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Sample records for 1st uk purine

  1. [Purine nucleoside phosphorylase].

    PubMed

    Pogosian, L G; Akopian, Zh I

    2013-01-01

    Purine nucleoside phosphorylase (PNP) is one of the most important enzymes of the purine metabolism, wich promotes the recycling of purine bases. Nowadays is the actual to search for effective inhibitors of this enzyme which is necessary for creation T-cell immunodeficient status of the organism in the organs and tissues transplantation, and chemotherapy of a number pathologies as well. For their successful practical application necessary to conduct in-depth and comprehensive study of the enzyme, namely a structure, functions, and an affinity of the reaction mechanism. In the review the contemporary achievements in the study of PNP from various biological objects are presented. New data describing the structure of PNP are summarised and analysed. The physiological role of the enzyme is discussed. The enzyme basic reaction mechanisms and actions are considered. The studies on enzyme physicochemical, kinetic, and catalytic research are presented. PMID:24479338

  2. Perspectives on purine analogues.

    PubMed

    Cheson, B D

    1996-12-01

    The purine analogs, fludarabine, 2-chlorodeoxy-adenosine, and 2'-deoxycoformycin, have revolutionized our approach to the treatment of a variety of indolent lymphoid malignancies. Because of their impressive single agent activity, they should be considered as an initial therapeutic option, not only for hairy cell leukemia, but also for chronic lymphocytic leukemia, indolent non-Hodgkin's lymphomas, and Waldenström's macroglobulenemia. Combinations of purine analogs with alkylatng agents, topisomerase II inhibitors, and other new compounds are in development, and their role as radiation sensitizers is being explored in clinical trials. Substantial activity has also been noted in several of the rheumatologic and immunologic disorders, and in multiple sclerosis. Continued progress requires innovative strategies which can modulate the biology and immunology of these diseases toward the goal of curing these patients. PMID:9137964

  3. Purine alkaloids in Paullinia.

    PubMed

    Weckerle, Caroline S; Stutz, Michael A; Baumann, Thomas W

    2003-10-01

    Among the few purine alkaloid-containing genera consumed as stimulants, Paullinia is the least investigated with respect to both chemotaxonomy and within-the-plant allocation of caffeine and its allies. Since purine alkaloids (PuA) have been proved to be valuable marker compounds in chemotaxonomy, 34 species of Paullinia and related genera were screened for them, but only one, P. pachycarpa, was positive in addition to the already known P. cupana and P. yoco. The PuA allocation in P. pachycarpa was examined and found to be restricted to theobromine in the stem, leaves and flowers. Moreover, the theobromine concentration in the stem cortex increased significantly towards the base of the plant. Since the stem cortex of P. yoco is traditionally used by the natives of Colombia and Ecuador to prepare a caffeine-rich beverage, we suspected that within the genus Paullinia the PuA are preferentially allocated to the older parts of the stem and not to young shoots like e.g., in the coffee plant (Coffea spp.). Indeed, the axis (greenhouse) of P. cupana (guaraná), known for its caffeine-rich seeds, exhibited a basipetal PuA gradient (0.005-0.145%). Moreover, the analysis of young cortex samples (herbarium) and of one piece of old stem (museum collection) revealed the same for P. yoco, even though we found much less (0.5 vs 2.5%) caffeine in the old cortex as compared to the only two analyses in 1926 of similar material. However, this discrepancy may be explained by the high variability of the PuA pattern we detected among yoco, the diversity of which the Indians take advantage.

  4. "Hard Science" for Gifted 1st Graders

    ERIC Educational Resources Information Center

    DeGennaro, April

    2006-01-01

    "Hard Science" is designed to teach 1st grade gifted students accurate and high level science concepts. It is based upon their experience of the world and attempts to build a foundation for continued love and enjoyment of science. "Hard Science" provides field experiences and opportunities for hands-on discovery working beside experts in the field…

  5. Lock No. 1 St. Lucie Canal. Sector gates, internal struts ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Lock No. 1- St. Lucie Canal. Sector gates, internal struts- nose beams. - St. Lucie Canal, St. Lucie Lock No. 1, St. Lucie, Cross State Canal, Okeechobee Intracoastal Waterway, Stuart, Martin County, FL

  6. Purine Metabolism During Neuronal Differentiation: The Relevance of Purine Synthesis and Recycling

    PubMed Central

    Göttle, Martin; Burhenne, Heike; Sutcliffe, Diane; Jinnah, H. A.

    2013-01-01

    Purines are a class of small organic molecules that are essential for all cells. They play critical roles in neuronal differentiation and function. Their importance is highlighted by several inherited disorders of purine metabolism, such as the Lesch-Nyhan disease, which is caused by a deficiency of the purine salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt). Despite the known importance of purines in the nervous system, knowledge regarding their metabolism in neurons is limited. In the current studies, purine pools and their metabolism were examined in rat PC6-3 cells, a PC12 pheochromocytoma subclone that undergoes robust differentiation with nerve growth factor. The results were compared with five new independent PC6-3 subclones with defective purine recycling due to different mutations affecting HGprt enzyme activity. The results demonstrate an increase in most purines and in energy state following neuronal differentiation, as well as specific abnormalities when purine recycling is lost. The loss of HGprt-mediated purine recycling also is associated with significant loss of dopamine and related metabolites in the mutant PC6-3 lines, suggesting an important connection between purine and dopamine pathways. These results provide insights into how purine pools and metabolism change with neuronal differentiation, and how specific enzyme defects may cause neuronal dysfunction. PMID:23859490

  7. EMSL Quarterly Highlights Report: 1st Quarter, FY08

    SciTech Connect

    Showalter, Mary Ann

    2008-01-28

    The EMSL Quarterly Highlights Report covers the science, staff and user recognition, and publication activities that occurred during the 1st quarter (October 2007 - December 2007) of Fiscal Year 2008.

  8. EMSL Quarterly Highlights Report: 1st Quarter, Fiscal Year 2009

    SciTech Connect

    Showalter, Mary Ann; Kathmann, Loel E.; Manke, Kristin L.

    2009-02-02

    The EMSL Quarterly Highlights Report covers the science, staff and user recognition, and publication activities that occurred during the 1st quarter (October 2008 - December 2008) of Fiscal Year 2009.

  9. ISS Update: 1st Annual ISS R&D Conference

    NASA Video Gallery

    NASA Public Affairs Officer Kelly Humphries talks by phone on Wednesday with Julie Robinson, ISS Program Scientist, about the 1st Annual International Space Station Research and Development Confere...

  10. 1st Baby Born with DNA from 3 Parents

    MedlinePlus

    ... news/fullstory_161176.html 1st Baby Born With DNA From 3 Parents Technique designed to help couples ... be born using a controversial technique that combines DNA from three people -- two women and a man. ...

  11. FDA OKs 1st Drug to Treat Duchenne Muscular Dystrophy

    MedlinePlus

    ... html FDA OKs 1st Drug to Treat Duchenne Muscular Dystrophy Exondys 51 seems to fill unmet need for ... the first drug for a rare form of muscular dystrophy. Exondys 51 (eteplirsen) was granted accelerated approval to ...

  12. Prebiotic syntheses of purines and pyrimidines

    NASA Technical Reports Server (NTRS)

    Basile, B.; Oro, J.; Lazcano, A.

    1984-01-01

    The results of experimental and theoretical investigations of the prebiotic synthesis of purines and pyramidines are surveyed. Topics examined include the synthesis of purines from HCN via 4,5-disubstituted imidazole derivatives in aqueous solutions or liquid NH3, simultaneous formation of amino acids and purines by electron irradiation of CH4-NH3-H2O mixtures, synthesis of pyrimadines from cynoacetylene, energetics, formation of bases under anhydrous or concentrated conditions, formation of bases under dilute conditions, Fischer-Tropsch-type reactions, and the role of activated intermediates. It is pointed out that the precursor compounds have been detected in the interstellar medium, on Titan, and in other solar-system bodies, and that solar-nebula HCN concentrations of the order of 1-10 mM have been estimated on the basis of meteorite measurements.

  13. 1st HPV Test for Use with Preservative Fluid

    MedlinePlus

    ... 159789.html 1st HPV Test for Use With Preservative Fluid Human papillomavirus responsible for 70 percent of ... Roberts Friday, July 8, 2016 FRIDAY, July 8, 2016 (HealthDay News) -- The U.S. Food and Drug Administration has approved Roche's cobas HPV ...

  14. Purine and pyrimidine excretion in psoriasis

    PubMed Central

    Simmonds, H. A.; Bowyer, A.

    1974-01-01

    1 Urinary purine excretion has been investigated in two healthy controls and two patients with psoriasis, one a hyperuricaemic, one a normouricaemic. No difference was detected between the patients and controls. Therapy with allopurinol effectively lowered blood and urinary uric acid levels and produced a deficit in total urinary oxypurine excretion in both controls and patients with psoriasis. The concomitant increase in xanthine excretion was greater than the increase in hypoxanthine excretion and xanthine/hypoxanthine ratios (average 0.70 and 1.0 prior to therapy) were increased by allopurinol to an average of 3.0 and 3.8 respectively in the two groups. Allopurinol also reduced the excretion of 8-hydroxy-7-methyl guanine but no effect on the excretion levels of other minor purine bases was noted. 2 Allopurinol was metabolized similarly by both patients and controls, 84% of the administered allopurinol being accounted for as urinary metabolites. 74% of the drug in the urine was excreted as oxipurinol, 26% as unchanged allopurinol plus allopurinol riboside, the remainder being oxipurinol riboside. 3 Pseudouridine excretion in 25 healthy controls was 86.5 ± 17.8 mg/24 hours. Pseudouridine excretion was not excessive in the patients with psoriasis and was not altered by allopurinol therapy. 4 No abnormality or difference in purine or pyrimidine excretion in either patient was detected prior to or during therapy which could be related to the epidermal lesion. PMID:22454896

  15. ["1st Therapeutic Red Cross Hospital" during the civil war].

    PubMed

    Simonenko, V B; Abashin, V G

    2014-04-01

    The article presents the documentary information about the founding, the establishment and early years of the 1st Therapeutic Red Cross Hospital - in the future - Mandryka Central Military Clinical Hospital of the Ministry of Defence of the Russian Federation. Presented the work of the Hospital during the dificult period of the Civil War, typhus epidemic, famine and devastation. Specified its staffing structure, command, medical and administrative staff, travel and accommodation till the moment of the deployment in the Silver Lane in Moscow. PMID:25051792

  16. The 1st All-Russian Workshop on Archaeoastronomy

    NASA Astrophysics Data System (ADS)

    Bochkarev, Nikolai G.

    2007-08-01

    The 1st All-Russia Workshop on Archaeoastronomy “Astronomical and World-Outlook Meaning of the Archaeological Monuments of South Ural” was held on June 19-25, 2006, at the ground of the archaeological center “Arkaim” (Chelyabinsk Region). Besides about 30 talks, astronomical measurements were performed at two archaeological objects under intensive study: Arkaim Site (Bronze Epoch, XVIII-XVI c. B.C.) and tumuli “with whiskers” complex Kondurovsky (V-VIII c. A.D.). The promising character of the megalithic complex on the Vera Island (Lake Turgoyak) was stated.

  17. Distinct Purine Distribution in Carbonaceous Chondrites

    NASA Technical Reports Server (NTRS)

    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

  18. 1st Stage Separation Aerodynamics Of VEGA Launcher

    NASA Astrophysics Data System (ADS)

    Genito, M.; Paglia, F.; Mogavero, A.; Barbagallo, D.

    2011-05-01

    VEGA is an European launch vehicle under development by the Prime Contractor ELV S.p.A. in the frame of an ESA contract. It is constituted by four stages, dedicated to the scientific/commercial market of small satellites (300 ÷ 2500 kg) into Low Earth Orbits, with inclinations ranging from 5.2° up to Sun Synchronous Orbits and with altitude ranging from 300 to 1500 km. Aim of this paper is to present a study of flow field due to retro-rockets impingement during the 1st stage VEGA separation phase. In particular the main goal of the present work is to present the aerodynamic activities performed for the justification of the separation phase.

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

    DOEpatents

    Gray, Nathanael S.; Schultz, Peter; Kim, Sung-Hou; Meijer, Laurent

    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.

  20. Purine and glycine metabolism by purinolytic clostridia.

    PubMed Central

    Dürre, P; Andreesen, J R

    1983-01-01

    Cell extracts of Clostridium acidiurici, C. cylindrosporum, and C. purinolyticum converted purine, hypoxanthine, 2-hydroxypurine, 6,8-dihydroxypurine, and uric acid into xanthine by the shortest possible route. Adenine was transformed to xanthine only by C. purinolyticum, whereas the other two species formed 6-amino-8-hydroxypurine, which was neither deaminated nor hydroxylated further. 8-Hydroxypurine was formed from purine by all three species. Xanthine dehydrogenase activity was constitutively expressed by C. purinolyticum. Due to the lability of the enzyme activity, comparative studies could not be done with a purified preparation. All enzymes reported to be involved in formiminoglycine metabolism of C. acidiurici and C. cylindrosporum were present in C. purinolyticum. However, glycine was reduced directly to acetate in all three species, as indicated by radiochemical data and by the detection of glycine reductase in cell extracts of C. cylindrosporum and C. purinolyticum. The expression of glycine reductase and the high ratio of glycine fermented to uric acid present points to an energetic advantage for the glycine reductase system, which is expressed when selenium compounds are added to the growth media. PMID:6833177

  1. [Natural purine compounds as radioprotective agents].

    PubMed

    Popova, N R; Gudkov, S V; Bruskov, V I

    2014-01-01

    Purine compounds xanthosine, caffeine, inosine-5'-monophosphate and guanosine-5'-monophosphate in the concentration range of 0.02-1 mmol/L exhibit antioxidant properties in vitro, significantly reducing the formation of hydrogen peroxide and hydroxyl radicals induced by X-rays in aqueous solutions and preventing the formation of 8-oxoguanine in DNA solutions. These compounds neutralize the long-lived protein radicals in vitro induced by radiation. In vivo they exhibit pronounced radiotherapeutic properties, increasing the survival rate of mice up to 50% by intraperitoneal injection (45 mg/kg) after the exposure to a lethal dose of 7 Gy. The tested compounds stimulate hemopoiesis, increasing the number of white blood cells and platelets in the peripheral blood of animals in postradiation period, as well as radiation recovery of DNA damage when administered both before and after irradiation. These purine compounds can be considered as potentially promising preventive and therapeutic agents to reduce the risk of the pathological effects of ionizing radiation on the body of mammals. PMID:25764844

  2. Allosteric Modulation of Purine and Pyrimidine Receptors

    PubMed Central

    Jacobson, Kenneth A.; Gao, Zhan-Guo; Göblyös, Anikó; IJzerman, Adriaan P.

    2011-01-01

    Among the purine and pyrimidine receptors, the discovery of small molecular allosteric modulators has been most highly advanced for the A1 and A3 ARs. These AR modulators have allosteric effects that are structurally separated from the orthosteric effects in SAR studies. The benzoylthiophene derivatives tend to act as allosteric agonists, as well as selective positive allosteric modulators (PAMs) of the A1 AR. A 2-amino-3-aroylthiophene derivative T-62 has been under development as a PAM of the A1 AR for the treatment of chronic pain. Several structurally distinct classes of allosteric modulators of the human A3 AR have been reported: 3-(2-pyridinyl)isoquinolines, 2,4-disubstituted quinolines, 1H-imidazo-[4,5-c]quinolin-4-amines, endocannabinoid 2-arachidonylglycerol and the food dye Brilliant Black BN. Site-directed mutagenesis of A1 and A3 ARs has identified residues associated with the allosteric effect, distinct from those that affect orthosteric binding. A few small molecular allosteric modulators have been reported for several of the P2X ligand-gated ion channels and the G protein-coupled P2Y receptor nucleotides. Metal ion modulation of the P2X receptors has been extensively explored. The allosteric approach to modulation of purine and pyrimidine receptors looks promising for development of drugs that are event-specific and site-specific in action. PMID:21586360

  3. Highlights of the 2 nd Bioinformatics Student Symposium by ISCB RSG-UK

    PubMed Central

    White, Benjamen; Fatima, Vayani; Fatima, Nazeefa; Das, Sayoni; Rahman, Farzana; Hassan, Mehedi

    2016-01-01

    Following the success of the 1 st Student Symposium by ISCB RSG-UK, a 2 nd Student Symposium took place on 7 th October 2015 at The Genome Analysis Centre, Norwich, UK. This short report summarizes the main highlights from the 2 nd Bioinformatics Student Symposium. PMID:27239284

  4. Purine metabolism in adenosine deaminase deficiency.

    PubMed Central

    Mills, G C; Schmalstieg, F C; Trimmer, K B; Goldman, A S; Goldblum, R M

    1976-01-01

    Purine and pyrimidine metabolites were measured in erythrocytes, plasma, and urine of a 5-month-old infant with adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) deficiency. Adenosine and adenine were measured using newly devised ion exchange separation techniques and a sensitive fluorescence assay. Plasma adenosine levels were increased, whereas adenosine was normal in erythrocytes and not detectable in urine. Increased amounts of adenine were found in erythrocytes and urine as well as in the plasma. Erythrocyte adenosine 5'-monophosphate and adenosine diphosphate concentrations were normal, but adenosine triphosphate content was greatly elevated. Because of the possibility of pyrimidine starvation, pyrimidine nucleotides (pyrimidine coenzymes) in erythrocytes and orotic acid in urine were measured. Pyrimidine nucleotide concentrations were normal, while orotic acid was not detected. These studies suggest that the immune deficiency associated with adenosine deaminase deficiency may be related to increased amounts of adenine, adenosine, or adenine nucleotides. PMID:1066699

  5. Acceleration of purine degradation by periodontal diseases.

    PubMed

    Barnes, V M; Teles, R; Trivedi, H M; Devizio, W; Xu, T; Mitchell, M W; Milburn, M V; Guo, L

    2009-09-01

    Periodontal diseases, such as gingivitis and periodontitis, are characterized by bacterial plaque accumulation around the gingival crevice and the subsequent inflammation and destruction of host tissues. To test the hypothesis that cellular metabolism is altered as a result of host-bacteria interaction, we performed an unbiased metabolomic profiling of gingival crevicular fluid (GCF) collected from healthy, gingivitis, and periodontitis sites in humans, by liquid and gas chromatography mass spectrometry. The purine degradation pathway, a major biochemical source for reactive oxygen species (ROS) production, was significantly accelerated at the disease sites. This suggests that periodontal-disease-induced oxidative stress and inflammation are mediated through this pathway. The complex host-bacterial interaction was further highlighted by depletion of anti-oxidants, degradation of host cellular components, and accumulation of bacterial products in GCF. These findings provide new mechanistic insights and a panel of comprehensive biomarkers for periodontal disease progression. PMID:19767584

  6. Acceleration of purine degradation by periodontal diseases.

    PubMed

    Barnes, V M; Teles, R; Trivedi, H M; Devizio, W; Xu, T; Mitchell, M W; Milburn, M V; Guo, L

    2009-09-01

    Periodontal diseases, such as gingivitis and periodontitis, are characterized by bacterial plaque accumulation around the gingival crevice and the subsequent inflammation and destruction of host tissues. To test the hypothesis that cellular metabolism is altered as a result of host-bacteria interaction, we performed an unbiased metabolomic profiling of gingival crevicular fluid (GCF) collected from healthy, gingivitis, and periodontitis sites in humans, by liquid and gas chromatography mass spectrometry. The purine degradation pathway, a major biochemical source for reactive oxygen species (ROS) production, was significantly accelerated at the disease sites. This suggests that periodontal-disease-induced oxidative stress and inflammation are mediated through this pathway. The complex host-bacterial interaction was further highlighted by depletion of anti-oxidants, degradation of host cellular components, and accumulation of bacterial products in GCF. These findings provide new mechanistic insights and a panel of comprehensive biomarkers for periodontal disease progression.

  7. THEOS: The1st Thailand EO System and

    NASA Astrophysics Data System (ADS)

    Peanvijarnpong, Chanchai

    Thailand has engaged in remote sensing satellite technological and scientific development many years since early 1980s. Thailand Landsat Station was established as a regional center of data processing and dissemination for Thai scientists for data applications. Over the years, GISTDA and Thai user community have been gaining technical experience and expertise in satellite data applications around the country such natural resources and environmental management, forest inventory, forest change detections, soil mapping, land-use and land cover mapping, crop type mapping, coastal shrimp farming, flood zone mapping, base mapping, water and drought management. The Government of Thailand realizes that remote sensing satellite technology is an important mechanism for social and economic development of the country. So the 1st Thailand Earth Observation System (THEOS) development program was approved by the Government since 2003. THEOS system is sub-synchronous satellite orbiting around the earth at 822 km. altitude same as SPOT satellites. It carries two imaging instruments; 2-m Panchromatic telescope with 22 km. swath width and 15-m resolution camera with four-multi-spectral band and 90-km swath wide. THEOS is scheduled to launch around March 2008. A number of technological and scientific activities has been implementing for Thailand and international scientific user community. Therefore THEOS is strong endorsement from the Government of Thailand on the value of remote sensing technology. This paper presents Thailand EO activities including THEOS System and its plans.

  8. 1st Advanced Marine Renewable Energy Instrumentation Experts Workshop

    SciTech Connect

    none,

    2011-10-01

    The U.S. marine energy industry is actively pursuing development of offshore wind and marine hydrokinetic (MHK) energy systems. Experience in the wind energy sector demonstrates that new technology development requires thorough measurement and characterization of the environmental conditions prevalent at installation sites and of technology operating in the field. Presently, there are no turn-key instrumentation system solutions that meet the measurement needs of the marine energy industry. The 1st Advanced Marine Renewable Energy Instrumentation Experts Workshop brought together technical experts from government laboratories, academia, and industry representatives from marine energy, wind, offshore oil and gas, and instrumentation developers to present and discuss the instrumentation needs of the marine energy industry. The goals of the meeting were to: 1. Share the latest relevant knowledge among technical experts; 2. Review relevant state-of-the-art field measurement technologies and methods; 3. Review lessons learned from recent field deployments; 4. Identify synergies across different industries; 5. Identify gaps between existing and needed instrumentation capabilities; 6. Understand who are the leading experts; 7. Provide a forum where stakeholders from the marine energy industry could provide substantive input in the development of new marine energy field deployable instrumentation packages.

  9. Purine Salvage Pathways among Borrelia Species▿

    PubMed Central

    Pettersson, Jonas; Schrumpf, Merry E.; Raffel, Sandra J.; Porcella, Stephen F.; Guyard, Cyril; Lawrence, Kevin; Gherardini, Frank C.; Schwan, Tom G.

    2007-01-01

    Genome sequencing projects on two relapsing fever spirochetes, Borrelia hermsii and Borrelia turicatae, revealed differences in genes involved in purine metabolism and salvage compared to those in the Lyme disease spirochete Borrelia burgdorferi. The relapsing fever spirochetes contained six open reading frames that are absent from the B. burgdorferi genome. These genes included those for hypoxanthine-guanine phosphoribosyltransferase (hpt), adenylosuccinate synthase (purA), adenylosuccinate lyase (purB), auxiliary protein (nrdI), the ribonucleotide-diphosphate reductase alpha subunit (nrdE), and the ribonucleotide-diphosphate reductase beta subunit (nrdF). Southern blot assays with multiple Borrelia species and isolates confirmed the presence of these genes in the relapsing fever group of spirochetes but not in B. burgdorferi and related species. TaqMan real-time reverse transcription-PCR demonstrated that the chromosomal genes (hpt, purA, and purB) were transcribed in vitro and in mice. Phosphoribosyltransferase assays revealed that, in general, B. hermsii exhibited significantly higher activity than did the B. burgdorferi cell lysate, and enzymatic activity was observed with adenine, hypoxanthine, and guanine as substrates. B. burgdorferi showed low but detectable phosphoribosyltransferase activity with hypoxanthine even though the genome lacks a discernible ortholog to the hpt gene in the relapsing fever spirochetes. B. hermsii incorporated radiolabeled hypoxanthine into RNA and DNA to a much greater extent than did B. burgdorferi. This complete pathway for purine salvage in the relapsing fever spirochetes may contribute, in part, to these spirochetes achieving high cell densities in blood. PMID:17502392

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

    PubMed

    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.

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

    PubMed

    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. PMID:24940702

  12. 1st meeting on topical drug delivery to the nail.

    PubMed

    Murdan, Sudaxshina

    2007-07-01

    The first ever symposium dedicated solely to drug delivery to the nail following topical application was held on the 2nd April 2007, in London, UK, organised by Dr Clive Roper (Charles River Laboratories, Scotland) and Dr Sudaxshina Murdan (School of Pharmacy, University of London, UK), under the auspices of Skin Forum. The 1-day meeting was attended by approximately 35 delegates from industry, academia and hospitals, and provided a much-needed forum for the presentation and discussion of research and problems in this emerging field. Topical drug delivery is especially suitable for onychomycosis (fungal infections of the nail plate and/or nail bed) and nail psoriasis, which affect 2 - 13 and 1 - 3% of the general population, respectively, and make up the bulk of nail disorders. Topical therapy would avoid the adverse events and drug interactions of systemic antifungal agents and the pain of injection when antipsoriatic agents are injected into affected nail folds. However, successful topical therapy is extremely challenging due to the very low permeability of the nail plate. Five speakers spoke about various aspects of topical drug delivery to the nail, including review of the nail plate structure, function, diseases, their existing therapies (systemic and topical), limitations and global sales. The need for effective topical drug delivery to the nail to overcome the problems associated with present treatment, and the fact that there are few topical formulations available for the treatment of nail fungal infections and psoriasis, and the even fewer effective formulations, was highlighted. PMID:17683257

  13. 1st meeting on topical drug delivery to the nail.

    PubMed

    Murdan, Sudaxshina

    2007-07-01

    The first ever symposium dedicated solely to drug delivery to the nail following topical application was held on the 2nd April 2007, in London, UK, organised by Dr Clive Roper (Charles River Laboratories, Scotland) and Dr Sudaxshina Murdan (School of Pharmacy, University of London, UK), under the auspices of Skin Forum. The 1-day meeting was attended by approximately 35 delegates from industry, academia and hospitals, and provided a much-needed forum for the presentation and discussion of research and problems in this emerging field. Topical drug delivery is especially suitable for onychomycosis (fungal infections of the nail plate and/or nail bed) and nail psoriasis, which affect 2 - 13 and 1 - 3% of the general population, respectively, and make up the bulk of nail disorders. Topical therapy would avoid the adverse events and drug interactions of systemic antifungal agents and the pain of injection when antipsoriatic agents are injected into affected nail folds. However, successful topical therapy is extremely challenging due to the very low permeability of the nail plate. Five speakers spoke about various aspects of topical drug delivery to the nail, including review of the nail plate structure, function, diseases, their existing therapies (systemic and topical), limitations and global sales. The need for effective topical drug delivery to the nail to overcome the problems associated with present treatment, and the fact that there are few topical formulations available for the treatment of nail fungal infections and psoriasis, and the even fewer effective formulations, was highlighted.

  14. 94. DETAIL, SAME BEAN AS ABOVE, MARKED 'PATENTED DEC. 1ST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    94. DETAIL, SAME BEAN AS ABOVE, MARKED 'PATENTED DEC. 1ST 1857' - Smithsonian Institution Building, 1000 Jefferson Drive, between Ninth & Twelfth Streets, Southwest, Washington, District of Columbia, DC

  15. The biochemistry of nitrogen mobilization: purine ring catabolism.

    PubMed

    Werner, Andrea K; Witte, Claus-Peter

    2011-07-01

    The enzymatic route of purine ring catabolism has recently been completed by the discovery of several novel enzymes identified through comparative genome analyses. Here, we review these recent discoveries and present an overview of purine ring catabolism in plants. Xanthine is oxidized to urate in the cytosol, followed by three enzymatic steps taking place in the peroxisome and four reactions in the endoplasmic reticulum releasing the four ring nitrogen as ammonia. Although the main physiological function of purine degradation might lie in the remobilization of nitrogen resources, it has also emerged that catabolic intermediates, the ureides allantoin and allantoate, are likely to be involved in protecting plants against abiotic stress. Conserved alternative splicing mediating the peroxisomal as well as cytosolic localization of allantoin synthase potentially links purine ring catabolism to brassinosteroid signaling.

  16. Purine alkaloids from the South China Sea gorgonian Subergorgia suberosa.

    PubMed

    Qi, Shu-Hua; Zhang, Si; Huang, Hui

    2008-04-01

    Four new purine alkaloids, namely, 6-(1'-purine-6',8'-dionyl)suberosanone ( 1), 3,9-(2-imino-1-methyl-4-imidazolidinone-5-yl)isopropenylpurine-6,8-dione ( 2), 1-(3'-carbonylbutyl)purine-6,8-dione ( 3), and 9-(3'-carbonylbutyl)purine-6,8-dione ( 4), together with three known compounds, guanosine ( 5), thymidine ( 6), and adenosine ( 7), were isolated from the EtOH/CH 2Cl 2 extracts of the South China Sea gorgonian Subergorgia suberosa. The structures of 1- 4 were determined on the basis of extensive spectroscopic analysis, including 1D and 2D NMR data. Compounds 1- 4 all showed weak cytotoxicity toward human cancer cell lines MDA-MB-231 and A435.

  17. PREFACE: 1st Conference on Light and Particle Beams in Materials Science 2013 (LPBMS2013)

    NASA Astrophysics Data System (ADS)

    Kumai, Reiji; Murakami, Youichi

    2014-04-01

    From 29-31 August 2013, the 1st International Conference on Light and Particle Beams in Materials Science, LPBMS 2013, took place in the Tsukuba International Congress Center in the city of Tsukuba, Japan. The conference was a continuation of the international series Synchrotron Radiation in Materials Science (SRMS), which started in 1994. The last one, SRMS-7, was held in Oxford UK 11-14 July 2010, where the International Advisory Committee (IAC) recommended the conference be enlarged to incorporate Materials Research from Neutron, Muon, and Slow Positron Sources, as well as the science emerging from Synchrotron Light Sources. The conference brought together contributions from academics and industrial researchers with a diverse background and experience from the physics, chemistry and engineering communities. The topics covered in the LPBMS2013 include strongly correlated electron systems, magnetism and magnetic materials, soft matter, interface and surface defects, catalysts, biomaterials, and ceramics. In the 3-day scientific program, the conference consisted of 9 plenary talks, 33 invited talks, 20 oral presentations, and 126 poster presentations. We are pleased to publish the proceedings of the LPBMS2013 in this volume of Journal of Physics: Conference Series. This volume contains 58 papers representing the work that was presented and discussed at the conference. We hope that this volume will promote further development of this interdisciplinary materials research emerging from synchrotron light, neutron, muon, and slow positron sciences. Finally, we would like to thank the International Advisory Committee (Chair: Professor G N Greaves), sponsors, all the participants and contributors for making possible this international meeting of researchers. Reiji Kumai & Youichi Murakami Conference photograph Details of the program and organizing committees are available in the pdf

  18. Proceedings of the 1st Puerto Rico Biobanking Workshop

    PubMed Central

    Mora, Edna; Robb, James A.; Stefanoff, Gustavo; Mellado, Robert Hunter; Coppola, Domenico; Muñoz-Antonia, Teresita; Flores, Idhaliz

    2015-01-01

    The 1st Puerto Rico Biobanking Workshop took place on August 20th, 2014 in the Auditorium of the Comprehensive Cancer Center of the University of Puerto Rico, Medical Sciences Campus in San Juan Puerto Rico. The program for this 1-day, live workshop included lectures by three biobanking experts, followed by presentations from existing biobanks in Puerto Rico and audience discussion. The need for increasing biobanking expertise in Puerto Rico stems from the fact that Hispanics in general are underrepresented in the biobanks in existence in the US, which limits the research conducted specifically to understand the molecular differences in cancer cells compared to other better studied populations. In turn, this lack of information impairs the development of better diagnostic and therapeutic approaches for our population. Dr. James Robb, M.D., F.C.A.P., consulting pathologist to the National Cancer Institute (NCI) and the Office of Biorepositories and Biospecimen Research (OBBR), opened the workshop with a discussion on the basic aspects of the science of biobanking (e.g., what is a biobank; its goals and objectives; protocols and procedures) in his talk addressing the importance of banking tissues for advancing biomedical research. Next, Dr. Gustavo Stefanoff, from the Cancer Institutes Network of Latin America (RINC by its name in Spanish), explained the mission, objectives, and structure of the Network of Latin-American and Caribbean Biobanks (REBLAC by its name in Spanish), which despite limited resources and many challenges, currently accrue high quality human tissue specimens and data to support cancer research in the region. Dr. Robert Hunter-Mellado, Professor of Internal Medicine, Universidad Central del Caribe, followed with an examination of the ethical and regulatory aspects of biobanking tissues for future research, including informed consent of subjects; protection of human subjects rights; and balancing risks and benefit ratios. In the afternoon, the

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

    SciTech Connect

    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.

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

    PubMed

    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

    2014-02-01

    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.

  1. Psychiatric Diagnosis and Concomitant Medical Treatment for 1st and 2nd Grade Children

    ERIC Educational Resources Information Center

    Cornell-Swanson, La Vonne; Frankenberger, William; Ley, Katie; Bowman, Krista

    2007-01-01

    This study examined the proportion of children in 1st and 2nd grade classes who were currently prescribed medication for psychotropic disorders. The study also examined the attitudes of 1st and 2nd grade teachers toward diagnosis of psychiatric disorders and use of psychiatric medication to treat children. Results of the current study indicate…

  2. Purine Salvage Pathway in Mycobacterium tuberculosis.

    PubMed

    Ducati, R G; Breda, A; Basso, L A; Santos, D S

    2011-01-01

    Millions of deaths worldwide are caused by the aetiological agent of tuberculosis, Mycobacterium tuberculosis. The increasing prevalence of this disease, the emergence of drug-resistant strains, and the devastating effect of human immunodeficiency virus coinfection have led to an urgent need for the development of new and more efficient antimycobacterial drugs. The modern approach to the development of new chemical compounds against complex diseases, especially the neglected endemic ones, such as tuberculosis, is based on the use of defined molecular targets. Among the advantages, this approach allows (i) the search and identification of lead compounds with defined molecular mechanisms against a specific target (e.g. enzymes from defined pathways), (ii) the analysis of a great number of compounds with a favorable cost/benefit ratio, and (iii) the development of compounds with selective toxicity. The present review describes the enzymes of the purine salvage pathway in M. tuberculosis as attractive targets for the development of new antimycobacterial agents. Enzyme kinetics and structural data have been included to provide a thorough knowledge on which to base the search for compounds with biological activity. We have focused on the mycobacterial homologues of this pathway as potential targets for the development of new antitubercular agents.

