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Sample records for purine base derivatives

  1. Excretion of purine base derivatives after intake of bacterial protein meal in pigs

    DEFF Research Database (Denmark)

    Hellwing, Anne Louise Frydendahl; Tauson, Anne-Helene; Skrede, A.

    2007-01-01

    Bacterial protein meal has a high content ofprotein but also of RNA and DNA. Sixteen barrows were allocated to four diets containing increasing levels of bacterial protein meal (BPM), from weaning to 80 kg live weight, to evaluate whether the RNA and DNA contents of BPM influenced the retention...... of nitrogen. It was hypothesised that an increased intake of RNA and DNA would lead to an increased urinary excretion of purine base derivatives and increased plasma concentrations. Retention of nitrogen was unaffected by dietary content of BPM (P=0.08) and the urinary excretion of purine base derivatives...... increased with increasing dietary content of BPM. No differences in fasting plasma concentration of uric acid, xanthine and hypoxanthine were observed. It can therefore be concluded that increasing levels of dietary BPM maintained protein accretion and led to changes in excretion of purine detrivatices...

  2. [Determination of purine compounds and purine bases in food].

    Science.gov (United States)

    Colling, M; Wolfram, G

    1987-10-01

    The total purine content and the content of RNA, DNA, nucleotides, nucleosides and free purine bases has been determined in commercial raw food. After hydrolysing food samples with acid, the total purine content is enzymatically determined as uric acid. For the determination of the nucleic acid content, a method is chosen that allows for the analysis of the composition of nucleic acids. The amount of purine bound in nucleic acids and of purine bound in nucleotides, nucleosides and free bases is very different. The content of nucleic acids is especially high in the innards of veal, pork and beef. In these samples the quantity of purine bound in nucleotides, nucleosides and bases is very small. In trout and herring, however, more purine is bound in RNA and DNA. The same is true of roe, pork and beef muscle. Peas and beans have the lowest total purine content of all the samples examined.

  3. Crystallographic and Computational Study of Purine: Caffeine Derivative

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    Ahmed F. Mabied

    2014-01-01

    Full Text Available The crystal structure of substituted purine derivative, 8-(3-butyl-4-phenyl-2,3-dihydrothiazol-2-ylidenehydrazino-3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-diones, caffeine derivative, has been determined. It crystallized in monoclinic system and space group P21/c with unit cell parameters a = 15.2634 (9, b = 13.4692 (9, c = 11.9761 (7 Å, and β = 108.825 (3°. Although each constituting moiety of the structure individually is planar, nonplanar configuration for the whole molecule was noticed. Molecular mechanics computations indicated the same nonplanar feature of the whole molecule. A network of intermolecular hydrogen bonds contacts and π interactions stabilized the structure.

  4. Synthesis, spectral, antitumor and antimicrobial studies on Cu(II) complexes of purine and triazole Schiff base derivatives

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    Amer, Said; El-Wakiel, Nadia; El-Ghamry, Hoda

    2013-10-01

    A series of copper (II) complexes of Schiff bases derived from 7H-2,6-diaminopurine and 4H-3,5-diamino-1,2,4-triazole with 2-pyridinecarbaldehyde, salicylaldehyde, 2,4-dihydroxybenzaldehyde and 2-hydroxy-1-naphthaldehyde have been prepared. The donor atoms and the possible geometry of the complexes were investigated by means of elemental and thermal analyses, molar conductance, magnetic moment, UV-Vis, IR, ESR and mass spectra. The ligands behaved as tetradentate, coordinating through the nitrogen atom of the azomethine group and the nearest nitrogen atom to it or oxygen atom of α-hydroxyl group. The results of simultaneous DTA & TGA analyses of the complexes showed the final degradation product for these complexes is CuO. The spectral studies confirmed a four coordinate environment around the metal ion. The obtained results were supported by 3D molecular modeling of complexes using molecular mechanics (MM+) and semiempirical molecular orbital calculations (PM3). These complexes were also tested for their in vitro antimicrobial activities against some bacterial and fungal strains. Complex 2 was investigated for its cyctotoxic effect against human breast cancer (MCF7), liver carcinoma (HEPG2) and colon carcinoma cell lines (HCT116). This compound exhibited a moderate activity against the tested cell lines with IC50 of 10.3, 9.8 and 8.7 μg/ml against MCF7, HCT116 and HEPG2, respectively.

  5. Serotonin transporter activity of imidazolidine-2,4-dione and imidazo[2,1-f]purine-2,4-dione derivatives in aspect of their acid-base properties.

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    Zagórska, Agnieszka; Czopek, Anna; Pawłowski, Maciej; Dybała, Małgorzata; Siwek, Agata; Nowak, Gabriel

    2012-11-01

    Affinities of arylpiperazinylalkyl derivatives of imidazo[2,1-f]purine-2,4-dione and imidazolidine-2,4-dione for serotonin transporter and their acid-base properties were evaluated. The dissociation constant (pK(a)) of compounds 1-22 were determinated by potentiometric titration and calculated using pKalc 3.1 module of the Pallas system. The data from experimental methods and computational calculations were compared and suitable conclusions were reached.

  6. Total purine and purine base content of common foodstuffs for facilitating nutritional therapy for gout and hyperuricemia.

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    Kaneko, Kiyoko; Aoyagi, Yasuo; Fukuuchi, Tomoko; Inazawa, Katsunori; Yamaoka, Noriko

    2014-01-01

    Purines are natural substances found in all of the body's cells and in virtually all foods. In humans, purines are metabolized to uric acid, which serves as an antioxidant and helps to prevent damage caused by active oxygen species. A continuous supply of uric acid is important for protecting human blood vessels. However, frequent and high intake of purine-rich foods reportedly enhances serum uric acid levels, which results in gout and could be a risk factor for cardiovascular disease, kidney disease, and metabolic syndrome. In Japan, the daily intake of dietary purines is recommended to be less than 400 mg to prevent gout and hyperuricemia. We have established an HPLC method for purine analysis and determined purines in a total of 270 foodstuffs. A relatively small number of foods contained concentrated amounts of purines. For the most part, purine-rich foods are also energy-rich foods, and include animal meats, fish meats, organs such as the liver and fish milt, and yeast. When the ratio of the four purine bases (adenine, guanine, hypoxanthine, and xanthine) was compared, two groups of foods were identified: one that contained mainly adenine and guanine and one that contained mainly hypoxanthine. For patients with gout and hyperuricemia, the amount of total purines and the types of purines consumed, particularly hypoxanthine, are important considerations. In this context, the data from our analysis provide a purine content reference, and thereby clinicians and patients could utilize that reference in nutritional therapy for gout and hyperuricemia.

  7. Antimalarial activity of thiosemicarbazones and purine derived nitriles

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    Mallari, Jeremy P.; Guiguemde, Wendyam A.; Guy, R. Kiplin

    2009-01-01

    Malaria is a devastating illness caused by multiple species of the Plasmodium genus. The parasite’s food vacuole of falcipain proteases have been extensively studied as potential drug targets. Here we report the testing of two established cysteine protease inhibitor scaffolds against both chloroquine sensitive and chloroquine resistant parasites. A subset of purine derived nitriles killed the parasite with moderate potency, and these inhibitors do not seem to exert their antiproliferative effects as cysteine protease inhibitors. Compound potency was determined to be similar against both parasite strains, indicating a low probability of cross resistance with chloroquine. These compounds represent a novel antimalarial scaffold, and a potential starting point for the development new inhibitors. PMID:19447616

  8. Synthesis of novel chiral compounds of purine and pyrimidine bases

    Institute of Scientific and Technical Information of China (English)

    汪毓海; 陈庆华

    1999-01-01

    The physiologically active groups such as purine and pyrimidine bases are introduced to the asymmetric ynthesis. The optically pure compounds bearing purine and pyrimidine bases (5a—5e) were prepared via the asymetric Michael addition reaction of purines and pyrimidines as Michael donators with the chiral source 5-(R)-[(1R, 2S, 5R)-menthyloxy]-2(5H)-furanone (3a), which was prepared from the natural chiral auxiliary (-)-menthol. The synthetic method was studied in detail and the new compounds were identified on the basis of their analytical data and spectroscopic data, such as [α]D20, IR, UV, 1H NMR, 13C NMR and MS. The absolute configuration of 5a was established by X-ray crystallography. The results provided an efficient synthetic route to chiral purines and pyrimidine analogues, and offered chiral sources for further research on the physiologically active compounds of chiral nucleotides.

  9. Purine derivate content and amino acid profile in larval stages of three edible insects.

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    Bednářová, Martina; Borkovcová, Marie; Komprda, Tomáš

    2014-01-15

    Considering their high content of protein, insects are a valuable alternative protein source. However, no evaluation of their purine content has so far been done. High content of purine derivates may lead to the exclusion of such food from the diet of people with specific diseases. The aim of this study was to analyse the content of selected purine derivates and amino acid profile in the three insect species most often used for entomophagy in Europe and compare them with the purine content in egg white and chicken breast. The content of individual purine derivates and their total content were significantly dependent on insect species. The purine content in all three species was significantly higher (P content was 548.9 g kg(-1) dry matter (DM) in mealworm (Tenebrio molitor), 551.6 g kg(-1) DM in superworm (Zophobas atratus) and 564.9 g kg(-1) DM in cricket (Gryllus assimilis). Larvae of mealworm and superworm are protein-rich and purine-low meat alternatives. In contrast, cricket nymphs are protein-rich and purine-rich and cannot be recommended for people with hyperuricemia or gout. © 2013 Society of Chemical Industry.

  10. Effect of purine alkaloids on the proliferation of lettuce cells derived from protoplasts.

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    Sasamoto, Hamako; Fujii, Yoshiharu; Ashihara, Hiroshi

    2015-05-01

    To investigate the ecological role of caffeine, theobromine, theophylline and paraxanthine, which are released from purine alkaloid forming plants, the effects of these purine alkaloids on the division and colony formation of lettuce cells were assessed at concentrations up to 1 mM. Five days after treatment with 500 μM caffeine, theophylline and paraxanthine, division of isolated protoplasts was significantly inhibited. Thirteen days treatment with > 250 μM caffeine had a marked inhibitory effect on the colony formation of cells derived from the protoplasts. Other purine alkaloids also acted as inhibitors. The order of the inhibition was caffeine > theophylline > paraxanthine > theobromine. These observations suggest that a relatively low concentration of caffeine is toxic for proliferation of plant cells. In contrast, theobromine is a weak inhibitor of proliferation. Possible allelopathic roles of purine alkaloids in natural ecosystems are discussed.

  11. TD-DFT Investigation of the Magnetic Circular Dichroism Spectra of Some Purine and Pyrimidine Bases of Nucleic Acids

    DEFF Research Database (Denmark)

    Fahleson, Tobias; Kauczor, Joanna; Norman, Patrick

    2015-01-01

    We present a computational study of the magnetic circular dichroism (MCD) spectra in the 200–300 nm wavelength region of purine and its derivative hypoxanthine, as well as of the pyrimidine bases of nucleic acids uracil, thymine, and cytosine, using the B3LYP and CAM–B3LYP functionals. Solvent...... effects are investigated within the polarizable continuum model and by inclusion of explicit water molecules. In general, the computed spectra are found to be in good agreement with the experimental ones, apart from some overall blue shifts. Both the pseudo-A term shape of the MCD spectra of the purines...... and the B term shape of the spectra of pyrimidine bases are reproduced. Our calculations also correctly reproduce the reversed phase of the MCD bands in purine compared to that of its derivatives present in nucleic acids. Solvent effects are sizable and system specific, but they do not in general alter...

  12. Structural assignment of 6-oxy purine derivatives through computational modeling, synthesis, X-ray diffraction, and spectroscopic analysis.

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    Zhao, Xinyun; Chen, Xi; Yang, Guang-Fu; Zhan, Chang-Guo

    2010-05-27

    6-Oxy purine derivatives have been considered as potential therapeutic agents in various drug discovery efforts reported in the literature. However, the structural assignment of this important class of compounds has been controversial concerning the specific position of a hydrogen atom in the structure. To theoretically determine the most favorable type of tautomeric form of 6-oxy purine derivatives, we have carried out first-principles electronic structure calculations on the possible tautomeric forms (A, B, and C) and their relative stability of four representative 6-oxy purine derivatives (compounds 1-4). The computational results in both the gas phase and aqueous solution clearly reveal that the most favorable type of tautomeric form of these compounds is A, in which a hydrogen atom bonds with the N1 atom on the purine ring. To examine the computational results, one of the 6-oxy purine derivatives (i.e., compound 4) has been synthesized and its structure has been characterized by X-ray diffraction and spectroscopic analysis. All of the obtained computational and experimental data are consistent with the conclusion that the 6-oxy purine derivative exists in tautomer A. The conclusive structural assignment reported here is expected to be valuable for future computational studies on 6-oxy purine derivative binding with proteins and for computational drug design involving this type of compounds.

  13. Purine Bases in Blood Plasma of Patients with Chronic Pulmonary Diseases

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    Larissa E. Muravluyova

    2012-09-01

    Full Text Available The article is focused on the study of purine bases and intermediates of purine catabolism in plasma of patients with chronic obstructive bronchitis and idiopathic interstitial pneumonia. Decrease of adenine and hypoxantine in plasma of patients with idiopathic interstitial pneumonia was registered. Increase of guanine in plasma of patients with chronic obstructive pulmonary disease was established.

  14. TD-DFT investigation of the magnetic circular dichroism spectra of some purine and pyrimidine bases of nucleic acids.

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    Fahleson, Tobias; Kauczor, Joanna; Norman, Patrick; Santoro, Fabrizio; Improta, Roberto; Coriani, Sonia

    2015-05-28

    We present a computational study of the magnetic circular dichroism (MCD) spectra in the 200-300 nm wavelength region of purine and its derivative hypoxanthine, as well as of the pyrimidine bases of nucleic acids uracil, thymine, and cytosine, using the B3LYP and CAM-B3LYP functionals. Solvent effects are investigated within the polarizable continuum model and by inclusion of explicit water molecules. In general, the computed spectra are found to be in good agreement with the experimental ones, apart from some overall blue shifts. Both the pseudo-A term shape of the MCD spectra of the purines and the B term shape of the spectra of pyrimidine bases are reproduced. Our calculations also correctly reproduce the reversed phase of the MCD bands in purine compared to that of its derivatives present in nucleic acids. Solvent effects are sizable and system specific, but they do not in general alter the qualitative shape of the spectra. The bands are dominated by the bright π → π* transitions, and our calculations in solution nicely reproduce their energy differences, improving the estimates obtained in the gas phase. Shoulders are predicted for purine and uracil due to n → π* excitations, but they are too weak to be observed in the experiment.

  15. Effect of tempe waste on excreation of purine derivatives and microbial–N supply in lactating Etawah crossbred goats

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    D.A Astuti

    2002-10-01

    Full Text Available The aim of this study was to evaluate excretion of purine derivatives and microbial–N supply in lactating Etawah crossbred goats fed with fermented soybean waste. Sixteen first lactating goats were randomly allotted into four dietary treatment groups that received 50% king grass plus R1: 50% concentrate, R2: 25% concentrate and 25% fresh tempe waste, R3: 25% concentrate and 25% fermented tempe waste, and R4: 25% concentrate and 25% gelatinizing of liquid tempe waste. Fermented tempe waste was made by fermentation of tempe waste (seed content of soybean using Aspergillus niger, while for the gellatinizing of liquid tempe waste was made by gelatinized with maize flour. Protein balance studies were conducted during two week trial and at the end of the research. Urinary protein and purine derivatives were collected for analysis. Microbial–N supply was calculated from purine derivatives excretion. Results showed that nitrogen consumptions were significantly different between R4 and three other treatments and apparent digestible nitrogen in R3 were higher than that of R4 (P<0.05. The nitrogen retention in R1 and R3 were higher than that of R2 and R4. Urinary purine derivatives in this study showed that allantoin, xanthine and hypoxanthine in R3 were higher than that of R4, while R1 and R2 were the same and the highest uric acid excretion and total purine derivatives were observed in R3. Microbial–N supply were significantly different between all treatments where R3 was the highest. This research concluded that fermented soybean waste had the highest total purine derivatives excretion and microbial–N supply to the lactating Etawah crossbred goats.

  16. Response of urinary purine derivatives excretion to different levels of ruminal glucose infusion in heifers.

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    Dickhoefer, Uta; Ahnert, Sandra; Schoof, Hartwig; Moritz, Niels; Susenbeth, Andreas

    2015-01-01

    This study investigated the response of urinary purine derivatives (PD) excretion to increasing levels of intraruminal glucose infusion to evaluate how well this indicator reflects induced changes in microbial crude protein flow. Four rumen-cannulated heifers (482 ± 25 kg body weight) were fed at maintenance energy level with a basal diet (on fresh matter basis) of 4 kg/d hay, 1.5 kg/d concentrate and 60 g/d minerals in two equal meals. The trial comprised a control period (Control I) without glucose infusion followed by four consecutive periods in which all animals received 125 g, 250 g, 500 g or 1000 g/d of glucose, respectively. For this, daily dosages of glucose and urea (90 g/d during all periods) were divided into three portions that were dissolved in water and directly administered into the rumen during morning and afternoon feedings and once during noon. After the highest glucose dosage, a second control period was carried out (Control II). Urinary PD excretion increased with glucose infusion of 125 g/d (71.4 mmol/d) and 1000 g/d (74.2 mmol/d) over the level at Control I (53.9 mmol/d (standard error of the mean (SEM) 3.4; p = 0.012). After withdrawing glucose infusion, PD excretion (79.0 mmol/d) did not return to Control I level (p = 0.001). In contrast, faecal nitrogen (N) excretions linearly increased with incremental glucose infusion (p infusions highlight the limited accuracy of the PD excretion as a non-invasive indicator when incremental dosages of rapidly fermentable carbohydrates are supplied.

  17. Roles of the Amino Group of Purine Bases in the Thermodynamic Stability of DNA Base Pairing

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    Shu-ichi Nakano

    2014-08-01

    Full Text Available The energetic aspects of hydrogen-bonded base-pair interactions are important for the design of functional nucleotide analogs and for practical applications of oligonucleotides. The present study investigated the contribution of the 2-amino group of DNA purine bases to the thermodynamic stability of oligonucleotide duplexes under different salt and solvent conditions, using 2'-deoxyriboinosine (I and 2'-deoxyribo-2,6-diaminopurine (D as non-canonical nucleotides. The stability of DNA duplexes was changed by substitution of a single base pair in the following order: G•C > D•T ≈ I•C > A•T > G•T > I•T. The apparent stabilization energy due to the presence of the 2-amino group of G and D varied depending on the salt concentration, and decreased in the water-ethanol mixed solvent. The effects of salt concentration on the thermodynamics of DNA duplexes were found to be partially sequence-dependent, and the 2-amino group of the purine bases might have an influence on the binding of ions to DNA through the formation of a stable base-paired structure. Our results also showed that physiological salt conditions were energetically favorable for complementary base recognition, and conversely, low salt concentration media and ethanol-containing solvents were effective for low stringency oligonucleotide hybridization, in the context of conditions employed in this study.

  18. The comparative study digestion and metabolism of nitrogen and purine derivatives in male, Thai, Swamp buffalo and Thai, Brahman cattle.

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    Jetana, Thongsuk; Tasripoo, Kringsak; Vongpipatana, Cheerapath; Kitsamraj, Suriya; Sophon, Sunpeth

    2009-04-01

    Studies on in vivo digestion, rates of passages, metabolism of nitrogen, urinary purine derivative excretion and blood metabolites were carried out in Thai Brahman cattle and Thai swamp buffaloes (16 months old). The animals were fed mixed diets based on pineapple (Ananas comusus) waste silage containing urea-N (NPN) and true protein from a concentrate (TP). The Brahman cattle (310 +/- 15 kg) were heavier than the swamp buffaloes (195 +/- 9.4 kg) and had higher dry matter (DM), organic matter (OM) and neutral detergent fiber (NDF) intakes when compared on the basis of their metabolic body weight (BW(0.75)), but these intakes did not differ significantly when the diets of each animal species were compared. The total tract, apparent digestibilities of dry matter (DM) and organic matter (OM) were not significantly different between the animal species when comparing the two types of diets. The NDF digestibility was significantly (P 0.05) different in animals fed different diets. The present study demonstrated that Brahman cattle were better in fiber digestibility than swamp buffaloes at utilizing pineapple waste silage with both N sources.

  19. Contents and retentions of free and total purine bases in lamb meat cooked by several household methods

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    P. Anfossi

    2011-03-01

    Full Text Available Concerns about the content of total and free purine bases in muscle foods and their retentions upon cooking have been since long established (Brulé et al., 1988. Recently, though, an important rôle has been acknowledged to dietary sources of preformed purines for the growth of tissues with a rapid turnover and for optimal function of the cellular immune response, up to the point that the positive features of these nutrients seem to outweigh by far the negative ones (ILSI, 1998. Scanty information exists about the total purine content of raw ovine meat, the only available sources of data being a survey by Herbel and Montag (1987 on purine and pyrimidine contents of protein-rich foods and the comprehensive collection of food composition tables compiled by Scherz and Senser (1994...

  20. Interactions between DNA purinic bases and amodiaquine: A theoretical approach

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    Valdemar Lacerda Júnior

    2010-06-01

    Full Text Available We study theoretically the amodiaquine-adenine and amodiaquine-guanine adducts formation using Density Functional Theory (B3LYP and the 6-31G(d basis set for the geometry optimizations and 6-31+G(d,p for the analysis of the global indexes: electrophilicity (w, electronic chemical potential (m, hardness (h and softness (S, based in the Frontier Molecular Orbital Theory – FMO. Local softness for nucleophilic reaction (sk+ sites over guanine was evaluated using Fukui function (f k. We also evaluated the guanine Electrostatic Potential (EP values using the (MSK charge scheme. The theoretical calculations had demonstrated that the amodiaquine has greater electronic affinity for the guanine, with irreversible formation of the amodiaquine-guanine adduct, as reported before on a previous experimental work.

  1. Measurement of small scalar and dipolar couplings in purine and pyrimidine bases.

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    Zídek, L; Wu, H; Feigon, J; Sklenár, V

    2001-10-01

    A suite of spin-state-selective excitation (S3E) NMR experiments for the measurements of small one-bond (13C-13C, 15N-13C) and two-bond (1H-13C, 1H-15N) coupling constants in 13C,15N labeled purine and pyrimidine bases is presented. The incorporation of band-selective shaped pulses, elimination of the cross talk between alpha and beta sub-spectra, and accuracy and precision of the proposed approach are discussed. Merits of using S3E rather than alpha/beta-half-filter are demonstrated using results obtained on isotopically labeled DNA oligonucleotides.

  2. Pyrrolopyrimidine derivatives and purine analogs as novel activators of Multidrug Resistance-associated Protein 1 (MRP1, ABCC1).

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    Schmitt, Sven Marcel; Stefan, Katja; Wiese, Michael

    2017-01-01

    Multidrug resistance (MDR) is the main cause of diminished success in cancer chemotherapy. ABC transport proteins are considered to be one important factor of MDR. Besides P-glycoprotein (P-gp, ABCB1) and Breast Cancer Resistance Protein (BCRP, ABCG2), Multidrug Resistance-associated Protein 1 (MRP1, ABCC1) is associated with non-response to chemotherapy in different cancers. While considerable effort was spent in overcoming MDR during the last two decades, almost nothing is known with respect to activators of transport proteins. In this work we present certain pyrrolo[3,2-d]pyrimidine derivatives with variations at positions 4 and 5 and purine analogs with variations at position 6 as novel activators of MRP1-mediated transport of the MRP1 substrate calcein AM and the anticancer drug daunorubicin in low nanomolar concentration range. Two different MRP1 overexpressing cell lines were used, the doxorubicin-selected human lung cancer cell line H69 AR and the transfected Madin-Darby Canine Kidney cell line MDCK II MRP1. No effect was observed in the sensitive counterparts H69 and MDCK II wild type (wt). Derivatives with higher molecular weight possessed also inhibitory properties at low micromolar concentrations, although most compounds were rather poor MRP1 inhibitors. Purine analogs derived from potent MRP1 inhibitors of the pyrrolopyrimidine class showed equal activating, but no inhibiting effects at all. All tested compounds were non-toxic and had only minor impact on P-gp or BCRP, showing no inhibition or activation. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. [Principles of the hydrolysis of bound purine and pyrimidine bases in foods and program-controlled calculation of nucleic acid content].

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    Herbel, W; Montag, A

    1987-01-01

    In order to determine the amount of combined purine and pyrimidine bases in foods we investigated the chemical fundamentals of their hydrolytic digestion it was demonstrated that the digestion mixture used, containing trifluoracetic- and formic acids, protected the purine bases during hydrolysis from oxidative degradation due to carbon monoxide formation. Further, a time-saving computer-program was developed and presented. This program allows, depending on the purine composition, the calculation of the corresponding nucleic acids, the nucleotides and the purine-nitrogen-content of the food.

  4. Stereoselective synthesis of 2'-purine and pyrimidine derivatives of 1',4'-anhydro-2'-deoxy D-arabitol and D-altritol

    Institute of Scientific and Technical Information of China (English)

    YANG, Bing-Hui; WU, Xue-Jun

    2000-01-01

    A series of 2'-purine and pyrimidine derivatives of 1',4'-anhydro-2'-deoxy-D-arabitol (1) and 1', 4'-anhydro-2'-deoxy-Daltritoi (2) were synthesized regio- and stereo-selectively from D-sorbitol through some conversion in high yields.

  5. Adenylosuccinate Is an Insulin Secretagogue Derived from Glucose-Induced Purine Metabolism

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    Jessica R. Gooding

    2015-10-01

    Full Text Available Pancreatic islet failure, involving loss of glucose-stimulated insulin secretion (GSIS from islet β cells, heralds the onset of type 2 diabetes (T2D. To search for mediators of GSIS, we performed metabolomics profiling of the insulinoma cell line 832/13 and uncovered significant glucose-induced changes in purine pathway intermediates, including a decrease in inosine monophosphate (IMP and an increase in adenylosuccinate (S-AMP, suggesting a regulatory role for the enzyme that links the two metabolites, adenylosuccinate synthase (ADSS. Inhibition of ADSS or a more proximal enzyme in the S-AMP biosynthesis pathway, adenylosuccinate lyase, lowers S-AMP levels and impairs GSIS. Addition of S-AMP to the interior of patch-clamped human β cells amplifies exocytosis, an effect dependent upon expression of sentrin/SUMO-specific protease 1 (SENP1. S-AMP also overcomes the defect in glucose-induced exocytosis in β cells from a human donor with T2D. S-AMP is, thus, an insulin secretagogue capable of reversing β cell dysfunction in T2D.

  6. 1,3,5-Triazine-based analogues of purine: from isosteres to privileged scaffolds in medicinal chemistry.

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    Lim, Felicia Phei Lin; Dolzhenko, Anton V

    2014-10-06

    Purines can be considered as the most ubiquitous and functional N-heterocyclic compounds in nature. Structural modifications of natural purines, particularly using isosteric ring systems, have been in the focus of many drug discovery programs. Fusion of 1,3,5-triazine ring with pyrrole, pyrazole, imidazole, 1,2,3-triazole or 1,2,4-triazole results in seven bicyclic heterocyclic systems isosteric to purine. Application of the isosterism concept for the development of new compounds with therapeutic potential in areas involving purinergic regulation or purine metabolism led to significant advances in medicinal chemistry of the azolo[1,3,5]triazines. These 1,3,5-triazine-based purine-like scaffolds significantly increase level of molecular diversity and allow covering chemical space in the important areas of medicinal chemistry. Some of these azolo[1,3,5]triazine systems have become privileged scaffolds in the development of inhibitors of various kinases, phosphodiesterase, xanthine oxidase, and thymidine phosphorylase, antagonists of adenosine and corticotropin-releasing hormone receptors, anticancer and antiviral agents.

  7. Prebiotic syntheses of purines and pyrimidines.

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    Basile, B; Lazcano, A; Oró, J

    1984-01-01

    The work done in many laboratories during the last two decades has confirmed that hydrogen cyanide and cyanoacetylene are the two major precursors for the prebiotic synthesis of purines and pyrimidines, respectively. Although several different pathways for the synthesis of purines have been described, they are all variations of the initial mechanism proposed by Oró and Kimball, where hydrogen cyanide leads first to the formation of a 4,5-di-substituted imidazole derivative, and then to the closing of the purine ring with a C1 compound. A number of experiments have shown that purines and pyrimidines can also be obtained from methane, ammonia (nitrogen), and water mixtures, provided an activating source of energy (radiation, electric discharges, etc.) is available. However, in this case the yields are lower by about two orders of magnitude because of the intermediate formation of hydrogen cyanide and cyanoacetylene. The latter two compounds have been found in interstellar space, Titan and other bodies of the solar system. They were probably present in the primordial parent bodies from the solar nebula in concentrations of 10(-2) to 10(-3) M as inferred from recent calculations by Miller and coworkers obtained for the Murchison meteorite. These concentrations should have been sufficient to generate relatively large amounts of purine and pyrimidine bases on the primitive Earth.

  8. Ambiguous base pairing of the purine analogue 1-(2-deoxy-beta-D-ribofuranosyl)-imidazole-4-carboxamide during PCR.

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    Sala, M; Pezo, V; Pochet, S; Wain-Hobson, S

    1996-09-01

    In principle the hydrogen bonding capacities of 1-(2-deoxy-beta-D-ribofuranosyl)-imidazole-4-carboxamide (dY), and its N-propyl derivative (dYPr), allow them to pair to all four deoxynucleosides. Their triphosphate derivatives (dYTP and dYPrTP) are preferentially incorporated as dATP analogues in a PCR reaction. However, once incorporated into a DNA template their ambiguous hydrogen bonding potential gave rise to misincorporation at frequencies of approximately 3 x 10(-2) per base per amplification. Most of the substitutions were transitions resulting from rotation about the carboxamide bond when part of the template. Between 11-15% of transversions were noted implying rotation of purine or imidazole moieties about the glycosidic bond. As part of a DNA template, dYPr behaved in the same way as dY, despite its propyl moiety. These deoxyimidazole derivatives are among the most radical departures from the canonical bases used so far as substrates in PCR and could be used to generate mutant gene libraries.

  9. Purine (N)-Methanocarba Nucleoside Derivatives Lacking an Exocyclic Amine as Selective A3 Adenosine Receptor Agonists.

    Science.gov (United States)

    Tosh, Dilip K; Ciancetta, Antonella; Warnick, Eugene; O'Connor, Robert; Chen, Zhoumou; Gizewski, Elizabeth; Crane, Steven; Gao, Zhan-Guo; Auchampach, John A; Salvemini, Daniela; Jacobson, Kenneth A

    2016-04-14

    Purine (N)-methanocarba-5'-N-alkyluronamidoriboside A3 adenosine receptor (A3AR) agonists lacking an exocyclic amine resulted from an unexpected reaction during a Sonogashira coupling and subsequent aminolysis. Because the initial C6-Me and C6-styryl derivatives had unexpectedly high A3AR affinity, other rigid nucleoside analogues lacking an exocyclic amine were prepared. Of these, the C6-Me-(2-phenylethynyl) and C2-(5-chlorothienylethynyl) analogues were particularly potent, with human A3AR Ki values of 6 and 42 nM, respectively. Additionally, the C2-(5-chlorothienyl)-6-H analogue was potent and selective at A3AR (MRS7220, Ki 60 nM) and also completely reversed mouse sciatic nerve mechanoallodynia (in vivo, 3 μmol/kg, po). The lack of a C6 H-bond donor while maintaining A3AR affinity and efficacy could be rationalized by homology modeling and docking of these hypermodified nucleosides. The modeling suggests that a suitable combination of stabilizing features can partially compensate for the lack of an exocyclic amine, an otherwise important contributor to recognition in the A3AR binding site.

  10. Site-specific control of N7-metal coordination in DNA by a fluorescent purine derivative.

    Science.gov (United States)

    Dumas, Anaëlle; Luedtke, Nathan W

    2012-01-01

    A synthetic strategy that utilizes O6-protected 8-bromoguanosine gives broad access to C8-guanine derivatives with phenyl, pyridine, thiophene, and furan substituents. The resulting 8-substituted 2'-deoxyguanosines are push-pull fluorophores that can exhibit environmentally sensitive quantum yields (Φ=0.001-0.72) due to excited-state proton-transfer reactions with bulk solvent. Changes in nucleoside fluorescence were used to characterize metal-binding affinity and specificity of 8-substituted 2'-deoxyguanosines. One derivative, 8-(2-pyridyl)-2'-deoxyguanosine (2PyG), exhibits selective binding of Cu(II), Ni(II), Cd(II), and Zn(II) through a bidentate effect provided by the N7 position of guanine and the 2-pyridyl nitrogen atom. Upon incorporation into DNA, 2-pyridine-modified guanine residues selectively bind to Cu(II) and Ni(II) with equilibrium dissociation constants (K(d)) that range from 25 to 850 nM; the affinities depend on the folded state of the oligonucleotide (duplex>G-quadruplex) as well as the identity of the metal ion (Cu>Ni≫Cd). These binding affinities are approximately 10 to 1 000 times higher than for unmodified metal binding sites in DNA, thereby providing site-specific control of metal localization in alternatively folded nucleic acids. Temperature-dependent circular-dichroism studies reveal metal-dependent stabilization of duplexes, but destabilization of G-quadruplex structures upon adding Cu(II) to 2PyG-modified oligonucleotides. These results demonstrate how the addition of a single pyridine group to the C8 position of guanine provides a powerful new tool for studying the effects of N7 metalation on the structure, stability, and electronic properties of nucleic acids.

  11. Synthesis, Characterization, and Thermal and Antimicrobial Activities of Some Novel Organotin(IV: Purine Base Complexes

    Directory of Open Access Journals (Sweden)

    Reena Jain

    2013-01-01

    Full Text Available A new series of organotin(IV complexes with purine bases theophylline (HL1 and theobromine (L2 of the types R3Sn(L1, R2Sn(L1Cl, R3Sn(L2Cl, and R2Sn(L2Cl2 (R = C6H5CH2–; p-ClC6H4CH2– have been synthesized in anhydrous THF. The complexes were characterized by elemental analysis, conductance measurements, molecular weight determinations, UV-vis, IR, 1H, 13C NMR, and mass spectral studies. Various kinetic and thermodynamic parameters of these complexes have also been determined using TG/DTA technique. The thermal decomposition techniques indicate the formation of SnO2 as a residue. The results show that the ligands act as bidentate, forming a five-member chelate ring. All the complexes are 1 : 1 metal-ligand complexes. In order to assess their antimicrobial activity, the ligands and their corresponding complexes have also been tested in vitro against bacteria (E. coli, S. aureus, and P. pyocyanea and fungi (Rhizopus oryzae and Aspergillus flavus. All the complexes exhibit remarkable activity, and the results provide evidence that the studied complexes might indeed be a potential source of antimicrobial agents.

  12. Urinary excretion of purine derivatives, microbial protein synthesis, nitrogen use, and ruminal fermentation in sheep and goats fed diets of different quality.

    Science.gov (United States)

    Carro, M D; Cantalapiedra-Hijar, G; Ranilla, M J; Molina-Alcaide, E

    2012-11-01

    The objective of this study was to compare N balance, microbial N flow (MNF) estimated from purine derivatives (PD) urinary excretion, and its variation when estimated using purine bases:N ratios in liquid associated bacteria (LAB) from models reported in the literature (MNF - response models) or measured ratios in liquid and solid-associated bacterial (SAB) pellets (MNF-LAB+SAB), diet digestibility, and rumen fermentation variables in sheep and goats fed 3 different practical, quality diets to study interspecies differences concerning N use as accurately as possible. Four mature female Merino sheep and 4 mature female Granadina goats, each fitted with a ruminal cannula, were used in 3 × 3 Latin square design with an extra animal. Two experimental diets had a forage-to-concentrate ratio of 70:30 (DM basis) with alfalfa hay (ALC) or grass hay (GRC) as forage, and the third diet contained 70% concentrate and 30% alfalfa hay (CAL). All animals were fed the diets at a daily rate of 56 g/kg BW(0.75) to minimize feed selection. Digestibility of nutrients was similar (P = 0.16 to 0.88) in the 2 species, but some animal species × diet interactions (P = 0.01 to 0.04) were detected. There were small differences between the fermentation patterns of both animal species. Goats showed decreased VFA concentrations (P = 0.005) and butyrate proportions (P = 0.04), and greater acetate proportions (P = 0.02) compared with sheep, whereas N intake and percentage of N intake excreted in feces were similar in both species (P = 0.58 and 0.15, respectively), the percentage excreted via the urine was greater in goats compared with sheep (P goats (averaged across diets, 32.6% and 16.1% of N intake, respectively). There were no differences (P = 0.95) between animal species in total PD excretion, but goats showed a greater excretion of allantoin (P = 0.01) and decreased excretion of xanthine (P = 0.008) and hypoxanthine (P = 0.007) compared with sheep. In general, differences between sheep

  13. Absorption and Intermediary Metabolism of Purines and Pyrimidines in Lactating Dairy Cows

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Stentoft; Røjen, Betina Amdisen; Jensen, Søren Krogh

    2015-01-01

    About 20 % of ruminal microbial N in dairy cows derives from purines and pyrimidines; however, their intermediary metabolism and contribution to the overall N metabolism has sparsely been described. In the present study, the postprandial patterns of net portal-drained viscera (PDV) and hepatic...... metabolism were assessed to evaluate purine and pyrimidine N in dairy cows. Blood was sampled simultaneously from four veins with eight hourly samples from four multi-catheterised Holstein cows. Quantification of twenty purines and pyrimidines was performed with HPLC–MS/MS, and net fluxes were estimated...... across the PDV, hepatic tissue and total splanchnic tissue (TSP). Concentration differences between veins of fifteen purine and pyrimidine nucleosides (NS), bases (BS) and degradation products (DP) were different from zero (P≤ 0·05), resulting in the net PDV releases of purine NS (0·33–1·3 mmol...

  14. Genome-wide screening for genes whose deletions confer sensitivity to mutagenic purine base analogs in yeast

    Directory of Open Access Journals (Sweden)

    Kozmin Stanislav G

    2005-06-01

    Full Text Available Abstract Background N-hydroxylated base analogs, such as 6-hydroxylaminopurine (HAP and 2-amino-6-hydroxylaminopurine (AHA, are strong mutagens in various organisms due to their ambiguous base-pairing properties. The systems protecting cells from HAP and related noncanonical purines in Escherichia coli include specialized deoxyribonucleoside triphosphatase RdgB, DNA repair endonuclease V, and a molybdenum cofactor-dependent system. Fewer HAP-detoxification systems have been identified in yeast Saccharomyces cerevisiae and other eukaryotes. Cellular systems protecting from AHA are unknown. In the present study, we performed a genome-wide search for genes whose deletions confer sensitivity to HAP and AHA in yeast. Results We screened the library of yeast deletion mutants for sensitivity to the toxic and mutagenic action of HAP and AHA. We identified novel genes involved in the genetic control of base analogs sensitivity, including genes controlling purine metabolism, cytoskeleton organization, and amino acid metabolism. Conclusion We developed a method for screening the yeast deletion library for sensitivity to the mutagenic and toxic action of base analogs and identified 16 novel genes controlling pathways of protection from HAP. Three of them also protect from AHA.

  15. Purine and pyrimidine metabolism.

    Science.gov (United States)

    Zöllner, N

    1982-09-01

    The pathways of purine biosynthesis and degradation have been elucidated during the last 30 years; the regulation of the mechanisms involved is not yet fully understood, particularly with respect to quantitative aspects. Research into inborn errors of purine metabolism has provided valuable insights into purine synthesis and salvage pathways. Nutrition experiments using purine-free formula diets and supplements with defined purine sources permit precise descriptions of the influence of various dietary purines on uric acid formation. Supplements of dietary purines produce dose-proportional increases in plasma uric acid concentrations, uric acid pool size and renal uric acid excretion. The magnitude of these increases depends on the type of purine compound administered, which may limit the value of food tables for human dietetics. Purine content of food must be related not only to weight but also to energy and to protein, particularly if new foodstuffs or a vegetarian diet are ingested. Dietary purines appear to influence the biosynthesis of pyrimidines. In contrast to dietary purines, pyrimidines in the diet, if administered as nucleosides or nucleotides, are utilized in animals for the synthesis of nucleic acids. Much further work is necessary for a better understanding of the inter-relationships of purine and pyrimidine metabolism.

  16. Metabolic Interactions of Purine Derivatives with Human ABC Transporter ABCG2: Genetic Testing to Assess Gout Risk

    Directory of Open Access Journals (Sweden)

    Kiyoko Kaneko

    2013-11-01

    Full Text Available In mammals, excess purine nucleosides are removed from the body by breakdown in the liver and excretion from the kidneys. Uric acid is the end product of purine metabolism in humans. Two-thirds of uric acid in the human body is normally excreted through the kidney, whereas one-third undergoes uricolysis (decomposition of uric acid in the gut. Elevated serum uric acid levels result in gout and could be a risk factor for cardiovascular disease and diabetes. Recent studies have shown that human ATP-binding cassette transporter ABCG2 plays a role of renal excretion of uric acid. Two non-synonymous single nucleotide polymorphisms (SNPs, i.e., 421C>A (major and 376C>T (minor, in the ABCG2 gene result in impaired transport activity, owing to ubiquitination-mediated proteosomal degradation and truncation of ABCG2, respectively. These genetic polymorphisms are associated with hyperuricemia and gout. Allele frequencies of those SNPs are significantly higher in Asian populations than they are in African and Caucasian populations. A rapid and isothermal genotyping method has been developed to detect the SNP 421C>A, where one drop of peripheral blood is sufficient for the detection. Development of simple genotyping methods would serve to improve prevention and early therapeutic intervention for high-risk individuals in personalized healthcare.

  17. Modeling compositional dynamics based on GC and purine contents of protein-coding sequences

    KAUST Repository

    Zhang, Zhang

    2010-11-08

    Background: Understanding the compositional dynamics of genomes and their coding sequences is of great significance in gaining clues into molecular evolution and a large number of publically-available genome sequences have allowed us to quantitatively predict deviations of empirical data from their theoretical counterparts. However, the quantification of theoretical compositional variations for a wide diversity of genomes remains a major challenge.Results: To model the compositional dynamics of protein-coding sequences, we propose two simple models that take into account both mutation and selection effects, which act differently at the three codon positions, and use both GC and purine contents as compositional parameters. The two models concern the theoretical composition of nucleotides, codons, and amino acids, with no prerequisite of homologous sequences or their alignments. We evaluated the two models by quantifying theoretical compositions of a large collection of protein-coding sequences (including 46 of Archaea, 686 of Bacteria, and 826 of Eukarya), yielding consistent theoretical compositions across all the collected sequences.Conclusions: We show that the compositions of nucleotides, codons, and amino acids are largely determined by both GC and purine contents and suggest that deviations of the observed from the expected compositions may reflect compositional signatures that arise from a complex interplay between mutation and selection via DNA replication and repair mechanisms.Reviewers: This article was reviewed by Zhaolei Zhang (nominated by Mark Gerstein), Guruprasad Ananda (nominated by Kateryna Makova), and Daniel Haft. 2010 Zhang and Yu; licensee BioMed Central Ltd.

  18. Novel Coumarin Derivatives Containing 1,2,4-Triazole, 4,5-Dicyanoimidazole and Purine Moieties: Synthesis and Evaluation of Their Cytostatic Activity

    Directory of Open Access Journals (Sweden)

    Mladen Mintas

    2012-09-01

    Full Text Available We report here on the synthesis and in vitro anti-tumor effects of a series of novel 1,2,4-triazole (compounds 3–6, 4,5-dicyanoimidazole (compound 7, and purine (compounds 8–13 coumarin derivatives and their acyclic nucleoside analogues 14–18. Structures of novel compounds 3–18 were deduced from their 1H- and 13C-NMR and corresponding mass spectra. Results of anti-proliferative assays performed on a panel of selected human tumor cell lines revealed that compound 6 had moderate cytostatic activity against the HeLa cell line (IC50 = 35 µM, whereas compound 10 showed moderate activity against the HeLa (IC50 = 33 µM, HepG2 (IC50 = 25 µM and SW620 (IC50 = 35 µM cell lines. These compounds showed no cytotoxic effects on normal (diploid human fibroblasts.

  19. Synthesis and Pharmacophore Modelling of 2,6,9-Trisubstituted Purine Derivatives and Their Potential Role as Apoptosis-Inducing Agents in Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Jeannette Calderón-Arancibia

    2015-04-01

    Full Text Available A series of 2,6,9-trisubstituted purine derivatives have been synthesized and investigated for their potential role as antitumor agents. Twelve compounds were obtained by a three step synthetic procedure using microwave irradiation in a pivotal step. All compounds were evaluated in vitro to determine their potential effect on cell toxicity by the MTT method and flow cytometry analysis on four cancer cells lines and Vero cells. Three out of twelve compounds were found to be promising agents compared to a known and effective anticancer drug, etoposide, in three out of four cancer cell lines assayed with considerable selectivity. Preliminary flow cytometry data suggests that compounds mentioned above induce apoptosis on these cells. The main structural requirements for their activity for each cancer cell line were characterized with a preliminary pharmacophore model, which identified aromatic centers, hydrogen acceptor/donor center and a hydrophobic area. These features were consistent with the cytotoxic activity of the assayed compounds.

  20. New 7-arylpiperazinylalkyl-8-morpholin-4-yl-purine-2,6-dione derivatives with anxiolytic activity - Synthesis, crystal structure and structure-activity study

    Science.gov (United States)

    Chłoń-Rzepa, Grażyna; Żmudzki, Paweł; Pawłowski, Maciej; Wesołowska, Anna; Satała, Grzegorz; Bojarski, Andrzej J.; Jabłoński, Mateusz; Kalinowska-Tłuścik, Justyna

    2014-06-01

    On the basis of our earlier studies with serotonin (5-HT) receptor ligands in the group of long-chain arylpiperazines (LCAPs), a new series of 7-arylpiperazinylalkyl-8-morpholin-4-yl-purine-2,6-dione derivatives (5-12) has been designed, synthesised and studied in vitro for their affinity for 5-HT1A, 5-HT2A, 5-HT6 and 5-HT7 receptors. The introduction of o-OCH3 and m-Cl into the phenylpiperazinyl moiety as well as the elongation of the linker between purine-2,6-dione core and arylpiperazine fragment modified the affinity for the tested 5-HT receptors. The structures of compounds 9-11 (hydrochloride salts) were confirmed by an X-ray diffraction method. All molecules adopted a different conformation in the crystal. The strongest observed type of interaction is a charge assisted hydrogen bond N+-H⋯Cl-. Additionally, the π-π interactions between 1,3-dimethyl-3,7-dihydropurine-2,6-dione cores of the neighbouring molecules were also observed. As it is observed in the presented crystal structures, the morpholine ring (a potential donor and acceptor of the hydrogen bonds) seems to be an attractive substituent, that may support binding to the non-specific sites of 5-HT receptors. Another interesting feature is the mutual orientation of rings in the arylpiperazine fragment, with plausible influence on ligand-receptor recognition. For compound 10, with strong 5-HT1A binding affinity, the mutual orientation of rings is determined by the intramolecular weak C-H⋯O hydrogen bond. This observation may contribute to a better understanding of the more selective binding of o-OCH3 arylpiperazine derivatives to the 5-HT1A receptor.

  1. Effect of feeding tannin degrading bacterial culture (Streptococcus gallolyticus strain TDGB 406) on nutrient utilization, urinary purine derivatives and growth performance of goats fed on Quercus semicarpifolia leaves.

    Science.gov (United States)

    Kumar, K; Chaudhary, L C; Agarwal, N; Kamra, D N

    2014-10-01

    To study the effect of supplementation of tannin degrading bacterial culture (Streptococcus gallolyticus strain TDGB 406) on growth performance, nutrient utilization and urinary purine derivatives of goats fed on oak (Quercus semicarpifolia) leaves. For growth study, eighteen billy goats (4 month old, average body weight 9.50 ± 1.50 kg) were distributed into three groups of six animals each. The animals of group 1 served as control while animals of groups 2 (T1) and 3 (T2) were given (@ 5 ml/kg live weight) autoclaved and live culture of isolate TDGB 406 (10(6) cells/ml) respectively. The animals were fed measured quantity of dry oak leaves as the main roughage source and ad libitum maize hay along with fixed quantity of concentrate mixture. The feeding of live culture of isolate TDGB 406 (probiotic) did not affect dry matter intake and digestibility of nutrients except that of dry matter and crude protein, which was higher in T2 group as compared to control. All the animals were in positive nitrogen balance. There was no significant effect of feeding isolate TDGB 406 on urinary purine derivatives (microbial protein production) in goats. The body weight gain and average live weight gain was significantly higher (p = 0.071) in T2 group as compared to control. Feed conversion efficiency was also better in the goats fed on live culture of TDGB 406 (T2). The feeding of tannin degrading bacterial isolate TDGB 406 as probiotic resulted in improved growth performance and feed conversion ratio in goats fed on oak leaves as one of the main roughage source. Journal of Animal Physiology and Animal Nutrition © 2013 Blackwell Verlag GmbH.

  2. N-&-N, a new class of cell death-inducing kinase inhibitors derived from the purine roscovitine.

    Science.gov (United States)

    Bettayeb, Karima; Sallam, Hatem; Ferandin, Yoan; Popowycz, Florence; Fournet, Guy; Hassan, Moustapha; Echalier, Aude; Bernard, Philippe; Endicott, Jane; Joseph, Benoît; Meijer, Laurent

    2008-09-01

    Cyclin-dependent kinases (CDKs) and their regulators show frequent abnormalities in tumors. Ten low molecular weight pharmacologic inhibitors of CDKs are currently in clinical trials against various cancers, including the 2,6,9-trisubstituted purine (R)-roscovitine (CYC202/Seliciclib). We here report the characterization of N-&-N1, a bioisoster of roscovitine displaying improved antitumoral properties. N-&-N1 shows exquisite selectivity for CDKs, with 2- to 3-fold enhanced potency compared with (R)-roscovitine. Inhibition of retinoblastoma protein phosphorylation and RNA polymerase II Ser2 phosphorylation in neuroblastoma SH-SY5Y cells exposed to N-&-N1 indicates that N-&-N1 is able to inhibit CDKs in a cellular context. N-&-N1 also down-regulates the expression of RNA polymerase. Cocrystal structures of N-&-N1 and (R)-roscovitine in complex with CDK2/cyclin A reveal that both inhibitors adopt similar binding modes. A competitive assay shows that, compared with (R)-roscovitine, N-&-N1 has reduced affinity for Erk2 and pyridoxal kinase. N-&-N1 triggers cell death in a panel of diverse cell lines. Cell death is accompanied by events characteristic of apoptosis: cytochrome c release, activation of effector caspases, and poly(ADP-ribose) polymerase cleavage. Induction of p53 and p21CIP1 and down-regulation of the Mcl-1 antiapoptotic factor were also observed. Studies in mice show that N-&-N1 has pharmacokinetics properties similar to those of (R)-roscovitine. Altogether, these results show that analogues of (R)-roscovitine can be designed with improved antitumor potential.

  3. Purine metabolism in Toxoplasma gondii

    Energy Technology Data Exchange (ETDEWEB)

    Krug, E.C.; Marr, J.J.; Berens, R.L.

    1989-06-25

    We have studied the incorporation and interconversion of purines into nucleotides by freshly isolated Toxoplasma gondii. They did not synthesize nucleotides from formate, glycine, or serine. The purine bases hypoxanthine, xanthine, guanine, and adenine were incorporated at 9.2, 6.2, 5.1, and 4.3 pmol/10(7) cells/h, respectively. The purine nucleosides adenosine, inosine, guanosine, and xanthosine were incorporated at 110, 9.0, 2.7, and 0.3 pmol/10(7) cells/h, respectively. Guanine, xanthine, and their respective nucleosides labeled only guanine nucleotides. Inosine, hypoxanthine, and adenine labeled both adenine and guanine nucleotide pools at nearly equal ratios. Adenosine kinase was greater than 10-fold more active than the next most active enzyme in vitro. This is consistent with the metabolic data in vivo. No other nucleoside kinase or phosphotransferase activities were found. Phosphorylase activities were detected for guanosine and inosine; no other cleavage activities were detected. Deaminases were found for adenine and guanine. Phosphoribosyltransferase activities were detected for all four purine nucleobases. Interconversion occurs only in the direction of adenine to guanine nucleotides.

  4. Structural and catalytic effects of an invariant purine substitution in the hammerhead ribozyme: implications for the mechanism of acid-base catalysis.

    Science.gov (United States)

    Schultz, Eric P; Vasquez, Ernesto E; Scott, William G

    2014-09-01

    The hammerhead ribozyme catalyzes RNA cleavage via acid-base catalysis. Whether it does so by general acid-base catalysis, in which the RNA itself donates and abstracts protons in the transition state, as is typically assumed, or by specific acid-base catalysis, in which the RNA plays a structural role and proton transfer is mediated by active-site water molecules, is unknown. Previous biochemical and crystallographic experiments implicate an invariant purine in the active site, G12, as the general base. However, G12 may play a structural role consistent with specific base catalysis. To better understand the role of G12 in the mechanism of hammerhead catalysis, a 2.2 Å resolution crystal structure of a hammerhead ribozyme from Schistosoma mansoni with a purine substituted for G12 in the active site of the ribozyme was obtained. Comparison of this structure (PDB entry 3zd4), in which A12 is substituted for G, with three previously determined structures that now serve as important experimental controls, allows the identification of structural perturbations that are owing to the purine substitution itself. Kinetic measurements for G12 purine-substituted schistosomal hammerheads confirm a previously observed dependence of rate on the pK(a) of the substituted purine; in both cases inosine, which is similar to G in pK(a) and hydrogen-bonding properties, is unexpectedly inactive. Structural comparisons indicate that this may primarily be owing to the lack of the exocyclic 2-amino group in the G12A and G12I substitutions and its structural effect upon both the nucleotide base and phosphate of A9. The latter involves the perturbation of a previously identified and well characterized metal ion-binding site known to be catalytically important in both minimal and full-length hammerhead ribozyme sequences. The results permit it to be suggested that G12 plays an important role in stabilizing the active-site structure. This result, although not inconsistent with the potential

  5. Determination and profiling of purines in foods by using HPLC and LC-MS.

    Science.gov (United States)

    Inazawa, K; Sato, A; Kato, Y; Yamaoka, N; Fukuuchi, T; Yasuda, M; Mawatari, K; Nakagomi, K; Kaneko, K

    2014-01-01

    Purines in food are known to raise serum uric acid levels. We determined the purine content of sweet potato and beef by high-performance liquid chromatography and liquid chromatography-mass spectrometry. The purine content of the samples was 118-1,034 μmol/100 g. The total purine content was also divided into purine bases, nucleosides, nucleotides, and nucleic acids. Our results suggest that differences in total purine content and in the ratio of purine types between vegetables and beef cause a difference in elevation of serum uric acid levels.

  6. Rumen microbial protein supply as estimated from purine derivative excretion on sheep receiving faba beans (vicia faba as supplement delivered at different feeding frequencies

    Directory of Open Access Journals (Sweden)

    Asmuddin Natsir

    2008-06-01

    Full Text Available Rapid and extensive degradation of faba beans (Vicia faba by ruminal microbes can result in substantial and undesirable N loss from the rumen. The purpose of this study was to test the hypothesis that offering faba beans as a supplement more than once a day to sheep receiving a combination of oaten chaff and lucerne chaff as a basal diet will increase microbial protein supply to the intestines. The experiment was conducted in a Latin square design (4 x 4 using four mature merino sheep. The treatments were: T0 = basal diet ad libitum + nil supplements, T1 = T0 + faba beans (FB fed once daily, T2 = T0 + FB fed twice daily, T3 = T0 + FB fed 8 times daily. The basal diet was given once per day at 09:00 in the morning while FB were given at the rate of approximately 0.5% of live body weight and delivered according to the treatment protocol. Urinary excretion of purine derivative (PD was used to estimate microbial protein supply. The results indicated that even though treatment statistically had no effects on total urine output, PD excretion in the urine, PD absorbed, estimated microbial N supply, and the efficiency of rumen microbial protein synthesis, provision of supplement to sheep numerically improved microbial N supply by 92% compared to that of control group. However, there were no differences within the supplemented group. Therefore, it is concluded that feeding faba beans more than once a day was unnecessary.

  7. Dietary purines in vegetarian meat analogues.

    Science.gov (United States)

    Havlik, Jaroslav; Plachy, Vladimir; Fernandez, Javier; Rada, Vojtech

    2010-11-01

    The meat alternatives market offers a wide range of products resembling meat in taste, flavour or texture but based on vegetable protein sources. These high protein-low purine foods may find application in a low purine or purine-free diet, which is sometimes suggested for subjects with increased serum urate levels, i.e. hyperuricaemia. We determined purine content (uric acid, adenine, guanine, hypoxanthine, xanthine) in 39 commercially available meat substitutes and evaluated them in relation to their protein content. Some of the products contained a comparable sum of adenine and hypoxanthine per protein as meat. Analysis of variance showed an influence of protein source used. Mycoprotein-based products had significantly higher contents (2264 mg kg(-1)) of adenine and hypoxanthine per kg of 100% protein than soybean-based products (1648 mg kg(-1)) or mixtures consisting of soybean protein and wheat protein (1239 mg kg(-1)). Protein-rich vegetable-based meat substitutes might be generally accepted as meat alternatives for individuals on special diets. The type of protein used to manufacture these products determines the total content of purines, which is relatively higher in the case of mycoprotein or soybean protein, while appearing lower in wheat protein and egg white-based products. These are therefore more suitable for dietary considerations in a low-purine diet for hyperuricaemic subjects. 2010 Society of Chemical Industry

  8. Synthesis and Biological Evaluation of Novel Aryl-2H-pyrazole Derivatives as Potent Non-purine Xanthine Oxidase Inhibitors.

    Science.gov (United States)

    Sun, Zhi-Gang; Zhou, Xiao-Jing; Zhu, Ming-Li; Ding, Wen-Ze; Li, Zhen; Zhu, Hai-Liang

    2015-01-01

    A series of aryl-2H-pyrazole derivatives were synthesized and evaluated for inhibitory activity against xanthine oxidase in vitro as potent xanthine oxidase inhibitors. Among them, 2 aryl-2H-pyrazole derivatives showed significant inhibitory activities against xanthine oxidase. Compound 19 emerged as the most potent xanthine oxidase inhibitor (IC50=9.8 µM) in comparison with allopurinol (IC50=9.5 µM). The docking study revealed that compound 19 might have strong interactions with the active site of xanthine oxidase. This compound is thus a new candidate for further development for the treatment of gout.

  9. Three-dimensional structure of E. Coli purine nucleoside phosphorylase at 0.99 Å resolution

    Science.gov (United States)

    Timofeev, V. I.; Abramchik, Yu. A.; Zhukhlistova, N. E.; Muravieva, T. I.; Esipov, R. S.; Kuranova, I. P.

    2016-03-01

    Purine nucleoside phosphorylases (PNPs) catalyze the reversible phosphorolysis of nucleosides and are key enzymes involved in nucleotide metabolism. They are essential for normal cell function and can catalyze the transglycosylation. Crystals of E. coli PNP were grown in microgravity by the capillary counterdiffusion method through a gel layer. The three-dimensional structure of the enzyme was determined by the molecular-replacement method at 0.99 Å resolution. The structural features are considered, and the structure of E. coli PNP is compared with the structures of the free enzyme and its complexes with purine base derivatives established earlier. A comparison of the environment of the purine base in the complex of PNP with formycin A and of the pyrimidine base in the complex of uridine phosphorylase with thymidine revealed the main structural features of the base-binding sites. Coordinates of the atomic model determined with high accuracy were deposited in the Protein Data Bank (PDB_ID: 4RJ2).

  10. Functionalized Solid Electrodes for Electrochemical Biosensing of Purine Nucleobases and Their Analogues: A Review

    Directory of Open Access Journals (Sweden)

    Vimal Kumar Sharma

    2015-01-01

    Full Text Available Interest in electrochemical analysis of purine nucleobases and few other important purine derivatives has been growing rapidly. Over the period of the past decade, the design of electrochemical biosensors has been focused on achieving high sensitivity and efficiency. The range of existing electrochemical methods with carbon electrode displays the highest rate in the development of biosensors. Moreover, modification of electrode surfaces based on nanomaterials is frequently used due to their extraordinary conductivity and surface to volume ratio. Different strategies for modifying electrode surfaces facilitate electron transport between the electrode surface and biomolecules, including DNA, oligonucleotides and their components. This review aims to summarize recent developments in the electrochemical analysis of purine derivatives, as well as discuss different applications.

  11. 6-Methylpurine derived sugar modified nucleosides: Synthesis and evaluation of their substrate activity with purine nucleoside phosphorylases.

    Science.gov (United States)

    Hassan, Abdalla E A; Abou-Elkhair, Reham A I; Parker, William B; Allan, Paula W; Secrist, John A

    2016-04-01

    6-Methylpurine (MeP) is cytotoxic adenine analog that does not exhibit selectivity when administered systemically, and could be very useful in a gene therapy approach to cancer treatment involving Escherichia coli PNP. The prototype MeP releasing prodrug, 9-(β-d-ribofuranosyl)-6-methylpurine, MeP-dR has demonstrated good activity against tumors expressing E. coli PNP, but its antitumor activity is limited due to toxicity resulting from the generation of MeP from gut bacteria. Therefore, we have embarked on a medicinal chemistry program to identify non-toxic MeP prodrugs that could be used in conjunction with E. coli PNP. In this work, we report on the synthesis of 9-(6-deoxy-β-d-allofuranosyl)-6-methylpurine (3) and 9-(6-deoxy-5-C-methyl-β-d-ribo-hexofuranosyl)-6-methylpurine (4), and the evaluation of their substrate activity with several phosphorylases. The glycosyl donors; 1,2-di-O-acetyl-3,5-di-O-benzyl-α-d-allofuranose (10) and 1-O-acetyl-3-O-benzyl-2,5-di-O-benzoyl-6-deoxy-5-C-methyl-β-d-ribohexofuran-ose (15) were prepared from 1,2:5,6-di-O-isopropylidine-α-d-glucofuranose in 9 and 11 steps, respectively. Coupling of 10 and 15 with silylated 6-methylpurine under Vorbrüggen glycosylation conditions followed conventional deprotection of the hydroxyl groups furnished 5'-C-methylated-6-methylpurine nucleosides 3 and 4, respectively. Unlike 9-(6-deoxy-α-l-talo-furanosyl)-6-methylpurine, which showed good substrate activity with E. coli PNP mutant (M64V), the β-d-allo-furanosyl derivative 3 and the 5'-di-C-methyl derivative 4 were poor substrates for all tested glycosidic bond cleavage enzymes.

  12. Effects of dietary supplementation of rumen-protected folic acid on rumen fermentation, degradability and excretion of urinary purine derivatives in growing steers.

    Science.gov (United States)

    Wang, Cong; Liu, Qiang; Guo, Gang; Huo, WenJie; Ma, Le; Zhang, YanLi; Pei, CaiXia; Zhang, ShuanLin; Wang, Hao

    2016-12-01

    The present experiment was undertaken to determine the effects of dietary addition of rumen-protected folic acid (RPFA) on ruminal fermentation, nutrient degradability, enzyme activity and the relative quantity of ruminal cellulolytic bacteria in growing beef steers. Eight rumen-cannulated Jinnan beef steers averaging 2.5 years of age and 419 ± 1.9 kg body weight were used in a replicated 4 × 4 Latin square design. The four treatments comprised supplementation levels of 0 (Control), 70, 140 and 210 mg RPFA/kg dietary dry matter (DM). On DM basis, the ration consisted of 50% corn silage, 47% concentrate and 3% soybean oil. The DM intake (averaged 8.5 kg/d) was restricted to 95% of ad libitum intake. The intake of DM, crude protein (CP) and net energy for growth was not affected by treatments. In contrast, increasing RPFA supplementation increased average daily gain and the concentration of total volatile fatty acid and reduced ruminal pH linearly. Furthermore, increasing RPFA supplementation enhanced the acetate to propionate ratio and reduced the ruminal ammonia N content linearly. The ruminal effective degradability of neutral detergent fibre from corn silage and CP from concentrate improved linearly and was highest for the highest supplementation levels. The activities of cellobiase, xylanase, pectinase and α-amylase linearly increased, but carboxymethyl-cellulase and protease were not affected by the addition of RPFA. The relative quantities of Butyrivibrio fibrisolvens, Ruminococcus albus, Ruminococcus flavefaciens and Fibrobacter succinogenes increased linearly. With increasing RPFA supplementation levels, the excretion of urinary purine derivatives was also increased linearly. The present results indicated that the supplementation of RPFA improved ruminal fermentation, nutrient degradability, activities of microbial enzymes and the relative quantity of the ruminal cellulolytic bacteria in a dose-dependent manner. According to the conditions of this

  13. SYNTHESIS OF NEW TWO DERIVATIVES OF 6-MERCAPTOPURINE (6MP 6-[5-PYRIDINE-4-YL- 1, 2, 3, 4-OXADIAZOLE-2-YLDITHIOL]-9H-PURINE (38 AND 9H-PURINE-6-YL-BENYLDITHIOCARBAMATE (45 WITH CYTOTOXICITY RESULTS FROM THE NATIONAL CANCER INSTITUTE'S ANTICANCER DRUG SCREEN

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    Mohammed Hassan Mohammed et al

    2012-08-01

    Full Text Available 6-[(5-pyridine-yl-1, 2, 3, 4-oxadiazole-2-yldithiol]-9H-purine (38 and 9H-purine-6yl-benzyldithiocarbamate (45 are synthesized as possible prodrugs for 6-mercaptopurine(6-MP. The generation of the compounds 38, 42, 45 and 48 were accomplished following multistep reaction procedures. The reaction and purity of the products were checked by TLC, the structure of the final compounds and their intermediates were confirmed by their melting points, infra red spectroscopy and whether differences elemental microanalysis. To determine exist among in sensitivity different tissue types toward treatment with 38 and 45. The cytotoxicity of the two compounds and their intermediates were confirmed by their melting points, infra red spectroscopy and elemental microanalysis. The cytotoxicity of two derivatives (38 and 45 was assessed in National Cancer Institute's anticancer screening program, and the results were compared with the cytotoxicity of 6-MP obtained in the same screen. The results show that the compound 38 and 45 were more cytotoxic than 6-MP. Additionally the prodrugs are less effective against leukemia cell line than 6-MP. Both derivatives exhibited high growth-inhibitory activities in renal cell line. However, compound 45 is more cytotoxic than 38 against ovarian cell line.

  14. Genomic evidence for complementary purine metabolism in the pea aphid, Acyrthosiphon pisum, and its symbiotic bacterium Buchnera aphidicola.

    Science.gov (United States)

    Ramsey, J S; MacDonald, S J; Jander, G; Nakabachi, A; Thomas, G H; Douglas, A E

    2010-03-01

    The purine salvage pathway recycles purines to nucleotides, promoting efficient utilization of purine nucleotides. Exceptionally among animals with completely sequenced genomes, the pea aphid lacks key purine recycling genes that code for purine nucleoside phosphorylase and adenosine deaminase, indicating that the aphid can neither metabolize nucleosides to the corresponding purines, nor adenosine to inosine. Purine metabolism genes in the symbiotic bacterium Buchnera complement aphid genes, and Buchnera can meet its nucleotide requirement from aphid-derived guanosine. Buchnera demand for nucleosides may have relaxed the selection for purine recycling in the aphid, leading to the loss of key aphid purine salvage genes. Further, the coupled purine metabolism of aphid and Buchnera could contribute to the dependence of the pea aphid on this symbiosis.

  15. Targeting a Novel Plasmodium falciparum Purine Recycling Pathway with Specific Immucillins

    Energy Technology Data Exchange (ETDEWEB)

    Ting, L; Shi, W; Lewandowicz, A; Singh, V; Mwakingwe, A; Birck, M R; Taylor Ringia, E A; Bench, G; Madrid, D C; Tyler, P C; Evans, G B; Furneaux, R H; Schramm, V L; Kim, K

    2004-05-19

    Plasmodium falciparum is unable to synthesize purine bases and relies upon purine salvage and purine recycling to meet its purine needs. We report that purines formed as products of the polyamine pathway are recycled in a novel pathway in which 5'-methylthioinosine is generated by adenosine deaminase. The action of P. falciparum purine nucleoside phosphorylase is a convergent step of purine salvage, converting both 5'-methylthioinosine and inosine to hypoxanthine. We used accelerator mass spectrometry to verify that 5'-methylthioinosine is an active nucleic acid precursor in P. falciparum. Prior studies have shown that inhibitors of purine salvage enzymes kill malaria, but potent malaria-specific inhibitors of these enzymes have not previously been described. 5'-methylthio-Immucillin-H, a transition state analogue inhibitor that is selective for malarial over human purine nucleoside phosphorylase, kills P. falciparum in culture. Immucillins are currently in clinical trials for other indications and may have application as antimalarials.

  16. 6-Methylpurine derived sugar modified nucleosides: Synthesis and in vivo antitumor activity in D54 tumor expressing M64V-Escherichia coli purine nucleoside phosphorylase.

    Science.gov (United States)

    Hassan, Abdalla E A; Abou-Elkhair, Reham A I; Parker, William B; Allan, Paula W; Secrist, John A

    2016-01-27

    Impressive antitumor activity has been observed with fludarabine phosphate against tumors that express Escherichia coli purine nucleoside phosphorylase (PNP) due to the liberation of 2-fluoroadenine in the tumor tissue. 6-Methylpurine (MeP) is another cytotoxic adenine analog that does not exhibit selectivity when administered systemically, and could be very useful in a gene therapy approach to cancer treatment involving E. coli PNP. The prototype MeP releasing prodrug 9-(2-deoxy-β-d-ribofuranosyl)-6-methylpurine (1) [MeP-dR] has demonstrated good activity against tumors expressing E. coli PNP, but its antitumor activity is limited due to toxicity resulting from the generation of MeP from gut bacteria. Therefore, we have embarked on a medicinal chemistry program to identify a combination of non-toxic MeP prodrugs and non-human adenosine glycosidic bond cleaving enzymes. The two best MeP-based substrates with M64V-E coli PNP, a mutant which was engineered to tolerate modification at the 5'-position of adenosine and its analogs, were 9-(6-deoxy-α-l-talofuranosyl)-6-methylpurine (3) [methyl(talo)-MeP-R] and 9-(α-l-lyxofuranosyl)6-methylpurine (4) [lyxo-MeP-R]. The detailed synthesis methyl(talo)-MeP-R and lyxo-MeP-R, and the evaluation of their substrate activity with 4 enzymes not normally associated with cancer patients is described. In addition, we have determined the intraperitoneal pharmacokinetic (ip-PK) properties of methyl(talo)-MeP-R and have determined its in vivo bystander activity in mice bearing D54 tumors that express M64V PNP. The observed good in vivo bystander activity of [methyl(talo)-MeP-R/M64V-E coli PNP combination suggests that these agents could be useful for the treatment of cancer.

  17. Connectivity patterns and rotamer states of nucleobases determine acid-base properties of metalated purine quartets.

    Science.gov (United States)

    Lüth, Marc Sven; Freisinger, Eva; Kampf, Gunnar; Garijo Anorbe, Marta; Griesser, Rolf; Operschall, Bert P; Sigel, Helmut; Lippert, Bernhard

    2015-07-01

    Potentiometric pH titrations and pD dependent (1)H NMR spectroscopy have been applied to study the acidification of the exocyclic amino group of adenine (A) model nucleobases (N9 position blocked by alkyl groups) when carrying trans-a2Pt(II) (with a=NH3 or CH3NH2) entities both at N1 and N7 positions. As demonstrated, in trinuclear complexes containing central A-Pt-A units, it depends on the connectivity pattern of the adenine bases (N7/N7 or N1/N1) and their rotamer states (head-head or head-tail), how large the acidifying effect is. Specifically, a series of trinuclear complexes with (A-N7)-Pt-(N7-A) and (A-N1)-Pt-(N1-A) cross-linking patterns and terminal 9-alkylguanine ligands (9MeGH, 9EtGH) have been analyzed in this respect, and it is shown that, for example, the 9MeA ligands in trans-,trans-,trans-[Pt(NH3)2(N7-9MeA-N1)2{Pt(NH3)2(9EtGH-N7)}2](ClO4)6·6H2O (4a) and trans-,trans-,trans-[Pt(NH3)2(N7-9EtA-N1)2{Pt(CH3NH2)2(9-MeGH-N7)}2](ClO4)6·3H2O (4b) are more acidic, by ca. 1.3 units (first pKa), than the linkage isomer trans-,trans-,trans-[Pt(CH3NH2)2(N1-9MeA-N7)2{Pt(NH3)2(9MeGH-N7)}2](NO3)6·6.25H2O (1b). Overall, acidifications in these types of complexes amount to 7-9 units, bringing the pKa values of such adenine ligands in the best case close to the physiological pH range. Comparison with pKa values of related trinuclear Pt(II) complexes having different co-ligands at the Pt ions, confirms this picture and supports our earlier proposal that the close proximity of the exocyclic amino groups in a head-head arrangement of (A-N7)-Pt-(N7-A), and the stabilization of the resulting N6H(-)⋯H2N6 unit, is key to this difference.

  18. Effect of dietary Quebracho tannin extract on feed intake, digestibility, excretion of urinary purine derivatives and milk production in dairy cows.

    Science.gov (United States)

    Henke, Anika; Dickhoefer, Uta; Westreicher-Kristen, Edwin; Knappstein, Karin; Molkentin, Joachim; Hasler, Mario; Susenbeth, Andreas

    2017-02-01

    The aim of this study was to evaluate the effects of dietary Quebracho tannin extract (QTE) on feed intake, apparent total tract digestibility (ATTD), excretion of urinary purine derivatives (PD) and milk composition and yield in dairy cows. Fifty Holstein cows were divided into two groups. To reach a similar performance of both groups, cows were divided according to their milk yield, body weight, days in milk and number of lactations at the start of the experiment averaging 33.2 ± 8.2 kg/d, 637 ± 58 kg, 114 ± 73 d and 2.3 ± 1.6 lactations, respectively. The cows were fed a basal diet as total mixed ration containing on dry matter (DM) basis 34% grass silage, 32% maize silage and 34% concentrate feeds. Three dietary treatments were tested, the control (CON, basal diet without QTE), QTE15 (basal diet with QTE at 15 g/kg DM) and QTE30 (basal diet with QTE at 30 g/kg DM). Two treatments were arranged along six periods each 21 d (13 d adaptation phase and 8 d sampling phase). The ATTD of DM and organic matter were reduced only in Diet QTE30, whereas both QTE treatments reduced ATTD of fibre and nitrogen (N), indicating that QTE impaired rumen fermentation. Nevertheless, feed intake was unaffected by QTE. In Diet CON, urinary N excretion accounted for 29.8% of N intake and decreased in treatments QTE15 and QTE30 to 27.5% and 17.9%, respectively. Daily faecal N excretion increased in treatments CON, QTE15 and QTE30 from 211 to 237 and 273 g/d, respectively, which amounted to 39.0%, 42.4% and 51.7% of the N intake, respectively. Hence, QTE shifted N excretion from urine to faeces, whereas the proportion of ingested N appearing in milk was not affected by QTE (average 30.7% of N intake). Daily PD excretion as indicator for microbial crude protein (CP) flow at the duodenum decreased in treatment QTE30 compared with Diet CON from 413 to 280 mmol/d. The ratios of total PD to creatinine suggest that urinary PD excretion was already lower when feeding Diet

  19. Application of Surfactant Micellar Solutions as Extractants and Mobile Phases for TLC-Determination of Purine Bases and Doping Agents in Biological Liquids

    Directory of Open Access Journals (Sweden)

    Daria Victorovna Yedamenko

    2015-04-01

    Full Text Available Separation of caffeine and its metabolites (theophylline and theobromine and doping agents (spironolactone, propranolol, and ephedrine and determination of caffeine in serum sample and propranolol and ephedrine in urine were studied on normal-phase thin layers (“Sorbfil-UV-254”. Aqueous organic solvents and aqueous micellar surfactant solutions were compared as the mobile phases for separation. The acceptable separation of purine bases and doping agents was achieved by micellar Thin Layer Chromatography and normal-phase Thin Layer Chromatography. Anionic surfactant solution with added 1-propanol was the best eluent as for caffeine, theophylline, and theobromine separation, as for doping agents. The best characteristics of caffeine extraction from serum, and propranolol and ephedrine from urine were achieved when micellar eluent based on non-ionic Tween-80 surfactant was used. DOI: http://dx.doi.org/10.17807/orbital.v7i1.632

  20. A Theoretical Study of the Binding of [Re6Se8(OH2(H2O4] Rhenium Clusters to DNA Purine Base Guanine

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    Leonor Alvarado-Soto

    2015-06-01

    Full Text Available Hexanuclear rhenium complexes are promising candidates for use as antitumor drugs. However, to date, there has been no investigation into the nature of their binding to DNA. In this study, density functional theory (DFT was used to examine the binding of [Re6Se8(OH2(H2O4] to the DNA purine base guanine. The geometrical structures of cluster-guanine adducts in water were modeled at the zero order regular approximation (ZORA-PW91 level. Calculating the bond energies allowed us to compare the cis and trans forms of the cluster, and a possible manners of interaction between [Re6Se8(OH2(H2O3] clusters and DNA was obtained and explained.

  1. Níveis de uréia na ração de novilhos de quatro grupos genéticos: estimativa da produção de proteína microbiana por meio dos derivados de purinas na urina utilizando duas metodologias de coleta Urea levels in diet for steers of four genetic groups: microbial protein production by the urinary purine derivatives, using two collection methodologies

    Directory of Open Access Journals (Sweden)

    Luciana Navajas Rennó

    2008-03-01

    urinary purine derivatives was evaluated by using two collection methodologies in steers of four genetic groups: Holstein in, ½ Holstein-Guzera, ½ Holstein-Gir and Zebu. Animals were fed diets with 50:50 tifton-85 bermudagrass hay to concentrate ratio and assigned to four 4 ´ 4 latin squares (genetic groups: four animals, four experimental periods and four treatments (diets and were. Diets approximately contained 12% CP. The urine samples, from each experimental period, were obtained from 24-h collection and spot urine collection, when the animals spontaneously urinated. Analyses of purine derivatives, allantoin and uric acid were performed in the urine. A comparison among the microbial production using the purine bases in the abomasum and urinary purine derivatives; determination of microbial production by purine derivatives using two different equations or purine bases method in the abomasum; and estimate of urinary of purine derivatives and microbial production by means of spot urine collection and by 24-h total urine collection, were performed. Production and microbial efficiency showed higher values for Holstein animals, intermediary values for crossbred and smaller values for Zebu. The estimation of microbial nitrogen compounds production could be performed from the excretion of urinary purine derivatives. The spot urine collection is a fast and efficient methodology to estimate the excretion of urinary purine derivatives and the microbial nitrogen compounds production.

