Thermal performance enhancement of erythritol/carbon foam composites via surface modification of carbon foam

Science.gov (United States)

Li, Junfeng; Lu, Wu; Luo, Zhengping; Zeng, Yibing

2017-03-01

The thermal performance of the erythritol/carbon foam composites, including thermal diffusivity, thermal capacity, thermal conductivity and latent heat, were investigated via surface modification of carbon foam using hydrogen peroxide as oxider. It was found that the surface modification enhanced the wetting ability of carbon foam surface to the liquid erythritol of the carbon foam surface and promoted the increase of erythritol content in the erythritol/carbon foam composites. The dense interfaces were formed between erythritol and carbon foam, which is due to that the formation of oxygen functional groups C=O and C-OH on the carbon surface increased the surface polarity and reduced the interface resistance of carbon foam surface to the liquid erythritol. The latent heat of the erythritol/carbon foam composites increased from 202.0 to 217.2 J/g through surface modification of carbon foam. The thermal conductivity of the erythritol/carbon foam composite before and after surface modification further increased from 40.35 to 51.05 W/(m·K). The supercooling degree of erythritol also had a large decrease from 97 to 54 °C. Additionally, the simple and effective surface modification method of carbon foam provided an extendable way to enhance the thermal performances of the composites composed of carbon foams and PCMs.

The plastidial retrograde signal methyl erythritol cyclopyrophosphate is a regulator of salicylic acid and jasmonic acid crosstalk

Science.gov (United States)

Lemos, Mark; Xiao, Yanmei; Bjornson, Marta; Wang, Jin-zheng; Hicks, Derrick; de Souza, Amancio; Wang, Chang-Quan; Yang, Panyu; Ma, Shisong; Dinesh-Kumar, Savithramma; Dehesh, Katayoon

2016-01-01

The exquisite harmony between hormones and their corresponding signaling pathways is central to prioritizing plant responses to simultaneous and/or successive environmental trepidations. The crosstalk between jasmonic acid (JA) and salicylic acid (SA) is an established effective mechanism that optimizes and tailors plant adaptive responses. However, the underlying regulatory modules of this crosstalk are largely unknown. Global transcriptomic analyses of mutant plants (ceh1) with elevated levels of the stress-induced plastidial retrograde signaling metabolite 2-C-methyl-D-erythritol cyclopyrophosphate (MEcPP) revealed robustly induced JA marker genes, expected to be suppressed by the presence of constitutively high SA levels in the mutant background. Analyses of a range of genotypes with varying SA and MEcPP levels established the selective role of MEcPP-mediated signal(s) in induction of JA-responsive genes in the presence of elevated SA. Metabolic profiling revealed the presence of high levels of the JA precursor 12-oxo-phytodienoic acid (OPDA), but near wild type levels of JA in the ceh1 mutant plants. Analyses of coronatine-insensitive 1 (coi1)/ceh1 double mutant plants confirmed that the MEcPP-mediated induction is JA receptor COI1 dependent, potentially through elevated OPDA. These findings identify MEcPP as a previously unrecognized central regulatory module that induces JA-responsive genes in the presence of high SA, thereby staging a multifaceted plant response within the environmental context. PMID:26733689

Synthesis of methyl 3-O-{alpha}-d-glucopyranosyl-C{sub 6}{sup 14}-{beta}-d-xylopyranoside and methyl 2-O-{alpha}-d-Glucopyranosyl-C{sub 6}{sup 14}-l-noviopyranoside; Synthese de methyl-3-O-alpha-D-glucopyranosyl-C{sup 14}-beta-D-xylophranoside et methyl-2-O-alpha-D-glucopyranosyl-C{sub 6}{sup 14}-L-noviopyranoside; Sintez metil-3-O-{alpha}-D-glyukopiranozila-C{sub 6}{sup 14}-{beta}-D-ksilopiranozid i metil 2-O-{alpha}-D-glyukopiranozil-C{sub 6}{sup 14}-L-noviopiranozid; Sintesis de la metil 3-O-{alpha}-D-glucopiranosil-{sup 14}C{sub 6}-{beta}-D-xilopiranosido y de la metil 2-O-{alpha}-D-glucopiranosil-{sup 14}C{sub 6}-L-noviopiranosido

Energy Technology Data Exchange (ETDEWEB)

Barker, S A; Keith, M C; Stacey, M; Stroud, D B.E. [Chemistry Department, University of Birmingham (United Kingdom)

1962-03-15

Where difficulty is encountered in the chemical synthesis of a disaccharide glycoside labelled with C{sub 6}{sup 14} specifically in only one of its sugar moieties it is often convenient to resort to a synthesis catalysed by microbial transglycosylases. Two examples of the application of this technique are reported; the syntheses: Maltose-C{sub 12}{sup 14} + Methyl {beta}-d-xylopyranoside Penicillium lilacinum/transglucosylase {yields} Methyl 3-0-{alpha}-d-Glucopyranosyl-C{sub 6}{sup 14}-{beta}-d-xylopyranoside (I) + Glucose-C{sub 6}{sup 14} Maltose-C{sub 12}{sup 14} + Methyl l-noviopyranoside Fusarium moniliforme/transglucosylase Methyl-2-0-{alpha}d-Glucopyranosyl-C{sub 6}{sup 14}-l-noviopyranoside (II) + Glucose-C{sub 6}{sup 14}. In such syntheses, it is predictable that the anomeric character of the glycosidic linkage of the donor disaccharide will be retained in the disaccharide synthezised and that the glycosyl residue transferred will be attached, through its reducing group, to the receptor monosaccharide glycoside. By using either a C{sup 14}-labelled donor disaccharide or a C{sup 14}-labelled receptor glycoside, a disaccharide can be synthesized with only one of its sugar moieties labelled. In the synthesis of II the only hydroxyl group free in the receptor methyl novioside is on C{sub 2} and the transferred glucosyl residue can only be attached here. In the synthesis of I the methyl xyloside has free hydroxyls on C{sub 2}, C{sub 3} and C{sub 4} and the microbial enzyme has been found to transfer the glucosyl residue specifically to the hydroxyl on C{sub 3}. The structures of I and I I have been established by the results of elemental analysis, optical rotation, infrared spectra together with an examination of the products of acid hydrolysis and periodate oxidation. (author) [French] Lorsqu'on se heurte a des difficultes dans la synthese chimique d'un glucoside de disaccharide marque au carbone-14 specifiquement dans un seul des deux sucres qui le

Thermal properties of an erythritol derivative

Science.gov (United States)

Trhlikova, Lucie; Prikryl, Radek; Zmeskal, Oldrich

2016-06-01

Erythritol (C4H10O4) is a sugar alcohol (or polyol) that is commonly used in the food industry. Its molar mass is 122.12 g.mol-1 and mass density 1450 kg.m-3. Erythritol, an odorless crystalline powder, can also be characterized by other physical parameters like melting temperature (121 °C) and boiling temperature (329 °C). The substance can be used for the accumulation of energy in heat exchangers based on various oils or water. The PlusICE A118 product manufactured by the PCM Products Ltd. company (melting temperature Θ = 118 °C, specific heat capacity cp = 2.70 kJ.K-1.kg-1, mass density 1450 kg.m-3, latent heat capacity 340 kJ.kg-1, volumetric heat capacity 493 MJ.m-3) is based on an erythritol-type medium. Thermal properties of the PlusICE A118 product in both solid and liquid phase were investigated for this purpose in terms of potential applications. Temperature dependences of its thermal parameters (thermal diffusivity, thermal conductivity, and specific heat) were determined using a transient (step-wise) method. A fractal model of heat transport was used for determination of the above thermal parameters. This model is independent of geometry and type of sample heating. Moreover, it also considers heat losses. The experiment confirmed the formerly declared value of phase change temperature, about 120 °C.

The plastidial retrograde signal methyl erythritol cyclopyrophosphate is a regulator of salicylic acid and jasmonic acid crosstalk.

Science.gov (United States)

Lemos, Mark; Xiao, Yanmei; Bjornson, Marta; Wang, Jin-Zheng; Hicks, Derrick; Souza, Amancio de; Wang, Chang-Quan; Yang, Panyu; Ma, Shisong; Dinesh-Kumar, Savithramma; Dehesh, Katayoon

2016-03-01

The exquisite harmony between hormones and their corresponding signaling pathways is central to prioritizing plant responses to simultaneous and/or successive environmental trepidations. The crosstalk between jasmonic acid (JA) and salicylic acid (SA) is an established effective mechanism that optimizes and tailors plant adaptive responses. However, the underlying regulatory modules of this crosstalk are largely unknown. Global transcriptomic analyses of mutant plants (ceh1) with elevated levels of the stress-induced plastidial retrograde signaling metabolite 2-C-methyl-D-erythritol cyclopyrophosphate (MEcPP) revealed robustly induced JA marker genes, expected to be suppressed by the presence of constitutively high SA levels in the mutant background. Analyses of a range of genotypes with varying SA and MEcPP levels established the selective role of MEcPP-mediated signal(s) in induction of JA-responsive genes in the presence of elevated SA. Metabolic profiling revealed the presence of high levels of the JA precursor 12-oxo-phytodienoic acid (OPDA), but near wild type levels of JA in the ceh1 mutant plants. Analyses of coronatine-insensitive 1 (coi1)/ceh1 double mutant plants confirmed that the MEcPP-mediated induction is JA receptor COI1 dependent, potentially through elevated OPDA. These findings identify MEcPP as a previously unrecognized central regulatory module that induces JA-responsive genes in the presence of high SA, thereby staging a multifaceted plant response within the environmental context. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

LytB1 and LytB2 of Mycobacterium tuberculosis Are Not Genetically Redundant.

Directory of Open Access Journals (Sweden)

Amanda Claire Brown

Full Text Available Mycobacterium tuberculosis synthesises isoprenoid precursors via the MEP/DOXP pathway and at least five enzymes in the pathway (Dxs1, Dxr/IspC, IspD, IspF, and GcpE/IspG are required for growth in vitro. We investigated the role of LytB (IspH in M. tuberculosis; M. tuberculosis is unusual in that it has two homologs-LytB1 and LytB2. We were unable to delete the lytB2 gene unless we provided an additional copy elsewhere, demonstrating that this is the essential homolog. We expressed lytB1 from the lytB2 promoter and confirmed that this could not complement for loss of function of lytB2, despite LytB1 possessing all the previously described conserved critical residues. Interestingly the sole LytB homolog of Mycobacterium smegmatis was able to compensate for loss of LytB2 in M. tuberculosis. We tested translational fusions of LytB1 and LytB2 for functionality in M. tuberculosis, but only a fusion with 90% N-terminal LytB2 and 10% C-terminal LytB1 was functional. In order to identify the key difference between the two proteins, site directed mutagenesis was used to change LytB2 residues into their counterparts in LytB1. None of these amino acid substitutions was essential for function and all lytB2 mutant alleles were functional. In contrast, mutation of the key residues for [Fe4S4] cluster formation, as well as a catalytic residue in LytB1 did not result in functional complementation. Thus, although LytB1 and LytB2 are not genetically redundant, this is not dependent on small amino acid changes, but is likely to be a result of major overall structural differences.

A Gene Cluster for Biosynthesis of Mannosylerythritol Lipids Consisted of 4-O-β-D-Mannopyranosyl-(2R,3S-Erythritol as the Sugar Moiety in a Basidiomycetous Yeast Pseudozyma tsukubaensis.

Directory of Open Access Journals (Sweden)

Azusa Saika

Full Text Available Mannosylerythritol lipids (MELs belong to the glycolipid biosurfactants and are produced by various fungi. The basidiomycetous yeast Pseudozyma tsukubaensis produces diastereomer type of MEL-B, which contains 4-O-β-D-mannopyranosyl-(2R,3S-erythritol (R-form as the sugar moiety. In this respect it differs from conventional type of MELs, which contain 4-O-β-D-mannopyranosyl-(2S,3R-erythritol (S-form as the sugar moiety. While the biosynthetic gene cluster for conventional type of MELs has been previously identified in Ustilago maydis and Pseudozyma antarctica, the genetic basis for MEL biosynthesis in P. tsukubaensis is unknown. Here, we identified a gene cluster involved in MEL biosynthesis in P. tsukubaensis. Among these genes, PtEMT1, which encodes erythritol/mannose transferase, had greater than 69% identity with homologs from strains in the genera Ustilago, Melanopsichium, Sporisorium and Pseudozyma. However, phylogenetic analysis placed PtEMT1p in a separate clade from the other proteins. To investigate the function of PtEMT1, we introduced the gene into a P. antarctica mutant strain, ΔPaEMT1, which lacks MEL biosynthesis ability owing to the deletion of PaEMT1. Using NMR spectroscopy, we identified the biosynthetic product as MEL-A with altered sugar conformation. These results indicate that PtEMT1p catalyzes the sugar conformation of MELs. This is the first report of a gene cluster for the biosynthesis of diastereomer type of MEL.

A convenient photosynthesis of uniformly [14C]-labelled D-glucose, D-fructose and sucrose, and chemical synthesis of methyl-α-D-glucopyranoside ([U-14C]-glucose)

International Nuclear Information System (INIS)

Srinivas, G.; Unny, V.K.P.; Mukkanti, K.; Choudary, B.M.

2013-01-01

This paper describes a convenient procedure for the radiochemical preparation of D-[U- 14 C]-glucose, D-[U- 14 C]-fructose and [U- 14 C]-sucrose with high specific activity by photosynthesis using ‘canna indica’ leaf, [ 14 C]-carbon dioxide and water in presence of light in a closed system. The [ 14 C]-sugars formed were extracted, separated and then purified by paper chromatography. Further, the pure D-[U- 14 C]-glucose obtained was converted to methyl-α-D-glucopyranoside ([U- 14 C]-glucose) by glycosidation with methanol using (i) HCl, the conventional Fischer method (ii) heterogeneous organic cation exchange resin (Amberlite IR-120 (H + )) and (iii) heterogeneous inorganic cation exchanged montmorillonites called metal M +n -monts. The results indicated that the latter in the form of Fe +3 -montmorillonite gave a better yield ( 65%) as compared to others (40–56%). The radiochemical purity of the no-carrier added product was more than 98%. The product retained its specific activity as that of the starting material which is in the range of 250–300 mCi/mmole (9.25–11.1 GBq/mmole), suitable for use as a radiotracer in biochemical investigations. - Graphical abstract: A convenient photosynthesis of uniformly [ 14 C]-labelled D-glucose, D-fructose and sucrose, and chemical synthesis of methyl-α-D-glucopyranoside ([U- 14 C]-glucose)/[ 14 C]–AMG, in short. The photosynthesis of D-[U- 14 C]-glucose, and two other [ 14 C]-sugars (fructose and sucrose) with high specific activity using ‘Canna indica’ leaf, 14 CO 2 and water in presence of light is presented in this paper. Further, the D-[U- 14 C]-glucose obtained was converted to methyl-α-D-glucopyranoside ([U- 14 C]-glucose)/[ 14 C]–AMG having 98% radiochemical purity and specific activity in the range of 250–300 mCi/mmole, using montmorillonites (M +n -monts). Highlights: ► Synthesis of methyl α D-glucopyranoside ([U- 14 C] glucose) has not been reported using M +n -monts. ► M +n -monts are

Promoter de-methylation of cyclin D2 by sulforaphane in prostate cancer cells

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Hsu Anna

2011-10-01

Full Text Available Abstract Sulforaphane (SFN, an isothiocyanate derived from cruciferous vegetables, induces potent anti-proliferative effects in prostate cancer cells. One mechanism that may contribute to the anti-proliferative effects of SFN is the modulation of epigenetic marks, such as inhibition of histone deacetylase (HDAC enzymes. However, the effects of SFN on other common epigenetic marks such as DNA methylation are understudied. Promoter hyper-methylation of cyclin D2, a major regulator of cell cycle, is correlated with prostate cancer progression, and restoration of cyclin D2 expression exerts anti-proliferative effects on LnCap prostate cancer cells. Our study aimed to investigate the effects of SFN on DNA methylation status of cyclin D2 promoter, and how alteration in promoter methylation impacts cyclin D2 gene expression in LnCap cells. We found that SFN significantly decreased the expression of DNA methyltransferases (DNMTs, especially DNMT1 and DNMT3b. Furthermore, SFN significantly decreased methylation in cyclin D2 promoter regions containing c-Myc and multiple Sp1 binding sites. Reduced methlyation of cyclin D2 promoter corresponded to an increase in cyclin D2 transcript levels, suggesting that SFN may de-repress methylation-silenced cyclin D2 by impacting epigenetic pathways. Our results demonstrated the ability of SFN to epigenetically modulate cyclin D2 expression, and provide novel insights into the mechanisms by which SFN may regulate gene expression as a prostate cancer chemopreventive agent.

(a, deletion; b, methylation; c, overall alterations) of SLIT2, ROBO1

Indian Academy of Sciences (India)

author

Table 3. Associations between alterations (a, deletion; b, methylation; c, overall alterations) of SLIT2, ROBO1/ ROBO2. genes in BC. *P≤0.05. SLIT2. ROBO1. ROBO2. SLIT2. ROBO1. ROBO2. SLIT2. ROBO1. ROBO2. D+. D-. D+. D-. D+. D-. M+. M-. M+. M-. M+. M-. A+. A-. A+. A-. A+. A-. SLIT2. D+. -. -. 21. 37. 4. 54. SLIT2. M+.

Apparent molar volumes and apparent molar heat capacities of aqueous adonitol, dulcitol, glycerol, meso-erythritol, myo-inositol, D-sorbitol, and xylitol at temperatures from (278.15 to 368.15) K and at the pressure 0.35 MPa

Energy Technology Data Exchange (ETDEWEB)

Blodgett, M.B. [Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602-5700 (United States); Ziemer, S.P. [Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602-5700 (United States); Brown, B.R. [Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602-5700 (United States); Niederhauser, T.L. [Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602-5700 (United States); Woolley, E.M. [Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602-5700 (United States)]. E-mail: earl_woolley@byu.edu

2007-04-15

Apparent molar volumes V {sub {phi}} were determined for aqueous adonitol, dulcitol, glycerol, meso-erythritol, myo-inositol, D-sorbitol, and xylitol at temperatures from (278.15 to 368.15) K and at the pressure 0.35 MPa, and apparent molar heat capacities C {sub p,{phi}} of the same solutions were determined at temperatures from (278.15 to 363.15) K at the same pressure. Molalities m/(mol . kg{sup -1}) of the solutions were in the range (0.02 {<=} m {<=} 3.2) for adonitol, (0.02 {<=} m {<=} 0.15) for dulcitol, (0.02 {<=} m {<=} 5.0) for glycerol, (0.02 {<=} m {<=} 3.0) for meso-erythritol, (0.02 {<=} m {<=} 0.5) for myo-inositol, (0.02 {<=} m {<=} 2.0) for D-sorbitol, and (0.02 {<=} m {<=} 2.7) for xylitol. A vibrating tube densimeter was used to obtain solution densities and a fixed-cell temperature scanning calorimeter was used to obtain heat capacities. Values of V {sub {phi}} and C {sub p,{phi}} for these sugar alcohols are discussed relative to one another and compared to values from the literature, where available.

Sterol partitioning by HMGR and DXR for routing intermediates toward withanolide biosynthesis.

Science.gov (United States)

Singh, Shefali; Pal, Shaifali; Shanker, Karuna; Chanotiya, Chandan Singh; Gupta, Madan Mohan; Dwivedi, Upendra Nath; Shasany, Ajit Kumar

2014-12-01

Withanolides biosynthesis in the plant Withania somnifera (L.) Dunal is hypothesized to be diverged from sterol pathway at the level of 24-methylene cholesterol. The conversion and translocation of intermediates for sterols and withanolides are yet to be characterized in this plant. To understand the influence of mevalonate (MVA) and 2-C-methyl-d-erythritol-4-phosphate (MEP) pathways on sterols and withanolides biosynthesis in planta, we overexpressed the WsHMGR2 and WsDXR2 in tobacco, analyzed the effect of transient suppression through RNAi, inhibited MVA and MEP pathways and fed the leaf tissue with different sterols. Overexpression of WsHMGR2 increased cycloartenol, sitosterol, stigmasterol and campesterol compared to WsDXR2 transgene lines. Increase in cholesterol was, however, marginally higher in WsDXR2 transgenic lines. This was further validated through transient suppression analysis, and pathway inhibition where cholesterol reduction was found higher due to WsDXR2 suppression and all other sterols were affected predominantly by WsHMGR2 suppression in leaf. The transcript abundance and enzyme analysis data also correlate with sterol accumulation. Cholesterol feeding did not increase the withanolide content compared to cycloartenol, sitosterol, stigmasterol and campesterol. Hence, a preferential translocation of carbon from MVA and MEP pathways was found differentiating the sterols types. Overall results suggested that MVA pathway was predominant in contributing intermediates for withanolides synthesis mainly through the campesterol/stigmasterol route in planta. © 2014 Scandinavian Plant Physiology Society.

UARS PEM Level 2 MEPS V001

Data.gov (United States)

National Aeronautics and Space Administration — The Particle Environment Monitor (PEM) level 2 Medium-Energy Particle Spectrometer (MEPS) daily product contains the electron and proton high-resolution spectral...

Apparent molar volumes and apparent molar heat capacities of aqueous adonitol, dulcitol, glycerol, meso-erythritol, myo-inositol, D-sorbitol, and xylitol at temperatures from (278.15 to 368.15) K and at the pressure 0.35 MPa

International Nuclear Information System (INIS)

Blodgett, M.B.; Ziemer, S.P.; Brown, B.R.; Niederhauser, T.L.; Woolley, E.M.

2007-01-01

Apparent molar volumes V φ were determined for aqueous adonitol, dulcitol, glycerol, meso-erythritol, myo-inositol, D-sorbitol, and xylitol at temperatures from (278.15 to 368.15) K and at the pressure 0.35 MPa, and apparent molar heat capacities C p,φ of the same solutions were determined at temperatures from (278.15 to 363.15) K at the same pressure. Molalities m/(mol . kg -1 ) of the solutions were in the range (0.02 ≤ m ≤ 3.2) for adonitol, (0.02 ≤ m ≤ 0.15) for dulcitol, (0.02 ≤ m ≤ 5.0) for glycerol, (0.02 ≤ m ≤ 3.0) for meso-erythritol, (0.02 ≤ m ≤ 0.5) for myo-inositol, (0.02 ≤ m ≤ 2.0) for D-sorbitol, and (0.02 ≤ m ≤ 2.7) for xylitol. A vibrating tube densimeter was used to obtain solution densities and a fixed-cell temperature scanning calorimeter was used to obtain heat capacities. Values of V φ and C p,φ for these sugar alcohols are discussed relative to one another and compared to values from the literature, where available

Enhanced limonene production in cyanobacteria reveals photosynthesis limitations.

Science.gov (United States)

Wang, Xin; Liu, Wei; Xin, Changpeng; Zheng, Yi; Cheng, Yanbing; Sun, Su; Li, Runze; Zhu, Xin-Guang; Dai, Susie Y; Rentzepis, Peter M; Yuan, Joshua S

2016-12-13

Terpenes are the major secondary metabolites produced by plants, and have diverse industrial applications as pharmaceuticals, fragrance, solvents, and biofuels. Cyanobacteria are equipped with efficient carbon fixation mechanism, and are ideal cell factories to produce various fuel and chemical products. Past efforts to produce terpenes in photosynthetic organisms have gained only limited success. Here we engineered the cyanobacterium Synechococcus elongatus PCC 7942 to efficiently produce limonene through modeling guided study. Computational modeling of limonene flux in response to photosynthetic output has revealed the downstream terpene synthase as a key metabolic flux-controlling node in the MEP (2-C-methyl-d-erythritol 4-phosphate) pathway-derived terpene biosynthesis. By enhancing the downstream limonene carbon sink, we achieved over 100-fold increase in limonene productivity, in contrast to the marginal increase achieved through stepwise metabolic engineering. The establishment of a strong limonene flux revealed potential synergy between photosynthate output and terpene biosynthesis, leading to enhanced carbon flux into the MEP pathway. Moreover, we show that enhanced limonene flux would lead to NADPH accumulation, and slow down photosynthesis electron flow. Fine-tuning ATP/NADPH toward terpene biosynthesis could be a key parameter to adapt photosynthesis to support biofuel/bioproduct production in cyanobacteria.

Subchronic oral toxicity studies with erythritol in mice and rats

NARCIS (Netherlands)

Til, H.P.; Kuper, C.F.; Falke, H.E.; Bär, A.

1996-01-01

Erythritol is a sugar alcohol (polyol) with potential applications as a low-calorie, bulk sweetener. Ingested erythritol is efficiently absorbed and excreted unchanged via the urine since it is not metabolized systemically by the animal or human body. Erythritol was administered to four groups of 10

Synthesis of 14C-labelled α-methyl tyrosine

International Nuclear Information System (INIS)

Rajagopal, S.; Venkatachalam, T.K.; Conway, T.; Diksic, M.

1992-01-01

A new route for the preparation of radioactively labelled α-methyl L-tyrosine is described. The labelling at the α position has been successfully achieved with 14 C-, 11 C- (very preliminary, unpublished), and 3 H-labelled methyl iodide. A detailed report on 14 C-labelling at the α position and the hydrolysis of 4-methoxy α-methyl phenylalanine is presented. The alkylation proceeds via the methylation of the carbanion of N-benzylidene 4-methoxy phenylalanine methyl ester 2. Hydrolysis of 4-O methyl tyrosine to tyrosine by HBr and HI were analysed and used in the optimization of the hydrolysis conditions of 4. Enantiomeric purity of the isolated L-isomer has been found to be 99% as judged by HPLC. Pseudo first-order rate constant for the hydrolysis of 14 C-labelled α-methyl 4-methoxy phenyl alanine methyl ester was determined. Preliminary findings of the 3 H- and 11 C-radiolabelled α-methyl tyrosine (methyl labelled) are also mentioned. For the first time it was shown that α-methyl D,L-tyrosine can be separated into enantiomerically pure α-methyl D- and L-tyrosine using a CHIRALPAK WH column. (author)

Genetic engineering of Synechocystis PCC6803 for the photoautotrophic production of the sweetener erythritol.

Science.gov (United States)

van der Woude, Aniek D; Perez Gallego, Ruth; Vreugdenhil, Angie; Puthan Veetil, Vinod; Chroumpi, Tania; Hellingwerf, Klaas J

2016-04-08

Erythritol is a polyol that is used in the food and beverage industry. Due to its non-caloric and non-cariogenic properties, the popularity of this sweetener is increasing. Large scale production of erythritol is currently based on conversion of glucose by selected fungi. In this study, we describe a biotechnological process to produce erythritol from light and CO2, using engineered Synechocystis sp. PCC6803. By functionally expressing codon-optimized genes encoding the erythrose-4-phosphate phosphatase TM1254 and the erythrose reductase Gcy1p, or GLD1, this cyanobacterium can directly convert the Calvin cycle intermediate erythrose-4-phosphate into erythritol via a two-step process and release the polyol sugar in the extracellular medium. Further modifications targeted enzyme expression and pathway intermediates. After several optimization steps, the best strain, SEP024, produced up to 2.1 mM (256 mg/l) erythritol, excreted in the medium.

Jasmonate-induced biosynthesis of andrographolide in Andrographis paniculata.

Science.gov (United States)

Sharma, Shiv Narayan; Jha, Zenu; Sinha, Rakesh Kumar; Geda, Arvind Kumar

2015-02-01

Andrographolide is a prominent secondary metabolite found in Andrographis paniculata that exhibits enormous pharmacological effects. In spite of immense value, the normal biosynthesis of andrographolide results in low amount of the metabolite. To induce the biosynthesis of andrographolide, we attempted elicitor-induced activation of andrographolide biosynthesis in cell cultures of A. paniculata. This was carried out by using methyl jasmonate (MeJA) as an elicitor. Among the various concentrations of MeJA tested at different time periods, 5 µM MeJA yielded 5.25 times more andrographolide content after 24 h of treatment. The accumulation of andrographolide was correlated with the expression level of known regulatory genes (hmgs, hmgr, dxs, dxr, isph and ggps) of mevalonic acid (MVA) and 2-C-methyl-d-erythritol-4-phosphate (MEP) pathways. These results established the involvement of MeJA in andrographolide biosynthesis by inducing the transcription of its biosynthetic pathways genes. The coordination of isph, ggps and hmgs expression highly influenced the andrographolide biosynthesis. © 2014 Scandinavian Plant Physiology Society.

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

Science.gov (United States)

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.

Biosynthesis of sesquiterpenes in grape berry exocarp of Vitis vinifera L.: evidence for a transport of farnesyl diphosphate precursors from plastids to the cytosol.

Science.gov (United States)

May, Bianca; Lange, B Markus; Wüst, Matthias

2013-11-01

The participation of the mevalonic acid (MVA) and 1-deoxy-d-xylulose 5-phosphate/2-C-methyl-d-erythritol-4-phosphate (DOXP/MEP) pathways in sesquiterpene biosynthesis of grape berries was investigated. There is an increasing interest in this class of terpenoids, since the oxygenated sesquiterpene rotundone was identified as the peppery aroma impact compound in Australian Shiraz wines. To investigate precursor supply pathway utilization, in vivo feeding experiments were performed with the deuterium labeled, pathway specific, precursors [5,5-(2)H2]-1-deoxy-d-xylulose and [5,5-(2)H2]-mevalonic acid lactone. Head Space-Solid Phase Micro Extraction-Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS) analysis of the generated volatile metabolites demonstrated that de novo sesquiterpene biosynthesis is mainly located in the grape berry exocarp (skin), with no detectable activity in the mesocarp (flesh) of the Lemberger variety. Interestingly, precursors from both the (primarily) cytosolic MVA and plastidial DOXP/MEP pathways were incorporated into grape sesquiterpenes in the varieties Lemberger, Gewürztraminer and Syrah. Our labeling data provide evidence for a homogenous, cytosolic pool of precursors for sesquiterpene biosynthesis, indicating that a transport of precursors occurs mostly from plastids to the cytosol. The labeling patterns of the sesquiterpene germacrene D were in agreement with a cyclization mechanism analogous to that of a previously cloned enantioselective (R)-germacrene D synthase from Solidago canadensis. This observation was subsequently confirmed by enantioselective GC-MS analysis demonstrating the exclusive presence of (R)-germacrene D, and not the (S)-enantiomer, in grape berries. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Role of a Newly Identified Isomerase From Yarrowia lipolytica in Erythritol Catabolism

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Aleksandra M. Mirończuk

2018-05-01

Full Text Available Erythritol is a natural sweetener produced by microorganisms as an osmoprotectant. It belongs to the group of polyols and it can be utilized by the oleaginous yeast Yarrowia lipolytica. Despite the recent identification of the transcription factor of erythritol utilization (EUF1, the metabolic pathway of erythritol catabolism remains unknown. In this study we identified a new gene, YALI0F01628g, involved in erythritol assimilation. In silico analysis showed that YALI0F01628g is a putative isomerase and it is localized in the same region as EUF1. qRT-PCR analysis of Y. lipolytica showed a significant increase in YALI0F01628g expression during growth on erythritol and after overexpression of EUF1. Moreover, the deletion strain ΔF01628 showed significantly impaired erythritol assimilation, whereas synthesis of erythritol remained unchanged. The results showed that YALI0F1628g is involved in erythritol assimilation; thus we named the gene EYI1. Moreover, we suggest the metabolic pathway of erythritol assimilation in yeast Y. lipolytica.

Vitamin D Deficiency in Patients with Tuberculosis

International Nuclear Information System (INIS)

Iftikhar, R.; Kamran, S. M.; Haider, E.; Qadir, A.; Usman, H. B.

2013-01-01

Objective: To determine the frequency and association of Vitamin D deficiency in patients with tuberculosis. Study Design: Case control study. Place and Duration of Study: Medical Department, Combined Military Hospital, Kharian, from July 2010 to June 2012. Methodology: One hundred and five outdoor patients of tuberculosis were selected with 255 gender matched controls. Tuberculosis was diagnosed by presence of acid fast bacilli in sputum smears, positive culture for Mycobacterium tuberculosis or demonstration of chronic caseating granulomatous inflammation in tissue specimens. Controls were drawn randomly from general population. Serum 25 hydroxyvitamin D [25 (OH) D3] levels < 25 ng/ml was considered Vitamin D deficiency. The results were analyzed on SPSS version 17. Results: Mean Vitamin D levels were 23.23 A+- 6.81 ng/ml in cases, 29.27 A+- 8.89 ng/ml in controls (p < 0.0001). Vitamin D deficiency was found in 57% of cases and 33% controls (p < 0.0001). Mean Vitamin D levels were significantly lower in females with tuberculosis (20.84 ng/ml) as compared to males (25.03 ng/ml, p = 0.002). Mean BMI in patients of tuberculosis with Vitamin D deficiency were 19.51 A+- 1.77 kg/m2 and in patients with normal Vitamin D were 21.65 A+- 1.79 kg/m2 (p < 0.0001). Mean Vitamin D levels in patients with multi-drug resistant tuberculosis was lower to a mean of 15.41 A+- 4.67 ng/ml (p < 0.0001). Conclusion: There is significant deficiency of Vitamin D in patients with tuberculosis as compared to controls. This deficiency is more pronounced in females, individuals with low BMI, extra pulmonary and MDR tuberculosis. (author)

Increased amounts of D-enantiomer dependent on alkaline concentration in the synthesis of L-[methyl-11C]methionine

International Nuclear Information System (INIS)

Ishiwata, Kiichi; Ido, Tatsuo; Vaalburg, W.

1988-01-01

The presence of D-enantiomer in L-[methyl- 11 C]methionine prepared from [ 11 C]CH 3 I and L-homocysteine thiolactone, was measured by high performance liquid chromatography using a reverse-phase column with an eluent containing L-proline and cupric acetate. The amount of D-enantiomer increased with concentration of NaOH used. The reaction time, 2-10 min, and the reaction temperature, 40 0 -80 0 C, have only minor effect on the formation of D-enantiomer. No significant difference was found for three different lots of L-homocysteine thiolactone. At the highest concentration investigated, 1.0 M NaOH in 50% aqueous acetone, the percentage of D-enantiomer was found to be 7.7%. With 0.025 M NaOH used only 2.1% was measured. When L-[methyl- 11 C]methionine was incubated in 1.0 M NaOH, no conversion of L- into D-enantiomer was observed. (author)

Thermophysical Characterization of MgCl2·6H2O, Xylitol and Erythritol as Phase Change Materials (PCM) for Latent Heat Thermal Energy Storage (LHTES)

Science.gov (United States)

Höhlein, Stephan; König-Haagen, Andreas; Brüggemann, Dieter

2017-01-01

The application range of existing real scale mobile thermal storage units with phase change materials (PCM) is restricted by the low phase change temperature of 58 ∘C for sodium acetate trihydrate, which is a commonly used storage material. Therefore, only low temperature heat sinks like swimming pools or greenhouses can be supplied. With increasing phase change temperatures, more applications like domestic heating or industrial process heat could be operated. The aim of this study is to find alternative PCM with phase change temperatures between 90 and 150 ∘C. Temperature dependent thermophysical properties like phase change temperatures and enthalpies, densities and thermal diffusivities are measured for the technical grade purity materials xylitol (C5H12O5), erythritol (C4H10O4) and magnesiumchloride hexahydrate (MCHH, MgCl2·6H2O). The sugar alcohols xylitol and erythritol indicate a large supercooling and different melting regimes. The salt hydrate MgCl2·6H2O seems to be a suitable candidate for practical applications. It has a melting temperature of 115.1 ± 0.1 ∘C and a phase change enthalpy of 166.9 ± 1.2 J/g with only 2.8 K supercooling at sample sizes of 100 g. The PCM is stable over 500 repeated melting and solidification cycles at differential scanning calorimeter (DSC) scale with only small changes of the melting enthalpy and temperature. PMID:28772806

Thermophysical Characterization of MgCl2·6H2O, Xylitol and Erythritol as Phase Change Materials (PCM for Latent Heat Thermal Energy Storage (LHTES

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Stephan Höhlein

2017-04-01

Full Text Available The application range of existing real scale mobile thermal storage units with phase change materials (PCM is restricted by the low phase change temperature of 58 ∘ C for sodium acetate trihydrate, which is a commonly used storage material. Therefore, only low temperature heat sinks like swimming pools or greenhouses can be supplied. With increasing phase change temperatures, more applications like domestic heating or industrial process heat could be operated. The aim of this study is to find alternative PCM with phase change temperatures between 90 and 150 ∘ C . Temperature dependent thermophysical properties like phase change temperatures and enthalpies, densities and thermal diffusivities are measured for the technical grade purity materials xylitol (C 5 H 12 O 5 , erythritol (C 4 H 10 O 4 and magnesiumchloride hexahydrate (MCHH, MgCl 2 · 6H 2 O. The sugar alcohols xylitol and erythritol indicate a large supercooling and different melting regimes. The salt hydrate MgCl 2 · 6H 2 O seems to be a suitable candidate for practical applications. It has a melting temperature of 115.1 ± 0.1 ∘ C and a phase change enthalpy of 166.9 ± 1.2 J / g with only 2.8 K supercooling at sample sizes of 100 g . The PCM is stable over 500 repeated melting and solidification cycles at differential scanning calorimeter (DSC scale with only small changes of the melting enthalpy and temperature.

Synthesis of [methyl-14C]crotonobetaine from DL-[methyl-14C]carnitine

International Nuclear Information System (INIS)

Loester, H.; Seim, H.

1996-01-01

The causes of carnitine deficiency syndromes are not completely understood, but decomposition of L-carnitine in vivo is likely to be involved. Carnitine is metabolized to γ-butyrobetaine, and crotonobetaine is probably an intermediate in this pathway. To validate experimentally the precursor-product relationship between the three physiologically occuring γ-betaines - L-carnitine, crotonobetaine, γ-butyrobetaine - labelling with stable or radioactive isotopes became necessary. Methyl-labelled carnitine isomers (L(-)-, D(+)- or DL-) or γ-butyrobetaine can be easily synthesized by methylation of 4-amino-3-hydroxybutyric acid isomers or 4-aminobutyric acid, respectively. Because of problems with the 4-aminocrotonic acid, we synthesized labelled crotonbetaine from labelled carnitine. Thus, DL-[methyl- 14 C]carnitine was dehydrated by reaction with concentrated sulfuric acid. After removal of the latter the products were separated and purified by ion exchange chromatography on DOWEX 50 WX8 (200 - 400 mesh) and gradient elution with hydrochloric acid. In addition to the labelled main product [methyl- 14 C]crotonobetaine (yield about 50 %), [methyl- 14 C]glycine betaine and [methyl- 14 C]acetonyl-trimethylammonium (ATMA) were formed. The end products were identified by combined thin layer chromatography/autoradiography and quantified by liquid scintillation counting. (Author)

Preparation and thermal properties of short carbon fibers/erythritol phase change materials

International Nuclear Information System (INIS)

Zhang, Qiang; Luo, Zhiling; Guo, Qilin; Wu, Gaohui

2017-01-01

Highlights: • Short carbon fiber (SCF)/erythritol phase change composites (PCCs) are prepared and tested. • The PCCs possess large heat capacity and high thermal conductivity. • The size of SCFs can affect thermal conductivities of SCF/erythritol PCCs. • The size of SCFs has negligible effects on melting points and enthalpies. • The SCF/erythritol PCCs show good temperature-regulated property. - Abstract: The thermal properties of the short carbon fibers (SCFs) filled erythritol phase change composites (PCCs) were investigated experimentally. The samples were prepared with different mass loadings of two kinds of SCFs, 1%, 2%, 4%, 7% and 10%. The melting points and phase change enthalpies were measured by differential scanning calorimeter (DSC). The effects of SCFs on the melting points are relatively small but the enthalpies were reduced with the loadings of SCFs. The greatest loss of enthalpies is 11.3% for composites filled with 10% SCFs. The thermal conductivities increased with the loadings of SCFs but not linearly. The highest thermal conductivity is 3.92 W/(m⋅K) for the composites with 10% longer SCFs, which was enhanced by 407.8% compared to pure erythritol (0.77 W/(m⋅K)). Composites filled with longer SCFs possess higher thermal conductivity and the mechanisms were discussed. A simple setup was made to test the temperature-regulated property of these materials. These include pure erythritol and phase change composites with different loading of SCFs. The PCCs have shown good application potential and the longer SCFs can lead to the better performance of PCCs.

Virus-Induced Silencing of Key Genes Leads to Differential Impact on Withanolide Biosynthesis in the Medicinal Plant, Withania somnifera.

Science.gov (United States)

Agarwal, Aditya Vikram; Singh, Deeksha; Dhar, Yogeshwar Vikram; Michael, Rahul; Gupta, Parul; Chandra, Deepak; Trivedi, Prabodh Kumar

2018-02-01

Withanolides are a collection of naturally occurring, pharmacologically active, secondary metabolites synthesized in the medicinally important plant, Withania somnifera. These bioactive molecules are C28-steroidal lactone triterpenoids and their synthesis is proposed to take place via the mevalonate (MVA) and 2-C-methyl-d-erythritol-4-phosphate (MEP) pathways through the sterol pathway using 24-methylene cholesterol as substrate flux. Although the phytochemical profiles as well as pharmaceutical activities of Withania extracts have been well studied, limited genomic information and difficult genetic transformation have been a major bottleneck towards understanding the participation of specific genes in withanolide biosynthesis. In this study, we used the Tobacco rattle virus (TRV)-mediated virus-induced gene silencing (VIGS) approach to study the participation of key genes from MVA, MEP and triterpenoid biosynthesis for their involvement in withanolide biosynthesis. TRV-infected W. somnifera plants displayed unique phenotypic characteristics and differential accumulation of total Chl as well as carotenoid content for each silenced gene suggesting a reduction in overall isoprenoid synthesis. Comprehensive expression analysis of putative genes of withanolide biosynthesis revealed transcriptional modulations conferring the presence of complex regulatory mechanisms leading to withanolide biosynthesis. In addition, silencing of genes exhibited modulated total and specific withanolide accumulation at different levels as compared with control plants. Comparative analysis also suggests a major role for the MVA pathway as compared with the MEP pathway in providing substrate flux for withanolide biosynthesis. These results demonstrate that transcriptional regulation of selected Withania genes of the triterpenoid biosynthetic pathway critically affects withanolide biosynthesis, providing new horizons to explore this process further, in planta.

Synthesis of [5,6-13C2, 1-14C]olivetolic acid, methyl [1'-13C]olivetolate and [5,6-13C2, 1-14C]cannabigerolic acid

International Nuclear Information System (INIS)

Porwoll, J.P.; Leete, E.

1985-01-01

Potential advanced intermediates in the biosynthesis of delta 9 -tetrahydrocannabinol, the major psychoactive principle of marijuana, have been synthesized labeled with two contiguous 13 C atoms and 14 C. Methyl [5,6- 13 C 2 , 1- 14 C]olivetolate was prepared from lithium [ 13 C 2 ]acetylide and dimethyl [2- 14 C]malonate. Reaction with geranyl bromide afforded methyl [5,6- 13 C 2 , 1- 14 C]cannabigerolate, and hydrolysis of these methyl esters with lithium propyl mercaptide yielded the corresponding labeled acids. The 13 C- 13 C couplings observable in the 13 C NMR spectra of these 13 C-enriched compounds and their synthetic precursors are recorded. Methyl [1'- 14 C]olivetolate was prepared from 13 CO 2 to confirm assignments of the 13 C chemical shifts in the pentyl side chain of these compounds. (author)

5-Azacytidine combined with 2,4-D improves somatic embryogenesis of Acca sellowiana (O. Berg) Burret by means of changes in global DNA methylation levels.

Science.gov (United States)

Fraga, Hugo P F; Vieira, Leila N; Caprestano, Clarissa A; Steinmacher, Douglas A; Micke, Gustavo A; Spudeit, Daniel A; Pescador, Rosete; Guerra, Miguel P

2012-12-01

DNA methylation is an epigenetic regulatory mechanism of gene expression which can be associated with developmental phases and in vitro morphogenetic competence in plants. The present work evaluated the effects of 5-azacytidine (AzaC) and 2,4-dichlorophenoxyacetic acid (2,4-D) on Acca sellowiana somatic embryogenesis (SE) and global DNA methylation levels by high-performance liquid chromatography mass spectrometry (HPLC/MS/MS). 2,4-D-free treatments revealed no somatic embryo formation in both accessions tested. Treatments supplemented with 2,4-D pulse plus AzaC in the culture medium resulted in increased embryo formation. In AzaC-free treatment, HPLC/MS/MS analysis showed a gradual increase in methylation levels in cultures of both accessions tested during SE induction. Treatment with AzaC and 2,4-D-free resulted in a marked decrease in methylation for both accessions, ranging from 37.6 to 20.8 %. In treatment with 2,4-D and AzaC combined, the 85 accession showed increasing global methylation levels. Otherwise, the 101X458 accession, in the same treatment, showed a decrease between 10 and 20 days, followed by an increase after 30 days (39.5, 36.2 and 41.6 %). These results indicate that 2,4-D pulse combined with AzaC improves SE induction. However, the conversion phase showed that although positively influencing SE induction, AzaC had a dysregulatory effect on the stage of autotrophic plant formation, resulting in significantly lower conversion rates. The results suggest that DNA methylation dramatically influences SE in Acca sellowiana, and global DNA methylation dynamics are related to morphogenetic response. 5-Azacytidine combined with 2,4-D increases the number of Acca sellowiana somatic embryos. Global DNA methylation is directly affected by these compounds.

Medidas de control de tuberculosis en una institución de salud de Bogotá D.C

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Alba I. Muñoz-Sánchez

2016-02-01

Full Text Available Resumen Objetivo: evaluar la implementación de medidas de control, de tipo administrativo, ambiental y de protección respiratoria, de la infección de tuberculosis en un hospital de III nivel de atención en la ciudad de Bogotá D.C. Metodología: estudio de tipo descriptivo, transversal. Para la recolección de datos se aplicó una herramienta de autorreporte a 158 trabajadores de la salud del hospital, se realizó una entrevista estructurada al responsable del programa institucional de control de tuberculosis y una visita de observación de un experto en salud y seguridad laboral a las diferentes áreas de trabajo, para indagar por la implementación de medidas de control de infección de tuberculosis en la institución. Resultados: el responsable del programa institucional de control de tuberculosis y 158 trabajadores de la salud del hospital objeto de estudio reportaron una deficiente implementación de medidas de control de tuberculosis, de tipo administrativo, ambiental y de protección respiratoria en la institución, lo cual fue corroborado por el experto. Conclusiones: la deficiente implementación de medidas de control de infección de tuberculosis en instituciones de la salud, y algunas condiciones de trabajo presentes pueden favorecer la exposición ocupacional de los trabajadores de la salud al Mycobacterium Tuberculosis. Abstract Objective: to evaluate the implementation of tuberculosis infection control measures in administrative, environmental and respiratory protection equipment in a third level hospital in Bogota D.C. Methodology: a descriptive, cross-sectional study. Data were collected through a self-reporting instrument applied on 158 health care workers. The chief officer of the institutional program for tuberculosis control participated in a structured interview. In addition, an expert in occupational health and safety conducted an observational visit to the different workplaces in order to inquire on the implementation

Multi-targeted mechanisms underlying the endothelial protective effects of the diabetic-safe sweetener erythritol.

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Daniëlle M P H J Boesten

Full Text Available Diabetes is characterized by hyperglycemia and development of vascular pathology. Endothelial cell dysfunction is a starting point for pathogenesis of vascular complications in diabetes. We previously showed the polyol erythritol to be a hydroxyl radical scavenger preventing endothelial cell dysfunction onset in diabetic rats. To unravel mechanisms, other than scavenging of radicals, by which erythritol mediates this protective effect, we evaluated effects of erythritol in endothelial cells exposed to normal (7 mM and high glucose (30 mM or diabetic stressors (e.g. SIN-1 using targeted and transcriptomic approaches. This study demonstrates that erythritol (i.e. under non-diabetic conditions has minimal effects on endothelial cells. However, under hyperglycemic conditions erythritol protected endothelial cells against cell death induced by diabetic stressors (i.e. high glucose and peroxynitrite. Also a number of harmful effects caused by high glucose, e.g. increased nitric oxide release, are reversed. Additionally, total transcriptome analysis indicated that biological processes which are differentially regulated due to high glucose are corrected by erythritol. We conclude that erythritol protects endothelial cells during high glucose conditions via effects on multiple targets. Overall, these data indicate a therapeutically important endothelial protective effect of erythritol under hyperglycemic conditions.