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

    SciTech Connect

    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.

  4. Macroscopic lithotype characterisation of the 1st Middle-Polish (1st Lusatian) Lignite Seam in the Miocene of central Poland

    NASA Astrophysics Data System (ADS)

    Widera, Marek

    2012-03-01

    The 1st Middle-Polish (1st Lusatian) Lignite Seam is exploited in open-cast mines in central Poland. A large number of lignite lithotypes, grouped in four lithotype associations, are distinguished: xylitic, detritic, xylo-detritic and detro-xylitic lithotype associations, which show various structures. Each lithotype association was produced under specific peat-forming environmental conditions. In the case of the lignite seams under study they represent all the main environments that are known from Neogene mires, i.e.: fen or open water, bush moor, wet forest swamp and dry forest swamp. For a simple and practical description in the field of both the lignite sections and borehole cores, a new codification for lignite lithotypes is proposed. It is based on the codification of clastic deposits (lithofacies). The practical value of the new lignite lithotype codification is examined in three vertical sections of the 1st Middle-Polish Lignite Seam.

  5. Isolation of Purines and Pyrimidines from the Murchison Meteorite

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

    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 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 play a major role in terrestrial biochemistry and are integral components of proteins, DNA and RNA. In this study we developed a new extraction technique using sublimation in order to isolate purines and pyrimidines from Murchison2, which is cleaner and more time efficient that traditional methods3. Several purines including adenine, guanine, hypoxanthine and xanthine were positively identified by high performance liquid chromatography and ultraviolet absorption detection in our Murchison extracts. The purines detected in Murchison do not correlate with the distribution of nucleobases found in geological environments on Earth4. Moreover, the abundance of extraterrestrial amino acids and the low level of terrestrial amino acid contaminants found in Murchison', support the idea that the purines in t h s meteorite are extraterrestrial in origin.

  6. Double functionalization of carbon nanotubes with purine and pyrimidine derivatives.

    PubMed

    Singh, Prabhpreet; Ménard-Moyon, Cécilia; Battigelli, Alessia; Toma, Francesca Maria; Raya, Jesus; Kumar, Jitendra; Nidamanuri, Nagapradeep; Verma, Sandeep; Bianco, Alberto

    2013-07-01

    Herein, we have developed a synthetic strategy for the covalent double functionalization of single-walled carbon nanotubes (SWCNTs) with a combination of purine-pyrimidine and purine-purine nucleobase systems. The nucleobases were introduced on the sidewall of oxidized SWCNTs through 1,3-dipolar cycloaddition and by amidation of the carboxylic acids located at the tips and defect sites of the nanotubes. The new nanohybrids were characterized by transmission electron microscopy, thermogravimetric analysis, FTIR and Raman spectroscopy, magic-angle spinning NMR spectroscopy, and Kaiser test. The nucleobase/SWCNT conjugates can be envisaged for the modulation of the interactions with nucleic acids by means of base pairing, thereby opening new possibilities in the development of DNA/CNT nanobioconjugates. PMID:23703975

  7. Computational studies of the purine-functionalized graphene sheets

    NASA Astrophysics Data System (ADS)

    Mirzaei, Mahmoud; Yousefi, Mohammad

    2012-10-01

    We performed a computational work to investigate the properties of functionalized graphene sheets (S) by adenine (A) and guanine (G) purine nucleobases. To achieve the purpose of this work, we examined the functionalization of armchair and zigzag tips of the S model by each of the A and G purines. The results indicated that the optimized properties for the investigated hybrid structures are different depending on the tip of functionalization and the used purine nucleobase. Moreover, the atomic level properties of the investigated structures were investigated by evaluating quadrupole coupling constants (CQ) for the atoms of the optimized structures. The remarkable trend of the CQ parameters is that the changes of atomic properties are many more significant for the functionalization of the zigzag-tip by the G nucleobase, which is in agreement with the results of the optimized properties.

  8. Plasticity in the purine-thiamine metabolic network of Salmonella.

    PubMed

    Bazurto, Jannell V; Downs, Diana M

    2011-02-01

    In Salmonella enterica, 5-aminoimidazole ribonucleotide (AIR) is the precursor of the 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) pyrophosphate moiety of thiamine and the last intermediate in the common HMP/purine biosynthetic pathway. AIR is synthesized de novo via five reactions catalyzed by the purF, -D, -T, -G, and -I gene products. In vivo genetic analysis demonstrated that in the absence of these gene products AIR can be generated if (i) methionine and lysine are in the growth medium, (ii) PurC is functional, and (iii) 5-amino-4-imidazolecarboxamide ribotide (AICAR) has accumulated. This study provides evidence that the five steps of the common HMP/purine biosynthetic pathway can be bypassed in the synthesis of AIR and thus demonstrates that thiamine synthesis can be uncoupled from the early purine biosynthetic pathway in bacteria.

  9. Purine metabolism in mesophyll protoplasts of tobacco (Nicotiana tabacum) leaves.

    PubMed Central

    Barankiewicz, J; Paszkowski, J

    1980-01-01

    The overall metabolism of purines was studied in tobacco (Nicotiana tabacum) mesophyll protoplasts. Metabolic pathways were studied by measuring the conversion of radioactive adenine, adenosine, hypoxanthine and guanine into purine ribonucleotides, ribonucleosides, bases and nucleic acid constituents. Adenine was extensively deaminated to hypoxanthine, whereupon it was also converted into AMP and incorporated into nucleic acids. Adenosine was mainly hydrolysed to adenine. Inosinate formed from hypoxanthine was converted into AMP and GMP, which were then catabolized to adenine and guanosine respectively. Guanine was mainly deaminated to xanthine and also incorporated into nucleic acids via GTP. Increased RNA synthesis in the protoplasts resulted in enhanced incorporation of adenine and guanine, but not of hypoxanthine and adenosine, into the nucleic acid fraction. The overall pattern of purine-nucleotide metabolic pathways in protoplasts of tobacco leaf mesophyll is proposed. PMID:6154458

  10. [Purine regulon of gamma-proteobacteria: a detailed description].

    PubMed

    Ravcheev, D A; Gel'fand, M S; Mironov, A A; Rakhmaninova, A B

    2002-09-01

    The structure of the purine regulon was studied by a comparative genomic approach in seven genomes of gamma-proteobacteria: Escherichia coli, Salmonella typhi, Yersinia pestis, Haemophilus influenzae, Pasteurella multocida, Actinobacillus actinomycetemcomitans, and Vibrio cholerae. The palindromic binding site of the purine repressor (consensus ACGCAAACGTTTGCGT) is fairly well retained of genes encoding enzymes that participate in the synthesis of inosinemonophosphate from phosphoribozylpyrophosphate and in transfer of unicarbon groups, and also upstream of some transport protein genes. These genes may be regarded as the main part of the purine regulon. In terms of physiology, the regulation of the purC and gcvTHP/folD genes seems to be especially important, because the PurR site was found upstream of nonorthologous but functionally replaceable genes. However, the PurR site is poorly retained in front of orthologs of some genes belonging to the E. coli purine regulon, such as genes involved in general nitrogen metabolism, biosynthesis of pyrimidines, and synthesis of AMP and GMP from IMP, and also upstream of the purine repressor gene. It is predicted that purine regulons of the examined bacteria include the following genes: upp participating in synthesis of pyrimidines; uraA encoding an uracil transporter gene; serA involved in serine biosynthesis; folD responsible for the conversion of N5,N10-methenyl tetrahydrofolate into N10-formyltetrahydrofolate; rpiA involved in ribose metabolism; and protein genes with an unknown function (yhhQ and ydiK). The PurR site was shown to have different structure in different genomes. Thus, the tendency for a decline of the conservatism of site positions 2 and 15 was observed in genomes of bacteria belonging to the Pasteurellaceae and Vibrionaceae groups.

  11. Texas Reports 1st U.S. Case of Zika from Travel to Another State

    MedlinePlus

    ... 160450.html Texas Reports 1st U.S. Case of Zika From Travel to Another State Resident had recently ... what appears to be the first case of Zika infection traveling across state lines, Texas health officials ...

  12. 45. MISSISSIPPI, LOWNDES CO. COLUMBUS RAILROAD BRIDGE End of 1st ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    45. MISSISSIPPI, LOWNDES CO. COLUMBUS RAILROAD BRIDGE End of 1st St. S., Columbus, Ms. Turn span from SE. Sarcone Photography, Columbus, Ms. Sep 1978. - Bridges of the Upper Tombigbee River Valley, Columbus, Lowndes County, MS

  13. 46. MISSISSIPPI, LOWNDES CO. COLUMBUS RAILROAD BRIDGE End of 1st ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    46. MISSISSIPPI, LOWNDES CO. COLUMBUS RAILROAD BRIDGE End of 1st St. S., Columbus, Ms. Overall view, from S. Sarcone Photography, Columbus, Ms. Sep 1978. - Bridges of the Upper Tombigbee River Valley, Columbus, Lowndes County, MS

  14. BLOEDNER MONUMENT (32ND INDIANA, 1ST GERMAN MONUMENT), SECTION C, FRONT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    BLOEDNER MONUMENT (32ND INDIANA, 1ST GERMAN MONUMENT), SECTION C, FRONT ELEVATION DETAIL OF GERMAN TEXT. VIEW TO NORTHEAST. - Cave Hill National Cemetery, 701 Baxter Avenue, Louisville, Jefferson County, KY

  15. U.S. Premature Births Rise for 1st Time in 8 Years

    MedlinePlus

    ... 161792.html U.S. Premature Births Rise for 1st Time in 8 Years March of Dimes' report finds ... United States increased in 2015 for the first time in eight years, and rates are especially high ...

  16. 28. ENGINE CLUSTER OF 1ST STAGE OF A SATURN I ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    28. ENGINE CLUSTER OF 1ST STAGE OF A SATURN I ROCKET ENGINE LOCATED ON NORTH SIDE OF STATIC TEST STAND. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

  17. VIEW SOUTH/SOUTHEAST LOOKING DOWN ON 2ND AQUEDUCT AND 1ST AQUEDUCT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW SOUTH/SOUTHEAST LOOKING DOWN ON 2ND AQUEDUCT AND 1ST AQUEDUCT CASCADES TOWARDS FILTRATION PLANT AND LOS ANGELES RESERVOIR - Los Angeles Aqueduct, Cascades Structures, Los Angeles, Los Angeles County, CA

  18. 4. VIEW WEST, WEST SIDE, SHOWING CHANNELS 1ST AND 2ND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. VIEW WEST, WEST SIDE, SHOWING CHANNELS 1ST AND 2ND VERTICAL BRACED DOUBLE ANGLES, DIAGONAL BRACING AND CROSS BRACED RAILING - Thirty-Sixth Street Bridge, Spanning Rabbit River, Hamilton, Allegan County, MI

  19. 14. Building 105, Facilities Engineering Building, 1830, interior, 1st floor, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. Building 105, Facilities Engineering Building, 1830, interior, 1st floor, crib area of building, showing electrical and plumbing cribs, wall and ceiling detail, looking S. - Watervliet Arsenal, Building 105, South Broadway, on Hudson River, Watervliet, Albany County, NY

  20. 7. 1ST FLOOR, LOOKING SOUTH SHOWING DINING ROOM FIREPLACE (LEFT); ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. 1ST FLOOR, LOOKING SOUTH SHOWING DINING ROOM FIREPLACE (LEFT); ENTRY SITTING ROOM FIREPLACE (RIGHT) AND LIVING ROOM (BACKGROUND). - Fort Riley, Building No. 4, 4 Barry Avenue, Riley, Riley County, KS

  1. Florida Reports 1st Locally Transmitted Zika Infections in U.S.

    MedlinePlus

    ... fullstory_160151.html Florida Reports 1st Locally Transmitted Zika Infections in U.S. 4 cases likely originated from ... apparently experiencing its first local outbreak of the Zika virus, with four human infections reported in South ...

  2. 62. Neg. No. F75A, Jun 18, 1930, INTERIORWAREHOUSE, 1ST FLOOR, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    62. Neg. No. F-75A, Jun 18, 1930, INTERIOR-WAREHOUSE, 1ST FLOOR, STORAGE OF AUTOMOBILE COMPONENTS - Ford Motor Company Long Beach Assembly Plant, Assembly Building, 700 Henry Ford Avenue, Long Beach, Los Angeles County, CA

  3. MAGAZINE E30. VIEW FROM BETWEEN 1ST AND 2ND BLAST WALL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MAGAZINE E-30. VIEW FROM BETWEEN 1ST AND 2ND BLAST WALL LOOKING TO THE REAR OF THE MAGAZINE. - Naval Magazine Lualualei, Waikele Branch, Tunnel Magazine Type, Waikakalaua & Kipapa Gulches, Pearl City, Honolulu County, HI

  4. 19. Detail of brick courses 116, back side, between 1st ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    19. Detail of brick courses 1-16, back side, between 1st and 2nd windows from the right - Oklahoma State University, Boys Dormitory, Northwest corner of Hester Street & Athletic Avenue, Stillwater, Payne County, OK

  5. 20. Detail of brick courses 4675, back side, between 1st ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Detail of brick courses 46-75, back side, between 1st and 2nd windows from the right - Oklahoma State University, Boys Dormitory, Northwest corner of Hester Street & Athletic Avenue, Stillwater, Payne County, OK

  6. If 1st Baby's Early, 2nd Will Be Too: Study

    MedlinePlus

    ... If 1st Baby's Early, 2nd Will Be Too: Study Chances just as high for women who go ... it really is a potent factor," said senior study author Laura Jelliffe-Pawlowski. She is associate director ...

  7. PREFACE: 1st International Conference on Sensing for Industry, Control, Communication & Security Technologies

    NASA Astrophysics Data System (ADS)

    Shuja Syed, Ahmed

    2013-12-01

    The 1st International Conference on Sensing for Industry, Control, Communication & Security Technologies (ICSICCST-2013), took place in Karachi, Pakistan, from 24-26 June 2013. It was organized by Indus University, Karachi, in collaboration with HEJ Research Institute of Chemistry, University of Karachi, Karachi. More than 80 abstracts were submitted to the conference and were double blind-reviewed by an international scientific committee. The topics of the Conference were: Video, Image & Voice Sensing Sensing for Industry, Environment, and Health Automation and Controls Laser Sensors and Systems Displays for Innovative Applications Emerging Technologies Unmanned, Robotic, and Layered Systems Sensing for Defense, Homeland Security, and Law Enforcement The title of the conference, 'Sensing for Industry, Control, Communication & Security Technologies' is very apt in capturing the main issues facing the industry of Pakistan and the world. We believe the sensing industry, particularly in Pakistan, is currently at a critical juncture of its development. The future of the industry will depend on how the industry players choose to respond to the challenge of global competition and opportunities arising from strong growth in the Asian region for which we are pleased to note that the conference covered a comprehensive spectrum of issues with an international perspective. This will certainly assist industry players to make informed decisions in shaping the future of the industry. The conference gathered qualified researchers from developed countries like USA, UK, Sweden, Saudi Arabia, China, South Korea and Malaysia etc whose expertise resulting from the research can be drawn upon to build an exploitable area of new technology that has potential Defense, Homeland Security, and Military applicability. More than 250 researchers/students attended the event and made the event great success as the turnout was 100%. An exceptional line-up of speakers spoke at the occasion. We want

  8. 1st- and 2nd-order motion and texture resolution in central and peripheral vision

    NASA Technical Reports Server (NTRS)

    Solomon, J. A.; Sperling, G.

    1995-01-01

    STIMULI. The 1st-order stimuli are moving sine gratings. The 2nd-order stimuli are fields of static visual texture, whose contrasts are modulated by moving sine gratings. Neither the spatial slant (orientation) nor the direction of motion of these 2nd-order (microbalanced) stimuli can be detected by a Fourier analysis; they are invisible to Reichardt and motion-energy detectors. METHOD. For these dynamic stimuli, when presented both centrally and in an annular window extending from 8 to 10 deg in eccentricity, we measured the highest spatial frequency for which discrimination between +/- 45 deg texture slants and discrimination between opposite directions of motion were each possible. RESULTS. For sufficiently low spatial frequencies, slant and direction can be discriminated in both central and peripheral vision, for both 1st- and for 2nd-order stimuli. For both 1st- and 2nd-order stimuli, at both retinal locations, slant discrimination is possible at higher spatial frequencies than direction discrimination. For both 1st- and 2nd-order stimuli, motion resolution decreases 2-3 times more rapidly with eccentricity than does texture resolution. CONCLUSIONS. (1) 1st- and 2nd-order motion scale similarly with eccentricity. (2) 1st- and 2nd-order texture scale similarly with eccentricity. (3) The central/peripheral resolution fall-off is 2-3 times greater for motion than for texture.

  9. 40 CFR 721.4685 - Substituted purine metal salt (generic name).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Substituted purine metal salt (generic... Specific Chemical Substances § 721.4685 Substituted purine metal salt (generic name). (a) Chemical... as a substituted purine metal salt (PMN P-95-175) is subject to reporting under this section for...

  10. 40 CFR 721.4685 - Substituted purine metal salt (generic name).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Substituted purine metal salt (generic... Specific Chemical Substances § 721.4685 Substituted purine metal salt (generic name). (a) Chemical... as a substituted purine metal salt (PMN P-95-175) is subject to reporting under this section for...

  11. 40 CFR 721.4685 - Substituted purine metal salt (generic name).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Substituted purine metal salt (generic... Specific Chemical Substances § 721.4685 Substituted purine metal salt (generic name). (a) Chemical... as a substituted purine metal salt (PMN P-95-175) is subject to reporting under this section for...

  12. 40 CFR 721.4685 - Substituted purine metal salt (generic name).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted purine metal salt (generic... Specific Chemical Substances § 721.4685 Substituted purine metal salt (generic name). (a) Chemical... as a substituted purine metal salt (PMN P-95-175) is subject to reporting under this section for...

  13. 40 CFR 721.4685 - Substituted purine metal salt (generic name).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Substituted purine metal salt (generic... Specific Chemical Substances § 721.4685 Substituted purine metal salt (generic name). (a) Chemical... as a substituted purine metal salt (PMN P-95-175) is subject to reporting under this section for...

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

    PubMed

    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. PMID:21880467

  15. Inhibition and Structure of Toxoplasma gondii Purine Nucleoside Phosphorylase

    PubMed Central

    Donaldson, Teraya M.; Cassera, María B.; Ho, Meng-Chiao; Zhan, Chenyang; Merino, Emilio F.; Evans, Gary B.; Tyler, Peter C.; Almo, Steven C.; Schramm, Vern L.

    2014-01-01

    The intracellular pathogen Toxoplasma gondii is a purine auxotroph that relies on purine salvage for proliferation. We have optimized T. gondii purine nucleoside phosphorylase (TgPNP) stability and crystallized TgPNP with phosphate and immucillin-H, a transition-state analogue that has high affinity for the enzyme. Immucillin-H bound to TgPNP with a dissociation constant of 370 pM, the highest affinity of 11 immucillins selected to probe the catalytic site. The specificity for transition-state analogues indicated an early dissociative transition state for TgPNP. Compared to Plasmodium falciparum PNP, large substituents surrounding the 5′-hydroxyl group of inhibitors demonstrate reduced capacity for TgPNP inhibition. Catalytic discrimination against large 5′ groups is consistent with the inability of TgPNP to catalyze the phosphorolysis of 5′-methylthioinosine to hypoxanthine. In contrast to mammalian PNP, the 2′-hydroxyl group is crucial for inhibitor binding in the catalytic site of TgPNP. This first crystal structure of TgPNP describes the basis for discrimination against 5′-methylthioinosine and similarly 5′-hydroxy-substituted immucillins; structural differences reflect the unique adaptations of purine salvage pathways of Apicomplexa. PMID:24585883

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

    NASA Technical Reports Server (NTRS)

    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.

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

    PubMed

    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.

  18. Highly efficient -1st-order reflection in Littrow mounted dielectric double-groove grating

    NASA Astrophysics Data System (ADS)

    Ito, Kota; Iizuka, Hideo

    2013-06-01

    We show that in a silicon double-groove grating with two different groove widths per period attached on top of a semi-infinite SiO2 substrate, almost 100% reflectivity is achieved for the -1st-order reflection with an incident angle of 60° in the Littrow mounting condition. The modal analysis reveals that modes propagating in the upward and downward directions have nearly the same amplitudes at resonance. They are added constructively for the -1st-order reflection and destructively for the 0th-order reflection and the -1st-order and 0th-order transmission. The asymmetric structure with a dielectric material poses a unique feature as a four port device.

  19. Minimally Invasive Arthrodesis of 1st Metatarsophalangeal Joint for Hallux Rigidus.

    PubMed

    Sott, A H

    2016-09-01

    First metatarsophalangeal joint arthrodesis plays a significant role in the management of symptomatic hallux rigidus/osteoarthritis of the 1st metatarsophalangeal joint. Several open and few percutaneous techniques have been described in the literature. This article describes and discusses a percutaneous technique that has been successfully used to achieve a pain-free stable and functional 1st metatarsophalangeal joint. All aspects of surgical indication and operative technique and details of patient-reported outcomes are presented with a referenced discussion. PMID:27524706

  20. Synthesis and anticonvulsant activity of novel purine derivatives.

    PubMed

    Wang, Shi-Ben; Jin, Peng; Li, Fu-Nan; Quan, Zhe-Shan

    2014-09-12

    A series of new purines containing triazole and other heterocycle substituents was synthesized and evaluated for their preliminary anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and rotarod neurotoxicity (TOX) tests. Among the compounds studied, 9-decyl-6-(1H-1,2,4-triazol-1-yl)-9H-purine (5e) was the most potent compound, with a median effective dose of 23.4 mg/kg and a high protective index of more than 25.6 after intraperitoneal administration in mice. Compound 5e showed significant oral activity against MES-induced seizures in mice, with an ED50 of 39.4 mg/kg and a PI above 31.6. These results demonstrate that compound 5e possesses better anticonvulsant activity and is safer than the commercially available drugs carbamazepine and valproate in MES, scPTZ and TOX models.

  1. Infrared Spectroscopy of Charge Transfer Complexes of Purines and Pyrimidines

    SciTech Connect

    Rathod, Pravinsinh I.; Oza, A. T.

    2011-10-20

    The FTIR spectra of charge transfer complexes of purines and pyrimidines with organic acceptors such as TCNQ, TCNE, DDQ, chloranil and iodine are obtained and studied in the present work. Adenine, guanine, thymine, cytosine and uracil are the purines and pyrimidines which are found as constituent of DNA and RNA. Charge transfer induced hydrogen bonding is concluded on the basis of indirect transitions observed in the infrared range in these CTCs. Some CTCs show gaussian bands revealing delocalization of charge carriers. The CTCs show interband transition in three-dimensions rather than two-dimensions unlike CTCs of amino acids. There is no extended hydrogen bonded network spanning the whole crystal. This leads to indirect transition due to locally deformed lattice furnishing a phonon-assisted transition.

  2. Inhibition of gene transcription by purine rich triplex forming oligodeoxyribonucleotides.

    PubMed Central

    Roy, C

    1993-01-01

    Several oligodeoxynucleotides (ODNs) were designed in order to interact with the purine rich element of the IRE (Interferon Responsive Element) of the 6-16 gene by triplex formation. An ODN of 21 bases, the sequence being identical to that of the purine strand of the IRE (48% G), but in reverse orientation, was able to interact with the IRE (KD: 20 nM). The binding was Mg2+ dependent. The two purine strands of the triplex were oriented antiparallel as confirmed by DNAase I and copper-phenanthroline footprinting experiments. An ODN in which A were replaced by T, also interacted with the same target, but with a lower affinity. Exonuclease III action indicated that the two IRE repeats of the 6-16 promoter interacted with each other through Hoogsteen base pairing, the third strand being parallel to the paired Watson-Crick strand. This led to a potential H-DNA structure which could be destabilized by adding ODNs able to form a triplex structure. 6-16 IRE driven-reporter gene constructs lost their interferon stimulability when co-transfected with triplex forming ODNs. The range of effective ODN concentrations was compatible with the affinity determined when measuring their direct interactions with the DNA. Images PMID:7687346

  3. Biosynthesis of purines by a proplastid fraction from soybean nodules.

    PubMed

    Boland, M J; Schubert, K R

    1983-01-01

    A proplastid-containing fraction was rapidly prepared from soybean nodules by a combination of differential and step gradient centrifugation. This fraction was capable of incorporating [U-14C]glycine into purines in the presence of added phosphoribosylpyrophosphate or ribose 5-phosphate, glutamine, aspartate, ATP, bicarbonate, methenyl tetrahydrofolate, MgCl2, and KCl. The primary product was IMP; some inosine was also formed. Soluble and bacteroid fractions from soybean nodules gave considerably lower rates of incorporation. Labeled carbon from both [U-14C]serine and [3-14C]serine was incorporated into purines when tetrahydrofolate and NADP+ were substituted for methenyl tetrahydrofolate. In this case, small amounts of label were also found in AMP and xanthine monophosphate (XMP). Labeled bicarbonate was incorporated into IMP and inosine by the proplastid fraction. Labeled formate, however, was not a competent substrate for purine synthesis, indicating the absence of formyl tetrahydrofolate synthetase activity in this fraction. When labeled IMP was incubated with a proplastid preparation, most of the label appeared in inosine. XMP and xanthosine were also formed if NAD+ or NADP+ was added to the incubation mixture indicating the presence of IMP dehydrogenase activity in the proplastid fraction.

  4. 130. Post1911. Photograph labeled, 'SEASON 1913. CAPTAIN, 1st MATE, SUPT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    130. Post-1911. Photograph labeled, 'SEASON 1913. CAPTAIN, 1st MATE, SUPT AND STOREKEEPER, A.P. ASS'N CANNERY, SHIP STAR OF ALASKA.' View forward from mizzenmast, post side. - Ship BALCLUTHA, 2905 Hyde Street Pier, San Francisco, San Francisco County, CA

  5. 47. MISSISSIPPI, LOWNDES CO. COLUMBUS RAILROAD BRIDGE End of 1st ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    47. MISSISSIPPI, LOWNDES CO. COLUMBUS RAILROAD BRIDGE End of 1st St. S., Columbus, Ms. Latching mechanism, E end of turn span, viewed from W. Sarcone Photography, Columbus, Ms. Sep 1978. - Bridges of the Upper Tombigbee River Valley, Columbus, Lowndes County, MS

  6. 42. MISSISSIPPI, LOWNDES CO. COLUMBUS RAILROAD BRIDGE End of 1st ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    42. MISSISSIPPI, LOWNDES CO. COLUMBUS RAILROAD BRIDGE End of 1st St. S., Columbus, Ms. Copy of postcard ca. 1900. Copy owned and made by Jack Donnell, Columbus, Ms. Shows two-span steel truss, built by Phoenix Bridge Co. in 1878. Negative copied by: Sarcone Photography, Columbus, Ms. Sep 1978. - Bridges of the Upper Tombigbee River Valley, Columbus, Lowndes County, MS

  7. 48. MISSISSIPPI, LOWNDES CO. COLUMBUS RAILROAD BRIDGE End of 1st ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    48. MISSISSIPPI, LOWNDES CO. COLUMBUS RAILROAD BRIDGE End of 1st St. S., Columbus, Ms Latching mechanism, E end of turn span, view from N. Sarcone Photography, Columbus, MS. Sep 1978. - Bridges of the Upper Tombigbee River Valley, Columbus, Lowndes County, MS

  8. 49. MISSISSIPPI, LOWNDES CO. COLUMBUS RAILROAD BRIDGE End of 1st ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    49. MISSISSIPPI, LOWNDES CO. COLUMBUS RAILROAD BRIDGE End of 1st St. S., Columbus, Ms. Top of pier and underside of w end of turn span. Sarcone Photography, Columbus, Ms. Sep 1978. - Bridges of the Upper Tombigbee River Valley, Columbus, Lowndes County, MS

  9. The Student View of 1st Year Laboratory Work in the Biosciences--Score Gamma?

    ERIC Educational Resources Information Center

    Collis, Mike; Gibson, Alan; Hughes, Ian; Sayers, Gill; Todd, Martin

    2008-01-01

    Students registered on 1st year bioscience courses in 9 universities were surveyed for their views on the laboratory classes they were taking. Returns were obtained from 695 (70%). Student views were varied, some viewing particular features of laboratory classes as "good" while others viewed the same features as "bad". Students identified as the…

  10. How Many Attempts Until Success in Some Core 1st. Year Disciplines?

    ERIC Educational Resources Information Center

    Fernandes, Graça Leão; Andrade e Silva, João; Lopes, Margarida Chagas

    2012-01-01

    Due to a general development in education brought about by democracy, Portugal has witnessed tremendous development in Higher Education (HE) since the beginning of the 1980s. Nevertheless, the percentage of graduates among the Portuguese population still ranks far below most European countries. This is why academic performance in HE 1st cycle…

  11. First-Generation College Students' 1st-Year College Experiences: Challenges Attending a Private University

    ERIC Educational Resources Information Center

    Reid, Josephine

    2013-01-01

    First-generation college students (FGCS) face challenges when switching from high school to college and during their 1st-year in college. Additionally, FGCS may have difficulty understanding the steps required to prepare for and enroll in postsecondary education. The social capital theory examines support of social, academic, and cultural networks…

  12. 24. OVERALL OF 1st FLOOR OF MILL NO. 1. PALLETS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    24. OVERALL OF 1st FLOOR OF MILL NO. 1. PALLETS HELD CLOTH IN STORAGE IN LATE 20th CENTURY. IRON POSTS IN LEFT DISTANCE FRONTED CLOTH BINS. HISTORIAN LEEANN LANDS IN BACKGROUND WITH LIGHT. - Prattville Manufacturing Company, Number One, 242 South Court Street, Prattville, Autauga County, AL

  13. 77 FR 22574 - Filing Dates for the Washington Special Election In the 1st Congressional District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-16

    ... From the Federal Register Online via the Government Publishing Office FEDERAL ELECTION COMMISSION Filing Dates for the Washington Special Election In the 1st Congressional District AGENCY: Federal Election Commission. ACTION: Notice of filing dates for special election. SUMMARY: Washington has...

  14. The Course of Psychological Disorders in the 1st Year After Cancer Diagnosis

    ERIC Educational Resources Information Center

    Kangas, Maria; Henry, Jane L.; Bryant, Richard A.

    2005-01-01

    This study investigated the relationship between acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) and comorbid anxiety, depressive, and substance use disorders over the first 12-month period following a cancer diagnosis. Individuals recently diagnosed with 1st onset head and neck or lung malignancy were assessed for ASD within…

  15. Perceptual Narrowing of Linguistic Sign Occurs in the 1st Year of Life

    ERIC Educational Resources Information Center

    Palmer, Stephanie Baker; Fais, Laurel; Golinkoff, Roberta Michnick; Werker, Janet F.

    2012-01-01

    Over their 1st year of life, infants' "universal" perception of the sounds of language narrows to encompass only those contrasts made in their native language (J. F. Werker & R. C. Tees, 1984). This research tested 40 infants in an eyetracking paradigm and showed that this pattern also holds for infants exposed to seen language--American Sign…

  16. Requirement of copper for 1st-log growth of the yeast Saccharomyces cerevisiae

    SciTech Connect

    Como, S.A.; Valerio, V.; Nickless, S.; Connelly, J.L.

    1986-05-01

    Routine evaluation of the role of copper (Cu) in the growth of various mutants of the yeast Saccharomyces Cerevisiae disclosed an unexpected effect of Cu on the fermentative first-log growth. The authors subsequent studies are attempting to ascertain the nature and significance of this observation. Cells are grown on glucose in a supplemented minimal media at 29/sup 0/C for 48-72 hrs. using New Brunswick incubator shaking at 200 rpm. Cu concentration was varied by addition of Cu salts or bathocuproine disulfonate (BC), a highly specific Cu chelator. Samples were removed periodically from flasks and dry weights were determined. Growth curve plots of normal yeasts grown in the presence of 1mM to 38mM Cu showed little variation in the expected 1st log; diauxi; 2nd log; stationary phase picture. However, in the presence of BC growth rate in the 1st log was significantly slowed and as expected 2nd log growth was essentially stopped. The low 1st log growth rate could be titrated to normal (+Cu) levels by increments of added Cu but not by added iron. The effect was not seen when Rho-minus strains were used nor when growth was followed under anaerobic conditions. Results to date implicate a mitochondrial protein, oxygen and copper in the 1st log growth of S Cerevisiae. The character of the protein agent and the possible contribution of cytochrome oxidase activity to the lst log growth are being evaluated.

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Idaho National Laboratory Quarterly Performance Analysis - 1st Quarter FY2015

    SciTech Connect

    Mitchell, Lisbeth A.

    2015-03-01

    This report is published quarterly by the Idaho National Laboratory (INL) Quality and Performance Management Organization. The Department of Energy (DOE) Occurrence Reporting and Processing System (ORPS), as prescribed in DOE Order 232.2, “Occurrence Reporting and Processing of Operations Information,” requires a quarterly analysis of events, both reportable and not reportable, for the previous 12 months. This report is the analysis of 73 reportable events (27 from the 1St Qtr FY-15 and 46 from the prior three reporting quarters), as well as 38 other issue reports (including nine not reportable events and Significant Category A and B conditions reported during the1st Qtr FY-15) identified at INL during the past 12 months.

