiaohu; Chen, Guang; Jiang, Xuewu

    2015-01-01

    Background Severe trauma can cause secondary multiple organ dysfunction syndrome (MODS) and death. Oxidative stress and/or excitatory neurotoxicity are considered as the final common pathway in nerve cell injuries. Zinc is the cofactor of the redox enzyme, and the effect of the excitatory neurotoxicity is related to N-methyl-D-aspartic acid receptor (NMDAR). Material/Methods We investigated the levels of zinc and brainstem NMDAR in a rabbit model of severe trauma. Zinc and serum biochemical profiles were determined. Immunohistochemistry was used to detect brainstem N-methyl-D-aspartic acid receptor 1 (NR1), N-methyl-D-aspartic acid receptor 2A (NR2A), and N-methyl-D-aspartic acid receptor 2B (NR2B) expression. Results Brain and brainstem Zn levels increased at 12 h, but serum Zn decreased dramatically after the trauma. NR1 in the brainstem dorsal regions increased at 6 h after injury and then decreased. NR2A in the dorsal regions decreased to a plateau at 12 h after trauma. The levels of NR2B were lowest in the death group in the brainstem. Serum zinc was positively correlated with NR2A and 2B and negatively correlated with zinc in the brain. Correlations were also found between the brainstem NR2A and that of the dorsal brainstem, as well as between brainstem NR2A and changes in NR2B. There was a negative correlation between zinc and NR2A. Conclusions Severe trauma led to an acute reduction of zinc enhancing oxidative stress and the changes of NMDAR causing the neurotoxicity of the nerve cells. This may be a mechanism for the occurrence of MODS or death after trauma. PMID:26335029

  3. Topographic Quantification of the Transcorneal Electrical Stimulation (TES)-Induced Protective Effects on N-Methyl-N-Nitrosourea-Treated Retinas.

    PubMed

    Tao, Ye; Chen, Tao; Liu, Zhong-Yu; Wang, Li-Qiang; Xu, Wei-Wei; Qin, Li-Min; Peng, Guang-Hua; Yi-Fei, Huang

    2016-09-01

    To quantify the transcorneal electrical stimulation (TES)-induced effects on regional photoreceptors and visual signal pathway of N-methyl-N-nitrosourea (MNU)-treated retinas via topographic measurements. N-methyl-N-nitrosourea-administered mice received TES or sham stimulations and were subsequently subjected to electroretinography (ERG), multielectrode array (MEA), and histologic and immunohistochemistry examinations. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses were also performed to determine the mRNA levels of Bax, Bcl-2, Calpain-2, Caspase-3, brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF). Amplitudes of ERG b-wave in the TES-treated mice were significantly larger than those in the sham controls (P < 0.01). Microelectrode array examination revealed that the photoreceptors in TES-treated retina were efficiently preserved (P < 0.01). Morphologic measurements showed that the central retina region was more consolidated than the other areas in the TES-treated mice. Together with the disproportionate distribution of immunostaining in retinal flat mounts, these findings indicated that different rescuing kinetics existed among regional photoreceptors. Compared with the sham controls, a significantly increased signal-to-noise ratio was also found in the TES-treated mice (TES100: 2.02 ± 1.12; TES200: 4.42 ± 1.51; sham: 0.25 ± 0.13; P < 0.01). Moreover, qRT-PCR measurements suggested that the altered expression of several apoptotic factors and neurotrophic cytokines was correlated with TES-induced protection. Regional photoreceptors in the MNU-administered retinas exhibit different sensitivities to TES. Transcorneal electrical stimulation is capable of ameliorating MNU-induced photoreceptor degeneration and rectifying abnormalities in the inner visual signal pathways.

  4. Effects of Phase Separation Behavior on Morphology and Performance of Polycarbonate Membranes

    PubMed Central

    Idris, Alamin; Man, Zakaria; Maulud, Abdulhalim S.; Khan, Muhammad Saad

    2017-01-01

    The phase separation behavior of bisphenol-A-polycarbonate (PC), dissolved in N-methyl-2-pyrrolidone and dichloromethane solvents in coagulant water, was studied by the cloud point method. The respective cloud point data were determined by titration against water at room temperature and the characteristic binodal curves for the ternary systems were plotted. Further, the physical properties such as viscosity, refractive index, and density of the solution were measured. The critical polymer concentrations were determined from the viscosity measurements. PC/NMP and PC/DCM membranes were fabricated by the dry-wet phase inversion technique and characterized for their morphology, structure, and thermal stability using field emission scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis, respectively. The membranes’ performances were tested for their permeance to CO2, CH4, and N2 gases at 24 ± 0.5 °C with varying feed pressures from 2 to 10 bar. The PC/DCM membranes appeared to be asymmetric dense membrane types with appreciable thermal stability, whereas the PC/NMP membranes were observed to be asymmetric with porous structures exhibiting 4.18% and 9.17% decrease in the initial and maximum degradation temperatures, respectively. The ideal CO2/N2 and CO2/CH4 selectivities of the PC/NMP membrane decreased with the increase in feed pressures, while for the PC/DCM membrane, the average ideal CO2/N2 and CO2/CH4 selectivities were found to be 25.1 ± 0.8 and 21.1 ± 0.6, respectively. Therefore, the PC/DCM membranes with dense morphologies are appropriate for gas separation applications. PMID:28379173

  5. Crystal structure of N'-[(E)-(4-chloro-phen-yl)(phen-yl)methyl-idene]-4-methyl-benzene-sulfono-hydrazide.

    PubMed

    Balaji, J; Prabu, S; Xavier, J J F; Srinivasan, P

    2015-01-01

    The title compound, C20H17ClN2O2S, was obtained by a condensation reaction between 4-chloro-benzo-phenone and tosyl hydrazide. The plane of the methyl-substituted benzene ring forms dihedral angles of 20.12 (12) and 78.43 (13)° with those of the chlorine-substituted benzene ring and the benzene ring, respectively, with the last two rings forming a dihedral angle of 67.81 (13)°. The chlorine substituent was also found to be 0.868 (2):0.132 (2) disordered over these two rings. In the crystal, mol-ecules are linked through pairs of N-H⋯O hydrogen bonds, giving centrosymmetric cyclic dimers [graph set R 2 (2)(8)], which are linked by weak C-H⋯O and C-H⋯Cl inter-actions into a chain structure which extends along the a-axis direction.

  6. (2-{[2-(1H-Benzimidazol-2-yl-κN 3)phen­yl]imino­methyl-κN}-5-methyl­phenolato-κO)chloridozinc(II)

    PubMed Central

    Eltayeb, Naser Eltaher; Teoh, Siang Guan; Chantrapromma, Suchada; Fun, Hoong-Kun

    2011-01-01

    In the title mononuclear complex, [Zn(C21H16N3O)Cl], the ZnII ion is coordinated in a distorted tetra­hedral geometry by two benzimidazole N atoms and one phenolate O atom from the tridentate Schiff base ligand and a chloride ligand. The benzimidazole ring system forms dihedral angles of 26.68 (9) and 56.16 (9)° with the adjacent benzene ring and the methyl­phenolate group benzene ring, respectively. In the crystal, mol­ecules are linked by N—H⋯Cl hydrogen bonds into chains along [100]. Furthermore, weak C—H⋯O and C—H⋯π inter­actions, in addition to π–π inter­actions with centroid–centroid distances in the range 3.5826 (13)–3.9681 (13) Å, are also observed. PMID:22065469

  7. Gestational intake of methyl donors and global LINE-1 DNA methylation in maternal and cord blood: prospective results from a folate-replete population.

    PubMed

    Boeke, Caroline E; Baccarelli, Andrea; Kleinman, Ken P; Burris, Heather H; Litonjua, Augusto A; Rifas-Shiman, Sheryl L; Tarantini, Letizia; Gillman, Matthew

    2012-03-01

    Maternal diet affects offspring DNA methylation in animal models, but evidence from humans is limited. We investigated the extent to which gestational intake of methyl donor nutrients affects global DNA methylation in maternal and umbilical cord blood. Among mother-infant pairs in Project Viva, a folate-replete US population, we estimated maternal intakes of vitamin B12, betaine, choline, folate, cadmium, zinc and iron periconceptionally and during the second trimester. We examined associations of these nutrients with DNA methylation, measured as %5-methyl cytosines (%5mC) in Long Interspersed Nuclear Element-1 (LINE-1), in first trimester (n = 830) and second trimester (n = 671) maternal blood and in cord blood at delivery (n = 516). Cord blood methylation was higher for male than female infants {mean [standard deviation (SD)] 84.8 [0.6] vs. 84.4 [0.7]%}. In the multivariable-adjusted model, maternal intake of methyl donor nutrients periconceptionally and during the second trimester of pregnancy was not positively associated with first trimester, second trimester or cord blood LINE-1 methylation. Periconceptional betaine intake was inversely associated with cord blood methylation [regression coefficient = -0.08% (95% confidence interval (CI): -0.14,-0.01)] but this association was attenuated after adjustment for dietary cadmium, which itself was directly associated with first trimester methylation and inversely associated with cord blood methylation. We also found an inverse association between periconceptional choline [-0.10%, 95% CI: -0.17,-0.03 for each SD (~63 mg/day)] and cord blood methylation in males only. In this folate-replete population, we did not find positive associations between intake of methyl donor nutrients during pregnancy and DNA methylation overall, but among males, higher early pregnancy intakes of choline were associated with lower cord blood methylation.

  8. Vanillin as a modulator agent in SMART test: inhibition in the steps that precede N-methyl-N-nitrosourea-, N-ethyl-N-nitrosourea-, ethylmethanesulphonate- and bleomycin-genotoxicity.

    PubMed

    Sinigaglia, Marialva; Lehmann, Maurício; Baumgardt, Paula; do Amaral, Viviane Souza; Dihl, Rafael Rodrigues; Reguly, Maria Luíza; de Andrade, Heloísa Helena Rodrigues

    2006-09-05

    Vanillin (VA), the world's major flavoring compound used in food industry and confectionery products - that has antimutagenic and anticarcinogenic activity against a variety of mutagenic/carcinogenic agents - was tested for the interval between the formation of premutational lesion and it is finalization as a DNA lesion. The overall findings using co-treatment protocols in SMART test suggest that VA can lead to a significant protection against the general genotoxicity of ethylmethanesulphonate (EMS), N-ethyl-N-nitrosourea (ENU), N-methyl-N-nitrosourea (MNU) and bleomycin sulphate (BLEO). Considering MNU, ENU and EMS the desmutagenic activity observed could result from VA-stimulation of detoxification, via induction of glutathione S-transferase. However, the protector effect related to BLEO could be attributed to its powerful scavenger ability, which has the potential to prevent oxidative damage induced by BLEO.

  9. Endogenous 5-methylcytosine protects neighboring guanines from N7 and O6-methylation and O6-pyridyloxobutylation by the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

    PubMed

    Ziegel, Rebecca; Shallop, Anthony; Upadhyaya, Pramod; Jones, Roger; Tretyakova, Natalia

    2004-01-20

    All CG dinucleotides along exons 5-8 of the p53 tumor suppressor gene contain endogenous 5-methylcytosine (MeC). These same sites (e.g., codons 157, 158, 245, 248, and 273) are mutational hot spots in smoking-induced lung cancer. Several groups used the UvrABC endonuclease incision assay to demonstrate that methylated CG dinucleotides of the p53 gene are the preferred binding sites for the diol epoxides of bay region polycyclic aromatic hydrocarbons (PAH). In contrast, effects of endogenous cytosine methylation on the distribution of DNA lesions induced by tobacco-specific nitrosamines, e.g., 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), have not been elucidated. In the work presented here, a stable isotope labeling HPLC-ESI-MS/MS approach was employed to analyze the reactivity of the N7 and O6 positions of guanines within hemimethylated and fully methylated CG dinucleotides toward NNK-derived methylating and pyridyloxobutylating species. 15N3-labeled guanine bases were placed within synthetic DNA sequences representing endogenously methylated p53 codons 154, 157, and 248, followed by treatment with acetylated precursors to NNK diazohydroxides. HPLC-ESI-MS/MS analysis was used to determine the relative yields of N7- and O6-guanine adducts at the 15N3-labeled position. In all cases, the presence of MeC inhibited the formation of N7-methylguanine, O6-methylguanine, and O6-pyridyloxobutylguanine at a neighboring G, with the greatest decrease observed in fully methylated dinucleotides and at guanines preceded by MeC. Furthermore, the O6-Me-dG/N7-Me-G molar ratios were decreased in the presence of the 5'-neighboring MeC, suggesting that the observed decline in O6-alkylguanine adduct yields is, at least partially, a result of an altered reactivity pattern in methylated CG dinucleotides. These results indicate that, unlike N2-guanine adducts of PAH diol epoxides, NNK-induced N7- and O6-alkylguanine adducts are not preferentially formed at the endogenously

  10. Benchmark Dose Analysis from Multiple Datasets: The Cumulative Risk Assessment for the N-Methyl Carbamate Pesticides

    EPA Science Inventory

    The US EPA’s N-Methyl Carbamate (NMC) Cumulative Risk assessment was based on the effect on acetylcholine esterase (AChE) activity of exposure to 10 NMC pesticides through dietary, drinking water, and residential exposures, assuming the effects of joint exposure to NMCs is dose-...

  11. Photophysical and Photochemical Properties of Naturally Occurring normelinonine F and Melinonine F Alkaloids and Structurally Related N(2)- and/or N(9)-methyl-β-carboline Derivatives.

    PubMed

    Rasse-Suriani, Federico A O; García-Einschlag, Fernando S; Rafti, Matías; Schmidt De León, Tobías; David Gara, Pedro M; Erra-Balsells, Rosa; Cabrerizo, Franco M

    2018-01-01

    In the present work, we have synthesized and fully characterized the photophysical and photochemical properties of a selected group of N-methyl-β-carboline derivatives (9-methyl-β-carbolines and iodine salts of 2-methyl- and 2,9-dimethyl-β-carbolinium) in aqueous solutions, in the pH range 4.0-14.5. Moreover, despite the quite extensive studies reported in the literature regarding the overall photophysical behavior of N-unsubstituted βCs, this work constitutes the first full and unambiguous characterization of anionic species of N-unsubstituted βCs (norharmane, harmane and harmine), present in aqueous solution under highly alkaline conditions (pH > 13.0). Acid dissociation constants (K a ), thermal stabilities, room temperature UV-visible absorption and fluorescence emission and excitation spectra, fluorescence quantum yields (Ф F ) and fluorescence lifetimes (τ F ), as well as quantum yields of singlet oxygen production (Ф Δ ) have been measured for all the studied compounds. Furthermore, for the first time to our knowledge, chemometric techniques (MCR-ALS and PARAFAC) were applied on these systems, providing relevant information about the equilibria and species involved. The impact of all the foregoing observations on the biological role, as well as the potential biotechnological applications of these compounds, is discussed. © 2017 The American Society of Photobiology.

  12. A hit to lead discovery of novel N-methylated imidazolo-, pyrrolo-, and pyrazolo-pyrimidines as potent and selective mTOR inhibitors.

    PubMed

    Lee, Wendy; Ortwine, Daniel F; Bergeron, Philippe; Lau, Kevin; Lin, Lichuan; Malek, Shiva; Nonomiya, Jim; Pei, Zhonghua; Robarge, Kirk D; Schmidt, Stephen; Sideris, Steve; Lyssikatos, Joseph P

    2013-09-15

    A series of N-7-methyl-imidazolopyrimidine inhibitors of the mTOR kinase have been designed and prepared, based on the hypothesis that the N-7-methyl substituent on imidazolopyrimidine would impart selectivity for mTOR over the related PI3Kα and δ kinases. The corresponding N-Me substituted pyrrolo[3,2-d]pyrimidines and pyrazolo[4,3-d]pyrimidines also show potent mTOR inhibition with selectivity toward both PI3α and δ kinases. The most potent compound synthesized is pyrazolo[4,3-d]pyrimidine 21c. Compound 21c shows a Ki of 2 nM against mTOR inhibition, remarkable selectivity (>2900×) over PI3 kinases, and excellent potency in cell-based assays. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Documents for SBAR Panel: Methylene Chloride and N-Methylpyrrolidone; Regulation of Certain Uses Under TSCA Section 6(a)

    EPA Pesticide Factsheets

    SBAR panel to to address the risks resulting from the manufacture, import, processing, distribution in commerce, and use of chemicals, as well as any manner or method of disposal of chemicals: n-methylpyrrolidone (NMP) and methylene chloride

  14. 40 CFR 180.451 - Tribenuron methyl; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... residues of the herbicide tribenuron methyl and its metabolites and degradates in or on the commodities in... defined in § 180.1(l) are established for residues of the herbicide tribenuron methyl (methyl-2-[[[[N-(4...

  15. 40 CFR 180.451 - Tribenuron methyl; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... residues of the herbicide tribenuron methyl and its metabolites and degradates in or on the commodities in... defined in § 180.1(l) are established for residues of the herbicide tribenuron methyl (methyl-2-[[[[N-(4...

  16. 40 CFR 180.451 - Tribenuron methyl; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... residues of the herbicide tribenuron methyl and its metabolites and degradates in or on the commodities in... defined in § 180.1(l) are established for residues of the herbicide tribenuron methyl (methyl-2-[[[[N-(4...

  17. Developmental regulation of N-methyl-D-aspartate- and kainate-type glutamate receptor expression in the rat spinal cord

    NASA Technical Reports Server (NTRS)

    Stegenga, S. L.; Kalb, R. G.

    2001-01-01

    Spinal motor neurons undergo experience-dependent development during a critical period in early postnatal life. It has been suggested that the repertoire of glutamate receptor subunits differs between young and mature motor neurons and contributes to this activity-dependent development. In the present study we examined the expression patterns of N-methyl-D-aspartate- and kainate-type glutamate receptor subunits during the postnatal maturation of the spinal cord. Young motor neurons express much higher levels of the N-methyl-D-aspartate receptor subunit NR1 than do adult motor neurons. Although there are eight potential splice variants of NR1, only a subgroup is expressed by motor neurons. With respect to NR2 receptor subunits, young motor neurons express NR2A and C, while adult motor neurons express only NR2A. Young motor neurons express kainate receptor subunits GluR5, 6 and KA2 but we are unable to detect these or any other kainate receptor subunits in the adult spinal cord. Other spinal cord regions display a distinct pattern of developmental regulation of N-methyl-D-aspartate and kainate receptor subunit expression in comparison to motor neurons. Our findings indicate a precise spatio-temporal regulation of individual subunit expression in the developing spinal cord. Specific combinations of subunits in developing neurons influence their excitable properties and could participate in the emergence of adult neuronal form and function.

  18. N-heterocyclic carbene-catalyzed tandem aza-benzoin/Michael reactions: on site reversal of the reactivity of N-Boc imines.

    PubMed

    Wu, Ke-Jia; Li, Gong-Qiang; Li, Yi; Dai, Li-Xin; You, Shu-Li

    2011-01-07

    A tandem NHC-catalyzed aza-benzoin/Michael reaction has been developed as a method to efficiently produce dihydroindenones and pyrrolidinone-containing tricycles. The novel reaction pattern involves tert-butyl aryl(tosyl)methylcarbamates reacting as both electrophile and nucleophile on the same carbon.

  19. Plasma trimethylamine N-oxide concentration is associated with choline, phospholipids, and methyl metabolism.

    PubMed

    Obeid, Rima; Awwad, Hussain M; Rabagny, Yannick; Graeber, Stefan; Herrmann, Wolfgang; Geisel, Juergen

    2016-03-01

    Elevated plasma concentrations of the gut bacteria choline metabolite trimethylamine N-oxide (TMAO) are associated with atherosclerosis. However, the determinants of TMAO in humans require additional assessment. We examined cardiometabolic risk factors and pathways associated with TMAO concentrations in humans. A total of 283 individuals (mean ± SD age: 66.7 ± 9.0 y) were included in this observational study. Plasma concentrations of trimethylamine, TMAO, choline, lipids, phospholipids, and methyl metabolites were measured. Study participants were divided into 4 groups by median concentrations of TMAO and choline (4.36 and 9.7 μmol/L, respectively). Compared with the group with TMAO and choline concentrations that were less than the median (n = 82), the group with TMAO and choline concentrations that were at least the median (n = 83) was older and had lower high-density lipoprotein (HDL) cholesterol, phospholipids, and methylation potential, higher creatinine, betaine, S-adenosylhomocysteine (SAH), and S-adenosylmethionine (SAM), and higher percentages of men and subjects with diabetes. The difference in plasma TMAO concentrations between men and women (7.3 ± 10.0 compared with 5.4 ± 5.6 μmol/L, respectively) was NS after adjustment for age and creatinine (P = 0.455). The TMAO:trimethylamine ratio was higher in men (P < 0.001). Diabetes was associated with significantly higher plasma TMAO concentration (8.6 ± 12.2 compared with 5.4 ± 5.2 μmol/L) even after adjustments. Sex and diabetes showed an interactive effect on trimethylamine concentrations (P = 0.010) but not on TMAO concentrations (P = 0.950). Positive determinants of TMAO in a stepwise regression model that applied to the whole group were SAH, trimethylamine, choline, and female sex, whereas plasma phosphatidylcholine was a negative determinant. High TMAO and choline concentrations are associated with an advanced cardiometabolic risk profile. Diabetes is related to higher plasma TMAO

  20. Synthesis of N-oleyl O-sulfate chitosan from methyl oleate with O-sulfate chitosan as edible film material

    NASA Astrophysics Data System (ADS)

    Daniel; Sihaloho, O.; Saleh, C.; Magdaleni, A. R.

    2018-04-01

    The research on the synthesis of N-oleyl O-sulfate chitosan through sulfonation reaction on chitosan with ammonium sulfate and followed by amidation reaction using methyl oleate has been done. In this study, chitosan was chemically modified into N-oleyl O-sulfatechitosan as an edible film making material. N-oleyl O-sulfate chitosan was synthesized by reaction between methyl oleate and O-sulfate chitosan. Wherein the depleted chitosan of O-sulfate chitosan into O-sulfate chitosan was obtained by reaction of sulfonation between ammonium sulfate and chitosan aldimine. While chitosan aldimine was obtained through reaction between chitosan with acetaldehyde. The structure of N-oleyl O-sulfate chitosan was characterized by FT-IR analysis which showed vibration uptake of C-H sp3 group, S=O group, and carbonyl group C=O of the ester. The resulting of N-oleyl O-sulfate chitosan yielded a percentage of 93.52%. Hydrophilic-Lipophilic Balance (HLB) test results gave a value of 6.68. In the toxicity test results of N-oleyl O-sulfate chitosan obtained LC50 value of 3738.4732 ppm. In WVTR (Water Vapor Transmission Rate) test results for chitosan film was 407.625 gram/m2/24 hours and N-oleylO-sulfate chitosan film was 201.125 gram/m2/24 hours.

  1. Fabrication of Polyimide-Matrix/Carbon and Boron-Fiber Tape

    NASA Technical Reports Server (NTRS)

    Belvin, Harry L.; Cano, Roberto J.; Treasure, Monte; Shahood, Thomas W.

    2007-01-01

    The term HYCARB denotes a hybrid composite of polyimide matrices reinforced with carbon and boron fibers. HYCARB and an improved process for fabricating dry HYCARB tapes have been invented in a continuing effort to develop lightweight, strong composite materials for aerospace vehicles. Like other composite tapes in this line of development, HYCARB tapes are intended to be used to build up laminated structures having possibly complex shapes by means of automated tow placement (ATP) - a process in which a computer-controlled multiaxis machine lays down prepreg tape or tows. The special significance of the present process for making dry HYCARB for ATP is that it contributes to the reduction of the overall cost of manufacturing boron-reinforced composite-material structures while making it possible to realize increased compression strengths. The present process for making HYCARB tapes incorporates a "wet to dry" process developed previously at Langley Research Center. In the "wet to dry" process, a flattened bundle of carbon fiber tows, pulled along a continuous production line between pairs of rollers, is impregnated with a solution of a poly(amide acid) in N-methyl-2-pyrrolidinone (NMP), then most of the NMP is removed by evaporation in hot air. In the present case, the polyamide acid is, more specifically, that of LaRC. IAX (or equivalent) thermoplastic polyimide, and the fibers are, more specifically, Manganite IM7 (or equivalent) polyacrylonitrile- based carbon filaments that have a diameter of 5.2 m and are supplied in 12,000-filament tows. The present process stands in contrast to a prior process in which HYCARB tape was made by pressing boron fibers into the face of a wet carbon-fiber/ poly(amide acid) prepreg tape . that is, a prepreg tape from which the NMP solvent had not been removed. In the present process, one or more layer(s) of side-by-side boron fibers are pressed between dry prepreg tapes that have been prepared by the aforementioned gwet to dry h

  2. Effect of thiopental sodium on N-methyl-D-aspartate-gated currents.

    PubMed

    Liu, Hongliang; Dai, Tijun; Yao, Shanglong

    2006-05-01

    N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex (PFC) are closely related with the excitability of pyramidal neurons and PFC function. As the effect of thiopental sodium on the central nervous system may partly result from the inhibition of PFC NMDA receptors, we investigated the effect of thiopental sodium with different concentrations on NMDA-gated currents in acutely dissociated rat PFC pyramidal neurons. We sought to determine whether thiopental sodium inhibits NMDA receptor function. Three to four week old male Sprague-Dawley rats were sacrificed and the PFC was dissected. Pyramidal neurons from the PFC were prepared and standard whole-cell patch clamp recordings were performed. Escalating concentrations from 3-1000 microM NMDA were applied 100 microm from the pyramidal cells, and the concentration in the effect compartment related to 50% effect (EC50) of NMDA was determined for the ensuing experiments. One hundred microM NMDA alone (control) or NMDA with different concentrations (10-1000 microM) of thiopental sodium were applied. After the inhibitory concentration, in 50% of NMDA effect (IC50) of thiopental sodium was established this IC50 and NMDA 3-1000 microM were applied 100 microm from the pyramidal cells. The EC50 value of NMDA under the effect of IC50 thiopental sodium was determined. N-methyl-D-aspartate induced inward currents in a concentration-dependent manner, which were completely antagonized by 50 microM AP5. The maximal amplitude of NMDA-induced current was 1.15 +/- 0.27 nA. The EC50 of NMDA was 53.6 +/- 12.4 microM. The NMDA (100 microM)-gated current was inhibited by thiopental sodium in a concentration-dependent manner, and the IC50 of thiopental sodium was 33.6 +/- 6.1 microM. Under the effect of 33.6 microM thiopental sodium, the maximal amplitude of NMDA-induced current was 0.87 +/- 0.17 nA. The concentration-response curve of NMDA was shifted rightwards. The EC50 of NMDA was 128 +/- 15 microM, which was greater than that

  3. N-methyl-D-aspartate neurotoxicity in hippocampal slices: protection by aniracetam.

    PubMed

    Pizzi, M; Consolandi, O; Memo, M; Spano, P

    1995-03-14

    Aniracetam, a drug known to elicit cognition enhancing properties in both animals and humans, was found to counteract the neurotoxicity induced by excitatory amino acids in primary cultures of cerebellar neurons. We report here that aniracetam prevents the neurotoxic effect induced by N-methyl-D-aspartate (NMDA) in rat hippocampal slices. Time-course experiments showed that the aniracetam-induced neuroprotection does not require preincubation of the slices with the drug. Maximal effective concentration of aniracetam was 10 microM. Since the NMDA-mediated cell death in hippocampal slices is considered a valuable experimental model of ischemia, these results suggest a possible novel therapeutic application for aniracetam.

  4. Radical-mediated enzymatic methylation: a tale of two SAMS.

    PubMed

    Zhang, Qi; van der Donk, Wilfred A; Liu, Wen

    2012-04-17

    Methylation is an essential and ubiquitous reaction that plays an important role in a wide range of biological processes. Most biological methylations use S-adenosylmethionine (SAM) as the methyl donor and proceed via an S(N)2 displacement mechanism. However, researchers have discovered an increasing number of methylations that involve radical chemistry. The enzymes known to catalyze these reactions all belong to the radical SAM superfamily. This family of enzymes utilizes a specialized [4Fe-4S] cluster for reductive cleavage of SAM to yield a highly reactive 5'-deoxyadenosyl (dAdo) radical. Radical chemistry is then imposed on a variety of organic substrates, leading to a diverse array of transformations. Until recently, researchers had not fully understood how these enzymes employ radical chemistry to mediate a methyl transfer reaction. Sequence analyses reveal that the currently identified radical SAM methyltransferases (RSMTs) can be grouped into three classes, which appear distinct in protein architecture and mechanism. Class A RSMTs mainly include the rRNA methyltransferases RlmN and Cfr from various origins. As exemplified by Escherichia coli RlmN, these proteins have a single canonical radical SAM core domain that includes an (βα)(6) partial barrel most similar to that of pyruvate formate lyase-activase. The exciting recent studies on RlmN and Cfr are beginning to provide insights into the intriguing chemistry of class A RSMTs. These enzymes utilize a methylene radical generated on a unique methylated cysteine residue. However, based on the variety of substrates used by the other classes of RSMTs, alternative mechanisms are likely to be discovered. Class B RSMTs contain a proposed N-terminal cobalamin binding domain in addition to a radical SAM domain at the C-terminus. This class of proteins methylates diverse substrates at inert sp(3) carbons, aromatic heterocycles, and phosphinates, possibly involving a cobalamin-mediated methyl transfer process. Class

  5. Synthesis of methyl 2-O-alpha-D-mannopyranosyl-alpha-D-talopyranoside and methyl 2-O-alpha-D-talopyranosyl-alpha-D-talopyranoside.

    PubMed

    Jain, R K; Dubey, R; Abbas, S A; Matta, K L

    1987-03-15

    Treatment of methyl 3-O-benzyl-2-O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl)-alpha-D- mannopyranoside (1) with tert-butyldiphenylsilyl chloride in N,N-dimethylformamide afforded methyl 3-O-benzyl-6-O-tert-butyldiphenylsilyl-2-O-(2,3,4,6-tetra-O-acetyl -alpha-D- mannopyranosyl)-alpha-D-mannopyranoside (2). Oxidation of 2 with pyridinium chlorochromate, followed by reduction of the carbonyl group, and subsequent O-deacetylation afforded methyl 3-O-benzyl-6-O-tert-butyldiphenylsilyl-2-O-alpha-D-mannopyranosyl- alpha-D- talopyranoside (5). Cleavage of the tert-butyldiphenylsilyl group of 5 with tetrabutylammonium fluoride in oxolane, followed by hydrogenolysis, gave methyl 2-O-alpha-D-mannopyranosyl-alpha-D-talopyranoside (7). O-Deacetylation of 1 gave methyl 3-O-benzyl-2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside (8). Treatment of 8 with tert-butyldiphenylsilyl chloride afforded a 6,6'-disilyl derivative, which was converted into a 2',3'-O-isopropylidene derivative, and then further oxidized with pyridinium chlorochromate. The resulting diketone was reduced and removal of the protecting groups gave methyl 2-O-alpha-D-talopyranosyl-alpha-D-talopyranoside (15). The structures of both 7 and 15 were established by 13C-n.m.r. spectroscopy.

  6. How does methylation suppress the electron-induced decomposition of 1-methyl-nitroimidazoles?

    NASA Astrophysics Data System (ADS)

    Kossoski, F.; Varella, M. T. do N.

    2017-10-01

    The efficient decomposition of nitroimidazoles (NIs) by low energy electrons is believed to underlie their radiosensitizing properties. Recent dissociative electron attachment (DEA) measurements showed that methylation at the N1 site unexpectedly suppresses the electron-induced reactions in 4(5)-NI. We report theoretical results that provide a clear interpretation of that astounding finding. Around 1.5 eV, DEA reactions into several fragments are initiated by a π* resonance, not considered in previous studies. The autoionization lifetime of this anion state, which limits the predissociation dynamics, is considerably shorter in the methylated species, thereby suppressing the DEA signals. On the other hand, the lifetime of the π* resonance located around 3 eV is less affected by methylation, which explains why DEA is still observed at these energies. Our results demonstrate how even a simple methylation can significantly modify the probabilities for DEA reactions, which may be significant for NI-based cancer therapy.

  7. Phenylethynyl Phthalic Anhydride

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M. (Inventor); Smith, Joseph G., Jr. (Inventor)

    1997-01-01

    Controlled molecular weight PhenylEthynyl Terminated Imide oligomers (PETIs) have been prepared by the cyclodehydration of precursor phenylethynyl terminated amic acid oligomers. Amino terminated amic acid oligomers are prepared from the reaction of dianhydride(s) with an excess of diamine(s) and subsequently endcapped with PhenylEthynyl Phthalic Anhydride(s) (PEPA). The polymerizations are carried out in polar aprotic solvents such as N-methyl-2pyrrolidinone or N N-dimethylacetamide under nitrogen at room temperature. The amic acid oligomers are subsequently cyclodehydrated either thermally or chemically to the corresponding imide oligomers. Direct preparation of PETIs from the reaction of dianhydride(s) with an excess of diamine(s) and endcapped with phenylethynyl phthalic anhydride(s) has been performed in m-cresol. Phenylethynyl phthalic anhydrides are synthesized by the palladium catalyzed reaction of phenylacetylene with bromo substituted phthalic anhydrides in triethylamine. These new materials exhibit excellent properties and are potentially useful as adhesives, coatings, films, moldings and composite matrices.

  8. Imide Oligomers Endcapped with Phenylethynl Phthalic Anhydrides and Polymers Therefrom

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M. (Inventor); Smith, Joseph G., Jr. (Inventor)

    1998-01-01

    Controlled molecular weight phenylethynyl terminated imide oligomers (PETIs) have been prepared by the cyclodehydration of precursor phenylethynyl terminated amic acid oligomers. Amino terminated amic acid oligomers are prepared from the reaction of dianhydride(s) with an excess of diamine(s) and subsequently endcapped with phenylethynyl phthalic anhydride(s) (PEPA). The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N.N-dimethylacetamide under nitrogen at room temperature. The amic acid oligomers are subsequently cyclodehydrated either thermally or cheznicauy to the corresponding imide oligomers. Direct preparation of PETIs from the reaction of dianhydxide(s) with an excess of diamine(s) and endcapped with phenylethynyl phthalic anhydride(s) has been performed in m-cresol. Phenylethynyl phthalic anhydrides are synthesized by the palladium catalyzed reaction of phenylacetylene with bromo substituted phthalic anhydrides in triethylamine. These new materials exhibit excellent properties and are potentially useful as adhesives, coatings, films, moldings and composite matrices.

  9. Imide oligomers endcapped with phenylethynyl phthalic anhydrides and polymers therefrom

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M. (Inventor); Smith, Jr., Joseph G. (Inventor)

    1996-01-01

    Controlled molecular weight phenylethynyl terminated imide oligomers (PETIs) have been prepared by the cyclodehydration of precursor phenylethynyl terminated amic acid oligomers. Amino terminated amic acid oligomers are prepared from the reaction of dianhydride(s) with an excess of diamine(s) and subsequently endcapped with phenylethynyl phthalic anhydride(s) (PEPA). The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide under nitrogen at room temperature. The amic acid oligomers are subsequently cyclodehydrated either thermally or chemically to the corresponding imide oligomers. Direct preparation of PETIs from the reaction of dianhydride(s) with an excess of diamine(s) and endcapped with phenylethynyl phthalic anhydride(s) has been performed in m-cresol. Phenylethynyl phthalic anhydrides are synthesized by the palladium catalyzed reaction of phenylacetylene with bromo substituted phthalic anhydrides in triethylamine. These new materials exhibit excellent properties and are potentially useful as adhesives, coatings, films, moldings and composite matrices.

  10. Geissoschizine methyl ether N-oxide, a new alkaloid with antiacetylcholinesterase activity from Uncaria rhynchophylla.

    PubMed

    Jiang, Wei-Wei; Su, Jia; Wu, Xing-De; He, Juan; Peng, Li-Yan; Cheng, Xiao; Zhao, Qin-Shi

    2015-01-01

    Geissoschizine methyl ether N-oxide, a new oxindole alkaloid, along with 14 known alkaloids, was isolated from the aerial part of Uncaria rhynchophylla. Their structures were identified by comprehensive spectral methods, including 2D NMR experiments, and confirmed by comparing with the literature data. In vitro acetylcholinesterase (AChE) inhibitory activity assay showed that the new compound exhibited anti-AChE activity with IC₅₀ value of 23.4 μM.

  11. Structure and conformation of N-(2-methyl-5-chlorophenyl)salicylaldimine

    NASA Astrophysics Data System (ADS)

    Elmali, A.; Elerman, Y.

    1998-02-01

    N-(2-methyl-5-chlorophenyl)salicylaldimine (C 14H 12ClNO) has been studied by X-ray analysis and AM1 molecular orbital methods. It crystallises in the orthorhombic space group P2 12 12 1 with a = 7.474(1) Å, b = 12.155(1) Å, c = 13.378(1) Å, V = 1215.3(2) Å3, Z = 4, Dc = 1.343 g cm -3 and μ(Mo Kα) = 0.296 mm -1. The structure was solved by direct methods and refined to R = 0.0374 for 1689 reflections [ I > 2 σ( I)]. The title compound is photochromic and the molecule is not planar. There is a strong intramolecular hydrogen bond of distance 2.604(3) Å between the hydroxyl oxygen atom and imine nitrogen atom, the hydrogen atom essentially being bonded to the oxygen atom. Minimum energy conformations from AM1 were calculated as a function of the three torsion angles θ1(C8N1C7C6), θ2(C9C8N1C7) and θ3(N1C7C6C5), varied every 10°. The optimised geometry of the crystal structure corresponding to a non-planar conformation is the most stable conformation in all calculations.

  12. m6A RNA Degradation Products are Catabolized by an Evolutionarily Conserved N6-methyl-AMP Deaminase in Plant and Mammalian Cells.

    PubMed

    Chen, Mingjia; Urs, Mounashree J; Sánchez-González, Ismael; Olayioye, Monilola A; Herde, Marco; Witte, Claus-Peter

    2018-06-08

    N6-methylated adenine (m6A) is the most frequent posttranscriptional modification in eukaryotic mRNA. Turnover of RNA generates N6-methylated AMP (N6-mAMP), which has an unclear metabolic fate. We show that Arabidopsis thaliana and human cells require an N6-mAMP deaminase (ADAL, renamed MAPDA) to catabolize N6-mAMP to inosine monophosphate (IMP) in vivo by hydrolytically removing the aminomethyl group. A phylogenetic, structural, and biochemical analysis revealed that many fungi partially or fully lack MAPDA, which coincides with a minor role of N6A-RNA methylation in these organisms. MAPDA likely protects RNA from m6A mis-incorporation. This is required because eukaryotic RNA polymerase can use N6-mATP as a substrate. Upon abrogation of MAPDA, root growth is slightly reduced, and the N6-methyladenosine, N6-mAMP, and N6-mATP concentrations are increased in Arabidopsis. Although this will potentially lead to m6A mis-incorporation into RNA, we show that the frequency is too low to be reliably detected in vivo. Since N6-mAMP was several fold more abundant than N6-mATP in MAPDA mutants, we speculate that additional molecular filters suppress the generation of N6-mATP. Enzyme kinetic data indicate that adenylate kinases represent such filters being highly selective for AMP versus N6-mAMP phosphorylation. We conclude that a multilayer molecular protection system is in place preventing N6-mAMP accumulation and salvage. © 2018 American Society of Plant Biologists. All rights reserved.

  13. Methylation of nuclear proteins by dimethylnitrosamine and by methionine in the rat in vivo

    PubMed Central

    Turberville, C.; Craddock, V. M.

    1971-01-01

    1. The incorporation of methyl groups into histones from dimethylnitrosamine and from methionine was studied by injection of the labelled compounds, isolation of rat liver and kidney histones, and analysis of hydrolysates by column chromatography. 2. Labelled methionine gave rise to labelled ∈-N-methyl-lysine, di-∈-N-methyl-lysine and an amino acid presumed to be ω-N-methyl-arginine. 3. Administration of labelled dimethylnitrosamine gave rise to labelled S-methylcysteine, 1-methylhistidine, 3-methylhistidine and ∈-N-methyl-lysine derived from the alkylating metabolite of dimethylnitrosamine. In addition, labelled formaldehyde released by metabolism of dimethylnitrosamine leads to the formation of labelled S-adenosylmethionine, and hence to labelling of ∈-N-methyl-lysine, di-∈-N-methyl-lysine and ω-N-methylarginine by enzymic methylation. 4. The formation of ∈-N-methyl-lysine by alkylation of liver histones was confirmed by using doubly labelled dimethylnitrosamine to discriminate between direct chemical alkylation and enzymic methylation via S-adenosylmethionine. These experiments also suggested the possibility that methionine residues in the histones were alkylated to give methylmethionine sulphonium residues. 5. The extent of alkylation of liver histones was maximal at about 5h after dosing and declined between 5 and 24h. The methylated amino acids resulting from direct chemical alkylation were preferentially lost: this is ascribed to necrosis of the more highly alkylated cells. 6. Liver histones were about four times as alkylated as kidney histones; the extent of alkylation of liver histones was similar to that of liver total nuclear proteins. 7. Methyl methanesulphonate (120mg/kg) alkylated liver histones to a greater extent than did dimethylnitrosamine. Diethylnitrosamine also alkylated liver histones. 8. The results are discussed with regard to the possible effects of alkylation on histone function, and the possible role of histone alkylation in

  14. Solubility of pioglitazone hydrochloride in binary mixtures of polyethylene glycol 400 with ethanol, propylene glycol, N-methyl-2-pyrrolidone, and water at 25 degrees C.

    PubMed

    Jouyban, Abolghasem; Soltanpour, Shahla

    2010-09-01

    The solubility of pioglitazone hydrochloride in binary mixtures of polyethylene glycol 400 with ethanol, N-methyl-2-pyrrolidone, propylene glycol, and water at 25 degrees C are reported. The generated data are fitted to the Jouyban-Acree model and the mean relative deviations are 2.6%, 1.5%, 5.8%, and 7.4%, respectively for ethanol, N-methyl-2-pyrrolidone, propylene glycol, and water.