Gut hormone secretion, gastric emptying, and glycemic responses to erythritol and xylitol in lean and obese subjects.

Science.gov (United States)

Wölnerhanssen, Bettina K; Cajacob, Lucian; Keller, Nino; Doody, Alison; Rehfeld, Jens F; Drewe, Juergen; Peterli, Ralph; Beglinger, Christoph; Meyer-Gerspach, Anne Christin

2016-06-01

With the increasing prevalence of obesity and a possible association with increasing sucrose consumption, nonnutritive sweeteners are gaining popularity. Given that some studies indicate that artificial sweeteners might have adverse effects, alternative solutions are sought. Xylitol and erythritol have been known for a long time and their beneficial effects on caries prevention and potential health benefits in diabetic patients have been demonstrated in several studies. Glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) are released from the gut in response to food intake, promote satiation, reduce gastric emptying (GE), and modulate glucose homeostasis. Although glucose ingestion stimulates sweet taste receptors in the gut and leads to incretin and gastrointestinal hormone release, the effects of xylitol and erythritol have not been well studied. Ten lean and 10 obese volunteers were given 75 g of glucose, 50 g of xylitol, or 75 g of erythritol in 300 ml of water or placebo (water) by a nasogastric tube. We examined plasma glucose, insulin, active GLP-1, CCK, and GE with a [(13)C]sodium acetate breath test and assessed subjective feelings of satiation. Xylitol and erythritol led to a marked increase in CCK and GLP-1, whereas insulin and plasma glucose were not (erythritol) or only slightly (xylitol) affected. Both xylitol and erythritol induced a significant retardation in GE. Subjective feelings of appetite were not significantly different after carbohydrate intake compared with placebo. In conclusion, acute ingestion of erythritol and xylitol stimulates gut hormone release and slows down gastric emptying, whereas there is no or only little effect on insulin release. Copyright © 2016 the American Physiological Society.

Distribution of Insertion- and Deletion-Associated Genetic Polymorphisms among Four Mycobacterium tuberculosis Phospholipase C Genes and Associations with Extrathoracic Tuberculosis: a Population-Based Study

OpenAIRE

Kong, Y.; Cave, M. D.; Yang, D.; Zhang, L.; Marrs, C. F.; Foxman, B.; Bates, J. H.; Wilson, F.; Mukasa, L. N.; Yang, Z. H.

2005-01-01

The Mycobacterium tuberculosis genome contains four phospholipase C (PLC)-encoding genes, designated plcA, plcB, plcC, and plcD, respectively. Each of the four genes contributes to the overall PLC activity of M. tuberculosis. PLC is hypothesized to contribute to M. tuberculosis virulence. Infection of M. tuberculosis strains carrying a truncated plcD gene is associated with the occurrence of extrathoracic tuberculosis. However, whether the other three plc genes are also associated with extrat...

Synthesis of (R,S)-[2,3-13C2]-1-(1'-methyl-2'-pyrrolidinyl)propan-2-one; {(R,S)-[2',3'-13C2]hygrinePound right bracePound

International Nuclear Information System (INIS)

Abraham, T.W.; Leete, Edward

1996-01-01

2-Ethoxy-1-methyl-5-pyrrolidinone (1) was reacted with ethyl [3,4- 13 C 2 ]-acetoacetate (2) in the presence of TiCl 4 to give ethyl [3,4- 13 C 2 ]-2-(1'-methyl-5'-oxo-2'-pyrrolidinyl)-3-oxobutanoate (3) in 85% yield. Decarboethoxylation of ethyl [3,4- 13 C 2 ]-2-(1'-methyl-5'-oxo-2'-pyrrolidinyl)-3-oxobutan-oate (3) was accomplished using NaCl and H 2 O in DMSO to give (R,S)-[2,3- 13 C 2 ]-1-(1'-methyl-5'-oxo-2'-pyrrolidinyl)propan-2-o ne (4) in 91% yield. Protection of the ketone as a ketal (ethylene glycol, H + ), followed by reduction of the amide to the amine using LiAlH 4 and subsequent deprotection of the ketal gave (R,S)-[2,3- 13 C 2 ]-1-(1'-methyl-2'-pyrrolidinyl)propan-2-one ((R,s)-[2', 3'- 13 C 2 ]Hygrine) (8) in 78% yield. (61% overall yield from ethyl [3,4- 13 C 2 ]acetoacetate). (Author)

Relationship between methylation status of vitamin D-related genes, vitamin D levels, and methyl-donor biochemistry

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Emma Louise Beckett

2016-12-01

Full Text Available Vitamin D is known for its role in the regulation of gene expression via the vitamin D receptor, a nuclear transcription factor. More recently, a role for vitamin D in regulating DNA methylation has been identified as an additional mechanism of modulation of gene expression. How methylation status influences vitamin D metabolism and response pathways is not yet clear. Therefore, we aimed to assess the relationship between plasma 25-hydroxycholecalciferol (25(OHD and the methylation status of vitamin D metabolism enzyme genes (CYP2R1, CYP27B1 and CYP24A1 and the vitamin D receptor gene (VDR. This analysis was conducted in the context of dietary vitamin D, and background methyl donor related biochemistry, with adjustment for several dietary and lifestyle variables. Percentage methylation at CpG sites was assessed in peripheral blood cells using methylation sensitive and dependent enzymes and qPCR. Standard analytical techniques were used to determine plasma 25(OHD and homocysteine, and serum folate and B12, with the relationship to methylation status assessed using multi-variable regression analysis. CYP2R1 and VDR methylation were found to be independent predictors of plasma 25(OHD, when adjusted for vitamin D intake and other lifestyle variables. CYP24A1 was related to plasma 25(OHD directly, but not in the context of vitamin D intake. Methyl-group donor biochemistry was associated with the methylation status of some genes, but did not alter the relationship between methylation and plasma 25(OHD. Modulation of methylation status of CYP2R1, CYP24A1 and VDR in response to plasma 25(OHD may be part of feedback loops involved in maintaining vitamin D homeostasis, and may explain a portion of the variance in plasma 25(OHD levels in response to intake and sun exposure. Methyl-group donor biochemistry, while a potential independent modulator, did not alter this effect.

Identification of AICP as a GluN2C-Selective N-Methyl-d-Aspartate Receptor Superagonist at the GluN1 Glycine Site

DEFF Research Database (Denmark)

Jessen, Maja; Frederiksen, Kristen; Yi, Feng

2017-01-01

N-methyl-d-aspartate (NMDA)-type ionotropic glutamate receptors mediate excitatory neurotransmission in the central nervous system and are critically involved in brain function. NMDA receptors are also implicated in psychiatric and neurological disorders and have received considerable attention....../2A-D), in which DCS is a superagonist at GluN2C-containing receptors compared with glycine and a partial agonist at GluN2B-containing receptors. Here, we identify (R)-2-amino-3-(4-(2-ethylphenyl)-1H-indole-2-carboxamido)propanoic acid (AICP) as a glycine site agonist with unique GluN2-dependent...

Liberia MEP WMS

Data.gov (United States)

US Agency for International Development — L-MEP WMS provides USAID, Implementing Partners, and L-MEP Staff the ability to view M view sector specific trend or base information; and answer questions about...

Thermodynamic behavior of erythritol in aqueous solutions and in gelatine gels and its quantification

International Nuclear Information System (INIS)

Tyapkova, Oxana; Bader-Mittermaier, Stephanie; Schweiggert-Weisz, Ute

2013-01-01

Highlights: • Differential scanning calorimetry as a method to determine erythritol crystallization. • Determination of crystallization using solution enthalpy. • Erythritol crystallization influenced by area of air–water-interfaces. • DSC method is applicable for both aqueous solutions and gels. • Adaption of DSC method to other, more complex food matrices is possible. - Abstract: As crystallization of erythritol can cause a sandy mouth-feel in sugar-free products, strategies to avoid crystallization or adaption of food formulation should be elucidated. However, until now erythritol crystallization was only quantified in aqueous solutions, but not in model food systems. Differential scanning calorimetry (DSC) is a simple method for the quantification of phase transition in various systems. However, no methods for the quantification of crystallization from aqueous systems based on DSC have been published until now. In the present study DSC was found to be suitable for the quantification of crystallization using supersaturated aqueous solutions of erythritol and erythritol containing gelatine gels for the first time. The developed method was validated by comparing the crystallization values determined by gravimetric measurement of erythritol crystals and the values obtained by DSC. No significant differences (p < 0.05) have been obtained between the results of the two methods if an appropriate design of measurements was applied. Additionally, the method was adapted to gelatine gels to elucidate the transferability to model food systems. Hence, the method is suitable for quantification of the amount of erythritol crystals present in aqueous solutions and gels, respectively

Acute and sub-chronic oral toxicity studies of erythritol in Beagle dogs.

Science.gov (United States)

Eapen, Alex K; de Cock, Peter; Crincoli, Christine M; Means, Charlotte; Wismer, Tina; Pappas, Christopher

2017-07-01

Polyols, also known as sugar alcohols, are widely used in the formulation of tooth-friendly and reduced-calorie foods. Considering the significant health benefits of polyols in products formulated for human use, there is increased interest in evaluating potential uses in companion animal applications. Erythritol and xylitol are two polyols which are currently widely used in products ranging from reduced-sugar foods to personal care and cosmetics. Published studies have shown that both of these compounds are well-tolerated in rodents. Their toxicity profiles differ when comparing canine safety data. Doses of xylitol as low as 0.15 g/kg-BW in dogs can result in life-threatening hypoglycemia and acute liver failure, whereas erythritol is well-tolerated in dogs with reported No Adverse Effect Levels upwards of 5 g/kg-BW/day in repeat-dose studies. While pivotal studies substantiating the safe use of erythritol in humans have been published, there are limited published studies to support the safe use of erythritol in dogs. Here we present the results of an acute oral and a sub-chronic oral toxicity study in Beagle dogs. Given the potential health benefits of oral products formulated with erythritol and the data presented herein substantiating the safe use in dogs, erythritol can be safely used in products for canines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Peptidoglycan-associated outer membrane protein Mep45 of rumen anaerobe Selenomonas ruminantium forms a non-specific diffusion pore via its C-terminal transmembrane domain.

Science.gov (United States)

Kojima, Seiji; Hayashi, Kanako; Tochigi, Saeko; Kusano, Tomonobu; Kaneko, Jun; Kamio, Yoshiyuki

2016-10-01

The major outer membrane protein Mep45 of Selenomonas ruminantium, an anaerobic Gram-negative bacterium, comprises two distinct domains: the N-terminal S-layer homologous (SLH) domain that protrudes into the periplasm and binds to peptidoglycan, and the remaining C-terminal transmembrane domain, whose function has been unknown. Here, we solubilized and purified Mep45 and characterized its function using proteoliposomes reconstituted with Mep45. We found that Mep45 forms a nonspecific diffusion channel via its C-terminal region. The channel was permeable to solutes smaller than a molecular weight of roughly 600, and the estimated pore radius was 0.58 nm. Truncation of the SLH domain did not affect the channel property. On the basis of the fact that Mep45 is the most abundant outer membrane protein in S. ruminantium, we conclude that Mep45 serves as a main pathway through which small solutes diffuse across the outer membrane of this bacterium.

Optimization of a low-cost hyperosmotic medium and establishing the fermentation kinetics of erythritol production by Yarrowia lipolytica from crude glycerol.

Science.gov (United States)

Yang, Li-Bo; Zhan, Xiao-Bei; Zhu, Li; Gao, Min-Jie; Lin, Chi-Chung

2016-05-18

The production of erythritol by Yarrowia lipolytica from low-cost substitutable substrates for high yield was investigated. Crude glycerol, urea, and NaCl related to osmotic pressure were the most significant factors affecting erythritol production. An artificial neural network model and genetic algorithm were used to search the optimal composition of the significant factors and locate the resulting erythritol yield. Medium with 232.39 g/L crude glycerol, 1.57 g/L urea, and 31.03 g/L NaCl led to predictive maximum erythritol concentration of 110.7 g/L. The erythritol concentration improved from 50.4 g/L to 109.2 g/L with the optimized medium, which was reproducible. Erythritol fermentation kinetics were investigated in a batch system. Multistep fermentation kinetic models with hyperosmotic inhibitory effects were developed. The resulting mathematical equations provided a good description of temporal variations such as microbial growth (X), substrate consumption (S), and product formation (P) in erythritol fermentation. The accordingly derived model is the first reported model for fermentative erythritol production from glycerol, providing useful information to optimize the growth of Y. lipolytica and contributing visual description for the erythritol fermentation process under high osmotic pressure, as well as improvement of productivity and efficiency.

Erythritol Is More Effective Than Xylitol and Sorbitol in Managing Oral Health Endpoints

Directory of Open Access Journals (Sweden)

Peter de Cock

2016-01-01

Full Text Available Objective. To provide a comprehensive overview of published evidence on the impact of erythritol, a noncaloric polyol bulk sweetener, on oral health. Methods. A literature review was conducted regarding the potential effects of erythritol on dental plaque (biofilm, dental caries, and periodontal therapy. The efficacy of erythritol on oral health was compared with xylitol and sorbitol. Results. Erythritol effectively decreased weight of dental plaque and adherence of common streptococcal oral bacteria to tooth surfaces, inhibited growth and activity of associated bacteria like S. mutans, decreased expression of bacterial genes involved in sucrose metabolism, reduced the overall number of dental caries, and served as a suitable matrix for subgingival air-polishing to replace traditional root scaling. Conclusions. Important differences were reported in the effect of individual polyols on oral health. The current review provides evidence demonstrating better efficacy of erythritol compared to sorbitol and xylitol to maintain and improve oral health.

Stereoselective synthesis of the Halaven C14-C26 fragment from D-quinic acid: crystallization-induced diastereoselective transformation of an α-methyl nitrile.

Science.gov (United States)

Belanger, Francis; Chase, Charles E; Endo, Atsushi; Fang, Francis G; Li, Jing; Mathieu, Steven R; Wilcoxen, Annie Z; Zhang, Huiming

2015-04-20

Crystallization-induced diastereoselective transformation (CIDT) of an α-methyl nitrile completes an entirely non-chromatographic synthesis of the halichondrin B C14-C26 stereochemical array. The requisite α-methyl nitrile substrate is derived from D-quinic acid through a series of substrate-controlled stereoselective reactions via a number of crystalline intermediates that benefit from a rigid polycyclic template. Therefore, all four stereogenic centers in the Halaven C14-C26 fragment were derived from the single chiral source D-quinic acid. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of [methyl-{sup 14}C]crotonobetaine from DL-[methyl-{sup 14}C]carnitine

Energy Technology Data Exchange (ETDEWEB)

Loester, H.; Seim, H. [Leipzig Univ. (Germany). Inst. of Clinical Chemistry and Pathobiochemistry

1996-02-01

The causes of carnitine deficiency syndromes are not completely understood, but decomposition of L-carnitine in vivo is likely to be involved. Carnitine is metabolized to {gamma}-butyrobetaine, and crotonobetaine is probably an intermediate in this pathway. To validate experimentally the precursor-product relationship between the three physiologically occuring {gamma}-betaines - L-carnitine, crotonobetaine, {gamma}-butyrobetaine - labelling with stable or radioactive isotopes became necessary. Methyl-labelled carnitine isomers (L(-)-, D(+)- or DL-) or {gamma}-butyrobetaine can be easily synthesized by methylation of 4-amino-3-hydroxybutyric acid isomers or 4-aminobutyric acid, respectively. Because of problems with the 4-aminocrotonic acid, we synthesized labelled crotonbetaine from labelled carnitine. Thus, DL-[methyl-{sup 14}C]carnitine was dehydrated by reaction with concentrated sulfuric acid. After removal of the latter the products were separated and purified by ion exchange chromatography on DOWEX 50 WX8 (200 - 400 mesh) and gradient elution with hydrochloric acid. In addition to the labelled main product [methyl-{sup 14}C]crotonobetaine (yield about 50 %), [methyl-{sup 14}C]glycine betaine and [methyl-{sup 14}C]acetonyl-trimethylammonium (ATMA) were formed. The end products were identified by combined thin layer chromatography/autoradiography and quantified by liquid scintillation counting. (Author).

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.

Science.gov (United States)

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

N-[11C]methyl-3,4-methylenedioxyamphetamine (Ecstasy) and 2-methyl-N-[11C]methyl-4,5-methylenedioxyamphetamine. Synthesis and biodistribution studies

International Nuclear Information System (INIS)

Patt, M.; Machulla, H.J.; Guendisch, D.; Kovar, K.A.; Wuellner, U.; Blocher, A.

1999-01-01

In order to evaluate the neurobiological mechanism causing the psychogenic effects of methylenedioxy-derivatives of amphetamine, the carbon-11 labeled analogues of 3,4-methylenedioxymethamphetamine (MDMA), 2 and 2,N-dimethyl-4,5-methylenedioxyamphetamine (MADAM-6) 4 were prepared for application in in-vivo PET studies by methylation of 3,4-methylenedioxyamphetamine (MDA) 1 and 2-methyl-4,5-methylenedioxyamphetamine 3 with [ 11 C]CH 3 I. The radiochemical yield was determined in dependence on time, temperature and amount of precursor. The best conditions for a fast labeling reaction with carbon-11 on a preparative scale were found to be a reaction time of 10 min using 1 mg of the corresponding dimethyl-precursors 1 or 3, thus obtaining radiochemical yields of 60% (based on produced [ 11 C]CH 3 I). Biodistribution studies were performed in rats, a high brain to blood ratio of 7.5 was observed for [ 11 C]MDMA in contrast to a ratio of 3.7 for [ 11 C]MADAM-6. (author)

CCL2 responses to Mycobacterium tuberculosis are associated with disease severity in tuberculosis.

Directory of Open Access Journals (Sweden)

Zahra Hasan

Full Text Available BACKGROUND: Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFNgamma, TNFalpha and downmodulatory IL10 play a central role in the restriction of M. tuberculosis infections, but is unclear whether these markers are indicative of tuberculosis disease severity. METHODOLOGY: We investigated live M. tuberculosis- and M. bovis BCG-induced peripheral blood mononuclear cell responses in patients with tuberculosis (TB and healthy endemic controls (ECs, n = 36. TB patients comprised pulmonary (PTB, n = 34 and extrapulmonary groups, subdivided into those with less severe localized extrapulmonary TB (L-ETB, n = 16 or severe disseminated ETB (D-ETB, n = 16. Secretion of CCL2, IFNgamma, IL10 and CCL3, and mRNA expression of CCL2, TNFalpha, CCL3 and CXCL8 were determined. RESULTS: M. tuberculosis- and BCG-induced CCL2 secretion was significantly increased in both PTB and D-ETB (p<0.05, p<0.01 as compared with L-ETB patients. CCL2 secretion in response to M. tuberculosis was significantly greater than to BCG in the PTB and D-ETB groups. M. tuberculosis-induced CCL2 mRNA transcription was greater in PTB than L-ETB (p = 0.023, while CCL2 was reduced in L-ETB as compared with D-ETB (p = 0.005 patients. M. tuberculosis-induced IFNgamma was greater in L-ETB than PTB (p = 0.04, while BCG-induced IFNgamma was greater in L-ETB as compared with D-ETB patients (p = 0.036. TNFalpha mRNA expression was raised in PTB as compared with L-ETB group in response to M. tuberculosis (p = 0.02 and BCG (p = 0.03. Mycobacterium-induced CCL3 and CXCL8 was comparable between TB groups. CONCLUSIONS: The increased CCL2 and TNFalpha in PTB patients may support effective leucocyte recruitment and M. tuberculosis localization. CCL2 alone is associated with severity of TB, possibly due to increased systemic inflammation found in severe disseminated TB or due to increased monocyte infiltration to lung parenchyma in pulmonary disease.

SDE Plus, SDE and MEP. Annual review 2012; SDE+, SDE en MEP. Jaarbericht 2012

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-05-15

This annual report describes the applications for SDE subsidy (renewable energy support scheme) in the period 2008-2012, the new SDE Plus which starts in 2013, and the MEP transition scheme (MEP stands for 'Environmental quality of electricity production', predecessor of SDE for the period 2003-2006) and applications from the MEP scheme [Dutch] Het jaarbericht 2012 voor de SDE+, SDE en MEP presenteert de resultaten van de regeling Stimulering Duurzame Energieproductie (SDE+ vanaf 2013 en SDE, 2008-2012) en de voorganger van de SDE, de subsidieregeling Milieukwaliteit van de Elektriciteitsproductie.

Integrated multidimensional and comprehensive 2D GC analysis of fatty acid methyl esters.

Science.gov (United States)

Zeng, Annie Xu; Chin, Sung-Tong; Marriott, Philip J

2013-03-01

Fatty acid methyl ester (FAME) profiling in complex fish oil and milk fat samples was studied using integrated comprehensive 2D GC (GC × GC) and multidimensional GC (MDGC). Using GC × GC, FAME compounds--cis- and trans-isomers, and essential fatty acid isomers--ranging from C18 to C22 in fish oil and C18 in milk fat were clearly displayed in contour plot format according to structural properties and patterns, further identified based on authentic standards. Incompletely resolved regions were subjected to MDGC, with Cn (n = 18, 20) zones transferred to a (2)D column. Elution behavior of C18 FAME on various (2)D column phases (ionic liquids IL111, IL100, IL76, and modified PEG) was evaluated. Individual isolated Cn zones demonstrated about four-fold increased peak capacities. The IL100 provided superior separation, good peak shape, and utilization of elution space. For milk fat-derived FAME, the (2)D chromatogram revealed at least three peaks corresponding to C18:1, more than six peaks for cis/trans-C18:2 isomers, and two peaks for C18:3. More than 17 peaks were obtained for the C20 region of fish oil-derived FAMEs using MDGC, compared with ten peaks using GC × GC. The MDGC strategy is useful for improved FAME isomer separation and confirmation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of DL-adrenaline (methyl C{sup 14}) (1961); Synthese de la DL-adrenaline (methyle {sup 14}C) (1961)

Energy Technology Data Exchange (ETDEWEB)

Pichat, L; Audinot, M [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1961-07-01

The sodium derivative of 5-3-4 dibenzyl oxyphenyl 2-oxazolidinone reacted with methyl iodide {sup 14}C, in stoichiometric quantity, gives rise to the corresponding N-methyl {sup 14}C derivative. The oxazolidinone ring is opened by concentrated hydrochloric acid and the benzyl groups removed by catalytic hydrogenolysis. Adrenaline methyl {sup 14}C is then purified on Dowex 50 X-12 exchange resin. Overall-yield is 45 per cent based upon methyl iodide {sup 14}C. (author) [French] Le derive sode de la (dibenzyloxy-3-4-phenyl)-5 oxazolidinone-2 traite par l'iodure de methyle {sup 14}C, en proportion stoechiometrique, fournit le derive N-methyle {sup 14}C correspondant. Apres ouverture du cycle oxazolidinone par HCL concentre et debenzylation par hydrogenation catalytique, on purifie l'adrenaline (methyle {sup 14}C) par chromatographie sur resine echangeuse Dowex 50 X-12. Le rendement est de 45 pour cent par rapport a l'iodure de methyle {sup 14}C. (auteurs)

Synthesis of DL-adrenaline (methyl C{sup 14}) (1961); Synthese de la DL-adrenaline (methyle {sup 14}C) (1961)

Energy Technology Data Exchange (ETDEWEB)

Pichat, L.; Audinot, M. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1961-07-01

The sodium derivative of 5-3-4 dibenzyl oxyphenyl 2-oxazolidinone reacted with methyl iodide {sup 14}C, in stoichiometric quantity, gives rise to the corresponding N-methyl {sup 14}C derivative. The oxazolidinone ring is opened by concentrated hydrochloric acid and the benzyl groups removed by catalytic hydrogenolysis. Adrenaline methyl {sup 14}C is then purified on Dowex 50 X-12 exchange resin. Overall-yield is 45 per cent based upon methyl iodide {sup 14}C. (author) [French] Le derive sode de la (dibenzyloxy-3-4-phenyl)-5 oxazolidinone-2 traite par l'iodure de methyle {sup 14}C, en proportion stoechiometrique, fournit le derive N-methyle {sup 14}C correspondant. Apres ouverture du cycle oxazolidinone par HCL concentre et debenzylation par hydrogenation catalytique, on purifie l'adrenaline (methyle {sup 14}C) par chromatographie sur resine echangeuse Dowex 50 X-12. Le rendement est de 45 pour cent par rapport a l'iodure de methyle {sup 14}C. (auteurs)

Erythritol Availability in Bovine, Murine and Human Models Highlights a Potential Role for the Host Aldose Reductase during Brucella Infection

Science.gov (United States)

Barbier, Thibault; Machelart, Arnaud; Zúñiga-Ripa, Amaia; Plovier, Hubert; Hougardy, Charlotte; Lobet, Elodie; Willemart, Kevin; Muraille, Eric; De Bolle, Xavier; Van Schaftingen, Emile; Moriyón, Ignacio; Letesson, Jean-Jacques

2017-01-01

Erythritol is the preferential carbon source for most brucellae, a group of facultative intracellular bacteria that cause a worldwide zoonosis. Since this polyol is abundant in genital organs of ruminants and swine, it is widely accepted that erythritol accounts at least in part for the characteristic genital tropism of brucellae. Nevertheless, proof of erythritol availability and essentiality during Brucella intracellular multiplication has remained elusive. To investigate this relationship, we compared ΔeryH (erythritol-sensitive and thus predicted to be attenuated if erythritol is present), ΔeryA (erythritol-tolerant but showing reduced growth if erythritol is a crucial nutrient) and wild type B. abortus in various infection models. This reporting system indicated that erythritol was available but not required for B. abortus multiplication in bovine trophoblasts. However, mice and humans have been considered to lack erythritol, and we found that it was available but not required for B. abortus multiplication in human and murine trophoblastic and macrophage-like cells, and in mouse spleen and conceptus (fetus, placenta and envelopes). Using this animal model, we found that B. abortus infected cells and tissues contained aldose reductase, an enzyme that can account for the production of erythritol from pentose cycle precursors. PMID:28659902

Failure of sucrose replacement with the non-nutritive sweetener erythritol to alter GLP-1 or PYY release or test meal size in lean or obese people.

Science.gov (United States)

Overduin, Joost; Collet, Tinh-Hai; Medic, Nenad; Henning, Elana; Keogh, Julia M; Forsyth, Faye; Stephenson, Cheryl; Kanning, Marja W; Ruijschop, Rianne M A J; Farooqi, I Sadaf; van der Klaauw, Agatha A

2016-12-01

There is considerable interest in the effect of foods containing high intensity sweeteners on satiation. However, less is known about low-calorie bulk sweeteners such as erythritol. In this randomized three-way crossover study, we studied 10 lean and 10 obese volunteers who consumed three test meals on separate occasions: (a) control sucrose meal; (b) isovolumic meal with partial replacement of sucrose by erythritol; (c) isocaloric meal which contained more erythritol but equivalent calories to the control meal. We measured gut hormone levels, hunger and satiety scores, ad libitum food intake, sucrose preference and intake after the manipulations. There was a greater post-prandial excursion in glucose and insulin levels after sucrose than after the erythritol meals. There was no difference in GLP-1/PYY levels or subsequent energy intake and sucrose preference between sucrose control and isovolumic erythritol meals. In lean (but not obese) participants, hunger decreased to a greater extent after the isocaloric erythritol meal compared to the control meal (p = 0.003) reflecting the larger volume of this meal. Replacing sucrose with erythritol leads to comparable hunger and satiety scores, GLP-1 and PYY levels, and subsequent sucrose preference and intake. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Methylation of zebularine: a quantum mechanical study incorporating interactive 3D pdf graphs.

Science.gov (United States)

Selvam, Lalitha; Vasilyev, Vladislav; Wang, Feng

2009-08-20

Methylation of a cytidine deaminase inhibitor, 1-(beta-D-ribofuranosyl)-2-pyrimidone (i.e., zebularine (zeb)), which produces 1-(beta-D-ribofuranosyl)-5-methyl-2-pyrimidinone (d5), has been investigated using density functional theory models. The optimized structures of zeb and d5 and the valence orbitals primarily responsible for the methylation in d5 are presented using state-of-the-art interactive (on a computer or online) three-dimensional (3D) graphics in a portable document format (pdf) file, 3D-PDF (http://www.web3d.org/x3d/vrml/ ). The facility to embed 3D molecular structures into pdf documents has been developed jointly at Swinburne University of Technology and the National Computational Infrastructure, the Australian National University. The methyl fragment in the base moiety shows little effect on the sugar puckering but apparently affects anisotropic properties, such as condensed Fukui functions. Binding energy spectra, both valence space and core space, are noticeably affected; in particular, in the outer-valence space (e.g., IP < 20 eV). The methyl fragment delocalizes and diffuses into almost all valence space, but orbitals 8 (57a, IP = 12.57 eV), 18 (47a, IP = 14.70 eV), and 37 (28a, IP = 22.15 eV) are identified as fingerprint for the methyl fragment. In the inner shell, however, the impact of the methyl can be localized and identified by chemical shift. A small, global, red shift is found for the O-K, N-K and sugar C-K spectra, whereas the base C-K spectrum exhibits apparent methyl-related changes.

Synthesis of two S-(methyl-3H)-labelled enkephalins and S-(methyl-14C) substance P

International Nuclear Information System (INIS)

Naegren, K.; Laangstroem, B.; Franzen, H.M.; Ragnarsson, U.

1988-01-01

The synthesis of 3 H-labelled Met-enkephalin and Tyr-D-Ala-Gly-Phe-Met-NH 2 (DALA) and 14 C-labelled Substance P (SP) from previously described, fully protected intermediates is reported. The labelled peptides were prepared by methylation with ( 3 H)- or ( 14 C)methyl iodide of the sulphide anions formed on deprotection of the corresponding S-benzyl-homocysteine precursors with sodium in liquid ammonia. After purification by LC, the labelled peptides were obtained in radiochemical yields in the range of 9 to 24% with a radiochemical purity higher than 97%. The specific radioactivities of the 3 H- and 14 C- labelled products, corresponding to the labelled methyl iodides used, were 80 mCi/μmol and 60 μCi/μmol, respectively. (author)

Vitamin D: Immuno-modulation and tuberculosis treatment.

Science.gov (United States)

Selvaraj, Paramasivam; Harishankar, Murugesan; Afsal, Kolloli

2015-05-01

Tuberculosis (TB) is a major global health problem and often coincides with vitamin D deficiency. High doses of vitamin D were widely used to treat TB during the pre-antibiotic era. Vitamin D exerts its action through vitamin D receptor (VDR), and VDR gene polymorphisms are associated with susceptibility or resistance to tuberculosis as well as sputum smear and culture conversion during anti-TB treatment. In-vitro studies have revealed that 1,25-dihydroxyvitamin D3 enhances innate immunity by increased expression of various antimicrobial peptides, including cathelicidin, and induction of autophagy of the infected cells thus restricts the intracellular growth of Mycobacterium tuberculosis in macrophages. On the other hand, vitamin D has been shown to suppress the pro-inflammatory cytokine response and enhance the anti-inflammatory response. Supplementation with vitamin D in concert with treatment for TB may be beneficial with respect to minimizing the excessive tissue damage that occurs during the active stage of tuberculosis disease. Several clinical trials have evaluated vitamin D supplementation as an adjunct therapy in the treatment for tuberculosis. However, results are conflicting, owing to variations in dose regimens and outcomes. Further investigations are needed to find the optimal concentration of vitamin D for supplementation with standard anti-TB drugs to optimize treatment, which could help to effectively manage both drug-sensitive and drug-resistant tuberculosis.

Advice on MEP tariff for cogeneration in 2004

International Nuclear Information System (INIS)

Ten Donkelaar, M.; Harmsen, R.; Scheepers, M.J.J.

2004-05-01

The title analysis is part of the monitoring of combined heat and power generation (CHP) in the Netherlands, and concerns the impact of the new Dutch subsidy scheme MEP (environmental quality of power generation) on the cost-effectiveness of CHP investments based on a number of CHP reference cases. The MEP scheme provides a reward for the additional kWhs of electricity produced by CHP units compared to separate production of heat and power. This means that the MEP rewards the 'CO2 free kWhs' produced by CHP units, providing an incentive for the most efficient CHP units. In the first chapter a description of the calculation of 'CO2 free kWhs' is given followed by the physical developments of CHP in the Netherlands. The third and final chapter calculates the impact of the MEP regulation on the cost effectiveness of CHP and compares it with the European Community Guidelines on Aid for Environmental Protection. The results of the calculations show that the Dutch MEP scheme complies with the European guidelines for all CHP reference cases [nl

Synthesis of (5,6-/sup 13/C/sub 2/, 1-/sup 14/C)olivetolic acid, methyl (1'-/sup 13/C)olivetolate and (5,6-/sup 13/C/sub 2/, 1-/sup 14/C)cannabigerolic acid

Energy Technology Data Exchange (ETDEWEB)

Porwoll, J P; Leete, E [Minnesota Univ., Minneapolis (USA). Dept. of Chemistry

1985-03-01

Potential advanced intermediates in the biosynthesis of delta/sup 9/-tetrahydrocannabinol, the major psychoactive principle of marijuana, have been synthesized labeled with two contiguous /sup 13/C atoms and /sup 14/C. Methyl (5,6-/sup 13/C/sub 2/, 1-/sup 14/C)olivetolate was prepared from lithium (/sup 13/C/sub 2/)acetylide and dimethyl (2-/sup 14/C)malonate. Reaction with geranyl bromide afforded methyl (5,6-/sup 13/C/sub 2/, 1-/sup 14/C)cannabigerolate, and hydrolysis of these methyl esters with lithium propyl mercaptide yielded the corresponding labeled acids. The /sup 13/C-/sup 13/C couplings observable in the /sup 13/C NMR spectra of these /sup 13/C-enriched compounds and their synthetic precursors are recorded. Methyl (1'-/sup 14/C)olivetolate was prepared from /sup 13/CO/sub 2/ to confirm assignments of the /sup 13/C chemical shifts in the pentyl side chain of these compounds.

13C and 1H nuclear magnetic resonance of methyl-substituted acetophenones and methyl benzoates: steric hindrance and inhibited conjugation.

Science.gov (United States)

Budesínský, Milos; Kulhánek, Jirí; Böhm, Stanislav; Cigler, Petr; Exner, Otto

2004-10-01

The 1H and 13C NMR spectra of 14 methyl-substituted acetophenones and 14 methyl-substituted methyl benzoates were assigned and interpreted with respect to the conformation of the C(ar)-C(O) bond. The substituent effects are proportional in the two series and can be divided into polar and steric: each has different effects on the 13C SCS of the individual atoms. In the case of C atoms C(O), C(1) and CH3(CO), the steric effects were quantitatively separated by comparing SCS in the ortho and para positions. The steric effects are proportional for the individual C atoms and also to steric effects estimated from other physical quantities. However, they do not depend simply on the angle of torsion phi of the functional group as anticipated hitherto. A better description distinguishes two classes of compounds: sterically not hindered or slightly hindered planar molecules and strongly sterically hindered, markedly non-planar. In order to confirm this reasoning without empirical correlations, the J(C,C) coupling constants were measured for three acetophenone derivatives labeled with 13C in the acetyl methyl group. The constants confirm unambiguously the conformation of 2-methylacetophenone; their zero values are in accord with the conformation of 2,6-dimethylacetophenone. The zero values in the unsubstituted acetophenone are at variance with previous erroneous report but all J(C,C) values are in accord with calculations at the B3LYP/6-311++G(2d,2p)//B3LYP/6-311+G(d,p) level. Copyright 2004 John Wiley & Sons, Ltd.

Nature of the C2-methylation effect on the properties of imidazolium ionic liquids.

Science.gov (United States)

Rodrigues, Ana S M C; Lima, Carlos F R A C; Coutinho, João A P; Santos, Luís M N B F

2017-02-15

Methylation at the C2 position of 1,3-disubstituted imidazolium-based ionic liquids (ILs) is one of the structural features that has gained attention due to its drastic impact on thermophysical and transport properties. Several hypotheses have been proposed to explain this effect but there is still much discrepancy. Aiming for the rationalization of the effects of these structural features on the properties of imidazolium ILs, we present a thermodynamic and computational study of two methylated ILs at the C2 position of imidazolium, [ 1 C 4 2 C 1 3 C 1 im][NTf 2 ] and [ 1 C 3 2 C 1 3 C 1 im][NTf 2 ]. The phase behaviour (glass transition and vaporization equilibrium) and computational studies of the anion rotation around the cation and ion pair interaction energies for both ILs were explored. The results have shown that C2-methylation has no impact on the enthalpy of vaporization. However, it decreases the entropy of vaporization, which is a consequence of the change in the ion pair dynamics that affects both the liquid and gas phases. In addition, the more hindered dynamics of the ion pair are also reflected in the increase in the glass transition temperature, T g . The entropic contribution of anion-around-cation rotation in the imidazolium [NTf 2 ] ILs was quantified experimentally by the comparative analysis of the entropy of vaporization, and computationally by the calculation of the entropies of hindered internal rotation. The global results exclude the existence of significant H-bonding in the C2-protonated (non-methylated) ILs and explain the C2-methylation effect in terms of reduced entropy of the ion pair in the liquid and gas phases. In light of these results, the C2-methylation effect is intrinsically entropic and originates from the more hindered anion-around-cation rotation as a consequence of the substitution of the -H with a bulkier -CH 3 group.

A comparative study on glycerol metabolism to erythritol and citric acid in Yarrowia lipolytica yeast cells.

Science.gov (United States)

Tomaszewska, Ludwika; Rakicka, Magdalena; Rymowicz, Waldemar; Rywińska, Anita

2014-09-01

Citric acid and erythritol biosynthesis from pure and crude glycerol by three acetate-negative mutants of Yarrowia lipolytica yeast was investigated in batch cultures in a wide pH range (3.0-6.5). Citric acid biosynthesis was the most effective at pH 5.0-5.5 in the case of Wratislavia 1.31 and Wratislavia AWG7. With a decreasing pH value, the direction of biosynthesis changed into erythritol synthesis accompanied by low production of citric acid. Pathways of glycerol conversion into erythritol and citric acid were investigated in Wratislavia K1 cells. Enzymatic activity was compared in cultures run at pH 3.0 and 4.5, that is, under conditions promoting the production of erythritol and citric acid, respectively. The effect of pH value (3.0 and 4.5) and NaCl presence on the extracellular production and intracellular accumulation of citric acid and erythritol was compared as well. Low pH and NaCl resulted in diminished activity of glycerol kinase, whereas such conditions stimulated the activity of glycerol-3-phosphate dehydrogenase. The presence of NaCl strongly influenced enzymes activity - the effective erythritol production was correlated with a high activity of transketolase and erythrose reductase. Therefore, presented results confirmed that transketolase and erythrose reductase are involved in the overproduction of erythritol in the cells of Y. lipolytica yeast. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Synthesis of (5,6-/sup 13/C/sub 2/, 1-/sup 14/C)olivetolic acid, methyl (1'-/sup 13/C)olivetolate and (5,6-/sup 13/C/sub 2/, 1-/sup 14/C)cannabigerolic acid

Energy Technology Data Exchange (ETDEWEB)

Porwoll, J.P.; Leete, E. (Minnesota Univ., Minneapolis (USA). Dept. of Chemistry)

1985-03-01

Potential advanced intermediates in the biosynthesis of delta/sup 9/-tetrahydrocannabinol, the major psychoactive principle of marijuana, have been synthesized labeled with two contiguous /sup 13/C atoms and /sup 14/C. Methyl (5,6-/sup 13/C/sub 2/, 1-/sup 14/C)olivetolate was prepared from lithium (/sup 13/C/sub 2/)acetylide and dimethyl (2-/sup 14/C)malonate. Reaction with geranyl bromide afforded methyl (5,6-/sup 13/C/sub 2/, 1-/sup 14/C)cannabigerolate, and hydrolysis of these methyl esters with lithium propyl mercaptide yielded the corresponding labeled acids. The /sup 13/C-/sup 13/C couplings observable in the /sup 13/C NMR spectra of these /sup 13/C-enriched compounds and their synthetic precursors are recorded. Methyl (1'-/sup 14/C)olivetolate was prepared from /sup 13/CO/sub 2/ to confirm assignments of the /sup 13/C chemical shifts in the pentyl side chain of these compounds.

Synthesis of (R,S)-[2,3-{sup 13}C{sub 2}]-1-(1`-methyl-2`-pyrrolidinyl)propan-2-one; {l_brace}(R,S)-[2`,3`-{sup 13}C{sub 2}]hygrinePound right bracePound

Energy Technology Data Exchange (ETDEWEB)

Abraham, T.W.; Leete, Edward [Minnesota Univ., Minneapolis, MN (United States). Dept. of Chemistry

1996-05-01

2-Ethoxy-1-methyl-5-pyrrolidinone (1) was reacted with ethyl [3,4-{sup 13}C{sub 2}]-acetoacetate (2) in the presence of TiCl{sub 4} to give ethyl [3,4-{sup 13}C{sub 2}]-2-(1`-methyl-5`-oxo-2`-pyrrolidinyl)-3-oxobutanoate (3) in 85% yield. Decarboethoxylation of ethyl [3,4-{sup 13}C{sub 2}]-2-(1`-methyl-5`-oxo-2`-pyrrolidinyl)-3-oxobutan-oate (3) was accomplished using NaCl and H{sub 2}O in DMSO to give (R,S)-[2,3-{sup 13}C{sub 2}]-1-(1`-methyl-5`-oxo-2`-pyrrolidinyl)propan-2-o ne (4) in 91% yield. Protection of the ketone as a ketal (ethylene glycol, H{sup +}), followed by reduction of the amide to the amine using LiAlH{sub 4} and subsequent deprotection of the ketal gave (R,S)-[2,3-{sup 13}C{sub 2}]-1-(1`-methyl-2`-pyrrolidinyl)propan-2-one ((R,s)-[2`, 3`-{sup 13}C{sub 2}]Hygrine) (8) in 78% yield. (61% overall yield from ethyl [3,4-{sup 13}C{sub 2}]acetoacetate). (Author).

[Tuberculosis: plasma levels of vitamin D and its relation with infection and disease].

Science.gov (United States)

Esteve Palau, Erika; Sánchez Martínez, Francesca; Knobel Freud, Hernando; López Colomés, José-Luís; Diez Pérez, Adolfo

2015-02-02

Vitamin D (vitD) is involved in the phosphor-calcium metabolism and bone pathology, but also in inflammatory and infectious processes such as tuberculosis. The present study evaluates the clinical and epidemiological aspects of active tuberculosis cases and latently infected contacts in whom plasma concentrations of vitD were obtained to determine whether the deficiency of vitD is a risk factor to develop active tuberculosis, especially the more severe forms. Observational, retrospective study that included 86 tuberculosis patients and 80 contacts with latent infection in a 2-year period. When comparing active tuberculosis cases with latent infection contacts, deficiency of vitD (vitD levels <10 ng/mL, odds ratio [OR]: 2.02, 95% confidence interval [CI]: 1.04 to 3.93), male sex (OR: 1.9, 95% CI: 0.96 to 3.71) and non-white race (OR: 0.7, 95% CI: 0.34 to 1.42) were factors independently associated with the diagnosis of tuberculosis. Despite the limited number of subjects studied, there was a association between severe deficit of vitD and the presentation of tuberculosis. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Genetic engineering of Synechocystis PCC6803 for the photoautotrophic production of the sweetener erythritol

NARCIS (Netherlands)

van der Woude, A.D.; Perez Gallego, R.; Vreugdenhil, A.; Puthan Veetil, V.; Chroumpi, T.; Hellingwerf, K.J.

2016-01-01

BACKGROUND: Erythritol is a polyol that is used in the food and beverage industry. Due to its non-caloric and non-cariogenic properties, the popularity of this sweetener is increasing. Large scale production of erythritol is currently based on conversion of glucose by selected fungi. In this study,

Radiosynthesis of [11C]D.P.A.-713, [11C]D.P.A.-715 and [11C]clinme, selected carbon-11-labelled novel potential radioligands for imaging the peripheral benzodiazepine receptors with PET

International Nuclear Information System (INIS)

Dolle, F.; Thominiaux, C.; Hinnen, F.; Demphel, S.; Le helleix, S.; Chauveau, F.; Boutin, H.; Herard, A.S.; Hantraye, P.; Tavitian, B.; Kassiou, M.; James, M.; Creelman, A.; Fulton, R.; Kassiou, M.; Katsifis, A.; Greguric, I.; Mattner, F.; Loch, C.; Selleri, S.

2008-01-01

11 C P.K.11195 is not only the oldest, but also the most widely used PET radiotracer for in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.). With the aim of developing a new PET imaging probe for the in vivo study of the P.B.R., two pyrazol [1,5-a]pyrimidineacetamides (D.P.A.-713 and D.P.A.-715) and one imidazol[1,2-a]pyridine-acetamide (C.L.I.N.M.E.) were radiolabelled with the positron emitters carbon 11 (half life: 20.38 min) [1-5]. Briefly, C.L.I.N.M.E. (2-[6-chloro-2(4-iodophenyl)-imidazol[1,2-a]pyridin-3-yl] -N-ethyl-N-methyl-acetamide) was labelled at its methyl-acetamide moity chain from the corresponding nor-analogue using[ 11 C]methyl iodide (in D.M.S.O./D.M.F (100/200 μL) containing powdered K.O.H. (3-5 mg) at 110 degrees C for 3 min. D.P.A.-713 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin -3-yl]acetamide) and D.P.A.-715 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-bis-tri-fluoro-methyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) were labelled at their aromatic methoxy groups from the corresponding nor-derivatives using [ 11 C]methyl triflate (in acetone (300μL) containing aq. 3 M NaOH (4μL) at 110 degrees C for 1 min). All radioligands were purified using semi preparative Zorbax reverse phase H.P.L.C., were adequately formulated for in vivo injection within 30 min and were found to be > 95% chemically and radiochemically pure. (N.C.)

34 CFR 200.86 - Use of MEP funds in schoolwide projects.

Science.gov (United States)

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Use of MEP funds in schoolwide projects. 200.86 Section... SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE DISADVANTAGED Migrant Education Program § 200.86 Use of MEP funds in schoolwide projects. Funds available under part C...

Serum cystatin C and anti-N-methyl-D-aspartate receptor encephalitis.

Science.gov (United States)

Shu, Y; Chang, Y; Wu, H; Li, J; Cao, B; Sun, X; Wang, J; Peng, L; Hu, X; Yu, X; Qiu, W

2018-05-01

Cystatin C (CysC) is associated with many neurodegenerative disorders and autoimmune diseases, but its relationship with anti-N-Methyl-D-aspartate receptor (anti-NMDAR) encephalitis is unknown. Serum levels of CysC were determined in 66 patients with anti-NMDAR encephalitis and 115 healthy controls. Of the 66 patients, 30 had a follow-up evaluation at 3 months after admission. Association of CysC with anti-NMDAR encephalitis and its clinical parameters were evaluated in the patients. The serum levels of CysC were significantly lower in patients with anti-NMDAR encephalitis than in controls (0.70 ± 0.13 vs 0.83 ± 0.17 mg/mL, P anti-NMDAR encephalitis patients had significantly increased serum CysC levels (P anti-NMDAR encephalitis and its clinical parameters and that the changes in CysC levels correlate with therapeutic effect. Therefore, our findings provide new insights into the association between serum CysC and anti-NMDAR encephalitis. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prerequisite for highly efficient isoprenoid production by cyanobacteria discovered through the over-expression of 1-deoxy-d-xylulose 5-phosphate synthase and carbon allocation analysis.