  19. Effect of 1st-trimester loss on restoration of the hypothalamic-pituitary-ovarian axis.

    PubMed

    Elkas, J C; Cunningham, D S

    1995-01-01

    This randomized prospective study was conducted to determine the length of time required for re-establishment of the reproductive axis following a 1st-trimester spontaneous abortion. The spontaneous gonadotropin secretion was significantly depressed during the first menstrual cycle after pregnancy loss, while the estradiol levels had normalized. Provocative testing revealed blunted gonadotropin release in the first menstrual cycle with return to normal during the first menstrual cycle after a spontaneous abortion. Endometrial biopsy specimens were also abnormal during the first menstrual cycle with normal histological characteristics by the second menstrual cycle. Therefore, restoration of the hypothalamic-pituitary- ovarian axis after a 1st-trimester loss is achieved within two menstrual cycles, as determined by return of normal pituitary function.

  20. [Identification and quantitation of purine derivatives in urinary calculi as markers of abnormal purine metabolism by using high-performance liquid chromatography (HPLC)].

    PubMed

    Safranow, K

    2000-01-01

    The objective of this study was to develop a practical method for the analysis of purine derivatives in urinary calculi using high-performance liquid chromatography (HPLC). The method presented herein includes extraction of purine derivatives from urinary stones, followed by chromatography on a reversed-phase column with UV detection. A simpler isocratic method was applied to quantitate 6 purines known to be components of urinary stones, namely uric acid, xanthine, hypoxanthine, 2,8-dihydroxyadenine, oxypurinol and allopurinol. Gradient method separated 10 additional peaks representing methyl derivatives of uric acid or xanthine (1-, 3-, 7-, and 9-methyluric acid, 1,3-,1,7-, and 3,7-dimethyluric acid, and 1-, 3-, and 7-methylxanthine) (Fig. 1). Detection limits for individual compounds ranged from 25 to 140 micrograms purine per g stone weight and precision (RSD%) was 0.5-2.4%. Both methods were next used to analyze purine derivatives in urinary calculi from 48 residents of Western Pomerania. Uric acid was the main component of 9 stones. All of the uric acid stones showed admixtures of 9 other purine derivatives: natural metabolites (hypoxanthine, xanthine, 2,8-dihydroxyadenine) and methyl derivatives of uric acid (1-,3-, and 7-methyluric acid, 1,3-dimethyluric acid, 3-, and 7-methylxanthine) originating from the metabolism of exogenous methylxanthines (caffeine, theophylline and theobromine) (Tab. 1,2). Methyl derivatives of uric acid and xanthine, with a maximal content in stones of 1.7%, have hitherto not been considered constituents of urinary calculi. Statistical analysis of the results revealed strong positive correlations between the level of uric acid and of other purine derivatives in stones (Fig. 2). Correlations were also found between levels of some purines and inorganic compounds (Tab. 3). The sensitivity and specificity of HPLC with UV detection satisfy the requirements of a reference method for the analysis of purines in urinary stones. Isocratic

  1. 44. MISSISSIPPI, LOWNDES CO. COLUMBUS RAILROAD BRIDGE End of 1st ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    44. MISSISSIPPI, LOWNDES CO. COLUMBUS RAILROAD BRIDGE End of 1st St. S., Columbus, Ms. Detail from Camille Drie's map: A Bird's Eye View of Columbus, Mississippi ca. 1875-76. Shows M&O RR bridge before the Phoenix Bridge Co. erected iron truss spans in 1878. Credit: Photostat of map in Lowndes Co. Public Library Sarcone Photography, Columbus, Ms. 1978. - Bridges of the Upper Tombigbee River Valley, Columbus, Lowndes County, MS

  2. 43. MISSISSIPPI, LOWNDES CO. COLUMBUS RAILROAD BRIDGE End of 1st ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    43. MISSISSIPPI, LOWNDES CO. COLUMBUS RAILROAD BRIDGE End of 1st St. S., Columbus, Ms. Copy of photo 1900. Shows 1878 M&O RR bridge. The steamboat, 'Gopher,' in foreground, was an archeological survey vessel from the Franklin Institute in Philadelphia. Published in Art in Mississippi (1901). Credit: Copied from print in Lowndes Co. Public Library by Sarcone Photography, Columbus, Ms. 1978. - Bridges of the Upper Tombigbee River Valley, Columbus, Lowndes County, MS

  3. 46. NORTH END OF MILL NO. 2, 1st FLOOR, BELOW ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    46. NORTH END OF MILL NO. 2, 1st FLOOR, BELOW PICKER AND CLOTH ROOM AREA. FUNCTION OF THIS SPACE UNKNOWN AT PRESENT. NOTE THAT EYE BEAM REPLACES ORIGINAL WALL OF 1892 PICKER HOUSE. CENTER (OR LEFT) DOOR IS ENTRY TO MILL NO. 2. RIGHT DOOR IS ENTRY TO 1892 NAPPER ROOM. - Prattville Manufacturing Company, Number One, 242 South Court Street, Prattville, Autauga County, AL

  4. 7. Photographic copy of original construction drawing, ELECTRICAL 1ST AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Photographic copy of original construction drawing, ELECTRICAL 1ST AND 2ND FLOOR PLANS, SHEET 10 of 11, DRAWING NO. 35-03-05 SF 5/1677, U.S. Army Engineer District, Detroit, Corps of Engineers, 9 June, 1959, on file Selfridge Base Museum. - Selfridge Field, Building No. 1041, West of E Street, north of D Street, Mount Clemens, Macomb County, MI

  5. Ruthenium indenylidene "1(st) generation" olefin metathesis catalysts containing triisopropyl phosphite.

    PubMed

    Guidone, Stefano; Nahra, Fady; Slawin, Alexandra M Z; Cazin, Catherine S J

    2015-01-01

    The reaction of triisopropyl phosphite with phosphine-based indenylidene pre-catalysts affords "1(st) generation" cis-complexes. These have been used in olefin metathesis reactions. The cis-Ru species exhibit noticeable differences with the trans-Ru parent complexes in terms of structure, thermal stability and reactivity. Experimental data underline the importance of synergistic effects between phosphites and L-type ligands.

  6. Ruthenium indenylidene “1st generation” olefin metathesis catalysts containing triisopropyl phosphite

    PubMed Central

    Guidone, Stefano; Nahra, Fady; Slawin, Alexandra M Z

    2015-01-01

    Summary The reaction of triisopropyl phosphite with phosphine-based indenylidene pre-catalysts affords “1st generation” cis-complexes. These have been used in olefin metathesis reactions. The cis-Ru species exhibit noticeable differences with the trans-Ru parent complexes in terms of structure, thermal stability and reactivity. Experimental data underline the importance of synergistic effects between phosphites and L-type ligands. PMID:26425210

  7. Ruthenium indenylidene "1(st) generation" olefin metathesis catalysts containing triisopropyl phosphite.

    PubMed

    Guidone, Stefano; Nahra, Fady; Slawin, Alexandra M Z; Cazin, Catherine S J

    2015-01-01

    The reaction of triisopropyl phosphite with phosphine-based indenylidene pre-catalysts affords "1(st) generation" cis-complexes. These have been used in olefin metathesis reactions. The cis-Ru species exhibit noticeable differences with the trans-Ru parent complexes in terms of structure, thermal stability and reactivity. Experimental data underline the importance of synergistic effects between phosphites and L-type ligands. PMID:26425210

  8. Computer-generated Model of Purine Nucleoside Phosphorylase (PNP)

    NASA Technical Reports Server (NTRS)

    1987-01-01

    Purine Nucleoside Phosphorylase (PNP) is an important target enzyme for the design of anti-cancer and immunosuppressive drugs. Bacterial PNP, which is slightly different from the human enzyme, is used to synthesize chemotherapuautic agents. Knowledge of the three-dimensional structure of the bacterial PNP molecule is useful in efforts to engineer different types of PNP enzymes, that can be used to produce new chemotherapeutic agents. This picture shows a computer model of bacterial PNP, which looks a lot like a display of colorful ribbons. Principal Investigator was Charles Bugg.

  9. The electrochemical properties of the purine bases : at the interface between biological conjugates to inorganic surfaces

    NASA Technical Reports Server (NTRS)

    Hays, Charles C.

    2003-01-01

    The study of the charge transfer and interfacial reactions of the purine bases in physiological solutions provides valuable knowledge, as these processes are relevant to the origins of life. It has been proposed that the adsorption of the adsorption of the purine bases on an inorganic surface could serve as a template for specifying the arrangement of amino acids in peptides.

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

    SciTech Connect

    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.

  11. Lie Markov models with purine/pyrimidine symmetry.

    PubMed

    Fernández-Sánchez, Jesús; Sumner, Jeremy G; Jarvis, Peter D; Woodhams, Michael D

    2015-03-01

    Continuous-time Markov chains are a standard tool in phylogenetic inference. If homogeneity is assumed, the chain is formulated by specifying time-independent rates of substitutions between states in the chain. In applications, there are usually extra constraints on the rates, depending on the situation. If a model is formulated in this way, it is possible to generalise it and allow for an inhomogeneous process, with time-dependent rates satisfying the same constraints. It is then useful to require that, under some time restrictions, there exists a homogeneous average of this inhomogeneous process within the same model. This leads to the definition of "Lie Markov models" which, as we will show, are precisely the class of models where such an average exists. These models form Lie algebras and hence concepts from Lie group theory are central to their derivation. In this paper, we concentrate on applications to phylogenetics and nucleotide evolution, and derive the complete hierarchy of Lie Markov models that respect the grouping of nucleotides into purines and pyrimidines-that is, models with purine/pyrimidine symmetry. We also discuss how to handle the subtleties of applying Lie group methods, most naturally defined over the complex field, to the stochastic case of a Markov process, where parameter values are restricted to be real and positive. In particular, we explore the geometric embedding of the cone of stochastic rate matrices within the ambient space of the associated complex Lie algebra.

  12. Antiparasitic chemotherapy: tinkering with the purine salvage pathway.

    PubMed

    Datta, Alok Kumar; Datta, Rupak; Sen, Banibrata

    2008-01-01

    Distinguishable differences between infectine organisms and their respective hosts with respect to metabolism and macromolecular structure provide scopes for detailed characterization of target proteins and/or macromolecules as the focus for the development of selective inhibitors. In order to develop a rational approach to antiparasitic chemotherapy, finding differences in the biochemical pathways of the parasite with respect to the host it infects is therefore of primary importance. Like most parasitic protozoan, the genus Leishmania is an obligate auxotroph of purines and hence for requirement of purine bases depends on its own purine salvage pathways. Among various purine acquisition routes used by the parasite, the pathway involved in assimilation of adenosine nucleotide is unique and differs significantly in the extracellular form of the parasite (promastigotes) from its corresponding intracellular form (amastigotes). Adenosine kinase (AdK) is the gateway enzyme of this pathway and displays stage-specific activity pattern. Therefore, understanding the catalytic mechanism of the enzyme, its structural complexities and mode of its regulation have emerged as one of the major areas of investigation. This review, in general, discusses possible strategies to validate several purine salvage enzymes as targets for chemotherapeutic manipulation with special reference to adenosine kinase of Leishmania donovani. Systemic endotheliosis, commonly known as Kala-azar in India, is caused by the parasitic protozoon Leishmania donovani. The spread of leishmaniases follows the distribution of these vectors in the temperate, tropical and subtropical regions of the world leading to loss of thousands of human lives.' WHO has declared leishmaniasis among one of the six major diseases namely leishmaniasis, malaria, amoebiasis, filariasis, Chagas disease and schistosomiasis in its Special Programme for Research and Training in Tropical Diseases. Strategies for better prophylaxis and

  13. Characterization of purine catabolic pathway genes in coelacanths.

    PubMed

    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.

  14. Leishmania Metacyclogenesis Is Promoted in the Absence of Purines

    PubMed Central

    Serafim, Tiago Donatelli; Figueiredo, Amanda Braga; Costa, Pedro Augusto Carvalho; Marques-da-Silva, Eduardo Almeida; Gonçalves, Ricardo; de Moura, Sandra Aparecida Lima; Gontijo, Nelder Figueiredo; da Silva, Sydnei Magno; Michalick, Marilene Suzan Marques; Meyer-Fernandes, José Roberto; de Carvalho, Roberto Paes; Uliana, Silvia Reni Bortolin; Fietto, Juliana Lopes Rangel; Afonso, Luís Carlos Crocco

    2012-01-01

    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. PMID:23050028

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

    PubMed

    Serafim, Tiago Donatelli; Figueiredo, Amanda Braga; Costa, Pedro Augusto Carvalho; Marques-da-Silva, Eduardo Almeida; Gonçalves, Ricardo; de Moura, Sandra Aparecida Lima; Gontijo, Nelder Figueiredo; da Silva, Sydnei Magno; Michalick, Marilene Suzan Marques; Meyer-Fernandes, José Roberto; de Carvalho, Roberto Paes; Uliana, Silvia Reni Bortolin; Fietto, Juliana Lopes Rangel; Afonso, Luís Carlos Crocco

    2012-01-01

    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.

  16. Pathway Engineered Enzymatic de novo Purine Nucleotide Synthesis

    PubMed Central

    Schultheisz, Heather L.; Szymczyna, Blair R.; Scott, Lincoln G.; Williamson, James R.

    2009-01-01

    A general method for isotopic labeling of the purine base moiety of nucleotides and RNA has been developed through biochemical pathway engineering in vitro. A synthetic scheme was designed and implemented utilizing recombinant enzymes from the pentose phosphate and de novo purine synthesis pathways, with regeneration of folate, aspartate, glutamine, ATP, and NADPH cofactors, in a single-pot reaction. Syntheses proceeded quickly and efficiently in comparison to chemical methods with isolated yields up to 66% for 13C, 15N enriched ATP and GTP. The scheme is robust and flexible, requiring only serine, NH4+, glucose and CO2 as stoichiometric precursors in labeled form. Using this approach, U-13C- GTP, U-13C,15N- GTP, 13C2,8- ATP and U-15N- GTP were synthesized on a millimole scale, and the utility of the isotope labeling is illustrated in NMR spectra of HIV-2 transactivation region (TAR) RNA containing 13C 2,8-adenosine and 15N-1,3,7,9,2-guanosine. Pathway engineering in vitro permits complex synthetic cascades to be effected expanding the applicability of enzymatic synthesis. PMID:18707057

  17. Riboswitch structure: an internal residue mimicking the purine ligand

    PubMed Central

    Delfosse, Vanessa; Bouchard, Patricia; Bonneau, Eric; Dagenais, Pierre; Lemay, Jean-François; Lafontaine, Daniel A.; Legault, Pascale

    2010-01-01

    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. PMID:20022916

  18. Deregulation of purine pathway in Bacillus subtilis and its use in riboflavin biosynthesis

    PubMed Central

    2014-01-01

    Background Purine nucleotides are essential metabolites for living organisms because they are involved in many important processes, such as nucleic acid synthesis, energy supply, and biosynthesis of several amino acids and riboflavin. Owing to the pivotal roles of purines in cell physiology, the pool of intracellular purine nucleotides must be maintained under strict control, and hence the de novo purine biosynthetic pathway is tightly regulated by transcription repression and inhibition mechanism. Deregulation of purine pathway is essential for this pathway engineering in Bacillus subtilis. Results Deregulation of purine pathway was attempted to improve purine nucleotides supply, based on a riboflavin producer B. subtilis strain with modification of its rib operon. To eliminate transcription repression, the pur operon repressor PurR and the 5’-UTR of pur operon containing a guanine-sensing riboswitch were disrupted. Quantitative RT-PCR analysis revealed that the relative transcription levels of purine genes were up-regulated about 380 times. Furthermore, site-directed mutagenesis was successfully introduced into PRPP amidotransferase (encoded by purF) to remove feedback inhibition by homologous alignment and analysis. Overexpression of the novel mutant PurF (D293V, K316Q and S400W) significantly increased PRPP amidotransferase activity and triggered a strong refractory effect on purine nucleotides mediated inhibition. Intracellular metabolite target analysis indicated that the purine nucleotides supply in engineered strains was facilitated by a stepwise gene-targeted deregulation. With these genetic manipulations, we managed to enhance the metabolic flow through purine pathway and consequently increased riboflavin production 3-fold (826.52 mg/L) in the purF-VQW mutant strain. Conclusions A sequential optimization strategy was applied to deregulate the rib operon and purine pathway of B. subtilis to create genetic diversities and to improve riboflavin production

  19. Purine and pyrimidine derivatives from the South China Sea gorgonian Subergorgia suberosa.

    PubMed

    Qi, Shu-Hua; Zhang, Si; Gao, Cheng-Hai; Li, Qin-Xing

    2008-07-01

    Three new purine derivatives, namely, 4-caryboxy-5,6-dihydro-4H,8H-pyrimido[1,2,3-cd]purine-8,10(9H)-dione (1), 7,9-dihydro-1-(3-oxobutyl)-1H-purine-6,8-dione (2), and 7-hydro-9-(3-oxobutyl)-1H-purine-6,8-dione (3) together with six known purine and pyrimidine derivatives were isolated from the EtOH/CH(2)Cl(2) extracts of the South China Sea gorgonian Subergorgia suberosa. The structures of 1-3 were determined on the bases of extensive spectroscopic analysis, including 1D and 2D NMR data.

  20. RETURN TO DIVISION IA FOOTBALL FOLLOWING A 1ST METATARSOPHALANGEAL JOINT DORSAL DISLOCATION

    PubMed Central

    Cook, Chad; Zarzour, Hap; Moorman, Claude T.

    2010-01-01

    Background. Although rare in occurrence, a dorsal dislocation of the 1st metatarsophalangeal (MTP) joint has been successfully treated using surgical and/or non-operative treatment. No descriptions of conservative intervention following a dorsal dislocation of the MTP joint in an athlete participating in a high contact sport are present in the literature. Objectives. The purpose of this case report is to describe the intervention and clinical reasoning during the rehabilitative process of a collegiate football player diagnosed with a 1st MTP joint dorsal dislocation. The plan of care and return to play criteria used for this athlete are presented. Case Description. The case involved a 19-year-old male Division IA football player, who suffered a traumatic dorsal dislocation of the 1st MTP joint during practice. The dislocation was initially treated on-site by closed reduction. Non-operative management included immobilization, therapeutic exercises, non-steroidal anti-inflammatories, manual treatment, modalities, prophylactic athletic taping, gait training, and a sport specific progression program for full return to Division IA football. Outcomes. Discharge from physical therapy occurred after six weeks of treatment. At discharge, no significant deviations existed during running, burst, and agility related drills. At a six-month follow-up, the patient reported full return to all football activities including contact drills without restrictions. Discussion. This case describes an effective six-week rehabilitation intervention for a collegiate football player who sustained a traumatic great toe dorsal dislocation. Further study is suggested to evaluate the intervention strategies and timeframe for return to contact sports. PMID:21589669

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

    SciTech Connect

    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.

  2. Evidence from CD spectra that d(purine).r(pyrimidine) and r(purine).d(pyrimidine) hybrids are in different structural classes.

    PubMed Central

    Hung, S H; Yu, Q; Gray, D M; Ratliff, R L

    1994-01-01

    CD spectra and difference CD spectra of four d(oligopurine).r(oligopyrimidine) and four r(oligopurine).d(oligopyrimidine) hybrid duplexes containing mixed A.T(U) and G.C base pairs were compared with the spectra of four DNA.DNA and four RNA.RNA oligomer duplexes of similar repeating sequences. The 16 duplexes were formed by mixing oligomers that were 24 nucleotides long. The buffer was 0.05 M Na+ (phosphate), pH 7.0. DNA.DNA and RNA.RNA oligomer duplexes were used as reference B-form and A-form structures. We found that the CD spectra of d(purine).r(pyrimidine) and r(purine).d(pyrimidine) hybrid duplexes were different from the CD spectra of either DNA.DNA or RNA.RNA duplexes. The data suggested that these hybrids have intermediate structures between A-form RNA and B-form DNA structures. The CD spectra of d(purine).r(pyrimidine) and r(purine).d(pyrimidine) hybrid duplexes were different from each other, but the hybrids in each class had consistent CD spectra as indicated by nearest-neighbor comparisons. Thus, it appeared that the two types of hybrids belonged to different structural classes. The negative 210 nm band found in difference CD spectra was correlated with the presence of an r(purine) strand in the hybrid duplexes. The melting temperatures (Tm values) of these hybrids were compared with the Tm values of the DNA.DNA and RNA.RNA duplexes. The order of the thermal stability was: RNA.RNA duplex > r(purine).d(pyrimidine) hybrid > DNA.DNA duplex > d(purine).r(pyrimidine) hybrid, when comparing analogous sequences. PMID:7937162

  3. [Metformin impact on purine metabolism in breast cancer].

    PubMed

    Shatova, O P; Butenko, Eu V; Khomutov, Eu V; Kaplun, D S; Sedakov, I Eu; Zinkovych, I I

    2016-03-01

    Large-scale epidemiological and clinical studies have demonstrated the efficacy of metformin in oncology practice. However, the mechanisms of implementation of the anti-tumor effect of this drug there is still need understanding. In this study we have investigated the effect of metformin on the activity of adenosine deaminase and respectively adenosinergic immunosuppression in tumors and their microenvironment. The material of the study was taken during surgery of breast cacer patients receiveing metformin, and also patients which did not take this drug. The adenosine deaminase activity and substrate (adenosine) and products (inosine, hypoxanthine) concentrations were determined by HPLC. Results of this study suggest that metformin significantly alters catabolism of purine nucleotides in the node breast adenocarcinoma tisue. However, the metformin-induced increase in the adenosine deaminase activity is not sufficient to reduce the level of adenosine in cancer tissue. Thus, in metformin treated patients the adenosine concentration remained unchanged, and inosine and hypoxanthine concentration significantly increased. PMID:27420623

  4. [Metformin impact on purine metabolism in breast cancer].

    PubMed

    Shatova, O P; Butenko, Eu V; Khomutov, Eu V; Kaplun, D S; Sedakov, I Eu; Zinkovych, I I

    2016-03-01

    Large-scale epidemiological and clinical studies have demonstrated the efficacy of metformin in oncology practice. However, the mechanisms of implementation of the anti-tumor effect of this drug there is still need understanding. In this study we have investigated the effect of metformin on the activity of adenosine deaminase and respectively adenosinergic immunosuppression in tumors and their microenvironment. The material of the study was taken during surgery of breast cacer patients receiveing metformin, and also patients which did not take this drug. The adenosine deaminase activity and substrate (adenosine) and products (inosine, hypoxanthine) concentrations were determined by HPLC. Results of this study suggest that metformin significantly alters catabolism of purine nucleotides in the node breast adenocarcinoma tisue. However, the metformin-induced increase in the adenosine deaminase activity is not sufficient to reduce the level of adenosine in cancer tissue. Thus, in metformin treated patients the adenosine concentration remained unchanged, and inosine and hypoxanthine concentration significantly increased.

  5. Folate-Dependent Purine Nucleotide Biosynthesis in Humans1

    PubMed Central

    Baggott, Joseph E; Tamura, Tsunenobu

    2015-01-01

    Purine nucleotide biosynthesis de novo (PNB) requires 2 folate-dependent transformylases—5′-phosphoribosyl-glycinamide (GAR) and 5′-phosphoribosyl-5-aminoimidazole-4-carboxamide (AICAR) transformylases—to introduce carbon 8 (C8) and carbon 2 (C2) into the purine ring. Both transformylases utilize 10-formyltetrahydrofolate (10-formyl-H4folate), where the formyl-carbon sources include ring-2-C of histidine, 3-C of serine, 2-C of glycine, and formate. Our findings in human studies indicate that glycine provides the carbon for GAR transformylase (exclusively C8), whereas histidine and formate are the predominant carbon sources for AICAR transformylase (C2). Contrary to the previous notion, these carbon sources may not supply a general 10-formyl-H4folate pool, which was believed to equally provide carbons to C8 and C2. To explain these phenomena, we postulate that GAR transformylase is in a complex with the trifunctional folate-metabolizing enzyme (TFM) and serine hydroxymethyltransferase to channel carbons of glycine and serine to C8. There is no evidence for channeling carbons of histidine and formate to AICAR transformylase (C2). GAR transformylase may require the TFM to furnish 10-formyl-H4folate immediately after its production from serine to protect its oxidation to 10-formyldihydrofolate (10-formyl-H2folate), whereas AICAR transformylase can utilize both 10-formyl-H2folate and 10-formyl-H4folate. Human liver may supply AICAR to AICAR transformylase in erythrocytes/erythroblasts. Incorporation of ring-2-C of histidine and formate into C2 of urinary uric acid presented a circadian rhythm with a peak in the morning, which corresponds to the maximum DNA synthesis in the bone marrow, and it may be useful in the timing of the administration of drugs that block PNB for the treatment of cancer and autoimmune disease. PMID:26374178

  6. Folate-Dependent Purine Nucleotide Biosynthesis in Humans.

    PubMed

    Baggott, Joseph E; Tamura, Tsunenobu

    2015-09-01

    Purine nucleotide biosynthesis de novo (PNB) requires 2 folate-dependent transformylases-5'-phosphoribosyl-glycinamide (GAR) and 5'-phosphoribosyl-5-aminoimidazole-4-carboxamide (AICAR) transformylases-to introduce carbon 8 (C8) and carbon 2 (C2) into the purine ring. Both transformylases utilize 10-formyltetrahydrofolate (10-formyl-H4folate), where the formyl-carbon sources include ring-2-C of histidine, 3-C of serine, 2-C of glycine, and formate. Our findings in human studies indicate that glycine provides the carbon for GAR transformylase (exclusively C8), whereas histidine and formate are the predominant carbon sources for AICAR transformylase (C2). Contrary to the previous notion, these carbon sources may not supply a general 10-formyl-H4folate pool, which was believed to equally provide carbons to C8 and C2. To explain these phenomena, we postulate that GAR transformylase is in a complex with the trifunctional folate-metabolizing enzyme (TFM) and serine hydroxymethyltransferase to channel carbons of glycine and serine to C8. There is no evidence for channeling carbons of histidine and formate to AICAR transformylase (C2). GAR transformylase may require the TFM to furnish 10-formyl-H4folate immediately after its production from serine to protect its oxidation to 10-formyldihydrofolate (10-formyl-H2folate), whereas AICAR transformylase can utilize both 10-formyl-H2folate and 10-formyl-H4folate. Human liver may supply AICAR to AICAR transformylase in erythrocytes/erythroblasts. Incorporation of ring-2-C of histidine and formate into C2 of urinary uric acid presented a circadian rhythm with a peak in the morning, which corresponds to the maximum DNA synthesis in the bone marrow, and it may be useful in the timing of the administration of drugs that block PNB for the treatment of cancer and autoimmune disease. PMID:26374178

  7. Autopsy as a tool for learning gross anatomy during 1st year MBBS

    PubMed Central

    Goyal, Parmod Kumar; Gupta, Monika; Kaur, Jaswinder

    2016-01-01

    Introduction: Embalmed cadavers are the primary tool for teaching anatomy. However, difficulties are encountered due to changed color/texture of organs, hardening of tissues, and smell of formaldehyde. To overcome these difficulties, dissections on a fresh human body were shown to the 1st year MBBS students, and their perception was noted. Materials and Methods: After taking universal precautionary measures, postmortem dissections were shown to students on voluntary donated bodies in the dissection hall, in addition to the traditional teaching on embalmed cadavers. Feedback was taken from students and faculty regarding the utility of these sessions. Results: Better appreciation of texture, orientation, location, and relations of organs in fresh body, integration of teaching, awareness of the process and laws related to body donations were the outcomes of the study. However, the smell and sight of blood was felt to be nauseating by some students, and some students were worried about the spread of infectious diseases. Conclusions: Visualizing single fresh body dissection during 1st year professional MBBS is recommended either on medicolegal autopsy or on voluntarily-donated bodies. PMID:27563594

  8. The role of purine degradation in methane biosynthesis and energy production in Methanococcus vannielii

    SciTech Connect

    DeMoll, E.

    1990-10-22

    Research continues on the role of purine degradation in methane biosynthesis and energy production in Methanococcus vannielii. This report summarizes current progress of the research. Topics include: A survey of other methanogens for the purine degradation pathway; isolate and characterize the enzyme and products of formiminoglycine cleavage; ascertain the fate of glycine from the formiminoglycine cleavage; elucidate the route of incorporation of the formyl moiety of formiminoglycine into methane biosynthesis; determine the percent methane and amino acid synthesis from purine degradation; and related studies on xanthine dehydrogenase and pyrimidine degradation of M. Vannielii. (SM)

  9. Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

    PubMed Central

    Ren, Hang; Hatala, Paul J; Stevens, William C; He, Baicheng

    2015-01-01

    Summary A unified synthetic strategy accessing novel 3'-fluorinated purine nucleoside derivatives and their biological evaluation were achieved. Novel 3’-fluorinated analogues were constructed from a common 3’-deoxy-3’-fluororibofuranose intermediate. Employing Suzuki and Stille cross-coupling reactions, fifteen 3’-fluororibose purine nucleosides 1–15 and eight 3’-fluororibose 2-chloro/2-aminopurine nucleosides 16–23 with various substituents at position 6 of the purine ring were efficiently synthesized. Furthermore, 3’-fluorine analogs of natural products nebularine and 6-methylpurine riboside were constructed via our convergent synthetic strategy. Synthesized nucleosides were tested against HT116 (colon cancer) and 143B (osteosarcoma cancer) tumor cell lines. We have demonstrated 3’-fluorine purine nucleoside analogues display potent tumor cell growth inhibition activity at sub- or low micromolar concentration. PMID:26734098

  10. mTORC1 Induces Purine Synthesis Through Control of the Mitochondrial Tetrahydrofolate Cycle

    PubMed Central

    Ricoult, Stéphane J.H.; Asara, John M.; Manning, Brendan D.

    2016-01-01

    In response to growth signals, mTOR complex 1 (mTORC1) stimulates anabolic processes underlying cell growth. We found that mTORC1 increases metabolic flux through the de novo purine synthesis pathway in various mouse and human cells, thereby influencing the nucleotide pool available for nucleic acid synthesis. mTORC1 had transcriptional effects on multiple enzymes contributing to purine synthesis, with expression of the mitochondrial tetrahydrofolate (mTHF) cycle enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) being closely associated with mTORC1 signaling in both normal and cancer cells. MTHFD2 expression and purine synthesis were stimulated by ATF4, which was activated by mTORC1 independent of its canonical induction downstream of eIF2α phosphorylation. Thus, mTORC1 stimulates the mTHF cycle, which contributes one-carbon units to enhance production of purine nucleotides in response to growth signals. PMID:26912861

  11. Biosynthesis of the pyrimidine moiety of thiamine. A new route of pyrimidine biosynthesis involving purine intermediates

    PubMed Central

    Newell, P. C.; Tucker, R. G.

    1968-01-01

    1. The pattern of distribution on the purine pathway of mutants of Salmonella typhimurium LT2 that had the double growth requirement for a purine plus the pyrimidine moiety of thiamine (ath mutants) indicated that purines and the pyrimidine moiety of thiamine share the early part of their biosynthetic pathways, and that 4-aminoimidazole ribonucleotide (AIR) is the last common intermediate. Two mutants that at first appeared anomalous were further investigated and found not to affect this deduction. 2. The ribonucleoside form of AIR (AIRs) satisfied the requirements both for a purine and for the pyrimidine moiety of thiamine of an ath mutant. 3. Methionine was required for the conversion of AIR into the pyrimidine moiety. 4. Radioactive AIRs was converted into radioactive pyrimidine moiety by an ath mutant without significant dilution of specific radioactivity. 5. Possible mechanisms for pyrimidine-moiety biosynthesis from AIR are discussed. PMID:4889364

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

    PubMed

    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.

  13. Structure of purine nucleoside phosphorylase (DeoD) from Bacillus anthracis

    SciTech Connect

    Grenha, Rosa; Levdikov, Vladimir M.; Fogg, Mark J.; Blagova, Elena V.; Brannigan, James A. Wilkinson, Anthony J.; Wilson, Keith S.

    2005-05-01

    The crystal structure of purine nucleoside phosphorylase (DeoD) from B. anthracis was solved by X-ray crystallography using molecular replacement and refined at a resolution of 2.24 Å. Protein structures from the causative agent of anthrax (Bacillus anthracis) are being determined as part of a structural genomics programme. Amongst initial candidates for crystallographic analysis are enzymes involved in nucleotide biosynthesis, since these are recognized as potential targets in antibacterial therapy. Purine nucleoside phosphorylase is a key enzyme in the purine-salvage pathway. The crystal structure of purine nucleoside phosphorylase (DeoD) from B. anthracis has been solved by molecular replacement at 2.24 Å resolution and refined to an R factor of 18.4%. This is the first report of a DeoD structure from a Gram-positive bacterium.