  15. Neuroprotection against traumatic brain injury by xenon, but not argon, is mediated by inhibition at the N-methyl-D-aspartate receptor glycine site.

    PubMed

    Harris, Katie; Armstrong, Scott P; Campos-Pires, Rita; Kiru, Louise; Franks, Nicholas P; Dickinson, Robert

    2013-11-01

    Xenon, the inert anesthetic gas, is neuroprotective in models of brain injury. The authors investigate the neuroprotective mechanisms of the inert gases such as xenon, argon, krypton, neon, and helium in an in vitro model of traumatic brain injury. The authors use an in vitro model using mouse organotypic hippocampal brain slices, subjected to a focal mechanical trauma, with injury quantified by propidium iodide fluorescence. Patch clamp electrophysiology is used to investigate the effect of the inert gases on N-methyl-D-aspartate receptors and TREK-1 channels, two molecular targets likely to play a role in neuroprotection. Xenon (50%) and, to a lesser extent, argon (50%) are neuroprotective against traumatic injury when applied after injury (xenon 43±1% protection at 72 h after injury [N=104]; argon 30±6% protection [N=44]; mean±SEM). Helium, neon, and krypton are devoid of neuroprotective effect. Xenon (50%) prevents development of secondary injury up to 48 h after trauma. Argon (50%) attenuates secondary injury, but is less effective than xenon (xenon 50±5% reduction in secondary injury at 72 h after injury [N=104]; argon 34±8% reduction [N=44]; mean±SEM). Glycine reverses the neuroprotective effect of xenon, but not argon, consistent with competitive inhibition at the N-methyl-D-aspartate receptor glycine site mediating xenon neuroprotection against traumatic brain injury. Xenon inhibits N-methyl-D-aspartate receptors and activates TREK-1 channels, whereas argon, krypton, neon, and helium have no effect on these ion channels. Xenon neuroprotection against traumatic brain injury can be reversed by increasing the glycine concentration, consistent with inhibition at the N-methyl-D-aspartate receptor glycine site playing a significant role in xenon neuroprotection. Argon and xenon do not act via the same mechanism.

  16. Perfluoro anion based binary and ternary ionic liquids as electrolytes for dye-sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Lin, Hsi-Hsin; Peng, Jia-De; Suryanarayanan, V.; Velayutham, D.; Ho, Kuo-Chuan

    2016-04-01

    In this work, eight new ionic liquids (ILs) based on triethylammonium (TEA) or n-methylpiperidinium (NMP) cations and perfluoro carboxylate (PFC) anions having different carbon chain lengths are synthesized and their physico-chemical properties such as density, decomposition temperature, viscosity and conductivity are determined. Photovoltaic characteristics of dye-sensitized solar cells (DSSCs) with binary ionic liquids electrolytes, containing the mixture of the synthesized ILs and 1-methyl-3-propyl imidazolium iodide (PMII) (v/v = 35/65), are evaluated. Among the different ILs, solar cells containing NMP based ILs show higher VOC than that of TEA, whereas, higher JSC is noted for the DSSCs incorporated with the latter when compared to the former. Further, the photo-current of the DSSCs decreases with the increase of the carbon chain length of perfluoro carboxylate anionic group of ILs. The cell performance of the DSSC containing ternary ionic liquids-based electrolytes compose of NMP-2C/TEA-2C/PMII (v/v/v = 28/7/65) exhibits a JSC of 12.99 mA cm-2, a VOC of 639.0 mV, a FF of 0.72, and a cell efficiency of 6.01%. The extraordinary durability of the DSSC containing the above combination of electrolytes stored in dark at 50 °C is proved to be unfailing up to 1200 h.

  17. Influence of the Ionic Liquid Type on the Gel Polymer Electrolytes Properties

    PubMed Central

    Tafur, Juan P.; Santos, Florencio; Fernández Romero, Antonio J.

    2015-01-01

    Gel Polymer Electrolytes (GPEs) composed by ZnTf2 salt, poly(vinylidene fluoride-co-hexafluoropropylene) (PVdF-HFP), and different ionic liquids are synthesized using n-methyl-2-pyrrolidone (NMP) as solvent. Three different imidazolium-based ionic liquids containing diverse cations and anions have been explored. Structural and electrical properties of the GPEs varying the ZnTf2 concentration are analyzed by ATR-FTIR, DSC, TG, and cyclic voltammetry. Free salt IL-GPEs present distinct behavior because they are influenced by the different IL cations and anions composition. However, inclusion of ZnTf2 salt inside the polymers provide GPEs with very similar characteristics, pointing out that ionic transport properties are principally caused by Zn2+ and triflate movement. Whatever the IL used, the presence of NMP solvent inside the polymer’s matrix turns out to be a key factor for improving the Zn2+ transport inside the GPE due to the interaction between Zn2+ cations and carbonyl groups of the NMP. High values of ionic conductivity, low activation energy values, and good voltammetric reversibility obtained regardless of the ionic liquid used enable these GPEs to be applied in Zn batteries. Capacities of 110–120 mAh·g−1 have been obtained for Zn/IL-GPE/MnO2 batteries discharged at −1 mA·cm−2. PMID:26610580

  18. Probes for narcotic receptor mediated phenomena. 42. Synthesis and in vitro pharmacological characterization of the N-methyl and N-phenethyl analogues of the racemic ortho-c and para-c oxide-bridged phenylmorphans

    PubMed Central

    Kim, Jin-Hee; Deschamps, Jeffrey R.; Rothman, Richard B.; Dersch, Christina M.; Folk, John E.; Cheng, Kejun; Jacobson, Arthur E.; Rice, Kenner C.

    2011-01-01

    A new synthesis of N-methyl and N-phenethyl substituted ortho-c and para-c oxide-bridged phenylmorphans, using N-benzyl- rather than N-methyl-substituted intermediates, was used and the pharmacological properties of these compounds were determined. The N-phenethyl substituted ortho-c oxide-bridged phenylmorphan (rac-(3R,6aS,11aS)-2-phenethyl-2,3,4,5,6,11a-hexahydro-1H-3,6a-methanobenzofuro[2,3-c]azocin-10-ol (12)) was found to have the highest μ-opioid receptor affinity (Ki = 1.1 nM) of all of the a- through f-oxide-bridged phenylmorphans. Functional data ([35S]GTP-γ-S) showed that the racemate 12 was more than three times more potent than naloxone as an μ-opioid antagonist. PMID:21570305

  19. Designing Solvent Exchange-Induced In Situ Forming Gel from Aqueous Insoluble Polymers as Matrix Base for Periodontitis Treatment.

    PubMed

    Srichan, Tharatree; Phaechamud, Thawatchai

    2017-01-01

    An in situ forming gel is a dosage form which is promised for site-specific therapy such as periodontal pocket of periodontitis treatment. Ethylcellulose, bleached shellac, and Eudragit RS were applied in this study as a polymeric matrix for in situ forming gel employing N-methyl pyrrolidone (NMP) as solvent. Solutions comprising ethylcellulose, bleached shellac, and Eudragit RS in NMP were evaluated for viscosity, rheology, and rate of water penetration. Ease of administration by injection was determined as the force required to expel polymeric solutions through a needle using texture analyzer. In vitro gel formation and in vitro gel degradation were conducted after injection into phosphate buffer solution pH 6.8. Ethylcellulose, bleached shellac, and Eudragit RS could form the in situ gel, in vitro. Gel viscosity and pH value depended on percentage amount of the polymer, whereas the water diffusion at early period likely relied on types of polymer. Furthermore, the solutions containing higher polymer concentration exhibited the lower degree of degradation. All the preparations were acceptable as injectable dosage forms because the applied force was lower than 50 N. All of them inhibited Staphylococcus aureus, Escherichia coli, Candida albicans, Streptococcus mutans, and Porphyrommonas gingivalis growth owing to antimicrobial activity of NMP which exhibited a potential use for periodontitis treatment. Moreover, the developed systems presented as the solvent exchange induced in situ forming gel and showed capability to be incorporated with the suitable antimicrobial active compounds for periodontitis treatment which should be further studied.

  20. Attenuation by d-limonene of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

    PubMed

    Yano, H; Tatsuta, M; Iishi, H; Baba, M; Sakai, N; Uedo, N

    1999-08-27

    The effects of prolonged administration of d-limonene, a monocyclic monoterpene, on sodium chloride-enhanced induction of gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine, the labeling and apoptotic indices, and ornithine decarboxylase (ODC) activity of gastric cancers were investigated in Wistar rats. After 25 weeks of carcinogen treatment, rats were given chow pellets containing 10% sodium chloride and 1% limonene ad libitum. In week 52, the incidence of gastric cancers, the labeling index and ODC activity were significantly higher and the apoptotic index was significantly lower in rats given sodium chlolide than in untreated control rats. However, in rats given both sodium chloride and d-limonene, the incidence of gastric cancers, the labeling index and ODC activity were significantly lower and the apoptotic index was significantly higher than in rats given sodium chloride alone. Our findings suggest that limonene attenuates the gastric carcinogenesis enhanced by sodium chloride via increased apoptosis and decreased ODC activity in gastric cancers. Copyright 1999 Wiley-Liss, Inc.

  1. Conformations and Barriers to Methyl Group Internal Rotation in Two Asymmetric Ethers: Propyl Methyl Ether and Butyl Methyl Ether

    NASA Astrophysics Data System (ADS)

    Long, B. E.; Dechirico, F.; Cooke, S. A.

    2012-06-01

    The conformational preferences of the O-C-C-C unit are important in many biological systems with the unit generally preferring a gauche configuration compared to an anti configuration. Butyl methyl ether and propyl methyl ether provide very simple systems for this phenomenom to manifest. Pure rotational spectra of the title molecules have been recorded using chirped pulse Fourier transform microwave spectroscopy (CP-FTMW). In the case of butyl methyl ether, only one conformer has been observed. This conformer has torsional angles of COCC = 180°, OCCC = 62° and CCCC = 180° (anti-gauche-anti) and rotational constants of A = 10259.4591(33) MHz, B = 1445.6470(13) MHz, and C = 1356.2944(14) MHz. The rotational spectrum was doubled and has been analyzed to produce an effective barrier to methyl group internal rotation of 780(35) cm-1. A prior rotational spectroscopic study on propyl methyl ether had focused only on the high energy anti-anti conformer. We have analyzed spectra from the lowest energy anti-gauche conformer and the spectroscopic constants will be presented. A summary of the differences in conformational energies and methyl group internal rotation barriers for the class of aliphatic asymmetric ethers will be presented. K. N. Houk, J. E. Eksterowicz, Y.-D. Wu, C. D. Fuglesang, D. B. Mitchell. J. Am. Chem. Soc. 115 (4170), 1993. Hiroshi Kato, Jun Nakagawa, Michiro Hayashi. J. Mol. Spectrosc. 80 (272), 1980.

  2. Interaction of amphotericin B and its low toxic derivative, N-methyl-N-D-fructosyl amphotericin B methyl ester, with fungal, mammalian and bacterial cells measured by the energy transfer method.

    PubMed

    Szlinder-Richert, Joanna; Cybulska, Barbara; Grzybowska, Jolanta; Bolard, Jacques; Borowski, Edward

    2004-04-01

    Amphotericin B (AMB) derivative, N-methyl-N-D-fructosyl amphotericin B methyl ester (MFAME) retains the broad antifungal spectrum and potency of the parent antibiotic, whereas its toxicity towards mammalian cells is reduced by about two orders of magnitude. The purpose of this work was to find out whether the differences observed in the toxicity of MFAME and native AMB are due to the differential drugs affinity to fungal and mammalian cell membranes. Comparative studies on AMB and MFAME biological activity and their affinity to fungal, mammalian and bacterial cells were performed. The interaction of AMB and MFAME with cells have been studied by fluorescence method based on the energy transfer between membrane fluorescent probe (donor) and the polyenic chromophore of the antibiotic (acceptor) simultaneously present in the cell membrane. The amount of the antibiotic bound to cells was indicated by the extent of fluorescence quenching of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) or 1,6-diphenyl-1,3,5-hexatriene (DPH) by polyenic chromophore of the antibiotic. The results obtained indicate that binding extent and characteristics for both antibiotics are comparable in the three types of cells studied. Dramatically lower toxicity of MFAME as compared to AMB towards mammalian cells is not related to the antibiotic-cell affinity, but rather to different consequences of these interactions for cells, reflected in membrane permeabilization. MFAME is definitely less effective than parent AMB in the permeabilizing species formation in mammalian cell membrane.

  3. Poly[[tetra-μ-cyanido-κ8 C:N-dodeca-cyanido-κ12 C-tris­(N,N-di­methyl­formamide-κO)tris­(methanol-κO)tris­(3,4,7,8-tetra­methyl-1,10-phenanthroline-κ2 N,N′)trimanganese(II)ditungstate(V)] dihydrate

    PubMed Central

    Yang, Fei-Lin; Yang, Dan

    2014-01-01

    The asymmetric unit of the title compound, {[Mn3{W(CN)8}2(C16H16N2)3(C3H7NO)3(CH3OH)3]·2H2O}n, consists of three [Mn(N,N-di­methyl­formamide)(methanol)(3,4,7,8-tetra­methyl-1,10-phenanthroline)]2+ cations, two [W(CN)8]3− anions and two water mol­ecules. Each water mol­ecule is disordered over three sets of sites, with a refined occupancy ratio of 0.310 (9):0.275 (9):0.415 (9) for one mol­ecule and 0.335 (9):0.288 (9):0.377 (9) for the other mol­ecule. The MnII atoms exhibit a distorted octa­hedral geometry, while the WV atoms adopt a distorted square-anti­prismatic geometry. The MnII and WV atoms are linked alternatively through cyanide groups, forming a tetra­nuclear 12-atom rhombic metallacycle. Adjacent metallacycles are further connected by μ2-bridging cyanide anions, generating a 3,2-chain structure running parallel to [101]. Inter­chain π–π inter­actions are observed [centroid–centroid distances = 3.763 (3) and 3.620 (2) Å]. PMID:24860305

  4. Solution-phase synthesis of a hindered N-methylated tetrapeptide using Bts-protected amino acid chlorides: efficient coupling and methylation steps allow purification by extraction.

    PubMed

    Vedejs, E; Kongkittingam, C

    2000-04-21

    N-Benzothiazole-2-sulfonyl (Bts)-protected amino acid chlorides were used to prepare the hindered cyclosporin 8-11 tetrapeptide subunit 1. The synthesis was performed via 3a and the deprotected amines 5a, 13, and 19, including three repeated cycles involving N-methylation using iodomethane/potassium carbonate, deprotection of the Bts group, and N-acylation with a N-Bts-amino acid chloride such as 9b or 9c. Among three Bts cleavage methods compared (H3PO2/THF; NaBH4/EtOH; PhSH/K2CO3), the third gave somewhat higher overall yields. N-Acylation of 5a with the Bts-protected N-methylamino acid chloride 10b followed by deprotection was also highly efficient and could be used as an alternative route to 11. Each of the deprotected amines was isolated without chromatography using simple extraction methods to remove neutral byproducts. The tetrapeptide 1 was obtained in analytically pure form as the monohydrate.

  5. Chemistry and Properties of Imide Oligomers from Phenylethynyl-Containing Diamines

    NASA Technical Reports Server (NTRS)

    Smith, J. G., Jr.; Connell, J. W.

    2000-01-01

    As an extension of work on pendent phenylethynlyl-containing imide oligomer, three new diamines containing pendent phenylethynyl groups were prepared and characterized. These diamines were used to prepare pendent and pendent and terminal phenylethynyl imide oliogomers via the amide acid route in N-methyl-2-pyrrolidinone at a calculated number average molecular weight of 5000 g mol (exp -1). The pendent phenylethynyl groups were randomly distributed along the oliogomer backbone and provided a means of controlling the distance between reactive sites. The imide oligomers were characterized and thermally cured, and the cured polymers evaluated as thin films and compared with materials of similar composition prepared from 3,5-diamino-4'-phenylethynylbenzophenone. This work was performed as part of a continuing research effort to develop structural resins for potential aeronautical applications.

  6. Gas-phase reactions of glycine, alanine, valine and their N-methyl derivatives with the nitrosonium ion, NO+.

    PubMed

    Freitas, M A; O'Hair, R A; Schmidt, J A; Tichy, S E; Plashko, B E; Williams, T D

    1996-10-01

    The gas-phase reactions of the nitrosonium ion, NO+ with the amino acids glycine, alanine and valine and their N-methyl derivatives were investigated under chemical ionization mass spectrometric (CIMS) conditions. Two products were observed in all cases: the formation of the iminium ion and the formation of an [M-H]+ ion. The latter product is consistent with a reaction channel involving hydride abstraction by NO+, and was confirmed by (i) examining the Ar+CI mass spectra of the same amino acids under similar source conditions and (ii) examining the unimolecular fragmentation reactions of the [M + H]+ ions of the N-nitroso-N-methyl derivatives of each of the amino acids in a tandem mass spectrometer. Further insights into the reaction of glycine with NO+ were obtained by performing ab initio calculations (at the MP2/6-31G* parallel HF/6-31G* level). These results indicate that four reactions are thermodynamically viable for glycine: (i) hydride abstraction; (ii) iminium ion formation (with concomitant loss of HONO and CO); (iii) diazonium ion formation; and (iv) diazonium ion formation followed by loss of N2. Possible reasons why reactions (iii) and (iv) are not observed are discussed, and comparisons with solution reactivity and the gas-phase reactivity of NO+ are also made.

  7. Preventive effect of rebamipide on N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats.

    PubMed

    Tsukamoto, Hironobu; Mizoshita, Tsutomu; Katano, Takahito; Hayashi, Noriyuki; Ozeki, Keiji; Ebi, Masahide; Shimura, Takaya; Mori, Yoshinori; Tanida, Satoshi; Kataoka, Hiromi; Tsukamoto, Tetsuya; Tatematsu, Masae; Joh, Takashi

    2015-03-01

    Chemoprevention strategies against gastric cancer (GC) need to be explored in light of the fact that stomach cancer still occurs in the absence of Helicobacter pylori (HP) infection and following HP eradication. We evaluated the effect of rebamipide on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced carcinogenesis in SD rats. Thirty-nine male rats were divided into four groups based on whether or not they were treated with rebamipide and/or MNNG: Control, Rebamipide, Control-M, and Rebamipide-M groups. From 8 weeks of age, rats in the Control-M and Rebamipide-M groups received MNNG in drinking water for 30 weeks. The Rebamipide and Rebamipide-M groups were administered 5mg/kg/day of rebamipide. At 50 weeks, cancerous lesions were not observed in either the Control or Rebamipide groups. Nine rats in the Control-M group had developed GC, while four rats in the Rebamipide-M group had developed GC. The incidence of cancer in the Rebamipide-M group was significantly less than in the Control-M group (p<0.05), with a trend toward a lower incidence of invasive carcinoma in the Rebamipide-M group. Carcinomatous invasion into the muscularis propria was not observed in the Rebamipide-M group. In conclusion, the present study demonstrates that rebamipide suppresses. MNNG-induced carcinogenesis and may also inhibit progression of cancer in rats. Copyright © 2015 Elsevier GmbH. All rights reserved.

  8. N-methyl-N'-nitro-N-nitrosoguanidine interferes with the epidermal growth factor receptor-mediated signaling pathway.

    PubMed

    Gao, Zhihua; Yang, Jun; Huang, Yun; Yu, Yingnian

    2005-03-01

    Many environmental factors, such as ultraviolet (UV) and arsenic, can induce the clustering of cell surface receptors, including epidermal growth factor receptor (EGFR). This is accompanied by the phosphorylation of the receptors and the activation of ensuing cellular signal transduction pathways, which are implicated in the various cellular responses caused by the exposure to these factors. In this study, we have shown that N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), an alkylating agent, also induced the clustering of EGFR in human amnion FL cells, which was similar in morphology to that of epidermal growth factor treatment. However, MNNG treatment did not activate Ras, the downstream mediator in EGFR signaling pathway, as compared to EGF treatment. The autophosphorylation of tyrosine residues Y1068 and Y1173 at the intracellular domain of EGFR, which is related to Ras activation under EGF treatment, was also not observed by MNNG exposure. Interestingly, although MNNG did not affect the binding of EGF to EGFR, MNNG can interfere with EGF function. For instance, pre-incubating FL cells with MNNG inhibited the autophosphorylation of EGFR by EGF treatment, as well as the activation of Ras. In addition, the phosphorylation of Y845 on EGFR by EGF, which is mediated through c-Src or related kinases but not autophosphorylation, was also affected by MNNG. Therefore, MNNG may influence the tyrosine kinase activity as well as the phosphorylation of EGFR through its interaction with EGFR.

  9. New Synthesis, Structure and Analgesic Properties of Methyl 1-R-4-Methyl-2,2-Dioxo-1H-2λ⁶,1-Benzothiazine-3-Carboxylates.

    PubMed

    Azotla-Cruz, Liliana; Lijanova, Irina V; Ukrainets, Igor V; Likhanova, Natalya V; Olivares-Xometl, Octavio; Bereznyakova, Natalya L

    2017-01-12

    According to the principles of the methodology of bioisosteric replacements a series of methyl 1-R-4-methyl-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylates has been obtained as potential analgesics. In addition, a fundamentally new strategy for the synthesis of compounds of this chemical class involving the introduction of N -alkyl substituent at the final stage in 2,1-benzothiazine nucleus already formed has been proposed. Using nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry and X-ray diffraction analysis it has been proven that in the DMSO/K₂CO₃ system the reaction of methyl 4-methyl-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylate and alkyl halides leads to formation of N -substituted derivatives with good yields regardless of the structure of the alkylating agent. The peculiarities of NMR (¹Н and 13 С) spectra of the compounds synthesized, their mass spectrometric behavior and the spatial structure are discussed. In N -benzyl derivative the ability to form a monosolvate with methanol has been found. According to the results of the pharmacological testing conducted on the model of the thermal tail-flick it has been determined that replacement of 4-ОН-group in methyl 1-R-4-hydroxy-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylates for the methyl group is actually bioisosteric since all methyl 1-R-4-methyl-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylates synthesized demonstrated a statistically significant analgesic effect. The majority of the substances can inhibit the thermal pain response much more effective than piroxicam in the same dose. Under the same conditions as an analgesic the N- methyl-substituted analog exceeds not only piroxicam, but more active meloxicam as well. Therefore, it deserves in-depth biological studies on other experimental models.

  10. A novel ropivacaine-loaded in situ forming implant prolongs the effect of local analgesia in rats

    PubMed Central

    Lu, Lei; Zhang, Wei; Wu, Xin; Wang, Xiaoyu; Zhang, Min; Zhu, Quangang; Ding, Xueying; Xu, Zhiyun

    2012-01-01

    Introduction Prolonged postoperative analgesia cannot be achieved by a single injection of local anesthetic solution. The objective of this study was to optimize the formulation of a ropivacaine hydrochloride (Ropi-HCl) loaded in situ forming implant (ISI) by addition of different co-solvents, and evaluate the in vitro release of Ropi-HCl, and the analgesic effect and toxicity of the optimized formulation in rats. Material and methods Triacetin (TA), benzyl benzoate (BB) and polyethylene glycol 400 (PEG 400) were used as additives and added to the solvent of N-methyl-2-pyrrolidone (NMP). Drug release to the surface and inner structural properties of the formed implant were evaluated by scanning electron microscopy (SEM). The analgesic effect was determined by injection near the rat sciatic nerve. Results The solvent system added with TA or BB significantly decreased the burst release, whereas PEG 400 increased the Ropi-HCl burst release from the formulation. Over 70% of the incorporated Ropi-HCl was released from all formulations in 14 days in the in vitro assay. The SEM showed that the surface of NMP-BB formulation was less porous and more homogeneous, compared with the other formulations. Compared with Ropi-HCl injection, the optimized formulation (NMP-BB) significantly prolonged the analgesic effect in 48 h (p < 0.05), with a mild degree of motor block from 3 h to 12 h. Histological evaluation of the injection site revealed only mild inflammatory infiltration without obvious pathological nerve alterations. Conclusions The biodegradable Ropi-HCl-loaded ISI system with NMP-BB may prove to be an attractive and safe alternative for the delivery of parenteral local anesthetics to prolong pain relief. PMID:24049519

  11. Ethanol Inhibition of Constitutively Open N-Methyl-d-Aspartate Receptors

    PubMed Central

    Xu, Minfu; Smothers, C. Thetford; Trudell, James

    2012-01-01

    N-Methyl-d-aspartate (NMDA) receptors gate a slow and calcium-rich component of the postsynaptic glutamate response. Like all ionotropic glutamate receptors, NMDA subunits contain a highly conserved motif (SYTANLAAF) in the transmembrane (TM) 3 domain that is critically involved in channel gating. Mutation of an alanine in this domain (A7; underlined above) results in constitutively open receptors that show reduced sensitivity to several allosteric modulators. In this study, we examined the effects of ethanol, a substance that inhibits NMDA currents via an unknown mechanism, on tonically active NMDA receptors expressed in human embryonic kidney 293 cells. Ethanol (100 mM) inhibited currents from GluN1(A7R)/GluN2A and GluN1(A7R)/GluN2B receptors by approximately 50%, whereas those from GluN1/GluN2B(A7R) receptors were reduced by less than 10%. In cysteine-substituted GluN1 and GluN2 A7 mutants, estimated ethanol IC50 values for agonist-gated currents were 101, 117, 103, and 69 mM for GluN1(A7C)/GluN2A, GluN1(A7C)/GluN2B, GluN1/GluN2A(A7C), and GluN1/GluN2B(A7C) receptors, respectively. After exposure to the thiol-modifying reagent 2-(trimethylammonium)ethyl methanethiosulfonate (MTSET), A7C mutants showed robust agonist-independent currents and reduced sensitivity to ethanol (IC50 values of 371, 256, 715, and 958 mM, respectively, as above). In contrast, cysteine modification of the ligand-binding domain resulted in constitutively open receptors that showed robust ethanol inhibition. Ethanol inhibition of MTSET-treated GluN1(A7C) receptors was further reduced by TM3/TM4 mutations previously shown to reduce ethanol sensitivity of agonist-gated receptors. Overall, these results show that ethanol affects NMDA receptor function at a site distal from agonist binding and appears to exert greater effects via perturbation of GluN2 subunits. PMID:22005043

  12. Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation.

    PubMed

    Yehuda, Rachel; Daskalakis, Nikolaos P; Bierer, Linda M; Bader, Heather N; Klengel, Torsten; Holsboer, Florian; Binder, Elisabeth B

    2016-09-01

    The involvement of epigenetic mechanisms in intergenerational transmission of stress effects has been demonstrated in animals but not in humans. Cytosine methylation within the gene encoding for FK506 binding protein 5 (FKBP5) was measured in Holocaust survivors (n = 32), their adult offspring (n = 22), and demographically comparable parent (n = 8) and offspring (n = 9) control subjects, respectively. Cytosine-phosphate-guanine sites for analysis were chosen based on their spatial proximity to the intron 7 glucocorticoid response elements. Holocaust exposure had an effect on FKBP5 methylation that was observed in exposed parents as well in their offspring. These effects were observed at bin 3/site 6. Interestingly, in Holocaust survivors, methylation at this site was higher in comparison with control subjects, whereas in Holocaust offspring, methylation was lower. Methylation levels for exposed parents and their offspring were significantly correlated. In contrast to the findings at bin 3/site 6, offspring methylation at bin 2/sites 3 to 5 was associated with childhood physical and sexual abuse in interaction with an FKBP5 risk allele previously associated with vulnerability to psychological consequences of childhood adversity. The findings suggest the possibility of site specificity to environmental influences, as sites in bins 3 and 2 were differentially associated with parental trauma and the offspring's own childhood trauma, respectively. FKBP5 methylation averaged across the three bins examined was associated with wake-up cortisol levels, indicating functional relevance of the methylation measures. This is the first demonstration of an association of preconception parental trauma with epigenetic alterations that is evident in both exposed parent and offspring, providing potential insight into how severe psychophysiological trauma can have intergenerational effects. Published by Elsevier Inc.

  13. Design, Synthesis, and Structure–Activity Relationship of a Novel Series of GluN2C-Selective Potentiators

    PubMed Central

    2015-01-01

    NMDA receptors are tetrameric complexes composed of GluN1 and GluN2A–D subunits that mediate a slow Ca2+-permeable component of excitatory synaptic transmission. NMDA receptors have been implicated in a wide range of neurological diseases and thus represent an important therapeutic target. We herein describe a novel series of pyrrolidinones that selectively potentiate only NMDA receptors that contain the GluN2C subunit. The most active analogues tested were over 100-fold selective for recombinant GluN2C-containing receptors over GluN2A/B/D-containing NMDA receptors as well as AMPA and kainate receptors. This series represents the first class of allosteric potentiators that are selective for diheteromeric GluN2C-containing NMDA receptors. PMID:24512267

  14. RNA N6-adenosine methylation (m6A) steers epitranscriptomic control of herpesvirus replication

    PubMed Central

    Ye, Fengchun

    2017-01-01

    Latency is a hallmark of all herpesviruses, during which the viral genomes are silenced through DNA methylation and suppressive histone modifications. When latent herpesviruses reactivate to undergo productive lytic replication, the suppressive epigenetic marks are replaced with active ones to allow for transcription of viral genes. Interestingly, by using Kaposi’s sarcoma-associated herpesvirus (KSHV) as a model, we recently demonstrated that the newly transcribed viral RNAs are also subjected to post-transcriptional N6-adenosine methylation (m6A). Blockade of this post-transcriptional event abolishes viral protein expression and halts virion production. We found that m6A modification controls RNA splicing, stability, and protein translation to regulate viral lytic gene expression and replication. Thus, our finding for the first time reveals a critical role of this epitranscriptomic mechanism in the control of herpesviral replication, which shall shed lights on development of novel strategies for the control of herpesviral infection. PMID:29082271

  15. Crystal structure of catena-poly[N,N,N′,N′-tetra­methyl­guanidinium [(chlorido­cadmate)-di-μ-chlorido

    PubMed Central

    Ndiaye, Mamadou; Samb, Abdoulaye; Diop, Libasse; Maris, Thierry

    2016-01-01

    In the structure of the title salt, {(C5H14N3)[CdCl3]}n, the CdII atom of the complex anion is five-coordinated by one terminal and four bridging Cl atoms. The corresponding coordination polyhedron is a distorted trigonal bipyramid, with Cd—Cl distances in the range 2.4829 (4)–2.6402 (4) Å. The bipyramids are condensed into a polyanionic zigzag chain extending parallel to [101]. The tetra­methyl­guanidinium cations are situated between the polyanionic chains and are linked to them through N—H⋯Cl hydrogen bonds, forming a layered network parallel to (010). PMID:26870572

  16. N-linked glycosylation of cortical N-methyl-D-aspartate and kainate receptor subunits in schizophrenia.

    PubMed

    Tucholski, Janusz; Simmons, Micah S; Pinner, Anita L; McMillan, Laurence D; Haroutunian, Vahram; Meador-Woodruff, James H

    2013-08-21

    Dysfunctional glutamate neurotransmission has been implicated in the pathophysiology of schizophrenia. Abnormal expressions in schizophrenia of ionotropic glutamate receptors (iGluRs) and the proteins that regulate their trafficking have been found to be region and subunit specific in brain, suggesting that abnormal trafficking of iGluRs may contribute toward altered glutamatergic neurotransmission. The post-translational modification N-glycosylation of iGluR subunits can be used as a proxy for their intracellular localization. Receptor complexes assemble in the lumen of the endoplasmic reticulum, where N-glycosylation begins with the addition of N-linked oligomannose glycans, and is subsequently trimmed and replaced by more elaborate glycans while trafficking through the Golgi apparatus. Previously, we found abnormalities in N-glycosylation of the GluR2 AMPA receptor subunit in schizophrenia. Here, we investigated N-glycosylation of N-methyl-D-aspartate and kainate (KA) receptor subunits in the dorsolateral prefrontal cortex from patients with schizophrenia and a comparison group. We used enzymatic deglycosylation with two glycosidases: endoglycosidase H (Endo H), which removes immature high mannose-containing sugars, and peptide-N-glycosidase F (PNGase F), which removes all N-linked sugars. The NR1, NR2A, NR2B, GluR6, and KA2 subunits were all sensitive to treatment with Endo H and PNGase F. The GluR6 KA receptor subunit was significantly more sensitive to Endo H-mediated deglycosylation in schizophrenia, suggesting a larger molecular mass of N-linked high mannose and/or hybrid sugars on GluR6. This finding, taken with our previous work, suggests that a cellular mechanism underlying abnormal glutamate neurotransmission in schizophrenia may involve abnormal trafficking of both AMPA and KA receptors.

  17. Flexible free-standing TiO2/graphene/PVdF films as anode materials for lithium-ion batteries

    NASA Astrophysics Data System (ADS)

    Ren, H. M.; Ding, Y. H.; Chang, F. H.; He, X.; Feng, J. Q.; Wang, C. F.; Jiang, Y.; Zhang, P.

    2012-12-01

    Graphene composites were prepared by hydrothermal method using titanium dioxide (TiO2) adsorbed graphene oxide (GO) sheets as precursors. Free-standing hybrid films for lithium-ion batteries were prepared by adding TiO2/graphene composites to the polyvinylidene fluoride (PVdF)/N-methyl-2-pyrrolidone (NMP) solution, followed by a solvent evaporation technique. These films were characterized by atomic force microscopy (AFM), X-ray diffraction (XRD), scanning electron microscopy (SEM) and various electrochemical techniques. Flexible films show an excellent cycling performance, which was attributed to the interconnected graphene conducting network, which depressed the increasing of electric resistance during the cycling.

  18. Edge-Functionalization of Pyrene as a Miniature Graphene via Friedel–Crafts Acylation Reaction in Poly(Phosphoric Acid)

    PubMed Central

    2010-01-01

    The feasibility of edge-functionalization of graphite was tested via the model reaction between pyrene and 4-(2,4,6-trimethylphenyloxy)benzamide (TMPBA) in poly(phosphoric acid) (PPA)/phosphorous pentoxide (P2O5) medium. The functionalization was confirmed by various characterization techniques. On the basis of the model study, the reaction condition could be extended to the edge-functionalization of graphite with TMPBA. Preliminary results showed that the resultant TMPBA-grafted graphite (graphite-g-TMPBA) was found to be readily dispersible in N-methyl-2-pyrrolidone (NMP) and can be used as a precursor for edge-functionalized graphene (EFG). PMID:21076664

  19. Phase separation of in situ forming poly (lactide-co-glycolide acid) implants investigated using a hydrogel-based subcutaneous tissue surrogate and UV-vis imaging.

    PubMed

    Sun, Yu; Jensen, Henrik; Petersen, Nickolaj J; Larsen, Susan W; Østergaard, Jesper

    2017-10-25

    Phase separation of in situ forming poly (lactide-co-glycolide acid) (PLGA) implants with agarose hydrogels as the provider of nonsolvent (water) mimicking subcutaneous tissue was investigated using a novel UV-vis imaging-based analytical platform. In situ forming implants of PLGA-1-methyl-2-pyrrolidinone and PLGA-triacetin representing fast and slow phase separating systems, respectively, were evaluated using this platform. Upon contact with the agarose hydrogel, the phase separation of the systems was followed by the study of changes in light transmission and absorbance as a function of time and position. For the PLGA-1-methyl-2-pyrrolidinone system, the rate of spatial phase separation was determined and found to decrease with increasing the PLGA concentration from 20% to 40% (w/w). Hydrogels with different agarose concentrations (1% and 10% (w/v)) were prepared for providing the nonsolvent, water, to the in situ forming PLGA implants simulating the injection site environment. The resulting implant morphology depended on the stiffness of hydrogel matrix, indicating that the matrix in which implants are formed is of importance. Overall, the work showed that the UV-vis imaging-based platform with an agarose hydrogel mimicking the subcutaneous tissue holds potential in providing bio-relevant and mechanistic information on the phase separation processes of in situ forming implants. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Analysis of the expression level and methylation of tumor protein p53, phosphatase and tensin homolog and mutS homolog 2 in N-methyl-N-nitrosourea-induced thymic lymphoma in C57BL/6 mice.

    PubMed

    Huo, Xueyun; Li, Zhenkun; Zhang, Shuangyue; Li, Changlong; Guo, Meng; Lu, Jing; Lv, Jianyi; Du, Xiaoyan; Chen, Zhenwen

    2017-10-01

    Tumorigenesis is often caused by somatic mutation or epigenetic changes in genes that regulate aspects of cell death, proliferation and survival. Although the functions of multiple tumor suppressor genes have been well studied in isolation, how these genes cooperate during the progression of a single tumor remains unclear in numerous cases. The present study used N-methyl-N-nitrosourea (MNU), one of the most potent mutagenic nitrosourea compounds, to induce thymic lymphoma in C57BL/6J mice. Subsequently, the protein expression levels of phosphatase and tensin homolog (PTEN), transformation protein 53 and mutS homolog 2 (MSH2) were evaluated concomitantly in the thymus, liver, kidney and spleen of MNU-treated mice by western blotting. To determine whether changes in expression level were due to aberrant epigenetic regulation, the present study further examined the methylation status of each gene by MassARRAY analysis. During the tumorigenesis process of an MNU-induced single thymic lymphoma, the expression level of PTEN was revealed to be reduced in thymic lymphoma samples but not in normal or non-tumor thymus tissue samples. Furthermore, a marked reduction of P53 expression levels were demonstrated in thymic lymphomas and spleens with a metastatic tumor. Conversely, MSH2 upregulation was identified only in liver, kidney, and spleen samples that were infiltrated by thymic lymphoma cells. Furthermore, the present study revealed that a number of 5'-C-phosphate-G-3' sites located in the promoter of aberrantly expressed genes had significantly altered methylation statuses. These results improve the understanding of the course of mutagen-induced cancer, and highlight that epigenetic regulation may serve an important function in cancer.

  1. Thermal and Optical Properties of New Poly(amide-imide)/Nanocomposite Reinforced by Layer Silicate Containing Diphenyl Ether Moieties

    NASA Astrophysics Data System (ADS)

    Faghihi, Khalil; Faramarzi, Ellahe; Shabanian, Meisam

    2011-04-01

    New poly(amide-imide)-montmorillonite reinforced nanocomposites containing Bis(4-N-trimellitylimido) diphenyl ether moiety in the main chain were synthesized by a convenient solution intercalation technique. Poly(amide-imide) (PAI) 4 was synthesized by the direct polycondensation reaction of Bis(4-N-trimellitylimido) diphenyl ether 3 with 4,4'-diamino diphenyl ether 2 in the presence of triphenyl phosphite (TPP), CaCl2, pyridine and N-methyl-2-pyrrolidone (NMP). Morphology and structure of the resulting PAI-nanocomposite films 4a and 4b with 10 and 20 mass% silicate particles respectively, were characterized by FT-IR spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM). The properties of nanocomposites films were investigated by using Uv-vis spectroscopy, thermogravimetric analysis (TGA) and water uptake measurements.

  2. Dopaminergic neurotoxicity of S-ethyl N,N-dipropylthiocarbamate (EPTC), molinate, and S-methyl-N,N-diethylthiocarbamate (MeDETC) in Caenorhabditis elegans

    PubMed Central

    Caito, Samuel W.; Valentine, William M.; Aschner, Michael

    2013-01-01

    Epidemiological studies corroborate a correlation between pesticide use and Parkinson’s disease (PD). Thiocarbamate and dithiocarbamate pesticides are widely used and produce neurotoxicity in the peripheral nervous system. Recent evidence from rodent studies suggests that these compounds also cause dopaminergic (DAergic) dysfunction and altered protein processing, two hallmarks of PD. However, DAergic neurotoxicity has yet to be documented. We assessed DAergic dysfunction in Caenorhabditis elegans (C. elegans) to investigate the ability of thiocarbamate pesticides to induce DAergic neurodegeneration. Acute treatment with either S-ethyl N,N-dipropylthiocarbamate (EPTC), molinate, or a common reactive intermediate of dithiocarbamate and thiocarbamate metabolism, S-methyl-N,N-diethylthiocarbamate (MeDETC), to gradual loss of DAergic cell morphology and structure over the course of 6 days in worms expressing green fluorescent protein (GFP) under a DAergic cell specific promoter. HPLC analysis revealed decreased DA content in the worms immediately following exposure to MeDETC, EPTC, and molinate. Additionally, worms treated with the three test compounds showed a drastic loss of DAergic-dependent behavior over a time course similar to changes in DAergic cell morphology. Alterations in the DAergic system were specific, as loss of cell structure and neurotransmitter content was not observed in cholinergic, glutamatergic, or GABAergic systems. Overall, our data suggest that thiocarbamate pesticides promote neurodegeneration and DAergic cell dysfunction in C. elegans, and may be an environmental risk factor for PD. PMID:23786526

  3. Identification of methylated genes associated with aggressive bladder cancer.

    PubMed

    Marsit, Carmen J; Houseman, E Andres; Christensen, Brock C; Gagne, Luc; Wrensch, Margaret R; Nelson, Heather H; Wiemels, Joseph; Zheng, Shichun; Wiencke, John K; Andrew, Angeline S; Schned, Alan R; Karagas, Margaret R; Kelsey, Karl T

    2010-08-23

    Approximately 500,000 individuals diagnosed with bladder cancer in the U.S. require routine cystoscopic follow-up to monitor for disease recurrences or progression, resulting in over $2 billion in annual expenditures. Identification of new diagnostic and monitoring strategies are clearly needed, and markers related to DNA methylation alterations hold great promise due to their stability, objective measurement, and known associations with the disease and with its clinical features. To identify novel epigenetic markers of aggressive bladder cancer, we utilized a high-throughput DNA methylation bead-array in two distinct population-based series of incident bladder cancer (n = 73 and n = 264, respectively). We then validated the association between methylation of these candidate loci with tumor grade in a third population (n = 245) through bisulfite pyrosequencing of candidate loci. Array based analyses identified 5 loci for further confirmation with bisulfite pyrosequencing. We identified and confirmed that increased promoter methylation of HOXB2 is significantly and independently associated with invasive bladder cancer and methylation of HOXB2, KRT13 and FRZB together significantly predict high-grade non-invasive disease. Methylation of these genes may be useful as clinical markers of the disease and may point to genes and pathways worthy of additional examination as novel targets for therapeutic treatment.