Science.gov (United States)

Kudoh, Kai; Kawano, Yusuke; Hotta, Shingo; Sekine, Midori; Watanabe, Takafumi; Ihara, Masaki

2014-07-01

Cyanobacteria have recently been receiving considerable attention owing to their potential as photosynthetic producers of biofuels and biomaterials. Here, we focused on the production of isoprenoids by cyanobacteria, and aimed to provide insight into metabolic engineering design. To this end, we examined the over-expression of a key enzyme in 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway, 1-deoxy-d-xylulose 5-phosphate synthase (DXS) in the cyanobacterium Synechocystis sp. PCC6803. In the DXS-over-expression strain (Dxs_ox), the mRNA and protein levels of DXS were 4-times and 1.5-times the levels in the wild-type (WT) strain, respectively. The carotenoid content of the Dxs_ox strain (8.4 mg/g dry cell weight [DCW]) was also up to 1.5-times higher than that in the WT strain (5.6 mg/g DCW), whereas the glycogen content dramatically decreased to an undetectable level. These observations suggested that the carotenoid content in the Dxs_ox strain was increased by consuming glycogen, which is a C-storage compound in cyanobacteria. We also quantified the total sugar (145 and 104 mg/g DCW), total fatty acids (31 and 24 mg/g DCW) and total protein (200 and 240 mg/g DCW) content in the WT and Dxs_ox strains, respectively, which were much higher than the carotenoid content. In particular, approximately 54% of the proteins were phycobiliproteins. This study demonstrated the major destinations of carbon flux in cyanobacteria, and provided important insights into metabolic engineering. Target yield can be improved through optimization of gene expression, the DXS protein stabilization, cell propagation depression and restriction of storage compound synthesis. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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.

Styrylpyrylium Salts: 1H and 13C NMR High-Resolution Spectroscopy (1D and 2D

Directory of Open Access Journals (Sweden)

Jean Claude W. Ouédraogo

2010-01-01

Full Text Available 1H and 13C NMR high-resolution spectroscopy (1D and 2D (1H, 1H-COSY, HSQC, HMBC for four styrylpyrylium perchlorates were carried out and signal attributions are reported. Chemical shifts observed on 13C NMR spectra for the styrylpyrylium salts were compared with net atomic charge for carbon obtained by AM1 semiempirical calculations. The position of the styryl group present low effect on chemical shifts for carbon atoms, while the presence of methyl group led to the unshielding of the substituted carbon.

Setting MEPS for electronic products

International Nuclear Information System (INIS)

Siderius, Hans-Paul

2014-01-01

When analysing price, performance and efficiency data for 15 consumer electronic and information and communication technology products, we found that in general price did not relate to the efficiency of the product. Prices of electronic products with comparable performance decreased over time. For products where the data allowed fitting the relationship, we found an exponential decrease in price with an average time constant of −0.30 [1/year], meaning that every year the product became 26% cheaper on average. The results imply that the classical approach of setting minimum efficiency performance standards (MEPS) by means of life cycle cost calculations cannot be applied to electronic products. Therefore, an alternative approach based on the improvement of efficiency over time and the variation in efficiency of products on the market, is presented. The concept of a policy action window can provide guidance for the decision on whether setting MEPS for a certain product is appropriate. If the (formal) procedure for setting MEPS takes longer than the policy action window, this means that the efficiency improvement will also be achieved without setting MEPS. We found short, i.e. less than three years, policy action windows for graphic cards, network attached storage products, network switches and televisions. - Highlights: • For electronic consumer products price does not relate to efficiency. • Average price decrease of selected electronic products is 26 % per year. • We give an alternative approach to life cycle cost calculations for setting MEPS. • The policy action window indicates whether setting MEPS is appropriate

Vibrational spectroscopic (FT-IR, FT-Raman) and quantum mechanical study of 4-(2-chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4] diazepine

Science.gov (United States)

Kuruvilla, Tintu K.; Prasana, Johanan Christian; Muthu, S.; George, Jacob

2018-04-01

The spectroscopic properties of 4-(2-chlorophenyl)-2-ethyl-9-methyl-6H-thieno [3,2-f] [1,2,4] triazolo [4,3-a] [1,4] diazepine were investigated in the present study using FT-IR and FT-Raman techniques. The results obtained were compared with quantum mechanical methods, as it serves as an important tool in interpreting and predicting vibrational spectra. The optimized molecular geometry, the vibrational wavenumbers, the infrared intensities and Raman scattering were calculated using density functional theory B3LYP method with 6-311++g (d,p) basis set. All the experimental results were in line with the theoretical data. The molecular electrostatic potential (MEP) and HOMO LUMO energies of the title compound were accounted. The results indicated that the title compound has a lower softness value (0.27) and high electrophilicity index (4.98) hence describing its biological activity. Further, natural bond orbital was also analyzed as part of the work. Fukui functions were calculated in order to explain the chemical selectivity or the reactivity site in 4-(2-chlorophenyl)-2-ethyl-9-methyl-6H-thieno [3,2-f] [1,2,4] triazolo [4,3-a] [1,4] diazepine. The thermodynamic properties of the title compound were closely examined at different temperatures. It revealed the correlations between heat capacity (C), entropy (S) and enthalpy changes (H) with temperatures. The paper further explains that the title compound can act as good antidepressant through molecular docking studies.

Mechanish of dTTP Inhibition of the Bifunctional dCTP Deaminase:dUTPase Encoded by Mycobacterium tuberculosis

DEFF Research Database (Denmark)

Helt, Signe Smedegaard; Thymark, Majbritt; Harris, Pernille

2008-01-01

Recombinant deoxycytidine triphosphate (dCTP) deaminase from Mycobacterium tuberculosis was produced in Escherichia coli and purified. The enzyme proved to be a bifunctional dCTP deaminase:deoxyuridine triphosphatase. As such, the M. tuberculosis enzyme is the second bifunctional enzyme to be cha......Recombinant deoxycytidine triphosphate (dCTP) deaminase from Mycobacterium tuberculosis was produced in Escherichia coli and purified. The enzyme proved to be a bifunctional dCTP deaminase:deoxyuridine triphosphatase. As such, the M. tuberculosis enzyme is the second bifunctional enzyme...

Recommendation on the Dutch MEP subsidy 2006 for cogeneration

International Nuclear Information System (INIS)

Harmsen, R.

2005-11-01

The results of an analysis of the impact of the Dutch subsidy scheme 'MEP' (environmental quality of electric power generation) on the cost-effectiveness of CHP (combined heat and power production) plants. The MEP scheme provides a reward for the CO2 reduction by CHP plants and offers therefore an incentive for energy efficient operation. In 2006 the MEP subsidy is available for CHP plants that started their operation after 1 January 1997. The subsidy will be differentiated based on CHP type and power capacity. Main outcome of the report is a subsidy advise, which complies with the European Community Guidelines on Aid for Environmental Protection. Based on the subsidy advise a budget for the CHP MEP scheme has been estimated [nl

Systemic catechol-O-methyl transferase inhibition enables the D1 agonist radiotracer R-[11C]SKF 82957

International Nuclear Information System (INIS)

Palner, Mikael; McCormick, Patrick; Parkes, Jun; Knudsen, Gitte M.; Wilson, Alan A.

2010-01-01

Introduction: R-[ 11 C]-SKF 82957 is a high-affinity and potent dopamine D 1 receptor agonist radioligand, which gives rise to a brain-penetrant lipophilic metabolite. In this study, we demonstrate that systemic administration of catechol-O-methyl transferase (COMT) inhibitors blocks this metabolic pathway, facilitating the use of R-[ 11 C]-SKF 82957 to image the high-affinity state of the dopamine D 1 receptor with PET. Methods: R-[ 11 C]SKF 82957 was administered to untreated and COMT inhibitor-treated conscious rats, and the radioactive metabolites present in the brain and plasma were quantified by HPLC. Under optimal conditions, cerebral uptake and dopamine D 1 binding of R-[ 11 C]SKF 82957 were measured ex vivo. In addition, pharmacological challenges with the receptor antagonist SCH 23390, amphetamine, the dopamine reuptake inhibitor RTI-32 and the dopamine hydroxylase inhibitor α-methyl-p-tyrosine were performed to study the specificity and sensitivity of R-[ 11 C]-SKF 82957 dopamine D 1 binding in COMT-inhibited animals. Results: Treatment with the COMT inhibitor tolcapone was associated with a dose-dependent (EC 90 5.3±4.3 mg/kg) reduction in the lipophilic metabolite. Tolcapone treatment (20 mg/kg) also resulted in a significant increase in the striatum/cerebellum ratio of R-[ 11 C]SKF 82957, from 15 (controls) to 24. Treatment with the dopamine D 1 antagonist SCH 23390 reduced the striatal binding to the levels of the cerebellum, demonstrating a high specificity and selectivity of R-[ 11 C]SKF 82957 binding. Conclusions: Pre-treatment with the COMT inhibitor tolcapone inhibits formation of an interfering metabolite of R-[ 11 C]SKF 82957. Under such conditions, R-[ 11 C]SKF 82957 demonstrates high potential as the first agonist radiotracer for imaging the dopamine D 1 receptor by PET.

Structure of 1-deoxy-d-xylulose 5-phosphate reductoisomerase in a quaternary complex with a magnesium ion, NADPH and the antimalarial drug fosmidomycin

International Nuclear Information System (INIS)

Yajima, Shunsuke; Hara, Kodai; Iino, Daisuke; Sasaki, Yasuyuki; Kuzuyama, Tomohisa; Ohsawa, Kanju; Seto, Haruo

2007-01-01

The crystal structure of 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) from Escherichia coli complexed with Mg 2+ , NADPH and fosmidomycin was determined at 2.2 Å resolution. The structure showed a well defined loop conformation at the active site of DXR. The crystal structure of 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) from Escherichia coli complexed with Mg 2+ , NADPH and fosmidomycin was solved at 2.2 Å resolution. DXR is the key enzyme in the 2-C-methyl-d-erythritol 4-phosphate pathway and is an effective target of antimalarial drugs such as fosmidomycin. In the crystal structure, electron density for the flexible loop covering the active site was clearly observed, indicating the well ordered conformation of DXR upon substrate binding. On the other hand, no electron density was observed for the nicotinamide-ribose portion of NADPH and the position of Asp149 anchoring Mg 2+ was shifted by NADPH in the active site

Radiosynthesis of [{sup 11}C]D.P.A.-713, [{sup 11}C]D.P.A.-715 and [{sup 11}C]clinme, selected carbon-11-labelled novel potential radioligands for imaging the peripheral benzodiazepine receptors with PET

Energy Technology Data Exchange (ETDEWEB)

Dolle, F.; Thominiaux, C.; Hinnen, F.; Demphel, S.; Le helleix, S.; Chauveau, F.; Boutin, H.; Herard, A.S.; Hantraye, P.; Tavitian, B. [Service Hospitalier Frederic Joliot, I2BM/DSV, 91 - Orsay (France); Kassiou, M.; James, M.; Creelman, A.; Fulton, R. [Sydney Univ., Brain and Mind Research Institute, NSW (Australia); Kassiou, M. [Sydney Univ., Discipline of Medical Radiations, Sciences and School of Chemistry, NSW (Australia); Katsifis, A.; Greguric, I.; Mattner, F.; Loch, C. [Radiopharmaceuticals Research Institute, ANSTO, NSW (Australia); Selleri, S. [Degli Studi di Firenze Univ., Dipt. di Scienze Farmaceutiche (Italy)

2008-02-15

{sup 11}C P.K.11195 is not only the oldest, but also the most widely used PET radiotracer for in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.). With the aim of developing a new PET imaging probe for the in vivo study of the P.B.R., two pyrazol [1,5-a]pyrimidineacetamides (D.P.A.-713 and D.P.A.-715) and one imidazol[1,2-a]pyridine-acetamide (C.L.I.N.M.E.) were radiolabelled with the positron emitters carbon{sup 11} (half life: 20.38 min) [1-5]. Briefly, C.L.I.N.M.E. (2-[6-chloro-2(4-iodophenyl)-imidazol[1,2-a]pyridin-3-yl] -N-ethyl-N-methyl-acetamide) was labelled at its methyl-acetamide moity chain from the corresponding nor-analogue using[{sup 11}C]methyl iodide (in D.M.S.O./D.M.F (100/200 {mu}L) containing powdered K.O.H. (3-5 mg) at 110 degrees C for 3 min. D.P.A.-713 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin -3-yl]acetamide) and D.P.A.-715 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-bis-tri-fluoro-methyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) were labelled at their aromatic methoxy groups from the corresponding nor-derivatives using [{sup 11}C]methyl triflate (in acetone (300{mu}L) containing aq. 3 M NaOH (4{mu}L) at 110 degrees C for 1 min). All radioligands were purified using semi preparative Zorbax reverse phase H.P.L.C., were adequately formulated for in vivo injection within 30 min and were found to be > 95% chemically and radiochemically pure. (N.C.)

2-Acetyl-amino-1,3,4,6-tetra-O-(tri-methyl-silyl)-2-de-oxy-α-d-gluco-pyran-ose.

Science.gov (United States)

Cheng, Zhao-Dong; Cui, Yan-Li; Mao, Jian-Wei

2013-06-01

The title compound, C20H47NO6Si4, was synthesized by per-O-tri-methyl-silylation of N-acetyl-d-glucosa-mine using chloro-tri-methyl-silane in the presence of hexa-methyl-disiloxane. The tri-methyl-silyl group and acetamido group are located on the same side of the pyran ring, showing an α-configuration glycoside. One of the tri-methyl-silyl groups is disordered over two orientations, with site-occupancy factors of 0.625 (9) and 0.375 (9). In the crystal, N-H⋯O hydrogen bonds link the mol-ecules into supra-molecular chains along the a-axis direction.

Transcriptome analysis of thermogenic Arum concinnatum reveals the molecular components of floral scent production.

Science.gov (United States)

Onda, Yoshihiko; Mochida, Keiichi; Yoshida, Takuhiro; Sakurai, Tetsuya; Seymour, Roger S; Umekawa, Yui; Pirintsos, Stergios Arg; Shinozaki, Kazuo; Ito, Kikukatsu

2015-03-04

Several plant species can generate enough heat to increase their internal floral temperature above ambient temperature. Among thermogenic plants, Arum concinnatum shows the highest respiration activity during thermogenesis. However, an overall understanding of the genes related to plant thermogenesis has not yet been achieved. In this study, we performed de novo transcriptome analysis of flower organs in A. concinnatum. The de novo transcriptome assembly represented, in total, 158,490 non-redundant transcripts, and 53,315 of those showed significant homology with known genes. To explore genes associated with thermogenesis, we filtered 1266 transcripts that showed a significant correlation between expression pattern and the temperature trend of each sample. We confirmed five putative alternative oxidase transcripts were included in filtered transcripts as expected. An enrichment analysis of the Gene Ontology terms for the filtered transcripts suggested over-representation of genes involved in 1-deoxy-D-xylulose-5-phosphate synthase (DXS) activity. The expression profiles of DXS transcripts in the methyl-D-erythritol 4-phosphate (MEP) pathway were significantly correlated with thermogenic levels. Our results suggest that the MEP pathway is the main biosynthesis route for producing scent monoterpenes. To our knowledge, this is the first report describing the candidate pathway and the key enzyme for floral scent production in thermogenic plants.

Anaerobic C1 metabolism of the O-methyl-14C-labeled substituent of vanillate

International Nuclear Information System (INIS)

Frazer, A.C.; Young, L.Y.

1986-01-01

The O-methyl substituents of aromatic compounds constitute a C 1 growth substrate for a number of taxonomically diverse anaerobic acetogens. In this study, strain TH-001, an O-demethylating obligate anaerobe, was chosen to represent this physiological group, and the carbon flow when cells were grown on O-methyl substituents as a C 1 substrate was determined by 14 C radiotracer techniques. O-[methyl- 14 C]vanillate (4-hydroxy-3-methoxy-benzoate) was used as the labeled C 1 substrate. The data showed that for every O-methyl carbon converted to [ 14 C]acetate, two were oxidized to 14 CO 2 . Quantitation of the carbon recovered in the two products, acetate and CO 2 , indicated that acetate was formed in part by the fixation of unlabeled CO 2 . The specific activity of 14 C in acetate was 70% of that in the O-methyl substrate, suggesting that only one carbon of acetate was derived from the O-methyl group. Thus, it is postulated that the carboxyl carbon of the product acetate is derived from CO 2 and the methyl carbon is derived from the O-methyl substituent of vanillate

A preliminary PET evaluation of the new dopamine D2 receptor agonist [11C]MNPA in cynomolgus monkey

International Nuclear Information System (INIS)

Finnema, Sjoerd J.; Seneca, Nicholas; Farde, Lars; Shchukin, Evgeny; Sovago, Judit; Gulyas, Balazs; Wikstroem, Hakan V.; Innis, Robert B.; Neumeyer, John L.; Halldin, Christer

2005-01-01

This study describes the preliminary positron emission tomography (PET) evaluation of a dopamine D 2 -like receptor agonist (R)-2- 11 CH 3 O-N-n-propylnorapomorphine ([ 11 C]MNPA), as a potential new radioligand for in vivo imaging of the high-affinity state of the dopamine D 2 receptor (D 2 R). MNPA is a selective D 2 -like receptor agonist with a high affinity (K i =0.17 nM). [ 11 C]MNPA was successfully synthesized by direct O-methylation of (R)-2-hydroxy-NPA using [ 11 C]methyl iodide and was evaluated in cynomolgus monkeys. This study included baseline PET experiments and a pretreatment study using unlabeled raclopride (1 mg/kg). High uptake of radioactivity was seen in regions known to contain high D 2 R, with a maximum striatum-to-cerebellum ratio of 2.23±0.21 at 78 min and a maximum thalamus-to-cerebellum ratio of 1.37±0.06 at 72 min. The pretreatment study demonstrated high specific binding to D 2 R by reducing the striatum-to-cerebellum ratio to 1.26 at 78 min. This preliminary study indicates that the dopamine agonist [ 11 C]MNPA has potential as an agonist radioligand for the D 2 -like receptor and has potential for examination of the high-affinity state of the D 2 R in human subjects and patients with neuropsychiatric disorders

Mechanisms of Insertion of dCTP and dTTP Opposite the DNA Lesion O6-Methyl-2′-deoxyguanosine by Human DNA Polymerase η*

Science.gov (United States)

Patra, Amitraj; Zhang, Qianqian; Guengerich, F. Peter; Egli, Martin

2016-01-01

O6-Methyl-2′-deoxyguanosine (O6-MeG) is a ubiquitous DNA lesion, formed not only by xenobiotic carcinogens but also by the endogenous methylating agent S-adenosylmethionine. It can introduce mutations during DNA replication, with different DNA polymerases displaying different ratios of correct or incorrect incorporation opposite this nucleoside. Of the “translesion” Y-family human DNA polymerases (hpols), hpol η is most efficient in incorporating equal numbers of correct and incorrect C and T bases. However, the mechanistic basis for this specific yet indiscriminate activity is not known. To explore this question, we report biochemical and structural analysis of the catalytic core of hpol η. Activity assays showed the truncated form displayed similar misincorporation properties as the full-length enzyme, incorporating C and T equally and extending from both. X-ray crystal structures of both dC and dT paired with O6-MeG were solved in both insertion and extension modes. The structures revealed a Watson-Crick-like pairing between O6-MeG and 2"-deoxythymidine-5"-[(α, β)-imido]triphosphate (approximating dT) at both the insertion and extension stages with formation of two H-bonds. Conversely, both the structures with O6- MeG opposite dCTP and dC display sheared configuration of base pairs but to different degrees, with formation of two bifurcated H-bonds and two single H-bonds in the structures trapped in the insertion and extension states, respectively. The structural data are consistent with the observed tendency of hpol η to insert both dC and dT opposite the O6-MeG lesion with similar efficiencies. Comparison of the hpol η active site configurations with either O6-MeG:dC or O6-MeG:dT bound compared with the corresponding situations in structures of complexes of Sulfolobus solfataricus Dpo4, a bypass pol that favors C relative to T by a factor of ∼4, helps rationalize the more error-prone synthesis opposite the lesion by hpol η. PMID:27694439

A novel synthesis of octahydropyrido[3,2-c]carbazole framework of aspidospermidine alkaloids and a combined computational, FT-IR, NMR, NBO, NLO, FMO, MEP study of the cis-4a-Ethyl-1-(2hydroxyethyl)-2,3,4,4a,5,6,7,11c-octahydro-1H-pyrido[3,2-c]carbazole

Science.gov (United States)

Uludağ, Nesimi; Serdaroğlu, Goncagul; Yinanc, Abdullah

2018-06-01

In this study, we performed a novel synthesis of the octahydropyrido[3,2-c]carbazole derivative 6 from 1 in five steps with a 34% overall yield. We also developed a unique compound 2 by a cyclization reaction from the cyanoethylation of compound 1, which is an intermediate step in the synthesis of Aspidospermidine. The parent compound of Aspidospermidine alkaloids, comprise a large family of diverse structures. As a result, we obtained octahydropyrido[3,2-c]carbazole (6)and the proposed method may be applicable to other alkaloids. All quantum chemical calculations of the cis-4a-Ethyl-1-(2-hydroxyethyl)-2,3,4,4a,5,6,7,11c-octahydro-1H-pyrido[3,2-c]carbazole have been performed with the DFT/B3LYP and HF methods by using the Gaussian 09W software package. The most stable conformer obtained from the Potential Energy Surface (PES) scan analysis at the B3LYP/6-31G** level of theory in the gas phase was used as the starting structure of the title compound to further computational analysis. The Natural Bond Orbital (NBO) and NLO analyses were performed to evaluate the intra-molecular interactions contributing to the molecular stability and to predict the optical properties of the title compound, respectively. Gauge-Independent Atomic Orbital (GIAO) approach was used to determine the 1H and 1C NMR chemical shifts of the title compound by subtracting the shielding constants of TMS at both methods. The calculated vibrational frequencies of the title compound were assigned by using the VEDA program and were scaled down by using the scaling factor 0.9668 for B3LYP/6-311++G(d, p) and 0.9050 for HF/6-311++G(d, p) to improve the calculated vibrational frequencies. The FMO (frontier molecular orbital) analysis was evaluated to predict the chemical and physical properties of the title compound and the HOMO, LUMO, and MEP diagrams were visualized by GaussView 4.1 program to present the reactive site of the title compound.

Radiosynthesis of the D2/3 agonist [3-11C]-(+)-PHNO using [11C]iodomethane

International Nuclear Information System (INIS)

Francisco Garcia-Arguello, Segundo; Fortt, Robin; Steel, Colin J.; Brickute, Diana; Glaser, Matthias; Turton, David R.; Robins, Edward G.; Årstad, Erik; Luthra, Sajinder K.

2013-01-01

We report here a radiosynthesis for the D 2/3 agonist (+)-4-([3- 11 C]propyl)-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4] oxazin-9-ol (3-[ 11 C]-(+)-PHNO) labelled at the terminal carbon of the N-propyl chain. The protocol is based on 11 C-methylation of an N-acetyl precursor. This initial step is followed by a reduction with LiAlH 4 to give ([3- 11 C]-(+)-PHNO). We first applied the method for the synthesis of a model compound, N-3-([ 11 C]propyl)-1,2,3,4-tetrahydroisoquinoline, which we obtained in 77–97% analytical radiochemical yield (n=6) in 20 min. Similarly, we prepared ([3- 11 C]-(+)-PHNO) in 55–60% analytical radiochemical yield (n=5) using a one-pot procedure. We have also been able to implement the complete process on a semi-automated module. This platform delivered purified and formulated [3- 11 C]PHNO with an average radiochemical yield of 9% (n=13, range 2–30%, non-decay corrected), a radiochemical purity >95%, and a specific radioactivity of 26.8–81.1 GBq/μmol in a total time of 63–65 min. - Highlights: ► We report an alternative method to obtain carbon-11 labelled PHNO. ► The method is based on readily available [ 11 C]methyl iodide as starting material. ► We have automated the alkylation/reduction protocol including purification and formulation

Dopamine transporter binding in rat striatum: a comparison of [O-methyl-{sup 11}C]{beta}-CFT and [N-methyl-{sup 11}C]{beta}-CFT

Energy Technology Data Exchange (ETDEWEB)

Yoder, Karmen K.; Hutchins, Gary D.; Mock, Bruce H.; Fei, Xiangshu; Winkle, Wendy L. [Department of Radiology, Indiana University School of Medicine, L3-208, Indianapolis, IN 46202 (United States); Gitter, Bruce D.; Territo, Paul R. [Lilly Center for Anatomical and Molecular Imaging, Integrative Biology Division, Lilly Research Laboratories, Greenfield, IN 46140 (United States); Zheng Qihuang [Department of Radiology, Indiana University School of Medicine, L3-208, Indianapolis, IN 46202 (United States)], E-mail: qzheng@iupui.edu

2009-01-15

Introduction: Positron emission tomography scanning with radiolabeled phenyltropane cocaine analogs is important for quantifying the in vivo density of monoamine transporters, including the dopamine transporter (DAT). [{sup 11}C]{beta}-CFT is useful for studying DAT as a marker of dopaminergic innervation in animal models of psychiatric and neurological disorders. [{sup 11}C]{beta}-CFT is commonly labeled at the N-methyl position. However, labeling of [{sup 11}C]{beta}-CFT at the O-methyl position is a simpler procedure and results in a shorter synthesis time [desirable in small-animal studies, where specific activity (SA) is crucial]. In this study, we sought to validate that the O-methylated form of [{sup 11}C]{beta}-CFT provides equivalent quantitative results to that of the more commonly reported N-methyl form. Methods: Four female Sprague-Dawley rats were scanned twice on the IndyPET II small-animal scanner, once with [N-methyl-{sup 11}C]{beta}-CFT and once with [O-methyl-{sup 11}C]{beta}-CFT. DAT binding potentials (BP{identical_to}B'{sub avail}/K{sub d}) were estimated for right and left striata with a nonlinear least-squares algorithm, using a reference region (cerebellum) as the input function. Results: [N-Methyl-{sup 11}C]{beta}-CFT and [O-methyl-{sup 11}C]{beta}-CFT were synthesized with 40-50% radiochemical yields (HPLC purification). Radiochemical purity was >99%. SA at end of bombardment was 258{+-}30 GBq/{mu}mol. Average BP values for right and left striata with [N-methyl-{sup 11}C]{beta}-CFT were 1.16{+-}0.08 and 1.23{+-}0.14, respectively. BP values for [O-methyl-{sup 11}C]{beta}-CFT were 1.18{+-}0.08 (right) and 1.22{+-}0.16 (left). Paired t tests demonstrated that labeling position did not affect striatal DAT BP. Conclusions: These results suggest that [O-methyl-{sup 11}C]{beta}-CFT is quantitatively equivalent to [N-methyl-{sup 11}C]{beta}-CFT in the rat striatum.

Systemic catechol-O-methyl transferase inhibition enables the D1 agonist radiotracer R-[11C]SKF 82957

DEFF Research Database (Denmark)

Palner, Mikael; McCormick, Patrick; Parkes, Jun

2010-01-01

R-[(11)C]-SKF 82957 is a high-affinity and potent dopamine D(1) receptor agonist radioligand, which gives rise to a brain-penetrant lipophilic metabolite. In this study, we demonstrate that systemic administration of catechol-O-methyl transferase (COMT) inhibitors blocks this metabolic pathway, f...

Effects of single and repeated administration of 1,2,3,4-tetrahydroisoquinoline analogs on the binding of [11C]raclopride to dopamine D2 receptors in the mouse brain

International Nuclear Information System (INIS)

Ishiwata, K.; Senda, M.; Saitoh, T.; Taguchi, K.; Toda, J.; Sano, T.; Koyanagi, Y.

2001-01-01

We investigated the effects of intraperitoneal injection of 1,2,3,4-tetrahydroisoquinoline (TIQ) analogs and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the binding of [ 11 C]raclopride to striatal dopamine D 2 receptors in mice. The binding of [ 11 C]raclopride, but not of [ 11 C]N-methylspiperone or [ 11 C]nemonapride with higher affinity, to the receptors was significantly decreased immediately after TIQ injection. Neither a dopamine transporter blocker induced such effect nor TIQ affected the dopamine transporter-radioligand binding. Among the compounds investigated, including parkinsonism-inducing TIQ and (R/S)-1-benzyl-TIQ, parkinsonism-preventing (R)- and (S)-1-methyl-TIQ, and probable N-methylated metabolites of TIQ and 1-methyl-TIQ, TIQ and (S)-1-methyl-TIQ had the strongest effect on the binding of [ 11 C]raclopride, and N-methylated derivatives showed less of an effect than the respective parent compounds. The decrease in the binding of [ 11 C]raclopride continued for 7 hours and was followed by an increase until 10 days after the single and subchronic administration of TIQ. These findings suggest that TIQ analogs profoundly stimulated dopamine release which resulted in the competitive inhibition of the binding of [ 11 C]raclopride to dopamine D 2 receptors, but did not induce degeneration of the receptors. (author)

Increased complement C1q level marks active disease in human tuberculosis.

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Yi Cai

Full Text Available BACKGROUND: Complement functions as an important host defense system and complement C5 and C7 have been implicated in immunopathology of tuberculosis. However, little is known about the role of other complement components in tuberculosis. METHODS: Complement gene expression in peripheral blood mononuclear cells of tuberculosis patients and controls were determined using whole genome transcriptional microarray assays. The mRNA and protein levels of three C1q components, C1qA, C1qB, and C1qC, were further validated by qRT-PCR and enzyme-linked immunosorbent assay, respectively. The percentages of C1q expression in CD14 positive cells were determined by flow cytometry. Finally, C1qC protein level was quantified in the pleural fluid of tuberculosis and non-tuberculosis pleurisy. RESULTS: C1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α. CONCLUSIONS: C1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy.

El cas estrany d'una nena amb tuberculosi renal

OpenAIRE

Martínez Roig, Antonio

2009-01-01

La tuberculosi és una afecció més pròpia de localitzar-se als pulmons, a través del contagi per via aèria, que no pas fora d'ells. La que es produeix als ronyons seria només un 3% i la infecció estaria vinculada a la disseminació per via sanguínia i limfàtica de la tuberculosi pulmonar. Si considerem que la tuberculosi es diagnostica principalment a l'adolescència, trobarem força peculiar el cas d'una nena que va desenvolupar una tuberculosi renal amb tretze mesos de vida. La nena patia una d...

Erythritol, a non-nutritive sugar alcohol sweetener and the main component of truvia®, is a palatable ingested insecticide.

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Kaitlin M Baudier

Full Text Available Insecticides have a variety of commercial applications including urban pest control, agricultural use to increase crop yields, and prevention of proliferation of insect-borne diseases. Many pesticides in current use are synthetic molecules such as organochlorine and organophosphate compounds. Some synthetic insecticides suffer drawbacks including high production costs, concern over environmental sustainability, harmful effects on human health, targeting non-intended insect species, and the evolution of resistance among insect populations. Thus, there is a large worldwide need and demand for environmentally safe and effective insecticides. Here we show that Erythritol, a non-nutritive sugar alcohol, was toxic to the fruit fly Drosophila melanogaster. Ingested erythritol decreased fruit fly longevity in a dose-dependent manner, and erythritol was ingested by flies that had free access to control (sucrose foods in choice and CAFE studies. Erythritol was US FDA approved in 2001 and is used as a food additive in the United States. Our results demonstrate, for the first time, that erythritol may be used as a novel, environmentally sustainable and human safe approach for insect pest control.

Biosynthetic origin of the isoprene units in chromenes of Piper aduncum (Piperaceae)

International Nuclear Information System (INIS)

Leite, Ana C.; Lopes, Adriana A.; Bolzani, Vanderlan da S.; Furlan, Maysa; Kato, Massuo J.

2007-01-01

Metabolic studies involving the incorporation of [1- 13 C]-D-glucose into intact leaves of Piper aduncum (Piperaceae) have indicated that both the mevalonate (MVA) and the pyruvate-triose (MEP) non-mevalonate pathways are implicated in the biosynthesis of isoprene moieties present in methyl 2,2-dimethyl-2H-1-chromene-6-carboxylate (1) and methyl 2,2-dimethyl-8-(3'-methyl- 2'-butenyl)-2H-1-chromene-6-carboxylate (2). The pattern of incorporation of label from [1- 13 C]-D-glucose into these chromenes was determined by quantitative 13 C NMR spectroscopy. The results confirmed that biosynthetic compartment of 1 and 2 could either be the plastid and/ or the cytosol or, possibly, an additional compartment such as the plastid inter-membrane space. (author)

Improvement of erythrose reductase activity, deletion of by-products and statistical media optimization for enhanced erythritol production from Yarrowia lipolytica mutant 49.

Science.gov (United States)

Ghezelbash, Gholam Reza; Nahvi, Iraj; Emamzadeh, Rahman

2014-08-01

The purpose of the present investigation was to produce erythritol by Yarrowia lipolytica mutant without any by-products. Mutants of Y. lipolytica were generated by ultra-violet for enhancing erythrose reductase (ER) activity and erythritol production. The mutants showing the highest ER activity were screened by triphenyl tetrazolium chloride agar plate assay. Productivity of samples was analyzed by thin-layer chromatography and high-performance liquid chromatography equipped with the refractive index detector. One of the mutants named as mutant 49 gave maximum erythritol production without any other by-products (particularly glycerol). Erythritol production and specific ER activity in mutant 49 increased to 1.65 and 1.47 times, respectively, in comparison with wild-type strain. The ER gene of wild and mutant strains was sequenced and analyzed. A general comparison of wild and mutant gene sequences showed the replacement of Asp(270) with Glu(270) in ER protein. In order to enhance erythritol production, we used a three component-three level-one response Box-Behnken of response surface methodology model. The optimum medium composition for erythritol production was found to be (g/l) glucose 279.49, ammonium sulfate 9.28, and pH 5.41 with 39.76 erythritol production.

Molecular structure, vibrational, HOMO-LUMO, MEP and NBO analysis of hafnium selenite

Science.gov (United States)

Yankova, Rumyana; Genieva, Svetlana; Dimitrova, Ginka

2017-08-01

In hydrothermal condition hafnium selenite with estimated chemical composition Hf(SeO3)2·n(H2O) was obtained and characterized by powder X-Ray diffraction, IR spectroscopy and thermogravimetrical analysis. The composition of the obtained crystalline phase was established as dihydrate of tetraaqua complex of the hafnium selenite [Hf(SeO3)2(H2O)4]·2H2O. The results of the thermogravimetrical analysis are shown that the two hydrated water molecules are released in the temperature interval 80-110°C, while the four coordinated water molecules - at 210-300°C. By DFT method, with Becke's three parameter exchange-functional combined with gradient-corrected correlation functional of Lee, Yang and Parr and 6-31G(d), 6-311 + G(d,p) basis sets and LANL2DZ for Hf atom were calculated the molecular structure, vibrational frequencies and thermodynamic properties of the structure. The UV-Vis spectra and electronic properties are presented. The energy and oscillator strength calculated by time-dependent density functional theory corresponds well with the experimental ones. Molecular electrostatic potential (MEP) was performed. Mulliken population analysis on atomic charges was also calculated. The stability and intramolecular interactions are interpreted by NBO analysis.

Theoretical study of the regioselectivity of the interaction of 3-methyl-4-pyrimidone and 1-methyl-2-pyrimidone with Lewis acids.

Science.gov (United States)

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.

Induced expression of hepatic N-methyl-D-aspartate receptor 2C subunit gene during liver enlargement induced by lead nitrate, a hepatocellular mitogen.

Science.gov (United States)

Nemoto, Kiyomitsu; Ikeda, Ayaka; Hikida, Tokihiro; Kojima, Misaki; Degawa, Masakuni

2013-02-01

We previously demonstrated the super-induced expression of the Grin2c gene encoding the N-methyl-D-aspartate receptor 2C subunit during the development of liver enlargement with hepatocellular hypertrophy induced by phenobarbital, clofibrate, or piperonyl butoxide. In the present study, we assessed whether or not Grin2c gene expression was induced during the development of chemically induced liver enlargement with hyperplasia. Male Sprague-Dawley (SD) rats, stroke-prone spontaneously hypertensive rats (SHRSPs), and SHRSP's normotensive control, Wistar-Kyoto (WKY) rats, were administered lead nitrate (LN) (0.1 mmol/kg, single i.v.), a direct inducer of liver hyperplasia, and changes in the level of Grin2c mRNA in the liver were assessed by real-time RT-PCR. The level of hepatic Grin2c mRNA was significantly higher 6-48 hr after the injection in SD rats (about 30~40- and 70-fold over the control at 6~24 hr and 48 hr, respectively) and in WKY rats (about 20-fold over the control only at 12 hr), but was not significantly higher in SHRSPs. Such differences in LN-induced levels of Grin2c mRNA among SD rats, WKY rats, and SHRSPs were closely correlated with those in the previously reported increase in liver weight 48 hr after LN administration. The present findings suggest that the increase in the level of hepatic Grin2c mRNA relates to development of chemically induced liver enlargement with hyperplasia.

The Mycobacterium tuberculosis Complex has a Pathway for the Biosynthesis of 4-Formamido-4,6-Dideoxy-d-Glucose.

Science.gov (United States)

Brown, Haley A; Vinogradov, Evgeny; Gilbert, Michel; Holden, Hazel M

2018-05-15

Recent studies have demonstrated that the O-antigens of some pathogenic bacteria such as Brucella abortus, Francisella tularensis, and Campylobacter jejuni contain quite unusual N-formylated sugars (3-formamido-3,6-dideoxy-d-glucose or 4-formamido-4,6-dideoxy-d-glucose). Typically, four enzymes are required for the formation of such sugars: a thymidylyltransferase, a 4,6-dehydratase, a pyridoxal 5'-phosphate or PLP-dependent aminotransferase, and an N-formyltransferase. To date, there have been no published reports of N-formylated sugars associated with Mycobacterium tuberculosis. A recent investigation from our laboratories, however, has demonstrated that one gene product from M. tuberculosis, Rv3404c, functions as a sugar N-formyltransferase. Given that M. tuberculosis produces l-rhamnose, both a thymidylyltransferase (Rv0334) and a 4,6-dehydratase (Rv3464) required for its formation have been identified. Thus, there is one remaining enzyme needed for the production of an N-formylated sugar in M. tuberculosis, namely a PLP-dependent aminotransferase. Here we demonstrate that the M. tuberculosis rv3402c gene encodes such an enzyme. Our data prove that M. tuberculosis contains all of the enzymatic activities required for the formation of dTDP-4-formamido-4,6-dideoxy-d-glucose. Indeed, the rv3402c gene product likely contributes to virulence or persistence during infection, though its temporal expression and location remain to be determined. This article is protected by copyright. All rights reserved. © 2018 The Protein Society.

Patchoulol Production with Metabolically Engineered Corynebacterium glutamicum

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Nadja A. Henke

2018-04-01

Full Text Available Patchoulol is a sesquiterpene alcohol and an important natural product for the perfume industry. Corynebacterium glutamicum is the prominent host for the fermentative production of amino acids with an average annual production volume of ~6 million tons. Due to its robustness and well established large-scale fermentation, C. glutamicum has been engineered for the production of a number of value-added compounds including terpenoids. Both C40 and C50 carotenoids, including the industrially relevant astaxanthin, and short-chain terpenes such as the sesquiterpene valencene can be produced with this organism. In this study, systematic metabolic engineering enabled construction of a patchoulol producing C. glutamicum strain by applying the following strategies: (i construction of a farnesyl pyrophosphate-producing platform strain by combining genomic deletions with heterologous expression of ispA from Escherichia coli; (ii prevention of carotenoid-like byproduct formation; (iii overproduction of limiting enzymes from the 2-c-methyl-d-erythritol 4-phosphate (MEP-pathway to increase precursor supply; and (iv heterologous expression of the plant patchoulol synthase gene PcPS from Pogostemon cablin. Additionally, a proof of principle liter-scale fermentation with a two-phase organic overlay-culture medium system for terpenoid capture was performed. To the best of our knowledge, the patchoulol titers demonstrated here are the highest reported to date with up to 60 mg L−1 and volumetric productivities of up to 18 mg L−1 d−1.

Thermophysical Characterization of MgCl₂·6H₂O, Xylitol and Erythritol as Phase Change Materials (PCM) for Latent Heat Thermal Energy Storage (LHTES).

Science.gov (United States)

Höhlein, Stephan; König-Haagen, Andreas; Brüggemann, Dieter

2017-04-24

The application range of existing real scale mobile thermal storage units with phase change materials (PCM) is restricted by the low phase change temperature of 58 ∘ C for sodium acetate trihydrate, which is a commonly used storage material. Therefore, only low temperature heat sinks like swimming pools or greenhouses can be supplied. With increasing phase change temperatures, more applications like domestic heating or industrial process heat could be operated. The aim of this study is to find alternative PCM with phase change temperatures between 90 and 150 ∘ C . Temperature dependent thermophysical properties like phase change temperatures and enthalpies, densities and thermal diffusivities are measured for the technical grade purity materials xylitol (C 5 H 12 O 5 ), erythritol (C 4 H 10 O 4 ) and magnesiumchloride hexahydrate (MCHH, MgCl 2 · 6H 2 O). The sugar alcohols xylitol and erythritol indicate a large supercooling and different melting regimes. The salt hydrate MgCl 2 · 6H 2 O seems to be a suitable candidate for practical applications. It has a melting temperature of 115.1 ± 0.1 ∘ C and a phase change enthalpy of 166.9 ± 1.2 J / g with only 2.8 K supercooling at sample sizes of 100 g . The PCM is stable over 500 repeated melting and solidification cycles at differential scanning calorimeter (DSC) scale with only small changes of the melting enthalpy and temperature.

The Inhibition of Folylpolyglutamate Synthetase (folC in the Prevention of Drug Resistance in Mycobacterium tuberculosis by Traditional Chinese Medicine

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Tzu-Chieh Hung

2014-01-01

Full Text Available Tuberculosis (TB is an infectious disease caused by many strains of mycobacteria, but commonly Mycobacterium tuberculosis. As a possible method of reducing the drug resistance of M. tuberculosis, this research investigates the inhibition of Folylpolyglutamate synthetase, a protein transcript from the resistance association gene folC. After molecular docking to screen the traditional Chinese medicine (TCM database, the candidate TCM compounds, with Folylpolyglutamate synthetase, were selected by molecular dynamics. The 10,000 ps simulation in association with RMSD analysis and total energy and structural variation defined the protein-ligand interaction. The selected TCM compounds Saussureamine C, methyl 3-O-feruloylquinate, and Labiatic acid have been found to inhibit the activity of bacteria and viruses and to regulate immunity. We also suggest the possible pathway in protein for each ligand. Compared with the control, similar interactions and structural variations indicate that these compounds might have an effect on Folylpolyglutamate synthetase. Finally, we suggest Saussureamine C is the best candidate compound as the complex has a high score, maintains its structural composition, and has a larger variation value than the control, thus inhibiting the drug resistance ability of Mycobacterium tuberculosis.

Medidas de control de tuberculosis en una institución de salud de Bogotá D.C

OpenAIRE

Muñoz-Sánchez, Alba I; Castro-Cely, Yesenia

2016-01-01

Objetivo: evaluar la implementación de medidas de control, de tipo administrativo, ambiental y de protección respiratoria, de la infección de tuberculosis en un hospital de III nivel de atención en la ciudad de Bogotá D.C. Metodología: estudio de tipo descriptivo, transversal. Para la recolección de datos se aplicó una herramienta de autorreporte a 158 trabajadores de la salud del hospital, se realizó una entrevista estructurada al responsable del programa institucional de control de tubercul...

Medidas de control de tuberculosis en una institución de salud de Bogotá D.C

OpenAIRE

Alba I. Muñoz-Sánchez; Yesenia Castro-Cely

2016-01-01

Resumen Objetivo: evaluar la implementación de medidas de control, de tipo administrativo, ambiental y de protección respiratoria, de la infección de tuberculosis en un hospital de III nivel de atención en la ciudad de Bogotá D.C. Metodología: estudio de tipo descriptivo, transversal. Para la recolección de datos se aplicó una herramienta de autorreporte a 158 trabajadores de la salud del hospital, se realizó una entrevista estructurada al responsable del programa institucional de control ...

1.55 Å resolution X-ray crystal structure of Rv3902c from Mycobacterium tuberculosis

Energy Technology Data Exchange (ETDEWEB)

Reddy, Bharat G.; Moates, Derek B. [University of Alabama at Birmingham, 1025 18th Street South, Birmingham, AL 35233 (United States); Kim, Heung-Bok [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Green, Todd J. [University of Alabama at Birmingham, 1025 18th Street South, Birmingham, AL 35233 (United States); Kim, Chang-Yub; Terwilliger, Thomas C. [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); DeLucas, Lawrence J., E-mail: duke2@uab.edu [University of Alabama at Birmingham, 1025 18th Street South, Birmingham, AL 35233 (United States)

2014-03-25

The 1.55 Å resolution X-ray crystal structure of Rv3902c from M. tuberculosis reveals a novel fold. The crystallographic structure of the Mycobacterium tuberculosis (TB) protein Rv3902c (176 residues; molecular mass of 19.8 kDa) was determined at 1.55 Å resolution. The function of Rv3902c is unknown, although several TB genes involved in bacterial pathogenesis are expressed from the operon containing the Rv3902c gene. The unique structural fold of Rv3902c contains two domains, each consisting of antiparallel β-sheets and α-helices, creating a hand-like binding motif with a small binding pocket in the palm. Structural homology searches reveal that Rv3902c has an overall structure similar to that of the Salmonella virulence-factor chaperone InvB, with an r.m.s.d. for main-chain atoms of 2.3 Å along an aligned domain.

1.55 Å resolution X-ray crystal structure of Rv3902c from Mycobacterium tuberculosis

International Nuclear Information System (INIS)

Reddy, Bharat G.; Moates, Derek B.; Kim, Heung-Bok; Green, Todd J.; Kim, Chang-Yub; Terwilliger, Thomas C.; DeLucas, Lawrence J.

2014-01-01

The 1.55 Å resolution X-ray crystal structure of Rv3902c from M. tuberculosis reveals a novel fold. The crystallographic structure of the Mycobacterium tuberculosis (TB) protein Rv3902c (176 residues; molecular mass of 19.8 kDa) was determined at 1.55 Å resolution. The function of Rv3902c is unknown, although several TB genes involved in bacterial pathogenesis are expressed from the operon containing the Rv3902c gene. The unique structural fold of Rv3902c contains two domains, each consisting of antiparallel β-sheets and α-helices, creating a hand-like binding motif with a small binding pocket in the palm. Structural homology searches reveal that Rv3902c has an overall structure similar to that of the Salmonella virulence-factor chaperone InvB, with an r.m.s.d. for main-chain atoms of 2.3 Å along an aligned domain

Micro-syntheses for the use of carbon 13 or carbon 14. Micro-preparations of methyl alcohol, methyl iodide, and sodium acetate labeled in the methyl group; Microsyntheses pour l'emploi de carbone 13 ou de carbone 14. Micropreparations d'alcool methylique, d'iodure de methyle et d'acetate de sodium marque sur le groupement methyle

Energy Technology Data Exchange (ETDEWEB)

Baret, C; Pichat, L

1951-11-01

Apparatus and technique are described in detail for (1) reduction of CO{sub 2} to CH{sub 3}OH with LiAlH{sub 4}, (2) conversion of the methanol to CH{sub 3}I by HI, (3) formation of the Mg Grignard reagent, and (4) addition of inactive CO{sub 2} to form CH{sub 3}COOH. All these operations have been carried out on 0.005 moles. Methyl-labeled Na acetate has been prepared in 67% yield based on the Ba{sup 14}CO{sub 3} used as starting material. (author) [French] Description detaillee d'une technique deja connue pour la reduction du gaz carbonique en alcool methylique par LiAlH{sub 4}. Conversion du methanol en iodure de methyle. Ce dernier transforme en reactif de Grigard, et carbonate, fournit de l'acide acetique. Toutes ces operations on ete effectuees sur 5 x 10{sup -3} moles. La methode a ete appliquee a la synthese d'acetate de sodium marque par le groupement methyle par {sup 14}C avec un rendement global de 67% base sur le carbonate de baryum radioactif mis en oeuvre. (auteurs)

Biosynthetic origin of the isoprene units in chromenes of Piper aduncum (Piperaceae)

Energy Technology Data Exchange (ETDEWEB)

Leite, Ana C.; Lopes, Adriana A.; Bolzani, Vanderlan da S.; Furlan, Maysa [UNESP, Araraquara, SP (Brazil). Inst. de Quimica]. E-mail: maysaf@iq.unesp.br; Kato, Massuo J. [Universidade de Sao Paulo (USP), SP (Brazil). Inst. de Quimica

2007-07-01

Metabolic studies involving the incorporation of [1-{sup 13}C]-D-glucose into intact leaves of Piper aduncum (Piperaceae) have indicated that both the mevalonate (MVA) and the pyruvate-triose (MEP) non-mevalonate pathways are implicated in the biosynthesis of isoprene moieties present in methyl 2,2-dimethyl-2H-1-chromene-6-carboxylate (1) and methyl 2,2-dimethyl-8-(3'-methyl- 2'-butenyl)-2H-1-chromene-6-carboxylate (2). The pattern of incorporation of label from [1- {sup 13}C]-D-glucose into these chromenes was determined by quantitative {sup 13}C NMR spectroscopy. The results confirmed that biosynthetic compartment of 1 and 2 could either be the plastid and/ or the cytosol or, possibly, an additional compartment such as the plastid inter-membrane space. (author)

TNF-a-induced down-regulation of CDX2 suppresses MEP1A expression in colitis

DEFF Research Database (Denmark)

Coskun, Mehmet; Olsen, Anders Krüger; Holm, Thomas Lindebo

2012-01-01

was investigated in colonic biopsies of ulcerative colitis (UC) patients and in dextran sodium sulfate (DSS)-induced colitis. CDX2 protein expression was investigated by immunoblotting and immunohistochemical procedures. CDX2 and MEP1A regulation was examined in TNF-a-treated Caco-2 cells by reverse transcription...