  14. EDITORIAL: The 1st International Conference on Nanomanufacturing (NanoMan2008) The 1st International Conference on Nanomanufacturing (NanoMan2008)

    NASA Astrophysics Data System (ADS)

    Luo, Jack Jiqui; Fang, Fengzhou

    2009-05-01

    Nanomanufacturing is an emerging technology in the field of synthesis of nanomaterials, manufacture of nanodevices, nanosystems and the relevant characterization technologies, and will greatly impact our society and environment: speeding up scientific discovery, technological development, improving healthcare and living standards and slowing down the exhaustion of energy resources, to name but few. The 1st International Conference on Nanomanufacturing (NanoMan2008) was held on the 13-16 July 2008 in Singapore in conjunction with ThinFilm2008 (The 4th International Conference on Technological Advances of Thin Films & Surface Coatings). Approximately 140 delegates from all over the world have participated in the conference and presented their latest discoveries and technological developments. The main focuses of the conference were modern nanomanufacturing by laser machining, focused ion beam fabrication, nano/micro-molding/imprinting, nanomaterial synthesis and characterization, nanometrology and nano/microsystems fabrication and characterization. There was also great interest in applications of nanomanufacturing technologies in traditional areas such as free form machining, polishing and grinding with nano-scale precision and the smoothness of surfaces of objects, and applications in space exploration, military and medicine. This special issue is devoted to NanoMan2008 with a collection of 9 invited talks presented at the conference, covering all the topics of nanomanufacturing technology and development. These papers have been upgraded by the authors with new results and discoveries since the preparation of the conference manuscripts, hence presenting the latest developments. We would like to take this opportunity to thank all the delegates who attended the conference and made the conference successful, and to the authors who contributed papers to this special issue. Thanks also go to the conference committee for their efforts and devotion to the conference. We

  15. Perceptual narrowing of linguistic sign occurs in the 1st year of life.

    PubMed

    Palmer, Stephanie Baker; Fais, Laurel; Golinkoff, Roberta Michnick; Werker, Janet F

    2012-01-01

    Over their 1st year of life, infants'"universal" perception of the sounds of language narrows to encompass only those contrasts made in their native language (J. F. Werker & R. C. Tees, 1984). This research tested 40 infants in an eyetracking paradigm and showed that this pattern also holds for infants exposed to seen language-American Sign Language (ASL). Four-month-old, English-only, hearing infants discriminated an ASL handshape distinction, while 14-month-old hearing infants did not. Fourteen-month-old ASL-learning infants, however, did discriminate the handshape distinction, suggesting that, as in heard language, exposure to seen language is required for maintenance of visual language discrimination. Perceptual narrowing appears to be a ubiquitous learning mechanism that contributes to language acquisition. PMID:22277043

  16. Meeting report for the 1st skin microbiota workshop, boulder, CO October 15-16 2012

    PubMed Central

    2014-01-01

    This report details the outcome of the 1st Skin Microbiota Workshop, Boulder, CO, held on October 15th-16th 2012. The workshop was arranged to bring Department of Defense personnel together with experts in microbial ecology, human skin physiology and anatomy, and computational techniques for interrogating the microbiome to define research frontiers at the intersection of these important areas. The workshop outlined a series of questions and created several working groups to address those questions, specifically to promote interdisciplinary activity and potential future collaboration. The US Army provided generous grant support and the meeting was organized and hosted by the University of Colorado at Boulder. A primary forward vision of the meeting was the importance of understanding skin microbial communities to improve the health and stealth of US Army warfighters.

  17. 1st ESMO Consensus Conference in lung cancer; Lugano 2010: small-cell lung cancer.

    PubMed

    Stahel, R; Thatcher, N; Früh, M; Le Péchoux, C; Postmus, P E; Sorensen, J B; Felip, E

    2011-09-01

    The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21st and 22nd May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics and medical, surgical and radiation oncology. Before the conference, the expert panel prepared clinically relevant questions concerning five areas as follows: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer (SCLC) to be addressed through discussion at the Consensus Conference. All relevant scientific literature for each question was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The consensus agreement in SCLC is reported in this article. The recommendations detailed here are based on an expert consensus after careful review of published data. All participants have approved this final update.

  18. 4th generation of the 1st level surface detector trigger in the Pierre Auger Observator

    NASA Astrophysics Data System (ADS)

    Szadkowski, Z.

    The proposal of a new 4th generation of the Front-End with the advanced 1st level triggers for the Infill Array of the Pierre Auger Observatory and for the Auger North is described. Newest FPGA chips offer much higher capacity of logic registers and memories, as well as DSP blocks. The calibration channel, previously supported by an external dual-port RAM, has been fully implemented into FPGA chip, through a large internal memory. In turn DSP blocks allowed on implementation of much more sophisticated spectral trigger algorithms. A single chip simplified board design, newer architecture of FPGA reduced resouces utilization and power consumption. Higher sampling in the new Front- End in comparison with previous 40 MHz designs as well as free resources for new detection algotithms can be a good platform for CR radio detection technique at Auger enhancing a duty cycle for the detection of UHECR’s.

  19. [The 1st International Youth Ecologist Forum in China, 2009: a review].

    PubMed

    Xiong, You-cai; Xiong, Jun-lan; Li, Pu-fang; Li, Zhi-hua; Kong, Hai-yan; Wang, Shao-ming

    2011-04-01

    To promote the communication and cooperation between Chinese and overseas youth ecologists, a conference entitled "The 1st International Young Ecologist Forum" was held at Lanzhou University in June 29-30, 2009. This conference was organized by outstanding overseas ecologists and hosted by Lanzhou University. The presentations covered broad areas of ecology, including plant-soil interactions, structure and function of regional ecosystems, ecological security and ecological planning, global change ecology, and environmental sustainability, demonstrating that the development of China ecology is gradually from traditional basic research transforming into applied research. The presentations also reflected in some extent the development characteristics, evolution direction, and distribution pattern of China ecological research. China ecological research has gradually formed four centers, the Northeast, North, Northwest, and Southeast China, and each of them has its definite regional characteristics. Some suggestions about the organization form and future planning of the forum were put forward.

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

    PubMed

    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.

  1. Results from the UK 3rd generation programme: Albion

    NASA Astrophysics Data System (ADS)

    McEwen, R. K.; Axcell, C.; Knowles, P.; Hoade, K. P.; Wilson, M.; Dennis, P. N. J.; Backhouse, P.; Gordon, N. T.

    2008-10-01

    Following the development of 1st Generation systems in the 1970s, thermal imaging has been in service with the UK armed forces for over 25 years and has proven itself to be a battle winning technology. More recently the wider accessibility to similar technologies within opposing forces has reduced the military advantage provided by these 1st Generation systems and a clear requirement has been identified by the UK MOD for thermal imaging sensors providing increased detection, recognition and identification (DRI) ranges together with a simplified logistical deployment burden and reduced through-life costs. In late 2005, the UK MOD initiated a programme known as "Albion" to develop high performance 3rd Generation single waveband infrared detectors to meet this requirement. At the same time, under a separate programme supporting higher risk technology, a dual waveband infrared detector was also developed. The development phase of the Albion programme has now been completed and prototype detectors are now available and have been integrated into demonstration thermal imaging cameras. The Albion programme has now progressed into the second phase, incorporating both single and dual waveband devices, focussing on low rate initial production (LRIP) and qualification of the devices for military applications. All of the detectors have been fabricated using cadmium mercury telluride material (CMT), grown by metal organic vapour phase epitaxy (MOVPE) on low cost, gallium arsenide (GaAs) substrates and bump bonded to the silicon read out circuit (ROIC). This paper discusses the design features of the 3rd Generation detectors developed in the UK together with the results obtained from the prototype devices both in the laboratory and when integrated into field deployable thermal imaging cameras.

  2. Borrelia burgdorferi Harbors a Transport System Essential for Purine Salvage and Mammalian Infection

    PubMed Central

    Jain, Sunny; Sutchu, Selina; Rosa, Patricia A.; Byram, Rebecca

    2012-01-01

    Borrelia burgdorferi is the tick-borne bacterium that causes the multistage inflammatory disease Lyme disease. B. burgdorferi has a reduced genome and lacks the enzymes required for de novo synthesis of purines for synthesis of RNA and DNA. Therefore, this obligate pathogen is dependent upon the tick vector and mammalian host environments for salvage of purine bases for nucleic acid biosynthesis. This pathway is vital for B. burgdorferi survival throughout its infectious cycle, as key enzymes in the purine salvage pathway are essential for the ability of the spirochete to infect mice and critical for spirochete replication in the tick. The transport of preformed purines into the spirochete is the first step in the purine salvage pathway and may represent a novel therapeutic target and/or means to deliver antispirochete molecules to the pathogen. However, the transport systems critical for purine salvage by B. burgdorferi have yet to be identified. Herein, we demonstrate that the genes bbb22 and bbb23, present on B. burgdorferi's essential plasmid circular plasmid 26 (cp26), encode key purine transport proteins. BBB22 and/or BBB23 is essential for hypoxanthine transport and contributes to the transport of adenine and guanine. Furthermore, B. burgdorferi lacking bbb22-23 was noninfectious in mice up to a dose of 1 × 107 spirochetes. Together, our data establish that bbb22-23 encode purine permeases critical for B. burgdorferi mammalian infectivity, suggesting that this transport system may serve as a novel antimicrobial target for the treatment of Lyme disease. PMID:22710875

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

    PubMed Central

    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

  4. Regional differences in the electrically stimulated release of endogenous and radioactive adenosine and purine derivatives from rat brain slices.

    PubMed

    Pedata, F; Pazzagli, M; Tilli, S; Pepeu, G

    1990-10-01

    The release of both radioactive and endogenous purines was investigated in rat brain cortical, hippocampal and striatal slices at rest and following stimulation with electrical fields. Purines were labelled by incubating the slices with 3H-adenine. The purine efflux at rest and that evoked by electrical stimulation (10 Hz. 5 min) was analyzed by HPLC with ultraviolet absorbance detection. Both radioactive and endogenous purines in the effluent consisted mainly of hypoxanthine, xanthine, inosine and adenosine. No qualitative differences in the composition of the released purines were found in the three areas investigated. Electrical stimulation evoked a net increase in both radioactive and endogenous purine release. However the increase in 3H-adenosine following electrical stimulation was twice as large as that of endogenous adenosine. The electrically evoked release of both radioactive and endogenous purines was greatest in hippocampal slices and progressively smaller in cortical and striatal slices. In the three areas the addition of 0.5 microM tetrodotoxin to the superfusing Krebs solution brought about a similar (83-100%) reduction in evoked 3H-purine and endogenous purine release. Superfusion of the slices with calcium-free Krebs solution containing 0.5 mM EGTA reduced evoked release of 3H-purines by 58-60% and that of endogenous purine components by 54-89%. The results demonstrate similar characteristics for both radioactive and endogenous purine release but indicate that the most recently synthetized adenosine is the most readily available for release. The features of the electrically evoked purine release support a neuronal origin of adenosine and derivatives and are consistent with the hypothesis of discrete regional differences in adenosine neuromodulation. PMID:2255336

  5. Interaction of Bacillus subtilis purine repressor with DNA.

    PubMed

    Shin, B S; Stein, A; Zalkin, H

    1997-12-01

    A purine repressor (PurR) mediates adenine nucleotide-dependent regulation of transcription initiation of the Bacillus subtilis pur operon. This repressor has been purified for the first time, and binding to control site DNA was characterized. PurR binds in vitro to four operons. Apparent Kd values for binding were 7 nM for the pur operon, 8 nM for purA, 13 nM for purR, and 44 nM for the pyr operon. In each case, DNase I footprints exhibited a pattern of protected and hypersensitive sites that extended over more than 60 bp. A GAAC-N24-GTTC sequence in the pur operon was necessary but not sufficient for the PurR-DNA interaction. However, this motif, which is conserved in the four binding sites, was not required for binding of PurR to purA. Thus, the common DNA recognition element for binding of PurR to the four operons is not known. Multiple PurR-pur operon DNA complexes having a binding stoichiometry that was either approximately two or six repressor molecules per DNA fragment were detected. The results of a torsional constraint experiment suggest that control site DNA forms one right-handed turn around PurR.

  6. Purine nucleoside phosphorylase polymorphism in the genus Littorina (Prosobranchia: Mollusca).

    PubMed

    Knight, A J; Ward, R D

    1986-06-01

    Examination of eight Atlantic species of the genus Littorina by starch gel electrophoresis of purine nucleoside phosphorylase revealed extensive polymorphism within the L. saxatilis complex. In this group, four alleles have been identified. Heterozygotes are four banded, and thus, as in vertebrates, the enzyme is likely to be a trimer. Breeding experiments confirmed the genetic interpretation of the phenotype patterns. Where species of the saxatilis complex [L. saxatilis (=L. rudis), L. arcana, L. nigrolineata, L. neglecta] are sympatric, there are sometimes significant allele frequency differences between them. A fifth allele was present at a high frequency in L. obtusata and L. mariae, and L. littorea and L. neritoides each possessed unique alleles. A total of eight alleles was identified. Densitometric scanning of heterozygote patterns pointed to activity differences between alleles and also showed that, while the heterotrimeric bands were never less intense than the homotrimeric bands, the heterotrimeric bands were sometimes less intense than expected. It is not clear whether this represents nonrandom association of subunits, decreased stability of heterotrimers, or simply an artifact of the staining and quantifying process. PMID:3091000

  7. Deprotonated purine dissociation: experiments, computations, and astrobiological implications.

    PubMed

    Cole, Callie A; Wang, Zhe-Chen; Snow, Theodore P; Bierbaum, Veronica M

    2015-01-15

    A central focus of astrobiology is the determination of abiotic formation routes to important biomolecules. The dissociation mechanisms of these molecules lend valuable insights into their synthesis pathways. Because of the detection of organic anions in the interstellar medium (ISM), it is imperative to study their role in these syntheses. This work aims to experimentally and computationally examine deprotonated adenine and guanine dissociation in an effort to illuminate potential anionic precursors to purine formation. Collision-induced dissociation (CID) products and their branching fractions are experimentally measured using an ion trap mass spectrometer. Deprotonated guanine dissociates primarily by deammoniation (97%) with minor losses of carbodiimide (HNCNH) and/or cyanamide (NH2CN), and isocyanic acid (HNCO). Deprotonated adenine fragments by loss of hydrogen cyanide and/or isocyanide (HCN/HNC; 90%) and carbodiimide (HNCNH) and/or cyanamide (NH2CN; 10%). Tandem mass spectrometry (MS(n)) experiments reveal that deprotonated guanine fragments lose additional HCN and CO, while deprotonated adenine fragments successively lose HNC and HCN. Every neutral fragment observed in this study has been detected in the ISM, highlighting the potential for nucleobases such as these to form in such environments. Lastly, the acidity of abundant fragment ions is experimentally bracketed. Theoretical calculations at the B3LYP/6-311++G(d,p) level of theory are performed to delineate the mechanisms of dissociation and analyze the energies of reactants, intermediates, transition states, and products of these CID processes. PMID:25559322

  8. 6-(2-Methoxy­benzyl­amino)purine

    PubMed Central

    Trávníček, Zdeněk; Matiková-Maľarová, Miroslava; Mikulík, Jiří

    2008-01-01

    The title compound, C13H13N5O, consists of discrete mol­ecules connected by N—H⋯N hydrogen bonds to form infinite chains, with N⋯N separations of 3.0379 (15) and 2.8853 (15) Å. The benzene and purine ring systems make a dihedral angle of 77.58 (3)°. The crystal structure is further stabilized by intra­molecular N⋯O inter­actions [2.9541 (12) Å] and inter­molecular C—H⋯C and C⋯C contacts [3.304 (2), 3.368 (2), 3.667 (2), 3.618 (2) and 3.512 (2) Å] which arrange the mol­ecules into graphite-like layers. The inter­layer separations are 3.248 and 3.256 Å. PMID:21202313

  9. CAP in the UK

    NASA Astrophysics Data System (ADS)

    Haley, P.

    2008-06-01

    This poster highlights some of the experiential learning activities used by The SHARE Initiative (TSI) in the UK. Past, present and future projects are described and the possibility of linking up internationally with other projects is invited. Digital media, scientific heritage and solar physics are three areas which Paul Haley (Director - TSI) is particularly keen to develop. Operating as a community interest company TSI outreaches astronomy activities directly into rural areas in the UK.

  10. PREFACE: 1st European Conference on Gas Micro Flows (GasMems 2012)

    NASA Astrophysics Data System (ADS)

    Frijns, Arjan; Valougeorgis, Dimitris; Colin, Stéphane; Baldas, Lucien

    2012-05-01

    The aim of the 1st European Conference on Gas Micro Flows is to advance research in Europe and worldwide in the field of gas micro flows as well as to improve global fundamental knowledge and to enable technological applications. Gas flows in microsystems are of great importance and touch almost every industrial field (e.g. fluidic microactuators for active control of aerodynamic flows, vacuum generators for extracting biological samples, mass flow and temperature micro-sensors, pressure gauges, micro heat-exchangers for the cooling of electronic components or for chemical applications, and micro gas analyzers or separators). The main characteristic of gas microflows is their rarefaction, which for device design often requires modelling and simulation both by continuous and molecular approaches. In such flows various non-equilibrium transport phenomena appear, while the role played by the interaction between the gas and the solid device surfaces becomes essential. The proposed models of boundary conditions often need an empirical adjustment strongly dependent on the micro manufacturing technique. The 1st European Conference on Gas Micro Flows is organized under the umbrella of the recently established GASMEMS network (www.gasmems.eu/) consisting of 13 participants and six associate members. The main objectives of the network are to structure research and train researchers in the fields of micro gas dynamics, measurement techniques for gaseous flows in micro experimental setups, microstructure design and micro manufacturing with applications in lab and industry. The conference takes place on June 6-8 2012, at the Skiathos Palace Hotel, on the beautiful island of Skiathos, Greece. The conference has received funding from the European Community's Seventh Framework Programme FP7/2007-2013 under grant agreement ITN GASMEMS no. 215504. It owes its success to many people. We would like to acknowledge the support of all members of the Scientific Committee and of all

  11. PREFACE: 1st International Conference on Rheology and Modeling of Materials

    NASA Astrophysics Data System (ADS)

    Gömze, László A.

    2015-04-01

    Understanding the rheological properties of materials and their rheological behaviors during their manufacturing processes and in their applications in many cases can help to increase the efficiency and competitiveness not only of the finished goods and products but the organizations and societies also. The more scientific supported and prepared organizations develop more competitive products with better thermal, mechanical, physical, chemical and biological properties and the leading companies apply more competitive knowledge, materials, equipment and technology processes. The idea to organize in Hungary the 1st International Conference on Rheology and Modeling of Materials we have received from prospective scientists, physicists, chemists, mathematicians and engineers from Asia, Europe, North and South America including India, Korea, Russia, Turkey, Estonia, France, Italy, United Kingdom, Chile, Mexico and USA. The goals of ic-rmm1 the 1st International Conference on Rheology and Modeling of Materials are the following: • Promote new methods and results of scientific research in the fields of modeling and measurements of rheological properties and behavior of materials under processing and applications. • Change information between the theoretical and applied sciences as well as technical and technological implantations. • Promote the communication between the scientists of different disciplines, nations, countries and continents. The international conference ic-rmm1 provides a platform among the leading international scientists, researchers, PhD students and engineers for discussing recent achievements in measurement, modeling and application of rheology in materials technology and materials science of liquids, melts, solids, crystals and amorphous structures. Among the major fields of interest are the influences of material structures, mechanical stresses temperature and deformation speeds on rheological and physical properties, phase transformation of

  12. Promoting SETI in the UK

    NASA Astrophysics Data System (ADS)

    Penny, Alan

    2013-10-01

    MEETING REPORT What does the UK presently do in the search for extraterrestrial intelligence and what are the plans for the future? Alan Penny reports on a meeting of UK academics active in SETI, held as sessions in the recent National Astronomy Meeting in Scotland - and the formation of the UK SETI Research Network to promote UK academic work.

  13. Identifying 1st instar larvae for three forensically important blowfly species using "fingerprint" cuticular hydrocarbon analysis.

    PubMed

    Moore, Hannah E; Adam, Craig D; Drijfhout, Falko P

    2014-07-01

    Calliphoridae are known to be the most forensically important insects when it comes to establishing the minimum post mortem interval (PMImin) in criminal investigations. The first step in calculating the PMImin is to identify the larvae present to species level. Accurate identification which is conventionally carried out by morphological analysis is crucial because different insects have different life stage timings. Rapid identification in the immature larvae stages would drastically cut time in criminal investigations as it would eliminate the need to rear larvae to adult flies to determine the species. Cuticular hydrocarbon analysis on 1st instar larvae has been applied to three forensically important blowflies; Lucilia sericata, Calliphora vicina and Calliphora vomitoria, using gas chromatography-mass spectrometry (GC-MS) and principal component analysis (PCA). The results show that each species holds a distinct "fingerprint" hydrocarbon profile, allowing for accurate identification to be established in 1-day old larvae, when it can be challenging to apply morphological criteria. Consequently, this GC-MS based technique could accelerate and strengthen the identification process, not only for forensically important species, but also for other entomological samples which are hard to identify using morphological features.

  14. The relation between 1st grade grey matter volume and 2nd grade math competence.

    PubMed

    Price, Gavin R; Wilkey, Eric D; Yeo, Darren J; Cutting, Laurie E

    2016-01-01

    Mathematical and numerical competence is a critical foundation for individual success in modern society yet the neurobiological sources of individual differences in math competence are poorly understood. Neuroimaging research over the last decade suggests that neural mechanisms in the parietal lobe, particularly the intraparietal sulcus (IPS) are structurally aberrant in individuals with mathematical learning disabilities. However, whether those same brain regions underlie individual differences in math performance across the full range of math abilities is unknown. Furthermore, previous studies have been exclusively cross-sectional, making it unclear whether variations in the structure of the IPS are caused by or consequences of the development of math skills. The present study investigates the relation between grey matter volume across the whole brain and math competence longitudinally in a representative sample of 50 elementary school children. Results show that grey matter volume in the left IPS at the end of 1st grade relates to math competence a year later at the end of 2nd grade. Grey matter volume in this region did not change over that year, and was still correlated with math competence at the end of 2nd grade. These findings support the hypothesis that the IPS and its associated functions represent a critical foundation for the acquisition of mathematical competence. PMID:26334946

  15. The relation between 1st grade grey matter volume and 2nd grade math competence.

    PubMed

    Price, Gavin R; Wilkey, Eric D; Yeo, Darren J; Cutting, Laurie E

    2016-01-01

    Mathematical and numerical competence is a critical foundation for individual success in modern society yet the neurobiological sources of individual differences in math competence are poorly understood. Neuroimaging research over the last decade suggests that neural mechanisms in the parietal lobe, particularly the intraparietal sulcus (IPS) are structurally aberrant in individuals with mathematical learning disabilities. However, whether those same brain regions underlie individual differences in math performance across the full range of math abilities is unknown. Furthermore, previous studies have been exclusively cross-sectional, making it unclear whether variations in the structure of the IPS are caused by or consequences of the development of math skills. The present study investigates the relation between grey matter volume across the whole brain and math competence longitudinally in a representative sample of 50 elementary school children. Results show that grey matter volume in the left IPS at the end of 1st grade relates to math competence a year later at the end of 2nd grade. Grey matter volume in this region did not change over that year, and was still correlated with math competence at the end of 2nd grade. These findings support the hypothesis that the IPS and its associated functions represent a critical foundation for the acquisition of mathematical competence.

  16. The U.S. Naval Observatory Robotic Astrometric Telescope 1st Catalog (URAT1)

    NASA Astrophysics Data System (ADS)

    Zacharias, Norbert; Finch, Charlie T.; Subasavage, John P.; Tilleman, Trudy; DiVittorio, Mike; Harris, Hugh C.; Rafferty, Ted; Wieder, Gary; Eric Ferguson, Chris Kilian, Albert Rhodes, Mike Schultheis

    2015-01-01

    The 1st USNO Robotic Astrometric Telescope Catalog (URAT1) is about tobe released. It contains accurate positions (typically 10 to 30 mas std.error) of 220 million stars, mainly on the northern hemisphere. Propermotions were obtained for 85% of these stars utilizing the 2MASS as 1stepoch. URAT1 is supplemented by 2MASS and APASS photometry. The URAT1catalog was derived from 2 years of operations (April 2012 to April 2014)of the USNO "redlens" astrograph with its 474 Mpx 4-shooter camera at theNaval Observatory Flagstaff Station (NOFS) in a joint effort betweenUSNO's Astrometry Department and NOFS. Due to a combination of longexposures and short exposures with objective grating, URAT1 observationscover the large 3 to 18.5 magnitude range in a single 680-750 nm bandpass.The catalog properties are presented together with a brief summary ofobservations and reductions methods. URAT1 has on average about 4-timesthe number of stars per square degree and is 4-times more accurate thanUCAC4. URAT1 will serve as the currently most accurate astrometric anddeep photometric optical reference star catalog until the delivery ofthe Gaia catalog.

  17. 1st Advanced Marine Renewable Energy Instrumentation Experts Workshop: April 5-7, 2011

    SciTech Connect

    Not Available

    2011-10-01

    The U.S. marine energy industry is actively pursuing development of offshore wind and marine hydrokinetic (MHK) energy systems. Experience in the wind energy sector demonstrates that new technology development requires thorough measurement and characterization of the environmental conditions prevalent at installation sites and of technology operating in the field. Presently, there are no turn-key instrumentation system solutions that meet the measurement needs of the marine energy industry. The 1st Advanced Marine Renewable Energy Instrumentation Experts Workshop brought together technical experts from government laboratories, academia, and industry representatives from marine energy, wind, offshore oil and gas, and instrumentation developers to present and discuss the instrumentation needs of the marine energy industry. The goals of the meeting were to: (1) Share the latest relevant knowledge among technical experts; (2) Review relevant state-of-the-art field measurement technologies and methods; (3) Review lessons learned from recent field deployments; (4) Identify synergies across different industries; (5) Identify gaps between existing and needed instrumentation capabilities; (6) Understand who are the leading experts; (7) Provide a forum where stakeholders from the marine energy industry could provide substantive input in the development of new marine energy field deployable instrumentation packages.

  18. 1st paleomagnetic investigation of Nubia Sandstone at Kalabsha, south Western Desert of Egypt

    NASA Astrophysics Data System (ADS)

    Mostafa, R.; Khashaba, A.; El-Hemaly, I. A.; Takla, E. M.; Abdel Aal, E.; Odah, H.

    2016-06-01

    Two profiles have been sampled from the Nubia Sandstone at Aswan, south Western Desert: the 1st profile has been taken from Abu Aggag Formation and the 2nd one was from Sabaya Formation (23.25 °N, 32.75 °E). 136 oriented cores (from 9 sites) have been sampled. Abu Aggag Formation is of Late Cretaceous (Turonian) and Sabaya Formation is of early Cretaceous (Albian-Cenomanian). The studied rocks are subjected to rock magnetic measurements as well as demagnetization treatment. It has been found that hematite is the main magnetic mineral in both formations. Four profile sections from Abu Aggag Formation, yielded a magnetic component with D = 352.7°, I = 36.6° with α95 = 5.2° and the corresponding pole lies at Lat. = 82.8 °N and Long. = 283.1 °E. Five profile sections from Sabaya Formation, yielded a magnetic component with D = 348.6°, I = 33.3° with α95 = 5.8° and the corresponding pole lies at Lat. = 78.3 °N and Long. = 280.4 °E. The obtained paleopole for the two formations lies at Lat. = 80.5 °N and Long. = 281.7 °E. The obtaind magnetic components are considered primary and the corresponding paleopole reflects the age of Nubia Sandstone when compared with the previously obtained Cretaceous poles for Egypt.

  19. Wind-US Results for the AIAA 1st Propulsion Aerodynamics Workshop

    NASA Technical Reports Server (NTRS)

    Yoder, Dennis; Dippold, Vance, III; Georgiadis, Nicholas

    2012-01-01

    This presentation contains Wind-US results presented at the 1st Propulsion Aerodynamics Workshop. The The workshop was organized by the American Institute of Aeronautics and Astronautics, Air Breathing Propulsion Propulsion Systems Integration Technical Committee with the purpose of assessing the accuracy of computational computational fluid dynamics for air breathing propulsion applications. Attendees included representatives from representatives from government, industry, academia, and commercial software companies. Participants were were encouraged to explore and discuss all aspects of the simulation process including the effects of mesh type and mesh type and refinement, solver numerical schemes, and turbulence modeling. The first set of challenge cases involved computing the thrust and discharge coefficients for a series of convergent convergent nozzles for a range of nozzle pressure ratios between 1.4 and 7.0. These configurations included a included a reference axisymmetric nozzle as well as 15deg , 25deg , and 40deg conical nozzles. Participants were also asked also asked to examine the plume shock structure for two cases where the 25deg conical nozzle was bifurcated by a bifurcated by a solid plate. The final test case was a serpentine inlet diffuser with an outlet to inlet area ratio of 1.52 ratio of 1.52 and an offset of 1.34 times the inlet diameter. Boundary layer profiles, wall static pressure, and total and total pressure at downstream rake locations were examined.

  20. PROPAGATION AND EVOLUTION OF THE JUNE 1st 2008 CME IN THE INTERPLANETARY MEDIUM

    NASA Astrophysics Data System (ADS)

    Nieves-Chinchilla, T.; Lamb, D. A.; Davila, J. M.; Vinas, A. F.; Moestl, C.; Hidalgo, M. A.; Farrugia, C. J.; Malandraki, O.; Dresing, N.; Gómez-Herrero, R.

    2009-12-01

    In this work we present a study of the coronal mass ejection (CME) of June 1st of 2008 in the interplanetary medium. This event has been extensively studied by others because of its favorable geometry and the possible consequences of its peculiar initiation for space weather forecasting. We show an analysis of the evolution of the CME in the interplanetary medium in order to shed some light on the propagation mechanism of the ICME. We have determined the typical shock associated characteristics of the ICME in order to understand the propagation properties. Using two different non force-free models of the magnetic cloud allows us to incorporate expansion of the cloud. We use in-situ measurements from STEREO B/IMPACT to characterize the ICME. In addition, we use images from STEREO A/SECCHI-HI to analyze the propagation and visual evolution of the associated flux rope in the interplanetary medium. We compare and contrast these observations with the results of the analytical models.

  1. Which Electronic and Structural Factors Control the Photostability of DNA and RNA Purine Nucleobases?

    NASA Astrophysics Data System (ADS)

    Pollum, Marvin; Reichardt, Christian; Crespo-Hernández, Carlos E.; Martínez-Fernández, Lara; Corral, Inés; Rauer, Clemens; Mai, Sebastian; Marquetand, Philipp; González, Leticia

    2015-06-01

    Following ultraviolet excitation, the canonical purine nucleobases, guanine and adenine, are able to efficiently dissipate the absorbed energy within hundreds of femtoseconds. This property affords these nucleobases with great photostability. Conversely, non-canonical purine nucleobases exhibit high fluorescence quantum yields or efficiently populate long-lived triplet excited states from which chemistry can occur. Using femtosecond broadband transient absorption spectroscopy in combination with ab initio static and surface hopping dynamics simulations we have determined the electronic and structural factors that regulate the excited state dynamics of the purine nucleobase derivatives. Importantly, we have uncovered that the photostability of the guanine and adenine nucleobases is not due to the structure of the purine core itself and that the substituent at the C6 position of the purine nucleobase plays a more important role than that at the C2 position in the ultrafast relaxation of deleterious electronic energy. [The authors acknowledge the CAREER program of the National Science Foundation (Grant No. CHE-1255084) for financial support.

  2. Identification of a chemoreceptor that specifically mediates chemotaxis toward metabolizable purine derivatives.

    PubMed

    Fernández, Matilde; Morel, Bertrand; Corral-Lugo, Andrés; Krell, Tino

    2016-01-01

    Chemotaxis is an essential mechanism that enables bacteria to move toward favorable ecological niches. Escherichia coli, the historical model organism for studying chemotaxis, has five well-studied chemoreceptors. However, many bacteria with different lifestyle have more chemoreceptors, most of unknown function. Using a high throughput screening approach, we identified a chemoreceptor from Pseudomonas putida KT2440, named McpH, which specifically recognizes purine and its derivatives, adenine, guanine, xanthine, hypoxanthine and uric acid. The latter five compounds form part of the purine degradation pathway, permitting their use as sole nitrogen sources. Isothermal titration calorimetry studies show that these six compounds bind McpH-Ligand Binding Domain (LBD) with very similar affinity. In contrast, non-metabolizable purine derivatives (caffeine, theophylline, theobromine), nucleotides, nucleosides or pyrimidines are unable to bind McpH-LBD. Mutation of mcpH abolished chemotaxis toward the McpH ligands identified - a phenotype that is restored by complementation. This is the first report on bacterial chemotaxis to purine derivatives and McpH the first chemoreceptor described that responds exclusively to intermediates of a catabolic pathway, illustrating a clear link between metabolism and chemotaxis. The evolution of McpH may reflect a saprophytic lifestyle, which would have exposed the studied bacterium to high concentrations of purines produced by nucleic acid degradation.

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

    PubMed

    Donaldson, Teraya M; Ting, Li-Min; Zhan, Chenyang; Shi, Wuxian; Zheng, Renjian; Almo, Steven C; Kim, Kami

    2014-01-01

    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. PMID:24416224

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

    PubMed

    Donaldson, Teraya M; Ting, Li-Min; Zhan, Chenyang; Shi, Wuxian; Zheng, Renjian; Almo, Steven C; Kim, Kami

    2014-01-01

    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.

  5. Metabolic Engineering of the Purine Pathway for Riboflavin Production in Ashbya gossypii†

    PubMed Central

    Jiménez, Alberto; Santos, María A.; Pompejus, Markus; Revuelta, José L.

    2005-01-01

    Purine nucleotides are essential precursors for living organisms because they are involved in many important processes, such as nucleic acid synthesis, energy supply, and the biosynthesis of several amino acids and vitamins such as riboflavin. GTP is the immediate precursor for riboflavin biosynthesis, and its formation through the purine pathway is subject to several regulatory mechanisms in different steps. Extracellular purines repress the transcription of most genes required for de novo ATP and GTP synthesis. Additionally, three enzymes of the pathway, phosphoribosyl pyrophosphate (PRPP) amidotransferase, adenylosuccinate synthetase, and IMP dehydrogenase, are subject to feedback inhibition by their end products. Here we report the characterization and manipulation of the committed step in the purine pathway of the riboflavin overproducer Ashbya gossypii. We report that phosphoribosylamine biosynthesis in A. gossypii is negatively regulated at the transcriptional level by extracellular adenine. Furthermore, we show that ATP and GTP exert a strong inhibitory effect on the PRPP amidotransferase from A. gossypii. We constitutively overexpressed the AgADE4 gene encoding PRPP amidotransferase in A. gossypii, thereby abolishing the adenine-mediated transcriptional repression. In addition, we replaced the corresponding residues (aspartic acid310, lysine333, and alanine417) that have been described to be important for PRPP amidotransferase feedback inhibition in other organisms by site-directed mutagenesis. With these manipulations, we managed to enhance metabolic flow through the purine pathway and to increase the production of riboflavin in the triple mutant strain 10-fold (228 mg/liter). PMID:16204483

  6. 78 FR 47698 - Notice to all Interested Parties of the Termination of the Receivership of 10183, 1st American...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-06

    ... From the Federal Register Online via the Government Publishing Office FEDERAL DEPOSIT INSURANCE CORPORATION Notice to all Interested Parties of the Termination of the Receivership of 10183, 1st American State Bank of Minnesota Hancock, MN Notice is hereby given that the Federal Deposit...