  4. Maternal melatonin or N-acetylcysteine therapy regulates hydrogen sulfide-generating pathway and renal transcriptome to prevent prenatal NG-Nitro-L-arginine-methyl ester (L-NAME)-induced fetal programming of hypertension in adult male offspring.

    PubMed

    Tain, You-Lin; Lee, Chien-Te; Chan, Julie Y H; Hsu, Chien-Ning

    2016-11-01

    Pregnancy is a critical time for fetal programming of hypertension. Nitric oxide deficiency during pregnancy causes hypertension in adult offspring. We examined whether maternal melatonin or N-acetylcysteine therapy can prevent N G -nitro-L-arginine-methyl ester-induced fetal programming of hypertension in adult offspring. Next, we aimed to identify potential gatekeeper pathways that contribute to N G -nitro-L-arginine-methyl ester -induced programmed hypertension using the next generation RNA sequencing technology. Pregnant Sprague-Dawley rats were assigned to 4 groups: control, N G -nitro-L-arginine-methyl ester, N G -nitro-L-arginine-methyl ester +melatonin, and N G -nitro-L-arginine-methyl ester+N-acetylcysteine. Pregnant rats received N G -nitro-L-arginine-methyl ester administration at 60 mg/kg/d subcutaneously during pregnancy alone, with additional 0.01% melatonin in drinking water, or with additional 1% N-acetylcysteine in drinking water during the entire pregnancy and lactation. Male offspring (n=8/group) were killed at 12 weeks of age. N G -nitro-L-arginine-methyl ester exposure during pregnancy induced programmed hypertension in adult male offspring, which was prevented by maternal melatonin or N-acetylcysteine therapy. Protective effects of melatonin and N-acetylcysteine against N G -nitro-L-arginine-methyl ester-induced programmed hypertension were associated with an increase in hydrogen sulfide-generating enzymes and hydrogen sulfide synthesis in the kidneys. Nitric oxide inhibition by N G -nitro-L-arginine-methyl ester in pregnancy caused >2000 renal transcripts to be modified during nephrogenesis stage in 1-day-old offspring kidney. Among them, genes belong to the renin-angiotensin system, and arachidonic acid metabolism pathways were potentially involved in the N G -nitro-L-arginine-methyl ester-induced programmed hypertension. However, melatonin and N-acetylcysteine reprogrammed the renin-angiotensin system and arachidonic acid pathway

  5. Experimental and numerical investigations on spray characteristics of fatty acid methyl esters

    NASA Astrophysics Data System (ADS)

    Lanjekar, R. D.; Deshmukh, D.

    2018-02-01

    A comparative experimental and numerical study is conducted to establish the significance of the use of single-component over multi-component representatives of biodiesel, diesel and their blend for predicting spray tip penetration. Methyl oleate and methyl laurate are used as single-component representative fuels for biodiesel. The pure components n-heptane, n-dodecane and n-tetradecane are used as single-component representative fuels for diesel. Methyl laurate is found to represent biodiesel of coconut, whereas methyl oleate is found to represent biodiesel having high percentage of long-chain fatty acid esters. The spray tip penetration of methyl oleate is found to be in good agreement with the measured spray tip penetration of karanja biodiesel. The spray tip penetration prediction of n-heptane fuel is closely following diesel spray tip penetration along with that of n-tetradecane and n-dodecane. The study suggests that the knowledge of the single-component representatives of biodiesel, diesel and their blend is sufficient to predict the spray tip penetration of the corresponding biodiesel, diesel and their blend under non-evaporating environment.

  6. Experimental and numerical investigations on spray characteristics of fatty acid methyl esters.

    PubMed

    Lanjekar, R D; Deshmukh, D

    2018-02-01

    A comparative experimental and numerical study is conducted to establish the significance of the use of single-component over multi-component representatives of biodiesel, diesel and their blend for predicting spray tip penetration. Methyl oleate and methyl laurate are used as single-component representative fuels for biodiesel. The pure components n -heptane, n -dodecane and n -tetradecane are used as single-component representative fuels for diesel. Methyl laurate is found to represent biodiesel of coconut, whereas methyl oleate is found to represent biodiesel having high percentage of long-chain fatty acid esters. The spray tip penetration of methyl oleate is found to be in good agreement with the measured spray tip penetration of karanja biodiesel. The spray tip penetration prediction of n -heptane fuel is closely following diesel spray tip penetration along with that of n -tetradecane and n -dodecane. The study suggests that the knowledge of the single-component representatives of biodiesel, diesel and their blend is sufficient to predict the spray tip penetration of the corresponding biodiesel, diesel and their blend under non-evaporating environment.

  7. Experimental and numerical investigations on spray characteristics of fatty acid methyl esters

    PubMed Central

    Deshmukh, D.

    2018-01-01

    A comparative experimental and numerical study is conducted to establish the significance of the use of single-component over multi-component representatives of biodiesel, diesel and their blend for predicting spray tip penetration. Methyl oleate and methyl laurate are used as single-component representative fuels for biodiesel. The pure components n-heptane, n-dodecane and n-tetradecane are used as single-component representative fuels for diesel. Methyl laurate is found to represent biodiesel of coconut, whereas methyl oleate is found to represent biodiesel having high percentage of long-chain fatty acid esters. The spray tip penetration of methyl oleate is found to be in good agreement with the measured spray tip penetration of karanja biodiesel. The spray tip penetration prediction of n-heptane fuel is closely following diesel spray tip penetration along with that of n-tetradecane and n-dodecane. The study suggests that the knowledge of the single-component representatives of biodiesel, diesel and their blend is sufficient to predict the spray tip penetration of the corresponding biodiesel, diesel and their blend under non-evaporating environment. PMID:29515835

  8. Identification of organically associated trace elements in wood and coal by inductively coupled plasma mass spectrometry.

    PubMed

    Richaud, R; Lazaro, M J; Lachas, H; Miller, B B; Herod, A A; Dugwell, D R; Kandiyoti, R

    2000-01-01

    1-Methyl-2-pyrrolidinone (NMP) was used to extract samples of wood (forest residue) and coal; the extracts were analysed by inductively coupled plasma mass spectrometry (ICP-MS) using two different sample preparation methods, in order to identify trace elements associated with the organic part of the samples. A sample of fly ash was similarly extracted and analysed in order to assess the behaviour of the mineral matter contained within the wood and coal samples. 32% of the biomass was extracted at the higher temperature and 12% at room temperature while only 12% of the coal was extracted at the higher temperature and 3% at room temperature. Less than 2% of the ash dissolved at the higher temperature. Size exclusion chromatograms of the extracts indicated the presence of significant amounts of large molecular mass materials (>1000 mu) in the biomass and coal extracts but not in the ash extract. Trace element analyses were carried out using ICP-MS on the acid digests prepared by 'wet ashing' and microwave extraction. Sixteen elements (As, Ba, Be, Cd, Co, Cr, Cu, Ga, Mn, Mo, Ni, Pb, Sb, Se, V and Zn) were quantified, in the samples before extraction, in the extracts and in the residues. Concentrations of trace elements in the original biomass sample were lower than in the coal sample while the concentrations in the ash sample were the highest. The major trace elements in the NMP extracts were Ba, Cu, Mn and Zn from the forest residue; Ba, Cu, Mn, Pb and Zn from the coal; Cu and Zn from the ash. These elements are believed to be associated with the organic extracts from the forest residue and coal, and also from the ash. Be and Sb were not quantified in the extracts because they were present at too low concentrations; up to 40% of Mn was extracted from the biomass sample at 202 degrees C, while Se was totally extracted from the ash sample. For the forest residue, approximately 7% (at room temperature) and 45% (at 202 degrees C) of the total trace elements studied were

  9. Evaluation of N-[(11)C]methyl-AMD3465 as a PET tracer for imaging of CXCR4 receptor expression in a C6 glioma tumor model.

    PubMed

    Hartimath, S V; van Waarde, A; Dierckx, R A J O; de Vries, E F J

    2014-11-03

    The chemokine receptor CXCR4 and its ligand CXCL12 play an important role in tumor progression and metastasis. CXCR4 receptors are expressed by many cancer types and provide a potential target for treatment. Noninvasive detection of CXCR4 may aid diagnosis and improve therapy selection. It has been demonstrated in preclinical studies that positron emission tomography (PET) with a radiolabeled small molecule could enable noninvasive monitoring of CXCR4 expression. Here, we prepared N-[(11)C]methyl-AMD3465 as a new PET tracer for CXCR4. N-[(11)C]Methyl-AMD3465 was readily prepared by N-methylation with [(11)C]CH3OTf. The tracer was obtained in a 60 ± 2% yield (decay corrected), the purity of the tracer was >99%, and specific activity was 47 ± 14 GBq/μmol. Tracer stability was tested in vitro using liver microsomes and rat plasma; excellent stability was observed. The tracer was evaluated in rat C6 glioma and human PC-3 cell lines. In vitro cellular uptake of N-[(11)C]methyl-AMD3465 was receptor mediated. The effect of transition metal ions (Cu(2+), Ni(2+), and Zn(2+)) on cellular binding was examined in C6 cells, and the presence of these ions increased the cellular binding of the tracer 9-, 7-, and 3-fold, respectively. Ex vivo biodistribution and PET imaging of N-[(11)C]methyl-AMD3465 were performed in rats with C6 tumor xenografts. Both PET and biodistribution studies demonstrated specific accumulation of the tracer in the tumor (SUV 0.6 ± 0.2) and other CXCR4 expressing organs, such as lymph node (1.5 ± 0.2), liver (8.9 ± 1.0), bone marrow (1.0 ± 0.3), and spleen (1.0 ± 0.1). Tumor uptake was significantly reduced (66%, p < 0.01) after pretreatment with Plerixafor (AMD3100). Biodistribution data indicates a tumor-to-muscle ratio of 7.85 and tumor-to-plasma ratio of 1.14, at 60 min after tracer injection. Our data demonstrated that N-[(11)C]methyl-AMD3465 is capable of detecting physiologic CXCR4 expression in tumors and other CXCR4 expressing tissues

  10. Identification of ω-N-Methyl-4-hydroxytryptamine (Norpsilocin) as a Psilocybe Natural Product.

    PubMed

    Lenz, Claudius; Wick, Jonas; Hoffmeister, Dirk

    2017-10-27

    We report the identification of ω-N-methyl-4-hydroxytryptamine (norpsilocin, 1) from the carpophores of the hallucinogenic mushroom Psilocybe cubensis. The structure was elucidated by 1D and 2D NMR spectroscopy and high-resolution mass spectrometry. Norpsilocin has not previously been reported as a natural product. It likely represents the actual psychotropic agent liberated from its 4-phosphate ester derivative, the known natural product baeocystin. We further present a simple and artifact-free extraction method that prevents dephosphorylation and therefore helps reflect the naturally occurring metabolic profile of Psilocybe mushrooms in subsequent analyses.

  11. Examination of Global Methylation and Targeted Imprinted Genes in Prader-Willi Syndrome.

    PubMed

    Manzardo, A M; Butler, M G

    2016-01-01

    Methylation changes observed in Prader-Willi syndrome (PWS) may impact global methylation as well as regional methylation status of imprinted genes on chromosome 15 (in cis) or other imprinted obesity-related genes on other chromosomes (in trans) leading to differential effects on gene expression impacting obesity phenotype unique to (PWS). Characterize the global methylation profiles and methylation status for select imprinted genes associated with obesity phenotype in a well-characterized imprinted, obesity-related syndrome (PWS) relative to a cohort of obese and non-obese individuals. Global methylation was assayed using two methodologies: 1) enriched LINE-1 repeat sequences by EpigenDx and 2) ELISA-based immunoassay method sensitive to genomic 5-methylcytosine by Epigentek. Target gene methylation patterns at selected candidate obesity gene loci were determined using methylation-specific PCR. Study participants were recruited as part of an ongoing research program on obesity-related genomics and Prader-Willi syndrome. Individuals with non-syndromic obesity (N=26), leanness (N=26) and PWS (N=39). A detailed characterization of the imprinting status of select target genes within the critical PWS 15q11-q13 genomic region showed enhanced cis but not trans methylation of imprinted genes. No significant differences in global methylation were found between non-syndromic obese, PWS or non-obese controls. None. Percentage methylation and the methylation index. The methylation abnormality in PWS due to errors of genomic imprinting effects both upstream and downstream effectors in the 15q11-q13 region showing enhanced cis but not trans methylation of imprinted genes. Obesity in our subject cohorts did not appear to impact global methylation levels using the described methodology.

  12. Brain MRI Characteristics of Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis and Their Associations with 2-Year Clinical Outcome.

    PubMed

    Zhang, T; Duan, Y; Ye, J; Xu, W; Shu, N; Wang, C; Li, K; Liu, Y

    2018-05-01

    Anti- N -methyl-D-aspertate receptor encephalitis is an autoimmune-mediated disease without specific brain MRI features. Our aim was to investigate the brain MR imaging characteristics of anti- N -methyl-D-aspartate receptor encephalitis and their associations with clinical outcome at a 2-year follow-up. We enrolled 53 patients with anti- N -methyl-D-aspartate receptor encephalitis and performed 2-year follow-up. Brain MRIs were acquired for all patients at the onset phase. The brain MR imaging manifestations were classified into 4 types: type 1: normal MR imaging findings; type 2: only hippocampal lesions; type 3: lesions not involving the hippocampus; and type 4: lesions in both the hippocampus and other brain areas. The modified Rankin Scale score at 2-year follow-up was assessed, and the association between the mRS and onset brain MR imaging characteristics was evaluated. Twenty-eight (28/53, 53%) patients had normal MR imaging findings (type 1), and the others (25/53, 47%) had abnormal MRI findings: type 2: 7 patients (13%); type 3: seven patients (13%); and type 4: eleven patients (21%). Normal brain MRI findings were more common in female patients ( P = .02). Psychiatric and behavioral abnormalities were more common in adults ( P = .015), and autonomic symptoms ( P = .025) were more common in pediatric patients. The presence of hippocampal lesions ( P = .008, OR = 9.584; 95% CI, 1.803-50.931) and relapse ( P = .043, OR = 0.111; 95% CI, 0.013-0.930) was associated with poor outcome. Normal brain MRI findings were observed in half of the patients. Lesions in the hippocampus were the most common MR imaging abnormal finding. The presence of hippocampal lesions is the main MR imaging predictor for poor prognosis in patients with anti- N -methyl-D-aspartate receptor encephalitis. © 2018 by American Journal of Neuroradiology.

  13. Crystal structure of di-μ-chlorido-bis-(chlorido-{N1,N1-diethyl-N4-[(pyridin-2-yl-κN)methyl-idene]benzene-1,4-di-amine-κN4}mercury(II)).

    PubMed

    Faizi, Md Serajul Haque; Dege, Necmi; Goleva, Kateryna

    2017-06-01

    The title dinuclear mercury(II) complex, [Hg 2 Cl 4 (C 16 H 19 N 3 ) 2 ], synthesized from the pyridine-derived Schiff base ( E )- N 1 , N 1 -diethyl- N 4 -[(pyridin-2-yl)methyl-idene]benzene-1,4-di-amine (DPMBD), has inversion symmetry. The five-coordinated Hg II atoms have distorted square-pyramidal stereochemistry comprising two N-atom donors from bidentate chelate BPMBD ligands and three Cl-atom donors, two bridging and one monodentate. The dihedral angle between the benzene and the pyridine rings in the BPMBD ligand is 7.55 (4)°. In the crystal, the dinuclear mol-ecules are linked by weak C-H⋯Cl hydrogen bonds, forming zigzag ribbons lying parallel to [001]. Also present in the structure are π-π inter-actions between benzene and pyridine rings [minimum ring-centroid separation = 3.698 (8) Å].

  14. N-(/sup 11/C)-methyl-p-substituted phentermine analogs as potential brain blood flow agents for positron tomography

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kizuka, H.; Elmaleh, D.R.; Boudreaux, G.J.

    The addition of a methyl group to the ..cap alpha..-position of amphetamine increases both the lipophilicity of the agent and its resistance to metabolism by monoamine oxidase. In addition, since tritium substituted phenteramine analog studies suggested that the p-halo phentermines had a greater concentration in the brain and prolonged retention time, the authors evaluated the biological behavior of positron labeled ..cap alpha..-methylamphetamine (phenteramine) in rats, dogs and monkeys. The N-(/sup 11/C) methyl analogs of p-chloro (I) and p-fluoro (II) phentermines were prepared by methylation of their primary amines using /sup 11/Ch/sub 3/I. Biodistribution studies in rats shows brain uptake ismore » in the range of 1% dose/gr at 5 and 15 min for both agents. The activity in blood and eyes is low. Sequential images of the dogs' brain over 1 hour revealed a clearance of <15%. Images of the monkey brain were also obtained using a MGH positron camera PCR-I.« less

  15. -HPLC determination of acidic d-amino acids and their N-methyl derivatives in biological tissues

    PubMed Central

    Tsesarskaia, Mara; Galindo, Erika; Szókán, Gyula; Fisher, George

    2015-01-01

    d-aspartate (d-Asp) and N-methyl-d-aspartate (NMDA) occur in the neuroendocrine systems of vertebrates and invertebrates where they play a role in hormone release and synthesis, neurotransmission, and memory and learning. N-methyl-d-glutamate (NMDG) has also been detected in marine bivalves. Several methods have been used to detect these amino acids, but they require pretreatment of tissue samples with o-phthaldialdehyde (OPA) to remove primary amino acids which interfere with the detection of NMDA and NMDG. We report here a one step derivatization procedure with the chiral reagent N-α-(5-fluoro-2,4-dinitrophenyl)-(d or l)-valine amide, FDNP-Val-NH2, a close analog of Marfey’s reagent but with better resolution and higher molar absorptivity. The diastereomers formed are separated by HPLC on an ODS-Hypersil column eluted with TFA/water – TFA/MeCN. UV absorption at 340 nm permits detection levels as low as 5–10 picomoles. D-Asp, NMDA and NMDG peaks are not obscured by other primary or secondary amino acids; hence pretreatment of tissues with OPA is not required. This method is highly reliable and fast (less than 40 minutes HPLC run). Using this method, we have detected D-Asp, NMDA and NMDG in several biological tissues (octopus brain, optical lobe, and bucchal mass; foot and mantle of the mollusk Scapharca broughtonii), confirming the results of other researchers. PMID:19277955

  16. 49 CFR 173.193 - Bromoacetone, methyl bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... methyl bromide or methyl chloride mixtures, etc. 173.193 Section 173.193 Transportation Other Regulations... bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc. (a) Bromoacetone must be...) Bromoacetone, methyl bromide, chloropicrin and methyl bromide mixtures, chloropicrin and methyl chloride...

  17. Methyl-DEAE-dextran: a candidate biomaterial.

    PubMed

    Zambito, Ylenia; Baggiani, Andrea; Carelli, Vera; Serafini, Maria Francesca; Di Colo, Giacomo

    2004-01-01

    The full quaternisation of DEAE-dextran was successfully attempted and an application of the quaternised product was suggested. Commercial DEAE-dextran was reacted with iodomethane at 60 degrees C in the presence of NaOH. The raw product was purified by dialysis, during which the iodide ion was replaced by chloride. N-methylation and O-methylation resulted from the reaction. A second methylation step produced no further changes in the molecule. Alkalimetry indicated the absence of amino groups in the methylated polymer molecule, thus testifying to a complete quaternisation. N-acetylcysteine (AcCy) was neutralised with the polymer in the hydroxide form, thus obtaining the methyl DEAE-dextran salt of AcCy (Me-DEAE-dextran/AcCy), whereby an ophthalmic formulation for the treatment of the dry eye syndrome was prepared. For comparison, the neutral AcCy salt of commercial DEAE-dextran (DEAE-dextran/AcCy) was prepared. The AcCy content in Me-DEAE-dextran/AcCy was higher than in DEAE-dextran/AcCy (23 vs 13%), while the viscosity of a solution containing the salt concentration corresponding to the therapeutic AcCy concentration (4%w/v) was lower with the former compared to the latter salt (20.5 vs 23.9 mPa s). Both solutions were ipotonic (245 mOsm/kg), whereas the commercial Tirocular is strongly hypertonic (900 mOsm/kg) and irritant.

  18. Discovery of 5-substituted tetrahydronaphthalen-2yl-methyl with N-phenyl-N-(piperidin-4-yl)propionamide derivatives as potent opioid receptor ligands.

    PubMed

    Deekonda, Srinivas; Wugalter, Lauren; Kulkarni, Vinod; Rankin, David; Largent-Milnes, Tally M; Davis, Peg; Bassirirad, Neemah M; Lai, Josephine; Vanderah, Todd W; Porreca, Frank; Hruby, Victor J

    2015-09-15

    A new series of novel opioid ligands have been designed and synthesized based on the 4-anilidopiperidine scaffold containing a 5-substituted tetrahydronaphthalen-2yl)methyl group with different N-phenyl-N-(piperidin-4-yl)propionamide derivatives to study the biological effects of these substituents on μ and δ opioid receptor interactions. Recently our group reported novel 4-anilidopiperidine analogues, in which several aromatic ring-contained amino acids were conjugated with N-phenyl-N-(piperidin-4-yl)propionamide and examined their biological activities at the μ and δ opioid receptors. In continuation of our efforts in these novel 4-anilidopiperidine analogues, we took a peptidomimetic approach in the present design, in which we substituted aromatic amino acids with tetrahydronaphthalen-2yl methyl moiety with amino, amide and hydroxyl substitutions at the 5th position. In in vitro assays these ligands, showed very good binding affinity and highly selective toward the μ opioid receptor. Among these, the lead ligand 20 showed excellent binding affinity (2 nM) and 5000 fold selectivity toward the μ opioid receptor, as well as functional selectivity in GPI assays (55.20 ± 4.30 nM) and weak or no agonist activities in MVD assays. Based on the in vitro bioassay results the lead compound 20 was chosen for in vivo assessment for efficacy in naïve rats after intrathecal administration. Compound 20 was not significantly effective in alleviating acute pain. This discrepancy between high in vitro binding affinity, moderate in vitro activity, and low in vivo activity may reflect differences in pharmacodynamics (i.e., engaging signaling pathways) or pharmacokinetics (i.e., metabolic stability). In sum, our data suggest that further optimization of this compound 20 is required to enhance in vivo activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Synthesis and polymorphic control for visible light active titania nanoparticles

    NASA Astrophysics Data System (ADS)

    Kaewgun, Sujaree

    Titania (TiO2) is useful for many applications in photocatalysis, antimicrobials, pigment, deodorization, and decomposition of harmful organics and undesirable compounds in the air and waste water under UV irradiation. Among the three phases of TiO2, Rutile, Anatase, and Brookite, studies have been more focused on the anatase and rutile phases. Pure brookite is the most difficult phase to prepare, even under hydrothermal conditions. Predominantly brookite phase TiO2 nanoparticles were prepared by the Water-based Ambient Condition Sol (WACS) process in our laboratory. The objectives of this research were to enhance visible light active (VLA) photocatalytic properties of polymorphic brookite TiO2 by minimizing the lattice defects and narrowing band gap of titania by nitrogen and/or carbon chromophone, and to investigate the deactivation, reusability, and regeneration of the VLA titania in order to design better titania catalysts for organic compound degradation applications. In order to study the influence of hydroxyl content on photocatalytic activities (PCAs) of polymorphic titania nanoparticles, the WACS samples were post-treated by a Solvent-based Ambient Condition Sol (SACS) process in sec-butanol (sec-BuOH). All samples were characterized for phase composition, surface area, hydroxyl contamination, and particle morphology by x-ray diffraction, N2 physisorption, FT-IR, solid state 1H NMR and scanning electron microscopy, and then compared to a commercial titania, Degussa P25. Evaluation of methyl orange (MO) degradation under UV irradiation results showed that the lower lattice hydroxyl content in SACS titania enhanced the PCA. As-prepared titania and SACS samples, which have similar surface areas and crystallinity, were compared in order to prove that the superior PCA came from the reduction in the lattice hydroxyl content. To enhance PCA and VLA properties of WACS, an alternative high boiling point polar solvent, N-methylpyrrolidone (NMP), was utilized in the

  20. Examination of Global Methylation and Targeted Imprinted Genes in Prader-Willi Syndrome

    PubMed Central

    Manzardo, AM; Butler, MG

    2016-01-01

    Context Methylation changes observed in Prader-Willi syndrome (PWS) may impact global methylation as well as regional methylation status of imprinted genes on chromosome 15 (in cis) or other imprinted obesity-related genes on other chromosomes (in trans) leading to differential effects on gene expression impacting obesity phenotype unique to (PWS). Objective Characterize the global methylation profiles and methylation status for select imprinted genes associated with obesity phenotype in a well-characterized imprinted, obesity-related syndrome (PWS) relative to a cohort of obese and non-obese individuals. Design Global methylation was assayed using two methodologies: 1) enriched LINE-1 repeat sequences by EpigenDx and 2) ELISA-based immunoassay method sensitive to genomic 5-methylcytosine by Epigentek. Target gene methylation patterns at selected candidate obesity gene loci were determined using methylation-specific PCR. Setting Study participants were recruited as part of an ongoing research program on obesity-related genomics and Prader-Willi syndrome. Participants Individuals with non-syndromic obesity (N=26), leanness (N=26) and PWS (N=39). Results A detailed characterization of the imprinting status of select target genes within the critical PWS 15q11-q13 genomic region showed enhanced cis but not trans methylation of imprinted genes. No significant differences in global methylation were found between non-syndromic obese, PWS or non-obese controls. Intervention None. Main outcome measures Percentage methylation and the methylation index. Conclusion The methylation abnormality in PWS due to errors of genomic imprinting effects both upstream and downstream effectors in the 15q11-q13 region showing enhanced cis but not trans methylation of imprinted genes. Obesity in our subject cohorts did not appear to impact global methylation levels using the described methodology. PMID:28111641

  1. Synthesis of methyl 3-O-alpha-D-mannopyranosyl-alpha-D-talopyranoside and methyl 3-O-alpha-D-talopyranosyl-alpha-D-talopyranoside.

    PubMed

    Dubey, R; Jain, R K; Abbas, S A; Matta, K L

    1987-08-01

    Methyl 2-O-benzyl-3-O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl)-alpha- D-mannopyranoside (4) and methyl 2-O-benzyl-3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside (6) were prepared from a common intermediate, namely, methyl 2-O-benzyl-4,6-O-benzylidene-3-O-(2,3,4,6-tetra-O-acetyl-alpha-D- mannopyranosyl)-alpha-D-mannopyranoside. On treatment with tert-butylchlorodiphenylsilane, in N,N-dimethylformamide in the presence of imidazole, 4 and 6 afforded methyl 2-O-benzyl-6-O-tert-butyldiphenylsilyl-3-O-(2,3,4,6-tetra-O-acetyl -alpha-D- mannopyranosyl)-alpha-D-mannopyranoside (7), and methyl 2-O-benzyl-6-O-tert-butyldiphenylsilyl-3-O-(6-O-tert- butyldiphenylsilyl-alpha-D-mannopyranosyl)-alpha-D-mannopyranoside (8), respectively. Compound 8 was converted into its 2,3-O-isopropylidene derivative (9), and oxidation of 7 and 9 with pyridinium chlorochromate, and reduction of the resulting carbonyl intermediates gave methyl 2-O-benzyl-6-O-tert-butyldiphenylsilyl-3-O-(2,3,4,6-tetra-O-acetyl -alpha-D- mannopyranosyl)-alpha-D-talopyranoside and methyl 2-O-benzyl-6-O-tert-butyldiphenylsilyl-3-O-(6-O-tert-butyldiphe nylsilyl- 2,3-O-isopropylidene-alpha-D-talopyranosyl)-alpha-D-talopyranoside , respectively. Removal of the protecting groups furnished the title disaccharides.

  2. Mechanism of error-free DNA synthesis across N1-methyl-deoxyadenosine by human DNA polymerase-ι

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jain, Rinku; Choudhury, Jayati Roy; Buku, Angeliki

    N1-methyl-deoxyadenosine (1-MeA) is formed by methylation of deoxyadenosine at the N1 atom. 1-MeA presents a block to replicative DNA polymerases due to its inability to participate in Watson-Crick (W-C) base pairing. Here we determine how human DNA polymerase-ι (Polι) promotes error-free replication across 1-MeA. Steady state kinetic analyses indicate that Polι is ~100 fold more efficient in incorporating the correct nucleotide T versus the incorrect nucleotide C opposite 1-MeA. To understand the basis of this selectivity, we determined ternary structures of Polι bound to template 1-MeA and incoming dTTP or dCTP. In both structures, template 1-MeA rotates to the synmore » conformation but pairs differently with dTTP versus dCTP. Thus, whereas dTTP partakes in stable Hoogsteen base pairing with 1-MeA, dCTP fails to gain a “foothold” and is largely disordered. Together, our kinetic and structural studies show how Polι maintains discrimination between correct and incorrect incoming nucleotide opposite 1-MeA in preserving genome integrity.« less

  3. Rotational Spectrum and Conformational Analysis of N-methyl-2-aminoethanol: Insights into the Shape of Adrenergic Neurotransmitters

    NASA Astrophysics Data System (ADS)

    Calabrese, Camilla; Maris, Assimo; Evangelisti, Luca; Piras, Anna; Parravicini, Valentina; Melandri, Sonia

    2018-02-01

    Abstract We describe an experimental and quantum chemical study for the accurate determination of the conformational space of small molecular systems governed by intramolecular non-covalent interactions. The model systems investigated belong to the biological relevant aminoalcohol’s family, and include 2-aminophenylethanol, 2-methylaminophenylethanol, noradrenaline, adrenaline 2-aminoethanol and N-methyl-2-aminoethanol. For the latter molecule, the rotational spectrum in the 6-18 and 59.6-74.4 GHz ranges was recorded in the isolated conditions of a free jet expansion. Based on the analysis of the rotational spectra, two different conformational species and 11 isotopologues were observed and their spectroscopic constants, including 14N-nuclear hyperfine coupling constants and methyl internal rotation barriers, were determined. From the experimental data a structural determination was obtained, which was also used to benchmark accurate quantum chemical calculations on the whole conformational space. Atom in molecules and non-covalent interactions theories allowed the characterization of the position of the intramolecular non-covalent interactions and the energies involved, highlighting the subtle balance responsible of the stabilization of all the molecular systems.

  4. A ring to rule them all: a cyclic ketene acetal comonomer controls the nitroxide-mediated polymerization of methacrylates and confers tunable degradability.

    PubMed

    Delplace, Vianney; Guégain, Elise; Harrisson, Simon; Gigmes, Didier; Guillaneuf, Yohann; Nicolas, Julien

    2015-08-18

    2-Methylene-4-phenyl-1,3-dioxolane (MPDL) was successfully used as a controlling comonomer in NMP with oligo(ethylene glycol) methyl ether methacrylate (MeOEGMA) to prepare well-defined and degradable PEG-based P(MeOEGMA-co-MPDL) copolymers. The level of ester group incorporation is controlled, leading to reductions in molecular weight of up to 95% on hydrolysis. Neither the polymer nor its degradation products displayed cytoxicity. The method was also successfully applied to methyl methacrylate.

  5. Protein methylation in pea chloroplasts. [Pisum sativum

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Niemi, K.J.; Adler, J.; Selman, B.R.

    1990-07-01

    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. Onemore » 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.« less

  6. PEGylated N-methyl-S-methyl dithiocarbazate as a new reagent for the high-yield preparation of nitrido Tc-99m and Re-188 radiopharmaceuticals.

    PubMed

    Boschi, Alessandra; Massi, Alessandro; Uccelli, Licia; Pasquali, Micol; Duatti, Adriano

    2010-11-01

    A novel nitrido nitrogen atom donor for the preparation of (99m)Tc and (188)Re radiopharmaceuticals containing a metal-nitrogen multiple bond is presented. HO(2)C-PEG(600)-DTCZ was obtained by conjugation of N-methyl-S-methyl dithiocarbazate [H(2)N-N(CH(3))-C(S)SCH(3), HDTCZ] with polyethylene glycol 600 (PEG(600)). Asymmetrical heterocomplexes of the type [M(N)(PNP)(B)](0/+) (M=(99m)Tc, (188)Re; PNP=diphosphine ligands, B=DBODC, DEDC, NSH, H(2)OS, CysNAc, HDTCZ) and symmetrical nitride compounds of the type [M(N)(L)(2)] (L=DEDC, DPDC) have been prepared in high yield by using the newly designed nitride nitrogen atom donor HO(2)C-PEG(600)-DTCZ. A two-step procedure was applied for preparing the above symmetrical and asymmetrical complexes. The first step involved the preliminary formation of a mixture of nitride Tc-99m or Re-188 precursors, which contained the [M≡N](2+) core, through reduction of generator-eluted (99m)Tc-pertechnetate or (188)Re-perrhenate with thin (II) chloride in the presence of HO(2)C-PEG(600)-DTCZ. In the second step, the intermediate mixture was converted either in the final mixed asymmetrical complex by the simultaneous addition of diphosphine ligand and the suitable bidentate ligand B, or in the final symmetrical complex by the only addition of the bidentate ligand L. It was also demonstrated that the novel water-soluble nitride nitrogen atom donor HO(2)C-PEG(600)-DTCZ did not show coordinating properties toward the M≡N ((99m)Tc, (188)Re) core. Biodistribution studies in rats of the hitherto unreported [(99m)Tc(N)(PNP(3))DTCZ](+) and [(99m)Tc(N)(PNP(5))DTCZ](+) complexes showed that they selectively localize in the myocardium of rats with a favourable heart-to-lung and heart-to-liver uptake ratios. In particular, the heart-to-lung and heart-to-liver uptake ratios dramatically increased in the interval between 60 and 120 min postinjection. Hence, the combination of the favourable chemical and biological properties of HO(2)C-PEG(600)-DTCZ

  7. Physicochemical and electrochemical properties of N-methyl-N-methoxymethylpyrrolidinium bis(fluorosulfonyl)amide and its lithium salt composites

    NASA Astrophysics Data System (ADS)

    Horiuchi, Shunsuke; Yoshizawa-Fujita, Masahiro; Takeoka, Yuko; Rikukawa, Masahiro

    2016-09-01

    The ionic liquid (IL) N-Methyl-N-methoxymethylpyrrolidinium bis(fluorosulfonyl)amide ([Pyr1,1O1][FSA]) was synthesized, and its physicochemical and electrochemical properties were investigated with respect to its application as an electrolyte in lithium-ion secondary batteries operating over a wide temperature range. [Pyr1,1O1][FSA]/Li salt (0.34 mol kg-1) composites were prepared by adding lithium bis(trifluoromethylsulfonyl)amide (LiTFSA) into the IL. [Pyr1,1O1][FSA] and [Pyr1,1O1][FSA]/LiTFSA exhibited melting temperatures (Tm) below -30 °C. [Pyr1,1O1][FSA] exhibited a higher ionic conductivity value as compared with that of the corresponding IL with only alkyl substituents. The electrochemical window for both [Pyr1,1O1][FSA] and [Pyr1,1O1][FSA]/LiTFSA was 5.1 V. Stable lithium deposition and dissolution occurred on a Ni electrode at 25 °C.

  8. Crystal structures of N-(3-fluoro-benzo-yl)benzene-sulfonamide and N-(3-fluoro-benzo-yl)-4-methyl-benzene-sulfonamide.

    PubMed

    Suchetan, P A; Naveen, S; Lokanath, N K; Lakshmikantha, H N; Srivishnu, K S; Supriya, G M

    2016-04-01

    The crystal structures of two N-(aryl-sulfon-yl)aryl-amides, namely N-(3-fluoro-benzo-yl)benzene-sulfonamide, C13H10FNO3S, (I), and N-(3-fluoro-benzo-yl)-4-methyl-benzene-sulfonamide, C14H12FNO3S, (II), are described and compared with related structures. The dihedral angle between the benzene rings is 82.73 (10)° in (I) compared to 72.60 (12)° in (II). In the crystal of (I), the mol-ecules are linked by C-H⋯O and C-H⋯π inter-actions, resulting in a three-dimensional grid-like architecture, while C-H⋯O inter-actions lead to one-dimensional ribbons in (II). The crystals of both (I) and (II) feature strong but non-structure-directing N-H⋯O hydrogen bonds with R 2 (2)(8) ring motifs. The structure of (I) also features π-π stacking inter-actions.

  9. Increased Frequency of CpG Island Methylator Phenotype and CDH1 Methylation in a Gastric Cancer High-Risk Region of China1

    PubMed Central

    Zhang, Kai-Li; Sun, Yuan; Li, Yan; Liu, Ming; Qu, Bo; Cui, Shu-Hong; Kong, Qing-You; Chen, Xiao-Yan; Li, Hong; Liu, Jia

    2008-01-01

    This study aimed to profile the methylation statuses of CDH1/E-cadherin and five CpG island methylator phenotype (CIMP)-associated genes (p16, hMLH1, MINT1, MINT2, and MINT31) in gastric specimens of 47 Dalian long-term residents with and 31 without gastric cancers (GCs). CIMP patterns were classified as CIMP-H with over three methylated genes, CIMP-L with one to two methylated genes, and CIMP-N without methylation. Of 47 GC cases, 24 (51.1%) were CIMP-H, 18 (38.3%) were CIMP-L, and 5 (10.6%) were CIMP-N, whereas 5 of 21 (23.8%) premalignant lesions were CIMP-H and 15 (71.4%) were CIMP-L. CIMP-L was found in 75% (12/16) of GC-adjacent mucosa and in 38.7% (12/31) of mucosa from GC-free patients. CDH1 methylation occurred in 48.9% (23/47) of cancer, in 23.8% (5/21) of premalignant, and in 25% (4/16) of noncancerous tissues and was correlated with patients' age (P = .01), lymph node metastasis, and CIMP severity (P = .000–.028). Our results demonstrated that the frequencies of CIMP-H in Dalian GCs, CIMP-L, and p16 methylation in GC-adjacent tissues and in GC-free mucosa were much higher than those reported previously, indicating the elevated methylation pressure in this GC high-risk region. The close correlation between CDH1 methylation and CIMP severity suggests the necessity of their combination in GC prevention and earlier diagnosis. PMID:18607505

  10. Characterization of N-methyl-D-aspartate-evoked taurine release in the developing and adult mouse hippocampus.

    PubMed

    Saransaari, P; Oja, S S

    2003-01-01

    Taurine is an inhibitory amino acid acting as an osmoregulator and neuroromodulator in the brain, with neuroprotective properties. The ionotropic glutamate receptor agonist N-methyl-D-aspartate (NMDA) greatly potentiates taurine release from brain preparations in both normal and ischemic conditions, the effect being particularly marked in the developing hippocampus. We now characterized the regulation of NMDA-stimulated taurine release from hippocampal slices from adult (3-month-old) and developing (7-day-old) mouse using a superfusion system. The NMDA-stimulated taurine release was receptor-mediated in both adult and developing mouse hippocampus. In adults, only NO-generating compounds, sodium nitroprusside, S-nitroso-N-acetylpenicillamine and hydroxylamine reduced the release, as did also NO synthase inhibitors, 7-nitroindazole and nitroarginine, indicating that the release is mediated by the NO/cGMP pathway. On the other hand, the regulation of the NMDA-evoked taurine release proved to be somewhat complex in the immature hippocampus. It was not affected by the NOergic compounds, but enhanced by the protein kinase C activator 4 beta-phorbol 12-myristate 13-acetate and adenosine receptor A(1) agonists, N(6)-cyclohexyladenosine and R(-)N(6)-(2-phenylisopropyl)adenosine in a receptor-mediated manner. The activation of both ionotropic 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors and metabotropic glutamate group I receptors also enhanced the evoked release. The NMDA-receptor-stimulated taurine release could be a part of the neuroprotective properties of taurine, being important particularly under cell-damaging conditions in the developing hippocampus and hence preventing excitotoxicity.

  11. Acetone improves the topographical homogeneity of liquid phase exfoliated few-layer black phosphorus flakes.

    PubMed

    Gomez Perez, Juan; Konya, Zoltan; Kukovecz, Akos

    2018-06-12

    Liquid phase exfoliation of 2D materials has issues related to the sorption of the solvent, the oxidation of the sample during storage, and the topographical inhomogeneity of the exfoliated material. N-methyl-2-pyrrolidone (NMP), a common solvent for black phosphorus (BP) exfoliation, has additional drawbacks like the formation of by-products during sonication and poor solvent volatility. Here we demonstrate an improvement in the topographical homogeneity (i.e. thickness and lateral dimensions) of NMP-exfoliated BP flakes after resuspension in acetone. The typical size of monolayers and bilayers stabilised in acetone was 99.8±27.4 nm and 159.1±57 nm, respectively. These standard deviations represent a threefold improvement over those of the NMP-exfoliated originals. Phosphorene can also be exfoliated directly in acetone by very long ultrasonication. The product suspension enjoys the same dimensional homogeneity benefits, which confirms that this effect is an intrinsic property of the acetone-BP system. The quality and stability of the exfoliated flakes was checked by XRD, TEM, electron diffraction and Raman spectroscopy. Thermal expansion coefficients of the A1g, B2g and A2g Raman modes were calculated for drop-casted samples as -0.01828 cm-1/K, -0.03056 cm-1/K and -0.03219 cm-1/K, respectively. The flakes withstand 20 minutes in O2 flow at 373 K without lattice distortion. . © 2018 IOP Publishing Ltd.