Four-week oral toxicity study with erythritol in rats

NARCIS (Netherlands)

Til, H.P.; Modderman, J.

1996-01-01

Erythritol was orally administered to Wistar rats at dietary levels of 0, 5, and 10% for 4 weeks. Soft stools and diarrhea were observed in male and female animals of the 10% group and in female animals of the 5% group. These symptoms disappeared during the course of the study. Mean body weights of

Experimental and computational approaches of a novel methyl (2E)-2-{[N-(2-formylphenyl)(4-methylbenzene)sulfonamido]methyl}-3-(4-chlorophenyl)prop-2-enoate: A potential antimicrobial agent and an inhibition of penicillin-binding protein

Science.gov (United States)

Murugavel, S.; Vetri velan, V.; Kannan, Damodharan; Bakthadoss, Manickam

2016-07-01

The title compound methyl(2E)-2-{[N-(2-formylphenyl) (4-methylbenzene)sulfonamido]methyl}-3-(4-chlorophenyl) prop-2-enoate (MFMSC) has been synthesized and single crystals were grown by slow evaporation solution growth technique at room temperature. Structural and vibrational spectroscopic studies were carried out by using single crystal X-ray diffraction, FT-IR and NMR spectral analysis together with DFT method using GAUSSIAN'03 software. The detailed interpretation of the vibrational spectra has been carried out by VEDA program. NBO analysis, Mulliken charge analysis, HOMO-LUMO, MEP, Global chemical reactivity descriptors and thermodynamic properties have been analyzed. The hyperpolarisability calculation reveals the present material has a reasonably good propensity for nonlinear optical activity. The obtained antimicrobial activity results indicate that the compound shows good to moderate activity against all tested bacterial and fungal pathogens. A computational study was also carried out to predict the drug-likeness and ADMET properties of the title compound. Due to the different potential biological activity of the title compound, molecular docking study is also reported and the compound might exhibit inhibitory activity against penicillin-binding protein PBP-2X.

MeCP2 Expression and Promoter Methylation of Cyclin D1 Gene Are Associated with Cyclin D1 Expression in Developing Rat Epididymal Duct

International Nuclear Information System (INIS)

Darwanto, Agus; Kitazawa, Riko; Mori, Kiyoshi; Kondo, Takeshi; Kitazawa, Sohei

2008-01-01

Hypermethylation-dependent silencing of the gene is achieved by recruiting methyl-CpG binding proteins (MeCPs). Among the MeCPs, MeCP2 is the most abundantly and ubiquitously expressed in various types of cells. We first screened the distribution and expression pattern of MeCP2 in adult and developing rat tissues and found strong MeCP2 expression, albeit rather ubiquitously among normal tissues, in ganglion cells and intestinal epithelium in the small intestine, in Purkinje cells and neurons in the brain, in spermatogonia and in epithelial cells in the epididymal duct of the testis. We then assessed the expression and the methylation pattern of the promoter region of cyclin D1 by immunohistochemistry and sodium bisulfite mapping, and found that cyclin D1 expression in the epididymal duct decreased rapidly during rat development: strong in newborn rats and very weak or almost negative in 7-day-old rats. Mirroring the decrease of cyclin D1 expression, methylated cytosine at both CpG and non-CpG loci in the cyclin D1 promoter was frequently observed in the epididymal duct of 7-day-old rats but not in that of newborn rats. Interestingly, MeCP2 expression also increased concomitant with the increase of methylation. Cyclin D1 expression in the epididymal duct may be efficiently regulated by the epigenetic mechanism of the cooperative increase of MeCP2 expression and promoter methylation

Synthesis of methyl (13(2)R/S)-alkyl-pyropheophorbide a and a non-epimerized chlorophyll a mimic.

Science.gov (United States)

Ogasawara, Shin; Tamiaki, Hitoshi

2015-10-15

The (13(2)R/S)-methoxycarbonyl group of methyl pheophorbides a/a' (chlorophyll a/a' derivatives) was converted to methyl, ethyl, propyl, and isopropyl groups through the C13(2)-alkylation under basic conditions followed by pyrolysis in 2,4,6-collidine with lithium iodide. All the resulting products, methyl 13(2)-alkyl-pyropheophorbides a, predominantly gave the (13(2)R)-stereoisomers with about one tenth of the (13(2)S)-epimers. Their stereochemistry was determined by 1D/2D NMR and their optical properties were characterized by visible absorption and circular dichroism spectroscopy. Methyl (13(2)R)-propyl-pyropheophorbide a was converted to (13(2)R)-propyl-pyrochlorophyll a by ester exchanging and magnesium chelating reactions. The synthetic chlorophyll a analogue showed non-epimerization at the 13(2)-position in pyridine-d5 at 40°C, while naturally occurring chlorophyll a was easily epimerized under the same conditions to give its epimeric mixture. Copyright © 2015 Elsevier Ltd. All rights reserved.

Systemic catechol-O-methyl transferase inhibition enables the D{sub 1} agonist radiotracer R-[{sup 11}C]SKF 82957

Energy Technology Data Exchange (ETDEWEB)

Palner, Mikael, E-mail: mikael.palner@nru.d [Neurobiology Research Unit, Rigshospitalet and University of Copenhagen, Copenhagen (Denmark); Center for Integrated Molecular Brain Imaging, Rigshospitalet (Denmark); McCormick, Patrick; Parkes, Jun [PET Center, Center for Addiction and Mental Health, Toronto, Ontario (Canada); Knudsen, Gitte M. [Neurobiology Research Unit, Rigshospitalet and University of Copenhagen, Copenhagen (Denmark); Center for Integrated Molecular Brain Imaging, Rigshospitalet (Denmark); Wilson, Alan A. [PET Center, Center for Addiction and Mental Health, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario (Canada)

2010-10-15

Introduction: R-[{sup 11}C]-SKF 82957 is a high-affinity and potent dopamine D{sub 1} receptor agonist radioligand, which gives rise to a brain-penetrant lipophilic metabolite. In this study, we demonstrate that systemic administration of catechol-O-methyl transferase (COMT) inhibitors blocks this metabolic pathway, facilitating the use of R-[{sup 11}C]-SKF 82957 to image the high-affinity state of the dopamine D{sub 1} receptor with PET. Methods: R-[{sup 11}C]SKF 82957 was administered to untreated and COMT inhibitor-treated conscious rats, and the radioactive metabolites present in the brain and plasma were quantified by HPLC. Under optimal conditions, cerebral uptake and dopamine D{sub 1} binding of R-[{sup 11}C]SKF 82957 were measured ex vivo. In addition, pharmacological challenges with the receptor antagonist SCH 23390, amphetamine, the dopamine reuptake inhibitor RTI-32 and the dopamine hydroxylase inhibitor {alpha}-methyl-p-tyrosine were performed to study the specificity and sensitivity of R-[{sup 11}C]-SKF 82957 dopamine D{sub 1} binding in COMT-inhibited animals. Results: Treatment with the COMT inhibitor tolcapone was associated with a dose-dependent (EC{sub 90} 5.3{+-}4.3 mg/kg) reduction in the lipophilic metabolite. Tolcapone treatment (20 mg/kg) also resulted in a significant increase in the striatum/cerebellum ratio of R-[{sup 11}C]SKF 82957, from 15 (controls) to 24. Treatment with the dopamine D{sub 1} antagonist SCH 23390 reduced the striatal binding to the levels of the cerebellum, demonstrating a high specificity and selectivity of R-[{sup 11}C]SKF 82957 binding. Conclusions: Pre-treatment with the COMT inhibitor tolcapone inhibits formation of an interfering metabolite of R-[{sup 11}C]SKF 82957. Under such conditions, R-[{sup 11}C]SKF 82957 demonstrates high potential as the first agonist radiotracer for imaging the dopamine D{sub 1} receptor by PET.

Synthesis of MoS_2/g-C_3N_4 nanosheets as 2D heterojunction photocatalysts with enhanced visible light activity

International Nuclear Information System (INIS)

Li, Juan; Liu, Enzhou; Ma, Yongning; Hu, Xiaoyun; Wan, Jun; Sun, Lin; Fan, Jun

2016-01-01

Graphical abstract: TEM image and schematic diagram of photocatalytic mechanism of 2D MoS_2/g-C_3N_4 composites. - Highlights: • g-C_3N_4 nanosheets coupled with MoS_2 nanosheets as 2D heterojunction photocatalysts were synthesized successfully. • The 2D MoS_2/g-C_3N_4 heterojunctions show higher photocatalytic activity than pure g-C_3N_4. • The photocatalytic mechanism of the 2D MoS_2/g-C_3N_4 heterojunction was described. - Abstract: g-C_3N_4 nanosheets coupled with MoS_2 nanosheets as 2D heteroconjuction were prepared via a facile impregnation and calcination method. The structure characterization clearly indicated that MoS_2 nanosheets were successfully horizontal loaded on g-C_3N_4 nanosheets. The investigation indicated that the formation of 2D heterojunction between the g-C_3N_4 nanosheets and MoS_2 nanosheets promoted the charge transfer and enhanced separation efficiency of photoinduced electron–hole pairs. Furthermore, the measurement of photocatalytic activity for the degradation of rhodamine B and methyl orange revealed that the as-prepared 2D MoS_2/g-C_3N_4 heterojunction exhibited the significantly enhanced photocatalytic activity and considerable stability under visible light irradiation. The 2D MoS_2/g-C_3N_4 heterojunction prepared with 3 wt% of MoS_2 exhibited the optimal photodegradable efficiency. The present work shows that the formation of 2D heterojunction should be a good strategy to design efficient photocatalysts.

Overexpressing 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR in the lactococcal mevalonate pathway for heterologous plant sesquiterpene production.

Directory of Open Access Journals (Sweden)

Adelene Ai-Lian Song

Full Text Available Isoprenoids are a large and diverse group of metabolites with interesting properties such as flavour, fragrance and therapeutic properties. They are produced via two pathways, the mevalonate pathway or the 2-C-methyl-D-erythritol-4-phosphate (MEP pathway. While plants are the richest source of isoprenoids, they are not the most efficient producers. Escherichia coli and yeasts have been extensively studied as heterologous hosts for plant isoprenoids production. In the current study, we describe the usage of the food grade Lactococcus lactis as a potential heterologous host for the production of sesquiterpenes from a local herbaceous Malaysian plant, Persicaria minor (synonym Polygonum minus. A sesquiterpene synthase gene from P. minor was successfully cloned and expressed in L. lactis. The expressed protein was identified to be a β-sesquiphellandrene synthase as it was demonstrated to be functional in producing β-sesquiphellandrene at 85.4% of the total sesquiterpenes produced based on in vitro enzymatic assays. The recombinant L. lactis strain developed in this study was also capable of producing β-sesquiphellandrene in vivo without exogenous substrates supplementation. In addition, overexpression of the strain's endogenous 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR, an established rate-limiting enzyme in the eukaryotic mevalonate pathway, increased the production level of β-sesquiphellandrene by 1.25-1.60 fold. The highest amount achieved was 33 nM at 2 h post-induction.

From 2D to 3D turbulence through 2D3C configurations

Science.gov (United States)

Buzzicotti, Michele; Biferale, Luca; Linkmann, Moritz

2017-11-01

We study analytically and numerically the geometry of the nonlinear interactions and the resulting energy transfer directions of 2D3C flows. Through a set of suitably designed Direct Numerical Simulations we also study the coupling between several 2D3C flows, where we explore the transition between 2D and fully 3D turbulence. In particular, we find that the coupling of three 2D3C flows on mutually orthogonal planes subject to small-scale forcing leads to a stationary 3D out-of-equilibrium dynamics at the energy containing scales where the inverse cascade is directly balanced by a forward cascade carried by a different subsets of interactions. ERC AdG Grant No 339032 NewTURB.

Vitamin D status did not related to calcium status in active tuberculosis patients in North Sumatera, Indonesia

Science.gov (United States)

Keumala Sari, Dina; Khairina Arrasyid, Nurfida

2018-03-01

Background: Tuberculosis is one of the highest mortality caused in a tropical country with abundant sunlight such Indonesia. Vitamin D and calcium plays important roles in tuberculosis pathogenesis. Objective:We sought to determine whether there is an association between vitamin D status and calcium status in tuberculosis patients. Design: We conducted a cross-sectional study of 32 man and women aged 18-60 years with active tuberculosis in North Sumatera, Indonesia. Parameters were 25(OH)D and calcium serum level, body mass index, fat mass, and others lifestyles factors also assessed. The association was analysis using chi-square or fischer test. Results: the mean of study subjects age were 37.2±14.9 years old and BMI were 20.8±4.4 kg/m2 There were 81.2% subjects categorized into vitamin D deficiency-insufficiency and 18.8% categorized into vitamin D sufficiency. There were 29% subjects categorized into normal calcium level, and 3% were hypocalcemia. Based on food recall analysis, there were found lower vitamin D and calcium intake. There is no association between vitamin D and calcium classification. Conclusions: based on this result, although there is no association between vitamin D and calcium, but there could be altered by lower food intake and tuberculosis progression.

Financial incentive for the Environmental Quality of Electricity Production (MEP)

International Nuclear Information System (INIS)

2007-01-01

With the MEP subsidy regulation 'Environmental quality of electricity production' The Dutch minister of Economic Affairs focussed mainly on reaching the policy objective of the EU according to which 9% of all electricity used in the Netherlands should be generated with sustainable sources. According to the opinion of the Dutch Court of Audits not enough attention has been paid to the coherence of the MEP regulation with other policy objectives in the area of sustainability, such as air quality and CO2 reduction. The same goes for the effectiveness and the financial management of the MEP regulation. Moreover, the study, which was carried out by request of the Dutch Lower House, demonstrates that it is still uncertain if the policy objective for 2010 will be reached. The report consists of two parts: part 1: Conclusions, recommendations and administrative reactions, and Part 2: Answering Lower House questions.(mk) [nl

[Determination methods for the content of methyl salicylate-2-O-beta-D-galactopyranoside (1-4)-beta-D-glucopyranoside].

Science.gov (United States)

He, Xiu-Feng; Xia, Peng-Fei; Wang, Ai-Guo; Liu, Dong; Zhao, Li-Min

2012-07-01

The paper is to report the establishment of three methods for determination of methyl salicylate-2-O-beta-D-galactopyranoside (1-4)-beta-D-glucopyranoside (MSG) by HPLC, UV or potentiometric titration. The results determined by the three methods turned out to be of no significant difference (P>0.05). The method was chosen according to MSG difference test demands.

A new C-methylated flavonoid glycoside from Pinus densiflora.

Science.gov (United States)

Jung, M J; Choi, J H; Chung, H Y; Jung, J H; Choi, J S

2001-12-01

A new C-methyl flavonol glycoside, 5,7,8,4'-tetrahydroxy-3-methoxy-6-methylflavone 8-O-beta-D-glucopyranoside (1), has been isolated from the needles of Pinus densiflora, together with kaempferol 3-O-beta-(6"-acetyl)-galactopyranoside.

C-11 production with MC-50 cyclotron and synthesis of L-[11C-methyl] methionine

International Nuclear Information System (INIS)

Kim, Sang Wook; Hur, Min Goo; Yang, Seung Dae; Ahn, Soon Hyuk; Chun, Kweon Soo

2003-01-01

L-[ 11 C-methyl] methionine was prepared via no-carrier-added(nca) fast S-alkylation of L-homocysteine with [ 11 C]CH 3 I using solid support (Al 2 O 3 /KF)at room temperature in ethanol. The radiochemical yield of methylation was 90.2%. After reaction, no radiochemical impurity was detected but traces of L-homocysteine precursor were monitored by UV detector. The purification was archived by passing successively through a C 18 and alumina sep-pak. the radiochemical purity of L-[ 11 C-methyl] methionine was over 98% after purification and total elapsed time to prepare was 10min from [ 11 C]CH 3 I delivery

Cost effectiveness of the Dutch incentive for the environmental quality of power generation (MEP)

International Nuclear Information System (INIS)

Melgerd, R.

2005-01-01

This article relates to research on the cost effectiveness of the MEP scheme ('Milieukwaliteit Elektriciteitsproductie' or Environmental Quality of Electricity Generation), carried out as a graduation project at the Vrije Universiteit, Amsterdam, Netherlands. MEP subsidies are intended to promote investment in sustainable energy sources in the Netherlands by offering investors more certainty and a simpler structure than previous energy subsidies. The MEP also helps prevent Dutch taxpayers' money 'leaking' abroad to purchase sustainable electricity produced cheaper elsewhere. This makes the MEP measurably more effective than its predecessors. The scheme is moreover a step towards the effective deployment of state funds for the reduction of CO2 emission [nl

NMR study of temperature-induced phase separation and polymer-solvent interactions in poly(vinyl methyl ether)/D.sub.2./sub.O/ethanol solutions

Czech Academy of Sciences Publication Activity Database

Hanyková, L.; Labuta, J.; Spěváček, Jiří

2006-01-01

Roč. 47, č. 17 (2006), s. 6107-6116 ISSN 0032-3861 Grant - others:GA UK 294/2004/B Institutional research plan: CEZ:AV0Z40500505 Keywords : poly(vinyl methyl ether)/D2O/ ethanol solutions * temperature-induced phase separation * 1H and 13C NMR spectroscopy Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.773, year: 2006

Gut hormone secretion, gastric emptying, and glycemic responses to erythritol and xylitol in lean and obese subjects

DEFF Research Database (Denmark)

Wölnerhanssen, Bettina K; Cajacob, Lucian; Keller, Nino

2016-01-01

With the increasing prevalence of obesity and a possible association with increasing sucrose consumption, nonnutritive sweeteners are gaining popularity. Given that some studies indicate that artificial sweeteners might have adverse effects, alternative solutions are sought. Xylitol and erythritol...... satiation, reduce gastric emptying (GE), and modulate glucose homeostasis. Although glucose ingestion stimulates sweet taste receptors in the gut and leads to incretin and gastrointestinal hormone release, the effects of xylitol and erythritol have not been well studied. Ten lean and 10 obese volunteers...

Co-expression of peppermint geranyl diphosphate synthase small subunit enhances monoterpene production in transgenic tobacco plants.

Science.gov (United States)

Yin, Jun-Lin; Wong, Woon-Seng; Jang, In-Cheol; Chua, Nam-Hai

2017-02-01

Monoterpenes are important for plant survival and useful to humans. In addition to their function in plant defense, monoterpenes are also used as flavors, fragrances and medicines. Several metabolic engineering strategies have been explored to produce monoterpene in tobacco but only trace amounts of monoterpenes have been detected. We investigated the effects of Solanum lycopersicum 1-deoxy-d-xylulose-5-phosphate synthase (SlDXS), Arabidopsis thaliana geranyl diphosphate synthase 1 (AtGPS) and Mentha × piperita geranyl diphosphate synthase small subunit (MpGPS.SSU) on production of monoterpene and geranylgeranyl diphosphate (GGPP) diversities, and plant morphology by transient expression in Nicotiana benthamiana and overexpression in transgenic Nicotiana tabacum. We showed that MpGPS.SSU could enhance the production of various monoterpenes such as (-)-limonene, (-)-linalool, (-)-α-pinene/β-pinene or myrcene, in transgenic tobacco by elevating geranyl diphosphate synthase (GPS) activity. In addition, overexpression of MpGPS.SSU in tobacco caused early flowering phenotype and increased shoot branching by elevating contents of GA 3 and cytokinins due to upregulated transcript levels of several plastidic 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway genes, geranylgeranyl diphosphate synthases 3 (GGPPS3) and GGPPS4. Our method would allow the identification of new monoterpene synthase genes using transient expression in N. benthamiana and the improvement of monoterpene production in transgenic tobacco plants. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

C- Reactive Protein in Tuberculosis and Human Immunodeficiency ...

African Journals Online (AJOL)

This study was conducted to evaluate C-reactive protein (CRP) levels in Mycobacterium tuberculosis and human immunodeficiency virus (HIV) infections and the follow-up therapeutic response to tuberculosis (TB) among patients aged 19-68 years attending out-patient clinics of two hospitals in Abeokuta, Southwestern ...

Vitamin D Status in South Africa and Tuberculosis.

Science.gov (United States)

Abhimanyu; Meyer, Vanessa; Jeffery, Tamsyn Jacki; Bornman, Liza

2015-12-01

According to the World Health Organisation South Africa has the third highest tuberculosis (TB) incidence in the world, with an estimated 60 % incident cases having both TB and HIV. The South African National Tuberculosis Association (SANTA) recognized the importance of nutrition in the prevention and management of TB by including feeding schemes in community outreach programs. Vitamin D enhances innate immunity against mycobacterial infection through the antimicrobial peptide, cathelicidin. We reviewed studies on vitamin D status, its link with TB, and potential use in therapy in multiethnic South Africa with sunlight as primary source of vitamin D. Ethnicity, season, disease state, latitude, and urbanization are critical factors to be considered in vitamin D supplementation for prevention and treatment of TB.

Autoradiographic disposition of [1-methyl-14C]- and [2-14C]caffeine in mice

International Nuclear Information System (INIS)

Lachance, M.P.; Marlowe, C.; Waddell, W.J.

1983-01-01

Male, C57B1/6J mice received either [1-methyl-14C]caffeine or [2-14C]caffeine via the tail vein at a dose of 0.7 or 11 mg/kg, respectively. At 0.1, 0.33, 1, 3, 9, and 24 hr after treatment, the mice were anesthetized with ether and frozen by immersion in dry ice/hexane. The mice were processed for whole-body autoradiography by the Ullberg technique; this procedure does not allow thawing or contact with solvents. All autoradiographs revealed some retention of radioactivity at early time intervals in the lacrimal glands, seminal vesicle fluid, nasal and olfactory epithelium, and retinal melanocytes. The remaining portion of the animal was densitometrically uniform except for the lower levels noted in the CNS and adipose tissues. Excretion of radioactivity by the liver and kidneys seems to be the major routes of elimination. Localization in the liver at late time intervals was confined principally to the centrilobular region. Late sites of retention, observed only after [1-methyl-14C]caffeine administration, included the pancreas, minor and major salivary glands, splenic red pulp, thymal cortex, bone marrow, and gastrointestinal epithelium. Sites of localization present in both studies included the olfactory epithelium, lacrimal glands, hair follicles, and retinal melanocytes. Further studies are needed to determine whether the localization at these various sites is due to metabolic degradation, active transport, or possibly a specific receptor interaction

The role of experience curves for setting MEPS for appliances

International Nuclear Information System (INIS)

Siderius, Hans-Paul

2013-01-01

Minimum efficiency performance standards (MEPS) are an important policy instrument to raise the efficiency of products. In most schemes the concept of life cycle costs (LCC) is used to guide setting the MEPS levels. Although a large body of literature shows that product cost is decreasing with increasing cumulative production, the experience curve, this is currently not used for setting MEPS. This article shows how to integrate the concept of the experience curve into LCC calculations for setting MEPS in the European Union and applies this to household laundry driers, refrigerator-freezers and televisions. The results indicate that for driers and refrigerator-freezers at least twice the energy savings compared to the current approach can be achieved. These products also show that energy label classes can successfully be used for setting MEPS. For televisions an experience curve is provided, showing a learning rate of 29%. However, television prices do not show a relation with energy efficiency but are to a large extent determined by the time the product is placed on the market. This suggests to policy makers that for televisions and other products with a short (re)design and market cycle timing is more important than the MEPS levels itself. - Highlights: • We integrate experience curves into life cycle cost calculations for MEPS. • For driers and refrigerators this results in at least twice the energy savings. • For flat panel televisions an experience curve is provided

Humoral Responses to Rv1733c, Rv0081, Rv1735c, and Rv1737c DosR Regulon-Encoded Proteins of Mycobacterium tuberculosis in Individuals with Latent Tuberculosis Infection

Directory of Open Access Journals (Sweden)

Simon G. Kimuda

2017-01-01

Full Text Available Latent tuberculosis infection (LTBI is evidence of immunological control of tuberculosis. Dormancy survival regulator (DosR regulon-encoded proteins may have a role in the maintenance of LTBI. T cell responses to Rv1733c, Rv0081, Rv1735c, and Rv1737c DosR regulon-encoded proteins were found to be most frequent among household contacts of TB cases from Uganda compared to other DosR proteins, but antibody responses were not described. We characterized antibody responses to these proteins in individuals from Uganda. Antibodies to Rv1733c, Rv0081, Rv1735c, and Rv1737c DosR regulon-encoded proteins were measured in 68 uninfected individuals, 62 with LTBI, and 107 with active pulmonary tuberculosis (APTB cases. There were no differences in the concentrations of antibodies to Rv0081, Rv1735c, and Rv1737c DosR regulon-encoded proteins between individuals with LTBI and APTB and those who were uninfected. LTBI was associated with higher concentrations of antibodies to Rv1733c in female participants [adjusted geometric mean ratio: 1.812, 95% confidence interval (CI: 1.105 2.973, and p=0.019] but not in males (p value for interaction = 0.060. Antibodies to the four DosR regulon-encoded proteins investigated may not serve as good biomarkers of LTBI in the general population. More of the M.tb proteome needs to be screened to identify proteins that induce strong antibody responses in LTBI.

Erythritol: crystal growth from the melt.

Science.gov (United States)

Lopes Jesus, A J; Nunes, Sandra C C; Ramos Silva, M; Matos Beja, A; Redinha, J S

2010-03-30

The structural changes occurring on erythritol as it is cooled from the melt to low temperature, and then heated up to the melting point have been investigated by differential scanning calorimetry (DSC), polarized light thermal microscopy (PLTM), X-ray powder diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR). By DSC, it was possible to set up the conditions to obtain an amorphous solid, a crystalline solid, or a mixture of both materials in different proportions. Two crystalline forms have been identified: a stable and a metastable one with melting points of 117 and 104 degrees C, respectively. The fusion curve decomposition of the stable form revealed the existence of three conformational structures. The main paths of the crystallization from the melt were followed by PLTM. The texture and colour changes allowed the characterization of the different phases and transitions in which they are involved on cooling as well as on heating processes. The type of crystallization front and its velocity were also followed by microscopic observation. These observations, together with the data provided by PXRD, allowed elucidating the transition of the metastable form into the stable one. The structural changes occurring upon the cooling and subsequent heating processes, namely those arising from intermolecular hydrogen bonds, were also accompanied by infrared spectroscopy. Particular attention was given to the spectral changes occurring in the OH stretching region. Copyright (c) 2009 Elsevier B.V. All rights reserved.

9 CFR 311.2 - Tuberculosis.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Tuberculosis. 311.2 Section 311.2... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.2 Tuberculosis. The... pathogenesis of tuberculosis in swine, cattle, sheep, goats, and equines. (a) Carcasses condemned. The entire...

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

Science.gov (United States)

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

Identification of 2-aminothiazole-4-carboxylate derivatives active against Mycobacterium tuberculosis H37Rv and the beta-ketoacyl-ACP synthase mtFabH.

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Qosay Al-Balas

Full Text Available BACKGROUND: Tuberculosis (TB is a disease which kills two million people every year and infects approximately over one-third of the world's population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration. METHODOLOGY/PRINCIPAL FINDINGS: Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM to the more tractable 2-aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM's novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H(37R(v and, dissociatively, against the beta-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H(37R(v with an MIC of 0.06 microg/ml (240 nM, but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido-5-(3-chlorophenylthiazole-4-carboxylate inhibited mtFabH with an IC(50 of 0.95+/-0.05 microg/ml (2.43+/-0.13 microM but was not active against the whole cell organism. CONCLUSIONS/SIGNIFICANCE: These findings clearly identify the 2-aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents.

Supramolecular architecture of 5-bromo-7-methoxy-1-methyl-1H-benzoimidazole.3H2O: Synthesis, spectroscopic investigations, DFT computation, MD simulations and docking studies

Science.gov (United States)

Murthy, P. Krishna; Smitha, M.; Sheena Mary, Y.; Armaković, Stevan; Armaković, Sanja J.; Rao, R. Sreenivasa; Suchetan, P. A.; Giri, L.; Pavithran, Rani; Van Alsenoy, C.

2017-12-01

Crystal and molecular structure of newly synthesized compound 5-bromo-7-methoxy-1-methyl-1H-benzoimidazole (BMMBI) has been authenticated by single crystal X-ray diffraction, FT-IR, FT-Raman, 1H NMR, 13C NMR and UV-Visible spectroscopic techniques; compile both experimental and theoretical results which are performed by DFT/B3LYP/6-311++G(d,p) method at ground state in gas phase. Visualize nature and type of intermolecular interactions and crucial role of these interactions in supra-molecular architecture has been investigated by use of a set of graphical tools 3D-Hirshfeld surfaces and 2D-fingerprint plots analysis. The title compound stabilized by strong intermolecular hydrogen bonds N⋯Hsbnd O and O⋯Hsbnd O, which are envisaged by dark red spots on dnorm mapped surfaces and weak Br⋯Br contacts envisaged by red spot on dnorm mapped surface. The detailed fundamental vibrational assignments of wavenumbers were aid by with help of Potential Energy distribution (PED) analysis by using GAR2PED program and shows good agreement with experimental values. Besides frontier orbitals analysis, global reactivity descriptors, natural bond orbitals and Mullikan charges analysis were performed by same basic set at ground state in gas phase. Potential reactive sites of the title compound have been identified by ALIE, Fukui functions and MEP, which are mapped to the electron density surfaces. Stability of BMMBI have been investigated from autoxidation process and pronounced interaction with water (hydrolysis) by using bond dissociation energies (BDE) and radial distribution functions (RDF), respectively after MD simulations. In order to identify molecule's most important reactive spots we have used a combination of DFT calculations and MD simulations. Reactivity study encompassed calculations of a set of quantities such as: HOMO-LUMO gap, MEP and ALIE surfaces, Fukui functions, bond dissociation energies and radial distribution functions. To confirm the potential

Demethylation by 5-aza-2'-deoxycytidine in colorectal cancer cells targets genomic DNA whilst promoter CpG island methylation persists

International Nuclear Information System (INIS)

Mossman, David; Kim, Kyu-Tae; Scott, Rodney J

2010-01-01

DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. Aberrant epigenetic gene silencing in tumours is a frequent event, yet the factors which dictate which genes are targeted for inactivation are unknown. DNA methylation and histone acetylation can be modified with the chemical agents 5-aza-2'-deoxycytidine (5-aza-dC) and Trichostatin A (TSA) respectively. The aim of this study was to analyse de-methylation and re-methylation and its affect on gene expression in colorectal cancer cell lines treated with 5-aza-dC alone and in combination with TSA. We also sought to identify methylation patterns associated with long term reactivation of previously silenced genes. Colorectal cancer cell lines were treated with 5-aza-dC, with and without TSA, to analyse global methylation decreases by High Performance Liquid Chromatography (HPLC). Re-methylation was observed with removal of drug treatments. Expression arrays identified silenced genes with differing patterns of expression after treatment, such as short term reactivation or long term reactivation. Sodium bisulfite sequencing was performed on the CpG island associated with these genes and expression was verified with real time PCR. Treatment with 5-aza-dC was found to affect genomic methylation and to a lesser extent gene specific methylation. Reactivated genes which remained expressed 10 days post 5-aza-dC treatment featured hypomethylated CpG sites adjacent to the transcription start site (TSS). In contrast, genes with uniformly hypermethylated CpG islands were only temporarily reactivated. These results imply that 5-aza-dC induces strong de-methylation of the genome and initiates reactivation of transcriptionally inactive genes, but this does not require gene associated CpG island de-methylation to occur. In addition, for three of our selected genes, hypomethylation at the TSS of an epigenetically silenced gene is associated with the long term reversion of

Molecular characterization of tlyA gene product, Rv1694 of Mycobacterium tuberculosis: A non-conventional hemolysin and a ribosomal RNA methyl transferase

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Ahmed Neesar

2010-09-01

was significantly slower than mock vector transformed E. coli. The S30 extract of E. coli expressing the Rv1694 had poor translational activity in presence of capreomycin, further confirming its methylation activity. Finally, incorporation of methyl group of [3H]-S-adenosylmethionine in isolated ribosomes also confirmed its methylation activity. Conclusions The Rv1694 has an unusual dual activity. It appears to contain two diverse functions such as haemolytic activity and ribosomal RNA methylation activity. It is possible that the haemolytic activity might be relevant to intra-cellular compartments such as phagosomes rather than cell lysis of erythrocytes and the self-assembly trait may have a potential role after successful entry into macrophages by Mycobacterium tuberculosis.

Characterization of a distonic isomer C6H5C+(OH)OCH2 of methyl benzoate radical cation by associative ion-molecule reactions

Science.gov (United States)

Dechamps, Noémie; Flammang, Robert; Gerbaux, Pascal; Nam, Pham-Cam; Nguyen, Minh Tho

2006-03-01

The C6H5C+(OH)OCH2 radical cation, formally a distonic isomer of ionized methyl benzoate, has been prepared by dissociative ionization of neopentyl benzoate, as earlier suggested by Audier et al. [H.E. Audier, A. Milliet, G. Sozzi, S. Hammerum, Org. Mass. Spectrom. 25 (1990) 44]. Its distonic character has now been firmly established by its high reactivity towards neutral methyl isocyanide (ionized methylene transfer) producing N-methyl ketenimine ions. Other mass spectrometric experiments and ab initio quantum chemical calculations also concur with each other pointing toward the existence of a stable distonic radical cation.

Rapid analysis of heterogeneously methylated DNA using digital methylation-sensitive high resolution melting: application to the CDKN2B (p15) gene

DEFF Research Database (Denmark)

Candiloro, Ida Lm; Mikeska, Thomas; Hokland, Peter

2008-01-01

ABSTRACT: BACKGROUND: Methylation-sensitive high resolution melting (MS-HRM) methodology is able to recognise heterogeneously methylated sequences by their characteristic melting profiles. To further analyse heterogeneously methylated sequences, we adopted a digital approach to MS-HRM (dMS-HRM) t......ABSTRACT: BACKGROUND: Methylation-sensitive high resolution melting (MS-HRM) methodology is able to recognise heterogeneously methylated sequences by their characteristic melting profiles. To further analyse heterogeneously methylated sequences, we adopted a digital approach to MS-HRM (d......MS-HRM) that involves the amplification of single templates after limiting dilution to quantify and to determine the degree of methylation. We used this approach to study methylation of the CDKN2B (p15) cell cycle progression inhibitor gene which is inactivated by DNA methylation in haematological malignancies...... the methylated alleles and assess the degree of methylation. Direct sequencing of selected dMS-HRM products was used to determine the exact DNA methylation pattern and confirmed the degree of methylation estimated by dMS-HRM. CONCLUSION: dMS-HRM is a powerful technique for the analysis of methylation in CDKN2B...

Quantum mechanical and spectroscopic (FT-IR, 13C, 1H NMR and UV) investigations of 2-(5-(4-Chlorophenyl)-3-(pyridin-2-yl)-4,5-dihydropyrazol-1-yl)benzo[d]thiazole by DFT method

Science.gov (United States)

Diwaker

2014-07-01

The electronic, NMR, vibrational, structural properties of a new pyrazoline derivative: 2-(5-(4-Chlorophenyl)-3-(pyridine-2-yl)-4,5-dihydropyrazol-1-yl)benzo[d]thiazole has been studied using Gaussian 09 software package. Using VEDA 4 program we have reported the PED potential energy distribution of normal mode of vibrations of the title compound. We have also reported the 1H and 13C NMR chemical shifts of the title compound using B3LYP level of theory with 6-311++G(2d,2p) basis set. Using time dependent (TD-DFT) approach electronic properties such as HOMO and LUMO energies, electronic spectrum of the title compound has been studied and reported. NBO analysis and MEP surface mapping has also been calculated and reported using ab initio methods.

DNA methylation regulates expression of VEGF-C, and S-adenosylmethionine is effective for VEGF-C methylation and for inhibiting cancer growth

Energy Technology Data Exchange (ETDEWEB)

Da, M.X. [Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou (China); Zhang, Y.B. [Department of Surgery, Ningxia Medical University, Yinchuan (China); Yao, J.B. [Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou (China); Duan, Y.X. [Department of Surgery, Ningxia Medical University, Yinchuan (China)

2014-09-30

DNA hypomethylation may activate oncogene transcription, thus promoting carcinogenesis and tumor development. S-adenosylmethionine (SAM) is a methyl donor in numerous methylation reactions and acts as an inhibitor of intracellular demethylase activity, which results in hypermethylation of DNA. The main objectives of this study were to determine whether DNA hypomethylation correlated with vascular endothelial growth factor-C (VEGF-C) expression, and the effect of SAM on VEGF-C methylation and gastric cancer growth inhibition. VEGF-C expression was assayed by Western blotting and RT-qPCR in gastric cancer cells, and by immunohistochemistry in tumor xenografts. VEGF-C methylation was assayed by bisulfite DNA sequencing. The effect of SAM on cell apoptosis was assayed by flow cytometry analyses and its effect on cancer growth was assessed in nude mice. The VEGF-C promoters of MGC-803, BGC-823, and SGC-7901 gastric cancer cells, which normally express VEGF-C, were nearly unmethylated. After SAM treatment, the VEGF-C promoters in these cells were highly methylated and VEGF-C expression was downregulated. SAM also significantly inhibited tumor growth in vitro and in vivo. DNA methylation regulates expression of VEGF-C. SAM can effectively induce VEGF-C methylation, reduce the expression of VEGF-C, and inhibit tumor growth. SAM has potential as a drug therapy to silence oncogenes and block the progression of gastric cancer.

Synthesis and preclinical evaluation of carbon-11 labelled N-((5-(4-fluoro-2-[11C]methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine as a PET tracer for NR2B subunit-containing NMDA receptors

International Nuclear Information System (INIS)

Christiaans, Johannes A.M.; Klein, Pieter J.; Metaxas, Athanasios; Kooijman, Esther J.M.; Schuit, Robert C.; Leysen, Josée E.; Lammertsma, Adriaan A.; Berckel, Bart N.M. van; Windhorst, Albert D.

2014-01-01

Introduction: The N-methyl-D-Aspartate (NMDA) receptor plays an important role in learning and memory. Overactivation is thought to play an important role in neurodegenerative disorders such as Alzheimer's disease. Currently, it is not possible to assess N-methyl-D-aspartate receptor (NMDAr) bio-availability in vivo. The purpose of this study was to develop a positron emission tomography (PET) ligand for the NR2B binding site of the NMDA receptor. Methods: N-((5-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine was radiolabelled with carbon-11 in the phenyl moiety. Biodistribution and blocking studies were carried out in anaesthetized mice and in non-anaesthetized rats. Results: N-((5-(4-fluoro-2-[ 11 C]methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine was prepared in 49 ± 3% (decay-corrected) yield, affording 4.1 ± 0.3 GBq of formulated product at the end of synthesis with a radiochemical purity of > 99% and with a specific activity of 78 ± 10 GBq/μmol. Conclusion: A new NR2B PET ligand was developed in high yield. [ 11 C]4 readily enters the brain and binds to the NR2B subunit-containing NMDAr in the rodent brain. High sigma-1 receptor binding may, however, limit its future application as a PET probe for imaging the NR2B subunit-containing NMDAr. Anaesthesia has an effect on NMDAr function and therefore can complicate interpretation of preclinical in vivo results. In addition, effects of endogenous compounds cannot be excluded. Despite these potential limitations, further studies are warranted to investigate the values of [ 11 C]4 as an NR2B PET ligand

Cocrystals of 6-methyl-2-thiouracil: presence of the acceptor-donor-acceptor/donor-acceptor-donor synthon.

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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).

Crossed cerebellar diaschisis. A positron emission tomography study with L-[methyl-11C]methionine and 2-deoxy-2-[18F]fluoro-D-glucose

International Nuclear Information System (INIS)

Kajimoto, Katsufumi; Oku, Naohiko; Kimura, Yasuyuki

2007-01-01

Crossed cerebellar diaschisis (CCD) is defined as a depression of blood flow and oxidative metabolism of glucose in the cerebellum contralateral to a supratentorial brain lesion, as detected with positron emission tomography (PET) and single photon emission computed tomography. We examined whether L-[methyl- 11 C]methionine (MET) uptake is affected in CCD. In 12 patients with a unilateral supratentorial brain tumor, we evaluated the uptake of 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG) and MET in the cerebellar hemispheres by means of PET. Asymmetry index (AI) was defined as a difference in the average count between the ipsilateral and contralateral cerebellar hemispheres divided by the average count in both cerebellar hemispheres. Patients with AI of FDG PET more than 0.1 and those with AI equal to 0.1 or less than 0.1 were classified as CCD-positive and CCD-negative, respectively. Six patients were CCD-positive and others were CCD-negative in the FDG PET study. Between CCD-positive and CCD-negative patients, mean AI of MET was not significantly different (0.017±0.023 and 0.014±0.039, respectively). Different from glucose metabolism, cerebellar MET uptake was not affected in CCD. The present study may indicate that cerebellar MET uptake is independent of suppression of cerebellar neuronal activity. (author)

Methionine kinetics in adult men: effects of dietary betaine on L-[2H3-methyl-1-13C]methionine

International Nuclear Information System (INIS)

Storch, K.J.; Wagner, D.A.; Young, V.R.

1991-01-01

The effects of a daily 3-g supplement of betaine on kinetic aspects of L-[2H3-methyl-1-13C]methionine (MET) metabolism in healthy young adult men were explored. Four groups of four subjects each were given a control diet, based on an L-amino acid mixture supplying 29.5 and 21.9 mg.kg-1.d-1 of L-methionine and L-cystine for 4 d before the tracer study, conducted on day 5 during the fed state. Two groups received the control diet and two groups received the betaine supplement. Tracer was given intravenously (iv) or orally. The transmethylation rate of MET (TM), homocysteine remethylation (RM), and oxidation of methionine were estimated from plasma methionine labeling and 13C enrichment of expired air. RM tended to increase (P = 0.14) but the TM and methionine oxidation were significantly (P less than 0.05) higher after betaine supplementation when estimated with the oral tracer. No differences were detected with the intravenous tracer. Methionine concentration in plasma obtained from blood taken from subjects in the fed state was higher (P less than 0.01) with betaine supplementation. These results suggest that excess methyl-group intake may increase the dietary requirement for methionine

N-methyl-D-aspartic acid receptor agonists

DEFF Research Database (Denmark)

Madsen, U; Frydenvang, Karla Andrea; Ebert, B

1996-01-01

(R,S)-2-Amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid [(R,S)-AMAA, 4] is a potent and selective agonist at the N-methyl-D-aspartic acid (NMDA) subtype of excitatory amino acid receptors. Using the Ugi "four-component condensation" method, the two diastereomers (2R)- and (2S)-2-[3-(benzyloxy......) showed peak affinity for [3H]AMPA receptor sites (IC50 = 72 +/- 13 microM) and was shown to be a more potent inhibitor of [3H]CPP binding (IC50 = 3.7 +/- 1.5 microM) than (S)-AMAA (9) (IC50 = 61 +/- 6.4 microM). Neither enantiomer of AMAA affected [3H]kainic acid receptor binding significantly...

Selective production of deacetylated mannosylerythritol lipid, MEL-D, by acetyltransferase disruption mutant of Pseudozyma hubeiensis.

Science.gov (United States)

Konishi, Masaaki; Makino, Motoki

2018-01-01

Mannosylerythritol lipids (MELs) are produced by several smut fungi of the Ustilaginaceae family; they are promising microbial biosurfactants and have excellent surface-active and self-assembling properties. Pseudozyma hubeiensis is a candidate for abundant MEL production and produces large amounts of 4-O-[(4'-mono-O-acetyl-2',3'-di-O-alkanoyl)-β-d-mannopyranosyl]-meso-erythritol (MEL-C). An acetyltransferase disruption mutant of P. hubeiensis, SY62-MM36, was obtained to selectively produce deacetylated 4-O-[(2',3'-di-O-alkanoyl)-β-d-mannopyranosyl]-meso-erythritol (MEL-D), and the structures of the products were determined. Lower mobility of major spots of the mutant on silica gel thin-layer chromatography verified its more hydrophilic nature than that of wild-type MEL-A, B, and C. Structural analyses confirmed the product to be MEL-D, which comprises acyl chains of caproic acid (C6:0), capric acid (C10:0), and lauric acid (C12:0). The critical micelle concentration (CMC) and the surface tension (γCMC) of the MEL-D were 2.0 × 10 -5  M and 29.7 mN/m, respectively. SY62-MM36 also produced a minor product that was estimated as triacylated MEL-D. The triacylated MEL-D had a CMC of 3.5 × 10 -5  M and a γCMC of 29.6 mN/m. In water, MEL-D formed a lamella liquid crystal phase over a broad range of concentrations. By fed-batch cultivation, the mutant produced 91.6 ± 6.3 g/L of MEL-D for 7 days. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Molecular insight on the non-covalent interactions between carbapenems and uc(l,d)-transpeptidase 2 from Mycobacterium tuberculosis: ONIOM study

Science.gov (United States)

Ntombela, Thandokuhle; Fakhar, Zeynab; Ibeji, Collins U.; Govender, Thavendran; Maguire, Glenn E. M.; Lamichhane, Gyanu; Kruger, Hendrik G.; Honarparvar, Bahareh

2018-05-01

Tuberculosis remains a dreadful disease that has claimed many human lives worldwide and elimination of the causative agent Mycobacterium tuberculosis also remains elusive. Multidrug-resistant TB is rapidly increasing worldwide; therefore, there is an urgent need for improving the current antibiotics and novel drug targets to successfully curb the TB burden. uc(l,d)-Transpeptidase 2 is an essential protein in Mtb that is responsible for virulence and growth during the chronic stage of the disease. Both uc(d,d)- and uc(l,d)-transpeptidases are inhibited concurrently to eradicate the bacterium. It was recently discovered that classic penicillins only inhibit uc(d,d)-transpeptidases, while uc(l,d)-transpeptidases are blocked by carbapenems. This has contributed to drug resistance and persistence of tuberculosis. Herein, a hybrid two-layered ONIOM (B3LYP/6-31G+(d): AMBER) model was used to extensively investigate the binding interactions of LdtMt2 complexed with four carbapenems (biapenem, imipenem, meropenem, and tebipenem) to ascertain molecular insight of the drug-enzyme complexation event. In the studied complexes, the carbapenems together with catalytic triad active site residues of LdtMt2 (His187, Ser188 and Cys205) were treated at with QM [B3LYP/6-31+G(d)], while the remaining part of the complexes were treated at MM level (AMBER force field). The resulting Gibbs free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) for all complexes showed that the carbapenems exhibit reasonable binding interactions towards LdtMt2. Increasing the number of amino acid residues that form hydrogen bond interactions in the QM layer showed significant impact in binding interaction energy differences and the stabilities of the carbapenems inside the active pocket of LdtMt2. The theoretical binding free energies obtained in this study reflect the same trend of the experimental observations. The electrostatic, hydrogen bonding and Van der Waals interactions between the carbapenems and Ldt

2-Acetyl­amino-1,3,4,6-tetra-O-(tri­methyl­silyl)-2-de­oxy-α-d-gluco­pyran­ose

Science.gov (United States)

Cheng, Zhao-Dong; Cui, Yan-Li; Mao, Jian-Wei

2013-01-01

The title compound, C20H47NO6Si4, was synthesized by per-O-tri­methyl­silylation of N-acetyl-d-glucosa­mine using chloro­tri­methyl­silane in the presence of hexa­methyl­disiloxane. The tri­methyl­silyl group and acetamido group are located on the same side of the pyran ring, showing an α-configuration glycoside. One of the tri­methyl­silyl groups is disordered over two orientations, with site-occupancy factors of 0.625 (9) and 0.375 (9). In the crystal, N—H⋯O hydrogen bonds link the mol­ecules into supra­molecular chains along the a-axis direction. PMID:23795087

Crystal structures of eight mono-methyl alkanes (C26–C32 via single-crystal and powder diffraction and DFT-D optimization

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Lee Brooks

2015-09-01

Full Text Available The crystal structures of eight mono-methyl alkanes have been determined from single-crystal or high-resolution powder X-ray diffraction using synchrotron radiation. Mono-methyl alkanes can be found on the cuticles of insects and are believed to act as recognition pheromones in some social species, e.g. ants, wasps etc. The molecules were synthesized as pure S enantiomers and are (S-9-methylpentacosane, C26H54; (S-9-methylheptacosane and (S-11-methylheptacosane, C28H58; (S-7-methylnonacosane, (S-9-methylnonacosane, (S-11-methylnonacosane and (S-13-methylnonacosane, C30H62; and (S-9-methylhentriacontane, C32H66. All crystallize in space group P21. Depending on the position of the methyl group on the carbon chain, two packing schemes are observed, in which the molecules pack together hexagonally as linear rods with terminal and side methyl groups clustering to form distinct motifs. Carbon-chain torsion angles deviate by less than 10° from the fully extended conformation, but with one packing form showing greater curvature than the other near the position of the methyl side group. The crystal structures are optimized by dispersion-corrected DFT calculations, because of the difficulties in refining accurate structural parameters from powder diffraction data from relatively poorly crystalline materials.