  7. Laying a Foundation for Lifelong Learning: Case Studies of E-Assessment in Large 1st-Year Classes

    ERIC Educational Resources Information Center

    Nicol, David

    2007-01-01

    Concerns about noncompletion and the quality of the 1st-year student experience have been linked to recent changes in higher education such as modularisation, increased class sizes, greater diversity in the student intake and reduced resources. Improving formative assessment and feedback processes is seen as one way of addressing academic failure,…

  8. 78 FR 7781 - Filing Dates for the South Carolina Special Elections in the 1st Congressional District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-04

    ... From the Federal Register Online via the Government Publishing Office FEDERAL ELECTION COMMISSION Filing Dates for the South Carolina Special Elections in the 1st Congressional District AGENCY: Federal Election Commission. ACTION: Notice of filing dates for special elections. SUMMARY: South Carolina...

  9. Bills to Increase Employment Opportunities through the Youth Conservation Corps and Other Means, 95th Congress, 1st Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC.

    This packet contains nine Senate bills and eight House bills from the 95th Congress, 1st session, all dealing with various means of increasing employment opportunities. Most of the bills deal with the creation of new jobs or with programs for job training, counseling, or placement. Seven of the bills constitute amendments to the Youth Conservation…

  10. Jordanian Kindergarten and 1st-Grade Teachers' Beliefs about Child-Based Dimensions of School Readiness

    ERIC Educational Resources Information Center

    Fayez, Merfat; Ahmad, Jamal Fathi; Oliemat, Enass

    2016-01-01

    The purpose of this study was to explore the beliefs of Jordanian kindergarten and 1st-grade teachers regarding six child-based dimensions of school readiness: academic knowledge, basic thinking skills, socioemotional maturity, physical well-being and motor development, self-discipline, and communication skills. Questionnaires were used to collect…

  11. Maternal Sleep-Related Cognitions and Infant Sleep: A Longitudinal Study from Pregnancy through the 1st Year

    ERIC Educational Resources Information Center

    Tikotzky, Liat; Sadeh, Avi

    2009-01-01

    Infant sleep is a major source of concern for many parents. The aims of this longitudinal study were to assess: (a) the development of sleep patterns among infants, (b) the development of maternal cognitions regarding infant sleep, and (c) the relations between these domains during the 1st year of life. Eighty-five mothers were recruited during…

  12. Addressing the Effects of Reciprocal Teaching on the Receptive and Expressive Vocabulary of 1st-Grade Students

    ERIC Educational Resources Information Center

    Mandel, Eliana; Osana, Helena P.; Venkatesh, Vivek

    2013-01-01

    This study evaluated the effects of Adapted Reciprocal Teaching (ART) on the receptive and expressive flight-word vocabulary of 1st-grade students. During ART, classroom interactions produced narrative contexts within which students assumed responsibility for applying new flight words in personally meaningful ways. Students in the control group…

  13. Global update: UK.

    PubMed

    Culme-Seymour, Emily J

    2012-11-01

    2012 has been an exciting year in the UK with substantial development on every front - research, clinical, industry and government. In particular, the focus has now moved to encompass far more post-research activities, with the continued enrolment of patients onto two pioneering Phase I clinical trials: ReNeuron's ReN001 stem cell therapy for stroke (PISCES) in Southern General Hospital, Greater Glasgow and Advanced Cell Technology's retinal pigment epithelial cells derived from human embryonic stem cells for Stargardts macular dystrophy and dry age-related macular degeneration at Moorfields Eye Hospital, London. The funding landscape for the sector has evolved from previous years to more fully embrace development and translation, including the provision of £180 million available for biomedical research via the Biomedical Catalyst Fund (joint Technology Strategy Board and Medical Research Council [MRC] funding) and a further £25 million through the UK Research Council's UK Regenerative Medicine Platform initiative, as well as ongoing developments with the Cell Therapy Catapult, which all act to further encourage a pan-UK collaborative environment. Overall, the UK cell therapy community continues to thrive and impact heavily upon the worldwide sector, with an established research base, a solid approach to translation and a small but growing commercial sector that is going from strength to strength.

  14. Foreword to Selected presentations from the 1st European Hip Sport Meeting.

    PubMed

    Dallari, Dante; Ribas, Manuel

    2016-05-14

    Recent years have witnessed a growing number of people practising sports both at professional and amateur level. This trend led to a progressive rise in the incidence and prevalence of acute and chronic hip damage. The treatment of hip disease in subjects practising sports is a major challenge for the orthopaedic surgeon. The evaluation of patients, in particular those of young age with high functional demands, is inevitably complex and should be performed with a multidisciplinary approach; from a surgical point of view, it is essential to carefully assess whether the indication is towards conservative surgery or hip replacement surgery. The advent of arthroscopic surgery in recent years has allowed us to improve our knowledge of hip joint diseases, such as femoroacetabular impingement that is typical of sports and overuse activity. A correct and early diagnosis of the disease can direct the patient promptly to a conservative surgical treatment that could reduce the progression of degenerative pathology. However, when the joint is permanently damaged, the only reliable solution remains prosthetic surgery, leading to a series of issues that the orthopaedic surgeon should be able to master, leading to a thoughtful decision on, for example, which implant to use, which biomaterials, which surgical approach or which sport to practise after surgery. This supplement contains selected contributions stemming from the work performed by internationally recognised experts in the field and presented during the 1st European Hip Sport Meeting held in Bologna on May 19th, 20th, 2016 that we had the honour to co-chair. We hope that these contributions will help the orthopaedic surgeon, the sports physician and physiotherapist in their day-to-day practice, and will help in fulfilling our ultimate aim to improve the knowledge of the hip pathology related to sports and overuse activities. PMID:27174057

  15. Patterns of Irregular Burials in Western Europe (1st-5th Century A.D.)

    PubMed Central

    Milella, Marco; Mariotti, Valentina; Belcastro, Maria Giovanna; Knüsel, Christopher J.

    2015-01-01

    Background Irregular burials (IB—burials showing features that contrast with the majority of others in their geographic and chronological context) have been the focus of archaeological study because of their relative rarity and enigmatic appearance. Interpretations of IB often refer to supposed fear of the dead or to social processes taking place in time-specific contexts. However, a comprehensive and quantitative analysis of IB for various geographical contexts is still lacking, a fact that hampers any discussion of these burials on a larger scale. Methods Here, we collected a bibliographic dataset of 375 IB from both Britain and Continental Europe, altogether spanning a time period from the 1st to the 5th century AD. Each burial has been coded according to ten dichotomous variables, further analyzed by means of chi-squared tests on absolute frequencies, non-metric multidimensional scaling, and cluster analysis. Results Even acknowledging the limits of this study, and in particular the bias represented by the available literature, our results point to interesting patterns. Geographically, IB show a contrast between Britain and Continental Europe, possibly related to historical processes specific to these regions. Different types of IB (especially prone depositions and depositions with the cephalic extremity displaced) present a series of characteristics and associations between features that permit a more detailed conceptualization of these occurrences from a socio-cultural perspective that aids to elucidate their funerary meaning. Conclusions and Significance Altogether, the present work stresses the variability of IB, and the need to contextualize them in a proper archaeological and historical context. It contributes to the discussion of IB by providing a specific geographic and chronological frame of reference that supports a series of hypotheses about the cultural processes possibly underlying their occurrence. PMID:26115408

  16. Computational Simulations of Convergent Nozzles for the AIAA 1st Propulsion Aerodynamics Workshop

    NASA Technical Reports Server (NTRS)

    Dippold, Vance F., III

    2014-01-01

    Computational Fluid Dynamics (CFD) simulations were completed for a series of convergent nozzles in participation of the American Institute of Aeronautics and Astronautics (AIAA) 1st Propulsion Aerodynamics Workshop. The simulations were performed using the Wind-US flow solver. Discharge and thrust coefficients were computed for four axisymmetric nozzles with nozzle pressure ratios (NPR) ranging from 1.4 to 7.0. The computed discharge coefficients showed excellent agreement with available experimental data; the computed thrust coefficients captured trends observed in the experimental data, but over-predicted the thrust coefficient by 0.25 to 1.0 percent. Sonic lines were computed for cases with NPR >= 2.0 and agreed well with experimental data for NPR >= 2.5. Simulations were also performed for a 25 deg. conic nozzle bifurcated by a flat plate at NPR = 4.0. The jet plume shock structure was compared with and without the splitter plate to the experimental data. The Wind-US simulations predicted the shock structure well, though lack of grid resolution in the plume reduced the sharpness of the shock waves. Unsteady Reynolds-Averaged Navier-Stokes (URANS) simulations and Detached Eddy Simulations (DES) were performed at NPR = 1.6 for the 25 deg conic nozzle with splitter plate. The simulations predicted vortex shedding from the trailing edge of the splitter plate. However, the vortices of URANS and DES solutions appeared to dissipate earlier than observed experimentally. It is believed that a lack of grid resolution in the region of the vortex shedding may have caused the vortices to break down too soon

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

    PubMed Central

    Sharma, Vimal Kumar; Jelen, Frantisek; Trnkova, Libuse

    2015-01-01

    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. PMID:25594595

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

    NASA Astrophysics Data System (ADS)

    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).

  19. Adaptive ligand binding by the purine riboswitch in the recognition of guanine and adenine analogs

    PubMed Central

    Gilbert, Sunny D.; Reyes, Francis E.; Edwards, Andrea L.; Batey, Robert T.

    2009-01-01

    SUMMARY Purine riboswitches discriminate between guanine and adenine by at least 10,000-fold based on the identity of a single pyrimidine (Y74) that forms a Watson-Crick base pair with the ligand. To understand how this high degree of specificity for closely related compounds is achieved through simple pairing, we investigated their interaction with purine analogs with varying functional groups at the 2- and 6-positions that have the potential to alter interactions with Y74. Using a combination of crystallographic and calorimetric approaches, we find that binding these purines is often facilitated by either small structural changes in the RNA or tautomeric changes in the ligand. This work also reveals that, along with base pairing, conformational restriction of Y74 significantly contributes to nucleobase selectivity. These results reveal that compounds that exploit the inherent local flexibility within riboswitch binding pockets can alter their ligand specificity. PMID:19523903

  20. Purine biosynthesis-deficient Burkholderia mutants are incapable of symbiotic accommodation in the stinkbug.

    PubMed

    Kim, Jiyeun Kate; Jang, Ho Am; Won, Yeo Jin; Kikuchi, Yoshitomo; Han, Sang Heum; Kim, Chan-Hee; Nikoh, Naruo; Fukatsu, Takema; Lee, Bok Luel

    2014-03-01

    The Riptortus-Burkholderia symbiotic system represents a promising experimental model to study the molecular mechanisms involved in insect-bacterium symbiosis due to the availability of genetically manipulated Burkholderia symbiont. Using transposon mutagenesis screening, we found a symbiosis-deficient mutant that was able to colonize the host insect but failed to induce normal development of host's symbiotic organ. The disrupted gene was identified as purL involved in purine biosynthesis. In vitro growth impairment of the purL mutant and its growth dependency on adenine and adenosine confirmed the functional disruption of the purine synthesis gene. The purL mutant also showed defects in biofilm formation, and this defect was not rescued by supplementation of purine derivatives. When inoculated to host insects, the purL mutant was initially able to colonize the symbiotic organ but failed to attain a normal infection density. The low level of infection density of the purL mutant attenuated the development of the host's symbiotic organ at early instar stages and reduced the host's fitness throughout the nymphal stages. Another symbiont mutant-deficient in a purine biosynthesis gene, purM, showed phenotypes similar to those of the purL mutant both in vitro and in vivo, confirming that the purL phenotypes are due to disrupted purine biosynthesis. These results demonstrate that the purine biosynthesis genes of the Burkholderia symbiont are critical for the successful accommodation of symbiont within the host, thereby facilitating the development of the host's symbiotic organ and enhancing the host's fitness values.

  1. Selective DNA purine base photooxidation by bis-terdentate iridium(III) polypyridyl and cyclometalated complexes.

    PubMed

    Jacques, Alexandre; Kirsch-De Mesmaeker, Andrée; Elias, Benjamin

    2014-02-01

    Two bis-terdentate iridium(III) complexes with polypyridyl and cyclometalated ligands have been prepared and characterized. Their spectroscopic and electrochemical properties have been studied, and a photophysical scheme addressing their properties is proposed. Different types of excited states have been considered to account for the deactivation processes in each complex. Interestingly, in the presence of mono- or polynucleotides, a photoinduced electron-transfer process from a DNA purine base (i.e., guanine or adenine) to the excited complex is shown through luminescence quenching experiments. For the first time, this work reports evidence for selective DNA purine bases oxidation by excited iridium(III) bis-terdentate complexes.

  2. Anti‐flavivirus Activity of Different Tritylated Pyrimidine and Purine Nucleoside Analogues

    PubMed Central

    Serpi, Michaela; Slusarczyk, Magdalena; Ferrari, Valentina; Pertusati, Fabrizio; Meneghesso, Silvia; Derudas, Marco; Farleigh, Laura; Zanetta, Paola; Bugert, Joachim

    2016-01-01

    Abstract A series of tritylated and dimethoxytritylated analogues of selected pyrimidine and purine nucleosides were synthesized and evaluated for their in vitro inhibitory activity against two important members of the genus Flavivirus in the Flaviviridae family, the yellow fever (YFV) and dengue viruses (DENV). Among all compounds tested, the 5′‐O‐tritylated and the 5′‐O‐dimethoxytritylated 5‐fluorouridine derivatives exerted potency against YFV. Interestingly in the series of purine analogues, the 5′O, N‐bis‐tritylated fludarabine derivative revealed strong inhibitory activity against DENV at μm concentrations, however significantly weaker potency against YFV. PMID:27551659

  3. Anti-flavivirus Activity of Different Tritylated Pyrimidine and Purine Nucleoside Analogues.

    PubMed

    McGuigan, Christopher; Serpi, Michaela; Slusarczyk, Magdalena; Ferrari, Valentina; Pertusati, Fabrizio; Meneghesso, Silvia; Derudas, Marco; Farleigh, Laura; Zanetta, Paola; Bugert, Joachim

    2016-06-01

    A series of tritylated and dimethoxytritylated analogues of selected pyrimidine and purine nucleosides were synthesized and evaluated for their in vitro inhibitory activity against two important members of the genus Flavivirus in the Flaviviridae family, the yellow fever (YFV) and dengue viruses (DENV). Among all compounds tested, the 5'-O-tritylated and the 5'-O-dimethoxytritylated 5-fluorouridine derivatives exerted potency against YFV. Interestingly in the series of purine analogues, the 5'O, N-bis-tritylated fludarabine derivative revealed strong inhibitory activity against DENV at μm concentrations, however significantly weaker potency against YFV. PMID:27551659

  4. The role of purine degradation in methane biosynthesis and energy production in Methanococcus vannielii. Progress report

    SciTech Connect

    DeMoll, E.

    1998-11-01

    Firstly, characterization of a purine degrading pathway in Methanococcus vannielii was determined. The pathway is similar to that described for Clostridia. The M. vannielli pathway differs in a few respects from the Clostridial pathway. The pathway of Clostridia uses tetrahydrofolic acid (THF), whereas the pathway of M. vannielii uses tetrahydromethanopterin (H{sub 4}MPt) as a cofactor in the transfer of both the formimino moiety of formiminoglycine and apparently in the cleavage of glycine by a glycin decarboxylase type mechanism that is dependent upon at least H{sub 4}MPt and either NAD{sup +} or NADP{sup +}. Secondly, the relationship of purine degradation to methanogenesis was investigated.

  5. Copper-catalyzed intramolecular cyclization of N-propargyl-adenine: synthesis of purine-fused tricyclics.

    PubMed

    Li, Ren-Long; Liang, Lei; Xie, Ming-Sheng; Qu, Gui-Rong; Niu, Hong-Ying; Guo, Hai-Ming

    2014-04-18

    A novel protocol to construct fluorescent purine-fused tricyclic products via intramolecular cyclization of N-propargyl-adenine has been developed. With CuBr as the catalyst, a series of purine-fused tricyclic products were obtained in good to excellent yields (19 examples, 75-89% yields). When R2 was a hydrogen atom in N-propargyl-adenines, the reactions only afforded the endocyclic double bond products. When R2 was an aryl group, the electron-donating groups favored the endocyclic double bond products, while the electron-withdrawing groups favored the exocyclic double bond products. PMID:24678722

  6. Infection of soybean and pea nodules by Rhizobium spp. purine auxotrophs in the presence of 5-aminoimidazole-4-carboxamide riboside.

    PubMed Central

    Newman, J D; Diebold, R J; Schultz, B W; Noel, K D

    1994-01-01

    Purine auxotrophs of various Rhizobium species are symbiotically defective, usually unable to initiate or complete the infection process. Earlier studies demonstrated that, in the Rhizobium etli-bean symbiosis, infection by purine auxotrophs is partially restored by supplementation of the plant medium with 5-amino-imidazole-4-carboxamide (AICA) riboside, the unphosphorylated form of the purine biosynthetic intermediate AICAR. The addition of purine to the root environment does not have this effect. In this study, purine auxotrophs of Rhizobium fredii HH303 and Rhizobium leguminosarum 128C56 (bv. viciae) were examined. Nutritional and genetic characterization indicated that each mutant was blocked in purine biosynthesis prior to the production of AICAR. R. fredii HH303 and R. leguminosarum 128C56 appeared to be deficient in AICA riboside transport and/or conversion into AICAR, and the auxotrophs derived from them grew very poorly with AICA riboside as a purine source. All of the auxotrophs elicited poorly developed, uninfected nodules on their appropriate hosts. On peas, addition of AICA riboside or purine to the root environment led to enhanced nodulation; however, infection threads were observed only in the presence of AICA riboside. On soybeans, only AICA riboside was effective in enhancing nodulation and promoting infection. Although AICA riboside supplementation of the auxotrophs led to infection thread development on both hosts, the numbers of bacteria recovered from the nodules were still 2 or more orders of magnitude lower than in fully developed nodules populated by wild-type bacteria. The ability to AICA riboside to promote infection by purine auxotrophs, despite serving as a very poor purine source for these strains, supports the hypothesis that AICAR plays a role in infection other than merely promoting bacterial growth. Images PMID:8195084

  7. PREFACE: 1st International Conference on Mechanical Engineering Research 2011 (ICMER2011)

    NASA Astrophysics Data System (ADS)

    Abu Bakar, Rosli

    2012-09-01

    The year 2010 represented a significant milestone in the history of the Mechanical Engineering community with the organization of the first and second national level conferences (National Conference in Mechanical Engineering for Research, 1st and 2nd NCMER) at Universiti Malaysia Pahang on 26-27 May and 3-4 December 2010. The conferences attracted a large number of delegates from different premier academic and research institutions in the country to participate and share their research experiences at the conference. The International Conference on Mechanical Engineering Research (ICMER 2011) followed on from the first and second conferences due to good support from researchers. The ICMER 2011 is a good platform for researchers and postgraduate students to present their latest finding in research. The conference covers a wide range of topics including the internal combustion engine, machining processes, heat and mass transfer, fuel, biomechanical analysis, aerodynamic analysis, thermal comfort, computational techniques, design and simulation, automotive transmission, optimization techniques, hybrid electric vehicles, engine vibration, heat exchangers, finite element analysis, computational fluid dynamics, green energy, vehicle dynamics renewable energy, combustion, design, product development, advanced experimentation techniques, to name but a few. The international conference has helped to bridge the gap between researchers working at different institutions and in different countries to share their knowledge and has helped to motivate young scientists with their research. This has also given some clear direction for further research from the deliberations of the conference. Several people have contributed in different ways to the success of the conference. We thank the keynote speakers and all authors of the contributed papers, for the cooperation rendered to us in the publication of the CD conference proceedings. In particular, we would like to place on record our

  8. Effects of the April 1st, 2014 GLONASS Outage on GNSS Receivers

    NASA Astrophysics Data System (ADS)

    Blume, F.; Berglund, H. T.; Romero, I.; D'Anastasio, E.

    2014-12-01

    The use of multi-constellation GNSS receivers has been assumed as a way to increase system integrity both by increased coverage during normal operations and failover redundancy in the event of a constellation failure. At approximately 21:00 UTC on April 1st the entire GLONASS constellation was disrupted as illegal ephemeris uploaded to each satellite took effect simultaneously. The outage continued for more than 10 hours. While ephemeris were incorrect, pseudoranges were correctly broadcast on both L1 and L2 and carrier phases were not affected; in the best case, GNSS receivers could be expected to continue to track all signals including GLONASS and at the worst to continue to track GPS and other constellations. It became clear to operators of the GeoNet network in New Zealand that the majority of their 79 GLONASS-enabled receivers experienced total tracking failures. Further detailed analysis of data from these and 315 additional GLONASS-enabled stations worldwide showed that receiver tracking behavior was affected for most receiver brands and models, both for GLONASS and GPS. Findings regarding the impacts of the GLONASS outage on receiver behavior will be highlighted. We use data recorded by GLONASS enabled global sites for the days during, preceding and following the outage to evaluate the impact of the outage on tracking and positioning performance. We observe that for some receiver types the onboard receiver autonomous integrity monitoring (RAIM) failed to ignore the incorrect messages, resulting in degraded GLONASS and GPS tracking and in some cases complete tracking failures and significant data loss. In addition, many of the receivers with clock steering enabled showed outliers in their receiver clock bias estimates that also coincided with the outage. Our results show in detail how different brands, configurations, and distributions of receivers were affected to varying extents, but no common factors are apparent. This event shows that many manufacturers

  9. Teachers' Spatial Anxiety Relates to 1st-and 2nd-Graders' Spatial Learning

    ERIC Educational Resources Information Center

    Gunderson, Elizabeth A.; Ramirez, Gerardo; Beilock, Sian L.; Levine, Susan C.

    2013-01-01

    Teachers' anxiety about an academic domain, such as math, can impact students' learning in that domain. We asked whether this relation held in the domain of spatial skill, given the importance of spatial skill for success in math and science and its malleability at a young age. We measured 1st-and 2nd-grade teachers' spatial anxiety…

  10. Educational impact of a clinical anatomy workshop on 1st-year orthopedic and rheumatology fellows in Mexico City.

    PubMed

    Saavedra, M A; Villaseñor-Ovies, P; Harfush, L A; Navarro-Zarza, J E; Canoso, J J; Cruz-Domínguez, P; Vargas, A; Hernández-Díaz, C; Chiapas-Gasca, K; Camacho-Galindo, J; Alvarez-Nemegyei, J; Kalish, R A

    2016-05-01

    We aim to study the educational impact of a clinical anatomy workshop in 1st-year orthopedic and rheumatology fellows. First-year rheumatology fellows (N = 17) and a convenience sample of 1st-year orthopedic fellows (N = 14) from Mexico City in the 9th month of training participated in the study. The pre- and the post- workshop tests included the same 20 questions that had to be answered by identification or demonstration of relevant anatomical items. The questions, arranged by anatomical regions, were asked in five dynamic stations. Overall, the 31 participants showed an increase of correct answers, from a median of 6 (range 1 to 12) in the pre-workshop test, to a median of 14 (range 7 to 19) in the post-workshop test. In the pre-workshop test, the correct median answers were 7 (range 2 to 12) in the orthopedic fellows and 5 (range 1 to 10) in the rheumatology fellows (p = 0.297). Corresponding scores in the post-workshop were 15 (range 10 to 19) and 12 (range 7 to 18) (p = 0.026) showing a significant difference favoring the orthopedic group. Our clinical anatomy workshop was efficacious, in the short term, as a teaching instrument for 1st-year orthopedic and rheumatology fellows. The post-workshop scores, although significantly improved in both groups, particularly in the orthopedic fellows, were still suboptimal. Further refinements of our workshop might yield better results.

  11. Gene-Environment Interaction Effects on the Development of Immune Responses in the 1st Year of Life

    PubMed Central

    Hoffjan, Sabine; Nicolae, Dan; Ostrovnaya, Irina; Roberg, Kathy; Evans, Michael; Mirel, Daniel B.; Steiner, Lori; Walker, Karen; Shult, Peter; Gangnon, Ronald E.; Gern, James E.; Martinez, Fernando D.; Lemanske, Robert F.; Ober, Carole

    2005-01-01

    Asthma is a common disease that results from both genetic and environmental risk factors. Children attending day care in the 1st year of life have lower risks for developing asthma, although the mechanism for this “day care” effect is largely unknown. We investigated the interactions between day care exposure in the 1st 6 mo of life and genotypes for 72 polymorphisms at 45 candidate loci and their effects on cytokine response profiles and on the development of atopic phenotypes in the 1st year of life in the Childhood Onset of Asthma (COAST) cohort of children. Six interactions (at four polymorphisms in three loci) with “day care” that had an effect on early-life immune phenotypes were significant at P<.001. The estimated false-discovery rate was 33%, indicating that an estimated four P values correspond to true associations. Moreover, the “day care” effect at some loci was accounted for by the increased number of viral infections among COAST children attending day care, whereas interactions at other loci were independent of the number of viral infections, indicating the presence of additional risk factors associated with day care environment. This study identified significant gene-environment interactions influencing the early patterning of the immune system and the subsequent development of asthma and highlights the importance of considering environmental risk factors in genetic analyses. PMID:15726497

  12. In vivo effect of mutations at the PRPP binding site of the Bacillus subtilis purine repressor.

    PubMed

    Rappu, Pekka; Pullinen, Terhi; Mäntsälä, Pekka

    2003-11-01

    The Bacillus subtilis PurR mediates adenine repression and guanosine induction of purA. PRPP inhibits binding of PurR to DNA in vitro. Mutations in the PRPP binding motif of PurR caused strong repression regardless of purine exclusions or additions, establishing the role of PRPP as regulator of PurR.

  13. 76 FR 80955 - Prospective Grant of Exclusive License: Use of Methanocarba Analogues of Purine and Pyrimidine...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-27

    ... treat and/or prevent cardiac diseases in humans.'' Upon the expiration or termination of the exclusive... HUMAN SERVICES National Institutes of Health Prospective Grant of Exclusive License: Use of Methanocarba Analogues of Purine and Pyrimidine Nucleosides and Nucleotides to Treat or Prevent Cardiac Diseases...

  14. A First Microwave-Assisted Synthesis of a New Class of Purine and Guanine Thioglycoside Analogs.

    PubMed

    Elgemeie, Galal; Abu-Zaied, Mamdouh; Hebishy, Ali; Abbas, Nermen; Hamed, Mai

    2016-09-01

    A first microwave-assisted synthesis of a new class of novel purine thioglycoside analogs from readily available starting materials has been described. The key step of this protocol is the formation of sodium pyrazolo[1,5-a]pyrimidine-7-thiolate and 7-mercaptopyrazolo[1,5-a]pyrimidine derivatives via condensation of 5-amino-1H-pyrazoles with sodium 2,2-dicyanoethene-1,1-bis(thiolate) salts or 2-(dimercaptomethylene)malononitrile, respectively, under microwave irradiation, followed by coupling with halo sugars to give the corresponding purine thioglycoside analogs. The obtained purines and purines thioglycosides derivatives were evaluated in vitro against lung (A549), colon (HCT116), liver (HEPG2), and prostate (PC3) cancer cell lines. Some of these compounds (5b, 5d, 5f, and 9a-d) exhibited little potency toward the four cell lines. On the other hand, compound 5a elicited higher cytotoxicity on both prostate (PC3) and colon (HCT116), respectively, while it was found moderate on lung (A549), and inactive on liver (HEPG2). Moreover, compound 5c was found moderate with LC50 values 52.0-88.9 μM for almost all the cell lines. PMID:27556784

  15. Changes in Purines Concentration in the Cerebrospinal Fluid of Pregnant Women Experiencing Pain During Active Labor.

    PubMed

    Schmidt, André P; Böhmer, Ana E; Hansel, Gisele; Soares, Félix A; Oses, Jean P; Giordani, Alex T; Posso, Irimar P; Auler, José Otávio C; Mendes, Florentino F; Félix, Elaine A; Portela, Luís V; Souza, Diogo O

    2015-11-01

    Labor pain has been reported as a severe pain and can be considered as a model of acute visceral pain. It is well known that extracellular purines have an important role in pain signaling in the central nervous system. This study analyzes the relationship between extracellular purines and pain perception during active labor. A prospective observational study was performed. Cerebrospinal fluid (CSF) levels of the purines and their metabolites were compared between women at term pregnancy with labor pain (n = 49) and without labor pain (Caesarian section; n = 47). Control groups (healthy men and women without chronic or acute pain-n = 40 and 32, respectively) were also investigated. The CSF levels of adenosine were significantly lower in the labor pain group (P = 0.026) and negatively correlated with pain intensity measured by a visual analogue scale (r = -0.48, P = 0.0005). Interestingly, CSF levels of uric acid were significantly higher in healthy men as compared to women. Additionally, pregnant women showed increased CSF levels of ADP, GDP, adenosine and guanosine and reduced CSF levels of AMP, GTP, and uric acid as compared to non-pregnant women (P < 0.05). These findings suggest that purines, in special the nucleoside adenosine, are associated with pregnancy and labor pain.

  16. Structure and Electronic Spectra of Purine-Methyl Viologen Charge Transfer Complexes

    PubMed Central

    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 (MV) 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 1H 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 (TD) 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 GMP (DAD′DAD′ type) and 7-deazaguanosine zG (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. PMID:24294996

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

    PubMed

    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.

  18. mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle.

    PubMed

    Ben-Sahra, Issam; Hoxhaj, Gerta; Ricoult, Stéphane J H; Asara, John M; Manning, Brendan D

    2016-02-12

    In response to growth signals, mechanistic target of rapamycin complex 1 (mTORC1) stimulates anabolic processes underlying cell growth. We found that mTORC1 increases metabolic flux through the de novo purine synthesis pathway in various mouse and human cells, thereby influencing the nucleotide pool available for nucleic acid synthesis. mTORC1 had transcriptional effects on multiple enzymes contributing to purine synthesis, with expression of the mitochondrial tetrahydrofolate (mTHF) cycle enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) being closely associated with mTORC1 signaling in both normal and cancer cells. MTHFD2 expression and purine synthesis were stimulated by activating transcription factor 4 (ATF4), which was activated by mTORC1 independent of its canonical induction downstream of eukaryotic initiation factor 2α eIF2α phosphorylation. Thus, mTORC1 stimulates the mTHF cycle, which contributes one-carbon units to enhance production of purine nucleotides in response to growth signals. PMID:26912861

  19. From Purines to Basic Biochemical Concepts: Experiments for High School Students

    ERIC Educational Resources Information Center

    Marini, Isabella; Ipata, Piero Luigi

    2007-01-01

    Many high school biology courses address mainly the molecular and cellular basis of life. The complexity that underlies the most essential processes is often difficult for the students to understand; possibly, in part, because of the inability to see and explore them. Six simple practical experiments on purine catabolism as a part of a…

  20. Purine synthesis de novo and salvage in hypoxanthine phosphoribosyltransferase-deficient mice.

    PubMed

    Allsop, J; Watts, R W

    1990-01-01

    Extreme degrees of hypoxanthine phosphoribosyltransferase (HPRT) deficiency in man are associated with gross sex-linked neurological dysfunction, gout and urinary stones (the Lesch-Nyhan or 'complete HPRT-deficiency' syndrome). The less severe degrees of enzyme deficiency (sex-linked recessive gout and/or urolithiasis or the 'partial HPRT-deficiency' syndrome) may be associated with minor neurological manifestations. Whole body purine synthesis de novo is accelerated in both these groups of patients. A strain of mice with an experimentally produced mutation at the HPRT locus showed some residual 'apparent HPRT activity' in brain, liver, testicular, splenic, kidney and ovarian tissues but not in erythrocyte haemolysates. The mutation removes exons 1 and 2 of the coding region of the gene together with the promotor and about 10 kb of upstream sequence from the gene. It is therefore possible that the observed 'apparent HPRT activity' in these mice is due to the operation of an alternative metabolic pathway. Purine synthesis de novo was markedly accelerated in their brain, testicular, splenic and kidney tissues. It was not accelerated in the liver tissue of male mice hemizygous for the mutation and the degree of acceleration in the female homozygotes only just reached statistical significance at the p = 0.02 level. This observation casts doubt on the importance of modulations in the rate of hepatic purine synthesis de novo as a mechanism for maintaining a steady supply of purines for translocation to other organs.

  1. The purine efflux pump PbuE in Bacillus subtilis modulates expression of the PurR and G-box (XptR) regulons by adjusting the purine base pool size.

    PubMed

    Nygaard, Per; Saxild, Hans H

    2005-01-01

    In Bacillus subtilis, the expression of genes encoding enzymes and other proteins involved in purine de novo synthesis and salvage is affected by purine bases and phosphoribosylpyrophosphate (PRPP). The transcription of the genes belonging to the PurR regulon is negatively regulated by the PurR protein and PRPP. The expression of the genes belonging to the G-box (XptR) regulon, including the pbuE gene, is negatively regulated by a riboswitch-controlled transcription termination mechanism. The G-box regulon effector molecules are hypoxanthine and guanine. pbuE encodes a purine base efflux pump and is now recognized as belonging to a third purine regulon. The expression of the pbuE gene is positively regulated by a riboswitch that recognizes adenine. Here we show that the expression of pbuE'-lacZ transcriptional fusions are induced by adenine to the highest extent in mutants which do not express a functional PbuE pump. In a mutant defective in the metabolism of adenine, the ade apt mutant, we found a high intracellular level of adenine and constitutive high levels of PbuE. A growth test using a purine auxotroph provided further evidence for the role of PbuE in lowering the intracellular concentration of purine bases, including adenine. Purine analogs also affect the expression of pbuE, which might be of importance for the protection against toxic analogs. In a mutant that overexpresses PbuE, the expression of genes belonging to the PurR regulon was increased. Our findings provide further evidence for important functions of the PbuE protein, such as acting as a pump that lowers the purine base pool and affects the expression of the G-box and PurR regulons, including pbuE itself, and as a pump involved in protection against toxic purine base analogs.