  12. The thermoregulatory mechanism of melatonin-induced hypothermia in chicken.

    PubMed

    Rozenboim, I; Miara, L; Wolfenson, D

    1998-01-01

    The involvement of melatonin (Mel) in body temperature (Tb) regulation was studied in White Leghorn layers. In experiment 1, 35 hens were injected intraperitoneally with seven doses of Mel (0, 5, 10, 20, 40, 80, or 160 mg Mel/kg body wt) dissolved in ethanol. Within 1 h, Mel had caused a dose-dependent reduction in Tb. To eliminate a possible vehicle effect, 0, 80, and 160 mg/kg body wt Mel dissolved in N-methyl-2-pyrrolidone (NMP) was injected. NMP had no effect on Tb, with Mel again causing a dose-dependent hypothermia. In experiment 2 (n = 30), Mel injected before exposure of layers to heat reduced Tb and prevented heat-induced hyperthermia. Injection after heat stress had begun did not prevent hyperthermia. Under cold stress, Mel induced hypothermia, which was not observed in controls. In experiment 3 (n = 12), Mel injection reduced Tb and increased metatarsal and comb temperatures (but not feathered-skin temperature), respiratory rate, and evaporative water loss. Heart rate rose and then declined, and blood pressure increased 1 h after Mel injection. Heat production rose slightly during the first hour, then decreased in parallel to the Tb decline. We conclude that pharmacological doses of Mel induce hypothermia in hens by increasing nonevaporative skin heat losses and slightly increasing respiratory evaporation.

  13. Increased levels of N(ε)- Carboxy methyl lysine (N(ε)-CML) are associated with topographic alterations in retinal pigment epithelium: A preliminary study.

    PubMed

    Mishra, Nibha; Saxena, Sandeep; Ruia, Surabhi; Prasad, Senthamizh; Singh, Vinita; Khanna, Vinay; Staffa, Robert; Gaspar, Ludovit; Kruzliak, Peter

    2016-07-01

    To evaluate the association of serum levels of N(ε)- Carboxy methyl lysine (N(ε)-CML), an advanced glycation end product with topographic alterations in retinal pigment epithelium (RPE) in diabetic retinopathy on spectral domain optical coherence tomography (SD-OCT). Consecutive cases of type 2 diabetes mellitus with no retinopathy (n=20); non-proliferative diabetic retinopathy (n=20); proliferative diabetic retinopathy (n=20) and healthy controls (n=20) between the ages of 40 and 65years were included. RPE alterations were graded on segmentation map of SD-OCT: grade 0, No RPE alterations; grade 1, RPE alterations in up to two quadrants and grade 2, RPE alterations in more than two quadrants. Serum level of N(ε)-CML and glycated hemoglobin (HbA1c) was analyzed using the standard protocol. Statistical analysis was done. Significant increase in N(ε)-CML was observed with increased severity of diabetic retinopathy (F=34.1; p<0.0001). Fisher exact test revealed significant increase in grades of RPE alterations with increased severity of diabetic retinopathy (p<0.001). Univariate ordinal regression analysis was done to calculate the risk of progression in grades of RPE alteration with individual changes in variables like duration of diabetes (odds ratio=1.37; p=0.001), HbA1c (odds ratio=1.37; p=0.002) and Nε-CML (odds ratio=1.37; p<0.0001). Multivariate ordinal regression analysis for predicting progression in grades of RPE alteration revealed Nε-CML to be an independent predictor of increase in grades of RPE alteration (adjusted odds ratio=1.07; p<0.01) when duration of diabetes and HbA1c were held constant. Increase in serum levels of N(ε)- Carboxy methyl lysine is significantly associated with topographic alterations in RPE. Grades of RPE alteration increase significantly with increased severity of diabetic retinopathy. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. The impact of methylation quantitative trait loci (mQTLs) on active smoking-related DNA methylation changes.

    PubMed

    Gao, Xu; Thomsen, Hauke; Zhang, Yan; Breitling, Lutz Philipp; Brenner, Hermann

    2017-01-01

    Methylation quantitative trait loci (mQTLs) are the genetic variants that may affect the DNA methylation patterns of CpG sites. However, their roles in influencing the disturbances of smoking-related epigenetic changes have not been well established. This study was conducted to address whether mQTLs exist in the vicinity of smoking-related CpG sites (± 50 kb) and to examine their associations with smoking exposure and all-cause mortality in older adults. We obtained DNA methylation profiles in whole blood samples by Illumina Infinium Human Methylation 450 BeadChip array of two independent subsamples of the ESTHER study (discovery set, n  = 581; validation set, n  = 368) and their corresponding genotyping data using the Illumina Infinium OncoArray BeadChip. After correction for multiple testing (FDR), we successfully identified that 70 out of 151 previously reported smoking-related CpG sites were significantly associated with 192 SNPs within the 50 kb search window of each locus. The 192 mQTLs significantly influenced the active smoking-related DNA methylation changes, with percentage changes ranging from 0.01 to 18.96%, especially for the weakly/moderately smoking-related CpG sites. However, these identified mQTLs were not directly associated with active smoking exposure or all-cause mortality. Our findings clearly demonstrated that if not dealt with properly, the mQTLs might impair the power of epigenetic-based models of smoking exposure to a certain extent. In addition, such genetic variants could be the key factor to distinguish between the heritable and smoking-induced impact on epigenome disparities. These mQTLs are of special importance when DNA methylation markers measured by Illumina Infinium assay are used for any comparative population studies related to smoking-related cancers and chronic diseases.

  15. N-acetylcysteine reverses immunotoxic effects of methyl mercury and augments murine lymphocyte proliferation in vitro

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Omara, F.; Fournier, M.; Bernier, J.

    1995-12-31

    N-Acetylcysteine (NAC) is a thiol antioxidant used clinically to treat chronic inflammatory lung disorders and acetaminophen poisoning in humans. The authors evaluated in vitro the effect of NAC on mitogen-induced blastogenesis in C57BI/6 mouse splenocytes by {sup 3}H-thymidine uptake, and its ability to protect against the immunotoxic effects of methyl mercury on lymphocyte proliferation. Lymphocyte proliferation stimulated by optimal and suboptimal concentrations of concanavalin A (Con A), lipopolysaccharide (LPS), or a combination of calcium ionophore A23187 and phorbol-12-myristate-13-acetate (PMA) were markedly enhanced by NAC. NAC itself was a weak mitogen. The kinetics of the NAC effect on splenocyte proliferation weremore » mitogen dependent. NAC enhanced Con A-induced splenocyte proliferation in a dose-dependent and linear manner but enhanced the LPS-induced response at 50--400 {micro}g/ml of NAC followed by a decline in response to control value at higher concentrations. In splenocytes stimulated with PMA plus A23187, NAC increased proliferation at 50--200 pg/ml followed by a constant response at 200--1,000 {micro}g/ml NAC. When splenocytes were stimulated with higher concentrations of Con A (10 {micro}g/ml) or LPS (150 {micro}g/ml) which markedly suppress splenocyte proliferation, NAC significantly enhanced the Con A-induced response and reversed the inhibitory effect of high concentrations of LPS. NAC also protected lymphocytes against mitogen activation-induced cell death. Methyl mercury at 5 {times} 10{sup {minus}7}--1 {times} 10{sup {minus}6} suppressed Con A- and LPS-induced splenocyte proliferation by over 80%. However, NAC completely reversed the immunotoxic effects of methyl mercury on the mitogen-induced splenocyte proliferation even when the cells were pre-incubated with methyl mercury for 6 or 24 hr before stimulation with the mitogens.« less

  16. N4-cytosine DNA methylation regulates transcription and pathogenesis in Helicobacter pylori

    PubMed Central

    Kumar, Sumith; Karmakar, Bipul C; Nagarajan, Deepesh; Mukhopadhyay, Asish K; Morgan, Richard D; Rao, Desirazu N

    2018-01-01

    Abstract Many bacterial genomes exclusively display an N4-methyl cytosine base (m4C), whose physiological significance is not yet clear. Helicobacter pylori is a carcinogenic bacterium and the leading cause of gastric cancer in humans. Helicobacter pylori strain 26695 harbors a single m4C cytosine methyltransferase, M2.HpyAII which recognizes 5′ TCTTC 3′ sequence and methylates the first cytosine residue. To understand the role of m4C modification, M2.hpyAII deletion strain was constructed. Deletion strain displayed lower adherence to host AGS cells and reduced potential to induce inflammation and apoptosis. M2.hpyAII gene deletion strain exhibited reduced capacity for natural transformation, which was rescued in the complemented strain carrying an active copy of M2.hpyAII gene in the genome. Genome-wide gene expression and proteomic analysis were carried out to discern the possible reasons behind the altered phenotype of the M2.hpyAII gene deletion strain. Upon the loss of m4C modification a total of 102 genes belonging to virulence, ribosome assembly and cellular components were differentially expressed. The present study adds a functional role for the presence of m4C modification in H. pylori and provides the first evidence that m4C signal acts as a global epigenetic regulator in H. pylori. PMID:29481677

  17. Garlic and associated allyl sulfur components inhibit N-methyl-N-nitrosourea induced rat mammary carcinogenesis.

    PubMed

    Schaffer, E M; Liu, J Z; Green, J; Dangler, C A; Milner, J A

    1996-04-19

    Our previous studies demonstrated that dietary garlic powder supplementation inhibits N-nitrosamine induced DNA alkylation in liver and mammary tissue. The present studies compared the impact of dietary supplementation with garlic powder or two garlic constituents, water-soluble S-allyl cysteine (SAC) and oil-soluble diallyl disulfide (DADS), on the incidence of mammary tumorigenesis induced by N-methyl-N-nitrosourea (MNU). Female Sprague-Dawley rats were fed semi-purified casein based diets with or without supplements of garlic powder(20g/kg), SAC (57 micromol/kg) or DADS (57 micromol/kg) for 2 weeks prior to treatment with MNU (15 mg/kg body wt). Garlic powder, SAC and DADS supplementation significantly delayed the onset of mammary tumors compared to rats receiving the unsupplemented diet. Tumor incidence 23 weeks after MNU treatment was reduced by 76, 41 and 53% in rats fed garlic, SAC and DADS, respectively, compared to controls (P<0.05). Total tumor number was reduced 81, 35 and 65% by these supplements, respectively (P<0.05). In a separate study the quantity of mammary DNA alkylation occurring 3 h after MNU treatment was reduced in rats fed garlic, SAC or DADS (P<0.05). Specifically, O(6)-methylguanine adducts were reduced by 27, 18 and 23% in rats fed supplemental garlic, SAC and DADS, respectively, compared to controls. N(7)-Methylguanine adducts decreased by 48, 22 and 21% respectively, compared to rats fed the control diet. These studies demonstrate that garlic and associated allyl sulfur components, SAC and DADS, are effective inhibitors of MNU-induced mammary carcinogenesis.

  18. Alpha-Synuclein Produces Early Behavioral Alterations via Striatal Cholinergic Synaptic Dysfunction by Interacting With GluN2D N-Methyl-D-Aspartate Receptor Subunit.

    PubMed

    Tozzi, Alessandro; de Iure, Antonio; Bagetta, Vincenza; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Costa, Cinzia; Di Filippo, Massimiliano; Ghiglieri, Veronica; Latagliata, Emanuele Claudio; Wegrzynowicz, Michal; Decressac, Mickael; Giampà, Carmela; Dalley, Jeffrey W; Xia, Jing; Gardoni, Fabrizio; Mellone, Manuela; El-Agnaf, Omar Mukhtar; Ardah, Mustafa Taleb; Puglisi-Allegra, Stefano; Björklund, Anders; Spillantini, Maria Grazia; Picconi, Barbara; Calabresi, Paolo

    2016-03-01

    Advanced Parkinson's disease (PD) is characterized by massive degeneration of nigral dopaminergic neurons, dramatic motor and cognitive alterations, and presence of nigral Lewy bodies, whose main constituent is α-synuclein (α-syn). However, the synaptic mechanisms underlying behavioral and motor effects induced by early selective overexpression of nigral α-syn are still a matter of debate. We performed behavioral, molecular, and immunohistochemical analyses in two transgenic models of PD, mice transgenic for truncated human α-synuclein 1-120 and rats injected with the adeno-associated viral vector carrying wild-type human α-synuclein. We also investigated striatal synaptic plasticity by electrophysiological recordings from spiny projection neurons and cholinergic interneurons. We found that overexpression of truncated or wild-type human α-syn causes partial reduction of striatal dopamine levels and selectively blocks the induction of long-term potentiation in striatal cholinergic interneurons, producing early memory and motor alterations. These effects were dependent on α-syn modulation of the GluN2D-expressing N-methyl-D-aspartate receptors in cholinergic interneurons. Acute in vitro application of human α-syn oligomers mimicked the synaptic effects observed ex vivo in PD models. We suggest that striatal cholinergic dysfunction, induced by a direct interaction between α-syn and GluN2D-expressing N-methyl-D-aspartate receptors, represents a precocious biological marker of the disease. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Random Mutagenesis of the Multidrug Transporter AcrB from Escherichia coli for Identification of Putative Target Residues of Efflux Pump Inhibitors

    PubMed Central

    Kohler, Samay; Buck, Annika; Dambacher, Christine; König, Armin; Bohnert, Jürgen A.; Kern, Winfried V.

    2014-01-01

    Efflux is an important mechanism of bacterial multidrug resistance (MDR), and the inhibition of MDR pumps by efflux pump inhibitors (EPIs) could be a promising strategy to overcome MDR. 1-(1-Naphthylmethyl)-piperazine (NMP) and phenylalanine-arginine-β-naphthylamide (PAβN) are model EPIs with activity in various Gram-negative bacteria expressing AcrB, the major efflux pump of Escherichia coli, or similar homologous pumps of the resistance-nodulation-cell division class. The aim of the present study was to generate E. coli AcrB mutants resistant to the inhibitory action of the two model EPIs and to identify putative EPI target residues in order to better understand mechanisms of pump inhibition. Using an in vitro random mutagenesis approach focusing on the periplasmic domain of AcrB, we identified the double mutation G141D N282Y, which substantially compromised the synergistic activity of NMP with linezolid, was associated with similar intracellular linezolid concentrations in the presence and absence of NMP, and did not impair the intrinsic MICs of various pump substrates and dye accumulation. We propose that these mutations near the outer face of the distal substrate binding pocket reduce NMP trapping. Other residues found to be relevant for efflux inhibition by NMP were G288 and A279, but mutations at these sites also changed the susceptibility to several pump substrates. Unlike with NMP, we were unable to generate AcrB periplasmic domain mutants with resistance or partial resistance to the EPI activity of PAβN, which is consistent with the modes of action of PAβN differing from those of NMP. PMID:25182653

  20. The role of N-methyl-D-aspartate receptors and nitric oxide in cochlear dopamine release.

    PubMed

    Halmos, G; Horváth, T; Polony, G; Fekete, A; Kittel, A; Vizi, E S; van der Laan, B F A M; Zelles, T; Lendvai, B

    2008-06-23

    Dopamine (DA) released from lateral olivocochlear (LOC) terminals may have a neuroprotective effect in the cochlea. To explore the role of N-methyl-d-aspartate (NMDA) receptors and nitric oxide (NO) in the modulation of a cochlear DA release, we measured the release of [3H]DA from isolated mouse cochlea in response to the application of NMDA. NMDA at 100 muM significantly increased the electrical-field stimulation-evoked and resting release of DA from the cochlea. The NO donor sodium nitroprusside enhanced the basal outflow of DA but failed to influence the evoked release. The administration of the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) alone was ineffective, but it significantly inhibited the initial phase of the NMDA-induced elevation of DA outflow, which suggested the role of NO in the NMDA-induced DA release. The DA uptake inhibitor nomifensine increased the electrically evoked release of DA. Nomifensine failed to change the effect of NMDA on the resting or electrically-evoked DA release, which suggested that the uptake mechanism does not play a role in NMDA-evoked and NO-mediated DA release. In summary, we provide evidence that NO can modulate the release of DA from the cochlea following NMDA receptor activation, but does not affect the uptake of DA.

  1. Theoretical study of the regioselectivity of the interaction of 3-methyl-4-pyrimidone and 1-methyl-2-pyrimidone with Lewis acids.

    PubMed

    Kasende, Okuma Emile; Muya, Jules Tshishimbi; Broeckaert, Lies; Maes, Guido; Geerlings, Paul

    2012-08-23

    A density functional theory (DFT) study is performed to determine the stability of the complexes formed between either the N or O site of 3-methyl-4-pyrimidone and 1-methyl-2-pyrimidone molecules and different ligands. The studied ligands are boron and alkali Lewis acids, namely, B(CH(3))(3), HB(CH(3))(2), H(2)B(CH(3)), BH(3), H(2)BF, HBF(2), BF(3), Li(+), Na(+), and K(+). The acids are divided into two groups according to their hardness. The reactivity predictions, according to the molecular electrostatic potential (MEP) map and the natural bond orbital (NBO) analysis, are in agreement with the calculated relative stabilities. Our findings reveal a strong regioselectivity with borane and its derivatives preferring the nitrogen site in both pyrimidone isomers, while a preference for oxygen is observed for the alkali acids in the 3-methyl-4-pyrimidone molecule. The complexation of 1-methyl-2-pyrimidone with these hard alkali acids does not show any discrimination between the two sites due to the presence of a continuous delocalized density region between the nitrogen and the oxygen atoms. The preference of boron Lewis acids toward the N site is due to the stronger B-N bond as compared to the B-O bond. The influence of fluorine or methyl substitution on the boron atom is discussed through natural orbital analysis (NBO) concentrating on the overlap of the boron empty p-orbital with the F lone pairs and methyl hyperconjugation, respectively. The electrophilicity of the boron acids gives a good overall picture of the interaction capabilities with the Lewis base.

  2. N-(Diphenyl­carbamo­yl)-N,N′,N′,N′′,N′′-penta­methyl­guanidinium tetra­phenyl­borate

    PubMed Central

    Tiritiris, Ioannis

    2013-01-01

    In the title salt, C19H25N4O+·C24H20B−, the C=N and C—N bond lengths in the CN3 unit are 1.3327 (8)/1.3364 (9) and 1.3802 (9) Å, indicating double- and single-bond character, respectively. The N—C—N angles are 118.77 (6), 120.29 (6) and 120.81 (6)°, showing only a small deviation of the CN3 plane from an ideal trigonal-planar geometry. The bonds between the N atoms and the terminal methyl C atoms all have values close to a typical single bond [1.4636 (9)–1.4772 (9) Å]. The crystal packing is caused by electrostatic inter­actions between cations and anions. PMID:23476477

  3. Aberrant DNA methylation patterns of spermatozoa in men with unexplained infertility.

    PubMed

    Urdinguio, Rocío G; Bayón, Gustavo F; Dmitrijeva, Marija; Toraño, Estela G; Bravo, Cristina; Fraga, Mario F; Bassas, Lluís; Larriba, Sara; Fernández, Agustín F

    2015-05-01

    between DNA hypomethylation and regions corresponding to those which, in somatic cells, are enriched in the repressive histone mark H3K9me3, and between DNA hypermethylation and regions enriched in H3K4me1 and CTCF, suggesting that the relationship between chromatin context and aberrant DNA methylation of sperm in infertile men could be locus-dependent. Finally, we also show that DNA methylation patterns, not only at specific loci but also at several repetitive sequences (LINE-1, Alu Yb8, NBL2, D4Z4), were lower in sperm than in somatic cells. Interestingly, sperm samples at Alu Yb8 repetitive sequences of infertile patients showed significantly lower DNA methylation levels than controls. Our results are descriptive and further studies would be needed to elucidate the functional effects of aberrant DNA methylation on male fertility. Overall, our data suggest that aberrant sperm DNA methylation might contribute to fertility impairment in couples with unexplained infertility and they provide a promising basis for future research. This work has been financially supported by Fundación Cientifica de la AECC (to R.G.U.); IUOPA (to G.F.B.); FICYT (to E.G.T.); the Spanish National Research Council (CSIC; 200820I172 to M.F.F.); Fundación Ramón Areces (to M.F.F); the Plan Nacional de I+D+I 2008-2011/2013-2016/FEDER (PI11/01728 to AF.F., PI12/01080 to M.F.F. and PI12/00361 to S.L.); the PN de I+D+I 2008-20011 and the Generalitat de Catalunya (2009SGR01490). A.F.F. is sponsored by ISCIII-Subdirección General de Evaluación y Fomento de la Investigación (CP11/00131). S.L. is sponsored by the Researchers Stabilization Program from the Spanish National Health System (CES09/020). The IUOPA is supported by the Obra Social Cajastur, Spain. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Effects of n-alkanols and a methyl ester on a transient potassium (IA) current in identified neurones from Helix aspersa.

    PubMed Central

    Winpenny, J P; Elliott, J R; Harper, A A

    1992-01-01

    1. A two-microelectrode voltage clamp was used to determine the effects of n-butanol, n-hexanol, n-octanol, n-decanol and methyl hexanoate on a transient potassium (IA) current in identified Helix aspersa neurones. Experiments were carried out at a temperature of 10-12 degrees C. 2. Each n-alkanol reversibly reduced the amplitude of the IA current. Logarithmic dose-response curves for the current reduction by each homologue were sigmoidal and had slope factors of around four. The concentrations required to reduce the peak (with time) current at -30 mV by 50% (ED50 +/- fitted standard error) were: 57 +/- 5 mM (n-butanol); 2.0 +/- 0.1 mM (n-hexanol); 0.28 +/- 0.02 mM (n-octanol) and 0.016 +/- 0.001 mM (n-decanol). Methyl hexanoate also reduced the current amplitude, with an ED50 of 1-2 mM. The Helix IA current thus showed a similar sensitivity to n-alkanols to that of squid and rat sodium currents but was rather more sensitive than the squid delayed rectifier potassium current. 3. The n-alkanol ED50 concentrations were used to calculate a standard free energy per methylene group for adsorption to a site of action in the cell of -3.1 +/- 0.2 kJ/mol. This suggested a hydrophobic site or sites of action. The regularity of the change in free energy with chain length was maintained up to, and including, n-decanol. This implied that the site(s) could accommodate a ten-carbon chain as readily as an eight-carbon chain. 4. The voltage dependencies of IA current activation and steady-state inactivation were not consistently altered by treatment with n-alkanols at concentrations around or above their current suppression ED50 concentrations. 5. The kinetics of current activation and inactivation were affected, particularly by lower chain length compounds. At 60 mM n-butanol reduced the time constant for development of inactivation of open channels (tau b) by 56%, while 0.016 mM n-decanol produced only a 13% reduction. n-Butanol (60 mM) also caused a substantial (76%) reduction

  5. A sensitive and efficient method for determination of N-acetylhexosamines and N-acetylneuraminic acid in breast milk and milk-based products by high-performance liquid chromatography via UV detection and mass spectrometry identification.

    PubMed

    Chuanxiang, Wu; Lian, Xia; Lijie, Liu; Fengli, Qu; Zhiwei, Sun; Xianen, Zhao; Jinmao, You

    2016-02-01

    A sensitive and efficient method of high performance liquid chromatography using 1-(2-naphthyl)-3-methyl-5-pyrazolone (NMP) as pre-column derivatization reagent coupled with UV detection (HPLC-UV) and online mass spectrometry identification was established for determination of the most common N-Acetylhexosamines (N-acetyl-d-glucosamine (GlcNAc) and N-acetyl-d-galactosamine (GalNAc)) and N-acetylneuraminic acid (Neu5Ac). In order to obtain the highest liberation level of the three monosaccharides without destruction of Neu5Ac or conversion of GlcNAc/GalNAc to GlcN/GalN in the hydrolysis procedure, the pivotal parameters affecting the liberation of N-acetylhexosamines/Neu5Ac from sample were investigated with response surface methodology (RSM). Under the optimized condition, maximum yield was obtained. The effects of key parameters on derivatization, separation and detection were also investigated. At optimized conditions, three monosaccharides were labeled fast and entirely, and all derivatives exhibited a good baseline resolution and high detection sensitivity. The developed method was linear over the calibration range 0.25-12μM, with R(2)>0.9991. The detection limits of the method were between 0.48 and 2.01pmol. Intra- and inter-day precisions for the three monosaccharides (GlcNAc, GalNAc and Neu5Ac) were found to be in the range of 3.07-4.02% and 3.69-4.67%, respectively. Individual monosaccharide recovery from spiked milk was in the range of 81%-97%. The sensitivity of the method, the facility of the derivatization procedure and the reliability of the hydrolysis conditions suggest the proposed method has a high potential for utilization in routine trace N-acetylhexosamines and Neu5Ac analysis in biological samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Synthesis, characterization, DNA-Binding, enzyme inhibition and antioxidant studies of new N-methylated derivatives of pyridinium amine

    NASA Astrophysics Data System (ADS)

    Zafar, Muhammad Naveed; Perveen, Fouzia; Nazar, Muhammad Faizan; Mughal, Ehsan Ullah; Rafique, Humera; Tahir, Muhammad Nawaz; Akbar, Muhammad Sharif; Zahra, Sabeen

    2017-06-01

    A series of novel N-methylated derivatives of pyridinium amine, [L1][Tf]-[L5][Tf], were synthesized and characterized by FTIR, NMR, MS and XRD analyses. Preliminary biological screening of these compounds including antioxidant, enzyme inhibition and DNA (salmon sperm) interaction studies were also carried out. The targeted compounds were synthesized by a melt reaction between 4-chloro-N-methyl pyridinium triflate and corresponding amines (1-naphthyl amine, o-ansidine, 2-nitroaniline, p-ansidine and cyclohexyl amine) at temperature of 230 °C. The DPPH radical antioxidant scavenging activities of these compounds at maximum concentration of 50 μg/mL were observed in the range of 60-70%. Acetylcholine esterase (AChE) and Butylcholine esterase (BChE) inhibitory activities of synthesized compounds at 2 mM concentration were also measured to be at maximum of 79 and 71% respectively. The spectral behavior of ligand-DNA obtained from photo-luminescent measurements showed that all ligands bind with DNA via non-covalent interactions. The binding constant values were determined by UV-visible and fluorescence spectroscopy and were quite close to that obtained from molecular docking studies.

  7. Identification of Differentially Methylated Sites with Weak Methylation Effects

    PubMed Central

    Tran, Hong; Zhu, Hongxiao; Wu, Xiaowei; Kim, Gunjune; Clarke, Christopher R.; Larose, Hailey; Haak, David C.; Westwood, James H.; Zhang, Liqing

    2018-01-01

    Deoxyribonucleic acid (DNA) methylation is an epigenetic alteration crucial for regulating stress responses. Identifying large-scale DNA methylation at single nucleotide resolution is made possible by whole genome bisulfite sequencing. An essential task following the generation of bisulfite sequencing data is to detect differentially methylated cytosines (DMCs) among treatments. Most statistical methods for DMC detection do not consider the dependency of methylation patterns across the genome, thus possibly inflating type I error. Furthermore, small sample sizes and weak methylation effects among different phenotype categories make it difficult for these statistical methods to accurately detect DMCs. To address these issues, the wavelet-based functional mixed model (WFMM) was introduced to detect DMCs. To further examine the performance of WFMM in detecting weak differential methylation events, we used both simulated and empirical data and compare WFMM performance to a popular DMC detection tool methylKit. Analyses of simulated data that replicated the effects of the herbicide glyphosate on DNA methylation in Arabidopsis thaliana show that WFMM results in higher sensitivity and specificity in detecting DMCs compared to methylKit, especially when the methylation differences among phenotype groups are small. Moreover, the performance of WFMM is robust with respect to small sample sizes, making it particularly attractive considering the current high costs of bisulfite sequencing. Analysis of empirical Arabidopsis thaliana data under varying glyphosate dosages, and the analysis of monozygotic (MZ) twins who have different pain sensitivities—both datasets have weak methylation effects of <1%—show that WFMM can identify more relevant DMCs related to the phenotype of interest than methylKit. Differentially methylated regions (DMRs) are genomic regions with different DNA methylation status across biological samples. DMRs and DMCs are essentially the same concepts, with

  8. p-Chlorophenyl methyl sulfide

    Integrated Risk Information System (IRIS)

    p - Chlorophenyl methyl sulfide ; CASRN 123 - 09 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for N

  9. Gestational N-hexane inhalation alters the expression of genes related to ovarian hormone production and DNA methylation states in adult female F1 rat offspring.

    PubMed

    Li, Hong; Zhang, Chenyun; Ni, Feng; Guo, Suhua; Wang, Wenxiang; Liu, Jing; Lu, Xiaoli; Huang, Huiling; Zhang, Wenchang

    2015-12-15

    Research has revealed that n-hexane can disrupt adult female endocrine functions; however, few reports have focused on endocrine changes in adult F1 females after maternal exposure during gestation. In this study, female Wistar rats inhaled 100, 500, 2500, or 12,500 ppm n-hexane for 4 h daily during their initial 20 gestational days. The F1 female offspring exhibited abnormal oestrus cycles. Compared with the controls, the in vitro-cultured ovarian granulosa cells of the 12,500 ppm group showed significantly reduced in vitro progesterone and oestradiol secretion. Elevated progesterone secretion was observed in the 500 ppm group, and decreased and significantly upregulated mRNA expression of the Star, Cyp11a1, Cyp17a1, and Hsd3b genes was observed in the 12,500 ppm and 500 ppm groups, respectively. The protein expression levels were consistent with the mRNA expression levels. Methylation screening of the promoter regions of these genes was performed using MeDIP-chip and confirmed by methylation-sensitive high-resolution melting (MS-HRM), and the observed methylation state changes of the promoter regions were correlated with the gene expression levels. The results suggest that the hormone levels in the female offspring after gestational n-hexane inhalation correspond to the expression levels and DNA methylation states of the hormone production genes. Copyright © 2015. Published by Elsevier Ireland Ltd.

  10. Promoter CpG methylation of multiple genes in pituitary adenomas: frequent involvement of caspase-8.

    PubMed

    Bello, M Josefa; De Campos, Jose M; Isla, Alberto; Casartelli, Cacilda; Rey, Juan A

    2006-02-01

    The epigenetic changes in pituitary adenomas were identified by evaluating the methylation status of nine genes (RB1, p14(ARF), p16(INK4a), p73, TIMP-3, MGMT, DAPK, THBS1 and caspase-8) in a series of 35 tumours using methylation-specific PCR analysis plus sequencing. The series included non-functional adenomas (n=23), prolactinomas (n=6), prolactinoma plus thyroid-stimulating hormone adenoma (n=1), growth hormone adenomas (n=4), and adrenocorticotropic adenoma (n=1). All of the tumours had methylation of at least one of these genes and 40% of samples (14 of 35) displayed concurrent methylation of at least three genes. The frequencies of aberrant methylation were: 20% for RB1, 17% for p14(ARF), 34% for p16(INK4a), 29% for p73, 11% for TIMP-3, 23% for MGMT, 6% for DAPK, 43% for THBS1 and 54% for caspase-8. No aberrant methylation was observed in two non-malignant pituitary samples from healthy controls. Although some differences in the frequency of gene methylation between functional and non-functional adenomas were detected, these differences did not reach statistical significance. Our results suggest that promoter methylation is a frequent event in pituitary adenoma tumourigenesis, a process in which inactivation of apoptosis-related genes (DAPK, caspase-8) might play a key role.

  11. DNA methylation markers for oral pre-cancer progression: A critical review.

    PubMed

    Shridhar, Krithiga; Walia, Gagandeep Kaur; Aggarwal, Aastha; Gulati, Smriti; Geetha, A V; Prabhakaran, Dorairaj; Dhillon, Preet K; Rajaraman, Preetha

    2016-02-01

    Although oral cancers are generally preceded by a well-established pre-cancerous stage, there is a lack of well-defined clinical and morphological criteria to detect and signal progression from pre-cancer to malignant tumours. We conducted a critical review to summarize the evidence regarding aberrant DNA methylation patterns as a potential diagnostic biomarker predicting progression. We identified all relevant human studies published in English prior to 30th April 2015 that examined DNA methylation (%) in oral pre-cancer by searching PubMed, Web-of-Science and Embase databases using combined key-searches. Twenty-one studies (18-cross-sectional; 3-longitudinal) were eligible for inclusion in the review, with sample sizes ranging from 4 to 156 affected cases. Eligible studies examined promoter region hyper-methylation of tumour suppressor genes in pathways including cell-cycle-control (n=15), DNA-repair (n=7), cell-cycle-signalling (n=4) and apoptosis (n=3). Hyper-methylated loci reported in three or more studies included p16, p14, MGMT and DAPK. Two longitudinal studies reported greater p16 hyper-methylation in pre-cancerous lesions transformed to malignancy compared to lesions that regressed (57-63.6% versus 8-32.1%; p<0.01). The one study that explored epigenome-wide methylation patterns reported three novel hyper-methylated loci (TRHDE; ZNF454; KCNAB3). The majority of reviewed studies were small, cross-sectional studies with poorly defined control groups and lacking validation. Whilst limitations in sample size and study design preclude definitive conclusions, current evidence suggests a potential utility of DNA methylation patterns as a diagnostic biomarker for oral pre-cancer progression. Robust studies such as large epigenome-wide methylation explorations of oral pre-cancer with longitudinal tracking are needed to validate the currently reported signals and identify new risk-loci and the biological pathways of disease progression. Copyright © 2015 The

  12. DNA methylation markers for oral pre-cancer progression: A critical review

    PubMed Central

    Shridhar, Krithiga; Walia, Gagandeep Kaur; Aggarwal, Aastha; Gulati, Smriti; Geetha, A.V.; Prabhakaran, Dorairaj; Dhillon, Preet K.; Rajaraman, Preetha

    2016-01-01

    Summary Although oral cancers are generally preceded by a well-established pre-cancerous stage, there is a lack of well-defined clinical and morphological criteria to detect and signal progression from pre-cancer to malignant tumours. We conducted a critical review to summarize the evidence regarding aberrant DNA methylation patterns as a potential diagnostic biomarker predicting progression. We identified all relevant human studies published in English prior to 30th April 2015 that examined DNA methylation (%) in oral pre-cancer by searching PubMed, Web-of-Science and Embase databases using combined key-searches. Twenty-one studies (18-cross-sectional; 3-longitudinal) were eligible for inclusion in the review, with sample sizes ranging from 4 to 156 affected cases. Eligible studies examined promoter region hyper-methylation of tumour suppressor genes in pathways including cell-cycle-control (n = 15), DNA-repair (n = 7), cell-cycle-signalling (n = 4) and apoptosis (n = 3). Hyper-methylated loci reported in three or more studies included p16, p14, MGMT and DAPK. Two longitudinal studies reported greater p16 hyper-methylation in pre-cancerous lesions transformed to malignancy compared to lesions that regressed (57–63.6% versus 8–32.1%; p < 0.01). The one study that explored epigenome-wide methylation patterns reported three novel hyper-methylated loci (TRHDE; ZNF454; KCNAB3). The majority of reviewed studies were small, cross-sectional studies with poorly defined control groups and lacking validation. Whilst limitations in sample size and study design preclude definitive conclusions, current evidence suggests a potential utility of DNA methylation patterns as a diagnostic biomarker for oral pre-cancer progression. Robust studies such as large epigenome-wide methylation explorations of oral pre-cancer with longitudinal tracking are needed to validate the currently reported signals and identify new risk-loci and the biological pathways of disease

  13. Addition reaction of methyl cinnamate with 2-amino-4- nitrophenol

    NASA Astrophysics Data System (ADS)

    Suryanti, Venty; Rakhman Wibowo, Fajar; Pranoto; Robingatun Isnaeni, Siti; Ratna Kumala Sari, Meiyanti; Handayani, Sekar

    2016-02-01

    A novel compound which have one N-H fragment and nitrophenyl group has been designed and synthesized from cinnamaldehyde. The reaction was conducted in 3 step reactions to give the final product. Firstly, cinnamaldehyde was converted into cinnamic acid, which was then esterified with methyl alcohol to obtained methyl cinnamate. The last step was the addition reaction between methyl cinnamate and 2-amino-4-nitrophenol to give a cinnamaldehyde derivative, namely methyl-3-(2-hidroksi-5-nitrophenyl amino)-3- phenylpropanoate.

  14. RlmCD-mediated U747 methylation promotes efficient G748 methylation by methyltransferase RlmAII in 23S rRNA in Streptococcus pneumoniae; interplay between two rRNA methylations responsible for telithromycin susceptibility

    PubMed Central

    Shoji, Tatsuma; Takaya, Akiko; Sato, Yoshiharu; Kimura, Satoshi; Suzuki, Tsutomu; Yamamoto, Tomoko

    2015-01-01

    Adenine at position 752 in a loop of helix 35 from positions 745 to 752 in domain II of 23S rRNA is involved in binding to the ribosome of telithromycin (TEL), a member of ketolides. Methylation of guanine at position 748 by the intrinsic methyltransferase RlmAII enhances binding of telithromycin (TEL) to A752 in Streptococcus pneumoniae. We have found that another intrinsic methylation of the adjacent uridine at position 747 enhances G748 methylation by RlmAII, rendering TEL susceptibility. U747 and another nucleotide, U1939, were methylated by the dual-specific methyltransferase RlmCD encoded by SP_1029 in S. pneumoniae. Inactivation of RlmCD reduced N1-methylated level of G748 by RlmAII in vivo, leading to TEL resistance when the nucleotide A2058, located in domain V of 23S rRNA, was dimethylated by the dimethyltransferase Erm(B). In vitro methylation of rRNA showed that RlmAII activity was significantly enhanced by RlmCD-mediated pre-methylation of 23S rRNA. These results suggest that RlmCD-mediated U747 methylation promotes efficient G748 methylation by RlmAII, thereby facilitating TEL binding to the ribosome. PMID:26365244

  15. Inhibition of N-methyl-D-aspartate receptors increases paraoxon-induced apoptosis in cultured neurons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wu Xuan; Tian Feng; Okagaki, Peter

    2005-10-01

    Organophosphorus (OP) compounds, used as insecticides and chemical warfare agents, are potent neurotoxins. We examined the neurotoxic effect of paraoxon (O,O-diethyl O-p-nitrophenyl phosphate), an organophosphate compound, and the role of NMDA receptors as a mechanism of action in cultured cerebellar granule cells. Paraoxon is neurotoxic to cultured rat cerebellar granule cells in a time- and concentration-dependent manner. Cerebellar granule cells are less sensitive to the neurotoxic effects of paraoxon on day in vitro (DIV) 4 than neurons treated on DIV 8. Surprisingly, the N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, enhances paraoxon-mediated neurotoxicity suggesting that NMDA receptors may play a protective role.more » Pretreatment with a subtoxic concentration of N-methyl-D-aspartate (NMDA) [100 {mu}M] protects about 40% of the vulnerable neurons that would otherwise die from paraoxon-induced neurotoxicity. Moreover, addition of a neuroprotective concentration of NMDA 3 h after treatment with paraoxon provides the same level of protection. Because paraoxon-mediated neuronal cell death is time-dependent, we hypothesized that apoptosis may be involved. Paraoxon increases apoptosis about 10-fold compared to basal levels. The broad-spectrum caspase inhibitor (Boc-D-FMK) and the caspase-9-specific inhibitor (Z-LEHD-FMK) protect against paraoxon-mediated apoptosis, paraoxon-stimulated caspase-3 activity and neuronal cell death. MK-801 increases, whereas NMDA blocks paraoxon-induced apoptosis and paraoxon-stimulated caspase-3 activity. These results suggest that activation of NMDA receptors protect neurons against paraoxon-induced neurotoxicity by blocking apoptosis initiated by paraoxon.« less

  16. Effects of Dietary Xanthophylls, Canthaxanthin and Astaxanthin on N-Methyl-N-nitrosourea-induced Rat Mammary Carcinogenesis.

    PubMed

    Yuri, Takashi; Yoshizawa, Katsuhiko; Emoto, Yuko; Kinoshita, Yuichi; Yuki, Michiko; Tsubura, Airo

    Natural xanthophylls, canthaxanthin and astaxanthin are known to exhibit anticancer activity. However, the dietary effects of canthaxanthin and astaxanthin on N-methyl-N-nitrosourea (MNU)-induced mammary cancer remain controversial, and their mechanisms of action have not been clearly identified. Three-week-old female Sprague-Dawley rats were fed a xanthophyll-free (basal diet) diet or experimental diets containing canthaxanthin or astaxanthin (0.04% and 0.4%) for 5 weeks (until 8 weeks of age), after which all rats were provided the basal diet (n=15 each). Rats were administered MNU at 6 weeks of age, and the incidence of mammary tumors at 20 weeks of age was compared. The expression of adiponectin in mammary adipose tissues taken at 7 weeks of age was also compared. Compared to the basal diet group, the 0.4% (but not the 0.04%) astaxanthin diet significantly reduced the incidence of palpable mammary carcinoma (92% vs. 42%; p<0.05), while the low and high canthaxanthin diets produced no significant inhibition. Adiponectin immunoblotting showed significantly higher expression in the 0.4% astaxanthin diet group, while the other groups were similar to the basal diet group. High concentrations of astaxanthin suppress MNU-induced mammary carcinoma. Changes in adiponectin may be involved in the mechanism of action. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  17. Synthesis of water-soluble polyamine derivatives effective as N-methyl-D-aspartate receptor antagonists.

    PubMed

    Masuko, Takashi; Yoshida, Shuhei; Metori, Koichi; Kizawa, Yasuo; Kusama, Tadashi; Miyake, Muneharu

    2010-06-01

    The novel water-soluble N-methyl-D-aspartate (NMDA) receptor antagonists, N-{4-[4-(4-Guanidinobutylamino)butylamino]butyl}-p-toluenesulfonamide trihydrochloride (1a, TsHSPMG), N-{4-[4-(4-Guanidinobutylamino)butylamino]butyl}butane-1-sulfonamide trihydrochloride (1b, BsHSPMG), N-{3-[4-(3-Guanidinopropylamino)butylamino]propyl}-p-toluenesulfonamide trihydrochroride (2a, TsSPMG) and N-{3-[4-(3-Guanidinopropylamino)butylamino]propyl}butane-1-sulfonamide trihydrochroride (2b, BsSPMG), were synthesized, and the effects of these polyamine derivatives on NMDA receptors were studied using voltage-clamp recordings of recombinant NMDA receptors expressed in Xenopus oocytes. Although spermine potentiates 153% and 310% of NMDA (NR1A/NR2B) receptors in the presence of saturated and unsaturated glycine, respectively, all the novel polyamine derivatives, TsHSPMG (1a), BsHSPMG (1b), TsSPMG (2a) and BsSPMG (2b), significantly inhibited NR1A/NR2B receptors in both conditions. The degree of NMDA receptor inhibition by TsHSPMG (1a) and BsHSPMG (1b) was stronger than that by TsSPMG (2a) and BsSPMG (2b).