  2. Occurrence of theobromine synthase genes in purine alkaloid-free species of Camellia plants.

    Science.gov (United States)

    Ishida, Mariko; Kitao, Naoko; Mizuno, Kouichi; Tanikawa, Natsu; Kato, Misako

    2009-02-01

    Caffeine (1,3,7-trimethylxanthine) and theobromine (3,7-dimethylxanthine) are purine alkaloids that are present in high concentrations in plants of some species of Camellia. However, most members of the genus Camellia contain no purine alkaloids. Tracer experiments using [8-(14)C]adenine and [8-(14)C]theobromine showed that the purine alkaloid pathway is not fully functional in leaves of purine alkaloid-free species. In five species of purine alkaloid-free Camellia plants, sufficient evidence was obtained to show the occurrence of genes that are homologous to caffeine synthase. Recombinant enzymes derived from purine alkaloid-free species showed only theobromine synthase activity. Unlike the caffeine synthase gene, these genes were expressed more strongly in mature tissue than in young tissue.

  3. Structure and dynamics of near-threshold leptons driven by dipolar interactions: an accurate computational study for the DNA purinic bases

    Science.gov (United States)

    Carelli, Fabio; Gianturco, Francesco Antonio

    2016-06-01

    The interaction of low-energy scattering electrons/positrons with molecular targets characterized by a "supercritical" permanent dipole moment (≳2.0 D) presents special physical characteristics that affect their spatial distributions, around the nuclear network of the molecular partners, both above and below the energy thresholds. Such special states are described as either dipole scattering states (DSS) above thresholds or as dipole bound states (DBS) below thresholds. The details of their respective behaviour will be presented and discussed in this work in the case of the purinic DNA bases of adenine and guanine. The behavior of the additional electron, in particular, will be discussed in detail by providing new computational results that will be related to the findings from recent experiments on the same DNA bases, confirming the transient electron's behaviour surmised by them. This work is affectionately dedicated to Michael Allan on the occasion of his official retirement. We wish to this dear friend and outstanding scientist many years to come in the happy pursuit of his many scientific interests.Contribution to the Topical Issue "Advances in Positron and Electron Scattering", edited by Paulo Limao-Vieira, Gustavo Garcia, E. Krishnakumar, James Sullivan, Hajime Tanuma and Zoran Petrovic.

  4. The effects of concentrate added to pineapple (Ananas comosus Linn. Mer.) waste silage in differing ratios to form complete diets, on digestion, excretion of urinary purine derivatives and blood metabolites in growing, male, Thai swamp buffaloes.

    Science.gov (United States)

    Jetana, T; Suthikrai, W; Usawang, S; Vongpipatana, C; Sophon, S; Liang, J B

    2009-04-01

    Four, male, growing Thai swamp buffaloes (197 +/- 5.3 kg and all 1 year old) were used to evaluate the effects of concentrate added to pineapple waste silage in differing ratios, to form a complete diet, studying in vivo digestion, the rate of passage, microbial protein synthesis and blood metabolites. Animals were fed ad libitum with 4 diets, using four combinations of pineapple waste silage (P) and concentrate (C), in the proportions (on a dry matter basis) of 0.8:0.2 (P80:C20), 0.6:0.4 (P60:C40), 0.4:0.6 (P40:C60) and 0.2:0.8 (P20:C80). The results showed that the intakes of dry matter (DM), organic matter (OM), nitrogen (N), the N-balance, urinary purine derivatives (PD) excretion, the ratios of allantoin to creatinine (CR), PD to CR, the plasma urea-N (PUN) and insulin increased in the animals, but the intake of neutral detergent fiber (NDF), the coefficient of whole tract, apparent digestibility of NDF, the transit time (TT) and the mean retention time (TMRT) decreased, when the proportion of concentrate in the diet increased. This study indicated that the proportion of P40:C60 in the diet produced the best efficiency of urinary PD excretion (mmol) per digestible OM intake (kg DOMI).

  5. Thermodynamic and kinetic characterization of ligand binding to the purine riboswitch aptamer domain.

    Science.gov (United States)

    Gilbert, Sunny D; Stoddard, Colby D; Wise, Sarah J; Batey, Robert T

    2006-06-09

    Riboswitches are cis-acting genetic regulatory elements found commonly in bacterial mRNAs that consist of a metabolite-responsive aptamer domain coupled to a regulatory switch. Purine riboswitches respond to intracellular concentrations of either adenine or guanine/hypoxanthine to control gene expression. The aptamer domain of the purine riboswitch contains a pyrimidine residue (Y74) that forms a Watson-Crick base-pairing interaction with the bound purine nucleobase ligand that discriminates between adenine and guanine. We sought to understand the structural basis of this specificity and the mechanism of ligand recognition by the purine riboswitch. Here, we present the 2,6-diaminopurine-bound structure of a C74U mutant of the xpt-pbuX guanine riboswitch, along with a detailed thermodynamic and kinetic analysis of nucleobase recognition by both the native and mutant riboswitches. These studies demonstrate clearly that the pyrimidine at position 74 is the sole determinant of purine riboswitch specificity. In addition, the mutant riboswitch binds adenine and adenine derivatives well compared with the guanine-responsive riboswitch. Under our experimental conditions, 2,6-diaminopurine binds the RNA with DeltaH=-40.3 kcal mol(-1), DeltaS=-97.6 cal mol(-1)K(-1), and DeltaG=-10.73 kcal mol(-1). A kinetic determination of the slow rate (0.15 x 10(5)M(-1)s(-1) and 2.1 x 10(5)mM(-1)s(-1) for 2-aminopurine binding the adenine-responsive mutant riboswitch and 7-deazaguanine-binding guanine riboswitch, respectively) of association under varying experimental conditions allowed us to propose a mechanism for ligand recognition by the purine riboswitch. A conformationally dynamic unliganded state for the binding pocket is stabilized first by the Watson-Crick base pairing between the ligand and Y74, and by the subsequent ordering of the J2/3 loop, enclosing the ligand within the three-way junction.

  6. Can an Excess Electron Localise on a Purine Moiety in the Adenine-thymine Watson-Crick Base Pair? A Computational Study

    Energy Technology Data Exchange (ETDEWEB)

    Mazurkiewicz, Kamil; Haranczyk, Maciej; Gutowski, Maciej S.; Rak, Janusz

    2007-04-17

    The electron affinity and the propensity to electron-induced proton transfer (PT) of hydrogen-bonded complexes between the Watson–Crick adenine–thymine pair (AT) and simple organic acid (HX), attached to adenine in the Hoogsteen-type configuration, were studied at the B3LYP/6-31+G** level. Although the carboxyl group is deprotonated at physiological pH, its neutral form, COOH, resembles the peptide bond or the amide fragment in the side chain of asparagine (Asn) or glutamine (Gln). Thus, these complexes mimic the interaction between the DNA environment (e.g., proteins) and nucleobase pairs incorporated in the biopolymer. Electron attachment is thermodynamically feasible and adiabatic electron affinities range from 0.41 to 1.28 eV, while the vertical detachment energies of the resulting anions span the range of 0.39 –2.88 eV. Low-energy activation barriers separate the anionic minima: aHX(AT) from the more stable single-PT anionic geometry, aHX(AT)-SPT, and aHX(AT)-SPT from the double-PT anionic geometry, aHX(AT)-DPT. Interaction between the adenine of the Watson–Crick AT base pair with an acidic proton donor probably counterbalances the larger EA of isolated thymine, as SOMO is almost evenly delocalized over both types of nucleic bases in the aHX(AT) anions. Moreover, as a result of PT the excess electron localizes entirely on adenine. Thus, in DNA interacting with its physiological environment, damage induced by low-energy electrons could begin, contrary to the current view, with the formation of purine anions, which are not formed in isolated DNA because of the greater stability of anionic pyrimidines.

  7. Can an excess electron localize on a purine moiety in the adenine-thymine Watson-Crick base pair? A computational study

    Science.gov (United States)

    Mazurkiewicz, Kamil; Harańczyk, Maciej; Gutowski, Maciej; Rak, Janusz

    The electron affinity and the propensity to electron-induced proton transfer (PT) of hydrogen-bonded complexes between the Watson-Crick adenine-thymine pair (AT) and simple organic acid (HX), attached to adenine in the Hoogsteen-type configuration, were studied at the B3LYP/6-31+G** level. Although the carboxyl group is deprotonated at physiological pH, its neutral form, COOH, resembles the peptide bond or the amide fragment in the side chain of asparagine (Asn) or glutamine (Gln). Thus, these complexes mimic the interaction between the DNA environment (e.g., proteins) and nucleobase pairs incorporated in the biopolymer. Electron attachment is thermodynamically feasible and adiabatic electron affinities range from 0.41 to 1.28 eV, while the vertical detachment energies of the resulting anions span the range of 0.39-2.88 eV. Low-energy activation barriers separate the anionic minima: aHX(AT) from the more stable single-PT anionic geometry, aHX(AT)-SPT, and aHX(AT)-SPT from the double-PT anionic geometry, aHX(AT)-DPT. Interaction between the adenine of the Watson-Crick AT base pair with an acidic proton donor probably counterbalances the larger EA of isolated thymine, as SOMO is almost evenly delocalized over both types of nucleic bases in the aHX(AT) anions. Moreover, as a result of PT the excess electron localizes entirely on adenine. Thus, in DNA interacting with its physiological environment, damage induced by low-energy electrons could begin, contrary to the current view, with the formation of purine anions, which are not formed in isolated DNA because of the greater stability of anionic pyrimidines.0

  8. Purine molecules as hypnogenic factors role of adenosine, ATP, and caffeine.

    Science.gov (United States)

    Díaz-Muñoz, M; Salín-Pascual, R

    2010-12-01

    Purines are ubiquitous molecules with important roles in the regulation of metabolic networks and signal transduction events. In the central nervous system, adenosine and ATP modulate the sleep-wake cycle, acting as ligands of specific transmembrane receptors and as allosteric effectors of key intracellular enzymes for brain energy expenditure. Two types of adenosine receptors seem to be relevant to the sleep function, A1 and A2A. Caffeine, an antagonist of adenosine receptors, has been used as a tool in some of the studies reviewed in the present chapter. Possible changes in adenosine functioning due to the aging process have been observed in animal models and abnormalities in the adenosine system could also explain primary insomnia or the reduced amount of delta sleep and increased sensitivity to caffeine in some subjects with sleep deficits. Caffeine is a methylated-derivate of xanthine with profound effects on the onset and quality of sleep episodes. This purine acts principally as an antagonist of the A2A receptors. Adenosine and ATP in the nervous system are the bridge between metabolic activity, recovery function, and purinergic transmission that underlies the daily wake-sleep cycle in mammals. Modulators of purine actions have the potential to alleviate insomnia and other sleep disorders based on their physiopathological role during the sleep process.

  9. LC-MS-Based Metabolomics Discovers Purine Endogenous Associations with Low-Dose Salbutamol in Urine Collected for Antidoping Tests.

    Science.gov (United States)

    Wang, Yaoyao; Caldwell, Richard; Cowan, David A; Legido-Quigley, Cristina

    2016-02-16

    Current antidoping analytical methods are tailored mainly to the targeting of known drugs and endogenous molecules. This causes difficulties in rapidly reacting to emerging threats, such as designer drugs, biological therapeutic agents, and technologies. Biomarkers are considered as a promising approach for the fight against these threats to sport. The main purpose of this study was to find surrogate biomarkers induced by the intake of small amounts of the model compound salbutamol and explore a sensitive approach to help screen for possible drug misuse. Urine samples (91) from athletes with detectable salbutamol (30) and negative samples (61) were analyzed using a UHPLC-MS. A third group (30) was created by spiking salbutamol into negative samples to eliminate confounding effects. Data were then analyzed in XCMS to extract metabolic features. Orthogonal partial least squares-discriminant analysis was performed to select features correlated with detectable salbutamol (p(corr) > 0.5) and ROC analysis was performed to measure the predictive potential of the markers. Univariate analysis including Mann-Whitney U test and Spearman's correlation was conducted on selected markers. A total of 7000 metabolic features were parsed, one feature identified as hypoxanthine increased with salbutamol (p salbutamol (r = 0.415, p salbutamol administration. This surrogate discovery approach needs further PK studies but in the meantime can be used as an intelligence-based complementary approach for targeting of athletes to be further tested.

  10. Distinct Purine Distribution in Carbonaceous Chondrites

    Science.gov (United States)

    Callahan, Michael P.; Smith, Karen E.; Cleaves, Henderson J.; Ruzicka, Josef; Stern, Jennifer C.; Glavin, Daniel P.; House, Christopher H.; Dworkin, Jason P.

    2011-01-01

    Carbonaceous chondrite meteorites are known to contain a diverse suite of organic compounds, many of which are essential components of biochemistry. Amino acids, which are the monomers of proteins, have been extensively studied in such meteorites (e.g. Botta and Bada 2002; Pizzarello et aI., 2006). The origin of amino acids in meteorites has been firmly established as extraterrestrial based on their detection typically as racemic mixtures of amino acids, the presence of many non-protein amino acids, and non-terrestrial values for compound-specific deuterium, carbon, and nitrogen isotopic measurements. In contrast to amino acids, nucleobases in meteorites have been far less studied. Nucleobases are substituted one-ring (pyrimidine) or two-ring (purine) nitrogen heterocyclic compounds and serve as the information carriers of nucleic acids and in numerous coenzymes. All of the purines (adenine, guanine, hypoxanthine, and xanthine) and pyrimidines (uracil) previously reported in meteorites are biologically common and could be interpreted as the result of terrestrial contamination (e.g. van del' Velden and Schwartz, 1974.) Unlike other meteoritic organics, there have been no observations of stochastic molecular diversity of purines and pyrimidines in meteorites, which has been a criterion for establishing extraterrestrial origin. Maltins et al. (2008) performed compound-specific stable carbon isotope measurements for uracil and xanthine in the Murchison meteorite. They assigned a non-terrestrial origin for these nucleobases; however, the possibility that interfering indigenous molecules (e.g. carboxylic acids) contributed to the 13C-enriched isotope values for these nucleobases cannot be completely ruled out. Thus, the origin of these meteoritic nucleobases has never been established unequivocally. Here we report on our investigation of extracts of II different carbonaceous chondrites covering various petrographic types (Cl, CM, and CR) and degrees of aqueous alteration

  11. Deficiency of the purine metabolic gene HPRT dysregulates microRNA-17 family cluster and guanine-based cellular functions: a role for EPAC in Lesch-Nyhan syndrome.

    Science.gov (United States)

    Guibinga, Ghiabe-Henri; Murray, Fiona; Barron, Nikki; Pandori, William; Hrustanovic, Gorjan

    2013-11-15

    Lesch-Nyhan syndrome (LNS) is a neurodevelopmental disorder caused by mutations in the gene encoding the purine metabolic enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). A series of motor, cognitive and neurobehavioral anomalies characterize this disease phenotype, which is still poorly understood. The clinical manifestations of this syndrome are believed to be the consequences of deficiencies in neurodevelopmental pathways that lead to disordered brain function. We have used microRNA array and gene ontology analysis to evaluate the gene expression of differentiating HPRT-deficient human neuron-like cell lines. We set out to identify dysregulated genes implicated in purine-based cellular functions. Our approach was based on the premise that HPRT deficiency affects preeminently the expression and the function of purine-based molecular complexes, such as guanine nucleotide exchange factors (GEFs) and small GTPases. We found that several microRNAs from the miR-17 family cluster and genes encoding GEF are dysregulated in HPRT deficiency. Most notably, our data show that the expression of the exchange protein activated by cAMP (EPAC) is blunted in HPRT-deficient human neuron-like cell lines and fibroblast cells from LNS patients, and is altered in the cortex, striatum and midbrain of HPRT knockout mouse. We also show a marked impairment in the activation of small GTPase RAP1 in the HPRT-deficient cells, as well as differences in cytoskeleton dynamics that lead to increased motility for HPRT-deficient neuron-like cell lines relative to control. We propose that the alterations in EPAC/RAP1 signaling and cell migration in HPRT deficiency are crucial for neuro-developmental events that may contribute to the neurological dysfunctions in LNS.

  12. Bias of purine stretches in sequenced chromosomes

    DEFF Research Database (Denmark)

    Ussery, David; Soumpasis, Dikeos Mario; Brunak, Søren

    2002-01-01

    We examined more than 700 DNA sequences (full length chromosomes and plasmids) for stretches of purines (R) or pyrimidines (Y) and alternating YR stretches; such regions will likely adopt structures which are different from the canonical B-form. Since one turn of the DNA helix is roughly 10 bp, we...... measured the fraction of each genome which contains purine (or pyrimidine) tracts of lengths of 10 by or longer (hereafter referred to as 'purine tracts'), as well as stretches of alternating pyrimidines/purine ('pyr/pur tracts') of the same length. Using this criteria, a random sequence would be expected......, in eukaryotes there is an abundance of long stretches of purines or alternating purine/pyrimidine tracts, which cannot be explained in this way; these sequences are likely to play an important role in eukaryotic chromosome organisation....

  13. Stretches of alternating pyrimidine/purines and purines are respectively linked with pathogenicity and growth temperature in prokaryotes

    DEFF Research Database (Denmark)

    Ussery, David; Bohlin, J; Hardy, SP

    2009-01-01

    -tracts are associated with phylum, AT content, oxygen requirement, growth temperature and halotolerance. All associations described were statistically significant with p factors......BACKGROUND: The genomic fractions of purine (RR) and alternating pyrimidine/purine (YR) stretches of 10 base pairs or more, have been linked to genomic AT content, the formation of different DNA helices, strand-biased gene distribution, DNA structure, and more. Although some of these factors...... regression analysis to investigate how AT content, habitat, growth temperature, pathogenicity, phyla, oxygen requirement and halotolerance correlated with the distribution of RR and YR stretches in prokaryotes. RESULTS: Our results indicate that RR and YR-stretches are differently distributed in prokaryotic...

  14. Microwave-assisted one step synthesis of 8-arylmethyl-9H-purin-6-amines.

    Science.gov (United States)

    Tao, Hui; Kang, Yanlong; Taldone, Tony; Chiosis, Gabriela

    2009-01-15

    Molecular chaperone heat shock protein 90 (Hsp90) is an important target in cancer and neurodegenerative diseases, and has rapidly become the focus of several drug discovery efforts. Among small molecule Hsp90 inhibitors with clinical applicability are derivatives of 8-arylmethyl-9H-purin-6-amine class. Here we report the use of microwave-assisted chemistry for the successful one-pot delivery of 8-arylmethyl-9H-purin-6-amines. We discuss the applicability as well as the limitations of this method towards the creation of a large chemical diversity in the 8-arylmethyl-9H-purin-6-amine series.

  15. Enantioselective and Regiodivergent Addition of Purines to Terminal Allenes: Synthesis of Abacavir.

    Science.gov (United States)

    Thieme, Niels; Breit, Bernhard

    2017-02-01

    The rhodium-catalyzed atom-economic asymmetric N-selective intermolecular addition of purine derivatives to terminal allenes is reported. Branched allylic purines were obtained in high yields, regioselectivity and outstanding enantioselectivity utilizing a Rh/Josiphos catalyst. Conversely, linear selective allylation of purines could be realized in good to excellent regio- and E/Z-selectivity with a Pd/dppf catalyst system. Furthermore, the new methodology was applied to a straightforward asymmetric synthesis of carbocyclic nucleoside abacavir. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. [Total purine content in selected foods].

    Science.gov (United States)

    Wolfram, G; Colling, M

    1987-12-01

    For the dietary treatment of hyperuricemia and gout, it is necessary to know the total purine content of food. A new method determining the purine content enzymatically, as uric acid, allows routine analysis. Many foods of animal and plant origin were brought in usual or alternative stores and analysed.

  17. [Quantum-chemical investigation of the elementary molecular mechanisms of pyrimidine-purine transversions].

    Science.gov (United States)

    Brovarets', O O; Govorun D M

    2010-01-01

    Purine-purine mispairs of DNA (thus involving template base in anti-conformation along the glycosidic bond and base of the incoming nucleotide - in syn-conformation) leading to pyrimidine-purine "transversions"-type point mutations were revealed and characterized at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory in vacuum approach adequately modeling hydrophobic environment of the active centre of high-fidelity replicative DNA-polymerases.

  18. Distinct Distribution of Purines in CM and CR Carbonaceous Chondrites

    Science.gov (United States)

    Callahan, Michael P.; Stern, Jennifer C.; Glavin, Daniel P.; Smith, Karen E.; Martin, Mildred G.; Dworkin, Jason P.

    2010-01-01

    Carbonaceous meteorites contain a diverse suite of organic molecules and delivered pre biotic organic compounds, including purines and pyrimidines, to the early Earth (and other planetary bodies), seeding it with the ingredients likely required for the first genetic material. We have investigated the distribution of nucleobases in six different CM and CR type carbonaceous chondrites, including fivc Antarctic meteorites never before analyzed for nucleobases. We employed a traditional formic acid extraction protocol and a recently developed solid phase extraction method to isolate nucleobases. We analyzed these extracts by high performance liquid chromatography with UV absorbance detection and tandem mass spectrometry (HPLC-UV -MS/MS) targeting the five canonical RNAIDNA bases and hypoxanthine and xanthine. We detected parts-per-billion levels of nucleobases in both CM and CR meteorites. The relative abundances of the purines found in Antarctic CM and CR meteorites were clearly distinct from each other suggesting that these compounds are not terrestrial contaminants. One likely source of these purines is formation by HCN oligomerization (with other small molecules) during aqueous alteration inside the meteorite parent body. The detection of the purines adenine (A), guanine (0), hypoxanthine (HX), and xanthine (X) in carbonaceous meteorites indicates that these compounds should have been available on the early Earth prior to the origin of the first genetic material.

  19. Effect of urea inclusion in diets containing corn dried distillers grains on feedlot cattle performance, carcass characteristics, ruminal fermentation, total tract digestibility, and purine derivatives-to-creatinine index.

    Science.gov (United States)

    Ceconi, I; Ruiz-Moreno, M J; DiLorenzo, N; DiCostanzo, A; Crawford, G I

    2015-01-01

    Increased availability of rapidly fermentable carbohydrates and a great proportion of corn-derived CP in the diet may result in a degradable intake protein (DIP) deficit. Therefore, ruminal DIP deficit may result from high dietary inclusion of processed corn grain and small to moderate inclusion of corn distillers grains (DG). Two experiments were conducted to evaluate the effect of increasing dietary DIP concentration through the inclusion of urea on feedlot cattle performance, carcass characteristics, ruminal fermentation, total tract digestibility, and purine derivatives-to-creatinine (PDC) index. In Exp. 1, 42 steers (428 ± 5 kg initial BW) were assigned randomly to 1 of 3 diets containing (DM basis) 0 (control [CON]), 0.4 (low urea [LU]), or 0.6% urea (high urea [HU]) to provide 6.4, 7.5, or 8.0% dietary DIP, respectively, and 12% high-moisture corn (HMC), 20% corn dried DG with solubles (DDGS), 10% ryegrass haylage, 2.9% dry supplement, and dry-rolled corn (DRC). Steers were fed ad libitum once daily using a Calan gate system. Carcass-adjusted final BW and DMI were similar among treatments (P ≥ 0.58). Carcass-adjusted ADG was greater (P ≤ 0.04) for the HU diet compared with the LU and CON diets and was similar (P = 0.73) between the LU and CON diets. Carcass-adjusted G:F was greater (P = 0.03) for the HU diet compared with the LU diet, tended (P = 0.09) to be greater compared with the CON diet, and was similar (P = 0.61) between the LU and CON diets. Carcass characteristics were similar (P ≥ 0.34) among treatments. In Exp. 2, 4 ruminally cannulated steers (347 ± 18 kg initial BW) were randomly assigned to a replicated 2 × 2 Latin square design. Steers were fed the same CON or HU diet used in Exp. 1 ad libitum once daily. Differences in the PDC index were used as indicators of differences in microbial CP synthesis. Ruminal pH, OM intake, and starch and CP digestibility were not affected by treatment (P ≥ 0.13). Digestibility of OM and NDF and

  20. [Purine in common plant food in China].

    Science.gov (United States)

    Rong, Shengzhong; Zou, Lina; Wang, Zhaoxu; Pan, Hongzhi; Yang, Yuexin

    2012-01-01

    To determine the content of purine in plant food in China with HPLC. HPLC analysis was applied on Waters Atlantis T3 column (4.6mm x 250mm x 5 microm), using 10.0 mmol/L NH4COOH (pH 3.6) and CH3OH (99%/1%) as mobile phase and running at a flow rate of 1.0 ml/min. The column temperature was 30 degrees C, and the detection wavelength was at 254nm. The content of purine varied significantly in different kinds of plant food. The content of purine in dried fungi and dried legumes and legume products was higher than that in other food, the content of purine in vegetables and vegetable products and fruits and fruit products was low. As a whole, the content of purine was: dried fungi and algae > dried legumes and legume products > nuts and fresh > seeds fungi and algae > cereal and cereals products > vegetables and vegetable products > fruit and fruit products > tubers, starches and products. The content of purine of dried fungi and algae and dried legumes and legume products in plant food was high. The content of purine was varied significantly in different kinds of plant food.

  1. Variações diárias nas excreções de creatinina e derivados de purinas em novilhas Daily variation in the urinary excretion of creatinine and purine derivatives in heifers

    Directory of Open Access Journals (Sweden)

    Thalita Lázaro Leal

    2007-08-01

    microbial protein synthesis is affected by the number of urinary sampling days. Eleven dairy Holstein heifers averaging 287 ± 49 kg of body weight (BW in the beginning of the trial were used. Samples of urine were collected during six consecutive days using N. 22 or 26 Folley catheters. Number of sampling days was compared by analysis of variance. The model included animal as random and sampling day as fixed effects. Animals were fed corn silage "ad libitum" plus 2 kg of concentrate. Urinary excretions of creatinine, urea, allantoin, uric acid, and total purine derivatives and estimation of microbial protein synthesis were not affected by the number of urinary sampling days. Excretion of creatinine in urine averaged 30.5 mg/kg BW, 124.84 mg/kg0.75 or 1.1 mmol/kg0.75. It can be concluded that no more than 24 h (one sampling day of urine collection was required to accurate determine excretion of nitrogenous compounds, which has important practical applications due to labor and costs reductions.

  2. Study of Copper and Purine-Copper Complexes on Modified Carbon Electrodes by Cyclic and Elimination Voltammetry

    Science.gov (United States)

    Trnkova, Libuse; Zerzankova, Lenka; Dycka, Filip; Mikelova, Radka; Jelen, Frantisek

    2008-01-01

    Using a paraffin impregnated graphite electrode (PIGE) and mercury-modified pyrolytic graphite electrode with basal orientation (Hg-PGEb) copper(II) and Cu(II)-DNA purine base solutions have been studied by cyclic (CV) and linear sweep voltammetry (LSV) in connection with elimination voltammetry with linear scan (EVLS). In chloride and bromide solutions (pH 6), the redox process of Cu(II) proceeded on PIGE with two cathodic and two anodic potentially separated signals. According to the elimination function E4, the first cathodic peak corresponds to the reduction Cu(II) + e- → Cu(I) with the possibility of fast disproportionation 2Cu(I) → Cu(II)+ Cu(0). The E4 of the second cathodic peak signalized an electrode process controlled by a surface reaction. The electrode system of Cu(II) on Hg-PGEb in borate buffer (pH 9.2) was characterized by one cathodic and one anodic peak. Anodic stripping voltammetry (ASV) on PIGE and cathodic stripping voltammetry (CSV) on Hg-PGEb were carried out at potentials where the reduction of copper ions took place and Cu(I)-purine complexes were formed. By using ASV and CSV in combination with EVLS, the sensitivity of Cu(I)-purine complex detection was enhanced relative to either ASV or CSV alone, resulting in higher peak currents of more than one order of magnitude. The statistical treatment of CE data was used to determine the reproducibility of measurements. Our results show that EVLS in connection with the stripping procedure is useful for both qualitative and quantitative microanalysis of purine derivatives and can also reveal details of studied electrode processes. PMID:27879715

  3. New arylpiperazinylalkyl derivatives of 8-alkoxy-purine-2,6-dione and dihydro[1,3]oxazolo[2,3-f]purinedione targeting the serotonin 5-HT1A /5-HT2A /5-HT7 and dopamine D2 receptors.

    Science.gov (United States)

    Chłoń-Rzepa, Grażyna; Zagórska, Agnieszka; Bucki, Adam; Kołaczkowski, Marcin; Pawłowski, Maciej; Satała, Grzegorz; Bojarski, Andrzej J; Partyka, Anna; Wesołowska, Anna; Pękala, Elżbieta; Słoczyńska, Karolina

    2015-04-01

    To obtain potential antidepressants and/or antipsychotics, a series of new long-chain arylpiperazine derivatives of 8-alkoxy-purine-2,6-dione (10-24) and dihydro[1,3]oxazolo[2,3-f]purinedione (30-34) were synthesized and their serotonin (5-HT1A , 5-HT2A , 5-HT6 , 5-HT7 ) and dopamine (D2 ) receptor affinities were determined. The study allowed the identification of some potent 5-HT1A /5-HT7 /D2 ligands with moderate affinity for 5-HT2A sites. The binding mode of representative compounds from both chemical classes (11 and 31) in the site of 5-HT1A receptor was analyzed in computational studies. In functional in vitro studies, the selected compounds 15 and 16 showed antagonistic properties for the evaluated receptors. 8-Methoxy-7-{4-[4-(2-methoxyphenyl)-piperazin-1-yl]-butyl}-1,3-dimethyl-purine-2,6-dione (15) showed a lack of activity in terms and under the conditions of the forced swim, four plate and amphetamine-induced hyperactivity tests in mice, probably as a result of its high first pass effect in the liver.

  4. The salivary purine nucleosidase of the mosquito, Aedes aegypti.

    Science.gov (United States)

    Ribeiro, José M C; Valenzuela, Jesus G

    2003-01-01

    A cDNA clone originating from adult female Aedes aegypti mosquitoes was found with substantial similarity to nucleosidases of the EC 3.2.2.1 enzyme class. Although this type of enzyme is unusual in animals, abundant enzyme activity was found in salivary homogenates of this mosquito, but not in salivary homogenates of the mosquitoes Anopheles gambiae and Culex quinquefasciatus, or the sand fly Lutzomyia longipalpis. Aedes salivary homogenate hydrolyses inosine and guanosine to hypoxanthine and xanthine plus the ribose moiety, but does not hydrolyse the pyrimidines uridine and cytidine, thus characterizing the presence of a purine nucleosidase activity. The enzyme is present in oil-induced saliva, indicating that it is secreted. Male Ae. aegypti salivary gland homogenates (SGH) have very low purine nucleosidase activity, suggesting that the enzyme plays a role in mosquito blood feeding. A novel isocratic HPLC method to separate nucleosides and their bases is described.

  5. View-based Propagator Derivation

    CERN Document Server

    Schulte, Christian

    2009-01-01

    When implementing a propagator for a constraint, one must decide about variants: When implementing min, should one also implement max? Should one implement linear constraints both with unit and non-unit coefficients? Constraint variants are ubiquitous: implementing them requires considerable (if not prohibitive) effort and decreases maintainability, but will deliver better performance than resorting to constraint decomposition. This paper shows how to use views to derive perfect propagator variants. A model for views and derived propagators is introduced. Derived propagators are proved to be indeed perfect in that they inherit essential properties such as correctness and domain and bounds consistency. Techniques for systematically deriving propagators such as transformation, generalization, specialization, and type conversion are developed. The paper introduces an implementation architecture for views that is independent of the underlying constraint programming system. A detailed evaluation of views implement...

  6. Financial Derivatives (Based on Two Supports Evaluation

    Directory of Open Access Journals (Sweden)

    Tiberiu Socaciu

    2011-10-01

    Full Text Available In this paper we build a PDE like Black-Scholes equation in hypothesis of a financial derivative that is dependent on two supports (usual is dependent only on one support, like am
    option based on gold, when national currency has a great float.
    Keywords: Financial derivatives, derivatives evaluation, derivatives based on two supports, extended Itō like lemma.

  7. Variações diárias nas excreções de creatinina e derivados de purinas em novilhos Daily variation in the excretion of creatinine and purine derivatives in steers

    Directory of Open Access Journals (Sweden)

    Thalita Lázaro Leal

    2007-08-01

    Full Text Available Objetivou-se estimar as variações nas excreções diárias de creatinina, uréia e derivados de purinas (DP na urina utilizando coletas durante seis dias consecutivos e avaliar as concentrações de nitrogênio uréico no plasma (NUP em novilhos. Utilizaram-se quatro animais, machos castrados, de grau de sangue predominantemente Holandês, peso médio de 445 kg, distribuídos em quadrado latino 4 x 4, com os tratamentos definidos em esquema fatorial 2 x 2 (dois níveis de uréia em substituição ao farelo de soja: 0 e 100%; e dois níveis de oferta de concentrado: 0,75 e 1,25% do PV e a comparação entre dias de avaliação, em esquema de parcelas subdivididas. O volumoso, constituído de silagem de capim-elefante (80% e silagem de sorgo (20%, foi fornecido à vontade. A síntese de compostos nitrogenados microbianos, estimada a partir da excreção de DP, foi maior quando houve maior oferta de concentrado e menor quando a proteína do farelo de soja foi substituída pela uréia. Não houve efeito da interação níveis de concentrado ´ níveis de uréia nem efeito de níveis de uréia sobre a concentração de NUP e a excreção de N-uréico na urina. As excreções urinárias de uréia, alantoína, ácido úrico e a quantidade estimada de proteína microbiana não foram afetadas pelos dias de coleta de urina. Não houve diferença na excreção de creatinina entre os dias de coleta, sendo obtido valor médio de 25,47 mg/kgPV, 117,92 mg/kg0,75 ou 1,04 mmol/kg0,75. A ausência de efeito de número de dias sobre a excreção de creatinina tem grande aplicação prática. Na estimativa da excreção de creatinina e de derivados de purinas, recomendam-se coletas de urina com duração de 24 horas.The objective of this trial was to investigate the daily variation in the urinary excretions of creatinine, urea and purine derivatives (PD as well as the plasma concentration of urea-N (PUN in steers. Four castrated Holstein steers averaging 445 kg

  8. Electrochemical Synthesis of 5-Purin-6'-ylthiocatechols in Aqueous Medium

    Institute of Scientific and Technical Information of China (English)

    LIU Fu-Jian; ZENG Cheng-Chu; PING Da-Wei; CAI Yuan-Li; ZHONG Ru-Gang

    2008-01-01

    The electrochemical synthesis of 5-purin-6'-ylthiocatechols was carried out by anodic oxidation of catechol derivatives la--ld in the presence of 6-mercaptopurine (2) in aqueous solution.Results of cyclic voltammetry and controlled-potential electrolysis indicated that the starting catechols were first oxidized to the corresponding o-benzoquinone,which underwent further Michael addition with 6-mercaptopurine to produce titled products 3a--3d following an EC (E=electrochemical and C=chemical step) mechanism.Such work further demonstrates the versatility of the anodic oxidation of catechols and their in-situ transformation for the synthesis of derivatized catechols.

  9. Extracellular-purine metabolism in blood vessels (part I). Extracellular-purine level in blood of patients with abdominal aortic aneurysm.

    Science.gov (United States)

    Lecka, Joanna; Molski, Stanislaw; Komoszynski, Michal

    2010-09-01

    Adenosine and adenosine derivatives are the main regulators of purinoceptors (P1 and P2) mediated hemostasis and blood pressure. Since impaired hemostasis and high blood pressure lead to atherosclerosis and to the development of aneurysm, in this study we tested and compared the concentration of extracellular purines (e-purines) in the blood in of patients having abdominal aortic aneurysm with that from healthy volunteers. Whereas adenine nucleosides and nucleotides level in human blood plasma was analysed using reverse phase high performance liquid chromatography (HPLC), cholesterol concentration was estimated by an enzymatic assay. We did not find any correlation between e-purines concentration and the age of healthy volunteers. Furthermore, the sum level of e-purines (ATP, ADP, AMP, adenosine, and inosine) in the control group did not exceed 70 microM, while it was nearly two-fold higher in the blood of patients having abdominal aortic aneurysm, (123 microM). In a special case of people with Leriche Syndrome, a disease characterized by deep atherosclerotic changes, the e-purines level had further increased. Additionally, we also report typical atherosclerotic changes in the aorta using histological assays as well as total cholesterol rise. The significant rise in cholesterol concentration in the blood of the patients with abdominal aortas aneurysm, compared with the control groups, was not unique since 23% of the healthy people also exceeded the normal level of cholesterol. Therefore, our results strongly indicate that the estimation of e-purines concentration in the blood may serve as another indicator of atherosclerosis and warrant further consideration as a futuristic diagnostic tool.

  10. Purine Metabolism in Acute Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Ye. V. Oreshnikov

    2008-01-01

    Full Text Available Objective: to study the specific features of purine metabolism in clinically significant acute cerebral ischemia. Subjects and materials. Three hundred and fifty patients with the acutest cerebral ischemic stroke were examined. The parameters of gas and electrolyte composition, acid-base balance, the levels of malonic dialdehyde, adenine, guanine, hypox-anthine, xanthine, and uric acid, and the activity of xanthine oxidase were determined in arterial and venous bloods and spinal fluid. Results. In ischemic stroke, hyperuricemia reflects the severity of cerebral metabolic disturbances, hemodynamic instability, hypercoagulation susceptiility, and the extent of neurological deficit. In ischemic stroke, hyperuri-corachia is accompanied by the higher spinal fluid levels of adenine, guanine, hypoxanthine, and xanthine and it is an indirect indicator of respiratory disorders of central genesis, systemic acidosis, hypercoagulation susceptibility, free radical oxidation activation, the intensity of a stressor response to cerebral ischemia, cerebral metabolic disturbances, the depth of reduced consciousness, and the severity of neurological deficit. Conclusion. The high venous blood activity of xanthine oxidase in ischemic stroke is associated with the better neurological parameters in all follow-up periods, the better early functional outcome, and lower mortality rates. Key words: hyperuricemia, stroke, xanthine oxidase, uric acid, cerebral ischemia.

  11. Generalized Derivative Based Kernelized Learning Vector Quantization

    NARCIS (Netherlands)

    Schleif, Frank-Michael; Villmann, Thomas; Hammer, Barbara; Schneider, Petra; Biehl, Michael; Fyfe, Colin; Tino, Peter; Charles, Darryl; Garcia-Osoro, Cesar; Yin, Hujun

    2010-01-01

    We derive a novel derivative based version of kernelized Generalized Learning Vector Quantization (KGLVQ) as an effective, easy to interpret, prototype based and kernelized classifier. It is called D-KGLVQ and we provide generalization error bounds, experimental results on real world data, showing t

  12. [Effect of cooking on the purine content of foods].

    Science.gov (United States)

    Colling, M; Wolfram, G

    1987-12-01

    The total purine content and the content of purines bound in RNA and DNA was determined in selected food (veal meat, pork meat, pork liver, pork spleen, soja meat). Raw and boiled food samples were analysed. During preparation of food the total purine content is changed by losses of water or of purines into cooking water. Simultaneously, a great part of nucleic acids is hydrolysed.

  13. Microwave-assisted one step synthesis of 8-arylmethyl-9H-purin-6-amines

    OpenAIRE

    2008-01-01

    Molecular chaperone heat shock protein 90 (Hsp90) is an important target in cancer and neurodegenerative diseases, and has rapidly become the focus of several drug discovery efforts. Among small molecule Hsp90 inhibitors with clinical applicability are derivatives of 8-arylmethyl-9H-purin-6-amine class. Here we report the use of microwave-assisted chemistry for the successful one-pot delivery of 8-arylmethyl-9H-purin-6-amines. We discuss the applicability as well as the limitations of this me...

  14. Functional and Structural Characterization of Purine Nucleoside Phosphorylase from Kluyveromyces lactis and Its Potential Applications in Reducing Purine Content in Food

    Science.gov (United States)

    Mahor, Durga; Priyanka, Anu; Prasad, Gandham S; Thakur, Krishan Gopal

    2016-01-01

    Consumption of foods and beverages with high purine content increases the risk of hyperuricemia, which causes gout and can lead to cardiovascular, renal, and other metabolic disorders. As patients often find dietary restrictions challenging, enzymatically lowering purine content in popular foods and beverages offers a safe and attractive strategy to control hyperuricemia. Here, we report structurally and functionally characterized purine nucleoside phosphorylase (PNP) from Kluyveromyces lactis (KlacPNP), a key enzyme involved in the purine degradation pathway. We report a 1.97 Å resolution crystal structure of homotrimeric KlacPNP with an intrinsically bound hypoxanthine in the active site. KlacPNP belongs to the nucleoside phosphorylase-I (NP-I) family, and it specifically utilizes 6-oxopurine substrates in the following order: inosine > guanosine > xanthosine, but is inactive towards adenosine. To engineer enzymes with broad substrate specificity, we created two point variants, KlacPNPN256D and KlacPNPN256E, by replacing the catalytically active Asn256 with Asp and Glu, respectively, based on structural and comparative sequence analysis. KlacPNPN256D not only displayed broad substrate specificity by utilizing both 6-oxopurines and 6-aminopurines in the order adenosine > inosine > xanthosine > guanosine, but also displayed reversal of substrate specificity. In contrast, KlacPNPN256E was highly specific to inosine and could not utilize other tested substrates. Beer consumption is associated with increased risk of developing gout, owing to its high purine content. Here, we demonstrate that KlacPNP and KlacPNPN256D could be used to catalyze a key reaction involved in lowering beer purine content. Biochemical properties of these enzymes such as activity across a wide pH range, optimum activity at about 25°C, and stability for months at about 8°C, make them suitable candidates for food and beverage industries. Since KlacPNPN256D has broad substrate specificity, a

  15. Functional and Structural Characterization of Purine Nucleoside Phosphorylase from Kluyveromyces lactis and Its Potential Applications in Reducing Purine Content in Food.

    Science.gov (United States)

    Mahor, Durga; Priyanka, Anu; Prasad, Gandham S; Thakur, Krishan Gopal

    2016-01-01

    Consumption of foods and beverages with high purine content increases the risk of hyperuricemia, which causes gout and can lead to cardiovascular, renal, and other metabolic disorders. As patients often find dietary restrictions challenging, enzymatically lowering purine content in popular foods and beverages offers a safe and attractive strategy to control hyperuricemia. Here, we report structurally and functionally characterized purine nucleoside phosphorylase (PNP) from Kluyveromyces lactis (KlacPNP), a key enzyme involved in the purine degradation pathway. We report a 1.97 Å resolution crystal structure of homotrimeric KlacPNP with an intrinsically bound hypoxanthine in the active site. KlacPNP belongs to the nucleoside phosphorylase-I (NP-I) family, and it specifically utilizes 6-oxopurine substrates in the following order: inosine > guanosine > xanthosine, but is inactive towards adenosine. To engineer enzymes with broad substrate specificity, we created two point variants, KlacPNPN256D and KlacPNPN256E, by replacing the catalytically active Asn256 with Asp and Glu, respectively, based on structural and comparative sequence analysis. KlacPNPN256D not only displayed broad substrate specificity by utilizing both 6-oxopurines and 6-aminopurines in the order adenosine > inosine > xanthosine > guanosine, but also displayed reversal of substrate specificity. In contrast, KlacPNPN256E was highly specific to inosine and could not utilize other tested substrates. Beer consumption is associated with increased risk of developing gout, owing to its high purine content. Here, we demonstrate that KlacPNP and KlacPNPN256D could be used to catalyze a key reaction involved in lowering beer purine content. Biochemical properties of these enzymes such as activity across a wide pH range, optimum activity at about 25°C, and stability for months at about 8°C, make them suitable candidates for food and beverage industries. Since KlacPNPN256D has broad substrate specificity, a

  16. INTERMOLECULAR FORCES IN ASSOCIATION OF PURINES WITH POLYBENZENOID HYDROCARBONS.

    Science.gov (United States)

    PULLMAN, B; CLAVERIE, P; CAILLET, J

    1965-03-12

    The interactions in solution between purine or pyrimidine bases and polybenzenoid aromatic hydrocarbons probably consist in a vertical, stacking-type physical association. By molecular orbital calculations the role of the Van der Waals-London intermolecular forces in these interactions is determined. The electrostatic dipole-dipole forces are negligible, the polarization (or induction) dipole-induced dipole forces are contributory, but most important are the dispersion (or fluctuation) forces. This loose, physical type of interaction should not show any specificity with respect to the carcinogenic activity of the hydrocarbons.

  17. Study of Copper and Purine-Copper Complexes on Modified Carbon Electrodes by Cyclic and Elimination Voltammetry

    Directory of Open Access Journals (Sweden)

    Frantisek Jelen

    2008-01-01

    Full Text Available Using a paraffin impregnated graphite electrode (PIGE and mercury-modifiedpyrolytic graphite electrode with basal orientation (Hg-PGEb copper(II and Cu(II-DNApurine base solutions have been studied by cyclic (CV and linear sweep voltammetry(LSV in connection with elimination voltammetry with linear scan (EVLS. In chlorideand bromide solutions (pH 6, the redox process of Cu(II proceeded on PIGE with twocathodic and two anodic potentially separated signals. According to the eliminationfunction E4, the first cathodic peak corresponds to the reduction Cu(II e- → Cu(I withthe possibility of fast disproportionation 2Cu(I → Cu(II Cu(0. The E4 of the secondcathodic peak signalized an electrode process controlled by a surface reaction. Theelectrode system of Cu(II on Hg-PGEb in borate buffer (pH 9.2 was characterized by onecathodic and one anodic peak. Anodic stripping voltammetry (ASV on PIGE and cathodicstripping voltammetry (CSV on Hg-PGEb were carried out at potentials where thereduction of copper ions took place and Cu(I-purine complexes were formed. By usingASV and CSV in combination with EVLS, the sensitivity of Cu(I-purine complexdetection was enhanced relative to either ASV or CSV alone, resulting in higher peakcurrents of more than one order of magnitude. The statistical treatment of CE data wasused to determine the reproducibility of measurements. Our results show that EVLS inconnection with the stripping procedure is useful for both qualitative and quantitativemicroanalysis of purine derivatives and can also reveal details of studied electrodeprocesses.

  18. Study of Copper and Purine-Copper Complexes on Modified Carbon Electrodes by Cyclic and Elimination Voltammetry.

    Science.gov (United States)

    Trnkova, Libuse; Zerzankova, Lenka; Dycka, Filip; Mikelova, Radka; Jelen, Frantisek

    2008-01-24

    Using a paraffin impregnated graphite electrode (PIGE) and mercury-modifiedpyrolytic graphite electrode with basal orientation (Hg-PGEb) copper(II) and Cu(II)-DNApurine base solutions have been studied by cyclic (CV) and linear sweep voltammetry(LSV) in connection with elimination voltammetry with linear scan (EVLS). In chlorideand bromide solutions (pH 6), the redox process of Cu(II) proceeded on PIGE with twocathodic and two anodic potentially separated signals. According to the eliminationfunction E4, the first cathodic peak corresponds to the reduction Cu(II) e⁻ → Cu(I) withthe possibility of fast disproportionation 2Cu(I) → Cu(II) Cu(0). The E4 of the secondcathodic peak signalized an electrode process controlled by a surface reaction. Theelectrode system of Cu(II) on Hg-PGEb in borate buffer (pH 9.2) was characterized by onecathodic and one anodic peak. Anodic stripping voltammetry (ASV) on PIGE and cathodicstripping voltammetry (CSV) on Hg-PGEb were carried out at potentials where thereduction of copper ions took place and Cu(I)-purine complexes were formed. By usingASV and CSV in combination with EVLS, the sensitivity of Cu(I)-purine complexdetection was enhanced relative to either ASV or CSV alone, resulting in higher peakcurrents of more than one order of magnitude. The statistical treatment of CE data wasused to determine the reproducibility of measurements. Our results show that EVLS inconnection with the stripping procedure is useful for both qualitative and quantitativemicroanalysis of purine derivatives and can also reveal details of studied electrodeprocesses.

  19. Tailoring Imprinted Titania Nanoparticles for Purines Recognition

    Directory of Open Access Journals (Sweden)

    Adnan Mujahid

    2015-01-01

    Full Text Available Molecular imprinted titania nanoparticles were developed for selective recognition of purines, for example, guanine and its final oxidation product uric acid. Titania nanoparticles were prepared by hydrolysis of titanium butoxide as precursor in the presence of pattern molecules. The morphology of synthesized nanoparticles is evaluated by SEM images. Recognition characteristics of imprinted titania nanoparticles are studied by exposing them to standard solution of guanine and uric acid, respectively. The resultant change in their concentration is determined by UV/Vis analysis that indicated imprinted titania nanoparticles possess high affinity for print molecules. In both cases, nonimprinted titania is taken as control to observe nonspecific binding interactions. Cross sensitivity studies suggested that imprinted titania is at least five times more selective for binding print molecules than competing analyte thus indicating its potential for bioassay of purines.

  20. Derivation of GFDM Based on OFDM Principles

    Energy Technology Data Exchange (ETDEWEB)

    Hussein Moradi; Behrouz Farhang-Boroujeny

    2015-06-01

    This paper starts with discussing the principle based on which the celebrated orthogonal frequency division multiplexing (OFDM) signals are constructed. It then extends the same principle to construct the newly introduced generalized frequency division multiplexing (GFDM) signals. This novel derivation sheds light on some interesting properties of GFDM. In particular, our derivation seamlessly leads to an implementation of GFDM transmitter which has significantly lower complexity than what has been reported so far. Our derivation also facilitates a trivial understanding of how GFDM (similar to OFDM) can be applied in MIMO channels.

  1. 拉沙里菌素对西门塔尔牛瘤胃发酵和尿中嘌呤衍生物含量的影响%Effects of Lasalocid on Rumen Fermentation and the Contents of Purine Derivatives in Urine in Simmental Cattle

    Institute of Scientific and Technical Information of China (English)

    张艳梅; 师周戈; 焦光月

    2015-01-01

    The objective of this study was to evaluate the effects of lasalocid on rumen fermentation and urinary purine derivatives in Simmental cattle. Forty-eight 12-months-old Simmental bulls with good body condition and similar body weight were divided into four groups at random. The control group was fed basic diet. The supplement of lasalocid with 100, 200 and 300 mg per cattle per day was added to the basic diet, respectively. Three cattles in each group were selected randomly to do digestion metabolism experiments after feeding experiments. The results showed that ruminal acetate content, ammonia N concentration in groups supplemented lasalocid at 200mg/d and 300mg/d were lower than that of in control group (P<0.05). Concentrations of urinary allantion and purine derivatives in groups supplemented lasalocid at 200mg/d and 300mg/d were higher than that of in control group and group supplemented lasalocid at 100mg/d (P<0.05). The study showed that the addition of lasalocid in beef cattle diet could improve rumen fermentation and nitrogen utilization, the optimal dose of lasalocid was 200mg/d.%本试验旨在评价拉沙里菌素对西门塔尔牛瘤胃发酵的影响.选取12月龄左右、体重相近、体况良好的西门塔尔牛48头,随机分为4组.对照组饲喂基础日粮,处理组分别在基础日粮基础上添加拉沙里菌素100、200和300mg/(头·d).结果表明,日粮中添加拉沙里菌素200mg/(头·d)和300mg/(头·d)时,瘤胃内乙酸含量、氨态氮浓度显著低于对照组(P<0.05),尿中嘌呤衍生物含量显著增加(P<0.05).试验表明,日粮添加拉沙里菌素能改善瘤胃发酵和氮的利用,从而提高生产性能和减少甲烷排放,其适宜添加量为200mg/(头·d).

  2. Stretches of alternating pyrimidine/purines and purines are respectively linked with pathogenicity and growth temperature in prokaryotes

    Directory of Open Access Journals (Sweden)

    Hardy Simon P

    2009-07-01

    Full Text Available Abstract Background The genomic fractions of purine (RR and alternating pyrimidine/purine (YR stretches of 10 base pairs or more, have been linked to genomic AT content, the formation of different DNA helices, strand-biased gene distribution, DNA structure, and more. Although some of these factors are a consequence of the chemical properties of purines and pyrimidines, a thorough statistical examination of the distributions of YR/RR stretches in sequenced prokaryotic chromosomes has to the best of our knowledge, not been undertaken. The aim of this study is to expand upon previous research by using regression analysis to investigate how AT content, habitat, growth temperature, pathogenicity, phyla, oxygen requirement and halotolerance correlated with the distribution of RR and YR stretches in prokaryotes. Results Our results indicate that RR and YR-stretches are differently distributed in prokaryotic phyla. RR stretches are overrepresented in all phyla except for the Actinobacteria and β-Proteobacteria. In contrast, YR tracts are underrepresented in all phyla except for the β-Proteobacterial group. YR-stretches are associated with phylum, pathogenicity and habitat, whilst RR-tracts are associated with phylum, AT content, oxygen requirement, growth temperature and halotolerance. All associations described were statistically significant with p . Conclusion Analysis of chromosomal distributions of RR/YR sequences in prokaryotes reveals a set of associations with environmental factors not observed with mono- and oligonucleotide frequencies. This implies that important information can be found in the distribution of RR/YR stretches that is more difficult to obtain from genomic mono- and oligonucleotide frequencies. The association between pathogenicity and fractions of YR stretches is assumed to be linked to recombination and horizontal transfer.

  3. Deriving Framework Usages Based on Behavioral Models

    Science.gov (United States)

    Zenmyo, Teruyoshi; Kobayashi, Takashi; Saeki, Motoshi

    One of the critical issue in framework-based software development is a huge introduction cost caused by technical gap between developers and users of frameworks. This paper proposes a technique for deriving framework usages to implement a given requirements specification. By using the derived usages, the users can use the frameworks without understanding the framework in detail. Requirements specifications which describe definite behavioral requirements cannot be related to frameworks in as-is since the frameworks do not have definite control structure so that the users can customize them to suit given requirements specifications. To cope with this issue, a new technique based on satisfiability problems (SAT) is employed to derive the control structures of the framework model. In the proposed technique, requirements specifications and frameworks are modeled based on Labeled Transition Systems (LTSs) with branch conditions represented by predicates. Truth assignments of the branch conditions in the framework models are not given initially for representing the customizable control structure. The derivation of truth assignments of the branch conditions is regarded as the SAT by assuming relations between termination states of the requirements specification model and ones of the framework model. This derivation technique is incorporated into a technique we have proposed previously for relating actions of requirements specifications to ones of frameworks. Furthermore, this paper discuss a case study of typical use cases in e-commerce systems.

  4. Riboswitch Structure: an Internal Residue Mimicking the Purine Ligand

    Energy Technology Data Exchange (ETDEWEB)

    Delfosse, V.; Bouchard, P; Bonneau, E; Dagenais, P; Lemay, J; Lafontaine, D; Legault, P

    2009-01-01

    The adenine and guanine riboswitches regulate gene expression in response to their purine ligand. X-ray structures of the aptamer moiety of these riboswitches are characterized by a compact fold in which the ligand forms a Watson-Crick base pair with residue 65. Phylogenetic analyses revealed a strict restriction at position 39 of the aptamer that prevents the G39-C65 and A39-U65 combinations, and mutational studies indicate that aptamers with these sequence combinations are impaired for ligand binding. In order to investigate the rationale for sequence conservation at residue 39, structural characterization of the U65C mutant from Bacillus subtilis pbuE adenine riboswitch aptamer was undertaken. NMR spectroscopy and X-ray crystallography studies demonstrate that the U65C mutant adopts a compact ligand-free structure, in which G39 occupies the ligand-binding site of purine riboswitch aptamers. These studies present a remarkable example of a mutant RNA aptamer that adopts a native-like fold by means of ligand mimicking and explain why this mutant is impaired for ligand binding. Furthermore, this work provides a specific insight into how the natural sequence has evolved through selection of nucleotide identities that contribute to formation of the ligand-bound state, but ensures that the ligand-free state remains in an active conformation.

  5. Purine nucleoside phosphorylase and xanthine oxidase activities in erythrocytes and plasma from marine, semiaquatic and terrestrial mammals.

    Science.gov (United States)

    López-Cruz, Roberto I; Pérez-Milicua, Myrna Barjau; Crocker, Daniel E; Gaxiola-Robles, Ramón; Bernal-Vertiz, Jaime A; de la Rosa, Alejandro; Vázquez-Medina, José P; Zenteno-Savín, Tania

    2014-05-01

    Purine nucleoside phosphorylase (PNP) and xanthine oxidase (XO) are key enzymes involved in the purine salvage pathway. PNP metabolizes purine bases to synthetize purine nucleotides whereas XO catalyzes the oxidation of purines to uric acid. In humans, PNP activity is reported to be high in erythrocytes and XO activity to be low in plasma; however, XO activity increases after ischemic events. XO activity in plasma of northern elephant seals has been reported during prolonged fasting and rest and voluntary associated apneas. The objective of this study was to analyze circulating PNP and XO activities in marine mammals adapted to tolerate repeated cycles of ischemia/reperfusion associated with diving (bottlenose dolphin, northern elephant seal) in comparison with semiaquatic (river otter) and terrestrial mammals (human, pig). PNP activities in plasma and erythrocytes, as well as XO activity in plasma, from all species were quantified by spectrophotometry. No clear relationship in circulating PNP or XO activity could be established between marine, semiaquatic and terrestrial mammals. Erythrocytes from bottlenose dolphins and humans are highly permeable to nucleosides and glucose, intraerythrocyte PNP activity may be related to a release of purine nucleotides from the liver. High-energy costs will probably mean a higher ATP degradation rate in river otters, as compared to northern elephant seals or dolphins. Lower erythrocyte PNP activity and elevated plasma XO activity in northern elephant seal could be associated with fasting and/or sleep- and dive-associated apneas.

  6. Theoretical Study of Nonclassical Platinum Complexes Bonding to Purine Bases: How the Long-lived Monofunctional Adducts Can Be in Existence?

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The B3LYP/6-31G* level of theory was used for the optimization of nonclassical platinum drugs with planar aromatic heterocycle ligands in addition to their monoaqua species, diaqua species and monofunctional adducts. Single point calculations were performed on optimized geometries using the MP2/6-31G** method, and the Lanl2dz pseudo potential for the Pt atom remained constant in all calculations. It can be easily seen that the trans effect can influence both geometrical structures and bond dissociating energies (BDEs). On the basis of our calculation, we get that the long-lived monofunctional adducts with chloride ligand may be in existence, because they possessed higher stability energies, easily dissociated chloride compared with the monoaqua species dissociating chloride and that replacement of the first chloride by bases became exothermic in solution. Our calculated results also demonstrate that the strongest H-bonds appear in the complexes of q-wG and t-wG using different methods. In comparison with adenine complexes, the corresponding guanine complexes possess larger interaction energies as well as higher stability energies either corrected by basis set superposition error (bsse) of Boys-Bernardi counterpoise method or uncorrected both in gas phase and in solution with one exception that the stability energy of q-ClA complex in solution is larger than that of q-ClG complex. Finally, the nature of bond was analyzed in terms of partial charges distribution based on NBO population.

  7. Purines: from premise to promise.

    Science.gov (United States)

    Williams, M

    2000-07-01

    Geoff Burnstock's remarkable insight and tenacity has established the area of purinergic research as a bona fide target for drug discovery. While efforts in P1 receptor-based medicinal chemistry and biology efforts over the past 25 years have not reached the level of success that the pharmaceutical industry investment may have anticipated, the P2 area, with knowledge of the selective localization of members of the P2X and P2Y family members and data from transgenic knockouts, has identified several potential therapeutic areas of major promise including cystic fibrosis, chronic bronchitis, male contraception and neurodegeneration. In addition, interest in the potential of purinergic therapeutics has extended outside the major pharmaceutical companies to the 'biotech industry' resulting in an environment where the inherent risks of 'first in field' in a therapeutic area may be more appropriately nurtured.

  8. Purine inhibitors of protein kinases, G proteins and polymerases

    Energy Technology Data Exchange (ETDEWEB)

    Gray, Nathanael S. (Berkeley, CA); Schultz, Peter (Oakland, CA); Kim, Sung-Hou (Moraga, CA); Meijer, Laurent (Roscoff, FR)

    2001-07-03

    The present invention relates to purine analogs that inhibit, inter alia, protein kinases, G-proteins and polymerases. In addition, the present invention relates to methods of using such purine analogs to inhibit protein kinases, G-proteins, polymerases and other cellular processes and to treat cellular proliferative diseases.

  9. Structure and electronic spectra of purine-methyl viologen charge transfer complexes.

    Science.gov (United States)

    Jalilov, Almaz S; Patwardhan, Sameer; Singh, Arunoday; Simeon, Tomekia; Sarjeant, Amy A; Schatz, George C; Lewis, Frederick D

    2014-01-01

    The structure and properties of the electron donor-acceptor complexes formed between methyl viologen and purine nucleosides and nucleotides in water and the solid state have been investigated using a combination of experimental and theoretical methods. Solution studies were performed using UV-vis and (1)H NMR spectroscopy. Theoretical calculations were performed within the framework of density functional theory (DFT). Energy decomposition analysis indicates that dispersion and induction (charge-transfer) interactions dominate the total binding energy, whereas electrostatic interactions are largely repulsive. The appearance of charge transfer bands in the absorption spectra of the complexes are well-described by time-dependent DFT and are further explained in terms of the redox properties of purine monomers and solvation effects. Crystal structures are reported for complexes of methyl viologen with the purines 2'-deoxyguanosine 3'-monophosphate (DAD'DAD' type) and 7-deazaguanosine (DAD'ADAD' type). Comparison of the structures determined in the solid state and by theoretical methods in solution provides valuable insights into the nature of charge-transfer interactions involving purine bases as electron donors.

  10. Ligand Binding and Conformational Changes in the Purine-Binding Riboswitch Aptamer Domains

    Science.gov (United States)

    Noeske, Jonas; Buck, Janina; Wöhnert, Jens; Schwalbe, Harald

    Riboswitches are highly structured mRNA elements that regulate gene expression upon specific binding of small metabolite molecules. The purine-binding riboswitches bind different purine ligands by forming both canonical Watson—Crick and non-canonical intermolecular base pairs, involving a variety of hydrogen bonds between the riboswitch aptamer domain and the purine ligand. Here, we summarize work on the ligand binding modes of both purine-binding aptamer domains, their con-formational characteristics in the free and ligand-bound forms, and their ligand-induced folding. The adenine- and guanine-binding riboswitch aptamer domains display different conformations in their free forms, despite nearly identical nucleotide loop sequences that form a loop—loop interaction in the ligand-bound forms. Interestingly, the stability of helix II is crucial for the formation of the loop—loop interaction in the free form. A more stable helix II in the guanine riboswitch leads to a preformed loop—loop interaction in its free form. In contrast, a less stable helix II in the adenine riboswitch results in a lack of this loop—loop interaction in the absence of ligand and divalent cations.

  11. Hypoxanthine production by ischemic heart demonstrated by high pressure liquid chromatography of blood purine nucleosides and oxypurines

    NARCIS (Netherlands)

    E. Harmsen; J.W. de Jong (Jan Willem); P.W.J.C. Serruys (Patrick)

    1981-01-01

    textabstractAn isocratic high pressure liquid chromatographic system was developed for the estimation of purine nucleosides and oxypurines in blood. Use was made of a reversed-phase column. Nucleotides derived from erythrocytes affected the separation; these compounds were removed with A12O3. The

  12. Symbolic derivation of potential based constitutive equations

    Science.gov (United States)

    Arnold, S. M.; Tan, H. Q.

    1990-05-01

    Structural alloys used in high temperature applications exhibit complex thermomechanical behavior that is inherently time dependent and hereditary, as the current behavior depends not only on current conditions but on the thermomechanical history. Derivation of mathematical expressions (constitutive equations) which describe this high temperature material behavior can be quite time consuming, involved, and error-prone, thus intelligent application of symbolic systems to facilitate this tedious processes can be of significant benefit. Here a computerized package, running under MACSYMA, capable of efficiently deriving potential based constitutive models, in analytical form (involving tensors, partial differentiation, invariants, and the like) is presented. Special purpose utility algorithms are designed and implemented to perform partial differentiation (chain rule), tensor manipulation, case distinction and simplification. Four constitutive theories reported in the literature are utilized to verify implementation accuracy. It is expected that this symbolic package can and will provide a significant incentive to the development of new constitutive theories.

  13. Inhibition of DNA glycosylases via small molecule purine analogs.

    Directory of Open Access Journals (Sweden)

    Aaron C Jacobs

    Full Text Available Following the formation of oxidatively-induced DNA damage, several DNA glycosylases are required to initiate repair of the base lesions that are formed. Recently, NEIL1 and other DNA glycosylases, including OGG1 and NTH1 were identified as potential targets in combination chemotherapeutic strategies. The potential therapeutic benefit for the inhibition of DNA glycosylases was validated by demonstrating synthetic lethality with drugs that are commonly used to limit DNA replication through dNTP pool depletion via inhibition of thymidylate synthetase and dihydrofolate reductase. Additionally, NEIL1-associated synthetic lethality has been achieved in combination with Fanconi anemia, group G. As a prelude to the development of strategies to exploit the potential benefits of DNA glycosylase inhibition, it was necessary to develop a reliable high-throughput screening protocol for this class of enzymes. Using NEIL1 as the proof-of-principle glycosylase, a fluorescence-based assay was developed that utilizes incision of site-specifically modified oligodeoxynucleotides to detect enzymatic activity. This assay was miniaturized to a 1536-well format and used to screen small molecule libraries for inhibitors of the combined glycosylase/AP lyase activities. Among the top hits of these screens were several purine analogs, whose postulated presence in the active site of NEIL1 was consistent with the paradigm of NEIL1 recognition and excision of damaged purines. Although a subset of these small molecules could inhibit other DNA glycosylases that excise oxidatively-induced DNA adducts, they could not inhibit a pyrimidine dimer-specific glycosylase.

  14. Novel purine nucleoside analogues for hematological malignancies.

    Science.gov (United States)

    Korycka, Anna; Lech-Marańda, Ewa; Robak, Tadeusz

    2008-06-01

    Recently, the search for more effective and safer antineoplastic agents has led to synthesis and introduction into preclinical and clinical studies of a few new purine nucleoside analogues (PNA). Three of them: clofarabine (CAFdA), nelarabine, and forodesine (immucillin H, BCX-1777), despite belonging to the same group of drugs such as PNA, have shown some differences concerning their active forms, metabolic properties and mechanism of action. However, all these drugs have demonstrated promising activity in patients with relapsed and refractory acute lymphoblastic leukemia (ALL). CAFdA was approved for the therapy of relapsed or refractory ALL in the third line of treatment. It has proved promising in pediatric patients as well as in some patients who are able to proceed to allogenic hematopietic stem cell transplantation (HSCT). Moreover, the drug exhibits an efficacy in acute myeloid leukemia (AML), blast crisis of chronic myelogenous leukemia (CML-BP) and myelodysplastic syndrome (MDS). Nelarabine is recommended for T-ALL and T-cell lymphoblastic lymphoma (T-LBL) with the overall response rates ranging from 11 to 60%. However, the use of the drug is limited by potentially severe neurotoxicity. Forodesine is a purine nucleoside phosphorylase (PNP) inhibitor and it has shown activity in relapsed and refractory T- and B-cells leukemias as well as in cutaneous T-cell lymphoma (CTCL). Recently patented, a few of inventions in the field of pharmaceutical preparation of new PNA have also been published. Great hopes are currently set on the use of these drugs in the treatment of lymphoid and myeloid malignancies in adult and in pediatric patients, however ongoing studies will help to define their role in the standard therapy.

  15. Consequences of impaired purine recycling on the proteome in a cellular model of Lesch-Nyhan disease.

    Science.gov (United States)

    Dammer, Eric B; Göttle, Martin; Duong, Duc M; Hanfelt, John; Seyfried, Nicholas T; Jinnah, H A

    2015-04-01

    The importance of specific pathways of purine metabolism for normal brain function is highlighted by several inherited disorders, such as Lesch-Nyhan disease (LND). In this disorder, deficiency of the purine recycling enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt), causes severe neurological and behavioral abnormalities. Despite many years of research, the mechanisms linking the defect in purine recycling to the neurobehavioral abnormalities remain unclear. In the current studies, an unbiased approach to the identification of potential mechanisms was undertaken by examining changes in protein expression in a model of HGprt deficiency based on the dopaminergic rat PC6-3 line, before and after differentiation with nerve growth factor (NGF). Protein expression profiles of 5 mutant sublines carrying different mutations affecting HGprt enzyme activity were compared to the HGprt-competent parent line using the method of stable isotopic labeling by amino acids in cell culture (SILAC) followed by denaturing gel electrophoresis with liquid chromatography and tandem mass spectrometry (LC-MS/MS) of tryptic digests, and subsequent identification of affected biochemical pathways using the Database for Annotation, Visualization and Integrated Discovery (DAVID) functional annotation chart analysis. The results demonstrate that HGprt deficiency causes broad changes in protein expression that depend on whether the cells are differentiated or not. Several of the pathways identified reflect predictable consequences of defective purine recycling. Other pathways were not anticipated, disclosing previously unknown connections with purine metabolism and novel insights into the pathogenesis of LND. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Prolonged fasting increases purine recycling in post-weaned northern elephant seals.

    Science.gov (United States)

    Soñanez-Organis, José Guadalupe; Vázquez-Medina, José Pablo; Zenteno-Savín, Tania; Aguilar, Andres; Crocker, Daniel E; Ortiz, Rudy M

    2012-05-01

    Northern elephant seals are naturally adapted to prolonged periods (1-2 months) of absolute food and water deprivation (fasting). In terrestrial mammals, food deprivation stimulates ATP degradation and decreases ATP synthesis, resulting in the accumulation of purines (ATP degradation byproducts). Hypoxanthine-guanine phosphoribosyl transferase (HGPRT) salvages ATP by recycling the purine degradation products derived from xanthine oxidase (XO) metabolism, which also promotes oxidant production. The contributions of HGPRT to purine recycling during prolonged food deprivation in marine mammals are not well defined. In the present study we cloned and characterized the complete and partial cDNA sequences that encode for HGPRT and xanthine oxidoreductase (XOR) in northern elephant seals. We also measured XO protein expression and circulating activity, along with xanthine and hypoxanthine plasma content in fasting northern elephant seal pups. Blood, adipose and muscle tissue samples were collected from animals after 1, 3, 5 and 7 weeks of their natural post-weaning fast. The complete HGPRT and partial XOR cDNA sequences are 771 and 345 bp long and encode proteins of 218 and 115 amino acids, respectively, with conserved domains important for their function and regulation. XOR mRNA and XO protein expression increased 3-fold and 1.7-fold with fasting, respectively, whereas HGPRT mRNA (4-fold) and protein (2-fold) expression increased after 7 weeks in adipose tissue and muscle. Plasma xanthine (3-fold) and hypoxanthine (2.5-fold) levels, and XO (1.7- to 20-fold) and HGPRT (1.5- to 1.7-fold) activities increased during the last 2 weeks of fasting. Results suggest that prolonged fasting in elephant seal pups is associated with increased capacity to recycle purines, which may contribute to ameliorating oxidant production and enhancing the supply of ATP, both of which would be beneficial during prolonged food deprivation and appear to be adaptive in this species.

  17. Direct Isolation of Purines and Pyrimidines from Nucleic Acids Using Sublimation

    Science.gov (United States)

    Glavin, Daniel P.; Schubert, Michael; Bada, Jeffrey L.

    2003-01-01

    A sublimation technique was developed to isolate purines and pyrimidines directly from lambda-deoxyribonucleic acid (lambda-DNA) and Escherichia coli cells. The sublimation of adenine, cytosine, guanine, and thymine from lambda-DNA was tested under reduced pressure (approx. 0.5 Torr) at temperatures of >150 C. With the exception of guanine, approximately 60 -75% of each base was sublimed directly from the lambda-DNA and recovered on a coldfinger of the sublimation apparatus after heating to 450 C. Several nucleobases including adenine, cytosine, thymine, and uracil were also recovered from E. coli bacteria after heating the cells to the same temperature, although some thermal decomposition of the bases also occurred. These results demonstrate the feasibility of using sublimation to isolate purines and pyrimidines from native E. coli DNA and RNA without any chemical treatment of the cells.

  18. Multi-stress resistance in Lactococcus lactis is actually escape from purine-induced stress sensitivity

    DEFF Research Database (Denmark)

    Ryssel, Mia; Hviid, Anne-Mette Meisner; Dawish, Mohamed S.

    2014-01-01

    in the rich and complex M17 medium. When salvage of purines and subsequent conversion to GTP was permitted in various genetic backgrounds of L. lactis MG1363, the cells became sensitive to acid stress, indicating that an excess of guanine nucleotides induces stress sensitivity. The addition of phosphate......Multi-stress resistance is a widely documented and fascinating phenotype of lactococci where single mutations, preferentially in genes involved in nucleotide metabolism and phosphate uptake, result in elevated tolerance to multiple stresses simultaneously. In this report, we have analysed...... nucleotides is formed as a result of an improved conversion of guanosine in the salvage pathway. Based upon our findings, we suggest that L. lactis MG1363 is naturally multi-stress resistant in habitats devoid of any purine source. However, any exogenous purine that results in increased guanine nucleotide...

  19. Associations between purine metabolites and clinical symptoms in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Jeffrey K Yao

    Full Text Available BACKGROUND: The antioxidant defense system, which is known to be dysregulated in schizophrenia, is closely linked to the dynamics of purine pathway. Thus, alterations in the homeostatic balance in the purine pathway may be involved in the pathophysiology of schizophrenia. METHODOLOGY/PRINCIPAL FINDINGS: Breakdown products in purine pathway were measured using high-pressure liquid chromatography coupled with a coulometric multi-electrode array system for 25 first-episode neuroleptic-naïve patients with schizophrenia at baseline and at 4-weeks following initiation of treatment with antipsychotic medication. Associations between these metabolites and clinical and neurological symptoms were examined at both time points. The ratio of uric acid and guanine measured at baseline predicted clinical improvement following four weeks of treatment with antipsychotic medication. Baseline levels of purine metabolites also predicted clinical and neurological symtpoms recorded at baseline; level of guanosine was associated with degree of clinical thought disturbance, and the ratio of xanthosine to guanosine at baseline predicted degree of impairment in the repetition and sequencing of actions. CONCLUSIONS/SIGNIFICANCE: Findings suggest an association between optimal levels of purine byproducts and dynamics in clinical symptoms and adjustment, as well as in the integrity of sensory and motor processing. Taken together, alterations in purine catabolism may have clinical relevance in schizophrenia pathology.

  20. Development, validation and application of a 96-well enzymatic assay based on LC-ESI-MS/MS quantification for the screening of selective inhibitors against Mycobacterium tuberculosis purine nucleoside phosphorylase.

    Science.gov (United States)

    Cattaneo, Giulia; Ubiali, Daniela; Calleri, Enrica; Rabuffetti, Marco; Höfner, Georg C; Wanner, Klaus T; De Moraes, Marcela C; Martinelli, Leonardo K B; Santos, Diógenes Santiago; Speranza, Giovanna; Massolini, Gabriella

    2016-11-02

    Mycobacterium tuberculosis (Mtb) purine nucleoside phosphorylase (PNP, EC 2.4.2.1) has been identified as a target for the development of specific inhibitors with potential antimycobacterial activity. We hereby described the development and validation of a new 96-well LC-ESI-MS/MS method to assess the inhibition activity of nucleoside analogues towards MtbPNP and the human PNP (HsPNP). Enzyme activity was determined by monitoring the phosphorolysis of inosine (Ino) to hypoxanthine (Hpx). The enzymatic assay (v = 0.5 mL, enzymeplate for sample processing and 2 min/sample for LC-MS analysis. Validation of the quantification method met the criteria of the CDER guidance of FDA. Kinetic parameters were in agreement with those reported in literature (HsPNP KM = 0.150 ± 0.020 mM vs 0.133 ± 0.015 mM; MtbPNP KM = 0.060 ± 0.009 mM vs 0.040 ± 0.003 mM for Ino), thus demonstrating the reliability of the newly developed enzymatic assay. Preliminary inhibition assays confirmed the effects reported for Acyclovir (Acv) and Formycin A (FA) against HsPNP and MtbPNP. The validated enzymatic assay was applied to the evaluation of a set of 8-halo-, 8-amino-, 8-O-alkyl-substituted purine ribonucleosides synthesized on purpose as potential inhibitors against MtbPNP. The assayed 8-substituted ribonucleosides did not exert a significant inhibitory effect against the tested enzymes up to 1 mM.

  1. Metabolic Reprogramming During Purine Stress in the Protozoan Pathogen Leishmania donovani

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Jessica L.; Yates, Phillip A.; Soysa, Radika; Alfaro, Joshua F.; Yang, Feng; Burnum-Johnson, Kristin E.; Petyuk, Vladislav A.; Weitz, Karl K.; Camp, David G.; Smith, Richard D.; Wilmarth, Phillip A.; David, Larry L.; Ramasamy, Gowthaman; Myler, Peter J.; Carter, Nicola S.

    2014-02-27

    The ability of Leishmania to survive in their insect or mammalian host is dependent upon an ability to sense and adapt to changes in the microenvironment. However, little is known about the molecular mechanisms underlying the parasite response to environmental changes, such as nutrient availability. To elucidate nutrient stress response pathways in Leishmania donovani, we have used purine starvation as the paradigm. The salvage of purines from the host milieu is obligatory for parasite replication; nevertheless, purine-starved parasites can persist in culture without supplementary purine for over 3 months, indicating that the response to purine starvation is robust and engenders parasite survival under conditions of extreme scarcity. To understand metabolic reprogramming during purine starvation we have employed global approaches. Whole proteome comparisons between purine-starved and purine-replete parasites over a 6-48 h span have revealed a temporal and coordinated response to purine starvation. Purine transporters and enzymes involved in acquisition at the cell surface are upregulated within a few hours of purine removal from the media, while other key purine salvage components are upregulated later in the time-course and more modestly. After 48 h, the proteome of purine-starved parasites is extensively remodeled and adaptations to purine stress appear tailored to deal with both purine deprivation and general stress. To probe the molecular mechanisms affecting proteome remodeling in response to purine starvation, comparative RNA-seq analyses, qRT-PCR, and luciferase reporter assays were performed on purine-starved versus purine-replete parasites. While the regulation of a minority of proteins tracked with changes at the mRNA level, for many regulated proteins it appears that proteome remodeling during purine stress occurs primarily via translational and/or post-translational mechanisms.