  2. PREFACE: PAGES 1st Young Scientists Meeting (YSM) - 'Retrospective views on our planet's future'

    NASA Astrophysics Data System (ADS)

    Margrethe Basse, Ellen

    2010-03-01

    more recent pollution. The concept and format of the 1st PAGES YSM worked very well, and

  3. Molecular Dissection of a Borrelia burgdorferi In Vivo Essential Purine Transport System

    PubMed Central

    Jain, Sunny; Showman, Adrienne C.

    2015-01-01

    The Lyme disease spirochete Borrelia burgdorferi is dependent on purine salvage from the host environment for survival. The genes bbb22 and bbb23 encode purine permeases that are essential for B. burgdorferi mouse infectivity. We now demonstrate the unique contributions of each of these genes to purine transport and murine infection. The affinities of spirochetes carrying bbb22 alone for hypoxanthine and adenine were similar to those of spirochetes carrying both genes. Spirochetes carrying bbb22 alone were able to achieve wild-type levels of adenine saturation but not hypoxanthine saturation, suggesting that maximal hypoxanthine uptake requires the presence of bbb23. Moreover, the purine transport activity conferred by bbb22 was dependent on an additional distal transcriptional start site located within the bbb23 open reading frame. The initial rates of uptake of hypoxanthine and adenine by spirochetes carrying bbb23 alone were below the level of detection. However, these spirochetes demonstrated a measurable increase in hypoxanthine uptake over a 30-min time course. Our findings indicate that bbb22-dependent adenine transport is essential for B. burgdorferi survival in mice. The bbb23 gene was dispensable for B. burgdorferi mouse infectivity, yet its presence was required along with that of bbb22 for B. burgdorferi to achieve maximal spirochete loads in infected mouse tissues. These data demonstrate that both genes, bbb22 and bbb23, are critical for B. burgdorferi to achieve wild-type infection of mice and that the differences in the capabilities of the two transporters may reflect distinct purine salvage needs that the spirochete encounters throughout its natural infectious cycle. PMID:25776752

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

    PubMed Central

    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

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

    PubMed

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

    PubMed

    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

  7. Lack of relationship between purine biosynthesis and vancomycin resistance in Staphylococcus aureus: a cautionary tale for microarray interpretation.

    PubMed

    Fox, Paige M; Climo, Michael W; Archer, Gordon L

    2007-04-01

    Previous microarray data (E. Mongodin, J. Finan, M. W. Climo, A. Rosato, S. Gill, and G. L. Archer, J. Bacteriol. 185:4638-4643, 2003) noted an association in two vancomycin-intermediate Staphylococcus aureus (VISA) strains between high-level, passage-induced vancomycin resistance, a marked increase in the transcription of purine biosynthetic genes, and mutation of the putative purine regulator purR. Initial studies to report on the possible association between vancomycin resistance and alterations in purine metabolism in one of these strains (VP-32) confirmed, by Western analysis, an increase in the translation of PurH and PurM, two purine pathway enzymes. In addition, PurR was identified, by knockout and complementation in a vancomycin-susceptible strain, as a repressor of the purine biosynthetic operon in S. aureus, and the PurR missense mutation was shown to inactivate the repressor. However, despite the apparent relationship between increased purine biosynthesis and increased vancomycin resistance in VP-32, neither the addition of exogenous purines to a defined growth medium nor the truncation or inactivation of purR improved the growth of vancomycin-susceptible S. aureus in the presence of vancomycin. Furthermore, the passage of additional vancomycin-susceptible and VISA strains to high-level vancomycin resistance occurred without changes in cellular purine metabolism or mutation of purR despite the development of thickened cell walls in passaged strains. Thus, we could confirm neither a role for altered purine metabolism in the development of vancomycin resistance nor its requirement for the maintenance of a thickened cell wall. The failure of biochemical and physiological studies to support the association between transcription and phenotype initially found in careful microarray studies emphasizes the importance of follow-up investigations to confirm microarray observations.

  8. The proceedings of the 1st international workshop on laboratory astrophysics experiments with large lasers

    SciTech Connect

    Remington, B.A.; Goldstein, W.H.

    1996-08-09

    The world has stood witness to the development of a number of highly sophisticated and flexible, high power laser facilities (energies up to 50 kJ and powers up to 50 TW), driven largely by the world-wide effort in inertial confinement fusion (ICF). The charter of diagnosing implosions with detailed, quantitative measurements has driven the ICF laser facilities to be exceedingly versatile and well equipped with diagnostics. Interestingly, there is considerable overlap in the physics of ICF and astrophysics. Both typically involve compressible radiative hydrodynamics, radiation transport, complex opacities, and equations of state of dense matter. Surprisingly, however, there has been little communication between these two communities to date. With the recent declassification of ICF in the USA, and the approval to commence with construction of the next generation ``superlasers``, the 2 MJ National Ignition Facility in the US, and its equivalent, the LMJ laser in France, the situation is ripe for change. . Given the physics similarities that exist between ICF and astrophysics, one strongly suspects that there should exist regions of overlap where supporting research on the large lasers could be beneficial to the astrophysics community. As a catalyst for discussions to this end, Lawrence Livermore National Laboratory sponsored this workshop. Approximately 100 scientists attended from around the world, representing eight countries: the USA, Canada, UK, France, Germany, Russia, Japan, and Israel. A total of 30 technical papers were presented. The two day workshop was divided into four sessions, focusing on nonlinear hydrodynamics, radiative hydrodynamics, radiation transport, and atomic physics-opacities. Copies of the presentations are contained in these proceedings.

  9. Synthesis and antimycobacterial activity of N-(2-aminopurin-6-yl) and N-(purin-6-yl) amino acids and dipeptides.

    PubMed

    Krasnov, Victor P; Vigorov, Alexey Yu; Musiyak, Vera V; Nizova, Irina A; Gruzdev, Dmitry A; Matveeva, Tatyana V; Levit, Galina L; Kravchenko, Marionella A; Skornyakov, Sergey N; Bekker, Olga B; Danilenko, Valery N; Charushin, Valery N

    2016-06-01

    Synthetic routes to novel N-(purin-6-yl)- and N-(2-aminopurin-6-yl) conjugates with amino acids and glycine-containing dipeptides were developed. In vitro testing of 42 new and known compounds made it possible to reveal a series of N-(purin-6-yl)- and N-(2-aminopurin-6-yl) conjugates exhibiting significant antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium avium, Mycobacterium terrae, and multidrug-resistant M. tuberculosis strain isolated from tuberculosis patients in the Ural region (Russia). N-(2-Aminopurin-6-yl)- and N-(purin-6-yl)-glycyl-(S)-glutamic acids were the most active compounds. PMID:27107949

  10. Specific and non-specific purine trap in the T-loop of normal and suppressor tRNAs.

    PubMed

    Doyon, Félix R; Zagryadskaya, Ekaterina I; Chen, Jianhong; Steinberg, Sergey V

    2004-10-01

    To elucidate the general constraints imposed on the structure of the D and T-loops in functional tRNAs, active suppressor tRNAs were selected in vivo from a combinatorial tRNA gene library in which several nucleotide positions in these loops were randomized. Analysis of the nucleotide sequences of the selected clones demonstrates that most of them contain combination U54-A58 allowing the formation of the standard reverse-Hoogsteen base-pair 54-58 in the T-loop. With only one exception, all these clones fall into two groups, each characterized by a distinct sequence pattern. Analysis of these two groups has allowed us to suggest two different types of nucleotide arrangement in the DT region. The first type, the so-called specific purine trap, is found in 12 individual tRNA clones and represents a generalized version of the standard D-T loop interaction. It consists of purine 18 sandwiched between the reverse-Hoogsteen base-pair U54-A58 and purine 57. The identity of purine 18 is restricted by the specific base-pairing with nucleotide 55. Depending on whether nucleotide 55 is U or G, purine 18 should be, respectively, G or A. The second structural type, the so-called non-specific purine trap, corresponds to the nucleotide sequence pattern found in 16 individual tRNA clones and is described here for the first time. It consists of purine 18 sandwiched between two reverse-Hoogsteen base-pairs U54-A58 and A55-C57 and, unlike the specific purine trap, requires the T-loop to contain an extra eighth nucleotide. Since purine 18 does not form a base-pair in the non-specific purine trap, both purines, G18 and A18, fit to the structure equally well. The important role of both the specific and non-specific purine traps in the formation of the tRNA L-shape is discussed.

  11. PREFACE: PAGES 1st Young Scientists Meeting (YSM) - 'Retrospective views on our planet's future'

    NASA Astrophysics Data System (ADS)

    Margrethe Basse, Ellen

    2010-03-01

    more recent pollution. The concept and format of the 1st PAGES YSM worked very well, and created a high degree of enthusiasm and stimulation among the participants (as is demonstrated by this special issue). The 2nd YSM is therefore firmly planned to take place in 2013, back-to-back with the 4th PAGES OSM. Crucial and gratefully acknowledged contributions to the success of the YSM were made by the numerous co-sponsors (see logos below), who provided the financial basis for the YSM and supported the attendance of many early-career researchers from various parts of the world. Furthermore, we cordially thank all reviewers for shaping this proceeding issue with their insightful and helpful reviews. Conference photograph

  12. UK Parkinson's Excellence Network: empowering service improvement across the UK.

    PubMed

    Burn, David

    2015-01-01

    Parkinson's UK, together with leading Parkinson's professionals, has set up the UK Parkinson's Excellence Network to bring together the passion and expertise of leading clinicians with the strategic leadership and resources of Parkinson's UK underpinned by the voice of people affected by Parkinson's. Launched in London in February 2015, the Excellence Network aims to drive sustainable improvements in health and social care services. It will provide a more strategic approach to clinical development so that Parkinson's services across health and social care can be transformed to provide the best quality care across the UK.

  13. Study on the activity of non-purine xanthine oxidase inhibitor by 3D-QSAR modeling and molecular docking

    NASA Astrophysics Data System (ADS)

    Li, Peizhen; Tian, Yueli; Zhai, Honglin; Deng, Fangfang; Xie, Meihong; Zhang, Xiaoyun

    2013-11-01

    Non-purine derivatives have been shown to be promising novel drug candidates as xanthine oxidase inhibitors. Based on three-dimensional quantitative structure-activity relationship (3D-QSAR) methods including comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), two 3D-QSAR models for a series of non-purine xanthine oxidase (XO) inhibitors were established, and their reliability was supported by statistical parameters. Combined 3D-QSAR modeling and the results of molecular docking between non-purine xanthine oxidase inhibitors and XO, the main factors that influenced activity of inhibitors were investigated, and the obtained results could explain known experimental facts. Furthermore, several new potential inhibitors with higher activity predicted were designed, which based on our analyses, and were supported by the simulation of molecular docking. This study provided some useful information for the development of non-purine xanthine oxidase inhibitors with novel structures.

  14. Amide-controlled, one-pot synthesis of tri-substituted purines generates structural diversity and analogues with trypanocidal activity.

    PubMed

    Pineda de las Infantas y Villatoro, Maria J; Unciti-Broceta, Juan D; Contreras-Montoya, Rafael; Garcia-Salcedo, Jose A; Gallo Mezo, Miguel A; Unciti-Broceta, Asier; Diaz-Mochon, Juan J

    2015-01-01

    A novel one-pot synthesis of tri-substituted purines and the discovery of purine analogues with trypanocidal activity are reported. The reaction is initiated by a metal-free oxidative coupling of primary alkoxides and diaminopyrimidines with Schiff base formation and subsequent annulation in the presence of large N,N-dimethylamides (e.g. N,N-dimethylpropanamide or larger). This synthetic route is in competition with a reaction previously-reported by our group, allowing the generation of a combinatorial library of tri-substituted purines by the simple modification of the amide and the alkoxide employed. Among the variety of structures generated, two purine analogues displayed trypanocidal activity against the protozoan parasite Trypanosoma brucei with IC50 < 5 μM, being each of those compounds obtained through each of the synthetic pathways.

  15. [Effect of 5-FU on the utilization of purine and pyrimidine by human gastric cancer cells (KATO III)].

    PubMed

    Usami, M; Wang, J; Yasuda, I; Saitoh, Y; Yumisashi, T; Abe, K

    1995-05-01

    Effect of utilization of purine and pyrimidine in the culture medium by human gastric cancer cells (KATO III) was evaluated. Nucleosides mixture solution (OG-VI), consisting of inosine, guanosine 5' monophosphate (5'GMP), cytidine, uridine and thymidine (4: 4: 4: 3: 1 in molar ratio) was used and their levels in the culture medium was measured by HPLC after 3 day culture. Purine, inosine and 5' GMP, in the medium almost decreased and purine base, xanthine and hypoxanthine levels increased, but changes in pyrimidine level were minimal. 5-FU decreased purine and increased pyrimidine consumption. Addition of nucleosides mixture did not enhance the cellular proliferation, but inhibited growth when given in higher concentrations. Nucleoside mixture solution enhanced growth inhibition by 5-FU and it is a potential biochemical modulator of 5-FU metabolism in human cancer cells. PMID:7755382

  16. 2,3-Dicyclohexylsuccinimide as a directing/protecting group for the regioselective glycosylation or alkylation of purines.

    PubMed

    Pal, Ayan; Salandria, Kerry J; Arico, Joseph W; Schlegel, Mark K; McLaughlin, Larry W

    2013-04-11

    Here we describe the synthesis and application of a novel 2,3-dicyclohexylsuccinimide (Cy2SI) protecting group towards regioselective purine glycosylation and alkylation reactions. This bulky protecting group promotes high regioselectivity during the glycosylation (as well as diastereoselectivity) or alkylation of purines using Hoffer's chlorosugar or tert-butyl bromoacetate, respectively. Cy2SI offers the additional synthetic advantage that other base-labile protecting groups, such as toluoyl esters, can be selectively removed in its presence without affecting the imide.

  17. [Mutation analysis of the purine operon leader region in Bacillus subtilis].

    PubMed

    Lobanov, K V; korol'kova, N V; Eremina, S Iu; Érrais Lopes, L; Mironov, A S

    2011-07-01

    Expression of Bacillus subtilis purine (purE) operon is a subject of double negative control involving repressor protein PurR and a transcription terminator located in the operon leader region. We have performed site-directed mutagenesis of the specific motives, which are involved in formation of alternative hairpin structures, one of which produces transcription termination at the leader region ofpurEoperon. In vivo and in vitro analyses of the generated mutants have shown that purine bases, guanine and hypoxantine, serve as effector metabolites capable of increasing stability of terminating hairpin within the leader mRNA. Therefore, the leader RNA of purE operon serves as a sensor towards these metabolites and a riboswitch that provides premature termination of the operon transcription. The synergistic effect of the PurR repressor protein and a transcription terminator located at the leader region on the expression of purE operon was also revealed.

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

    NASA Technical Reports Server (NTRS)

    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.

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

    SciTech Connect

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

    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.

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

    PubMed

    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. PMID:27174989

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

    NASA Technical Reports Server (NTRS)

    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.

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

    NASA Technical Reports Server (NTRS)

    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.

  3. Purine pathway implicated in mechanism of resistance to aspirin therapy: pharmacometabolomics-informed pharmacogenomics.

    PubMed

    Yerges-Armstrong, L M; Ellero-Simatos, S; Georgiades, A; Zhu, H; Lewis, J P; Horenstein, R B; Beitelshees, A L; Dane, A; Reijmers, T; Hankemeier, T; Fiehn, O; Shuldiner, A R; Kaddurah-Daouk, R

    2013-10-01

    Although aspirin is a well-established antiplatelet agent, the mechanisms of aspirin resistance remain poorly understood. Metabolomics allows for measurement of hundreds of small molecules in biological samples, enabling detailed mapping of pathways involved in drug response. We defined the metabolic signature of aspirin exposure in subjects from the Heredity and Phenotype Intervention Heart Study. Many metabolites, including known aspirin catabolites, changed on exposure to aspirin, and pathway enrichment analysis identified purine metabolism as significantly affected by drug exposure. Furthermore, purines were associated with aspirin response, and poor responders had higher postaspirin adenosine and inosine levels than did good responders (n = 76; both P < 4 × 10(-3)). Using our established "pharmacometabolomics-informed pharmacogenomics" approach, we identified genetic variants in adenosine kinase associated with aspirin response. Combining metabolomics and genomics allowed for more comprehensive interrogation of mechanisms of variation in aspirin response--an important step toward personalized treatment approaches for cardiovascular disease. PMID:23839601

  4. Coexpression of two closely linked avian genes for purine nucleotide synthesis from a bidirectional promoter.

    PubMed Central

    Gavalas, A; Dixon, J E; Brayton, K A; Zalkin, H

    1993-01-01

    Two avian genes encoding essential steps in the purine nucleotide biosynthetic pathway are transcribed divergently from a bidirectional promoter element. The bidirectional promoter, embedded in a CpG island, directs coexpression of GPAT and AIRC genes from distinct transcriptional start sites 229 bp apart. The bidirectional promoter can be divided in half, with each half retaining partial activity towards the cognate gene. GPAT and AIRC genes encode the enzymes that catalyze step 1 and steps 6 plus 7, respectively, in the de novo purine biosynthetic pathway. This is the first report of genes coding for structurally unrelated enzymes of the same pathway that are tightly linked and transcribed divergently from a bidirectional promoter. This arrangement has the potential to provide for regulated coexpression comparable to that in a prokaryotic operon. Images PMID:8336716

  5. Determination of Caffeine and Other Purine Compounds in Food and Pharmaceuitcals by Micellar Electrokinetic Chrmoatography

    NASA Astrophysics Data System (ADS)

    Vogt, Carla; Contradi, S.; Rohde, E.

    1997-09-01

    Capillary elctrophoresis is a modern separation technique, especially the extremely high efficiencies and minimal requirements with regard to buffers, samples and solvents lead to a dramatic increase of applications in the last few years. This paper offers an introduction to the technique of micellar elektrokinetic chromatography as a special kind of capillary electrophoresis. Caffeine and other purine compounds have been determined in foodstuff (tea, coffee, cocoa) as well as in pharmaceutical formulations. Different sample preparation procedures which have been developed with regard to the special properties of the sample matrices are discussed in the paper.This preparation facilitates the separation in many cases. So students have to solve a relatively simple separation problem by variation of buffer pH, buffer components and separation parameters. By doing a calibration for the analyzed purine compounds they will learn about reproducibility in capillary electrophoresis.

  6. Extraction of purine alkaloids from maté (Ilex paraguariensis) using supercritical CO(2).

    PubMed

    Saldaña, M D; Mohamed, R S; Baer, M G; Mazzafera, P

    1999-09-01

    Experimental data for the supercritical CO(2) extraction of purine alkaloids (caffeine, theobromine, and theophylline) from ground herbal maté tea (Ilex paraguaryensis) using a high-pressure apparatus are presented. Caffeine, theophylline, and theobromine were identified in the extracted fractions using HPLC. Results indicated a much higher CO(2) selectivity for caffeine in comparison with those for theophylline and theobromine. Solubilities of pure compounds in carbon dioxide were also determined at 313.2, 323.2, 338.2, and 343.2 K, and pressures ranging from 14 to 24 MPa. Caffeine solubility exhibited a retrograde behavior with temperature while theophylline and theobromine manifested a normal behavior at conditions explored in this study. Solubilities in binary CO(2)/purine alkaloid model systems were much higher than those obtained during extraction of maté tea, demonstrating the difficulty of using binary data in predicting complex multicomponent behavior.

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

    PubMed

    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.

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

    PubMed

    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. PMID:24530799

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

    PubMed Central

    Strom, Shane; Shiskova, Evgenia; Hahm, Yaeeun

    2015-01-01

    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 MgCl2 or 1 M KCl. The ΔG37∘ 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 ΔG37∘ 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. PMID:26022248

  10. Stacking of purines in water: the role of dipolar interactions in caffeine.

    PubMed

    Tavagnacco, L; Di Fonzo, S; D'Amico, F; Masciovecchio, C; Brady, J W; Cesàro, A

    2016-05-11

    During the last few decades it has been ascertained that base stacking is one of the major contributions stabilizing nucleic acid conformations. However, the understanding of the nature of the interactions involved in the stacking process remains under debate and it is a subject of theoretical and experimental studies. Structural similarity between purine bases (guanine and adenine) in DNA and the caffeine molecule makes caffeine an excellent model for the purine bases. The present study clearly shows that dipolar interactions play a fundamental role in determining stacking of purine molecules in solution. In order to reach this achievement, polarized ultraviolet Raman resonant scattering experiments have been carried out on caffeine aqueous solutions as a function of concentration and temperature. The investigation pointed out at the aggregation and solvation properties, particularly at elevated temperatures. Kubo-Anderson theory was used as a framework to investigate the non-coincidence effect (NCE) occurring in the totally symmetric breathing modes of the purine rings, and in the bending modes of the methyl groups of caffeine. The NCE concentration dependence shows that caffeine aggregation at 80 °C occurs by planar stacking of the hydrophobic faces. The data clearly indicate that dipolar interactions determine the reorientational motion of the molecules in solution and are the driving force for the stacking of caffeine. In parallel, the observed dephasing times imply a change in caffeine interactions as a function of temperature and concentration. A decrease, at low water content, of the dephasing time for the ring breathing vibration mode indicates that self-association alters the solvation structure that is detectable at low concentration. These results are in agreement with simulation predictions and serve as an important validation of the models used in those calculations. PMID:27127808

  11. Stacking of purines in water: the role of dipolar interactions in caffeine.

    PubMed

    Tavagnacco, L; Di Fonzo, S; D'Amico, F; Masciovecchio, C; Brady, J W; Cesàro, A

    2016-05-11

    During the last few decades it has been ascertained that base stacking is one of the major contributions stabilizing nucleic acid conformations. However, the understanding of the nature of the interactions involved in the stacking process remains under debate and it is a subject of theoretical and experimental studies. Structural similarity between purine bases (guanine and adenine) in DNA and the caffeine molecule makes caffeine an excellent model for the purine bases. The present study clearly shows that dipolar interactions play a fundamental role in determining stacking of purine molecules in solution. In order to reach this achievement, polarized ultraviolet Raman resonant scattering experiments have been carried out on caffeine aqueous solutions as a function of concentration and temperature. The investigation pointed out at the aggregation and solvation properties, particularly at elevated temperatures. Kubo-Anderson theory was used as a framework to investigate the non-coincidence effect (NCE) occurring in the totally symmetric breathing modes of the purine rings, and in the bending modes of the methyl groups of caffeine. The NCE concentration dependence shows that caffeine aggregation at 80 °C occurs by planar stacking of the hydrophobic faces. The data clearly indicate that dipolar interactions determine the reorientational motion of the molecules in solution and are the driving force for the stacking of caffeine. In parallel, the observed dephasing times imply a change in caffeine interactions as a function of temperature and concentration. A decrease, at low water content, of the dephasing time for the ring breathing vibration mode indicates that self-association alters the solvation structure that is detectable at low concentration. These results are in agreement with simulation predictions and serve as an important validation of the models used in those calculations.

  12. Endonucleolytic activity directed towards 8-(2-hydroxy-2-propyl) purines in double-stranded DNA.

    PubMed

    Livneh, Z; Elad, D; Sperling, J

    1979-11-01

    Photoalkylation of circular covalently closed DNA from phage PM2 with isopropyl alcohol by using a free radical photoinitiator and UV light of lambda greater than 305 nm led to the specific 8-substitution of purine moieties in the DNA, yielding 8-(2-hydroxy-2-propyl)adenine and 8-(2-hydroxy-2-propyl)guanine as the only detectable damage in the DNA. Using this specifically photoalkylated DNA as a substrate, we discovered in extracts of Micrococcus luteus an endonucleolytic activity that is directed towards 8-(2-hydroxy-2-propyl) purines in DNA. The activity is not a combination of a DNA-glycosylase and an apurinic site endonuclease. It is not inhibited by single-stranded DNA, by UV- or gamma-irradiated single-stranded DNA, or by normal or depurinated double-stranded DNA. however, gamma- or UV-(254 nm) irradiated double-stranded DNAs to inhibit the activity, hinting at the possibility of a common type of lesion in these damaged DNAs. Divalent cations are not required for the incising activity, and it is fully active in 1 mM EDTA, whereas caffeine and ATP cause inhibition. Extracts of mutant M. luteus lacking pyrimidine-dimer-directed endonucleases were found to contain the endonucleolytic activity in levels comparable to those present in the wild type. After the incision, we could demonstrate the specific excision of the 8-alkylated purines from the damaged DNA. The special conformational consequences of the 8-alkylation of purines, at the nucleotide level, namely their nonregular syn conformation, suggest that it is the distortion in the DNA that is recognized by the endonuclease. PMID:293658

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

    PubMed

    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.

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

    PubMed

    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.

  15. L-Enantiomers of Transition State Analogue Inhibitors Bound to Human Purine Nucleoside Phosphorylase

    SciTech Connect

    Rinaldo-Matthis,A.; Murkin, A.; Ramagopal, U.; Clinch, K.; Mee, S.; Evans, G.; Tyler, P.; Furneaux, R.; Almo, S.; Schramm, v.

    2008-01-01

    Human purine nucleoside phosphorylase (PNP) was crystallized with transition-state analogue inhibitors Immucillin-H and DADMe-Immucillin-H synthesized with ribosyl mimics of l-stereochemistry. The inhibitors demonstrate that major driving forces for tight binding of these analogues are the leaving group interaction and the cationic mimicry of the transition state, even though large geometric changes occur with d-Immucillins and l-Immucillins bound to human PNP.

  16. Electronic and Structural Elements That Regulate the Excited-State Dynamics in Purine Nucleobase Derivatives

    PubMed Central

    2015-01-01

    The excited-state dynamics of the purine free base and 9-methylpurine are investigated using experimental and theoretical methods. Femtosecond broadband transient absorption experiments reveal that excitation of these purine derivatives in aqueous solution at 266 nm results primarily in ultrafast conversion of the S2(ππ*) state to the vibrationally excited 1nπ* state. Following vibrational and conformational relaxation, the 1nπ* state acts as a doorway state in the efficient population of the triplet manifold with an intersystem crossing lifetime of hundreds of picoseconds. Experiments show an almost 2-fold increase in the intersystem crossing rate on going from polar aprotic to nonpolar solvents, suggesting that a solvent-dependent energy barrier must be surmounted to access the singlet-to-triplet crossing region. Ab initio static and surface-hopping dynamics simulations lend strong support to the proposed relaxation mechanism. Collectively, the experimental and computational results demonstrate that the accessibility of the nπ* states and the topology of the potential energy surfaces in the vicinity of conical intersections are key elements in controlling the excited-state dynamics of the purine derivatives. From a structural perspective, it is shown that the purine chromophore is not responsible for the ultrafast internal conversion in the adenine and guanine monomers. Instead, C6 functionalization plays an important role in regulating the rates of radiative and nonradiative relaxation. C6 functionalization inhibits access to the 1nπ* state while simultaneously facilitating access to the 1ππ*(La)/S0 conical intersection, such that population of the 1nπ* state cannot compete with the relaxation pathways to the ground state involving ring puckering at the C2 position. PMID:25763596

  17. BMI differences in 1st and 2nd generation immigrants of Asian and European origin to Australia.

    PubMed

    Hauck, Katharina; Hollingsworth, Bruce; Morgan, Lawrie

    2011-01-01

    We estimate assimilation of immigrants' body mass index (BMI) to the host population of Australia over one generation, conducting separate analyses for immigrants from 7 regions of Europe and Asia. We use quantile regressions to allow for differing impact of generational status across 19 quantiles of BMI from under-weight to morbidly obese individuals. We find that 1st generation South European immigrants have higher, and South and East Asian immigrants have lower BMI than Australians, but have assimilated to the BMI of their hosts in the 2nd generation. There are no or only small BMI differences between Australians and 1st and 2nd generation immigrants from East Europe, North-West Europe, Middle East and Pacific regions. We conclude that both upward and downward assimilation in some immigrant groups is most likely caused by factors which can change over one generation (such as acculturation), and not factors which would take longer to change (such as genetics). Our results suggest that public health policies targeting the lifestyles of well educated Asian immigrants may be effective in preventing BMI increase in this subgroup.

  18. Attitudes towards General Practice: a comparative cross-sectional survey of 1st and 5th year medical students

    PubMed Central

    Kruschinski, Carsten; Wiese, Birgitt; Hummers-Pradier, Eva

    2012-01-01

    Objective: Positive attitudes towards General Practice can be understood as a prerequisite for becoming a General Practitioner (GP) and for collaboration with GPs later on. This study aimed to assess attitudes of medical students at the beginning and the end of medical school. Methods: A total of 160 1st year students at Hannover Medical School were surveyed. Their attitudes were compared to those of 287 5th year students. Descriptive, bi- and multivariate analyses were performed to investigate influences of year of study and gender. Results: Year of study and gender both were associated with the attitudes towards General Practice. The interest in General Practice and patient-orientation (communication, care of older patients with chronic diseases) was higher in 1st year students compared to more advanced students. Female students valued such requirements more than male students, the differences in attitudes between the years of study being more pronounced in male students. Conclusion: Despite some limitations caused by the cross-sectional design, the attitudes towards General Practice competencies changed to their disadvantage during medical school. This suggests a formative influence of the strategies used in medical education. Educational strategies, however, could be used to bring about a change of attitudes in the other direction. PMID:23255966

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

    NASA Technical Reports Server (NTRS)

    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.

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

    PubMed Central

    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

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

    SciTech Connect

    Speiser, D.M.; Ortiz, D.F.; Kreppel, L.; Scheel, G.; McDonald, G.; Ow, D.W. Univ. of California, Berkeley )

    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.

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

    PubMed Central

    Speiser, D M; Ortiz, D F; Kreppel, L; Scheel, G; McDonald, G; Ow, D W

    1992-01-01

    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. Images PMID:1448066

  3. Purine catabolic pathway revealed by transcriptomics in the model marine bacterium Ruegeria pomeroyi DSS-3.

    PubMed

    Cunliffe, Michael

    2016-01-01

    Purines are nitrogen-rich compounds that are widely distributed in the marine environment and are an important component of the dissolved organic nitrogen (DON) pool. Even though purines have been shown to be degraded by bacterioplankton, the identities of marine bacteria capable of purine degradation and their underlying catabolic mechanisms are currently unknown. This study shows that Ruegeria pomeroyi, a model marine bacterium and Marine Roseobacter Clade (MRC) representative, utilizes xanthine as a source of carbon and nitrogen. The R. pomeroyi genome contains putative genes that encode xanthine dehydrogenase (XDH), which is expressed during growth with xanthine. RNAseq-based analysis of the R. pomeroyi transcriptome revealed that the transcription of an XDH-initiated catabolic pathway is up-regulated during growth with xanthine, with transcription greatest when xanthine was the only available carbon source. The RNAseq-deduced pathway indicates that glyoxylate and ammonia are the key intermediates from xanthine degradation. Utilising a laboratory model, this study has identified the potential genes and catabolic pathway active during xanthine degradation. The ability of R. pomeroyi to utilize xanthine provides novel insights into the capabilities of the MRC that may contribute to their success in marine ecosystems and the potential biogeochemical importance of the group in processing DON.

  4. [Degradation of purine nucleotides in patients with chronic obstruction to airflow].

    PubMed

    Mateos Antón, F; García Puig, J; Gómez Fernández, P; Ramos Hernández, T; López Jiménez, M

    1989-03-11

    The increase in hypoxanthine (Hx), xanthine (X), uric acid (VA) and total purines (TP) that may be found in several clinical conditions associated with tissue hypoxia has been attributed to an increase in adenine nucleotides degradation by a reduced ATP synthesis caused by oxygen deprivation. To test this hypothesis we have investigated the urinary excretion of Hx, X, VA, TP and radioactivity elimination after labeling the adenine nucleotides with adenine (8-14C) in 5 patients with chronic airflow obstruction (CAFO), in the basal state and after oxygen therapy (FiO2, 24%). The results were compared with those from 4 normal individuals. Patients with COFA showed an increase of the renal elimination of Hx, X, VA, TP and radioactivity, which was significantly different from the control group (p less than 0.05). Oxygen administration was associated with a significant reduction in the excretion of purines and radioactivity (p less than 0.01), which decreased to values similar to those found in normal individuals. These findings suggest that in patients with COFA and severe hypoxemia there is a marked increase in the degradation of adenine nucleotides. The normalization of the purine and radioactivity excretion after oxygen therapy points to a basic role of oxygen in the catabolism of adenine nucleotides. PMID:2716427

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

    NASA Technical Reports Server (NTRS)

    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.

  6. Ab initio molecular orbital study of the structures of purine hydrates

    SciTech Connect

    Colson, A.O.; Sevilla, M.D.

    1996-03-14

    The structures of the isomers of purine hydrates [4(5)-hydroxy-5(4)-hydropurines] have been geometry optimized with ab initio quantum chemical methods at the 6-31G{sup *} basis set and with the semiempirical method PM3. These hydrates which can result from reduction of radical species formed by attack of hydroxyl radical at the 4,5 double bond in the purines, show significant geometrical distortion when compared to the natural bases. More specifically, the cis isomers adopt a `butterfly` conformation, while in the trans isomers, the pyrimidine and imidazole rings tilt opposite to each other. Our results predict the cis purine hydrate isomers are far more stable than the trans isomers by 10-18 kcal/mol at the 6-31G{sup *} level, whereas the 4-hydroxy-5-hydropurines are found to be slightly more energetically stable than the 5-hydroxy-4-hydropurines. The `butterfly` conformation of the cis isomers constitutes a bulky lesion which will result in a significant distortion of the DNA helix. 33 refs., 2 figs., 3 tabs.