Synthesis of [methyl-[sup 14]C]-N-methylputrescine

Energy Technology Data Exchange (ETDEWEB)

Secor, H.V.; Izac, R.R.; Hassam, S.B.; Frisch, A.F. (Philip Morris Research Center, Richmond, VA (United States))

1994-05-01

[Methyl-[sup 14]C]-N-methylputrescine was prepared from [[sup 14]C]methylamine hydrochloride in five steps. Reaction of benzaldehyde and [[sup 14]C]methylamine (10 mCi) followed by catalytic hydrogenation yielded [methyl-[sup 14]C]-N-methylbenzylamine. The key step in this process is the alkylation of [methyl-[sup 14]C]-N-methylbenzylamine in aqueous medium with 4-bromobutyronitrile. The radiochemical purity of the final product after two successive catalytic hydrogenations was in excess of 97%. The radiochemical yields in two successive runs were 26 and 38%, based on starting [[sup 14]C]methylamine, with specific activities of 22 and 23 mCi/mmol, respectively. This sequence provides a convenient and efficient regioselective radiosynthesis of [methyl-[sup 14]C]-N-methylputrescine. (author).

Degradation of Triazine-2-(14C Metsulfuron-Methyl in Soil from an Oil Palm Plantation.

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B S Ismail

Full Text Available Triazine-2-(14C metsulfuron-methyl is a selective, systemic sulfonylurea herbicide. Degradation studies in soils are essential for the evaluation of the persistence of pesticides and their breakdown products. The purpose of the present study was to investigate the degradation of triazine-2-(14C metsulfuron-methyl in soil under laboratory conditions. A High Performance Liquid Chromatograph (HPLC equipped with an UV detector and an on-line radio-chemical detector, plus a Supelco Discovery column (250 x 4.6 mm, 5 μm, and PRP-1 column (305 x 7.0 mm, 10 μm was used for the HPLC analysis. The radioactivity was determined by a Liquid Scintillation Counter (LSC in scintillation fluid. The soil used was both sterilized and non-sterilized in order to observe the involvement of soil microbes. The estimated DT50 and DT90 values of metsulfuron-methyl in a non-sterile system were observed to be 13 and 44 days, whereas in sterilized soil, the DT50 and DT90 were 31 and 70 days, respectively. The principal degradation product after 60 days was CO2. The higher cumulative amount of (14CO2 in (14C-triazine in the non-sterilized soil compared to that in the sterile system suggests that biological degradation by soil micro-organisms significantly contributes to the dissipation of the compound. The major routes of degradation were O-demethylation, sulfonylurea bridge cleavage and the triazine "ring-opened."

Synthesis of 7-[α-(2-amino-[2-14C]thiazol-4-yl)-α-(Z)-methoxyimin oacetamido]-3-(1-methylpyrrolidinio)methyl-3-cephem-4-carboxylate hydrochloride ([14C]cefepime hydrochloride)

International Nuclear Information System (INIS)

Standridge, R.T.; Swigor, J.E.

1993-01-01

The title compound ([ 14 C]cefepime hydrochloride) was prepared as follows:- [ 14 C]Thiourea was condensed with ethyl 4-bromo-3-oxo-2-methoxyimino-acetate providing ethyl 2-(2-amino-4-[2- 14 C] thiazolyl)-2-methoxyi-minoacetate as the pure Z-isomer. Saponification gave the amino acid this was reacted with 1-hydroxybenzotriazole to give the activated ester. Condensation in situ with 7-amino-3-(1-methylpyrrolidinio) methyl-3-cephem-4-carboxylate yielded the product as the pure sulfate salt. Treatment of the sulfate salt with base provided the zwitterion isolated as the stable N-methyl-2-pyrrolidinone adduct. An aqueous solution of the adduct was converted to the crystalline title compound, [ 14 C]Cefepime hydrochloride hydrate, with hydrochloric acid/acetone. Radiochemical purity was 99.0% and specific activity, 34.2 μCi/mg. Overall yield from [ 14 C]thiourea was 18%. (Author)

Blockade of N-methyl-D-aspartate induced convulsions by 1-aminocyclopropanecarboxylates

International Nuclear Information System (INIS)

Skolnick, P.; Marvizon, J.C.G.; Jackson, B.W.; Monn, J.A.; Rice, K.C.; Lewin, A.H.

1989-01-01

1-Aminocyclopropanecarboxylic acid is a potent and selective ligand for the glycine modulatory site on the N-methyl-D-aspartate receptor complex. This compound blocks the convulsions and deaths produced by N-methyl-D-aspartate in a dose dependent fashion. In contrast, 1-aminocyclopropanecarboxylic acid does not protect mice against convulsions induced by pentylenetetrazole, strychnine, bicuculline, or maximal electroshock, and does not impair motor performance on either a rotarod or horizontal wire at doses of up to 2 g/kg. The methyl- and ethyl- esters of 1-aminocyclopropanecarboxylic acid are 5- and 2.3-fold more potent, respectively, than the parent compound in blocking the convulsant and lethal effects of N-methyl-D-aspartate. However, these esters are several orders of magnitude less potent than 1-aminocyclopropanecarboxylic acid as inhibitors of strychnine-insensitive [ 3 H]glycine binding, indicating that conversion to the parent compound may be required to elicit an anticonvulsant action

Epitope mapping of Ebola virus dominant and subdominant glycoprotein epitopes facilitates construction of an epitope-based DNA vaccine able to focus the antibody response in mice

Science.gov (United States)

2017-04-06

Homo sapiens and...6D8 A B C Figure 1 D GP Figure 2 A B C D EL IS A OD EL IS A OD EL IS A OD EL IS A OD Amino Acid # Amino Acid Sequence Mouse...Figure 3 Furin cleavage 497-501 Figure 4 DAPI 6D8 Merge Mep1 Mock WT GP Mep2 Figure 5 A 0.0 0.5 1.0 1.5 2.0 Mep1 Mock Mep2 B C EL

Effect of three-year consumption of erythritol, xylitol and sorbitol candies on various plaque and salivary caries-related variables.

Science.gov (United States)

Runnel, Riina; Mäkinen, Kauko K; Honkala, Sisko; Olak, Jana; Mäkinen, Pirkko-Liisa; Nõmmela, Rita; Vahlberg, Tero; Honkala, Eino; Saag, Mare

2013-12-01

The objective of the present paper is to report results from oral biologic studies carried out in connection with a caries study. Samples of whole-mouth saliva and dental plaque were collected from initially 7- to 8-year-old subjects who participated in a 3-year school-based programme investigating the effect of the consumption of polyol-containing candies on caries rates. The subjects were randomized in three cohorts, consumed erythritol, xylitol, or sorbitol candies. The daily polyol consumption from the candies was approximately 7.5 g. A significant reduction in dental plaque weight from baseline (psorbitol groups. Usage of polyol candies had no significant or consistent effect on the levels of plaque protein, glucose, glycerol, or calcium, determined yearly in connection with caries examinations. After three years, the plaque of erythritol-receiving subjects contained significantly (psorbitol. Lactic acid levels partly followed the same pattern. The consumption of erythritol was generally associated with significantly (psorbitol candies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reinvestigation of the synthesis and evaluation of [N-methyl-11C]vorozole, a radiotracer targeting cytochrome P450 aromatase

International Nuclear Information System (INIS)

Kim, Sung Won; Biegon, Anat; Katsamanis, Zachary E.; Ehrlich, Carolin W.; Hooker, Jacob M.; Shea, Colleen; Muench, Lisa; Xu Youwen; King, Payton; Carter, Pauline; Alexoff, David L.; Fowler, Joanna S.

2009-01-01

Introduction: We reinvestigated the synthesis of [N-methyl- 11 C]vorozole, a radiotracer for aromatase, and discovered the presence of an N-methyl isomer which was not removed in the original purification method. Herein we report the preparation and positron emission tomography (PET) studies of pure [N-methyl- 11 C]vorozole. Methods: Norvorozole was alkylated with [ 11 C]methyl iodide as previously described and also with unlabeled methyl iodide. A high-performance liquid chromatography (HPLC) method was developed to separate the regioisomers. Nuclear magnetic resonance (NMR) spectroscopy ( 13 C and 2D-nuclear Overhauser effect spectroscopy NMR) was used to identify and assign structures to the N-methylated products. Pure [N-methyl- 11 C]vorozole and the contaminating isomer were compared by PET imaging in the baboon. Results: Methylation of norvorozole resulted in a mixture of isomers (1:1:1 ratio) based on new HPLC analysis using a pentafluorophenylpropyl bonded silica column, in which vorozole coeluted one of its isomers under the original HPLC conditions. Baseline separation of the three labeled isomers was achieved. The N-3 isomer was the contaminant of vorozole, thus correcting the original assignment of isomers. PET studies of pure [N-methyl- 11 C]vorozole with and without the contaminating N-3 isomer revealed that only [N-methyl- 11 C]vorozole binds to aromatase. [N-methyl- 11 C]Vorozole accumulated in all brain regions with highest accumulation in the aromatase-rich amygdala and preoptic area. Accumulation was blocked with vorozole and letrozole consistent with reports of some level of aromatase in many brain regions. Conclusions: The discovery of a contaminating labeled isomer and the development of a method for isolating pure [N-methyl- 11 C]vorozole combine to provide a new scientific tool for PET studies of the biology of aromatase and for drug research and development.

Dietary D-psicose reduced visceral fat mass in high-fat diet-induced obese rats.

Science.gov (United States)

Chung, Young-Mee; Hyun Lee, Joo; Youl Kim, Deuk; Hwang, Se-Hee; Hong, Young-Ho; Kim, Seong-Bo; Jin Lee, Song; Hye Park, Chi

2012-02-01

D-Psicose, a C-3 epimer of D-fructose, has shown promise in reducing body fat accumulation in normal rats and plasma glucose level in genetic diabetic mice. Effects of D-psicose on diet-induced obesity are not clearly elucidated, and we investigated food intake, body weight, and fat accumulation in rats fed high-fat (HF) diet. Sprague-Dawley rats became obese by feeding HF diet for 4 wk, and were assigned either to normal or HF diet supplemented with or without D-psicose, sucrose, or erythritol for 8 wk. Changing HF to normal diet gained less body weight and adipose tissue due to different energy intake. D-psicose-fed rats exhibited lower weight gain, food efficiency ratio, and fat accumulation than erythritol- and sucrose-fed rats. This effect was more prominent in D-psicose-fed rats with normal diet than with HF diet, suggesting combination of psicose and calorie restriction further reduced obesity. There was no difference in serum cholesterol/high-density lipoprotein (HDL)-C and low-density lipoprotein (LDL)-C/HDL-C ratios between D-psicose group and other groups. Liver weight in 5% psicose group with normal diet was higher than in other groups, but histopathological examination did not reveal any psicose-related change. D-Psicose inhibited the differentiation of mesenchymal stem cell (MSC) to adipose tissue in a concentration-dependent manner. These results demonstrate that D-psicose produces a marked decrease, greater than erythritol, in weight gain and visceral fat in an established obesity model by inhibiting MSC differentiation to adipocyte. Thus, D-psicose can be useful in preventing and reducing obesity as a sugar substitute and food ingredient. We can develop D-psicose as a sugar substitute and food ingredient since it can prevent obesity in normal people, but also suppress adiposity as a sugar substitute or food ingredients with antiobesity effect in obese people. D-psicose can be unique functional sweetener because of its function of reducing visceral

Structure of HsaD, a steroid-degrading hydrolase, from Mycobacterium tuberculosis

International Nuclear Information System (INIS)

Lack, Nathan; Lowe, Edward D.; Liu, Jie; Eltis, Lindsay D.; Noble, Martin E. M.; Sim, Edith; Westwood, Isaac M.

2007-01-01

The structure of HsaD, a carbon–carbon bond serine hydrolase involved in steroid catabolism that is critical for the survival of M. tuberculosis inside human macrophages, has been solved by X-ray crystallography. Data were collected at the Diamond Light Source in Oxfordshire, England: this paper describes one of the first structures determined at the new synchrotron. Tuberculosis is a major cause of death worldwide. Understanding of the pathogenicity of Mycobacterium tuberculosis has been advanced by gene analysis and has led to the identification of genes that are important for intracellular survival in macrophages. One of these genes encodes HsaD, a meta-cleavage product (MCP) hydrolase that catalyzes the hydrolytic cleavage of a carbon–carbon bond in cholesterol metabolism. This paper describes the production of HsaD as a recombinant protein and, following crystallization, the determination of its three-dimensional structure to 2.35 Å resolution by X-ray crystallography at the Diamond Light Source in Oxfordshire, England. To the authors’ knowledge, this study constitutes the first report of a structure determined at the new synchrotron facility. The volume of the active-site cleft of the HsaD enzyme is more than double the corresponding active-site volumes of related MCP hydrolases involved in the catabolism of aromatic compounds, consistent with the specificity of HsaD for steroids such as cholesterol. Knowledge of the structure of the enzyme facilitates the design of inhibitors

Effect of erythritol formulation on the mortality, fecundity and physiological excretion in Drosophila suzukii

Science.gov (United States)

Previously, we studied various combinations of non-nutritive sugars including erythritol and erythrose having a potentially insecticidal effect on Drosophila suzukii. The study suggested two potential physiological changes causing fly mortality: 1) starvation from the feeding of non-metabolizable er...

Fragrance material review on methyl-2,6,10-trimethylcyclododeca-2,5,9-trien-1-yl ketone.

Science.gov (United States)

Scognamiglio, J; Letizia, C S; Api, A M

2013-12-01

A toxicologic and dermatologic review of methyl 2,6,10-trimethylcyclododeca-2,5,9-trien-1-yl ketone when used as a fragrance ingredient is presented. Methyl 2,6,10-trimethylcyclododeca-2,5,9-trien-1-yl ketone is a member of the fragrance structural group Alkyl Cyclic Ketones. These fragrances can be described as being composed of an alkyl, R1, and various substituted and bicyclic saturated or unsaturated cyclic hydrocarbons, R2, in which one of the rings may include up to 12 carbons. Alternatively, R2 may be a carbon bridge of C2-C4 carbon chain length between the ketone and cyclic hydrocarbon. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for methyl 2,6,10-trimethylcyclododeca-2,5,9-trien-1-yl ketone were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, repeated dose, and genotoxicity data. A safety assessment of the entire Alkyl Cyclic Ketones will be published simultaneously with this document; please refer to Belsito et al. (Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2013. A Toxicologic and Dermatologic Assessment of Alkyl Cyclic Ketones When Used as Fragrance Ingredients (submitted for publication)) for an overall assessment of the safe use of this material and all Alkyl Cyclic Ketones in fragrances. Copyright © 2013 Elsevier Ltd. All rights reserved.

Donor age and C1orf132/MIR29B2C determine age-related methylation signature of blood after allogeneic hematopoietic stem cell transplantation.

Science.gov (United States)

Spólnicka, Magdalena; Piekarska, Renata Zbieć; Jaskuła, Emilia; Basak, Grzegorz W; Jacewicz, Renata; Pięta, Agnieszka; Makowska, Żanetta; Jedrzejczyk, Maciej; Wierzbowska, Agnieszka; Pluta, Agnieszka; Robak, Tadeusz; Berent, Jarosław; Branicki, Wojciech; Jędrzejczak, Wiesław; Lange, Andrzej; Płoski, Rafał

2016-01-01

Our recent study demonstrated that DNA methylation status in a set of CpGs located in ELOVL2, C1orf132, TRIM59, KLF14, and FHL2 can accurately predict calendar age in blood. In the present work, we used these markers to evaluate the effect of allogeneic hematopoietic stem cell transplantation (HSCT) on the age-related methylation signature of human blood. DNA methylation in 32 CpGs was investigated in 16 donor-recipient pairs using pyrosequencing. DNA was isolated from the whole blood collected from recipients 27-360 days (mean 126) after HSCT and from the donors shortly before the HSCT. It was found that in the recipients, the predicted age did not correlate with their calendar age but was correlated with the calendar age (r = 0.94, p = 4 × 10(-8)) and predicted age (r = 0.97, p = 5 × 10(-10)) of a respective donor. Despite this strong correlation, the predicted age of a recipient was consistently lower than the predicted age of a donor by 3.7 years (p = 7.8 × 10(-4)). This shift was caused by hypermethylation of the C1orf132 CpGs, for C1orf132 CpG_1. Intriguingly, the recipient-donor methylation difference correlated with calendar age of the donor (r = 0.76, p = 6 × 10(-4)). This finding could not trivially be explained by shifts of the major cellular factions of blood. We confirm the single previous report that after HSCT, the age of the donor is the major determinant of age-specific methylation signature in recipient's blood. A novel finding is the unique methylation dynamics of C1orf132 which encodes MIR29B2C implicated in the self-renewing of hematopoietic stem cells. This observation suggests that C1orf132 could influence graft function after HSCT.

Boron-Catalyzed C3-Polymerization of ω-2-Methyl Allylarsonium Ylide and Its C3/C1 Copolymers with Dimethylsulfoxonium Methylide

KAUST Repository

Wang, De

2016-03-01

A novel arsonium ylide, ω-2-methylallylarsonium ylide, was synthesized and used as monomer for polyhomologation with triethyborane as initiator. It was found that the terminal methyl group leads to C3 polymerization. Furthermore, the copolyhomologation of arsonium ylide with dimethylsulfoxonium methylide is reported for the first time. (Chemical Equation Presented). © 2016 American Chemical Society.

Semi-automated preparation of a 11C-labelled antibiotic - [N-methyl-11C]erythromycin A lactobionate

International Nuclear Information System (INIS)

Pike, V.W.; Palmer, A.J.; Horlock, P.L.; Liss, R.H.

1984-01-01

A fast semi-automated method is described for labelling the antibiotic, erythromycin A (1), with the short-lived positron-emitting radionuclide, 11 C(tsub(1/2)=20.4 min), in order to permit the non-invasive study of its tissue uptake in vivo. Labelling was achieved by the fast reductive methylation of N-demethylerythromycin A (2) with [ 11 C]formaldehyde, itself prepared from cyclotron-produced [ 11 C]-carbon dioxide. Rapid chemical and radiochemical purification of the [N-methyl- 11 C]erythromycin A (3) were achieved by HPLC and verified by TLC with autoradiography. The purified material was formulated for human i.v. injection as a sterile apyrogenic solution of the lactobionate salt. The preparation takes 42 min from the end of radionuclide production and from [ 11 C]carbon dioxide produces [N-methyl- 11 C]erythromycin A lactobionate in 4-12% radiochemical yield, corrected for radioactive decay. (author)

The nematode Caenorhabditis elegans displays a chemotaxis behavior to tuberculosis-specific odorants

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Mário F. Neto

2016-08-01

Full Text Available A simple, affordable diagnostic test for pulmonary tuberculosis (TB is urgently needed to improve detection of active Mycobacterium tuberculosis. Recently, it has been suggested that animal behavior can be used as a biosensor to signal the presence of human disease. For example, the giant African pouched rats can detect tuberculosis by sniffing sputum specimens while trained honeybees respond to three of the volatile organic compounds (VOCs detected in the breath of TB positive patients by proboscis extension. However, both rats and honeybees require animal housing facilities and professional trainers, which are outside the scope of most disease testing facilities. Here, we report that the innate olfactory behavioral response of the roundworm nematode Caenorhabditis elegans can be used to detect the TB-specific VOCs methyl p-anisate, methyl nicotinate, methyl phenylacetate and o-phenylanisole, in chemotaxis assays. Dauer larvae, a long-lived stress resistant alternative development state of C. elegans in which the animals can survive for extended periods of time in dry conditions with no food, were also demonstrated to detect the VOCs. We propose that exposing naive dauer larvae to TB-related VOCs and recording their response in this behavioral assay could lead to the development of a new method for TB diagnostics using breath as the sample type. Keywords: Tuberculosis, Caenorhabditis elegans, Chemotaxis, Volatile organic compounds, Diagnostics, Odorants

Assignment of methyl NMR resonances of a 52 kDa protein with residue-specific 4D correlation maps

International Nuclear Information System (INIS)

Mishra, Subrata H.; Frueh, Dominique P.

2015-01-01

Methyl groups have become key probes for structural and functional studies by nuclear magnetic resonance. However, their NMR signals cluster in a small spectral region and assigning their resonances can be a tedious process. Here, we present a method that facilitates assignment of methyl resonances from assigned amide groups. Calculating the covariance between sensitive methyl and amide 3D spectra, each providing correlations to C α and C β separately, produces 4D correlation maps directly correlating methyl groups to amide groups. Optimal correlation maps are obtained by extracting residue-specific regions, applying derivative to the dimensions subject to covariance, and multiplying 4D maps stemming from different 3D spectra. The latter procedure rescues weak signals that may be missed in traditional assignment procedures. Using these covariance correlation maps, nearly all assigned isoleucine, leucine, and valine amide resonances of a 52 kDa nonribosomal peptide synthetase cyclization domain were paired with their corresponding methyl groups

Quantification of 5-methyl-2'-deoxycytidine in the DNA.

Science.gov (United States)

Giel-Pietraszuk, Małgorzata; Insińska-Rak, Małgorzata; Golczak, Anna; Sikorski, Marek; Barciszewska, Mirosława; Barciszewski, Jan

2015-01-01

Methylation at position 5 of cytosine (Cyt) at the CpG sequences leading to formation of 5-methyl-cytosine (m(5)Cyt) is an important element of epigenetic regulation of gene expression. Modification of the normal methylation pattern, unique to each organism, leads to the development of pathological processes and diseases, including cancer. Therefore, quantification of the DNA methylation and analysis of changes in the methylation pattern is very important from a practical point of view and can be used for diagnostic purposes, as well as monitoring of the treatment progress. In this paper we present a new method for quantification of 5-methyl-2'deoxycytidine (m(5)C) in the DNA. The technique is based on conversion of m(5)C into fluorescent 3,N(4)-etheno-5-methyl-2'deoxycytidine (εm(5)C) and its identification by reversed-phase high-performance liquid chromatography (RP-HPLC). The assay was used to evaluate m(5)C concentration in DNA of calf thymus and peripheral blood of cows bred under different conditions. This approach can be applied for measuring of 5-methylcytosine in cellular DNA from different cells and tissues.

Methyl 3-(Quinolin-2-ylindolizine-1-carboxylate

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Roumaissa Belguedj

2015-12-01

Full Text Available A novel compound, methyl 3-(quinolin-2-ylindolizine-1-carboxylate (2 has been synthesized by cycloaddition reaction of 1-(quinolin-2-ylmethylpyridinium ylide (1 with methyl propiolate in presence of sodium hydride in THF. The structure of this compound was established by IR, 1H-NMR, 13C-NMR and MS data

Influence of pesticide applications on degradation of the herbicide 14C - 2,4-D in different soils

International Nuclear Information System (INIS)

Marcondes, Marcilio Amaral

2001-01-01

Despite the importance of pesticide usage for the food production, its indiscriminate use may cause changes in the soil fertility, because pesticides influence soil microorganisms which are important for the biogeochemical cycles. The influence of applications of several pesticides, as recommended for cotton culture, was studied on the bioactivity of different soils (from Sao Paulo and Tatui, SP) by using radiometric techniques and a closed system for detection of bio mineralization of ''1 4 C-2,4-D ( 14 C-2,4-dichlorophenoxyacetic acid) and production of 14 C-volatile compounds. The 14 C-2,4-D dissipation under influence of other pesticide applications was also studied by determination of 14 C-extractable residues, 14 C-bound residues and qualitative and quantitative analysis of the 14 C-extractable residues by high pressure liquid chromatography (HPLC) and thin layer chromatography (TLC). 14 C-volatile compounds were never detected but increases and decreases of bio mineralization were detected in both soils after different treatments. The mixture of deltamethrin + methyl parathion increased significantly the bioactivity in both soils; nevertheless, monocrotophos did not have any influence. The applications of different pesticides have also influenced the 14 C-2,4-D dissipation, because the radiocarbon recovered as 14 C-extractable residues differed between the treated and untreated samples of both soils. On the other hand, the pesticide applications did not influence the production of 14 C-bound residues. This 14 C-residue was produced in larger amounts by the richest in organic matter soil (Sao Paulo). Although radiocarbon had been detected not only as 14 'C-2,4-D but also as a 14 C-metabolite, in both soils and treatments, results indicate that the ' 14 C-2,4-D dissipation varied in the two studied soils and was influenced by treatments with others pesticides. (author)

Reinvestigation of the synthesis and evaluation of [N-methyl-{sup 11}C]vorozole, a radiotracer targeting cytochrome P450 aromatase

Energy Technology Data Exchange (ETDEWEB)

Kim, Sung Won [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)], E-mail: swkim@bnl.gov; Biegon, Anat; Katsamanis, Zachary E. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Ehrlich, Carolin W. [Johannes-Gutenberg Universitaet Mainz, Institut fuer Organische Chemie, Duesbergweg 10-14, Mainz (Germany); Hooker, Jacob M.; Shea, Colleen [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Muench, Lisa [National Institute on Alcoholism and Alcohol Abuse, Bethesda, MD (United States); Xu Youwen; King, Payton; Carter, Pauline; Alexoff, David L. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Fowler, Joanna S. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Psychiatry, Mount Sinai School of Medicine, New York, NY (United States); Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY (United States)

2009-04-15

Introduction: We reinvestigated the synthesis of [N-methyl-{sup 11}C]vorozole, a radiotracer for aromatase, and discovered the presence of an N-methyl isomer which was not removed in the original purification method. Herein we report the preparation and positron emission tomography (PET) studies of pure [N-methyl-{sup 11}C]vorozole. Methods: Norvorozole was alkylated with [{sup 11}C]methyl iodide as previously described and also with unlabeled methyl iodide. A high-performance liquid chromatography (HPLC) method was developed to separate the regioisomers. Nuclear magnetic resonance (NMR) spectroscopy ({sup 13}C and 2D-nuclear Overhauser effect spectroscopy NMR) was used to identify and assign structures to the N-methylated products. Pure [N-methyl-{sup 11}C]vorozole and the contaminating isomer were compared by PET imaging in the baboon. Results: Methylation of norvorozole resulted in a mixture of isomers (1:1:1 ratio) based on new HPLC analysis using a pentafluorophenylpropyl bonded silica column, in which vorozole coeluted one of its isomers under the original HPLC conditions. Baseline separation of the three labeled isomers was achieved. The N-3 isomer was the contaminant of vorozole, thus correcting the original assignment of isomers. PET studies of pure [N-methyl-{sup 11}C]vorozole with and without the contaminating N-3 isomer revealed that only [N-methyl-{sup 11}C]vorozole binds to aromatase. [N-methyl-{sup 11}C]Vorozole accumulated in all brain regions with highest accumulation in the aromatase-rich amygdala and preoptic area. Accumulation was blocked with vorozole and letrozole consistent with reports of some level of aromatase in many brain regions. Conclusions: The discovery of a contaminating labeled isomer and the development of a method for isolating pure [N-methyl-{sup 11}C]vorozole combine to provide a new scientific tool for PET studies of the biology of aromatase and for drug research and development.

Conocimientos sobre tuberculosis en trabajadores de la salud en una localidad de Bogotá D. C Conhecimentos sobre tuberculose entre trabalhadores da saúde em uma localidade de Bogotá D.C Knowledge on tuberculosis In health workers in a sector of Bogotá D.C

Directory of Open Access Journals (Sweden)

Óscar Andrés Cruz Martínez

2011-07-01

Full Text Available El presente artículo es producto de una monografía de pre-grado para la obtención del título de enfermero-a profesional, el cual tuvo como objetivo identificar los conocimientos sobre tuberculosis en 117 trabajadores de la salud de 12 instituciones de salud públicas y privadas vinculadas al programa de prevención y control de tuberculosis, de la Secretaría Distrital de Salud, en una localidad de Bogotá. Para la recolección de datos se diseñó un instrumento de evaluación, el cual se aplicó a los trabajadores previa lectura y aceptación de participación mediante su consentimiento informado. Se realizó una caracterización general de los trabajadores y se evaluaron conocimientos básicos sobre tuberculosis. Los resultados evidenciaron que un 34% de trabajadores alcanzó un nivel de conocimientos medio, un 32% nivel inferior, un 27% nivel bajo y solo un 7% alcanzó el nivel alto. Se evidenció, en general, déficit de conocimientos sobre la enfermedad, principalmente en temas como diagnóstico, tratamiento, periodo de transmisibilidad y medidas de bioseguridad. Se verifica la necesidad de orientar acciones que amplíen los conocimientos sobre tuberculosis en los trabajadores de la salud, mediante la formación académica, la facilitación de espacios para capacitación, el mejoramiento de las condiciones de trabajo y la articulación de actividades de investigación y extensión entre la academia y el Programa Distrital de Control de Tuberculosis.Este artigo é produto duma monografia de pré-graduação para a obtenção do título de enfermeiro(a profissional, que objetivou identificar os conhecimentos sobre tuberculose em 177 trabalhadores da saúde de 12 instituições de saúde públicas e particulares vinculadas ao programa de prevenção e controle de tuberculose, da Secretaria Distrital de Saúde, em uma localidade de Bogotá. Para reunir os dados, desenhou-se um instrumento de avaliação que foi administrado entre os

Molecular analysis of Rv0679c and Rv0180c genes of Mycobacterium tuberculosis from clinical isolates of pulmonary tuberculosis

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L Rupa

2016-01-01

Full Text Available Context: Two novel proteins/genes Rv0679c and Rv0180c of Mycobacterium tuberculosis (MTB H37Rv were classified as a hypothetical membrane and transmembrane proteins which might have a role in the invasion. Molecular analysis of these genes in human clinical isolates of pulmonary tuberculosis (PTB patients was not well characterised. Aims: To assess the molecular diversity of Rv0679c and Rv0180c genes of MTB from clinical isolates of PTB patients. Settings and Design: DNA from 97 clinical isolates was extracted and subjected to amplification using selective primers by polymerase chain reaction (PCR. The PCR product obtained was sequenced commercially. Patients and Methods: Clinical isolates obtained from tuberculosis patients were investigated for polymorphisms in the Rv0679c and Rv0180c genes by PCR and DNA sequencing. Genomic DNA isolated by cetyltrimethylammonium bromide method was used for amplification of genes. Results: Rv0679c gene was highly conserved in 61 out of 65 clinical isolates assessed for sequence homology with wild-type H37Rv gene and was identical using ClustalW. Fifty-five out of 78 (70.5% clinical isolates assessed for Rv0180c were positive for single nucleotide polymorphism (SNP at 258th position where the nucleotide G was replaced with T (G to T. In clinical isolates of untreated cases, the frequency was 54.5% for SNP at 258th position which is low compared to cases undergoing treatment where the frequency was 73.1%. Conclusions: Molecular analysis of Rv0180c in clinical isolates of PTB assessed in this study was the first report, where an SNP at 258th position G to T was identified within the gene. Rv0679c gene was highly conserved (94%, within Indian clinical isolates as compared to reports from other nations.

Fragrance material review on 3-methyl-5-(2,2,3-trimethyl-3-cyclopenten-1-yl)pent-3-en-2-one.

Science.gov (United States)

Scognamiglio, J; Letizia, C S; Api, A M

2013-12-01

A toxicologic and dermatologic review of 3-methyl-5-(2,2,3-trimethyl-3-cyclopenten-1-yl)pent-3-en-2-one when used as a fragrance ingredient is presented. 3-Methyl-5-(2,2,3-trimethyl-3-cyclopenten-1-yl)pent-3-en-2-one is a member of the fragrance structural group Alkyl Cyclic Ketones. These fragrances can be described as being composed of an alkyl, R1, and various substituted and bicyclic saturated or unsaturated cyclic hydrocarbons, R2, in which one of the rings may include up to 12 carbons. Alternatively, R2 may be a carbon bridge of C2-C4 carbon chain length between the ketone and cyclic hydrocarbon. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 3-methyl-5-(2,2,3-trimethyl-3-cyclopenten-1-yl)pent-3-en-2-one were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, sensitization, phototoxicity, photoallergy, and genotoxicity data. A safety assessment of the entire Alkyl Cyclic Ketones will be published simultaneously with this document; please refer to Belsito et al. (Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2013. A Toxicologic and Dermatologic Assessment of Alkyl Cyclic Ketones when used as fragrance ingredients. Submitted for publication) for an overall assessment of the safe use of this material and all Alkyl Cyclic Ketones in fragrances. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structural basis for substrate placement by an archaeal box C/D ribonucleoprotein particle.

Science.gov (United States)

Xue, Song; Wang, Ruiying; Yang, Fangping; Terns, Rebecca M; Terns, Michael P; Zhang, Xinxin; Maxwell, E Stuart; Li, Hong

2010-09-24

Box C/D small nucleolar and Cajal body ribonucleoprotein particles (sno/scaRNPs) direct site-specific 2'-O-methylation of ribosomal and spliceosomal RNAs and are critical for gene expression. Here we report crystal structures of an archaeal box C/D RNP containing three core proteins (fibrillarin, Nop56/58, and L7Ae) and a half-mer box C/D guide RNA paired with a substrate RNA. The structure reveals a guide-substrate RNA duplex orientation imposed by a composite protein surface and the conserved GAEK motif of Nop56/58. Molecular modeling supports a dual C/D RNP structure that closely mimics that recently visualized by electron microscopy. The substrate-bound dual RNP model predicts an asymmetric protein distribution between the RNP that binds and methylates the substrate RNA. The predicted asymmetric nature of the holoenzyme is consistent with previous biochemical data on RNP assembly and provides a simple solution for accommodating base-pairing between the C/D guide RNA and large ribosomal and spliceosomal substrate RNAs. Copyright © 2010 Elsevier Inc. All rights reserved.

The Impact of Minimum Energy Performance Standards (MEPS) Regulation on Electricity Saving in Malaysia

Science.gov (United States)

Fatihah Salleh, Siti; Eqwan Roslan, Mohd; Isa, Aishah Mohd; Faizal Basri Nair, Mohd; Syafiqah Salleh, Siti

2018-03-01

One of Malaysia’s key strategies to promote efficient energy use in the country is to implement the minimum energy performance standards (MEPS) through the Electricity Regulations (Amendment) 2013. Five selected electrical appliances (refrigerator, air conditioner, television, domestic fans and lamp fittings) must comply with MEPS requirement in order to be sold in Malaysian market. Manufacturers, importers or distributors are issued Certificate of Approval (COA) if products are MEPS-compliant. In 2015, 1,215 COAs were issued but the number of MEPS products in the market is unknown. This work collects sales data from major manufacturers to estimate the annual sales of MEPS appliances and the cumulative electricity consumption and electricity saving. It was found that most products sold have 3-star rating and above. By year 2015, total cumulative electricity savings gained from MEPS implementation is 3,645 GWh, with air conditioner being the highest contributor (30%). In the future, it is recommended that more MEPS products and related incentives be introduced to further improve efficiency of energy use in Malaysia.

Syntheses of DNA adducts of two heterocyclic amines, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) and 2-amino-9H-pyrido[2,3-b]indole (A alpha C) and identification of DNA adducts in organs from rats dosed with MeA alpha C

DEFF Research Database (Denmark)

Frederiksen, Hanne; Frandsen, Henrik Lauritz; Pfau, W.

2004-01-01

2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (AalphaC) are mutagenic and carcinogenic heterocyclic amines formed during ordinary cooking. MeAalphaC and AalphaC are activated to mutagenic metabolites by cytochrome P450-mediated N-oxidation...... by reaction of the parent amines with acetylated guanine N3-oxide. N-2-OH-MeAalphaC and N-2-OH-AalphaC reacted with calf thymus DNA after addition of acetic anhydride. P-32-postlabelling analysis of modified DNA showed one major adduct co-migrating with N-2-(3',5'-diphospho-2'-deoxyguanosin-8-yl...

11C-labelling of the analgesic Tramadol and its major metabolites by selective O- and N-methylation

International Nuclear Information System (INIS)

Gail, R.; Coenen, H.H.; Hamacher, K.; Stoecklin, G.

1992-01-01

For in vivo pharmacokinetic studies with PET, the analgesic Tramadol(1-(3-methoxyphenyl)-2-dimethylaminomethyl-cyclohexan-1-ol) and its major O- and N-desmethylated metabolites M1 and M2 were labelled with carbon-11. Starting with the corresponding desmethyl precursors, [O-methyl- 11 C]Tramadol and racemic[N-methyl- 11 C]Tramadol were prepared by methylation with n.c.a. [ 11 C]methyl iodide in DMSO with radiochemical yields of 85 and 90%, respectively. Specific n.c.a. N-methylation of bis-desmethyl-Tramadol (M5) was achieved with 90% radiochemical yield. However, a selective O-methylation of M5 was not possible even with an excess of NaOH, and only 70% of [O-methyl- 11 C]M2 was obtained. Quaternization of Tramadol or M1 was >15 times slower than O-methylation, and was only observed in the presence of added CH 3 I carrier. (author)

Facile syntheses of isotope-labeled chiral octahydroindole-2-carboxylic acid and its N-methyl analog

International Nuclear Information System (INIS)

Yinsheng Zhang

2012-01-01

We have synthesized deuterium and carbon-14 labeled enantiomerically pure octahydroindole-2-carboxylic acid (PD0140417), N-methyl octahydroindole-2-carboxylic acid (PD0348183) and their racemic analogs (PD0108405 and PD0338055). [ring-U- 14 C]PD0140417 was prepared from [ring-U- 14 C]benzoic acid in a seven-step synthesis in 6.2% overall radiochemical yield. [ 14 C]PD0348183 was prepared from [ 14 C]BaCO 3 in a five-step synthesis in 16% radiochemical yield. Additionally, [D]PD0108405 and [D]PD0338055 were synthesized by direct platinum-catalyzed hydrogenation with deuterium gas. (author)

PRMT5 regulates IRES-dependent translation via methylation of hnRNP A1

Science.gov (United States)

Gao, Guozhen; Dhar, Surbhi

2017-01-01

Abstract The type II arginine methyltransferase PRMT5 is responsible for the symmetric dimethylation of histone to generate the H3R8me2s and H4R3me2s marks, which correlate with the repression of transcription. However, the protein level of a number of genes (MEP50, CCND1, MYC, HIF1a, MTIF and CDKN1B) are reported to be downregulated by the loss of PRMT5, while their mRNA levels remain unchanged, which is counterintuitive for PRMT5's proposed role as a transcription repressor. We noticed that the majority of the genes regulated by PRMT5, at the posttranscriptional level, express mRNA containing an internal ribosome entry site (IRES). Using an IRES-dependent reporter system, we established that PRMT5 facilitates the translation of a subset of IRES-containing genes. The heterogeneous nuclear ribonucleoprotein, hnRNP A1, is an IRES transacting factor (ITAF) that regulates the IRES-dependent translation of Cyclin D1 and c-Myc. We showed that hnRNP A1 is methylated by PRMT5 on two residues, R218 and R225, and that this methylation facilitates the interaction of hnRNP A1 with IRES RNA to promote IRES-dependent translation. This study defines a new role for PRMT5 regulation of cellular protein levels, which goes beyond the known functions of PRMT5 as a transcription and splicing regulator. PMID:28115626

Fabrication and characterization of 2.5D and 3D SiC{sub f}/SiC composites

Energy Technology Data Exchange (ETDEWEB)

Zhao, Shuang, E-mail: zhsh6007@126.co [Key Laboratory of Advanced Ceramic Fibers and Composites, National University of Defense Technology, Changsha 410073 (China); School of Mechanical, Aerospace, and Civil Engineering, University of Manchester, Manchester M13 9PL (United Kingdom); Zhou, Xingui; Yu, Jinshan [Key Laboratory of Advanced Ceramic Fibers and Composites, National University of Defense Technology, Changsha 410073 (China); Mummery, Paul [School of Mechanical, Aerospace, and Civil Engineering, University of Manchester, Manchester M13 9PL (United Kingdom)

2013-10-15

Highlights: • 2.5D and 3D KD-I SiC fiber fabrics were used as the reinforcement. • Closed porosity was investigated by X-ray tomographic techniques. • The properties of the composites were improved by the CVD process. -- Abstract: SiC{sub f}/SiC composites are considered promising candidate materials for fusion applications. 2.5D and 3D KD-I SiC fiber fabrics were used as the reinforcement and SiC{sub f}/SiC composites were fabricated via polymer impregnation and pyrolysis (PIP) process and coated with chemical vapor deposited (CVD) SiC. The porosity, thermal conductivity and mechanical property of the composites were characterized. The results indicated that 2.5D and 3D SiC{sub f}/SiC composites fabricated via PIP process exhibited high porosity, and hence low thermal conductivity. After the CVD process, the density, thermal conductivity and mechanical properties of the composites were increased.

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.

Science.gov (United States)

Wegner, Florian; Wilke, Florian; Raab, Peter; Tayeb, Said Ben; Boeck, Anna-Lena; Haense, Cathleen; Trebst, Corinna; Voss, Elke; Schrader, Christoph; Logemann, Frank; Ahrens, Jörg; Leffler, Andreas; Rodriguez-Raecke, Rea; Dengler, Reinhard; Geworski, Lilli; Bengel, Frank M; Berding, Georg; Stangel, Martin; Nabavi, Elham

2014-06-20

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. 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. 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. 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.

Imaging of musculoskeletal tuberculosis

International Nuclear Information System (INIS)

Boussel, L.; Marchand, B.; Blineau, N.; Picaud, G.; Emn, M.; Coulon, A.; Pagnon, P.; Rode, A.; Pin-Leveugle, J.; Berthezene, Y.; Pariset, C.; Boibieux, A.; Hermier, M.

2002-01-01

Purpose and methods. To perform an illustrated and educational review of musculoskeletal tuberculosis. Results. As the incidence of musculoskeletal tuberculosis still increases, a review appears justified. The following four main presentations are detailed and illustrated, by emphasizing the value of both CT and MR imaging: a) spine tuberculosis (∼ 50 %/) commonly involves two adjacent vertebral bodies with usual large paravertebral abscesses. The following lesions are highly suggestive of tuberculosis: solitary vertebral involvement, solitary epidural abscess with or without erosive spondylitis; b) osteo-arthritis: peripherally located erosions at synovial insertions with gradual narrowing of the joint space are highly suggestive; c) osteomyelitis: unusual, may involve any bones; d) tenosynovitis and bursitis. Conclusion. Imaging studies are essential for diagnosis and to assess the extent of musculo-skeletal tuberculosis. (author)

Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial

DEFF Research Database (Denmark)

Wejse, Christian; Gomes, Victor F; Rabna, Paulo

2009-01-01

RATIONALE: Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis. OBJECTIVES: To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality. METHODS: We conducted a randomized, double-blind...

Hydrothermal synthesis of 3D hierarchical flower-like MoSe{sub 2} microspheres and their adsorption performances for methyl orange

Energy Technology Data Exchange (ETDEWEB)

Tang, Hua, E-mail: tanghua@mail.ujs.edu.cn; Huang, Hong; Wang, Xiaoshuai; Wu, Kongqiang; Tang, Guogang; Li, Changsheng

2016-08-30

Highlights: • 3D hierarchical flower-like MoSe{sub 2} microspheres have been fabricated via a hydrothermal method. • A possible evolution process of 3D hierarchical flower-like MoSe{sub 2} microspheres was discussed. • Flower-like MoSe{sub 2} microspheres exhibit excellent adsorption properties for dye methyl orange removal from aqueous solution. - Abstract: In this paper, we report a facile and versatile modified hydrothermal method for synthesis of three-dimensional (3D) hierarchical flower-like MoSe{sub 2} microspheres using selenium powders and sodium molybdate as raw materials. The as-prepared MoSe{sub 2} was investigated for application as an adsorbent for the removal of dye contaminants from water. Power X-ray diffraction (XRD), energy dispersive spectroscopy (EDS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscope (XPS) and N{sub 2} adsorption-desorption analysis were carried out to study the microstructure of the as-synthesized product. A possible growth mechanism of MoSe{sub 2} flower-like microspheres was preliminarily proposed on the basis of observation of a time-dependent morphology evolution process. Moreover, the MoSe{sub 2} sample exhibited good adsorption properties, with maximum adsorption capacity of 36.91 mg/g for methyl orange. The adsorption process of methyl orange on 3D hierarchical flower-like MoSe{sub 2} microspheres was systematically investigated, which was found to obey the pseudo-second-order rate equation and Langmuir adsorption model.

Sc2C2@D3h(14246)-C74: A Missing Piece of the Clusterfullerene Puzzle.

Science.gov (United States)

Wang, Yaofeng; Tang, Qiangqiang; Feng, Lai; Chen, Ning

2017-02-20

Clusterfullerenes with variable carbon cages have been extensively studied in recent years. However, despite all these efforts, C 74 cage-based clusterfullerene remains a missing piece of the puzzle. Herein, we show that single-crystal X-ray crystallographic analysis unambiguously assigns the previously reported dimetallofullerene Sc 2 @C 76 to a novel carbide clusterfullerene, Sc 2 C 2 @D 3h (14246)-C 74 , the first experimentally proven clusterfullerene with a C 74 cage. In addition, Sc 2 C 2 @D 3h (14246)-C 74 was charaterized by mass spectrometry, ultraviolet-visible-near-infrared absorption spectroscopy, 45 Sc nuclear magnetic resonance, and cyclic voltammetry. Comparative studies of the motion of the carbide cluster in Sc 2 C 2 @D 3h (14246)-C 74 and Sc 2 C 2 @C 2n (n = 40-44) revealed that a combination of factors, involving both the shape and size of the cage, is crucial in dictating the cluster motion. Moreover, structural studies of D 3h (14246)-C 74 revealed that it can be easily converted to C s (10528)-C 72 and T d (19151)-C 76 cages via C 2 desertion/insertion and Stone-Wales transformation. This suggests that D 3h (14246)-C 74 might play an important role in the growth pathway of clusterfullerenes.