  18. Cocrystals of 6-methyl-2-thiouracil: presence of the acceptor-donor-acceptor/donor-acceptor-donor synthon.

    PubMed

    Hützler, Wilhelm Maximilian; Egert, Ernst

    2015-03-01

    The results of seven cocrystallization experiments of the antithyroid drug 6-methyl-2-thiouracil (MTU), C(5)H(6)N(2)OS, with 2,4-diaminopyrimidine, 2,4,6-triaminopyrimidine and 6-amino-3H-isocytosine (viz. 2,6-diamino-3H-pyrimidin-4-one) are reported. MTU features an ADA (A = acceptor and D = donor) hydrogen-bonding site, while the three coformers show complementary DAD hydrogen-bonding sites and therefore should be capable of forming an ADA/DAD N-H...O/N-H...N/N-H...S synthon with MTU. The experiments yielded one cocrystal and six cocrystal solvates, namely 6-methyl-2-thiouracil-2,4-diaminopyrimidine-1-methylpyrrolidin-2-one (1/1/2), C(5)H(6)N(2)OS·C(4)H(6)N(4)·2C(5)H(9)NO, (I), 6-methyl-2-thiouracil-2,4-diaminopyrimidine (1/1), C(5)H(6)N(2)OS·C(4)H(6)N(4), (II), 6-methyl-2-thiouracil-2,4-diaminopyrimidine-N,N-dimethylacetamide (2/1/2), 2C(5)H(6)N(2)OS·C(4)H(6)N(4)·2C(4)H(9)NO, (III), 6-methyl-2-thiouracil-2,4-diaminopyrimidine-N,N-dimethylformamide (2/1/2), C(5)H(6)N(2)OS·0.5C(4)H(6)N(4)·C(3)H(7)NO, (IV), 2,4,6-triaminopyrimidinium 6-methyl-2-thiouracilate-6-methyl-2-thiouracil-N,N-dimethylformamide (1/1/2), C(4)H(8)N(5)(+)·C(5)H(5)N(2)OS(-)·C(5)H(6)N(2)OS·2C(3)H(7)NO, (V), 6-methyl-2-thiouracil-6-amino-3H-isocytosine-N,N-dimethylformamide (1/1/1), C(5)H(6)N(2)OS·C(4)H(6)N(4)O·C(3)H(7)NO, (VI), and 6-methyl-2-thiouracil-6-amino-3H-isocytosine-dimethyl sulfoxide (1/1/1), C(5)H(6)N(2)OS·C(4)H(6)N(4)O·C(2)H(6)OS, (VII). Whereas in cocrystal (I) an R(2)(2)(8) interaction similar to the Watson-Crick adenine/uracil base pair is formed and a two-dimensional hydrogen-bonding network is observed, the cocrystals (II)-(VII) contain the triply hydrogen-bonded ADA/DAD N-H...O/N-H...N/N-H...S synthon and show a one-dimensional hydrogen-bonding network. Although 2,4-diaminopyrimidine possesses only one DAD hydrogen-bonding site, it is, due to orientational disorder, triply connected to two MTU molecules in (III) and (IV).

  19. GC-MS studies on the regioisomeric methoxy-methyl-phenethylamines related to MDEA, MDMMA, and MBDB.

    PubMed

    Thigpen, Ashley; Awad, Tamer; Deruiter, Jack; Clark, C Randall

    2008-01-01

    Three regioisomeric 3,4-methylenedioxyphenethylamines having the same molecular weight and major mass spectral fragments of equal mass have been reported as drugs of abuse in forensic studies in recent years. These compounds are 3,4-methylenedioxy-N-ethylamphetamine (MDEA), 3,4-methylenedioxy-N-N-dimethylamphetamine (MDMMA), and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB). The mass spectra of the regioisomers (4-methoxy-3-methyl and 4-methoxy-2-methyl-phenethylamines) are essentially equivalent to the three compounds reported as drugs of abuse. This project focused on the synthesis, mass spectral characterization, and chromatographic analysis of these six regioisomeric methoxy methyl phenethylamines. Additionally, the mass spectral and chromatographic properties of these compounds will be compared to the isobaric 2,3- and 3,4-methylenedioxyphenethyl-amines of the same side chain. The six regioisomeric methoxy-methyl-phenethylamines were synthesized from commercially available starting materials. Side chain differentiation by mass spectrometry was possible after the formation of the perfluoroacyl derivatives, pentafluoropropionylamides (PFPA) and heptafluorobutrylamides (HFBA). Gas chromatographic separation on Rtx-1 was successful at resolving the perfluoroacyl derivatives of the 4-methoxy-3-methyl phenethylamines from those of the 4-methoxy-2-methyl phenethylamines. The 4-methoxy-3-methyl-phenethylamine derivatives eluted before the 4-methoxy-2-methyl-phenethylamine derivatives as both the PFPA and HFBA derivatives.

  20. Blockade of N-methyl-D-aspartate Receptors May Protect against Ischemic Damage in the Brain

    NASA Astrophysics Data System (ADS)

    Simon, R. P.; Swan, J. H.; Griffiths, T.; Meldrum, B. S.

    1984-11-01

    In rats ischemia of the forebrain induced by a 30-minute occlusion of the carotid artery, followed by 120 minutes of arterial reperfusion, produced ischemic lesions of selectively vulnerable pyramidal cells in both hippocampi. Focal microinfusion into the dorsal hippocampus of 2-amino-7-phosphonoheptanoic acid, an antagonist of excitation at the N-methyl-d-asparate-preferring receptor, before ischemia was induced protected against the development of ischemic damage. It is proposed that excitatory neurotransmission plays an important role in selective neuronal loss due to cerebral ischemia.

  1. Serial urinary IL-2, IL-6, IL-8, TNFalpha, UBC, CYFRA 21-1 and NMP22 during follow-up of patients with bladder cancer receiving intravesical BCG.

    PubMed

    Sanchez-Carbayo, M; Urrutia, M; Romani, R; Herrero, M; Gonzalez de Buitrago, J M; Navajo, J A

    2001-01-01

    We evaluated the potential role of serial preinstillation levels of several interleukins, TNFalpha and urinary tumor markers to monitor patients with bladder cancer receiving intravesical BCG. 121 urine samples were collected from: patients with bladder cancer treated with BCG (group 1); patients with bladder cancer receiving other intravesical treatment (group 2) and patients with urinary tract infections (group 3). Cytokines [IL-2, IL6 and [L8] and TNFalpha and urinary tumor markers [UBC, CYFRA 21-1 and NMP22] were measured by immunoassays. In 3 out of 15 BCG non-responders that recurred over the period of the study, no cytokine peak for IL-2, IL-6 or TNFa were detected. Urinary tumor markers increased in 2 out of 3 of these patients earlier than scheduled cystoscopies. Cytokine measurement was heterogeneous among 12 out of 15 BCG-responding patients: there were low levels of IL-6 and TNFalpha and peaks of IL-2 and IL-8 in 10 out of 12 and 4 out of 12 patients, respectively. During responding patients' follow-up we observed false-positive results in 7 out of 65 urine samples for UBC, 8 out of 65 for CYFRA 21-1 and 20 out of 65 for NMP22. Urinary tract infections were the main factor associated with non-specific elevations of IL-6 and IL-8 and urinary tumor markers in all groups of patients. Although larger series are required to confirn our preliminary observations, our data argue for a potential predictive role for IL-2 of favourable response to BCG therapy. Monitoring BCG with urinary tumor markers could early detect recurrence in non-responding patients.

  2. DNA methylation pattern of apoptosis-related genes in ameloblastoma.

    PubMed

    Costa, Sfs; Pereira, N B; Pereira, Kma; Campos, K; de Castro, W H; Diniz, M G; Gomes, C C; Gomez, R S

    2017-09-01

    DNA methylation is an important mechanism of gene control expression, and it has been poorly addressed in odontogenic tumours. On this basis, we aimed to assess the methylation pattern of 22 apoptosis-related genes in solid ameloblastomas. Ameloblastoma fresh samples (n = 10) and dental follicles (n = 8) were included in the study. The percentage fraction of methylated and unmethylated DNA promoter of 22 apoptosis-related genes was determined using enzymatic restriction digestion and quantitative real-time PCR (qPCR) array. The relative expressions of the genes that showed the most discrepant methylation profile between tumours and controls were analysed by reverse-transcription quantitative PCR (RT-qPCR). Lower methylation percentages of TNFRSF25 (47.2%) and BCL2L11 (33.2%) were observed in ameloblastomas compared with dental follicles (79.3% and 59.5%, respectively). The RT-qPCR analysis showed increased expression of BCL2L11 in ameloblastomas compared with dental follicles, in agreement with the methylation analysis results, while there was no difference between the expression levels of TNFRSF25 between both groups. On the basis of our results, the transcription of the apoptosis-related gene BCL2L11 is possibly regulated by promoter DNA methylation in ameloblastoma. The biological significance of this finding in ameloblastoma pathobiology remains to be clarified. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. 5-Bromo-2-methyl­pyridine N-oxide

    PubMed Central

    Liu, Bo-Nian; Tang, Shi-Gui; Li, Hao-Yuan; Xu, Ye-Ming; Guo, Cheng

    2008-01-01

    In the mol­ecule of the title compound, C6H6BrNO, the methyl C and oxide O atoms lie in the pyridine ring plane, while the Br atom is displaced by 0.103 (3) Å. In the crystal structure, inter­molecular C—H⋯O hydrogen bonds link the mol­ecules into centrosymmetric dimers. PMID:21202579

  4. Grafting of poly[(methyl methacrylate)-block-styrene] onto cellulose via nitroxide-mediated polymerization, and its polymer/clay nanocomposite.

    PubMed

    Karaj-Abad, Saber Ghasemi; Abbasian, Mojtaba; Jaymand, Mehdi

    2016-11-05

    For the first time, nitroxide-mediated polymerization (NMP) was used for synthesis of graft and block copolymers using cellulose (Cell) as a backbone, and polystyrene (PSt) and poly(methyl metacrylate) (PMMA) as the branches. For this purpose, Cell was acetylated by 2-bromoisobutyryl bromide (BrBiB), and then the bromine group was converted to 4-oxy-2,2,6,6-tetramethylpiperidin-1-oxyl group by a substitution nucleophilic reaction to afford a macroinitiator (Cell-TEMPOL). The macroinitiator obtained was subsequently used in controlled graft and block copolymerizations of St and MMA monomers to yield Cell-g-PSt and Cell-g-(PMMA-b-PSt). The chemical structures of all samples as representatives were characterized by FTIR and (1)H NMR spectroscopies. In addition, Cell-g-(PMMA-b-PSt)/organophilic montmorillonite nanocomposite was prepared through a solution intercalation method. TEM was used to evaluate the morphological behavior of the polymer-clay system. It was demonstrated that the addition of small percent of organophilic montmorillonite (O-MMT; 3wt.%) was enough to improve the thermal stability of the nanocomposite. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Methylation matters

    PubMed Central

    Costello, J.; Plass, C.

    2001-01-01

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


Keywords: methylation; cancer PMID:11333864

  6. Alternation of histone and DNA methylation in human atherosclerotic carotid plaques.

    PubMed

    Greißel, A; Culmes, M; Napieralski, R; Wagner, E; Gebhard, H; Schmitt, M; Zimmermann, A; Eckstein, H-H; Zernecke, A; Pelisek, J

    2015-08-01

    Little is known about epigenetics and its possible role in atherosclerosis. We here analysed histone and DNA methylation and the expression of corresponding methyltransferases in early and advanced human atherosclerotic carotid lesions in comparison to healthy carotid arteries. Western Blotting was performed on carotid plaques from our biobank with early (n=60) or advanced (n=60) stages of atherosclerosis and healthy carotid arteries (n=12) to analyse di-methylation patterns of histone H3 at positions K4, K9 and K27. In atherosclerotic lesions, di-methylation of H3K4 was unaltered and that of H3K9 and H3K27 significantly decreased compared to control arteries. Immunohistochemistry revealed an increased appearance of di-methylated H3K4 in smooth muscle cells (SMCs), a decreased expression of di-methylated H3K9 in SMCs and inflammatory cells, and reduced di-methylated H3K27 in inflammatory cells in advanced versus early atherosclerosis. Expression of corresponding histone methyltransferases MLL2 and G9a was increased in advanced versus early atherosclerosis. Genomic DNA hypomethylation, as determined by PCR for methylated LINE1 and SAT-alpha, was observed in early and advanced plaques compared to control arteries and in cell-free serum of patients with high-grade carotid stenosis compared to healthy volunteers. In contrast, no differences in DNA methylation were observed in blood cells. Expression of DNA-methyltransferase DNMT1 was reduced in atherosclerotic plaques versus controls, DNMT3A was undetectable, and DNMT3B not altered. DNA-demethylase TET1 was increased in atherosclerosisc plaques. The extent of histone and DNA methylation and expression of some corresponding methyltransferases are significantly altered in atherosclerosis, suggesting a possible contribution of epigenetics in disease development.

  7. Design and in vitro activities of N-alkyl-N-[(8-R-2,2-dimethyl-2H-chromen-6-yl)methyl]heteroarylsulfonamides, novel small molecule Hypoxia Inducible Factor-1 (HIF-1) pathway inhibitors and anti-cancer agents

    PubMed Central

    Mun, Jiyoung; Jabbar, Adnan Abdul; Devi, Narra Sarojini; Yin, Shaoman; Wang, Yingzhe; Tan, Chalet; Culver, Deborah; Snyder, James P.; Van Meir, Erwin G.; Goodman, Mark M.

    2013-01-01

    The Hypoxia Inducible Factor (HIF) pathway is an attractive target for cancer as it controls tumor adaptation to growth under hypoxia and mediates chemo- and radiation resistance. We previously discovered 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide, as a novel small molecule HIF-1 pathway inhibitor in a high-throughput cell-based assay, but its in vivo delivery is hampered by poor aqueous solubility (0.009 μM in water; logP7.4: 3.7). Here we describe the synthesis of twelve N-alkyl-N-[(8-R-2,2-dimethyl-2H-chromen-6-yl)methyl]heteroarylsulfonamides, which were designed to possess optimal lipophilicities and aqueous solubilities by in silico calculations. Experimental logP7.4 values of 8 of the 12 new analogs ranged from 1.2 ∼ 3.1. Aqueous solubilities of 3 analogs were measured, among which the most soluble N-[(8-methoxy-2,2-dimethyl-2H-chromen-6-yl)methyl]-N-(propan-2-yl)pyridine-2-sulfonamide had an aqueous solubility of 80 μM, e.g. a solubility improvement of ∼9,000-fold. The pharmacological optimization had minimal impact on drug efficacy as the compounds retained IC50 values at or below 5 μM in our HIF-dependent reporter assay. PMID:22746274

  8. Histone arginine methylations: their roles in chromatin dynamics and transcriptional regulation

    PubMed Central

    LITT, Michael; QIU, Yi; HUANG, Suming

    2017-01-01

    Synopsis PRMTs (protein arginine N-methyltransferases) specifically modify the arginine residues of key cellular and nuclear proteins as well as histone substrates. Like lysine methylation, transcriptional repression or activation is dependent upon the site and type of arginine methylation on histone tails. Recent discoveries imply that histone arginine methylation is an important modulator of dynamic chromatin regulation and transcriptional controls. However, under the shadow of lysine methylation, the roles of histone arginine methylation have been under-explored. The present review focuses on the roles of histone arginine methylation in the regulation of gene expression, and the interplays between histone arginine methylation, histone acetylation, lysine methylation and chromatin remodelling factors. In addition, we discuss the dynamic regulation of arginine methylation by arginine demethylases, and how dysregulation of PRMTs and their activities are linked to human diseases such as cancer. PMID:19220199

  9. Measurement of the methyl cyanide E/A ratio in TMC-1

    NASA Technical Reports Server (NTRS)

    Minh, Y. C.; Irvine, W. M.; Ohishi, M.; Ishikawa, S.; Saito, S.; Kaifu, N.

    1993-01-01

    We have observed the methyl cyanide (CH3CN) J = 2-1 K = 0 and 1 transitions toward the cyanopolyyne peak of TMC-1 and have derived an E/A (ortho/para)abundance ratio N(E)/N(A) = 0.75 +/- 0.10. The total methyl cyanide column density is N(total) = 5 x 10 exp 12/sq cm toward TMC-1, in agreement with earlier results from the J = 1-0 lines.

  10. MeT-DB V2.0: elucidating context-specific functions of N6-methyl-adenosine methyltranscriptome

    PubMed Central

    Liu, Hui; Wang, Huaizhi; Wei, Zhen; Zhang, Songyao; Hua, Gang; Zhang, Shao-Wu; Zhang, Lin; Gao, Shou-Jiang

    2018-01-01

    Abstract Methyltranscriptome is an exciting new area that studies the mechanisms and functions of methylation in transcripts. A knowledge base with the systematic collection and curation of context specific transcriptome-wide methylations is critical for elucidating their biological functions as well as for developing bioinformatics tools. Since its inception in 2014, the Met-DB (Liu, H., Flores, M.A., Meng, J., Zhang, L., Zhao, X., Rao, M.K., Chen, Y. and Huang, Y. (2015) MeT-DB: a database of transcriptome methylation in mammalian cells. Nucleic Acids Res., 43, D197–D203), has become an important resource for methyltranscriptome, especially in the N6-methyl-adenosine (m6A) research community. Here, we report Met-DB v2.0, the significantly improved second version of Met-DB, which is entirely redesigned to focus more on elucidating context-specific m6A functions. Met-DB v2.0 has a major increase in context-specific m6A peaks and single-base sites predicted from 185 samples for 7 species from 26 independent studies. Moreover, it is also integrated with a new database for targets of m6A readers, erasers and writers and expanded with more collections of functional data. The redesigned Met-DB v2.0 web interface and genome browser provide more friendly, powerful, and informative ways to query and visualize the data. More importantly, MeT-DB v2.0 offers for the first time a series of tools specifically designed for understanding m6A functions. Met-DB V2.0 will be a valuable resource for m6A methyltranscriptome research. The Met-DB V2.0 database is available at http://compgenomics.utsa.edu/MeTDB/ and http://www.xjtlu.edu.cn/metdb2. PMID:29126312

  11. Research on Hydrophilic Nature of Polyvinylpyrrolidone on Polysulfone Membrane Filtration

    NASA Astrophysics Data System (ADS)

    Tiron, L. G.; Vlad, M.; Baltă, Ş.

    2018-06-01

    The membranes used in wastewater filtration are obtained from polymers, this technique is widely applied because of the small installations and low costs as against conventional systems. The polymeric membranes have high mechanical strength and flexibility, but is a challenge to improve in the same time the permeability and retention capacity of the membranes. A process that can improve the membrane properties is the addition of additives to the polymer solution, resulting in noticeable changes in the resulting membrane structure. Polyvinylpyrrolidone (PVP) is a highly hydrophilic polymer, used as a food additive that acts as stabilizer and thickening agent, which brings improvements in membrane properties. This study analyses the effect of polyvinylpyrrolidone (PVP) on the casting solution of the prepared membranes. The polymer solution was prepared from polysulfone (PSf) and N-methyl-2-pyrrolidone (NMP) at different concentrations. The membranes were obtained by phase inversion method. The PSf/PVP/NMP membranes with different concentrations were characterized by contact angle measurements, surface roughness, morphological structure and permeation tests. The results show that the hydrophilic nature of PVP improve the pure water flux, the contact angle and exhibit a higher anti-fouling property.

  12. An investigation on the effect of deposition parameters on nanostructured electrode of lithium ion batteries and their performance

    NASA Astrophysics Data System (ADS)

    Dorri, Mehrdad; Zamani, Cyrus; Babaei, Alireza

    2018-01-01

    Nanostructured plate-like manganese cobalt oxide (MCO) was synthesized as the anode material for lithium-ion batteries. Under basic conditions and using a molar ratio of OH- /NO3-= 1.5, crystallite size of 14 nm was found for samples calcined at 350°C. The electrodes were fabricated by mixing MCO as the active material, Super P carbon as the conducting material and polyvinylidene fluoride (PVDF) as the binder in N-methyl-2-pyrrolidone (NMP) solvent. The slurry was coated onto a copper foil substrate. The aim of this investigation is the assessment of deposition parameters on different plausible defects (such as agglomeration/blisters, pinholes/divots, cracks and non-uniform coating) and also electrical behavior of the deposited layer. Because of high degree of agglomeration, mortar method was found to be ineffective while mixing using magnetic stirrer was proved to be more appropriate in terms of final rheology. The optimum value for the binder was found to be 2.73 wt% of the NMP solvent. Effective drying was achieved using hotplate followed by oven drying. SEM analysis revealed the disappearance of the surface cracks when samples are pressed after drying stage.

  13. Studies on the Mechanism of Action of Hydrazine-Induced Methylation of DNA Guanne

    DTIC Science & Technology

    1984-10-03

    potent methylating agent , diazomethane (-CH -N+-N). Several in vivo studies were carried out to determine the role of aldehydes in the alkylation of DNA...methylating agent available to interact with DNA. If such a mechanism occurs, it may explain why disulfiram appears to inhibit the alkylation of DNA...a much slower/poorer alkylating agent for DNA. Effect of the 1-Carbon Pool on DNA Methylation in Hydrazine Toxicity: In Vitro In vitro studies were

  14. N-demethylation of N-methyl-4-aminoantipyrine, the main metabolite of metamizole.

    PubMed

    Bachmann, Fabio; Duthaler, Urs; Rudin, Deborah; Krähenbühl, Stephan; Haschke, Manuel

    2018-05-08

    Metamizole is an old analgesic used frequently in some countries. Active metabolites of metamizole are the non-enzymatically generated N-methyl-4-aminoantipyrine (4-MAA) and its demethylation product 4-aminoantipyrine (4-AA). Previous studies suggested that 4-MAA demethylation can be performed by hepatic cytochrome P450 (CYP) 3A4, but the possible contribution of other CYPs remains unclear. Using human liver microsomes (HLM), liver homogenate and HepaRG cells, we could confirm 4-MAA demethylation by CYPs. Based on CYP induction (HepaRG cells) and CYP inhibition (HLM) we could identify CYP2B6, 2C8, 2C9 and 3A4 as major contributors to 4-MAA demethylation. The 4-MAA demethylation rate by HLM was 280 pmol/mg protein/h, too low to account for in vivo 4-MAA demethylation in humans. Since peroxidases can perform N-demethylation, we investigated horseradish peroxidase and human myeloperoxidase (MPO). Horse radish peroxidase efficiently demethylated 4-MAA, depending on the hydrogen peroxide concentration. This was also true for MPO; this reaction was saturable with a K m of 22.5 μM and a maximal velocity of 14 nmol/min/mg protein. Calculation of the entire body MPO capacity revealed that the demethylation capacity by granulocyte/granulocyte precursors was approximately 600 times higher than the liver capacity and could account for 4-MAA demethylation in humans. 4-MAA demethylation could also be demonstrated in MPO-expressing granulocyte precursor cells (HL-60). In conclusion, 4-MAA can be demethylated in the liver by several CYPs, but hepatic metabolism cannot fully explain 4-MAA demethylation in humans. The current study suggests that the major part of 4-MAA is demethylated by circulating granulocytes and granulocyte precursors in bone marrow. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening

    PubMed Central

    LING, SHIZHANG; RETTIG, ELENI M.; TAN, MARIETTA; CHANG, XIAOFEI; WANG, ZHIMING; BRAIT, MARIANA; BISHOP, JUSTIN A.; FERTIG, ELANA J.; CONSIDINE, MICHAEL; WICK, MICHAEL J.; HA, PATRICK K.

    2016-01-01

    Salivary gland adenoid cystic carcinoma (ACC) is a rare head and neck malignancy without molecular biomarkers that can be used to predict the chemotherapeutic response or prognosis of ACC. The regulation of gene expression of oncogenes and tumor suppressor genes (TSGs) through DNA promoter methylation may play a role in the carcinogenesis of ACC. To identify differentially methylated genes in ACC, a global demethylating agent, 5-aza-2′-deoxycytidine (5-AZA) was utilized to unmask putative TSG silencing in ACC xenograft models in mice. Fresh xenografts were passaged, implanted in triplicate in mice that were treated with 5-AZA daily for 28 days. These xenografts were then evaluated for genome-wide DNA methylation patterns using the Illumina Infinium HumanMethylation27 BeadChip array. Validation of the 32 candidate genes was performed by bisulfite sequencing (BS-seq) in a separate cohort of 6 ACC primary tumors and 6 normal control salivary gland tissues. Hypermethylation was identified in the HCN2 gene promoter in all 6 control tissues, but hypomethylation was found in all 6 ACC tumor tissues. Quantitative validation of HCN2 promoter methylation level in the region detected by BS-seq was performed in a larger cohort of primary tumors (n=32) confirming significant HCN2 hypomethylation in ACCs compared with normal samples (n=10; P=0.04). HCN2 immunohistochemical staining was performed on an ACC tissue microarray. HCN2 staining intensity and H-score, but not percentage of the positively stained cells, were significantly stronger in normal tissues than those of ACC tissues. With our novel screening and sequencing methods, we identified several gene candidates that were methylated. The most significant of these genes, HCN2, was actually hypomethylated in tumors. However, promoter methylation status does not appear to be a major determinant of HCN2 expression in normal and ACC tissues. HCN2 hypomethylation is a biomarker of ACC and may play an important role in the

  16. RlmCD-mediated U747 methylation promotes efficient G748 methylation by methyltransferase RlmAII in 23S rRNA in Streptococcus pneumoniae; interplay between two rRNA methylations responsible for telithromycin susceptibility.

    PubMed

    Shoji, Tatsuma; Takaya, Akiko; Sato, Yoshiharu; Kimura, Satoshi; Suzuki, Tsutomu; Yamamoto, Tomoko

    2015-10-15

    Adenine at position 752 in a loop of helix 35 from positions 745 to 752 in domain II of 23S rRNA is involved in binding to the ribosome of telithromycin (TEL), a member of ketolides. Methylation of guanine at position 748 by the intrinsic methyltransferase RlmA(II) enhances binding of telithromycin (TEL) to A752 in Streptococcus pneumoniae. We have found that another intrinsic methylation of the adjacent uridine at position 747 enhances G748 methylation by RlmA(II), rendering TEL susceptibility. U747 and another nucleotide, U1939, were methylated by the dual-specific methyltransferase RlmCD encoded by SP_1029 in S. pneumoniae. Inactivation of RlmCD reduced N1-methylated level of G748 by RlmA(II) in vivo, leading to TEL resistance when the nucleotide A2058, located in domain V of 23S rRNA, was dimethylated by the dimethyltransferase Erm(B). In vitro methylation of rRNA showed that RlmA(II) activity was significantly enhanced by RlmCD-mediated pre-methylation of 23S rRNA. These results suggest that RlmCD-mediated U747 methylation promotes efficient G748 methylation by RlmA(II), thereby facilitating TEL binding to the ribosome. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. Microwave assisted synthesis and structure-activity relationship of 4-hydroxy-N'-[1-phenylethylidene]-2H/2-methyl-1,2-benzothiazine-3-carbohydrazide 1,1-dioxides as anti-microbial agents.

    PubMed

    Ahmad, Naveed; Zia-ur-Rehman, Muhammad; Siddiqui, Hamid Latif; Ullah, Muhammad Fasih; Parvez, Masood

    2011-06-01

    A series of 4-hydroxy-N'-[1-phenylethylidene]-2H/2-methyl, 1,2-benzothiazine-3-carbohydrazide 1,1-dioxides was synthesized from commercially available sodium saccharin. Base catalyzed ring expansion of methyl (1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)acetate followed by ultrasound mediated hydrazinolysis and subsequent reaction with 1-phenylethanones under the influence of microwaves yielded the title compounds. Besides, microwave assisted synthesis of 1,4-dihydropyrazolo[4,3-c][1,2]benzothiazin-3-ol 5,5-dioxide and 4-methyl-1,4-dihydropyrazolo[4,3-c][1,2]benzothiazin-3-ol 5,5-dioxide is also discussed. Most of the synthesized compounds were found to possess moderate to significant anti-microbial (anti-bacterial and anti-fungal) activities. It is found that compounds with greater lipophilicity (N-methyl analogues) possessed higher anti-bacterial activities. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  18. Attenuation by genistein of sodium-chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

    PubMed

    Tatsuta, M; Iishi, H; Baba, M; Yano, H; Uehara, H; Nakaizumi, A

    1999-01-29

    The effects of prolonged administration of genistein, a tyrosine-kinase inhibitor, on sodium-chloride-enhanced induction of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine, and the labeling and apoptotic indices and vessel counts in the gastric mucosa and gastric cancers, were investigated in Wistar rats. After 25 weeks of the carcinogen treatment, rats were fed chow pellets containing 10% sodium chloride and were given s.c. injections of genistein at dosages of 15 mg/kg or 30 mg/kg body weight every other day. In week 52, the incidence of gastric cancers was significantly greater in rats fed sodium chloride than in untreated control rats. Prolonged administration of genistein at a dosage of 30 mg/kg, but not 15 mg/kg, body weight significantly reduced the incidence of gastric cancers, which was increased by oral treatment with sodium chloride. Genistein at the higher dose significantly decreased the labeling index and vessel counts of the antral mucosa and the gastric cancers (which were increased by treatment with sodium chloride) and significantly increased the apoptotic index of the antral mucosa and the cancers (which was lowered by the treatment with sodium chloride). These findings suggest that genistein attenuates gastric carcinogenesis promoted by sodium chloride, by inducing increased apoptosis and lower cell proliferation and angiogenesis of antral mucosa and gastric cancers.

  19. Low-protein diet promotes sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

    PubMed

    Iishi, H; Tatsuta, M; Baba, M; Hirasawa, R; Sakai, N; Yano, H; Uehara, H; Nakaizumi, A

    1999-07-01

    Sodium chloride (NaCl) initiates and promotes experimental carcinogenesis in rats. We recently found that a high-protein diet attenuates NaCl-enhanced gastric carcinogenesis in Wistar rats. To investigate the effect of a purified low-protein diet on NaCl-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Wistar rats, rats were fed a purified diet with an equalized caloric content containing 1% or 2% NaCl and 25% casein (normal-protein diet) or 10% casein (low-protein diet) after oral treatment with MNNG for 25 weeks. In week 52, neither 1% nor 2% NaCl had a significant effect on gastric carcinogenesis in rats fed a normal-protein diet. However, oral administration of 2%, but not 1%, NaCl significantly increased the incidence of gastric cancers in rats fed a low-protein diet. Oral administration of 2% NaCl also significantly increased the bromodeoxyuridine (BrdU)-labeling index and the ornithine decarboxylase (ODC) activity and decreased apoptosis of gastric cancers in rats fed a low-protein diet. However, 2% NaCl had no significant effect on these three parameters in rats fed a normal-protein diet. These findings indicate that a low-protein diet enhances the effect of NaCl in gastric carcinogenesis and that this enhancement may be mediated by increased cell proliferation and reduced apoptosis of gastric cancers.

  20. Effects of pimobendan on myocardial perfusion and pulmonary transit time in dogs with myxomatous mitral valve disease: a pilot study.

    PubMed

    Apple, S M; Menciotti, G; Braz-Ruivo, L; Crosara, S; Häggström, J; Borgarelli, M

    2016-09-01

    To describe pulmonary transit time (nPTT) and myocardial perfusion (nMP) normalised to heart rate in dogs with stable ACVIM stage C myxomatous mitral valve disease (MMVD) and to assess short-term effects of pimobendan on these variables. We hypothesised that nPTT and nMP would increase in dogs with MMVD compared with normal dogs. Additionally, we hypothesised that treatment with pimobendan would decrease nMP and nPTT in dogs with MMVD. Prospective, single-blind study involving 6 normal dogs and 12 dogs with MMVD. Dogs with MMVD were treated with enalapril and furosemide for at least 1 month prior to examination. All dogs underwent standard and contrast echocardiographic examinations at the beginning of the study (T0). At this time, MMVD dogs were randomly assigned to receive either pimobendan (0.4-0.6 mg/kg) or not. All dogs with MMVD were re-evaluated by standard and contrast echocardiography after 1 week (T1) and nPTT and nMP were measured. nPTT was significantly increased in dogs with MMVD (P = 0.0063), compared with normal dogs. It was significantly decreased at T1 in dogs receiving pimobendan (P = 0.0250). The nMP was not significantly different in dogs with MMVD, compared with healthy dogs (P = 0.2552), and it was not significantly different at T1 in the treatment group (P = 0.8798). Contrast echocardiography was a valid, complementary tool for echocardiographic analysis of dogs with MMVD. Pimobendan decreased nPTT in dogs affected by MMVD. Myocardial perfusion was not different in dogs with severe MMVD. © 2016 Australian Veterinary Association.

  1. Epigenetic Gene Promoter Methylation at Birth Is Associated With Child’s Later Adiposity

    PubMed Central

    Godfrey, Keith M.; Sheppard, Allan; Gluckman, Peter D.; Lillycrop, Karen A.; Burdge, Graham C.; McLean, Cameron; Rodford, Joanne; Slater-Jefferies, Joanne L.; Garratt, Emma; Crozier, Sarah R.; Emerald, B. Starling; Gale, Catharine R.; Inskip, Hazel M.; Cooper, Cyrus; Hanson, Mark A.

    2011-01-01

    OBJECTIVE Fixed genomic variation explains only a small proportion of the risk of adiposity. In animal models, maternal diet alters offspring body composition, accompanied by epigenetic changes in metabolic control genes. Little is known about whether such processes operate in humans. RESEARCH DESIGN AND METHODS Using Sequenom MassARRAY we measured the methylation status of 68 CpGs 5′ from five candidate genes in umbilical cord tissue DNA from healthy neonates. Methylation varied greatly at particular CpGs: for 31 CpGs with median methylation ≥5% and a 5–95% range ≥10%, we related methylation status to maternal pregnancy diet and to child’s adiposity at age 9 years. Replication was sought in a second independent cohort. RESULTS In cohort 1, retinoid X receptor-α (RXRA) chr9:136355885+ and endothelial nitric oxide synthase (eNOS) chr7:150315553+ methylation had independent associations with sex-adjusted childhood fat mass (exponentiated regression coefficient [β] 17% per SD change in methylation [95% CI 4–31], P = 0.009, n = 64, and β = 20% [9–32], P < 0.001, n = 66, respectively) and %fat mass (β = 10% [1–19], P = 0.023, n = 64 and β =12% [4–20], P = 0.002, n = 66, respectively). Regression analyses including sex and neonatal epigenetic marks explained >25% of the variance in childhood adiposity. Higher methylation of RXRA chr9:136355885+, but not of eNOS chr7:150315553+, was associated with lower maternal carbohydrate intake in early pregnancy, previously linked with higher neonatal adiposity in this population. In cohort 2, cord eNOS chr7:150315553+ methylation showed no association with adiposity, but RXRA chr9:136355885+ methylation showed similar associations with fat mass and %fat mass (β = 6% [2–10] and β = 4% [1–7], respectively, both P = 0.002, n = 239). CONCLUSIONS Our findings suggest a substantial component of metabolic disease risk has a prenatal developmental basis. Perinatal epigenetic analysis may have utility in

  2. Antinociceptive effect and mechanism of action of isatin, N-methyl isatin and oxopropyl isatin in mice.

    PubMed

    Giorno, Thais Biondino Sardella; Silva, Bárbara Vasconcellos da; Pinto, Angelo da Cunha; Fernandes, Patricia Dias

    2016-04-15

    There has been growing interest in the synthesis of new derivatives from isatin, found in Isatis genus. Our objectives were to characterize the antinociceptive mechanism of action of isatin, N-methyl-isatin (MI) and N-methyl-3-(2-oxopropyl)-3-hydroxy-2-oxindole (MOI). Substances (0.1-10mg/kg, p.o.) were studied in chemical (paw licking induced by formalin, capsaicin or glutamate) or thermal (hot plate) models of nociception. The involvement of several systems was evaluated using different receptor antagonists. All three substances inhibit both phases of formalin-induced licking, increase the area under the curve and MI and MOI have a higher effect than that of morphine (in hot plate). Capsaicin and glutamate-induced licking were also reduced by all three substances. In the hot plate model, the antinociceptive effect of isatin was reduced by naloxone and atropine; naloxone, atropine and L-NAME reduced MI effect while naloxone, atropine, L-NAME, mecamylamine and ondansetron reduced MOI effect. Our results suggest that isatin, MI and MOI: 1) present activity in models of nociception; 2) capsaicin and glutamate receptors seems to participate in the mechanism of action; 3) opioid, cholinergic, serotoninergic, nitrergic and adrenergic systems may be involved, at least in part, in the mechanism of action of some of these substances. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Molecular recognition at methyl methacrylate/n-butyl acrylate (MMA/nBA) monomer unit boundaries of phospholipids at p-MMA/nBA copolymer surfaces.

    PubMed

    Yu, Min; Urban, Marek W; Sheng, Yinghong; Leszczynski, Jerzy

    2008-09-16

    Lipid structural features and their interactions with proteins provide a useful vehicle for further advances in membrane proteins research. To mimic one of potential lipid-protein interactions we synthesized poly(methyl methacrylate/ n-butyl acrylate) (p-MMA/nBA) colloidal particles that were stabilized by phospholipid (PLs). Upon the particle coalescence, PL stratification resulted in the formation of surface localized ionic clusters (SLICs). These entities are capable of recognizing MMA/nBA monomer interfaces along the p-MMA/nBA copolymer backbone and form crystalline SLICs at the monomer interface. By utilizing attenuated total reflectance Fourier transform infrared (ATR FT-IR) spectroscopy and selected area electron diffraction (SAD) combined with ab initio calculations, studies were conducted that identified the origin of SLICs as well as their structural features formed on the surface of p-MMA/nBA copolymer films stabilized by 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) PL. Specific entities responsible for SLIC formation are selective noncovalent bonds of anionic phosphate and cationic quaternary ammonium segments of DLPC that interact with two neighboring carbonyl groups of nBA and MMA monomers of the p-MMA/nBA polymer backbone. To the best of our knowledge this is the first example of molecular recognition facilitated by coalescence of copolymer colloidal particles and the ability of PLs to form SLICs at the boundaries of the neighboring MMA and nBA monomer units of the p-MMA/nBA chain. The dominating noncovalent bonds responsible for the molecular recognition is a combination of H-bonding and electrostatic interactions.

  4. N-methyl-d-aspartate (NMDA) receptor antibodies encephalitis mimicking an autistic regression.

    PubMed

    Hacohen, Yael; Wright, Sukhvir; Gadian, Jonathan; Vincent, Angela; Lim, Ming; Wassmer, Evangeline; Lin, Jean-Pierre

    2016-10-01

    Expressive dysphasia and mutism are common clinical features in children and adults with N-methyl-d-aspartate receptor antibodies (NMDAR-Ab) encephalitis, and are likely to result from NMDAR hypofunction. A prodromal loss of social and communication skills can typify that of an autistic regression, particularly when presenting under the age of 3 years. Here we describe two toddlers who presented with developmental regression, particularly of their social communication skills, mimicking an autistic regression, who were found to have NMDAR-Ab in the serum and cerebrospinal fluid. Although both patients had some other neurological features, they were subtle, which resulted in delayed diagnosis of NMDAR-Ab encephalitis. Importantly, immunotherapy was beneficial in both patients, with significant improvement of their language skills and behaviour. © 2016 Mac Keith Press.

  5. Physicochemical properties of an insensitive munitions compound, N-methyl-4-nitroaniline (MNA).

    PubMed

    Boddu, Veera M; Abburi, Krishnaiah; Maloney, Stephen W; Damavarapu, Reddy

    2008-06-30

    Accurate information on physicochemical properties of an organic contaminant is essential for predicting its environmental impact and fate. These properties also provide invaluable information for the overall understanding of environmental distribution, biotransformation, and potential treatment processes. In this study the aqueous solubility (Sw), octanol-water partition coefficient (Kow), and Henry's law constant (K(H)) were determined for an insensitive munitions (IM) compound, N-methyl-4-nitroaniline (MNA), at 298.15, 308.15, and 318.15 K. Effect of ionic strength on solubility, using electrolytes such as NaCl and CaCl2, was also studied. The data on the physicochemical parameters were correlated using the standard Van't Hoff equation. All three properties exhibited a linear relationship with reciprocal temperature. The enthalpy and entropy of phase transfer were derived from the experimental data.

  6. Radio-methyl vorozole and methods for making and using the same

    DOEpatents

    Kim, Sung Won; Biegon, Anat; Fowler, Joanna S.

    2014-08-12

    Radiotracer vorozole compounds for in vivo and in vitro assaying, studying and imaging cytochrome P450 aromatase enzymes in humans, animals, and tissues and methods for making and using the same are provided. [N-radio-methyl] vorozole substantially separated from an N-3 radio-methyl isomer of vorozole is provided. Separation is accomplished through use of chromatography resins providing multiple mechanisms of selectivity.

  7. Radio-methyl vorozole and methods for making and using the same

    DOEpatents

    Kim, Sung Won; Biegon, Anat; Fowler, Joanna S.

    2014-08-05

    Radiotracer vorozole compounds for in vivo and in vitro assaying, studying and imaging cytochrome P450 aromatase enzymes in humans, animals, and tissues and methods for making and using the same are provided. [N-radio-methyl] vorozole substantially separated from an N-3 radio-methyl isomer of vorozole is provided. Separation is accomplished through use of chromatography resins providing multiple mechanisms of selectivity.

  8. SYNERGISTIC EFFECT OF HALIDE IONS ON THE CORROSION INHIBITION OF MILD STEEL IN SULPHURIC ACID USING METHYL, N-METHYL ETHYL AND ETHYL SUBSTITUTED γ-2,c-6-DIPHENYL PIPERIDIN-4-ONE SEMICARBAZONES

    NASA Astrophysics Data System (ADS)

    Priya, V. Shanmuga; Rani, C. Uma; Velrani, S.