  7. Entrepreneurship and UK Doctoral Graduates

    ERIC Educational Resources Information Center

    Hooley, Tristram; Bentley, Kieran; Marriott, John

    2011-01-01

    This paper discusses the experience of UK doctoral graduates in pursuing entrepreneurial careers: there is evidence that this applies to a substantial number--about 10%--of doctoral graduates. The nature of their experience was explored using 37 interviews with doctoral entrepreneurs. The research was funded by Vitae (www.vitae.ac.uk), an…

  8. Role of ATP and related purines in inhibitory neurotransmission to the pig urinary bladder neck

    PubMed Central

    Hernández, Medardo; Knight, Gillian E; Wildman, Scott SP; Burnstock, Geoffrey

    2009-01-01

    Background and purpose: As adenosine 5′-triphosphate (ATP) is one of the inhibitory mediators of the bladder outflow region, this study investigates the possible release of ATP or related purines in response to electrical field stimulation (EFS) and the purinoceptor(s) involved in nerve-mediated relaxations of the pig urinary bladder neck. Experimental approach: Urothelium-denuded and intact phenylephrine-precontracted strips were mounted in organ baths containing physiological saline solution at 37°C and gassed with 95% O2 and 5% CO2 for isometric force recordings. Key results: EFS, in the presence of atropine, guanethidine and NG-nitro-L-arginine, and exogenous purines, produced frequency- and concentration-dependent relaxations respectively. Adenosine 5′-diphosphate (ADP) and adenosine were more potent than ATP in producing relaxation, while uridine 5′-triphosphate, uridine 5′-diphosphate and α,β-methylene ATP were less effective. The non-selective P2 antagonist suramin, and the P2Y1 and P1 receptor blockers 2′-deoxy-N6-methyladenosine 3′,5′-bisphosphate tetrasodium and 8-(p-sulphophenyl)theophylline, respectively, inhibited the responses to EFS and ATP. The P1 agonist's potency was: 5′-N-ethylcarboxamidoadenosine (NECA)>4-2[[6-amino-9-(N-ethyl-b-D-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzene propanoic acid hydrochloride>2-chloro-N6-cyclopentyladenosine>-2-chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-b-D-ribofuranuronamide = adenosine. 4-(-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl) phenol, an A2A antagonist, reduced the relaxations to EFS, adenosine and NECA. In urothelium-intact samples, relaxations to EFS and purines were smaller than in urothelium-denuded preparations. Neuronal voltage-gated Na+ channels blockade failed to modify ATP relaxations. At basal tension, EFS- and ATP-induced contractions were resistant to desensitization or blockade of P2X1 and P2X3 receptors

  9. Impact of volcanic eruptions on the climate of the 1st millennium AD in a comprehensive climate simulation

    NASA Astrophysics Data System (ADS)

    Wagner, Sebastian; Zorita, Eduardo

    2015-04-01

    The climate of the 1st millennium AD shows some remarkable differences compared to the last millennium concerning variation in external forcings. Together with an orbitally induced increased solar insolation during the northern hemisphere summer season and a general lack of strong solar minima, the frequency and intensity of large tropical and extratropical eruptions is decreased. Here we present results of a new climate simulation carried out with the comprehensive Earth System Model MPI-ESM-P forced with variations in orbital, solar, volcanic and greenhouse gas variations and land use changes for the last 2,100 years. The atmospheric model has a horizontal resolution of T63 (approx. 125x125 km) and therefore also allows investigations of regional-to-continental scale climatic phenomena. The volcanic forcing was reconstructed based on a publication by Sigl et al. (2013) using the sulfate records of the NEEM and WAIS ice cores. To obtain information on the aerosol optical depth (AOD) these sulfate records were scaled to an established reconstruction from Crowley and Unterman (2010), which is also a standard forcing in the framework of CMIP5/PMIP3. A comparison between the newly created data set with the Crowley and Unterman dataset reveals that the new reconstruction shows in general weaker intensities, especially of the large tropical outbreaks and fewer northern hemispheric small-to-medium scale eruptions. However, the general pattern in the overlapping period is similar. A hypothesis that can be tested with the simulation is whether the reduced volcanic intensity of the 1st millennium AD contributed to the elevated temperature levels over Europe, evident within a new proxy-based reconstruction. On the other hand, the few but large volcanic eruptions, e.g. the 528 AD event, also induced negative decadal-scale temperature anomalies. Another interesting result of the simulation relates to the 79 AD eruption of the Vesuvius, which caused the collapse of the city of

  10. The purine degradation pathway: possible role in paralytic shellfish toxin metabolism in the cyanobacterium Planktothrix sp. FP1.

    PubMed

    Pomati, F; Manarolla, G; Rossi, O; Vigetti, D; Rossetti, C

    2001-12-01

    The paralytic shellfish toxins (PSTs) are potent neurotoxic alkaloids and their major biological effect is due to the blockage of voltage-gated sodium channels in excitable cells. They have been recognised as an important health risk for humans, animals, and ecosystems worldwide. The metabolic pathways that lead to the production and the degradation of these toxic metabolites are still unknown. In this study, we investigated the possible link between PST accumulation and the activation of the metabolism that leads to purine degradation in the filamentous freshwater cyanobacterium Planktothrix sp. FP1. The purine catabolic pathway is related to the nitrogen microcycle in water environments, in which cyanobacteria use traces of purines and ureides as a nitrogen source for growth. Thus, the activity of allantoicase, a key inducible enzyme of this metabolism, was used as tool for assaying the activation of the purine degradation pathway. The enzyme and the pathway were induced by allantoic acid, the direct substrate of allantoicase, as well as by adenine and, to a lower degree, by urea, one of the main products of purine catabolism. Crude cell extract of Escherichia coli was also employed and showed the best induction of allantoicase activity. In culture, Planktothrix sp. FP1 showed a differential accumulation of PST in consequence of the induction with different substrates. The cyanobacterial culture induced with allantoic acid accumulated 61.7% more toxins in comparison with the control. On the other hand, the cultures induced with adenine, urea, and the E. coli extract showed low PST accumulation, respectively, 1%, 38%, and 5% of the total toxins content detected in the noninduced culture. A degradation pathway for the PSTs can be hypothesised: as suggested for purine alkaloids in higher plants, saxitoxin (STX) and derivatives may also be converted into xanthine, urea, and further to CO2 and NH4+ or recycled in the primary metabolism through the purine degradation

  11. Improving conversion yield of fermentable sugars into fuel ethanol in 1st generation yeast-based production processes.

    PubMed

    Gombert, Andreas K; van Maris, Antonius J A

    2015-06-01

    Current fuel ethanol production using yeasts and starch or sucrose-based feedstocks is referred to as 1st generation (1G) ethanol production. These processes are characterized by the high contribution of sugar prices to the final production costs, by high production volumes, and by low profit margins. In this context, small improvements in the ethanol yield on sugars have a large impact on process economy. Three types of strategies used to achieve this goal are discussed: engineering free-energy conservation, engineering redox-metabolism, and decreasing sugar losses in the process. Whereas the two former strategies lead to decreased biomass and/or glycerol formation, the latter requires increased process and/or yeast robustness.

  12. Plasma properties from the multi-wavelength analysis of the November 1st 2003 CME/shock event

    PubMed Central

    Benna, Carlo; Mancuso, Salvatore; Giordano, Silvio; Gioannini, Lorenzo

    2012-01-01

    The analysis of the spectral properties and dynamic evolution of a CME/shock event observed on November 1st 2003 in white-light by the LASCO coronagraph and in the ultraviolet by the UVCS instrument operating aboard SOHO, has been performed to compute the properties of some important plasma parameters in the middle corona below about 2R⊙. Simultaneous observations obtained with the MLSO/Mk4 white-light coronagraph, providing both the early evolution of the CME expansion in the corona and the pre-shock electron density profile along the CME front, were also used to study this event. By combining the above information with the analysis of the metric type II radio emission detected by ground-based radio spectrographs, we finally derive estimates of the values of the local Alfvén speed and magnetic field strength in the solar corona. PMID:25685432

  13. The genomes of the South American opossum (Monodelphis domestica) and platypus (Ornithorhynchus anatinus) encode a more complete purine catabolic pathway than placental mammals

    PubMed Central

    Keebaugh, Alaine C.; Thomas, James W.

    2009-01-01

    The end product of purine catabolism varies amongst vertebrates and is a consequence of independent gene inactivation events that have truncated the purine catabolic pathway. Mammals have traditionally been grouped into two classes based on their end product of purine catabolism: most mammals, whose end product is allantoin due to an ancient loss of allantoinase (ALLN), and the hominoids, whose end product is uric acid due to recent inactivations of urate oxidase (UOX). However little is known about purine catabolism in marsupials and monotremes. Here we report the results of a comparative genomics study designed to characterize the purine catabolic pathway in a marsupial, the South American opossum (Monodelphis domestica), and a monotreme, the platypus (Ornithorhynchus anatinus). We found that both genomes encode a more complete set of genes for purine catabolism than do eutherians and conclude that a near complete purine catabolic pathway was present in the common ancestor of all mammals, and that the loss of ALLN is specific to placental mammals. Our results therefore provide a revised history for gene loss in the purine catabolic pathway and suggest that marsupials and monotremes represent a third class of mammals with respect to their end products of purine catabolism. PMID:20161190

  14. Levels of innate immune factors in preterm and term mothers' breast milk during the 1st month postpartum.

    PubMed

    Trend, Stephanie; Strunk, Tobias; Lloyd, Megan L; Kok, Chooi Heen; Metcalfe, Jessica; Geddes, Donna T; Lai, Ching Tat; Richmond, Peter; Doherty, Dorota A; Simmer, Karen; Currie, Andrew

    2016-04-14

    There is a paucity of data on the effect of preterm birth on the immunological composition of breast milk throughout the different stages of lactation. We aimed to characterise the effects of preterm birth on the levels of immune factors in milk during the 1st month postpartum, to determine whether preterm milk is deficient in antimicrobial factors. Colostrum (days 2-5 postpartum), transitional milk (days 8-12) and mature milk (days 26-30) were collected from mothers of extremely preterm (<28 weeks of gestation, n 15), very preterm (28-<32 weeks of gestation, n 15), moderately preterm (32-<37 weeks of gestation, n 15) and term infants (37-41 weeks of gestation, n 15). Total protein, lactoferrin, secretory IgA, soluble CD14 receptor (sCD14), transforming growth factor-β2 (TGF-β2), α defensin 5 (HD5), β defensins 1 (HBD1) and 2, IL-6, IL-10, IL-13, interferon-γ, TNF-α and lysozyme (LZ) were quantified in milk. We examined the effects of lactation stage, gestational age, volume of milk expressed, mode of delivery, parity and maternal infection on milk immune factor concentrations using repeated-measures regression analysis. The concentrations of all factors except LZ and HD5 decreased over the 1st month postpartum. Extremely preterm mothers had significantly higher concentrations of HBD1 and TGF-β2 in colostrum than term mothers did. After controlling for other variables in regression analyses, preterm birth was associated with higher concentrations of HBD1, LZ and sCD14 in milk samples. In conclusion, preterm breast milk contains significantly higher concentrations of some immune proteins than term breast milk.

  15. Fluoride in UK rivers.

    PubMed

    Neal, Colin; Neal, Margaret; Davies, Helen; Smith, Jennifer

    2003-10-01

    Fluoride concentrations in eastern UK rivers (the Humber, Tweed, Wear, Great Ouse and Thames) are described based on information collected within the Land-Ocean Interaction Study (LOIS) and by the Environment Agency (EA) of England and Wales. The results show varied fluoride concentrations across the region, with a range from <0.01 to >10 mg l(-1); and mean, median and range in mean concentrations of 0.30, 0.21 and 0.05-3.38 mg l(-1) (excluding one outlier point), respectively. Within the main rivers and tributaries, the mean fluoride concentration varied from approximately 0.5 to over 2 mg l(-1) and the highest values occurred within the Don basin (Don, Dearne and Rother) and parts of the Trent basin (upper Tame and mid-upper Derbyshire Derwent) in highly industrialised and urbanised areas (Sheffield and Rotherham in the Don basin; Birmingham and Derby on the Trent). For localised inputs to the rivers, fluoride concentrations were slightly higher, and considerably higher in one outlier case. Correspondingly, the other rivers examined typically had mean fluoride concentrations between approximately 0.2 and 0.5 mg l(-1), but fluoride concentrations were lower in the headwater areas. As there is much less information on fluoride levels in upland areas, extensive data collected as part of an acid waters survey are used to show that fluoride concentrations are generally less than 0.1 mg l(-1) for the upland UK. The data are summarised in terms of both fluoride concentrations and flux, and the values are cross-referenced to other determinands collected within LOIS. The high positive correlation with boron and negative correlation with flow show the importance of point source (sewage) inputs of fluoride, while strong positive correlations between fluoride and barium indicate the relative importance of vein mineralisation in the bedrock in supplying fluoride to the waters of the Yorkshire Ouse and its tributaries. There seems to be some process that limits the fluoride

  16. Fluoride in UK rivers.

    PubMed

    Neal, Colin; Neal, Margaret; Davies, Helen; Smith, Jennifer

    2003-10-01

    Fluoride concentrations in eastern UK rivers (the Humber, Tweed, Wear, Great Ouse and Thames) are described based on information collected within the Land-Ocean Interaction Study (LOIS) and by the Environment Agency (EA) of England and Wales. The results show varied fluoride concentrations across the region, with a range from <0.01 to >10 mg l(-1); and mean, median and range in mean concentrations of 0.30, 0.21 and 0.05-3.38 mg l(-1) (excluding one outlier point), respectively. Within the main rivers and tributaries, the mean fluoride concentration varied from approximately 0.5 to over 2 mg l(-1) and the highest values occurred within the Don basin (Don, Dearne and Rother) and parts of the Trent basin (upper Tame and mid-upper Derbyshire Derwent) in highly industrialised and urbanised areas (Sheffield and Rotherham in the Don basin; Birmingham and Derby on the Trent). For localised inputs to the rivers, fluoride concentrations were slightly higher, and considerably higher in one outlier case. Correspondingly, the other rivers examined typically had mean fluoride concentrations between approximately 0.2 and 0.5 mg l(-1), but fluoride concentrations were lower in the headwater areas. As there is much less information on fluoride levels in upland areas, extensive data collected as part of an acid waters survey are used to show that fluoride concentrations are generally less than 0.1 mg l(-1) for the upland UK. The data are summarised in terms of both fluoride concentrations and flux, and the values are cross-referenced to other determinands collected within LOIS. The high positive correlation with boron and negative correlation with flow show the importance of point source (sewage) inputs of fluoride, while strong positive correlations between fluoride and barium indicate the relative importance of vein mineralisation in the bedrock in supplying fluoride to the waters of the Yorkshire Ouse and its tributaries. There seems to be some process that limits the fluoride

  17. Social and moral norm differences among Portuguese 1st and 6th year medical students towards their intention to comply with hand hygiene.

    PubMed

    Roberto, Magda S; Mearns, Kathryn; Silva, Silvia A

    2012-01-01

    This study examines social and moral norms towards the intention to comply with hand hygiene among Portuguese medical students from 1st and 6th years (N = 175; 121 from the 1st year, 54 from the 6th year). The study extended the theory of planned behaviour theoretical principles and hypothesised that both subjective and moral norms will be the best predictors of 1st and 6th year medical students' intention to comply with hand hygiene; however, these predictors ability to explain intention variance will change according to medical students' school year. Results indicated that the subjective norm, whose referent focuses on professors, is a relevant predictor of 1st year medical students' intention, while the subjective norm that emphasises the relevance of colleagues predicts the intentions of medical students from the 6th year. In terms of the moral norm, 6th year students' intention is better predicted by a norm that interferes with compliance; whereas intentions from 1st year students are better predicted by a norm that favours compliance. Implications of the findings highlight the importance of role models and mentors as key factors in teaching hand hygiene in medical undergraduate curricula. PMID:22111788

  18. Functional identification of SLC43A3 as an equilibrative nucleobase transporter involved in purine salvage in mammals

    PubMed Central

    Furukawa, Junji; Inoue, Katsuhisa; Maeda, Junya; Yasujima, Tomoya; Ohta, Kinya; Kanai, Yoshikatsu; Takada, Tappei; Matsuo, Hirotaka; Yuasa, Hiroaki

    2015-01-01

    The purine salvage pathway plays a major role in the nucleotide production, relying on the supply of nucleobases and nucleosides from extracellular sources. Although specific transporters have been suggested to be involved in facilitating their transport across the plasma membrane in mammals, those which are specifically responsible for utilization of extracellular nucleobases remain unknown. Here we present the molecular and functional characterization of SLC43A3, an orphan transporter belonging to an amino acid transporter family, as a purine-selective nucleobase transporter. SLC43A3 was highly expressed in the liver, where it was localized to the sinusoidal membrane of hepatocytes, and the lung. In addition, SLC43A3 expressed in MDCKII cells mediated the uptake of purine nucleobases such as adenine, guanine, and hypoxanthine without requiring typical driving ions such as Na+ and H+, but it did not mediate the uptake of nucleosides. When SLC43A3 was expressed in APRT/HPRT1-deficient A9 cells, adenine uptake was found to be low. However, it was markedly enhanced by the introduction of SLC43A3 with APRT. In HeLa cells, knock-down of SLC43A3 markedly decreased adenine uptake. These data suggest that SLC43A3 is a facilitative and purine-selective nucleobase transporter that mediates the cellular uptake of extracellular purine nucleobases in cooperation with salvage enzymes. PMID:26455426

  19. [High-sensitivity analysis of purines in alcoholic beverages using hydrophilic interaction chromatography coupled with tandem mass spectrometry].

    PubMed

    Kakigi, Yasuhiro; Yoshioka, Toshiaki; Nagatomi, Yasushi; Uyama, Atsuo; Mochizuki, Naoki

    2014-01-01

    In this study, we established a high-sensitivity analytical method for purines in alcoholic beverages using hydrophilic interaction chromatography coupled with tandem mass spectrometry. The alcoholic beverages were hydrolyzed with perchloric acid (60%) and subjected to strong cation exchange solid-phase extraction (Bond Elut SCX). The four purine bases (hypoxanthine, adenine, xanthine, guanine) in the extracted solution were separated by hydrophilic interaction chromatography with TSKgel Amide-80 as a separation column, 10 mM ammonium formate (pH 2.0) as mobile phase A, and acetonitrile/100 mM ammonium formate (pH 2.0) (90/10) as mobile phase B. The detection of purine bases was performed by tandem mass spectrometry with ESI. The linearity of this analytical method was not less than 0.996, and the repeatability was not more than 8.4% for each purine base. The recovery was in the range of 60-105%, and the detection limit was not more than 0.005 mg/100 mL. This established method is expected to be useful for quality control and surveillance of purines in alcoholic beverages.

  20. Structure and function of nucleoside hydrolases from Physcomitrella patens and maize catalyzing the hydrolysis of purine, pyrimidine, and cytokinin ribosides.

    PubMed

    Kopecná, Martina; Blaschke, Hanna; Kopecny, David; Vigouroux, Armelle; Koncitíková, Radka; Novák, Ondrej; Kotland, Ondrej; Strnad, Miroslav; Moréra, Solange; von Schwartzenberg, Klaus

    2013-12-01

    We present a comprehensive characterization of the nucleoside N-ribohydrolase (NRH) family in two model plants, Physcomitrella patens (PpNRH) and maize (Zea mays; ZmNRH), using in vitro and in planta approaches. We identified two NRH subclasses in the plant kingdom; one preferentially targets the purine ribosides inosine and xanthosine, while the other is more active toward uridine and xanthosine. Both subclasses can hydrolyze plant hormones such as cytokinin ribosides. We also solved the crystal structures of two purine NRHs, PpNRH1 and ZmNRH3. Structural analyses, site-directed mutagenesis experiments, and phylogenetic studies were conducted to identify the residues responsible for the observed differences in substrate specificity between the NRH isoforms. The presence of a tyrosine at position 249 (PpNRH1 numbering) confers high hydrolase activity for purine ribosides, while an aspartate residue in this position confers high activity for uridine. Bud formation is delayed by knocking out single NRH genes in P. patens, and under conditions of nitrogen shortage, PpNRH1-deficient plants cannot salvage adenosine-bound nitrogen. All PpNRH knockout plants display elevated levels of certain purine and pyrimidine ribosides and cytokinins that reflect the substrate preferences of the knocked out enzymes. NRH enzymes thus have functions in cytokinin conversion and activation as well as in purine and pyrimidine metabolism.

  1. GMP synthase is essential for viability and infectivity of Trypanosoma brucei despite a redundant purine salvage pathway

    PubMed Central

    Li, Qiong; Leija, Christopher; Rijo-Ferreira, Filipa; Chen, Jun; Cestari, Igor; Stuart, Kenneth; Tu, Benjamin P.; Phillips, Margaret A.

    2015-01-01

    Summary The causative agent of human African trypanosomiasis, Trypanosoma brucei, lacks de novo purine biosynthesis and depends on purine salvage from the host. The purine salvage pathway is redundant and contains two routes to guanosine-5′-monophosphate (GMP) formation: conversion from xanthosine-5′-monophosphate (XMP) by GMP synthase (GMPS) or direct salvage of guanine by hypoxanthine-guanine phosphoribosyltransferase (HGPRT). We show recombinant T. brucei GMPS efficiently catalyzes GMP formation. Genetic knockout of GMPS in bloodstream parasites led to depletion of guanine nucleotide pools and was lethal. Growth of gmps null cells was only rescued by supraphysiological guanine concentrations (100 μM) or by expression of an extrachromosomal copy of GMPS. Hypoxanthine was a competitive inhibitor of guanine rescue, consistent with a common uptake/metabolic conversion mechanism. In mice, gmps null parasites were unable to establish an infection demonstrating that GMPS is essential for virulence and that plasma guanine is insufficient to support parasite purine requirements. These data validate GMPS as a potential therapeutic target for treatment of HAT. The ability to strategically inhibit key metabolic enzymes in the purine pathway unexpectedly bypasses its functional redundancy by exploiting both the nature of pathway flux and the limited nutrient environment of the parasite's extracellular niche. PMID:26043892

  2. UK nurses are needed overseas.

    PubMed

    2016-09-28

    Could UK nurse volunteers working overseas be instrumental in reducing healthcare inequalities? João Marçal-Grilo, writing in Nursing Older People, is adamant that UK-trained nurses have the potential to eradicate poverty worldwide and should be offered opportunities to volunteer abroad and practise alongside colleagues in low and middle-income countries. Not only will this have a positive effect on older adults who are affected by a lack of qualified staff working in developing countries, UK-trained nurses can gain new skills that can benefit nursing practice in the UK. The article provides examples of current voluntary projects in older person care taking place in Sri Lanka and Nepal. PMID:27682572

  3. UK businesses bag innovation awards

    NASA Astrophysics Data System (ADS)

    Banks, Michael

    2015-09-01

    Five UK firms have received innovation awards from the Institute of Physics (IOP), which publishes Physics World. Hallmarq Veterinary Imaging, Metrasens, M Squared Lasers, Silixa and Tracerco have all won an IOP award for developing new innovative products.

  4. UK nurses are needed overseas.

    PubMed

    2016-09-28

    Could UK nurse volunteers working overseas be instrumental in reducing healthcare inequalities? João Marçal-Grilo, writing in Nursing Older People, is adamant that UK-trained nurses have the potential to eradicate poverty worldwide and should be offered opportunities to volunteer abroad and practise alongside colleagues in low and middle-income countries. Not only will this have a positive effect on older adults who are affected by a lack of qualified staff working in developing countries, UK-trained nurses can gain new skills that can benefit nursing practice in the UK. The article provides examples of current voluntary projects in older person care taking place in Sri Lanka and Nepal.

  5. The purine repressor of Bacillus subtilis: a novel combination of domains adapted for transcription regulation.

    PubMed

    Sinha, Sangita C; Krahn, Joseph; Shin, Byung Sik; Tomchick, Diana R; Zalkin, Howard; Smith, Janet L

    2003-07-01

    The purine repressor from Bacillus subtilis, PurR, represses transcription from a number of genes with functions in the synthesis, transport, and metabolism of purines. The 2.2-A crystal structure of PurR reveals a two-domain protein organized as a dimer. The larger C-terminal domain belongs to the PRT structural family, in accord with a sequence motif for binding the inducer phosphoribosylpyrophosphate (PRPP). The PRT domain is fused to a smaller N-terminal domain that belongs to the winged-helix family of DNA binding proteins. A positively charged surface on the winged-helix domain likely binds specific DNA sequences in the recognition site. A second positively charged surface surrounds the PRPP site at the opposite end of the PurR dimer. Conserved amino acids in the sequences of PurR homologs in 21 gram-positive bacteria cluster on the proposed recognition surface of the winged-helix domain and around the PRPP binding site at the opposite end of the molecule, supporting a common function of DNA and PRPP binding for all of the proteins. The structure supports a binding mechanism in which extended regions of DNA interact with extensive protein surface. Unlike most PRT proteins, which are phosphoribosyltransferases (PRTases), PurR lacks catalytic activity. This is explained by a tyrosine side chain that blocks the site for a nucleophile cosubstrate in PRTases. Thus, B. subtilis has adapted an enzyme fold to serve as an effector-binding domain and has used it in a novel combination with the DNA-binding winged-helix domain as a repressor of purine genes.

  6. ATP and related purines stimulate motility, spatial congregation, and coalescence in red algal spores.

    PubMed

    Huidobro-Toro, Juan P; Donoso, Verónica; Flores, Verónica; Santelices, Bernabé

    2015-04-01

    Adenosine 5'-triphosphate (ATP) is a versatile extracellular signal along the tree of life, whereas cAMP plays a major role in vertebrates as an intracellular messenger for hormones, transmitters, tastants, and odorants. Since red algal spore coalescence may be considered analogous to the congregation process of social amoeba, which is stimulated by cAMP, we ascertained whether exogenous applications of ATP, cAMP, adenine, or adenosine modified spore survival and motility, spore settlement and coalescence. Concentration-response studies were performed with carpospores of Mazzaella laminarioides (Gigartinales), incubated with and without added purines. Stirring of algal blades released ADP/ATP to the cell media in a time-dependent manner. 10-300 μM ATP significantly increased spore survival; however, 1,500 μM ATP, cAMP or adenine induced 100% mortality within less than 24 h; the exception was adenosine, which up to 3,000 μM, did not alter spore survival. ATP exposure elicited spore movement with speeds of 2.2-2.5 μm · s(-1) . 14 d after 1,000 μM ATP addition, spore abundance in the central zone of the plaques was increased 2.7-fold as compared with parallel controls. Likewise, 1-10 μM cAMP or 30-100 μM adenine also increased central zone spore abundance, albeit these purines were less efficacious than ATP; adenosine up to 3,000 μM did not influence settlement. Moreover, 1,000 μM ATP markedly accelerated coalescence, the other purines caused a variable effect. We conclude that exogenous cAMP, adenine, but particularly ATP, markedly influence red algal spore physiology; effects are compatible with the expression of one or more membrane purinoceptor(s), discarding adenosine receptor participation. PMID:26986520

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

    PubMed Central

    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. PMID:27799897

  8. ATP and related purines stimulate motility, spatial congregation, and coalescence in red algal spores.

    PubMed

    Huidobro-Toro, Juan P; Donoso, Verónica; Flores, Verónica; Santelices, Bernabé

    2015-04-01

    Adenosine 5'-triphosphate (ATP) is a versatile extracellular signal along the tree of life, whereas cAMP plays a major role in vertebrates as an intracellular messenger for hormones, transmitters, tastants, and odorants. Since red algal spore coalescence may be considered analogous to the congregation process of social amoeba, which is stimulated by cAMP, we ascertained whether exogenous applications of ATP, cAMP, adenine, or adenosine modified spore survival and motility, spore settlement and coalescence. Concentration-response studies were performed with carpospores of Mazzaella laminarioides (Gigartinales), incubated with and without added purines. Stirring of algal blades released ADP/ATP to the cell media in a time-dependent manner. 10-300 μM ATP significantly increased spore survival; however, 1,500 μM ATP, cAMP or adenine induced 100% mortality within less than 24 h; the exception was adenosine, which up to 3,000 μM, did not alter spore survival. ATP exposure elicited spore movement with speeds of 2.2-2.5 μm · s(-1) . 14 d after 1,000 μM ATP addition, spore abundance in the central zone of the plaques was increased 2.7-fold as compared with parallel controls. Likewise, 1-10 μM cAMP or 30-100 μM adenine also increased central zone spore abundance, albeit these purines were less efficacious than ATP; adenosine up to 3,000 μM did not influence settlement. Moreover, 1,000 μM ATP markedly accelerated coalescence, the other purines caused a variable effect. We conclude that exogenous cAMP, adenine, but particularly ATP, markedly influence red algal spore physiology; effects are compatible with the expression of one or more membrane purinoceptor(s), discarding adenosine receptor participation.

  9. Targeting the Parasite's DNA with Methyltriazenyl Purine Analogs Is a Safe, Selective, and Efficacious Antitrypanosomal Strategy

    PubMed Central

    Wanner, Martin J.; Alkhaldi, Abdulsalam A. M.; Ebiloma, Godwin U.; Barnes, Rebecca L.; Kaiser, Marcel; Brun, Reto; McCulloch, Richard; Koomen, Gerrit-Jan

    2015-01-01

    The human and veterinary disease complex known as African trypanosomiasis continues to inflict significant global morbidity, mortality, and economic hardship. Drug resistance and toxic side effects of old drugs call for novel and unorthodox strategies for new and safe treatment options. We designed methyltriazenyl purine prodrugs to be rapidly and selectively internalized by the parasite, after which they disintegrate into a nontoxic and naturally occurring purine nucleobase, a simple triazene-stabilizing group, and the active toxin: a methyldiazonium cation capable of damaging DNA by alkylation. We identified 2-(3-acetyl-3-methyltriazen-1-yl)-6-hydroxypurine (compound 1) as a new lead compound, which showed submicromolar potency against Trypanosoma brucei, with a selectivity index of >500, and it demonstrated a curative effect in animal models of acute trypanosomiasis. We investigated the mechanism of action of this lead compound and showed that this molecule has significantly higher affinity for parasites over mammalian nucleobase transporters, and it does not show cross-resistance with current first-line drugs. Once selectively accumulated inside the parasite, the prodrug releases a DNA-damaging methyldiazonium cation. We propose that ensuing futile cycles of attempted mismatch repair then lead to G2/M phase arrest and eventually cell death, as evidenced by the reduced efficacy of this purine analog against a mismatch repair-deficient (MSH2−/−) trypanosome cell line. The observed absence of genotoxicity, hepatotoxicity, and cytotoxicity against mammalian cells revitalizes the idea of pursuing parasite-selective DNA alkylators as a safe chemotherapeutic option for the treatment of human and animal trypanosomiasis. PMID:26282430

  10. Modulation of AMP deaminase in rat hearts subjected to ischemia and reperfusion by purine riboside.

    PubMed

    Borkowski, T; Lipinski, M; Kaminski, R; Krzyminska-Stasiuk, E; Langowska, M; Raczak, G; Slominska, E M; Smolenski, R T

    2008-06-01

    Changes in AMP deaminase (AMPD) activity influence heart function and progression of heart disease, but the underlying mechanism is unknown. We evaluated the effect of purine riboside (Purr) on the activity of AMPD in perfused rat hearts and in isolated rat cardiomyocytes. Brief perfusion of the pre-ischemic heart with 200 micro M Purr resulted in activation of AMPD, more pronounced degradation of the adenine nucleotides, and reduced recovery of the adenine nucleotide pool during reperfusion. Brief incubation of rat cardiomyocytes with 200 micro M Purr also activated AMPD, while prolonged exposure resulted in enzyme inhibition. We conclude that Purr activates AMPD, whereas metabolites of this compound may inhibit the enzyme.

  11. HCN - A plausible source of purines, pyrimidines and amino acids on the primitive earth

    NASA Technical Reports Server (NTRS)

    Ferris, J.-P.; Joshi, P. C.; Edelson, E. H.; Lawless, J. G.

    1978-01-01

    Dilute (0.1 M) solutions of HCN condense to oligomers at pH 9.2, and hydrolysis of these oligomers yields 4,5-dihydroxypyrimidine, orotic acid, 5-hydroxyuracil, adenine, 4-aminoimidazole-5-carboxamide, and amino acids. It is suggested that the three main classes of nitrogen-containing biomolecules - purines, pyrimidines, and amino acids may have originated from HCN on the primitive earth. It is also suggested that the presence of orotic acid and 4-aminoimidazole-5-carboxamide might indicate that contemporary biosynthetic pathways for nucleotides evolved from the compounds released on hydrolysis of HCN oligomers.

  12. Crystallographic and docking studies of purine nucleoside phosphorylase from Mycobacterium tuberculosis.

    PubMed

    Ducati, Rodrigo G; Basso, Luiz A; Santos, Diógenes S; de Azevedo, Walter F

    2010-07-01

    This work describes for the first time the structure of purine nucleoside phosphorylase from Mycobacterium tuberculosis (MtPNP) in complex with sulfate and its natural substrate, 2'-deoxyguanosine, and its application to virtual screening. We report docking studies of a set of molecules against this structure. Application of polynomial empirical scoring function was able to rank docking solutions with good predicting power which opens the possibility to apply this new criterion to analyze docking solutions and screen small-molecule databases for new chemical entities to inhibit MtPNP.