2′-O Methylation of Internal Adenosine by Flavivirus NS5 Methyltransferase

Science.gov (United States)

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

tert-Butyl 2-methyl-2-(4-nitrobenzoylpropanoate

Directory of Open Access Journals (Sweden)

Chelsey M. Crosse

2010-02-01

Full Text Available The title compound, C15H19NO5, is bent with a dihedral angle of 61.8 (2° between the mean planes of the benzene ring and a group encompassing the ester functionality (O=C—O—C. The dihedral angle of 0.8 (2° between the mean planes of the nitro group and the benzene ring indicates near coplanarity. In the crystal, each molecule is linked to four adjacent molecules by weak C—H...O hydrogen-bonding interactions. Both benzene H atoms ortho to the ketone O atom form C—H...O hydrogen bonds with the keto O atoms of two neighboring molecules (of the keto and ester groups, respectively, and the two other interactions involve the H atoms from a methyl group of the dimethyl residue, displaying C—H...O interactions with the O atoms of the nitro groups. These four interactions for each molecule lead to the formation of two-dimensional sheets with a hydrophilic interior, held together by weak hydrogen-bonded interactions, and a hydrophobic exterior composed of protruding methyl groups which interstack with the methyl groups in adjacent sheets.

A high-throughput screen against pantothenate synthetase (PanC identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis.

Directory of Open Access Journals (Sweden)

Anuradha Kumar

Full Text Available The enzyme pantothenate synthetase, PanC, is an attractive drug target in Mycobacterium tuberculosis. It is essential for the in vitro growth of M. tuberculosis and for survival of the bacteria in the mouse model of infection. PanC is absent from mammals. We developed an enzyme-based assay to identify inhibitors of PanC, optimized it for high-throughput screening, and tested a large and diverse library of compounds for activity. Two compounds belonging to the same chemical class of 3-biphenyl-4- cyanopyrrole-2-carboxylic acids had activity against the purified recombinant protein, and also inhibited growth of live M. tuberculosis in manner consistent with PanC inhibition. Thus we have identified a new class of PanC inhibitors with whole cell activity that can be further developed.

A high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis.

Science.gov (United States)

Kumar, Anuradha; Casey, Allen; Odingo, Joshua; Kesicki, Edward A; Abrahams, Garth; Vieth, Michal; Masquelin, Thierry; Mizrahi, Valerie; Hipskind, Philip A; Sherman, David R; Parish, Tanya

2013-01-01

The enzyme pantothenate synthetase, PanC, is an attractive drug target in Mycobacterium tuberculosis. It is essential for the in vitro growth of M. tuberculosis and for survival of the bacteria in the mouse model of infection. PanC is absent from mammals. We developed an enzyme-based assay to identify inhibitors of PanC, optimized it for high-throughput screening, and tested a large and diverse library of compounds for activity. Two compounds belonging to the same chemical class of 3-biphenyl-4- cyanopyrrole-2-carboxylic acids had activity against the purified recombinant protein, and also inhibited growth of live M. tuberculosis in manner consistent with PanC inhibition. Thus we have identified a new class of PanC inhibitors with whole cell activity that can be further developed.

A Cytosolic Arabidopsis d-Xylulose Kinase Catalyzes the Phosphorylation of 1-Deoxy-d-Xylulose into a Precursor of the Plastidial Isoprenoid Pathway1

Science.gov (United States)

Hemmerlin, Andréa; Tritsch, Denis; Hartmann, Michael; Pacaud, Karine; Hoeffler, Jean-François; van Dorsselaer, Alain; Rohmer, Michel; Bach, Thomas J.

2006-01-01

Plants are able to integrate exogenous 1-deoxy-d-xylulose (DX) into the 2C-methyl-d-erythritol 4-phosphate pathway, implicated in the biosynthesis of plastidial isoprenoids. Thus, the carbohydrate needs to be phosphorylated into 1-deoxy-d-xylulose 5-phosphate and translocated into plastids, or vice versa. An enzyme capable of phosphorylating DX was partially purified from a cell-free Arabidopsis (Arabidopsis thaliana) protein extract. It was identified by mass spectrometry as a cytosolic protein bearing d-xylulose kinase (XK) signatures, already suggesting that DX is phosphorylated within the cytosol prior to translocation into the plastids. The corresponding cDNA was isolated and enzymatic properties of a recombinant protein were determined. In Arabidopsis, xylulose kinases are encoded by a small gene family, in which only two genes are putatively annotated. The additional gene is coding for a protein targeted to plastids, as was proved by colocalization experiments using green fluorescent protein fusion constructs. Functional complementation assays in an Escherichia coli strain deleted in xk revealed that the cytosolic enzyme could exclusively phosphorylate xylulose in vivo, not the enzyme that is targeted to plastids. xk activities could not be detected in chloroplast protein extracts or in proteins isolated from its ancestral relative Synechocystis sp. PCC 6803. The gene encoding the plastidic protein annotated as “xylulose kinase” might in fact yield an enzyme having different phosphorylation specificities. The biochemical characterization and complementation experiments with DX of specific Arabidopsis knockout mutants seedlings treated with oxo-clomazone, an inhibitor of 1-deoxy-d-xylulose 5-phosphate synthase, further confirmed that the cytosolic protein is responsible for the phosphorylation of DX in planta. PMID:16920870

Ferrocene Compounds. XXVI. C- and O-Ferrocenylalkylation of Methyl Salicylate

OpenAIRE

Kovač, Veronika; Rapić, Vladimir; Alagić, Jasmina; Barišić, Lidija

1999-01-01

Reaction of equimolar amounts of methyl salicylate, sodium and N,N,N-trimethylferrocylammonium iodide (1a) in ethanol gave 55% of ethyl 1-ferrocenylethyl ether (4). By refluxing a solution of 9 mmol sodium and 3 mmol of FcCHRNMe3I (1a, R = H; 1b, R = Me; 1c, R = Ph) in a large excess of methyl salicylate for 2-3 hours, the corresponding methyl 5-ferrocylsalicylates (5) (10-23%) and methyl-3-ferrocylsalicylates (6) (12-20%) were obtained. During conversion of salt 1b, besides of 5b and 6b, 20%...

Synthesis of N-methyl and N-11C-methyl spiperone by phase transfer catalysis in anhydrous solvent

International Nuclear Information System (INIS)

Omokawa, Hiroyoshi; Tanaka, Akira; Iio, Mayumi; Nishihara, Yoshiaki; Inoue, Osamu; Yamazaki, Toshio.

1985-01-01

Spiperone, a butyrophenone neuroleptic drug, has been used in binding studies of dopamine receptors. Langstrom et al. developed N- 11 C-methyl spiperone, and, in cooperate with Wagner et al., made it possible to visualize the distribution of dopamine receptors in the human brain in vivo. In this paper, we independently developed another synthetic method of N- 11 C-methyl spiperone using the phase transfer catalyst in an anhydrous solvent. Separation of the product is feasible only by passing the reactant solution through a Millipore filter and injecting it onto high pressure liquid chromatography (HPLC). The time required for the synthesis and purification of N- 11 C-methyl spiperone from 11 C-methyl iodide and spiperone was 20 min. Radiochemical yield exceeded 35 % against 11 C-methyl iodide without correcting decay of the radioactivity. (author)

[On the way to shortening tuberculosis treatments: clinical trials of the Unitat d' Investagació en Tuberculosi de Barcelona supported by the Centers for Disease Control and Prevention].

Science.gov (United States)

Moreno, Antonio; Sánchez, Francesca; Nelson, Jeanne; Miró, José M; Caylà, Joan A

2010-01-01

New treatment guidelines are required to improve the tuberculosis control strategies that have been used for 30 years. Seven centers of the Barcelona Tuberculosis Research Unit (BTRU) (Unitat d'Investigació en Tuberculosi de Barcelona) are collaborating with the Division of Tuberculosis Elimination of the United States Centers for Disease Control and Prevention in a series of clinical trials on latent tuberculosis infection and tuberculosis disease. BTRU participation began in 2004 with Study 26, an evaluation of the efficacy and tolerability of rifapentine plus isoniazid administered once weekly for 3 months compared with the standard treatment for latent tuberculosis infection. The BTRU centers together enrolled 246 patients (3% of the total). General enrollment was completed in February, 2008. HIV-infected patient and child enrollment continues. Treatment with 12 doses instead of 270 doses is expected to be a clear success. However, the analysis will be completed in 2010. Study 28 (started in 2006), designed for the treatment of pulmonary tuberculosis, compared standard treatment with an experimental regimen substituting moxifloxacin for isoniazid. BTRU centers together enrolled 15 patients (3.5% of the total). The provisional results (presented at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago, 2007) showed no difference between the sputum conversion rate of each regimen at week 8 of treatment. Study 29 is currently underway, in which rifapentine was introduced in the experimental regimen for active tuberculosis treatment. Copyright (c) 2009 SESPAS. Published by Elsevier Espana. All rights reserved.

Thermal diffusivity measurement of erythritol and numerical analysis of heat storage performance on a fin-type heat exchanger

International Nuclear Information System (INIS)

Zamengo, Massimiliano; Funada, Tomohiro; Morikawa, Junko

2017-01-01

Highlights: • Thermal diffusivity of Erythritol was measured by temperature wave method. • Thermal diffusivity was measured in function of temperature and during phase change. • Database of temperature-dependent thermal properties is used for numerical analysis. • Heat transfer and heat storage were analyzed in a fin-type heat exchanger. • Use of temperature-dependent properties in calculations lead to longer melting time. - Abstract: Temperature dependency of thermal diffusivity of erythritol was measured by temperature wave analysis (TWA) method. This modulating technique allowed measuring thermal diffusivity continuously, even during the phase transition solid-liquid. Together with specific heat capacity and specific enthalpy measured by differential scanning calorimetry, the values of measured properties were utilized in a bi-dimensional numerical model for analysis of heat transfer and heat storage performance. The geometry of the model is representative of a cross section of a fin-type heat exchanger, in which erythritol is filling the interspaces between fins. Time-dependent temperature change and heat storage performance were analyzed by considering the variation of thermophysical properties as a function of temperature. The numerical method can be utilized for a fast parametric analysis of heat transfer and heat storage performance into heat storage systems of phase-change materials and composites.

Crystal and molecular structure studies of (Z)-N-methyl-C-4-substituted phenyl nitrones by XRD, DFT, FTIR and NMR methods

Science.gov (United States)

Lasri, Jamal; Eltayeb, Naser Eltaher; Haukka, Matti; Alghamdi, Yousef

2017-01-01

(Z)-N-methyl-C-4-substituted phenyl nitrones -O+N(Me)=C(H)R (Z-2a R = 4-ClC6H4, Z-2b R = 4-NO2C6H4, Z-2c R = 4-CH3OC6H4) were synthesized and characterized by elemental analyses, FTIR, 1H, 13C and DEPT-135 NMR spectroscopy and also by single crystal X-ray diffraction (in the case of Z-2a and Z-2b). The geometries of the nitrone molecules Z-2a, Z-2b and Z-2c and their E-isomers; (E)-N-methyl-C-4-chlorophenyl nitrone E-2a, (E)-N-methyl-C-4-nitrophenyl nitrone E-2b and (E)-N-methyl-C-4-methoxyphenyl nitrone E-2c were optimized using density functional theory (DFT) at the B3LYP/6-311++G(d,p) level of theory. The theoretical vibrational frequencies obtained by DFT calculations are in good agreement with the experimental values. The electronics structures were described in terms of the distribution of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). Gauge independent atomic orbital (GIAO) method was used to calculate the NMR spectra, the correlation between the calculated and experimental chemical shifts is mostly in the range of 0.94-0.97 for 1H, whereas, the correlation for 13C is 0.99. Thermodynamics study showed that the Z-isomer is favoured than E-isomer with energy barrier of 7.1, 7.2 and 7.1 kcal/mol for Z-2a, Z-2b and Z-2c, respectively. The abundance of the most stable species Z-isomers is equal to 99.99% for all three compounds at 298 K in gas phase.

Probing ligand binding modes of Mycobacterium tuberculosis MurC ligase by molecular modeling, dynamics simulation and docking.

Science.gov (United States)

Anuradha, C M; Mulakayala, Chaitanya; Babajan, Banaganapalli; Naveen, M; Rajasekhar, Chikati; Kumar, Chitta Suresh

2010-01-01

Multi drug resistance capacity for Mycobacterium tuberculosis (MDR-Mtb) demands the profound need for developing new anti-tuberculosis drugs. The present work is on Mtb-MurC ligase, which is an enzyme involved in biosynthesis of peptidoglycan, a component of Mtb cell wall. In this paper the 3-D structure of Mtb-MurC has been constructed using the templates 1GQQ and 1P31. Structural refinement and energy minimization of the predicted Mtb-MurC ligase model has been carried out by molecular dynamics. The streochemical check failures in the energy minimized model have been evaluated through Procheck, Whatif ProSA, and Verify 3D. Further torsion angles for the side chains of amino acid residues of the developed model were determined using Predictor. Docking analysis of Mtb-MurC model with ligands and natural substrates enabled us to identify specific residues viz. Gly125, Lys126, Arg331, and Arg332, within the Mtb-MurC binding pocket to play an important role in ligand and substrate binding affinity and selectivity. The availability of Mtb-MurC ligase built model, together with insights gained from docking analysis will promote the rational design of potent and selective Mtb-MurC ligase inhibitors as antituberculosis therapeutics.

Analysis of variations in the glutamate receptor, N-methyl D-aspartate 2A (GRIN2A gene reveals their relative importance as genetic susceptibility factors for heroin addiction.

Directory of Open Access Journals (Sweden)

Bin Zhao

Full Text Available The glutamate receptor, N-methyl D-aspartate 2A (GRIN2A gene that encodes the 2A subunit of the N-methyl D-aspartate (NMDA receptor was recently shown to be involved in the development of opiate addiction. Genetic polymorphisms in GRIN2A have a plausible role in modulating the risk of heroin addiction. An association of GRIN2A single-nucleotide polymorphisms (SNPs with heroin addiction was found earlier in African Americans. To identify markers that contribute to the genetic susceptibility to heroin addiction, we examined the potential association between heroin addiction and forty polymorphisms of the GRIN2A gene using the MassARRAY system and GeneScan in this study. The frequency of the (GT26 repeats (rs3219790 in the heroin addiction group was significantly higher than that in the control group (χ(2 = 5.360, P = 0.021. The allele frequencies of three polymorphisms (rs1102972, rs1650420, and rs3104703 in intron 3 were strongly associated with heroin addiction (P<0.001, 0.0002, and <0.001, after Bonferroni correction. Three additional SNPs from the same intron (rs1071502, rs6497730, and rs1070487 had nominally significant P values for association (P<0.05, but did not pass the threshold value. Haplotype analysis revealed that the G-C-T-C-C-T-A (block 6 and T-T (block 10 haplotypes of the GRIN2A gene displayed a protective effect (P = <0.001 and 0.003. These findings point to a role for GRIN2A polymorphisms in heroin addiction among the Han Chinese from Shaanxi province, and may be informative for future genetic or neurobiological studies on heroin addiction.

PREVENTION AND CONTROL OF TUBERCULOSIS *A.C. Okoh ...

African Journals Online (AJOL)

drclement

*A.C. Okoh. Department of Community Health, University of Teaching Hospital Benin City,. Nigeria ... tuberculosis to be a global emergency. There is an ... laboratory capacity as few laboratories are ... control: Survelliance, planning, financing.

2-Bromo-2-methyl-N-p-tolylpropanamide

Directory of Open Access Journals (Sweden)

Rodolfo Moreno-Fuquen

2011-06-01

Full Text Available In the title molecule, C11H14BrNO, there is twist between the mean plane of the amide group and the benzene ring [C(=O—N—C...;C torsion angle = −31.2 (5°]. In the crystal, intermolecular N—H...O and weak C—H...O hydrogen bonds link molecules into chains along [100]. The methyl group H atoms are disordered over two sets of sites with equal occupancy.

Vitamin C supplementation improve the sputum conversion culture rate in pulmonary tuberculosis treatment while rifampicin susceptible

Science.gov (United States)

Susanto, L.; Siregar, Y.; Kusumawati, L.

2018-03-01

The failure of first-line tuberculosis treatment greatly affects multiple drug-resistant tuberculosis. In vitro study of vitamin C induces the death of M. tuberculosis bacteria and accelerates healing of tuberculosis, so the multiple drug-resistant tuberculosis can be avoided. This research aimed to identify the effect of vitamin C as a supportive treatment on the sputum conversion rate. The randomizedand double group with a parallel design by matching pair method was used to collect samples. The first group was treated with standard tuberculosis treatment, and the other was given vitamin C supplementation. Vitamin C plasma level analyzation was performed before and after two months of treatment. Sputum conversion was evaluated every week for eight weeks. The comparison of vitamin C plasma level in pre and post-treatment group was significant (p=0.03) but not in the other group. There was no significant difference in vitamin C plasma level between two groups (p=0.21). The proportion of sputum conversion rate in both group in the first week was 0% vs. 9.6% (p=0.83) and the last week of study was 83.9% vs. 100% (p=0.02). In conclusion, vitamin C supplementation has effects in improving the healing process of tuberculosis patients as indicated by higher in sputum conversion rate.

Hydroxylation of methylated DNA by TET1 in chondrocyte differentiation of C3H10T1/2 cells

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Ryo Ito

2016-03-01

Full Text Available DNA methylation is closely involved in the regulation of cellular differentiation, including chondrogenic differentiation of mesenchymal stem cells. Recent studies showed that Ten–eleven translocation (TET family proteins converted 5-methylcytosine (5mC to 5-hydroxymethylcytosine, 5-formylcytosine and 5carboxylcytosine by oxidation. These reactions constitute potential mechanisms for active demethylation of methylated DNA. However, the relationship between the DNA methylation patterns and the effects of TET family proteins in chondrocyte differentiation is still unclear. In this study, we showed that DNA hydroxylation of 5mC was increased during chondrocytic differentiation of C3H10T1/2 cells and that the expression of Tet1 was particularly enhanced. Moreover, knockdown experiments revealed that the downregulation of Tet1 expression caused decreases in chondrogenesis markers such as type 2 and type 10 collagens. Furthermore, we found that TET proteins had a site preference for hydroxylation of 5mC on the Insulin-like growth factor 1 (Igf1 promoter in chondrocytes. Taken together, we showed that the expression of Tet1 was specifically facilitated in chondrocyte differentiation and Tet1 can regulate chondrocyte marker gene expression presumably through its hydroxylation activity for DNA.

Synthesis and characteristics in tumor-bearing mice of N-[11C]methyl-1-deoxynojirimycin and N-[11C]methyl-1-deoxymannojirimycin

International Nuclear Information System (INIS)

Ishiwata, Kiichi; Sasaki, Toru; Ishii, Shin-ichi; Senda, Michio; Seki, Hiroyuki; Kitasato Univ.; Nozaki, Tadashi

1993-01-01

N-[ 11 C]Methyl-1-deoxynojirimycin ([ 11 C]MDNM) and N-[ 11 C]methyl-1-deoxymannojirimycin ([ 11 C]MDMM) were prepared by 11 C-methylation of 1-deoxynojirimycin (DNM) and 1-deoxymannojirimycin (DMM), which are specific inhibitors of glucosidase and mannosidase, respectively. In mice bearing Ehrich ascitic tumor, the highest uptake of the [ 11 C]MDNM was observed in the kidney, followed by the liver and small intestine, while the tumour uptake was moderate. By MDNM loading, saturable uptake was observed in these tissues. In homogenates of the kidney and tumor tissues, a considerable amount of radioactivity was detected in a high-molecular weight fraction. These results demonstrate that the [ 11 C]MDNM has a potential for imaging the glucosidase activity by positron emission tomography. On the other hand, [ 11 C]MDMM showed lower uptake than [ 11 C]MDNM in the kidney, liver and small intestine and no effect of carrier DMM, suggesting that the [ 11 C]MDMM would not reflect mannosidase activity. (Author)

Synthesis of racemic [methyl-d3]-labeled cis- and trans-3'-hydroxycotinine

International Nuclear Information System (INIS)

Ravard, A.; Crooks, P.A.

1994-01-01

A method is described for the synthesis of the racemic [methyl-d 3 ] forms of the nicotine metabolites cis-3'-hydroxycotinine and trans-3'-hydroxycotinine. The key intermediate was [methyl-d 3 ]-N-methylhydroxylamine, obtained from a selective hydrogenation of d 3 -nitro-methane. This intermediate was converted to [methyl-d 3 ]-α-3-pyridyl-N-methylnitrone, which was condensed with methyl acrylate to give a mixture of isomeric isoxazolidines. The hydrogenolysis of this mixture afforded a 70:30 mixture of [methyl-d 3 ] cis- and trans-3'-hydroxycotinine, from which the pure cis-isomer could be isolated by recrystallization from acetone. [Methyl-d 3 ]-trans-3'-hydroxycotinine could be prepared in high yield from the cis-isomer via chiral inversion utilizing a Mitsunobu reaction, or by chromatographic separation from a mixture of the cis- and trans-3'-benzoyloxycotinine, followed by O-debenzoylation in methanolic NaOH. (author)

ASSOCIATION OF VITAMIN D DEFICIENCY WITH TUBERCULOSIS IN ADULT PATIENTS REPORTING TO A TERTIARY CARE HOSPITAL OF RAWALPINDI

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Syed Fawad Mashhadi

2014-09-01

Full Text Available Objectives: To compare the mean vitamin D levels in pulmonary tuberculosis patients and healthy controls and to find out the frequency and association of vitamin D deficiency in patients with tuberculosis. Study Design: Case control study. Place and Duration of Study: Pulmonology department, Military Hospital Rawalpindi from Jan 2013 to Dec 2013. Patients and Methods: Fifty two incident outdoor pulmonary tuberculosis patients were selected with 52 age and gender matched controls. Tuberculosis was diagnosed by the sputum examination through gene Xpert technique from National Institute of Health (NIH, Islamabad. Serum 25-hydroxvitamin D level 0.05. Conclusion: Significant vitamin D deficiency was seen in newly diagnosed TB patients. It was found that vitamin D deficiency is associated with tuberculosis, but its causal role has not been established.

Rifampicin resistance in Mycobacterium tuberculosis - rapid ...

African Journals Online (AJOL)

PH.D. T. C. VJCtor. PH.O. National Tuberculosis Research Programme, Pretoria ... together with. MDR profiles of clinical isolates of M. tuberculosis to assess ..... values in a population." This analysis ..... increased after the mid-1980s but the contribution of social science has ... Schall argues that this is a worst- case scenario ...

The Effects of First-Line Anti-Tuberculosis Drugs on the Actions of Vitamin D in Human Macrophages.

Science.gov (United States)

Chesdachai, Supavit; Zughaier, Susu M; Hao, Li; Kempker, Russell R; Blumberg, Henry M; Ziegler, Thomas R; Tangpricha, Vin

2016-12-01

Tuberculosis (TB) is a major global health problem. Patients with TB have a high rate of vitamin D deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. Although data on the efficacy of vitamin D supplementation on Mycobacterium tuberculosis (Mtb) clearance is uncertain from randomized controlled trials (RCTs), vitamin D enhances the expression of the anti-microbial peptide human cathelicidin (hCAP18) in cultured macrophages in vitro. One possible explanation for the mixed (primarily negative) results of RCTs examining vitamin D treatment in TB infection is that anti-TB drugs given to enrolled subjects may impact actions of vitamin D to enhance cathelicidin in macrophages. To address this hypothesis, human macrophage-like monocytic (THP-1) cells were treated with varying doses of first-line anti-tuberculosis drugs in the presence of the active form of vitamin D, 1N1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ). The expression of hCAP18 was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). 1,25(OH) 2 D 3 strongly induced expression of hCAP18 mRNA in THP-1 cells (fold-change from control). The combination of the standard 4-drug TB therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) in the cultured THP-1 cells demonstrated a significant decrease of hCAP18 mRNA at the dosage of 10 ug/mL. In 31 subjects with newly diagnosed drug-sensitive TB randomized to either high-dose vitamin D 3 (1.2 million IU over 8 weeks, n=13) versus placebo (n=18), there was no change from baseline to week 8 in hCAP18 mRNA levels in peripheral blood mononuclear cells or in plasma concentrations of LL-37, the protein product of hCAP18.These data suggest that first-line anti-TB drugs may alter the vitamin D-dependent increase in hCAP18 and LL-37 human macrophages.

DNA methylation of loci within ABCG1 and PHOSPHO1 in blood DNA is associated with future type 2 diabetes risk

DEFF Research Database (Denmark)

Dayeh, Tasnim; Tuomi, Tiinamaija; Almgren, Peter

2016-01-01

Identification of subjects with a high risk of developing type 2 diabetes (T2D) is fundamental for prevention of the disease. Consequently, it is essential to search for new biomarkers that can improve the prediction of T2D. The aim of this study was to examine whether 5 DNA methylation loci...... muscle from diabetic vs. non-diabetic subjects. DNA methylation at the ABCG1 locus cg06500161 in blood DNA was associated with an increased risk for future T2D (OR = 1.09, 95% CI = 1.02-1.16, P-value = 0.007, Q-value = 0.018), while DNA methylation at the PHOSPHO1 locus cg02650017 in blood DNA...... was associated with a decreased risk for future T2D (OR = 0.85, 95% CI = 0.75-0.95, P-value = 0.006, Q-value = 0.018) after adjustment for age, gender, fasting glucose, and family relation. Furthermore, the level of DNA methylation at the ABCG1 locus cg06500161 in blood DNA correlated positively with BMI, HbA1c...

Synthesis of no-carrier-added alpha-[11C]methyl-L-tryptophan

International Nuclear Information System (INIS)

Chaly, T.; Diksic, M.

1988-01-01

Described here is a synthesis of no-carrier-added alpha-[ 11 C]methyl-L-tryptophan based on alkylation with 11 CH 3 I of an anion generated by reacting the Schiff base of L-tryptophan methyl ester with di-isopropylamine. The synthesis requires approximately 30 min after the end of 11 CO 2 collection and gives alpha-[ 11 C]methyl-L-tryptophan in a 20-25% radiochemical yield calculated at the end of the synthesis and without correction for radioactive decay. The specific activity of the final radiopharmaceutical, measured at the end of the synthesis, was around 2000 Ci/mmol. Data confirming the stereospecificity of the synthesis are also presented

Association of vitamin d deficiency with tuberculosis in adult patients reporting to a tertiary care hospital of rawalpindi

International Nuclear Information System (INIS)

Mashhadi, S.F.; Rahman, M.U.; Hashim, R.; Azam, N.

2014-01-01

To compare the mean vitamin Dlevels in pulmonary tuberculosis patients and healthy controls and to find out the frequency and association of vitamin D deficiency in patients with tuberculosis. Study Design: Case control study. Place and Duration of Study: Pulmonology department, Military Hospital Rawalpindi from Jan 2013 to Dec 2013. Patients and Methods:Fifty two incident outdoor pulmonary tuberculosis patients were selected with 52 age and gender matched controls. Tuberculosis was diagnosed by the sputum examination through gene Xpert technique from National Institute of Health (NIH), Islamabad. Serum 25-hydroxvitamin D level 0.05). Conclusion: Significant vitamin D deficiency was seen in newly diagnosed TB patients. It was found that vitamin D deficiency is associated with tuberculosis, but its causal role has not been established. (author)

Antimicrobial screening of some derivatives of methyl alpha-D-glucopyranoside

International Nuclear Information System (INIS)

Abdul, K.M.S.; Kawsar, S.M.S.; Rehman, S.

2009-01-01

In vitro antimicrobial functionality test of methyl 4,6-O-cyclohexylidene-alpha-D-glucopyranoside and its twelve acylated derivatives against ten human pathogenic bacteria and six phytopathogenic fungi comparative to Ampicillin and Nystatin revealed the tested chemicals to possess moderate to good antibacterial and antifungal activity and to be more effective against fungal phytopathogens. Many of these chemicals exhibited better antimicrobial activity than the standard antibiotics. Minimum Inhibition Concentration (MIC) of methyl 4,6-O-cyclohexylidene-2-O-myristoyl- 3-O-palmitoyl-alpha-D-glucopyranoside against Bacillus cereus, Bacillus subtilis and Staphylococcus aureus was 25, 12.5 and 25 macro g/disc, respectively. (author)

Synthesis, NMR spectral and antimicrobial studies of some [N-methyl-3t-alkyl-2r,6c-diarylpiperidin-4-ylidine]-5‧-methylthiazolidine-4-ones

Science.gov (United States)

Prakash, S. M.; Pandiarajan, K.; Kumar, S.

2013-06-01

Four new [N-methyl-3t-alkyl-2r,6c-diaryl-4-ylidine]-5'-methylthiozolidin-4-ones 9-12 have been synthesized by the condensation of N-methyl-3t-alkyl-2r,6c-diarylpiperidin-4-one thiosemicarbazones with ethyl 2-bromopropionate. These compounds have been characterized using FT-IR, 1H NMR, 13C NMR spectral techniques. HOMOCOSY, HSQC and HMBC spectral study have been done for [N-methyl-3,3-dimethyl-2r,6c-bis(p-methoxyphenyl)piperidin-4-ylidine]-5'-methylthiazolidine-4-one (12). Two geometrical isomers are formed in this reaction. In all these compounds piperidin rings adopt chair conformation. The rotation of the aryl group at C-2 is rather slow in 10-12. Antimicrobial activities have also been studied for 9-12. These compounds are active against all the tested bacterial and fungal strains.

A facile preparation of alkyl α-glycosides of the methyl ester of N-acetyl-D-neuraminic acid

NARCIS (Netherlands)

Vliegenthart, J.F.G.; Vleugel, D.J.M. van der; Heeswijk, W.A.R. van

1982-01-01

The reaction of methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2-chloro-2,3,5-trideoxy-β-D-glycero-D-galacto-2-nonulopyranosonate with primary and secondary alcohols in the presence of silver salicylate affords, after O-deacetylation, stereo-specifically the corresponding methyl (alkyl

(E-2-Methyl-6-{[(5-methylpyridin-2-ylimino]methyl}phenol

Directory of Open Access Journals (Sweden)

Md. Azharul Arafath

2017-01-01

Full Text Available In the title compound, C14H14N2O, the dihedral angle between the aromatic rings is 5.54 (9°. The conformation is reinforced by an intramolecular O—H...N hydrogen bond, which closes an S(6 ring. The pyridine N atom and methyl group lie to opposite sides of the molecule. In the crystal, the molecules are linked into a zigzag chain propagating in [0-11] by weak C—H...O hydrogen bonds.

Selective terminal C–C scission of C5-carbohydrates

NARCIS (Netherlands)

Klis, van der F.; Gootjes, L.; Haveren, van J.; Es, van D.S.; Bitter, J.H.

2015-01-01

The selective catalytic production of C4-tetritols (erythritol and threitol) from C5-sugars is an attractive route for the conversion of non-digestible sugars to C4-building blocks from agro residues. Here we show that an unprecedented high selectivity of 20–25% C4-tertritols can be achieved under

The synthesis of [O-methyl-{sup 11}C]venlafaxine: a non-classical, fast-acting antidepressant

Energy Technology Data Exchange (ETDEWEB)

Gee, A.D.; Gjedde, A. [Aarhus Univ. Hospital, PET Center, Aarhus (Denmark); Smith, D.F. [Aarhus Univ. Psychiatric Hospital, Inst. for Biological Psychiatry, Risskov (Denmark)

1997-01-01

As part of our program to develop PET tracers for the 5-HT reuptake site, venlafaxine, a non-classical, fast-acting antidepressant, was selected as a candidate for labelling with {sup 11}C for in vivo evaluation. [O-methyl-{sup 11}C]venlafaxine was produced by the alkylation of O-desmethyl venlafaxine with [{sup 11}C]methyl iodide followed by HPLC purification and formulation. Radiochemically pure [O-methyl-{sup 11}C]venlafaxine was obtained in a 30 {+-} 5% decay corrected radiochemical yield and a specific activity > 50 GBq/{mu}mol(1.4 Ci/{mu}mol) at the end of synthesis. For a typical production starting with 46 GBq (1.3 Ci) [{sup 11}C]CO{sub 2}, 5.2 GBq (140 mCi) [O-methyl-{sup 11}C]venlafaxine was obtained as a sterile, formulated solution in a synthesis time of 30 min (counted from EOB). (Author).

Reconciling medical expenditure estimates from the MEPS and NHEA, 2007.

Science.gov (United States)

Bernard, Didem; Cowan, Cathy; Selden, Thomas; Cai, Liming; Catlin, Aaron; Heffler, Stephen

2012-01-01

Provide a comparison of health care expenditure estimates for 2007 from the Medical Expenditure Panel Survey (MEPS) and the National Health Expenditure Accounts (NHEA). Reconciling these estimates serves two important purposes. First, it is an important quality assurance exercise for improving and ensuring the integrity of each source's estimates. Second, the reconciliation provides a consistent baseline of health expenditure data for policy simulations. Our results assist researchers to adjust MEPS to be consistent with the NHEA so that the projected costs as well as budgetary and tax implications of any policy change are consistent with national health spending estimates. The Medical Expenditure Panel Survey produced by the Agency for Healthcare Research and Quality, and the National Health Center for Health Statistics and the National Health Expenditures produced by the Centers for Medicare & Medicaid Service's Office of the Actuary. In this study, we focus on the personal health care (PHC) sector, which includes the goods and services rendered to treat or prevent a specific disease or condition in an individual. The official 2007 NHEA estimate for PHC spending is $1,915 billion and the MEPS estimate is $1,126 billion. Adjusting the NHEA estimates for differences in underlying populations, covered services, and other measurement concepts reduces the NHEA estimate for 2007 to $1,366 billion. As a result, MEPS is $240 billion, or 17.6 percent, less than the adjusted NHEA total.

Tuberculosis 2: Pathophysiology and microbiology of pulmonary ...

African Journals Online (AJOL)

2005-08-01

Aug 1, 2005 ... February 2013 Downloaded from www.southsudanmedicaljournal.com. MaIN arTIClES. 10. Tuberculosis 2: Pathophysiology and microbiology of pulmonary tuberculosis. Robert L. Serafino Wania MBBS, MrCP, MSc (Trop Med). Pathophysiology. Inhalation of Mycobacterium tuberculosis leads to one of.

2-[(4-Bromophenylimino)methyl]-5-pentadecylphenol

OpenAIRE

Basavaraj Padmashali; Patchanita Thamyongkit; Amorn Petsom; Gadada Naganagowda

2012-01-01

2-[(4-Bromophenylimino)methyl]-5-pentadecylphenol has been synthesized by reaction of 2-hydroxy-4-pentadecylbenzaldehyde with 4-bromoaniline in 1,4-dioxane and its IR, ¹H-NMR, ¹³C-NMR and MS spectroscopic data are presented.

Synthesis of 2-[11C]cyano-isonicotinic acid hydrazide

International Nuclear Information System (INIS)

Somwardhana, C.W.; Sajjad, M.; Lambrecht, R.M.

1990-01-01

Isonicotinic acid hydrazide (isoniazid), a drug used in treating tuberculosis has been labelled with carbon-11 at the 2-position. The labelling synthesis starts with methyl isonicotinate treated with dimethyl sulfate. The resulting salt solution is loaded onto silica gel and dried, followed by treatment with carbon-11 labelled hydrocyanic acid. Work-up gave the labelled compound with an average 32% radiochemical yield. Subsequent treatment with hydrazine hydrate yielded isoniazid

Fragrance material review on 1-[5(or 6)-methyl-7(or 8)-1-(methylethyl)bicyclo[2.2.2]oct-5-en-2-yl]ethan-1-one.

Science.gov (United States)

Scognamiglio, J; Letizia, C S; Api, A M

2013-12-01

A toxicologic and dermatologic review of 1-[5(Or 6)-Methyl-7(or 8)-1-(methylethyl)bicyclo[2.2.2]oct-5-en-2-yl]ethan-1-one when used as a fragrance ingredient is presented. 1-[5(Or 6)-Methyl-7(or 8)-1-(methylethyl)bicyclo[2.2.2]oct-5-en-2-yl]ethan-1-one is a member of the fragrance structural group Alkyl Cyclic Ketones. These fragrances can be described as being composed of an alkyl, R1, and various substituted and bicyclic saturated or unsaturated cyclic hydrocarbons, R2, in which one of the rings may include up to 12 carbons. Alternatively, R2 may be a carbon bridge of C2-C4 carbon chain length between the ketone and cyclic hydrocarbon. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 1-[5(Or 6)-Methyl-7(or 8)-1-(methylethyl)bicyclo[2.2.2]oct-5-en-2-yl]ethan-1-one were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, phototoxicity, photoallergy, and genotoxicity, data. A safety assessment of the entire Alkyl Cyclic Ketones will be published simultaneously with this document; please refer to Belsito et al., Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2013. A Toxicologic and Dermatologic Assessment of Alkyl Cyclic Ketones When Used as Fragrance Ingredients. (submitted for publication)). for an overall assessment of the safe use of this material and all Alkyl Cyclic Ketones in fragrances. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cholinergic cells in the nucleus basalis of mice express the N-methyl-D-aspartate-receptor subunit NR2C and its replacement by the NR2B subunit enhances frontal and amygdaloid acetylcholine levels

NARCIS (Netherlands)

De Souza Silva, M. A.; Dolga, Amalia; Pieri, I.; Marchetti, L.; Eisel, U. L. M.; Huston, J. P.; Dere, E.

2006-01-01

It is known that glutamatergic and cholinergic systems interact functionally at the level of the cholinergic basal forebrain. The N-methyl-D-aspartate receptor (NMDA-R) is a multiprotein complex composed of NR1, NR2 and/or NR3 subunits. The subunit composition of NMDA-R of cholinergic cells in the

Crystallization and preliminary X-ray analysis of a novel esterase Rv0045c from Mycobacterium tuberculosis

International Nuclear Information System (INIS)

Xu, Lipeng; Guo, Jiubiao; Zheng, Xiangdong; Wen, Tingyi; Sun, Fei; Liu, Siguo; Pang, Hai

2010-01-01

The novel esterase Rv0045c from M. tuberculosis was expressed and purified to homogeneity. The crystals of native and SeMet-labelled Rv0045c protein that were obtained diffracted to resolutions of 2.7 and 3.0 Å, respectively. The Rv0045c protein is predicted to be an esterase that is involved in lipid metabolism in Mycobacterium tuberculosis. The protein was overproduced in Escherichia coli, purified and crystallized using the hanging-drop vapour-diffusion method. The Rv0045c protein crystals diffracted to a resolution of 2.7 Å using a synchrotron-radiation source and belonged to space group P3 1 or P3 2 , with unit-cell parameters a = b = 73.465, c = 48.064 Å, α = β = 90, γ = 120°. Purified SeMet-labelled Rv0045c protein was also crystallized and formed crystals that diffracted to a resolution of 3.0 Å using an in-house X-ray radiation source

Functional effect of grapevine 1-deoxy-D-xylulose 5-phosphate synthase substitution K284N on Muscat flavour formation

Science.gov (United States)

Battilana, Juri; Emanuelli, Francesco; Gambino, Giorgio; Gribaudo, Ivana; Gasperi, Flavia; Boss, Paul K.; Grando, Maria Stella

2011-01-01

Grape berries of Muscat cultivars (Vitis vinifera L.) contain high levels of monoterpenols and exhibit a distinct aroma related to this composition of volatiles. A structural gene of the plastidial methyl-erythritol-phosphate (MEP) pathway, 1-deoxy-D-xylulose 5-phosphate synthase (VvDXS), was recently suggested as a candidate gene for this trait, having been co-localized with a major quantitative trait locus for linalool, nerol, and geraniol concentrations in berries. In addition, a structured association study discovered a putative causal single nucleotide polymorphism (SNP) responsible for the substitution of a lysine with an asparagine at position 284 of the VvDXS protein, and this SNP was significantly associated with Muscat-flavoured varieties. The significance of this nucleotide difference was investigated by comparing the monoterpene profiles with the expression of VvDXS alleles throughout berry development in Moscato Bianco, a cultivar heterozygous for the SNP mutation. Although correlation was detected between the VvDXS transcript profile and the accumulation of free monoterpenol odorants, the modulation of VvDXS expression during berry development appears to be independent of nucleotide variation in the coding sequence. In order to assess how the non-synonymous mutation may enhance Muscat flavour, an in vitro characterization of enzyme isoforms was performed followed by in vivo overexpression of each VvDXS allele in tobacco. The results showed that the amino acid non-neutral substitution influences the enzyme kinetics by increasing the catalytic efficiency and also dramatically affects monoterpene levels in transgenic lines. These findings confirm a functional effect of the VvDXS gene polymorphism and may pave the way for metabolic engineering of terpenoid contents in grapevine. PMID:21868399

Mineralization of 14C-Pirimiphos-Methyl in Soil Under Aerobic and Anaerobic Conditions

International Nuclear Information System (INIS)

Zayed, S.M.A.D.; Farghly, M.; El-Maghrby, S.

2006-01-01

The mineralization of 14 C-ring labelled pirimiphos-methyl in clay loam soil was determined in a three months laboratory incubation period under anaerobic and aerobic conditions. Evolution of 14 CO2 increased with time and reached 9.2% and 12 %, of the initial 14 C-concentration , within 90 days in case of anaerobic and aerobic conditions, respectively, at that time, soil contained about 61.5% of the applied dose as extractable residues under anaerobic conditions and 59% under aerobic conditions. the unextractable pesticide residues gradually increased with time and the highest binding capacity of about 11%-13% was observed after 90 days of incubation. the total 14 C-activity recovered from soil was generally between 82% and 92% of the applied radiocarbon. the nature of methanolic 14 C-residues was determined by chromatographic analysis and the results revealed the presence of pirimiphos- methyl as a main product together with its phenol. the principle of radio-respirometry has been used for evaluating the effect of different application rates of pirimiphos-methyl on soil microbial activity using U- 14 C-glucose as a substrate. At two concentrations used, pirimiphos-methyl showed an inhibition in the rate of 14 Co2 evolution over 14 days of incubation as a result of oxidation of 14 C-glucose by microorganisms especially in case of high concentration

Analysis of expression profile of mce operon genes (mce1, mce2, mce3 operon) in different Mycobacterium tuberculosis isolates at different growth phases.

Science.gov (United States)

Singh, Pratibha; Katoch, V M; Mohanty, K K; Chauhan, Devendra Singh

2016-04-01

Mycobacterium tuberculosis (M. tuberculosis) has four homologous mammalian cell entry (mce) operons (mce1-4) that encode exported proteins and have a possible role in the virulence mechanism of this pathogen. The expression of mce operon is considered to be complex and not completely understood. Although expression of mce operon at different in vitro growth phases has been studied earlier, its expression in different M. tuberculosis isolates under different growth phases is not yet studied. The present preliminary study was conducted on a limited number of isolates to know the trend of expression pattern of mce operon genes in different M. tuberculosis isolates under different growth stages. In this study, we monitored the transcriptional profile of selected mce operon genes (mce1A, mce1D, mce2A, mce2D, mce3A, mce3C) in different M.tuberculosis isolates (MDR1, MDR2, and sensitive isolate) at early exponential and stationary phases using real-time quantitative PCR. The expression ratio of all selected mce operon genes in all M. tuberculosis isolates was reduced at the initial phase and increased substantially at a later phase of growth. Higher expression of mce1 operon genes was found in all M. tuberculosis isolates as compared to other mce operon genes (mce2 and mce3 operons) at stationary growth phase. the higher expression of mce operon genes at stationary phase (as compared to early exponential phase) suggested growth phase dependent expression of mce operon genes. This indicated that the mce operon genes might have a role in M. tuberculosis survival and adaptation on the onset of adverse condition like stationary phase. Identification of differentially expressed genes will add to our understanding of the bacilli involved in adaptation to different growth conditions.

PET studie4s of dopamine D2 receptors in subclinical and clinical hemi-parkinsonism monkeys with 11C-Raclopride

International Nuclear Information System (INIS)

Bian Yanzhu; Zhang Jinming; Tian Jiahe; Yao Shulin; Liu Huaijun

2005-01-01

Objective: To explore the characters of dopamine D 2 receptors (D 2 R) of subclinical and clinical hemi-parkinsonism monkeys. Methods: Four subclinical hemi-pakinsonism monkeys were developed by given one dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropridine (MPTP) 0.3 mg/kg through fight internal carotid artery. Two clinical hemi-pakinsonism monkeys were developed by given 2 doses of MPTP 0.7 mg/kg through right internal carotid artery and the 2 doses were 4 weeks apart. 11 C-Raclopride was synthesized as an imaging agent of D 2 R. Four normal, 4 subclinical and 2 clinical hemi-parkinsonism monkeys underwent 11 C-Raclopride D 2 R PET, and the striatum D 2 R function was evaluated by region of interest (ROI) technique. Results: Symmetric striatal uptake was observed in normal and subclinical hemi-parkinsonism monkeys, the radioactivity ratios of striatum/cerebellum were 5.00±0.74, 5.04±0.72, respectively (t=1.016, P>0.05). There was a significant increase in 11 C-Raclopride binding in the fight striatum (lesioned side) of the two clinical hemi-pakinsonism monkeys; up-regulation of leisoned side striatum D 2 R was found; compared to the left sides, the radioactivity ratios of striatum cerebellum of right sides (lesioned sides) of the two monkeys were increased by 19.69%, 22.68%, respectively. Conclusions: 11 C-Raclopride was successfully synthesized as a D 2 R PET agent. The striatum D 2 R function was of no evident changes in subclinical hemi-parkinsonism monkeys. The striatum 132 R function was upregulated in lesioned side in clinical hemi-parkinsonism monkeys. (authors)

Plasma vitamins and essential trace elements in newly diagnosed pulmonary tuberculosis patients and at different durations of anti-tuberculosis chemotherapy

Directory of Open Access Journals (Sweden)

V.F. Edem

2015-07-01

This study concluded that there is micronutrient (Fe, Zn, Cu, Vit A, C, D and E malnutrition in tuberculosis patients at diagnosis and throughout the duration (6 months of chemotherapy. Supplementation with vitamins and zinc is advised within the first 4 months of commencing anti-tuberculosis chemotherapy.

Study of the factors affecting the performance of microextraction by packed sorbent (MEPS) using liquid scintillation counter and liquid chromatography-tandem mass spectrometry

International Nuclear Information System (INIS)

Altun, Zeki; Abdel-Rehim, Mohamed

2008-01-01

Microextraction by packed sorbent (MEPS) is a new technique for sample preparation that can be connected on-line with LC or GC. In MEPS, approximately 1-2 mg of the solid packing material is inserted into a syringe (100-250 μL) as a plug. Sample preparation takes place on the packed bed. The bed can be packed or coated to provide selective and suitable sampling conditions. The new method is very promising for extraction of drugs and metabolites from biological samples. In this paper, some factors affecting the performance of MEPS such as recovery, carry-over, leakage, washing volume and elution volume were studied using C18 and hydroxylated polystyrene-divinylbenzene copolymer (ENV+) as sorbents. Radioactively labelled bupivacaine in plasma samples was used as test analyte. For the extraction of this drug, using methanol/water 95:5 (v/v) (0.25% ammonium hydroxide) was used as elution solvent. The analyte response increased with increasing the elution volume and it was linear upp up to 100 μL utilizing liquid scintillation counter. Further, for concentrating the sample, we found that MEPS may be used such that the sample can be drawn through the needle, up and down, several times. The analyte leakage increases as the volume washing increases, though higher washing volumes may also result in cleaner extracts. To eliminate analyte carry-over, the sorbents were washed first with 3 x 250 μL elution solution and then with 3 x 250 μL washing solution. In addition, the reproducibility measurements show relatively good relative standard deviation (RSD) % values concerning analyte recovery and analyte leakage. The present study provides an understanding of basic aspects when optimizing methods for MEPS. In this study, MEPS was used off-line with liquid scintillation counter and on-line with LC-MS/MS

Study of the factors affecting the performance of microextraction by packed sorbent (MEPS) using liquid scintillation counter and liquid chromatography-tandem mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Altun, Zeki [Karlstad University, Faculty of Technology and Science, SE-651 88 Karlstad (Sweden); Abdel-Rehim, Mohamed [Karlstad University, Faculty of Technology and Science, SE-651 88 Karlstad (Sweden); Clinical Pharmacology and DMPK, AstraZeneca R and D Soedertaelje, SE-151 85 Soedertaelje (Sweden)], E-mail: Mohamed.Abdel-Rehim@Astrazeneca.com

2008-12-23

Microextraction by packed sorbent (MEPS) is a new technique for sample preparation that can be connected on-line with LC or GC. In MEPS, approximately 1-2 mg of the solid packing material is inserted into a syringe (100-250 {mu}L) as a plug. Sample preparation takes place on the packed bed. The bed can be packed or coated to provide selective and suitable sampling conditions. The new method is very promising for extraction of drugs and metabolites from biological samples. In this paper, some factors affecting the performance of MEPS such as recovery, carry-over, leakage, washing volume and elution volume were studied using C18 and hydroxylated polystyrene-divinylbenzene copolymer (ENV+) as sorbents. Radioactively labelled bupivacaine in plasma samples was used as test analyte. For the extraction of this drug, using methanol/water 95:5 (v/v) (0.25% ammonium hydroxide) was used as elution solvent. The analyte response increased with increasing the elution volume and it was linear upp up to 100 {mu}L utilizing liquid scintillation counter. Further, for concentrating the sample, we found that MEPS may be used such that the sample can be drawn through the needle, up and down, several times. The analyte leakage increases as the volume washing increases, though higher washing volumes may also result in cleaner extracts. To eliminate analyte carry-over, the sorbents were washed first with 3 x 250 {mu}L elution solution and then with 3 x 250 {mu}L washing solution. In addition, the reproducibility measurements show relatively good relative standard deviation (RSD) % values concerning analyte recovery and analyte leakage. The present study provides an understanding of basic aspects when optimizing methods for MEPS. In this study, MEPS was used off-line with liquid scintillation counter and on-line with LC-MS/MS.