    The synergistic effect of halide ions such as KCl, KBr and KI on the corrosion inhibition of mild steel in 1 N sulphuric acid by γ-2,c-6-diphenyl-t-3-methyl piperdin-4-ones with semicarbazone (01SC), γ-2,c-6-diphenyl-N-methyl-t-3-ethyl piperdin-4-ones with semicarbazone (02SC) and 2,6-diphenyl-t-3-ethyl piperdin-4-one with semicarbazone (03SC) has been examined by weight loss method, potentiodynamic polarization measurements and electrochemical AC impedance spectroscopy. Results show that substituted γ-2,c-6-diphenyl piperidin-4-ones with semicarbazone act as the perfect corrosion inhibitors and their inhibition efficiency increases with the addition of halide ions. The inhibitor (01SC) shows the inhibition efficiency of 78.28% (0.2mM) by using a weight loss method. The influence of I-, Br- and Cl- anions raises the inhibition efficiency of the substituted 2,6-diphenyl piperidin-4-ones with semicarbazone due to the synergistic effect. The synergistic effect of halide ions was formed in the following order: KI > KBr > KCl.

  9. Volatile Organic Compounds Enhance Allergic Airway Inflammation in an Experimental Mouse Model

    PubMed Central

    Bönisch, Ulrike; Böhme, Alexander; Kohajda, Tibor; Mögel, Iljana; Schütze, Nicole; von Bergen, Martin; Simon, Jan C.; Lehmann, Irina; Polte, Tobias

    2012-01-01

    Background Epidemiological studies suggest an association between exposure to volatile organic compounds (VOCs) and adverse allergic and respiratory symptoms. However, whether VOCs exhibit a causal role as adjuvants in asthma development remains unclear. Methods To investigate the effect of VOC exposure on the development of allergic airway inflammation Balb/c mice were exposed to VOCs emitted by new polyvinylchloride (PVC) flooring, sensitized with ovalbumin (OVA) and characterized in acute and chronic murine asthma models. Furthermore, prevalent evaporated VOCs were analyzed and mice were exposed to selected single VOCs. Results Exposure of mice to PVC flooring increased eosinophilic lung inflammation and OVA-specific IgE serum levels compared to un-exposed control mice. The increased inflammation was associated with elevated levels of Th2-cytokines. Long-term exposure to PVC flooring exacerbated chronic airway inflammation. VOCs with the highest concentrations emitted by new PVC flooring were N-methyl-2-pyrrolidone (NMP) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB). Exposure to NMP or TXIB also increased the allergic immune response in OVA-sensitized mice. In vitro or in vivo exposure to NMP or TXIB reduced IL-12 production in maturing dendritic cells (DCs) and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. At higher concentrations both VOCs induced oxidative stress demonstrated by increased isoprostane and glutathione-S-transferase-pi1 protein levels in the lung of non-sensitized mice. Treatment of PVC flooring-exposed mice with N-acetylcysteine prevented the VOC-induced increase of airway inflammation. Conclusions Our results demonstrate that exposure to VOCs may increase the allergic immune response by interfering with DC function and by inducing oxidative stress and has therefore to be considerate as risk factor for the development of allergic diseases. PMID:22802943

  10. Volatile organic compounds enhance allergic airway inflammation in an experimental mouse model.

    PubMed

    Bönisch, Ulrike; Böhme, Alexander; Kohajda, Tibor; Mögel, Iljana; Schütze, Nicole; von Bergen, Martin; Simon, Jan C; Lehmann, Irina; Polte, Tobias

    2012-01-01

    Epidemiological studies suggest an association between exposure to volatile organic compounds (VOCs) and adverse allergic and respiratory symptoms. However, whether VOCs exhibit a causal role as adjuvants in asthma development remains unclear. To investigate the effect of VOC exposure on the development of allergic airway inflammation Balb/c mice were exposed to VOCs emitted by new polyvinylchloride (PVC) flooring, sensitized with ovalbumin (OVA) and characterized in acute and chronic murine asthma models. Furthermore, prevalent evaporated VOCs were analyzed and mice were exposed to selected single VOCs. Exposure of mice to PVC flooring increased eosinophilic lung inflammation and OVA-specific IgE serum levels compared to un-exposed control mice. The increased inflammation was associated with elevated levels of Th2-cytokines. Long-term exposure to PVC flooring exacerbated chronic airway inflammation. VOCs with the highest concentrations emitted by new PVC flooring were N-methyl-2-pyrrolidone (NMP) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB). Exposure to NMP or TXIB also increased the allergic immune response in OVA-sensitized mice. In vitro or in vivo exposure to NMP or TXIB reduced IL-12 production in maturing dendritic cells (DCs) and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. At higher concentrations both VOCs induced oxidative stress demonstrated by increased isoprostane and glutathione-S-transferase-pi1 protein levels in the lung of non-sensitized mice. Treatment of PVC flooring-exposed mice with N-acetylcysteine prevented the VOC-induced increase of airway inflammation. Our results demonstrate that exposure to VOCs may increase the allergic immune response by interfering with DC function and by inducing oxidative stress and has therefore to be considerate as risk factor for the development of allergic diseases.

  11. Weak Maser Emission of Methyl Formate toward Sagittarius B2(N) in the Green Bank Telescope PRIMOS Survey

    NASA Astrophysics Data System (ADS)

    Faure, A.; Remijan, A. J.; Szalewicz, K.; Wiesenfeld, L.

    2014-03-01

    A non-LTE radiative transfer treatment of cis-methyl formate (HCOOCH3) rotational lines is presented for the first time using a set of theoretical collisional rate coefficients. These coefficients have been computed in the temperature range 5-30 K by combining coupled-channel scattering calculations with a high accuracy potential energy surface for HCOOCH3-He. The results are compared to observations toward the Sagittarius B2(N) molecular cloud using the publicly available PRIMOS survey from the Green Bank Telescope. A total of 49 low-lying transitions of methyl formate, with upper levels below 25 K, are identified. These lines are found to probe a presumably cold (~30 K), moderately dense (~104 cm-3), and extended region surrounding Sgr B2(N). The derived column density of ~4 × 1014 cm-2 is only a factor of ~10 larger than the column density of the trans conformer in the same source. Provided that the two conformers have the same spatial distribution, this result suggests that strongly non-equilibrium processes must be involved in their synthesis. Finally, our calculations show that all detected emission lines with a frequency below 30 GHz are (collisionally pumped) weak masers amplifying the continuum of Sgr B2(N). This result demonstrates the importance and generality of non-LTE effects in the rotational spectra of complex organic molecules at centimeter wavelengths.

  12. Continuous treatment of N-Methyl-p-nitro aniline (MNA) in an Upflow Anaerobic Sludge Blanket (UASB) bioreactor

    PubMed Central

    Olivares, Christopher I.; Wang, Junqin; Silva Luna, Carlos D.; Field, Jim A.; Abrell, Leif; Sierra-Alvarez, Reyes

    2017-01-01

    N-methyl-p-nitroaniline (MNA) is an ingredient of insensitive munitions (IM) compounds that serves as a plasticizer and helps reduce unwanted detonations. As its use becomes widespread, MNA waste streams will be generated, necessitating viable treatment options. We studied MNA biodegradation and its inhibition potential to, a representative anaerobic microbial population in wastewater treatment, methanogens. Anaerobic biodegradation and toxicity assays were performed and an up-flow anaerobic sludge blanket reactor (UASB) was operated to test continuous degradation of MNA. MNA was transformed almost stoichiometrically to N-methyl-p-phenylenediamine (MPD). MPD was not mineralized, however, it was readily autoxidized and polymerized extensively upon aeration at pH = 9. In the UASB reactor, MNA was fully degraded up to a loading rate of 297.5 μM MNA d-1). Regarding toxicity, MNA was very inhibitory to acetoclastic methanogens (IC50 = 103 μM) whereas MPD was much less toxic, causing only 13.9% inhibition at the highest concentration tested (1025 μM). The results taken as a whole indicate that anaerobic sludge can transform MNA to MPD continuously, and that the transformation decreases the cytotoxicity of the parent pollutant. MPD can be removed through extensive polymerization. These insights could help define efficient treatment options for waste streams polluted with MNA. PMID:26454121

  13. Anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis show distinct patterns of brain glucose metabolism in 18F-fluoro-2-deoxy-d-glucose positron emission tomography

    PubMed Central

    2014-01-01

    Background Pathogenic autoantibodies targeting the recently identified leucine rich glioma inactivated 1 protein and the subunit 1 of the N-methyl-D-aspartate receptor induce autoimmune encephalitis. A comparison of brain metabolic patterns in 18F-fluoro-2-deoxy-d-glucose positron emission tomography of anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis patients has not been performed yet and shall be helpful in differentiating these two most common forms of autoimmune encephalitis. Methods The brain 18F-fluoro-2-deoxy-d-glucose uptake from whole-body positron emission tomography of six anti-N-methyl-D-aspartate receptor encephalitis patients and four patients with anti-leucine rich glioma inactivated 1 protein encephalitis admitted to Hannover Medical School between 2008 and 2012 was retrospectively analyzed and compared to matched controls. Results Group analysis of anti-N-methyl-D-aspartate encephalitis patients demonstrated regionally limited hypermetabolism in frontotemporal areas contrasting an extensive hypometabolism in parietal lobes, whereas the anti-leucine rich glioma inactivated 1 protein syndrome was characterized by hypermetabolism in cerebellar, basal ganglia, occipital and precentral areas and minor frontomesial hypometabolism. Conclusions This retrospective 18F-fluoro-2-deoxy-d-glucose positron emission tomography study provides novel evidence for distinct brain metabolic patterns in patients with anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis. PMID:24950993

  14. Effects of methyl p-hydroxybenzoate (methyl paraben) on Ca2+ concentration and histamine release in rat peritoneal mast cells

    PubMed Central

    Fukugasako, Sanae; Ito, Shinichi; Ikemoto, Yoshimi

    2003-01-01

    Mechanisms of methyl p-hydroxybenzoate (methyl paraben) action in allergic reactions were investigated by measuring the intracellular Ca2+ concentration ([Ca2+]i) and histamine release in rat peritoneal mast cells (RPMCs). In the presence or absence of extracellular Ca2+, methyl paraben (0.1–10 mM) increased [Ca2+]i, in a concentration-dependent manner. Under both the conditions, methyl paraben alone did not evoke histamine release. In RPMCs pretreated with a protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate (PMA) 3 and 10 nM), methyl paraben (0.3–3 mM) induced histamine release. However, a high concentration (10 mM) of the agent did not increase the histamine release. U73122 (0.1 and 0.5 μM), an inhibitor of phospholipase C (PLC), significantly inhibited the methyl paraben-induced histamine release in PMA-pretreated RPMCs. U73343 (0.5 μM), an inactive analogue of U73122, did not inhibit the histamine release caused by methyl paraben. In Ca2+-free solution, PLC inhibitors (U73122 0.1 and 0.5 μM, D609 1–10 μM) inhibited the methyl paraben-induced increase in [Ca2+]i, whereas U73343 (0.5 μM) did not. Xestospongin C (2–20 μM) and 2 aminoethoxydiphenyl borate (30 and 100 μM), blockers of the inositol 1,4,5-trisphosphate (IP3) receptor, inhibited the methyl paraben-induced increase in [Ca2+]i in Ca2+-free solution. In conclusion, methyl paraben causes an increase in [Ca2+]i, which may be due to release of Ca2+ from storage sites by IP3 via activation of PLC in RPMCs. In addition, methyl paraben possibly has some inhibitory effects on histamine release via unknown mechanisms. PMID:12770943

  15. Ancestry Dependent DNA Methylation and Influence of Maternal Nutrition

    PubMed Central

    Mozhui, Khyobeni; Smith, Alicia K.; Tylavsky, Frances A.

    2015-01-01

    There is extensive variation in DNA methylation between individuals and ethnic groups. These differences arise from a combination of genetic and non-genetic influences and potential modifiers include nutritional cues, early life experience, and social and physical environments. Here we compare genome-wide DNA methylation in neonatal cord blood from African American (AA; N = 112) and European American (EA; N = 91) participants of the CANDLE Study (Conditions Affecting Neurocognitive Development and Learning in Early Childhood). Our goal is to determine if there are replicable ancestry-specific methylation patterns that may implicate risk factors for diseases that have differential prevalence between populations. To identify the most robust ancestry-specific CpG sites, we replicate our results in lymphoblastoid cell lines from Yoruba African and CEPH European panels of HapMap. We also evaluate the influence of maternal nutrition—specifically, plasma levels of vitamin D and folate during pregnancy—on methylation in newborns. We define stable ancestry-dependent methylation of genes that include tumor suppressors and cell cycle regulators (e.g., APC, BRCA1, MCC). Overall, there is lower global methylation in African ancestral groups. Plasma levels of 25-hydroxy vitamin D are also considerably lower among AA mothers and about 60% of AA and 40% of EA mothers have concentrations below 20 ng/ml. Using a weighted correlation analysis, we define a network of CpG sites that is jointly modulated by ancestry and maternal vitamin D. Our results show that differences in DNA methylation patterns are remarkably stable and maternal micronutrients can exert an influence on the child epigenome. PMID:25742137

  16. A 2:1 co-crystal of 2-methyl-benzoic acid and N,N'-bis-(pyridin-4-ylmeth-yl)ethanedi-amide: crystal structure and Hirshfeld surface analysis.

    PubMed

    Syed, Sabrina; Jotani, Mukesh M; Halim, Siti Nadiah Abdul; Tiekink, Edward R T

    2016-03-01

    The asymmetric unit of the title 2:1 co-crystal, 2C8H8O2·C14H14N4O2, comprises an acid mol-ecule in a general position and half a di-amide mol-ecule, the latter being located about a centre of inversion. In the acid, the carb-oxy-lic acid group is twisted out of the plane of the benzene ring to which it is attached [dihedral angle = 28.51 (8)°] and the carbonyl O atom and methyl group lie approximately to the same side of the mol-ecule [hy-droxy-O-C-C-C(H) torsion angle = -27.92 (17)°]. In the di-amide, the central C4N2O2 core is almost planar (r.m.s. deviation = 0.031 Å), and the pyridyl rings are perpendicular, lying to either side of the central plane [central residue/pyridyl dihedral angle = 88.60 (5)°]. In the mol-ecular packing, three-mol-ecule aggregates are formed via hy-droxy-O-H⋯N(pyrid-yl) hydrogen bonds. These are connected into a supra-molecular layer parallel to (12[Formula: see text]) via amide-N-H⋯O(carbon-yl) hydrogen bonds, as well as methyl-ene-C-H⋯O(amide) inter-actions. Significant π-π inter-actions occur between benzene/benzene, pyrid-yl/benzene and pyrid-yl/pyridyl rings within and between layers to consolidate the three-dimensional packing.

  17. Identification of endometrial cancer methylation features using combined methylation analysis methods

    PubMed Central

    Trimarchi, Michael P.; Yan, Pearlly; Groden, Joanna; Bundschuh, Ralf; Goodfellow, Paul J.

    2017-01-01

    Background DNA methylation is a stable epigenetic mark that is frequently altered in tumors. DNA methylation features are attractive biomarkers for disease states given the stability of DNA methylation in living cells and in biologic specimens typically available for analysis. Widespread accumulation of methylation in regulatory elements in some cancers (specifically the CpG island methylator phenotype, CIMP) can play an important role in tumorigenesis. High resolution assessment of CIMP for the entire genome, however, remains cost prohibitive and requires quantities of DNA not available for many tissue samples of interest. Genome-wide scans of methylation have been undertaken for large numbers of tumors, and higher resolution analyses for a limited number of cancer specimens. Methods for analyzing such large datasets and integrating findings from different studies continue to evolve. An approach for comparison of findings from a genome-wide assessment of the methylated component of tumor DNA and more widely applied methylation scans was developed. Methods Methylomes for 76 primary endometrial cancer and 12 normal endometrial samples were generated using methylated fragment capture and second generation sequencing, MethylCap-seq. Publically available Infinium HumanMethylation 450 data from The Cancer Genome Atlas (TCGA) were compared to MethylCap-seq data. Results Analysis of methylation in promoter CpG islands (CGIs) identified a subset of tumors with a methylator phenotype. We used a two-stage approach to develop a 13-region methylation signature associated with a “hypermethylator state.” High level methylation for the 13-region methylation signatures was associated with mismatch repair deficiency, high mutation rate, and low somatic copy number alteration in the TCGA test set. In addition, the signature devised showed good agreement with previously described methylation clusters devised by TCGA. Conclusion We identified a methylation signature for a

  18. Solubility of nitrous oxide in aqueous blends of N-methyldiethanolamine and 2-amino-2-methyl-1-propanol

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Davis, R.A.; Pogainis, B.J.

    1995-11-01

    Aqueous solutions of alkanolamines have applications in acid gas treatment for the removal of acid gases such as carbon dioxide and hydrogen sulfide. The solubility of nitrous oxide in aqueous blends of N-methyldiethanolamine and 2-amino-2-methyl-1 propanol was measured over the temperature range 10--60 C. The total composition of the alkanolamines in water ranged from 30 to 50 mass %. The experimental results were interpreted in terms of Henry`s constants.

  19. Effects of Phase Separation Behavior on Morphology and Performance of Polycarbonate Membranes.

    PubMed

    Idris, Alamin; Man, Zakaria; Maulud, Abdulhalim S; Khan, Muhammad Saad

    2017-04-05

    The phase separation behavior of bisphenol-A-polycarbonate (PC), dissolved in N -methyl-2-pyrrolidone and dichloromethane solvents in coagulant water, was studied by the cloud point method. The respective cloud point data were determined by titration against water at room temperature and the characteristic binodal curves for the ternary systems were plotted. Further, the physical properties such as viscosity, refractive index, and density of the solution were measured. The critical polymer concentrations were determined from the viscosity measurements. PC/NMP and PC/DCM membranes were fabricated by the dry-wet phase inversion technique and characterized for their morphology, structure, and thermal stability using field emission scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis, respectively. The membranes' performances were tested for their permeance to CO₂, CH₄, and N₂ gases at 24 ± 0.5 °C with varying feed pressures from 2 to 10 bar. The PC/DCM membranes appeared to be asymmetric dense membrane types with appreciable thermal stability, whereas the PC/NMP membranes were observed to be asymmetric with porous structures exhibiting 4.18% and 9.17% decrease in the initial and maximum degradation temperatures, respectively. The ideal CO₂/N₂ and CO₂/CH₄ selectivities of the PC/NMP membrane decreased with the increase in feed pressures, while for the PC/DCM membrane, the average ideal CO₂/N₂ and CO₂/CH₄ selectivities were found to be 25.1 ± 0.8 and 21.1 ± 0.6, respectively. Therefore, the PC/DCM membranes with dense morphologies are appropriate for gas separation applications.

  20. USE OF EXPOSURE-RELATED DOSE ESTIMATING MODEL (ERDEM) FOR ASSESSMENT OF AGGREGATE EXPOSURE OF INFANT AND CHILDREN TO N-METHYL CARBAMATE INSECTICIDES

    EPA Science Inventory

    A physiologically based pharmacokinetic (PBPK) model was developed within the Exposure Related Dose Estimating Model (ERDEM) framework to investigate selected exposure inputs related to recognized exposure scenarios of infants and children to N-methyl carbamate pesticides as spec...

  1. Crystal structures of HIV-1 nonnucleoside reverse transcriptase inhibitors: N-benzyl-4-methyl-benzimidazoles

    NASA Astrophysics Data System (ADS)

    Ziółkowska, Natasza E.; Michejda, Christopher J.; Bujacz, Grzegorz D.

    2009-07-01

    HIV-1 nonnucleoside reverse transcriptase inhibitors are potentially specific and effective drugs in AIDS therapy. The presence of two aromatic systems with an angled orientation in the molecule of the inhibitor is crucial for interactions with HIV-1 RT. The inhibitor drives like a wedge into the cluster of aromatic residues of RT HIV-1 and restrains the enzyme in a conformation that blocks the chemical step of nucleotide incorporation. Structural studies provide useful information for designing new, more active inhibitors. The crystal structures of four NNRTIs are presented here. The investigated compounds are derivatives of N-benzyl-4-methyl-benzimidazole with various aliphatic and aromatic substituents at carbon 2 positions and a 2,6-dihalogeno-substituted N-benzyl moiety. Structural data reported here show that the conformation of the investigated compounds is relatively rigid. Such feature is important for the nonnucleoside inhibitor binding to HIV-1 reverse transcriptase.

  2. Selective Impairment of Spatial Cognition Caused by Autoantibodies to the N-Methyl-d-Aspartate Receptor

    PubMed Central

    Chang, Eric H.; Volpe, Bruce T.; Mackay, Meggan; Aranow, Cynthia; Watson, Philip; Kowal, Czeslawa; Storbeck, Justin; Mattis, Paul; Berlin, RoseAnn; Chen, Huiyi; Mader, Simone; Huerta, Tomás S.; Huerta, Patricio T.; Diamond, Betty

    2015-01-01

    Patients with systemic lupus erythematosus (SLE) experience cognitive abnormalities in multiple domains including processing speed, executive function, and memory. Here we show that SLE patients carrying antibodies that bind DNA and the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), termed DNRAbs, displayed a selective impairment in spatial recall. Neural recordings in a mouse model of SLE, in which circulating DNRAbs penetrate the hippocampus, revealed that CA1 place cells exhibited a significant expansion in place field size. Structural analysis showed that hippocampal pyramidal cells had substantial reductions in their dendritic processes and spines. Strikingly, these abnormalities became evident at a time when DNRAbs were no longer detectable in the hippocampus. These results suggest that antibody-mediated neurocognitive impairments may be highly specific, and that spatial cognition may be particularly vulnerable to DNRAb-mediated structural and functional injury to hippocampal cells that evolves after the triggering insult is no longer present. PMID:26286205

  3. DNA Methylation as a Biomarker for Preeclampsia

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Anderson, Cindy M.; Ralph, Jody L.; Wright, Michelle L.

    Background: Preeclampsia contributes significantly to pregnancy-associated morbidity and mortality as well as future risk of cardiovascular disease in mother and offspring, and preeclampsia in offspring. The lack of reliable methods for early detection limits the opportunities for prevention, diagnosis, and timely treatment. Purpose: The purpose of this study was to explore distinct DNA methylation patterns associated with preeclampsia in both maternal cells and fetal-derived tissue that represent potential biomarkers to predict future preeclampsia and inheritance in children. Method: A convenience sample of nulliparous women (N = 55) in the first trimester of pregnancy was recruited for this prospective study. Genome-widemore » DNA methylation was quantified in first-trimester maternal peripheral white blood cells and placental chorionic tissue from normotensive women and those with preeclampsia (n = 6/group). Results: Late-onset preeclampsia developed in 12.7% of women. Significant differences in DNA methylation were identified in 207 individual linked cytosine and guanine (CpG) sites in maternal white blood cells collected in the first trimester (132 sites with gain and 75 sites with loss of methylation), which were common to approximately 75% of the differentially methylated CpG sites identified in chorionic tissue of fetal origin. Conclusion: This study is the first to identify maternal epigenetic targets and common targets in fetal-derived tissue that represent putative biomarkers for early detection and heritable risk of preeclampsia. Findings may pave the way for diagnosis of preeclampsia prior to its clinical presentation and acute damaging effects, and the potential for prevention of the detrimental long-term sequelae.« less

  4. Attenuation by all-trans-retinoic acid of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

    PubMed

    Tatsuta, M; Iishi, H; Baba, M; Hirasawa, R; Yano, H; Sakai, N; Nakaizumi, A

    1999-02-01

    The effect of prolonged administration of all-trans-retinoic acid (RA) on sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine, and the labelling and apoptotic indices and immunoreactivity of transforming growth factor (TGF) alpha in the gastric cancers was investigated in Wistar rats. After 25 weeks of carcinogen treatment, the rats were given chow pellets containing 10% sodium chloride and subcutaneous injections of RA at doses of 0.75 or 1.5 mg kg(-1) body weight every other day. In week 52, oral supplementation with sodium chloride significantly increased the incidence of gastric cancers compared with the untreated controls. Long-term administration of RA at both doses significantly reduced the incidence of gastric cancers, which was enhanced by oral administration of sodium chloride. RA at both doses significantly decreased the labelling index and TGF-alpha immunoreactivity of gastric cancers, which were enhanced by administration of sodium chloride, and significantly increased the apoptotic index of cancers, which was lowered by administration of sodium chloride. These findings suggest that RA attenuates gastric carcinogenesis, enhanced by sodium chloride, by increasing apoptosis, decreasing DNA synthesis, and reducing TGF-alpha expression in gastric cancers.

  5. High performance screen-printed electrodes prepared by a green solvent approach for lithium-ion batteries

    NASA Astrophysics Data System (ADS)

    Gören, A.; Mendes, J.; Rodrigues, H. M.; Sousa, R. E.; Oliveira, J.; Hilliou, L.; Costa, C. M.; Silva, M. M.; Lanceros-Méndez, S.

    2016-12-01

    New inks based on lithium iron phosphate and graphite for cathode and anode, respectively, were developed for printable lithium-ion batteries using the "green solvent" N,N‧-dimethylpropyleneurea (DMPU) and poly(vinylidene fluoride), PVDF, as a binder. The results were compared with the ones from inks developed with the conventionally used solvent N-methyl-2-pyrrolidone, NMP. The rheological properties of the PVDF/DMPU binder solution shows a more pronounced shear thinning behavior than the PVDF/NMP solution. Cathode inks prepared with 2.25 mL and 2.50 mL of DMPU for 1 g of electrode mass show an apparent viscosity of 3 Pa s and 2 Pa s for a shear rate of 100 s-1, respectively, being therefore processable by screen-printing or doctor blade techniques. The electrodes prepared with DMPU and processed by screen-printing show a capacity of 52 mAh g-1 at 2C for the cathode and 349 mAh g-1 at C/5 for the anode, after 45 charge-discharge cycles. The electrochemical performance of both electrodes was evaluated in a full-cell and after 9 cycles, the discharge capacity value is 81 mAh g-1, showing a discharge capacity retention of 64%. The new inks presented in this work are thus suitable for the development of printed batteries and represent a step forward towards more environmental friendly processes.

  6. A multi-responsive luminescent sensor based on a super-stable sandwich-type terbium(iii)-organic framework.

    PubMed

    Wen, Guo-Xuan; Han, Min-Le; Wu, Xue-Qian; Wu, Ya-Pan; Dong, Wen-Wen; Zhao, Jun; Li, Dong-Sheng; Ma, Lu-Fang

    2016-10-04

    A super-stable multifunctional terbium(iii)-organic framework, namely {[Tb(TATAB) (H 2 O) 2 ]·NMP·H 2 O} n (Tb-MOF, H 3 TATAB = 4,4',4''-s-triazine-1,3,5-triyltri-m-aminobenzoic acid, NMP = N-methyl-2-pyrrolidone) was synthesized. Tb-MOF exhibits a 2D sql structure with binuclear [Tb 2 (COO) 4 (H 2 O) 4 ] 2+ units as 4-connected nodes, and free water and NMP molecules are inserted between 2D layers through hydrogen-bonding interactions, forming a sandwich-type architecture. Observably, such a framework remains intact in a remarkable variety of environments such as common solvents and aqueous solutions with metal cations and inorganic anions, as well as with a pH ranging from 1 to 13. In particular, Tb-MOF can not only detect small organic molecules, metal cations and inorganic anions with high sensitivity and high selectivity, but also can accurately detect explosive 2-nitrophenol, 3-nitrophenol, 4-nitrophenol and 2,4,6-trinitrophenol in water. Its luminescence quenching response to Fe 3+ and Cr 2 O 7 2- ions can be explained in terms of the competitive absorption mechanism. In addition, the luminescence intensity of Tb-MOF is strongly correlated with the pH value in a pH range from 1 to 13. Thus, this material can be potentially used as a multi-responsive luminescent sensor.

  7. (R)-N-Methyl-3-(3′-[18F]fluoropropyl)phenoxy)-3-phenylpropanamine (18F-MFP3) as a potential PET imaging agent for norepinephrine transporter

    PubMed Central

    Nguyen, Vivien L.; Pichika, Rama; Bhakta, Paayal H.; Kant, Ritu; Mukherjee, Jogeshwar

    2010-01-01

    A decline of norepinephrine transporter (NET) level is associated with several psychiatric and neurological disorders. Therefore positron emission tomography (PET) imaging agents are greatly desired to study the NET pathway. We have developed a C-fluoropropyl analog of nisoxetine: (R)-N-methyl-3-(3′-[18F]fluoropropyl)phenoxy)-3-phenylpropanamine (18F-MFP3) as a new potential PET radiotracer for NET with the advantage of the longer half-life of fluorine-18 (110 min compared with carbon-11 (20 min). Synthesis of (R)-N-methyl-3-(3′-fluoropropyl)phenoxy)-3-phenylpropanamine (MFP3) was achieved in five steps starting from (S)-N-methyl-3-ol-3-phenylpropanamine in approx. 3–5% overall yields. In vitro binding affinity of nisoxetine and MFP3 in rat brain homogenates labeled with 3H-nisoxetine gave Ki values of 8.02 nM and 23 nM, respectively. For radiosynthesis of 18F-MFP3, fluorine-18 was incorporated into a tosylate precursor, followed by the deprotection of the N-BOC-protected amine group with a 15% decay corrected yield in 2.5 h. Reverse-phase chromatographic purification provided 18F-MFP3 in specific activities of >2000 Ci/mmol. Fluorine-18 labeled 18F-MFP3 has been produced in modest radiochemical yields and in high specific activities. Evaluation of 18F-MFP3 in animal imaging studies is in progress in order to validate this new fluorine-18 radiotracer for PET imaging of NET. PMID:20495670

  8. Failure of dietary alpha-difluoromethylornithine to inhibit gastric carcinogenesis in rats after 8 weeks of treatment with N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride.

    PubMed

    Tanakamaru, Z; Nishikawa, A; Furukawa, F; Imazawa, T; Lee, I S; Kasahara, K; Tanaka, T; Takahashi, M

    1997-11-25

    The modifying effects of alpha-difluoromethylomithine (DFMO) on glandular stomach carcinogenesis after initiation with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride were investigated in male outbred Wistar rats. Animals were simultaneously given MNNG solution (100 ppm) as their drinking water and diet supplemented with 10% sodium chloride for 8 weeks, and administered DFMO (dietary levels of 2000 ppm or 500 ppm) and tap water for the following 70 weeks. The DFMO treatment did not show any tendency to inhibit the development of gastric adenocarcinomas. The incidences and multiplicities of atypical hyperplasias in the glandular stomachs were also comparable in all groups of rats given MNNG/sodium chloride. Neither gastric carcinomas nor atypical hyperplasias were observed without the carcinogen treatment. Thus, DFMO did not exert any inhibitory effects when given during the post-initiation phase of two-stage glandular stomach carcinogenesis in rats initiated with MNNG and sodium chloride for 8 weeks.

  9. A general method for N-methylation of amines and nitro compounds with dimethylsulfoxide.

    PubMed

    Jiang, Xue; Wang, Chao; Wei, Yawen; Xue, Dong; Liu, Zhaotie; Xiao, Jianliang

    2014-01-03

    DMSO methylates a broad range of amines in the presence of formic acid, providing a novel, green and practical method for amine methylation. The protocol also allows the one-pot transformation of aromatic nitro compounds into dimethylated amines in the presence of a simple iron catalyst. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. [Autoimmune encephalitis associated to antibodies against the N-methyl-D-aspartate receptor: Report of two cases].

    PubMed

    Bustos, José; Sánchez, Yasmin; Medina, Jhon; Olivieri, Rommy; Mojica, Julián; Ortiz, Johan

    2017-04-01

    Anti-N-methyl-D-aspartate receptor encephalitis is a neurological syndrome that is more common in young women and is often associated with ovarian teratoma. It is characterized by acute general unspecific symptoms that evolve to neurological deterioration, psychosis and seizures. In its more advanced stage it is associated with abnormal movements and dysautonomia.We report two cases in women of 23 and 12 years of age. Given its low incidence, we present the clinical exercise that led to their diagnoses and the treatment options employed.

  11. Anti-N-Methyl-D-aspartate Receptor Encephalitis: A Severe, Potentially Reversible Autoimmune Encephalitis.

    PubMed

    Liu, Cai-Yun; Zhu, Jie; Zheng, Xiang-Yu; Ma, Chi; Wang, Xu

    2017-01-01

    Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is potentially lethal, but it is also a treatable autoimmune disorder characterized by prominent psychiatric and neurologic symptoms. It is often accompanied with teratoma or other neoplasm, especially in female patients. Anti-NMDAR antibodies in cerebrospinal fluid (CSF) and serum are characteristic features of the disease, thereby suggesting a pathogenic role in the disease. Here, we summarize recent studies that have clearly documented that both clinical manifestations and the antibodies may contribute to early diagnosis and multidisciplinary care. The clinical course of the disorder is reversible and the relapse could occur in some patients. Anti-NMDAR encephalitis coexisting with demyelinating disorders makes the diagnosis more complex; thus, clinicians should be aware of the overlapping diseases.

  12. Anti-N-Methyl-D-aspartate Receptor Encephalitis: A Severe, Potentially Reversible Autoimmune Encephalitis

    PubMed Central

    Liu, Cai-yun; Zheng, Xiang-Yu; Ma, Chi

    2017-01-01

    Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is potentially lethal, but it is also a treatable autoimmune disorder characterized by prominent psychiatric and neurologic symptoms. It is often accompanied with teratoma or other neoplasm, especially in female patients. Anti-NMDAR antibodies in cerebrospinal fluid (CSF) and serum are characteristic features of the disease, thereby suggesting a pathogenic role in the disease. Here, we summarize recent studies that have clearly documented that both clinical manifestations and the antibodies may contribute to early diagnosis and multidisciplinary care. The clinical course of the disorder is reversible and the relapse could occur in some patients. Anti-NMDAR encephalitis coexisting with demyelinating disorders makes the diagnosis more complex; thus, clinicians should be aware of the overlapping diseases. PMID:28698711

  13. Crystal structure of 1-methyl-3-([2,2-dimethyl-4,6-dioxo-1,3-dioxane-5-ylidene]methyl)urea

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Habibi, A., E-mail: habibi@khu.ac.ir; Ghorbani, H. S.; Bruno, G.

    2013-12-15

    The crystal structure of 1-Methyl-3-([2,2-dimethyl-4,6-dioxo-1,3-dioxane-5-ylidene]methyl)urea (C{sub 9}H{sub 12}N{sub 2}O{sub 5}) has been determined by single crystal X-ray diffraction analysis. The crystals are monoclinic, a = 5.3179(2), b = 18.6394(6), c =10.8124(3) Å, β = 100.015(2)°, Z = 4, sp. gr. P2{sub 1}/c, R = 0.0381 for 2537 reflections with I > 2σ(I). Except for C(CH{sub 3}){sub 2} group, the molecule is planar. The structure is stabilized by inter- and intramolecular N-H...O hydrogen bonds and weak C-H...O interactions.

  14. N-heterocycle carbene (NHC)-ligated cyclopalladated N,N-dimethylbenzylamine: a highly active, practical and versatile catalyst for the Heck-Mizoroki reaction.

    PubMed

    Peh, Guang-Rong; Kantchev, Eric Assen B; Zhang, Chi; Ying, Jackie Y

    2009-05-21

    The wide dissemination of catalytic protocols in academic and industrial laboratories is facilitated by the development of catalysts that are not only highly active but also user-friendly, stable to moisture, air and long term storage and easy to prepare on a large scale. Herein we describe a protocol for the Heck-Mizoroki reaction mediated by cyclopalladated N,N-dimethylbenzylamine (dmba) ligated with a N-heterocyclic carbene, 1,3-bis(mesityl)imidazol-2-ylidene (IMes), that fulfils these criteria. The precatalyst can be synthesized on approximately 100 g scale by a tri-component, sequential, one-pot reaction of N,N-dimethylbenzylamine, PdCl2 and IMes.HCl in refluxing acetonitrile in air in the presence of K2CO3. This single component catalyst is stable to air, moisture and long term storage and can be conveniently dispensed as a stock solution in NMP. It mediates the Heck-Mizoroki reaction of a range of aryl- and heteroaryl bromides in reagent grade NMP at the 0.1-2 mol% range without the need for rigorous anhydrous techniques or a glovebox, and is active even in air. The catalyst is capable of achieving very high levels of catalytic activity (TON of up to 5.22 x 10(5)) for the coupling of a deactivated arylbromide, p-bromoanisole, with tBu acrylate as a benchmark substrate pair. A wide range of aryl bromides, iodides and, for the first time with a NHC-Pd catalyst, a triflate was coupled with diverse acrylate derivatives (nitrile, tert-butyl ester and amides) and styrene derivatives. The use of excess (>2 equiv.) of the aryl bromide and tert-butyl acrylate leads to mixture of tert-butyl beta,beta-diarylacrylate and tert-butyl cinnamate derivatives depending on the substitution pattern of the aryl bromide. Electron rich m- and p-substituted arylbromides give the diarylated products exclusively, whereas electron-poor aryl bromides give predominantly mono-arylated products. For o-substituted aryl bromides, no doubly arylated products could be obtained under any

  15. QSPR models of n-octanol/water partition coefficients and aqueous solubility of halogenated methyl-phenyl ethers by DFT method.

    PubMed

    Zeng, Xiao-Lan; Wang, Hong-Jun; Wang, Yan

    2012-02-01

    The possible molecular geometries of 134 halogenated methyl-phenyl ethers were optimized at B3LYP/6-31G(*) level with Gaussian 98 program. The calculated structural parameters were taken as theoretical descriptors to establish two new novel QSPR models for predicting aqueous solubility (-lgS(w,l)) and n-octanol/water partition coefficient (lgK(ow)) of halogenated methyl-phenyl ethers. The two models achieved in this work both contain three variables: energy of the lowest unoccupied molecular orbital (E(LUMO)), most positive atomic partial charge in molecule (q(+)), and quadrupole moment (Q(yy) or Q(zz)), of which R values are 0.992 and 0.970 respectively, their standard errors of estimate in modeling (SD) are 0.132 and 0.178, respectively. The results of leave-one-out (LOO) cross-validation for training set and validation with external test sets both show that the models obtained exhibited optimum stability and good predictive power. We suggests that two QSPR models derived here can be used to predict S(w,l) and K(ow) accurately for non-tested halogenated methyl-phenyl ethers congeners. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Synthesis of a novel methyl(2E)-2-{[N-(2-formylphenyl)(4-methylbenzene) sulfonamido]methyl}-3-(2-methoxyphenyl)prop-2-enoate: Molecular structure, spectral, antimicrobial, molecular docking and DFT computational approaches

    NASA Astrophysics Data System (ADS)

    Murugavel, S.; Vetri velan, V.; Kannan, Damodharan; Bakthadoss, Manickam

    2017-01-01

    The title compound methyl(2E)-2-{[N-(2-formylphenyl)(4-methylbenzene)sulfonamido] methyl}-3-(2-methoxyphenyl)prop-2-enoate (MFMSM) has been synthesized and single crystals were grown by slow evaporation solution growth technique at room temperature. XRD, FT-IR and NMR spectra of MFMSM in the solid phase were recorded and analyzed. The optimized geometry and vibrational wave numbers were computed using DFT method. The NLO, Mulliken, MEP, HOMO-LUMO energy gap and thermodynamic properties were theoretically predicted. The NBO analysis explained the intramolecular hydrogen bonding. The global chemical reactivity descriptors are calculated for MFMSM and used to predict their relative stability and reactivity. All the calculations were carried out by B3LYP/6-311G (d,p) method. MFMSM has been screened for its antimicrobial activity and found to exhibit antifungal and antibacterial effects. Docking simulation has been performed.

  17. Novel Cobalt(II) complexes containing N,N-di(2-picolyl)amine based ligands; Synthesis, characterization and application towards methyl methacrylate polymerisation

    NASA Astrophysics Data System (ADS)

    Ahn, Seoung Hyun; Choi, Sang-Il; Jung, Maeng Joon; Nayab, Saira; Lee, Hyosun

    2016-06-01

    The reaction of [CoCl2·6H2O] with N‧-substituted N,N-di(2-picolyl)amine ligands such as 1-cyclohexyl-N,N-bis(pyridin-2-ylmethyl)methanamine (LA), 2-methoxy-N,N-bis(pyridin-2-ylmethyl)ethan-1-amine (LB), and 3-methoxy-N,N-bis(pyridin-2-ylmethyl)propan-1-amine (LC), yielded [LnCoCl2] (Ln = LA, LB and LC), respectively. The Co(II) centre in [LnCoCl2] (Ln = LA, and LC) adopted distorted bipyramidal geometries through coordination of nitrogen atoms of di(2-picolyl)amine moiety to the Co(II) centre along with two chloro ligands. The 6-coordinated [LBCoCl2] showed a distorted octahedral geometry, achieved through coordination of the two pyridyl units, two chloro units, and bidentate coordination of nitrogen and oxygen in the N‧-methoxyethylamine to the Co(II) centre. [LCCoCl2] (6.70 × 104 gPMMA/molCo h) exhibited higher catalytic activity for the polymerisation of methyl methacrylate (MMA) in the presence of modified methylaluminoxane (MMAO) compared to rest of Co(II) complexes. The catalytic activity was considered as a function of steric properties of ligand architecture and increased steric bulk around the metal centre resulted in the decrease catalytic activity. All Co(II) initiators yielded syndiotactic poly(methylmethacrylate) (PMMA).