  2. Metabolic reprogramming during purine stress in the protozoan pathogen Leishmania donovani.

    Directory of Open Access Journals (Sweden)

    Jessica L Martin

    2014-02-01

    Full Text Available The ability of Leishmania to survive in their insect or mammalian host is dependent upon an ability to sense and adapt to changes in the microenvironment. However, little is known about the molecular mechanisms underlying the parasite response to environmental changes, such as nutrient availability. To elucidate nutrient stress response pathways in Leishmania donovani, we have used purine starvation as the paradigm. The salvage of purines from the host milieu is obligatory for parasite replication; nevertheless, purine-starved parasites can persist in culture without supplementary purine for over three months, indicating that the response to purine starvation is robust and engenders parasite survival under conditions of extreme scarcity. To understand metabolic reprogramming during purine starvation we have employed global approaches. Whole proteome comparisons between purine-starved and purine-replete parasites over a 6-48 h span have revealed a temporal and coordinated response to purine starvation. Purine transporters and enzymes involved in acquisition at the cell surface are upregulated within a few hours of purine removal from the media, while other key purine salvage components are upregulated later in the time-course and more modestly. After 48 h, the proteome of purine-starved parasites is extensively remodeled and adaptations to purine stress appear tailored to deal with both purine deprivation and general stress. To probe the molecular mechanisms affecting proteome remodeling in response to purine starvation, comparative RNA-seq analyses, qRT-PCR, and luciferase reporter assays were performed on purine-starved versus purine-replete parasites. While the regulation of a minority of proteins tracked with changes at the mRNA level, for many regulated proteins it appears that proteome remodeling during purine stress occurs primarily via translational and/or post-translational mechanisms.

  3. 反应条件对苛求芽孢杆菌胞内尿酸酶与嘌呤衍生物作用的影响%Effects of Reaction Conditions on Interactions of Some Purine Derivatives with the Intracellular Uricase from Bacillus fastidiosus

    Institute of Scientific and Technical Information of China (English)

    李想; 冯娟; 张纯; 蒲军; 杨晓兰; 袁拥华; 廖飞

    2011-01-01

    用底物尿酸的紫外吸收变化跟踪反应,用单或双底物米氏方程和初速度估算苛求芽孢杆菌胞内尿酸酶最大反应速度,按Arrenius经验公式得到该尿酸酶在pH 9.2和pH 7.4的活化能,但这些活化不能解释其在两个pH下的催化活性差异.该酶同常见嘌呤衍生物氧嗪酸、黄嘌呤和尿酸有亲和力,但对尿酸亲和力最低,且亲和力与嘌呤衍生物解离成阴离子的能力相关.在生理条件下,该酶对尿酸的亲和力相对于最适条件有显著下降.据此推测,优化静电相互作用选择性增强该酶对尿酸的亲和力是提高其成药性的可能措施一.%By monitoring the changes of UV absorbance of uric acid, the activation free energies of the intracellular uricase from Bacillus fastidiosus at pH 9.2 and pH 7.4 were estimated with Arrhenius equation, and the maximal reaction rates approximated from initial rates, but they can not account for the difference in the catalytic activity of this uricase under the two pH values.Among common purine derivatives, oxonate, xanthine and uric acid had affinities to this uricase, and uric acid had the lowest affinity.These affinities had some relationships to the dissociated constants of the tested compounds.Under physiological conditions, this uricase had a much weaker affinity for uric acid than that under the optimum conditions.It was proposed that the selective enhancement of the affinity of this uricase for uric acid over xanthine by engineering ionic interactions was possible to improve its pharmaceutical properties.Fig 2, Tab 4, Ref 29

  4. The prebiotic synthesis of modified purines and their potential role in the RNA world

    Science.gov (United States)

    Levy, M.; Miller, S. L.; Bada, J. L. (Principal Investigator)

    1999-01-01

    Modified purines are found in all organisms in the tRNA, rRNA, and even DNA, raising the possibility of an early role for these compounds in the evolution of life. These include N6-methyladenine, 1-methyladenine, N6,N6-dimethyladenine, 1-methylhypoxanthine, 1-methylguanine, and N2-methylguanine. We find that these bases as well as a number of nonbiological modified purines can be synthesized from adenine and guanine by the simple reaction of an amine or an amino group with adenine and guanine under the concentrated conditions of the drying-lagoon or drying-beach model of prebiotic synthesis with yields as high as 50%. These compounds are therefore as prebiotic as adenine and guanine and could have played an important role in the RNA world by providing additional functional groups in ribozymes, especially for the construction of hydrophobic binding pockets.

  5. Determination of purine contents in different parts of pork and beef by high performance liquid chromatography.

    Science.gov (United States)

    Rong, Shengzhong; Zou, Lina; Zhang, Yannan; Zhang, Guangteng; Li, Xiaoxia; Li, Miaojing; Yang, Fenghua; Li, Chunmei; He, Yingjuan; Guan, Hongjun; Guo, Yupeng; Wang, Dong; Cui, Xinyu; Ye, Hongting; Liu, Fenghai; Pan, Hongzhi; Yang, Yuexin

    2015-03-01

    Determination of adenine, hypoxanthine, guanine and xanthine in different parts of pork and beef using high performance liquid chromatography was described. Chromatographic separation was carried out on Waters Atlantis T3 column (4.6 mm × 250 mm × 5 μm) with column temperature at 30 °C. The mobile phase contained 99% 10.0 mmol/L ammonium formate solution at pH 3.6 and 1.0% methanol. Chromatography was achieved at a flow rate of 1.0 mL/min and detection wavelength at 254 nm. The results indicated that total purine amounts in pork rump and beef sirloin were higher than those in other parts (Ppurine bases were hypoxanthine and adenine, and hypoxanthine content was the most highest in all samples (Ppurine and uricogenic purine base, we suggest that excess consumption of them be avoid, whereas pork loin chop and beef rib eye are more suitable for a low-purine diet. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Synthesis of Pharmacological Heterocyclic Derivatives Based Surfactants.

    Science.gov (United States)

    El-Sayed, Refat; Fadda, Ahmed A

    2016-01-01

    Synthesis of chromenopyrimidine derivatives and the related fused system carried out by the reaction of chromene derivative 1 with various reagents under suitable reaction conditions. Condensation of stearoyl chloride with these heterocycles, then, propoxylated the products using propylene oxide to produce surface active agents having a twofold capacity as surface and antimicrobial dynamic specialists which may be served in the production of medications, pesticides, beautifying agents or may be utilized as an antimicrobial. Some of the surface properties and antimicrobial activity were resolved.

  7. Chemical modification of the third strand: differential effects on purine and pyrimidine triple helix formation.

    Science.gov (United States)

    Mills, Martin; Arimondo, Paola B; Lacroix, Laurent; Garestier, Thérèse; Klump, Horst; Mergny, Jean-Louis

    2002-01-08

    DNA triple helices offer exciting perspectives toward oligonucleotide-directed control of gene expression. Oligonucleotide analogues are routinely used with modifications in either the backbone or the bases to form more stable triple-helical structures or to prevent their degradation in cells. In this article, different chemical modifications are tested in a model system, which sets up a competition between the purine and pyrimidine motifs. For most modifications, the DeltaH degrees of purine triplex formation is close to zero, implying a nearly temperature-independent affinity constant. In contrast, the pyrimidine triplex is strongly favored at lower temperatures. The stabilization induced by modifications previously known to be favorable to the pyrimidine motif was quantified. Interestingly, modifications favorable to the GT motif (propynyl-U and dU replacing T) were also discovered. In a system where two third strands compete for triplex formation, replacement of the GA or GT strand by a pyrimidine strand may be observed at neutral pH upon lowering the temperature. This purine-to-pyrimidine triplex conversion depends on the chemical nature of the triplex-forming strands and the stability of the corresponding triplexes.

  8. Purine biosynthetic genes are required for cadmium tolerance in Schizosaccharomyces pombe

    Energy Technology Data Exchange (ETDEWEB)

    Speiser, D.M.; Ortiz, D.F.; Kreppel, L.; Scheel, G.; McDonald, G.; Ow, D.W. (Dept. of Agriculture, Albany, CA (United States) Univ. of California, Berkeley (United States))

    1992-12-01

    Phytochelatins (PCs) are metal-chelating peptides produced in plants and some fungi in response to heavy metal exposure. A Cd-sensitive mutant of the fission yeast Schizosaccharomyces pombe, defective in production of a PC-Cd-sulfide complex essential for metal tolerance, was found to harbor mutations in specific genes of the purine biosynthetic pathway. Genetic analysis of the link between metal complex accumulation and purine biosynthesis enzymes revealed that genetic lesions blocking two segments of the pathway, before and after the IMP branchpoint, are required to produce the Cd-sensitive phenotype. The biochemical functions of these two segments of the pathway are similar, and a model based on the alternate use of a sulfur analog substrate is presented. The novel participation of purine biosynthesis enzymes in the conversion of the PC-Cd complex to the PC-Cd-sulfide complex in the fission yeast raises an intriguing possibility that these same enzymes might have a role in sulfur metabolism in the fission yeast S. pombe, and perhaps in other biological systems. 41 refs., 8 figs., 2 tabs.

  9. The Formation of Nucleobases from the Irradiation of Purine in Astophysical Ices and Comparisons with Meteorites.

    Science.gov (United States)

    Sandford, S. A.; Materese, C. K.; Nuevo, M.

    2016-01-01

    N-heterocycles have been identified in meteorites and their extraterrestrial origins are suggested by isotopic ratio measurements. Although small N- heterocycles have not been detected in the interstellar medium (ISM), recent experiments in our lab have shown that the irradiation of the aromatic molecules like benzene (C6H6) and naphthalene (C10H8) in mixed molecular ices leads to the formation of O- and N-heterocyclic molecules. Among the class of N-heterocycles are the nucleobases, which are of astrobiological interest because they are the information bearing units of DNA and RNA. Nucleobases have been detected in meteorites [3-5], with isotopic signatures that are also consistent with an extraterrestrial origin. Three of the biologically relevant nucleobases (uracil, cytosine, and guanine) have a pyrimidine core structure while the remaining two (adenine and guanine) possess a purine core. Previous experiments in our lab have demonstrated that all of the bio-logical nucleobases (and numerous other molecules) with a pyrimidine core structure can be produced by irradiating pyrimidine in mixed molecular ices of several compositions [6-8]. In this work, we study the formation of purine-based molecules, including the nucleobases adenine, and guanine, from the ultraviolet (UV) irradiation of purine in ices consisting mixtures of H2O and NH3 at low temperature. The experiments are designed to simulate the astrophysical conditions under which these species may be formed in dense molecular clouds, protoplanetary disks, or on the surfaces of icy bodies in planetary systems.

  10. Pricing Model of Multiattribute Derivatives Based on Mixed Process

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    By Analyzing the behavior and character of derivative security, the authorsestablished a pricing model of multiattribute derivative security whose underlying asset pricingprocess is a mixed process, and obtained a new model for option pricing of multiattribute derivatives based on mixed process, and improved some original results.

  11. A derivability criterion based on the existence of adjunctions

    CERN Document Server

    Rodriguez-Gonzalez, Beatriz

    2012-01-01

    In this paper we introduce a derivability criterion of functors based on the existence of adjunctions rather than on the existence of resolutions. It constitutes a converse of Quillen-Maltsiniotis derived adjunction theorem. We present two applications of our derivability criterion. On the one hand, we prove that the two notions for homotopy colimits corresponding to Grothendieck derivators and Quillen model categories are equivalent. On the other hand, we deduce that the internal hom for derived Morita theory constructed by B. To\\"en is indeed the right derived functor of the internal hom of dg-categories.

  12. Catalytic inhibition of topoisomerase II by a novel rationally designed ATP-competitive purine analogue

    Directory of Open Access Journals (Sweden)

    Schlaeppi Jean-Marc

    2009-01-01

    Full Text Available Abstract Background Topoisomerase II poisons are in clinical use as anti-cancer therapy for decades and work by stabilizing the enzyme-induced DNA breaks. In contrast, catalytic inhibitors block the enzyme before DNA scission. Although several catalytic inhibitors of topoisomerase II have been described, preclinical concepts for exploiting their anti-proliferative activity based on molecular characteristics of the tumor cell have only recently started to emerge. Topoisomerase II is an ATPase and uses the energy derived from ATP hydrolysis to orchestrate the movement of the DNA double strands along the enzyme. Thus, interfering with ATPase function with low molecular weight inhibitors that target the nucleotide binding pocket should profoundly affect cells that are committed to undergo mitosis. Results Here we describe the discovery and characterization of a novel purine diamine analogue as a potent ATP-competitive catalytic inhibitor of topoisomerase II. Quinoline aminopurine compound 1 (QAP 1 inhibited topoisomerase II ATPase activity and decatenation reaction at sub-micromolar concentrations, targeted both topoisomerase II alpha and beta in cell free assays and, using a quantitative cell-based assay and a chromosome segregation assay, displayed catalytic enzyme inhibition in cells. In agreement with recent hypothesis, we show that BRCA1 mutant breast cancer cells have increased sensitivity to QAP 1. Conclusion The results obtained with QAP 1 demonstrate that potent and selective catalytic inhibition of human topoisomerase II function with an ATP-competitive inhibitor is feasible. Our data suggest that further drug discovery efforts on ATP-competitive catalytic inhibitors are warranted and that such drugs could potentially be developed as anti-cancer therapy for tumors that bear the appropriate combination of molecular alterations.

  13. Beyond Crystallography: Investigating the Conformational Dynamics of the Purine Riboswitch

    Science.gov (United States)

    Stoddard, Colby D.; Batey, Robert T.

    Riboswitches are structured elements located in the 5'-untranslated regions of numerous bacterial mRNAs that serve to regulate gene expression via their ability to specifically bind metabolites. The purine riboswitch ligand-binding domain has emerged as an important model system for investigating the relationship between RNA structure and function. Directed by NMR and crystallographically generated structures of this RNA, a variety of biophysical and biochemical techniques have been utilized to understand its dynamic nature. In this review, we describe these various approaches and what they reveal about the purine riboswitch.

  14. Guanosina : uma nova abordagem do sistema purinérgico

    OpenAIRE

    Felix Alexandre Antunes Soares

    2005-01-01

    Durante as últimas décadas os estudos do sistema purinérgico concentraram seu foco de atenção nas ações dos derivados da adenina (como adenosina e o ATP). Seus efeitos, receptores, agonistas e antagonistas encontram-se muito bem estabelecidos dentro do sistema nervoso central. Os resultados obtidos com os diversos estudos dos derivados da guanina trazem uma nova perspectiva para o estudo do sistema purinérgico. Os nucleotídeos derivados da guanina são classicamente associados ao sistema de tr...

  15. The purine-utilizing bacterium Clostridium acidurici 9a: a genome-guided metabolic reconsideration.

    Directory of Open Access Journals (Sweden)

    Katrin Hartwich

    Full Text Available Clostridium acidurici is an anaerobic, homoacetogenic bacterium, which is able to use purines such as uric acid as sole carbon, nitrogen, and energy source. Together with the two other known purinolytic clostridia C. cylindrosporum and C. purinilyticum, C. acidurici serves as a model organism for investigation of purine fermentation. Here, we present the first complete sequence and analysis of a genome derived from a purinolytic Clostridium. The genome of C. acidurici 9a consists of one chromosome (3,105,335 bp and one small circular plasmid (2,913 bp. The lack of candidate genes encoding glycine reductase indicates that C. acidurici 9a uses the energetically less favorable glycine-serine-pyruvate pathway for glycine degradation. In accordance with the specialized lifestyle and the corresponding narrow substrate spectrum of C. acidurici 9a, the number of genes involved in carbohydrate transport and metabolism is significantly lower than in other clostridia such as C. acetobutylicum, C. saccharolyticum, and C. beijerinckii. The only amino acid that can be degraded by C. acidurici is glycine but growth on glycine only occurs in the presence of a fermentable purine. Nevertheless, the addition of glycine resulted in increased transcription levels of genes encoding enzymes involved in the glycine-serine-pyruvate pathway such as serine hydroxymethyltransferase and acetate kinase, whereas the transcription levels of formate dehydrogenase-encoding genes decreased. Sugars could not be utilized by C. acidurici but the full genetic repertoire for glycolysis was detected. In addition, genes encoding enzymes that mediate resistance against several antimicrobials and metals were identified. High resistance of C. acidurici towards bacitracin, acriflavine and azaleucine was experimentally confirmed.

  16. Purines and Neuronal Excitability: Links to the Ketogenic Diet

    Science.gov (United States)

    Masino, SA; Kawamura, M; Ruskin, DN; Geiger, JD; Boison, D

    2011-01-01

    ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A1 receptor (A1R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A1Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A1R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A1Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms. PMID:21880467

  17. Purines and neuronal excitability: links to the ketogenic diet.

    Science.gov (United States)

    Masino, S A; Kawamura, M; Ruskin, D N; Geiger, J D; Boison, D

    2012-07-01

    ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A(1) receptor (A(1)R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A(1)Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A(1)Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A(1)R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A(1)Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A(1)Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms.

  18. Direct N9-arylation of purines with aryl halides

    DEFF Research Database (Denmark)

    Larsen, Anders Foller; Ulven, Trond

    2014-01-01

    An efficient method for N-arylation of purines is reported. The N-arylation is catalysed by Cu(i) and 4,7-bis(2-hydroxyethylamino)-1,10-phenanthroline (BHPhen) in aqueous DMF or ethanol. The reaction generally proceeds with high selectivity for the N(9)-position....

  19. Asymmetric Schiff bases derived from diaminomaleonitrile and their metal complexes

    Science.gov (United States)

    Yang, Jianjie; Shi, Rufei; Zhou, Pei; Qiu, Qiming; Li, Hui

    2016-02-01

    Asymmetric Schiff bases, due to its asymmetric structure, can be used as asymmetric catalyst, antibacterial, and mimic molecules during simulate biological processes, etc. In recent years, research on synthesis and properties of asymmetric Schiff bases have become an increase interest of chemists. This review summarizes asymmetric Schiff bases derived from diaminomaleonitrile (DAMN) and DAMN-based asymmetric Schiff bases metal complexes. Applications of DAMN-based asymmetric Schiff bases are also discussed in this review.

  20. Mechanisms of the Formation of Adenine, Guanine, and Their Analogues in UV-Irradiated Mixed NH3:H2O Molecular Ices Containing Purine

    Science.gov (United States)

    Bera, Partha P.; Stein, Tamar; Head-Gordon, Martin; Lee, Timothy J.

    2017-08-01

    We investigated the formation mechanisms of the nucleobases adenine and guanine and the nucleobase analogues hypoxanthine, xanthine, isoguanine, and 2,6-diaminopurine in a UV-irradiated mixed 10:1 H2O:NH3 ice seeded with precursor purine by using ab initio and density functional theory computations. Our quantum chemical investigations suggest that a multistep reaction mechanism involving purine cation, hydroxyl and amino radicals, together with water and ammonia, explains the experimentally obtained products in an independent study. The relative abundances of these products appear to largely follow from relative thermodynamic stabilities. The key role of the purine cation is likely to be the reason why purine is not functionalized in pure ammonia ice, where cations are promptly neutralized by free electrons from NH3 ionization. Amine group addition to purine is slightly favored over hydroxyl group attachment based on energetics, but hydroxyl is much more abundant due to higher abundance of H2O. The amino group is preferentially attached to the 6 position, giving 6-aminopurine, that is, adenine, while the hydroxyl group is preferentially attached to the 2 position, leading to 2-hydroxypurine. A second substitution by hydroxyl or amino group occurs at either the 6 or the 2 position depending on the first substitution. Given that H2O is far more abundant than NH3 in the experimentally studied ices (as well as based on interstellar abundances), xanthine and isoguanine are expected to be the most abundant bi-substituted photoproducts.

  1. A Facile Synthesis of Indole-based Conjugated Derivatives

    Institute of Scientific and Technical Information of China (English)

    LI, Qian-Qian; ZHU, Zhi-Chao; LI,Zhen; QIN, Jin-Gui

    2007-01-01

    A novel synthetic method was developed for the preparation of indole-based conjugated derivatives with satisfied yields. By applying this strategy, a series of new compounds were prepared conveniently. All the obtained new indole derivatives were characterized by spectroscopic analyse s, giving satisfactory data corresponding to their expected molecular structures.

  2. Purine biosynthesis in archaea: variations on a theme

    Directory of Open Access Journals (Sweden)

    Brown Anne M

    2011-12-01

    Full Text Available Abstract Background The ability to perform de novo biosynthesis of purines is present in organisms in all three domains of life, reflecting the essentiality of these molecules to life. Although the pathway is quite similar in eukaryotes and bacteria, the archaeal pathway is more variable. A careful manual curation of genes in this pathway demonstrates the value of manual curation in archaea, even in pathways that have been well-studied in other domains. Results We searched the Integrated Microbial Genome system (IMG for the 17 distinct genes involved in the 11 steps of de novo purine biosynthesis in 65 sequenced archaea, finding 738 predicted proteins with sequence similarity to known purine biosynthesis enzymes. Each sequence was manually inspected for the presence of active site residues and other residues known or suspected to be required for function. Many apparently purine-biosynthesizing archaea lack evidence for a single enzyme, either glycinamide ribonucleotide formyltransferase or inosine monophosphate cyclohydrolase, suggesting that there are at least two more gene variants in the purine biosynthetic pathway to discover. Variations in domain arrangement of formylglycinamidine ribonucleotide synthetase and substantial problems in aminoimidazole carboxamide ribonucleotide formyltransferase and inosine monophosphate cyclohydrolase assignments were also identified. Manual curation revealed some overly specific annotations in the IMG gene product name, with predicted proteins without essential active site residues assigned product names implying enzymatic activity (21 proteins, 2.8% of proteins inspected or Enzyme Commission (E. C. numbers (57 proteins, 7.7%. There were also 57 proteins (7.7% assigned overly generic names and 78 proteins (10.6% without E.C. numbers as part of the assigned name when a specific enzyme name and E. C. number were well-justified. Conclusions The patchy distribution of purine biosynthetic genes in archaea is

  3. Metabolic engineering of the purine biosynthetic pathway in Corynebacterium glutamicum results in increased intracellular pool sizes of IMP and hypoxanthine

    Directory of Open Access Journals (Sweden)

    Peifer Susanne

    2012-10-01

    Full Text Available Abstract Background Purine nucleotides exhibit various functions in cellular metabolism. Besides serving as building blocks for nucleic acid synthesis, they participate in signaling pathways and energy metabolism. Further, IMP and GMP represent industrially relevant biotechnological products used as flavor enhancing additives in food industry. Therefore, this work aimed towards the accumulation of IMP applying targeted genetic engineering of Corynebacterium glutamicum. Results Blocking of the degrading reactions towards AMP and GMP lead to a 45-fold increased intracellular IMP pool of 22 μmol gCDW-1. Deletion of the pgi gene encoding glucose 6-phosphate isomerase in combination with the deactivated AMP and GMP generating reactions, however, resulted in significantly decreased IMP pools (13 μmol gCDW-1. Targeted metabolite profiling of the purine biosynthetic pathway further revealed a metabolite shift towards the formation of the corresponding nucleobase hypoxanthine (102 μmol gCDW-1 derived from IMP degradation. Conclusions The purine biosynthetic pathway is strongly interconnected with various parts of the central metabolism and therefore tightly controlled. However, deleting degrading reactions from IMP to AMP and GMP significantly increased intracellular IMP levels. Due to the complexity of this pathway further degradation from IMP to the corresponding nucleobase drastically increased suggesting additional targets for future strain optimization.

  4. Proteome analysis of the purine stimulon from Lactococcus lactis

    DEFF Research Database (Denmark)

    Beyer, N.H.; Roepstorff, P.; Hammer, Karin

    2003-01-01

    Box-Pribnov box structures resembling the PurR activated promoters for the purDEK and purCSQLF operons. Most, and possibly all members of the Psu stimulon are thus members of the PurR regulon. Five Psu proteins could not be identified. The second stimulon, the Psd stimulon (purine starvation decreased), whose...... members are down-regulated during purine depletion, contained proteins related to protein synthesis (PpsB, EF-TS, trigger factor), or to GTPases (FtsZ, EF-TS); or are involved in energy metabolism (GapB, CcpA). No common regulatory elements could be found for members of this stimulon. Two Psd proteins...

  5. Purine nucleoside phosphorylase deficiency in two unrelated Saudi patients

    OpenAIRE

    Alangari, Abdullah; Al-Harbi, Abdullah; Al-Ghonaium, Abdulaziz; Santisteban, Ines; Hershfield, Michael

    2009-01-01

    Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive metabolic disorder that results in combined immunodeficiency, neurologic dysfunction and autoimmunity. PNP deficiency has never been reported from Saudi Arabia or in patients with an Arabic ethnic background. We report on two Saudi girls with PNP deficiency. Both showed severe lymphopenia and neurological involvement. Sequencing of the PNP gene of one girl revealed a novel missense mutation Pro146>Leu in exon 4 due...

  6. Purine metabolism in patients with gout: the role of lead.

    Science.gov (United States)

    Miranda-Carús, E; Mateos, F A; Sanz, A G; Herrero, E; Ramos, T; Puig, J G

    1997-01-01

    Primary gout is characterized by increased plasma and decreased urinary concentrations of hypoxanthine, xanthine and uric acid. To examine whether lead could explain the disturbance of purine metabolism in gout, we determined hypoxanthine, xanthine and uric acid metabolism and 5-day cumulative urinary lead excretion rates after an EDTA (calcium disodium edetate) test in 27 patients with primary gout and reduced creatinine clearance (C(cr)) and in 50 patients with gout and normal C(cr). The results were compared to those obtained in 26 normal subjects matched for age. All gout patients evidenced a marked renal underexcretion of hypoxanthine, xanthine and uric acid relative to their increased plasma levels. Purine metabolism was remarkably similar in both gout groups except for a significantly lower uric acid excretion in patients with reduced C(cr). Blood lead levels and cumulative lead excretion rates were significantly higher in gout patients with renal failure as compared to patients with normal C(cr). Fourteen patients (52%) with renal insufficiency and 6 (12%) with normal C(cr) showed increased lead excretion rates (95% Cl for the difference, 29-51%, p < 0.001). Mobilizable lead was not significantly correlated with serum or urinary purine concentrations. Hypoxanthine, xanthine and uric acid underexcretion was similar in gout patients with increased or normal cumulative lead excretion rates. The prevalence of atheromatosis and arterial hypertension together was significantly higher in gout patients with renal failure than in patients with normal C(cr) (81 vs. 60%, 95% Cl for the difference, 11-31%, p < 0.005). These results indicate that lead is not a significant contributor to the renal underexcretion of purines in gout. An increased mobilizable lead is not by itself evidence that lead is the cause of the renal insufficiency in patients with primary gout. Atheromatous nephropathy and/or nephroangiosclerosis may explain impaired renal function in patients with

  7. A novel enzymatic approach in the production of food with low purine content using Arxula adeninivorans endogenous and recombinant purine degradative enzymes.

    Science.gov (United States)

    Jankowska, Dagmara A; Trautwein-Schult, Anke; Cordes, Arno; Bode, Rüdiger; Baronian, Keith; Kunze, Gotthard

    2015-01-01

    The purine degradation pathway in humans ends with uric acid, which has low water solubility. When the production of uric acid is increased either by elevated purine intake or by impaired kidney function, uric acid will accumulate in the blood (hyperuricemia). This increases the risk of gout, a disease described in humans for at least 1000 years. Many lower organisms, such as the yeast Arxula adeninivorans, possess the enzyme, urate oxidase that converts uric acid to 5-hydroxyisourate, thus preventing uric acid accumulation. We have examined the complete purine degradation pathway in A. adeninivorans and analyzed enzymes involved. Recombinant adenine deaminase, guanine deaminase, urate oxidase and endogenous xanthine oxidoreductase have been investigated as potential additives to degrade purines in the food. Here, we review the current model of the purine degradation pathway of A. adeninivorans and present an overview of proposed enzyme system with perspectives for its further development.

  8. Biological treatment in clarificated purines pilot plant; Depuracion biologica en plant piloto del clarificado de los purines

    Energy Technology Data Exchange (ETDEWEB)

    Bosque Hernandez, J. L. del; Martin Sanchez, J. L. [Universidad de Salamanca (Spain)

    2004-07-01

    With the purpose of eliminating the environmental problem that suppose the residuals, denominated. Purines, it is necessary to treat them so that they can take advantage. for it, in the part I of the work, the treatment that facilitates the operation of separation of the solid in suspension of the raw purin that allows to decrease the matter organic present in the liquid phase, settled down as well as, the increase of the power fertilizer in the solid phase. The part II of this investigation have as purpose the treatment of the phase it liquidates obtained previously to adapt it for their use like water of industrial type and the solid phase as fertilizer. (Author) 5 refs.

  9. A purine nucleoside phosphorylase in Solanum tuberosum L. (potato) with specificity for cytokinins contributes to the duration of tuber endodormancy.

    Science.gov (United States)

    Bromley, Jennifer R; Warnes, Barbara J; Newell, Christine A; Thomson, Jamie C P; James, Celia M; Turnbull, Colin G N; Hanke, David E

    2014-03-01

    StCKP1 (Solanum tuberosum cytokinin riboside phosphorylase) catalyses the interconversion of the N9-riboside form of the plant hormone CK (cytokinin), a subset of purines, with its most active free base form. StCKP1 prefers CK to unsubstituted aminopurines. The protein was discovered as a CK-binding activity in extracts of tuberizing potato stolon tips, from which it was isolated by affinity chromatography. The N-terminal amino acid sequence matched the translation product of a set of ESTs, enabling a complete mRNA sequence to be obtained by RACE-PCR. The predicted polypeptide includes a cleavable signal peptide and motifs for purine nucleoside phosphorylase activity. The expressed protein was assayed for purine nucleoside phosphorylase activity against CKs and adenine/adenosine. Isopentenyladenine, trans-zeatin, dihydrozeatin and adenine were converted into ribosides in the presence of ribose 1-phosphate. In the opposite direction, isopentenyladenosine, trans-zeatin riboside, dihydrozeatin riboside and adenosine were converted into their free bases in the presence of Pi. StCKP1 had no detectable ribohydrolase activity. Evidence is presented that StCKP1 is active in tubers as a negative regulator of CKs, prolonging endodormancy by a chill-reversible mechanism.

  10. Experimental and theoretical dipole moments of purines in their ground and lowest excited singlet states

    Science.gov (United States)

    Aaron, Jean-Jacques; Diabou Gaye, Mame; Párkányi, Cyril; Cho, Nam Sook; Von Szentpály, László

    1987-01-01

    The ground-state dipole moments of seven biologically important purines (purine, 6-chloropurine, 6-mercaptopurine, hypoxanthine, theobromine, theophylline and caffeine) were determined at 25°C in acetic acid (all the above compounds with the exception of purine) and in ethyl acetate (purine, theophylline and caffeine). Because of its low solubility, it was not possible to measure the dipole moment of uric acid. The first excited singlet-state dipole moments were obtained on the basis of the Bakhshiev and Chamma—Viallet equations using the variation of the Stokes shift with the solvent dielectric constant-refractive index term. The theoretical dipole moments for all the purines listed above and including uric acid were calculated by combining the use of the PPP (π-LCI-SCF-MO) method for the π-contribution to the overall dipole moment with the σ-contribution obtained as a vector sum of the σbond moments and group moments. The experimental and theoretical values were compared with the data available in the literature for some of the purines under study. For several purines, the calculations were carried out for different tautomeric forms. Excited singlet-state dipole moments are smaller than the ground-state values by 0.8 to 2.2 Debye units for all purines under study with the exception of 6-chloropurine. The effects of the structure upon the ground- and excited-state dipole moments of the purines are discussed.

  11. Modification of Purine and Pyrimidine Nucleosides by Direct C-H Bond Activation

    Directory of Open Access Journals (Sweden)

    Yong Liang

    2015-03-01

    Full Text Available Transition metal-catalyzed modifications of the activated heterocyclic bases of nucleosides as well as DNA or RNA fragments employing traditional cross-coupling methods have been well-established in nucleic acid chemistry. This review covers advances in the area of cross-coupling reactions in which nucleosides are functionalized via direct activation of the C8-H bond in purine and the C5-H or C6-H bond in uracil bases. The review focuses on Pd/Cu-catalyzed couplings between unactivated nucleoside bases with aryl halides. It also discusses cross-dehydrogenative arylations and alkenylations as well as other reactions used for modification of nucleoside bases that avoid the use of organometallic precursors and involve direct C-H bond activation in at least one substrate. The scope and efficiency of these coupling reactions along with some mechanistic considerations are discussed.

  12. Wobble↔Watson-Crick tautomeric transitions in the homo-purine DNA mismatches: a key to the intimate mechanisms of the spontaneous transversions.

    Science.gov (United States)

    Brovarets', Ol'ha O; Hovorun, Dmytro M

    2015-01-01

    The intrinsic capability of the homo-purine DNA base mispairs to perform wobble↔Watson-Crick/Topal-Fresco tautomeric transitions via the sequential intrapair double proton transfer was discovered for the first time using QM (MP2/DFT) and QTAIM methodologies that are crucial for understanding the microstructural mechanisms of the spontaneous transversions.

  13. Development of a new HPLC method using fluorescence detection without derivatization for determining purine nucleoside phosphorylase activity in human plasma.

    Science.gov (United States)

    Giuliani, Patricia; Zuccarini, Mariachiara; Buccella, Silvana; Rossini, Margherita; D'Alimonte, Iolanda; Ciccarelli, Renata; Marzo, Matteo; Marzo, Antonio; Di Iorio, Patrizia; Caciagli, Francesco

    2016-01-15

    Purine nucleoside phosphorylase (PNP) activity is involved in cell survival and function, since PNP is a key enzyme in the purine metabolic pathway where it catalyzes the phosphorolysis of the nucleosides to the corresponding nucleobases. Its dysfunction has been found in relevant pathological conditions (such as inflammation and cancer), so the detection of PNP activity in plasma could represent an attractive marker for early diagnosis or assessment of disease progression. Thus the aim of this study was to develop a simple, fast and sensitive HPLC method for the determination of PNP activity in plasma. The separation was achieved on a Phenomenex Kinetex PFP column using 0.1% formic acid in water and methanol as mobile phases in gradient elution mode at a flow rate of 1ml/min and purine compounds were detected using UV absorption and fluorescence. The analysis was fast since the run was achieved within 13min. This method improved the separation of the different purines, allowing the UV-based quantification of the natural PNP substrates (inosine and guanosine) or products (hypoxanthine and guanine) and its subsequent metabolic products (xanthine and uric acid) with a good precision and accuracy. The most interesting innovation is the simultaneous use of a fluorescence detector (excitation/emission wavelength of 260/375nm) that allowed the quantification of guanosine and guanine without derivatization. Compared with UV, the fluorescence detection improved the sensitivity for guanine detection by about 10-fold and abolished almost completely the baseline noise due to the presence of plasma in the enzymatic reaction mixture. Thus, the validated method allowed an excellent evaluation of PNP activity in plasma which could be useful as an indicator of several pathological conditions.

  14. Synthesis and antimicrobial evaluation of certain purine, benzothiazole and thiazole systems substituted with dialkylaminoalkyl-o-cresols

    Directory of Open Access Journals (Sweden)

    Khaled R.A. Abdellatif

    2015-03-01

    Full Text Available Novel series of dialkylaminoalkyl-o-cresols incorporated with purine nucleus 2a–b, benzothiazole nucleus 5a–b, 8a–b and thiazole nucleus 11a–d, 13a–d were synthesized through Mannich reaction. Structures of the newly synthesized compounds have been deduced on the basis of elemental analysis and spectral data. Antimicrobial activity evaluation was carried out for all synthesized compounds; most of them exerted comparable activity to ciprofloxacin and flucanazole. The thiazole derivatives 11a, 13c, 13d are the most potent compounds.

  15. High-hardness ceramics based on boron carbide fullerite derivatives

    Science.gov (United States)

    Ovsyannikov, D. A.; Popov, M. Yu.; Perfilov, S. A.; Prokhorov, V. M.; Kulnitskiy, B. A.; Perezhogin, I. A.; Blank, V. D.

    2017-02-01

    A new type of ceramics based on the phases of fullerite derivatives and boron carbide B4C is obtained. The material is synthesized at a temperature of 1500 K and a relatively low pressure of 4 GPa; it has a high hardness of 45 GPa and fracture toughness of 15 MPa m1/2.

  16. 9-Benzyl-6-benzylsulfanyl-9H-purin-2-amine

    Directory of Open Access Journals (Sweden)

    Maywan Hariono

    2014-03-01

    Full Text Available In the title compound, C19H17N5S, the dihedral angles between the purine ring system (r.m.s. deviation = 0.009 Å and the S-bound and methylene-bound phenyl rings are 74.67 (8 and 71.28 (7°, respectively. In the crystal, inversion dimers linked by pairs of N—H...N hydrogen bonds generate R22(8 loops. C—H...N interactions link the dimers into (100 sheets.

  17. Señales purinérgicas Purinergic signals

    OpenAIRE

    Lazarowski, Eduardo R.; Schwarzbaum, Pablo J.

    2009-01-01

    En la última década se ha aportado clara evidencia de que tanto nucleósidos como nucleótidos de adenina y uridina pueden funcionar como factores de señalización extracelular. Su acción es mediada por dos tipos principales de receptores de superficie denominados purinérgicos. Los receptores P1 se activan por adenosina, y son todos metabotrópicos, mientras que los receptores de nucleótidos (ATP, ADP, UTP y UDP) y nucleótidos-azúcares (UDP-glucosa y UDP-galactosa) pueden ser metabotrópicos (P2Y)...

  18. Associations between Purine Metabolites and Monoamine Neurotransmitters in First-Episode Psychosis

    Directory of Open Access Journals (Sweden)

    Jeffrey K Yao

    2013-06-01

    Full Text Available Schizophrenia (SZ is a biochemically complex disorder characterized by widespread defects in multiple metabolic pathways whose dynamic interactions, until recently, have been difficult to examine. Rather, evidence for these alterations has been collected piecemeal, limiting the potential to inform our understanding of the interactions amongst relevant biochemical pathways. We herein review perturbations in purine and neurotransmitter metabolism observed in early SZ using a metabolomic approach. Purine catabolism is an underappreciated, but important component of the homeostatic response of mitochondria to oxidant stress. We have observed a homeostatic imbalance of purine catabolism in first-episode neuroleptic-naive patients with SZ (FENNS. Precursor and product relationships within purine pathways are tightly correlated. Although some of these correlations persist across disease or medication status, others appear to be lost among FENNS suggesting that steady formation of the antioxidant uric acid via purine catabolism is altered early in the course of illness. As is the case for within-pathway correlations, there are also significant cross-pathway correlations between respective purine and tryptophan pathway metabolites. By contrast, purine metabolites show significant cross-pathway correlation only with tyrosine, and not with its metabolites. Furthermore, several purine metabolites (uric acid, guanosine, or xanthine are each significantly correlated with 5-hydroxyindoleacetic acid (5-HIAA in healthy controls, but not in FENNS at baseline or 4-week after antipsychotic treatment. Taken together, the above findings suggest that purine catabolism strongly associates with the tryptophan pathways leading to serotonin (5-HT and kynurenine metabolites. The Lack of a significant correlation between purine metabolites and 5-HIAA, suggests alterations in key 5-HT pathways that may both be modified by and contribute to oxidative stress via purine

  19. Gelatin Nanofiber Matrices Derived from Schiff Base Derivative for Tissue Engineering Applications.

    Science.gov (United States)

    Jaiswal, Devina; James, Roshan; Shelke, Namdev B; Harmon, Matthew D; Brown, Justin L; Hussain, Fazle; Kumbar, Sangamesh G

    2015-11-01

    Electrospinning of water-soluble polymers and retaining their mechanical strength and bioactivity remain challenging. Volatile organic solvent soluble polymers and their derivatives are preferred for fabricating electrospun nanofibers. We report the synthesis and characterization of 2-nitrobenzyl-gelatin (N-Gelatin)--a novel gelatin Schiff base derivative--and the resulting electrospun nanofiber matrices. The 2-nitrobenzyl group is a photoactivatable-caged compound and can be cleaved from the gelatin nanofiber matrices following UV exposure. Such hydrophobic modification allowed the fabrication of gelatin and blend nanofibers with poly(caprolactone) (PCL) having significantly improved tensile properties. Neat gelatin and their PCL blend nanofiber matrices showed a modulus of 9.08 ± 1.5 MPa and 27.61 ± 4.3 MPa, respectively while the modified gelatin and their blends showed 15.63 ± 2.8 MPa and 24.47 ± 8.7 MPa, respectively. The characteristic infrared spectroscopy band for gelatin Schiff base derivative at 1560 cm(-1) disappeared following exposure to UV light indicating the regeneration of free NH2 group and gelatin. These nanofiber matrices supported cell attachment and proliferation with a well spread morphology as evidenced through cell proliferation assay and microscopic techniques. Modified gelatin fiber matrices showed a 73% enhanced cell attachment and proliferation rate compared to pure gelatin. This polymer modification methodology may offer a promising way to fabricate electrospun nanofiber matrices using a variety of proteins and peptides without loss of bioactivity and mechanical strength.

  20. Changes in serum and urinary uric acid levels in normal human subjects fed purine-rich foods containing different amounts of adenine and hypoxanthine.

    Science.gov (United States)

    Brulé, D; Sarwar, G; Savoie, L

    1992-06-01

    The effect of ingesting some purine-rich foods (beef liver, haddock fillets and soybeans) on uric acid metabolism was investigated in 18 male subjects with no history of gout or kidney disorder. In a crossover design, three isoenergetic and isonitrogenous meals were fed to volunteers during a 3-week period. Only the content of uricogenic bases (adenine and hypoxanthine) varied among the test meals. Ingestion of all experimental meals caused an increase in serum uric acid levels at 120 minutes and this increase was more marked (about twofold) with haddock and soybean ingestion. In all groups, the postprandial serum uric acid levels at 240 minutes were lower than those obtained at 120 minutes, but still remained elevated in comparison to the fasting level. The test foods had little or no effect on serum and urinary creatinine values. As expected, 24-hour urinary uric acid excretion was similar for the three test meals due to the isonitrogenous load of proteins and purines. Assessment of each purine base content rather than the total purine content of foods should be considered in future recommendations for hyperuricemic individuals.

  1. Catalase increases ethanol oxidation through the purine catabolism in rat liver.

    Science.gov (United States)

    Villalobos-García, Daniel; Hernández-Muñoz, Rolando

    2017-08-01

    Hepatic ethanol oxidation increases according to its concentration and is raised to near-saturation levels of alcohol dehydrogenase (ADH); therefore, re-oxidation of NADH becomes rate limiting in ethanol metabolism by the liver. Adenosine is able to increase liver ethanol oxidation in both in vivo and in vitro conditions; the enhancement being related with the capacity of the nucleoside to accelerate the transport of cytoplasmic reducing equivalents to mitochondria, by modifying the subcellular distribution of the malate-aspartate shuttle components. In the present study, we explored the putative effects of adenosine and other purines on liver ethanol oxidation mediated by non-ADH pathways. Using the model of high precision-cut rat liver slices, a pronounced increase of ethanol oxidation was found in liver slices incubated with various intermediates of the purine degradation pathway, from adenosine to uric acid (175-230%, over controls). Of these, urate had the strongest (230%), whereas xanthine had the less pronounced effect (178% over controls). The enhancement was not abolished by 4-methylpyrazole, indicating that the effect was independent of alcohol dehydrogenase. Conversely, aminotriazole, a catalase inhibitor, completely abolished the effect, pointing out that this enhanced ethanol oxidation is mediated by catalase activity. It is concluded that the H2O2 needed for catalase activity is derived from the oxidation of (hypo)xanthine by xanthine oxidase and the oxidation of urate by uricase. The present and previous data led us to propose that, depending on the metabolic conditions, adenosine might be able to stimulate the metabolism of ethanol through different pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Two purine nucleoside phosphorylases in Bacillus subtilis. Purification and some properties of the adenosine-specific phosphorylase

    DEFF Research Database (Denmark)

    Jensen, Kaj Frank

    1978-01-01

    Two purine nucleoside phosphorylases (purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) were purified from vegetative Bacillus subtilis cells. One enzyme, inosine-guanosine phosphorylase, showed great similarity to the homologous enzyme of Bacillus cereus. It appeared...

  3. Morphine enhances the release of /sup 3/H-purines from rat brain cerebral cortical prisms

    Energy Technology Data Exchange (ETDEWEB)

    Wu, P.H.; Phillis, J.W.; Yuen, H.

    1982-10-01

    In vitro experiments have shown that /sup 3/H-purines can be released from /sup 3/H-adenosine preloaded rat brain cortical prisms by a KCl-evoked depolarization. The KCl-evoked release of /sup 3/H-purines is dependent on the concentration of KCl present in the superfusate. At concentrations of 10(-7) approximately 10(-5)M morphine did not influence the basal release of /sup 3/H-purines from the prisms, although it enhanced the KCl-evoked release of /sup 3/H-purines. The enhancement of KCl-evoked /sup 3/H-purine release by morphine was concentration-dependent and was antagonized by naloxone, suggesting the involvement of opiate receptors. Uptake studies with rat brain cerebral cortical synaptosomes show that morphine is a very weak inhibitor of adenosine uptake. Comparisons with dipyridamole, a potent inhibitor of adenosine uptake, suggest that this low level of inhibition of the uptake did not contribute significantly to the release of /sup 3/H-purine by morphine seen in our experiments. It is therefore suggested that morphine enhances KCl-evoked /sup 3/H-purine release by an interaction with opiate receptors and that the resultant increase in extracellular purine (adenosine) levels may account for some of the actions of morphine.

  4. Characterization of purine catabolic pathway genes in coelacanths.

    Science.gov (United States)

    Forconi, Mariko; Biscotti, Maria Assunta; Barucca, Marco; Buonocore, Francesco; De Moro, Gianluca; Fausto, Anna Maria; Gerdol, Marco; Pallavicini, Alberto; Scapigliati, Giuseppe; Schartl, Manfred; Olmo, Ettore; Canapa, Adriana

    2014-09-01

    Coelacanths are a critically valuable species to explore the gene changes that took place in the transition from aquatic to terrestrial life. One interesting and biologically relevant feature of the genus Latimeria is ureotelism. However not all urea is excreted from the body; in fact high concentrations are retained in plasma and seem to be involved in osmoregulation. The purine catabolic pathway, which leads to urea production in Latimeria, has progressively lost some steps, reflecting an enzyme loss during diversification of terrestrial species. We report the results of analyses of the liver and testis transcriptomes of the Indonesian coelacanth Latimeria menadoensis and of the genome of Latimeria chalumnae, which has recently been fully sequenced in the framework of the coelacanth genome project. We describe five genes, uricase, 5-hydroxyisourate hydrolase, parahox neighbor B, allantoinase, and allantoicase, each coding for one of the five enzymes involved in urate degradation to urea, and report the identification of a putative second form of 5-hydroxyisourate hydrolase that is characteristic of the genus Latimeria. The present data also highlight the activity of the complete purine pathway in the coelacanth liver and suggest its involvement in the maintenance of high plasma urea concentrations.

  5. Leishmania metacyclogenesis is promoted in the absence of purines.

    Directory of Open Access Journals (Sweden)

    Tiago Donatelli Serafim

    Full Text Available Leishmania parasites, the causative agent of leishmaniasis, are transmitted through the bite of an infected sand fly. Leishmania parasites present two basic forms known as promastigote and amastigote which, respectively, parasitizes the vector and the mammalian hosts. Infection of the vertebrate host is dependent on the development, in the vector, of metacyclic promastigotes, however, little is known about the factors that trigger metacyclogenesis in Leishmania parasites. It has been generally stated that "stressful conditions" will lead to development of metacyclic forms, and with the exception of a few studies no detailed analysis of the molecular nature of the stress factor has been performed. Here we show that presence/absence of nucleosides, especially adenosine, controls metacyclogenesis both in vitro and in vivo. We found that addition of an adenosine-receptor antagonist to in vitro cultures of Leishmania amazonensis significantly increases metacyclogenesis, an effect that can be reversed by the presence of specific purine nucleosides or nucleobases. Furthermore, our results show that proliferation and metacyclogenesis are independently regulated and that addition of adenosine to culture medium is sufficient to recover proliferative characteristics for purified metacyclic promastigotes. More importantly, we show that metacyclogenesis was inhibited in sand flies infected with Leishmania infantum chagasi that were fed a mixture of sucrose and adenosine. Our results fill a gap in the life cycle of Leishmania parasites by demonstrating how metacyclogenesis, a key point in the propagation of the parasite to the mammalian host, can be controlled by the presence of specific purines.

  6. Organic Field-effect Transistors Based on Tetrathiafulvalene Derivatives

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    1 Restults Tetrathiafulvalene (TTF) and its derivatives have been extensively investigated in the field of organic conductors and superconductors since 1973. Recently, their application in organic field-effect transistors (OFETs) has attracted considerable attention. So far, on the one hand, the fabrication techniques of the TTF-based FETs have been primarily limited to high vacuum evaporation, which is a relatively expensive process. On the other hand, low FET performances, such as the low on/off ratio...

  7. Low-complexity topological derivative-based segmentation.

    Science.gov (United States)

    Cho, Choong Sang; Lee, Sangkeun

    2015-02-01

    Topological derivative has been employed for image segmentation and restoration. The topological derivative-based segmentation uses two sparse matrices, and the computational complexity of the segmentation grows up dramatically as the image size increases due to the size of the sparse matrix. Therefore, to provide a fast and accurate segmentation with low complexity, an effective scheme is proposed with keeping the same segmentation performance. To further reduce the computational complexity, the parallel processing structure for the proposed scheme is designed and implemented on graphics processing unit (GPU). In particular, to reduce the computational cost of generating and multiplying sparse matrices that are squared symmetric, the 2D filters consisting of the coefficients at nonborder regions of sparse matrices are defined, and the multiplication is converted into a convolution filtering. In addition, to design a parallel processing for the segmentation with the proposed scheme on a GPU, an image is divided into several blocks and they are processed in parallel. Experimental results show that the proposed scheme for topological derivative-based segmentation reduces the computational complexity ~ 908 times, and the complexity of the proposed scheme is reduced ~ 17 times more from the parallel structure. In particular, the higher efficiency can be obtained from large sized images because the complexity of the proposed scheme does not depend on the image size. Moreover, the proposed scheme can provide almost identical segmentation result with the original sparse matrix-based approach. Therefore, we believe that the proposed scheme can be a useful tool for efficient topological derivative-based segmentation.

  8. Organic dyes based on fluorene and its derivatives

    Science.gov (United States)

    Kurdyukova, I. V.; Ishchenko, Aleksandr A.

    2012-03-01

    Data on various types of organic dyes based on fluorene and its derivatives, including polymethine, styryl, triphenylmethane, spiran, merocyanine, porphyrin and polymeric dyes, as well as azo dyes and donor-acceptor polyenes, are described systematically. The key methods for their synthesis are considered. The properties of the dyes are analyzed and summarized. The principles of development of modern functional materials based on these dyes are outlined. The use of these materials in advanced fields of science and technology such as photovoltaics, electroluminescence, nonlinear optics, holography, sensing photodynamic therapy are considered. The bibliography includes 476 references.

  9. Anopheles gambiae Purine Nucleoside Phosphorylase: Catalysis, Structure, and Inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Taylor,E.; Rinaldo-Matthis, A.; Li, L.; Ghanem, M.; Hazleton, K.; Cassera, M.; Almo, S.; Schramm, V.

    2007-01-01

    The purine salvage pathway of Anopheles gambiae, a mosquito that transmits malaria, has been identified in genome searches on the basis of sequence homology with characterized enzymes. Purine nucleoside phosphorylase (PNP) is a target for the development of therapeutic agents in humans and purine auxotrophs, including malarial parasites. The PNP from Anopheles gambiae (AgPNP) was expressed in Escherichia coli and compared to the PNPs from Homo sapiens (HsPNP) and Plasmodium falciparum (PfPNP). AgPNP has kcat values of 54 and 41 s-1 for 2'-deoxyinosine and inosine, its preferred substrates, and 1.0 s-1 for guanosine. However, the chemical step is fast for AgPNP at 226 s-1 for guanosine in pre-steady-state studies. 5'-Deaza-1'-aza-2'-deoxy-1'-(9-methylene)-Immucillin-H (DADMe-ImmH) is a transition-state mimic for a 2'-deoxyinosine ribocation with a fully dissociated N-ribosidic bond and is a slow-onset, tight-binding inhibitor with a dissociation constant of 3.5 pM. This is the tightest-binding inhibitor known for any PNP, with a remarkable Km/Ki* of 5.4 x 107, and is consistent with enzymatic transition state predictions of enhanced transition-state analogue binding in enzymes with enhanced catalytic efficiency. Deoxyguanosine is a weaker substrate than deoxyinosine, and DADMe-Immucillin-G is less tightly bound than DADMe-ImmH, with a dissociation constant of 23 pM for AgPNP as compared to 7 pM for HsPNP. The crystal structure of AgPNP was determined in complex with DADMe-ImmH and phosphate to a resolution of 2.2 Angstroms to reveal the differences in substrate and inhibitor specificity. The distance from the N1' cation to the phosphate O4 anion is shorter in the AgPNP{center_dot}DADMe-ImmH{center_dot}PO4 complex than in HsPNP{center_dot}DADMe-ImmH{center_dot}SO4, offering one explanation for the stronger inhibitory effect of DADMe-ImmH for AgPNP.

  10. Cyclin-dependent kinase inhibitors inspired by roscovitine: purine bioisosteres.

    Science.gov (United States)

    Jorda, Radek; Paruch, Kamil; Krystof, Vladimír

    2012-01-01

    Roscovitine is a synthetic inhibitor of cyclin-dependent kinases that is currently undergoing clinical trials as a candidate drug for some oncological indications. Its discovery prompted many research teams to further optimize its structure or to initiate their own related but independent studies. This article reviews known roscovitine bioisosteres that have been prepared as CDK inhibitors using different core heterocycles. The individual bioisostere types have been described and explored to a different extent, which complicates direct comparisons of their biochemical activity - only six direct analogs containing different purine bioisosteres have been prepared and evaluated side by side with roscovitine. Only four types of bioisosteres have demonstrated improved biological properties, namely pyrazolo[ 1,5-a]-1,3,5-triazines, pyrazolo[1,5-a]pyrimidines, pyrazolo[1,5-a]pyridines and pyrazolo[4,3-d]pyrimidines.

  11. Identification of sugarcane genes involved in the purine synthesis pathway

    Directory of Open Access Journals (Sweden)

    Mario A. Jancso

    2001-12-01

    Full Text Available Nucleotide synthesis is of central importance to all cells. In most organisms, the purine nucleotides are synthesized de novo from non-nucleotide precursors such as amino acids, ammonia and carbon dioxide. An understanding of the enzymes involved in sugarcane purine synthesis opens the possibility of using these enzymes as targets for chemicals which may be effective in combating phytopathogen. Such an approach has already been applied to several parasites and types of cancer. The strategy described in this paper was applied to identify sugarcane clusters for each step of the de novo purine synthesis pathway. Representative sequences of this pathway were chosen from the National Center for Biotechnology Information (NCBI database and used to search the translated sugarcane expressed sequence tag (SUCEST database using the available basic local alignment search tool (BLAST facility. Retrieved clusters were further tested for the statistical significance of the alignment by an implementation (PRSS3 of the Monte Carlo shuffling algorithm calibrated using known protein sequences of divergent taxa along the phylogenetic tree. The sequences were compared to each other and to the sugarcane clusters selected using BLAST analysis, with the resulting table of p-values indicating the degree of divergence of each enzyme within different taxa and in relation to the sugarcane clusters. The results obtained by this strategy allowed us to identify the sugarcane proteins participating in the purine synthesis pathway.A via de síntese de purino nucleotídeos é considerada uma via de central importância para todas as células. Na maioria dos organismos, os purino nucleotídeos são sintetizados ''de novo'' a partir de precursores não-nucleotídicos como amino ácidos, amônia e dióxido de carbono. O conhecimento das enzimas envolvidas na via de síntese de purinas da cana-de-açúcar vai abrir a possibilidade do uso dessas enzimas como alvos no desenho

  12. Potential activity of the purine compounds caffeine and aminophylline on bacteria

    Directory of Open Access Journals (Sweden)

    Ali Abdul Hussein S AL-Janabi

    2011-01-01

    Full Text Available Background: Purine compounds are special types of alkaloids. Caffeine and aminophylline are considered the most important members of purines due to their wide use in therapeutics. Aims: To detect any potential antibacterial effects on pathogenic bacteria of the widely prescribed members of purines caffeine and aminophylline. Materials and Methods: Two species of gram-positive bacteria and five species of gram-negative bacteria were exposed to these purine agents. Antibacterial effects of the tested purines were determined using the spectrophotometer method to assess the minimum inhibition concentrations (MIC. Results: Among the strains of bacteria tested, Bacillus subtilis showed the most susceptibility to purine agents. Staphylococcus aureus and Bacillus subtilis were found to be more susceptible to caffeine than the other strains. Aminophylline showed inhibitory action on many isolates, especially at the concentration of 10mg/ml. Paracoccus yeei demonstrated resistance to all tested purine compounds up to a concentration of 10.5mg/ml. Conclusions: Caffeine and aminophylline had the ability to inhibit many strains of pathogenic bacteria.

  13. Morphine enhances purine nucleotide catabolism in rive and in vitro

    Institute of Scientific and Technical Information of China (English)

    Chang LIU; Jian-kai LIU; Mu-jie KAN; Lin GAO; Hai-ying FU; Hang ZHOU; Min HONG

    2007-01-01

    Aim: To investigate the effect and mechanism of morphine on purine nucleotide catabolism. Methods: The rat model of morphine dependence and withdrawal and rat C6 glioma cells in culture were used. Concentrations of uric acid in the plasma were measured by the uricase-rap method, adenosine deaminase (ADA) and xan- thine oxidase (XO) in the plasma and tissues were measured by the ADA and XO test kit. RT-PCR and RT-PCR-Southern blotting were used to examine the relative amount of ADA and XO gene transcripts in tissues and C6 cells. Results: (i) the concentration of plasma uric acid in the morphine-administered group was signifi-cantly higher (P<0.05) than the control group; (ii) during morphine administration and withdrawal periods, the ADA and XO concentrations in the plasma increased significantly (P<0.05); (iii) the amount of ADA and XO in the parietal lobe, liver, small intestine, and skeletal muscles of the morphine-administered groups increased, while the level of ADA and XO in those tissues of the withdrawal groups decreased; (iv) the transcripts of the ADA and XO genes in the parietal lobe, liver, small intestine, and skeletal muscles were higher in the morphine-administered group. The expression of the ADA and XO genes in those tissues returned to the control level during morphine withdrawal, with the exception of the skeletal muscles; and (v) the upregulation of the expression of the ADA and XO genes induced by morphine treatment could be reversed by naloxone. Conclusion: The effects of morphine on purine nucleotide metabolism might be an important, new biochemical pharmacological mechanism of morphine action.

  14. Nanoporous Carbide-Derived Carbon Material-Based Linear Actuators

    Directory of Open Access Journals (Sweden)

    Janno Torop

    2009-12-01

    Full Text Available Devices using electroactive polymer-supported carbon material can be exploited as alternatives to conventional electromechanical actuators in applications where electromechanical actuators have some serious deficiencies. One of the numerous examples is precise microactuators. In this paper, we show for first time the dilatometric effect in nanocomposite material actuators containing carbide-derived carbon (CDC and polytetrafluoroetylene polymer (PTFE. Transducers based on high surface area carbide-derived carbon electrode materials are suitable for short range displacement applications, because of the proportional actuation response to the charge inserted, and high Coulombic efficiency due to the EDL capacitance. The material is capable of developing stresses in the range of tens of N cm-2. The area of an actuator can be dozens of cm2, which means that forces above 100 N are achievable. The actuation mechanism is based on the interactions between the high-surface carbon and the ions of the electrolyte. Electrochemical evaluations of the four different actuators with linear (longitudinal action response are described. The actuator electrodes were made from two types of nanoporous TiC-derived carbons with surface area (SA of 1150 m2 g-1 and 1470 m2 g-1, respectively. Two kinds of electrolytes were used in actuators: 1.0 M tetraethylammonium tetrafluoroborate (TEABF4 solution in propylene carbonate and pure ionic liquid 1-ethyl-3-methylimidazolium trifluoromethanesulfonate (EMITf. It was found that CDC based actuators exhibit a linear movement of about 1% in the voltage range of 0.8 V to 3.0 V at DC. The actuators with EMITf electrolyte had about 70% larger movement compared to the specimen with TEABF4 electrolyte.

  15. Transition Path Sampling Study of the Reaction Catalyzed by Purine Nucleoside Phosphorylase

    Science.gov (United States)

    Saen-oon, Suwipa; Schramm, Vern L.; Schwartz, Steven D.

    2010-01-01

    The Transition Path Sampling (TPS) method is a powerful technique for studying rare events in complex systems, that allows description of reactive events in atomic detail without prior knowledge of reaction coordinates and transition states. We have applied TPS in combination with a hybrid Quantum Mechanical/Molecular Mechanical (QM/MM) method to study the enzyme human purine nucleoside phosphorylase (hPNP). This enzyme catalyzes the reversible phosphorolysis of 6-oxypurine (deoxy)nucleosides to generate the corresponding purine base and (deoxy)ribose 1-phosphate. Hundreds of reactive trajectories were generated. Analysis of this transition path ensembles provides insight into the detailed mechanistic dynamics of reaction in the enzyme. Our studies have indicated a reaction mechanism involving the cleavage of the N-ribosidic bond to form transition states with substantial ribooxacarbenium ion character, that is then followed by conformational changes in the enzyme and the ribosyl group leading to migration of the anomeric carbon of the ribosyl group toward phosphate to form the product ribose 1-phosphate. This latter process is crucial in PNP, because several strong H-bonds form between active site residues in order to capture and align the phosphate nucleophile. Calculations of the commitment probability along reactive paths demonstrated the presence of a broad energy barrier at the transition state. Analysis of these transition state structures showed that bond-breaking and bond-forming distances are not a good choice for the reaction coordinate, but that the pseudorotational phase of the ribose ring is also a significant variable. PMID:20664707

  16. On the accessibility to conical intersections in purines: hypoxanthine and its singly protonated and deprotonated forms.

    Science.gov (United States)

    Villabona-Monsalve, Juan P; Noria, Raquel; Matsika, Spiridoula; Peón, Jorge

    2012-05-09

    The dynamics following electronic excitation of hypoxanthine and its nucleoside inosine were studied by femtosecond fluorescence up-conversion. Our objective was to explore variants of the purinic DNA bases in order to determine the molecular parameters that increase or reduce the accessibility to ground state conical intersections. From experiments in water and methanol solution we conclude that both dominant neutral tautomers of hypoxanthine exhibit ultrashort excited state lifetimes (τ conical intersection for the fluorescent state upon removal of the amino group, present in guanine but absent in hypoxanthine. The excited state dynamics of singly protonated hypoxanthine were also studied, showing biexponential decays with a 1.1 ps component (5%) besides a sub-0.2 ps ultrafast component. On the other hand, the S(1) lifetimes of the singly deprotonated forms of hypoxanthine and inosine show drastic differences, where the latter remains ultrafast but the singly deprotonated hypoxanthine shows a much longer lifetime of 19 ps. This significant variation is related to the different deprotonation sites in hypoxanthine versus inosine, which gives rise to significantly different resonance structures. In our study we also include multireference perturbation theory (MRMP2) excited state calculations in order to determine the nature of the initial electronic excitation in our experiments and clarify the ordering of the states in the singlet manifold at the ground state geometry. In addition, we performed multireference configuration interaction calculations (MR-CIS) that identify the presence of low-lying conical intersections for both prominent neutral tautomers of hypoxanthine. In both cases, the surface crossings occur at geometries reached by out of plane opposite motions of C2 and N3. The study of this simpler purine gives several insights into how small structural modifications, including amino substitution and protonation site and state, determine the accessibility

  17. Fast repair of purine deoxynucleotide radical cations by rutin and quercetin

    Institute of Scientific and Technical Information of China (English)

    ZHAO; Chenyang; (

    2001-01-01

    [1]Boon, P. J., Cullis, P. M., Symons, M. C. R. et al., Effects of ionizing radiation on deoxyribonucleic acid and related systems, Part 1, The role of oxygen, J. Chem. Soc. Perkin. Trans. 2, 1984, 1393-1399.[2]Boon, P. J., Cullis, P. M., Symons, M. C. R. et al., Effects of ionizing radiation on deoxyribonucleic acid and related systems, Part 2, The influence of nitroimidazole drugs on the course of radiation damage to aqueous doxyribonucleic acid, J. Chem. Soc. Perkin. Trans. 2, 1985, 1057-1061.[3]Teoule, R., Effects of Ionizing Radiation on DNA, Berlin, Heidelberg, New York: Springer, 1978, 153, 166, 187.[4]Wallace, S. S., Oxidative Damage to DNA and Its Repair, New York: Cold Spring Harbor Laboratory Press, 1997, 49-90.[5]Steenken, J., Purine bases, nucleosides, and nucleotides: aqueous solution redox chemistry and transformation reaction of their radical cations and e? and OH adducts, Chem. Rev., 1989, 89: 503-520.[6]Simic, M. G., Bergtold, D. S., Karam, L. R., Generation of oxy radicals in biosystems, Mutation Res., 1989, 214: 3-12.[7]O'Neill, P., Pulse radiolytic study of the interaction of thiols and ascorbate with OH adducts of dGMP and dG: implications for DNA repair process, Radiat. Res., 1983, 96: 198-210.[8]Jiang, Y., Yao, S. D., Lin, N. Y., Fast repair of oxidizing OH radical adduct of dGMP by hydroxycinnamic acid derivatives: a pulse radiolytic study, Radiat. Phys. Chem., 1997, 49: 447-450.[9]Li, W. Y., Zheng, R. L., Su, B. N. et al., Repair of dGMP hydroxyl radical adducts by verbascoside via electron transfer: a pulse radiolysis study, Int. J. Radiat. Biol., 1996, 69: 481-486.[10]Li, W. Y., Zou, Z. H., Zheng, R. L. et al., Fast repair of thymine-hydroxyl radical adduct by phenylpropanoid glycosides, Radiat. Phys. Chem., 1997, 49: 429-432.[11]Shi, Y. M., Wang, W. F., Shi, Y. P. et al., Fast repair of dAMP hydroxyl adducts by verbasicoside via electron transfer, Science in China, Ser. C, 1999, 42(6): 621

  18. UTILIZACION AGRONOMICA DE PURINES DE CERDO EN BROCOLI Y SANDIA EN CONDICIONES MEDITERRANEAS SEMIARIDAS. INFLUENCIA EN SISTEMA SUELO-PLANTA

    OpenAIRE

    LLONA CARRASCO, MIRIAM

    2005-01-01

    El hecho de que los purines de cerdo actualmente constituyan un problema medio ambiental grave se debe principalmente al cambio en el sistema de explotación ganadera, ligado a su intensificación. Entre los años 60 y 90, hubo en España una reducción de las explotaciones de porcino con tierra del 75% (Coll, 1993). Esta tendencia a un sistema productivo de tipo Intensivo, con explotaciones sin tierra, alta mecanización, alimentación a base de piensos compuestos, etc., lleva consigo una serie ...

  19. Single-molecular diodes based on opioid derivatives.

    Science.gov (United States)

    Siqueira, M R S; Corrêa, S M; Gester, R M; Del Nero, J; Neto, A M J C

    2015-12-01

    We propose an efficient single-molecule rectifier based on a derivative of opioid. Electron transport properties are investigated within the non-equilibrium Green's function formalism combined with density functional theory. The analysis of the current-voltage characteristics indicates obvious diode-like behavior. While heroin presents rectification coefficient R>1, indicating preferential electronic current from electron-donating to electron-withdrawing, 3 and 6-acetylmorphine and morphine exhibit contrary behavior, Rdiodes. In particular, the rectification rations for heroin diodes show microampere electron current with a maximum of rectification (R=9.1) at very low bias voltage of ∼0.6 V and (R=14.3)∼1.8 V with resistance varying between 0.4 and 1.5 M Ω. Once most of the current single-molecule diodes usually rectifies in nanoampere, are not stable over 1.0 V and present electrical resistance around 10 M. Molecular devices based on opioid derivatives are promising in molecular electronics.

  20. Dye-sensitized solar cells based on bisindolylmaleimide derivatives

    Institute of Scientific and Technical Information of China (English)

    Qiong ZHANG; Zhijun NING; Hongcui PEI; Wenjun WU

    2009-01-01

    Three organic dyes based on bisindolylmaleimide derivatives (11, 12 and 13) were synthesized and investigated as sensitizers for the application in nanocrystalline TiO2 solar cells. The indole group,maleimide group and carboxylic group functioned as electron donor, acceptor and anchoring group, respec-tively. Solar-to-electrical energy conversion efficiencies under simulated amplitude-modulated 1.5 irradiation based on 12 and of 1.87% and 1.50% for 13 and 11,respectively. The open circuit voltage Voc was demon-strated to be enhanced by the introduction of dodecyl or benzyl moieties on the indole groups. The nonplanar structure of bisindolylmaleimide was proven to be effective in aggregation resistance. This work suggests that organic sensitizers with maleimide as electron acceptor are promising candidates as organic sensiti-zers in dye-sensitized solar cells.

  1. Poly(alizarin red)/Graphene modified glassy carbon electrode for simultaneous determination of purine and pyrimidine

    Energy Technology Data Exchange (ETDEWEB)

    Ba Xi; Luo Liqiang [Department of Chemistry, Shanghai University, Shanghai 200444 (China); Ding Yaping, E-mail: wdingyp@sina.com [Department of Chemistry, Shanghai University, Shanghai 200444 (China); Zhang Zhen [Department of Chemistry, Shanghai University, Shanghai 200444 (China); Chu Yuliang [Instrumental Analysis and Research Center, Shanghai University, Shanghai 200444 (China); Wang Bijun; Ouyang Xiaoqian [Department of Chemistry, Shanghai University, Shanghai 200444 (China)

    2012-11-08

    Graphical abstract: DPVs of PAR/Graphene/GCE (a) and the bare GCE (c) in 0.1 M PBS containing 50.0 {mu}M G, 50.0 {mu}M A, 100.0 {mu}M T and 100.0 {mu}M C, (b) PAR/Graphene/GCE in 0.1 M PBS. Highlights: Black-Right-Pointing-Pointer The sensor exhibited well-separated peaks and low detection limit. Black-Right-Pointing-Pointer The sensor possesses high sensitivity and wide linear range. Black-Right-Pointing-Pointer The sensor was used for simultaneous detection of G, A, T and C successfully. Black-Right-Pointing-Pointer The sensor was applied in a fish sperm DNA sample with satisfactory results. Black-Right-Pointing-Pointer The proposed sensor has good stability and reproducibility. - Abstract: In this work, a poly(alizarin red)/Graphene composite film modified glassy carbon electrode (PAR/Graphene/GCE) was prepared for simultaneous determination of four DNA bases (guanine, adenine, thymine and cytosine) without any pretreatment. The morphology and interface property of PAR/Graphene films were examined by scanning electron microscopy and electrochemical impedance spectroscopy. The PAR/Graphene/GCE exhibited excellent electrocatalytic activity toward purine (guanine and adenine) and pyrimidine (thymine and cytosine) in 0.1 M phosphate buffer solution (pH 7.4). Under optimum conditions, differential pulse voltammetry was used to detect the oxidation of purine and pyrimidine. The results showed that PAR/Graphene/GCE exhibited well-separated peaks, low detection limit, high sensitivity and wide linear range for simultaneous detection of purine and pyrimidine. The proposed sensor also has good stability and reproducibility. Furthermore, the modified electrode was applied for the detection of DNA bases in a fish sperm DNA sample with satisfactory results.

  2. A simple HPLC method for determining the purine content of beer and beer-like alcoholic beverages.

    Science.gov (United States)

    Fukuuchi, Tomoko; Yasuda, Makoto; Inazawa, Katsunori; Ota, Tatsuhiro; Yamaoka, Noriko; Mawatari, Ken-ichi; Nakagomi, Kazuya; Kaneko, Kiyoko

    2013-01-01

    Several methods for quantifying the purine content in food and drink have been described using high-performance liquid chromatography (HPLC). We have developed an improved HPLC method that is based on a method reported by Kaneko et al. and that is more sensitive yet simple, and suitable for determining the purine content of beer and beer-like alcoholic beverages. Quantitative HPLC separation was performed on a Shodex Asahi Pak GS-320HQ column with an isocratic elution of 150 mmol/L sodium phosphate buffer (H(3)PO(4)/NaH(2)PO(4) = 20:100 (v/v)). The retention times for the four analytes, namely, adenine, guanine, hypoxanthine and xanthine, were 19.9, 25.0, 29.3 and 43.0 min, respectively. The resolution was good, and there was no excessive interference from the other compounds in the beverages at these retention times. Furthermore, the detection limit for all the analytes was improved to less than 0.0075 mg/L, and all the calibration curves showed good linearity (r(2) > 0.999) between 0.013 and 10 mg/L for adenine and guanine, and between 0.025 and 10 mg/L for hypoxanthine and xanthine. The pretreatment was simplified by removing some procedures and optimizing the perchloric acid hydrolysis and the enzymatic peak-shift assay. We reduced the sample dilution rate by almost 50%, and the time spent on pretreatment from 4 days to only 180 min. The recovery of the analytes from spiked samples was 94.8 - 103.8%. This method may be useful for evaluating quantitative and qualitative differences in the purine content of beer and beer-like alcoholic beverages.

  3. Monte Carlo evaluation of derivative-based global sensitivity measures

    Energy Technology Data Exchange (ETDEWEB)

    Kucherenko, S. [Centre for Process Systems Engineering, Imperial College London, London SW7 2AZ (United Kingdom)], E-mail: s.kucherenko@ic.ac.uk; Rodriguez-Fernandez, M. [Process Engineering Group, Instituto de Investigaciones Marinas, Spanish Council for Scientific Research (C.S.I.C.), C/ Eduardo Cabello, 6, 36208 Vigo (Spain); Pantelides, C.; Shah, N. [Centre for Process Systems Engineering, Imperial College London, London SW7 2AZ (United Kingdom)

    2009-07-15

    A novel approach for evaluation of derivative-based global sensitivity measures (DGSM) is presented. It is compared with the Morris and the Sobol' sensitivity indices methods. It is shown that there is a link between DGSM and Sobol' sensitivity indices. DGSM are very easy to implement and evaluate numerically. The computational time required for numerical evaluation of DGSM is many orders of magnitude lower than that for estimation of the Sobol' sensitivity indices. It is also lower than that for the Morris method. Efficiencies of Monte Carlo (MC) and quasi-Monte Carlo (QMC) sampling methods for calculation of DGSM are compared. It is shown that the superiority of QMC over MC depends on the problem's effective dimension, which can also be estimated using DGSM.

  4. De novo purine biosynthesis by two pathways in Burkitt lymphoma cells and in human spleen.

    Science.gov (United States)

    Reem, G H

    1972-05-01

    This study was designed to answer the question whether human lymphocytes and spleen cells were capable of de novo purine biosynthesis. Experiments were carried out in cell-free extracts prepared from human spleen, and from a cell line established from Burkitt lymphoma. Burkitt lymphoma cells and human spleen cells could synthesize the first and second intermediates of the purine biosynthetic pathway. Cell-free extracts of all cell lines studied contained the enzyme systems which catalyze the synthesis of phosphoribosyl-1-amine, the first intermediate unique to the purine biosynthetic pathway and of phosphoribosyl glycinamide, the second intermediate of this pathway. Phosphoribosyl-1-amine could be synthesized in cell-free extracts from alpha-5-phosphoribosyl-1-pyrophosphate (PRPP) and glutamine, from PRPP and ammonia, and by an alternative pathway, directly from ribose-5-phosphate and ammonia. These findings suggest that extrahepatic tissues may be an important source for the de novo synthesis of purine ribonucleotide in man. They also indicate that ammonia may play an important role in purine biosynthesis. The alternative pathway for the synthesis of phosphoribosyl-1-amine from ribose-5-phosphate and ammonia was found to be subject to inhibition by the end products of the purine synthetic pathway, particularly by adenylic acid and to a lesser degree by guanylic acid. The alternative pathway for phosphoribosyl-1-amine synthesis from ribose-5-phosphate and ammonia may contribute significantly towards the regulation of the rate of de novo purine biosynthesis in the normal state, in metabolic disorders in which purines are excessively produced and in myeloproliferative diseases.

  5. Identification of potential inhibitors for AIRS from de novo purine biosynthesis pathway through molecular modeling studies - a computational approach.

    Science.gov (United States)

    Rao, R Guru Raj; Biswal, Jayashree; Dhamodharan, Prabhu; Kanagarajan, Surekha; Jeyaraman, Jeyakanthan

    2016-10-01

    In cancer, de novo pathway plays an important role in cell proliferation by supplying huge demand of purine nucleotides. Aminoimidazole ribonucleotide synthetase (AIRS) catalyzes the fifth step of de novo purine biosynthesis facilitating in the conversion of formylglycinamidine ribonucleotide to aminoimidazole ribonucleotide. Hence, inhibiting AIRS is crucial due to its involvement in the regulation of uncontrollable cancer cell proliferation. In this study, the three-dimensional structure of AIRS from P. horikoshii OT3 was constructed based on the crystal structure from E. coli and the modeled protein is verified for stability using molecular dynamics for a time frame of 100 ns. Virtual screening and induced fit docking were performed to identify the best antagonists based on their binding mode and affinity. Through mutational studies, the residues necessary for catalytic activity of AIRS were identified and among which the following residues Lys35, Asp103, Glu137, and Thr138 are important in determination of AIRS function. The mutational studies help to understand the structural and energetic characteristics of the specified residues. In addition to Molecular Dynamics, ADME properties, binding free-energy, and density functional theory calculations of the compounds were carried out to find the best lead molecule. Based on these analyses, the compound from the NCI database, NCI_121957 was adjudged as the best molecule and could be suggested as the suitable inhibitor of AIRS. In future studies, experimental validation of these ligands as AIRS inhibitors will be carried out.