Identification of metabolites in urine and feces from rats dosed with the heterocyclic amine, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C)

DEFF Research Database (Denmark)

Frederiksen, H; Frandsen, H

2004-01-01

2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeA alpha C can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study, the in ......2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeA alpha C can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study...

Características clínicas y toxicidad del tratamiento de tuberculosis en pacientes con cáncer

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Luis Cuéllar

Full Text Available Objetivos. Evaluar las características clínico-epidemiológicas de la tuberculosis activa en pacientes portadores de neoplasia maligna y evaluar la influencia del tratamiento antituberculoso sobre el manejo de cáncer en el Instituto Nacional de Enfermedades Neoplásicas entre el 2008 y 2013. Materiales y métodos. Estudio observacional de casos de tuberculosis diagnosticados mediante baciloscopía positiva en pacientes con cáncer. Se revisó la información clínica, evolución, e información patológica de la neoplasia. Resultados. Se encontraron 76 casos de tuberculosis activa luego del diagnóstico de cáncer. La mediana de edad fue 51,3 años. La mediana de seguimiento fue 2,1 años. Las neoplasias más frecuentes fueron leucemia linfática aguda (14,5% para las hematológicas y cáncer de cérvix (14,5%, mama (10,5% y gástrico (7,9% para las no hematológicas. El 27,6% de los pacientes presentó recurrencia de la neoplasia; el diagnóstico de tuberculosis confundió el estadiaje inicial en 6,9% y se planteó inicialmente como recurrencia del cáncer en 11,1% (neoplasias de mama y colon. El diagnóstico de tuberculosis retrasó o influyó en la reducción de dosis del tratamiento antineoplásico en 11,1% de los casos (leucemia linfática aguda y linfoma no Hodgkin. El 8,3% de los pacientes presentó toxicidad al tratamiento antituberculoso. Conclusiones. Los pacientes con cáncer pueden presentar infección activa por tuberculosis. El efecto de interferencia del diagnóstico y tratamiento de tuberculosis sobre la evaluación del cáncer y el tratamiento antineoplásico en nuestra serie es mínimo.

4-Methyl-N-(2-methylbenzoylbenzenesulfonamide

Directory of Open Access Journals (Sweden)

B. Thimme Gowda

2010-06-01

Full Text Available In the title compound, C15H15NO3S, the conformation of the N—H bond in the C—SO2—NH—C(O segment is anti to the C=O bond. Further, the conformation of the C=O bond is syn to the ortho-methyl group in the benzoyl ring. The dihedral angle between the sulfonyl benzene ring and the —SO2—NH—C—O segment is 87.1 (1° and that between the sulfonyl and the benzoyl benzene rings is 58.2 (1°. In the crystal structure, molecules are linked by pairs of N—H...O(S hydrogen bonds, forming inversion dimers.

Synthesis of 2-acetamido-6-O-(5-acetamido-3,5-dideoxy-β-D-glycero-D-galacto-2-nonulo-pyranosylonic acid)-2-deoxy-D-glucose [2-acetamido-6-O-(N-acetyl-β-D-neuraminyl)-2-deoxy-D-glucose

NARCIS (Netherlands)

Vliegenthart, J.F.G.; Vleugel, D.J.M. van der; Zwikker, J.W.; Boeckel, S.A.A. van; Boom, J.H. van

1982-01-01

Silver triflate-promoted condensation of methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2-chloro-2,3,5-trideoxy-β-D-glycero-D-galacto -2-nonulopyranosonate (9) with benzyl-2-acetamido-2-deoxy-3,4-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-α-D-glucopyranoside, followed by removal of the

Vitamin D Counteracts Mycobacterium tuberculosis-Induced Cathelicidin Downregulation in Dendritic Cells and Allows Th1 Differentiation and IFNγ Secretion.

Science.gov (United States)

Rode, Anna K O; Kongsbak, Martin; Hansen, Marie M; Lopez, Daniel Villalba; Levring, Trine B; Woetmann, Anders; Ødum, Niels; Bonefeld, Charlotte M; Geisler, Carsten

2017-01-01

Tuberculosis (TB) presents a serious health problem with approximately one-third of the world's population infected with Mycobacterium tuberculosis in a latent state. Experience from the pre-antibiotic era and more recent clinical studies have established a beneficial role of sunlight and vitamin D in patients with TB. At the same time, experimental data have shown that Th1 cells through production of IFNγ are crucial for cathelicidin release by macrophages, bacterial killing, and containment of M. tuberculosis in granulomas. Paradoxically, vitamin D has repeatedly been ascribed an immune-suppressive function inhibiting Th1 differentiation and production of IFNγ in T cells. The aim of this study was to investigate this apparent paradox. We studied naïve human CD4 + T cells activated either with CD3 and CD28 antibodies or with allogeneic dendritic cells (DC) stimulated with heat-killed M. tuberculosis (HKMT) or purified toll-like receptor (TLR) ligands. We show that vitamin D does not block differentiation of human CD4 + T cells to Th1 cells and that interleukin (IL)-12 partially counteracts vitamin D-mediated inhibition of IFNγ production promoting production of equal amounts of IFNγ in Th1 cells in the presence of vitamin D as in T cells activated in the absence of vitamin D and IL-12. Furthermore, we show that HKMT and TLR2 ligands strongly downregulate cathelicidin expression in DC and that vitamin D counteracts this by upregulating cathelicidin expression. In conclusion, we demonstrate that vitamin D counteracts M. tuberculosis -induced cathelicidin downregulation and allows Th1 differentiation and IFNγ secretion.

Vitamin D Counteracts Mycobacterium tuberculosis-Induced Cathelicidin Downregulation in Dendritic Cells and Allows Th1 Differentiation and IFNγ Secretion

Directory of Open Access Journals (Sweden)

Anna K. O. Rode

2017-05-01

Full Text Available Tuberculosis (TB presents a serious health problem with approximately one-third of the world’s population infected with Mycobacterium tuberculosis in a latent state. Experience from the pre-antibiotic era and more recent clinical studies have established a beneficial role of sunlight and vitamin D in patients with TB. At the same time, experimental data have shown that Th1 cells through production of IFNγ are crucial for cathelicidin release by macrophages, bacterial killing, and containment of M. tuberculosis in granulomas. Paradoxically, vitamin D has repeatedly been ascribed an immune-suppressive function inhibiting Th1 differentiation and production of IFNγ in T cells. The aim of this study was to investigate this apparent paradox. We studied naïve human CD4+ T cells activated either with CD3 and CD28 antibodies or with allogeneic dendritic cells (DC stimulated with heat-killed M. tuberculosis (HKMT or purified toll-like receptor (TLR ligands. We show that vitamin D does not block differentiation of human CD4+ T cells to Th1 cells and that interleukin (IL-12 partially counteracts vitamin D-mediated inhibition of IFNγ production promoting production of equal amounts of IFNγ in Th1 cells in the presence of vitamin D as in T cells activated in the absence of vitamin D and IL-12. Furthermore, we show that HKMT and TLR2 ligands strongly downregulate cathelicidin expression in DC and that vitamin D counteracts this by upregulating cathelicidin expression. In conclusion, we demonstrate that vitamin D counteracts M. tuberculosis-induced cathelicidin downregulation and allows Th1 differentiation and IFNγ secretion.

Fragrance material review on 2-methyl-4-phenyl-2-butanol.

Science.gov (United States)

Scognamiglio, J; Jones, L; Letizia, C S; Api, A M

2012-09-01

A toxicologic and dermatologic review of 2-methyl-4-phenyl-2-butanol when used as a fragrance ingredient is presented. 2-methyl-4-phenyl-2-butanol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a tertiary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 2-methyl-4-phenyl-2-butanol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, and skin sensitization data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. assessment of aryl alkyl alcohols when used as fragrance ingredients. Copyright © 2011 Elsevier Ltd. All rights reserved.

An efficient protocol for the complete incorporation of methyl-protonated alanine in perdeuterated protein

International Nuclear Information System (INIS)

Ayala, Isabel; Sounier, Remy; Use, Nathalie; Gans, Pierre; Boisbouvier, Jerome

2009-01-01

A strategy for the introduction of ( 1 H, 13 C-methyl)-alanine into perdeuterated proteins is described. Specific protonation of alanine methyl groups to a level of 95% can be achieved by overexpressing proteins in M9/D 2 O based bacterial growth medium supplemented with 800 mg/l of 2-[ 2 H], 3-[ 13 C] l-alanine. However, though simple, this approach results in undesired, non-specific background labeling due to isotope scrambling via different amino acid metabolic pathways. Following a careful analysis of known metabolic pathways we found that co-addition of perdeuterated forms of α-ketoisovalerate-d 7 , succinate-d 4 and l-isoleucine-d 10 with labeled l-alanine, reduces undesired background labeling to <1%. When combined with recently developed methyl TROSY experiments, this methyl-specific labeling protocol permits the acquisition of excellent quality correlation spectra of alanine methyl groups in high molecular weight proteins. Our cost effective strategy offers a significant enhancement in the level of incorporation of methyl-labeled alanine in overexpressed proteins over previously reported methods

10. A case series report of Tuberculosis patients with Vitamin D ...

African Journals Online (AJOL)

user

An association of Vitamin D deficiency with. Tuberculosis remains a valid ... with darker skins are prone to vitamin D deficiency. The regions inhabited by people with darker skin coincides with high TB burden settings. Vitamin D has a key role in ... melanin which absorb sultraviolet B radiation rendering it less available for ...

Loss of GluN2D subunit results in social recognition deficit, social stress, 5-HT2C receptor dysfunction, and anhedonia in mice.

Science.gov (United States)

Yamamoto, Hideko; Kamegaya, Etsuko; Hagino, Yoko; Takamatsu, Yukio; Sawada, Wakako; Matsuzawa, Maaya; Ide, Soichiro; Yamamoto, Toshifumi; Mishina, Masayoshi; Ikeda, Kazutaka

2017-01-01

The N-methyl-d-aspartate (NMDA) receptor channel is involved in various physiological functions, including learning and memory. The GluN2D subunit of the NMDA receptor has low expression in the mature brain, and its role is not fully understood. In the present study, the effects of GluN2D subunit deficiency on emotional and cognitive function were investigated in GluN2D knockout (KO) mice. We found a reduction of motility (i.e., a depressive-like state) in the tail suspension test and a reduction of sucrose preference (i.e., an anhedonic state) in GluN2D KO mice that were group-housed with littermates. Despite apparently normal olfactory function and social interaction, GluN2D KO mice exhibited a decrease in preference for social novelty, suggesting a deficit in social recognition or memory. Golgi-Cox staining revealed a reduction of the complexity of dendritic trees in the accessory olfactory bulb in GluN2D KO mice, suggesting a deficit in pheromone processing pathway activation, which modulates social recognition. The deficit in social recognition may result in social stress in GluN2D KO mice. Isolation housing is a procedure that has been shown to reduce stress in mice. Interestingly, 3-week isolation and treatment with agomelatine or the 5-hydroxytryptamine-2C (5-HT 2C ) receptor antagonist SB242084 reversed the anhedonic-like state in GluN2D KO mice. In contrast, treatment with the 5-HT 2C receptor agonist CP809101 induced depressive- and anhedonic-like states in isolated GluN2D KO mice. These results suggest that social stress that is caused by a deficit in social recognition desensitizes 5-HT 2c receptors, followed by an anhedonic- and depressive-like state, in GluN2D KO mice. The GluN2D subunit of the NMDA receptor appears to be important for the recognition of individuals and development of normal emotionality in mice. 5-HT 2C receptor antagonism may be a therapeutic target for treating social stress-induced anhedonia. This article is part of the Special

DNA methylation is altered in B and NK lymphocytes in obese and type 2 diabetic human

DEFF Research Database (Denmark)

Simar, David; Versteyhe, Soetkin; Donkin, Ida

2014-01-01

(T2D). The aim of this study was to determine the global DNA methylation profile of immune cells in obese and T2D individuals in a cell type-specific manner. Material and methods Fourteen obese subjects and 11 age-matched lean subjects, as well as 12 T2D obese subjects and 7 age-matched lean subjects.......001). Results Global DNA methylation in peripheral blood mononuclear cells, monocytes, lymphocytes or T cells was not altered in obese or T2D subjects. However, analysis of blood fractions from lean, obese, and T2D subjects showed increased methylation levels in B cells from obese and T2D subjects...

Substituent effects on the photolysis of methyl 2-carboxylate substituted aliphatic 2 H-azirines

Science.gov (United States)

Gómez-Zavaglia, Andrea; Kaczor, Agnieszka; Cardoso, Ana L.; Pinho e Melo, Teresa M. V. D.; Fausto, Rui

2007-05-01

In this study, the UV induced photochemical reactions of two 2 H-azirines - methyl 2-chloro-3-methyl-2 H-azirine-2-carboxylate (MCMAC) and methyl 3-methyl-2 H-azirine-2-carboxylate (MMAC) - isolated in argon matrices are compared. For both compounds, irradiation with λ > 235 nm led to observation of two primary photoprocesses: (a) C sbnd C bond cleavage, with production of nitrile ylides (P1-type products), and (b) C sbnd N bond cleavage, with production of methylated ketene imines (P2-type products). However, subsequent photoprocesses were found to be different in the two cases. In MCMAC, both primary photoproducts were shown to undergo further reactions: P1-type products decarboxylate, giving [(1-chloroethylidene)imino]ethanide, which bears a C dbnd N +dbnd C - group (P3-type product); P2-type products decarbonylate, yielding a substituted ylidene methanamine (P4-type product). In MMAC, only P2-type primary photoproducts appeared to react, undergoing decarbonylation or decarboxylation (both reactions leading to P4-type products), whereas P1-type products were found to be non-reactive. The non-observation of any secondary photoproduct resulting from photolysis of P1-MMAC revealed the higher photostability of this species when compared with the corresponding photoproduct obtained from MCMAC. The C sbnd N photochemical cleavage is an unusual process in aliphatic 2 H-azirines. In the studied compounds, its preference over the commonly observed C sbnd C azirine-ring bond photocleavage is attributed to the presence of electron withdrawing substituents (methylcarboxy group in both azirines and also the chlorine atom in MCMAC), which accelerates intersystem crossing towards the triplet state from where the cleavage of the C sbnd N bond takes place. The lack of the chlorine atom in MMAC may be partially compensated by the significantly higher stabilization of the P2-type photoproduct derived from this molecule ( ca. -52 kJ mol -1) relatively to the reactant, when

Members of the European Parliament (MEP) Heart Group.

Science.gov (United States)

Tofield, Andros

2013-06-01

The MEP Heart Group is a discussion forum aimed at promoting measures to reduce the burden of cardiovascular disease in the European Union and raise cardiovascular disease as a priority on the EU political agenda.

Spatial control of protein phosphatase 2A (de)methylation

International Nuclear Information System (INIS)

Longin, Sari; Zwaenepoel, Karen; Martens, Ellen; Louis, Justin V.; Rondelez, Evelien; Goris, Jozef; Janssens, Veerle

2008-01-01

Reversible methylation of the protein phosphatase 2A catalytic subunit (PP2A C ) is an important regulatory mechanism playing a crucial role in the selective recruitment of regulatory B subunits. Here, we investigated the subcellular localization of leucine carboxyl methyltransferase (LCMT1) and protein phosphatase methylesterase (PME-1), the two enzymes catalyzing this process. The results show that PME-1 is predominantly localized in the nucleus and harbors a functional nuclear localization signal, whereas LCMT1 is underrepresented in the nucleus and mainly localizes to the cytoplasm, Golgi region and late endosomes. Indirect immunofluorescence with methylation-sensitive anti-PP2A C antibodies revealed a good correlation with the methylation status of PP2A C , demethylated PP2A C being substantially nuclear. Throughout mitosis, demethylated PP2A C is associated with the mitotic spindle and during cytokinesis with the cleavage furrow. Overexpression of PME-1, but not of an inactive mutant, results in increased demethylation of PP2A C in the nucleus, whereas overexpression of a cytoplasmic PME-1 mutant lacking the NLS results in increased demethylation in the cytoplasm-in all cases, however, without any obvious functional consequences. PME-1 associates with an inactive PP2A population, regardless of its esterase activity or localization. We propose that stabilization of this inactive, nuclear PP2A pool is a major in vivo function of PME-1

Theoretical studies on the electronic and optoelectronic properties of [A.2AP(w)/A*.2AP(WC)/C.2AP(w)/C*.2AP(WC)/C.A(w)/C*.A(WC)]-Au8 mismatch nucleobase complexes

Science.gov (United States)

Srivastava, Ruby

2018-01-01

The electronic and optoelectronic properties of [A.2AP(w)/A*.2AP(WC)/C.2AP(w)/C*.2AP(WC)/C.A(w)/ C*.A(WC)]-Au8 metal-mismatch nucleobase complexes are investigated by means of density functional theory and time-dependent methods. We selected these mispairs as 2-aminopurine (2AP) produces incorporation errors when binding with cytosine (C) into the wobble (w) C.2AP(w) mispair, and is tautomerised into Watson-Crick (WC)-like base mispair C*.2AP(WC) and less effectively produces A.2AP(w)/A*.2AP(WC) mispairs. The vertical ionisation potential, vertical electron affinity, hardness and electrophilicity index of these complexes have also been discussed. The modifications of energy levels and charge density distributions of the frontier orbitals are also analysed. The absorption spectra of these complexes lie in the visible region, which suggests their application in fluorescent-bio imaging. The mechanism of cooperativity effect is studied by molecular orbital potential (MEP), atoms-in-molecules (AIM) and natural bond orbital analyses. Most metalated pairs have smaller HOMO-LUMO band gaps than the isolated mismatch nucleobases which suggest interesting consequences for electron transfer through DNA duplexes.

Cloning and expression of the human N-methyl-D-aspartate receptor subunit NR3A

DEFF Research Database (Denmark)

Eriksson, Maria; Nilsson, Anna; Froelich-Fabre, Susanne

2002-01-01

Native N-methyl-D-aspartate (NMDA) receptors are heteromeric assemblies of four or five subunits. The NMDA receptor subunits, NR1, NR2A, NR2B, NR2C, and NR2D have been cloned in several species, including man. The NR3A subunit, which in rodents is predominantly expressed during early development......, seems to function by reducing the NMDA receptor response. The human homologue to the rat NR3A, however, had not been cloned. In order to study the functions of the human NR3A (hNR3A), we have cloned and sequenced the hNR3A. It was found to share 88% of the DNA sequence with the rat gene, corresponding...

Two new C-methyl flavanones from the rhizomes and frond bases of Matteuccia struthiopteris

Czech Academy of Sciences Publication Activity Database

Zhang, D.; Li, S. B.; Li, Y. J.; Zhu, X. X.; Kmoníčková, Eva; Zídek, Zdeněk; Fu, M. H.; Fang, J.

2013-01-01

Roč. 15, č. 11 (2013), s. 1163-1167 ISSN 1028-6020 R&D Projects: GA MŠk(CZ) ME10116 Institutional support: RVO:68378041 Keywords : Onocleaceae * Matteuccia struthiopteris * C-methyl flavanones Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 0.968, year: 2013

The -938C>A Polymorphism in MYD88 Is Associated with Susceptibility to Tuberculosis: A Pilot Study

Directory of Open Access Journals (Sweden)

Kalliopi Aggelou

2016-01-01

Full Text Available Introduction. Tuberculosis (TB is a major disease worldwide, caused by Mycobacterium tuberculosis (MTB infection. The Toll-Like Receptor (TLR pathway plays a crucial role in the recognition of MTB. Aim. The present study aimed to investigate the involvement of myeloid differentiation primary response protein 88 (MYD88 gene polymorphisms in TB. Materials and Methods. A total of 103 TB cases and 92 control subjects were genotyped for the MYD88 -938C>A (rs4988453 and 1944C>G (rs4988457 polymorphisms. Results. The MYD88 -938CA and -938AA genotypes were associated with an increased risk for tuberculosis with odds ratio (OR of 5.71 (95% confidence intervals [CIs] 2.89–11.28, p=0.01. Conclusions. The MYD88 -938C>A genetic polymorphism is associated with increased susceptibility to TB and may serve as a marker to screen individuals who are at risk.

Prenatal exposure to maternal depressed mood and the MTHFR C677T variant affect SLC6A4 methylation in infants at birth.

Directory of Open Access Journals (Sweden)

Angela M Devlin

2010-08-01

Full Text Available Prenatal and early postnatal exposure to maternal depression may "program" childhood behavior via epigenetic processes such as DNA methylation. Methylenetetrahydro-folate reductase (MTHFR is an important enzyme in the generation of methyl groups for DNA methylation. The common MTHFR C677T variant is associated with depression in men and non-pregnant women, and with global changes in DNA methylation. This study investigated the effect of maternal MTHFR C677T genotype on antenatal maternal mood, and their impact on the gene-specific methylation in pregnant women and their newborn infants. The methylation status of SLC6A4, which encodes the transmembrane serotonin transporter, and BDNF, which encodes brain derived neurotrophic factor, were assessed because of their potential role in behaviour.Depressed mood was assessed by the Edinburgh Postnatal Depression Scale (EPDS and the Hamilton Rating Scale for Depression (HAM-D in women (n = 82, all taking folate during the 2(nd and 3(rd trimesters of pregnancy. The methylation status of SLC6A4 and BDNF were assessed in 3rd trimester maternal peripheral leukocytes and in umbilical cord leukocytes collected from their infants at birth. Women with the MTHFR 677TT genotype had greater 2(nd trimester depressed mood (p<0.05. Increased 2(nd trimester maternal depressed mood (EPDS scores was associated with decreased maternal and infant SLC6A4 promoter methylation (p<0.05, but had no effect on BDNF promoter methylation.These findings show that the MTHFR C677T variant is associated with greater depressed mood during pregnancy. We further showed that prenatal exposure to maternal depressed mood affects gene-specific DNA methylation patterns. These findings support the concept that alterations in epigenetic processes may contribute to developmental programming of behaviour by maternal depression.

Paradoxical upgrading reaction in extra-pulmonary tuberculosis: association with vitamin D therapy

OpenAIRE

Barr, D.A.; Coussens, A.K.; Irvine, S.; Ritchie, N.D.; Herbert, K.; Choo-Kang, B.; Raeside, D.; Bell, D.J.; Seaton, R.A.

2017-01-01

SETTING: Glasgow, Scotland, UK.\\ud \\ud BACKGROUND: Paradoxical reactions in tuberculosis (TB) are a notable example of our incomplete understanding of host-pathogen interactions during anti-tuberculosis treatment.\\ud \\ud OBJECTIVES: To determine risk factors for a TB paradoxical reaction, and specifically to assess for an independent association with vitamin D use.\\ud \\ud DESIGN: Consecutive human immunodeficiency virus (HIV) negative adult patients treated for extra-pulmonary TB were identif...

Characterization of the Methylation Status of Pax7 and Myogenic Regulator Factors in Cell Myogenic Differentiation.

Science.gov (United States)

Chao, Zhe; Zheng, Xin-Li; Sun, Rui-Ping; Liu, Hai-Long; Huang, Li-Li; Cao, Zong-Xi; Deng, Chang-Yan; Wang, Feng

2016-07-01

Epigenetic processes in the development of skeletal muscle have been appreciated for over a decade. DNA methylation is a major epigenetic modification important for regulating gene expression and suppressing spurious transcription. Up to now, the importance of epigenetic marks in the regulation of Pax7 and myogenic regulatory factors (MRFs) expression is far less explored. In the present study, semi-quantitative the real-time polymerase chain reaction (RT-PCR) analyses showed MyoD and Myf5 were expressed in activated and quiescent C2C12 cells. MyoG was expressed in a later stage of myogenesis. Pax7 was weakly expressed in differentiated C2C12 cells. To further understand the regulation of expression of these genes, the DNA methylation status of Pax7, MyoD, and Myf5 was determined by bisulfite sequencing PCR. During the C2C12 myoblasts fusion process, the changes of promoter and exon 1 methylation of Pax7, MyoD, and Myf5 genes were observed. In addition, an inverse relationship of low methylation and high expression was found. These results suggest that DNA methylation may be an important mechanism regulating Pax7 and MRFs transcription in cell myogenic differentiation.

Promoter- and cell-specific epigenetic regulation of CD44, Cyclin D2, GLIPR1 and PTEN by Methyl-CpG binding proteins and histone modifications

International Nuclear Information System (INIS)

Müller, Imke; Wischnewski, Frank; Pantel, Klaus; Schwarzenbach, Heidi

2010-01-01

The aim of the current study was to analyze the involvement of methyl-CpG binding proteins (MBDs) and histone modifications on the regulation of CD44, Cyclin D2, GLIPR1 and PTEN in different cellular contexts such as the prostate cancer cells DU145 and LNCaP, and the breast cancer cells MCF-7. Since global chromatin changes have been shown to occur in tumours and regions of tumour-associated genes are affected by epigenetic modifications, these may constitute important regulatory mechanisms for the pathogenesis of malignant transformation. In DU145, LNCaP and MCF-7 cells mRNA expression levels of CD44, Cyclin D2, GLIPR1 and PTEN were determined by quantitative RT-PCR at the basal status as well as after treatment with demethylating agent 5-aza-2'-deoxycytidine and/or histone deacetylase inhibitor Trichostatin A. Furthermore, genomic DNA was bisulfite-converted and sequenced. Chromatin immunoprecipitation was performed with the stimulated and unstimulated cells using antibodies for MBD1, MBD2 and MeCP2 as well as 17 different histone antibodies. Comparison of the different promoters showed that MeCP2 and MBD2a repressed promoter-specifically Cyclin D2 in all cell lines, whereas in MCF-7 cells MeCP2 repressed cell-specifically all methylated promoters. Chromatin immunoprecipitation showed that all methylated promoters associated with at least one MBD. Treatment of the cells by the demethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR) caused dissociation of the MBDs from the promoters. Only MBD1v1 bound and repressed methylation-independently all promoters. Real-time amplification of DNA immunoprecipitated by 17 different antibodies showed a preferential enrichment for methylated lysine of histone H3 (H3K4me1, H3K4me2 and H3K4me3) at the particular promoters. Notably, the silent promoters were associated with unmodified histones which were acetylated following treatment by 5-aza-CdR. This study is one of the first to reveal the histone code and MBD profile

Synthesis of 6-O-(5-acetamido-3,5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranosylonic acid)-D-galactose [6-O-(N-acetyl-α-D-neuraminyl)-D-galactose

NARCIS (Netherlands)

Vliegenthart, J.F.G.; Vleugel, D.J.M. van der; Wassenburg, F.R.; Zwikker, J.W.

1982-01-01

Condensation of methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2-chloro-2,3,5-trideoxy-beta-D-glycero-D-galacto-2-nonulopyranosonate with benzyl 2,3,4-tri-O-benzyl-beta-D-galactopyranoside, using silver salicylate as promoter, gave benzyl 2,3,4-tri-O-benzyl-6-O-(methyl

SNP rs16906252C>T is an expression and methylation quantitative trait locus associated with an increased risk of developing MGMT-methylated colorectal cancer

Science.gov (United States)

Kuroiwa-Trzmielina, Joice; Wang, Fan; Rapkins, Robert W.; Ward, Robyn L.; Buchanan, Daniel D.; Win, Aung Ko; Clendenning, Mark; Rosty, Christophe; Southey, Melissa C.; Winship, Ingrid M.; Hopper, John L.; Jenkins, Mark A.; Olivier, Jake; Hawkins, Nicholas J.; Hitchins, Megan P.

2016-01-01

Purpose Methylation of the MGMT promoter is the major cause of O6-methylguanine methyltransferase deficiency in cancer and has been associated with the T variant of the promoter-enhancer SNP rs16906252C>T. We sought evidence for an association between the rs16906252C>T genotype and increased risk of developing a subtype of colorectal cancer (CRC) featuring MGMT methylation, mediated by genotype-dependent epigenetic silencing within normal tissues. Experimental design By applying a molecular pathological epidemiology case-control study design, associations between rs16906252C>T and risk for CRC overall, and CRC stratified by MGMT methylation status, were estimated using multinomial logistic regression in two independent retrospective series of CRC cases and controls. The test sample comprised 1054 CRC cases and 451 controls from Sydney, Australia. The validation sample comprised 612 CRC cases and 245 controls from the Australasian Colon Cancer Family Registry (ACCFR). To determine if rs16906252C>T was linked to a constitutively altered epigenetic state, quantitative allelic expression and methylation analyses were performed in normal tissues. Results An association between rs16906252C>T and increased risk of developing MGMT-methylated CRC in the Sydney sample was observed (OR 3.3; 95%CI=2.0–5.3; PT represents an expression and methylation quantitative trait locus. Conclusions We provide evidence that rs16906252C>T is associated with elevated risk for MGMT-methylated CRC, likely mediated by constitutive epigenetic repression of the T allele. PMID:27267851

Graphite-like carbon nitride coupled with tiny Bi2S3 nanoparticles as 2D/0D heterojunction with enhanced photocatalytic activity

Science.gov (United States)

Zhu, Chengzhang; Gong, Tingting; Xian, Qiming; Xie, Jimin

2018-06-01

Novel well-dispersed tiny Bi2S3 nanoparticles (NPs) with an average sizes of approximately 16.2 nm were used to decorate layered g-C3N4 nanosheets (NSs), with the purpose of constructing highly efficient 0D/2D heterojunction photocatalyst by a simple hydrothermal method in one step. The fabricated Bi2S3/g-C3N4 heterostructures exhibited superior visible-light-driven photocatalytic activity toward methyl orange (MO) degradation in contrast to that of individual Bi2S3 and g-C3N4, which could be mainly ascribed to the synergistic effect of the tiny size effect of 0D Bi2S3 NPs and 2D g-C3N4 NSs, the matched energy level positions, and the abundant coupling heterointerfaces between two moieties. More importantly, the photodegradation of methylene blue (MB), rhodamine B (RhB) and colorless tetracycline (TC), ciprofloxacin (CIP) further revealed the broad-spectrum photodegradation capacities of the heterojunction materials. The possible photoinduced charge transfer and pollutant degradation process over Bi2S3/g-C3N4 heterojunctions under visible-light irradiation were proposed. This work may provide a platform for constructing new visible light 0D/2D intimate contact heterostructures with stable and efficient photocatalytic performance.

Use of mep HyperCel for polishing of human serum albumin.

Science.gov (United States)

McCann, Karl B; Vucica, Yvonne; Wu, John; Bertolini, Joseph

2014-10-15

The manufacture of human serum albumin by chromatographic procedures involves gel filtration chromatography as a final polishing step. Despite this step being essential to remove high molecular weight impurity proteins and thus ensure a stable and safe final product, it is relatively inefficient. This paper explores the use of hydrophobic charge induction chromatographic media, MEP HyperCel as an alternative to Sephacryl S200HR gel filtration for the polishing of human serum albumin derived by ion exchange chromatographic purification of Cohn Supernatant I. The use of MEP HyperCel results in a product with a higher purity than achieved with gel filtration and in a less time consuming manner and with potential resource savings. MEP HyperCel appears to have great potential for incorporation into downstream processes in the plasma fractionation industry as an efficient means of achieving polishing of intermediates or capture of proteins of interest. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of Australian and US Cost-Benefit Approaches to MEPS

Energy Technology Data Exchange (ETDEWEB)

McMahon, James E.

2004-03-12

Assessments are similar; no changes are recommended. (2) The Australian approach to determining the relationship of price to energy efficiency is based on current market, while the US approach uses prospective estimates. Both approaches may benefit from increased retrospective analysis of impacts of MEPS on appliance and equipment prices. Under some circumstances, Australia may wish to consider analyzing two separate components leading to price impacts: (a) changes in manufacturing costs and (b) markups used to convert from manufacturing costs to consumer price. (3) The Life-Cycle Cost methods are similar, but the USA has statistical surveys that permit a more detailed analysis. Australia uses average values, while the US uses full distributions. If data and resources permit, Australia may benefit from greater depth here as well. If implemented, the changes will provide more information about the benefits and costs of the program, in particular identifying who benefits and who bears net costs so that programs can be designed to offset unintended negative consequences, and may assist the government in convincing affected parties of the justification for some MEPS. However, without a detailed and statistically representative national survey, such an approach may not be practical for Australia at this time. (4) The National Benefits and Costs methods are similar prospective estimates of shipments, costs and energy savings, as well as greenhouse gas emissions. Additional sensitivity studies could further illustrate the ranges in these estimates. Consideration of lower discount rates could lead to more stringent MEPS in some cases. (5) Both the Australian and US analyses of impacts on industry, competition, and trade ultimately depend upon sufficient consultation with industry experts. While the Australian analysis of financial impacts on manufacturers is less detailed than that of the US, the Australian treatment of impacts on market shares imported from different regions of the

Association of MEP1A gene variants with insulin metabolism in central European women with polycystic ovary syndrome.

Science.gov (United States)

Lam, Uyen D P; Lerchbaum, Elisabeth; Schweighofer, Natascha; Trummer, Olivia; Eberhard, Katharina; Genser, Bernd; Pieber, Thomas R; Obermayer-Pietsch, Barbara

2014-03-10

Polycystic ovary syndrome (PCOS) shows not only hyperandrogenemia, hirsutism and fertility problems, but also metabolic disturbances including obesity, cardiovascular events and type-2 diabetes. Accumulating evidence suggests some degree of inflammation associated with prominent aspects of PCOS. We aimed to investigate the association of genetic variants 3'UTR rs17468190 (G/T) of the inflammation-associated gene MEP1A (GenBank ID: NM_005588.2) with metabolic disturbances in PCOS and healthy control women. Genetic variants rs17468190 (G/T) of MEP1A gene were analyzed in 576 PCOS women and 206 controls by using the Taqman fluorogenic 5'-exonuclease assay. This polymorphism was tested for association with anthropometric, metabolic, hormonal, and functional parameters of PCOS. There was a borderline significant difference in genotype distribution between PCOS and control women (p=0.046). In overweight/obese PCOS patients, the variants rs17468190 (G/T) in the MEP1A gene are associated with glucose and insulin metabolism. In a dominant model, the GG genotype of the MEP1A gene was more strongly associated with insulin metabolism in overweight/obese PCOS women (body mass index, BMI>25 kg/m(2)), than in GT+TT genotypes. The MEP1A GG-carriers showed a significantly increased homeostatic model assessment - insulin resistance (HOMA-IR) (p=0.003), elevation of fasting insulin (p=0.004) and stimulated insulin (30 min, pdisease modification in PCOS. It might contribute to the abnormalities of glucose metabolism and insulin sensitivity and serve as a diagnostic or therapeutic target gene for PCOS. Copyright © 2014 Elsevier B.V. All rights reserved.

Fragrance material review on 2-methyl-5-phenylpentanol.

Science.gov (United States)

Scognamiglio, J; Jones, L; Letizia, C S; Api, A M

2012-09-01

A toxicologic and dermatologic review of 2-methyl-5-phenylpentanol when used as a fragrance ingredient is presented. 2-Methyl-5-phenylpentanol is a member of the fragrance structural group aryl alkyl alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 2-methyl-5-phenylpentanol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, repeated dose, and genotoxicity data. A safety assessment of the entire aryl alkyl alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all other branched chain saturated alcohols in fragrances. Copyright © 2011 Elsevier Ltd. All rights reserved.

Evaluation of D-isomers of 4-borono-2-18F-fluoro-phenylalanine and O-11C-methyl-tyrosine as brain tumor imaging agents: a comparative PET study with their L-isomers in rat brain glioma.

Science.gov (United States)

Kanazawa, Masakatsu; Nishiyama, Shingo; Hashimoto, Fumio; Kakiuchi, Takeharu; Tsukada, Hideo

2018-06-13

The potential of the D-isomerization of 4-borono-2- 18 F-fluoro-phenylalanine ( 18 F-FBPA) to improve its target tumor to non-target normal brain tissue ratio (TBR) was evaluated in rat brain glioma and compared with those of L- and D- 11 C-methyl-tyrosine ( 11 C-CMT). The L- or D-isomer of 18 F-FBPA was injected into rats through the tail vein, and their whole body kinetics and distributions were assessed using the tissue dissection method up to 90 min after the injection. The kinetics of L- and D- 18 F-FBPA or L- and D- 11 C-CMT in the C-6 glioma-inoculated rat brain were measured for 90 or 60 min, respectively, using high-resolution animal PET, and their TBRs were assessed. Tissue dissection analyses showed that D- 18 F-FBPA uptake was significantly lower than that of L- 18 F-FBPA in the brain and abdominal organs, except for the kidney and bladder, reflecting the faster elimination rate of D- 18 F-FBPA than L- 18 F-FBPA from the blood to the urinary tract. PET imaging using 18 F-FBPA revealed that although the brain uptake of D- 18 F-FBPA was significantly lower than that of L- 18 F-FBPA, the TBR of the D-isomer improved to 6.93 from 1.45 for the L-isomer. Similar results were obtained with PET imaging using 11 C-CMT with a smaller improvement in TBR to 1.75 for D- 11 C-CMT from 1.33 for L- 11 C-CMT. The present results indicate that D- 18 F-FBPA is a better brain tumor imaging agent with higher TBR than its original L-isomer and previously reported tyrosine-based PET imaging agents. This improved TBR of D- 18 F-FBPA without any pre-treatments, such as tentative blood-brain barrier disruption using hyperosmotic agents or sonication, suggests that the D-isomerization of BPA results in the more selective accumulation of 10 B in tumor cells that is more effective and less toxic than conventional L-BPA.

The Implementation of C-ID, R2D2 Model on Learning Reading Comprehension

Science.gov (United States)

Rayanto, Yudi Hari; Rusmawan, Putu Ngurah

2016-01-01

The purposes of this research are to find out, (1) whether C-ID, R2D2 model is effective to be implemented on learning Reading comprehension, (2) college students' activity during the implementation of C-ID, R2D2 model on learning Reading comprehension, and 3) college students' learning achievement during the implementation of C-ID, R2D2 model on…

Destruction of C2H4O2 isomers in ice-phase by X-rays: Implication on the abundance of acetic acid and methyl formate in the interstellar medium

Science.gov (United States)

Rachid, Marina G.; Faquine, Karla; Pilling, S.

2017-12-01

The C2H4O2 isomers methyl formate (HCOOCH3), acetic acid (CH3COOH) and glycoaldehyde (HOCH2CHO) have been detected in molecular clouds in the interstellar medium, as well as, hot cores, hot corinos and around protostellar objects. However, their abundances are very different, being methyl formate more abundant than the other two isomers. This fact may be related to the different destruction by ionizing radiation of these molecules. The goal of this work is experimentally study the photodissociation processes of methyl formate and acetic acid ices when exposed to broadband soft X-ray from 6 up to 2000 eV. The experiments were performed coupled to the SGM beamline in the Brazilian Synchrotron Light Source (LNLS/CNPEM) at Campinas, Brazil. The simulated astrophysical ices (12 K) were monitored throughout the experiment using infrared vibrational spectroscopy (FTIR). The analysis of processed ices allowed the determination of the effective destruction cross sections of the parent molecules as well as the effective formation cross section of daughter molecular species such as CO, CO2, H2O, CH4 and H2CO (only for methyl formate) and the hydrocarbons C2H6 and C5H10 (only for acetic acid). The half-lives of molecules at ices toward young stellar objects (YSOs) and inside molecular clouds (e.g. Sgr B2 and W51) due to the presence of incoming soft X-rays were estimated. We determined the effective formation rate and the branching ratios for assigned daughter species after the establishment of a chemical equilibrium. The main product from photodissociation of both methyl formate and acetic acid is CO, that can be formed by recombination of ions, formed during the photodissociation, in the ice surface. The relative abundance between methyl formate and acetic acid (NCH3COOH/NHCOOCH3) in different astronomical scenarios and their column density evolution in the presence of X-rays were calculated. Our results suggest that such radiation field can be one of the factors that

Natural variation in monoterpene synthesis in kiwifruit: transcriptional regulation of terpene synthases by NAC and ETHYLENE-INSENSITIVE3-like transcription factors.

Science.gov (United States)

Nieuwenhuizen, Niels J; Chen, Xiuyin; Wang, Mindy Y; Matich, Adam J; Perez, Ramon Lopez; Allan, Andrew C; Green, Sol A; Atkinson, Ross G

2015-04-01

Two kiwifruit (Actinidia) species with contrasting terpene profiles were compared to understand the regulation of fruit monoterpene production. High rates of terpinolene production in ripe Actinidia arguta fruit were correlated with increasing gene and protein expression of A. arguta terpene synthase1 (AaTPS1) and correlated with an increase in transcript levels of the 2-C-methyl-D-erythritol 4-phosphate pathway enzyme 1-deoxy-D-xylulose-5-phosphate synthase (DXS). Actinidia chinensis terpene synthase1 (AcTPS1) was identified as part of an array of eight tandemly duplicated genes, and AcTPS1 expression and terpene production were observed only at low levels in developing fruit. Transient overexpression of DXS in Nicotiana benthamiana leaves elevated monoterpene synthesis by AaTPS1 more than 100-fold, indicating that DXS is likely to be the key step in regulating 2-C-methyl-D-erythritol 4-phosphate substrate flux in kiwifruit. Comparative promoter analysis identified potential NAC (for no apical meristem [NAM], Arabidopsis transcription activation factor [ATAF], and cup-shaped cotyledon [CUC])-domain transcription factor) and ETHYLENE-INSENSITIVE3-like transcription factor (TF) binding sites in the AaTPS1 promoter, and cloned members of both TF classes were able to activate the AaTPS1 promoter in transient assays. Electrophoretic mobility shift assays showed that AaNAC2, AaNAC3, and AaNAC4 bind a 28-bp fragment of the proximal NAC binding site in the AaTPS1 promoter but not the A. chinensis AcTPS1 promoter, where the NAC binding site was mutated. Activation could be restored by reintroducing multiple repeats of the 12-bp NAC core-binding motif. The absence of NAC transcriptional activation in ripe A. chinensis fruit can account for the low accumulation of AcTPS1 transcript, protein, and monoterpene volatiles in this species. These results indicate the importance of NAC TFs in controlling monoterpene production and other traits in ripening fruits. © 2015 American

Natural Variation in Monoterpene Synthesis in Kiwifruit: Transcriptional Regulation of Terpene Synthases by NAC and ETHYLENE-INSENSITIVE3-Like Transcription Factors1

Science.gov (United States)

Nieuwenhuizen, Niels J.; Chen, Xiuyin; Wang, Mindy Y.; Matich, Adam J.; Perez, Ramon Lopez; Allan, Andrew C.; Green, Sol A.; Atkinson, Ross G.

2015-01-01

Two kiwifruit (Actinidia) species with contrasting terpene profiles were compared to understand the regulation of fruit monoterpene production. High rates of terpinolene production in ripe Actinidia arguta fruit were correlated with increasing gene and protein expression of A. arguta terpene synthase1 (AaTPS1) and correlated with an increase in transcript levels of the 2-C-methyl-d-erythritol 4-phosphate pathway enzyme 1-deoxy-d-xylulose-5-phosphate synthase (DXS). Actinidia chinensis terpene synthase1 (AcTPS1) was identified as part of an array of eight tandemly duplicated genes, and AcTPS1 expression and terpene production were observed only at low levels in developing fruit. Transient overexpression of DXS in Nicotiana benthamiana leaves elevated monoterpene synthesis by AaTPS1 more than 100-fold, indicating that DXS is likely to be the key step in regulating 2-C-methyl-d-erythritol 4-phosphate substrate flux in kiwifruit. Comparative promoter analysis identified potential NAC (for no apical meristem [NAM], Arabidopsis transcription activation factor [ATAF], and cup-shaped cotyledon [CUC])-domain transcription factor) and ETHYLENE-INSENSITIVE3-like transcription factor (TF) binding sites in the AaTPS1 promoter, and cloned members of both TF classes were able to activate the AaTPS1 promoter in transient assays. Electrophoretic mobility shift assays showed that AaNAC2, AaNAC3, and AaNAC4 bind a 28-bp fragment of the proximal NAC binding site in the AaTPS1 promoter but not the A. chinensis AcTPS1 promoter, where the NAC binding site was mutated. Activation could be restored by reintroducing multiple repeats of the 12-bp NAC core-binding motif. The absence of NAC transcriptional activation in ripe A. chinensis fruit can account for the low accumulation of AcTPS1 transcript, protein, and monoterpene volatiles in this species. These results indicate the importance of NAC TFs in controlling monoterpene production and other traits in ripening fruits. PMID:25649633

Distribution of radiolabeled 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride in rat brain tumor: intraarterial versus intravenous administration

International Nuclear Information System (INIS)

Yamada, K.; Ushio, Y.; Hayakawa, T.; Arita, N.; Huang, T.Y.; Nagatani, M.; Yamada, N.; Mogami, H.

1987-01-01

To assess the rationale of intraarterial (i.a.) 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea chemotherapy, distribution of 14 C-labeled 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea in rat glioma was studied after i.a. or i.v. infusion. Immediately after infusion, the tumor located in the hemisphere of intracarotid infusion received 4.6-fold higher radioactivity than the tumor located contralaterally to intracarotid infusion and 2.8-fold higher radioactivity than i.v. infusion. The difference was kept up to 30 min after i.a. infusion. Autoradiographic observation indicated rather uniform distribution of the tracer in the central portion of i.a. infusion. However, in the periphery of i.a. infusion, distribution of the tracer was nonhomogenous. The results indicate that i.a. 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea chemotherapy is useful when the tumor has high blood flow and is located in the center of an infused area

CRRES microelectronics test package (MEP)

International Nuclear Information System (INIS)

Mullen, E.G.; Ray, K.P.

1993-01-01

The Microelectronics Test Package (MEP) flown on board the Combined Release and Radiation Effects Satellite (CRRES) contained over 60 device types and approximately 400 total devices which were tested for both single event upset (SEU) and total dose (parametric degradation and annealing). A description of the experiment, the method of testing devices, and the structure of data acquisition are presented. Sample flight data are shown. These included SEUs from a GaAs 1 K RAM during the March 1991 solar flare, and a comparison between passive shielding and a specially designed spot shielding package

Important role for Mycobacterium tuberculosis UvrD1 in pathogenesis and persistence apart from its function in nucleotide excision repair.