  18. Photo and Thermal Behavior of New Reinforced Polyamide-nanocomposite Montmorillonite on 2,3-Pyrazin Dicarboxylic Acid

    NASA Astrophysics Data System (ADS)

    Faghihi, Khalil; Samiei, Mojtaba; Hajibeygi, Mohsen

    2012-06-01

    Two new samples of reinforce polyamidemontmorillonite nanocomposites were synthesized by a convenient solution intercalation technique. Polyamide (PA) 3 as a source of polymer matrix was synthesized by the direct polycondensation reaction of pyrazine 2,3-dicarboxylic acid 1 with 4,4'-diamino diphenyl ether 2 in the presence of triphenyl phosphite (TPP), CaCl2, pyridine and N-methyl-2-pyrrolidone (NMP). The resulting nanocomposite films were characterized by Fourier transform infrared spectra (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The results showed that organo-modified clay was dispersed homogeneously in PA matrix. TGA indicated an enhancement of thermal stability of new nanocomposites compared with the pure polymer.

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

    PubMed

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

    2014-01-01

    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

  20. Amplification of bovine papillomavirus DNA by N-methyl-N'-nitro-N-nitrosoguanidine, ultraviolet irradiation, or infection with herpes simplex virus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schmitt, J.; Schlehofer, J.R.; Mergener, K.

    1989-09-01

    Treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or irradiation with ultraviolet light (uv254 nm) induces amplification of integrated as well as episomal sequences of bovine papillomavirus (BPV) type 1 DNA in BPV-1-transformed mouse C127 cells (i.e., ID13 cells). This is shown by filter in situ hybridization and Southern blot analysis of cellular DNA. Similarly, infection of ID13 cells with herpes simplex virus (HSV) type 1 which has been shown to be mutagenic for host cell DNA leads to amplification of BPV DNA sequences. In contrast to this induction of DNA amplification by initiators, treatment of ID13 cells with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)more » does not result in increased synthesis of BPV DNA nor does TPA treatment modulate the initiator-induced DNA amplification. Similar to other cell systems infection with adeno-associated virus (AAV) type 2 inhibits BPV-1 DNA amplification irrespective of the inducing agent. In contrast to initiator-induced DNA amplification, treatment with carcinogen (MNNG) or tumor promoters or combination of MNNG and promoter of C127 cells prior to transformation by BPV-1 does not lead to an increase in the number of transformed foci. The induction of amplification of papillomavirus DNA by initiating agents possibly represents one of the mechanisms by which the observed synergism between papillomavirus infection and initiators in tumorigenesis might occur.« less

  1. An experimental study of the combined effects of n-hexane and methyl ethyl ketone.

    PubMed Central

    Takeuchi, Y; Ono, Y; Hisanaga, N; Iwata, M; Aoyama, M; Kitoh, J; Sugiura, Y

    1983-01-01

    This study was intended to determine whether or not methyl ethyl ketone (MEK) enhances the neurotoxicity of n-hexane at low concentration and after long term exposure. Separate groups of eight rats were exposed to 100 ppm n-hexane, 200 ppm MEK, 100 ppm n-hexane plus 200 ppm MEK, or fresh air in an exposure chamber for 12 hours a day for 24 weeks. The body weight, motor nerve conduction velocity (MCV), distal motor latency (DL), and mixed nerve conduction velocities (MNCVs) were measured before exposure and after four, eight, 12, 16, 20, and 24 weeks' exposure. One rat of each group was histopathologically examined after 24 weeks' exposure. Exposure of 100 ppm n-hexane did not significantly decrease the functions of the peripheral nerve throughout the experiment. Exposure to 200 ppm MEK significantly increased MCV and MNCVs and decreased DL after four weeks' exposure, but at this later stage no significant changes were found throughout the experiment by comparison with the controls. Mixed exposure to 100 ppm n-hexane plus 200 ppm MEK significantly decreased by comparison with the controls. On histopathological examination of the tail nerve, however, no changes were found in any of the exposed groups or the controls. These results suggest that MEK might enhance the neurotoxicity of n-hexane at a low concentration, and mixed exposures to n-hexane and MEK should be avoided. PMID:6830718

  2. NSUN2-Mediated m5C Methylation and METTL3/METTL14-Mediated m6A Methylation Cooperatively Enhance p21 Translation.

    PubMed

    Li, Qiu; Li, Xiu; Tang, Hao; Jiang, Bin; Dou, Yali; Gorospe, Myriam; Wang, Wengong

    2017-09-01

    N6-methyladenosine (m6A) and m5C methylation are two major types of RNA methylation, but the impact of joint modifications on the same mRNA is unknown. Here, we show that in p21 3'UTR, NSUN2 catalyzes m5C modification and METTL3/METTL14 catalyzes m6A modification. Interestingly, methylation at m6A by METTL3/METTL14 facilitates the methylation of m5C by NSUN2, and vice versa. NSUN2-mediated m5C and METTL3/METTL14-mediated m6A methylation synergistically enhance p21 expression at the translational level, leading to elevated expression of p21 in oxidative stress-induced cellular senescence. Our findings on p21 mRNA methylation and expression reveal that joint m6A and m5C modification of the same RNA may influence each other, coordinately affecting protein expression patterns. J. Cell. Biochem. 118: 2587-2598, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Metabolic, hormonal and immunological associations with global DNA methylation among postmenopausal women.

    PubMed

    Ulrich, Cornelia M; Toriola, Adetunji T; Koepl, Lisel M; Sandifer, Tracy; Poole, Elizabeth M; Duggan, Catherine; McTiernan, Anne; Issa, Jean-Pierre J

    2012-09-01

    DNA methylation is an epigenetic modification essential for the regulation of gene expression that has been implicated in many diseases, including cancer. Few studies have investigated the wide range of potential predictors of global DNA methylation, including biomarkers. Here, we investigated associations between DNA methylation and dietary factors, sex-steroid hormones, metabolic, lipid, inflammation, immune and one-carbon biomarkers. Data and baseline biomarker measurements were obtained from 173 overweight/obese postmenopausal women. Global DNA methylation in lymphocyte DNA was measured using the pyrosequencing assay for LINE-1 repeats. We used correlations and linear regression analyses to investigate associations between continuous data and DNA methylation, while t-tests were used for categorical data. Secondary analyses stratified by serum folate levels and multivitamin use were also conducted. There was little variability in LINE-1 methylation (66.3-79.5%). Mean LINE-1 methylation was significantly higher among women with elevated glucose levels. Mean LINE-1 methylation was also higher among women with high CD4+/CD8+ ratio, and lower among women with elevated vitamin B6, but neither reached statistical significance. In analyses stratified by folate status, DNA methylation was negatively associated with sex hormone concentrations (estrone, estradiol, testosterone and sex hormone binding globulin) among women with low serum folate levels (n = 53). Conversely, among women with high serum folate levels (n = 53), DNA methylation was positively associated with several immune markers (CD4/CD8 ratio, NK1656/lymphocytes and IgA). Results from this screening suggest that global DNA methylation is generally stable, with differential associations for sex hormones and immune markers depending on one-carbon status.

  4. Weak maser emission of methyl formate toward Sagittarius B2(N) in the green bank telescope PRIMOS survey

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Faure, A.; Wiesenfeld, L.; Remijan, A. J.

    A non-LTE radiative transfer treatment of cis-methyl formate (HCOOCH{sub 3}) rotational lines is presented for the first time using a set of theoretical collisional rate coefficients. These coefficients have been computed in the temperature range 5-30 K by combining coupled-channel scattering calculations with a high accuracy potential energy surface for HCOOCH{sub 3}-He. The results are compared to observations toward the Sagittarius B2(N) molecular cloud using the publicly available PRIMOS survey from the Green Bank Telescope. A total of 49 low-lying transitions of methyl formate, with upper levels below 25 K, are identified. These lines are found to probe a presumablymore » cold (∼30 K), moderately dense (∼10{sup 4} cm{sup –3}), and extended region surrounding Sgr B2(N). The derived column density of ∼4 × 10{sup 14} cm{sup –2} is only a factor of ∼10 larger than the column density of the trans conformer in the same source. Provided that the two conformers have the same spatial distribution, this result suggests that strongly non-equilibrium processes must be involved in their synthesis. Finally, our calculations show that all detected emission lines with a frequency below 30 GHz are (collisionally pumped) weak masers amplifying the continuum of Sgr B2(N). This result demonstrates the importance and generality of non-LTE effects in the rotational spectra of complex organic molecules at centimeter wavelengths.« less

  5. 6-Methyl-1,2,4-benzenetriol, a new intermediate in penicillic acid biosynthesis in Penicillium cyclopium

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sekiguchi, J.; Katayama, S.; Yamada, Y.

    1987-07-01

    Penicillic acid-negative mutants were obtained from a color mutant derived from Penicillium cyclopium NRRL 1888 through N-methyl-N'-nitro-N-nitrosoguanidine treatment. One mutant (SK2N6) accumulated 6-methyl-1,2,4-benzenetriol, which was not previously known to be a metabolite of P. cyclopium, in addition to orsellinic acid and orcinol. The radioactivity of (1-/sup 14/C)acetic acid was rapidly incorporated into 6-methyl-1,2,4-benzenetriol in a culture of P. cyclopium SK2N6. Moreover, the radioactivity of (/sup 14/C)6-methyl-1,2,4-benzenetriol was efficiently incorporated into penicillic acid in a culture of P. cyclopium NRRL 1888. These data indicate that 6-methyl-1,2,4-benzenetriol is a precursor for penicillic acid biosynthesis. The results on the addition of 1,4-dihydroxy-6-methoxy-2-methylbenzene, 6-methoxy-2-methylbenzoquinonemore » (1,4), and 1-O-methylorcinol to a culture of P. cyclopium SK2N6 indicated that only the former two compounds are converted to penicillic acid. Thus, a new portion of the penicillic acid biosynthetic pathway is proposed.« less

  6. Cfr and RlmN contain a single [4Fe-4S] cluster, which directs two distinct reactivities for S-adenosylmethionine: methyl transfer by SN2 displacement and radical generation.

    PubMed

    Grove, Tyler L; Radle, Matthew I; Krebs, Carsten; Booker, Squire J

    2011-12-14

    The radical SAM (RS) proteins RlmN and Cfr catalyze methylation of carbons 2 and 8, respectively, of adenosine 2503 in 23S rRNA. Both reactions are similar in scope, entailing the synthesis of a methyl group partially derived from S-adenosylmethionine (SAM) onto electrophilic sp(2)-hybridized carbon atoms via the intermediacy of a protein S-methylcysteinyl (mCys) residue. Both proteins contain five conserved Cys residues, each required for turnover. Three cysteines lie in a canonical RS CxxxCxxC motif and coordinate a [4Fe-4S]-cluster cofactor; the remaining two are at opposite ends of the polypeptide. Here we show that each protein contains only the one "radical SAM" [4Fe-4S] cluster and the two remaining conserved cysteines do not coordinate additional iron-containing species. In addition, we show that, while wild-type RlmN bears the C355 mCys residue in its as-isolated state, RlmN that is either engineered to lack the [4Fe-4S] cluster by substitution of the coordinating cysteines or isolated from Escherichia coli cultured under iron-limiting conditions does not bear a C355 mCys residue. Reconstitution of the [4Fe-4S] cluster on wild-type apo RlmN followed by addition of SAM results in rapid production of S-adenosylhomocysteine (SAH) and the mCys residue, while treatment of apo RlmN with SAM affords no observable reaction. These results indicate that in Cfr and RlmN, SAM bound to the unique iron of the [4Fe-4S] cluster displays two reactivities. It serves to methylate C355 of RlmN (C338 of Cfr), or to generate the 5'-deoxyadenosyl 5'-radical, required for substrate-dependent methyl synthase activity. © 2011 American Chemical Society

  7. Methods of DNA methylation analysis.

    USDA-ARS?s Scientific Manuscript database

    The purpose of this review was to provide guidance for investigators who are new to the field of DNA methylation analysis. Epigenetics is the study of mitotically heritable alterations in gene expression potential that are not mediated by changes in DNA sequence. Recently, it has become clear that n...

  8. 2′-O Methylation of Internal Adenosine by Flavivirus NS5 Methyltransferase

    PubMed Central

    Dong, Hongping; Chang, David C.; Hua, Maggie Ho Chia; Lim, Siew Pheng; Chionh, Yok Hian; Hia, Fabian; Lee, Yie Hou; Kukkaro, Petra; Lok, Shee-Mei; Dedon, Peter C.; Shi, Pei-Yong

    2012-01-01

    RNA modification plays an important role in modulating host-pathogen interaction. Flavivirus NS5 protein encodes N-7 and 2′-O methyltransferase activities that are required for the formation of 5′ type I cap (m7GpppAm) of viral RNA genome. Here we reported, for the first time, that flavivirus NS5 has a novel internal RNA methylation activity. Recombinant NS5 proteins of West Nile virus and Dengue virus (serotype 4; DENV-4) specifically methylates polyA, but not polyG, polyC, or polyU, indicating that the methylation occurs at adenosine residue. RNAs with internal adenosines substituted with 2′-O-methyladenosines are not active substrates for internal methylation, whereas RNAs with adenosines substituted with N6-methyladenosines can be efficiently methylated, suggesting that the internal methylation occurs at the 2′-OH position of adenosine. Mass spectroscopic analysis further demonstrated that the internal methylation product is 2′-O-methyladenosine. Importantly, genomic RNA purified from DENV virion contains 2′-O-methyladenosine. The 2′-O methylation of internal adenosine does not require specific RNA sequence since recombinant methyltransferase of DENV-4 can efficiently methylate RNAs spanning different regions of viral genome, host ribosomal RNAs, and polyA. Structure-based mutagenesis results indicate that K61-D146-K181-E217 tetrad of DENV-4 methyltransferase forms the active site of internal methylation activity; in addition, distinct residues within the methyl donor (S-adenosyl-L-methionine) pocket, GTP pocket, and RNA-binding site are critical for the internal methylation activity. Functional analysis using flavivirus replicon and genome-length RNAs showed that internal methylation attenuated viral RNA translation and replication. Polymerase assay revealed that internal 2′-O-methyladenosine reduces the efficiency of RNA elongation. Collectively, our results demonstrate that flavivirus NS5 performs 2′-O methylation of internal adenosine of

  9. Implication of Genes for the N-Methyl-D-Aspartate (NMDA) Receptor in Substance Addictions.

    PubMed

    Chen, Jiali; Ma, Yunlong; Fan, Rongli; Yang, Zhongli; Li, Ming D

    2018-02-10

    Drug dependence is a chronic brain disease with harmful consequences for both individual users and society. Glutamate is a primary excitatory neurotransmitter in the brain, and both in vivo and in vitro experiments have implicated N-methyl-D-aspartate (NMDA) receptor, a glutamate receptor, as an element in various types of addiction. Recent findings from genetics-based approaches such as genome-wide linkage, candidate gene association, genome-wide association (GWA), and next-generation sequencing have demonstrated the significant association of NMDA receptor subunit genes such as GluN3A, GluN2B, and GluN2A with various addiction-related phenotypes. Of these genes, GluN3A has been the most studied, and it has been revealed to play crucial roles in the etiology of addictions. In this communication, we provide an updated view of the genetic effects of NMDA receptor subunit genes and their functions in the etiology of addictions based on the findings from investigation of both common and rare variants as well as SNP-SNP interactions. To better understand the molecular mechanisms underlying addiction-related behaviors and to promote the development of specific medicines for the prevention and treatment of addictions, current efforts aim not only to identify more causal variants in NMDA receptor subunits by using large independent samples but also to reveal the molecular functions of these variants in addictions.

  10. Positive Modulators of the N-Methyl-d-aspartate Receptor: Structure-Activity Relationship Study of Steroidal 3-Hemiesters.

    PubMed

    Krausova, Barbora; Slavikova, Barbora; Nekardova, Michaela; Hubalkova, Pavla; Vyklicky, Vojtech; Chodounska, Hana; Vyklicky, Ladislav; Kudova, Eva

    2018-05-24

    Here, we report the synthesis of pregn-5-ene and androst-5-ene dicarboxylic acid esters and explore the structure-activity relationship (SAR) for their modulation of N-methyl-d-aspartate receptors (NMDARs). All compounds were positive modulators of recombinant GluN1/GluN2B receptors (EC 50 varying from 1.8 to 151.4 μM and E max varying from 48% to 452%). Moreover, 10 compounds were found to be more potent GluN1/GluN2B receptor modulators than endogenous pregnenolone sulfate (EC 50 = 21.7 μM). The SAR study revealed a relationship between the length of the residues at carbon C-3 of the steroid molecule and the positive modulatory effect at GluN1/GluN2B receptors for various D-ring modifications. A selected compound, 20-oxo-pregnenolone hemiadipate, potentiated native NMDARs to a similar extent as GluN1/GluN2A-D receptors and inhibited AMPARs and GABA A R responses. These results provide a unique opportunity for the development of new steroid based drugs with potential use in the treatment of neuropsychiatric disorders involving hypofunction of NMDARs.

  11. Molecular modeling of methyl-α-Neu5Ac analogues docked against cholera toxin--a molecular dynamics study.

    PubMed

    Blessy, J Jino; Sharmila, D Jeya Sundara

    2015-02-01

    Molecular modeling of synthetic methyl-α-Neu5Ac analogues modified in C-9 position was investigated by molecular docking and molecular dynamics (MD) simulation methods. Methyl-α-Neu5Ac analogues were docked against cholera toxin (CT) B subunit protein and MD simulations were carried out for three Methyl-α-Neu5Ac analogue-CT complexes (30, 10 and 10 ns) to estimate the binding activity of cholera toxin-Methyl-α-Neu5Ac analogues using OPLS_2005 force field. In this study, direct and water mediated hydrogen bonds play a vital role that exist between the methyl-α-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ)-cholera toxin active site residues. The Energy plot, RMSD and RMSF explain that the simulation was stable throughout the simulation run. Transition of phi, psi and omega angle for the complex was calculated. Molecular docking studies could be able to identify the binding mode of methyl-α-Neu5Ac analogues in the binding site of cholera toxin B subunit protein. MD simulation for Methyl-α-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ), Methyl-α-9-N-acetyl-9-deoxy-9-amino-Neu5Ac and Methyl-α-9-N-biphenyl-4-acetyl-deoxy-amino-Neu5Ac complex with CT B subunit protein was carried out, which explains the stable nature of interaction. These methyl-α-Neu5Ac analogues that have computationally acceptable pharmacological properties may be used as novel candidates for drug design for cholera disease.

  12. Oxidation of methyl halides by the facultative methylotroph strain IMB-1

    USGS Publications Warehouse

    Schaefer, J.K.; Oremland, R.S.

    1999-01-01

    Washed cell suspensions of the facultative methylotroph strain IMB-1 grown on methyl bromide (MeBr) were able to consume methyl chloride (MeCl) and methyl iodide (MeI) as well as MeBr. Consumption of >100 ??M MeBr by cells grown on glucose, acetate, or monomethylamine required induction. Induction was inhibited by chloramphenicol. However, cells had a constitutive ability to consume low concentrations (<20 nM) of MeBr. Glucose-grown cells were able to readily oxidize [14C]formaldehyde to 14CO2 but had only a small capacity for oxidation of [14C]methanol. Preincubation of cells with MeBr did not affect either activity, but MeBr-induced cells had a greater capacity for [14C]MeBr oxidation than did cells without preincubation. Consumption of MeBr was inhibited by MeI, and MeCl consumption was inhibited by MeBr. No inhibition of MeBr consumption occurred with methyl fluoride, propyl iodide, dibromomethane, dichloromethane, or difluoromethane, and in addition cells did not oxidize any of these compounds. Cells displayed Michaelis-Menten kinetics for the various methyl halides, with apparent K(s) values of 190, 280, and 6,100 nM for MeBr, MeI, and MeCl, respectively. These results suggest the presence of a single oxidation enzyme system specific for methyl halides (other than methyl fluoride) which runs through formaldehyde to CO2. The ease of induction of methyl halide oxidation in strain IMB-1 should facilitate its mass culture for the purpose of reducing MeBr emissions to the atmosphere from fumigated soils.

  13. Psychiatric Autoimmunity: N-Methyl-D-Aspartate Receptor IgG and Beyond.

    PubMed

    Kruse, Jennifer L; Lapid, Maria I; Lennon, Vanda A; Klein, Christopher J; Toole, Orna O'; Pittock, Sean J; Strand, Edythe A; Frye, Mark A; McKeon, Andrew

    2015-01-01

    Descriptions of psychiatric autoimmunity beyond N-methyl-D-aspartate (NMDA) receptor encephalitis are sparse. To report the autoimmune psychiatric spectrum currently recognized in Mayo Clinic practice. Medical record review, testing of stored serum and cerebrospinal fluid for IgGs reactive with synaptic receptors and ion channels, neuronal nuclear and cytoplasmic antigens (including glutamic acid decarboxylase 65-kDa isoform) and case-control comparison were conducted. Patients were categorized into group 1, all adult psychiatric inpatients tested for neural autoantibodies (2002-2011; n = 213), and group 2, all Mayo NMDA receptor IgG-positive patients (2009-2013; n = 13); healthy control subjects were also included (n = 173). In group 1, at least 1 serum autoantibody (but not NMDA receptor IgG) was detected in 36 of 213 psychiatric inpatients. In total, 12 patients were determined retrospectively to have high-likelihood autoimmune encephalitic diagnoses. The most commonly detected autoantibody specificities were voltage-gated potassium channel ([Kv1] VGKC) complex (6) and calcium channel (P/Q type or N type; 5). Symptoms seen were as follows: depressive (8), anxious (7), psychotic (7), disorganized (5), suicidal (3), manic (1) and catatonic (1). In group 2, among 13 NMDA receptor IgG-positive patients, 12 had encephalitis; their psychiatric symptoms were as follows: depressive (9), catatonic (9), disorganized (8), anxious (8), psychotic (7), manic (6), and suicidal (3). Catatonic symptoms were more common in the 12 NMDA receptor IgG-positive patients than in the 12 group 1 patients with high likelihood of encephalitis (p = 0.002). Antibody positivities were usually low positive in value among healthy controls (12 of 16 vs 3 of 12 group 1 encephalitis cases, p = 0.025). NMDA receptor IgG was not detected in any healthy control subject. A spectrum of psychiatric autoimmunity beyond NMDA-R IgG may be under-recognized. Diagnosis is facilitated by combining results of

  14. Neurosteroid-like Inhibitors of N-Methyl-d-aspartate Receptor: Substituted 2-Sulfates and 2-Hemisuccinates of Perhydrophenanthrene.

    PubMed

    Slavikova, Barbora; Chodounska, Hana; Nekardova, Michaela; Vyklicky, Vojtech; Ladislav, Marek; Hubalkova, Pavla; Krausova, Barbora; Vyklicky, Ladislav; Kudova, Eva

    2016-05-26

    N-Methyl-d-aspartate receptors (NMDARs) display a critical role in various diseases of the central nervous system. The activity of NMDARs can be modulated by neurosteroids. Herein, we report a structure-activity relationship study for perhydrophenanthrene analogues possessing a framework that mimics the steroidal ring system. This study comprises the design, synthesis, and assessment of the biological activity of a library of perhydrophenanthrene 2-sulfates and 2-hemisuccinates (1-10). Their ability to modulate NMDAR-induced currents was tested on recombinant GluN1/GluN2B receptors. Our results demonstrate that such structural optimization leads to compounds that are inhibitors of NMDARs. Notably, compound 9 (IC50 = 15.6 μM) was assessed as a more potent inhibitor of NMDAR-induced currents than the known endogenous neurosteroid, pregnanolone sulfate (IC50 = 24.6 μM).

  15. Methyl 4-amino-3-methyl­benzoate

    PubMed Central

    Li, Xiang; Yuan, Lian-Shan; Wang, Dan; Liu, Shan; Yao, Cheng

    2008-01-01

    In the mol­ecule of the title compound, C9H11NO2, the methyl C and amino N atoms bonded to the benzene ring lie in the ring plane. Intra­molecular C—H⋯O hydrogen bonding results in the formation of a five-membered planar ring, which is oriented at a dihedral angle of 2.73 (3)° with respect to the benzene ring, so they are nearly coplanar. In the crystal structure, inter­molecular N—H⋯O hydrogen bonds link the mol­ecules into chains elongated along the c axis and stacked along the b axis. PMID:21202370

  16. Investigation of J-shaped dose-responses induced by exposure to the alkylating agent N-methyl-N-nitrosourea.

    PubMed

    Chapman, Katherine E; Hoffmann, George R; Doak, Shareen H; Jenkins, Gareth J S

    2017-07-01

    Hormesis is defined as a biphasic dose-response where biological effects of low doses of a stressor demonstrate the opposite effect to high-dose effects of the same stressor. Hormetic, or J-shaped, dose-response relationships are relatively rarely observed in toxicology, resulting in a limited understanding and even some skepticism of the concept. Low dose-response studies for genotoxicity endpoints have been performed at Swansea University for over a decade. However, no statistically significant decreases below control genotoxicity levels have been detected until recently. A hormetic-style dose-response following a 24h exposure to the alkylating agent N-methyl-N-nitrosourea (MNU) was observed in a previous study for HPRT mutagenesis in the human lymphoblastoid cell line AHH-1. A second recent study demonstrated a J-shaped dose-response for the induction of micronuclei by MNU in a 24h treatment in a similar test system. Following mechanistic investigations, it was hypothesized that p53 may be responsible for the observed hormetic phenomenon. As genotoxic carcinogens are a major causative factor of many cancers, consideration of hormesis in carcinogenesis could be important in safety assessment. The data examined here offer possible insights into hormesis, including its estimated prevalence, underlying mechanisms and lack of generalizability. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. X-ray investigations of sulfur-containing fungicides. IV. 4'-[[Benzoyl(4-chlorophenylhydrazono)methyl]sulfonyl]acetanilide and 4'-[[benzoyl(4-methoxyphenylhydrazono)methyl]sulfonyl]acetanilide.

    PubMed

    Wolf, W M

    2001-09-01

    The conformations of the two approximately isomorphous structures 4'-[[benzoyl(4-chlorophenylhydrazono)methyl]sulfonyl]acetanilide, C(22)H(18)ClN(3)O(4)S, and 4'-[[benzoyl(4-methoxyphenylhydrazono)methyl]sulfonyl]acetanilide, C(23)H(21)N(3)O(5)S, are stabilized by resonance-assisted intramolecular hydrogen bonds linking the hydrazone moieties and sulfonyl groups. The stronger bond is observed in the former compound. The difference in electronic properties between the Cl atom and the methoxy group is too small to significantly alter the non-bonding interactions of the sulfonyl and beta-carbonyl groups.

  18. MGMT and MLH1 methylation in Helicobacter pylori-infected children and adults.

    PubMed

    Alvarez, Marisa C; Santos, Juliana C; Maniezzo, Nathália; Ladeira, Marcelo S; da Silva, Artur L C; Scaletsky, Isabel C A; Pedrazzoli, José; Ribeiro, Marcelo L

    2013-05-28

    To evaluate the association between Helicobacter pylori (H. pylori) infection and MLH1 and MGMT methylation and its relationship with microsatellite instability (MSI). The methylation status of the MLH1 and MGMT promoter region was analysed by methylation specific methylation-polymerase chain reaction (MSP-PCR) in gastric biopsy samples from uninfected or H. pylori-infected children (n = 50), from adults with chronic gastritis (n = 97) and from adults with gastric cancer (n = 92). MLH1 and MGMT mRNA expression were measured by real-time PCR and normalised to a constitutive gene (β actin). MSI analysis was performed by screening MSI markers at 4 loci (Bat-25, Bat-26, D17S250 and D2S123) with PCR; PCR products were analysed by single strand conformation polymorphism followed by silver staining. Statistical analyses were performed with either the χ(2) test with Yates continuity correction or Fisher's exact test, and statistical significance for expression analysis was assessed using an unpaired Student's t-test. Methylation was not detected in the promoter regions of MLH1 and MGMT in gastric biopsy samples from children, regardless of H. pylori infection status. The MGMT promoter was methylated in 51% of chronic gastritis adult patients and was associated with H. pylori infection (P < 0.05); this region was methylated in 66% of gastric cancer patients, and the difference in the percentage of methylated samples between these patients and those from H. pylori-infected chronic gastritis patients was statistically significant (P < 0.05). MLH1 methylation frequencies among H. pylori-infected and non-infected chronic gastritis adult patients were 13% and 7%, respectively. We observed methylation of the MLH1 promoter (39%) and increased MSI levels (68%) in samples from gastric cancer patients in comparison to samples from H. pylori-infected adult chronic gastritis patients (P < 0.001 and P < 0.01, respectively). The frequency of promoter methylation for both genes was

  19. A simple and sensitive fluorescent sensor for methyl parathion based on L-tyrosine methyl ester functionalized carbon dots.

    PubMed

    Hou, Juying; Dong, Jing; Zhu, Haishuang; Teng, Xue; Ai, Shiyun; Mang, Minglin

    2015-06-15

    In this paper, a simple and sensitive fluorescent sensor for methyl parathion is developed based on L-tyrosine methyl ester functionalized carbon dots (Tyr-CDs) and tyrosinase system. The carbon dots are obtained by simple hydrothermal reaction using citric acid as carbon resource and L-tyrosine methyl ester as modification reagent. The carbon dots are characterized by transmission electron microscope, high resolution transmission electron microscopy, X-ray diffraction spectrum, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The carbon dots show strong and stable photoluminescence with a quantum yield of 3.8%. Tyrosinase can catalyze the oxidation of tyrosine methyl ester on the surface of carbon dots to corresponding quinone products, which can quench the fluorescence of carbon dots. When organophosphorus pesticides (OPs) are introduced in system, they can decrease the enzyme activity, thus decrease the fluorescence quenching rate. Methyl parathion, as a model of OPs, was detected. Experimental results show that the enzyme inhibition rate is proportional to the logarithm of the methyl parathion concentration in the range 1.0×10(-10)-1.0×10(-4) M with the detection limit (S/N=3) of 4.8×10(-11) M. This determination method shows a low detection limit, wide linear range, good selectivity and high reproducibility. This sensing system has been successfully used for the analysis of cabbage, milk and fruit juice samples. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Poly(styrene-co-N-methacryloyl-l-phenylalanine methyl ester)-functionalized magnetic nanoparticles as sorbents for the analysis of sodium benzoate in beverages.

    PubMed

    Ji, Shilei; Li, Nan; Qi, Li; Wang, Minglin

    2017-01-01

    In this study, poly(styrene-co-N-methacryloyl-l-phenylalanine methyl ester)-functionalized magnetic nanoparticles were constructed and used as magnetic solid-phase extraction sorbents for analysis of food preservatives in beverages. To prepare the poly(amino acid)-based sorbents, N-methacryloyl-l-phenylalanine methyl ester, and styrene served as the functional monomers and modified onto the magnetic nanoparticles via free radical polymerization. Interestingly, compared with propylparaben and potassium sorbate, the proposed poly(amino acid)-based sorbents showed a good selectivity to sodium benzoate. The adsorption capacity of the sorbents to sodium benzoate was 6.08 ± 0.31 mg/g. Moreover, the fast adsorption equilibrium could be reached within 5 min. Further, the resultant poly(amino acid)-based sorbents were applied in the analysis of sodium benzoate in real beverage samples. The results proved that the proposed magnetic solid-phase extraction sorbents have a great potential for the analysis of preservatives in food samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Subsets of microsatellite-unstable colorectal cancers exhibit discordance between the CpG island methylator phenotype and MLH1 methylation status.

    PubMed

    Kim, Jung H; Rhee, Ye-Y; Bae, Jeong-M; Kwon, Hyeong-J; Cho, Nam-Y; Kim, Mi J; Kang, Gyeong H

    2013-07-01

    Although the presence of MLH1 methylation in microsatellite-unstable colorectal cancer generally indicates involvement of the CpG island methylator phenotype (CIMP) in the development of the tumor, these two conditions do not always correlate. A minority of microsatellite-unstable colorectal cancers exhibit discordance between CIMP and MLH1 methylation statuses. However, the clinicopathological features of such microsatellite-unstable colorectal cancers with discrepant MLH1 methylation and CIMP statuses remain poorly studied. Microsatellite-unstable colorectal cancers (n=220) were analyzed for CIMP and MLH1 methylation statuses using the MethyLight assay. Based on the combinatorial CIMP and MLH1 methylation statuses, the microsatellite-unstable colorectal cancers were grouped into four subtypes (CIMP-high (CIMP-H) MLH1 methylation-positive (MLH1m+), CIMP-H MLH1 methylation-negative, CIMP-low/0 (CIMP-L/0) MLH1m+, and CIMP-L/0 MLH1 methylation-negative), which were compared in terms of their associations with clinicopathological and molecular features. The CIMP-L/0 MLH1 methylation-negative and CIMP-H MLH1m+ subtypes were predominant, comprising 63.6 and 24.1% of total microsatellite-unstable colorectal cancers, respectively. The discordant subtypes, CIMP-H MLH1 methylation-negative and CIMP-L/0 MLH1m+, were found in 5 and 7% of microsatellite-unstable colorectal cancers, respectively. The CIMP-H MLH1 methylation-negative subtype exhibited elevated incidence rates in male patients and was associated with larger tumor size, more frequent loss of MSH2 expression, increased frequency of KRAS mutation, and advanced cancer stage. The CIMP-L/0 MLH1m+ subtype was associated with onset at an earlier age, a predominance of MLH1 loss, and earlier cancer stage. None of the CIMP-L/0 MLH1m+ subtype patients succumbed to death during the follow-up. Our findings suggest that the discordant subtypes of colorectal cancers exhibit distinct clinicopathological and molecular features

  2. Human T lymphocytes express N-methyl-D-aspartate receptors functionally active in controlling T cell activation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miglio, Gianluca; Varsaldi, Federica; Lombardi, Grazia

    2005-12-30

    The aim of this study was to investigate the expression and the functional role of N-methyl-D-aspartate (NMDA) receptors in human T cells. RT-PCR analysis showed that human resting peripheral blood lymphocytes (PBL) and Jurkat T cells express genes encoding for both NR1 and NR2B subunits: phytohemagglutinin (PHA)-activated PBL also expresses both these genes and the NR2A and NR2D genes. Cytofluorimetric analysis showed that NR1 expression increases as a consequence of PHA (10 {mu}g/ml) treatment. D-(-)-2-Amino-5-phosphonopentanoic acid (D-AP5), and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine [(+)-MK 801], competitive and non-competitive NMDA receptor antagonists, respectively, inhibited PHA-induced T cell proliferation, whereas they did not affect IL-2 (10more » U/ml)-induced proliferation of PHA blasts. These effects were due to the prevention of T cell activation (inhibition of cell aggregate formation and CD25 expression), but not to cell cycle arrest or death. These results demonstrate that human T lymphocytes express NMDA receptors, which are functionally active in controlling cell activation.« less

  3. Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC.

    PubMed

    Scarpa, Marco; Scarpa, Melania; Castagliuolo, Ignazio; Erroi, Francesca; Kotsafti, Andromachi; Basato, Silvia; Brun, Paola; D'Incà, Renata; Rugge, Massimo; Angriman, Imerio; Castoro, Carlo

    2016-03-01

    BACKGROUND PROMOTER: hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC. The expression of Dnmts 1 and 3A was significantly increased in UC-related carcinogenesis compared to non inflammatory colorectal carcinogenesis. In non-neoplastic colonic mucosa, the number of methylated genes resulted significantly higher in patients with CRC and in those with UC-related CRC compared to the HC and UC patients and patients with dysplastic lesion of the colon. The number of methylated genes in non-neoplastic colonic mucosa predicted the presence of CRC with good accuracy either in non inflammatory and inflammatory related CRC. Colonic mucosal samples were collected from healthy subjects (HC) (n = 30) and from patients with ulcerative colitis (UC) (n = 29), UC and dysplasia (n = 14), UC and cancer (n = 10), dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b, mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. Methylation status of APC, CDH13, MGMT, MLH1 and RUNX3 in the non-neoplastic mucosa may be used as a marker of CRC: these preliminary results could allow for the adjustment of a patient's surveillance interval and to select UC patients who should undergo intensive surveillance.

  4. Significant impact of amount of PCR input templates on various PCR-based DNA methylation analysis and countermeasure.

    PubMed

    Liu, Zhaojun; Zhou, Jing; Gu, Liankun; Deng, Dajun

    2016-08-30

    Methylation changes of CpG islands can be determined using PCR-based assays. However, the exact impact of the amount of input templates (TAIT) on DNA methylation analysis has not been previously recognized. Using COL2A1 gene as an input reference, TAIT difference between human tissues with methylation-positive and -negative detection was calculated for two representative genes GFRA1 and P16. Results revealed that TAIT in GFRA1 methylation-positive frozen samples (n = 332) was significantly higher than the methylation-negative ones (n = 44) (P < 0.001). Similar difference was found in P16 methylation analysis. The TAIT-related effect was also observed in methylation-specific PCR (MSP) and denatured high performance liquid chromatography (DHPLC) analysis. Further study showed that the minimum TAIT for a successful MethyLight PCR reaction should be ≥ 9.4 ng (CtCOL2A1 ≤ 29.3), when the cutoff value of the methylated-GFRA1 proportion for methylation-positive detection was set at 1.6%. After TAIT of the methylation non-informative frozen samples (n = 94; CtCOL2A1 > 29.3) was increased above the minimum TAIT, the methylation-positive rate increased from 72.3% to 95.7% for GFRA1 and 26.6% to 54.3% for P16, respectively (Ps < 0.001). Similar results were observed in the FFPE samples. In conclusion, TAIT critically affects results of various PCR-based DNA methylation analyses. Characterization of the minimum TAIT for target CpG islands is essential to avoid false-negative results.

  5. Synthesis and characterization of phosphonates from methyl linoleate and vegetable oils

    USDA-ARS?s Scientific Manuscript database

    Phosphonates were synthesized on a medium scale (~200 g) from three lipids: methyl linoleate (MeLin), high-oleic sunflower oil (HOSO), and soybean oil (SBO), and three dialkyl phosphites: methyl, ethyl, and n-butyl, using radical initiator. A staged addition of the lipid and the initiator was needed...

  6. Determination of 3-O- and 4-O-methylated monosaccharide constituents in snail glycans.

    PubMed

    Stepan, Herwig; Bleckmann, Christina; Geyer, Hildegard; Geyer, Rudolf; Staudacher, Erika

    2010-07-02

    The N- and O-glycans of Arianta arbustorum, Achatina fulica, Arion lusitanicus and Planorbarius corneus were analysed for their monosaccharide pattern by reversed-phase HPLC after labelling with 2-aminobenzoic acid or 3-methyl-1-phenyl-2-pyrazolin-5-one and by gas chromatography-mass spectrometry. Glucosamine, galactosamine, mannose, galactose, glucose, fucose and xylose were identified. Furthermore, three different methylated sugars were detected: 3-O-methyl-mannose and 3-O-methyl-galactose were confirmed to be a common snail feature; 4-O-methyl-galactose was detected for the first time in snails. Copyright 2010 Elsevier Ltd. All rights reserved.

  7. Syntheses, structures and characterization of isomorphous CoII and NiII coordination polymers based on 2-[(1H-imidazol-1-yl)methyl]-6-methyl-1H-benzimidazole and benzene-1,4-dicarboxylate.

    PubMed

    Huang, Qiu Ying; Zhao, Yang; Meng, Xiang Ru

    2017-08-01

    Careful choice of the organic ligands is one of the most important parameters in the rational design and synthesis of coordination polymers. Aromatic polycarboxylates have been widely used in the preparation of metal-organic polymers since they can utilize various coordination modes to form diverse structures and can act as hydrogen-bond acceptors and donors in the assembly of supramolecular structures. Nitrogen-heterocyclic organic compounds have also been used extensively as ligands for the construction of polymers with interesting structures. In the polymers catena-poly[[[diaquabis{2-[(1H-imidazol-1-yl)methyl]-6-methyl-1H-benzimidazole-κN 3 }cobalt(II)]-μ 2 -benzene-1,4-dicarboxylato-κ 2 O 1 :O 4 ] dihydrate], {[Co(C 8 H 4 O 4 )(C 12 H 11 N 4 ) 2 (H 2 O) 2 ]·2H 2 O} n , (I), and catena-poly[[[diaquabis{2-[(1H-imidazol-1-yl)methyl]-6-methyl-1H-benzimidazole-κN 3 }nickel(II)]-μ 2 -benzene-1,4-dicarboxylato-κ 2 O 1 :O 4 ] dihydrate], {[Ni(C 8 H 4 O 4 )(C 12 H 11 N 4 ) 2 (H 2 O) 2 ]·2H 2 O} n , (II), the Co II or Ni II ion lies on an inversion centre and exhibits a slightly distorted octahedral coordination geometry, coordinated by two N atoms from two imidazole rings and four O atoms from two monodentate carboxylate groups and two water molecules. The dicarboxylate ligands bridge metal ions forming a polymeric chain. The 2-[(1H-imidazol-1-yl)methyl]-6-methyl-1H-benzimidazole ligands coordinate to the Co II or Ni II centres in monodentate modes through an imidazole N atom and are pendant on opposite sides of the main chain. The two structures are isomorphous. In the crystal, the one-dimensional chains are further connected through O-H...O, O-H...N and N-H...O hydrogen bonds, leading to a three-dimensional supramolecular architecture. In addition, the IR spectroscopic properties, PXRD patterns, thermogravimetric behaviours and fluorescence properties of both polymers have been investigated.

  8. Synthesis and characterization of n-alkylamino derivatives of vitamin K3: Molecular structure of 2-propylamino-3-methyl-1,4-naphthoquinone and antibacterial activities

    NASA Astrophysics Data System (ADS)

    Chadar, Dattatray; Camilles, Maria; Patil, Rishikesh; Khan, Ayesha; Weyhermüller, Thomas; Salunke-Gawali, Sunita

    2015-04-01

    We would like to introduce eight analogues of n-alkylamino derivatives of vitamin K3 (2-methyl-1,4-naphthoquinone) viz, 2-(n-alkylamino)-3-methyl-1,4-naphthoquinone (where n-alkyl is methyl; LM-1, ethyl; LM-2, propyl; LM-3, butyl; LM-4, pentyl; LM-5, hexyl; LM-6, heptyl; LM-7, octyl; LM-8). All the above analogues have been successfully synthesized from vitamin K3 and characterized using different analytical techniques. Furthermore, in order to understand the mechanistic aspects of formation of LM-1 to LM-8 compounds, we could propose the mechanism. The FT-IR analysis of LM-1 to LM-8 indicate the presence of characteristic band of Nsbnd H group ∼3287-3364 cm-1, the variation was attributed to extensive intramolecular hydrogen bonding interaction. The molecular structure of LM-3 compound has been confirmed by single crystal X-ray diffraction analysis. LM-3 compound crystallises in triclinic space group P1. There were four independent molecules in asymmetric unit cell and their molecular interactions observed via Nsbnd H⋯O, Csbnd H⋯O and π-π stacking of quinonoid rings. Pharmacological potential of all compounds has been evaluated in terms of their antibacterial activities against Pseudomonas aeruginosa and Staphylococcus aureus. All the compounds were active against both the strains while LM-2 was found to be more effective with a minimum inhibition concentration of 0.3125 μg/mL and 0.156 μg/mL respectively.