  6. A Targeted Metabolomics Assay to Measure Eight Purines in the Diet of Common Bottlenose Dolphins, Tursiops truncatus.

    Science.gov (United States)

    Ardente, A J; Garrett, T J; Wells, R S; Walsh, M; Smith, C R; Colee, J; Hill, R C

    2016-10-01

    Bottlenose dolphins managed under human care, human beings and Dalmatian dogs are prone to forming urate uroliths. Limiting dietary purine intake limits urate urolith formation in people and dogs because purines are metabolized to uric acid, which is excreted in urine. Managed dolphins develop ammonium urate nephroliths, whereas free-ranging dolphins do not. Free-ranging dolphins consume live fish, whereas managed dolphins consume different species that have been stored frozen and thawed. Differences in the purine content of fish consumed by dolphins under human care versus in the wild may be responsible for the difference in urolith prevalence. Commercially available purine assays measure only four purines, but reported changes in purines during frozen storage suggest that a wider range of metabolites should be measured when comparing fresh and stored fish. A method using high performance liquid chromatography with tandem mass spectrometry was developed to quantify eight purine metabolites in whole fish and squid commonly consumed by dolphins. The coefficient of variation within and among days was sometimes high for purines present in small amounts but was acceptable (≤ 25%) for guanine, hypoxanthine, and inosine, which were present in high concentrations. This expanded assay identified a total purine content up to 2.5 times greater than the total that would be quantified if only four purines were measured. Assuming additional purines are absorbed, these results suggest that additional purine metabolites should be measured to better understand the associated risk when fish or other purine-rich foods are consumed by people or animals prone to developing uroliths.

  7. Topology optimization based on spline-based meshfree method using topological derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Hur, Junyoung; Youn, Sung-Kie [KAIST, Daejeon (Korea, Republic of); Kang, Pilseong [Korea Research Institute of Standards and Science, Daejeon (Korea, Republic of)

    2017-05-15

    Spline-based meshfree method (SBMFM) is originated from the Isogeometric analysis (IGA) which integrates design and analysis through Non-uniform rational B-spline (NURBS) basis functions. SBMFM utilizes trimming technique of CAD system by representing the domain using NURBS curves. In this work, an explicit boundary topology optimization using SBMFM is presented with an effective boundary update scheme. There have been similar works in this subject. However unlike the previous works where semi-analytic method for calculating design sensitivities is employed, the design update is done by using topological derivatives. In this research, the topological derivative is used to derive the sensitivity of boundary curves and for the creation of new holes. Based on the values of topological derivatives, the shape of boundary curves is updated. Also, the topological change is achieved by insertion and removal of the inner holes. The presented approach is validated through several compliance minimization problems.

  8. Arxula adeninivorans xanthine oxidoreductase and its application in the production of food with low purine content.

    Science.gov (United States)

    Jankowska, D A; Trautwein-Schult, A; Cordes, A; Hoferichter, P; Klein, C; Bode, R; Baronian, K; Kunze, G

    2013-09-01

    Isolation and characterization of xanthine oxidoreductase and its application in the production of food with low purine content. The A. adeninivorans xanthine oxidoreductase is an inducible enzyme. The best inducers were identified by enzyme activity tests and real-time PCR and used to produce large amounts of the protein. Xanthine oxidoreductase was partially purified and biochemically characterized, showing pH and temperature optimum of 8·5 and 43°C, respectively. The enzyme decreased xanthine and hypoxanthine concentrations in yeast extract and was active simultaneously with other purine-degrading enzymes so that all of the substrates for uric acid production were reduced in a single step. It was shown that induced A. adeninivorans can produce sufficient amount of xanthine dehydrogenase and that the enzyme is able to reduce xanthine and hypoxanthine content in food, and when used in conjunction with other enzymes of the pathway, uric acid concentration is significantly reduced. Reduction in dietary purines is recommended to people suffering from hyperuricemia. Elimination of most purine-rich foods may affect balanced nutrition. Food with lowered purine concentration will assist in controlling the disease. This study is a continuation of previous studies that characterized and overexpressed other enzymes of the purine degradation pathway. © 2013 The Society for Applied Microbiology.

  9. Divergent prebiotic synthesis of pyrimidine and 8-oxo-purine ribonucleotides

    Science.gov (United States)

    Stairs, Shaun; Nikmal, Arif; Bučar, Dejan-Krešimir; Zheng, Shao-Liang; Szostak, Jack W.; Powner, Matthew W.

    2017-05-01

    Understanding prebiotic nucleotide synthesis is a long standing challenge thought to be essential to elucidating the origins of life on Earth. Recently, remarkable progress has been made, but to date all proposed syntheses account separately for the pyrimidine and purine ribonucleotides; no divergent synthesis from common precursors has been proposed. Moreover, the prebiotic syntheses of pyrimidine and purine nucleotides that have been demonstrated operate under mutually incompatible conditions. Here, we tackle this mutual incompatibility by recognizing that the 8-oxo-purines share an underlying generational parity with the pyrimidine nucleotides. We present a divergent synthesis of pyrimidine and 8-oxo-purine nucleotides starting from a common prebiotic precursor that yields the β-ribo-stereochemistry found in the sugar phosphate backbone of biological nucleic acids. The generational relationship between pyrimidine and 8-oxo-purine nucleotides suggests that 8-oxo-purine ribonucleotides may have played a key role in primordial nucleic acids prior to the emergence of the canonical nucleotides of biology.

  10. Development of purine-scaffold small molecule inhibitors of Hsp90.

    Science.gov (United States)

    Chiosis, Gabriela; Lucas, Brian; Huezo, Henri; Solit, David; Basso, Andrea; Rosen, Neal

    2003-10-01

    The Hsp90 chaperones play a key role in regulating the physiology of cells exposed to environmental stress and in maintaining the malignant phenotype in tumor cells. Agents that interfere with the function of the chaperone may thus be beneficial in the treatment of cancers. The ansamycins (geldanamycin and herbimycin) and the unrelated natural product radicicol were found to bind to the N-terminal pocket of Hsp90 and inhibit its function. However, translation of these compounds to the clinic was impeded by stability and hepatoxicity issues. 17AAG, a derivative of geldanamycin, was found to be less hepatotoxic and is currently undergoing Phase I clinical trial. Unfortunately, 17AAG is insoluble, difficult to formulate and it is not yet clear if therapeutically effective doses can be administered without escalating non-Hsp90 associated toxicities. Additionally, for reasons not yet completely understood, a subset of tumor cells are insensitive to the action of the drug. The development of novel agents that lack the drawbacks of the natural products is thus necessary. Here we present an overview of such efforts with focus on a new class of purine-scaffold Hsp90 inhibitors developed by rational design.

  11. Effect of purine nucleoside analogue-acyclovir on the sperm parameters and testosterone production in rats.

    Science.gov (United States)

    Movahed, Elham; Sadrkhanlou, Rajabali; Ahmadi, Abbas; Nejati, Vahid; Zamani, Zahra

    2013-04-01

    Acyclovir (ACV), a synthetic purine nucleoside analogue derived from guanosine, is known to be toxic to gonads and the aim of this study was to evaluate the effect of ACV on the sperm parameters and testosterone production in rat. In this experimental study, forty adult male Wistar rats (220 ± 20 g) were randomly divided into five groups (n=8 for each group). One group served as control and one group served as sham control [distilled water was intraperitoneally (i.p.) injected]. ACV was administered intraperitoneally in the drug treatment groups (4, 16 and 48 mg/kg/day) for 15 days. Eighteen days after the last injection, rats were sacrificed by CO2 inhalation. After that, cauda epididymides were removed surgically. At the end, sperm concentrations in the cauda epididymis, sperm motility, morphology, viability, chromatin quality and DNA integrity were analyzed. Serum testosterone concentrations were determined. The results showed that ACV did not affect sperm count, but decreased sperm motility and sperm viability at 16 and 48 mg/kg dose-levels. Sperm abnormalities increased at 48 mg/kg dose-level of ACV. Further, ACV significantly increases DNA damage at 16 and 48 mg/kg dose-levels and chromatin abnormality at all doses. Besides, a significant decrease in serum testosterone concentrations was observed at 16 and 48 mg/ kg doses. The present results highly support the idea that ACV induces testicular toxicity by adverse effects on the sperm parameters and serum level of testosterone in male rats.

  12. Sulfonamide and carbamate derivatives of 6-chloropurine: synthesis, characterization and antimicrobial activity evaluation

    Directory of Open Access Journals (Sweden)

    K. Venkata Narayana

    2016-07-01

    Full Text Available A series of new sulfonamide derivatives, 9-(substitutedbenzenesulfonyl-6-chloro-9H-purines 7(a-e and carbamate derivatives, 6-chloro-purine-9-carboxylic acid substituted alkyl/arylester 9(a-d, have been synthesized through an intermediate, sodium salt of 6-chloro-9(H-purine (6 which was prepared by the treatment of 6-chloro-9(H-purine (4 with sodium hydride. Structures of the newly synthesized compounds were elucidated by IR, NMR ( 1H and 13C, mass spectra and elemental analysis. Antimicrobial activity against three bacterial strains and three fungal strains at two different concentrations, 100 and 200 µg/mL including MIC values was investigated. Bio-screening data disclosed that most of the sulfonamide derivatives, 7a, 7c and 7d, and one carbamate derivative 9a showed promising antimicrobial activity having MIC values in the range of 18.0-25.0 µg/mL.

  13. Antimalarial action of nitrobenzylthioinosine in combination with purine nucleoside antimetabolites.

    Science.gov (United States)

    Gero, A M; Scott, H V; O'Sullivan, W J; Christopherson, R I

    1989-04-01

    The infection of human erythrocytes by two strains of the human malarial parasite, Plasmodium falciparum (FCQ-27 or the multi-drug-resistant strain K-1), markedly changed the transport characteristics of the nucleosides, adenosine and tubercidin, compared to uninfected erythrocytes. A component of the transport of these nucleosides was insensitive to the classical mammalian nucleoside transport inhibitor nitrobenzylthioinosine (NBMPR). In vitro studies with tubercidin demonstrated ID50 values of 0.43 and 0.51 microM for FCQ-27 and K-1, respectively. In addition, the nucleoside transport inhibitors NBMPR, nitrobenzylthioguanosine (NBTGR), dilazep and dipyridamole also independently exhibited antimalarial activity in vitro. The combination of tubercidin and NBMPR or NBTGR in vitro demonstrated synergistic activity, whilst tubercidin together with dilazep or dipyridamole showed subadditive activity. Analysis by HPLC indicated that NBMPR could permeate the infected cell membrane and provided evidence for the catabolism of NBMPR in vitro, with subsequent alteration of the purine pool in the infected erythrocyte. These observations further indicated the possibility of the utilization of cytotoxic nucleosides against P. falciparum infection in conjunction with a nucleoside transport inhibitor to protect the host tissue.

  14. Purine and pyrimidine composition in 5S rRNA and its mutational significance

    Directory of Open Access Journals (Sweden)

    Subacius Sandra Maria Rodrigues

    1998-01-01

    Full Text Available Variations observed in 5S rRNA base compositions are almost entirely due to fixation of point mutations. As a consequence, 5S rRNA size has remained relatively constant during evolution and, therefore, dependencies among the four bases can be predicted. In order to characterize the nature and to determine the degree of such dependencies, correlation analysis followed by principal component factorial analysis was conducted on a large sample of 5S rRNA sequences. The results show that the purine and pyrimidine contents tend to remain constant, so that A + G = Kpur and C + U = Kpyr. The composition of the four bases expressed now by Kpur/Kpyr relationships is also constant (Ks. These relationships imply that the behavior of the mutations in the variable sites of the molecule follows rules imposed by the chemical nature of the bases involved. Consequently, transition mutations would be more favored than substitutions in transversion sites and also than insertion-deletion (rare in 5S rRNAs, since transitions would not significantly alter the values of the Ks-index.

  15. VUV photophysics and dissociative photoionization of pyrimidine, purine, imidazole and benzimidazole in the 7-18 eV photon energy range

    Energy Technology Data Exchange (ETDEWEB)

    Schwell, Martin [Laboratoire Interuniversitaire des Systemes Atmospheriques (LISA), CNRS-UMR 7583, Universite Paris 7 and 12, 61 Avenue du General de Gaulle, 94010 Creteil (France)], E-mail: schwell@lisa.univ-paris12.fr; Jochims, Hans-Werner; Baumgaertel, Helmut [Institut fuer Physikalische und Theoretische Chemie der Freien Universitaet Berlin, Takustr. 3, Berlin 14195 (Germany); Leach, Sydney [Laboratoire d' Etude du Rayonnement et de la Matiere en Astrophysique (LERMA), CNRS-UMR 8112, Observatoire de Paris-Meudon, 5 Place Jules-Janssen, 92195 Meudon (France)], E-mail: Sydney.Leach@obspm.fr

    2008-11-03

    Photoionization mass spectrometry is used to study ionization processes and fragmentation pathways of four prebiotic species, pyrimidine, purine, imidazole and benzimidazole, in the 7-18 eV photon energy region, with synchrotron radiation as excitation source. These molecules are possible precursors of the nucleic acid bases that occur in DNA and RNA. Ionization energies and ion appearance energies are reported. They are compared with electron impact and other studies and are discussed in terms of the electronic and nuclear structures of these species and their cations. The ion appearance energies, in conjunction with thermochemical data, were used to propose dissociative photoionization pathways, principally involving loss of HCN molecules in each of the four species. Astrophysical implications of the results concern the prospects for observation and survival of these molecules in the interstellar medium, in comets and in meteorites. Suggestions are made concerning suitable sites for radioastronomical searches for these purines and pyrimidines.

  16. [Hyperuricemia and disorders in content of amino acids-purine precursors in patients with autoimmune diseases and gout].

    Science.gov (United States)

    Nikolenko, Iu I; Siniachenko, O V; Anan'eva, M N; Nikolenko, V Iu; Dubiaga, V V; Shchukin, I N

    2005-06-01

    Patients with system lupus erythematosus, rheumatic arthritis, chronic active hepatitis and gout were found to have considerable hyperuricemia and be decreased in aminoacides content, which are the predecessors of purine. Hyperactivity of xanthineoxidase and POL content were also revealed. The close correlation relation of purine indices of such patients has been observed. The obtained data allow applying methods of correction of immunity system and purine metabolism to these patients by introducing in a complex therapy inhibitors of xanthineoxidase.

  17. A novel polymeric herbicide based on phenoxyacetic acid derivatives

    Directory of Open Access Journals (Sweden)

    Wimol Klaichim

    2009-01-01

    Full Text Available A novel polymeric herbicide based on phenoxyacetic acid derivatives was prepared by the reaction of epoxidised liquid natural rubber (ELNR with 2,4-dichlorophenoxyacetic acid (2,4-D or 2-methyl-4-chlorophenoxyacetic acid(MCPA. The liquid natural rubber (LNR was firstly obtained from the degradation of natural rubber latex with tert-butyl hydroperoxide and cobalt acetylacetonate at 65oC for 72 hrs. The epoxidised liquid natural rubber was prepared from thereaction of LNR with formic acid and hydrogen peroxide at 50oC for 6 hrs. The reaction of epoxidised liquid natural rubber with 2,4-D or MCPA using triethylamine as a catalyst in toluene was performed at 70, 80, and 90oC for 6, 9, 12, 18, and 24hrs. The polymeric herbicides obtained were characterized and the grafting percentage of 2,4-D or MCPA onto liquid natural rubber were also determined by FT-IR and 1H-NMR spectroscopy. It was found that the grafting percentage increased with increasing amount of reactants, temperature, and reaction time. The release of 2,4-D and MCPA from polymeric herbicides was investigated in pH 6, 7, and 8 buffers at room temperature. The results show that the slowest release of 2,4-D and MCPA was found to be constant at pH 7 for 14 and 10 days, respectively.

  18. Radar-Derived Quantitative Precipitation Estimation Based on Precipitation Classification

    Directory of Open Access Journals (Sweden)

    Lili Yang

    2016-01-01

    Full Text Available A method for improving radar-derived quantitative precipitation estimation is proposed. Tropical vertical profiles of reflectivity (VPRs are first determined from multiple VPRs. Upon identifying a tropical VPR, the event can be further classified as either tropical-stratiform or tropical-convective rainfall by a fuzzy logic (FL algorithm. Based on the precipitation-type fields, the reflectivity values are converted into rainfall rate using a Z-R relationship. In order to evaluate the performance of this rainfall classification scheme, three experiments were conducted using three months of data and two study cases. In Experiment I, the Weather Surveillance Radar-1988 Doppler (WSR-88D default Z-R relationship was applied. In Experiment II, the precipitation regime was separated into convective and stratiform rainfall using the FL algorithm, and corresponding Z-R relationships were used. In Experiment III, the precipitation regime was separated into convective, stratiform, and tropical rainfall, and the corresponding Z-R relationships were applied. The results show that the rainfall rates obtained from all three experiments match closely with the gauge observations, although Experiment II could solve the underestimation, when compared to Experiment I. Experiment III significantly reduced this underestimation and generated the most accurate radar estimates of rain rate among the three experiments.

  19. Multifunctional switches based on bis-imidazole derivative

    Indian Academy of Sciences (India)

    Abdullah M A Asiri; Gameel A Baghaffar; Khadija O Badahdah; Abdullah G M Al-Sehemi; Salman A Khan; Abeer A Bukhari

    2009-11-01

    multifunctional bis-imidazole derived from piperonal was prepared and found to have photo, thermo, solvato and peiezochromism with colour changes from pale green to deep blue. The multifunctionality colour changes and stability of the coloured species make the derivative candidates for various applications such as optical data storage. The photochromic properties and performance were found to be affected remarkably upon changing the solvent.

  20. Voltammetric characterization of montmorillonite-based organo derivatives

    OpenAIRE

    Navrátilová, Zuzana; Turčíková, Lenka; Plačková, Adriana

    2012-01-01

    Organo derivatives of clay mineral montmorillonite were prepared by modification of montmorillonite (type SAz-1) with three alkylammonium cations – hexadecyltrimethylammonium (HDTM), benzyldimethylhexadecylammonium (BDH), and hexadecylpyridinium bromide (HDP). The prepared organo-montmorillonites were characterized by X-Ray diffraction and infrared spectroscopy to test the alkylammonium cations presence in the organo derivatives. Multisweep cyclic voltammetry of copper at carbon paste e...

  1. Señales purinérgicas Purinergic signals

    Directory of Open Access Journals (Sweden)

    Eduardo R Lazarowski

    2009-04-01

    Full Text Available En la última década se ha aportado clara evidencia de que tanto nucleósidos como nucleótidos de adenina y uridina pueden funcionar como factores de señalización extracelular. Su acción es mediada por dos tipos principales de receptores de superficie denominados purinérgicos. Los receptores P1 se activan por adenosina, y son todos metabotrópicos, mientras que los receptores de nucleótidos (ATP, ADP, UTP y UDP y nucleótidos-azúcares (UDP-glucosa y UDP-galactosa pueden ser metabotrópicos (P2Y o ionotrópicos (P2X. La importancia y complejidad de este sistema de señalización se evidencia por la diversidad de mecanismos de liberación de nucleótidos al medio extracelular y por la distribución ubicua de varios grupos de ectonucleotidasas capaces de catalizar la degradación y conversión de nucleótidos. Hasta el momento se han descrito y clonado una veintena de estos receptores que modulan una variedad de respuestas, como el impulso nervioso, la respuesta inflamatoria, la secreción de insulina, la regulación del tono vascular y la percepción del dolor. En la presente revisión se describen las características estructurales y farmacológicas de los receptores purinérgicos y se analiza la interacción dinámica entre estos receptores, los nucleósidos y nucleótidos, y las ectonucleotidasas, con especial atención a la dinámica de la agregación plaquetaria, la respuesta inmune y la hidratación de las mucosas respiratorias.In the last decade evidence accumulated that nucleosides and nucleotides of both uridine and adenine can act as extracellular signaling factors. Their action is mediated by two main types of surface receptors commonly known as purinergic. P1 receptors are metabotropic and activated by adenosine, whereas receptors for nucleotides (ATP, ADP, UTP and UDP and nucleotide-sugars (UDP-glucose and UDP-galactose can be either metabotropic (P2Y or ionotropic (P2X. The importance and complexity of this signaling system

  2. Purine DNA adducts of 4,5-dioxovaleric acid and 2,4-decadienal.

    Science.gov (United States)

    Cadet, J; Carvalho, V M; Onuki, J; Douki, T; Medeiros, M H; Di Mascio, P D

    1999-01-01

    The present overview describes recent findings on the formation of cyclic adducts of purine DNA bases after reaction with two aldehyde compounds, 4,5-dioxovaleric acid (DOVA) and 2,4-decadlenal (DDE), which are involved in 5-aminolaevulinic acid (ALA) accumulation and lipid peroxidation, respectively. ALA accumulates under pathological conditions and is associated with an increased incidence of liver cancer. The final oxidation product of ALA, DOVA, is an efficient alkylating agent of the guanine moieties in both nucleoside and isolated DNA. Adducts were produced through the formation of a Schiff base involving the N2-amino group of 2'-deoxyguanosine and the ketone function of DOVA, respectively. DDE is an important breakdown product of lipid peroxidation. It is cytotoxic to mammalian cells and is known to be implicated in DNA damage. It can bind to 2'-deoxyadenosine, yielding highly fluorescent products, including 1,N6-etheno-2'-deoxyadenosine and two other, related adducts. The reaction mechanism for the formation of DDE-2'-deoxyadenosine adducts involves epoxidation of DDE and subsequent addition of the resulting reactive intermediates to the N6 amino group of 2'-deoxyadenosine, followed by cyclization at the N1 site. Formation of endogenous DNA adducts may contribute to the genotoxic potential of ALA and DDE.

  3. Nicotinamide riboside and nicotinic acid riboside salvage in fungi and mammals. Quantitative basis for Urh1 and purine nucleoside phosphorylase function in NAD+ metabolism.

    Science.gov (United States)

    Belenky, Peter; Christensen, Kathryn C; Gazzaniga, Francesca; Pletnev, Alexandre A; Brenner, Charles

    2009-01-02

    NAD+ is a co-enzyme for hydride transfer enzymes and an essential substrate of ADP-ribose transfer enzymes and sirtuins, the type III protein lysine deacetylases related to yeast Sir2. Supplementation of yeast cells with nicotinamide riboside extends replicative lifespan and increases Sir2-dependent gene silencing by virtue of increasing net NAD+ synthesis. Nicotinamide riboside elevates NAD+ levels via the nicotinamide riboside kinase pathway and by a pathway initiated by splitting the nucleoside into a nicotinamide base followed by nicotinamide salvage. Genetic evidence has established that uridine hydrolase, purine nucleoside phosphorylase, and methylthioadenosine phosphorylase are required for Nrk-independent utilization of nicotinamide riboside in yeast. Here we show that mammalian purine nucleoside phosphorylase but not methylthioadenosine phosphorylase is responsible for mammalian nicotinamide riboside kinase-independent nicotinamide riboside utilization. We demonstrate that so-called uridine hydrolase is 100-fold more active as a nicotinamide riboside hydrolase than as a uridine hydrolase and that uridine hydrolase and mammalian purine nucleoside phosphorylase cleave nicotinic acid riboside, whereas the yeast phosphorylase has little activity on nicotinic acid riboside. Finally, we show that yeast nicotinic acid riboside utilization largely depends on uridine hydrolase and nicotinamide riboside kinase and that nicotinic acid riboside bioavailability is increased by ester modification.

  4. The transition state analog inhibitor of Purine Nucleoside Phosphorylase (PNP) Immucillin-H arrests bone loss in rat periodontal disease models.

    Science.gov (United States)

    Deves, Candida; de Assunção, Thiago Milech; Ducati, Rodrigo Gay; Campos, Maria Martha; Basso, Luiz Augusto; Santos, Diogenes Santiago; Batista, Eraldo L

    2013-01-01

    Purine nucleoside phosphorylase (PNP) is a purine-metabolizing enzyme that catalyzes the reversible phosphorolysis of 6-oxypurine (deoxy)nucleosides to their respective bases and (deoxy)ribose-1-phosphate. It is a key enzyme in the purine salvage pathway of mammalian cells. The present investigation sought to determine whether the PNP transition state analog inhibitor (Immucillin-H) arrests bone loss in two models of induced periodontal disease in rats. Periodontal disease was induced in rats using ligature or LPS injection followed by administration of Immucillin-H for direct analysis of bone loss, histology and TRAP staining. In vitro osteoclast differentiation and activation of T CD4+ cells in the presence of Immucillin-H were carried out for assessment of RANKL expression, PNP and Cathepsin K activity. Immucillin-H inhibited bone loss induced by ligatures and LPS, leading to a reduced number of infiltrating osteoclasts and inflammatory cells. In vitro assays revealed that Immucillin-H could not directly abrogate differentiation of osteoclast precursor cells, but affected lymphocyte-mediated osteoclastogenesis. On the other hand, incubation of pre-activated T CD4+ with Immucillin-H decreased RANKL secretion with no compromise of cell viability. The PNP transition state analog Immucillin-H arrests bone loss mediated by T CD4+ cells with no direct effect on osteoclasts. PNP inhibitor may have an impact in the treatment of diseases characterized by the presence of pathogens and imbalances of bone metabolism.

  5. Structural determinants of the 5'-methylthioinosine specificity of Plasmodium purine nucleoside phosphorylase.

    Directory of Open Access Journals (Sweden)

    Teraya M Donaldson

    Full Text Available Plasmodium parasites rely upon purine salvage for survival. Plasmodium purine nucleoside phosphorylase is part of the streamlined Plasmodium purine salvage pathway that leads to the phosphorylysis of both purines and 5'-methylthiopurines, byproducts of polyamine synthesis. We have explored structural features in Plasmodium falciparum purine nucleoside phosphorylase (PfPNP that affect efficiency of catalysis as well as those that make it suitable for dual specificity. We used site directed mutagenesis to identify residues critical for PfPNP catalytic activity as well as critical residues within a hydrophobic pocket required for accommodation of the 5'-methylthio group. Kinetic analysis data shows that several mutants had disrupted binding of the 5'-methylthio group while retaining activity for inosine. A triple PfPNP mutant that mimics Toxoplasma gondii PNP had significant loss of 5'-methylthio activity with retention of inosine activity. Crystallographic investigation of the triple mutant PfPNP with Tyr160Phe, Val66Ile, andVal73Ile in complex with the transition state inhibitor immucillin H reveals fewer hydrogen bond interactions for the inhibitor in the hydrophobic pocket.

  6. Pertumbuhan Plantlet Anggrek Cattleya sp. dengan Perlakuan Benzyl Amino Purine pada Media Dasar Pupuk Daun Modifikasi

    Directory of Open Access Journals (Sweden)

    HESTIN YUSWANTI

    2015-09-01

    Full Text Available Growth of Plantlets of Cattleya Orchid on The Fooliar Fertilizer-Based Medium added with Benzyl Amino Purine. The aim of the current research was to investigate the appropriate concentrationof plant growth regulator BAP on the growth of Cattleya plantlet. The experiment was utilized a Randomized Completely Design with five treatments and six replications. The basal medium used was modification of foliar fertilizer of Growmore (trade mark with addition of fish emulsion, Vitamin B1 and active charcoal. BAP concentration used as treatment were 0 ppm, 0.5 ppm, 1.0 ppm, 1.5 ppm and 2.0 ppm. Variables observed were height, leaf number, root number, root length, fresh weight and dry weight of plantlets. The result showed that concentration of 1 ppm BAP resulted in the highest value for plantlet height (5.67 cm, leaf number (4.67, root length (2.07 cm, fresh weight (0.36 g and dry weight (0.043 g.

  7. The effect of purine and pyrimidine analogues and virazole on adenovirus replication.

    Science.gov (United States)

    Scheffler, P; Haghchenas, D; Wigand, R

    1975-04-01

    The multiplication of adenovirus 19 in HeLa cells was inhibited by various purine and pyrimidine analogues and by virazole. The formation of infectious virus and of capsid proteins (haemagglutin, group-specific complement-fixing antigen) was inhibited to the same degree, while the viral cytopathic effect (CPE) was not inhibited. The reversibility of the inhibition after removal of the substances was more complete for purine than for pyrimidine analogues. The inhibition was counteracted by simulataneous addition of the corresponding nucleosides. Adenosine was more effected than guanosine against purine analogues; both were partially effective against virazole, but none of them against arabinofuranosyladenine. The time-dependence of inhibition, the ensuing eclipse period after removal of the inhibitors, and the successive application of two inhibitors led to the conclusion that most of them affect the viral multiplication mainly by inhibition of DNA synthesis. Azacytidine inhibits the synthesis of structural proteins as well.

  8. Radical-induced purine lesion formation is dependent on DNA helical topology.

    Science.gov (United States)

    Terzidis, Michael A; Prisecaru, Andreea; Molphy, Zara; Barron, Niall; Randazzo, Antonio; Dumont, Elise; Krokidis, Marios G; Kellett, Andrew; Chatgilialoglu, Chryssostomos

    2016-11-01

    Herein we report the quantification of purine lesions arising from gamma-radiation sourced hydroxyl radicals (HO(•)) on tertiary dsDNA helical forms of supercoiled (SC), open circular (OC), and linear (L) conformation, along with single-stranded folded and non-folded sequences of guanine-rich DNA in selected G-quadruplex structures. We identify that DNA helical topology and folding plays major, and unexpected, roles in the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and 8-oxo-7,8-dihydro-2'-deoxyadenosine (8-oxo-dA), along with tandem-type purine lesions 5',8-cyclo-2'-deoxyguanosine (5',8-cdG) and 5',8-cyclo-2'-deoxyadenosine (5',8-cdA). SC, OC, and L dsDNA conformers together with folded and non-folded G-quadruplexes d[TGGGGT]4 (TG4T), d[AGGG(TTAGGG)3] (Tel22), and the mutated tel24 d[TTGGG(TTAGGG)3A] (mutTel24) were exposed to HO(•) radicals and purine lesions were then quantified via stable isotope dilution LC-MS/MS analysis. Purine oxidation in dsDNA follows L > OC ≫ SC indicating greater damage towards the extended B-DNA topology. Conversely, G-quadruplex sequences were significantly more resistant toward purine oxidation in their unfolded states as compared with G-tetrad folded topologies; this effect is confirmed upon comparative analysis of Tel22 (∼50% solution folded) and mutTel24 (∼90% solution folded). In an effort to identify the accessibly of hydroxyl radicals to quadruplex purine nucleobases, G-quadruplex solvent cavities were then modeled at 1.33 Å with evidence suggesting that folded G-tetrads may act as potential oxidant traps to protect against chromosomal DNA damage.

  9. Determination of four different purines and their content change in seafood by high-performance liquid chromatography.

    Science.gov (United States)

    Qu, Xin; Sui, Jianxin; Mi, Nasha; Lin, Hong

    2017-01-01

    Seafood is regarded as a high-purine food that may induce gout, which has attracted extensive attention concerning its safety. Therefore, the aim of this study was to develop a simple and reliable method to determine the purine content in seafood and its change during storage to offer consumers healthy diet information. Chromatographic separation was carried out using Waters Atlantis dC18 column, and potassium phosphate monobasic solution (0.02 mol L(-1) , pH 3.6) as a mobile phase. The average recovery yields of four purines were 91.5-105.0%, and relative standard deviation values were around 1.8-6.5%. Shrimp and snail contained higher amounts of purine than fish and bivalves; the livers and skins of fish contained higher amounts of purine than muscles; and the main purine varied depending on the type of seafood. Also, purine content of seafood changed during storage. The purine content of seafood differed depending on species, body part and degree of freshness, which could recommend consumers a healthy diet, especially for people with hyperuricemia and gout. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  10. A triphenylamine-based benzoxazole derivative as a high-contrast piezofluorochromic material induced by protonation.

    Science.gov (United States)

    Xue, Pengchong; Chen, Peng; Jia, Junhui; Xu, Qiuxia; Sun, Jiabao; Yao, Boqi; Zhang, Zhenqi; Lu, Ran

    2014-03-11

    A triphenylamine-based benzoxazole derivative exhibits a low contrast piezofluorochromic behavior under external pressure, and a high-contrast fluorescence change induced by protonation can be observed.

  11. Biological adhesive based on carboxymethyl chitin derivatives and chitin nanofibers.

    Science.gov (United States)

    Azuma, Kazuo; Nishihara, Masahiro; Shimizu, Haruki; Itoh, Yoshiki; Takashima, Osamu; Osaki, Tomohiro; Itoh, Norihiko; Imagawa, Tomohiro; Murahata, Yusuke; Tsuka, Takeshi; Izawa, Hironori; Ifuku, Shinsuke; Minami, Saburo; Saimoto, Hiroyuki; Okamoto, Yoshiharu; Morimoto, Minoru

    2015-02-01

    Novel biological adhesives made from chitin derivatives were prepared and evaluated for their adhesive properties and biocompatibility. Chitin derivatives with acrylic groups, such as 2-hydroxy-3-methacryloyloxypropylated carboxymethyl chitin (HMA-CM-chitin), were synthesized and cured by the addition of an aqueous hydrogen peroxide solution as a radical initiator. The adhesive strength of HMA-CM-chitin increased when it was blended with chitin nanofibers (CNFs) or surface-deacetylated chitin nanofibers (S-DACNFs). HMA-CM-chitin/CNFs or HMA-CM-chitin/S-DACNFs have almost equal adhesive strength compared to that of a commercial cyanoacrylate adhesive. Moreover, quick adhesion and induction of inflammatory cells migration were observed in HMA-CM-chitin/CNF and HMA-CM-chitin/S-DACNF. These findings indicate that the composites prepared in this study are promising materials as new biological adhesives.

  12. Electrodynamic Analysis of Dissipative Electromagnetic Materials Based on Fractional Derivative

    Institute of Scientific and Technical Information of China (English)

    TAN Kang-Bo; LIANG Chang-Hong; DANG Xiao-Jie

    2007-01-01

    The generalized Lagrangian is defined in a dissipative electromagnetic medium on the basis of the combination of dynamical analysis and fractional derivative.Lorentz medium models are obtained by formulating relevant EulerLagrange equations.The invariance is obtained subsequently by investigating the invariance of time variation in the system,and then the relation between the related Hamiltonian and electromagnetic energy density is investigated.Canonical equations are obtained eventually.The electrodynamic interpretation on dissipative electromagnetic systems is revesled.

  13. Circulating Human Neonatal Naïve B cells are Deficient in CD73 Impairing Purine Salvage

    Directory of Open Access Journals (Sweden)

    Matthew Aaron Pettengill

    2016-03-01

    Full Text Available Background: Extracellular purines, in particular adenosine (Ado and adenosine-triphosphate (ATP, are critical immunoregulatory molecules. Expression and activity of purine ecto-enzymes on B cells in neonatal and adult blood may influence their function and has been incompletely characterized. Methods: Mononuclear cells were isolated from human neonatal (cord blood or adult (peripheral blood subjects and evaluated directly by flow cytometry for expression of purine ecto-enzymes. Additionally, B cell subsets were isolated from mononuclear cell fractions by fluorescence-activated cell sorting and gene transcription of purine ecto-enzymes (CD39 and CD73, adenosine deaminase (ADA1, purine nucleoside phosphorylase (PNP and select purine receptors (A2a were evaluated by reverse transcription followed by qRT-PCR. Immuno-magnetic-bead isolated naïve B cells were evaluated for enzymatic activity by incubation with radio-labeled purines followed by thin-layer chromatography, and subsequent B cell Ado acquisition was evaluated by liquid scintillation quantitation of radio-labeled Ado uptake.Results: Relative to their adult counterparts, neonatal circulating naïve B cells were markedly and selectively deficient in CD73 as observed by gene transcription, surface protein expression, and enzyme activity. Neonatal naïve B cell deficiency of CD73 expression significantly impaired their capacity to acquire extracellular purines for purine salvage.Conclusions: Human neonatal circulating naïve B cells are selectively deficient in CD73, impairing extracellular purine acquisition and potentially contributing to impaired B cell responses in early life.

  14. Selective liquid CO2 extraction of purine alkaloids in different Ilex paraguariensis progenies grown under environmental influences.

    Science.gov (United States)

    Cardozo, Euclides Lara; Cardozo-Filho, Lucio; Filho, Osvaldo Ferrarese; Zanoelo, Everton Fernando

    2007-08-22

    In this investigation, liquid carbon dioxide at 20 degrees C and 150 bar was used for the selective extraction of caffeine and theobromine from dry leaves of mate. A comparison between the chromatograms from CO2 extraction and traditional solvent extraction supports the selectivity of carbon dioxide for these purine alkaloids. The advantages of selective liquid CO2 extraction in terms of speed and resolution of UV/HPLC is also evidenced. A randomized block design of experiments was proposed to investigate the influence of 16 progenies of Ilex paraguariensis grown in 3 diverse sites on the contents of caffeine and theobromine in liquors of mate leaves obtained by extraction with compressed CO2. A significant effect of both these factors on the parameters investigated was observed by involving the F distribution in the statistical analysis. A cluster analysis based on the experimental uncertainties in the contents of these two methylxanthines has identified from four to six different groups of mate progenies.

  15. Comparison of human erythrocyte purine nucleotide metabolism and blood purine and pyrimidine degradation product concentrations before and after acute exercise in trained and sedentary subjects.

    Science.gov (United States)

    Dudzinska, Wioleta; Suska, M; Lubkowska, A; Jakubowska, K; Olszewska, M; Safranow, K; Chlubek, D

    2017-04-21

    This study aimed at evaluating the concentration of erythrocyte purine nucleotides (ATP, ADP, AMP, IMP) in trained and sedentary subjects before and after maximal physical exercise together with measuring the activity of purine metabolism enzymes as well as the concentration of purine (hypoxanthine, xanthine, uric acid) and pyrimidine (uridine) degradation products in blood. The study included 15 male elite rowers [mean age 24.3 ± 2.56 years; maximal oxygen uptake (VO2max) 52.8 ± 4.54 mL/kg/min; endurance and strength training 8.2 ± 0.33 h per week for 6.4 ± 2.52 years] and 15 sedentary control subjects (mean age 23.1 ± 3.41 years; VO2max 43.2 ± 5.20 mL/kg/min). Progressive incremental exercise testing until refusal to continue exercising was conducted on a bicycle ergometer. The concentrations of ATP, ADP, AMP, IMP and the activities of adenine phosphoribosyltransferase (APRT), hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and phosphoribosyl pyrophosphate synthetase (PRPP-S) were determined in erythrocytes. The concentrations of hypoxanthine, xanthine, uric acid and uridine were determined in the whole blood before exercise, after exercise, and 30 min after exercise testing. The study demonstrated a significantly higher concentration of ATP in the erythrocytes of trained subjects which, in part, may be explained by higher metabolic activity on the purine re-synthesis pathway (significantly higher PRPP-S, APRT and HGPRT activities). The ATP concentration, just as the ATP/ADP ratio, as well as an exercise-induced increase in this ratio, correlates with the VO2max level in these subjects which allows them to be considered as the important factors characterising physical capacity and exercise tolerance. Maximal physical exercise in the group of trained subjects results not only in a lower post-exercise increase in the concentration of hypoxanthine, xanthine and uric acid but also in that of uridine. This indicates the possibility of

  16. Platelet-Rich Blood Derivatives for Stem Cell-Based Tissue Engineering and Regeneration

    NARCIS (Netherlands)

    Masoudi, E.A.; Ribas, J.; Kaushik, G.; Leijten, Jeroen Christianus Hermanus; Khademhosseini, A.

    2016-01-01

    Platelet-rich blood derivatives have been widely used in different fields of medicine and stem cell-based tissue engineering. They represent natural cocktails of autologous growth factors, which could provide an alternative for recombinant protein-based approaches. Platelet-rich blood derivatives,

  17. Platelet-Rich Blood Derivatives for Stem Cell-Based Tissue Engineering and Regeneration

    NARCIS (Netherlands)

    Masoudi, E.A.; Ribas, J.; Kaushik, G.; Leijten, J.C.H.; Khademhosseini, A.

    2016-01-01

    Platelet-rich blood derivatives have been widely used in different fields of medicine and stem cell-based tissue engineering. They represent natural cocktails of autologous growth factors, which could provide an alternative for recombinant protein-based approaches. Platelet-rich blood derivatives, s

  18. Purine and pyrimidine nucleosides preserve human astrocytoma cell adenylate energy charge under ischemic conditions.

    Science.gov (United States)

    Balestri, Francesco; Giannecchini, Michela; Sgarrella, Francesco; Carta, Maria Caterina; Tozzi, Maria Grazia; Camici, Marcella

    2007-02-01

    The brain depends on both glycolysis and mitochondrial oxidative phosphorylation for maintenance of ATP pools. Astrocytes play an integral role in brain functions providing trophic supports and energy substrates for neurons. In this paper, we report that human astrocytoma cells (ADF) undergoing ischemic conditions may use both purine and pyrimidine nucleosides as energy source to slow down cellular damage. The cells are subjected to metabolic stress conditions by exclusion of glucose and incubation with oligomycin (an inhibitor of oxidative phosphorylation). This treatment brings about a depletion of the ATP pool, with a concomitant increase in the AMP levels, which results in a significant decrease of the adenylate energy charge. The presence of purine nucleosides in the culture medium preserves the adenylate energy charge, and improves cell viability. Besides purine nucleosides, also pyrimidine nucleosides, such as uridine and, to a lesser extent, cytidine, are able to preserve the ATP pool. The determination of lactate in the incubation medium indicates that nucleosides can preserve the ATP pool through anaerobic glycolysis, thus pointing to a relevant role of the phosphorolytic cleavage of the N-glycosidic bond of nucleosides which generates, without energy expense, the phosphorylated pentose, which through the pentose phosphate pathway and glycolysis can be converted to energetic intermediates also in the absence of oxygen. In fact, ADF cells possess both purine nucleoside phosphorylase and uridine phosphorylase activities.

  19. An Efficient and Facile Methodology for Bromination of Pyrimidine and Purine Nucleosides with Sodium Monobromoisocyanurate (SMBI

    Directory of Open Access Journals (Sweden)

    Roger Stromberg

    2013-10-01

    Full Text Available An efficient and facile strategy has been developed for bromination of nucleosides using sodium monobromoisocyanurate (SMBI. Our methodology demonstrates bromination at the C-5 position of pyrimidine nucleosides and the C-8 position of purine nucleosides. Unprotected and also several protected nucleosides were brominated in moderate to high yields following this procedure.

  20. Dihydropyrimidine based hydrazine dihydrochloride derivatives as potent urease inhibitors.

    Science.gov (United States)

    Khan, Ajmal; Hashim, Jamshed; Arshad, Nuzhat; Khan, Ijaz; Siddiqui, Naureen; Wadood, Abdul; Ali, Muzaffar; Arshad, Fiza; Khan, Khalid Mohammed; Choudhary, M Iqbal

    2016-02-01

    Four series of heterocyclic compounds 4-dihydropyrimidine-2-thiones 7-12 (series A), N,S-dimethyl-dihydropyrimidines 13-18 (series B), hydrazine derivatives of dihydropyrimidine 19-24 (series C), and tetrazolo dihydropyrimidine derivatives 25-30 (series D), were synthesized and evaluated for in vitro urease inhibitory activity. The series B-D were first time examined for urease inhibition. Series A and C were found to be significantly active with IC50 values between 34.7-42.9 and 15.0-26.0 μM, respectively. The structure-activity relationship showed that the free S atom and hydrazine moiety are the key pharmacophores against urease enzyme. The kinetic studies of the active series A (7-12) and C (19-24) were carried out to determine their modes of inhibition and dissociation constants Ki. Compounds of series A (7-12) and series C (19-24) showed a mixed-type of inhibition with Ki values ranging between 15.76-25.66 and 14.63-29.42 μM, respectively. The molecular docking results showed that all the active compounds of both series have significant binding interactions with the active sites specially Ni-ion of the urease enzyme. Cytotoxicity of all series A-D was also evaluated against mammalian mouse fibroblast 3T3 cell lines, and no toxicity was observed in cellular model.

  1. Crystal structures of five 6-mercaptopurine derivatives

    Directory of Open Access Journals (Sweden)

    Lígia R. Gomes

    2016-03-01

    Full Text Available The crystal structures of five 6-mercaptopurine derivatives, viz. 2-[(9-acetyl-9H-purin-6-ylsulfanyl]-1-(3-methoxyphenylethan-1-one (1, C16H14N4O3S, 2-[(9-acetyl-9H-purin-6-ylsulfanyl]-1-(4-methoxyphenylethan-1-one (2, C16H14N4O3S, 2-[(9-acetyl-9H-purin-6-ylsulfanyl]-1-(4-chlorophenylethan-1-one (3, C15H11ClN4O2S, 2-[(9-acetyl-9H-purin-6-ylsulfanyl]-1-(4-bromophenylethan-1-one (4, C15H11BrN4O2S, and 1-(3-methoxyphenyl-2-[(9H-purin-6-ylsulfanyl]ethan-1-one (5, C14H12N4O2S. Compounds (2, (3 and (4 are isomorphous and accordingly their molecular and supramolecular structures are similar. An analysis of the dihedral angles between the purine and exocyclic phenyl rings show that the molecules of (1 and (5 are essentially planar but that in the case of the three isomorphous compounds (2, (3 and (4, these rings are twisted by a dihedral angle of approximately 38°. With the exception of (1 all molecules are linked by weak C—H...O hydrogen bonds in their crystals. There is π–π stacking in all compounds. A Cambridge Structural Database search revealed the existence of 11 deposited compounds containing the 1-phenyl-2-sulfanylethanone scaffold; of these, only eight have a cyclic ring as substituent, the majority of these being heterocycles.

  2. The advanced carbide-derived carbon based supercapacitor

    Science.gov (United States)

    Arulepp, M.; Leis, J.; Lätt, M.; Miller, F.; Rumma, K.; Lust, E.; Burke, A. F.

    The electrical double-layer (EDL) performance of three different TiC-derived nanoporous carbon materials was tested in prismatic capacitor assembly filled with 1.2 M triethylmethylammonium tetrafluoroborate (TEMA) acetonitrile solution. The electrical double-layer characteristics of supercapacitors were studied using the cyclic voltammetry (CV) and the electrochemical impedance spectroscopy (EIS) methods. Energy density versus power density, i.e. Ragone plots were constructed from the constant resistance and constant power (CP) charge/discharge data. The 1450F supercapacitor with novel nanoporous carbon made by halogen treatment of TiC/TiO 2 composite demonstrated the energy density of more than 10 Wh dm -3 at the cell voltage of 2.7 V.

  3. The advanced carbide-derived carbon based supercapacitor

    Energy Technology Data Exchange (ETDEWEB)

    Arulepp, M.; Leis, J.; Laett, M.; Miller, F.; Rumma, K. [Tartu Technologies Ltd., 185 Riia Str., 51014 Tartu (Estonia); Lust, E. [University of Tartu, 2 Jakobi Str., 51014 Tartu (Estonia); Burke, A.F. [University of California-Davis, 2003 Academic Surge, Davis, CA 95616 (United States)

    2006-11-22

    The electrical double-layer (EDL) performance of three different TiC-derived nanoporous carbon materials was tested in prismatic capacitor assembly filled with 1.2M triethylmethylammonium tetrafluoroborate (TEMA) acetonitrile solution. The electrical double-layer characteristics of supercapacitors were studied using the cyclic voltammetry (CV) and the electrochemical impedance spectroscopy (EIS) methods. Energy density versus power density, i.e. Ragone plots were constructed from the constant resistance and constant power (CP) charge/discharge data. The 1450F supercapacitor with novel nanoporous carbon made by halogen treatment of TiC/TiO{sub 2} composite demonstrated the energy density of more than 10Whdm{sup -3} at the cell voltage of 2.7V. (author)

  4. Antioxidant activity of N-acetyl-glucosamine based thiazolidine derivative

    Institute of Scientific and Technical Information of China (English)

    Li Chunlei; Yang Yan; Han Baoqin; Liu Wanshun

    2007-01-01

    N-acetyl-glucosamine,the monomer of chitin,was cyclo-condensed with L-cysteine to prepare thiazolidine derivative:2-N-acetyl-glucosamine-thiazolidine-4(R)-carboxylic acid(GlcNAcCys).The stability of GlcNAcCys was evaluated by high performance liquid chromatography(HPLC)measurement.The results showed that GlcNAcCys Was more stable than other TCA derivatives,especially in alkaline condition.The direct in vitro antioxidative properties of GlcNAcCys were investigated by using UV radiation-induced lipid peroxidation(LPO)in mitochondria and nuclei and.OH-induced LPO in red blood cell (RBC)ghosts models.UV radiation caused dose-dependent LPO in both mitochondria and nuclei,this effect Was catalvzed by addition of Fd2+ while prevented by co-incubation with GlcNAcCys.When nuclei and mitochondria Was treated with 100μl,300μl,500μl of GlcNAcCys and co-incubated at 37℃ for 30min,LPO was decreased to 96%,72%,68%in nuclei and 95%,72%,68% in mitochondria when compared to the UV radiation group respectively.Hydroxyl radicals(.OH)generated by Fenton reaction induced LPO in RBC ghosts.Pretreatment of RBC ghosts with GlcNAcCys could induce antioxidant RBC ghosts and inhibit concentration-dependent malondialdehyde(MDA)formation in antioxidant RBC ghosts.Its inhibition percent Was 14%,35%,36%,42%at 10,20,30,40ms/ml respectively.In a conclusion,the data suggest that GlcNAcCys has antioxidant ability and can significantly inhibit lipid peroxidation in biological samples tested in vitro.

  5. Plasma Hypoxanthine-Guanine Phosphoribosyl Transferase Activity in Bottlenose Dolphins Contributes to Avoiding Accumulation of Non-recyclable Purines.

    Science.gov (United States)

    López-Cruz, Roberto I; Crocker, Daniel E; Gaxiola-Robles, Ramón; Bernal, Jaime A; Real-Valle, Roberto A; Lugo-Lugo, Orlando; Zenteno-Savín, Tania

    2016-01-01

    Marine mammals are exposed to ischemia/reperfusion and hypoxia/reoxygenation during diving. During oxygen deprivation, adenosine triphosphate (ATP) breakdown implies purine metabolite accumulation, which in humans is associated with pathological conditions. Purine recycling in seals increases in response to prolonged fasting and ischemia. Concentrations of metabolites and activities of key enzymes in purine metabolism were examined in plasma and red blood cells from bottlenose dolphins (Tursiops truncatus) and humans. Hypoxanthine and inosine monophosphate concentrations were higher in plasma from dolphins than humans. Plasma hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity in dolphins suggests an elevated purine recycling rate, and a mechanism for avoiding accumulation of non-recyclable purines (xanthine and uric acid). Red blood cell concentrations of hypoxanthine, adenosine diphosphate, ATP and guanosine triphosphate were lower in dolphins than in humans; adenosine monophosphate and nicotinamide adenine dinucleotide concentrations were higher in dolphins. HGPRT activity in red blood cells was higher in humans than in dolphins. The lower concentrations of purine catabolism and recycling by-products in plasma from dolphins could be beneficial in providing substrates for recovery of ATP depleted during diving or vigorous swimming. These results suggest that purine salvage in dolphins could be a mechanism for delivering nucleotide precursors to tissues with high ATP and guanosine triphosphate requirements.

  6. Arxula adeninivorans recombinant guanine deaminase and its application in the production of food with low purine content.

    Science.gov (United States)

    Trautwein-Schult, Anke; Jankowska, Dagmara; Cordes, Arno; Hoferichter, Petra; Klein, Christina; Matros, Andrea; Mock, Hans-Peter; Baronian, Keith; Bode, Rüdiger; Kunze, Gotthard

    2014-01-01

    Purines of exogenous and endogenous sources are degraded to uric acid in human beings. Concentrations >6.8 mg uric acid/dl serum cause hyperuricemia and its symptoms. Pharmaceuticals and the reduction of the intake of purine-rich food are used to control uric acid levels. A novel approach to the latter proposition is the enzymatic reduction of the purine content of food by purine-degrading enzymes. Here we describe the production of recombinant guanine deaminase by the yeast Arxula adeninivorans LS3 and its application in food. In media supplemented with nitrogen sources hypoxanthine or adenine, guanine deaminase (AGDA) gene expression is induced and intracellular accumulation of guanine deaminase (Agdap) protein occurs. The characteristics of the guanine deaminase isolated from wild-type strain LS3 and a transgenic strain expressing the AGDA gene under control of the strong constitutive TEF1 promoter were determined and compared. Both enzymes were dimeric and had temperature optima of 55°C with high substrate specificity for guanine and localisation in both the cytoplasm and vacuole of yeast. The enzyme was demonstrated to reduce levels of guanine in food. A mixture of guanine deaminase and other purine degradation enzymes will allow the reduction of purines in purine-rich foods. © 2014 S. Karger AG, Basel.

  7. Plasma Hypoxanthine-Guanine Phosphoribosyl Transferase Activity in Bottlenose Dolphins Contributes to Avoiding Accumulation of Non-recyclable Purines

    Science.gov (United States)

    López-Cruz, Roberto I.; Crocker, Daniel E.; Gaxiola-Robles, Ramón; Bernal, Jaime A.; Real-Valle, Roberto A.; Lugo-Lugo, Orlando; Zenteno-Savín, Tania

    2016-01-01

    Marine mammals are exposed to ischemia/reperfusion and hypoxia/reoxygenation during diving. During oxygen deprivation, adenosine triphosphate (ATP) breakdown implies purine metabolite accumulation, which in humans is associated with pathological conditions. Purine recycling in seals increases in response to prolonged fasting and ischemia. Concentrations of metabolites and activities of key enzymes in purine metabolism were examined in plasma and red blood cells from bottlenose dolphins (Tursiops truncatus) and humans. Hypoxanthine and inosine monophosphate concentrations were higher in plasma from dolphins than humans. Plasma hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity in dolphins suggests an elevated purine recycling rate, and a mechanism for avoiding accumulation of non-recyclable purines (xanthine and uric acid). Red blood cell concentrations of hypoxanthine, adenosine diphosphate, ATP and guanosine triphosphate were lower in dolphins than in humans; adenosine monophosphate and nicotinamide adenine dinucleotide concentrations were higher in dolphins. HGPRT activity in red blood cells was higher in humans than in dolphins. The lower concentrations of purine catabolism and recycling by-products in plasma from dolphins could be beneficial in providing substrates for recovery of ATP depleted during diving or vigorous swimming. These results suggest that purine salvage in dolphins could be a mechanism for delivering nucleotide precursors to tissues with high ATP and guanosine triphosphate requirements. PMID:27375492

  8. Development of molecular resists based on Phenyl[4]calixarene derivatives.

    Science.gov (United States)

    Echigo, Masatoshi; Hayashi, Hiromi; Oizumi, Hiroaki; Matsumaro, Kazuyuki; Itani, Toshiro

    2010-04-01

    We have developed negative-tone molecular resist based on C-4-cyclohexylphenylcalix[4]resorcinarene(MGR108) and positive-tone molecular resist based on protected C-4-isopropylphenylcalix[4]resorcinarene (MGR104P). Both MGR108 and MGR104P showed high solubility in both conventional resist solvents such as propylene glycol monomethyl ether and conventional alkaline developer of 0.26N TMAHaq. In this paper, we show current performance of resists by EB lithography (EBL) and EUV lithography (EUVL).

  9. Nicotinamide riboside, an unusual, non-typical, substrate of purified purine-nucleoside phosphorylases.

    Science.gov (United States)

    Wielgus-Kutrowska, B; Kulikowska, E; Wierzchowski, J; Bzowska, A; Shugar, D

    1997-01-15

    Nicotinamide 1-beta-D-riboside (Nir), the cationic, reducible moiety of the coenzyme NAD+, has been confirmed as an unusual substrate for purified purine-nucleoside phosphorylase (PNP) from a mammalian source (calf spleen). It is also a substrate of the enzyme from Escherichia coli. The Km values at pH 7, 1.48 mM and 0.62 mM, respectively, were 1-2 orders of magnitude higher than for the natural substrate inosine, but the Vmax values were comparable, 96% and 35% that for Ino. The pseudo first-order rate constants, Vmax/Km, were 1.1% and 2.5% for the calf spleen and E. coli enzymes. The aglycon, nicotinamide, was neither a substrate nor an inhibitor of PNP. Nir was a weak inhibitor of inosine phosphorolysis catalyzed by both enzymes, with Ki values close to the Km for its phosphorolysis, consistent with simple competitive inhibition; this was further confirmed by Dixon plots. Phosphorolysis of the fluorescent positively charged substrate 7-methylguanosine was also inhibited in a competitive manner by both Ino and Nir. Phosphorolysis of Nir by both enzymes was inhibited competitively by several specific inhibitors of calf spleen and E. coli PNP, with Ki values similar to those for inhibition of other natural substrates. The pH dependence of the kinetic constants for the phosphorolysis of Nir and of a variety of other substrates, was extensively investigated, particularly in the alkaline pH range, where Nir exhibited abnormally high substrate activity relative to the reduced reaction rates of both enzymes towards other anionic or neutral substrates. The overall results are discussed in relation to present concepts regarding binding and phosphorolysis of substrates by PNP based on crystallographic data of enzyme-inhibitor complexes, and current studies on enzymatic and nonenzymatic mechanisms of the cleavage of the Nir glycosidic bond.

  10. Biobased Epoxy Nanocomposites Derived from Lignin-Based Monomers.

    Science.gov (United States)

    Zhao, Shou; Abu-Omar, Mahdi M

    2015-07-13

    Biobased epoxy nanocomposites were synthesized based on 2-methoxy-4-propylphenol (dihydroeugenol, DHE), a molecule that has been obtained from the lignin component of biomass. To increase the content of hydroxyl groups, DHE was o-demethylated using aqueous HBr to yield propylcatechol (DHEO), which was subsequently glycidylated to epoxy monomer. Optimal conditions in terms of yield and epoxy equivalent weight were found to be 60 °C with equal NaOH/phenolic hydroxyl molar ratio. The structural evolution from DHE to cured epoxy was followed by (1)H NMR and Fourier transform infrared spectroscopy. The nano-montmorillonite modified DHEO epoxy exhibited improved storage modulus and thermal stability as determined from dynamic mechanical analysis and thermogravimetric analysis. This study widens the synthesis routes of biobased epoxy thermosets from lignin-based molecules.

  11. Analytical Derivation: An Epistemic Game for Solving Mathematically Based Physics Problems

    Science.gov (United States)

    Bajracharya, Rabindra R.; Thompson, John R.

    2016-01-01

    Problem solving, which often involves multiple steps, is an integral part of physics learning and teaching. Using the perspective of the epistemic game, we documented a specific game that is commonly pursued by students while solving mathematically based physics problems: the "analytical derivation" game. This game involves deriving an…

  12. Disk-like Tiles Derived from Complex Bases

    Institute of Scientific and Technical Information of China (English)

    Jun LUO; Zuo Ling ZHOU

    2004-01-01

    For each positive integer k, the radix representation of the complex numbers in the base-k + i gives rise to a lattice self-affine tile Tk in the plane, which consists of all the complex numbers that can be expressed in the form ∑j≥1 dj(-k + i)-j, where dj ∈ {0, 1,2,……,k2}. We prove that Tk is homeomorphic to the closed unit disk {z ∈ C: |z| ≤ 1} if and only if k ≠ 2.

  13. Noncommutative Yang-Mills-Higgs actions from derivation-based differential calculus

    CERN Document Server

    Cagnache, Eric; Wallet, Jean-Christophe

    2008-01-01

    Derivations of a (noncommutative) algebra can be used to construct various consistent differential calculi, the so-called derivation-based differential calculi. We apply this framework to the noncommutative Moyal algebras for which all the derivations are inner and analyse in detail the case where the derivation algebras generating the differential calculus are related to area preserving diffeomorphisms. The ordinary derivations corresponding to spatial dimensions are supplemented by additional derivations necessarely related to additional covariant coordinates. It is shown that these latter have a natural interpretation as Higgs fields when involved in gauge invariant actions built from the noncommutative curvature. The UV/IR mixing problem for (some of) the resulting Yang-Mills-Higgs models is discussed. A comparition to other noncommutative geometries already considered in the litterature is given.

  14. Metabolically Derived Human Ventilation Rates: A Revised Approach Based Upon Oxygen Consumption Rates (Final Report, 2009)

    Science.gov (United States)

    EPA announced the availability of the final report, Metabolically Derived Human Ventilation Rates: A Revised Approach Based Upon Oxygen Consumption Rates. This report provides a revised approach for calculating an individual's ventilation rate directly from their oxygen c...

  15. Molecular analysis of "de novo" purine biosynthesis in solanaceous species and in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    van der Graaff, Eric; Hooykaas, Paul; Lein, Wolfgang

    2004-01-01

    , microorganisms and Arabidopsis, the first plant species with a completely sequenced genome, shows that plants principally use the same biochemical steps to synthesize purine nucleotides and possess all the essential genes and enzymes. Here we report on the cloning and molecular analysis of the complete purine...... biosynthesis pathway in plants, and the in planta functional analysis of PRPP (5-phosphoribosyl-1-pyrophoshate) amidotransferase (ATase), catalyzing the first committed step of the "de novo" purine biosynthesis. The cloning of the genes involved in the purine biosynthesis pathway was attained by a screening...... strategy with heterologous cDNA probes and by using S. cerevisiae mutants for complementation. Southern hybridization showed a complex genomic organization for these genes in solanaceous species and their organ- and developmental specific expression was analyzed by Northern hybridization. The specific role...

  16. Screening and characterization of purine nucleoside degrading lactic acid bacteria isolated from Chinese sauerkraut and evaluation of the serum uric acid lowering effect in hyperuricemic rats.

    Directory of Open Access Journals (Sweden)

    Ming Li

    Full Text Available Hyperuricemia is well known as the cause of gout. In recent years, it has also been recognized as a risk factor for arteriosclerosis, cerebrovascular and cardiovascular diseases, and nephropathy in diabetic patients. Foods high in purine compounds are more potent in exacerbating hyperuricemia. Therefore, the development of probiotics that efficiently degrade purine compounds is a promising potential therapy for the prevention of hyperuricemia. In this study, fifty-five lactic acid bacteria isolated from Chinese sauerkraut were evaluated for the ability to degrade inosine and guanosine, the two key intermediates in purine metabolism. After a preliminary screening based on HPLC, three candidate strains with the highest nucleoside degrading rates were selected for further characterization. The tested biological characteristics of candidate strains included acid tolerance, bile tolerance, anti-pathogenic bacteria activity, cell adhesion ability, resistance to antibiotics and the ability to produce hydrogen peroxide. Among the selected strains, DM9218 showed the best probiotic potential compared with other strains despite its poor bile resistance. Analysis of 16S rRNA sequences showed that DM9218 has the highest similarity (99% to Lactobacillus plantarum WCFS1. The acclimated strain DM9218-A showed better resistance to 0.3% bile salt, and its survival in gastrointestinal tract of rats was proven by PCR-DGGE. Furthermore, the effects of DM9218-A in a hyperuricemia rat model were evaluated. The level of serum uric acid in hyperuricemic rat can be efficiently reduced by the intragastric administration of DM9218-A (P<0.05. The preventive treatment of DM9218-A caused a greater reduction in serum uric acid concentration in hyperuricemic rats than the later treatment (P<0.05. Our results suggest that DM9218-A may be a promising candidate as an adjunctive treatment in patients with hyperuricemia during the onset period of disease. DM9218-A also has potential

  17. Structural Analysis of DFG-in and DFG-out Dual Src-Abl Inhibitors Sharing a Common Vinyl Purine Template

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Tianjun; Commodore, Lois; Huang, Wei-Sheng; Wang, Yihan; Sawyer, Tomi K.; Shakespeare, William C.; Clackson, Tim; Zhu, Xiaotian; Dalgarno, David C. (ARIAD)

    2010-09-30

    Bcr-Abl is the oncogenic protein tyrosine kinase responsible for chronic myeloid leukemia (CML). Treatment of the disease with imatinib (Gleevec) often results in drug resistance via kinase mutations at the advanced phases of the disease, which has necessitated the development of new mutation-resistant inhibitors, notably against the T315I gatekeeper mutation. As part of our efforts to discover such mutation resistant Abl inhibitors, we have focused on optimizing purine template kinase inhibitors, leading to the discovery of potent DFG-in and DFG-out series of Abl inhibitors that are also potent Src inhibitors. Here we present crystal structures of Abl bound by two such inhibitors, based on a common N9-arenyl purine, and that represent both DFG-in and -out binding modes. In each structure the purine template is bound deeply in the adenine pocket and the novel vinyl linker forms a non-classical hydrogen bond to the gatekeeper residue, Thr315. Specific template substitutions promote either a DFG-in or -out binding mode, with the kinase binding site adjusting to optimize molecular recognition. Bcr-Abl T315I mutant kinase is resistant to all currently marketed Abl inhibitors, and is the focus of intense drug discovery efforts. Notably, our DFG-out inhibitor, AP24163, exhibits modest activity against this mutant, illustrating that this kinase mutant can be inhibited by DFG-out class inhibitors. Furthermore our DFG-out inhibitor exhibits dual Src-Abl activity, absent from the prototypical DFG-out inhibitor, imatinib as well as its analog, nilotinib. The data presented here provides structural guidance for the further design of novel potent DFG-out class inhibitors against Src, Abl and Abl T315I mutant kinases.

  18. The role of derivational paradigms with adjectival base in Old English word-formation

    Directory of Open Access Journals (Sweden)

    Carmen Novo Urraca

    2014-05-01

    Full Text Available The aim of this article is to identify the primary adjectives of Old English as well as to gather the derivational paradigms that revolve around them. All in all, 459 primary adjectives are identified, which function as base of 6,587 derivatives. Two conclusions are drawn from the analysis. In the first place, the concept of derivational paradigm contributes to the explanation of the overall organization of the lexicon, while allowing for the discussion of questions that are at the core of current morphological theory, such as recursivity and productivity. The conclusion is drawn that primary adjectives play a significant role in Old English derivation. Even though they are not as productive as strong verbs, primary adjectives function as base of derivation of a significant number of non-basic terms, which, moreover, belong to all lexical categories and nearly all grammatical classes.

  19. A NEW DERIVATIVE FREE OPTIMIZATION METHOD BASED ON CONIC INTERPOLATION MODEL

    Institute of Scientific and Technical Information of China (English)

    倪勤; 胡书华

    2004-01-01

    In this paper, a new derivative free trust region method is developed based on the conic interpolation model for the unconstrained optimization. The conic interpolation model is built by means of the quadratic model function, the collinear scaling formula, quadratic approximation and interpolation. All the parameters in this model are determined by objective function interpolation condition. A new derivative free method is developed based upon this model and the global convergence of this new method is proved without any information on gradient.

  20. Abiotic synthesis of purines and other heterocyclic compounds by the action of electrical discharges

    Science.gov (United States)

    Yuasa, S.; Flory, D.; Basile, B.; Oro, J.

    1984-01-01

    The synthesis of purines and pyrimidines using Oparin-Urey-type primitive earth atmospheres has been demonstrated by reacting methane, ethane, and ammonia in electrical discharges. Adenine, guaine, 4-aminoimidazole-5-carboxamide (AICA), and isocytosine have been identified by UV spectrometry and paper chromatography as the products of the reaction. The total yields of the identified heterocyclic compounds are 0.0023 percent. It is concluded that adenine synthesis occurs at a much lower concentration of hydrogen cyanide than has been shown by earlier studies. Pathways for the synthesis of purines from hydrogen cyanide are discussed, and a comparison of the heterocyclic compounds that have been identified in meteorites and in prebiotic reactions is presented.

  1. Can Crystal Symmetry and Packing Influence the Active Site Conformation of Homohexameric Purine Nucleoside Phosphorylases?

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    Marija Luić

    2016-06-01

    Full Text Available It is generaly believed that enzymes retain most of their functionality in the crystal form due to the large solvent content of protein crystals. This is facilitated by the fact that their natural environment in solution is not too far from the one found in the crystal form. Nevertheless, if the nature of the enzyme is such to require conformational changes, overcoming of the crystal packing constraints may prove to be too difficult. Such conformational change is present in one class of enzymes (purine nucleoside phosphorylases, that is the subject of our scientific interest for many years. The influence of crystal symmetry and crystal packing on the conformation of the active sites in the case of homohexameric purine nucleoside phosphorylases is presented and analysed. This work is licensed under a Creative Commons Attribution 4.0 International License.

  2. A high-yielding, strictly regioselective prebiotic purine nucleoside formation pathway.

    Science.gov (United States)

    Becker, Sidney; Thoma, Ines; Deutsch, Amrei; Gehrke, Tim; Mayer, Peter; Zipse, Hendrik; Carell, Thomas

    2016-05-13

    The origin of life is believed to have started with prebiotic molecules reacting along unidentified pathways to produce key molecules such as nucleosides. To date, a single prebiotic pathway to purine nucleosides had been proposed. It is considered to be inefficient due to missing regioselectivity and low yields. We report that the condensation of formamidopyrimidines (FaPys) with sugars provides the natural N-9 nucleosides with extreme regioselectivity and in good yields (60%). The FaPys are available from formic acid and aminopyrimidines, which are in turn available from prebiotic molecules that were also detected during the Rosetta comet mission. This nucleoside formation pathway can be fused to sugar-forming reactions to produce pentosides, providing a plausible scenario of how purine nucleosides may have formed under prebiotic conditions.

  3. Structural characterization of purine nucleoside phosphorylase from human pathogen Helicobacter pylori.

    Science.gov (United States)

    Štefanić, Zoran; Mikleušević, Goran; Luić, Marija; Bzowska, Agnieszka; Leščić Ašler, Ivana

    2017-08-01

    Microaerophilic bacterium Helicobacer pylori is a well known human pathogen involved in the development of many diseases. Due to the evergrowing infection rate and increase of H. pylori antibiotic resistence, it is of utmost importance to find a new way to attack and eradicate H. pylori. The purine metabolism in H. pylori is solely dependant on the salvage pathway and one of the key enzymes in this pathway is purine nucleoside phosphorylase (PNP). In this timely context, we report here the basic biochemical and structural characterization of recombinant PNP from the H. pylori clinical isolate expressed in Escherichia coli. Structure of H. pylori PNP is typical for high molecular mass PNPs. However, its activity towards adenosine is very low, thus resembling more that of low molecular mass PNPs. Understanding the molecular mechanism of this key enzyme may lead to the development of new drug strategies and help in the eradication of H. pylori. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Purification, crystallization, and preliminary X-ray diffraction study of purine nucleoside phosphorylase from E. coli

    Science.gov (United States)

    Abramchik, Yu. A.; Timofeev, V. I.; Zhukhlistova, N. E.; Muravieva, T. I.; Esipov, R. S.; Kuranova, I. P.

    2015-07-01

    Crystals of E. coli purine nucleoside phosphorylase were grown in microgravity by the capillary counter-diffusion method through a gel layer. The X-ray diffraction data set suitable for the determination of the three-dimensional structure at atomic resolution was collected from one crystal at the Spring-8 synchrotron facility to 0.99 Å resolution. The crystals belong to sp. gr. P21 and have the following unit-cell parameters: a = 74.1 Å, b = 110.2 Å, c = 88.2 Å, α = γ = 90°, β = 111.08°. The crystal contains six subunits of the enzyme comprising a hexamer per asymmetric unit. The hexamer is the biological active form of E. coli. purine nucleoside phosphorylase.

  5. Purification, crystallization, and preliminary X-ray diffraction study of purine nucleoside phosphorylase from E. coli

    Energy Technology Data Exchange (ETDEWEB)

    Abramchik, Yu. A., E-mail: inna@ns.crys.ras.ru; Timofeev, V. I., E-mail: espiov@ibch.ru; Zhukhlistova, N. E., E-mail: tostars@mail.ru [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation); Muravieva, T. I.; Esipov, R. S. [Russian Academy of Sciences, Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry (Russian Federation); Kuranova, I. P. [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation)

    2015-07-15

    Crystals of E. coli purine nucleoside phosphorylase were grown in microgravity by the capillary counter-diffusion method through a gel layer. The X-ray diffraction data set suitable for the determination of the three-dimensional structure at atomic resolution was collected from one crystal at the Spring-8 synchrotron facility to 0.99 Å resolution. The crystals belong to sp. gr. P2{sub 1} and have the following unit-cell parameters: a = 74.1 Å, b = 110.2 Å, c = 88.2 Å, α = γ = 90°, β = 111.08°. The crystal contains six subunits of the enzyme comprising a hexamer per asymmetric unit. The hexamer is the biological active form of E. coli. purine nucleoside phosphorylase.

  6. An ancient riboswitch class in bacteria regulates purine biosynthesis and one-carbon metabolism.

    Science.gov (United States)

    Kim, Peter B; Nelson, James W; Breaker, Ronald R

    2015-01-22

    Over 30 years ago, ZTP (5-aminoimidazole-4-carboxamide riboside 5'-triphosphate), a modified purine biosynthetic intermediate, was proposed to signal 10-formyl-tetrahydrofolate (10f-THF) deficiency in bacteria. However, the mechanisms by which this putative alarmone or its precursor ZMP (5-aminoimidazole-4-carboxamide ribonucleotide, also known as AICAR) brings about any metabolic changes remain unexplained. Herein, we report the existence of a widespread riboswitch class that is most commonly associated with genes related to de novo purine biosynthesis and one-carbon metabolism. Biochemical data confirm that members of this riboswitch class selectively bind ZMP and ZTP with nanomolar affinity while strongly rejecting numerous natural analogs. Indeed, increases in the ZMP/ZTP pool, caused by folate stress in bacterial cells, trigger changes in the expression of a reporter gene fused to representative ZTP riboswitches in vivo. The wide distribution of this riboswitch class suggests that ZMP/ZTP signaling is important for species in numerous bacterial lineages.

  7. Synthesis and Cytotoxic Activity of Some New 2,6-Substituted Purines

    Directory of Open Access Journals (Sweden)

    Nageswara Rao Kode

    2011-07-01

    Full Text Available A seriesof twenty four acyclic unsaturated 2,6-substututed purines 5a-20b were synthesized. These compounds were evaluated for cytotoxic activity against NCI-60 DTP human tumor cell line screen at 10µMconcentration. N9-[(Z-4'-chloro-2'-butenyl-1'-yl]-2,6-dichloropurine(5a, N9-[4'-chloro-2'-butynyl-1'-yl]-2,6-dichloropurine(10a, N9-[(E-2',3'-dibromo-4'-chloro-2'-butenyl-1'-yl]-6-methoxypurine(14and N9-[4'-chloro-2'-butynyl-1'-yl]-6-(4-methoxyphenyl-purine(19exhibited highly potent cytotoxic activity with GI50 values in the 1–5 µM range for most human tumor cell lines. Other compounds exhibited moderate activity.

  8. Purine metabolism and oxidative stress in children with autistic spectrum disorders

    Directory of Open Access Journals (Sweden)

    Faisal Gh. Al-Rubaye

    2013-08-01

    Results: Serum ADA and SOD were significantly lower in boys with autism accompanied by significant higher serum MDA levels when compared with controls. Conclusion: Patients with ASD have impaired purine metabolism and increased oxidative stress which was supported by low levels of ADA and SOD, and high level of MDA. Further biochemical or genetic studies are required to explore the nature of autism. [J Exp Integr Med 2013; 3(4.000: 293-297

  9. [Glutathione redox system, immune status, antioxidant enzymes and metabolism of purine nucleotides in hypothyroidism].

    Science.gov (United States)

    Tapbergenov, S O; Sovetov, B S; Bekbosynova, R B; Bolysbekova, S M

    2015-01-01

    The immune status, components of the glutathione redox system, the activity of antioxidant enzymes and metabolism of purine nucleotides have been investigated in animals with experimental hypothyroidism. On day 8 after an increase in the number of leukocytes, lymphocytes, T-helpers and T-suppressors as well as increased number of B-lymphocytes was found in blood of thyroidectomized rats. This was accompanied by decreased activity of adenosine deaminase (AD), AMP-deaminase (AMPD), and 5'-nucleotidase (5'N) in blood, but the ratio of enzyme activity AD/AMPD increased. These changes in the activity of enzymes, involved in purine catabolism can be regarded as increased functional relationships between T and B lymphocytes in hypothyroidism. The functional changes of immune system cells were accompanied by increased activity of glutathione peroxidase (GPx), a decrease in the activity of superoxide dismutase (SOD), glutathione reductase (GR) and the ratio GH/GPx. Thyroidectomized rats had increased amounts of total, oxidized (GSSG) and reduced glutathione (GSH), but the ratio GSH/GSSG decerased as compared with control animals. In the liver, hypothyroidism resulted in activation of SOD, GPx, decreased activity of GR and decreased ratio GR/GPx. At the same time, the levels of total, oxidized, and reduced glutathione increased, but the ratio GSH/GSSG as well as activities of enzymes involved in purine nucleotide metabolism ratio (and their ratio 5'N/AD + AMPD) decreased. All these data suggest a functional relationship of the glutathione redox system not only with antioxidant enzymes, but also activity of enzymes involved purine nucleotide metabolism and immune status.

  10. Durabilidad de morteros de cemento en contacto con purines de cerdo

    OpenAIRE

    Massana Guitart, Jordi

    2010-01-01

    En el medio agrícola-ganadero el cemento y sus derivados, morteros y hormigones, son materiales ampliamente utilizados. Su uso se extiende desde la parte estructural de las edificaciones a elementos tales como revestimiento de paredes, comederos, o pavimentos tanto continuos como discontinuos o balsas de almacenamiento de purines, de hormigón en masa o armado o incluso de fábrica de ladrillo con revestimiento de mortero. Todos estos elementos se encuentran en ambientes de diversa agresividad,...