Science.gov (United States)

Houghton, Joanna; Townsend, Carolin; Williams, Alan R; Rodgers, Angela; Rand, Lucinda; Walker, K Barry; Böttger, Erik C; Springer, Burkhard; Davis, Elaine O

2012-06-01

Mycobacterium tuberculosis survives and replicates in macrophages, where it is exposed to reactive oxygen and nitrogen species that damage DNA. In this study, we investigated the roles of UvrA and UvrD1, thought to be parts of the nucleotide excision repair pathway of M. tuberculosis. Strains in which uvrD1 was inactivated either alone or in conjunction with uvrA were constructed. Inactivation of uvrD1 resulted in a small colony phenotype, although growth in liquid culture was not significantly affected. The sensitivity of the mutant strains to UV irradiation and to mitomycin C highlighted the importance of the targeted genes for nucleotide excision repair. The mutant strains all exhibited heightened susceptibility to representatives of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI). The uvrD1 and the uvrA uvrD1 mutants showed decreased intracellular multiplication following infection of macrophages. Most importantly, the uvrA uvrD1 mutant was markedly attenuated following infection of mice by either the aerosol or the intravenous route.

Polymerization of Methyl Methacrylate Catalyzed by Co(II), Cu(II), and Zn(II) Complexes Bearing N-Methyl-N-((pyridin-2-yl)methyl) cyclohexanamine

Energy Technology Data Exchange (ETDEWEB)

Ahn, Seoung Hyun; Lee, Hyosun [Kyungpook National University, Daegu (Korea, Republic of); Shin, Jongwon [POSTECH, Pohang (Korea, Republic of); Nayab, Saira [Shaheed Benazir Bhutto University, Sheringal (Pakistan)

2016-05-15

We demonstrated the synthesis and characterization of Co(II), Cu(II), and Zn(II) complexes ligated to N-methyl-N-((pyridin-2-yl)methyl)cyclohexanamine. The complex [Co(nmpc)Cl{sub 2}] in the presence of MMAO showed the highest catalytic activity for MMA polymerization at 60 °C compared with its Zn(II) and Cu(II) analogs. The metal center showed an obvious influence on the catalytic activity, although this appeared to have no effect on the stereo-regularity of the resultant PMMA. X-ray diffraction analysis revealed that [Co(nmpc)Cl{sub 2}] and [Zn(nmpc)Cl{sub 2}] crystallized in the monoclinic system with space group P2{sub 1}/c and existed as monomeric and solvent-free complexes.

2-[3-Furyl(hydroxy)methyl]-2,3-dimethylcyclohexanone.

Science.gov (United States)

García, Esther; Mendoza, Virgilio; Guzmán, José Agustín; Maldonado Graniel, Luis Angel; Hernández-Ortega, Simón

2002-06-01

Contribution No. 1750 of the Instituto de Quimica, UNAM, Mexico. In the molecule of the title compound, C(13)H(18)O(3), there is a syn relationship between the two vicinal methyl groups. The six-membered ring adopts a chair conformation, with one equatorial and two axial groups, and the furyl group is almost parallel to the ketone group. Intermolecular hydrogen bonds [O[bond]H...O[double bond]C 2.814 (3) A] form chains along [100].

Inactivation of Mycobacterium tuberculosis l,d-Transpeptidase LdtMt1 by Carbapenems and Cephalosporins

Science.gov (United States)

Dubée, Vincent; Triboulet, Sébastien; Mainardi, Jean-Luc; Ethève-Quelquejeu, Mélanie; Gutmann, Laurent; Marie, Arul; Dubost, Lionel

2012-01-01

The structure of Mycobacterium tuberculosis peptidoglycan is atypical since it contains a majority of 3→3 cross-links synthesized by l,d-transpeptidases that replace 4→3 cross-links formed by the d,d-transpeptidase activity of classical penicillin-binding proteins. Carbapenems inactivate these l,d-transpeptidases, and meropenem combined with clavulanic acid is bactericidal against extensively drug-resistant M. tuberculosis. Here, we used mass spectrometry and stopped-flow fluorimetry to investigate the kinetics and mechanisms of inactivation of the prototypic M. tuberculosis l,d-transpeptidase LdtMt1 by carbapenems (meropenem, doripenem, imipenem, and ertapenem) and cephalosporins (cefotaxime, cephalothin, and ceftriaxone). Inactivation proceeded through noncovalent drug binding and acylation of the catalytic Cys of LdtMt1, which was eventually followed by hydrolysis of the resulting acylenzyme. Meropenem rapidly inhibited LdtMt1, with a binding rate constant of 0.08 μM−1 min−1. The enzyme was unable to recover from this initial binding step since the dissociation rate constant of the noncovalent complex was low (carbapenem side chains affected both the binding and acylation steps, ertapenem being the most efficient LdtMt1 inactivator. Cephalosporins also formed covalent adducts with LdtMt1, although the acylation reaction was 7- to 1,000-fold slower and led to elimination of one of the drug side chains. Comparison of kinetic constants for drug binding, acylation, and acylenzyme hydrolysis indicates that carbapenems and cephems can both be tailored to optimize peptidoglycan synthesis inhibition in M. tuberculosis. PMID:22615283

Effect of experimental gingivitis induction and erythritol on the salivary metabolome and functional biochemistry of systemically healthy young adults

NARCIS (Netherlands)

Prodan, A.; Imangaliyev, S.; Brand, H.S.; Rosema, M.N.A.; Levin, E.; Crielaard, W.; Keijser, B.J.F.; Veerman, E.C.I.

2016-01-01

Introduction: Understanding the changes occurring in the oral ecosystem during development of gingivitis could help improve prevention and treatment strategies for oral health. Erythritol is a non-caloric polyol proposed to have beneficial effects on oral health. Objectives: To examine the effect of

Thermal Properties of Methyl Ester-Containing Poly(2-oxazolines

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Petra J. M. Bouten

2015-10-01

Full Text Available This paper describes the synthesis and thermal properties in solution and bulk of poly(2-alkyl-oxazolines (PAOx containing a methyl ester side chain. Homopolymers of 2-methoxycarbonylethyl-2-oxazoline (MestOx and 2-methoxycarbonylpropyl-2-oxazoline (C3MestOx, as well as copolymers with 2-ethyl-2-oxazoline (EtOx and 2-n-propyl-2-oxazoline (nPropOx, with systematic variations in composition were prepared. The investigation of the solution properties of these polymers revealed that the cloud point temperatures (TCPs could be tuned in between 24 °C and 108 °C by variation of the PAOx composition. To the best of our knowledge, the TCPs of PMestOx and PC3MestOx are reported for the first time and they closely resemble the TCPs of PEtOx and PnPropOx, respectively, indicating similar hydrophilicity of the methyl ester and alkyl side chains. Furthermore, the thermal transitions and thermal stability of these polymers were investigated by DSC and TGA measurements, respectively, revealing amorphous polymers with glass transition temperatures between -1 °C and 54 °C that are thermally stable up to >300 °C.

Promoter- and cell-specific epigenetic regulation of CD44, Cyclin D2, GLIPR1 and PTEN by Methyl-CpG binding proteins and histone modifications

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Schwarzenbach Heidi

2010-06-01

Full Text Available Abstract Background The aim of the current study was to analyze the involvement of methyl-CpG binding proteins (MBDs and histone modifications on the regulation of CD44, Cyclin D2, GLIPR1 and PTEN in different cellular contexts such as the prostate cancer cells DU145 and LNCaP, and the breast cancer cells MCF-7. Since global chromatin changes have been shown to occur in tumours and regions of tumour-associated genes are affected by epigenetic modifications, these may constitute important regulatory mechanisms for the pathogenesis of malignant transformation. Methods In DU145, LNCaP and MCF-7 cells mRNA expression levels of CD44, Cyclin D2, GLIPR1 and PTEN were determined by quantitative RT-PCR at the basal status as well as after treatment with demethylating agent 5-aza-2'-deoxycytidine and/or histone deacetylase inhibitor Trichostatin A. Furthermore, genomic DNA was bisulfite-converted and sequenced. Chromatin immunoprecipitation was performed with the stimulated and unstimulated cells using antibodies for MBD1, MBD2 and MeCP2 as well as 17 different histone antibodies. Results Comparison of the different promoters showed that MeCP2 and MBD2a repressed promoter-specifically Cyclin D2 in all cell lines, whereas in MCF-7 cells MeCP2 repressed cell-specifically all methylated promoters. Chromatin immunoprecipitation showed that all methylated promoters associated with at least one MBD. Treatment of the cells by the demethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR caused dissociation of the MBDs from the promoters. Only MBD1v1 bound and repressed methylation-independently all promoters. Real-time amplification of DNA immunoprecipitated by 17 different antibodies showed a preferential enrichment for methylated lysine of histone H3 (H3K4me1, H3K4me2 and H3K4me3 at the particular promoters. Notably, the silent promoters were associated with unmodified histones which were acetylated following treatment by 5-aza-CdR. Conclusions This study is one

Evaluation of vitamin status in patients with pulmonary tuberculosis.

Science.gov (United States)

Oh, Jongwon; Choi, Rihwa; Park, Hyung-Doo; Lee, Hyun; Jeong, Byeong-Ho; Park, Hye Yun; Jeon, Kyeongman; Kwon, O Jung; Koh, Won-Jung; Lee, Soo-Youn

2017-03-01

Vitamins are known to be associated with immunity and nutrition. Moreover, vitamin deficiency can affect host immunity to various infectious diseases, including tuberculosis. Although patients with tuberculosis often have vitamin D deficiency, little is known about the levels of other vitamins. Here, we aimed to investigate the status of vitamins A, B 12 , D, and E in patients with tuberculosis. We also aimed to investigate the clinical and laboratory variables related to vitamin status in patients with tuberculosis. We performed a case-control study to investigate the serum vitamin concentrations in 152 patients with tuberculosis and 137 control subjects. The concentrations of vitamin A, vitamin D, vitamin E, homocysteine, and methylmalonic acid were measured using high-performance liquid chromatography (HPLC) or HPLC-tandem mass spectrometry. Patient demographic data and other biochemical parameters were also analyzed. The serum concentrations of vitamins A, D, and E were significantly lower in patients with tuberculosis than in control subjects (1.4 vs. 2.0 μmol/L, P vitamin deficiencies were significantly higher in patients with tuberculosis. Moreover, multiple vitamin deficiencies were only observed in patients with tuberculosis (22.4% of all patients with tuberculosis vs. 0% of all control subjects). Positive correlations among vitamin A, D, and E concentrations were observed (vitamins A and D, r = 0.395; vitamins D and E, r = 0.342; and vitamins A and E, r = 0.427, P vitamin A, D, and E concentrations. Vitamin deficiencies are common in patients with tuberculosis. Further research investigating the clinical importance of vitamin and nutritional status in patients with tuberculosis is needed. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Pediatric Opsoclonus-Myoclonus-Ataxia Syndrome Associated With Anti-N-methyl-D-aspartate Receptor Encephalitis.

Science.gov (United States)

Player, Brittany; Harmelink, Matthew; Bordini, Brett; Weisgerber, Michael; Girolami, Michael; Croix, Michael

2015-11-01

The full clinical spectrum of anti-N-methyl-D-aspartate receptor encephalitis is unknown in the pediatric population. We describe a previously healthy 4-year-old girl presenting with opsoclonus-myoclonus together with ataxia who had NR1-specific, anti-N-methyl-D-aspartate receptor antibodies in the cerebral spinal fluid. The presence of NR1-specific, anti-N-methyl-D-aspartate receptor antibodies in the setting of opsoclonus-myoclonus and ataxia syndrome may represent an expansion of the clinical presentations of anti-N-methyl-D-aspartate receptor encephalitis. Copyright © 2015 Elsevier Inc. All rights reserved.

Energy Efficiency: The Implementation of Minimum Energy Performance Standard (MEPS Application on Home Appliances for Residential

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Rahman K.A

2016-01-01

Full Text Available Generally, Minimum Energy Performance Standard (MEPS has been widespread across the country especially developed country. However, most consumers do not even know about the MEPS. Without sufficient knowledge, much energy have been wasted before this. The aim of this study is to review the implementation of MEPS of Asia country and to compare electricity consumption of home appliances with star rating and without star rating. In order to fulfil the objectives of the study, the equipment must be chosen correctly and must be learned properly. The home appliances that will be used also need to be chosen so that the comparison between the appliances will be matched correctly. To understand the results, the analysis was done using graphs and table. The purpose of using graph and table is to understand the comparison between appliances more clearly. The results show that home appliances with MEPS is more efficient on energy saving rather than without MEPS. This is the evidence as a method to educate a consumer on energy saving.

Theoretical investigation of the oxidation pathways of the Cl-initiated reaction of 2-methyl-3-buten-2-ol

Science.gov (United States)

Zhang, Weichao; Zhang, Dongju

2012-12-01

The mechanism and products of the reaction of 2-methyl-3-buten-2-ol (MBO232) with Cl atoms in the presence of O2 have been elucidated by performing high-level quantum chemistry calculations. The geometries of the reactants, intermediates, transition states, and products are optimized at the MP2(full)/6-311G(d, p) level, and their single-point energies are refined at the CCSD(T)/6-311 + G(d, p) level. The potential energy surface profiles have been constructed at the CCSD(T)/6-311 + G(d, p)//MP2(full)/6-311G(d, p) + 0.95 × ZPE level of theory, and the possible channels involved in the reaction are also discussed. The calculations indicate that the reaction predominantly proceeds via the addition of Cl atoms to the double bond rather than the direct abstraction of the H atoms in MBO232. The nascent adducts (CH3)2C(OH)CHCH2Cl (IM1) and (CH3)2C(OH)CHClCH2 (IM2) do not undergo subsequent isomerization and dissociation reactions, but rather react with O2. The theoretical results show that the major products are CH2ClCHO and CH3C(O)CH3 for the reaction of MBO232 + Cl in the presence of O2, which is in good agreement with the experimental finding.

Design and synthesis of positional isomers of 5 and 6-bromo-1-[(phenyl)sulfonyl]-2-[(4-nitrophenoxy)methyl]-1H-benzimidazoles as possible antimicrobial and antitubercular agents.

Science.gov (United States)

Ranjith, P Karuvalam; Rajeesh, P; Haridas, Karickal R; Susanta, Nayak K; Row, Tayur N Guru; Rishikesan, R; Kumari, N Suchetha

2013-09-15

In this Letter, we report the structure-activity relationship (SAR) studies on series of positional isomers of 5(6)-bromo-1-[(phenyl)sulfonyl]-2-[(4-nitrophenoxy)methyl]-1H-benzimidazoles derivatives 7(a-j) and 8(a-j) synthesized in good yields and characterized by (1)H NMR, (13)C NMR and mass spectral analyses. The crystal structure of 7a was evidenced by X-ray diffraction study. The newly synthesized compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus, (Gram-positive), Escherichia coli and Klebsiella pneumoniae (Gram-negative), antifungal activity against Candida albicans, Aspergillus flavus and Rhizopus sp. and antitubercular activity against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis, Mycobacterium fortuitum and MDR-TB strains. The synthesized compounds displayed interesting antimicrobial activity. The compounds 7b, 7e and 7h displayed significant activity against Mycobacterium tuberculosis H37Rv strain. Copyright © 2013 Elsevier Ltd. All rights reserved.

The prevalence of pulmonary tuberculosis in Jeonbug Province

International Nuclear Information System (INIS)

Rhee, S. J.; Moon, M. C.; Song, H. Y.; Choi, K. C.

1981-01-01

A photofluorographic mass survey of P-A chest had been done to the 13136 residents (male 6264, female 6872) in Jeonbug province, Korea for about 2 years from May 5, to Dec.19, 1978 and from Mar. 5, to Dec. 22, 1979. The results are as follows: 1. The prevalence rate of all active pulmonary tuberculosis is 5.3%. 2. The prevalence rate of male(8.8%) is 4.2 times higher than that of female (2.1%). 3. The prevalence rates of all old age groups above fifty years are higher than that of remainder under fifty years of age. Of these, 61-70 years old age group is highest in prevalence rate. 4. According to extent of active pulmonary tuberculosis, 77.5% is minimal, 15.4% is moderately advanced, and 7.1% is far advanced. Inactive pulmonary tuberculosis are 39 cases (0.3% to objective population). 5. In the incidence of the involved side, right side is about 2 times higher than the left, and involvement of both sides is increased in moderately and far advance pulmonary tuberculosis. In all pulmonary tuberculosis, one or both upper lung fields are most commonly involved. The incidences of cavity in moderately and far advanced pulmonary tuberculosis show no significant difference. 6. The incidences of other intrathoracic lesions are as follows: suspected hypertensive heart disease 2.4%, dextrocardia with situs inversus 0.04%, pleural calcification 0.4%, pleural thickening 0.2%, pleural effusion 0.1%, pneumonia 0.02%, bronchiectasis 0.1%, lung abscess 0.02%, C.O.P.D. 0.2%, suspected lung tumor 0.06%, pneumothorax 0.0076%, and suspected mediastinal tumor 0.02%

Effects of pilocarpine and kainate-induced seizures on N-methyl-d-aspartate receptor gene expression in the rat hippocampus

Energy Technology Data Exchange (ETDEWEB)

Przewlocka, B.; Labuz, D.; Machelska, H.; Przewlocki, R.; Turchan, J.; Lason, W. [Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow (Poland)

1997-04-14

The effects of pilocarpine- and kainate-induced seizures on N-methyl-d-aspartate receptor subunit-1 messenger RNA and [{sup 3}H]dizocilpine maleate binding were studied in the rat hippocampal formation. Pilocarpine- but not kainate-induced seizures decreased N-methyl-d-aspartate receptor subunit-1 messenger RNA level in dentate gyrus at 24 and 72 h after drug injection. Both convulsants decreased the messenger RNA level in CA1 pyramidal cells at 24 and 72 h, the effects of kainate being more profound. Kainate also decreased the N-methyl-d-aspartate receptor subunit-1 messenger RNA level in CA3 region after 24 and 72 h, whereas pilocarpine decreased the messenger RNA level at 72 h only. At 3 h after kainate, but not pilocarpine, an increased binding of [{sup 3}H]dizocilpine maleate in several apical dendritic fields of pyramidal cells was found. Pilocarpine reduced the [{sup 3}H]dizocilpine maleate binding in stratum lucidum only at 3 and 24 h after the drug injection. Pilocarpine but not kainate induced prolonged decrease in N-methyl-d-aspartate receptor subunit-1 gene expression in dentate gyrus. However, at the latest time measured, kainate had the stronger effect in decreasing both messenger RNA N-methyl-d-aspartate receptor subunit-1 and [{sup 3}H]dizocilpine maleate binding in CA1 and CA3 hippocampal pyramidal cells. The latter changes corresponded, however, to neuronal loss and may reflect higher neurotoxic potency of kainate.These data point to some differences in hippocampal N-methyl-d-aspartate receptor regulation in pilocarpine and kainate models of limbic seizures. Moreover, our results suggest that the N-methyl-d-aspartate receptor subunit-1 messenger RNA level is more susceptible to limbic seizures than is [{sup 3}H]dizocilpine maleate binding in the rat hippocampal formation. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

Effects of pilocarpine and kainate-induced seizures on N-methyl-d-aspartate receptor gene expression in the rat hippocampus

International Nuclear Information System (INIS)

Przewlocka, B.; Labuz, D.; Machelska, H.; Przewlocki, R.; Turchan, J.; Lason, W.

1997-01-01

The effects of pilocarpine- and kainate-induced seizures on N-methyl-d-aspartate receptor subunit-1 messenger RNA and [ 3 H]dizocilpine maleate binding were studied in the rat hippocampal formation. Pilocarpine- but not kainate-induced seizures decreased N-methyl-d-aspartate receptor subunit-1 messenger RNA level in dentate gyrus at 24 and 72 h after drug injection. Both convulsants decreased the messenger RNA level in CA1 pyramidal cells at 24 and 72 h, the effects of kainate being more profound. Kainate also decreased the N-methyl-d-aspartate receptor subunit-1 messenger RNA level in CA3 region after 24 and 72 h, whereas pilocarpine decreased the messenger RNA level at 72 h only. At 3 h after kainate, but not pilocarpine, an increased binding of [ 3 H]dizocilpine maleate in several apical dendritic fields of pyramidal cells was found. Pilocarpine reduced the [ 3 H]dizocilpine maleate binding in stratum lucidum only at 3 and 24 h after the drug injection. Pilocarpine but not kainate induced prolonged decrease in N-methyl-d-aspartate receptor subunit-1 gene expression in dentate gyrus. However, at the latest time measured, kainate had the stronger effect in decreasing both messenger RNA N-methyl-d-aspartate receptor subunit-1 and [ 3 H]dizocilpine maleate binding in CA1 and CA3 hippocampal pyramidal cells. The latter changes corresponded, however, to neuronal loss and may reflect higher neurotoxic potency of kainate.These data point to some differences in hippocampal N-methyl-d-aspartate receptor regulation in pilocarpine and kainate models of limbic seizures. Moreover, our results suggest that the N-methyl-d-aspartate receptor subunit-1 messenger RNA level is more susceptible to limbic seizures than is [ 3 H]dizocilpine maleate binding in the rat hippocampal formation. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

Pharmacogenetic Variation at CYP2D6, CYP2C9, and CYP2C19: Population Genetic and Forensic Aspects

OpenAIRE

Sistonen, Johanna

2008-01-01

Pharmacogenetics deals with genetically determined variation in drug response. In this context, three phase I drug-metabolizing enzymes, CYP2D6, CYP2C9, and CYP2C19, have a central role, affecting the metabolism of about 20-30% of clinically used drugs. Since genes coding for these enzymes in human populations exhibit high genetic polymorphism, they are of major pharmacogenetic importance. The aims of this study were to develop new genotyping methods for CYP2D6, CYP2C9, and CYP2C19 that would...

N-methyl-D-aspartate promotes the survival of cerebellar granule cells: pharmacological characterization

DEFF Research Database (Denmark)

Balázs, R; Hack, N; Jørgensen, Ole Steen

1989-01-01

The survival of cerebellar granule cells in culture is promoted by chronic exposure to N-methyl-D-aspartate (NMDA). The effect is due to the stimulation of 'conventional' NMDA receptor-ionophore complex: it is concentration dependent, voltage dependent and blocked by the selective antagonists D-2...

Small Interfering RNA Specific for N-Methyl-D-Aspartate Receptor 2B Offers Neuroprotection to Dopamine Neurons through Activation of MAP Kinase

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Olivia T.W. Ng

2012-02-01

Full Text Available In the present study, N-methyl-D-aspartate receptor 2B (NR2B-specific siRNA was applied in parkinsonian models. Our previous results showed that reduction in expression of N-methyl-D-aspartate receptor 1 (NR1, the key subunit of N-methyl-D-aspartate receptors, by antisense oligos amelio-rated the motor symptoms in the 6-hydroxydopamine (6-OHDA-lesioned rat, an animal model of Parkinson's disease (PD [Lai et al.: Neurochem Int 2004;45:11-22]. To further the investigation on the efficacy of gene silencing, small interference RNA (siRNA specific for the NR2B subunit was designed and administered in the striatum of 6-OHDA-lesioned rats. The present results show that administration of NR2B-specific siRNA decreased the number of apomorphine-induced rotations in the lesioned rats and that there was a significant reduction in NR2B proteins levels after NR2B-specific siRNA administration. Furthermore, attenuation of the loss of dopaminergic neurons was found in both the striatal and substantia nigra regions of the 6-OHDA-lesioned rats that had been continuously infused with siRNA for 7 days. In addition, a significant upregulation of p-p44/42 MAPK (ERK1/2; Thr202/Tyr204 and p-CREB (Ser133 in striatal neurons was found. These results suggest that application of the gene silencing targeting NR2B could be a potential treatment of PD, and they also revealed the possibility of NR2B-specific siRNA being involved in the prosurvival pathway.

Decomposition reaction rate of BCl3-C3H6(propene)-H2 in the gas phase.

Science.gov (United States)

Xiao, Jun; Su, Kehe; Liu, Yan; Ren, Hongjiang; Zeng, Qingfeng; Cheng, Laifei; Zhang, Litong

2012-07-05

The decomposition reaction rate in the BCl(3)-C(3)H(6)-H(2) gas phase reaction system in preparing boron carbides was investigated based on the most favorable reaction pathways proposed by Jiang et al. [Theor. Chem. Accs. 2010, 127, 519] and Yang et al. [J. Theor. Comput. Chem. 2012, 11, 53]. The rate constants of all the elementary reactions were evaluated with the variational transition state theory. The vibrational frequencies for the stationary points as well as the selected points along the minimum energy paths (MEPs) were calculated with density functional theory at the B3PW91/6-311G(d,p) level and the energies were refined with the accurate model chemistry method G3(MP2). For the elementary reaction associated with a transition state, the MEP was obtained with the intrinsic reaction coordinates, while for the elementary reaction without transition state, the relaxed potential energy surface scan was employed to obtain the MEP. The rate constants were calculated for temperatures within 200-2000 K and fitted into three-parameter Arrhenius expressions. The reaction rates were investigated by using the COMSOL software to solve numerically the coupled differential rate equations. The results show that the reactions are, consistent with the experiments, appropriate at 1100-1500 K with the reaction time of 30 s for 1100 K, 1.5 s for 1200 K, 0.12 s for 1300 K, 0.011 s for 1400 K, or 0.001 s for 1500 K, for propene being almost completely consumed. The completely dissociated species, boron carbides C(3)B, C(2)B, and CB, have very low concentrations, and C(3)B is the main product at higher temperatures, while C(2)B is the main product at lower temperatures. For the reaction time 1 s, all these concentrations approach into a nearly constant. The maximum value (in mol/m(3)) is for the highest temperature 1500 K with the orders of -13, -17, and -23 for C(3)B, C(2)B, and CB, respectively. It was also found that the logarithm of the overall reaction rate and reciprocal

Assessment of terbium (III) as a luminescent probe for the detection of tuberculosis biomarkers

International Nuclear Information System (INIS)

Bamogo, W.; Mugherli, L.; Banyasz, A.; Novelli-Rousseau, A.; Mallard, F.; Tran-Thi, T.-H.

2015-01-01

A detection method for nicotinic acid, a specific metabolite marker of Mycobacterium tuberculosis present in cultures and patients' breath, is studied in complex solutions containing other metabolites and in biological media such as urine, saliva and breath condensate. The method is based on the analysis of the luminescence increase of Tb 3+ complexes in the presence of nicotinic acid due to the energy transfer from the excited ligand to the lanthanide ion. It is shown that other potential markers found in M. tuberculosis culture supernatant, such as methyl phenylacetate, p-methyl anisate, methyl nicotinate and 2-methoxy biphenyl, can interfere with nicotinic acid via a competitive absorption of the excitation photons. A new strategy to circumvent these interferences is proposed with an upstream trapping of volatile markers preceding the detection of nicotinic acid in the liquid phase via the luminescence of Tb 3+ complexes. The cost of the method is evaluated and compared with the Xpert MTB/RIF test endorsed by the World Health Organization. - Highlights: • Nicotinic acid, a specific marker of M. tuberculosis, can be detected via luminescence. • The detection limit with a commercial phosphorimeter is 0.4 µmol·L -1 . • Other metabolites of M. tuberculosis can interfere via absorbed excitation light. • The interference can be removed via trapping of the most volatile metabolites. • A breath analysis procedure's cost is compared with the Xpert TBM/RIF test.

Assessment of terbium (III) as a luminescent probe for the detection of tuberculosis biomarkers

Energy Technology Data Exchange (ETDEWEB)

Bamogo, W. [CNRS, IRAMIS, UMR 3685 NIMBE/LEDNA, F-91191 Gif-sur-Yvette (France); Mugherli, L. [CEA, IRAMIS, UMR 3685 NIMBE/LEDNA, F-91191 Gif-sur-Yvette (France); Banyasz, A. [CNRS, IRAMIS, LIDyL/Laboratoire Francis Perrin, URA 2453, F-91191 Gif-sur-Yvette (France); Novelli-Rousseau, A.; Mallard, F. [BioMérieux SA, F-38000 Grenoble (France); Tran-Thi, T.-H., E-mail: thu-hoa.tran-thi@cea.fr [CNRS, IRAMIS, UMR 3685 NIMBE/LEDNA, F-91191 Gif-sur-Yvette (France)

2015-10-08

A detection method for nicotinic acid, a specific metabolite marker of Mycobacterium tuberculosis present in cultures and patients' breath, is studied in complex solutions containing other metabolites and in biological media such as urine, saliva and breath condensate. The method is based on the analysis of the luminescence increase of Tb{sup 3+} complexes in the presence of nicotinic acid due to the energy transfer from the excited ligand to the lanthanide ion. It is shown that other potential markers found in M. tuberculosis culture supernatant, such as methyl phenylacetate, p-methyl anisate, methyl nicotinate and 2-methoxy biphenyl, can interfere with nicotinic acid via a competitive absorption of the excitation photons. A new strategy to circumvent these interferences is proposed with an upstream trapping of volatile markers preceding the detection of nicotinic acid in the liquid phase via the luminescence of Tb{sup 3+} complexes. The cost of the method is evaluated and compared with the Xpert MTB/RIF test endorsed by the World Health Organization. - Highlights: • Nicotinic acid, a specific marker of M. tuberculosis, can be detected via luminescence. • The detection limit with a commercial phosphorimeter is 0.4 µmol·L{sup -1}. • Other metabolites of M. tuberculosis can interfere via absorbed excitation light. • The interference can be removed via trapping of the most volatile metabolites. • A breath analysis procedure's cost is compared with the Xpert TBM/RIF test.

1H and 13C NMR studies of palladium(2) and platinium(2) complexes with S-Methyl-L-Cysteine

International Nuclear Information System (INIS)

Allain, A.; Jezowska-Trzebiatowska, B.; Kozlowski, H.

1979-01-01

Our recent 1 H NMR studies on Pd(2)-S-Methyl-L-Cysteine(SMC) complexes have shown that the use of a conformational analysis to establish the complexed species existing in solution may provide clearer results than considering the proton chemical shift only. However, the use of the vicinal coupling constant of ABC spectrum of αCH-βCH 2 proton unit to estimate the rotational isomer fractions, may contain some ambiguity, especially on the proton assignment of the methylene group. For this reason 13 C NMR method has been applied to study these systems. (author)

Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2, NPR2, AR, SP140 Methylation and Clinical Phenotype.

Science.gov (United States)

Chen, Yung-Che; Chen, Ting-Wen; Su, Mao-Chang; Chen, Chung-Jen; Chen, Kuang-Den; Liou, Chia-Wei; Tang, Petrus; Wang, Ting-Ya; Chang, Jen-Chieh; Wang, Chin-Chou; Lin, Hsin-Ching; Chin, Chien-Hung; Huang, Kuo-Tung; Lin, Meng-Chih; Hsiao, Chang-Chun

2016-04-01

We hypothesized that DNA methylation patterns may contribute to disease severity or the development of hypertension and excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA). Illumina's (San Diego, CA, USA) DNA methylation 27-K assay was used to identify differentially methylated loci (DML). DNA methylation levels were validated by pyrosequencing. A discovery cohort of 15 patients with OSA and 6 healthy subjects, and a validation cohort of 72 patients with sleep disordered breathing (SDB). Microarray analysis identified 636 DMLs in patients with OSA versus healthy subjects, and 327 DMLs in patients with OSA and hypertension versus those without hypertension. In the validation cohort, no significant difference in DNA methylation levels of six selected genes was found between the primary snoring subjects and OSA patients (primary outcome). However, a secondary outcome analysis showed that interleukin-1 receptor 2 (IL1R2) promoter methylation (-114 cytosine followed by guanine dinucleotide sequence [CpG] site) was decreased and IL1R2 protein levels were increased in the patients with SDB with an oxygen desaturation index > 30. Androgen receptor (AR) promoter methylation (-531 CpG site) and AR protein levels were both increased in the patients with SDB with an oxygen desaturation index > 30. Natriuretic peptide receptor 2 (NPR2) promoter methylation (-608/-618 CpG sites) were decreased, whereas levels of both NPR2 and serum C type natriuretic peptide protein were increased in the SDB patients with EDS. Speckled protein 140 (SP140) promoter methylation (-194 CpG site) was increased, and SP140 protein levels were decreased in the patients with SDB and EDS. IL1R2 hypomethylation and AR hypermethylation may constitute an important determinant of disease severity, whereas NPR2 hypomethylation and SP140 hypermethylation may provide a biomarker for vulnerability to EDS in OSA. A commentary on this article appears in this issue on page 723. © 2016

Purification, crystallization and preliminary X-ray crystallographic studies of Rv3705c from Mycobacterium tuberculosis

International Nuclear Information System (INIS)

Lu, Feifei; Gao, Feng; Li, Honglin; Gong, Weimin; Zhou, Lin; Bi, Lijun

2014-01-01

The cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of Rv3705c from M. tuberculosis are described. The conserved protein Rv3705c from Mycobacterium tuberculosis has been cloned, expressed, purified and crystallized by the sitting-drop vapour-diffusion method using PEG 3350 as a precipitant. The Rv3705c crystals exhibited space group P6 1 22 or P6 5 22, with unit-cell parameters a = b = 198.0, c = 364.1 Å, α = β = 90, γ = 120°, and diffracted to a resolution of 3.3 Å

Purification, crystallization and preliminary X-ray crystallographic studies of Rv3705c from Mycobacterium tuberculosis

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Lu, Feifei [East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, People’s Republic of (China); Gao, Feng [Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People’s Republic of (China); Li, Honglin [East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, People’s Republic of (China); Gong, Weimin [Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People’s Republic of (China); Zhou, Lin, E-mail: gdtb-bg@vip.163.com [Center for Tuberculosis Control of Guangdong Province, Guangzhou, People’s Republic of (China); Bi, Lijun, E-mail: gdtb-bg@vip.163.com [East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, People’s Republic of (China)

2014-07-23

The cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of Rv3705c from M. tuberculosis are described. The conserved protein Rv3705c from Mycobacterium tuberculosis has been cloned, expressed, purified and crystallized by the sitting-drop vapour-diffusion method using PEG 3350 as a precipitant. The Rv3705c crystals exhibited space group P6{sub 1}22 or P6{sub 5}22, with unit-cell parameters a = b = 198.0, c = 364.1 Å, α = β = 90, γ = 120°, and diffracted to a resolution of 3.3 Å.

Horizontal acquisition of a hypoxia-responsive molybdenum cofactor biosynthesis pathway contributed to Mycobacterium tuberculosis pathoadaptation.

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Levillain, Florence; Poquet, Yannick; Mallet, Ludovic; Mazères, Serge; Marceau, Michael; Brosch, Roland; Bange, Franz-Christoph; Supply, Philip; Magalon, Axel; Neyrolles, Olivier

2017-11-01

The unique ability of the tuberculosis (TB) bacillus, Mycobacterium tuberculosis, to persist for long periods of time in lung hypoxic lesions chiefly contributes to the global burden of latent TB. We and others previously reported that the M. tuberculosis ancestor underwent massive episodes of horizontal gene transfer (HGT), mostly from environmental species. Here, we sought to explore whether such ancient HGT played a part in M. tuberculosis evolution towards pathogenicity. We were interested by a HGT-acquired M. tuberculosis-specific gene set, namely moaA1-D1, which is involved in the biosynthesis of the molybdenum cofactor. Horizontal acquisition of this gene set was striking because homologues of these moa genes are present all across the Mycobacterium genus, including in M. tuberculosis. Here, we discovered that, unlike their paralogues, the moaA1-D1 genes are strongly induced under hypoxia. In vitro, a M. tuberculosis moaA1-D1-null mutant has an impaired ability to respire nitrate, to enter dormancy and to survive in oxygen-limiting conditions. Conversely, heterologous expression of moaA1-D1 in the phylogenetically closest non-TB mycobacterium, Mycobacterium kansasii, which lacks these genes, improves its capacity to respire nitrate and grants it with a marked ability to survive oxygen depletion. In vivo, the M. tuberculosis moaA1-D1-null mutant shows impaired survival in hypoxic granulomas in C3HeB/FeJ mice, but not in normoxic lesions in C57BL/6 animals. Collectively, our results identify a novel pathway required for M. tuberculosis resistance to host-imposed stress, namely hypoxia, and provide evidence that ancient HGT bolstered M. tuberculosis evolution from an environmental species towards a pervasive human-adapted pathogen.

The incorporation of [1-14C] acetate into the methyl ketones that occur in steam-distillates of bovine milk fat.

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Lawrence, R C; Hawke, J C

1966-01-01

1. The (14)C-labelling of the fatty acids and the methyl ketones in steam-distillates of milk fat from a lactating cow that had been injected intravenously with [1-(14)C]acetate was determined. 2. The labelling patterns of the C(6)-C(16) fatty acids and the corresponding methyl ketones with one fewer carbon atoms were similar, particularly so for the C(5)-C(10) compounds at 9 and 22hr. after the injection of [1-(14)C]acetate. The isolation of (14)C-labelled methyl ketones in the range C(3)-C(15) is evidence that the beta-oxo acid precursors, which are glyceride-bound in the milk fat, are synthesized in the mammary gland from acetate. The absence of heptadecan-2-one in steam-distillates and the extremely low specific radioactivity of stearic acid are further evidence for this biosynthetic pathway. 3. The specific radioactivities of the C(5)-C(15) methyl ketones were higher (with the exception of C(9) methyl ketone in the second milking) than the specific activities of the corresponding fatty acids with one more carbon atom. This is consistent with the methyl ketone precursors' being formed during the biosynthesis of fatty acids rather than being products of beta-oxidation of fatty acids.

Electrophysiological evidence for the presence of NR2C subunits of N-methyl-D-aspartate receptors in rat neurons of the nucleus tractus solitarius

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V. Baptista

2005-01-01

Full Text Available The nucleus tractus solitarius (NTS plays an important role in the control of autonomic reflex functions. Glutamate, acting on N-methyl-D-aspartate (NMDA and non-NMDA ionotropic receptors, is the major neurotransmitter in this nucleus, and the relative contribution of each receptor to signal transmission is unclear. We have examined NMDA excitatory postsynaptic currents (NMDA-EPSCs in the subpostremal NTS using the whole cell patch clamp technique on a transverse brainstem slice preparation. The NMDA-EPSCs were evoked by stimulation of the solitary tract over a range of membrane potentials. The NMDA-EPSCs, isolated pharmacologically, presented the characteristic outward rectification and were completely blocked by 50 µM DL-2-amino-5-phosphonopentanoic acid. The I-V relationship of the NMDA response shows that current, with a mean (± SEM amplitude of -41.2 ± 5.5 pA, is present even at a holding potential of -60 mV, suggesting that the NMDA receptors are weakly blocked by extracellular Mg2+ at near resting membrane potentials. This weak block can also be inferred from the value of 0.67 ± 0.17 for parameter delta obtained from a fit of the Woodhull equation to the I-V relationship. The maximal inward current measured on the I-V relationship was at -38.7 ± 4.2 mV. The decay phase of the NMDA currents was fitted with one exponential function with a decay time constant of 239 ± 51 and 418 ± 80 ms at a holding potential of -60 and +50 mV, respectively, which became slower with depolarization (e-fold per 145 mV. The biophysical properties of the NMDA receptors observed in the present study suggest that these receptors in the NTS contain NR2C subunits and may contribute to the synaptic signal integration.

Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study

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Chin, Melanie P.; Bakris, George L.; Block, Geoffrey A.; Chertow, Glenn M.; Goldsberry, Angie; Inker, Lesley A.; Heerspink, Hiddo J.L.; O'Grady, Megan; Pergola, Pablo E.; Wanner, Christoph; Warnock, David G.; Meyer, Colin J.

2018-01-01

Background Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Methods Patients in ­BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Results Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36–0.64]; p < 0.0001). Conclusions Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. PMID:29402767

[14C]-radiolabeling of {[trans-(8β)]-6-methyl-1-(1-methylethyl) ergoline-8-carboxylic acid, 4-methoxycyclohexyl ester (Z)-2-buteneidioate (1:1)}

International Nuclear Information System (INIS)

Marzoni, G.; Wheeler, W.J.; Garbrecht, W.L.

1988-01-01

The 5HT 2 -receptor antagonist, [ 14 C]-labeled brace[trans-(8β)]-6-methyl-1-(1-methylethyl)ergoline-8-carboxylic acid, 4-methoxycyclohexyl ester (Z)-2-butenedioate (1:1)brace (LY281067) was synthesized from unlabeled 6-methyl-1-(1-methylethyl)ergoline-8-carboxylic acid. The [ 14 C] label was introduced into the carboxyl group attached to the 8 position of the ergoline nucleus. This site is stable to metabolism. The synthesis involves removal of an unlabeled carboxyl group and subsequent reinsertion of a [ 14 C]-labeled carboxyl group into the same position. The radiolabel is not introduced until near the end of the synthesis which allows for ease of handling and scale-up of intermediates. (author)

Reduced Histone H3 Lysine 9 Methylation Contributes to the Pathogenesis of Latent Autoimmune Diabetes in Adults via Regulation of SUV39H2 and KDM4C

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Xi-yu Liu

2017-01-01

Full Text Available Aims. Latent autoimmune diabetes in adults (LADA is an autoimmune disease of which the mechanism is not clear. Emerging evidence suggests that histone methylation contributes to autoimmunity. Methods. Blood CD4+ T lymphocytes from 26 LADA patients and 26 healthy controls were isolated to detect histone H3 lysine 4 and H3 lysine 9 methylation status. Results. Reduced global H3 lysine 9 methylation was observed in LADA patients’ CD4+ T lymphocytes, compared to healthy controls (P < 0.05. H3 lysine 4 methylation was not statistically different. The reduced H3 lysine 9 methylation was associated with GADA titer but not correlated with glycosylated hemoglobin (HbA1c. When the LADA patient group was divided into those with complication and those without, relatively reduced global H3 lysine 9 methylation was observed in LADA patients with complication (P < 0.05. The expression of histone methyltransferase SUV39H2 for H3 lysine 9 methylation was downregulated in LADA patients, and the expression of histone demethylase KDM4C which made H3 lysine 9 demethylation was upregulated. Conclusion. The reduction of histone H3 lysine 9 methylation which may due to the downregulation of methyltransferase SUV39H2 and the upregulation of demethylase KDM4C was found in CD4+ T lymphocytes of LADA patients.

Carotenoid Derivates in Achiote (Bixa orellana Seeds: Synthesis and Health Promoting Properties

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Renata Rivera-Madrid

2016-09-01

Full Text Available Bixa orellana (family Bixaceae is a neotropical fast growing perennial tree of great agro-industrial value because its seeds have a high carotenoid content, mainly bixin. It has been used since pre-colonial times as a culinary colorant and spice, and for healing purposes. It is currently used as a natural pigment in the food, in pharmaceutical, and cosmetic industries, and it is commercially known as annatto. Recently, several studies have addressed the biological and medical properties of this natural pigment, both as potential source of new drugs or because its ingestion as a condiment or diet supplement may protect against several diseases. The most documented properties are anti-oxidative; but its anti-cancer, hypoglucemic, antibiotic and anti-inflammatory properties are also being studied. Bixin’s pathway elucidation and its regulation mechanisms are critical to improve the produce of this important carotenoid. Even though the bixin pathway has been established, the regulation of the genes involved in bixin production remains largely unknown. Our laboratory recently published B. orellana’s transcriptome and we have identified most of its MEP (methyl-D-erythritol 4-phosphate and carotenoid pathway genes. Annatto is a potential source of new drugs and can be a valuable nutraceutical supplement. However, its nutritional and healing properties require further study.

DNA methylation of candidate genes in peripheral blood from patients with type 2 diabetes or the metabolic syndrome.

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van Otterdijk, Sanne D; Binder, Alexandra M; Szarc Vel Szic, Katarzyna; Schwald, Julia; Michels, Karin B

2017-01-01

The prevalence of type 2 diabetes (T2D) and the metabolic syndrome (MetS) is increasing and several studies suggested an involvement of DNA methylation in the development of these metabolic diseases. This study was designed to investigate if differential DNA methylation in blood can function as a biomarker for T2D and/or MetS. Pyrosequencing analyses were performed for the candidate genes KCNJ11, PPARγ, PDK4, KCNQ1, SCD1, PDX1, FTO and PEG3 in peripheral blood leukocytes (PBLs) from 25 patients diagnosed with only T2D, 9 patients diagnosed with T2D and MetS and 11 control subjects without any metabolic disorders. No significant differences in gene-specific methylation between patients and controls were observed, although a trend towards significance was observed for PEG3. Differential methylation was observed between the groups in 4 out of the 42 single CpG loci located in the promoters regions of the genes FTO, KCNJ11, PPARγ and PDK4. A trend towards a positive correlation was observed for PEG3 methylation with HDL cholesterol levels. Altered levels of DNA methylation in PBLs of specific loci might serve as a biomarker for T2D or MetS, although further investigation is required.

DNA methylation of candidate genes in peripheral blood from patients with type 2 diabetes or the metabolic syndrome.

Directory of Open Access Journals (Sweden)

Sanne D van Otterdijk

Full Text Available The prevalence of type 2 diabetes (T2D and the metabolic syndrome (MetS is increasing and several studies suggested an involvement of DNA methylation in the development of these metabolic diseases. This study was designed to investigate if differential DNA methylation in blood can function as a biomarker for T2D and/or MetS.Pyrosequencing analyses were performed for the candidate genes KCNJ11, PPARγ, PDK4, KCNQ1, SCD1, PDX1, FTO and PEG3 in peripheral blood leukocytes (PBLs from 25 patients diagnosed with only T2D, 9 patients diagnosed with T2D and MetS and 11 control subjects without any metabolic disorders.No significant differences in gene-specific methylation between patients and controls were observed, although a trend towards significance was observed for PEG3. Differential methylation was observed between the groups in 4 out of the 42 single CpG loci located in the promoters regions of the genes FTO, KCNJ11, PPARγ and PDK4. A trend towards a positive correlation was observed for PEG3 methylation with HDL cholesterol levels.Altered levels of DNA methylation in PBLs of specific loci might serve as a biomarker for T2D or MetS, although further investigation is required.

Syntheses of {gamma}-aminobutyric-1-{sup 14}C and of {alpha}-aminoadipic-6-{sup 14}C acid from methoxy-3 chloropropyl-magnesium and marked carbon dioxide; Syntheses de l'acide {gamma}-aminobutyrique{sup 14}C-1 et de l'acide {alpha}-aminoadipique {sup 14}C-6 a partir de methoxy-3 chloropropylmagnesium et d'anhydride carbonique marque

Energy Technology Data Exchange (ETDEWEB)

Liem, Phung Nhu [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires, Departement des radioelements, Service des molecules marquees

1967-04-01

Carbonation of {gamma}-methoxypropyl-magnesium chloride by CO{sub 2} gives {gamma}-methoxy-butyric carboxylic-{sup 14}C acid with a yield of about 95 per cent. When the latter is treated successively with anhydrous HBr and with diazomethane, methyl carboxylic {gamma}-bromobutyrate-{sup 14}C is formed. This in turn gives {gamma}-amino-butyric carboxylic-{sup 14}C acid with an overall yield of 66 per cent with respect to Ba{sup 14}CO{sub 3}, when it is condensed with potassium phthalimide and hydrolyzed by acid. By reacting methyl-{gamma}-bromobutyrate-{sup 14}C with the sodium derivative of ethyl cyanacetamido-acetate in ethanol, followed by an acid hydrolysis, {alpha}-aminoadipic-6-{sup 14}C acid is obtained with an overall yield of 46 per cent with respect to Ba{sup 14}CO{sub 3}. (author) [French] La carbonatation du chlorure de {gamma}-methoxypropylmagnesium par {sup 14}CO{sub 2} donne l'acide {gamma}-methoxybutyrique carboxyle {sup 14}C avec un rendement d'environ 95 pour cent. Ce dernier traite successivement par HBr anhydre et par le diazomethane conduit au {gamma}-bromobutyrate de methyle carboxyle {sup 14}C. Celui-ci condense avec le phtalimide de potassium suivi d'une hydrolyse acide fournit l'acide {gamma}-aminobutyrique carboxyle {sup 14}C avec un rendement global de 66 pour cent par rapport a Ba{sup 14}CO{sub 3}. L'action du {gamma}-bromobutyrate de methyle {sup 14}C sur le derive sode du cyanacetamidoacetate d'ethyle dans l'ethanol suivie d'hydrolyse acide donne l'acide {alpha}-aminoadipique {sup 14}C-6 avec un rendement global de 46 pour cent par rapport a Ba{sup 14}CO{sub 3}. (auteur)

Design, Synthesis, and X-ray Crystal Structures of 2,4-Diaminofuro[2,3-d]pyrimidines as Multireceptor Tyrosine Kinase and Dihydrofolate Reductase Inhibitors