  9. DNA methylation and childhood asthma in the inner city.

    PubMed

    Yang, Ivana V; Pedersen, Brent S; Liu, Andrew; O'Connor, George T; Teach, Stephen J; Kattan, Meyer; Misiak, Rana Tawil; Gruchalla, Rebecca; Steinbach, Suzanne F; Szefler, Stanley J; Gill, Michelle A; Calatroni, Agustin; David, Gloria; Hennessy, Corinne E; Davidson, Elizabeth J; Zhang, Weiming; Gergen, Peter; Togias, Alkis; Busse, William W; Schwartz, David A

    2015-07-01

    Epigenetic marks are heritable, influenced by the environment, direct the maturation of T lymphocytes, and in mice enhance the development of allergic airway disease. Thus it is important to define epigenetic alterations in asthmatic populations. We hypothesize that epigenetic alterations in circulating PBMCs are associated with allergic asthma. We compared DNA methylation patterns and gene expression in inner-city children with persistent atopic asthma versus healthy control subjects by using DNA and RNA from PBMCs. Results were validated in an independent population of asthmatic patients. Comparing asthmatic patients (n = 97) with control subjects (n = 97), we identified 81 regions that were differentially methylated. Several immune genes were hypomethylated in asthma, including IL13, RUNX3, and specific genes relevant to T lymphocytes (TIGIT). Among asthmatic patients, 11 differentially methylated regions were associated with higher serum IgE concentrations, and 16 were associated with percent predicted FEV1. Hypomethylated and hypermethylated regions were associated with increased and decreased gene expression, respectively (P < 6 × 10(-12) for asthma and P < .01 for IgE). We further explored the relationship between DNA methylation and gene expression using an integrative analysis and identified additional candidates relevant to asthma (IL4 and ST2). Methylation marks involved in T-cell maturation (RUNX3), TH2 immunity (IL4), and oxidative stress (catalase) were validated in an independent asthmatic cohort of children living in the inner city. Our results demonstrate that DNA methylation marks in specific gene loci are associated with asthma and suggest that epigenetic changes might play a role in establishing the immune phenotype associated with asthma. Published by Elsevier Inc.

  10. DNA methylation and methylation polymorphism in ecotypes of Jatropha curcas L. using methylation-sensitive AFLP markers.

    PubMed

    Mastan, Shaik G; Rathore, Mangal S; Bhatt, Vacha D; Chikara, J; Ghosh, A

    2014-12-01

    We investigated DNA methylation and polymorphism in the methylated DNA using AFLP based methylation-sensitive amplification polymorphism (MS-AFLP) markers in ecotypes of Jatropha curcas L. growing in similar and different geo-ecological conditions. Three ecotypes growing in different geo-ecological conditions with environmental heterogeneity (Group-1) and five ecotypes growing in similar environmental conditions (Group-2) were assessed. In ecotypes growing in group-1, 44.32 % DNA was methylated and of which 93.59 % DNA was polymorphic. While in group-2, 32.27 % DNA was methylated, of which 51.64 % DNA was polymorphic. In site 1 and site 2 of group-1, overall methylation was 18.94 and 22.44 % respectively with difference of 3.5 %, while overall polymorphism was 41.14 and 39.23 % with a difference of 1.91 %. In site 1 and site 2 of group-2, overall methylation was 24.68 and 24.18 % respectively with difference of 0.5 %, while overall polymorphism was 12.19 and 12.65 % with a difference of 0.46 %. The difference of methylation percentage and percentage of methylation polymorphism throughout the genome of J. curcas at site 1 and 2 of group-1 is higher than that of J. curcas at site 1 and 2 of group-2. These results correlated the physico-chemical properties of soil at these sites. The variations of physico-chemical properties of soil at Chorwadla (site 1 in group-1 and site 2 in group-2) compared to the soil at Brahmapur (site 2 in group-1) is higher than that of soil at Neswad (site 1 in group-2). The study suggests that these homologous nucleotide sequences probably play important role in ecotype adaptation to environmental heterogeneity by creating epiallelic variations hence in evolution of ecotypes/clines or forms of species showing phenotypic/genotypic differences in different geographical areas.

  11. 40 CFR 721.10526 - 2-Propenoic acid, 2-methyl-, 2-hydroxyethyl ester, telomers with C18-26-alkyl acrylate, 1...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-dodecanethiol, N-(hydroxymethyl)-2-methyl-2-propenamide, polyfluorooctyl methacrylate and vinylidene chloride, 2...-alkyl acrylate, 1-dodecanethiol, N-(hydroxymethyl)-2-methyl-2-propenamide, polyfluorooctyl methacrylate... 40 Protection of Environment 32 2013-07-01 2013-07-01 false 2-Propenoic acid, 2-methyl-, 2...

  12. 40 CFR 721.10526 - 2-Propenoic acid, 2-methyl-, 2-hydroxyethyl ester, telomers with C18-26-alkyl acrylate, 1...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-dodecanethiol, N-(hydroxymethyl)-2-methyl-2-propenamide, polyfluorooctyl methacrylate and vinylidene chloride, 2...-alkyl acrylate, 1-dodecanethiol, N-(hydroxymethyl)-2-methyl-2-propenamide, polyfluorooctyl methacrylate... 40 Protection of Environment 31 2014-07-01 2014-07-01 false 2-Propenoic acid, 2-methyl-, 2...

  13. Learning and memory: regional changes in N-methyl-D-aspartate receptors in the chick brain after imprinting.

    PubMed Central

    McCabe, B J; Horn, G

    1988-01-01

    An extensive series of experiments has implicated a restricted region of the chick forebrain in the learning process of imprinting. The region is the intermediate and medial part of the hyperstriatum ventrale (IMHV). Previous studies have shown that training is associated with an increase in the area of the postsynaptic density of axospinous synapses in the left but not the right IMHV. The postsynaptic density is a site of high receptor density, and at least some axospinous synapses are excitatory. We found that imprinting is associated with a 59% increase in N-methyl-D-aspartate-sensitive binding of the excitatory amino acid L-[3H]glutamic acid in the left IMHV. The increase is probably due to an increased number of binding sites. The profile of sensitivity of the sites to a series of amino-, phosphono-substituted carboxylic acids (2-amino-3-phosphonopropionate to 2-amino-8-phosphonooctanoate) is characteristic of N-methyl-D-aspartate-type receptors. There were no significant effects of training on binding in the right IMHV. The effect of training on left IMHV binding could not be attributed to light exposure, arousal, or motor activity per se but was a function of how much the chicks learned. The changes in the left IMHV could increase the effectiveness of synaptic transmission in a region crucial for information storage and so form a neural basis for recognition memory. PMID:2833757

  14. Synthesis and characterization of phosphonates from methyl linoleate and vegetable oils

    USDA-ARS?s Scientific Manuscript database

    Phosphonates were synthesized on a medium scale (~200 g) from three lipids: methyl linoleate (MeLin), high-oleic sunflower oil (HOSO) and soybean oil (SBO), and three dialkyl phosphites: methyl, ethyl and n-butyl, using a radical initiator. A staged addition of the lipid and the initiator to the dia...

  15. Synthesis and characterization of phosphonates from methyl linoleate and vegetable oils

    USDA-ARS?s Scientific Manuscript database

    Phosphonates were synthesized on a medium scale (~200 g) from three lipids–methyl linoleate (MeLin), high-oleic sunflower oil (HOSO) and soybean oil (SBO), and three dialkyl phosphites–methyl, ethyl and n-butyl, using a radical initiator. A staged addition of the lipid and the initiator was used to ...

  16. The millimeter wave spectrum of methyl cyanate: a laboratory study and astronomical search in space.

    PubMed

    Kolesniková, L; Alonso, J L; Bermúdez, C; Alonso, E R; Tercero, B; Cernicharo, J; Guillemin, J-C

    2016-07-01

    The recent discovery of methyl isocyanate (CH 3 NCO) in Sgr B2(N) and Orion KL makes methyl cyanate (CH 3 OCN) a potential molecule in the interstellar medium. The aim of this work is to fulfill the first requirement for its unequivocal identification in space, i.e. the availability of transition frequencies with high accuracy. The room-temperature rotational spectrum of methyl cyanate was recorded in the millimeter wave domain from 130 to 350 GHz. All rotational transitions revealed A - E splitting owing to methyl internal rotation and were globally analyzed using the ERHAM program. The data set for the ground torsional state of methyl cyanate exceeds 700 transitions within J″ = 10 - 35 and [Formula: see text] and newly derived spectroscopic constants reproduce the spectrum close to the experimental uncertainty. Spectral features of methyl cyanate were then searched for in Orion KL, Sgr B2(N), B1-b, and TMC-1 molecular clouds. Upper limits to the column density of methyl cyanate are provided.

  17. Multiple programmed cell death pathways are involved in N-methyl-N-nitrosourea-induced photoreceptor degeneration.

    PubMed

    Reisenhofer, Miriam; Balmer, Jasmin; Zulliger, Rahel; Enzmann, Volker

    2015-05-01

    To identify programmed cell death (PCD) pathways involved in N-methyl-N-nitrosourea (MNU)-induced photoreceptor (PR) degeneration. Adult C57BL/6 mice received a single MNU i.p. injection (60 mg/kg bodyweight), and were observed over a period of 7 days. Degeneration was visualized by H&E overview staining and electron microscopy. PR cell death was measured by quantifying TUNEL-positive cells in the outer nuclear layer (ONL). Activity measurements of key PCD enzymes (calpain, caspases) were used to identify the involved cell death pathways. Furthermore, the expression level of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78), key players in endoplasmic reticulum (ER) stress-induced apoptosis, was analyzed using quantitative real-time PCR. A decrease in ONL thickness and the appearance of apoptotic PR nuclei could be detected beginning 3 days post-injection (PI). This was accompanied by an increase of TUNEL-positive cells. Significant upregulation of activated caspases (3, 9, 12) was found at different time periods after MNU injection. Additionally, several other players of nonconventional PCD pathways were also upregulated. Consequently, calpain activity increased in the ONL, with a maximum on day 7 PI and an upregulation of CHOP and GRP78 expression beginning on day 1 PI was found. The data indicate that regular apoptosis is the major cause of MNU-induced PR cell death. However, alternative PCD pathways, including ER stress and calpain activation, are also involved. Knowledge about the mechanisms involved in this mouse model of PR degeneration could facilitate the design of putative combinatory therapeutic approaches.

  18. DNA methylation signatures of educational attainment

    NASA Astrophysics Data System (ADS)

    van Dongen, Jenny; Bonder, Marc Jan; Dekkers, Koen F.; Nivard, Michel G.; van Iterson, Maarten; Willemsen, Gonneke; Beekman, Marian; van der Spek, Ashley; van Meurs, Joyce B. J.; Franke, Lude; Heijmans, Bastiaan T.; van Duijn, Cornelia M.; Slagboom, P. Eline; Boomsma, Dorret I.; BIOS consortium

    2018-03-01

    Educational attainment is a key behavioural measure in studies of cognitive and physical health, and socioeconomic status. We measured DNA methylation at 410,746 CpGs (N = 4152) and identified 58 CpGs associated with educational attainment at loci characterized by pleiotropic functions shared with neuronal, immune and developmental processes. Associations overlapped with those for smoking behaviour, but remained after accounting for smoking at many CpGs: Effect sizes were on average 28% smaller and genome-wide significant at 11 CpGs after adjusting for smoking and were 62% smaller in never smokers. We examined sources and biological implications of education-related methylation differences, demonstrating correlations with maternal prenatal folate, smoking and air pollution signatures, and associations with gene expression in cis, dynamic methylation in foetal brain, and correlations between blood and brain. Our findings show that the methylome of lower-educated people resembles that of smokers beyond effects of their own smoking behaviour and shows traces of various other exposures.

  19. Cosolvent effects on the drug release and depot swelling in injectable in situ depot-forming systems.

    PubMed

    Liu, Hui; Venkatraman, Subbu S

    2012-05-01

    Although injectable depot-forming solutions have been commercialized, the factors that influence the overall release kinetics from such systems are still not fully understood. In this work, we address the effect of cosolvent on the issue of excessive burst release of potent bioactives from injectable depot-forming solutions. Specifically, we have evaluated the influence of addition of a relatively hydrophobic cosolvent (triacetin) to more hydrophilic biocompatible solvents such as dimethyl sulfoxide (DMSO) and N-methyl-2-pyrrolidone (NMP) on the burst release. Drug release and solvent release results demonstrate that high burst release that occurred when only hydrophilic solvent was used as solvent was significantly reduced by adding triacetin as a cosolvent. The profiles of drug release were in good agreement with the profiles of the hydrophilic solvent DMSO or NMP release, and the suppression of the burst by triacetin addition is due to the suppression of the solvent release. Surprisingly, the swelling of the depot increased with triacetin amount and the depot morphology became more porous compared with the absence of triacetin. Usage of hydrophobic solvent as a cosolvent to reduce the burst release was shown to be more effective on the hydrophobic PdlLA depot and less effective on the relatively hydrophilic RG502 depot. Copyright © 2012 Wiley Periodicals, Inc.

  20. Characterization of Antimicrobial Agent Loaded Eudragit RS Solvent Exchange-Induced In Situ Forming Gels for Periodontitis Treatment.

    PubMed

    Phaechamud, Thawatchai; Jantadee, Takron; Mahadlek, Jongjan; Charoensuksai, Purin; Pichayakorn, Wiwat

    2017-02-01

    Eudragit RS (ERS), a quaternary polyacrylate positively charged polymer, exhibits a very low permeability and swells in aqueous media independently of pH without dissolving. Owing to its high solubility in N-methyl pyrrolidone (NMP), it was interesting to apply as polymer matrix for solvent-exchanged in situ forming gel. The aim of this research was to prepare in situ forming gels from ERS to deliver the antimicrobial agents (doxycycline hyclate, metronidazole, and benzoyl peroxide) for periodontitis treatment. They were evaluated for viscosity and rheology, gel formation, syringeability, drug release, and antimicrobial activities. The solvent exchange between NMP and an external aqueous simulated gingival crevicular fluid stimulated the dissolved ERS transforming into the opaque rigid gel. Antimicrobial agent loaded ERS systems exhibited Newtonian flow with acceptable syringeability. The higher-loaded ERS promoted the more prolongation of drug release because of the retardation of water diffusion into the precipitated matrix. Antimicrobial activities against Staphylococcus aureus, Escherichia coli, Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis depended on type of drugs and test microorganisms. Doxycycline hyclate loaded ERS systems showed these activities greater than the others; however, all of them could inhibit all test microorganisms. Thus, the solvent exchange-induced in situ forming gels comprising ERS-antimicrobial drugs exhibited potential use as localized delivery systems for periodontitis treatment.

  1. Cell Fate of Müller Cells During Photoreceptor Regeneration in an N-Methyl-N-nitrosourea-Induced Retinal Degeneration Model of Zebrafish.

    PubMed

    Ogai, Kazuhiro; Hisano, Suguru; Sugitani, Kayo; Koriyama, Yoshiki; Kato, Satoru

    2016-01-01

    Zebrafish can regenerate several organs such as the tail fin, heart, central nervous system, and photoreceptors. Very recently, a study has demonstrated the photoreceptor regeneration in the alkylating agent N-methyl-N-nitrosourea (MNU)-induced retinal degeneration (RD) zebrafish model, in which whole photoreceptors are lost within a week after MNU treatment and then regenerated within a month. The research has also shown massive proliferation of Müller cells within a week. To address the question of whether proliferating Müller cells are the source of regenerating photoreceptors, which remains unknown in the MNU-induced zebrafish RD model, we employed a BrdU pulse-chase technique to label the proliferating cells within a week after MNU treatment. As a result of the BrdU pulse-chase technique, a number of BrdU(+) cells were observed in the outer nuclear layer as well as the inner nuclear layer. This implies that regenerating photoreceptors are derived from proliferating Müller cells in the zebrafish MNU-induced RD model.

  2. No effect of folic acid supplementation on global DNA methylation in men and women with moderately elevated homocysteine.

    PubMed

    Jung, Audrey Y; Smulders, Yvo; Verhoef, Petra; Kok, Frans J; Blom, Henk; Kok, Robert M; Kampman, Ellen; Durga, Jane

    2011-01-01

    A global loss of cytosine methylation in DNA has been implicated in a wide range of diseases. There is growing evidence that modifications in DNA methylation can be brought about by altering the intake of methyl donors such as folate. We examined whether long-term daily supplementation with 0.8 mg of folic acid would increase global DNA methylation compared with placebo in individuals with elevated plasma homocysteine. We also investigated if these effects were modified by MTHFR C677T genotype. Two hundred sixteen participants out of 818 subjects who had participated in a randomized double-blind placebo-controlled trial were selected, pre-stratified on MTHFR C677T genotype and matched on age and smoking status. They were allocated to receive either folic acid (0.8 mg/d; n = 105) or placebo treatment (n = 111) for three years. Peripheral blood leukocyte DNA methylation and serum and erythrocyte folate were assessed. Global DNA methylation was measured using liquid chromatography-tandem mass spectrometry and expressed as a percentage of 5-methylcytosines versus the total number of cytosine. There was no difference in global DNA methylation between those randomized to folic acid and those in the placebo group (difference = 0.008, 95%CI = -0.05,0.07, P = 0.79). There was also no difference between treatment groups when we stratified for MTHFR C677T genotype (CC, n = 76; CT, n = 70; TT, n = 70), baseline erythrocyte folate status or baseline DNA methylation levels. In moderately hyperhomocysteinemic men and women, long-term folic acid supplementation does not increase global DNA methylation in peripheral blood leukocytes.ClinicalTrials.gov NCT00110604.

  3. Genome-wide analysis of day/night DNA methylation differences in Populus nigra.

    PubMed

    Ding, Chang-Jun; Liang, Li-Xiong; Diao, Shu; Su, Xiao-Hua; Zhang, Bing-Yu

    2018-01-01

    DNA methylation is an important mechanism of epigenetic modification. Methylation changes during stress responses and developmental processes have been well studied; however, their role in plant adaptation to the day/night cycle is poorly understood. In this study, we detected global methylation patterns in leaves of the black poplar Populus nigra 'N46' at 8:00 and 24:00 by methylated DNA immunoprecipitation sequencing (MeDIP-seq). We found 10,027 and 10,242 genes to be methylated in the 8:00 and 24:00 samples, respectively. The methylated genes appeared to be involved in multiple biological processes, molecular functions, and cellular components, suggesting important roles for DNA methylation in poplar cells. Comparing the 8:00 and 24:00 samples, only 440 differentially methylated regions (DMRs) overlapped with genic regions, including 193 hyper- and 247 hypo-methylated DMRs, and may influence the expression of 137 downstream genes. Most hyper-methylated genes were associated with transferase activity, kinase activity, and phosphotransferase activity, whereas most hypo-methylated genes were associated with protein binding, ATP binding, and adenyl ribonucleotide binding, suggesting that different biological processes were activated during the day and night. Our results indicated that methylated genes were prevalent in the poplar genome, but that only a few of these participated in diurnal gene expression regulation.

  4. Methyl group reorientation under ligand binding probed by pseudocontact shifts.

    PubMed

    Lescanne, Mathilde; Ahuja, Puneet; Blok, Anneloes; Timmer, Monika; Akerud, Tomas; Ubbink, Marcellus

    2018-06-02

    Liquid-state NMR spectroscopy is a powerful technique to elucidate binding properties of ligands on proteins. Ligands binding in hydrophobic pockets are often in close proximity to methyl groups and binding can lead to subtle displacements of methyl containing side chains to accommodate the ligand. To establish whether pseudocontact shifts can be used to characterize ligand binding and the effects on methyl groups, the N-terminal domain of HSP90 was tagged with caged lanthanoid NMR probe 5 at three positions and titrated with a ligand. Binding was monitored using the resonances of leucine and valine methyl groups. The pseudocontact shifts (PCS) caused by ytterbium result in enhanced dispersion of the methyl spectrum, allowing more resonances to be observed. The effects of tag attachment on the spectrum and ligand binding are small. Significant changes in PCS were observed upon ligand binding, indicating displacements of several methyl groups. By determining the cross-section of PCS iso-surfaces generated by two or three paramagnetic centers, the new position of a methyl group can be estimated, showing displacements in the range of 1-3 Å for methyl groups in the binding site. The information about such subtle but significant changes may be used to improve docking studies and can find application in fragment-based drug discovery.

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

    PubMed

    Amatruda, James F; Ross, Julie A; Christensen, Brock; Fustino, Nicholas J; Chen, Kenneth S; Hooten, Anthony J; Nelson, Heather; Kuriger, Jacquelyn K; Rakheja, Dinesh; Frazier, A Lindsay; Poynter, Jenny N

    2013-06-27

    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. 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. 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 < 0.05), including a number of CpGs in stem cell and pluripotency-related pathways. Both YST and germinoma showed significantly lower 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. 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.

  6. Crystal structures of 4-meth-oxy-N-(4-methyl-phenyl)benzene-sulfonamide and N-(4-fluoro-phenyl)-4-meth-oxy-benzene-sulfonamide.

    PubMed

    Rodrigues, Vinola Z; Preema, C P; Naveen, S; Lokanath, N K; Suchetan, P A

    2015-11-01

    Crystal structures of two N-(ar-yl)aryl-sulfonamides, namely, 4-meth-oxy-N-(4-methyl-phen-yl)benzene-sulfonamide, C14H15NO3S, (I), and N-(4-fluoro-phen-yl)-4-meth-oxy-benzene-sulfonamide, C13H12FNO3S, (II), were determined and analyzed. In (I), the benzene-sulfonamide ring is disordered over two orientations, in a 0.516 (7):0.484 (7) ratio, which are inclined to each other at 28.0 (1)°. In (I), the major component of the sulfonyl benzene ring and the aniline ring form a dihedral angle of 63.36 (19)°, while in (II), the planes of the two benzene rings form a dihedral angle of 44.26 (13)°. In the crystal structure of (I), N-H⋯O hydrogen bonds form infinite C(4) chains extended in [010], and inter-molecular C-H⋯πar-yl inter-actions link these chains into layers parallel to the ab plane. The crystal structure of (II) features N-H⋯O hydrogen bonds forming infinite one dimensional C(4) chains along [001]. Further, a pair of C-H⋯O inter-molecular inter-actions consolidate the crystal packing of (II) into a three-dimensional supra-molecular architecture.

  7. A PHYSIOLOGICALLY BASED PHARMACOKINETIC/PHARMACODYNAMIC (PBPK/PD) MODEL FOR ESTIMATION OF CUMULATIVE RISK FROM EXPOSURE TO THREE N-METHYL CARBAMATES: CARBARYL, ALDICARB, AND CARBOFURAN

    EPA Science Inventory

    A physiologically-based pharmacokinetic (PBPK) model for a mixture of N-methyl carbamate pesticides was developed based on single chemical models. The model was used to compare urinary metabolite concentrations to levels from National Health and Nutrition Examination Survey (NHA...

  8. Thermal coefficients of the methyl groups within ubiquitin

    PubMed Central

    Sabo, T Michael; Bakhtiari, Davood; Walter, Korvin F A; McFeeters, Robert L; Giller, Karin; Becker, Stefan; Griesinger, Christian; Lee, Donghan

    2012-01-01

    Physiological processes such as protein folding and molecular recognition are intricately linked to their dynamic signature, which is reflected in their thermal coefficient. In addition, the local conformational entropy is directly related to the degrees of freedom, which each residue possesses within its conformational space. Therefore, the temperature dependence of the local conformational entropy may provide insight into understanding how local dynamics may affect the stability of proteins. Here, we analyze the temperature dependence of internal methyl group dynamics derived from the cross-correlated relaxation between dipolar couplings of two CH bonds within ubiquitin. Spanning a temperature range from 275 to 308 K, internal methyl group dynamics tend to increase with increasing temperature, which translates to a general increase in local conformational entropy. With this data measured over multiple temperatures, the thermal coefficient of the methyl group order parameter, the characteristic thermal coefficient, and the local heat capacity were obtained. By analyzing the distribution of methyl group thermal coefficients within ubiquitin, we found that the N-terminal region has relatively high thermostability. These results indicate that methyl groups contribute quite appreciably to the total heat capacity of ubiquitin through the regulation of local conformational entropy. PMID:22334336

  9. Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam.

    PubMed

    Ito, I; Tanabe, S; Kohda, A; Sugiyama, H

    1990-05-01

    1. Allosteric potentiation of the ionotropic quisqualate (iQA) receptor by a nootropic drug aniracetam (1-p-anisoyl-2-pyrrolidinone) was investigated using Xenopus oocytes injected with rat brain mRNA and rat hippocampal slices. 2. Aniracetam potentiates the iQA responses induced in Xenopus oocytes by rat brain mRNA in a reversible manner. This effect was observed above the concentrations of 0.1 mM. Kainate. N-methyl-D-aspartate and gamma-aminobutyric acid responses induced in the same oocytes were not affected. 3. The specific potentiation of iQA responses was accompanied by an increase in the conductance change of iQA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) responses, but the affinity of receptors for agonist and the ion-selectivity of the channels (reversal potentials) were not changed. 4. Aniracetam reversibly potentiated the iQA responses recorded intracellularly from the pyramidal cells in the CA1 region of rat hippocampal slices. The excitatory postsynaptic potentials (EPSPs) in Schaffer collateral-commissural-CA1 synapses were also potentiated by aniracetam. 5. Population EPSPs recorded in the mossy fibre-CA3 synapses as well as Schaffer-commissural synapses were also potentiated by aniracetam. The amplitudes of the potentiation were not changed by the formation of long-term potentiation.

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

    PubMed Central

    Glaude, Pierre Alexandre; Herbinet, Olivier; Bax, Sarah; Biet, Joffrey; Warth, Valérie; Battin-Leclerc, Frédérique

    2013-01-01

    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. PMID:23710076

  11. Validation of SCT Methylation as a Hallmark Biomarker for Lung Cancers.

    PubMed

    Zhang, Yu-An; Ma, Xiaotu; Sathe, Adwait; Fujimoto, Junya; Wistuba, Ignacio; Lam, Stephen; Yatabe, Yasushi; Wang, Yi-Wei; Stastny, Victor; Gao, Boning; Larsen, Jill E; Girard, Luc; Liu, Xiaoyun; Song, Kai; Behrens, Carmen; Kalhor, Neda; Xie, Yang; Zhang, Michael Q; Minna, John D; Gazdar, Adi F

    2016-03-01

    The human secretin gene (SCT) encodes secretin, a hormone with limited tissue distribution. Analysis of the 450k methylation array data in The Cancer Genome Atlas (TCGA) indicated that the SCT promoter region is differentially hypermethylated in lung cancer. Our purpose was to validate SCT methylation as a potential biomarker for lung cancer. We analyzed data from TCGA and developed and applied SCT-specific bisulfite DNA sequencing and quantitative methylation-specific polymerase chain reaction assays. The analyses of TCGA 450K data for 801 samples showed that SCT hypermethylation has an area under the curve (AUC) value greater than 0.98 that can be used to distinguish lung adenocarcinomas or squamous cell carcinomas from nonmalignant lung tissue. Bisulfite sequencing of lung cancer cell lines and normal blood cells allowed us to confirm that SCT methylation is highly discriminative. By applying a quantitative methylation-specific polymerase chain reaction assay, we found that SCT hypermethylation is frequently detected in all major subtypes of malignant non-small cell lung cancer (AUC = 0.92, n = 108) and small cell lung cancer (AUC = 0.93, n = 40) but is less frequent in lung carcinoids (AUC = 0.54, n = 20). SCT hypermethylation appeared in samples of lung carcinoma in situ during multistage pathogenesis and increased in invasive samples. Further analyses of TCGA 450k data showed that SCT hypermethylation is highly discriminative in most other types of malignant tumors but less frequent in low-grade malignant tumors. The only normal tissue with a high level of methylation was the placenta. Our findings demonstrated that SCT methylation is a highly discriminative biomarker for lung and other malignant tumors, is less frequent in low-grade malignant tumors (including lung carcinoids), and appears at the carcinoma in situ stage. Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  12. Supplementation with N-3 Long-Chain Polyunsaturated Fatty Acids or Olive Oil in Men and Women with Renal Disease Induces Differential Changes in the DNA Methylation of FADS2 and ELOVL5 in Peripheral Blood Mononuclear Cells

    PubMed Central

    Hoile, Samuel P.; Clarke-Harris, Rebecca; Huang, Rae-Chi; Calder, Philip C.; Mori, Trevor A.; Beilin, Lawrence J.; Lillycrop, Karen A.; Burdge, Graham C.

    2014-01-01

    Background Studies in animal models and in cultured cells have shown that fatty acids can induce alterations in the DNA methylation of specific genes. There have been no studies of the effects of fatty acid supplementation on the epigenetic regulation of genes in adult humans. Methods and Results We investigated the effect of supplementing renal patients with 4 g daily of either n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) or olive oil (OO) for 8 weeks on the methylation status of individual CpG loci in the 5′ regulatory region of genes involved in PUFA biosynthesis in peripheral blood mononuclear cells from men and women (aged 53 to 63 years). OO and n-3 LCPUFA each altered (>10% difference in methylation) 2/22 fatty acid desaturase (FADS)-2 CpGs, while n-3 LCPUFA, but not OO, altered (>10%) 1/12 ELOVL5 CpGs in men. OO altered (>6%) 8/22 FADS2 CpGs and (>3%) 3/12 elongase (ELOVL)-5 CpGs, while n-3 LCPUFA altered (>5%) 3/22 FADS2 CpGs and 2/12 (>3%) ELOVL5 CpGs in women. FADS1 or ELOVL2 methylation was unchanged. The n-3 PUFA supplementation findings were replicated in blood DNA from healthy adults (aged 23 to 30 years). The methylation status of the altered CpGs in FADS2 and ELOVL5 was associated negatively with the level of their transcripts. Conclusions These findings show that modest fatty acid supplementation can induce altered methylation of specific CpG loci in adult humans, contingent on the nature of the supplement and on sex. This has implications for understanding the effect of fatty acids on PUFA metabolism and cell function. PMID:25329159

  13. One-Pot Synthesis of Graphene-Supported Monodisperse Pd Nanoparticles as Catalyst for Formic Acid Electro-oxidation

    PubMed Central

    Yang, Sudong; Dong, Jing; Yao, Zhaohui; Shen, Chengmin; Shi, Xuezhao; Tian, Yuan; Lin, Shaoxiong; Zhang, Xiaogang

    2014-01-01

    To synthesize monodisperse palladium nanoparticles dispersed on reduced graphene oxide (RGO) sheets, we have developed an easy and scalable solvothermal reduction method from an organic solution system. The RGO-supported palladium nanoparticles with a diameter of 3.8 nm are synthesized in N-methyl-2-pyrrolidone (NMP) and in the presence of oleylamine and trioctylphosphine, which facilitates simultaneous reduction of graphene oxide and formation of Pd nanocrystals. So-produced Pd/RGO was tested for potential use as electrocatalyst for the electro-oxidation of formic acid. Pd/RGO catalyzes formic acid oxidation very well compared to Pd/Vulcan XC-72 catalyst. This synthesis method is a new way to prepare excellent electrocatalysts, which is of great significance in energy-related catalysis. PMID:24675779

  14. APMP.QM-S8: determination of mass fraction of benzoic acid, methyl paraben and n-butyl paraben in soy sauce

    NASA Astrophysics Data System (ADS)

    Teo, Tang Lin; Gui, Ee Mei; Lu, Ting; Sze Cheow, Pui; Giannikopoulou, Panagiota; Kakoulides, Elias; Lampi, Evgenia; Choi, Sik-man; Yip, Yiu-chung; Chan, Pui-kwan; Hui, Sin-kam; Wollinger, Wagner; Carvalho, Lucas J.; Garrido, Bruno C.; Rego, Eliane C. P.; Ahn, Seonghee; Kim, Byungjoo; Li, Xiuqin; Guo, Zhen; Styarini, Dyah; Aristiawan, Yosi; Putri Ramadhaningtyas, Dillani; Aryana, Nurhani; Ebarvia, Benilda S.; Dacuaya, Aaron; Tongson, Alleni; Aganda, Kim Christopher; Junvee Fortune, Thippaya; Tangtrirat, Pradthana; Mungmeechai, Thanarak; Ceyhan Gören, Ahmet; Gündüz, Simay; Yilmaz, Hasibe

    2017-01-01

    The supplementary comparison APMP.QM-S8: determination of mass fraction of benzoic acid, methyl paraben and n-butyl paraben in soy sauce was coordinated by the Health Sciences Authority, Singapore under the auspices of the Organic Analysis Working Group (OAWG) of the Comité Consultatif pour la Quantité de Matière (CCQM). Ten national metrology institutes (NMIs) or designated institutes (DIs) participated in the comparison. All the institutes participated in the comparison for benzoic acid, while six NMIs/DIs participated in the comparison for methyl paraben and n-butyl paraben. The comparison was designed to enable participating institutes to demonstrate their measurement capabilities in the determination of common preservatives in soy sauce, using procedure(s) that required simple sample preparation and selective detection in the mass fraction range of 50 to 1000 mg/kg. The demonstrated capabilities can be extended to include other polar food preservatives (e.g. sorbic acid, propionic acid and other alkyl benzoates) in water, aqueous-based beverages (e.g. fruit juices, tea extracts, sodas, sports drinks, etc) and aqueous-based condiments (e.g. vinegar, fish sauce, etc). Liquid--liquid extraction and/or dilution were applied, followed by instrumental analyses using LC-MS/MS, LC-MS, GC-MS (with or without derivatisation) or HPLC-DAD. Isotope dilution mass spectrometry was used for quantification, except in the case of a participating institute, where external calibration method was used for quantification of all three measurands. The assigned Supplementary Comparison Reference Values (SCRVs) were the medians of ten results for benzoic acid, six results for methyl paraben and six results for n-butyl paraben. Benzoic acid was assigned a SCRV of 154.55 mg/kg with a combined standard uncertainty of 0.94 mg/kg, methyl paraben was assigned a SCRV of 100.95 mg/kg with a combined standard uncertainty of 0.40 mg/kg, and n-butyl paraben was assigned a SCRV of 99.05 mg

  15. Vitamin D receptor gene methylation is associated with ethnicity, tuberculosis and TaqI polymorphism

    PubMed Central

    Andraos, Charlene; Koorsen, Gerrit; Knight, Julian C; Bornman, Liza

    2014-01-01

    The Vitamin D Receptor (VDR) gene encodes a transcription factor which, on activation by vitamin D, modulates diverse biological processes including calcium homeostasis and immune function. Genetic variation involving VDR shows striking differences in allele frequency between populations and has been associated with disease susceptibility including tuberculosis and autoimmunity, although results have often been conflicting. We hypothesized that methylation of VDR may be population specific and that the combination of differential methylation and genetic variation may characterise TB predisposition. We use bisulphite conversion and/or pyrosequencing to analyse the methylation status of 17 CpGs of VDR and to genotype 7 SNPs in the 3′ CpG Island (CGI 1060), including the commonly studied SNPs ApaI (rs7975232) and TaqI (rs731236). We show that for lymphoblastoid cell lines from two ethnically diverse populations (Yoruba from HapMap, n=30 and Caucasians, n=30) together with TB cases (n=32) and controls (n=29) from the Venda population of South Africa there are methylation variable positions (MVPs) in the 3′ end that significantly distinguish ethnicity (9/17 CpGs) and TB status (3/17 CpGs). Moreover methylation status shows complex association with TaqI genotype highlighting the need to consider both genetic and epigenetic variants in genetic studies of VDR association with disease. PMID:21168462

  16. DNA Methylation and Sex Allocation in the Parasitoid Wasp Nasonia vitripennis.

    PubMed

    Cook, Nicola; Pannebakker, Bart A; Tauber, Eran; Shuker, David M

    2015-10-01

    The role of epigenetics in the control and evolution of behavior is being increasingly recognized. Here we test whether DNA methylation influences patterns of adaptive sex allocation in the parasitoid wasp Nasonia vitripennis. Female N. vitripennis allocate offspring sex broadly in line with local mate competition (LMC) theory. However, recent theory has highlighted how genomic conflict may influence sex allocation under LMC, conflict that requires parent-of-origin information to be retained by alleles through some form of epigenetic signal. We manipulated whole-genome DNA methylation in N. vitripennis females using the hypomethylating agent 5-aza-2'-deoxycytidine. Across two replicated experiments, we show that disruption of DNA methylation does not ablate the facultative sex allocation response of females, as sex ratios still vary with cofoundress number as in the classical theory. However, sex ratios are generally shifted upward when DNA methylation is disrupted. Our data are consistent with predictions from genomic conflict over sex allocation theory and suggest that sex ratios may be closer to the optimum for maternally inherited alleles.

  17. Methylation of DNA

    PubMed Central

    Gold, Marvin; Gefter, Malcolm; Hausmann, Rudolph; Hurwitz, Jerard

    1966-01-01

    The methylated bases of DNA are formed by the transfer of the methyl group from S-adenosylmethionine to a polynucleotide acceptor. This transfer is catalyzed by highly specific enzymes which recognize a limited number of available sites in the DNA. The mechanism for the recognition is presently unknown. In some instances, there is evidence that other cellular components, such as lipopolysaccharides, can influence the methylation reaction. Certain bacteriophages induce new methylases upon infection of their hosts. Phage T3 is unique in establishing an environment in which methylation of neither the phage nor the host nucleic acid can occur. By superinfecting T3-infected cells with other phages, the latter can be obtained with methyl-deficient DNA. Although a great deal is known about the enzymology of the methylation reaction, and there appears to be a strong correlation between the in vitro and in vivo reactions, studies in which DNA is either supermethylated or totally unmethylated have not yielded any insight as to what the possible function of the methylated bases may be. PMID:5338563

  18. Major impact of N-methylation on cytotoxicity and hydrolysis of salan Ti(IV) complexes: sterics and electronics are intertwined.

    PubMed

    Meker, Sigalit; Manna, Cesar M; Peri, Dani; Tshuva, Edit Y

    2011-10-14

    A series of Ti(IV) complexes containing diamino bis(phenolato) "salan" type ligands with NH coordination were prepared, and their hydrolysis and cytotoxicity were analyzed and compared to the N-methylated analogues. Substituting methyl groups on the coordinative nitrogen donor of highly active and stable Ti(IV) salan complexes with H atoms has two main consequences: the hydrolysis rate increases and the cytotoxic activity diminishes. In addition, the small modification of a single replacement of Me with H leads to a different major hydrolysis product, where a dinuclear Ti(IV) complex with two bridging oxo ligands is obtained, as characterized by X-ray crystallography, rather than a trinuclear cluster. A partial hydrolysis product containing a single oxo bridge was also crystallographically analyzed. Investigation of a series of complexes with NH donors of different steric and electronic effects revealed that cytotoxicity may be restored by fine tuning these parameters even for complexes of low stability.

  19. Histone Methylation and Epigenetic Silencing in Breast Cancer

    DTIC Science & Technology

    2011-02-01

    Chen, S., Bohrer, L.R., Nair-Rai, A., Pan , Y., Gan, L., Zhou, X., Bagchi, A., Simon, J.A. and Huang, H. (2010). Cyclin-dependent kinases regulate...EZH2 suppresses methylation of lysine 27 in histone H3. Science 310(5746): 306-310. Chen, S., Bohrer, L.R., Rai, A.N., Pan , Y., Gan, L., Zhou, X...recent study finds that ri-methyl-H3-K27 levels are decreased in breast, ovarian and pan - reatic cancer samples [65], which could reflect a shift in

  20. The effects of omega-3 polyunsaturated fatty acids and genetic variants on methylation levels of the interleukin-6 gene promoter

    PubMed Central

    Ma, Yiyi; Smith, Caren E.; Lai, Chao-Qiang; Irvin, Marguerite R.; Parnell, Laurence D.; Lee, Yu-Chi; Pham, Lucia D.; Aslibekyan, Stella; Claas, Steven A.; Tsai, Michael Y.; Borecki, Ingrid B.; Kabagambe, Edmond K.; Ordovás, José M.; Absher, Devin M.; Arnett, Donna K.

    2016-01-01

    Scope Omega-3 PUFAs (n-3 PUFAs) reduce IL-6 gene expression, but their effects on transcription regulatory mechanisms are unknown. We aimed to conduct an integrated analysis with both population and in vitro studies to systematically explore the relationships among n-3 PUFA, DNA methylation, single nucleotide polymorphisms (SNPs), gene expression, and protein concentration of IL6. Methods and results Using data in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study and the Encyclopedia of DNA Elements (ENCODE) consortium, we found that higher methylation of IL6 promoter cg01770232 was associated with higher IL-6 plasma concentration (p = 0.03) and greater IL6 gene expression (p = 0.0005). Higher circulating total n-3 PUFA was associated with lower cg01770232 methylation (p = 0.007) and lower IL-6 concentration (p = 0.02). Moreover, an allele of IL6 rs2961298 was associated with higher cg01770232 methylation (p = 2.55 × 10−7). The association between n-3 PUFA and cg01770232 methylation was dependent on rs2961298 genotype (p = 0.02), but higher total n-3 PUFA was associated with lower cg01770232 methylation in the heterozygotes (p = 0.04) not in the homozygotes. Conclusion Higher n-3 PUFA is associated with lower methylation at IL6 promoter, which may be modified by IL6 SNPs. PMID:26518637