  11. Thermodynamic examination of 1- to 5-nt purine bulge loops in RNA and DNA constructs.

    Science.gov (United States)

    Strom, Shane; Shiskova, Evgenia; Hahm, Yaeeun; Grover, Neena

    2015-07-01

    Bulge loops are common features of RNA structures that are involved in the formation of RNA tertiary structures and are often sites for interactions with proteins and ions. Minimal thermodynamic data currently exist on the bulge size and sequence effects. Using thermal denaturation methods, thermodynamic properties of 1- to 5-nt adenine and guanine bulge loop constructs were examined in 10 mM MgCl(2) or 1 M KCl. The [Formula: see text] loop parameters for 1- to 5-nt purine bulge loops in RNA constructs were between 3.07 and 5.31 kcal/mol in 1 M KCl buffer. In 10 mM magnesium ions, the ΔΔG° values relative to 1 M KCl were 0.47-2.06 kcal/mol more favorable for the RNA bulge loops. The [Formula: see text] loop parameters for 1- to 5-nt purine bulge loops in DNA constructs were between 4.54 and 5.89 kcal/mol. Only 4- and 5-nt guanine constructs showed significant change in stability for the DNA constructs in magnesium ions. A linear correlation is seen between the size of the bulge loop and its stability. New prediction models are proposed for 1- to 5-nt purine bulge loops in RNA and DNA in 1 M KCl. We show that a significant stabilization is seen for small bulge loops in RNA in the presence of magnesium ions. A prediction model is also proposed for 1- to 5-nt purine bulge loop RNA constructs in 10 mM magnesium chloride.

  12. Biochemical and physiological characterisation of the purine degradation pathway in plants

    OpenAIRE

    Werner, Andrea

    2013-01-01

    Plant growth is often limited by nitrogen availability in the soil. Not only do plants depend on efficient nitrogen uptake, they also require effective means to internally redistribute nitrogen during every stage of development. The purine degradation pathway contributes to this nitrogen recycling in plants. In tropical legumes it is also of central importance to the plants’ nitrogen supply under nitrogen-fixing conditions. This is the first time that the complete ureide degradation pathway h...

  13. Characterization of a purine permease family gene OsPUP7 involved in growth and development control in rice.

    Science.gov (United States)

    Qi, Zhuyun; Xiong, Lizhong

    2013-11-01

    In this study, PUP-type cytokinin transporter genes were identified in rice (Oryza sativa L.). The Oryza sativa purine permease (OsPUP) family has 12 members that show similar predicted protein sequences with AtPUPs. To reveal the functions of OsPUP genes, we searched the T-DNA mutant library of rice and found one mutant for the member OsPUP7. The T-DNA insertion caused a new transcript that encodes a protein with 26 amino acids different from the native OsPUP7 at the C-terminus. The mutant showed multiple phenotypic changes including increased plant height, big seeds, and delayed flowering. The mutant also showed increased sensitivity to drought and salt stresses and treatments with kinetin and abscisic acid. OsPUP7 is expressed mainly in the vascular bundle, pistil, and stamens. The measurement of cytokinins (CKs) showed that CK content in the mutant spikelets accumulated higher than that in the wild type. Moreover, uptake experiment in the yeast fcy2 mutant suggested that OsPUP7 has the ability to transport caffeine, a CK derivative. Our results indicate that the PUP transport system also exists in rice, and OsPUP7 has an important role in the transport of CK, thus affecting developmental process and stress responses.

  14. Isolation of Purines and Pyrimidines from the Murchison Meteorite Using Sublimation

    Science.gov (United States)

    Glavin, D. P.; Bada, J. L.

    2004-01-01

    The origin of life on Earth, and possibly on other planets such as Mars, would have required the presence of liquid water and a continuous supply of prebiotic organic compounds. The exogenous delivery of organic matter by asteroids, comets, and carbonaceous meteorites could have contributed to the early Earth s prebiotic inventory by seeding the planet with biologically important organic compounds. A wide variety of prebiotic organic compounds have previously been detected in the Murchison CM type carbonaceous chondrite including amino acids, purines and pyrimidines. These compounds dominate terrestrial biochemistry and are integral components of proteins, DNA and RNA. Several purines including adenine, guanine, hypoxanthine, and xanthine, as well as the pyrimidine uracil, have previously been detected in water or formic acid extracts of Murchison using ion-exclusion chromatography and ultraviolet spectroscopy. However, even after purification of these extracts, the accurate identification and quantification of nucleobases is difficult due to interfering UV absorbing compounds. In order to reduce these effects, we have developed an extraction technique using sublimation to isolate purines and pyrimidines from other non-volatile organic compounds in Murchison acid extracts.

  15. Purine and pyrimidine metabolism: Convergent evidence on chronic antidepressant treatment response in mice and humans

    Science.gov (United States)

    Park, Dong Ik; Dournes, Carine; Sillaber, Inge; Uhr, Manfred; Asara, John M.; Gassen, Nils C.; Rein, Theo; Ising, Marcus; Webhofer, Christian; Filiou, Michaela D.; Müller, Marianne B.; Turck, Christoph W.

    2016-01-01

    Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used drugs for the treatment of psychiatric diseases including major depressive disorder (MDD). For unknown reasons a substantial number of patients do not show any improvement during or after SSRI treatment. We treated DBA/2J mice for 28 days with paroxetine and assessed their behavioral response with the forced swim test (FST). Paroxetine-treated long-time floating (PLF) and paroxetine-treated short-time floating (PSF) groups were stratified as proxies for drug non-responder and responder mice, respectively. Proteomics and metabolomics profiles of PLF and PSF groups were acquired for the hippocampus and plasma to identify molecular pathways and biosignatures that stratify paroxetine-treated mouse sub-groups. The critical role of purine and pyrimidine metabolisms for chronic paroxetine treatment response in the mouse was further corroborated by pathway protein expression differences in both mice and patients that underwent chronic antidepressant treatment. The integrated -omics data indicate purine and pyrimidine metabolism pathway activity differences between PLF and PSF mice. Furthermore, the pathway protein levels in peripheral specimens strongly correlated with the antidepressant treatment response in patients. Our results suggest that chronic SSRI treatment differentially affects purine and pyrimidine metabolisms, which may explain the heterogeneous antidepressant treatment response and represents a potential biosignature. PMID:27731396

  16. Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naive patients with schizophrenia.

    Directory of Open Access Journals (Sweden)

    Jeffrey K Yao

    Full Text Available BACKGROUND: Purine catabolism may be an unappreciated, but important component of the homeostatic response of mitochondria to oxidant stress. Accumulating evidence suggests a pivotal role of oxidative stress in schizophrenia pathology. METHODOLOGY/PRINCIPAL FINDINGS: Using high-pressure liquid chromatography coupled with a coulometric multi-electrode array system, we compared 6 purine metabolites simultaneously in plasma between first-episode neuroleptic-naïve patients with schizophrenia (FENNS, n = 25 and healthy controls (HC, n = 30, as well as between FENNS at baseline (BL and 4 weeks (4w after antipsychotic treatment. Significantly higher levels of xanthosine (Xant and lower levels of guanine (G were seen in both patient groups compared to HC subjects. Moreover, the ratios of G/guanosine (Gr, uric acid (UA/Gr, and UA/Xant were significantly lower, whereas the ratio of Xant/G was significantly higher in FENNS-BL than in HC. Such changes remained in FENNS-4w with exception that the ratio of UA/Gr was normalized. All 3 groups had significant correlations between G and UA, and Xan and hypoxanthine (Hx. By contrast, correlations of UA with each of Xan and Hx, and the correlation of Xan with Gr were all quite significant for the HC but not for the FENNS. Finally, correlations of Gr with each of UA and G were significant for both HC and FENNS-BL but not for the FENNS-4w. CONCLUSIONS/SIGNIFICANCE: During purine catabolism, both conversions of Gr to G and of Xant to Xan are reversible. Decreased ratios of product to precursor suggested a shift favorable to Xant production from Xan, resulting in decreased UA levels in the FENNS. Specifically, the reduced UA/Gr ratio was nearly normalized after 4 weeks of antipsychotic treatment. In addition, there are tightly correlated precursor and product relationships within purine pathways; although some of these correlations persist across disease or medication status, others appear to be lost among FENNS

  17. Isolation of hydroxy-Y base from rat liver tRNAPhe.

    Science.gov (United States)

    Kasai, H; Yamaizumi, Z; Kuchino, Y; Nishimura, S

    1979-03-01

    A Y-base derivative was isolated from rat liver tRNAPhe and its structure was assigned to be alpha-(carboxyamino)-beta-hydroxy-4,9-dihydro-4,6-dimethyl-9-oxo-1H-imidazol[1,2-a]purine-7-butyric acid dimethyl ester (hydroxy-Y), based on the results of mass spectrometry and chemical degradation. This modified base seems to be the major fluorescent component of rat liver tRNAPhe; the peroxy-Y base previously isolated from rat liver tRNAPhe and characterized by Nakanishi and his coworkers (1,2) was not present in our preparation.

  18. Association of poly-purine/poly-pyrimidine sequences with meiotic recombination hot spots

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    Pitt Joel PW

    2006-07-01

    Full Text Available Abstract Background Meiotic recombination events have been found to concentrate in 1–2.5 kilo base regions, but these recombination hot spots do not share a consensus sequence and why they occur at specific sites is not fully understood. Some previous evidence suggests that poly-purine/poly-pyrimidine (poly-pu/py tracts (PPTs, a class of sequence with distinctive biochemical properties, could be involved in recombination, but no general association of PPTs with meiotic recombination hot spots has previously been reported. Results We used computational methods to investigate in detail the relationship between PPTs and hot spots. We show statistical associations of PPT frequency with hot spots of meiotic recombination initiating lesions, double-strand breaks, in the genome of the yeast S. cerevisiae and with experimentally well characterized human meiotic recombination hot spots. Supporting a possible role of poly-pu/py-rich sequences in hot spot recombination, we also found that all three single nucleotide polymorphisms previously shown to be associated with human hot spot activity changes occur within sequence contexts of 14 bp or longer that are 85% or more poly-pu/py and at least 70% G/C. These polymorphisms are all close to the hot spot mid points. Comparing the sequences of experimentally characterized human hot spots with the orthologous regions of the chimpanzee genome previously shown not to contain hot spots, we found that in all five cases in which comparisons for the hot spot central regions are possible with publicly available sequence data, there are differences near the human hot spot mid points within sequences 14 bp or longer consisting of more than 80% poly-pu/py and at least 50% G/C. Conclusion Our results, along with previous evidence for the unique biochemical properties and recombination-stimulating potential of poly-pu/py-rich sequences, suggest that the possible functional involvement of this type of sequence in meiotic

  19. Design and SAR of new substituted purines bearing aryl groups at N9 position as HIV-1 Tat-TAR interaction inhibitors.

    Science.gov (United States)

    Pang, Ruifang; Zhang, Chunlei; Yuan, Dekai; Yang, Ming

    2008-09-01

    Twenty-four purine derivatives bearing aryl groups at N9 position were designed and synthesized as HIV-1 Tat-TAR interaction inhibitors. All the compounds showed high antiviral activities in inhibiting the formation of SIV-induced syncytium in CEM174 cells. Ten of them with low cytotoxicities were evaluated by Tat dependent HIV-1 LTR-driven CAT gene expression colorimetric enzyme assay in human 293T cells at a concentration of 30 microM, indicating effective inhibitory activities of blocking the Tat-TAR interaction. The aryl groups at N9 position affected the binding affinities between compounds and TAR RNA, showing some specificities of aryl groups to TAR RNA.

  20. C60-Based Ebselen Derivative: Synthesis and Enhanced Protective Effect on Mouse Thymus Cells

    Institute of Scientific and Technical Information of China (English)

    LIU,Xu-Feng; GUAN,Wen-Chao; KE,Wen-Shan

    2008-01-01

    A C60-based ebselen derivative 3 was synthesized through a Bingel cyclopropanation of C60 with the ebselen malonate 2. It was obtained in a three-step synthesis starting from 2-(chloroseleno)benzoyl chloride and 2-(2-aminoethoxy)ethanol, in a 42% yield (based on consumed C60). Its structure was characterized by 1H NMR,13C NMR, IR, FAB-MS, and elemental analyses techniques. To verify that the C60-based ebselen derivative 3 had enhanced effect on viability of mouse thymus cells, the C60 derivative 4 and ebselen derivative 2 were selected to treat the mouse thymus cells using the same procedures as those with the C60-based ebselen derivative 3. The result shows that MTT(OD) values of compound 3 treated groups (0.335 ±0.021) were all higher than those of compound 4 (0.283±0.031) and compound 2 (0.247±0.025) treated groups, indicating that the compound 3 has an advantage over compounds 2 and 4 in promoting the viability of the mouse thymus cell.

  1. Synthesis, characterization and biological behavior of some Schiff's and Mannich base derivatives of Lamotrigine

    Directory of Open Access Journals (Sweden)

    A.A. Kulkarni

    2017-02-01

    Full Text Available A series of various Schiff's and Mannich base derivatives (N1–2 & ND1–6 of Lamotrigine with isatin and substituted isatin were synthesized to get more potent anticonvulsant agents. The starting material for the synthesis of various new Schiff's and Mannich base derivatives was isatin (1H-indole- 2, 3-dione which in turn was prepared from substituted isonitrosoacetanilide using aniline. Lamotrigine reacts with isatin & substituted isatin gave Schiff's bases (N1–2 which on reaction with various secondary amines (dimethylamine, diethylamine, morpholine produced Mannich bases (ND1–6. The structures of newly synthesized compounds were characterized by using TLC, UV, FT-IR, 1HNMR and studied for their anticonvulsant activity. Anticonvulsant activity of all the derivatives was evaluated by MES method using phenobarbitone sodium & Lamotrigine as standard drugs and % reduction of time spent by animals in extension, flexion, clonus, and stupor phase were noted. Compounds ND-4 and ND-6 showed significant anticonvulsant activity when compared with that of standard drugs. The remaining all compounds show moderate activity. Biological activity data of the synthesized derivatives revealed that, the synthesized derivatives are good anticonvulsant agents as compared to Lamotrigine.

  2. Synthesis, characterization and biological activity of C6-Schiff bases derivatives of chitosan.

    Science.gov (United States)

    Xu, Ruibo; Aotegen, Bayaer; Zhong, Zhimei

    2017-06-30

    C6-Schiff bases derivatives of chitosan were synthesized for the first time. C2-amino groups and C3-hydroxy groups were firstly protected by CuSO4·5H2O, and the C6-hydroxy was then transformed into aldehyde, which then reacted with anilines through nucleophilic addition to introduce the CN group at C6-position in chitosan chain. Finally, C6-Schiff bases derivatives of chitosan were got by the deprotection of C2-NH2 with cation exchange resin. The structures and properties of the new synthesized products were characterized by Fourier transform infrared spectroscopy, (13)C NMR, SEM image, and elemental analysis. The antibacterial activities of derivatives were tested in the experiment, and the results showed that the prepared chitosan derivatives had significantly improved antibacterial activity toward Staphylococcus aureus and Escherichia coli. The Cytotoxicity test showed that the prepared chitosan derivatives had low Cytotoxicity, compared with chitosan and C2-benzaldehyde Schiff bases of chitosan. This paper allowed a new method for the synthesis of Schiff bases of chitosan, which was enlightening. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Synthesis and characterization of nickel complexes derived from Schiff-Bases

    OpenAIRE

    Mirian Y. Matsumoto; Keila B. Dias; Vicente L. Kupfer; Elias B. O. Filho; Larisse G. Salazar; Adalberto V. Mezacasa; Persiely P. Rosa; Nelson Luis de Campos Domingues; Andrelson W. Rinaldi

    2012-01-01

    Aromatic Schiff-Bases constitute a large class of organic compounds containing the imine group (C=N) [1-3]. 2-hydroxybenzaldehyde (salicylaldehyde) which has been frequently used for the synthesis of aromatic Schiff-Bases, it has many biological applications, such as analgesics, anti-inflammatory, antibacterial, antiviral and bactericidal activities [4-6]. From above, this project proposed the synthesis of three Schiff bases derived from salicylaldehyde prepared by condensation between salicy...

  4. CFD Based Determination of Dynamic Stability Derivatives in Yaw for a Bird

    Institute of Scientific and Technical Information of China (English)

    M. A. Moelyadi; G. Sachs

    2007-01-01

    Dynamic yaw stability derivatives of a gull bird are determined using Computational Fluid Dynamics(CFD) method. Two kinds of motions are applied for calculating the dynamic yaw stability derivatives CNr and CNβ. The first one relates to a lateral translation and, separately, to a yaw rotation. The second one consists of a combined translational and rotational motion. To determine dynamic yaw stability derivatives, the simulation of an unsteady flow with a bird model showing a harmonic motion is performed. The flow solution for each time step is obtained by solving unsteady Euler equations based on a finite volume approach for a small reduced frequency. Then, an evaluation of unsteady forces and moments for one cycle is conducted using harmonic Fourier analysis. The results of the dynamic yaw stability derivatives for both simulations of the model show a good agreement.

  5. Sigmoid function based integral-derivative observer and application to autopilot design

    Science.gov (United States)

    Shao, Xingling; Wang, Honglun; Liu, Jun; Tang, Jun; Li, Jie; Zhang, Xiaoming; Shen, Chong

    2017-02-01

    To handle problems of accurate signal reconstruction and controller implementation with integral and derivative components in the presence of noisy measurement, motivated by the design principle of sigmoid function based tracking differentiator and nonlinear continuous integral-derivative observer, a novel integral-derivative observer (SIDO) using sigmoid function is developed. The key merit of the proposed SIDO is that it can simultaneously provide continuous integral and differential estimates with almost no drift phenomena and chattering effect, as well as acceptable noise-tolerance performance from output measurement, and the stability is established based on exponential stability and singular perturbation theory. In addition, the effectiveness of SIDO in suppressing drift phenomena and high frequency noises is firstly revealed using describing function and confirmed through simulation comparisons. Finally, the theoretical results on SIDO are demonstrated with application to autopilot design: 1) the integral and tracking estimates are extracted from the sensed pitch angular rate contaminated by nonwhite noises in feedback loop, 2) the PID(proportional-integral-derivative) based attitude controller is realized by adopting the error estimates offered by SIDO instead of using the ideal integral and derivative operator to achieve satisfactory tracking performance under control constraint.

  6. HPLC analysis for the clinical-biochemical diagnosis of inborn errors of metabolism of purines and pyrimidines.

    Science.gov (United States)

    Lazzarino, Giuseppe; Amorini, Angela Maria; Di Pietro, Valentina; Tavazzi, Barbara

    2011-01-01

    The determination of purines and pyrimidines in biofluids is useful for the clinical-biochemical characterization of acute and chronic pathological states that induce transient or permanent alterations of metabolism. In particular, the diagnosis of several inborn errors of metabolism (IEMs) is accomplished by the analysis of circulating and excreted purines and pyrimidines. It is certainly advantageous to simultaneously determine the full purine and pyrimidine profile, as well as to quantify other compounds of relevance (e.g., organic acids, amino acids, sugars) in various metabolic hereditary diseases, in order to screen for a large number of IEMs using a reliable and sensitive analytical method characterized by mild to moderate costs. Toward this end, we have developed an ion-pairing HPLC method with diode array detection for the synchronous separation of several purines and pyrimidines. This method also allows the quantification of additional compounds such as N-acetylated amino acids and dicarboxylic acids, the concentrations of which are profoundly altered in different IEMs. The application of the method in the analysis of biological samples from patients with suspected purine and pyrimidine disorders is presented to illustrate its applicability for the clinical-biochemical diagnosis of IEM.

  7. Poly purine.pyrimidine sequences upstream of the beta-galactosidase gene affect gene expression in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Brahmachari Samir K

    2001-10-01

    Full Text Available Abstract Background Poly purine.pyrimidine sequences have the potential to adopt intramolecular triplex structures and are overrepresented upstream of genes in eukaryotes. These sequences may regulate gene expression by modulating the interaction of transcription factors with DNA sequences upstream of genes. Results A poly purine.pyrimidine sequence with the potential to adopt an intramolecular triplex DNA structure was designed. The sequence was inserted within a nucleosome positioned upstream of the β-galactosidase gene in yeast, Saccharomyces cerevisiae, between the cycl promoter and gal 10Upstream Activating Sequences (UASg. Upon derepression with galactose, β-galactosidase gene expression is reduced 12-fold in cells carrying single copy poly purine.pyrimidine sequences. This reduction in expression is correlated with reduced transcription. Furthermore, we show that plasmids carrying a poly purine.pyrimidine sequence are not specifically lost from yeast cells. Conclusion We propose that a poly purine.pyrimidine sequence upstream of a gene affects transcription. Plasmids carrying this sequence are not specifically lost from cells and thus no additional effort is needed for the replication of these sequences in eukaryotic cells.

  8. Abnormal Purine Metabolism and Hearing Loss%嘌呤代谢异常与听力损失

    Institute of Scientific and Technical Information of China (English)

    王欣; 张璞; 张勋

    2015-01-01

    嘌呤,是存在于人体内的一种化学成分,参与组成核酸及ATP等人体多种重要物质。嘌呤的代谢异常会引起一系列的疾病,包括:痛风、免疫系统疾病、血液疾病、肾脏疾病等,但目前其与耳聋的关系报道甚少,且多集中在遗传性耳聋方面。本文将对嘌呤代谢异常与耳聋的关系进行综述,并探讨嘌呤代谢异常引起非遗传性耳聋的发病机制。%[Abstact]Purine, one chemical constituent existing in the human body, participates in the production of a variety of important substances including nucleic acids and ATP. Abnormal metabolism of purine leads to a series of diseases (e.g., gout, autoimmune diseases, blood diseases, kidney diseases, etc). However, reports on the relationship between purine and hearing loss as hereditary deafness are rare. In this paper, we will summa-rize study evidence on the association between abnormal purine metabolism and hearing loss, and discuss the pathogenesis of non-hereditary deafness resulting from abnormal purine metabolism.

  9. Enhancement of peripheral nerve regrowth by the purine nucleoside analog and cell cycle inhibitor, roscovitine

    Directory of Open Access Journals (Sweden)

    Vincent Law

    2016-10-01

    Full Text Available Peripheral nerve regeneration is a slow process that can be associated with limited outcomes and thus, a search for novel and effective therapy for peripheral nerve injury and disease is crucial. Here, we found that roscovitine, a synthetic purine nucleoside analog, enhances neurite outgrowth in neuronal-like PC12 cells. Furthermore, ex vivo analysis of pre-injured adult rat dorsal root ganglion neurons showed that roscovitine enhances neurite regrowth in these cells. Likewise, in vivo transected sciatic nerves in rats locally perfused with roscovitine had augmented repopulation of new myelinated axons beyond the transection zone. By mass spectrometry, we found that roscovitine interacts with tubulin and actin. It interacts directly with tubulin and causes a dose-dependent induction of tubulin polymerization as well as enhances GTP-dependent tubulin polymerization. Conversely, roscovitine interacts indirectly with actin and counteracts the inhibitory effect of Cdk5 on Arp2/3-dependent actin polymerization, and thus, causes actin polymerization. Moreover, in the presence of neurotrophic factors such as NGF, roscovitine-enhanced neurite outgrowth is mediated by increased activation of the ERK1/2 and p38 MAPK pathways. Since microtubule and F-actin dynamics are critical for axonal regrowth, the ability of roscovitine to activate the ERK1/2 and p38 MAPK pathways, and support polymerization of tubulin and actin indicate a major role for this purine nucleoside analog in the promotion of axonal regeneration. Together, our findings demonstrate a therapeutic potential for the purine nucleoside analog, roscovitine, in peripheral nerve injury.

  10. Enhancement of Peripheral Nerve Regrowth by the Purine Nucleoside Analog and Cell Cycle Inhibitor, Roscovitine.

    Science.gov (United States)

    Law, Vincent; Dong, Sophie; Rosales, Jesusa L; Jeong, Myung-Yung; Zochodne, Douglas; Lee, Ki-Young

    2016-01-01

    Peripheral nerve regeneration is a slow process that can be associated with limited outcomes and thus a search for novel and effective therapy for peripheral nerve injury and disease is crucial. Here, we found that roscovitine, a synthetic purine nucleoside analog, enhances neurite outgrowth in neuronal-like PC12 cells. Furthermore, ex vivo analysis of pre-injured adult rat dorsal root ganglion (DRG) neurons showed that roscovitine enhances neurite regrowth in these cells. Likewise, in vivo transected sciatic nerves in rats locally perfused with roscovitine had augmented repopulation of new myelinated axons beyond the transection zone. By mass spectrometry, we found that roscovitine interacts with tubulin and actin. It interacts directly with tubulin and causes a dose-dependent induction of tubulin polymerization as well as enhances Guanosine-5'-triphosphate (GTP)-dependent tubulin polymerization. Conversely, roscovitine interacts indirectly with actin and counteracts the inhibitory effect of cyclin-dependent kinases 5 (Cdk5) on Actin-Related Proteins 2/3 (Arp2/3)-dependent actin polymerization, and thus, causes actin polymerization. Moreover, in the presence of neurotrophic factors such as nerve growth factor (NGF), roscovitine-enhanced neurite outgrowth is mediated by increased activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) pathways. Since microtubule and F-actin dynamics are critical for axonal regrowth, the ability of roscovitine to activate the ERK1/2 and p38 MAPK pathways and support polymerization of tubulin and actin indicate a major role for this purine nucleoside analog in the promotion of axonal regeneration. Together, our findings demonstrate a therapeutic potential for the purine nucleoside analog, roscovitine, in peripheral nerve injury.

  11. Enhancement of Peripheral Nerve Regrowth by the Purine Nucleoside Analog and Cell Cycle Inhibitor, Roscovitine

    Science.gov (United States)

    Law, Vincent; Dong, Sophie; Rosales, Jesusa L.; Jeong, Myung-Yung; Zochodne, Douglas; Lee, Ki-Young

    2016-01-01

    Peripheral nerve regeneration is a slow process that can be associated with limited outcomes and thus a search for novel and effective therapy for peripheral nerve injury and disease is crucial. Here, we found that roscovitine, a synthetic purine nucleoside analog, enhances neurite outgrowth in neuronal-like PC12 cells. Furthermore, ex vivo analysis of pre-injured adult rat dorsal root ganglion (DRG) neurons showed that roscovitine enhances neurite regrowth in these cells. Likewise, in vivo transected sciatic nerves in rats locally perfused with roscovitine had augmented repopulation of new myelinated axons beyond the transection zone. By mass spectrometry, we found that roscovitine interacts with tubulin and actin. It interacts directly with tubulin and causes a dose-dependent induction of tubulin polymerization as well as enhances Guanosine-5′-triphosphate (GTP)-dependent tubulin polymerization. Conversely, roscovitine interacts indirectly with actin and counteracts the inhibitory effect of cyclin-dependent kinases 5 (Cdk5) on Actin-Related Proteins 2/3 (Arp2/3)-dependent actin polymerization, and thus, causes actin polymerization. Moreover, in the presence of neurotrophic factors such as nerve growth factor (NGF), roscovitine-enhanced neurite outgrowth is mediated by increased activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) pathways. Since microtubule and F-actin dynamics are critical for axonal regrowth, the ability of roscovitine to activate the ERK1/2 and p38 MAPK pathways and support polymerization of tubulin and actin indicate a major role for this purine nucleoside analog in the promotion of axonal regeneration. Together, our findings demonstrate a therapeutic potential for the purine nucleoside analog, roscovitine, in peripheral nerve injury.

  12. Analytical derivation: An epistemic game for solving mathematically based physics problems

    Science.gov (United States)

    Bajracharya, Rabindra R.; Thompson, John R.

    2016-06-01

    Problem solving, which often involves multiple steps, is an integral part of physics learning and teaching. Using the perspective of the epistemic game, we documented a specific game that is commonly pursued by students while solving mathematically based physics problems: the analytical derivation game. This game involves deriving an equation through symbolic manipulations and routine mathematical operations, usually without any physical interpretation of the processes. This game often creates cognitive obstacles in students, preventing them from using alternative resources or better approaches during problem solving. We conducted hour-long, semi-structured, individual interviews with fourteen introductory physics students. Students were asked to solve four "pseudophysics" problems containing algebraic and graphical representations. The problems required the application of the fundamental theorem of calculus (FTC), which is one of the most frequently used mathematical concepts in physics problem solving. We show that the analytical derivation game is necessary, but not sufficient, to solve mathematically based physics problems, specifically those involving graphical representations.

  13. Design of Chitosan and Its Water Soluble Derivatives-Based Drug Carriers with Polyelectrolyte Complexes

    Science.gov (United States)

    Wu, Qing-Xi; Lin, Dong-Qiang; Yao, Shan-Jing

    2014-01-01

    Chitosan, the cationic polysaccharide derived from the natural polysaccharide chitin, has been studied as a biomaterial for more than two decades. As a polycationic polymer with favorable properties, it has been widely used to form polyelectrolyte complexes with polyanions for various applications in drug delivery fields. In recent years, a growing number of studies have been focused on the preparation of polyelectrolyte complexes based on chitosan and its water soluble derivatives. They have been considered well-suited as biomaterials for a number of vital drug carriers with targeted/controlled release profiles, e.g., films, capsules, microcapsules. In this work, an overview highlights not only the favorable properties of chitosan and its water soluble derivatives but also the good performance of the polyelectrolyte complexes produced based on chitosan. Their various types of applications as drug carriers are reviewed in detail. PMID:25532565

  14. Purine and its analogues and radiation damage in Bacillus megaterium spores

    Energy Technology Data Exchange (ETDEWEB)

    Powers, E.L.

    1986-12-01

    As an extension of results obtained from radiation studies on caffeine both in other laboratories and more recently in this laboratory using the bacterial spore as the test system, six compounds with chemical structures closely resembling that of caffeine were tested as radiation modifiers. Of these compounds, purine, adenine and hypoxanthine resembled caffeine in sensitizing spores to radiation, while theobromine, xanthine and theophylline did not. These responses are discussed in relation to the electron sequestration hypothesis of cellular sensitization to high-energy radiation.

  15. Drosophila deoxyribonucleoside kinase mutants with enhanced ability to phosphorylate purine analogs

    DEFF Research Database (Denmark)

    Knecht, Wolfgang; Rozpedowska, E.; Le Breton, C.

    2007-01-01

    ability to phosphorylate pyrimidines, while the ability to phosphorylate purine analogs was relatively similar to the wild-type enzyme. We selected two mutants, for expression in the osteosarcoma 143B, the glioblastoma U-87M-G and the breast cancer MCF7 cell lines. The sensitivities of the transduced cell...... to create Dm-dNK mutants with increased specificity for several nucleoside analogs (NAs) used as anticancer or antiviral drugs. Four mutants were characterized for the ability to sensitize Escherichia coli toward analogs and for their substrate specificity and kinetic parameters. The mutants had a reduced...

  16. Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy.

    Science.gov (United States)

    Kudou, Naoki; Taniguchi, Akira; Sugimoto, Kenji; Matsuya, Yuji; Kawasaki, Masashi; Toyooka, Naoki; Miyoshi, Chika; Awale, Suresh; Dibwe, Dya Fita; Esumi, Hiroyasu; Kadota, Shigetoshi; Tezuka, Yasuhiro

    2013-02-01

    A series of new (-)-arctigenin derivatives with variably modified O-alkyl groups were synthesized and their preferential cytotoxicity was evaluated against human pancreatic cancer cell line PANC-1 under nutrient-deprived conditions. The results showed that monoethoxy derivative 4i (PC(50), 0.49 μM), diethoxy derivative 4h (PC(50), 0.66 μM), and triethoxy derivative 4m (PC(50), 0.78 μM) showed the preferential cytotoxicities under nutrient-deprived conditions, which were identical to or more potent than (-)-arctigenin (1) (PC(50), 0.80 μM). Among them, we selected the triethoxy derivative 4m and examined its in vivo antitumor activity using a mouse xenograft model. Triethoxy derivative 4m exhibited also in vivo antitumor activity with the potency identical to or slightly more than (-)-arctigenin (1). These results would suggest that a modification of (-)-arctigenin structure could lead to a new drug based on the antiausterity strategy.

  17. Evaluation of Ferrocene Derivatives as Burn Rate Modifiers in AP/HTPB-Based Composite Propellants

    Directory of Open Access Journals (Sweden)

    G. M. Gore

    1999-04-01

    Full Text Available Some ferrocene derivatives like 2,4-dinitrophenylhydrazine derivative of acetyl ferrocene, 1-pyrrolidinylmethyl ferrocene, di-ter-butyl ferrocene and 1,3-diferrocenyl-l-butene (DFB have been synthesised and characterised by infrared, nuclear magnetic resonance, ultraviolet, iron content, etc. To study the effect of their incorporation on performance, ammonium perchlorate/hydroxyl-terminated polybutadiene-based composite propellants containing these derivatives have been prepared and studied for burn rates, tensile strength and percentage elongation followed by their static test evaluation. A comparison of the properties of propellant containing solid and liquid ferrocene derivatives has been made with those containing Fe/sub 2/O/sub 3/ and n-butyl ferrocene, respectively. The data clearly indicates that these ferrocene derivatives are better than Fe/sub 2/O/sub 3/ and n-butyl errocene. Also, DFB is the best among these derivatives. Like composite propellants, DFB increases burn rate in fuel-rich propellants also.

  18. CONFAC Decomposition Approach to Blind Identification of Underdetermined Mixtures Based on Generating Function Derivatives

    NARCIS (Netherlands)

    de Almeida, Andre L. F.; Luciani, Xavier; Stegeman, Alwin; Comon, Pierre

    2012-01-01

    This work proposes a new tensor-based approach to solve the problem of blind identification of underdetermined mixtures of complex-valued sources exploiting the cumulant generating function (CGF) of the observations. We show that a collection of second-order derivatives of the CGF of the observation

  19. Single-phase Phase-locked Loop Based on Derivative Elements

    DEFF Research Database (Denmark)

    Guan, Qingxin; Zhang, Yu; Kang, Yong;

    2017-01-01

    High performance phase locked loops (PLLs) are critical for power control in grid-connected systems. This paper presents a new method of designing a PLL for single-phase systems based on derivative elements (DEs). The quadrature signal generator (QSG) is constructed by two DEs with the same main ...

  20. Heterocycles 38. Biocatalytic Synthesis of New Heterocyclic Mannich Bases and Derivatives

    Directory of Open Access Journals (Sweden)

    Denisa Leonte

    2015-07-01

    Full Text Available This paper describes the biocatalytic synthesis of new Mannich bases containing various heterocyclic rings (thiazole, furane, thiophene, pyridine by applying the lipase catalyzed trimolecular condensation of the corresponding heterocyclic aldehydes with acetone and primary aromatic amines, in mild and eco-friendly reaction conditions. The obtained Mannich bases were acylated to their corresponding N-acetyl derivatives. All compounds were characterized by 1H-NMR, 13C-NMR and MS spectrometry.

  1. A novel synthesis of chromone based unnatural α-amino acid derivatives

    Indian Academy of Sciences (India)

    VENU KANDULA; RAMAKRISHNA GUDIPATI; ANINDITA CHATTERJEE; MURALIDARAN KALIYAPERUMALA; SATYANARAYANA YENNAM; MANORANJAN BEHERA

    2017-08-01

    An efficient method for the preparation of chromone based α-amino acid derivatives by alkylation of glycinate schiff base with 3-bromomethyl chromone as well as 2-bromomethyl chromone has been described. Using this method, 2-amino-3-(4-oxo-2-chromenyl)propanoic acid and 2-amino-3-(4-oxo-3- chromenyl)propanoic acid, two novel chromone-amino acid conjugates have been prepared. Furthermore, the separation of chromone amino acid enantiomers by chiral column chromatography was accomplished.

  2. Synthesis, crystal structures and photoluminescence of anthracen- and pyrene-based coumarin derivatives.

    Science.gov (United States)

    Zhang, Hui; Tong, Hao; Zhao, Yuling; Yu, Tianzhi; Zhang, Peng; Li, Jianfeng; Fan, Duowang

    2015-11-01

    Two new anthracen- and pyrene-based coumarin derivatives, 3-(4-(anthracen-10-yl)phenyl)coumarin (4) and 3-(4-(pyrene-1-yl)phenyl)coumarin (5), were synthesized and characterized by FT-IR, (1)H NMR, element analysis and single crystal X-ray crystallography. The UV-vis absorption and photoluminescence spectra of these coumarin derivatives were investigated. The results show that compound 4 and 5 exhibit blue and blue-green emissions, respectively, under ultraviolet light excitation. Compared with the compound 4, the emission peak of compound 5 was bathochromically shifted by about 80 nm due to the more planar structure and larger π-conjugation.

  3. A new method based on Markov chains for deriving SB2 orbits directly from their spectra

    CERN Document Server

    Salomon, J -B; Guillout, P; Halbwachs, J -L; Arenou, F; Famaey, B; Lebreton, Y; Mazeh, T; Pourbaix, D; Tal-Or, L

    2012-01-01

    We present a new method to derive orbital elements of double-lined spectroscopic binaries (SB2). The aim is to have accurate orbital parameters of a selection of SB2 in order to prepare the exploitation of astrometric Gaia observations. Combined with our results, they should allow one to measure the mass of each star with a precision of better than 1%. The new method presented here consists of using the spectra at all epochs simultaneously to derive the orbital elements without templates. It is based on a Markov chain including a new method for disentangling the spectra.

  4. Separation of piracetam derivatives on polysaccharide-based chiral stationary phases.

    Science.gov (United States)

    Kažoka, H; Koliškina, O; Veinberg, G; Vorona, M

    2013-03-15

    High-performance liquid chromatography was used for the enantiomeric separation of two chiral piracetam derivatives. The suitability of six commercially available polysaccharide-based chiral stationary phases (CSPs) under normal phase mode for direct enantioseparation has been investigated. The influence of the CSPs as well the nature and content of an alcoholic modifier in the mobile phase on separation and elution order was studied. It was established that CSP Lux Amylose-2 shows high chiral recognition ability towards 4-phenylsubstituted piracetam derivatives. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Early Cellular Responses of Purine Nucleoside-mediated Protection of Hypoxia-induced Injuries of Neuronal PC12 Cells

    Directory of Open Access Journals (Sweden)

    Bettina Tomaselli

    2005-01-01

    Full Text Available Hypoxia in brain may lead to cell death by apoptosis and necrosis. In parallel adenosine, a powerful endogenous neuroprotectant is formed. We wanted to investigate the effect of adenosine and its purine nucleoside relatives, inosine and guanosine on early cellular responses to hypoxia. O2-sensitive neuronal PC12-cells were subjected to chemical hypoxia induced with rotenone, an inhibitor of mitochondrial complex I. Loss of viability after hypoxic insult was impressively rescued by adenosine, guanosine and inosine. PC12-cells mainly express the A2A adenosine receptor. Its inhibition with a specific antagonist (CSC induced cell death of PC12-cells, which could be salvaged by adenosine but not with guanosine or inosine. We have previously demonstrated the important role of mitogen activated protein kinases 1/2 (p42/44 MAPK in purine-mediated rescue. In this study we were interested in the involvement of protein kinases whose activities mediate these processes, including protein kinase A (PKA, phosphoinositide 3-kinase (PI3-K and protein kinase C-related kinases (PRK 1/2. Pharmacological inhibition of PKA and PI3-K increased hypoxia-induced toxicity and likewise also affected the rescue by purine nucleosides. Nerve growth factor (NGF and purine nucleosides induced an activation of PRK 1/2, which to our knowledge indicates for the first time that these kinases are potentially involved in purine nucleoside-mediated rescue of hypoxic neuronal cells. Results suggest that A2A receptor expressing cells are mainly dependent on the purine nucleoside adenosine for their rescue after hypoxic insult. In addition to PKA, PI3-K is an important effector molecule in A2A-mediated signaling and for the rescue of PC12-cells after hypoxic insult.

  6. Alcohol Dehydrogenase 5 Is a Source of Formate for De Novo Purine Biosynthesis in HepG2 Cells.

    Science.gov (United States)

    Bae, Sajin; Chon, James; Field, Martha S; Stover, Patrick J

    2017-04-01

    Background: Formate provides one-carbon units for de novo purine and thymidylate (dTMP) synthesis and is produced via both folate-dependent and folate-independent pathways. Folate-independent pathways are mediated by cytosolic alcohol dehydrogenase 5 (ADH5) and mitochondrial aldehyde dehydrogenase 2 (ALDH2), which generate formate by oxidizing formaldehyde. Formate is a potential biomarker of B-vitamin-dependent one-carbon metabolism.Objective: This study investigated the contributions of ADH5 and ALDH2 to formate production and folate-dependent de novo purine and dTMP synthesis in HepG2 cells.Methods:ADH5 knockout and ALDH2 knockdown HepG2 cells were cultured in folate-deficient [0 nM (6S) 5-formyltetrahydrofolate] or folate-sufficient [25 nM (6S) 5-formyltetrahydrofolate] medium. Purine biosynthesis was quantified as the ratio of [(14)C]-formate to [(3)H]-hypoxanthine incorporated into genomic DNA, which indicates the contribution of the de novo purine synthesis pathway relative to salvage synthesis. dTMP synthesis was quantified as the ratio of [(14)C]-deoxyuridine to [(3)H]-thymidine incorporation into genomic DNA, which indicates the capacity of de novo dTMP synthesis relative to salvage synthesis.Results: The [(14)C]-formate-to-[(3)H]-hypoxanthine ratio was greater in ADH5 knockout than in wild-type HepG2 cells, under conditions of both folate deficiency (+30%; P HepG2 cells, indicating decreased use of exogenous formate, or increased endogenous formate synthesis, for de novo purine biosynthesis.Conclusions: In HepG2 cells, ADH5 is a source of formate for de novo purine biosynthesis, especially during folate deficiency when folate-dependent formate production is limited. Formate is also shown to be limiting in the growth of HepG2 cells. © 2017 American Society for Nutrition.

  7. Genetic Screen Reveals the Role of Purine Metabolism in Staphylococcus aureus Persistence to Rifampicin

    Directory of Open Access Journals (Sweden)

    Rebecca Yee

    2015-12-01

    Full Text Available Chronic infections with Staphylococcus aureus such as septicemia, osteomyelitis, endocarditis, and biofilm infections are difficult to treat because of persisters. Despite many efforts in understanding bacterial persistence, the mechanisms of persister formation in S. aureus remain elusive. Here, we performed a genome-wide screen of a transposon mutant library to study the molecular mechanisms involved in persistence of community-acquired S. aureus. Screening of the library for mutants defective in persistence or tolerance to rifampicin revealed many genes involved in metabolic pathways that are important for antibiotic persistence. In particular, the identified mutants belonged to metabolic pathways involved in carbohydrate, amino acid, lipid, vitamin and purine biosynthesis. Five mutants played a role in purine biosynthesis and two mutants, purB, an adenylosuccinate lyase, and purM, a phosphoribosylaminoimidazole synthetase, were selected for further confirmation. Mutants purB and purM showed defective persistence compared to the parental strain USA300 in multiple stress conditions including various antibiotics, low pH, and heat stress. The defect in persistence was restored by complementation with the wildtype purB and purM gene in the respective mutants. These findings provide new insights into the mechanisms of persistence in S. aureus and provide novel therapeutic targets for developing more effective treatment for persistent infections due to S. aureus.

  8. Purine 5‧,8-cyclo-2‧-deoxynucleoside lesions in irradiated DNA

    Science.gov (United States)

    Chatgilialoglu, Chryssostomos; Krokidis, Marios G.; Papadopoulos, Kyriakos; Terzidis, Michael A.

    2016-11-01

    Having their position gained among the smallest bulky DNA lesions recognized by the nucleotide excision repair (NER) enzyme, purine 5‧,8-cyclo-2‧-deoxynucleosides (5‧,8-cPu) are increasingly attracting the interest in the field of genome integrity in health and diseases. Exclusively generated by one of the most harmful of the reactive oxygen species, the hydroxyl radical, 5‧,8-cPu can be utilized also for highly valuable information regarding the oxidative status nearby the area where the genetic information is stored. Herein, we have collected the most recently reported biological studies, focusing on the repair mechanism of these lesions and their biological significance particularly in transcription. The LC-MS/MS quantification protocols that appeared in the literature are discussed in details, along with the reported values for the four 5‧,8-cPu produced by in vitro γ-radiolysis experiments with calf thymus DNA. Mechanistic insights in the formation of the purine 5‧,8-cyclo-2‧-deoxynucleosides and their chemical stability are also given in the light of their potential to be utilized as DNA biomarkers of oxidative stress.

  9. Purine-benzimidazole hybrids: synthesis, single crystal determination and in vitro evaluation of antitumor activities.

    Science.gov (United States)

    Sharma, Alka; Luxami, Vijay; Paul, Kamaldeep

    2015-03-26

    In an effort to identify novel compounds for the treatment of cancer, a diverse array of potential bioactive hybrid, purine-benzimidazole was synthesized in good yields through nucleophilic substitution at C6 position of purine ring with versatile cyclic amines at C2 position. The structures of newly prepared compounds were confirmed by IR, (1)H, (13)C NMR, mass spectroscopy and, in case of 19, by single crystal X-ray diffraction analysis. The newly synthesized compounds were evaluated against 60 human tumour cell lines at one dose concentration level. Compound 6 exhibited significant growth inhibition and was evaluated as 60 cell panel at five dose concentration levels. Compound 6 proved to be 1.25 fold more active than the positive control 5-FU, with GI50 value of 18.12 μM (MG-MID). Interaction of the compounds with Aurora-A enzyme involved in the process of propagation of cancer, has also been investigated. Compound 6 showed selectivity towards Aurora-A kinase inhibition with IC50 value of 0.0l μM. Molecular docking studies in the active binding site provided theoretical support for the experimental biological data acquired.

  10. MINYAK ATSIRI KUNYIT SEBAGAI ANTI RADANG PADA PENDERIT GOUT ARTRITIS DENGAN DIET TINGGI PURIN

    Directory of Open Access Journals (Sweden)

    Rondius Solfaine

    2010-12-01

    Full Text Available Curcuma Domestica Volatile Oil (Curcuma domestica, Val as Anti Inflamation Agent on Gout Arthritis Patient with High Purin Diet. Increased concentrations of crystal monosodium urea at joint and soft tissue represent induced of inflammation at gout arthritis (GA. Incidence and prevalence GA disseminate wide in developed countries in Asian range from 2-15% and In Indonesia, GA prevalence was 29% and mostly found in Minahasa, Toraja, and Batak ethnics. This research was aimed to analyse application of curcuma domestica volatile oil as anti inflammation agent on gout arthritis patient who has high purin diet and to assess specific cellular mediator Tumor Necrosis Factor-α (TNF-α. The design of the study was randomized pretest-posttest control group design with single blind treatment. The GCMS test was performed to identify active component in volatile oil. The sample was the new gout arthritis patient in Haji Public Hospital Surabaya. For a week, treatment group was assigned with volatile oil with dose 25 mg/kg body weight and the control group was given indometasin 150 mg/kg body weight. Blood samples were taken before and after treatment. Volatile oil of curcuma domestica (Curcuma domestica, val has four fraction of active component. There was decreasing in blood urea level in treatment group (p = 0.001 and control group (p = 0.007. Both in control and treatment group, there was also decreasing in TNF-α, however it was not statistically significant.

  11. A chaotic communication system of improved performance based on the Derivative-free nonlinear Kalman filter

    Science.gov (United States)

    Rigatos, Gerasimos

    2016-07-01

    The Derivative-free nonlinear Kalman Filter is used for developing a communication system that is based on a chaotic modulator such as the Duffing system. In the transmitter's side, the source of information undergoes modulation (encryption) in which a chaotic signal generated by the Duffing system is the carrier. The modulated signal is transmitted through a communication channel and at the receiver's side demodulation takes place, after exploiting the estimation provided about the state vector of the chaotic oscillator by the Derivative-free nonlinear Kalman Filter. Evaluation tests confirm that the proposed filtering method has improved performance over the Extended Kalman Filter and reduces significantly the rate of transmission errors. Moreover, it is shown that the proposed Derivative-free nonlinear Kalman Filter can work within a dual Kalman Filtering scheme, for performing simultaneously transmitter-receiver synchronisation and estimation of unknown coefficients of the communication channel.

  12. The association of dietary intake of purine-rich vegetables, sugar-sweetened beverages and dairy with plasma urate, in a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Lina Zgaga

    Full Text Available Hyperuricemia is a strong risk factor for gout. The incidence of gout and hyperuricemia has increased recently, which is thought to be, in part, due to changes in diet and lifestyle. Objective of this study was to investigate the association between plasma urate concentration and: a food items: dairy, sugar-sweetened beverages (SSB and purine-rich vegetables; b related nutrients: lactose, calcium and fructose.A total of 2,076 healthy participants (44% female from a population-based case-control study in Scotland (1999-2006 were included in this study. Dietary data was collected using a semi-quantitative food frequency questionnaire (FFQ. Nutrient intake was calculated using FFQ and composition of foods information. Urate concentration was measured in plasma.Mean urate concentration was 283.8±72.1 mmol/dL (females: 260.1±68.9 mmol/dL and males: 302.3±69.2 mmol/dL. Using multivariate regression analysis we found that dairy, calcium and lactose intakes were inversely associated with urate (p = 0.008, p = 0.003, p = 0.0007, respectively. Overall SSB consumption was positively associated with urate (p = 0.008, however, energy-adjusted fructose intake was not associated with urate (p = 0.66. The intake of purine-rich vegetables was not associated to plasma urate (p = 0.38.Our results suggest that limiting purine-rich vegetables intake for lowering plasma urate may be ineffectual, despite current recommendations. Although a positive association between plasma urate and SSB consumption was found, there was no association with fructose intake, suggesting that fructose is not the causal agent underlying the SSB-urate association. The abundant evidence supporting the inverse association between plasma urate concentration and dairy consumption should be reflected in dietary guidelines for hyperuricemic individuals and gout patients. Further research is needed to establish which nutrients and food products influence plasma urate

  13. Structure-based designing of sordarin derivative as potential fungicide with pan-fungal activity.

    Science.gov (United States)

    Chakraborty, Biprashekhar; Sejpal, Nikunjkumar Vinodray; Payghan, Pavan V; Ghoshal, Nanda; Sengupta, Jayati

    2016-05-01

    Fungal infections have become a significant problem for immunosuppressed patients. Sordarin, a promising fungicidal agent, inhibits fungal protein synthesis by impairing elongation factor-2 (eEF2) function. Intriguingly, despite high sequence similarity among eEF2s from different species, sordarin has been shown to inhibit translation specifically in certain fungi while unable to do so in some other fungal species (e.g. Candida parapsilosis and Candida lusitaniae). The sordarin binding site on eEF2 as well as its mechanism of action is known. In a previous study, we have detailed the interactions between sordarin and eEF2 cavities from different fungal species at the molecular level and predicted the probable cause of sordarin sensitivity. Guided by our previous analysis, we aimed for computer-aided designing of sordarin derivatives as potential fungicidal agents that still remain ineffective against human eEF2. We have performed structural knowledge-based designing of several sordarin derivatives and evaluated predicted interactions of those derivatives with the sordarin-binding cavities of different eEF2s, against which sordarin shows no inhibitory action. Our analyses identify an amino-pyrrole derivative as a good template for further designing of promising broad-spectrum antifungal agents. The drug likeness and ADMET prediction on this derivative also supports its suitability as a drug candidate.

  14. An elementary derivation of the hard/soft-acid/base principle.

    Science.gov (United States)

    Ayers, Paul W

    2005-04-08

    The hard/soft-acid/base (HSAB) principle indicates that hard acids prefer binding to hard bases (often forming bonds with substantial ionic character) while soft acids prefer binding to soft bases (often forming bonds with substantial covalent character). Though the HSAB principle is a foundational concept of the modern theory of acids and bases, the theoretical underpinnings of the HSAB principle remain murky. This paper examines the exchange reaction, wherein two molecules, one the product of reacting a hard acid and a soft base and the other the product of reacting a soft acid with a hard base, exchange substituents to form the preferred hard-hard and soft-soft product. A simple derivation shows that this reaction is exothermic, proving the validity of the HSAB principle. The analysis leads to the simple and conceptually appealing conclusion that the HSAB principle is a driven by simple electron transfer effects.

  15. Stereochemistry and spectroscopic analysis of bis-Betti base derivatives of 2,3-dihydroxynaphthalene.

    Science.gov (United States)

    Zamani, Mehdi; Shafiee, Mehdi; Keshavarz, Mohammad Hossein

    2016-04-01

    Density functional theory (DFT) was used to study the stereochemistry, thermodynamic stability, and spectra of recently synthesized bis-Betti base derivatives of 2,3-dihydroxynaphthalene obtained through multicomponent reactions of 2,3-dihydroxynaphthalene with aminoisoxazole and benzaldehyde derivatives. The stereochemistry of the products was investigated by theoretically calculating the infrared (IR) and proton nuclear magnetic resonance ((1)H NMR) spectra of the diastereomers and comparing them to the corresponding experimental data. The thermochemical properties of the reactions, including the enthalpy, internal energy, entropy, and Gibbs free energy, were also calculated. The diastereoselectivity of the reactions was estimated from the equilibrium distribution of diastereomers. According to the results, the synthesis of bis-Betti bases is exothermic and accompanied by a decrease in entropy. The energy difference between the diastereomers is quite small, but the Gibbs free energy change for the equilibrium syn anti favors the anti over syn configuration. These results are in good agreement with experimental observations.

  16. Synthesis of indazole based diarylurea derivatives and their antiproliferative activity against tumor cell lines.

    Science.gov (United States)

    Zhao, Cui-rong; Wang, Rui-qi; Li, Gang; Xue, Xiao-xia; Sun, Chang-jun; Qu, Xian-jun; Li, Wen-bao

    2013-04-01

    New series of indazole based diarylureas were synthesized and their anticancer activity against cancer cells H460, A549, OS-RC-2, HT-29, Lovo, HepG2, Bel-7402, SGC-7901 and MDA-MB-231 were examined. These derivatives of diarylureas, except azaindazole based diarylureas 5f, 5l and 5m, showed superior or similar activity against most of these selected cancer cell lines to the reference compound sorafenib. The effect of substituents on the indazole ring was also investigated. Derivatives with trifluoromenthy or halogen substituent on the indazole ring showed higher activity against the selected cancer cell lines than sorafenib. The acute toxicity assay showed that compounds 5a, 5b and 5i possessed lower toxicity than sorafenib. Compound 5i with 4-(trifluoromenthy)-1H-indazole and 4-(trifluoromenthy) benzene moieties exhibited the most potent anticancer activity.

  17. Physics-based and human-derived information fusion for analysts

    Science.gov (United States)

    Blasch, Erik; Nagy, James; Scott, Steve; Okoth, Joshua; Hinman, Michael

    2017-05-01

    Recent trends in physics-based and human-derived information fusion (PHIF) have amplified the capabilities of analysts; however with the big data opportunities there is a need for open architecture designs, methods of distributed team collaboration, and visualizations. In this paper, we explore recent trends in the information fusion to support user interaction and machine analytics. Challenging scenarios requiring PHIF include combing physics-based video data with human-derived text data for enhanced simultaneous tracking and identification. A driving effort would be to provide analysts with applications, tools, and interfaces that afford effective and affordable solutions for timely decision making. Fusion at scale should be developed to allow analysts to access data, call analytics routines, enter solutions, update models, and store results for distributed decision making.

  18. Comparing antioxidant capacity of purine alkaloids: a new, efficient trio for screening and discovering potential antioxidants in vitro and in vivo.

    Science.gov (United States)

    Tsoi, Bun; Yi, Ruo-Nan; Cao, Ling-Fang; Li, Shan-Bing; Tan, Rui-Rong; Chen, Min; Li, Xiao-Xiao; Wang, Chen; Li, Yi-Fang; Kurihara, Hiroshi; He, Rong-Rong

    2015-06-01

    The most commonly applied strategies for the evaluation of antioxidant capacity are the chemical- or cell-based approaches. However, the results obtained from these methods might not reflect the antioxidant ability of test samples within organisms. In this study, we propose a combination of experiments, including oxygen radical absorbance capacity (ORAC), cellular antioxidant activity assay (CAA), and the chick embryo model, as an efficient trio to evaluate antioxidant capacity of food components. Taking purine alkaloids as example, results demonstrate that chemical and cellular method might misinterpret their true ability on antioxidation. In chick embryo model, caffeine and theacrine can significantly improve vessel density on chorioallantoic membrane and myocardial apoptosis. The mechanism can be involving multiple targets within the organism. We believe that the trio proposed can be widely utilized in screening massive number of antioxidant in a cost-effective way. It will also help discovering new antioxidants that are easily being omitted due to their relatively poor in vitro activities.

  19. Interlaminar Stresses by Refined Beam Theories and the Sinc Method Based on Interpolation of Highest Derivative

    Science.gov (United States)

    Slemp, Wesley C. H.; Kapania, Rakesh K.; Tessler, Alexander

    2010-01-01

    Computation of interlaminar stresses from the higher-order shear and normal deformable beam theory and the refined zigzag theory was performed using the Sinc method based on Interpolation of Highest Derivative. The Sinc method based on Interpolation of Highest Derivative was proposed as an efficient method for determining through-the-thickness variations of interlaminar stresses from one- and two-dimensional analysis by integration of the equilibrium equations of three-dimensional elasticity. However, the use of traditional equivalent single layer theories often results in inaccuracies near the boundaries and when the lamina have extremely large differences in material properties. Interlaminar stresses in symmetric cross-ply laminated beams were obtained by solving the higher-order shear and normal deformable beam theory and the refined zigzag theory with the Sinc method based on Interpolation of Highest Derivative. Interlaminar stresses and bending stresses from the present approach were compared with a detailed finite element solution obtained by ABAQUS/Standard. The results illustrate the ease with which the Sinc method based on Interpolation of Highest Derivative can be used to obtain the through-the-thickness distributions of interlaminar stresses from the beam theories. Moreover, the results indicate that the refined zigzag theory is a substantial improvement over the Timoshenko beam theory due to the piecewise continuous displacement field which more accurately represents interlaminar discontinuities in the strain field. The higher-order shear and normal deformable beam theory more accurately captures the interlaminar stresses at the ends of the beam because it allows transverse normal strain. However, the continuous nature of the displacement field requires a large number of monomial terms before the interlaminar stresses are computed as accurately as the refined zigzag theory.

  20. χ measurements in Schiff’s base derivatives: Effect of metal nanoparticles

    Science.gov (United States)

    Sudheesh, P.; Chandrasekharan, K.

    2012-02-01

    The third-order nonlinear optical properties of Schiff's base derivatives and the effect of metal nanoparticles (Ag & Au) on their nonlinear optical response were studied. Colloidal metal nanoparticles were prepared by laser ablation. Z-scan technique with a 7ns Nd:YAG laser pulses at 532 nm were employed for the measurements. The compounds exhibit good optical limiting properties at the wavelength used. The materials used in the present work indicate that these materials are promising candidates for photonics applications.

  1. Synthesis and research of derived oxazol-5-ones based on α,β – unsaturated ketones

    Directory of Open Access Journals (Sweden)

    Сергей Александрович Петров

    2015-11-01

    Full Text Available The article deals with the production of new fluorescent dyes derived oxazol-5-ones based on α, β-unsaturated ketones, as well as confirmation of the structure of the compounds obtained using NMR and IR spectroscopy. The dyes of this series are relevant because one of the important practical problems in organic chemistry and chemical technology is currently seeking new fluorescent dyes for dyeing polyester materials and polymers

  2. Synthesis and research of derived oxazol-5-ones based on α,β – unsaturated ketones

    OpenAIRE

    Сергей Александрович Петров

    2015-01-01

    The article deals with the production of new fluorescent dyes derived oxazol-5-ones based on α, β-unsaturated ketones, as well as confirmation of the structure of the compounds obtained using NMR and IR spectroscopy. The dyes of this series are relevant because one of the important practical problems in organic chemistry and chemical technology is currently seeking new fluorescent dyes for dyeing polyester materials and polymers

  3. Ubiquinol (QH(2)) functions as a negative regulator of purine nucleotide inhibition of Acanthamoeba castellanii mitochondrial uncoupling protein.

    Science.gov (United States)

    Woyda-Ploszczyca, Andrzej; Jarmuszkiewicz, Wieslawa

    2011-01-01

    We compared the influence of different adenine and guanine nucleotides on the free fatty acid-induced uncoupling protein (UCP) activity in non-phosphorylating Acanthamoeba castellanii mitochondria when the membranous ubiquinone (Q) redox state was varied. The purine nucleotides exhibit an inhibitory effect in the following descending order: GTP>ATP>GDP>ADP≫GMP>AMP. The efficiency of guanine and adenine nucleotides to inhibit UCP-sustained uncoupling in A. castellanii mitochondria depends on the Q redox state. Inhibition by purine nucleotides can be increased with decreasing Q reduction level (thereby ubiquinol, QH₂ concentration) even with nucleoside monophosphates that are very weak inhibitors at the initial respiration. On the other hand, the inhibition can be alleviated with increasing Q reduction level (thereby QH₂ concentration). The most important finding was that ubiquinol (QH₂) but not oxidised Q functions as a negative regulator of UCP inhibition by purine nucleotides. For a given concentration of QH₂, the linoleic acid-induced GTP-inhibited H(+) leak was the same for two types of A. castellanii mitochondria that differ in the endogenous Q content. When availability of the inhibitor (GTP) or the negative inhibition modulator (QH₂) was changed, a competitive influence on the UCP activity was observed. QH₂ decreases the affinity of UCP for GTP and, vice versa, GTP decreases the affinity of UCP for QH₂. These results describe the kinetic mechanism of regulation of UCP affinity for purine nucleotides by endogenous QH₂ in the mitochondria of a unicellular eukaryote.

  4. Consortium analysis of gene and gene–folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk

    DEFF Research Database (Denmark)

    Kelemen, Linda E; Terry, Kathryn L; Goodman, Marc T

    2014-01-01

    SCOPE: We reevaluated previously reported associations between variants in pathways of one-carbon (1-C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake. METHODS AND RESULTS: Odds rat...

  5. Subcellular location of the enzymes of purine breakdown in the yeast Candida famata grown on uric acid

    NARCIS (Netherlands)

    Large, Peter J.; Waterham, Hans R.; Veenhuis, Marten

    1990-01-01

    The subcellular location of the enzymes of purine breakdown in the yeast Candida famata, which grows on uric acid as sole carbon and nitrogen source, has been examined by subcellular fractionation methods. Uricase was confirmed as being peroxisomal, but the other three enzymes, allantoinase, allanto

  6. Involvement of the ribose operon repressor RbsR in regulation of purine nucleotide synthesis in Escherichia coli.

    Science.gov (United States)

    Shimada, Tomohiro; Kori, Ayako; Ishihama, Akira

    2013-07-01

    Escherichia coli is able to utilize d-ribose as its sole carbon source. The genes for the transport and initial-step metabolism of d-ribose form a single rbsDACBK operon. RbsABC forms the ABC-type high-affinity d-ribose transporter, while RbsD and RbsK are involved in the conversion of d-ribose into d-ribose 5-phosphate. In the absence of inducer d-ribose, the ribose operon is repressed by a LacI-type transcription factor RbsR, which is encoded by a gene located downstream of this ribose operon. At present, the rbs operon is believed to be the only target of regulation by RbsR. After Genomic SELEX screening, however, we have identified that RbsR binds not only to the rbs promoter but also to the promoters of a set of genes involved in purine nucleotide metabolism. Northern blotting analysis indicated that RbsR represses the purHD operon for de novo synthesis of purine nucleotide but activates the add and udk genes involved in the salvage pathway of purine nucleotide synthesis. Taken together, we propose that RbsR is a global regulator for switch control between the de novo synthesis of purine nucleotides and its salvage pathway.

  7. Prodrugs of purine and pyrimidine analogues for the intestinal di/tri-peptide transporter PepT1

    DEFF Research Database (Denmark)

    Thomsen, Anne Engelbrecht; Friedrichsen, Gerda Marie; Sørensen, Arne Hagsten

    2003-01-01

    A general drug delivery approach for increasing oral bioavailability of purine and pyrimidine analogues such as acyclovir may be to link these compounds reversibly to stabilized dipeptide pro-moieties with affinity for the human intestinal di/tri-peptide transporter, hPepT1. In the present study...

  8. Derivation of Relationships between Spectral Vegetation Indices from Multiple Sensors Based on Vegetation Isolines

    Directory of Open Access Journals (Sweden)

    Kenta Obata

    2012-02-01

    Full Text Available An analytical form of relationship between spectral vegetation indices (VI is derived in the context of cross calibration and translation of vegetation index products from different sensors. The derivation has been carried out based on vegetation isoline equations that relate two reflectance values observed at different wavelength ranges often represented by spectral band passes. The derivation was first introduced and explained conceptually by assuming a general functional form for VI model equation. This process is universal by which two VIs of different sensors and/or different model equations can be related conceptually. The general process was then applied to the actual case of normalized difference vegetation index (NDVI from two sensors in a framework of inter-sensor continuity. The derivation results indicate that the NDVI from one sensor can be approximated by a rational function of NDVI from the other sensor as a parameter. Similar result was obtained for the case of soil adjusted VI, enhanced VI, and two-band variance of enhanced VI.

  9. Facial Expression Recognition Based on Features Derived From the Distinct LBP and GLCM

    Directory of Open Access Journals (Sweden)

    Gorti Satyanarayana Murty

    2014-01-01

    Full Text Available Automatic recognition of facial expressions can be an important component of natural human-machine interfaces; it may also be used in behavioural science and in clinical practice. Although humans recognise facial expressions virtually without effort or delay, reliable expression recognition by machine is still a challenge. This paper, presents recognition of facial expression by integrating the features derived from Grey Level Co-occurrence Matrix (GLCM with a new structural approach derived from distinct LBP’s (DLBP ona 3 x 3 First order Compressed Image (FCI. The proposed method precisely recognizes the 7 categories of expressions i.e.: neutral, happiness, sadness, surprise, anger, disgust and fear. The proposed method contains three phases. In the first phase each 5 x 5 sub image is compressed into a 3 x 3 sub image. The second phase derives two distinct LBP’s (DLBP using the Triangular patterns between the upper and lower parts of the 3 x 3 sub image. In the third phase GLCM is constructed based on the DLBP’s and feature parameters are evaluated for precise facial expression recognition. The derived DLBP is effective because it integrated with GLCM and provides better classification performance. The proposed method overcomes the disadvantages of statistical and formal LBP methods in estimating the facial expressions. The experimental results demonstrate the effectiveness of the proposed method on facial expression recognition.

  10. Syntheses of Azo-Imine Derivatives from Vanillin as an Acid Base Indicator

    Directory of Open Access Journals (Sweden)

    Bambang Purwono

    2013-05-01

    Full Text Available Preparations of azo, imine and azo-imine derivatives from vanillin as an indicator of acid-base titration have been carried out. The azo derivative of 4-hydroxy-3-methoxy-5-(phenylazobenzaldehyde 2 was produced by diazotitation reaction of vanillin in 37.04% yield. The azo product was then refluxed with aniline in ethanol to yield azo-imine derivatives, 2-methoxy-6-(phenylazo-4-((phenyliminomethylphenol 1 in 82.21% yield. The imine derivative, 2-methoxy-4-((phenyliminomethyl-phenol 3 was obtained by refluxing of vanillin and aniline mixture in ethanol solvent and produced 82.17% yield. The imine product was then reacted with benzenediazonium chloride salt. However, the products indicated hydrolyzed product of 4-hydroxy-3-methoxy-5-(phenylazobenzaldehyde 2 in 22.15% yield. The 2-methoxy-4-((phenyliminomethylphenol 2 could be used as an indicator for titration of NaOH by H2C2O4 with maximum concentration of H2C2O4 0.1 M while the target compound 1 could be used as titration indicator for titration of NaOH with H2C2O4 with same result using phenolphthalein indicator.

  11. Site-specific water quality guidelines: 1. Derivation approaches based on physicochemical, ecotoxicological and ecological data.

    Science.gov (United States)

    van Dam, R A; Humphrey, C L; Harford, A J; Sinclair, A; Jones, D R; Davies, S; Storey, A W

    2014-01-01

    Generic water quality guidelines (WQGs) are developed by countries/regions as broad scale tools to assist with the protection of aquatic ecosystems from the impacts of toxicants. However, since generic WQGs cannot adequately account for the many environmental factors that may affect toxicity at a particular site, site-specific WQGs are often needed, especially for high environmental value ecosystems. The Australian and New Zealand Guidelines for Fresh and Marine Water Quality provide comprehensive guidance on methods for refining or deriving WQGs for site-specific purposes. This paper describes three such methods for deriving site-specific WQGs, namely: (1) using local reference water quality data, (2) using biological effects data from laboratory-based toxicity testing, and (3) using biological effects data from field surveys. Two case studies related to the assessment of impacts arising from mining operations in northern Australia are used to illustrate the application of these methods. Finally, the potential of several emerging methods designed to assess thresholds of ecological change from field data for deriving site-specific WQGs is discussed. Ideally, multiple lines of evidence approaches, integrating both laboratory and field data, are recommended for deriving site-specific WQGs.

  12. Design of quadrature mirror filter bank using Lagrange multiplier method based on fractional derivative constraints

    Directory of Open Access Journals (Sweden)

    B. Kuldeep

    2015-06-01

    Full Text Available Fractional calculus has recently been identified as a very important mathematical tool in the field of signal processing. Digital filters designed by fractional derivatives give more accurate frequency response in the prescribed frequency region. Digital filters are most important part of multi-rate filter bank systems. In this paper, an improved method based on fractional derivative constraints is presented for the design of two-channel quadrature mirror filter (QMF bank. The design problem is formulated as minimization of L2 error of filter bank transfer function in passband, stopband interval and at quadrature frequency, and then Lagrange multiplier method with fractional derivative constraints is applied to solve it. The proposed method is then successfully applied for the design of two-channel QMF bank with higher order filter taps. Performance of the QMF bank design is then examined through study of various parameters such as passband error, stopband error, transition band error, peak reconstruction error (PRE, stopband attenuation (As. It is found that, the good design can be obtained with the change of number and value of fractional derivative constraint coefficients.

  13. Synthesis of Some Novel Heterocyclic and Schiff Base Derivatives as Antimicrobial Agents

    Directory of Open Access Journals (Sweden)

    Mohamed E. Azab

    2015-10-01

    Full Text Available Treatment of 2,3-diaryloxirane-2,3-dicarbonitriles 1a–c with different nitrogen nucleophiles, e.g., hydrazine, methyl hydrazine, phenyl hydrazine, hydroxylamine, thiosemicarbazide, and/or 2-amino-5-phenyl-1,3,4-thiadiazole, afforded pyrazole, isoxazole, pyrrolotriazine, imidazolothiadiazole derivatives 2–5, respectively. Reacting pyrazoles 2a–c with aromatic aldehydes and/or methyl glycinate produced Schiff’s bases 7a–d and pyrazolo[3,4-b]-pyrazinone derivative 8, respectively. Treating 7 with ammonium acetate and/or hydrazine hydrate, furnished the imidazolopyrazole and pyrazolotriazine derivatives 9 and 10, respectively. Reaction of 8 with chloroacetic acid and/or diethyl malonate gave tricyclic compound 11 and triketone 12, respectively. On the other hand, compound 1 was reacted with active methylene precursors, e.g., acetylacetone and/or cyclopentanone producing adducts 14a,b which upon fusion with ammonium acetate furnished the 3-pyridone derivatives 15a,b, respectively. Some of newly synthesized compounds were screened for activity against bacterial and fungal strains and most of the newly synthesized compounds showed high antimicrobial activities. The structures of the new compounds were elucidated using IR, 1H-NMR, 13C-NMR and mass spectroscopy.

  14. The scenario-based approach adopted in the ELECTRA project for deriving innovate control room functionality

    DEFF Research Database (Denmark)

    Marinelli, Mattia; Heussen, Kai; Prostejovsky, Alexander

    2017-01-01

    . The paper intends to outline the methodology adopted, which is based on the cognitive work analysis framework, to provide an overview of the most interesting scenarios and to summarize the requirements analysis results. In order to derive required control room functionality, a set of relevant control room...... scenarios have been identified based on the Web-of-Cells control concept. We considered scenarios that challenge traditional control schemes, scenarios that caused major failures (i.e., blackouts) and scenarios that can be expected to appear in the future. For each scenario, information concerning network...

  15. Fluorescence Properties and Electrochemical Behavior of Some Schiff Bases Derived from N-Aminopyrimidine.

    Science.gov (United States)

    Gulcan, Mehmet; Doğru, Ümit; Öztürk, Gülsiye; Levent, Abdulkadir; Akbaş, Esvet

    2014-03-01

    A series of Schiff bases (L 1 , L 2 and L 3) were prepared by refluxing aromatic aldehydes with N-Aminopyrimidine derivatives in methanol and ethanol. The structures of synthesized compounds were characterized by FTIR, (1)H NMR, (13)C NMR and microanalysis. The electrochemical behaviors of the Schiff base ligands were also discussed. Moreover, the evaluation of absorption and emission properties of the structures were carried out in five different solvents. The products show visible absorption maxima in the range of 304-576 nm, and emission maxima from 636 to 736 nm in all solvents tested.

  16. Synthesis of vegetable oil based polyol with cottonseed oil and sorbitol derived from natural source

    Institute of Scientific and Technical Information of China (English)

    Lian Kun Jia; Li Xiang Gong; Wen Jiao Ji; Cheng You Kan

    2011-01-01

    In order to prepare the polyol with all bio-based components as raw materials, cottonseed oil was first epoxidized by peroxyformic acid generated in situ from hydrogen peroxide and formic acid, and the cottonseed oil based polyols with variable hydroxyl value were then prepared by the ring-opening of epoxidized cottonseed oil with sorbitol, which is a multi-functional hydroxyl compound derived from a natural source. The chemical structure of the products was characterized with FTIR analysis, and the residual epoxy oxygen content and hydroxyl value of the polyol versus the ring-opening time were investigated.

  17. Synthesis, crystal structure and redox properties of dihydropyrazole-bridged ferrocene-based derivatives

    Science.gov (United States)

    Li, Heng-Dong; Ma, Zai-He; Yang, Kun; Xie, Li-Li; Yuan, Yao-Feng

    2012-09-01

    Dihydropyrazole-bridged ferrocene-based derivatives were prepared by corresponding chalcones with hydrazine hydrate, then acylation with 3-(ethoxycarbonyl)propionyl chloride directly in high yields and purity. All of these compounds were characterized by MS, IR, 1H NMR, 13C NMR and elemental analysis. The relationship between the structure and redox properties was investigated based on the results of single crystal X-ray structure determinations and cyclic voltammetry. The mechanism of the electron transfer for representative compound 4b was verified by density functional theory (DFT) calculations.

  18. Insights into Phosphate Cooperativity and Influence of Substrate Modifications on Binding and Catalysis of Hexameric Purine Nucleoside Phosphorylases

    Science.gov (United States)

    de Giuseppe, Priscila O.; Martins, Nadia H.; Meza, Andreia N.; dos Santos, Camila R.; Pereira, Humberto D’Muniz; Murakami, Mario T.

    2012-01-01

    The hexameric purine nucleoside phosphorylase from Bacillus subtilis (BsPNP233) displays great potential to produce nucleoside analogues in industry and can be exploited in the development of new anti-tumor gene therapies. In order to provide structural basis for enzyme and substrates rational optimization, aiming at those applications, the present work shows a thorough and detailed structural description of the binding mode of substrates and nucleoside analogues to the active site of the hexameric BsPNP233. Here we report the crystal structure of BsPNP233 in the apo form and in complex with 11 ligands, including clinically relevant compounds. The crystal structure of six ligands (adenine, 2′deoxyguanosine, aciclovir, ganciclovir, 8-bromoguanosine, 6-chloroguanosine) in complex with a hexameric PNP are presented for the first time. Our data showed that free bases adopt alternative conformations in the BsPNP233 active site and indicated that binding of the co-substrate (2′deoxy)ribose 1-phosphate might contribute for stabilizing the bases in a favorable orientation for catalysis. The BsPNP233-adenosine complex revealed that a hydrogen bond between the 5′ hydroxyl group of adenosine and Arg43* side chain contributes for the ribosyl radical to adopt an unusual C3’-endo conformation. The structures with 6-chloroguanosine and 8-bromoguanosine pointed out that the Cl6 and Br8 substrate modifications seem to be detrimental for catalysis and can be explored in the design of inhibitors for hexameric PNPs from pathogens. Our data also corroborated the competitive inhibition mechanism of hexameric PNPs by tubercidin and suggested that the acyclic nucleoside ganciclovir is a better inhibitor for hexameric PNPs than aciclovir. Furthermore, comparative structural analyses indicated that the replacement of Ser90 by a threonine in the B. cereus hexameric adenosine phosphorylase (Thr91) is responsible for the lack of negative cooperativity of phosphate binding in this

  19. Insights into phosphate cooperativity and influence of substrate modifications on binding and catalysis of hexameric purine nucleoside phosphorylases.

    Directory of Open Access Journals (Sweden)

    Priscila O de Giuseppe

    Full Text Available The hexameric purine nucleoside phosphorylase from Bacillus subtilis (BsPNP233 displays great potential to produce nucleoside analogues in industry and can be exploited in the development of new anti-tumor gene therapies. In order to provide structural basis for enzyme and substrates rational optimization, aiming at those applications, the present work shows a thorough and detailed structural description of the binding mode of substrates and nucleoside analogues to the active site of the hexameric BsPNP233. Here we report the crystal structure of BsPNP233 in the apo form and in complex with 11 ligands, including clinically relevant compounds. The crystal structure of six ligands (adenine, 2'deoxyguanosine, aciclovir, ganciclovir, 8-bromoguanosine, 6-chloroguanosine in complex with a hexameric PNP are presented for the first time. Our data showed that free bases adopt alternative conformations in the BsPNP233 active site and indicated that binding of the co-substrate (2'deoxyribose 1-phosphate might contribute for stabilizing the bases in a favorable orientation for catalysis. The BsPNP233-adenosine complex revealed that a hydrogen bond between the 5' hydroxyl group of adenosine and Arg(43* side chain contributes for the ribosyl radical to adopt an unusual C3'-endo conformation. The structures with 6-chloroguanosine and 8-bromoguanosine pointed out that the Cl(6 and Br(8 substrate modifications seem to be detrimental for catalysis and can be explored in the design of inhibitors for hexameric PNPs from pathogens. Our data also corroborated the competitive inhibition mechanism of hexameric PNPs by tubercidin and suggested that the acyclic nucleoside ganciclovir is a better inhibitor for hexameric PNPs than aciclovir. Furthermore, comparative structural analyses indicated that the replacement of Ser(90 by a threonine in the B. cereus hexameric adenosine phosphorylase (Thr(91 is responsible for the lack of negative cooperativity of phosphate binding

  20. Carbon-Based Functional Materials Derived from Waste for Water Remediation and Energy Storage.

    Science.gov (United States)

    Ma, Qinglang; Yu, Yifu; Sindoro, Melinda; Fane, Anthony G; Wang, Rong; Zhang, Hua

    2017-04-01

    Carbon-based functional materials hold the key for solving global challenges in the areas of water scarcity and the energy crisis. Although carbon nanotubes (CNTs) and graphene have shown promising results in various fields of application, their high preparation cost and low production yield still dramatically hinder their wide practical applications. Therefore, there is an urgent call for preparing carbon-based functional materials from low-cost, abundant, and sustainable sources. Recent innovative strategies have been developed to convert various waste materials into valuable carbon-based functional materials. These waste-derived carbon-based functional materials have shown great potential in many applications, especially as sorbents for water remediation and electrodes for energy storage. Here, the research progress in the preparation of waste-derived carbon-based functional materials is summarized, along with their applications in water remediation and energy storage; challenges and future research directions in this emerging research field are also discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Lightweight and Distributed Connectivity-Based Clustering Derived from Schelling's Model

    Science.gov (United States)

    Tsugawa, Sho; Ohsaki, Hiroyuki; Imase, Makoto

    In the literature, two connectivity-based distributed clustering schemes exist: CDC (Connectivity-based Distributed node Clustering scheme) and SDC (SCM-based Distributed Clustering). While CDC and SDC have mechanisms for maintaining clusters against nodes joining and leaving, neither method assumes that frequent changes occur in the network topology. In this paper, we propose a lightweight distributed clustering method that we term SBDC (Schelling-Based Distributed Clustering) since this scheme is derived from Schelling's model — a popular segregation model in sociology. We evaluate the effectiveness of the proposed SBDC in an environment where frequent changes arise in the network topology. Our simulation results show that SBDC outperforms CDC and SDC under frequent changes in network topology caused by high node mobility.

  2. Single-Phase Phase-Locked Loop Based on Derivative Elements

    DEFF Research Database (Denmark)

    Guan, Qingxin; Zhang, Yu; Kang, Yong

    2017-01-01

    High-performance phase-locked loops (PLLs) are critical for power control in grid-connected systems. This paper presents a new method of designing a PLL for single-phase systems based on derivative elements (DEs). The quadrature signal generator (QSG) is constructed by two DEs with the same...... parameters. The PLL itself is realized by using the DE-based QSG. It avoids errors due to the overlap and accumulation that are present in PLLs based on integral elements, such as a PLL based on a second-order generalized integrator. Additionally, frequency feedback is not needed which allows the proposed...... PLL to achieve high performance when the grid frequency changes rapidly. This paper presents the model of the PLL and a theoretical performance analysis with respect to both the frequency-domain and time-domain behavior. The error arising from the discretization process is also compensated, ensuring...

  3. Fast repair of purine deoxynucleotide radical cations by rutin and quercetin

    Institute of Scientific and Technical Information of China (English)

    赵晨阳; 石益民; 王文锋; 贾忠建; 姚思德; 范波涛; 郑荣梁

    2001-01-01

    Repair effects of rutin and quercetin on purine deoxynucleotide radical cations were studied using pulse radiolysis technique. On electron pulse irradiation of N2 saturated deoxynucleotide aqueous solution containing 20 mmol/L K2S2O8, 200 mmol/L t-BuOH and rutin or quercetin, the transient absorption spectra of the deoxynucleotide radical cations decayed quickly. At the same time, the spectra of flavonoid phenoxyl radicals formed within several dozen microseconds. The results indicated that deoxynucleotide radical cations can be repaired by flavonoids. The rate constants of the repair reactions were 3.8×108-4.4×108 mol-1·L·s-1 and 1.3×108-1.8×108 mol-1·L·s-1 for dAMP and dGMP radical cations, respectively.

  4. Inhibition and Structure of Trichomonas vaginalis Purine Nucleoside Phosphorylase with Picomolar Transition State Analogues

    Energy Technology Data Exchange (ETDEWEB)

    Rinaldo-Matthis,A.; Wing, C.; Ghanem, M.; Deng, H.; Wu, P.; Gupta, A.; Tyler, P.; Evans, G.; Furneaux, R.; et al.

    2007-01-01

    Trichomonas vaginalis is a parasitic protozoan purine auxotroph possessing a unique purine salvage pathway consisting of a bacterial type purine nucleoside phosphorylase (PNP) and a purine nucleoside kinase. Thus, T. vaginalis PNP (TvPNP) functions in the reverse direction relative to the PNPs in other organisms. Immucillin-A (ImmA) and DADMe-Immucillin-A (DADMe-ImmA) are transition stte mimics of adenosine with geometric and electrostatic features that resemble early and late transition states of adenosine at the transition state stabilized by TvPNP. ImmA demonstrates slow-onset tight-binding inhibition with TvPNP, to give an equilibrium dissociation constant of 87 pM, an inhibitor release half-time of 17.2 min, and a K{sub m}/K{sub d} ratio of 70,100. DADMe-ImmA resembles a late ribooxacarbenium ion transition state for TvPNP to give a dissociation constant of 30 pM, an inhibitor release half-time of 64 min, and a K{sub m}/K{sub d} ratio of 203,300. The tight binding of DADMe-ImmA supports a late S{sub N}1 transition state. Despite their tight binding to TvPNP, ImmA and DADMe-ImmA are weak inhibitors of human and P. falciparum PNPs. The crystal structures of the TvPNP-ImmA{center_dot}PO{sub 4} and TvPNP{center_dot}DADMe-ImmA{center_dot}PO{sub 4} ternary complexes differ from previous structures with substrate anologues. The tight binding with DADMe-ImmA is in part due to a 2.7 {angstrom} ionic interaction between a PO{sub 4} oxygen and the N1 cation of the hydroxypyrrolidine and is weaker in the TvPNP{center_dot}ImmA{center_dot}PO{sub 4} structure at 3.5 {angstrom}. However, the TvPNP{center_dot}ImmA{center_dot}PO{sub 4} structure includes hydrogen bonds between the 2'-hydroxyl and the protein that are not present in TvPNP{center_dot}DADMe-ImmA{center_dot}PO{sub 4}. These structures explain why DADMe-ImmA binds tighter than ImmA. Immucillin-H is a 12 nM inhibitor of TvPNP but a 56 pM inhibitor of human PNP. And this difference is explained by isotope

  5. Synthesis, Characterization and Antimicrobial Activities of Some New Heterocyclic Schiff Bases Derived from Thiocarbohydrazide.

    Science.gov (United States)

    El-Mahdy, Kamelia; El-Kazak, Azza; Abdel-Megid, Mohamed; Seada, Magdyand; Farouk, Osama

    2016-01-01

    The reaction of prazolobenzothienopyrimidine-3-carbaldehyde 1 with thiocarbohydrazide afforded the Schiff's base 3. The latter compound reacted with some electrophilic reagents to give 1,2,4-triazoles 4-6 and 1,2,4-triazines 7-9. Treatment of compound 3 with 2-cyano-3,3-bis(methylthio)acrylonitrile gave the corresponding 5-amino-4-cyano-3-methylthiopyrazole derivative 11. The reaction of pyrazole 11 with carbon disulfide afforded dithioxopyrazolopyrimidine 12. Acylation of compound 11 by using acetic anhydride yielded acetamide 13. On the other hand, the cyclocondensation of pyrazole 11 with acetic anhydride in pyridine yielded pyrazolopyrimidine derivative 14. The reactivity of compound 11 towards formamide and phenylisothiocyanate to give the pyrazolopyrimidines 15 and 16 was studied. The newly synthesized compounds were screened for their antimicrobial activity.

  6. Induced cholesteric systems based on some cyano derivatives as host phases

    Science.gov (United States)

    Shkolnikova, Natalya I.; Kutulya, Lidiya A.; Vashchenko, V. V.; Fedoryako, A. P.; Lapanik, V. I.; Posledovich, N. R.

    2002-12-01

    Macroscopical properties of some induced cholesteric compositions based on 4-pentyl-4'-cyano derivatives of biphenyl and phenylcyclohexane as host phases have been investigated. The series of N-arylidene derivatives of (S)-1-phenylethylamine with varied both rigid moiety of the N-arylidene fragment and terminal substituent was used as chiral dopants. The influence of the chiral dopant molecular structure as well as of physical properties of the host phases used on the helical twisting power, the temperature dependence of the induced helical pitch and the N* mesophase thermal stability has been characterized. It has been concluded that the distinctions in properties of the LC systems containing the OCH2 and COO linking groups are caused by their different conformational states.

  7. Fingerprint Image Enhancement Based on Second Directional Derivative of the Digital Image

    Directory of Open Access Journals (Sweden)

    Onnia Vesa

    2002-01-01

    Full Text Available This paper presents a novel approach of fingerprint image enhancement that relies on detecting the fingerprint ridges as image regions where the second directional derivative of the digital image is positive. A facet model is used in order to approximate the derivatives at each image pixel based on the intensity values of pixels located in a certain neighborhood. We note that the size of this neighborhood has a critical role in achieving accurate enhancement results. Using neighborhoods of various sizes, the proposed algorithm determines several candidate binary representations of the input fingerprint pattern. Subsequently, an output binary ridge-map image is created by selecting image zones, from the available binary image candidates, according to a MAP selection rule. Two public domain collections of fingerprint images are used in order to objectively assess the performance of the proposed fingerprint image enhancement approach.

  8. Deformation analysis of polymers composites: rheological model involving time-based fractional derivative

    DEFF Research Database (Denmark)

    Zhou, H. W.; Yi, H. Y.; Mishnaevsky, Leon

    2016-01-01

    A modeling approach to time-dependent property of Glass Fiber Reinforced Polymers (GFRP) composites is of special interest for quantitative description of long-term behavior. An electronic creep machine is employed to investigate the time-dependent deformation of four specimens of dog......-bond-shaped GFRP composites at various stress level. A negative exponent function based on structural changes is introduced to describe the damage evolution of material properties in the process of creep test. Accordingly, a new creep constitutive equation, referred to fractional derivative Maxwell model...... by the fractional derivative Maxwell model proposed in the paper are in a good agreement with the experimental data. It is shown that the new creep constitutive model proposed in the paper needs few parameters to represent various time-dependent behaviors....

  9. Origami mechanical metamaterials based on the Miura-derivative fold patterns

    Science.gov (United States)

    Zhou, Xiang; Zang, Shixi; You, Zhong

    2016-07-01

    This paper presents two new types of origami-inspired mechanical metamaterials based on the Miura-derivative fold patterns that consist of non-identical parallelogram facets. The analytical models to predict dimension changes and deformation kinematics of the proposed metamaterials are developed. Furthermore, by modelling the creases as revolute hinges with certain rotational spring constants, we derived analytical models for stretching and bulk moduli. The analytical models are validated through finite-element simulation results. Numerical examples reveal that the proposed metamaterials possess some intriguing properties, including negative Poisson's ratios and bulk modulus. The work presented in this paper can provide a highly flexible framework for the design of versatile tunable mechanical metamaterials.

  10. Pre-conceptual-schema-based patterns for deriving key performance indicators from strategic objectives

    Directory of Open Access Journals (Sweden)

    Carlos Mario Zapata Jaramillo

    2017-05-01

    Full Text Available Performance measurement is crucial for achieving business success. Moreover, such success is also related to the fulfillment of the organizational strategic objectives. Hence, an adequate determination of relevant performance indicators—or key performance indicators (KPIs—and their relationships to organizational objectives is needed. Even though several approaches for treating KPIs and objective-KPI relationships have been proposed, they exhibit some drawbacks associated with the lack of reusability and traceability. We attempt to fill this gap by proposing a set of patterns based on pre-conceptual schemas for supporting the systematic derivation of KPIs and their relationships to organizational objectives. In this way, the proposed patterns guarantee a reusable and traceable derivation process of a set of candidate KPIs from organizational strategic objectives. Lastly, we provide a lab study in order to illustrate the usefulness of this proposal.

  11. Luminescent liquid crystalline materials based on palladium(II) imine derivatives containing the 2-phenylpyridine core.

    Science.gov (United States)

    Micutz, Marin; Iliş, Monica; Staicu, Teodora; Dumitraşcu, Florea; Pasuk, Iuliana; Molard, Yann; Roisnel, Thierry; Cîrcu, Viorel

    2014-01-21

    In this work we report our studies concerning the synthesis and characterisation of a series of imine derivatives that incorporate the 2-phenylpyridine (2-ppy) core. These derivatives were used in the cyclometalating reactions of platinum(II) or palladium(II) in order to prepare several complexes with liquid crystalline properties. Depending on the starting materials used as well as the solvents employed, different metal complexes were obtained, some of them showing both liquid crystalline behaviour and luminescence properties at room temperature. It was found that, even if there are two competing coordination sites, the cyclometalation process takes place always at the 2-ppy core with (for Pt) or without (for Pd) the imine bond cleavage. We successfully showed that it is possible to prepare emissive room temperature liquid crystalline materials based on double cyclopalladated heteroleptic complexes by varying the volume fraction of the long flexible alkyl tails on the ancillary benzoylthiourea (BTU) ligands.

  12. Molecular and biochemical characterization of caffeine synthase and purine alkaloid concentration in guarana fruit.

    Science.gov (United States)

    Schimpl, Flávia Camila; Kiyota, Eduardo; Mayer, Juliana Lischka Sampaio; Gonçalves, José Francisco de Carvalho; da Silva, José Ferreira; Mazzafera, Paulo

    2014-09-01

    Guarana seeds have the highest caffeine concentration among plants accumulating purine alkaloids, but in contrast with coffee and tea, practically nothing is known about caffeine metabolism in this Amazonian plant. In this study, the levels of purine alkaloids in tissues of five guarana cultivars were determined. Theobromine was the main alkaloid that accumulated in leaves, stems, inflorescences and pericarps of fruit, while caffeine accumulated in the seeds and reached levels from 3.3% to 5.8%. In all tissues analysed, the alkaloid concentration, whether theobromine or caffeine, was higher in young/immature tissues, then decreasing with plant development/maturation. Caffeine synthase activity was highest in seeds of immature fruit. A nucleotide sequence (PcCS) was assembled with sequences retrieved from the EST database REALGENE using sequences of caffeine synthase from coffee and tea, whose expression was also highest in seeds from immature fruit. The PcCS has 1083bp and the protein sequence has greater similarity and identity with the caffeine synthase from cocoa (BTS1) and tea (TCS1). A recombinant PcCS allowed functional characterization of the enzyme as a bifunctional CS, able to catalyse the methylation of 7-methylxanthine to theobromine (3,7-dimethylxanthine), and theobromine to caffeine (1,3,7-trimethylxanthine), respectively. Among several substrates tested, PcCS showed higher affinity for theobromine, differing from all other caffeine synthases described so far, which have higher affinity for paraxanthine. When compared to previous knowledge on the protein structure of coffee caffeine synthase, the unique substrate affinity of PcCS is probably explained by the amino acid residues found in the active site of the predicted protein.

  13. Purine-rich foods, protein intake, and the prevalence of hyperuricemia: the Shanghai Men's Health Study.

    Science.gov (United States)

    Villegas, R; Xiang, Y-B; Elasy, T; Xu, W H; Cai, H; Cai, Q; Linton, M F; Fazio, S; Zheng, W; Shu, X-O

    2012-05-01

    Diet may play an important role in the development of hyperuricemia and gout. However, the association between dietary factors and hyperuricemia remains unclear, and few studies have investigated direct links between food intake and hyperuricemia. The aim of this study was to investigate associations between high purine-content foods and protein intake with the prevalence of hyperuricemia by using data from a cross-sectional study of 3978 men aged 40-74 yrs living in Shanghai, China. Hyperuricemia was defined as blood uric acid level >7.0 mg/dl. One quarter of this population had hyperuricemia. Dietary information was collected by using a food frequency questionnaire. We collected information on anthropometric measurements and lifestyle factors and other potential confounding factors and disease history via interviews. Total protein consumption was not associated with hyperuricemia. We found a positive association between protein from animal sources and prevalence of hyperuricemia and an inverse association between protein from plant sources and hyperuricemia. However, these associations failed to reach significance in mutually adjusted analysis. Seafood intake was associated with higher prevalence of hyperuricemia. The ORs for quintiles of seafood intake (including fish and shellfish) were 1.00, 1.49, 1.35, 1.34, and 1.56 (p for trend: 0.01). An inverse association approaching significance between soy food consumption and hyperuricemia was observed (ORs: 1.00, 0.90, 0.70, 0.89, and 0.77 for quintiles of intake; p for trend: 0.07). No associations between consumption of purine-rich vegetables or meat and prevalence of hyperuricemia were observed. Our data suggest a direct association between seafood consumption and hyperuricemia and an inverse association between consumption of soy food and hyperuricemia among middle-aged, Chinese men. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Development of derived limits for radiological protection against ionizing radiation based on ICRP-60 recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Jang, S. Y.; Lee, B. S. [Korea Institute of Nuclear Safety, Taejon (Korea, Republic of)

    1999-07-01

    Derived limits such as the Annual Limit on Intake (ALI), Derived Air Concentration (DAC) and Effluent Concentration Limit (ECL) for radiological protection against ionizing radiation based on ICRP-60 recommendations were calculated using dose limits and committed effective dose coefficients of the basic Safety Standards of IAEA (i.e. safety series 115; BSS-96). Derived limits regarding occupational exposure were derived using methodologies of ICRP-61 and dose limit stated in ICRP -60. ECL in air and water for the control of radioactive discharge into the environment were derived using methodologies of 10 CFR part 20 and dose limit stated in ICRP-60. In order to analyze the impact of implementing derived limits on nuclear facilities, the derived values in this study were compared with those prescribed in 10 CFR part 20 as well as the Maximum Permissible Concentrations (MPC) of Notice No. 98-12 of the Ministry of Science and Technology (MOST). According to the comparison results, ECLs in air and water for the control of radioactive discharge into the environment in this study are shown to have lower values (i.e. more conservative), for most part, than those in Notice No. 98-12. These differences are due to the reduction of dose limit, adoption of a weighting factor for age-dependency in dose coefficients, and application of new respiratory tract model and bio-kinetics model. Especially, for uranium elements (i.e., {sup 235}U, {sup 238}U, etc.), which are governing ones in the nuclear fuel industries, ECLs in water are approximately a magnitude in the order of two lower than those in Notice No. 98-12. These are attributable to the adoption of a weighting factor for age-dependency in dose coefficients, newly recommended dose coefficients for ingestion pathway, and reduction of dose limit. It was found out that the differences in ECLs in water for uranium elements originated mostly from ingestion dose coefficients recommended by BSS-96. (author). 6 refs., 2 tabs., 5

  15. Purine analog-like properties of bendamustine underlie rapid activation of DNA damage response and synergistic effects with pyrimidine analogues in lymphoid malignancies.

    Directory of Open Access Journals (Sweden)

    Nobuya Hiraoka

    Full Text Available Bendamustine has shown considerable clinical activity against indolent lymphoid malignancies as a single agent or in combination with rituximab, but combination with additional anti-cancer drugs may be required for refractory and/or relapsed cases as well as other intractable tumors. In this study, we attempted to determine suitable anti-cancer drugs to be combined with bendamustine for the treatment of mantle cell lymphoma, diffuse large B-cell lymphoma, aggressive lymphomas and multiple myeloma, all of which are relatively resistant to this drug, and investigated the mechanisms underlying synergism. Isobologram analysis revealed that bendamustine had synergistic effects with alkylating agents (4-hydroperoxy-cyclophosphamide, chlorambucil and melphalan and pyrimidine analogues (cytosine arabinoside, gemcitabine and decitabine in HBL-2, B104, Namalwa and U266 cell lines, which represent the above entities respectively. In cell cycle analysis, bendamustine induced late S-phase arrest, which was enhanced by 4-hydroperoxy-cyclophosphamide, and potentiated early S-phase arrest by cytosine arabinoside (Ara-C, followed by a robust increase in the size of sub-G1 fractions. Bendamustine was able to elicit DNA damage response and subsequent apoptosis faster and with shorter exposure than other alkylating agents due to rapid intracellular incorporation via equilibrative nucleoside transporters (ENTs. Furthermore, bendamustine increased the expression of ENT1 at both mRNA and protein levels and enhanced the uptake of Ara-C and subsequent increase in Ara-C triphosphate (Ara-CTP in HBL-2 cells to an extent comparable with the purine analog fludarabine. These purine analog-like properties of bendamustine may underlie favorable combinations with other alkylators and pyrimidine analogues. Our findings may provide a theoretical basis for the development of more effective bendamustine-based combination therapies.

  16. Purine metabolism in response to hypoxic conditions associated with breath-hold diving and exercise in erythrocytes and plasma from bottlenose dolphins (Tursiops truncatus).

    Science.gov (United States)

    del Castillo Velasco-Martínez, Iris; Hernández-Camacho, Claudia J; Méndez-Rodríguez, Lía C; Zenteno-Savín, Tania

    2016-01-01

    In mammalian tissues under hypoxic conditions, ATP degradation results in accumulation of purine metabolites. During exercise, muscle energetic demand increases and oxygen consumption can exceed its supply. During breath-hold diving, oxygen supply is reduced and, although oxygen utilization is regulated by bradycardia (low heart rate) and peripheral vasoconstriction, tissues with low blood flow (ischemia) may become hypoxic. The goal of this study was to evaluate potential differences in the circulating levels of purine metabolism components between diving and exercise in bottlenose dolphins (Tursiops truncatus). Blood samples were taken from captive dolphins following a swimming routine (n=8) and after a 2min dive (n=8). Activity of enzymes involved in purine metabolism (hypoxanthine guanine phosphoribosyl transferase (HGPRT), inosine monophosphate deshydrogenase (IMPDH), xanthine oxidase (XO), purine nucleoside phosphorylase (PNP)), and purine metabolite (hypoxanthine (HX), xanthine (X), uric acid (UA), inosine monophosphate (IMP), inosine, nicotinamide adenine dinucleotide (NAD(+)), adenosine, adenosine monophosphate (AMP), adenosine diphosphate (ADP), ATP, guanosine diphosphate (GDP), guanosine triphosphate (GTP)) concentrations were quantified in erythrocyte and plasma samples. Enzymatic activity and purine metabolite concentrations involved in purine synthesis and degradation, were not significantly different between diving and exercise. Plasma adenosine concentration was higher after diving than exercise (p=0.03); this may be related to dive-induced ischemia. In erythrocytes, HGPRT activity was higher after diving than exercise (p=0.007), suggesting an increased capacity for purine recycling and ATP synthesis from IMP in ischemic tissues of bottlenose dolphins during diving. Purine recycling and physiological adaptations may maintain the ATP concentrations in bottlenose dolphins after diving and exercise.

  17. Nonrandom distribution of cryptic repeating triplets of purines and pyrimidines (RNY)(n) in gp120 of HIV Type1.

    Science.gov (United States)

    De Crignis, Elisa; Guglietta, Silvia; Foley, Brian T; Negroni, Matteo; Di Narzo, Antonio Fabio; Waelti Da Costa, Vreneli; Cavassini, Matthias; Bart, Pierre-Alexandre; Pantaleo, Giuseppe; Graziosi, Cecilia

    2012-05-01

    We have analyzed purine (R) and pyrimidine (Y) codon patterns in variable and constant regions of HIV-1 gp120 in seven patients infected with different HIV-1 subtypes and naive to antiretroviral therapy. We have calculated the relative frequency of each in-frame codon RNY, YNR, RNR, and YNY (N=any nucleotide) in variable and constant regions of gp120, in the sequence within indels and at indels' flanking sites. Our data show that hypervariable regions V1, V2, V4, and V5 are characterized by the presence of long stretches of RNY codons constituting the majority of the sequence portion within insertions/deletions. In full-length gp120 and within inserted/deleted fragments the number of AVT (V=A, C, G) codons did not exceed 50% of the total RNY codons. RNY strings in variable regions spanned up to 21 codons and were always in frame. In contrast, RNY strings in constant regions were mostly out of frame and their length was limited to five codons. The frequency of the codon RNY was found to be significantly higher in variable regions (p<0.0001; t-test), within indels, and at indels' flanking sites (p<0.0001; χ(2) test). Analysis of the distribution of RNY strings equal to or longer than five codons in the full genome of HXB2 also shows that these sequences are mostly out of frame, unless they contain a potential N-glycosylation site or an asparagine. These data suggest that cryptic repeats of RNY may play a role in the genesis of multiple base insertions and deletions in hypervariable regions of gp120.

  18. Identification of a purine-rich intronic enhancer element in the mouse eosinophil-associated ribonuclease 2 (mEar 2) gene.

    Science.gov (United States)

    Dyer, Kimberly D; Nitto, Takeaki; Moreau, Joanne M; McDevitt, Amanda L; Rosenberg, Helene F

    2004-02-01

    The Mus musculus eosinophil-associated ribonuclease (mEar) gene cluster includes multiple distinct coding sequences that are highly divergent orthologs of the human eosinophil ribonucleases, eosinophil-derived neurotoxin (EDN/RNase 2) and eosinophil cationic protein (ECP/RNase 3). We present a transcriptional analysis of the gene encoding mEar 2, the only member of this cluster with a well-defined expression profile. In this work, we demonstrate that the presence of non-coding exon 1 and the intron in tandem with a 361-bp 5' promoter of mEar 2 results in enhanced reporter gene expression, as much as 6-to 10-fold over the activity observed with the 5' promoter alone. We have identified a conserved purine-rich element in the intron of the mEar 2 gene that is necessary for maximum transcription and that interacts specifically with NFAT-binding proteins in nuclear extracts derived from the mouse LA4 epithelial cell line. Similar intronic enhancers have been described as regulating transcription of the human EDN gene, suggesting an overall conservation of an important regulatory strategy.

  19. Phytoceramide and sphingoid bases derived from brewer's yeast Saccharomyces pastorianus activate peroxisome proliferator-activated receptors

    Directory of Open Access Journals (Sweden)

    Mitsutake Susumu

    2011-08-01

    Full Text Available Abstract Background Peroxisome proliferator-activated receptors (PPARs are ligand-activated transcription factors that regulate lipid and glucose metabolism. PPARα is highly expressed in the liver and controls genes involved in lipid catabolism. We previously reported that synthetic sphingolipid analogs, part of which contains shorter-length fatty acid chains than natural sphingolipids, stimulated the transcriptional activities of PPARs. Sphingosine and dihydrosphingosine (DHS are abundant sphingoid bases, and ceramide and dihydroceramide are major ceramide species in mammals. In contrast, phytosphingosine (PHS and DHS are the main sphingoid bases in fungi. PHS and phytoceramide exist in particular tissues such as the epidermis in mammals, and involvement of ceramide species in PPARβ activation in cultured keratinocytes has been reported. The purpose of the present study is to investigate whether natural sphingolipids with C18 fatty acid and yeast-derived sphingoid bases activate PPARs as PPAR agonists. Method Lipids of brewer's yeast contain PHS- and DHS-based sphingolipids. To obtain the sphingoid bases, lipids were extracted from brewer's yeast and acid-hydrolyzed. The sphingoid base fraction was purified and quantified. To assess the effects of sphingolipids on PPAR activation, luciferase reporter assay was carried out. NIH/3T3 and human hepatoma (HepG2 cells were transfected with expression vectors for PPARs and retinoid × receptors, and PPAR responsive element reporter vector. When indicated, the PPAR/Gal4 chimera system was performed to enhance the credibility of experiments. Sphingolipids were added to the cells and the dual luciferase reporter assay was performed to determine the transcriptional activity of PPARs. Results We observed that phytoceramide increased the transcriptional activities of PPARs significantly, whereas ceramide and dihydroceramide did not change PPAR activities. Phytoceramide also increased transactivation of

  20. Phytoceramide and sphingoid bases derived from brewer's yeast Saccharomyces pastorianus activate peroxisome proliferator-activated receptors.

    Science.gov (United States)

    Murakami, Itsuo; Wakasa, Yukari; Yamashita, Shinji; Kurihara, Toshio; Zama, Kota; Kobayashi, Naoyuki; Mizutani, Yukiko; Mitsutake, Susumu; Shigyo, Tatsuro; Igarashi, Yasuyuki

    2011-08-24

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate lipid and glucose metabolism. PPARα is highly expressed in the liver and controls genes involved in lipid catabolism. We previously reported that synthetic sphingolipid analogs, part of which contains shorter-length fatty acid chains than natural sphingolipids, stimulated the transcriptional activities of PPARs. Sphingosine and dihydrosphingosine (DHS) are abundant sphingoid bases, and ceramide and dihydroceramide are major ceramide species in mammals. In contrast, phytosphingosine (PHS) and DHS are the main sphingoid bases in fungi. PHS and phytoceramide exist in particular tissues such as the epidermis in mammals, and involvement of ceramide species in PPARβ activation in cultured keratinocytes has been reported. The purpose of the present study is to investigate whether natural sphingolipids with C18 fatty acid and yeast-derived sphingoid bases activate PPARs as PPAR agonists. Lipids of brewer's yeast contain PHS- and DHS-based sphingolipids. To obtain the sphingoid bases, lipids were extracted from brewer's yeast and acid-hydrolyzed. The sphingoid base fraction was purified and quantified. To assess the effects of sphingolipids on PPAR activation, luciferase reporter assay was carried out. NIH/3T3 and human hepatoma (HepG2) cells were transfected with expression vectors for PPARs and retinoid × receptors, and PPAR responsive element reporter vector. When indicated, the PPAR/Gal4 chimera system was performed to enhance the credibility of experiments. Sphingolipids were added to the cells and the dual luciferase reporter assay was performed to determine the transcriptional activity of PPARs. We observed that phytoceramide increased the transcriptional activities of PPARs significantly, whereas ceramide and dihydroceramide did not change PPAR activities. Phytoceramide also increased transactivation of PPAR/Gal4 chimera receptors. Yeast-derived sphingoid

  1. [Research on the model of spectral unmixing for minerals based on derivative of ratio spectroscopy].

    Science.gov (United States)

    Zhao, Heng-Qian; Zhang, Li-Fu; Wu, Tai-Xia; Huang, Chang-Ping

    2013-01-01

    The precise analysis of mineral abundance is a key difficulty in hyperspectral remote sensing research. In the present paper, based on linear spectral mixture model, the derivative of ratio spectroscopy (DRS) was introduced for spectral unmixing of visible to short-wave infrared (Vis-SWIR; 0.4 - 2.5 microm) reflectance data. The mixtures of different proportions of plaster and allochite were analyzed to estimate the accuracy of the spectral unmixing model based on DRS. For the best 5 strong linear bands, the Pearson correlation coefficient (PCC) of the abundances and the actual abundances were higher than 99.9%, while the root mean square error (RMSE) is less than 2.2%. The result shows that the new spectral unmixing model based on DRS is simple, of rigorous mathematical proof, and highly precise. It has a great potential in high-precision quantitative analysis of spectral mixture with fixed endmembers.

  2. Study of the Molecular Recognition of Nucleotides and Bases by a Novel Calixarene Derivative Containing Uracil

    Institute of Scientific and Technical Information of China (English)

    SHI,Hui-Jie; SHI,Xian-Fa; YAO,Tian-Ming; JI,Liang-Nian

    2008-01-01

    A calix[4]arene derivative containing uracil, 5-(uracil-N1-acetamido)-25,26,27,28-tetrahy droxycalix[4]-arene (UC), was designed and synthesized. The interaction with nucleotides and bases has also been studied by ESI-MS and π-A isotherms. The results of ESI-MS showed that UC could recognize adenine and adenosine from other nucleotides and bases. In addition, π-A isotherms at the air-water interface indicated that there was interaction between UC and the species in the subphase, and the respective complexes were formed in the monolayer. The mean molecular area at zero surface pressure increased with the sizes of the nucleotides and bases in the subphase in the order: water<adenine<adenosine<ATP·Na2.

  3. Derivative Trade Optimizing Model Utilizing GP Based on Behavioral Finance Theory

    Science.gov (United States)

    Matsumura, Koki; Kawamoto, Masaru

    This paper proposed a new technique which makes the strategy trees for the derivative (option) trading investment decision based on the behavioral finance theory and optimizes it using evolutionary computation, in order to achieve high profitability. The strategy tree uses a technical analysis based on a statistical, experienced technique for the investment decision. The trading model is represented by various technical indexes, and the strategy tree is optimized by the genetic programming(GP) which is one of the evolutionary computations. Moreover, this paper proposed a method using the prospect theory based on the behavioral finance theory to set psychological bias for profit and deficit and attempted to select the appropriate strike price of option for the higher investment efficiency. As a result, this technique produced a good result and found the effectiveness of this trading model by the optimized dealings strategy.

  4. Deriving all minimal consistency-based diagnosis sets using SAT solvers

    Institute of Scientific and Technical Information of China (English)

    Xiangfu Zhao; Liming Zhang; Dantong Ouyang; Yu Jiao

    2009-01-01

    In this paper,a novel method is proposed for judging whether a component set is a consistency-based diagnostic set,using SAT solvers.Firstly,the model of the system to be diagnosed and all the observations are described with conjunctive normal forms (CNF).Then,all the related clauses in the CNF files to the components other than the considered ones are extracted,to be used for satisfiability checking by SAT solvers.Next,all the minimal consistency-based diagnostic sets are derived by the CSSE-tree or by other similar algorithms.We have implemented four related algorithms,by calling the gold medal SAT solver in SAT07 competition - RSAT.Experimental results show that all the minimal consistency-based diagnostic sets can be quickly computed.Especially our CSSE-tree has the best efficiency for the single-or double-fault diagnosis.

  5. SYNTHESIS AND DOCKING STUDIES OF SCHIFF BASES DERIVED FROM 4-AMINOPYRIDINE

    Directory of Open Access Journals (Sweden)

    Jayita Nandi

    2012-10-01

    Full Text Available A Schiff base is a compound with a functional group that contains a carbon-nitrogen double bond with the nitrogen atom connected to aryl or alkyl group. In the present study, schiff bases were synthesized using 4-amino pyridine and different aldehydes, after assessing the drug likeliness properties. The structure of synthesised compounds were characterized by IR, NMR and Mass spectroscopic techniques. Docking studies were carried out for the schiff bases derived from 4-amino pyridine using Molegro Virtual Docker and protein beta-ketoacyl acyl carrier protein synthase II (mtKasB enzyme was selected as the target for M. tuberculosis. The results of docking study was compared with the standard drug isoniazid and the significant results were obtained.

  6. Genetics-based pediatric warfarin dosage regimen derived using pharmacometric bridging.

    Science.gov (United States)

    Lala, Mallika; Burckart, Gilbert J; Takao, Cheryl M; Pravica, Vera; Momper, Jeremiah D; Gobburu, Jogarao V S

    2013-07-01

    Warfarin dosage regimens using CYP2C9 and VKORC1 polymorphisms have been extensively studied in adults and is included in US Food and Drug Administration-approved warfarin labeling. However, no dosage algorithm is available for pediatric patients. To derive a genetics-based pediatric dosge regimen for warfarin, including starting dose and titration scheme. A model-based approach was developed based on a previously validated warfarin dosage model in adults, with subsequent comparison to pediatric data from pediatric warfarin dose, genotyping, and international normalized ratio (INR) results. The adult model was based on a previously established model from the CROWN (CReating an Optimal Warfarin dosing Nomogram) trial. Pediatric warfarin data were obtained from a study conducted at the Children's Hospital of Los Angeles with 26 subjects. Variant alleles of CYP2C9 (rs1799853 or *2, and rs1057910 or *3) and the VKORC1 single nucleotide polymorphism (SNP) rs9923231 (-1639 G>A) were assessed, where the rs numbers are reference SNP identification tags assigned by the National Center for Biotechnology Information. A pediatric warfarin model was derived using the previously validated model and clinical pharmacology considerations. The model was validated, and clinical trial simulation and stochastic modeling were used to optimize pediatric dosage and titration. The final dosage regimen was optimized based on simulations targeting a high (≥60%) proportion of INRs within the therapeutic range by week 2 of warfarin therapy while minimizing INRs >3.5 or A) genotypes may offer improved dosage compared to current treatment strategies, especially in patients with variant CYP2C9 and VKORC1 alleles. This pilot study provides the foundation for a larger prospective evaluation of genetics-based warfarin dosage in pediatric patients.

  7. Metal-based biologically active azoles and β-lactams derived from sulfa drugs.

    Science.gov (United States)

    Ebrahimi, Hossein Pasha; Hadi, Jabbar S; Almayah, Abdulelah A; Bolandnazar, Zeinab; Swadi, Ali G; Ebrahimi, Amirpasha

    2016-03-01

    Metal complexes of Schiff bases derived from sulfamethoxazole (SMZ) and sulfathiazole (STZ), converted to their β-lactam derivatives have been synthesized and experimentally characterized by elemental analysis, spectral (IR, (1)H NMR, (13)C NMR, and EI-mass), molar conductance measurements and thermal analysis techniques. The structural and electronic properties of the studied molecules were investigated theoretically by performing density functional theory (DFT) to access reliable results to the experimental values. The spectral and thermal analysis reveals that the Schiff bases act as bidentate ligands via the coordination of azomethine nitrogen to metal ions as well as the proton displacement from the phenolic group through the metal ions; therefore, Cu complexes can attain the square planner arrangement and Zn complexes have a distorted tetrahedral structure. The thermogravimetric (TG/DTG) analyses confirm high stability for all complexes followed by thermal decomposition in different steps. In addition, the antibacterial activities of synthesized compounds have been screened in vitro against various pathogenic bacterial species. Inspection of the results revealed that all newly synthesized complexes individually exhibit varying degrees of inhibitory effects on the growth of the tested bacterial species, therefore, they may be considered as drug candidates for bacterial pathogens. The free Schiff base ligands (1-2) exhibited a broad spectrum antibacterial activity against Gram negative Escherichia coli, Pseudomonas aeruginosa, and Proteus spp., and Gram positive Staphylococcus aureus bacterial strains. The results also indicated that the β-lactam derivatives (3-4) have high antibacterial activities on Gram positive bacteria as well as the metal complexes (5-8), particularly Zn complexes, have a significant activity against all Gram negative bacterial strains. It has been shown that the metal complexes have significantly higher activity than corresponding

  8. Steganalysis of content-adaptive JPEG steganography based on Gauss partial derivative filter bank

    Science.gov (United States)

    Zhang, Yi; Liu, Fenlin; Yang, Chunfang; Luo, Xiangyang; Song, Xiaofeng; Lu, Jicang

    2017-01-01

    A steganalysis feature extraction method based on Gauss partial derivative filter bank is proposed in this paper to improve the detection performance for content-adaptive JPEG steganography. Considering that the embedding changes of content-adaptive steganographic schemes are performed in the texture and edge regions, the proposed method generates filtered images comprising rich texture and edge information using Gauss partial derivative filter bank, and histograms of absolute values of filtered subimages are extracted as steganalysis features. Gauss partial derivative filter bank can represent texture and edge information in multiple orientations with less computation load than conventional methods and prevent redundancy in different filtered images. These two properties are beneficial in the extraction of low-complexity sensitive features. The results of experiments conducted on three selected modern JPEG steganographic schemes-uniform embedding distortion, JPEG universal wavelet relative distortion, and side-informed UNIWARD-indicate that the proposed feature set is superior to the prior art feature sets-discrete cosine transform residual, phase aware rich model, and Gabor filter residual.

  9. Novel 2DG-based harmine derivatives for targeted cancer therapy

    Science.gov (United States)

    Wang, Aqin; Chen, Yuqi; Chen, Wei R.; Gu, Yueqing

    2013-02-01

    Harmine is a beta-carboline alkaloid from the plant Peganum harmala. These alkaloids were stimulated by their promising antitumor activities in the recent years. In this study, we designed and synthesized two harmine derivatives #1and #2 modified at position-9 of harmine with ethyl and phenylpropyl, respectively. To improve the tumor targeting capability, #1' and #2' were synthesized by conjugating 2-amino-2-deoxy-D-glucose (2DG) to the derivatives #1 and #2, respectively. The MTT assays of all these compounds in vitro against L02, HepG2 showed all compounds had low toxicity to normal cells (L02) and significantly enhanced carcinoma cell inhibitory rate compared to harmine. Cytotoxicity against liver cancer cell lines of compound #1' #2' is higher than #1 #2, and even the compound #2' is better than positive drug 5-FU. The compound #2', a novel 2DG-based harmine derivatives, could become a promising drug for targeted cancer therapy and combination therapy with other antitumor drugs.

  10. Deformation analysis of polymers composites: rheological model involving time-based fractional derivative

    Science.gov (United States)

    Zhou, H. W.; Yi, H. Y.; Mishnaevsky, L.; Wang, R.; Duan, Z. Q.; Chen, Q.

    2016-08-01

    A modeling approach to time-dependent property of Glass Fiber Reinforced Polymers (GFRP) composites is of special interest for quantitative description of long-term behavior. An electronic creep machine is employed to investigate the time-dependent deformation of four specimens of dog-bond-shaped GFRP composites at various stress level. A negative exponent function based on structural changes is introduced to describe the damage evolution of material properties in the process of creep test. Accordingly, a new creep constitutive equation, referred to fractional derivative Maxwell model, is suggested to characterize the time-dependent behavior of GFRP composites by replacing Newtonian dashpot with the Abel dashpot in the classical Maxwell model. The analytic solution for the fractional derivative Maxwell model is given and the relative parameters are determined. The results estimated by the fractional derivative Maxwell model proposed in the paper are in a good agreement with the experimental data. It is shown that the new creep constitutive model proposed in the paper needs few parameters to represent various time-dependent behaviors.

  11. Evaluation of deriving fire cycle of forested landscape based on time-since-fire distribution

    Institute of Scientific and Technical Information of China (English)

    ZHANG Quan-fa; Kurt S. Pregitzer; JIANG Ming-xi; CHEN Wen-jun

    2006-01-01

    Estimation of fire cycle has been conducted by using the negative exponential function as an approximation of time-since-fire distribution of a landscape assumed .to be homogeneous with respect to fire spread processes. The authors imposed predefined fire cycles on a virtual landscape of 100 cell ×100 cell, and obtained a mosaic composing of patches with different stand ages (i.e. time since fire). Graphical and statistical methods (Van Wagner 1978; Reed et al. 1998) were employed to derive fire cycle from the virtual landscape. By comparing the predefined and the derived fire cycles, the two methods and tested the effects of sample size and hazard of burning (i.e., stand's susceptibility to fire in relation to its stand age) were evaluated on fire cycle deviation. The simulation results indicated a minimum sample size of 10 times of the annual burnt area would be required for partitioning time-since-fire distribution into homogeneous epochs indicating temporal change in fire cycle. Statistically, there was significant difference among the imposed and the derived fire cycle, regardless of sample sizes with or without consideration of hazard of burning. Both methods underestimated the more recent fire cycle without significant difference between them. The results imply that deviation of fire cycle based on time-since-fire distribution warrants cautious interpretation, especially when a landscape is spatially partitioned into small units and temporal changes in fire cycle are involved.

  12. Perspectives for Titanium-Derived Fillers Usage on Denture Base Composite Construction: A Review Article

    Directory of Open Access Journals (Sweden)

    Nidal W. Elshereksi

    2014-01-01

    Full Text Available Poly(methyl methacrylate (PMMA is an extensively used material in dentistry because of its aesthetics, processability, and reparability. However, PMMA is still far from being ideal in fulfilling the mechanical requirements of prosthesis. PMMA-based denture base polymers exhibit low fracture resistance and radiopacity behavior. Efforts to improve the mechanical and radiopacity properties of denture base materials through inclusion of silica-based fillers are ongoing. Although silane-treated siliceous fillers are commonly used, they are not sufficiently strong. They also exhibit cracks, which either cut through the glass fillers or propagate around the filler particles. This defect occurs when the dental composites are placed in aqueous oral environment because of the hydrolytic degradation of silica-based fillers and silane-coupling agents. The clinical problem of using silanes in adhesion promotion is bond degradation over time in oral environment. In addition, silanes do not bond effectively to nonsilica-based dental restorative materials. This review presents titanium-derived fillers as alternatives to siliceous fillers. Titanate-coupling agents are found to be effective couplers in treating Ti-based fillers because of their chemical compatibility and relatively high stability in aqueous environment.

  13. New directions in medical biosensors employing poly(3,4-ethylenedioxy thiophene) derivative-based electrodes

    DEFF Research Database (Denmark)

    Rozlosnik, Noemi

    2009-01-01

    production and they are suitable for biosensor applications. Conducting polymer-based electrochemical sensors have shown numerous advantages in a number of areas related to human health, such as the diagnosis of infectious diseases, genetic mutations, drug discovery, forensics and food technology, due...... to their simplicity and high sensitivity. One of the most promising group of conductive polymers is poly(3,4-ethylenedioxythiophene) (PEDOT) and its derivatives due to their attractive properties: high stability, high conductivity (up to 400–600 S/cm) and high transparency. This review paper summarizes newly...

  14. Electrochemical Biosensors Based on Ferroceneboronic Acid and Its Derivatives: A Review

    Directory of Open Access Journals (Sweden)

    Baozhen Wang

    2014-07-01

    Full Text Available We review recent progress in the development of electrochemical biosensors based on ferroceneboronic acid (FcBA and ferrocene (Fc-modified boronic acids. These compounds can be used to construct electrochemical biosensors because they consist of a binding site (i.e., a boronic acid moiety and an electrochemically active part (i.e., an Fc residue. By taking advantage of the unique properties of FcBA and its derivatives, electrochemical sensors sensitive to sugars, glycated hemoglobin (HbA1c, fluoride (F− ions, and so forth have been widely studied. FcBA-based sugar sensors rely on the selective binding of FcBA to 1,2- or 1,3-diol residues of sugars through the formation of cyclic boronate ester bonds. The redox properties of FcBA-sugar adduct differ from those of free FcBA, which forms the basis of the electrochemical determination of sugars. Thus, non-enzymatic glucose sensors are now being actively studied using FcBA and Fc-modified boronic acids as redox markers. Using a similar principle, HbA1c can be detected by FcBA-based electrochemical systems because it contains hydrocarbon chains on the polypeptide chain. HbA1c sensors are useful for monitoring blood glucose levels over the preceding 8–12 weeks. In addition, FcBA and Fc-modified boronic acids have been used for the detection of F− ions due to the selective binding of boronic acid to F− ions. F−-ion sensors may be useful alternatives to conventional ion-selective electrodes sensitive to F− ion. Furthermore, FcBA derivatives have been studied to construct lectin; steroids; nucleotides; salicylic acid; and bacteria sensors. One of the limitations of FcBA-based sensors comes from the fact that FcBA derivatives are added in sample solutions as reagents. FcBA derivatives should be immobilized on the surface of electrodes for developing reagentless sensors.

  15. Synthesis and antimalarial evaluation of some 4-quinazolinone derivatives based on febrifugine

    Directory of Open Access Journals (Sweden)

    Debanjan Sen

    2010-01-01

    Full Text Available A series of 2-substituted and 2,3-substituted quinazolin -4(3H-one derivatives were designed and synthesized based on the structure of febrifugine. The structures of the new compounds were confirmed by spectral analysis. The in vivo biological activity test results indicated that those compounds exhibited antimalarial activities against Plasmodium berghei in mice, at a dose of 5 mg/kg. Compared to Chloroquine and Artemisinin, these compounds have the advantages of shorter synthetic routes and consequently are highly cost effective in nature.

  16. Development of Ni-Based Catalysts for Steam Reforming of Tar Derived from Biomass Pyrolysis

    Institute of Scientific and Technical Information of China (English)

    Dalin LI; Yoshinao NAKAGAWA; Keiichi TOMISHIGE

    2012-01-01

    Nickel catalysts are effective for the steam reforming of tar derived from biomass pyrolysis,but the improvement is needed in terms of activity,stability,suppression of coke deposition and aggregation,and regeneration.Our recent development of Ni-based catalysts for the steam reforming of tar is reviewed including the modification with CeO2 (or MnO),trace Pt,and MgO.The role of additives such as CeO2,MnO,Pt,and MgO is also discussed.

  17. A derives grid-based model for simulation of pedestrian flow

    Institute of Scientific and Technical Information of China (English)

    Min-jie CHEN; Günter B(A)RWOLFF; Hartmut SCHWANDT

    2009-01-01

    We present a derived grid-based model for the simulation of pedestrian flow. Interactions among pedestrians are considered as the result of forces within a certain neighbourhood. Unlike the social force model, the forces here, as in Newtonian physics, are proportional to the inverse of the square of the distance. Despite the notion of neighbourhood and the underlying grid, this model differs from the existing cellular automaton (CA) models in that the pedestrians are treated as individuals. Bresenham's algorithm for line rastering is applied in the step calculation.

  18. Integral Theorems Based on a New Gradient Operator Derived from Biomembranes (Part Ⅱ): Applications

    Institute of Scientific and Technical Information of China (English)

    YIN Yajun

    2005-01-01

    Based on the second gradient operator and corresponding integral theorems such as the second divergence theorem, the second gradient theorem, the second curl theorem, and the second circulation theorem on curved surfaces, a few new scalar differential operators are defined and a series of integral transformations are derived. Interesting transformations between the average curvature and the Gauss curvature are presented. Various conserved integrals related to the Gauss curvature and the second fundamental tensor are disclosed. The important applications of the results in disciplines such as the geometry, physics, mechanics, and biology are briefly discussed.

  19. An efficient nonviral gene-delivery vector based on hyperbranched cationic glycogen derivatives

    Directory of Open Access Journals (Sweden)

    Liang X

    2014-01-01

    Full Text Available Xuan Liang,1,* Xianyue Ren,2,* Zhenzhen Liu,1 Yingliang Liu,1 Jue Wang,2 Jingnan Wang,2 Li-Ming Zhang,1 David YB Deng,2 Daping Quan,1 Liqun Yang1 1Institute of Polymer Science, School of Chemistry and Chemical Engineering, Key Laboratory of Designed Synthesis and Application of Polymer Material, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-Sen University, Guangzhou, People's Republic of China; 2Research Center of Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China *Both these authors contributed equally to this work Background: The purpose of this study was to synthesize and evaluate hyperbranched cationic glycogen derivatives as an efficient nonviral gene-delivery vector. Methods: A series of hyperbranched cationic glycogen derivatives conjugated with 3-(dimethylamino-1-propylamine (DMAPA-Glyp and 1-(2-aminoethyl piperazine (AEPZ-Glyp residues were synthesized and characterized by Fourier-transform infrared and hydrogen-1 nuclear magnetic resonance spectroscopy. Their buffer capacity was assessed by acid–base titration in aqueous NaCl solution. Plasmid deoxyribonucleic acid (pDNA condensation ability and protection against DNase I degradation of the glycogen derivatives were assessed using agarose gel electrophoresis. The zeta potentials and particle sizes of the glycogen derivative/pDNA complexes were measured, and the images of the complexes were observed using atomic force microscopy. Blood compatibility and cytotoxicity were evaluated by hemolysis assay and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, respectively. pDNA transfection efficiency mediated by the cationic glycogen derivatives was evaluated by flow cytometry and fluorescence microscopy in the 293T (human embryonic kidney and the CNE2 (human nasopharyngeal carcinoma cell lines. In vivo delivery of pDNA in model animals (Sprague Dawley

  20. Real-Time Algebraic Derivative Estimations Using a Novel Low-Cost Architecture Based on Reconfigurable Logic

    OpenAIRE

    2014-01-01

    Time derivative estimation of signals plays a very important role in several fields, such as signal processing and control engineering, just to name a few of them. For that purpose, a non-asymptotic algebraic procedure for the approximate estimation of the system states is used in this work. The method is based on results from differential algebra and furnishes some general formulae for the time derivatives of a measurable signal in which two algebraic derivative estimators run simultaneously...

  1. Potential Biological Applications of Bio-Based Anacardic Acids and Their Derivatives

    Directory of Open Access Journals (Sweden)

    Fatma B. Hamad

    2015-04-01

    Full Text Available Cashew nut shells (CNS, which are agro wastes from cashew nut processing factories, have proven to be among the most versatile bio-based renewable materials in the search for functional materials and chemicals from renewable resources. CNS are produced in the cashew nut processing process as waste, but they contain cashew nut shell liquid (CNSL up to about 30–35 wt. % of the nut shell weight depending on the method of extraction. CNSL is a mixture of anacardic acid, cardanol, cardol, and methyl cardol, and the structures of these phenols offer opportunities for the development of diverse products. For anacardic acid, the combination of phenolic, carboxylic, and a 15-carbon alkyl side chain functional group makes it attractive in biological applications or as a synthon for the synthesis of a multitude of bioactive compounds. Anacardic acid, which is about 65% of a CNSL mixture, can be extracted from the agro waste. This shows that CNS waste can be used to extract useful chemicals and thus provide alternative green sources of chemicals, apart from relying only on the otherwise declining petroleum based sources. This paper reviews the potential of anacardic acids and their semi-synthetic derivatives for antibacterial, antitumor, and antioxidant activities. The review focuses on natural anacardic acids from CNS and other plants and their semi-synthetic derivatives as possible lead compounds in medicine. In addition, the use of anacardic acid as a starting material for the synthesis of various biologically active compounds and complexes is reported.

  2. Potential biological applications of bio-based anacardic acids and their derivatives.

    Science.gov (United States)

    Hamad, Fatma B; Mubofu, Egid B

    2015-04-16

    Cashew nut shells (CNS), which are agro wastes from cashew nut processing factories, have proven to be among the most versatile bio-based renewable materials in the search for functional materials and chemicals from renewable resources. CNS are produced in the cashew nut processing process as waste, but they contain cashew nut shell liquid (CNSL) up to about 30-35 wt. % of the nut shell weight depending on the method of extraction. CNSL is a mixture of anacardic acid, cardanol, cardol, and methyl cardol, and the structures of these phenols offer opportunities for the development of diverse products. For anacardic acid, the combination of phenolic, carboxylic, and a 15-carbon alkyl side chain functional group makes it attractive in biological applications or as a synthon for the synthesis of a multitude of bioactive compounds. Anacardic acid, which is about 65% of a CNSL mixture, can be extracted from the agro waste. This shows that CNS waste can be used to extract useful chemicals and thus provide alternative green sources of chemicals, apart from relying only on the otherwise declining petroleum based sources. This paper reviews the potential of anacardic acids and their semi-synthetic derivatives for antibacterial, antitumor, and antioxidant activities. The review focuses on natural anacardic acids from CNS and other plants and their semi-synthetic derivatives as possible lead compounds in medicine. In addition, the use of anacardic acid as a starting material for the synthesis of various biologically active compounds and complexes is reported.

  3. Emitting materials based on phenylanthracene-substituted naphthalene derivatives for organic light-emitting diodes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyun Woo; Kim, Hye Jeong; Kim, Young Seok; Kim, Jwajin [Department of Chemistry, Sungkyunkwan University, Suwon 440‐746 (Korea, Republic of); Lee, Song Eun; Lee, Ho Won [Department of Information Display, Hongik University, Seoul 121-791 (Korea, Republic of); Kim, Young Kwan, E-mail: kimyk@wow.hongik.ac.kr [Department of Information Display, Hongik University, Seoul 121-791 (Korea, Republic of); Yoon, Seung Soo, E-mail: ssyoon@skku.edu [Department of Chemistry, Sungkyunkwan University, Suwon 440‐746 (Korea, Republic of)

    2015-09-15

    This study reports the emitting materials based on phenylanthracene-substituted naphthalene derivatives to achieve efficient electroluminescent properties for OLED applications. An OLED device using 4,4′-bis(10-phenylanthracen-9-yl)-1,1′-binaphthalene exhibited the blue emission with the CIE coordinates of (0.19, 0.16) and efficient electroluminescent properties with the luminance, power and external quantum efficiency of 1.70 cd/A, 0.79 lm/W and 1.26% at 20 mA/cm{sup 2}, respectively. Also, the other device using 1,4-bis(10-phenylanthracene-9-yl)naphthalene exhibited white emission with the CIE coordinates of (0.34, 0.43) at 7V, respectively. This device exhibits the luminance, power and external quantum efficiency of 2.22 cd/A, 1.13 lm/W and 0.86% at 20 mA/cm{sup 2}, respectively. - Highlights: • We synthesized fluorescent materials based on phenylanthracene derivatives. • Electroluminescence properties of these materials depend on the molecular structures. • These blue and white materials have great potential for application in OLEDs.

  4. Microscopic derivation of particle-based coarse-grained dynamics: Exact expression for memory function

    Science.gov (United States)

    Izvekov, Sergei

    2017-03-01

    We consider the generalized Langevin equations of motion describing exactly the particle-based coarse-grained dynamics in the classical microscopic ensemble that were derived recently within the Mori-Zwanzig formalism based on new projection operators [S. Izvekov, J. Chem. Phys. 138(13), 134106 (2013)]. The fundamental difference between the new family of projection operators and the standard Zwanzig projection operator used in the past to derive the coarse-grained equations of motion is that the new operators average out the explicit irrelevant trajectories leading to the possibility of solving the projected dynamics exactly. We clarify the definition of the projection operators and revisit the formalism to compute the projected dynamics exactly for the microscopic system in equilibrium. The resulting expression for the projected force is in the form of a "generalized additive fluctuating force" describing the departure of the generalized microscopic force associated with the coarse-grained coordinate from its projection. Starting with this key expression, we formulate a new exact formula for the memory function in terms of microscopic and coarse-grained conservative forces. We conclude by studying two independent limiting cases of practical importance: the Markov limit (vanishing correlations of projected force) and the limit of weak dependence of the memory function on the particle momenta. We present computationally affordable expressions which can be efficiently evaluated from standard molecular dynamics simulations.

  5. Liquid chromatographic determination of beta-cyclodextrin derivatives based on fluorescence enhancement after inclusion complexation.

    Science.gov (United States)

    Reeuwijk, H J; Irth, H; Tjaden, U R; Merkus, F W; van der Greef, J

    1993-04-21

    A liquid chromatographic method using fluorescence detection for the determination of beta-cyclodextrin (beta CD) and its derivatives is presented. The chromatographic system is based on size-exclusion chromatography with the addition of the fluorophoric compound 1-naphthol to the mobile phase. Detection is based on fluorescence enhancement caused by the formation of inclusion complexes. By incorporating 10(-4) M 1-naphthol in the mobile phase, detection limits of 90, 27, 370 and 37 pmol were obtained for beta CD, hydroxypropyl-beta CD, trimethyl-beta CD and dimethyl-beta CD, respectively. The method was applied to the determination of dimethyl-beta CD in urine: the minimum detectable concentration was 0.2 microgram/ml after preconcentration of 10 ml of urine.

  6. Soot particle sizing based on analytical formula derived from laser-induced incandescence decay signals

    Science.gov (United States)

    Wu, Jian; Chen, Linghong; Yan, Mingming; Wu, Xuecheng; Gréhan, Gérard; Cen, Kefa

    2017-01-01

    The laser-induced incandescence (LII) signal during a heat-conduction-dominated cooling process was used to derive an analytical formula to describe the relationship between the soot particle size and the LII signal decay time by exponential fitting. The formula was used to determine particle sizes based on the experimental LII signals at different detection wavelengths for an atmospheric C2H4/air diffusion flame. The results agree with those obtained from temporal temperature measurements. The measurements and numerical calculations demonstrate that particle sizing depends weakly on the maximum temperature in the formula within a typical heat-up temperature range. The results show that based on this formula, a compact single-color LII detection system can be used for particle sizing with low uncertainty under most practical combustion conditions, at least in cases where heat conduction is dominant and occurs in a free molecular regime during particle cooling.

  7. Decomposition driven interface evolution for layers of binary mixtures: I. Model derivation and stratified base states

    CERN Document Server

    Thiele, Uwe; Frastia, Lubor

    2007-01-01

    A dynamical model is proposed to describe the coupled decomposition and profile evolution of a free surface film of a binary mixture. An example is a thin film of a polymer blend on a solid substrate undergoing simultaneous phase separation and dewetting. The model is based on model-H describing the coupled transport of the mass of one component (convective Cahn-Hilliard equation) and momentum (Navier-Stokes-Korteweg equations) supplemented by appropriate boundary conditions at the solid substrate and the free surface. General transport equations are derived using phenomenological non-equilibrium thermodynamics for a general non-isothermal setting taking into account Soret and Dufour effects and interfacial viscosity for the internal diffuse interface between the two components. Focusing on an isothermal setting the resulting model is compared to literature results and its base states corresponding to homogeneous or vertically stratified flat layers are analysed.

  8. Topological invariants of band insulators derived from the local-orbital based embedding potential

    Science.gov (United States)

    Ishida, H.; Liebsch, A.; Wortmann, D.

    2017-09-01

    We demonstrate that topological invariants of band insulators can be derived efficiently from the eigenvalues of the local-orbital (LO) based embedding potential, called also the contact (lead) self-energy. The LO based embedding potential is a bulk quantity. Given the tight-binding Hamiltonian describing the bulk valence and conduction bands, it is constructed straightforwardly from the bulk wave functions satisfying the generalized Bloch condition. When the one-electron energy ɛ is located within a projected bulk band gap at a given planar wave vector k , the embedding potential becomes Hermitian. Its real eigenvalues exhibit distinctly different behavior depending on the topological properties of the valence bands, thus enabling unambiguous identification of bulk topological invariants. We consider the Bernevig-Hughes-Zhang model as an example of a time-reversal invariant topological insulator and tin telluride (SnTe) crystallized in a rock-salt structure as an example of a topological crystalline insulator.

  9. Characterization of ι-carrageenan and its derivative based green polymer electrolytes

    Energy Technology Data Exchange (ETDEWEB)

    Jumaah, Fatihah Najirah; Mobaraka, Nadhratun Naiim; Ahmad, Azizan; Ramli, Nazaruddin [School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600, Bangi, Selangor Darul Ehsan (Malaysia)

    2013-11-27

    The new types of green polymer electrolytes based on ι-carrageenan derivative have been prepared. ι-carrageenan act as precursor was reacted with monochloroacetic acid to produce carboxymethyl ι-carrageenan. The powders were characterized by Attenuated Total Reflection Fourier Transform infrared (ATR-FTIR) spectroscopy and {sup 1}H nuclear magnetic resonance (NMR) to confirm the substitution of targeted functional group in ι-carrageenan. The green polymer electrolyte based on ι-carrageenan and carboxymethyl ι-carrageenan was prepared by solution-casting technique. The films were characterized by electrochemical impedance spectroscopy to determine the ionic conductivity. The ionic conductivity ι-carrageenan film were higher than carboxymethyl ι-carrageenan which 4.87 ×10{sup −6} S cm{sup −1} and 2.19 ×10{sup −8} S cm{sup −1}, respectively.

  10. Cell-based delivery of brain-derived neurotrophic factor in experimental allergic encephalomyelitis.

    Science.gov (United States)

    Makar, Tapas K; Nimmagadda, Vamshi K C; Trisler, David; Bever, Christopher T

    2014-08-01

    Brain-derived neurotrophic factor (BDNF) is a pleiotropic cytokine with neuroprotective properties that has been identified as a potential therapeutic agent for diseases of the central nervous system (CNS). The use of BDNF has been limited by a short serum half-life and poor penetration of the blood-brain barrier. To address this limitation we have explored cell-based approaches to delivery. We have used experimental allergic encephalomyelitis (EAE), an inflammatory disease of the CNS, as a model system. We engineered hematopoietic stem cells to produce BDNF to determine the feasibility and effectiveness of cell-based delivery of BDNF into the CNS in EAE. We review those studies here.

  11. Spectral Characterization and Antimicrobial Activity of Some Schiff Bases Derived from 4-Chloro-2-aminophenol and Various Salicylaldehyde Derivatives%Spectral Characterization and Antimicrobial Activity of Some Schiff Bases Derived from 4-Chloro-2-aminophenol and Various Salicylaldehyde Derivatives

    Institute of Scientific and Technical Information of China (English)

    Cinarli, Adem; Gurbuz, Demet; Tavman, Aydin; Birteksoz, A. Seher

    2012-01-01

    A series of N-(5-chloro-2-hydroxyphenyl)-(3/4/5-substituted)-salicylaldimines (I--XI) were synthesized using appropriate synthetic route. Their structures were characterized by FT-IR, UV-Visible, ESI-MS, 1H and 13C NMR spectroscopic techniques and analytical methods. The crystal structure of N-(5-chloro-2-hydroxyphenyl)-5-bromo- salicylaldimine (V) was determined by X-ray diffraction at room temperature. Relationship between the melting points and the structures of the compounds was examined. Antimicrobial activity of the compounds was evaluated against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis. Antifungal activities were reported for Candida albicans. Schiff bases showed considerable antimicrobial activity against S. aureus, S, epidermidis and C. albicans. N-(5-Chloro-2-hydroxyphenyl)-3-hydroxy-salieylaldimine (II) has the broadest and highest antimicrobial activity according to the others.

  12. An efficient hybrid causative event-based approach for deriving the annual flood frequency distribution

    Science.gov (United States)

    Thyer, Mark; Li, Jing; Lambert, Martin; Kuczera, George; Metcalfe, Andrew

    2015-04-01

    Flood extremes are driven by highly variable and complex climatic and hydrological processes. Derived flood frequency methods are often used to predict the flood frequency distribution (FFD) because they can provide predictions in ungauged catchments and evaluate the impact of land-use or climate change. This study presents recent work on development of a new derived flood frequency method called the hybrid causative events (HCE) approach. The advantage of the HCE approach is that it combines the accuracy of the continuous simulation approach with the computational efficiency of the event-based approaches. Derived flood frequency methods, can be divided into two classes. Event-based approaches provide fast estimation, but can also lead to prediction bias due to limitations of inherent assumptions required for obtaining input information (rainfall and catchment wetness) for events that cause large floods. Continuous simulation produces more accurate predictions, however, at the cost of massive computational time. The HCE method uses a short continuous simulation to provide inputs for a rainfall-runoff model running in an event-based fashion. A proof-of-concept pilot study that the HCE produces estimates of the flood frequency distribution with similar accuracy as the continuous simulation, but with dramatically reduced computation time. Recent work incorporated seasonality into the HCE approach and evaluated with a more realistic set of eight sites from a wide range of climate zones, typical of Australia, using a virtual catchment approach. The seasonal hybrid-CE provided accurate predictions of the FFD for all sites. Comparison with the existing non-seasonal hybrid-CE showed that for some sites the non-seasonal hybrid-CE significantly over-predicted the FFD. Analysis of the underlying cause of whether a site had a high, low or no need to use seasonality found it was based on a combination of reasons, that were difficult to predict apriori. Hence it is recommended

  13. First space-based derivation of the global atmospheric methanol emission fluxes

    Science.gov (United States)

    Stavrakou, T.; Guenther, A.; Razavi, A.; Clarisse, L.; Clerbaux, C.; Coheur, P.-F.; Hurtmans, D.; Karagulian, F.; de Mazière, M.; Vigouroux, C.; Amelynck, C.; Schoon, N.; Laffineur, Q.; Heinesch, B.; Aubinet, M.; Rinsland, C.; Müller, J.-F.

    2011-05-01

    This study provides improved methanol emission estimates on the global scale, in particular for the largest methanol source, the terrestrial biosphere, and for biomass burning. To this purpose, one complete year of spaceborne measurements of tropospheric methanol columns retrieved for the first time by the thermal infrared sensor IASI aboard the MetOp satellite are compared with distributions calculated by the IMAGESv2 global chemistry-transport model. Two model simulations are performed using a priori biogenic methanol emissions either from the new MEGANv2.1 emission model, which is fully described in this work and is based on net ecosystem flux measurements, or from a previous parameterization based on net primary production by Jacob et al. (2005). A significantly better model performance in terms of both amplitude and seasonality is achieved through the use of MEGANv2.1 in most world regions, with respect to IASI data, and to surface- and air-based methanol measurements, even though important discrepancies over several regions are still present. As a second step of this study, we combine the MEGANv2.1 and the IASI column abundances over continents in an inverse modelling scheme based on the adjoint of the IMAGESv2 model to generate an improved global methanol emission source. The global optimized source totals 187 Tg yr-1 with a contribution of 100 Tg yr-1 from plants, only slightly lower than the a priori MEGANv2.1 value of 105 Tg yr-1. Large decreases with respect to the MEGANv2.1 biogenic source are inferred over Amazonia (up to 55 %) and Indonesia (up to 58 %), whereas more moderate reductions are recorded in the Eastern US (20-25 %) and Central Africa (25-35 %). On the other hand, the biogenic source is found to strongly increase in the arid and semi-arid regions of Central Asia (up to a factor of 5) and Western US (factor of 2), probably due to a source of methanol specific to these ecosystems which is unaccounted for in the MEGANv2.1 inventory. The most

  14. Copper(II)-selective membrane electrode based on a recently synthesized naphthol-derivative Schiff's base

    Energy Technology Data Exchange (ETDEWEB)

    Alizadeh, N.; Ershad, S. [Dept. of Chemistry, Tarbiat Moderres Univ., Tehran (Iran); Naeimi, H.; Sharghi, H. [Dept. of Chemistry, Shiraz Univ. (Iran); Shamsipur, M. [Dept. of Chemistry, Razi Univ., Kermanshah (Iran)

    1999-11-01

    A PVC membrane electrode for copper(II) ions based on a recently synthesized naphthol-derivative Schiff's base as membrane carrier was prepared. The sensor exhibits a Nernstian response for Cu{sup 2+} ions over a wide concentration range (5.0 x 10{sup -6}-5.0 x 10{sup -2} mol/L) with a detection limit of 3.1 x 10{sup -6} mol/L (0.2 {mu}g/mL). It has a very short response time of about 5 s and can be used for 3 months without any divergence in potential. The proposed electrode revealed good selectivities over a wide variety of other cations including alkali, alkaline earth, transition and heavy metal ions and could be used in a pH range of 4.0-7.0. It was successfully applied to the direct determination and potentiometric titration of copper ion. (orig.)

  15. Comparison of function approximation, heuristic, and derivative-based methods for automatic calibration of computationally expensive groundwater bioremediation models

    Science.gov (United States)

    Mugunthan, Pradeep; Shoemaker, Christine A.; Regis, Rommel G.

    2005-11-01

    The performance of function approximation (FA) methods is compared to heuristic and derivative-based nonlinear optimization methods for automatic calibration of biokinetic parameters of a groundwater bioremediation model of chlorinated ethenes on a hypothetical and a real field case. For the hypothetical case, on the basis of 10 trials on two different objective functions, the FA methods had the lowest mean and smaller deviation of the objective function among all algorithms for a combined Nash-Sutcliffe objective and among all but the derivative-based algorithm for a total squared error objective. The best algorithms in the hypothetical case were applied to calibrate eight parameters to data obtained from a site in California. In three trials the FA methods outperformed heuristic and derivative-based methods for both objective functions. This study indicates that function approximation methods could be a more efficient alternative to heuristic and derivative-based methods for automatic calibration of computationally expensive bioremediation models.

  16. Analyzing Signal Attenuation in PFG Anomalous Diffusion via a Modified Gaussian Phase Distribution Approximation Based on Fractal Derivative Model

    CERN Document Server

    Lin, Guoxing

    2016-01-01

    Pulsed field gradient (PFG) has been increasingly employed to study anomalous diffusions in Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI). However, the analysis of PFG anomalous diffusion is complicated. In this paper, a fractal derivative model based modified Gaussian phase distribution method is proposed to describe PFG anomalous diffusion. By using the phase distribution obtained from the effective phase shift diffusion method based on fractal derivatives, and employing some of the traditional Gaussian phase distribution approximation techniques, a general signal attenuation expression for free fractional diffusion is derived. This expression describes a stretched exponential function based attenuation, which is distinct from both the exponential attenuation for normal diffusion obtained from conventional Gaussian phase distribution approximation, and the Mittag-Leffler function based attenuation for anomalous diffusion obtained from fractional derivative. The obtained signal attenu...

  17. (1-Adamantyl{4-[(2-chloro-9-isopropyl-9H-purin-6-ylaminomethyl]phenyl}methanone trichloromethane solvate

    Directory of Open Access Journals (Sweden)

    Michal Rouchal

    2009-06-01

    Full Text Available In the title compound, C26H30ClN5O·CHCl3, the purine molecule consists of essentially planar benzene and purine ring systems [maximum deviation 0.010 (4 Å for both ring systems] forming a dihedral angle of 85.52 (9°. Intermolecular N—H...N hydrogen bonds link adjacent molecules into centrosymmetric dimers. The structure also contains intermolecular C—H...O and C—H...N interactions. The benzene rings form offset face-to-face π–π stacking interactions with an interplanar distance of 3.541 (4 Å and a centroid-to-centroid distance of 4.022 (4 Å.

  18. Antipathogenic effects of structurally-related Schiff base derivatives: Structure–activity relationship

    Directory of Open Access Journals (Sweden)

    Soleiman Hisaindee

    2015-11-01

    Full Text Available Eighteen structurally-related Schiff base derivatives, which belong to salicylidenebenzylamine and 2-hydroxy-1-naphthylidenebenzylamine families were prepared and characterized by spectroscopic techniques. All the synthesized compounds were screened in vitro for their antibacterial and antifungal activities. Human pathogenic gram-negative (Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa and Serratia marcescens, gram-positive bacteria (Staphylococcus epidermidis, Staphylococcus aureus and Bacillus subtilis, and fungi (Alternaria alternata, Aspergillus niger, Penicillium roqueforti, and Saccharomyces cerevisiae were evaluated based on their toxicity to different concentrations of Schiff base compounds. For assessment of toxicity to pathogens, a disc diffusion assay was used to test the antimicrobial properties. The results revealed some antimicrobial activities of some of the synthesized compounds. Among the tested pathogens, the synthesized salicylidinaniline derivatives show highly potent action towards Alternaria alternata. Interestingly, a compound which contains the –Cl group is only effective against gram negative bacteria, but not gram positive bacteria. No remarkable antibacterial or antifungal activities were observed in the presence of –CH3 or –Br group. Furthermore, most of the naphthalene-containing compounds show no growth retardation towards bacterial or fungal pathogens. On the other hand, the presence of –OH or –SH group at para or ortho position, respectively, on the aniline site is correlated with an increased inhibitory drug effect on all pathogens. The importance of our findings to the drug research and developments is discussed in the context of finding a correlation between the structural properties of the new drugs and their biological activities.

  19. Deriving a probabilistic syntacto-semantic grammar for biomedicine based on domain-specific terminologies.

    Science.gov (United States)

    Fan, Jung-Wei; Friedman, Carol

    2011-10-01

    Biomedical natural language processing (BioNLP) is a useful technique that unlocks valuable information stored in textual data for practice and/or research. Syntactic parsing is a critical component of BioNLP applications that rely on correctly determining the sentence and phrase structure of free text. In addition to dealing with the vast amount of domain-specific terms, a robust biomedical parser needs to model the semantic grammar to obtain viable syntactic structures. With either a rule-based or corpus-based approach, the grammar engineering process requires substantial time and knowledge from experts, and does not always yield a semantically transferable grammar. To reduce the human effort and to promote semantic transferability, we propose an automated method for deriving a probabilistic grammar based on a training corpus consisting of concept strings and semantic classes from the Unified Medical Language System (UMLS), a comprehensive terminology resource widely used by the community. The grammar is designed to specify noun phrases only due to the nominal nature of the majority of biomedical terminological concepts. Evaluated on manually parsed clinical notes, the derived grammar achieved a recall of 0.644, precision of 0.737, and average cross-bracketing of 0.61, which demonstrated better performance than a control grammar with the semantic information removed. Error analysis revealed shortcomings that could be addressed to improve performance. The results indicated the feasibility of an approach which automatically incorporates terminology semantics in the building of an operational grammar. Although the current performance of the unsupervised solution does not adequately replace manual engineering, we believe once the performance issues are addressed, it could serve as an aide in a semi-supervised solution.

  20. Research progress in muscle-derived stem cells Literature retrieval results based on international database

    Institute of Scientific and Technical Information of China (English)

    Li Zhang; Wei Wang

    2012-01-01

    OBJECTIVE: To identify global research trends of muscle-derived stem cells (MDSCs) using a bibliometric analysis of the Web of Science, Research Portfolio Online Reporting Tools of the National Institutes of Health (NIH), and the Clinical Trials registry database (ClinicalTrials.gov). DATA RETRIEVAL: We performed a bibliometric analysis of data retrievals for MDSCs from 2002 to 2011 using the Web of Science, NIH, and ClinicalTrials.gov. MAIN OUTCOME MEASURES: (1) Type of literature; (2) annual publication output; (3) distribution according to journals; (4) distribution according to country; (5) distribution according to institution; (6) top cited authors over the last 10 years; (7) projects financially supported by the NIH; and (8) clinical trials registered.RESULTS: (1) In all, 802 studies on MDSCs appeared in the Web of Science from 2002 to 2011, almost half of which derived from American authors and institutes. The number of studies on MDSCs has gradually increased over the past 10 years. Most papers on MDSCs appeared in journals with a particular focus on cell biology research, such as Experimental Cell Research, Journal of Cell Science, and PLoS One. (2) Eight MDSC research projects have received over US$6 billion in funding from the NIH. The current project led by Dr. Johnny Huard of the University of Pittsburgh-"Muscle-Based Tissue Engineering to Improve Bone Healing"-is supported by the NIH. Dr. Huard has been the most productive and top-cited author in the field of gene therapy and adult stem cell research in the Web of Science over last 10 years. (3) On ClinicalTrials.gov, "Muscle Derived Cell Therapy for Bladder Exstrophy Epispadias Induced Incontinence" Phase 1 is registered and sponsored by Johns Hopkins University and has been led by Dr. John P. Gearhart since November 2009.CONCLUSION: From our analysis of the literature and research trends, we found that MDSCs may offer further benefits in regenerative medicine.

  1. Robust Analysis of Network-Based Real-Time Kinematic for GNSS-Derived Heights

    Directory of Open Access Journals (Sweden)

    Tae-Suk Bae

    2015-10-01

    Full Text Available New guidelines and procedures for real-time (RT network-based solutions are required in order to support Global Navigation Satellite System (GNSS derived heights. Two kinds of experiments were carried out to analyze the performance of the network-based real-time kinematic (RTK solutions. New test marks were installed in different surrounding environments, and the existing GPS benchmarks were used for analyzing the effect of different factors, such as baseline lengths, antenna types, on the final accuracy and reliability of the height estimation. The RT solutions are categorized into three groups: single-base RTK, multiple-epoch network RTK (mRTN, and single-epoch network RTK (sRTN. The RTK solution can be biased up to 9 mm depending on the surrounding environment, but there was no notable bias for a longer reference base station (about 30 km In addition, the occupation time for the network RTK was investigated in various cases. There is no explicit bias in the solution for different durations, but smoother results were obtained for longer durations. Further investigation is needed into the effect of changing the occupation time between solutions and into the possibility of using single-epoch solutions in precise determination of heights by GNSS.

  2. Robust Analysis of Network-Based Real-Time Kinematic for GNSS-Derived Heights.

    Science.gov (United States)

    Bae, Tae-Suk; Grejner-Brzezinska, Dorota; Mader, Gerald; Dennis, Michael

    2015-10-26

    New guidelines and procedures for real-time (RT) network-based solutions are required in order to support Global Navigation Satellite System (GNSS) derived heights. Two kinds of experiments were carried out to analyze the performance of the network-based real-time kinematic (RTK) solutions. New test marks were installed in different surrounding environments, and the existing GPS benchmarks were used for analyzing the effect of different factors, such as baseline lengths, antenna types, on the final accuracy and reliability of the height estimation. The RT solutions are categorized into three groups: single-base RTK, multiple-epoch network RTK (mRTN), and single-epoch network RTK (sRTN). The RTK solution can be biased up to 9 mm depending on the surrounding environment, but there was no notable bias for a longer reference base station (about 30 km) In addition, the occupation time for the network RTK was investigated in various cases. There is no explicit bias in the solution for different durations, but smoother results were obtained for longer durations. Further investigation is needed into the effect of changing the occupation time between solutions and into the possibility of using single-epoch solutions in precise determination of heights by GNSS.

  3. Synthesis, characterization and antibacterial studies of ruthenium(III) complexes derived from chitosan schiff base.

    Science.gov (United States)

    Vadivel, T; Dhamodaran, M

    2016-09-01

    Chitosan can be modified chemically by condensation reaction of deacetylated chitosan with aldehyde in homogeneous phase. This condensation is carried by primary amine (NH2) with aldehyde (CHO) to form corresponding schiff base. The chitosan biopolymer schiff base derivatives are synthesized with substituted aldehydes namely 4-hydroxy-3-methoxy benzaldehyde, 2-hydroxy benzaldehyde, and 2-hydroxy-3-methoxy benzaldehyde, becomes a complexing agent or ligand. The Ruthenium(III) complexes were obtained by complexation of Ruthenium with schiff base ligands and this product exhibits as an excellent solubility and more biocompatibility. The novel series of schiff base Ruthenium(III) complexes are characterized by Elemental analysis, FT-IR spectroscopy, and Thermo-gravimetric analysis (TGA). The synthesized complexes have been subjected to antibacterial study. The antibacterial results indicated that the antibacterial activity of the complexes were more effective against Gram positive and Gram negative pathogenic bacteria. These findings are giving suitable support for developing new antibacterial agent and expand our scope for applications.

  4. Synthesis and characterization of nickel complexes derived from Schiff-Bases

    Directory of Open Access Journals (Sweden)

    Mirian Y. Matsumoto

    2012-06-01

    Full Text Available Aromatic Schiff-Bases constitute a large class of organic compounds containing the imine group (C=N [1-3]. 2-hydroxybenzaldehyde (salicylaldehyde which has been frequently used for the synthesis of aromatic Schiff-Bases, it has many biological applications, such as analgesics, anti-inflammatory, antibacterial, antiviral and bactericidal activities [4-6]. From above, this project proposed the synthesis of three Schiff bases derived from salicylaldehyde prepared by condensation between salicylaldehyde with different p-substituted anilines (H, NO2 and MeO. Schiff-Bases synthesized were used as starting compound for the synthesis of nickel complexes. The synthesis of nickel complexes were carried out by adding of alcoholic solution of ligands (2 eq. in aqueous solution of NiCl2.6 H2O (1 eq. contain KOH (1eq. 3 hours. After thisMatsumoto et al. time, the reaction was kept to r.t. to obtain a precipitates. The precipitates were filtered under vacuum and they were characterized by GC-MS, FT-IR and UV-Vis

  5. Distribution coefficients of purine alkaloids in water-ammonium sulfate-alkyl acetate-dialkyl phthalate systems

    Science.gov (United States)

    Korenman, Ya. I.; Krivosheeva, O. A.; Mokshina, N. Ya.

    2012-12-01

    The distribution of purine alkaloids (caffeine, theobromine, theophylline) was studied in the systems: alkyl acetates-dialkyl phtalate-salting-out agent (ammonium sulfate). The quantitative characteristics of the extraction-distribution coefficients ( D) and the degree of extraction ( R, %) are calculated. The relationships between the distribution coefficients of alkaloids and the length of the hydrocarbon radical in the molecule of alkyl acetate (dialkyl phtalate) are determined. The possibility of predicting the distribution coefficients is demonstrated.

  6. Diisopropyl {[(R-2-(2-amino-6-chloro-9H-purin-9-yl-1-methylethoxy]methyl}phosphonate

    Directory of Open Access Journals (Sweden)

    Guobao Zhao

    2012-04-01

    Full Text Available In the title compound, C15H25ClN5O4P, the r.m.s. deviation for the purine ring system is 0.0165 Å. The coordination about the P atom is a distorted tetrahedron [O=P—O angles = 116.70 (6 and 109.87 (6°]. In the crystal, molecules are linked by N—H...O hydrogen bonds, generating a three-dimensional network.

  7. Purine salvage in the apicomplexan Sarcocystis neurona, and generation of hypoxanthine-xanthine-guanine phosphoribosyltransferase-deficient clones for positive-negative selection of transgenic parasites.

    Science.gov (United States)

    Dangoudoubiyam, Sriveny; Zhang, Zijing; Howe, Daniel K

    2014-09-01

    Sarcocystis neurona is an apicomplexan parasite that causes severe neurological disease in horses and marine mammals. The Apicomplexa are all obligate intracellular parasites that lack purine biosynthesis pathways and rely on the host cell for their purine requirements. Hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT) and adenosine kinase (AK) are key enzymes that function in two complementary purine salvage pathways in apicomplexans. Bioinformatic searches of the S. neurona genome revealed genes encoding HXGPRT, AK and all of the major purine salvage enzymes except purine nucleoside phosphorylase. Wild-type S. neurona were able to grow in the presence of mycophenolic acid (MPA) but were inhibited by 6-thioxanthine (6-TX), suggesting that the pathways involving either HXGPRT or AK are functional in this parasite. Prior work with Toxoplasma gondii demonstrated the utility of HXGPRT as a positive-negative selection marker. To enable the use of HXGPRT in S. neurona, the SnHXGPRT gene sequence was determined and a gene-targeting plasmid was transfected into S. neurona. SnHXGPRT-deficient mutants were selected with 6-TX, and single-cell clones were obtained. These Sn∆HXG parasites were susceptible to MPA and could be complemented using the heterologous T. gondii HXGPRT gene. In summary, S. neurona possesses both purine salvage pathways described in apicomplexans, thus allowing the use of HXGPRT as a positive-negative drug selection marker in this parasite.

  8. Polyurethane and polyurea nanoparticles based on polyoxyethylene castor oil derivative surfactant suitable for endovascular applications.

    Science.gov (United States)

    Morral-Ruíz, Genoveva; Melgar-Lesmes, Pedro; García, María Luísa; Solans, Conxita; García-Celma, María José

    2014-01-30

    The design of new, safe and effective nanotherapeutic systems is an important challenge for the researchers in the nanotechnology area. This study describes the formation of biocompatible polyurethane and polyurea nanoparticles based on polyoxyethylene castor oil derivative surfactant formed from O/W nano-emulsions by polymerization at the droplet interfaces in systems composed by aqueous solution/Kolliphor(®) ELP/medium chain triglyceride suitable for intravenous administration. Initial nano-emulsions incorporating highly hydrophilic materials were prepared by the phase inversion composition (PIC) method. After polymerization, nanoparticles with a small particle diameter (25-55 nm) and low polydispersity index were obtained. Parameters such as concentration of monomer, O/S weight ratio as well as the polymerization temperature were crucial to achieve a correct formation of these nanoparticles. Moreover, FT-IR studies showed the full conversion of the monomer to polyurethane and polyurea polymers. Likewise the involvement of the surfactant in the polymerization process through their nucleophilic groups to form the polymeric matrix was demonstrated. This could mean a first step in the development of biocompatible systems formulated with polyoxyethylene castor oil derivative surfactants. In addition, haemolysis and cell viability assays evidenced the good biocompatibility of KELP polyurethane and polyurea nanoparticles thus indicating the potential of these nanosystems as promising drug carriers.

  9. Properties of Thermosets Derived from Chemically Modified Triglycerides and Bio-Based Comonomers

    Directory of Open Access Journals (Sweden)

    Evan S. Beach

    2013-12-01

    Full Text Available A series of materials was prepared by curing acrylated epoxidized soybean oil (AESO and dibutyl itaconate (DBI or ethyl cinnamate (EC comonomers to provide examples of thermosets with a high proportion of bio-based carbon, in accordance with the principles of green chemistry. The comonomers, representative of cellulose-derived (DBI or potentially lignin-derived (EC raw materials, were tested at levels of 25%, 33%, and 50% by mass and the resulting products were characterized by infrared spectroscopy, thermogravimetric analysis, and dynamic mechanical analysis. Both DBI and EC were incorporated into the thermosets to a high extent (>90% at all concentrations tested. The AESO-DBI and AESO-EC blends showed substantial degradation at 390–400 °C, similar to pure AESO. Glass transition temperatures decreased as comonomer content increased; the highest Tg of 41.4 °C was observed for AESO-EC (3:1 and the lowest Tg of 1.4 °C was observed for AESO-DBI (1:1. Accordingly, at 30 °C the storage modulus values were highest for AESO-EC (3:1, 37.0 MPa and lowest for AESO-DBI (1:1, 1.5 MPa.

  10. White light generation by carbonyl based indole derivatives due to proton transfer: an efficient fluorescence sensor.

    Science.gov (United States)

    Singla, Nidhi; Bhadram, Venkata Srinu; Narayana, Chandrabhas; Chowdhury, Papia

    2013-04-01

    The motivation of the present work is to understand the optical, chemical, and electrical aspects of the proton transfer mechanism of indole (I) and some carbonyl based indole derivatives: indole-3-carboxaldehyde (I3C) and indole-7-carboxaldehyde (I7C) for both powder form and their liquid solution. Structural information for indole derivatives (isolated molecule and in solution) is obtained with density functional theory (DFT) and time dependent DFT (TD-DFT) methods. Calculated transition energies are used to generate UV-vis, FTIR, Raman, and NMR spectra which are later verified with the experimental spectra. The occurrence of different conformers [cis (N(c)), trans (N(t)), and zwitterion (Z*)] have been interpreted by Mulliken charge, natural bond orbital (NBO) analysis, and polarization versus electric field (P-E loop) studies. (1)H and (13)C NMR and molecular vibrational frequencies of the fundamental modes established the stability of Nc due to the presence of intramolecular hydrogen bonding (IHB) in the ground state (S0). Computed/experimental UV-vis absorption/emission studies reveal the creation of new species: zwitterion (Z*) and anion (A*) in the excited state (S1) due to excited state intramolecular and intermolecular proton transfer (ESI(ra)PT and ESI(er)PT). Increased electrical conductivity (σ(ac)) with temperature and increased ferroelectric polarization at higher field verifies proton conduction in I7C.

  11. New hybrid magnetic nanoparticles based on chitosan-maltose derivative for antitumor drug delivery.

    Science.gov (United States)

    Alupei, Liana; Peptu, Catalina Anisoara; Lungan, Andreea-Maria; Desbrieres, Jacques; Chiscan, Ovidiu; Radji, Sadia; Popa, Marcel

    2016-11-01

    The aim of the present study is to obtain, for the first time, polymer magnetic nanoparticles based on the chitosan-maltose derivative and magnetite. By chemically modifying the chitosan, its solubility in aqueous media was improved, which in turn facilitates the nanoparticles' preparation. Resulting polymers exhibit enhanced hydrophilia, which is an important factor in increasing the retention time of nanoparticles in the blood flow. The preparation of nanoparticles relied on the double crosslinking technique (ionic and covalent) in reverse emulsion which ensures the mechanical stability of the polymer carrier. The characterization of both the chitosan derivative and nanoparticles was accomplished by Fourier Transform Infrared Spectroscopy, Nuclear Magnetic Resonance Spectroscopy, Scanning Electron Microscopy, Transmission Electron Microscopy, Atomic Force Microscopy, Vibrating Sample Magnetometry, and Thermogravimetric Analysis. The evaluation of morphological, dimensional, structural, and magnetical properties, as well as thermal stability and swelling behavior of nanoparticles was made from the point of view of the polymer/magnetite ratio. The study of 5-Fluorouracil loading and release kinetics as well as evaluating the cytotoxicity and hemocompatibility of nanoparticles justify their adequate behavior in their potential use as devices for targeted transport of antitumor drugs.

  12. Organic sensitizers featuring thiophene derivative based donors with improved stability and photovoltaic performance.

    Science.gov (United States)

    Miao, Kai; Liang, Mao; Wang, Zhihui; Zhang, Chunyao; Sun, Zhe; Xue, Song

    2017-01-18

    Thiophene derivatives, including thieno[3,2-b][1]benzothiophene (TBT), benzo[b]thiophene (BT), 2-phenylthieno[3,2-b]thiophene (PTT) and 2-phenylthiophene (PT), have been introduced as donors for the construction of triarylamine organic dyes (M52, M53, M56, M57 and M52A). The absorption, electrochemical and photovoltaic properties as well as the stabilities of these dyes are systematically investigated and compared with the reference dye (M55), whose donor is composed of the hexyloxybenzene (HOB) unit. It is found that introducing the TBT, BT, PTT or PT donors positively shifted the HOMO and LUMO levels of the organic dyes, providing a larger driving force for regeneration and reducing the energy loss for electron injection. In addition, we found that M52, which contains the TBT unit, exhibited better photovoltaic performance and photostability as compared to the reference dye. In contrast, M53 displayed the lowest efficiency and stability of these dyes, indicating that the BT unit is not a good building block for donors. Interestingly, upon the incorporation of the mixed donor (TBT-HOB), M52A achieved a desirable driving force for regeneration without a loss in light absorption, thus resulting in a further improved photovoltaic performance with respect to that of M52. This work demonstrates that introducing donors based on thiophene derivatives is a good strategy for tuning the energy levels and thereby enhancing the efficiency of the resulting devices.

  13. Design of PID controller with incomplete derivation based on ant system algorithm

    Institute of Scientific and Technical Information of China (English)

    Guanzheng TAN; Qingdong ZENG; Wenbin LI

    2004-01-01

    A new and intelligent design method for PID controller with incomplete derivation is proposed based on the ant system algorithm (ASA).For a given control system with this kind of PID controller,a group of optimal PID controller parameters K*p,T*i, and T*d can be obtained by taking the overshoot,settling time,and steady-state error of the system's unit step response as the performance indexes and by use of our improved ant system algorithm.K*p,T*i, and T*d can be used in real-time control.This kind of controller is called the ASA-PID controller with incomplete derivation.To verify the performance of the ASA-PID controller,three different typical transfer functions were tested,and three existing typical tuning methods of PID controller parameters,including the Ziegler-Nichols method (ZN),the genetic algorithm (GA),and the simulated annealing (SA),were adopted for comparison.The simulation results showed that the ASA-PID controller can be used to control different objects and has better performance compared with the ZN-PID and GA-PID controllers,and comparable performance compared with the SA-PID controller.

  14. Analyzing signal attenuation in PFG anomalous diffusion via a modified Gaussian phase distribution approximation based on fractal derivative model

    Science.gov (United States)

    Lin, Guoxing

    2017-02-01

    Pulsed field gradient (PFG) technique is a noninvasive tool, and has been increasingly employed to study anomalous diffusions in Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI). However, the analysis of PFG anomalous diffusion is much more complicated than normal diffusion. In this paper, a fractal derivative model based modified Gaussian phase distribution method is proposed to describe PFG anomalous diffusion. By using the phase distribution obtained from the effective phase shift diffusion method based on fractal derivatives, and employing some of the traditional Gaussian phase distribution approximation techniques, a general signal attenuation expression for free fractional diffusion is derived. This expression describes a stretched exponential function based attenuation, which is distinct from both the exponential attenuation for normal diffusion obtained from conventional Gaussian phase distribution approximation, and the Mittag-Leffler function based attenuation for anomalous diffusion obtained from fractional derivative. The obtained signal attenuation expression can analyze the finite gradient pulse width (FGPW) effect. Additionally, it can generally be applied to all three types of PFG fractional diffusions classified based on time derivative order α and space derivative order β. These three types of fractional diffusions include time-fractional diffusion with { 0 reported results based on effective phase shift diffusion equation method and instantaneous signal attenuation method. This method provides a new, convenient approximation formalism for analyzing PFG anomalous diffusion experiments. The expression that can simultaneously interpret general fractional diffusion and FGPW effect could be especially important in PFG MRI, where the narrow gradient pulse limit cannot be satisfied.

  15. Profiles of phenolic compounds and purine alkaloids during the development of seeds of Theobroma cacao cv. Trinitario.

    Science.gov (United States)

    Pereira-Caro, Gema; Borges, Gina; Nagai, Chifumi; Jackson, Mel C; Yokota, Takao; Crozier, Alan; Ashihara, Hiroshi

    2013-01-16

    Changes occurring in phenolic compounds and purine alkaloids, during the growth of seeds of cacao (Theobroma cacao) cv. Trinitario, were investigated using HPLC-MS/MS. Extracts of seeds with a fresh weight of 125, 700, 1550, and 2050 mg (stages 1-4, respectively) were analyzed. The phenolic compounds present in highest concentrations in developing and mature seeds (stages 3 and 4) were flavonols and flavan-3-ols. Flavan-3-ols existed as monomers of epicatechin and catechin and as procyanidins. Type B procyanidins were major components and varied from dimers to pentadecamer. Two anthocyanins, cyanidin-3-O-arabinoside and cyanidin-3-O-galactoside, along with the N-phenylpropernoyl-l-amino acids, N-caffeoyl-l-aspartate, N-coumaroyl-l-aspartate, N-coumaroyl-3-hydroxytyrosine (clovamide), and N-coumaroyltyrosine (deoxyclovamide), and the purine alkaloids theobromine and caffeine, were present in stage 3 and 4 seeds. Other purine alkaloids, such as theophylline and additional methylxanthines, did not occur in detectable quantities. Flavan-3-ols were the only components to accumulate in detectable quantities in young seeds at developmental stages 1 and 2.

  16. Cyclic Benzimidazole Derivatives and Their Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Karminski-Zamola, G.

    2008-06-01

    Full Text Available Over the past years benzimidazole derivatives are one of the most extensively studied classes of heterocyclic compounds, and have received much attention from synthetic organic as well as medicinal chemists, because of their well known biological activities and their applications in several areas as materials in electronics, in electrochemistry as anticorrosive agents, as polymers or optical materials and fluorescent tags in DNA sequencing. The structure of vitamin B12, as an example, contains a benzimidazole group. Compounds containing benzimidazole nuclei show anticancer, antineoplastic, antiinfective, antibacterial, antifungal and many others activities. Due to the structural similarity of benzimidazole nuclei with some naturally occurring compounds such as purine, they can easily interact with biomolecules of the living systems. The introduction of an additional substituent on the benzimidazole nuclei has been increasing attention in the expectation that such changes could potentially affect the interaction of the molecules with biological targets. Fused cyclic benzimidazole derivatives, as benzimidazo[1,2-a]quinolines,benzimidazo[1,2-c]quinazolines, benzimidazo[2,1-b]isoquinolines and many others, have also interesting biological activities and most of them are very good anticancer agents.DNA is the molecular target of many anticancer drugs in clinical use and development. Compounds which can bind to DNA with intercalative or non-intercalative mechanism play a major role in biological processes such as gene transcription or DNA replication. Benzoannulated benzimidazole analogues contain a planar chromophore and have the ability to become inserted between adjacent base pairs of DNA double helix. Intercalators are recognized as one of the most important classes of anticancer agents. So an understanding of the drug-DNA interactions is a promising approach to developing novel reagents and plays a key role in pharmacology today.

  17. Smart photovoltaics based on dye-sensitized solar cells using photochromic spiropyran derivatives as photosensitizers

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Shengbo; Ting, Hungkit; Ma, Yingzhuang; Zheng, Lingling; Zhang, Miwei [State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, Department of Physics, Peking University, Beijing 100871 (China); Xiao, Lixin, E-mail: zjchen@pku.edu.cn, E-mail: lxxiao@pku.edu.cn; Chen, Zhijian, E-mail: zjchen@pku.edu.cn, E-mail: lxxiao@pku.edu.cn [State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, Department of Physics, Peking University, Beijing 100871 (China); Haixi Collaborative Innovation Center for New Display Devices and Systems Integration, Fuzhou University, Fuzhou 350002 (China)

    2015-05-15

    In this paper, smart photovoltaic (SPV) devices, integrating both functions of solar cells and smart windows, was fabricated based on dye-sensitized solar cells using photochromic spiropyran derivatives SIBT as photosensitizers. SPV devices have self-regulated power conversion efficiency (PCE) and light transmission responding to the incident spectra due to the photoisomerization of SIBT. SIBT isomerize from closed-ring form to open-ring form under UV illumination, accompanied with enhanced visible light absorption and electron delocalization. Therefore, increased PCE and absorption in SPV devices were observed under UV treatment and the devices can be restored gradually to the initial status when kept in dark. The SPV devices have self-regulation of PCE and sunlight transmission responding to the changing sun spectra in different times of a day, providing a proper energy usage and a better sun-shading.

  18. A simple derivation and classification of common probability distributions based on information symmetry and measurement scale

    CERN Document Server

    Frank, Steven A

    2010-01-01

    Commonly observed patterns typically follow a few distinct families of probability distributions. Over one hundred years ago, Karl Pearson provided a systematic derivation and classification of the common continuous distributions. His approach was phenomenological: a differential equation that generated common distributions without any underlying conceptual basis for why common distributions have particular forms and what explains the familial relations. Pearson's system and its descendants remain the most popular systematic classification of probability distributions. Here, we unify the disparate forms of common distributions into a single system based on two meaningful and justifiable propositions. First, distributions follow maximum entropy subject to constraints, where maximum entropy is equivalent to minimum information. Second, different problems associate magnitude to information in different ways, an association we describe in terms of the relation between information invariance and measurement scale....

  19. STRUCTURE BASED DRUG DESIGN STUDIES ON HETEROARYL PROPANOIC ACID DERIVATIVES AS PPARΓ AGONISTS

    Directory of Open Access Journals (Sweden)

    ARUN KUMAR,MANGA RATNAM,ARCHANA KUMARI, AJAY BABU

    2013-09-01

    Full Text Available Peroxisome proliferator-activated receptors (PPARs are a group of nuclear receptorproteins. Docking studies are based on several factors. Among 15 entries of PPARγ, 2Q6S wastaken for docking analysis, as it showed 418 most favored regions, 35 in additionally allowedregion and none of the residue in disallowed regions. To carry out drug designing, moleculeswere considered from the literature in which substitution of R1 position with dihydrofurylreported to have high dock score (-14.98 Kcal/mol than the remaining analogues, with bettergeometry and interactions. Hence docking analysis using heteroaryl propionic acid derivatives asanti-diabetic agents suggest the reproducibility of active molecules being predicted bycomputational docking studies using Auto dock software.

  20. The first genetic linkage map of Primulina eburnea (Gesneriaceae) based on EST-derived SNP marker

    Indian Academy of Sciences (India)

    CHEN FENG; CHAO FENG; MING KANG

    2016-06-01

    Primulina eburneais a promising candidate for domestication and floriculture, since it is easy to culture and has beautiful flow-ers. An F2population of 189 individuals was established for the construction of first-generation linkage maps based onexpressed sequence tags-derived single-nucleotide polymorphism markers using the massARRAY genotyping platform. Ofthe 232 screened markers, 215 were assigned to 18 LG according to the haploid number of chromosomes in the species. Thelinkage map spanned a total of 3774.7 cM with an average distance of 17.6 cM between adjacent markers. This linkage mapprovides a framework for identification of important genes in breeding programm

  1. Aliphatic amine responsive organogel system based on a simple naphthalimide derivative.

    Science.gov (United States)

    Cao, Xinhua; Zhang, Tingting; Gao, Aiping; Li, Keli; Cheng, Qiuli; Song, Lijuan; Zhang, Min

    2014-09-07

    A new gelator 1 based on a simple naphthalimide derivative was synthesized and fully characterized. It was found that the organogel 1 was formed only in a mixed solvent of methanol and H2O (1/1, v/v). The organogel was thoroughly characterized by using various microscopic techniques including field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), and UV-vis, fluorescence and Fourier transform infrared (FTIR) spectroscopy. Hydrogen bonds were the main driving force for the organogel formation. Interestingly, the organogel 1 exhibited the ability to distinguish aliphatic amines from aromatic amines. The gel state and fluorescence emission intensity were both changed after two minutes after the addition of aliphatic amines. This organogel system could be applied in the detection of aliphatic amine pollutants.

  2. Design of PID controller with incomplete derivation based on differential evolution algorithm

    Institute of Scientific and Technical Information of China (English)

    Wu Lianghong; Wang Yaonan; Zhou Shaowu; Tan Wen

    2008-01-01

    To determine the optimal or near optimal parameters of PID controller with incomplete derivation, a novel design method based on differential evolution (DE) algorithm is presented. The controller is called DE-PID controller. To overcome the disadvantages of the integral performance criteria in the frequency domain such as IAE, ISE, and ITSE, a new performance criterion in the time domain is proposed. The optimization procedures employing the DE algorithm to search the optimal or near optimal PID controller parameters of a control system are demonstrated in detail. Three typical control systems are chosen to test and evaluate the adaptation and robustness of the proposed DE-PID controller. The simulation results show that the proposed approach has superior features of easy implementation, stable convergence characteristic, and good computational efficiency. Compared with the ZN, GA, and ASA, the proposed design method is indeed more efficient and robust in improving the step response of a control system.

  3. The first genetic linkage map of Primulina eburnea (Gesneriaceae) based on EST-derived SNP markers.

    Science.gov (United States)

    Feng, Chen; Feng, Chao; Kang, Ming

    2016-06-01

    Primulina eburnea is a promising candidate for domestication and floriculture, since it is easy to culture and has beautiful flowers. An F₂ population of 189 individuals was established for the construction of first-generation linkage maps based on expressed sequence tags-derived single-nucleotide polymorphism markers using the massARRAY genotyping platform. Of the 232 screened markers, 215 were assigned to 18 LG according to the haploid number of chromosomes in the species. The linkage map spanned a total of 3774.7 cM with an average distance of 17.6 cM between adjacent markers. This linkage map provides a framework for identification of important genes in breeding programmes.

  4. SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF SCHIFF BASE DERIVATIVES OF 4-CHLORO-3-NITROBENZOIC ACID

    Directory of Open Access Journals (Sweden)

    Kumari Santosh

    2012-12-01

    Full Text Available 4-chloro-3-nitrobenzoic acid was selected as nucleus structure having good antibacterial property. It was thought worthwhile to synthesize Schiff base derivatives of 4-chloro-3-nitrobenzoic acid in search of better antibacterial agents. The compounds were synthesized by first reducing nitro group in presence of Sn/HCl to 3-amino-4-chlorobenzoic acid, which on treatment with substituted benzaldehyde afforded the synthesis of the envisaged compounds. The synthesized compounds were purified and chemically characterized. They were screened for their antibacterial activity and result suggested that SKY-1, SKY-5 and SKY-8 were highly active against both Gram (+ and Gram(- bacteria like B.subtilis, S.aureus and E.coli whereas all are were found moderately to inactive against P.aeruginosa.

  5. Image Clustering Method Based on Density Maps Derived from Self-Organizing Mapping: SOM

    Directory of Open Access Journals (Sweden)

    Kohei Arai

    2012-07-01

    Full Text Available A new method for image clustering with density maps derived from Self-Organizing Maps (SOM is proposed together with a clarification of learning processes during a construction of clusters. It is found that the proposed SOM based image clustering method shows much better clustered result for both simulation and real satellite imagery data. It is also found that the separability among clusters of the proposed method is 16% longer than the existing k-mean clustering. It is also found that the separability among clusters of the proposed method is 16% longer than the existing k-mean clustering. In accordance with the experimental results with Landsat-5 TM image, it takes more than 20000 of iteration for convergence of the SOM learning processes.

  6. Catecholase activity investigations using in situ copper complexes continuing Schiff base derivatives with a theoretical calculation

    Directory of Open Access Journals (Sweden)

    A. Djedouani

    2015-03-01

    Full Text Available The study of catecholase activity of a series of Schiff base compounds using in situ copper complexes of 4-hydroxy-6-methyl-3-(1-(phenyliminoethyl-2H-pyran-2-one derivatives has been reported. The reaction rate depends on four parameters: The nature of the substitution in para position to the benzene ring, the nature of counter anion, the concentration of ligand and the nature of solvent. The highest rate activity is given by complex resulting from one equivalent of ligand L2 and two equivalents of copper acetate in methanol, which equal to 62.25 µmol.min-1.L-1.In other part, a theoretical study of such ligands using the semi-empirical method AM1 were also investigated. A good relationship founded between the maximal reaction rate (Vmax and the HOMO energy (Pearson correlation: r=-0.794.

  7. Poly-Acrylic Acid Derivatives as Diesel Flow Improver for Paraffin-Based Daqing Diesel

    Institute of Scientific and Technical Information of China (English)

    Cuiyu Jiang; Ming Xu; Xiaoli Xi; Panlun Qi; Hongyan Shang

    2006-01-01

    Since the diesel products from paraffin-based Daqing crude oil showed low sensitivity to certain commercial diesel pour point depressant (PPDs) that resulted from the high content of paraffin, certain poly-acrylic acid derivatives (PADE) with-COOR,-COOH,-CONHR, and -COO-NH3+R groups by molecular design on the mechanics of diesel; PPDs were synthesized and evaluated as cold flow improver for Daqing 0# diesel in this paper. The pure PADE was superior to the commercial PPDs and displayed a substantial ability of wax crystals dispersion. There was a synergistic effect among the PADE and T1804 and secondary amine. The synergism clearly improved the low temperature performance of Daqing diesel products and could reduce the cold filter plugging point of 0# diesel by 6-7 ℃.

  8. Synthesis and Biological Evaluation of Mannich Bases of Isoxazoline Derivatives as Novel Anti-Microbial Agents

    Directory of Open Access Journals (Sweden)

    Pawar Sudhir

    2012-01-01

    Full Text Available A novel series of compounds were synthesized by condensation reaction of substituted acetophenone (1a-b with substituted aldehyde (2a-b in presence of alcoholic sodium hydroxide to get intermediate chalcones (3a-c, which were further treated with hydroxylamine hydrochloride in presence of sodium hydroxide to get isoxazolines derivatives (4a-c. The latter were refluxed with substituted primary amines and formaldehyde for 6-10 h to afford Mannich bases. The synthesized compounds were characterized on the basis of their spectral (IR, 1HNMR data and evaluated for the antimicrobial activity by using Zone of Inhibition by cup plate method and Minimum Inhibitory Concentration by broth dilution method.

  9. AN EXPLORATION ON THE SYNTHESIS AND BIO-APPLICATIONS OF DERIVATIVES OF HETEROCYCLIC MANNICH BASES

    Directory of Open Access Journals (Sweden)

    P. S. Manjula

    2016-01-01

    Full Text Available The Mannich reaction is a three-component reaction of an aldehyde, a primary or secondary amine and a ketone which is one of the most powerful C-C bond forming reactions in organic synthesis. It leads to β-amino carbonyl compounds, which are useful for the syntheses of nitrogen containing compounds, such as natural products and medicinally relevant compounds. The versatility and potential of these compounds to introduce both functional and structural diversity using the Mannich reaction have stimulated the creativity of chemists. Keeping in view of the importance of this organic moiety in the field of medicine and biology here an attempt has been made to review the synthesis and biological importance of heterocyclic Mannich base derivatives.

  10. Earth's gravity field modelling based on satellite accelerations derived from onboard GPS phase measurements

    Science.gov (United States)

    Guo, X.; Ditmar, P.; Zhao, Q.; Klees, R.; Farahani, H. H.

    2017-09-01

    GPS data collected by satellite gravity missions can be used for extracting the long-wavelength part of the Earth's gravity field. We propose a new data processing method which makes use of the `average acceleration' approach to gravity field modelling. In this method, satellite accelerations are directly derived from GPS carrier phase measurements with an epoch-differenced scheme. As a result, no ambiguity solutions are needed and the systematic errors that do not change much from epoch to epoch are largely eliminated. The GPS data collected by the Gravity Field and Steady-State Ocean Circulation Explorer (GOCE) satellite mission are used to demonstrate the added value of the proposed method. An analysis of the residual accelerations shows that accelerations derived in this way are more precise, with noise being reduced by about 20 and 5% at the cross-track component and the other two components, respectively, as compared to those based on kinematic orbits. The accelerations obtained in this way allow the recovery of the gravity field to a slightly higher maximum degree compared to the solution based on kinematic orbits. Furthermore, the gravity field solution has an overall better performance. Errors in spherical harmonic coefficients are smaller, especially at low degrees. The cumulative geoid height error is reduced by about 15 and 5% up to degree 50 and 150, respectively. An analysis in the spatial domain shows that large errors along the geomagnetic equator, which are caused by a high electron density coupled with large short-term variations, are substantially reduced. Finally, the new method allows for a better observation of mass transport signals. In particular, sufficiently realistic signatures of regional mass anomalies in North America and south-west Africa are obtained.

  11. Earth's gravity field modelling based on satellite accelerations derived from onboard GPS phase measurements

    Science.gov (United States)

    Guo, X.; Ditmar, P.; Zhao, Q.; Klees, R.; Farahani, H. H.

    2017-02-01

    GPS data collected by satellite gravity missions can be used for extracting the long-wavelength part of the Earth's gravity field. We propose a new data processing method which makes use of the `average acceleration' approach to gravity field modelling. In this method, satellite accelerations are directly derived from GPS carrier phase measurements with an epoch-differenced scheme. As a result, no ambiguity solutions are needed and the systematic errors that do not change much from epoch to epoch are largely eliminated. The GPS data collected by the Gravity Field and Steady-State Ocean Circulation Explorer (GOCE) satellite mission are used to demonstrate the added value of the proposed method. An analysis of the residual accelerations shows that accelerations derived in this way are more precise, with noise being reduced by about 20 and 5% at the cross-track component and the other two components, respectively, as compared to those based on kinematic orbits. The accelerations obtained in this way allow the recovery of the gravity field to a slightly higher maximum degree compared to the solution based on kinematic orbits. Furthermore, the gravity field solution has an overall better performance. Errors in spherical harmonic coefficients are smaller, especially at low degrees. The cumulative geoid height error is reduced by about 15 and 5% up to degree 50 and 150, respectively. An analysis in the spatial domain shows that large errors along the geomagnetic equator, which are caused by a high electron density coupled with large short-term variations, are substantially reduced. Finally, the new method allows for a better observation of mass transport signals. In particular, sufficiently realistic signatures of regional mass anomalies in North America and south-west Africa are obtained.

  12. High performance liquid chromatographic profiles of nucleosides, bases and tryptophan in the plasma of the Tasmanian devil and four other marsupial species.

    Science.gov (United States)

    Sallis, J D; Nicol, S C; Perrone, P; Brown, P R

    1984-01-01

    Plasma profiles of nucleosides, bases and trytophan of five marsupial species were established using the reversed-phase mode of high performance liquid chromatography (RHPLC). Within each species, the profiles were highly reproducible and between species there were distinct differences. In the Tasmanian devil, the circulating levels of constituents examined with one exception, were generally lower than in the other marsupials. The exception was a constituent present in large amounts and having the characteristics of a purine nucleoside derivative which was found only in the plasma of the devil.

  13. Current Status of Older and New Purine Nucleoside Analogues in the Treatment of Lymphoproliferative Diseases

    Directory of Open Access Journals (Sweden)

    Pawel Robak

    2009-03-01

    Full Text Available For the past few years more and more new cytotoxic agents active in the treatment of hematological malignancies have been synthesized and become available for either in vitro studies or clinical trials. Among them the class of antineoplastic drugs belonging to the purine nucleoside analogues group (PNAs plays an important role. Three of them: pentostatin (DCF, cladribine (2-CdA and fludarabine (FA were approved by Food and Drug Administration (FDA for the treatment of hematological malignancies. Recently three novel PNAs: clofarabine (CAFdA, nelarabine (ara-G and forodesine (immucillin H, BCX-1777 have been synthesized and introduced into preclinical studies and clinical trials. These agents seem to be useful mainly for the treatment of human T-cell proliferative disorders and they are currently undergoing clinical trials in lymphoid malignancies. However, there are also several studies suggesting the role of these drugs in B-cell malignancies. This review will summarize current knowledge concerning the mechanism of action, pharmacologic properties, clinical activity and toxicity of PNAs accepted for use in clinical practice, as well as new agents available for clinical trials.

  14. The role of a purine-specific nucleoside hydrolase in spore germination of Bacillus thuringiensis.

    Science.gov (United States)

    Liang, Liang; He, Xihong; Liu, Gang; Tan, Huarong

    2008-05-01

    A homologous gene (iunH) of a putative nucleoside hydrolase (NH), which had been identified from the exosporia of Bacillus cereus and Bacillus anthracis spores, was cloned from Bacillus thuringiensis subsp. kurstaki. Disruption of iunH did not affect the vegetative growth and sporulation of Bacillus thuringiensis, but promoted both inosine- and adenosine-induced spore germination. The inosine- or adenosine-induced germination rate decreased when the wild-type iunH gene was overexpressed in Bacillus thuringiensis. The iunH gene product was characterized as a purine-specific NH. The kinetic parameters of IunH with inosine as substrate were K(m)=399+/-115 microM, k(cat)=48.9+/-8.5 s(-1) and k(cat)/K(m)=1.23 x 10(5) M(-1) s(-1). The optimal pH and temperature for IunH were found to be pH 6 and 80 degrees C. Meanwhile, the specific activity of inosine hydrolase in intact spores of the wild-type strain with inosine as substrate was 2.89+/-0.23x10(-2) micromol min(-1) (mg dry wt)(-1). These results indicate that IunH is important in moderating inosine- or adenosine-induced germination of Bacillus thuringiensis spores.

  15. Solvent effects on the photochemistry of 4-aminoimidazole-5-carbonitrile, a prebiotically plausible precursor of purines.

    Science.gov (United States)

    Szabla, Rafał; Sponer, Judit E; Sponer, Jiří; Sobolewski, Andrzej L; Góra, Robert W

    2014-09-01

    4-Aminoimidazole-5-carbonitrile (AICN) was suggested as a prebiotically plausible precursor of purine nucleobases and nucleotides. Although it can be formed in a sequence of photoreactions, AICN is immune to further irradiation with UV-light. We present state-of-the-art multi-reference quantum-chemical calculations of potential energy surface cuts and conical intersection optimizations to explain the molecular mechanisms underlying the photostability of this compound. We have identified the N-H bond stretching and ring-puckering mechanisms that should be responsible for the photochemistry of AICN in the gas phase. We have further considered the photochemistry of AICN-water clusters, while including up to six explicit water molecules. The calculations reveal charge transfer to solvent followed by formation of an H3O(+) cation, both of which occur on the (1)πσ* hypersurface. Interestingly, a second proton transfer to an adjacent water molecule leads to a (1)πσ*/S0 conical intersection. We suggest that this electron-driven proton relay might be characteristic of low-lying (1)πσ* states in chromophore-water clusters. Owing to its nature, this mechanism might also be responsible for the photostability of analogous organic molecules in bulk water.

  16. Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Aust, M.R.; Norby-Slycord, C.J.; Andrews, L.G.; Markert, M.L. (Duke Univ. Medical Center, Durham, NC (United States)); Barrett, M.J. (Sunnyside Hospital, Clackamas, OR (United States))

    1992-10-01

    Purine nucleoside phosphorylase (PNP) deficiency is an inherited autosomal recessive disorder resulting in severe combined immunodeficiency. The purpose of this study was to determine the molecular defects responsible for PNP deficiency in one such patient. The patient's PNP cDNA was amplified by PCR and sequenced. Point mutations leading to amino acid substitutions were found in both alleles. One point mutation led to a Ser-to-Gly substitution at amino acid 51 and was common to both alleles. In addition, an Asp-to-Gly substitution at amino acid 128 and an Arg-to-Pro substitution at amino acid 234 were found in the maternal and paternal alleles, respectively. In order to prove that these mutations were responsible for the disease state, each of the three mutations was constructed separately by site-directed mutagenesis of the normal PNP cDNA, and each was transiently expressed in COS cells. Lysates from cells transfected with the allele carrying the substitution at amino acid 51 retained both function and immunoreactivity. Lysates from cells transfected with PNP alleles carrying a substitution at either amino acid 128 or amino acid 234 contained immunoreactive material but had no detectable human PNP activity. In summary, molecular analysis of this patient identified point mutations within the PNP gene which are responsible for the enzyme deficiency. 52 refs., 5 figs.

  17. Deriving pathway maps from automated text analysis using a grammar-based approach.

    Science.gov (United States)

    Olsson, Björn; Gawronska, Barbara; Erlendsson, Björn

    2006-04-01

    We demonstrate how automated text analysis can be used to support the large-scale analysis of metabolic and regulatory pathways by deriving pathway maps from textual descriptions found in the scientific literature. The main assumption is that correct syntactic analysis combined with domain-specific heuristics provides a good basis for relation extraction. Our method uses an algorithm that searches through the syntactic trees produced by a parser based on a Referent Grammar formalism, identifies relations mentioned in the sentence, and classifies them with respect to their semantic class and epistemic status (facts, counterfactuals, hypotheses). The semantic categories used in the classification are based on the relation set used in KEGG (Kyoto Encyclopedia of Genes and Genomes), so that pathway maps using KEGG notation can be automatically generated. We present the current version of the relation extraction algorithm and an evaluation based on a corpus of abstracts obtained from PubMed. The results indicate that the method is able to combine a reasonable coverage with high accuracy. We found that 61% of all sentences were parsed, and 97% of the parse trees were judged to be correct. The extraction algorithm was tested on a sample of 300 parse trees and was found to produce correct extractions in 90.5% of the cases.

  18. Microcalorimetric Study on the Inhibition of Escherichia coil by Some Novel Pyridine Amide Schiff Base Derivatives

    Institute of Scientific and Technical Information of China (English)

    LI Chao-Hong; ZHANG Li-Xia; CAI Li-Hua; LIU Yi; HU Pei-Zhi

    2008-01-01

    The antibacterial effect of a series of novel pyridine amide Schiff base compounds on Escherichia coli was investigated by a microcalorimetric method at 37℃.The metabolic power-time curves of the bacteria treated by the compounds were obtained,and the thermokinetic parameters were analyzed,from which the antibacterial activities of these compounds were evaluated.The results show that two compounds F and G have good activity on aerobic multiplying metabolism of E.coli,with the value of IC50 106 and 113 mg/L respectively,but have no effective action on the fermentation metabolism of E.coli.The action of the compounds on the non-multiplying metabolism was investigated by taking the heat output of E.coli in the stationary phase as the guideline of the activity.The experimental results revealed that the hydrophilicity of these Schiff bases had a great influence on their antibacterial activity,which results from the bacterial cell wall structure.The antibacterial structure-activity relationship of these Schiff base derivatives was also briefly discussed.The antibacterial activity of the compounds against E.coli was as follows:compound F>G>C>D>E>B>A.

  19. Base preferences in non-templated nucleotide incorporation by MMLV-derived reverse transcriptases.

    Directory of Open Access Journals (Sweden)

    Pawel Zajac

    Full Text Available Reverse transcriptases derived from Moloney Murine Leukemia Virus (MMLV have an intrinsic terminal transferase activity, which causes the addition of a few non-templated nucleotides at the 3' end of cDNA, with a preference for cytosine. This mechanism can be exploited to make the reverse transcriptase switch template from the RNA molecule to a secondary oligonucleotide during first-strand cDNA synthesis, and thereby to introduce arbitrary barcode or adaptor sequences in the cDNA. Because the mechanism is relatively efficient and occurs in a single reaction, it has recently found use in several protocols for single-cell RNA sequencing. However, the base preference of the terminal transferase activity is not known in detail, which may lead to inefficiencies in template switching when starting from tiny amounts of mRNA. Here, we used fully degenerate oligos to determine the exact base preference at the template switching site up to a distance of ten nucleotides. We found a strong preference for guanosine at the first non-templated nucleotide, with a greatly reduced bias at progressively more distant positions. Based on this result, and a number of careful optimizations, we report conditions for efficient template switching for cDNA amplification from single cells.

  20. Base Preferences in Non-Templated Nucleotide Incorporation by MMLV-Derived Reverse Transcriptases

    Science.gov (United States)

    Zajac, Pawel; Islam, Saiful; Hochgerner, Hannah; Lönnerberg, Peter; Linnarsson, Sten

    2013-01-01

    Reverse transcriptases derived from Moloney Murine Leukemia Virus (MMLV) have an intrinsic terminal transferase activity, which causes the addition of a few non-templated nucleotides at the 3´ end of cDNA, with a preference for cytosine. This mechanism can be exploited to make the reverse transcriptase switch template from the RNA molecule to a secondary oligonucleotide during first-strand cDNA synthesis, and thereby to introduce arbitrary barcode or adaptor sequences in the cDNA. Because the mechanism is relatively efficient and occurs in a single reaction, it has recently found use in several protocols for single-cell RNA sequencing. However, the base preference of the terminal transferase activity is not known in detail, which may lead to inefficiencies in template switching when starting from tiny amounts of mRNA. Here, we used fully degenerate oligos to determine the exact base preference at the template switching site up to a distance of ten nucleotides. We found a strong preference for guanosine at the first non-templated nucleotide, with a greatly reduced bias at progressively more distant positions. Based on this result, and a number of careful optimizations, we report conditions for efficient template switching for cDNA amplification from single cells. PMID:24392002

  1. GPS Interference Mitigation Using Derivative-free Kalman Filter-based RNN

    Directory of Open Access Journals (Sweden)

    W. L. Mao

    2016-09-01

    Full Text Available The global positioning system (GPS with accurate positioning and timing properties has become integral part of all applications around the world. Radio frequency interference can significantly decrease the performance of GPS receivers or even completely prohibit the acquisition or tracking of satellites. The approaches of system performances that can be further enhanced by preprocessing to reject the jamming signal will be investigated. A recurrent neural network (RNN predictor for the GPS anti-jamming applications will be proposed. The adaptive RNN predictor is utilized to accurately predict the narrowband waveform based on an unscented Kalman filter (UKF-based algorithm. The UKF algorithm as a derivative-free alternative to the extended Kalman filter (EKF in the framework of state-estimation is adopted to achieve better performance in terms of convergence rate and quality of solution. The adaptive RNN filter can be successfully applied for the suppression of interference with a number of different narrowband formats, i.e. continuous wave interference (CWI, multi-tone CWI, swept CWI and pulsed CWI, to emulate realistic circumstances. Simulation results show that the proposed UKF-based scheme can offer the superior performances to suppress the interference over the conventional methods by computing mean squared prediction error (MSPE and signal-to-noise ratio (SNR improvements.

  2. Deriving statistical significance maps for SVM based image classification and group comparisons.

    Science.gov (United States)

    Gaonkar, Bilwaj; Davatzikos, Christos

    2012-01-01

    Population based pattern analysis and classification for quantifying structural and functional differences between diverse groups has been shown to be a powerful tool for the study of a number of diseases, and is quite commonly used especially in neuroimaging. The alternative to these pattern analysis methods, namely mass univariate methods such as voxel based analysis and all related methods, cannot detect multivariate patterns associated with group differences, and are not particularly suitable for developing individual-based diagnostic and prognostic biomarkers. A commonly used pattern analysis tool is the support vector machine (SVM). Unlike univariate statistical frameworks for morphometry, analytical tools for statistical inference are unavailable for the SVM. In this paper, we show that null distributions ordinarily obtained by permutation tests using SVMs can be analytically approximated from the data. The analytical computation takes a small fraction of the time it takes to do an actual permutation test, thereby rendering it possible to quickly create statistical significance maps derived from SVMs. Such maps are critical for understanding imaging patterns of group differences and interpreting which anatomical regions are important in determining the classifier's decision.

  3. Gallic acid-based indanone derivative interacts synergistically with tetracycline by inhibiting efflux pump in multidrug resistant E. coli.

    Science.gov (United States)

    Dwivedi, Gaurav Raj; Tiwari, Nimisha; Singh, Aastha; Kumar, Akhil; Roy, Sudeep; Negi, Arvind Singh; Pal, Anirban; Chanda, Debabrata; Sharma, Ashok; Darokar, Mahendra P

    2016-03-01

    The purpose of the present study was to study the synergy potential of gallic acid-based derivatives in combination with conventional antibiotics using multidrug resistant cultures of Escherichia coli. Gallic acid-based derivatives significantly reduced the MIC of tetracycline against multidrug resistant clinical isolate of E. coli. The best representative, 3-(3',4,'5'-trimethoxyphenyl)-4,5,6-trimethoxyindanone-1, an indanone derivative of gallic acid, was observed to inhibit ethidium bromide efflux and ATPase which was also supported by in silico docking. This derivative extended the post-antibiotic effect and decreased the mutation prevention concentration of tetracycline. This derivative in combination with TET was able to reduce the concentration of TNFα up to 18-fold in Swiss albino mice. This derivative was nontoxic and well tolerated up to 300 mg/kg dose in subacute oral toxicity study in mice. This is the first report of gallic acid-based indanone derivative as drug resistance reversal agent acting through ATP-dependent efflux pump inhibition.

  4. Enzymic capacities of purine de Novo and salvage pathways for nucleotide synthesis in normal and neoplastic tissues.

    Science.gov (United States)

    Natsumeda, Y; Prajda, N; Donohue, J P; Glover, J L; Weber, G

    1984-06-01

    The enzymic capacities of the de novo and the salvage pathways for purine nucleotide synthesis were compared in rat in normal, differentiating, and regenerating liver, and in three hepatomas of widely different growth rates. The activities of the key de novo and salvage enzymes were also determined in mouse lung and Lewis lung carcinoma, in human kidney and liver, and in renal cell carcinoma and hepatocellular carcinomas. A precise and reproducible assay was worked out for measuring the activities of adenine phosphoribosyltransferase (EC 2.4.2.7) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT; EC 2.4.2.8) in crude liver and hepatoma systems. Kinetic studies on the salvage enzymes were carried out in the crude 100,000 X g supernatant fluid from normal liver and rapidly growing hepatoma 3924A. In both tissue extracts, Michaelis-Menten kinetics was observed for adenine phosphoribosyltransferase and HGPRT. The reciprocal plots for 5-phosphoribosyl-1-pyrophosphate (PRPP) of liver and hepatoma enzymes gave apparent KmS of 2 microM for adenine phosphoribosyltransferase and 4 microM for HGPRT, showing two orders of magnitude higher affinities for PRPP than that of the rate-limiting enzyme of de novo purine synthesis, amidophosphoribosyltransferase (EC 2.4.2.14) (Km = 400 to 900 microM). The apparent Km values for adenine of liver and hepatoma adenine phosphoribosyltransferase were 0.6 to 0.9 microM, respectively. For both liver and hepatoma HGPRT, the reciprocal plots for hypoxanthine and guanine yielded the same Km of 3 microM. The specific activities of purine phosphoribosyltransferases were markedly higher than that of amidophosphoribosyltransferase in rat thymus, spleen, testis, bone marrow, colon, liver, kidney cortex, lung, heart, brain, and skeletal muscle, but were lower in the small intestine. In hepatomas and regenerating and differentiating liver, the activities of the salvage enzymes were 2.1- to 32-fold higher than that of

  5. Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia.

    Science.gov (United States)

    Yao, Jeffrey K; Dougherty, George G; Reddy, Ravinder D; Keshavan, Matcheri S; Montrose, Debra M; Matson, Wayne R; McEvoy, Joseph; Kaddurah-Daouk, Rima

    2010-03-03

    Purine catabolism may be an unappreciated, but important component of the homeostatic response of mitochondria to oxidant stress. Accumulating evidence suggests a pivotal role of oxidative stress in schizophrenia pathology. Using high-pressure liquid chromatography coupled with a coulometric multi-electrode array system, we compared 6 purine metabolites simultaneously in plasma between first-episode neuroleptic-naïve patients with schizophrenia (FENNS, n = 25) and healthy controls (HC, n = 30), as well as between FENNS at baseline (BL) and 4 weeks (4w) after antipsychotic treatment. Significantly higher levels of xanthosine (Xant) and lower levels of guanine (G) were seen in both patient groups compared to HC subjects. Moreover, the ratios of G/guanosine (Gr), uric acid (UA)/Gr, and UA/Xant were significantly lower, whereas the ratio of Xant/G was significantly higher in FENNS-BL than in HC. Such changes remained in FENNS-4w with exception that the ratio of UA/Gr was normalized. All 3 groups had significant correlations between G and UA, and Xan and hypoxanthine (Hx). By contrast, correlations of UA with each of Xan and Hx, and the correlation of Xan with Gr were all quite significant for the HC but not for the FENNS. Finally, correlations of Gr with each of UA and G were significant for both HC and FENNS-BL but not for the FENNS-4w. During purine catabolism, both conversions of Gr to G and of Xant to Xan are reversible. Decreased ratios of product to precursor suggested a shift favorable to Xant production from Xan, resulting in decreased UA levels in the FENNS. Specifically, the reduced UA/Gr ratio was nearly normalized after 4 weeks of antipsychotic treatment. In addition, there are tightly correlated precursor and product relationships within purine pathways; although some of these correlations persist across disease or medication status, others appear to be lost among FENNS. Taken together, these results suggest that the potential for steady formation of

  6. Quenching of nucleotide-derived radicals by bisbenzimidazole derivative Hoechst-33258 in aqueous solution

    Indian Academy of Sciences (India)

    H Mohan; A Adhikary; V Jain; J P Mittal

    2000-08-01

    The pulse radiolysis technique has been employed to investigate the reaction of DNA-minor-groove ligand bisbenzimidazole Hoechst 33258 with pyrimidine and purine nucleotide-derived radicals. Formation of an N-centred Hoechst-33258 radical is observed. Bimolecular rate constants and the yields of Hoechst-33258 radical have been evaluated. While the rate constant for the reaction of pyrimidine-derived radicals with Hoechst-33258 remained the same (1-2) × 109 dm3 mol-1s-1, the yields of the Hoechst-33258 radical varied from 25% (5 -cytidine monophosphate) to 75% (5 -guanosine monophosphate) under anoxic conditions. The rate constant values for the reaction of purine-derived radicals with Hoechst-33258, under oxic and anoxic conditions, remained the same whereas with pyrimidine-derived radicals, the rate constant value under oxic conditions was about two orders of magnitude lower than under anoxic conditions. The difference in the yields of Hoechst-33258 radical with various nucleotide-derived radicals suggest the formation of different types of radicals and that the reaction mainly occurs by electron transfer from Hoechst-33258 to the nucleotide radicals.

  7. [Mass spectrometry of triterpene glycosides molecular complexation with purine bases of nucleic acids].

    Science.gov (United States)

    Lekar', A V; Vetrova, E V; Borisenko, N I; Iakovishin, L A; Grishkovets, V I

    2011-01-01

    The molecular complexation of adenine and guanine with hederagenin 3-O-alpha-L-rhamnopyranosyl-(1-->2)-O-alpha-L-arabinopyranoside (alpha-hederin) and its 28-O-alpha-L-rhamnopyranosyl-(1-->4)-O-beta-D-glucopyranosyl-(1-->6)-O-beta-D-glucopyranosyl ester (hederasaponin C) was investigated for the first time using the method of electrospray ionization mass spectrometry. Guanine forms complexes more diverse in composition than adenine.

  8. First space-based derivation of the global atmospheric methanol emission fluxes

    Directory of Open Access Journals (Sweden)

    T. Stavrakou

    2011-05-01

    Full Text Available This study provides improved methanol emission estimates on the global scale, in particular for the largest methanol source, the terrestrial biosphere, and for biomass burning. To this purpose, one complete year of spaceborne measurements of tropospheric methanol columns retrieved for the first time by the thermal infrared sensor IASI aboard the MetOp satellite are compared with distributions calculated by the IMAGESv2 global chemistry-transport model. Two model simulations are performed using a priori biogenic methanol emissions either from the new MEGANv2.1 emission model, which is fully described in this work and is based on net ecosystem flux measurements, or from a previous parameterization based on net primary production by Jacob et al. (2005. A significantly better model performance in terms of both amplitude and seasonality is achieved through the use of MEGANv2.1 in most world regions, with respect to IASI data, and to surface- and air-based methanol measurements, even though important discrepancies over several regions are still present. As a second step of this study, we combine the MEGANv2.1 and the IASI column abundances over continents in an inverse modelling scheme based on the adjoint of the IMAGESv2 model to generate an improved global methanol emission source. The global optimized source totals 187 Tg yr−1 with a contribution of 100 Tg yr−1 from plants, only slightly lower than the a priori MEGANv2.1 value of 105 Tg yr−1. Large decreases with respect to the MEGANv2.1 biogenic source are inferred over Amazonia (up to 55 % and Indonesia (up to 58 %, whereas more moderate reductions are recorded in the Eastern US (20–25 % and Central Africa (25–35 %. On the other hand, the biogenic source is found to strongly increase in the arid and semi-arid regions of Central Asia (up to a factor of 5 and Western US (factor of 2, probably due to a source of methanol specific to these ecosystems which

  9. A generic probability based algorithm to derive regional patterns of crops in time and space

    Science.gov (United States)

    Wattenbach, Martin; Oijen, Marcel v.; Leip, Adrian; Hutchings, Nick; Balkovic, Juraj; Smith, Pete

    2013-04-01

    Croplands are not only the key to human food supply, they also change the biophysical and biogeochemical properties of the land surface leading to changes in the water cycle, energy partitioning, influence soil erosion and substantially contribute to the amount of greenhouse gases entering the atmosphere. The effects of croplands on the environment depend on the type of crop and the associated management which both are related to the site conditions, economic boundary settings as well as preferences of individual farmers. However, at a given point of time the pattern of crops in a landscape is not only determined by environmental and socioeconomic conditions but also by the compatibility to the crops which had been grown in the years before at the current field and its surrounding cropping area. The crop compatibility is driven by factors like pests and diseases, crop driven changes in soil structure and timing of cultivation steps. Given these effects of crops on the biochemical cycle and their interdependence with the mentioned boundary conditions, there is a demand in the regional and global modelling community to account for these regional patterns. Here we present a Bayesian crop distribution generator algorithm that is used to calculate the combined and conditional probability for a crop to appear in time and space using sparse and disparate information. The input information to define the most probable crop per year and grid cell is based on combined probabilities derived from the a crop transition matrix representing good agricultural practice, crop specific soil suitability derived from the European soil database and statistical information about harvested area from the Eurostat database. The reported Eurostat crop area also provides the target proportion to be matched by the algorithm on the level of administrative units (Nomenclature des Unités Territoriales Statistiques - NUTS). The algorithm is applied for the EU27 to derive regional spatial and

  10. A plant derived multifunctional tool for nanobiotechnology based on Tomato bushy stunt virus.

    Science.gov (United States)

    Grasso, Simone; Lico, Chiara; Imperatori, Francesca; Santi, Luca

    2013-06-01

    Structure, size, physicochemical properties and production strategies make many plant viruses ideal protein based nanoscaffolds, nanocontainers and nano-building blocks expected to deliver a multitude of applications in different fields such as biomedicine, pharmaceutical chemistry, separation science, catalytic chemistry, crop pest control and biomaterials science. Functionalization of viral nanoparticles through modification by design of their external and internal surfaces is essential to fully exploit the potentiality of these objects. In the present paper we describe the development of a plant derived multifunctional tool for nanobiotechnology based on Tomato bushy stunt virus. We demonstrate the ability of this system to remarkably sustain genetic modifications and in vitro chemical derivatizations of its outer surface, which resulted in the successful display of large chimeric peptides fusions and small chemical molecules, respectively. Moreover, we have defined physicochemical conditions for viral swelling and reversible viral pore gating that we have successfully employed for foreign molecules loading and retention in the inner cavity of this plant virus nanoparticles system. Finally, a production and purification strategy from Nicotiana benthamiana plants has been addressed and optimized.

  11. Deriving Shape-Based Features for C. elegans Locomotion Using Dimensionality Reduction Methods

    Science.gov (United States)

    Gyenes, Bertalan; Brown, André E. X.

    2016-01-01

    High-throughput analysis of animal behavior is increasingly common following the advances of recording technology, leading to large high-dimensional data sets. This dimensionality can sometimes be reduced while still retaining relevant information. In the case of the nematode worm Caenorhabditis elegans, more than 90% of the shape variance can be captured using just four principal components. However, it remains unclear if other methods can achieve a more compact representation or contribute further biological insight to worm locomotion. Here we take a data-driven approach to worm shape analysis using independent component analysis (ICA), non-negative matrix factorization (NMF), a cosine series, and jPCA (a dynamic variant of principal component analysis [PCA]) and confirm that the dimensionality of worm shape space is close to four. Projecting worm shapes onto the bases derived using each method gives interpretable features ranging from head movements to tail oscillation. We use these as a comparison method to find differences between the wild type N2 worms and various mutants. For example, we find that the neuropeptide mutant nlp-1(ok1469) has an exaggerated head movement suggesting a mode of action for the previously described increased turning rate. The different bases provide complementary views of worm behavior and we expect that closer examination of the time series of projected amplitudes will lead to new results in the future. PMID:27582697

  12. Efficient Inverted Organic Solar Cells Based on a Fullerene Derivative-Modified Transparent Cathode.

    Science.gov (United States)

    Wang, Yifan; Cong, Hailin; Yu, Bing; Zhang, Zhiguo; Zhan, Xiaowei

    2017-09-11

    Indium tin oxide (ITO) is a transparent conductive material which is extensively used in organic solar cells (OSCs) as electrodes. In inverted OSCs, ITO is usually employed as a cathode, which should be modified by cathode buffer layers (CBLs) to achieve better contact with the active layers. In this paper, an amine group functionalized fullerene derivative (DMAPA-C60) is used as a CBL to modify the transparent cathode ITO in inverted OSCs based on PTB7 as a donor and PC71BM as an acceptor. Compared with traditional ZnO CBL, DMAPA-C60 exhibited comparable transmittance. OSCs based on DMAPA-C60 show much better device performance compared with their ZnO counterparts (power conversion efficiencies (PCEs) improved from 6.24 to 7.43%). This is mainly because a better contact between the DMAPA-C60 modified ITO and the active layer is formed, which leads to better electron transport and collection. Nanoscale morphologies also demonstrate that the surface of DMAPA-C60-modified ITO is plainer than the ZnO counterparts, which also leads to the better device performance.

  13. Proliferation of canine bone marrow derived mesenchymal stem cells on different nanomaterial based thin film scaffolds.

    Science.gov (United States)

    Das, Kinsuk; Mili, Bhabesh; A P, Madhusoodan; Saxena, Abhishek Chandra; Kumar, Ajay; Singh, Praveen; Verma, Med Ram; Sarkar, Mihir; Bag, Sadhan

    2017-04-01

    Stem cell niche research uses nanotechnologies to mimic the extra-cellular microenvironment to promote proliferation and differentiation. The aim of designing different scaffolds is to simulate the best structural and environmental pattern for extracellular matrix. This experiment was designed to study the proliferative behaviour of canine bone marrow deriver mesenchymal stem cells (MSCs) on different nanomaterial based thin film scaffolds of carbon nanotubes (CNT), chitosan and poly ε-caprolactone. Similar number of cells was seeded on the scaffolds and standard cell culture flask, taken as control. Cells were maintained on DMEM media and relative number of metabolically active cells was determined by MTT assay up to day six of culture. Cells proliferated on control and all the scaffolds as the days progressed. Although proliferation rate was slow but no decline of cell number was noticed on the scaffolds during the study period. Initially, the cell proliferation was lower on CNT but as time progressed no significant difference was observed compared to control. The result indicated that nanomaterial based scaffolds reduce the proliferation rate of canine MSCs. However, canine MSCs adapted and proliferated better on CNT substrate in vitro and may be used as a scaffold component in canine tissue engineering in future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Size Switchable Supramolecular Nanoparticle Based on Azobenzene Derivative within Anionic Pillar[5]arene

    Science.gov (United States)

    Zhang, Cai-Cai; Li, Sheng-Hua; Zhang, Cui-Fang; Liu, Yu

    2016-11-01

    A photo/thermal-switchable supramolecular nanoparticles assembly has been constructed based on an inclusion complex between anionic pillar[5]arene 2C-WP5A and azobenzene derivative Azo-py-OMe (G). The novel anionic pillar[5]arene-based host-guest inclusion complexation was investigated by the 1H NMR titration, 2D ROESY and isothermal titration microcalorimetry (ITC) showing high association constant (Ka) of (2.60 ± 0.06) × 104 M‑1 with 1:1 binding stoichiometry. Furthermore, the supramolecular nanoparticles assembly can be conveniently obtained from G and a small amount of 2C-WP5A in aqueous solution, which was so-called “host induced aggregating (HIA)”. The size and morphology of the supramolecular nanoparticles assembly were characterized by TEM and DLS. As a result of the photo/thermal-isomerization of G included in the cavity of 2C-WP5A, the size of these nanoparticles could reversibly change from ~800 nm to ~250 nm, which could switch the solution of this assembly from turbid to clear.

  15. Structure and physicochemical properties of thin film photosemiconductor cells based on porphine derivatives

    Science.gov (United States)

    Kazak, A. V.; Usol'tseva, N. V.; Smirnova, A. I.; Bodnarchuk, V. V.; Sul'yanov, S. N.; Yablonskii, S. V.

    2016-05-01

    Photosemiconductor thin films based on two organic porphine derivatives have been investigated. These compounds have different pendent groups; the film morphology, along with the specific fabrication technique, is determined to a great extent by these groups. The films have been fabricated by vacuum sputtering and using the Langmuir-Schaefer method. According to the atomic force microscopy (AFM) data, the Langmuir-Schaefer films are more homogeneous than the sputtered ones. It is shown that the sputtered films based on substituted porphine have a looser stacking than the initial analog. A spectroscopy study revealed a bathochromic shift of the Soret band in the Langmuir-Schaefer films-sputtered films series. This shift is explained by the increase in the concentration and size of molecular aggregates in sputtered films. It is shown that a polycrystalline C60 fullerene film deposited onto an amorphous substituted porphine layer improves the photoelectric characteristics of the latter. Both the time stability of the photodiode structure and its ampere‒watt sensitivity increase (by a factor of 10 in the transition regime). The steady-state current does not change. The effect of polarity reversal of the photovoltaic signal is observed in a planar C60‒substituted metalloporphine heterostructure, which is similar to the pyroelectric effect. The polarity reversal can be explained by the contribution of the trap charge and discharge current at the interface between the amorphous photosemiconductor and crystalline photosemiconductor to the resulting photoelectric current.

  16. Recent developments and future prospects on bio-based polyesters derived from renewable resources: A review.

    Science.gov (United States)

    Zia, Khalid Mahmood; Noreen, Aqdas; Zuber, Mohammad; Tabasum, Shazia; Mujahid, Mohammad

    2016-01-01

    A significantly growing interest is to design a new strategy for development of bio-polyesters from renewable resources due to limited fossil fuel reserves, rise of petrochemicals price and emission of green house gasses. Therefore, this review aims to present an overview on synthesis of biocompatible, biodegradable and cost effective polyesters from biomass and their prospective in different fields including packaging, coating, tissue engineering, drug delivery system and many more. Isosorbide, 2,4:3,5-di-O-methylene-d-mannitol, bicyclic diacetalyzed galactaric acid, 2,5-furandicarboxylic acid, citric, 2,3-O-methylene l-threitol, dimethyl 2,3-O-methylene l-threarate, betulin, dihydrocarvone, decalactone, pimaric acid, ricinoleic acid and sebacic acid, are some important monomers derived from biomass which are used for bio-based polyester manufacturing, consequently, replacing the petrochemical based polyesters. The last part of this review highlights some recent advances in polyester blends and composites in order to improve their properties for exceptional biomedical applications i.e. skin tissue engineering, guided bone regeneration, bone healing process, wound healing and wound acceleration. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. QSAR modeling for quinoxaline derivatives using genetic algorithm and simulated annealing based feature selection.

    Science.gov (United States)

    Ghosh, P; Bagchi, M C

    2009-01-01

    With a view to the rational design of selective quinoxaline derivatives, 2D and 3D-QSAR models have been developed for the prediction of anti-tubercular activities. Successful implementation of a predictive QSAR model largely depends on the selection of a preferred set of molecular descriptors that can signify the chemico-biological interaction. Genetic algorithm (GA) and simulated annealing (SA) are applied as variable selection methods for model development. 2D-QSAR modeling using GA or SA based partial least squares (GA-PLS and SA-PLS) methods identified some important topological and electrostatic descriptors as important factor for tubercular activity. Kohonen network and counter propagation artificial neural network (CP-ANN) considering GA and SA based feature selection methods have been applied for such QSAR modeling of Quinoxaline compounds. Out of a variable pool of 380 molecular descriptors, predictive QSAR models are developed for the training set and validated on the test set compounds and a comparative study of the relative effectiveness of linear and non-linear approaches has been investigated. Further analysis using 3D-QSAR technique identifies two models obtained by GA-PLS and SA-PLS methods leading to anti-tubercular activity prediction. The influences of steric and electrostatic field effects generated by the contribution plots are discussed. The results indicate that SA is a very effective variable selection approach for such 3D-QSAR modeling.

  18. Discovery and development of natural product-derived chemotherapeutic agents based on a medicinal chemistry approach.

    Science.gov (United States)

    Lee, Kuo-Hsiung

    2010-03-26

    Medicinal plants have long been an excellent source of pharmaceutical agents. Accordingly, the long-term objectives of the author's research program are to discover and design new chemotherapeutic agents based on plant-derived compound leads by using a medicinal chemistry approach, which is a combination of chemistry and biology. Different examples of promising bioactive natural products and their synthetic analogues, including sesquiterpene lactones, quassinoids, naphthoquinones, phenylquinolones, dithiophenediones, neo-tanshinlactone, tylophorine, suksdorfin, DCK, and DCP, will be presented with respect to their discovery and preclinical development as potential clinical trial candidates. Research approaches include bioactivity- or mechanism of action-directed isolation and characterization of active compounds, rational drug design-based modification and analogue synthesis, and structure-activity relationship and mechanism of action studies. Current clinical trial agents discovered by the Natural Products Research Laboratories, University of North Carolina, include bevirimat (dimethyl succinyl betulinic acid), which is now in phase IIb trials for treating AIDS. Bevirimat is also the first in a new class of HIV drug candidates called "maturation inhibitors". In addition, an etoposide analogue, GL-331, progressed to anticancer phase II clinical trials, and the curcumin analogue JC-9 is in phase II clinical trials for treating acne and in development for trials against prostate cancer. The discovery and development of these clinical trial candidates will also be discussed.

  19. Evaluation of a physically-based snow model with infrared and microwave satellite-derived estimates

    Science.gov (United States)

    Wang, L.

    2013-05-01

    Snow (with high albedo, as well as low roughness and thermal conductivity) has significant influence on the land-atmosphere interactions in the cold climate and regions of high elevation. The spatial and temporal variability of the snow distribution on a basin scale greatly determines the timing and magnitude of spring snowmelt runoff. For improved water resources management, a physically-based distributed snow model has been developed and applied to the upper Yellow River Basin to provide the outputs of snow variables as well as streamflows from 2001 to 2005. Remotely-sensed infrared information from MODIS satellites has been used to evaluate the model's outputs of spatially-distributed snow cover extent (SCE) and land surface temperature (LST); while the simulated snow depth (SD) and snow water equivalent (SWE) have been compared with the microwave information from SSM/I and AMSR-E satellites. In general, the simulated streamflows (including spring snowmelt) agree fairly well with the gauge-based observations; while the modeled snow variables show acceptable accuracies through comparing to various satellite-derived estimates from infrared or microwave information.;

  20. A novel acidic pH fluorescent probe based on a benzothiazole derivative.

    Science.gov (United States)

    Ma, Qiujuan; Li, Xian; Feng, Suxiang; Liang, Beibei; Zhou, Tiqiang; Xu, Min; Ma, Zhuoyi

    2017-04-15

    A novel acidic pH fluorescent probe 1 based on a benzothiazole derivative has been designed, synthesized and developed. The linear response range covers the acidic pH range from 3.44 to 6.46, which is valuable for pH researches in acidic environment. The evaluated pKa value of the probe 1 is 4.23. The fluorescence enhancement of the studied probe 1 with an increase in hydrogen ions concentration is based on the hindering of enhanced photo-induced electron transfer (PET) process. Moreover, the pH sensor possesses a highly selective response to H(+) in the presence of metal ions, anions and other bioactive small molecules which would be interfere with its fluorescent pH response. Furthermore, the probe 1 responds to acidic pH with short response time that was less than 1min. The probe 1 has been successfully applied to confocal fluorescence imaging in live HeLa cells and can selectively stain lysosomes. All of such good properties prove it can be used to monitoring pH fluctuations in acidic environment with high sensitivity, pH dependence and short response time.

  1. Synthesis of kaempferide Mannich base derivatives and their antiproliferative activity on three human cancer cell lines.

    Science.gov (United States)

    Nguyen, Van-Son; Shi, Ling; Luan, Fang-Qian; Wang, Qiu-An

    2015-01-01

    Kaempferide (3,5,7-trihydroxy-4'-methoxyflavone, 1), a naturally occurring flavonoid with potent anticancer activity in a number of human tumour cell lines, was first semisynthesized from naringin. Based on Mannich reaction of kaempferide with various secondary amines and formaldehyde, nine novel kaempferide Mannich base derivatives 2-10 were synthesized. The aminomethylation occurred preferentially in the position at C-6 and C-8 of the A-ring of kaempferide. All the synthetic compounds were tested for antiproliferative activity against three human cancer cell lines (Hela, HCC1954, SK-OV-3) by the standard MTT method. The results showed that compounds 1, 2 and 5-10 were more potent against Hela cells with IC50 values of 12.47-28.24 μM than the positive control cis-platin (IC50 41.25 μM), compounds 5, 6, 8 and 10 were more potent against HCC1954 cells with IC50 values of 8.82-14.97 μM than the positive control cis-platin (IC50 29.68 μM), and compounds 2, 3, 5, 6 and 10 were more potent against SK-OV-3 cells with IC50 values of 7.67-18.50 μM than the positive control cis-platin (IC50 21.27 μM).

  2. Semi-aromatic polyesters based on a carbohydrate-derived rigid diol for engineering plastics.

    Science.gov (United States)

    Wu, Jing; Eduard, Pieter; Thiyagarajan, Shanmugam; Noordover, Bart A J; van Es, Daan S; Koning, Cor E

    2015-01-01

    New carbohydrate-based polyesters were prepared from isoidide-2,5-dimethanol (extended isoidide, XII) through melt polymerization with dimethyl esters of terephthalic acid (TA) and furan-2,5-dicarboxylic acid (FDCA), yielding semi-crystalline prepolymers. Subsequent solid-state post-condensation (SSPC) gave high molecular weight (Mn =30 kg mol(-1) for FDCA) materials, the first examples of high Mn , semi-aromatic homopolyesters containing isohexide derivatives obtained via industrially relevant procedures. NMR spectroscopy showed that the stereo-configuration of XII was preserved under the applied conditions. The polyesters are thermally stable up to 380 °C. The TA- and FDCA-based polyesters have high Tg (105 °C and 94 °C, resp.) and Tm (284 °C and 250 °C, resp.) values. Its reactivity, stability, and ability to afford high Tg and Tm polyesters make XII a promising diol for the synthesis of engineering polymers.

  3. Catalytic wet air oxidation of 2-chlorophenol over sewage sludge-derived carbon-based catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Tu, Yuting [Institut de recherches sur la catalyse et l’environnement de Lyon (IRCELYON), CNRS – Université Claude Bernard Lyon 1, 2 Avenue Albert Einstein, 69626 Villeurbanne Cedex (France); School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou 510275 (China); Xiong, Ya; Tian, Shuanghong [School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou 510275 (China); Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology, Guangzhou 510275 (China); Kong, Lingjun [School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou 510275 (China); Descorme, Claude, E-mail: claude.descorme@ircelyon.univ-lyon1.fr [Institut de recherches sur la catalyse et l’environnement de Lyon (IRCELYON), CNRS – Université Claude Bernard Lyon 1, 2 Avenue Albert Einstein, 69626 Villeurbanne Cedex (France)

    2014-07-15

    Highlights: • A sewage sludge derived carbon-supported iron oxide catalyst (FeSC) was prepared. • FeSC exhibited high catalytic activity in the wet air oxidation of 2-chlorophenol. • A strong correlation was observed between the 2-CP conversion, the iron leaching and the pH. • Using an acetate buffer, the iron leaching was suppressed while keeping some catalytic activity. • A simplified reaction pathway was proposed for the CWAO of 2-CP over the FeSC catalyst. - Abstract: A sewage sludge derived carbon-supported iron oxide catalyst (FeSC) was prepared and used in the Catalytic Wet Air Oxidation (CWAO) of 2-chlorophenol (2-CP). The catalysts were characterized in terms of elemental composition, surface area, pH{sub PZC}, XRD and SEM. The performances of the FeSC catalyst in the CWAO of 2-CP was assessed in a batch reactor operated at 120 °C under 0.9 MPa oxygen partial pressure. Complete decomposition of 2-CP was achieved within 5 h and 90% Total Organic Carbon (TOC) was removed after 24 h of reaction. Quite a straight correlation was observed between the 2-CP conversion, the amount of iron leached in solution and the pH of the reaction mixture at a given reaction time, indicating a strong predominance of the homogeneous catalysis contribution. The iron leaching could be efficiently prevented when the pH of the solution was maintained at values higher than 4.5, while the catalytic activity was only slightly reduced. Upon four successive batch CWAO experiments, using the same FeSC catalyst recovered by filtration after pH adjustment, only a very minor catalyst deactivation was observed. Finally, based on all the identified intermediates, a simplified reaction pathway was proposed for the CWAO of 2-CP over the FeSC catalyst.

  4. Large-scale derived flood frequency analysis based on continuous simulation

    Science.gov (United States)

    Dung Nguyen, Viet; Hundecha, Yeshewatesfa; Guse, Björn; Vorogushyn, Sergiy; Merz, Bruno

    2016-04-01

    There is an increasing need for spatially consistent flood risk assessments at the regional scale (several 100.000 km2), in particular in the insurance industry and for national risk reduction strategies. However, most large-scale flood risk assessments are composed of smaller-scale assessments and show spatial inconsistencies. To overcome this deficit, a large-scale flood model composed of a weather generator and catchments models was developed reflecting the spatially inherent heterogeneity. The weather generator is a multisite and multivariate stochastic model capable of generating synthetic meteorological fields (precipitation, temperature, etc.) at daily resolution for the regional scale. These fields respect the observed autocorrelation, spatial correlation and co-variance between the variables. They are used as input into catchment models. A long-term simulation of this combined system enables to derive very long discharge series at many catchment locations serving as a basic for spatially consistent flood risk estimates at the regional scale. This combined model was set up and validated for major river catchments in Germany. The weather generator was trained by 53-year observation data at 528 stations covering not only the complete Germany but also parts of France, Switzerland, Czech Republic and Australia with the aggregated spatial scale of 443,931 km2. 10.000 years of daily meteorological fields for the study area were generated. Likewise, rainfall-runoff simulations with SWIM were performed for the entire Elbe, Rhine, Weser, Donau and Ems catchments. The validation results illustrate a good performance of the combined system, as the simulated flood magnitudes and frequencies agree well with the observed flood data. Based on continuous simulation this model chain is then used to estimate flood quantiles for the whole Germany including upstream headwater catchments in neighbouring countries. This continuous large scale approach overcomes the several

  5. Barotropic Mechanisms of Derivative-based Uncertainty Propagation in Drake Passage Transport Estimation

    Science.gov (United States)

    Kalmikov, A.; Heimbach, P.

    2013-12-01

    We apply derivative-based uncertainty quantification (UQ) and sensitivity methods to the estimation of Drake Passage transport in a global barotropic configuration of the MIT ocean general circulation model (MITgcm). Sensitivity and uncertainty fields are evaluated via first and second derivative codes of the MITgcm, generated via algorithmic differentiation (AD). Observation uncertainties are projected to uncertainties in the control variables by inversion of the Hessian of the nonlinear least-squares misfit function. Only data-supported components of Hessian information are retained through elimination of the unconstrained uncertainty nullspace. The assimilated observation uncertainty is combined with prior control variable uncertainties to reduce their posterior uncertainty. The spatial patterns of posterior uncertainty reduction and their temporal evolution are explained in terms of barotropic dynamics. Global uncertainty teleconnection mechanisms are identified as barotropic uncertainty waves. Uncertainty coupling across different control fields is demonstrated by assimilation of sea surface height uncertainty. A second step in our UQ scheme consists in propagating prior and posterior uncertainties of the model controls onto model output variables of interest, here Drake Passage transport. Forward uncertainty propagation amounts to matrix transformation of the uncertainty covariances via the model Jacobian and its adjoint. Sources of uncertainties of the transport are revealed through analysis of the adjoint wave dynamics in the model. These adjoint (reversed) mechanisms are associated with the evolution of sensitivity fields and our method formally extends sensitivity analysis to uncertainty quantification. Inverse uncertainty propagation mechanisms can be linked to adjoint dynamics in a similar manner. The posterior correlations of controls are found to dominate the reduction of the transport uncertainty compared to the marginal uncertainty reduction of the

  6. Design of two-channel filter bank using nature inspired optimization based fractional derivative constraints.

    Science.gov (United States)

    Kuldeep, B; Singh, V K; Kumar, A; Singh, G K

    2015-01-01

    In this article, a novel approach for 2-channel linear phase quadrature mirror filter (QMF) bank design based on a hybrid of gradient based optimization and optimization of fractional derivative constraints is introduced. For the purpose of this work, recently proposed nature inspired optimization techniques such as cuckoo search (CS), modified cuckoo search (MCS) and wind driven optimization (WDO) are explored for the design of QMF bank. 2-Channel QMF is also designed with particle swarm optimization (PSO) and artificial bee colony (ABC) nature inspired optimization techniques. The design problem is formulated in frequency domain as sum of L2 norm of error in passband, stopband and transition band at quadrature frequency. The contribution of this work is the novel hybrid combination of gradient based optimization (Lagrange multiplier method) and nature inspired optimization (CS, MCS, WDO, PSO and ABC) and its usage for optimizing the design problem. Performance of the proposed method is evaluated by passband error (ϕp), stopband error (ϕs), transition band error (ϕt), peak reconstruction error (PRE), stopband attenuation (As) and computational time. The design examples illustrate the ingenuity of the proposed method. Results are also compared with the other existing algorithms, and it was found that the proposed method gives best result in terms of peak reconstruction error and transition band error while it is comparable in terms of passband and stopband error. Results show that the proposed method is successful for both lower and higher order 2-channel QMF bank design. A comparative study of various nature inspired optimization techniques is also presented, and the study singles out CS as a best QMF optimization technique. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

  7. Silver ion recognition using potentiometric sensor based on recently synthesized isoquinoline-1,3-dione derivatives

    Directory of Open Access Journals (Sweden)

    AJAR KAMAL

    2012-08-01

    Full Text Available The four derivatives of isoquinoline-1,3-dione based on β-lactum (I-IV, have been explored as neutral ionophores for preparing poly(vinylchloride based polymeric membrane electrodes (PME selective to silver(I ions. The addition of sodium tetraphenylborate (NaTPB and dioctylsebacate (DOS as a plasticizer was found to improve the performance of ion selective electrodes. The best performance was obtained with PME-1 based on ionophore I having composition: ionophore (9.2 mg, PVC (100.1 mg, DOS (201.1 mg and NaTPB (1.5 mg in 5 mL tetrahydrofuran. The electrode response was linear with Nernstian slope of 58.44 mV/decade in the concentration range of 1.0 x 10-1 M to 5.0 x 10-6 M and detection limit of 5.83 x 10-6 M. It performs satisfactorily over wide pH range of 1.0-5.5. The proposed sensor can be used over a period of more than three months without any significant drift in potential and shows good selectivity to silver(I ion over a number of cations especially with no interference of mercury(II ions. Sharp end point was obtained when the sensor was used as an indicator electrode for the potentiometric titration of silver(I ions with chloride ions and therefore this electrode (PME-1 could be used for quantitative determination of silver(I ion in synthetic water, silver foil and dental amalgam samples.

  8. A knowledge-based scoring function for protein-RNA interactions derived from a statistical mechanics-based iterative method.

    Science.gov (United States)

    Huang, Sheng-You; Zou, Xiaoqin

    2014-04-01

    Protein-RNA interactions play important roles in many biological processes. Given the high cost and technique difficulties in experimental methods, computationally predicting the binding complexes from individual protein and RNA structures is pressingly needed, in which a reliable scoring function is one of the critical components. Here, we have developed a knowledge-based scoring function, referred to as ITScore-PR, for protein-RNA binding mode prediction by using a statistical mechanics-based iterative method. The pairwise distance-dependent atomic interaction potentials of ITScore-PR were derived from experimentally determined protein-RNA complex structures. For validation, we have compared ITScore-PR with 10 other scoring methods on four diverse test sets. For bound docking, ITScore-PR achieved a success rate of up to 86% if the top prediction was considered and up to 94% if the top 10 predictions were considered, respectively. For truly unbound docking, the respective success rates of ITScore-PR were up to 24 and 46%. ITScore-PR can be used stand-alone or easily implemented in other docking programs for protein-RNA recognition.

  9. A fungal phylogeny based on 42 complete genomes derived from supertree and combined gene analysis

    Directory of Open Access Journals (Sweden)

    Stajich Jason E

    2006-11-01

    Full Text Available Abstract Background To date, most fungal phylogenies have been derived from single gene comparisons, or from concatenated alignments of a small number of genes. The increase in fungal genome sequencing presents an opportunity to reconstruct evolutionary events using entire genomes. As a tool for future comparative, phylogenomic and phylogenetic studies, we used both supertrees and concatenated alignments to infer relationships between 42 species of fungi for which complete genome sequences are available. Results A dataset of 345,829 genes was extracted from 42 publicly available fungal genomes. Supertree methods were employed to derive phylogenies from 4,805 single gene families. We found that the average consensus supertree method may suffer from long-branch attraction artifacts, while matrix representation with parsimony (MRP appears to be immune from these. A genome phylogeny was also reconstructed from a concatenated alignment of 153 universally distributed orthologs. Our MRP supertree and concatenated phylogeny are highly congruent. Within the Ascomycota, the sub-phyla Pezizomycotina and Saccharomycotina were resolved. Both phylogenies infer that the Leotiomycetes are the closest sister group to the Sordariomycetes. There is some ambiguity regarding the placement of Stagonospora nodurum, the sole member of the class Dothideomycetes present in the dataset. Within the Saccharomycotina, a monophyletic clade containing organisms that translate CTG as serine instead of leucine is evident. There is also strong support for two groups within the CTG clade, one containing the fully sexual species Candida lusitaniae, Candida guilliermondii and Debaryomyces hansenii, and the second group containing Candida albicans, Candida dubliniensis, Candida tropicalis, Candida parapsilosis and Lodderomyces elongisporus. The second major clade within the Saccharomycotina contains species whose genomes have undergone a whole genome duplication (WGD, and their close

  10. Inulin Derivatives Obtained Via Enhanced Microwave Synthesis for Nucleic Acid Based Drug Delivery.

    Science.gov (United States)

    Sardo, Carla; Craparo, Emanuela Fabiola; Fiorica, Calogero; Giammona, Gaetano; Cavallaro, Gennara

    2015-01-01

    A new class of therapeutic agents with a high potential for the treatment of different socially relevant human diseases is represented by Nucleic Acid Based Drugs (NABD), including small interfering RNAs (siRNA), decoy oligodeoxynucleotides (decoy ODN) and antisense oligonucleotides (ASOs). Although NABD can be engineered to be specifically directed against virtually any target, their susceptibility to nuclease degradation and the difficulty of delivery into target tissues severely limit their use in clinical practice and require the development of an appropriate nanostructured delivery system. For delivery of NABD, Inulin (Inu), a natural, water soluble and biocompatible polysaccharide, was derivatized by Spermine (Spm), a flexible molecule with four amine groups that, having pKa values in the range between 8-11, is mainly in the protonated form at pH 7.4. The synthesis of related copolymers (Inu-Spm) was performed by a two step reaction, using a method termed Enhanced Microwave Synthesis (EMS) which has the advantage, compared to conventional microwave reaction, that high amount of energy can be applied to the reaction system, by administering microwave irradiation and simultaneously controlling the temperature in the reaction vessel with cooled air. The synthesized inulin derivatives were characterized by FT-IR spectra and (1)H-NMR. INU-Spm derivatives with a degree of derivatization of about 14 % mol/mol were obtained. These polycations were tested to evaluate their ability to form non covalent complexes with genetic material (polyplexes). Agarose gel retardation assays showed that the obtained copolymers are able to electrostatically interact with DNA duplex to form polyplexes at different c/p weight ratios. Moreover, light scattering studies, performed to analyze size and z-potential of polyplexes, evidenced that copolymers are able to interact with genetic material leading to the formation of nanoscaled systems. In addition, biocompatibility of polyplexes

  11. [Study on the characters of phytoplankton chlorophyll fluorescence excitation spectra based on fourth-derivative].

    Science.gov (United States)

    Lu, Lu; Su, Rong-Guo; Wang, Xiu-Lin; Zhu, Chen-Jian

    2007-11-01

    Chlorophyll fluorescence excitation spectra of six phytoplankton species, belonging to Bacillariophyta and Dinophyta, were dealt by fourth-derivative analysis with the Matlab program. The results show that between 350 nm and 550 nm six fluorescence peaks were found in the fourth-derivative spectra, which are representatives of non-pigments, chlorophylls and carotenoides respectively. The method makes Bacillariophyta and Dinophyta more distinguishable when the fourth-derivative spectra are compared with the chlorophyll fluorescence excitation spectra. It can be used not only to discriminate the two groups of algaes, but also to reduce the effect of noise. The fluorescence peaks in the fourth-derivative spectra are proved to be stable.

  12. Synthesis of Urea based Chalcone Derivatives and Evaluate its Biological Activity

    Directory of Open Access Journals (Sweden)

    Arpita Desai

    2016-05-01

    Full Text Available Chalcones have been the center of attraction for researchers from several decades due to nits innumerous therapeutic application, Efforts have been done in my research to synthesized chalcones and their derivatives that further reacts with various substituted aldehyde to give corresponding substituted chalcone derivatives. Now these derivatives on condensation with Guanidine nitrate gives the vast range of phenyl pyrimidine amine Derivatives. Structure elucidation of synthesized compound had been made on the basis of element analysis, 1H NMR Spectra studies. The microbial activity of the synthesized compounds has been studied against the species bacillus subtillis, staphylococcus aureus, Escherichia coli, and salmonella typhi.

  13. Metabolites of purine nucleoside phosphorylase (NP in serum have the potential to delineate pancreatic adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Shaiju K Vareed

    Full Text Available Pancreatic Adenocarcinoma (PDAC, the fourth highest cause of cancer related deaths in the United States, has the most aggressive presentation resulting in a very short median survival time for the affected patients. Early detection of PDAC is confounded by lack of specific markers that has motivated the use of high throughput molecular approaches to delineate potential biomarkers. To pursue identification of a distinct marker, this study profiled the secretory proteome in 16 PDAC, 2 carcinoma in situ (CIS and 7 benign patients using label-free mass spectrometry coupled to 1D-SDS-PAGE and Strong Cation-Exchange Chromatography (SCX. A total of 431 proteins were detected of which 56 were found to be significantly elevated in PDAC. Included in this differential set were Parkinson disease autosomal recessive, early onset 7 (PARK 7 and Alpha Synuclein (aSyn, both of which are known to be pathognomonic to Parkinson's disease as well as metabolic enzymes like Purine Nucleoside Phosphorylase (NP which has been exploited as therapeutic target in cancers. Tissue Microarray analysis confirmed higher expression of aSyn and NP in ductal epithelia of pancreatic tumors compared to benign ducts. Furthermore, extent of both aSyn and NP staining positively correlated with tumor stage and perineural invasion while their intensity of staining correlated with the existence of metastatic lesions in the PDAC tissues. From the biomarker perspective, NP protein levels were higher in PDAC sera and furthermore serum levels of its downstream metabolites guanosine and adenosine were able to distinguish PDAC from benign in an unsupervised hierarchical classification model. Overall, this study for the first time describes elevated levels of aSyn in PDAC as well as highlights the potential of evaluating NP protein expression and levels of its downstream metabolites to develop a multiplex panel for non-invasive detection of PDAC.

  14. Autoimmune dysregulation and purine metabolism in adenosine deaminase (ADA-deficiency

    Directory of Open Access Journals (Sweden)

    Aisha Vanessa Sauer

    2012-08-01

    Full Text Available Genetic defects in the adenosine deaminase (ADA gene are among the most common causes for severe combined immunodeficiency (SCID. ADA-SCID patients suffer from lymphopenia, severely impaired cellular and humoral immunity, failure to thrive and recurrent infections. Currently available therapeutic options for this otherwise fatal disorder include bone marrow transplantation (BMT, enzyme replacement therapy with bovine ADA (PEG-ADA or hematopoietic stem cell gene therapy (HSC-GT. Although varying degrees of immune reconstitution can be achieved by these treatments, breakdown of tolerance is a major concern in ADA-SCID. Immune dysregulation such as autoimmune hypothyroidism, diabetes mellitus, hemolytic anemia, and immune thrombocytopenia are frequently observed in milder forms of the disease. However, several reports document similar complications also in patients on long-term PEG-ADA and after BMT or GT treatment.A skewed repertoire and decreased immune functions have been implicated in autoimmunity observed in certain B-cell and/or T-cell immunodeficiencies, but it remains unclear to what extent specific mechanisms of tolerance are affected in ADA deficiency. Herein we provide an overview about ADA-SCID and the autoimmune manifestations reported in these patients before and after treatment. We also assess the value of the ADA-deficient mouse model as a useful tool to study both immune and metabolic disease mechanisms. With focus on regulatory T and B cells we discuss the lymphocyte subpopulations particularly prone to contribute to the loss of self-tolerance and onset of autoimmunity in ADA deficiency. Moreover we address which aspects of immune dysregulation are specifically related to alterations in purine metabolism caused by the lack of ADA and the subsequent accumulation of metabolites with immunomodulatory properties.

  15. Thermodynamics of the Purine Nucleoside Phosphorylase Reaction Revealed by Computer Simulations.

    Science.gov (United States)

    Isaksen, Geir Villy; Åqvist, Johan; Brandsdal, Bjørn Olav

    2017-01-10

    Enzymes are able to catalyze chemical reactions by reducing the activation free energy, yielding significant increases in the reaction rates. This can thermodynamically be accomplished by either reducing the activation enthalpy or increasing the activation entropy. The effect of remote mutations on the thermodynamic activation parameters of human purine nucleoside phosphorylase is examined using extensive molecular dynamics and free energy simulations. More than 2700 independent reaction free energy profiles for six different temperatures have been calculated to obtain high-precision computational Arrhenius plots. On the basis of these, the activation enthalpies and entropies were computed from linear regression of the plots with ΔG(⧧) as a function of 1/T, and the obtained thermodynamic activation parameters are in very good agreement with those from experiments. The Arrhenius plots immediately show that the 6-oxopurines (INO and GUO) have identical slopes, whereas the 6-aminopurine (ADO) has a significantly different slope, indicating that the substrate specificity is related to the difference in thermodynamic activation parameters. Furthermore, the calculations show that the human PNP specificity for 6-oxopurines over 6-aminopurines originates from significant differences in electrostatic preorganization. The effect of the remote double mutation, K22E and H104R (E:R), has also been examined, as it alters human PNP toward the bovine PNP. These residues are situated on the protein surface, 28-35 Å from the active site, and the mutation alters the enthalpy-entropy balance with little effect on the catalytic rates. It is thus quite remarkable that the empirical valence bond method can reproduce the enthalpies and entropies induced by these long-range mutations.

  16. Effect of Ground Corn Cob Replacement for Cassava Chip on Feed Intake, Rumen Fermentation and Urinary Derivatives in Swamp Buffaloes

    Directory of Open Access Journals (Sweden)

    M. Wanapat

    2012-08-01

    Full Text Available Four Thai - rumen fistulated male swamp buffaloes (Bubalus bubalis, about four years old with 400±20 kg liveweight, were randomly assigned according to a 4×4 Latin square design to receive dietary treatments. The treatments were: ground corn cob (GCC replacement for cassava chip (CC in concentrate at 0% (T1; GCC replacement at 33% (T2; GCC replacement at 67% (T3; and GCC replacement at 100% (T4, respectively. During the experiment, concentrate was offered at 0.5% BW while 5% urea-treated rice straw was given at ad libitum. The result revealed that there was no effect of GCC replacement on DMI among treatments. In addition, digestibilities of DM, OM and CP were not different while aNDF linearly increased with an increasing level of GCC replacement. However, GCC replacement did not affect rumen fermentation such as ruminal pH, NH3-N and VFA concentration; except C3 proportion which was the highest at 33% replacement while the lowest was at 100% replacement. All replacements of GCC resulted in similar protozoal and bacterial populations and microbial protein synthesis (MPS. Purine derivatives (PD concentration in urine and PD to creatinine (PDC index were varied with time of urination and among treatments at 0 to 8 and 8 to 16 h post feeding and higher values were shown among the GCC replacement groups. However at 16 to 24 h-post feeding, it was untraceable. In addition, creatinine concentration was similar among all treatments at every sampling time. Based on the above results, GCC can be used as an energy source for swamp buffalo fed with rice straw. Spot sampling of urine can be used for purine derivatives determination.

  17. Evaluation of methods to derive green-up dates based on daily NDVI satellite observations

    Science.gov (United States)

    Doktor, Daniel

    2010-05-01

    Bridging the gap between satellite derived green-up dates and in situ phenological observations has been the purpose of many studies over the last decades. Despite substantial advancements in satellite technology and data quality checks there is as yet no universally accepted method for extracting phenological metrics based on satellite derived vegetation indices. Dependent on the respective method derived green-up dates can vary up to serveral weeks using identical data sets. Consequently, it is difficult to compare various studies and to accurately determine an increased vegetation length due to changing temperature patterns as observed by ground phenological networks. Here, I compared how the characteristic NDVI increase over temperate deciduous forests in Germany in spring relates to respective budburst events observed on the ground. MODIS Terra daily surface reflectances with a 250 m resolution (2000-2008) were gathered to compute daily NDVI values. As ground truth, observations of the extensive phenological network of the German Weather Service were used. About 1500 observations per year and species (Beech, Oak and Birch) were available evenly distributed all over Germany. Two filtering methods were tested to reduce the noisy raw data. The first method only keeps NDVI values which are classified as ‚ideal global quality' and applies on those a temporal moving window where values are removed which differ more than 20% of the mean. The second method uses an adaptation of the BISE (Best Index Slope Extraction) algorithm. Subsequently, three functions were fitted to the selected observations: a simple linear interpolation, a sigmoidal function and a double logistic sigmoidal function allowing to approximate two temporally separated green-up signals. The green-up date was then determined at halfway between minimum and maximum (linear interpolation) or at the inflexion point of the sigmoidal curve. A number of global threshold values (NDVI 0.4,0.5,0.6) and

  18. Structure/Function Analysis of DNA-glycosylases That Repair Oxidized Purines and Pyrimidines and the Influence of Surrounding DNA Sequence on Their Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, Susan S.

    2005-08-22

    The overall goal of this project was to elucidate the structure/function relationships between oxidized DNA bases and the DNA repair enzymes that recognize and remove them. The NMR solution structure of formamidopyrimidine DNA glycosylase (Fpg) that recognizes oxidized DNA purines was to be determined. Furthermore, the solution structures of DNA molecules containing specific lesions recognized by Fpg was to be determined in sequence contexts that either facilitate or hinder this recognition. These objectives were in keeping with the long-term goals of the Principal Investigator's laboratory, that is, to understand the basic mechanisms that underpin base excision repair processing of oxidative DNA lesions and to elucidate the interactions of unrepaired lesions with DNA polymerases. The results of these two DNA transactions can ultimately determine the fate of the cell. These objectives were also in keeping with the goals of our collaborator, Dr. Michael Kennedy, who is studying the repair and recognition of damaged DNA. Overall the goals of this project were congruent with those of the Department of Energy's Health Effects and Life Sciences Research Program, especially to the Structural Biology, the Human Genome and the Health Effects Programs. The mission of the latter Program includes understanding the biological effects and consequences of DNA damages produced by toxic agents in the many DOE waste sites so that cleanup can be accomplished in a safe, effective and timely manner.

  19. Discovery of mono- and disubstituted 1H-pyrazolo[3,4]pyrimidines and 9H-purines as catalytic inhibitors of human DNA topoisomerase IIα.

    Science.gov (United States)

    Pogorelčnik, Barbara; Brvar, Matjaž; Žegura, Bojana; Filipič, Metka; Solmajer, Tom; Perdih, Andrej

    2015-02-01

    Human DNA topoisomerase IIα (htIIα) is a validated target for the development of anticancer agents. Based on structural data regarding the binding mode of AMP-PNP (5'-adenylyl-β,γ-imidodiphosphate) to htIIα, we designed a two-stage virtual screening campaign that combines structure-based pharmacophores and molecular docking. In the first stage, we identified several monosubstituted 9H-purine compounds and a novel class of 1H-pyrazolo[3,4]pyrimidines as inhibitors of htIIα. In the second stage, disubstituted analogues with improved cellular activities were discovered. Compounds from both classes were shown to inhibit htIIα-mediated DNA decatenation, and surface plasmon resonance (SPR) experiments confirmed binding of these two compounds on the htIIα ATPase domain. Proposed complexes and interaction patterns between both compounds and htIIα were further analyzed in molecular dynamics simulations. Two compounds identified in the second stage showed promising anticancer activities in hepatocellular carcinoma (HepG2) and breast cancer (MCF-7) cell lines. The discovered compounds are suitable starting points for further hit-to-lead development in anticancer drug discovery.

  20. Satellite-Based Derivation of High-Resolution Forest Information Layers for Operational Forest Management

    Directory of Open Access Journals (Sweden)

    Johannes Stoffels

    2015-06-01

    Full Text Available A key factor for operational forest management and forest monitoring is the availability of up-to-date spatial information on the state of forest resources. Earth observation can provide valuable contributions to these information needs. The German federal state of Rhineland-Palatinate transferred its inherited forest information system to a new architecture that is better able to serve the needs of centralized inventory and planning services, down to the level of forest districts. During this process, a spatially adaptive classification approach was developed to derive high-resolution forest information layers (e.g., forest type, tree species distribution, development stages based on multi-temporal satellite data. This study covers the application of the developed approach to a regional scale (federal state level and the further adaptation of the design to meet the information needs of the state forest service. The results confirm that the operational requirements for mapping accuracy can, in principle, be fulfilled. However, the state-wide mapping experiment also revealed that the ability to meet the required level of accuracy is largely dependent on the availability of satellite observations within the optimum phenological time-windows.

  1. Novel Organotin(IV) Schiff Base Complexes with Histidine Derivatives: Synthesis, Characterization, and Biological Activity

    Science.gov (United States)

    Garza-Ortiz, Ariadna; Camacho-Camacho, Carlos; Sainz-Espuñes, Teresita; Rojas-Oviedo, Irma; Gutiérrez-Lucas, Luis Raúl; Gutierrez Carrillo, Atilano; Vera Ramirez, Marco A.

    2013-01-01

    Five novel tin Schiff base complexes with histidine analogues (derived from the condensation reaction between L-histidine and 3,5-di-tert-butyl-2-hydroxybenzaldehyde) have been synthesized and characterized. Characterization has been completed by IR and high-resolution mass spectroscopy, 1D and 2D solution NMR (1H, 13C  and 119Sn), as well as solid state 119Sn NMR. The spectroscopic evidence shows two types of structures: a trigonal bipyramidal stereochemistry with the tin atom coordinated to five donating atoms (two oxygen atoms, one nitrogen atom, and two carbon atoms belonging to the alkyl moieties), where one molecule of ligand is coordinated in a three dentate fashion. The second structure is spectroscopically described as a tetrahedral tin complex with four donating atoms (one oxygen atom coordinated to the metal and three carbon atoms belonging to the alkyl or aryl substituents), with one molecule of ligand attached. The antimicrobial activity of the tin compounds has been tested against the growth of bacteria in vitro to assess their bactericidal properties. While pentacoordinated compounds 1, 2, and 3 are described as moderate effective to noneffective drugs against both Gram-positive and Gram-negative bacteria, tetracoordinated tin(IV) compounds 4 and 5 are considered as moderate effective and most effective compounds, respectively, against the methicillin-resistant Staphylococcus aureus strains (Gram-positive). PMID:23864839

  2. Novel Organotin(IV Schiff Base Complexes with Histidine Derivatives: Synthesis, Characterization, and Biological Activity

    Directory of Open Access Journals (Sweden)

    Ariadna Garza-Ortiz

    2013-01-01

    Full Text Available Five novel tin Schiff base complexes with histidine analogues (derived from the condensation reaction between L-histidine and 3,5-di-tert-butyl-2-hydroxybenzaldehyde have been synthesized and characterized. Characterization has been completed by IR and high-resolution mass spectroscopy, 1D and 2D solution NMR (1H, 13C  and 119Sn, as well as solid state 119Sn NMR. The spectroscopic evidence shows two types of structures: a trigonal bipyramidal stereochemistry with the tin atom coordinated to five donating atoms (two oxygen atoms, one nitrogen atom, and two carbon atoms belonging to the alkyl moieties, where one molecule of ligand is coordinated in a three dentate fashion. The second structure is spectroscopically described as a tetrahedral tin complex with four donating atoms (one oxygen atom coordinated to the metal and three carbon atoms belonging to the alkyl or aryl substituents, with one molecule of ligand attached. The antimicrobial activity of the tin compounds has been tested against the growth of bacteria in vitro to assess their bactericidal properties. While pentacoordinated compounds 1, 2, and 3 are described as moderate effective to noneffective drugs against both Gram-positive and Gram-negative bacteria, tetracoordinated tin(IV compounds 4 and 5 are considered as moderate effective and most effective compounds, respectively, against the methicillin-resistant Staphylococcus aureus strains (Gram-positive.

  3. Synthesis and biological evaluation of 3-thiazolocoumarinyl Schiff-base derivatives as cholinesterase inhibitors.

    Science.gov (United States)

    Raza, Rabia; Saeed, Aamer; Arif, Mubeen; Mahmood, Shamsul; Muddassar, Muhammad; Raza, Ahsan; Iqbal, Jamshed

    2012-10-01

    On the basis of the observed biological activity of the coumarins, a new set of 3-thiazolocoumarinyl Schiff-base derivatives with chlorine, hydroxy and methoxy functional group substitutions were designed and synthesized. These compounds were tested against acetylcholinesterase from Electrophorus electricus and butyrylcholinesterase from horse serum and their structure-activity relationship was established. Studies revealed them as the potential inhibitors of cholinesterase (acetylcholinesterase and butyrylcholinesterase). The 3f was found to be most potent against acetylcholinesterase with K(i) value of 1.05 ± 0.3 μM and 3l showed excellent inhibitory action against butyrylcholinesterase with K(i) value of 0.041 ± 0.002 μM. The synthesized compounds were also docked into the active sites of the homology models of acetylcholinesterase and butyrylcholinesterase to predict the binding modes of these compounds. It was predicted that most of the compounds have similar binding modes with reasonable binding affinities. Our docking studies have also shown that these synthesized compounds have better interaction patterns with butyrylcholinesterase over acetylcholinesterase. The main objective of the study was to develop new potent and selective compounds, which might be further optimized to prevent the progression of the Alzheimer's disease and could provide symptomatic treatment. © 2012 John Wiley & Sons A/S.

  4. Green synthesis of novel quinoline based imidazole derivatives and evaluation of their antimicrobial activity

    Directory of Open Access Journals (Sweden)

    N.C. Desai

    2014-12-01

    Full Text Available We have described the conventional and microwave method for the synthesis of N-(4-((2-chloroquinolin-3-ylmethylene-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl(arylamides 3a–l. It is observed that the solvent-free microwave thermolysis is a convenient, rapid, high-yielding, and environmental friendly protocol for the synthesis of quinoline based imidazole derivatives when compared with conventional reaction in a solution phase. Antimicrobial activity of the newly synthesized compounds is screened in vitro on the following microbial cultures: Escherichia coli (MTCC 443, Pseudomonas aeruginosa (MTCC 1688, Staphylococcus aureus (MTCC 96, Streptococcus pyogenes (MTCC 442, Candida albicans (MTCC 227, Aspergillus niger (MTCC 282, Aspergillus clavatus (MTCC 1323. All the synthesized bio-active molecules are tested for their in vitro antimicrobial activity by bioassay namely serial broth dilution. Among these compounds 3c, 3d, 3f, 3h and 3j show significant potency against different microbial strains. All the compounds have been characterized by IR, 1H NMR, 13C NMR and mass spectral data. On the basis of statistical analysis, it is observed that these compounds give significant co-relation.

  5. Synthesis, Spectroscopic Characterization and Biological Activities of Transition Metal Complexes Derived from a Tridentate Schiff Base

    Directory of Open Access Journals (Sweden)

    J. Senthil Kumaran

    2013-01-01

    Full Text Available A new series of Cu (II, Ni (II, Co (II and Zn (II complexes have been synthesized from the Schiff base derived from 4-hydroxy-3-methoxybenzylidine-4-aminoantipyrine and 2-aminophenol. The structural features have been determined from their elemental analysis, magnetic susceptibility, molar conductance, Mass, IR, UV-Vis, 1H-NMR, 13C-NMR and ESR spectral studies. The redox behavior of the copper complex has been studied by cyclic voltammetry. The data confirm that the complexes have composition of ML2 type. The electronic absorption spectral data of the complexes propose an octahedral geometry around the central metal ion. All the metal complexes with DNA structure were guided by the presence of inter-molecular C–H⋯O and C–H⋯N hydrogen bonds. The biological activity of the synthesized compounds were tested against the bacterial species such as Bacillus subtilis, Staphylococcus aureus, Proteus vulgaris and fungal species such as Candida albicans by the well-diffusion method.

  6. Derivation of an observation-based map of North African dust emission

    Energy Technology Data Exchange (ETDEWEB)

    Evan, Amato T.; Fiedler, Stephanie; Zhao, Chun; Menut, Laurent; Schepanski, Kerstin; Flamant, C.; Doherty, Owen

    2015-03-01

    Changes in the emission, transport and deposition of aeolian dust have profound effects on regional climate, so that characterizing the lifecycle of dust in observations and improving the representation of dust in global climate models is necessary. A fundamental aspect of characterizing the dust cycle is quantifying surface dust fluxes, yet no spatially explicit estimates of this flux exist for the World’s major source regions. Here we present a novel technique for creating a map of the annual mean emitted dust flux for North Africa based on retrievals of dust storm frequency from the Meteosat Second Generation Spinning Enhanced Visible and InfraRed Imager (SEVIRI) and the relationship between dust storm frequency and emitted mass flux derived from the output of five models that simulate dust. Our results suggest that 64 (±16)% of all dust emitted from North Africa is from the Bodélé depression, and that 13 (±3)% of the North African dust flux is from a depression lying in the lee of the Aïr and Hoggar Mountains, making this area the second most important region of emission within North Africa.

  7. Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents

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    Mehlika Dilek Altıntop

    2016-11-01

    Full Text Available New benzodioxole-based thiosemicarbazone derivatives were synthesized and evaluated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma and NIH/3T3 mouse embryonic fibroblast cells. In order to examine the correlation between anticancer activity and cholinesterases, the compounds were evaluated for their inhibitory effects on AChE and BuChE. The most effective anticancer agents were investigated for their effects on DNA synthesis, apoptosis and mitochondrial membrane potential. 4-(1,3-Benzodioxol-5-yl-1-([1,1′-biphenyl]-4-ylmethylenethiosemicarbazide (5 was identified as the most promising anticancer agent against C6 and A549 cell lines due to its inhibitory effects on C6 and A549 cells and low toxicity to NIH/3T3 cells. Compound 5 increased early and late apoptosis in A549 and C6 cells. Compound 5 also caused disturbance on mitochondrial membrane potential and showed DNA synthesis inhibitory activity in A549 and C6 cells. Compound 5 was investigated for SIRT1 inhibitory activity to provide mechanistic insight and for that purpose docking studies were also performed for this compound on SIRT1. On the other hand, compound 5 did not show any inhibitory activity against AChE and BuChE. This outcome pointed out that there is no relationship between anticancer activity of compound 5 and cholinesterases.

  8. Dynamic Covalent Chemistry-based Sensing: Pyrenyl Derivatives of Phenylboronic Acid for Saccharide and Formaldehyde

    Science.gov (United States)

    Chang, Xingmao; Fan, Jiayun; Wang, Min; Wang, Zhaolong; Peng, Haonan; He, Gang; Fang, Yu

    2016-01-01

    We synthesized two specially designed pyrenyl (Py) derivatives of phenylboronic acid, PSNB1 and PSNB2, of which PSNB2 self-assemble to form dynamic aggregate in methanol-water mixture (1:99, v/v) via intermolecular H-bonding and pi-pi stacking. Interestingly, the dynamic aggregate shows smart response to presence of fructose (F) as evidenced by fluorescence color change from green to blue. More interestingly, the fluorescence emission of the resulted PSNB2-F changes from blue to green with the addition of formaldehyde (FA). The reason behind is formation of a PSNB2-F dimer via FA cross-linking. Based upon the reactions as found, sensitive and fast sensing of F and FA in water was realized, of which the experimental DLs could be significantly lower than 10 μM for both analytes, and the response times are less than 1 min. It is believed that not only the materials as created may have the potential to find real-life applications but also the strategy as developed can be adopted to develop other dynamic materials. PMID:27498703

  9. Dynamic Covalent Chemistry-based Sensing: Pyrenyl Derivatives of Phenylboronic Acid for Saccharide and Formaldehyde

    Science.gov (United States)

    Chang, Xingmao; Fan, Jiayun; Wang, Min; Wang, Zhaolong; Peng, Haonan; He, Gang; Fang, Yu

    2016-08-01

    We synthesized two specially designed pyrenyl (Py) derivatives of phenylboronic acid, PSNB1 and PSNB2, of which PSNB2 self-assemble to form dynamic aggregate in methanol-water mixture (1:99, v/v) via intermolecular H-bonding and pi-pi stacking. Interestingly, the dynamic aggregate shows smart response to presence of fructose (F) as evidenced by fluorescence color change from green to blue. More interestingly, the fluorescence emission of the resulted PSNB2-F changes from blue to green with the addition of formaldehyde (FA). The reason behind is formation of a PSNB2-F dimer via FA cross-linking. Based upon the reactions as found, sensitive and fast sensing of F and FA in water was realized, of which the experimental DLs could be significantly lower than 10 μM for both analytes, and the response times are less than 1 min. It is believed that not only the materials as created may have the potential to find real-life applications but also the strategy as developed can be adopted to develop other dynamic materials.

  10. Structure based design, synthesis and biological evaluation of amino phosphonate derivatives as human glucokinase activators.

    Science.gov (United States)

    Yellapu, Nanda Kumar; Kilaru, Ravendra Babu; Chamarthi, Nagaraju; Pvgk, Sarma; Matcha, Bhaskar

    2017-06-01

    Glucokinase (GK) is a potential therapeutic target of type 2 diabetes and GK activators (GKAs) represent a promising class of small organic molecules which enhance GK activity. Based on the configuration and conformation of the allosteric site of GK, we have designed a novel class of amino phosphonate derivatives in order to develop potent GKAs. The QSAR model developed using numerous descriptors revealed its potential with the best effective statistical values of RMSE=1.52 and r(2)=0.30. Moreover, application of this model on the present test set GKAs proved to be worthy to predict their activities as a better linear relationship was observed with RMSE=0.14 and r(2)=0.88. ADME studies and Lipinski filters encouraged them as safer therapeutics. The molecular dynamics and docking studies against the GK allosteric site revealed that all GKAs bind with best affinities and the complexes are strengthened by H-bonding, phosphonate salt bridges, hydrophobic and arene cat ionic interactions. Finally, in vitro evaluation with human liver GK revealed their potential to increase the GK activity by different folds. The results from QSAR, ADME, molecular docking and in vitro assays strongly suggested that the present molecules could be used as effective and safer therapeutics to control and manage type 2 diabetes. Copyright © 2017. Published by Elsevier Ltd.

  11. Strategies to Automatically Derive a Process Model from a Configurable Process Model Based on Event Data

    Directory of Open Access Journals (Sweden)

    Mauricio Arriagada-Benítez

    2017-10-01

    Full Text Available Configurable process models are frequently used to represent business workflows and other discrete event systems among different branches of large organizations: they unify commonalities shared by all branches and describe their differences, at the same time. The configuration of such models is usually done manually, which is challenging. On the one hand, when the number of configurable nodes in the configurable process model grows, the size of the search space increases exponentially. On the other hand, the person performing the configuration may lack the holistic perspective to make the right choice for all configurable nodes at the same time, since choices influence each other. Nowadays, information systems that support the execution of business processes create event data reflecting how processes are performed. In this article, we propose three strategies (based on exhaustive search, genetic algorithms and a greedy heuristic that use event data to automatically derive a process model from a configurable process model that better represents the characteristics of the process in a specific branch. These strategies have been implemented in our proposed framework and tested in both business-like event logs as recorded in a higher educational enterprise resource planning system and a real case scenario involving a set of Dutch municipalities.

  12. Catalytic wet air oxidation of 2-chlorophenol over sewage sludge-derived carbon-based catalysts.

    Science.gov (United States)

    Tu, Yuting; Xiong, Ya; Tian, Shuanghong; Kong, Lingjun; Descorme, Claude

    2014-07-15

    A sewage sludge derived carbon-supported iron oxide catalyst (FeSC) was prepared and used in the Catalytic Wet Air Oxidation (CWAO) of 2-chlorophenol (2-CP). The catalysts were characterized in terms of elemental composition, surface area, pHPZC, XRD and SEM. The performances of the FeSC catalyst in the CWAO of 2-CP was assessed in a batch reactor operated at 120°C under 0.9MPa oxygen partial pressure. Complete decomposition of 2-CP was achieved within 5h and 90% Total Organic Carbon (TOC) was removed after 24h of reaction. Quite a straight correlation was observed between the 2-CP conversion, the amount of iron leached in solution and the pH of the reaction mixture at a given reaction time, indicating a strong predominance of the homogeneous catalysis contribution. The iron leaching could be efficiently prevented when the pH of the solution was maintained at values higher than 4.5, while the catalytic activity was only slightly reduced. Upon four successive batch CWAO experiments, using the same FeSC catalyst recovered by filtration after pH adjustment, only a very minor catalyst deactivation was observed. Finally, based on all the identified intermediates, a simplified reaction pathway was proposed for the CWAO of 2-CP over the FeSC catalyst.

  13. Solution properties and emulsification properties of amino acid-based gemini surfactants derived from cysteine.

    Science.gov (United States)

    Yoshimura, Tomokazu; Sakato, Ayako; Esumi, Kunio

    2013-01-01

    Amino acid-based anionic gemini surfactants (2C(n)diCys, where n represents an alkyl chain with a length of 10, 12, or 14 carbons and "di" and "Cys" indicate adipoyl and cysteine, respectively) were synthesized using the amino acid cysteine. Biodegradability, equilibrium surface tension, and dynamic light scattering were used to characterize the properties of gemini surfactants. Additionally, the effects of alkyl chain length, number of chains, and structure on these properties were evaluated by comparing previously reported gemini surfactants derived from cystine (2C(n)Cys) and monomeric surfactants (C(n)Cys). 2C(n)diCys shows relatively higher biodegradability than does C(n)Cys and previously reported sugar-based gemini surfactants. Both critical micelle concentration (CMC) and surface tension decrease when alkyl chain length is increased from 10 to 12, while a further increase in chain length to 14 results in increased CMC and surface tension. This indicates that long-chain gemini surfactants have a decreased aggregation tendency due to the steric hindrance of the bulky spacer as well as premicelle formation at concentrations below the CMC and are poorly packed at the air/water interface. Formation of micelles (measuring 2 to 5 nm in solution) from 2C(n)diCys shows no dependence on alkyl chain length. Further, shaking the mixtures of aqueous 2C(n)diCys surfactant solutions and squalane results in the formation of oil-in-water type emulsions. The highly stable emulsions are formed using 2C₁₂diCys or 2C₁₄diCys solution and squalane in a 1:1 or 2:1 volume ratio.

  14. Geocenter variations derived from a combined processing of LEO- and ground-based GPS observations

    Science.gov (United States)

    Männel, Benjamin; Rothacher, Markus

    2017-08-01

    GNSS observations provided by the global tracking network of the International GNSS Service (IGS, Dow et al. in J Geod 83(3):191-198, 2009) play an important role in the realization of a unique terrestrial reference frame that is accurate enough to allow a detailed monitoring of the Earth's system. Combining these ground-based data with GPS observations tracked by high-quality dual-frequency receivers on-board low earth orbiters (LEOs) is a promising way to further improve the realization of the terrestrial reference frame and the estimation of geocenter coordinates, GPS satellite orbits and Earth rotation parameters. To assess the scope of the improvement on the geocenter coordinates, we processed a network of 53 globally distributed and stable IGS stations together with four LEOs (GRACE-A, GRACE-B, OSTM/Jason-2 and GOCE) over a time interval of 3 years (2010-2012). To ensure fully consistent solutions, the zero-difference phase observations of the ground stations and LEOs were processed in a common least-squares adjustment, estimating all the relevant parameters such as GPS and LEO orbits, station coordinates, Earth rotation parameters and geocenter motion. We present the significant impact of the individual LEO and a combination of all four LEOs on the geocenter coordinates. The formal errors are reduced by around 20% due to the inclusion of one LEO into the ground-only solution, while in a solution with four LEOs LEO-specific characteristics are significantly reduced. We compare the derived geocenter coordinates w.r.t. LAGEOS results and external solutions based on GPS and SLR data. We found good agreement in the amplitudes of all components; however, the phases in x- and z-direction do not agree well.

  15. Deriving hydraulic roughness from camera-based high resolution topography in field and laboratory experiments

    Science.gov (United States)

    Kaiser, Andreas; Neugirg, Fabian; Ebert, Louisa; Haas, Florian; Schmidt, Jürgen; Becht, Michael; Schindewolf, Marcus

    2016-04-01

    The hydraulic roughness, represented by Manning's n, is an essential input parameter in physically based soil erosion modeling. In order to acquire the roughness values for certain areas, on-site flow experiments have to be carried out. These results are influenced by the selection of the location of the test plot and are thereby based on the subjectiveness of the researchers. The study aims on the methodological development to acquire Manning's n by creating very high-resolution surface models with structure-from-motion approaches. Data acquisition took place during several field experiments in the Lainbach valley, southern Germany, and on agricultural sites in Saxony, eastern Germany, and in central Brazil. Rill and interrill conditions were simulated by flow experiments. In order to validate our findings stream velocity as an input for the manning equation was measured with coloured dye. Grain and aggregate sizes were derived by measuring distances from a best fit line to the reconstructed soil surface. Several diameters from D50 to D90 were tested with D90 showing best correlation between tracer experiments and photogrammetrically acquired data. A variety of roughness parameters were tested (standard deviation, random roughness, Garbrecht's n and D90). Best agreement in between the particle size and the hydraulic roughness was achieved with a non-linear sigmoid function and D90 rather than with the Garbrecht equation or statistical parameters. To consolidate these findings a laboratory setup was created to reproduce field data under controlled conditions, excluding unknown influences like infiltration and changes in surface morphology by erosion.

  16. Development of a New Folate-Derived Ga-68-Based PET Imaging Agent.

    Science.gov (United States)

    Brand, Christian; Longo, Valerie A; Groaning, Mike; Weber, Wolfgang A; Reiner, Thomas

    2017-02-13

    The folate receptor (FR) has emerged as an interesting diagnostic and therapeutic drug target with many potential applications in oncologic and inflammatory disorders. It was therefore the aim of this study to develop a folate-derived Ga-68-based positron emission tomography (PET) imaging tracer that is straightforward to radiolabel and could be broadly used in clinical studies. We validated its target binding affinity and specificity and compared it to [(99m)Tc]EC20, the folate single-photon emission computed tomography (SPECT) imaging tracer that has been most extensively studied clinically so far. The new folic acid-derived PET imaging agent is linked via a polyethyleneglycol linker to the chelator 1,4,7-triazacyclononane-1,4,7-trisacetic acid (NOTA). This new compound, NOTA-folate, was labeled with gallium-68. We tested the probe's stability in human plasma and its selectivity in vitro, using the FR-positive KB cell line as well as the FR-negative A549 cell line. The pharmacokinetic profile of [(68)Ga]NOTA-folate was evaluated in FR-positive KB mouse xenografts. Following intravenous injection of [(68)Ga]NOTA-folate (383 ± 53 μCi), PET/computed tomography (CT) imaging studies as well as biodistribution studies were performed using KB tumor-bearing mice (n = 3). In vitro as well as in vivo studies were performed in parallel with the SPECT imaging tracer [(99m)Tc]EC20. In comparison to [(99m)Tc]EC20 (radiochemical yield (RCY) = 82.0 ± 2.9 %, 91.8 ± 2.0 % purity), similar radiochemical yield (87.2 ± 6.9 %) and radiochemical purity (95.6 ± 1.8 %) could be achieved for [(68)Ga]NOTA-folate. For both tracers, we observed high affinity for FR-positive cells in vitro and high plasma stability. In PET/CT and biodistribution studies, [(68)Ga]NOTA-folate appeared to display slightly superior in vivo performance in comparison to [(99m)Tc]EC20. In detail, (68)Ga-NOTA-folate showed very good tumor uptake and retention (6.6 ± 1.1 %ID/g), relatively

  17. Comparison of Cloud Base Height Derived from a Ground-Based Infrared Cloud Measurement and Two Ceilometers

    Directory of Open Access Journals (Sweden)

    Lei Liu

    2015-01-01

    Full Text Available The cloud base height (CBH derived from the whole-sky infrared cloud-measuring system (WSIRCMS and two ceilometers (Vaisala CL31 and CL51 from November 1, 2011, to June 12, 2012, at the Chinese Meteorological Administration (CMA Beijing Observatory Station are analysed. Significant differences can be found by comparing the measurements of different instruments. More exactly, the cloud occurrence retrieved from CL31 is 3.8% higher than that from CL51, while WSIRCMS data shows 3.6% higher than ceilometers. More than 75.5% of the two ceilometers’ differences are within ±200 m and about 89.5% within ±500 m, while only 30.7% of the differences between WSIRCMS and ceilometers are within ±500 m and about 55.2% within ±1000 m. These differences may be caused by the measurement principles and CBH retrieval algorithm. A combination of a laser ceilometer and an infrared cloud instrument is recommended to improve the capability for determining cloud occurrence and retrieving CBHs.

  18. An improved 3D MoF method based on analytical partial derivatives

    Science.gov (United States)

    Chen, Xiang; Zhang, Xiong

    2016-12-01

    MoF (Moment of Fluid) method is one of the most accurate approaches among various surface reconstruction algorithms. As other second order methods, MoF method needs to solve an implicit optimization problem to obtain the optimal approximate surface. Therefore, the partial derivatives of the objective function have to be involved during the iteration for efficiency and accuracy. However, to the best of our knowledge, the derivatives are currently estimated numerically by finite difference approximation because it is very difficult to obtain the analytical derivatives of the object function for an implicit optimization problem. Employing numerical derivatives in an iteration not only increase the computational cost, but also deteriorate the convergence rate and robustness of the iteration due to their numerical error. In this paper, the analytical first order partial derivatives of the objective function are deduced for 3D problems. The analytical derivatives can be calculated accurately, so they are incorporated into the MoF method to improve its accuracy, efficiency and robustness. Numerical studies show that by using the analytical derivatives the iterations are converged in all mixed cells with the efficiency improvement of 3 to 4 times.

  19. Purine-rich foods, protein intake, and the prevalence of hyperuricemia: The Shanghai Men’s Health Study

    Science.gov (United States)

    Villegas, Raquel; Xiang, Yong-Bang; Elasy, Tom; Xu, Wang-Hong; Cai, Hui; Cai, Qiuyin; Linton, MacRae; Fazio, Sergio; Zheng, Wei; Shu, Xiao-Ou

    2011-01-01

    Background and Aims Diet may play an important role in the development of hyperuricemia and gout. However, the association between dietary factors and hyperuricemia remains unclear, and few studies have investigated direct links between food intake and hyperuricemia. The aim of this study was to investigate associations between high purine-content foods and protein intake with the prevalence of hyperuricemia by using data from a cross-sectional study of 3,978 men aged 40–74 yrs living in Shanghai, China. PMID:21277179

  20. Disturbance of Antioxidant Enzymes and Purine Metabolism in the Ejaculate of Men Living in Disadvantaged Areas of Kyzylorda Region

    Directory of Open Access Journals (Sweden)

    Valentihna N. Kislitskaya

    2015-07-01

    CONCLUSIONS: According to the results of study, it was put the influence  of negative factors of the Aral Sea region in men’s sperm of reproductive  age gives to disability free-radical processes, that proves changing of ferments of ant oxidative protection Catalase and adenosine deaminase (ADA.  This disturbance in men’s sperm of reproductive age leading to increased level of oxidative stress and impaired activity of  antioxidant enzymes and purine metabolism, responsible for the abnormal transmembrane and intracellular processes, reflecting the degree of imbalance of enzymes.

  1. Regulation of purine biosynthetic genes expression in Salmonella typhimurium Ⅳ O~c mutation site of purG and its function analysis

    Institute of Scientific and Technical Information of China (English)

    刘奔; 黄谊; 王敖全

    1997-01-01

    Salmonella typhimurium 5 phosphoribosylformylglycinamide (FGAR) amidotransferase encoded by purG gene catalyzes the conversion of FGAR to formylglycinamide ribonucleotide (FGAM) in the presence of glu-tamine and ATP for the de novo purine nucleotide biosynthesis. purG gene is negatively regulated by a repressor-oper-ator system. The O+ purG and OC purG were cloned respectively in vivo. Restriction enzymes analysis of preliminary clones pLBG-1 (O + ) and pLBG-2 (OC) were carried out. The hybrid plasmids pLB1933 (O+ ) and pLB1927 (OC) containing 5 control region of purG were constructed and the DNA sequences were determined respectively. DNA se-quences data showed that Oc mutation of purG occurred at the 3rd position of 16 bp PUR box in the 5’ control region ( G→A). Gel retardation experiment indicated that the repressor bound well with O+ PUR box, but not with Oc PUR box. The result strongly supported the idea that PUR box is the binding region of represser protein and the 3rd posi-tion base G of PUR bo

  2. Stem cell-based delivery of brain-derived neurotrophic factor gene in the rat retina.

    Science.gov (United States)

    Park, Hae-Young Lopilly; Kim, Jie Hyun; Sun Kim, Hwa; Park, Chan Kee

    2012-08-21

    As an alternative to a viral vector, the application of stem cells to transfer specific genes is under investigation in various organs. Using this strategy may provide more effective method to supply neurotrophic factor to the neurodegenerative diseases caused by neurotrophic factor deprivation. This study investigated the possibility and efficacy of stem cell-based delivery of the brain-derived neurotrophic factor (BDNF) gene to rat retina. Rat BDNF cDNA was transduced into rat bone marrow mesenchymal stem cells (rMSCs) using a retroviral vector. Its incorporation into the experimental rat retina and the expression of BDNF after intravitreal injection or subretinal injection were detected by real-time PCR, western blot analysis, and immunohistochemical staining. For the incorporated rMSCs, retinal-specific marker staining was performed to investigate the changes in morphology and the characteristics of the stem cells. Transduction of the rMSCs by retrovirus was effective, and the transduced rMSCs expressed high levels of the BDNF gene and protein. The subretinal injection of rMSCs produced rMSC migration and incorporation into the rat retina (about 15.7% incorporation rate), and retinal BDNF mRNA and protein expression was increased at 4 weeks after transplantation. When subretinal injection of rMSCs was applied to axotomized rat retina, it significantly increased the expression of BDNF until 4 weeks after transplantation. Some of the transplanted rMSCs exhibited morphological changes, but the retinal-specific marker stain was not sufficient to indicate whether neuronal differentiation had occurred. Using mesenchymal stem cells to deliver the BDNF gene to the retina may provide new treatment for glaucoma.

  3. Degradation of carbofuran derivatives in restricted water environments: basic hydrolysis in AOT-based microemulsions.

    Science.gov (United States)

    Morales, Jorge; Manso, José A; Cid, Antonio; Lodeiro, Carlos; Mejuto, Juan Carlos

    2012-04-15

    The effect of sodium bis(2-ethylhexyl)sulfosuccinate/isooctane/water microemulsions on the stability of 2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl methylcarbamate (carbofuran, CF), 3-hydroxy-2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate (3-hydroxycarbofuran, HCF) and 3-keto-2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate (3-ketocarbofuran, KCF) in basic media has been studied. The presence of these microheterogeneous media implies a large basic hydrolysis of CF and HCF on increasing surfactant concentration and, also, on increasing water content in the microemulsion. The hydrolysis rate constants are approximately 2- and 10-fold higher than those in pure water for HCF and CF, respectively. In contrast, a steep descent in the rate of decomposition for KCF was observed. These behaviours can be ascribed to the presence of CF derivatives both in the hydrophilic phase and in the lipophilic phase, while the hydroxyl ions are only restricted to the water pool of the microemulsion (hydrophilic phase). The kinetic rate constants for the basic hydrolysis in AOT-based microemulsions have been obtained on the basis of a pseudophase model. Taking into account that an important part of soils are colloids, the possibility of the presence of restricted water environments implies that soil composition and its structure will play an important role in the stability of these carbamates. In fact, we observed that the presence of these restricted aqueous media in the environment, in particular in watersheds and in wastewaters, could reduce significantly the half-life of these pesticides (33% and 91% for HCF and CF, respectively).

  4. Synthesis of Triazole Schiff's Base Derivatives and Their Inhibitory Kinetics on Tyrosinase Activity.

    Directory of Open Access Journals (Sweden)

    Feng Yu

    Full Text Available In the present study, new Schiff's base derivatives: (Z-4-amino-5-(2-(3- fluorobenzylidenehydrazinyl-4H-1,2,4-triazole-3-thiol (Y1, (Z-3-((2-(4-amino-5- mercapto-4H-1,2,4-triazol-3-ylhydrazonomethylphenol (Y2, (Z-2-((2-(4-amino-5- mercapto-4H-1,2,4-triazol-3-ylhydrazonomethylphenol (Y3 and 3-((Z-(2-(4- (((E-3-hydroxybenzylideneamino-5-mercapto-4H-1,2,4-triazol-3-ylhydrazonomethylphenol (Y4 were synthesized and their structures were characterized by LC-MS, IR and 1H NMR. The inhibitory effects of these compounds on tyrosinase activites were evaluated. Compounds Y1, Y2 and Y3 showed potent inhibitory effects with respective IC50 value of 12.5, 7.0 and 1.5 μM on the diphenolase activities. Moreover, the inhibition mechanisms were determined to be reversible and mixed types. Interactions of the compounds with tyrosinase were further analyzed by fluorescence quenching, copper interaction, and molecular simulation assays. The results together with the anti-tyrosinase activities data indicated that substitution on the second position of benzene ring showed superior ant-ityrosinase activities than that on third position, and that hydroxyl substitutes were better than fluorine substitutes. In addition, two benzene rings connecting to the triazole ring would produce larger steric hindrance, and affect the bonding between tyrosinase and inhibitors to decrease the inhibitory effects. The anti-tyrosinase effects of these compounds were in contrast to their antioxidant activities. In summary, this research will contribute to the development and design of antityrosinase agents.

  5. Study on gadolinium complexes based on polysaccharide derivatives as a contrast agent for MRI

    Energy Technology Data Exchange (ETDEWEB)

    Hashiguchi, Yuji; Seri, Shigemi; Kubomura, Kan; Abe, Yukiko; Kamimura, Kenji; Fujimoto, Chieko; Iguchi, Toshio; Iwai, Kumiko (Nihon Medi-Physics Co., Ltd., Sodegaura, Chiba (Japan))

    1993-05-01

    The authors report new gadolinium compounds, polysaccharide-gadolinium chelate, that have the enhancement property in magnetic resonance imaging (MRI) as well as a longer half-life time in blood. Dialdehyde starch (DAS ; mol. wt. 7 x 10[sup 3]) and dialdehyde amylose (DAA ; mol. wt. 3 x 10[sup 3]) were synthesized to increase the half-life time in blood. The binding of gadolinium to DAS or DAA was facilitated by the newly synthesized bifunctional chelating agents N-[2-bis(carboxymethyl)aminoethyl] -N-[2-bis(carboxymethyl)amino -2(p-benzyl)ethyl]glycine (ABDTPA) and 10-[N-(2-aminoethyl)carbamoyl]methyl-[alpha], [alpha]', [alpha]''-trimethyl-1,4,7,10 -tetraazacyclododecane-1,4,7-triacetic acid (DO 3 MA). The enhancement properties of resulting gadolinium compounds were evaluated for biodistribution, relaxivity and enhancement effect. Biodistribution was examined by use of [sup 111]In labelled complex. Relaxivity was measured at 0.5T and 1.5T. Enhancement effect was examined in vivo by using rats that have brain occlusions. Gadolinium(Gd) complexes with DAS or DAA were found to be staying in the blood vessel for a longer period of time than other existing enhancers. The half-life time of DAS-ABDTPA-Gd is 2h, while as DAA-ABDTPA-Gd is 55 min, eighty to ninety percent of gadolinium complexes bound to DAS or DAA were excreted in urine 24 h after administration. Relaxivities of the above gadolinium complexes were 1.2[approx]2 times as high as those of ABDTPA-Gd or DO 3 MA-Gd. These results demonstrate that gadolinium complexes based on polysaccharide derivatives are promising compounds for future use as MRI enhancers. (author).

  6. Hot Corrosion of Nickel-Base Alloys in Biomass-Derived Fuel Simulated Atmosphere

    Energy Technology Data Exchange (ETDEWEB)

    Leyens, C.; Pint, B.A.; Wright, I.G.

    1999-02-28

    Biomass fuels are considered to be a promising renewable source of energy. However, impurities present in the fuel may cause corrosion problems with the materials used in the hot sections of gas turbines and only limited data are available so far. As part of the Advanced Turbine Systems Program initiated by the U.S. Department of Energy, the present study provides initial data on the hot corrosion resistance of different nickel-base alloys against sodium sulfate-induced corrosion as a baseline, and against salt compositions simulating biomass-derived fuel deposits. Single crystal nickel-superalloy Rene N5, a cast NiCrAlY alloy, a NiCoCrAlY alloy representing industrially used overlay compositions, and a model {beta}NiAl+Hf alloy were tested in 1h thermal cycles at 950 C with different salt coatings deposited onto the surfaces. Whereas the NiCoCrAlY alloy exhibited reasonable resistance against pure sodium sulfate deposits, the NiCrAiY alloy and Rene N5 were attacked severely. Although considered to be an ideal alumina former in air and oxygen at higher temperatures, {beta}NiAl+Hf also suffered from rapid corrosion attack at 950 C when coated with sodium sulfate. The higher level of potassium present in biomass fuels compared with conventional fuels was addressed by testing a NiCoCrAlY alloy coated with salts of different K/Na atomic ratios. Starting at zero Na, the corrosion rate increased considerably when sodium was added to potassium sulfate. In an intermediate region the corrosion rate was initially insensitive to the K/Na ratio but accelerated when very Na-rich compositions were deposited. The key driver for corrosion of the NiCoCrAlY alloy was sodium sulfate rather than potassium sulfate, and no simple additive or synergistic effect of combining sodium and potassium was found.

  7. A Quantitative Structure-Activity Relationships (QSAR Study of Piperine Based Derivatives with Leishmanicidal Activity

    Directory of Open Access Journals (Sweden)

    Edilson Beserra Alencar Filho

    2017-04-01

    Full Text Available Leishmaniasis is a parasitic disease which represents a serious public health problem in developing countries. It is considered a neglected tropical disease, for which there is little initiative in the search for therapeutic alternatives by pharmaceutical industry. Natural products remain a great source of inspiration for obtaining bioactive molecules. In 2010, Singh and co-workers published the synthesis and in vitro biological activity of piperoyl-aminoacid conjugates, as well as of piperine, against cellular cultures of Leishmania donovani. The piperine is an alkaloid isolated from Piper nigrum that has many activities described in the literature. In this work, we present a Quantitative Structure-Activity Study of piperine derivatives tested by Singh and co-workers, aiming to highlight important molecular features for leishmanicidal activity, obtaining a mathematical model to predict the activity of new analogs. Compounds were submitted to a geometry optimization computational procedure at semiempirical level of quantum theory. Molecular descriptors for the set of compounds were calculated by E-Dragon online plataform, followed by a variable selection procedure using Ordered Predictors Selection algorithm. Validation parameters obtained showed that a good QSAR model, based on multiple linear regression, was obtained (R2 = 0.85; Q2 = 0.69, and the following conclusions regarding the structure-activity relationship were elucidated: Compounds with electronegative atoms on different substituent groups of analogs, absence of unsaturation on lateral chain, presence of ester instead of carboxyl, and large volumes (due the presence of additional aromatic rings trends to increase the activity against promastigote forms of leishmania. DOI: http://dx.doi.org/10.17807/orbital.v9i1.893

  8. Synthesis and evaluation of phenylalanine-derived trifluoromethyl ketones for peptide-based oxidation catalysis.

    Science.gov (United States)

    Featherston, Aaron L; Miller, Scott J

    2016-10-15

    We report the synthesis of phenylalanine-derived trifluoromethyl ketones for the in situ generation of dioxiranes for the purpose of oxidation catalysis. The key features of this synthesis include the use of a masked ketone strategy and a Negishi cross-coupling to access the parent amino acid. The derivatives can be readily incorporated into a peptide for use in oxidation chemistry and exhibit good stability and reactivity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Synthesis, Characterization and Antimicrobial Activity of Imidazole Derivatives Based on 2-chloro-7-methyl-3-formylquinoline

    Directory of Open Access Journals (Sweden)

    R. H. Parab

    2012-01-01

    Full Text Available A series of oxazole and thereof imidazole derivatives were prepared from 2-chloro-7-methyl-3-formyl quinoline. The structures of all synthesized compounds were elucidated by elemental, IR, 1HNMR, 13CNMR spectra. Supplementary to these, they were assayed in vitro for their antimicrobial activity; it was revealed that some synthesized derivatives were exhibiting competent biological activity against both gram negative and gram positive bacterial species and fungal microorganisms.

  10. Nitrogen K-edge X-ray absorption near edge structure (XANES) spectra of purine-containing nucleotides in aqueous solution.

    Science.gov (United States)

    Shimada, Hiroyuki; Fukao, Taishi; Minami, Hirotake; Ukai, Masatoshi; Fujii, Kentaro; Yokoya, Akinari; Fukuda, Yoshihiro; Saitoh, Yuji

    2014-08-07

    The N K-edge X-ray absorption near edge structure (XANES) spectra of the purine-containing nucleotide, guanosine 5'-monophosphate (GMP), in aqueous solution are measured under various pH conditions. The spectra show characteristic peaks, which originate from resonant excitations of N 1s electrons to π* orbitals inside the guanine moiety of GMP. The relative intensities of these peaks depend on the pH values of the solution. The pH dependence is explained by the core-level shift of N atoms at specific sites caused by protonation and deprotonation. The experimental spectra are compared with theoretical spectra calculated by using density functional theory for GMP and the other purine-containing nucleotides, adenosine 5'-monophosphate, and adenosine 5'-triphosphate. The N K-edge XANES spectra for all of these nucleotides are classified by the numbers of N atoms with particular chemical bonding characteristics in the purine moiety.

  11. Complex coordinated extracellular metabolism: Acid phosphatases activate diluted human leukocyte proteins to generate energy flow as NADPH from purine nucleotide ribose.

    Science.gov (United States)

    Hibbs, John B; Vavrin, Zdenek; Cox, James E

    2016-08-01

    Complex metabolism is thought to occur exclusively in the crowded intracellular environment. Here we report that diluted enzymes from lysed human leukocytes produce extracellular energy. Our findings involve two pathways: the purine nucleotide catabolic pathway and the pentose phosphate pathway, which function together to generate energy as NADPH. Glucose6P fuel for NADPH production is generated from structural ribose of purine ribonucleoside monophosphates, ADP, and ADP-ribose. NADPH drives glutathione reductase to reduce an oxidized glutathione disulfide-glutathione redox couple. Acid phosphatases initiate ribose5P salvage from purine ribonucleoside monophosphates, and transaldolase controls the direction of carbon chain flow through the nonoxidative branch of the pentose phosphate pathway. These metabolic control points are regulated by pH. Biologically, this energy conserving metabolism could function in perturbed extracellular spaces.

  12. Chiral induction in phenanthroline-derived oligoamide foldamers: an acid- and base-controllable switch in helical molecular strands.

    Science.gov (United States)

    Hu, Hai-Yu; Xiang, Jun-Feng; Yang, Yong; Chen, Chuan-Feng

    2008-03-20

    A series of phenanthroline-derived oligoamides bearing a chiral (R)-phenethylamino end group were synthesized that displayed chiral helical induction and subsequently formed one-hand helical foldamers in solution. Moreover, an acid- and base-controllable switch in the helical molecular strands was observed, which has been demonstrated by NMR, UV-vis, and circular dichroism spectroscopy.

  13. Curriculum-Based Measurement of Oral Reading: Evaluation of Growth Estimates Derived with Pre-Post Assessment Methods

    Science.gov (United States)

    Christ, Theodore J.; Monaghen, Barbara D.; Zopluoglu, Cengiz; Van Norman, Ethan R.

    2013-01-01

    Curriculum-based measurement of oral reading (CBM-R) is used to index the level and rate of student growth across the academic year. The method is frequently used to set student goals and monitor student progress. This study examined the diagnostic accuracy and quality of growth estimates derived from pre-post measurement using CBM-R data. A…

  14. Imaging and Intracellular Tracking of Cancer-Derived Exosomes Using Single-Molecule Localization-Based Super-Resolution Microscope.

    Science.gov (United States)

    Chen, Chen; Zong, Shenfei; Wang, Zhuyuan; Lu, Ju; Zhu, Dan; Zhang, Yizhi; Cui, Yiping

    2016-10-05

    Exosomes are small membrane vesicles secreted by cells and enriched with plenty of proteins. Considering their significant roles in different physical activities and potential value for diagnostic drug delivery, researchers have put great efforts in in vitro tracking and content analysis of exosomes. Recently, the emergence of different kinds of super-resolution microscopy provides powerful tools for exosome study. Here, we demonstrate the application of single-molecule localization based super-resolution imaging technique in the imaging and tracking of cancer-derived exosomes. In the experiment, first, cancer-derived exosomes are extracted from the culture media of tumor cells. Then the exosome membrane receptors are labeled with photoswitchable probes, which allow super-resolution imaging of these membrane receptors via photoactivated localization microscopy (PALM) or stochastic optical reconstruction microscopy (STORM). By using human breast cancer cell-derived exosomes, we demonstrated simultaneous dual-color PALM/STORM imaging of two kinds of membrane receptors on the exosome membrane. Moreover, the successful labeling and imaging of exosomes make it possible to observe the interaction between cancer-derived exosomes and normal cells. Meanwhile, we realized the colocalization of cancer-derived exosomes and lysosomes in recipient cells with PALM/STORM imaging. Since exosomes play a vital role in intercellular communications, we anticipate that the presented PALM/STORM-based imaging and tracking of exosomes holds a great potential in the investigation of the mechanism of exosome-mediated cancer metastasis.

  15. Synthesis, Characterization and Biological Activity of Transition Metals with Schiff Base Derived from Adamantaneamine and o-Vanillin

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Five new solid complexes were synthesized about transition metals with Schiff base(L,C18H23NO2) derived from adamantaneamine and o-vanillin, and characterized by elemental analysis, molar conductance, infrared spectra, UV-vis spectra, thermal analysis. Their chemical formula are [ML2](ClO4)2 (M= Mn,Co,Ni,Cu,Zn),and the coordination numbers are four. The antibacterial activity of Schiff base ligand and its complexes was studied.

  16. Monte Carlo method based QSAR modeling of maleimide derivatives as glycogen synthase kinase-3β inhibitors.

    Science.gov (United States)

    Živković, Jelena V; Trutić, Nataša V; Veselinović, Jovana B; Nikolić, Goran M; Veselinović, Aleksandar M

    2015-09-01

    The Monte Carlo method was used for QSAR modeling of maleimide derivatives as glycogen synthase kinase-3β inhibitors. The first QSAR model was developed for a series of 74 3-anilino-4-arylmaleimide derivatives. The second QSAR model was developed for a series of 177 maleimide derivatives. QSAR models were calculated with the representation of the molecular structure by the simplified molecular input-line entry system. Two splits have been examined: one split into the training and test set for the first QSAR model, and one split into the training, test and validation set for the second. The statistical quality of the developed model is very good. The calculated model for 3-anilino-4-arylmaleimide derivatives had following statistical parameters: r(2)=0.8617 for the training set; r(2)=0.8659, and r(m)(2)=0.7361 for the test set. The calculated model for maleimide derivatives had following statistical parameters: r(2)=0.9435, for the training, r(2)=0.9262 and r(m)(2)=0.8199 for the test and r(2)=0.8418, r(av)(m)(2)=0.7469 and ∆r(m)(2)=0.1476 for the validation set. Structural indicators considered as molecular fragments responsible for the increase and decrease in the inhibition activity have been defined. The computer-aided design of new potential glycogen synthase kinase-3β inhibitors has been presented by using defined structural alerts.

  17. Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk

    Science.gov (United States)

    Kelemen, Linda E.; Terry, Kathryn L.; Goodman, Marc T.; Webb, Penelope M.; Bandera, Elisa V.; McGuire, Valerie; Rossing, Mary Anne; Wang, Qinggang; Dicks, Ed; Tyrer, Jonathan P.; Song, Honglin; Kupryjanczyk, Jolanta; Dansonka-Mieszkowska, Agnieszka; Plisiecka-Halasa, Joanna; Timorek, Agnieszka; Menon, Usha; Gentry-Maharaj, Aleksandra; Gayther, Simon A.; Ramus, Susan J.; Narod, Steven A.; Risch, Harvey A.; McLaughlin, John R.; Siddiqui, Nadeem; Glasspool, Rosalind; Paul, James; Carty, Karen; Gronwald, Jacek; Lubiński, Jan; Jakubowska, Anna; Cybulski, Cezary; Kiemeney, Lambertus A.; Massuger, Leon F. A. G.; van Altena, Anne M.; Aben, Katja K. H.; Olson, Sara H.; Orlow, Irene; Cramer, Daniel W.; Levine, Douglas A.; Bisogna, Maria; Giles, Graham G.; Southey, Melissa C.; Bruinsma, Fiona; Kjær, Susanne Krüger; Høgdall, Estrid; Jensen, Allan; Høgdall, Claus K.; Lundvall, Lene; Engelholm, Svend-Aage; Heitz, Florian; du Bois, Andreas; Harter, Philipp; Schwaab, Ira; Butzow, Ralf; Nevanlinna, Heli; Pelttari, Liisa M.; Leminen, Arto; Thompson, Pamela J.; Lurie, Galina; Wilkens, Lynne R.; Lambrechts, Diether; Van Nieuwenhuysen, Els; Lambrechts, Sandrina; Vergote, Ignace; Beesley, Jonathan; Fasching, Peter A.; Beckmann, Matthias W.; Hein, Alexander; Ekici, Arif B.; Doherty, Jennifer A.; Wu, Anna H.; Pearce, Celeste L.; Pike, Malcolm C.; Stram, Daniel; Chang-Claude, Jenny; Rudolph, Anja; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B.; Bogdanova, Natalia; Antonenkova, Natalia; Odunsi, Kunle; Edwards, Robert P.; Kelley, Joseph L.; Modugno, Francesmary; Ness, Roberta B.; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; Orsulic, Sandra; Fridley, Brooke L.; Vierkant, Robert A.; Cunningham, Julie M.; Wu, Xifeng; Lu, Karen; Liang, Dong; Hildebrandt, Michelle A.T.; Weber, Rachel Palmieri; Iversen, Edwin S.; Tworoger, Shelley S.; Poole, Elizabeth M.; Salvesen, Helga B.; Krakstad, Camilla; Bjorge, Line; Tangen, Ingvild L.; Pejovic, Tanja; Bean, Yukie; Kellar, Melissa; Wentzensen, Nicolas; Brinton, Louise A.; Lissowska, Jolanta; Garcia-Closas, Montserrat; Campbell, Ian G.; Eccles, Diana; Whittemore, Alice S.; Sieh, Weiva; Rothstein, Joseph H.; Anton-Culver, Hoda; Ziogas, Argyrios; Phelan, Catherine M.; Moysich, Kirsten B.; Goode, Ellen L.; Schildkraut, Joellen M.; Berchuck, Andrew; Pharoah, Paul D.P.; Sellers, Thomas A.; Brooks-Wilson, Angela; Cook, Linda S.; Le, Nhu D.

    2014-01-01

    Scope We re-evaluated previously reported associations between variants in pathways of one-carbon (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake. Methods and Results Odds ratios (OR) for 446 genetic variants were estimated among 13,410 OC cases and 22,635 controls and among 2,281 cases and 3,444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for DPYD variants rs11587873 (OR=0.92, P=6x10−5) and rs828054 (OR=1.06, P=1x10−4). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT and TYMS, also interacted significantly with folate in a multi-variant analysis (corrected P=9.9x10−6) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in SHMT1 in one-carbon transfer, previously reported with OC, suggested lower risk at higher folate (Pinteraction=0.03-0.006). Conclusions Variation in pyrimidine metabolism genes, particularly DPYD, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. SHMT1 SNP-byfolate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC. PMID:25066213

  18. Simultaneous determination of purine metabolites, creatinine and pseudouridine in ruminant urine by reversed-phase high-performance liquid chromatography.

    Science.gov (United States)

    Shingfield, K J; Offer, N W

    1999-02-19

    Determination of purine metabolites, pseudouridine and creatinine in both bovine and ovine urine using high-performance liquid chromatography (HPLC) is described. Following dilution and filtration, urine samples were analysed directly. Separation and quantification was achieved using a Spherisorb ODS II C18 column (250x4.6 mm I.D.) under isocratic conditions. The mobile phase contained 7.5 mM ammonium dihydrogen phosphate, 10 mM sodium 1-heptane sulphonic acid and 1.0 mM triethylamine at pH 3.0. Chromatography was achieved at a flow-rate of 1.0 ml/min and monitoring column effluent at 218 nm. Total analysis time was 60 min. Recovery of all compound standards added to urine was above 96%. In all cases, close spectral matches of compound standards and corresponding identified peaks in ovine and bovine urine were obtained. Lowest detectable concentrations of allantoin, uric acid, xanthine, hypoxanthine, creatinine and pseudouridine were 1.1, 1.0, 1.0, 3.0 and 0.4 micromol/l, respectively. Advantages of simultaneous determination of purine metabolites, creatinine and pseudouridine in ruminant urine collected from both sheep and cattle exist over current methods.

  19. 信息动态%Preparation of Polysaccharide Derivatives-based Composite Chiral Stationary Phases and Their Chiral Recognition

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Two coated-type composite chiral stationary phases (CSPs) were prepared based on cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC) and amylose tris (3,5-dimethylphenylcarbamate)(ADMPC) by coating the corresponding derivatives onto 3-aminopropyl silica gel separately and then mixing or by coating the mixed derivatives onto silica gel. The CSPs containing only CDMPC or ADMPC were also prepared for comparison. The mixing method does not significantly influence the enantioselectivities. The composite CSPs generally show chiral recognition abilities intermediate between those of the two individual phases, while some racemates were poorer and at the same time one was better resolved on the composite CSPs.