  13. Validation and steady-state analysis of a power-law model of purine metabolism in man.

    PubMed Central

    Curto, R; Voit, E O; Sorribas, A; Cascante, M

    1997-01-01

    The paper introduces a model of human purine metabolism in situ. Chosen from among several alternative system descriptions, the model is formulated as a Generalized Mass Action system within Biochemical Systems Theory and validated with analyses of steady-state and dynamic characteristics. Eigenvalue and sensitivity analyses indicate that the model has a stable and robust steady-state. The model quite accurately reproduces numerous biochemical and clinical observations in healthy subjects as well as in patients with disorders of purine metabolism. These results suggest that the model can be used to assess biochemical and clinical aspects of human purine metabolism. It provides a means of exploring effects of enzyme deficiencies and is a potential tool for identifying steps of the pathway that could be the target of therapeutical intervention. Numerous quantitative comparisons with data are given. The model can be used for biomathematical exploration of relationships between enzymic deficiencies and clinically manifested diseases. PMID:9210399

  14. Stereoselective synthesis of 9-beta-d-arabianofuranosyl guanine and 2-amino-9-(beta-d-arabianofuranosyl)purine.

    PubMed

    Yu, Xue-Jun; Li, Gai-Xia; Qi, Xiou-Xiang; Deng, You-Quan

    2005-02-01

    9-beta-d-Arabianofuranosyl guanine (6) and 2-amino-9-(beta-d-arabianofuranosyl)purine (8) were prepared from 2-amino-6-chloro-9-(2,3,5-triphenylmethoxyl-beta-d-arabianofuranosyl)purine (4), a key intermediate which was stereoselectively prepared from 2,3,5-triphenylmethoxyl-d-arabianofuranose and 2-amino-6-chloro-purine. The yield of the intermediate was obviously improved and only beta-isomer was formed by using the activated molecular sieve as environmental friendly catalyst, overcoming the defect that a 1:1 mixture of alpha- and beta-isomers was formed, which was difficult to separate, when toxic mercury cyanide was previously used as catalyst.

  15. A peripherally selective diphenyl purine antagonist of the CB1 receptor

    PubMed Central

    Fulp, Alan; Bortoff, Katherine; Zhang, Yanan; Mathews, James; Snyder, Rodney; Fennell, Tim; Marusich, Julie A.; Wiley, Jenny L.; Seltzman, Herbert; Maitra, Rangan

    2014-01-01

    Antagonists of the CB1 receptor can be useful in the treatment of several diseases including obesity, diabetes, and liver disease. However, to date, the only clinically approved CB1 receptor antagonist, rimonabant, was withdrawn due to adverse CNS related side effects such as depression and suicidal ideation. Since rimonabant’s withdrawal, several groups have begun pursuing peripherally selective CB1 antagonists. These compounds are expected to be devoid of undesirable CNS related effects but maintain efficacy through antagonism of peripherally expressed CB1 receptors within target tissues. Reported here are our latest results toward development of a peripherally selective analog of the diphenyl purine CB1 antagonist otenabant 1. Compound 9 (N-{1-[8-(2-Chlorophenyl)-9-(4-chlorophenyl)-9H-purin-6-yl]piperidin-4-yl}pentanamide) is a potent, orally absorbed antagonist of the CB1 receptor that is >50-fold selective for CB1 over CB2, highly selective for the periphery in a rodent model, and without efficacy in a series of in vivo assays designed to evaluate its ability to mitigate the central effects of Δ9-THC through the CB1 receptor. PMID:24041123

  16. The purine nucleotide cycle. A pathway for ammonia production in the rat kidney.

    PubMed Central

    Bogusky, R T; Lowenstein, L M; Lowenstein, J M

    1976-01-01

    Particle-free extracts prepared from kidney cortex of rat catalyze the formation of ammonia via the purine nucleotide cycle. The cycle generates ammonia and fumarate from aspartate, using catalytic amounts of inosine monophosphate, adenylosuccinate, and adenosine monophosphate. The specific activities of the enzymes of the cycle are 1.27+/-0.27 nmol/mg protein per min (SE) for adenoylosuccinate synthetase, 1.38+/-0.16 for adenylosuccinase, and 44.0+/-3.3 for AMP deaminase. Compared with controls, extracts prepared from kidneys of rats fed ammonium chloride for 2 days show a 60% increase in adenylosuccinate synthetase and a threefold increase in adenylosuccinase activity, and a greater and more rapid synthesis of ammonia and adenine nucleotide from aspartate and inosine monophosphate. Extracts prepared from kidneys of rats fed a potassium-deficient diet show a twofold increase in adenylosuccinate synthetase and a threefold increase in adenylosuccinase activity. In such extracts the rate of synthesis of ammonia and adenine nucleotide from aspartate and inosine monophosphate is also increased. These results show that the reactions of the purine nucleotide cycle are present and can operate in extracts of kidney cortex. The operational capacity of the cycle is accelerated by ammonium chloride feeding and potassium depletion, conditions known to increase renal ammonia excretion. Extracts of kidney cortex convert inosine monophosphate to uric acid. This is prevented by addition of allopurinol of 1-pyrophosphoryl ribose 5-phosphate to the reaction mixture. PMID:821968

  17. Purification and characterization of purine nucleoside phosphorylase from developing embryos of Hyalomma dromedarii.

    PubMed

    Kamel, M Y; Fahmy, A S; Ghazy, A H; Mohamed, M A

    1991-04-01

    Purine nucleoside phosphorylase from Hyalomma dromedarii, the camel tick, was purified to apparent homogeneity. A molecular weight of 56,000 - 58,000 was estimated for both the native and denatured enzyme, suggesting that the enzyme is monomeric. Unlike purine nucleoside phosphorylase preparations from other tissues, the H. dromedarii enzyme was unstable in the presence of beta-mercaptoethanol. The enzyme had a sharp pH optimum at pH 6.5. It catalyzed the phosphorolysis and arsenolysis of ribo- and deoxyribo-nucleosides of hypoxanthine and guanine, but not of adenine or pyrimidine nucleosides. The Km values of the enzyme at the optimal pH for inosine, deoxyinosine, guanosine, and deoxyguanosine were 0.31, 0.67, 0.55, and 0.33 mM, respectively. Inactivation and kinetic studies suggested that histidine and cysteine residues were essential for activity. The pKa values determined for catalytic ionizable groups were 6-7 and 8-9. The enzyme was completely inactivated by thiol reagents and reactivated by excess beta-mercaptoethanol. The enzyme was also susceptible to pH-dependent photooxidation in the presence of methylene blue, implicating histidine. Initial velocity studies showed an intersecting pattern of double-reciprocal plots of the data, consistent with a sequential mechanism. PMID:1905141

  18. Serine hydroxymethyltransferase: a key player connecting purine, folate and methionine metabolism in Saccharomyces cerevisiae.

    PubMed

    Saint-Marc, Christelle; Hürlimann, Hans C; Daignan-Fornier, Bertrand; Pinson, Benoît

    2015-11-01

    Previous genetic analyses showed phenotypic interactions between 5-amino-4-imidazole carboxamide ribonucleotide 5'-phosphate (AICAR) produced from the purine and histidine pathways and methionine biosynthesis. Here, we revisited the effect of AICAR on methionine requirement due to AICAR accumulation in the presence of the fau1 mutation invalidating folinic acid remobilization. We found that this methionine auxotrophy could be suppressed by overexpression of the methionine synthase Met6 or by deletion of the serine hydroxymethyltransferase gene SHM2. We propose that in a fau1 background, AICAR, by stimulating the transcriptional expression of SHM2, leads to a folinic acid accumulation inhibiting methionine synthesis by Met6. In addition, we uncovered a new methionine auxotrophy for the ade3 bas1 double mutant that can be rescued by overexpressing the SHM2 gene. We propose that methionine auxotrophy in this mutant is the result of a competition for 5,10-methylenetetrahydrofolate between methionine and deoxythymidine monophosphate synthesis. Altogether, our data show intricate genetic interactions between one-carbon units, purine and methionine metabolism through fine-tuning of serine hydroxymethyltransferase by AICAR and the transcription factor Bas1.

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

    PubMed Central

    Yee, Rebecca; Cui, Peng; Shi, Wanliang; Feng, Jie; Zhang, Ying

    2015-01-01

    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. PMID:27025643

  20. An Ancient Riboswitch Class in Bacteria Regulates Purine Biosynthesis and One-carbon Metabolism

    PubMed Central

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

    2015-01-01

    SUMMARY Over thirty years ago, ZTP (5-amino-4-imidazole 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 confirms 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. PMID:25616067

  1. Crystal structure and molecular dynamics studies of purine nucleoside phosphorylase from Mycobacterium tuberculosis associated with acyclovir.

    PubMed

    Caceres, Rafael A; Timmers, Luís F S M; Ducati, Rodrigo G; da Silva, Diego O N; Basso, Luiz A; de Azevedo, Walter F; Santos, Diógenes S

    2012-01-01

    Consumption has been a scourge of mankind since ancient times. This illness has charged a high price to human lives. Many efforts have been made to defeat Mycobacterium tuberculosis (Mt). The M. tuberculosis purine nucleoside phosphorylase (MtPNP) is considered an interesting target to pursuit new potential inhibitors, inasmuch it belongs to the purine salvage pathway and its activity might be involved in the mycobacterial latency process. Here we present the MtPNP crystallographic structure associated with acyclovir and phosphate (MtPNP:ACY:PO(4)) at 2.10 Å resolution. Molecular dynamics simulations were carried out in order to dissect MtPNP:ACY:PO(4) structural features, and the influence of the ligand in the binding pocket stability. Our results revealed that the ligand leads to active site lost of stability, in agreement with experimental results, which demonstrate a considerable inhibitory activity against MtPNP (K(i) = 150 nM). Furthermore, we observed that some residues which are important in the proper ligand's anchor into the human homologous enzyme do not present the same importance to MtPNP. Therewithal, these findings contribute to the search of new specific inhibitors for MtPNP, since peculiarities between the mycobacterial and human enzyme binding sites have been identified, making a structural-based drug design feasible.

  2. [THE DIAGNOSTICS OF HEREDITARY DISORDERS OF METABOLISM OF PURINES AND PYRIMIDINES IN CHILDREN USING HIGH PERFORMANCE LIQUID CHROMATOGRAPHY OF ELECTRO-SPRAY TANDEM MASS-SPECTROMETRY].

    PubMed

    Mamedov, I S; Zolkina, I V; Sukhorukov, V S

    2015-06-01

    The article presents data concerning new technique of diagnostic of diseases of metabolism of purines and pyrimidines using high performance liquid chromatography combined with electro-spray mass-spectrometry. The procedure of analysis is described in detail: from pre-analytical stage to interpretation of data of liquid chromatography mass-spectrometry, control of quality of data analysis, mass-spectrometry parameters and chromatographic conditions of analysis of purines, pyrimidines and their metabolites. The reference values are presented for purine and pyrimidine nucleosides and bases in urine of healthy individuals. The chemical structure of purines, pyrimidines and their metabolites and examples of chromato-mass-spectrograms under various hereditary disorders of metabolism of purines and pyrimidines are presented as well. The article is targeted to pediatricians of all profiles, medical geneticists and physicians of laboratory diagnostic. PMID:26466447

  3. Frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the European ENEST1st study

    PubMed Central

    Hochhaus, A; Rosti, G; Cross, N C P; Steegmann, J L; le Coutre, P; Ossenkoppele, G; Petrov, L; Masszi, T; Hellmann, A; Griskevicius, L; Wiktor-Jedrzejczak, W; Rea, D; Coriu, D; Brümmendorf, T H; Porkka, K; Saglio, G; Gastl, G; Müller, M C; Schuld, P; Di Matteo, P; Pellegrino, A; Dezzani, L; Mahon, F-X; Baccarani, M; Giles, F J

    2016-01-01

    The Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) study included 1089 patients with newly diagnosed chronic myeloid leukemia in chronic phase. The rate of deep molecular response (MR4 (BCR-ABL1⩽0.01% on the International Scale or undetectable BCR-ABL1 with ⩾10 000 ABL1 transcripts)) at 18 months was evaluated as the primary end point, with molecular responses monitored by the European Treatment and Outcome Study network of standardized laboratories. This analysis was conducted after all patients had completed 24 months of study treatment (80.9% of patients) or discontinued early. In patients with typical BCR-ABL1 transcripts and ⩽3 months of prior imatinib therapy, 38.4% (404/1052) achieved MR4 at 18 months. Six patients (0.6%) developed accelerated or blastic phase, and 13 (1.2%) died. The safety profile of nilotinib was consistent with that of previous studies, although the frequencies of some nilotinib-associated adverse events were lower (for example, rash, 21.4%). Ischemic cardiovascular events occurred in 6.0% of patients. Routine monitoring of lipid and glucose levels was not mandated in the protocol. These results support the use of frontline nilotinib, particularly when achievement of a deep molecular response (a prerequisite for attempting treatment-free remission in clinical trials) is a treatment goal. PMID:26437782

  4. Stem Cell Gene Therapy for Fanconi Anemia: Report from the 1st International Fanconi Anemia Gene Therapy Working Group Meeting

    PubMed Central

    Tolar, Jakub; Adair, Jennifer E; Antoniou, Michael; Bartholomae, Cynthia C; Becker, Pamela S; Blazar, Bruce R; Bueren, Juan; Carroll, Thomas; Cavazzana-Calvo, Marina; Clapp, D Wade; Dalgleish, Robert; Galy, Anne; Gaspar, H Bobby; Hanenberg, Helmut; Von Kalle, Christof; Kiem, Hans-Peter; Lindeman, Dirk; Naldini, Luigi; Navarro, Susana; Renella, Raffaele; Rio, Paula; Sevilla, Julián; Schmidt, Manfred; Verhoeyen, Els; Wagner, John E; Williams, David A; Thrasher, Adrian J

    2011-01-01

    Survival rates after allogeneic hematopoietic cell transplantation (HCT) for Fanconi anemia (FA) have increased dramatically since 2000. However, the use of autologous stem cell gene therapy, whereby the patient's own blood stem cells are modified to express the wild-type gene product, could potentially avoid the early and late complications of allogeneic HCT. Over the last decades, gene therapy has experienced a high degree of optimism interrupted by periods of diminished expectation. Optimism stems from recent examples of successful gene correction in several congenital immunodeficiencies, whereas diminished expectations come from the realization that gene therapy will not be free of side effects. The goal of the 1st International Fanconi Anemia Gene Therapy Working Group Meeting was to determine the optimal strategy for moving stem cell gene therapy into clinical trials for individuals with FA. To this end, key investigators examined vector design, transduction method, criteria for large-scale clinical-grade vector manufacture, hematopoietic cell preparation, and eligibility criteria for FA patients most likely to benefit. The report summarizes the roadmap for the development of gene therapy for FA. PMID:21540837

  5. Embryonic development of chicken (Gallus Gallus Domesticus) from 1st to 19th day-ectodermal structures.

    PubMed

    Toledo Fonseca, Erika; De Oliveira Silva, Fernanda Menezes; Alcântara, Dayane; Carvalho Cardoso, Rafael; Luís Franciolli, André; Sarmento, Carlos Alberto Palmeira; Fratini, Paula; José Piantino Ferreira, Antônio; Miglino, Maria Angélica

    2013-12-01

    Birds occupy a prominent place in the Brazilian economy not only in the poultry industry but also as an animal model in many areas of scientific research. Thus the aim of this study was to provide a description of macro and microscopic aspects of the ectoderm-derived structures in chicken embryos / fetuses poultry (Gallus gallus domesticus) from 1st to 19th day of incubation. 40 fertilized eggs, from a strain of domestic chickens, with an incubation period of 2-19 days were subjected to macroscopic description, biometrics, light, and scanning microscopy. All changes observed during the development were described. The nervous system, skin and appendages and organs related to vision and hearing began to be identified, both macro and microscopically, from the second day of incubation. The vesicles from the primitive central nervous system-forebrain, midbrain, and hindbrain-were identified on the third day of incubation. On the sixth day of incubation, there was a clear vascularization of the skin. The optic vesicle was first observed fourth day of development and on the fifth day there was the beginning of the lens formation. Although embryonic development is influenced by animal line as well as external factors such as incubation temperature, this paper provides a chronological description for chicken (Gallus gallus domesticus) during its embryonic development. PMID:24019213

  6. 1st Quarter Transportation Report FY 2015: Radioactive Waste Shipments to and from the Nevada National Security Site (NNSS)

    SciTech Connect

    Gregory, Louis

    2015-02-20

    This report satisfies the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Field Office (NNSA/NFO) commitment to prepare a quarterly summary report of radioactive waste shipments to and from the Nevada National Security Site (NNSS) Radioactive Waste Management Complex (RWMC) at Area 5. There were no shipments sent for offsite treatment and returned to the NNSS this quarter. This report summarizes the 1st quarter of Fiscal Year (FY) 2015 low-level radioactive waste (LLW) and mixed low-level radioactive waste (MLLW) shipments. Tabular summaries are provided which include the following: Sources of and carriers for LLW and MLLW shipments to and from the NNSS; Number and external volume of LLW and MLLW shipments; Highway routes used by carriers; and Incident/accident data applicable to LLW and MLLW shipments. In this report shipments are accounted for upon arrival at the NNSS, while disposal volumes are accounted for upon waste burial. The disposal volumes presented in this report include minor volumes of non-radioactive classified waste/material that were approved for disposal (non-radioactive classified or nonradioactive classified hazardous). Volume reports showing cubic feet generated using the Low-Level Waste Information System may vary slightly due to rounding conventions for volumetric conversions from cubic meters to cubic feet.

  7. A collaborative study to establish the 1st WHO International Standard for human cytomegalovirus for nucleic acid amplification technology.

    PubMed

    Fryer, Jacqueline F; Heath, Alan B; Minor, Philip D

    2016-07-01

    Variability in the performance of nucleic acid amplification technology (NAT)-based assays presents a significant problem in the diagnosis and management of human cytomegalovirus (HCMV) infections. Here we describe a collaborative study to evaluate the suitability of candidate reference materials to harmonize HCMV viral load measurements in a wide range of NAT assays. Candidate materials comprised lyophilized Merlin virus, liquid Merlin virus, liquid AD169 virus, and purified HCMV Merlin DNA cloned into a bacterial artificial chromosome. Variability in the laboratory mean HCMV concentrations determined for virus samples across the different assays was 2 log10. Variability for the purified DNA sample was higher (>3 log10). The agreement between laboratories was markedly improved when the potencies of the liquid virus samples were expressed relative to the lyophilized virus candidate. In contrast, the agreement between laboratories for the purified DNA sample was not improved. Results indicated the suitability of the lyophilized Merlin virus preparation as the 1st WHO International Standard for HCMV for NAT. It was established in October 2010, with an assigned potency of 5 × 10(6) International Units (IU) (NIBSC code 09/162). It is intended to be used to calibrate secondary references, used in HCMV NAT assays, in IU. PMID:27179913

  8. Embryonic development of chicken (Gallus Gallus Domesticus) from 1st to 19th day-ectodermal structures.

    PubMed

    Toledo Fonseca, Erika; De Oliveira Silva, Fernanda Menezes; Alcântara, Dayane; Carvalho Cardoso, Rafael; Luís Franciolli, André; Sarmento, Carlos Alberto Palmeira; Fratini, Paula; José Piantino Ferreira, Antônio; Miglino, Maria Angélica

    2013-12-01

    Birds occupy a prominent place in the Brazilian economy not only in the poultry industry but also as an animal model in many areas of scientific research. Thus the aim of this study was to provide a description of macro and microscopic aspects of the ectoderm-derived structures in chicken embryos / fetuses poultry (Gallus gallus domesticus) from 1st to 19th day of incubation. 40 fertilized eggs, from a strain of domestic chickens, with an incubation period of 2-19 days were subjected to macroscopic description, biometrics, light, and scanning microscopy. All changes observed during the development were described. The nervous system, skin and appendages and organs related to vision and hearing began to be identified, both macro and microscopically, from the second day of incubation. The vesicles from the primitive central nervous system-forebrain, midbrain, and hindbrain-were identified on the third day of incubation. On the sixth day of incubation, there was a clear vascularization of the skin. The optic vesicle was first observed fourth day of development and on the fifth day there was the beginning of the lens formation. Although embryonic development is influenced by animal line as well as external factors such as incubation temperature, this paper provides a chronological description for chicken (Gallus gallus domesticus) during its embryonic development.

  9. Child gender and weight status moderate the relation of maternal feeding practices to body esteem in 1st grade children.

    PubMed

    Shriver, Lenka H; Hubbs-Tait, Laura; Harrist, Amanda W; Topham, Glade; Page, Melanie

    2015-06-01

    Prevention of body dissatisfaction development is critical for minimizing adverse effects of poor body esteem on eating behaviors, self-esteem, and overall health. Research has examined body esteem and its correlates largely in pre-adolescents and adolescents; however, important questions remain about factors influencing body esteem of younger children. The main purpose of this study was to test moderation by children's gender and weight status of the relation of maternal controlling feeding practices to 1st graders' body esteem. The Body Esteem Scale (BES) and anthropometric measurements were completed during one-on-one child interviews at school. Mothers completed the Child Feeding Questionnaire (restriction, monitoring, concern, self-assessed maternal weight). A total of 410 mother/child dyads (202 girls) participated. Percent of children classified as overweight (BMI-for-age ≥85th) was: girls - 29%; boys - 27%. Gender moderated the relation between restriction and body esteem (β = -.140, p = .05), with maternal restriction predicting body esteem in girls but not boys. The hypothesized three-way interaction among gender, child weight status, and monitoring was confirmed. Monitoring was significantly inversely related to body esteem only for overweight/obese girls (b = -1.630). The moderating influence of gender or gender and weight status on the link between maternal feeding practices and body esteem suggests the importance of body esteem interventions for girls as early as first grade. PMID:25624022

  10. Dynamics of the 1st order phase transition between the nuclear ordered phases of solid 3He

    NASA Astrophysics Data System (ADS)

    Tanaka, Takayoshi; Ito, Hideaki; Sasaki, Yutaka; Mizusaki, Takao

    2005-08-01

    Dynamics of the 1st order phase transition between the U2D2 and the high field phases (HFP) was studied by field-cycling method between these phases by using ultra low temperature magnetic resonance imaging (ULT-MRI). Single Crystal of U2D2 3He was produced at the bottom of compressional cell in superfluid 3He-B at about 0.5 mK. Domain distribution in the U2D2 crystal was examined by ULT-MRI. We have measured the NMR signal intensity to extract the time-evolution of the HFP, after the static magnetic field was swept quickly through the critical field BC1 and was stayed at B=BC1+ΔB. The volume concentration of the U2D2 decreased exponentially in time during the early stage of the phase transition. The rate constant depended positively on ΔB. After the phase transition to the HFP was completed, the static field decreased through BC1 and was fixed at B=BC1-ΔB. The observed rate constant was similar to the value in the opposite direction with identical ΔB. This exponential evolution and ΔB dependence of its rate suggest that the early stage of the phase transition is controlled by the nucleation process.

  11. Synthesis of nanomagnetic fluids and their UV spectrophotometric response with aliphatic organic acids and 1st tier dendrimers

    NASA Astrophysics Data System (ADS)

    Pandya, Shivani R.; Singh, Man

    2016-04-01

    Synthesis of Magnetic nanoparticles were made using coprecipitation method on mixing Fe+3 and Fe+2 in 2:1 ratio with aqueous 8M NaOH which on heating at 90°C for 2 h has yielded 85% magnetic (Fe3O4) nanoparticles (MNPs), characterized by XRD, VSM, SEM, and HR-TEM. The formic acid (FA), oxalic acid (OA) and citric acid (CA), the series of aliphatic organic acids along with Trimesoyl 1, 3, 5 tridimethyl malonate (TTDMM), trimesoyl 1, 3, 5 tridiethyl malonate (TTDEM), trimesoyl 1, 3, 5 tridipropyl malonate (TTDPM), trimesoyl 1, 3, 5 tridibutyl malonate (TTDBM) and trimesoyl 1, 3, 5 tridihexyl malonate (TTDHM) 1st tier dendrimers were used separately for preparing nanomagnetic fluid. From 25 to 150 µM MNPs at an interval of 25 µM were dispersed in 150 µM of acids and dendrimers separately with DMSO. UV-VIS spectrophotometry showed a maximum MNPs dispersion with TTDMM against others and found to be most stable nanomagnetic fluid on account of capping type mechanism of acids.

  12. Child gender and weight status moderate the relation of maternal feeding practices to body esteem in 1st grade children.

    PubMed

    Shriver, Lenka H; Hubbs-Tait, Laura; Harrist, Amanda W; Topham, Glade; Page, Melanie

    2015-06-01

    Prevention of body dissatisfaction development is critical for minimizing adverse effects of poor body esteem on eating behaviors, self-esteem, and overall health. Research has examined body esteem and its correlates largely in pre-adolescents and adolescents; however, important questions remain about factors influencing body esteem of younger children. The main purpose of this study was to test moderation by children's gender and weight status of the relation of maternal controlling feeding practices to 1st graders' body esteem. The Body Esteem Scale (BES) and anthropometric measurements were completed during one-on-one child interviews at school. Mothers completed the Child Feeding Questionnaire (restriction, monitoring, concern, self-assessed maternal weight). A total of 410 mother/child dyads (202 girls) participated. Percent of children classified as overweight (BMI-for-age ≥85th) was: girls - 29%; boys - 27%. Gender moderated the relation between restriction and body esteem (β = -.140, p = .05), with maternal restriction predicting body esteem in girls but not boys. The hypothesized three-way interaction among gender, child weight status, and monitoring was confirmed. Monitoring was significantly inversely related to body esteem only for overweight/obese girls (b = -1.630). The moderating influence of gender or gender and weight status on the link between maternal feeding practices and body esteem suggests the importance of body esteem interventions for girls as early as first grade.

  13. Case Study of Severe Lightning Activity Prior to and During the Outbreak of the June 1st Greenbelt Tornado

    NASA Astrophysics Data System (ADS)

    Barnum, B. H.; Badesha, S.; Shishineh, A.; Adams, N. H.

    2012-12-01

    Surges in lightning activity have been known to be associated with the outbreak of tornado activity. We present a case study of a tornado that touched down near Greenbelt Maryland during the evening of June 1st 2012. Preceding the tornado touchdown, two single point lightning detection systems, a Boltek LD-250 and Vaisala SA20, recorded very high lightning activity rates. An electric field mill (EFM) was also making measurements and recorded large, rapid amplitude oscillations in the vertical electric fields. These electric field oscillations quickly subsided after the initial tornado touchdown. The lightning activity also generated significant RF interference in the S-band dish antenna operated at the Applied Physics Laboratory. It was somewhat surprising that the lightning activity produced enough radiation at these frequencies to cause measured levels of interference which could potentially impair satellite communications. Our interpretation of the EFM data is that intensive vertical forcing and rotation in the thunderstorm during the tornado formation caused the observed rapid electric field oscillations. At the same time, the vertical mixing in the storm caused a surge in lightning activity rates recorded by the Boltek and Vaisala sensors. Following the tornado touchdown, there was a rapid decrease in the lightning rates from the sensors. The EFM oscillations also abruptly ceased and went to a more normal slow-varying pattern typically observed during other thunderstorms without associated tornado activity. It is suggested that a network of field mills could provide realtime warning of imminent tornado activity.

  14. The Impact of Gender-Fair versus Gender-Stereotyped Basal Readers on 1st-Grade Children's Gender Stereotypes: A Natural Experiment

    ERIC Educational Resources Information Center

    Karniol, Rachel; Gal-Disegni, Michal

    2009-01-01

    Israeli 1st-grade children in two different schools in the same neighborhood who were using either a gender-stereotyped or a gender-fair basal reader were asked to judge for a series of female-stereotyped, male-stereotyped, and gender-neutral activities whether they were characteristic of females, of males, or of both. Children using the…

  15. Moving beyond the Lone Scientist: Helping 1st-Grade Students Appreciate the Social Context of Scientific Work Using Stories about Scientists

    ERIC Educational Resources Information Center

    Sharkawy, Azza

    2009-01-01

    While several studies have documented young children's (K-2) stereotypic views of scientists and scientific work, few have examined students' views of the social nature of scientific work and the strategies effective in broadening these views. The purpose of this study is to examine how stories about scientists influence 1st-grade students' views…

  16. Diagnostic Online Assessment of Basic IT Skills in 1st-Year Undergraduates in the Medical Sciences Division, University of Oxford

    ERIC Educational Resources Information Center

    Sieber, Vivien

    2009-01-01

    Attitude, experience and competence (broadly covered by the European Computer Driving Licence syllabus) in information technology (IT) were assessed in 846 1st-year Medical Sciences Division undergraduates (2003-06) at the start of their first term. Online assessments delivered during induction workshops were presented as an opportunity for…

  17. Hybrid distributed Raman amplification combining random fiber laser based 2nd-order and low-noise LD based 1st-order pumping.

    PubMed

    Jia, Xin-Hong; Rao, Yun-Jiang; Yuan, Cheng-Xu; Li, Jin; Yan, Xiao-Dong; Wang, Zi-Nan; Zhang, Wei-Li; Wu, Han; Zhu, Ye-Yu; Peng, Fei

    2013-10-21

    A configuration of hybrid distributed Raman amplification (H-DRA), that is formed by incorporating a random fiber laser (RFL) based 2nd-order pump and a low-noise laser-diode (LD) based 1st-order pump, is proposed in this paper. In comparison to conventional bi-directional 1st-order DRA, the effective noise figure (ENF) is found to be lower by amount of 0 to 4 dB due to the RFL-based 2nd-order pump, depending on the on-off gain, while the low-noise 1st-order Raman pump is used for compensating the worsened signal-to-noise ratio (SNR) in the vicinity towards the far end of the fiber and avoiding the potential nonlinear impact induced by excess injection of pump power and suppressing the pump-signal relative intensity noise (RIN) transfer. As a result, the gain distribution can be optimized along ultra-long fiber link, due to combination of the 2nd-order RFL and low-noise 1st-order pumping, making the transmission distance be extended significantly. We utilized such a configuration to achieve ultra-long-distance distributed sensing based on Brillouin optical time-domain analysis (BOTDA). A repeater-less sensing distance record of up to 154.4 km with 5 m spatial resolution and ~ ± 1.4 °C temperature uncertainty is successfully demonstrated.

  18. LSAMO forum UK strategic plan.

    PubMed

    Richards, Julie

    2012-01-01

    Over the years, the LSA role and function have developed and strengthened significantly and it is crucial that this development continues in the new NHS. The biennial LSAMO UK conference which is entitled Future proofing supervision will launch the strategic plan for 2012-2015. It is essential that LSAMOs and supervisors of midwives (SoMs) look to the future to continue to maintain safety and protect the public, but within a modernised forward thinking framework. The forum will work collaboratively to encourage a greater consistency in the provision of supervision to ensure the standards set by the NMC for the LSAs and the supervision of midwives are met. Protecting the public and supporting safe midwifery practice will continue to be the driving principles behind the LSAMO UK forum's work plan. The specific challenges to LSAMOs will be to continue providing leadership and support and be pivotal in addressing the future significant challenges faced by the NHS throughout the UK.

  19. Computer Simulations Reveal Substrate Specificity of Glycosidic Bond Cleavage in Native and Mutant Human Purine Nucleoside Phosphorylase.

    PubMed

    Isaksen, Geir Villy; Hopmann, Kathrin Helen; Åqvist, Johan; Brandsdal, Bjørn Olav

    2016-04-12

    Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of purine ribonucleosides and 2'-deoxyribonucleosides, yielding the purine base and (2'-deoxy)ribose 1-phosphate as products. While this enzyme has been extensively studied, several questions with respect to the catalytic mechanism have remained largely unanswered. The role of the phosphate and key amino acid residues in the catalytic reaction as well as the purine ring protonation state is elucidated using density functional theory calculations and extensive empirical valence bond (EVB) simulations. Free energy surfaces for adenosine, inosine, and guanosine are fitted to ab initio data and yield quantitative agreement with experimental data when the surfaces are used to model the corresponding enzymatic reactions. The cognate substrates 6-aminopurines (inosine and guanosine) interact with PNP through extensive hydrogen bonding, but the substrate specificity is found to be a direct result of the electrostatic preorganization energy along the reaction coordinate. Asn243 has previously been identified as a key residue providing substrate specificity. Mutation of Asn243 to Asp has dramatic effects on the substrate specificity, making 6-amino- and 6-oxopurines equally good as substrates. The principal effect of this particular mutation is the change in the electrostatic preorganization energy between the native enzyme and the Asn243Asp mutant, clearly favoring adenosine over inosine and guanosine. Thus, the EVB simulations show that this particular mutation affects the electrostatic preorganization of the active site, which in turn can explain the substrate specificity. PMID:26985580

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

    PubMed

    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.

  1. Increasing Occurrences and Functional Roles for High Energy Purine-Pyrimidine Base-Pairs in Nucleic Acids

    PubMed Central

    Kimsey, Isaac; Al-Hashimi, Hashim M.

    2014-01-01

    There are a growing number of studies reporting the observation of purine-pyrimidine base-pairs that are seldom observed in unmodified nucleic acids because they entail the loss of energetically favorable interactions or require energetically costly base ionization or tautomerization. These high energy purine-pyrimidine base-pairs include G•C+ and A•T Hoogsteen base-pairs, which entail ~180° rotation of the purine base in a Watson-Crick base-pair, protonation of cytosine N3, and constriction of the C1′–C1′ distance by ~2.5 Å. Other high energy pure-pyrimidine base-pairs include G•T, G•U, and A•C mispairs that adopt Watson-Crick like geometry through either base ionization or tautomerization. Although difficult to detect and characterize using biophysical methods, high energy purine-pyrimidine base-pairs appear to be more common than once thought. They further expand the structural and functional diversity of canonical and noncanonical nucleic acid base-pairs. PMID:24721455

  2. New approaches for improving the production of the 1st and 2nd generation ethanol by yeast.

    PubMed

    Kurylenko, Olena; Semkiv, Marta; Ruchala, Justyna; Hryniv, Orest; Kshanovska, Barbara; Abbas, Charles; Dmytruk, Kostyantyn; Sibirny, Andriy

    2016-01-01

    Increase in the production of 1st generation ethanol from glucose is possible by the reduction in the production of ethanol co-products, especially biomass. We have developed a method to reduce biomass accumulation of Saccharomyces cerevisiae by the manipulation of the intracellular ATP level due to overexpression of genes of alkaline phosphatase, apyrase or enzymes involved in futile cycles. The strains constructed accumulated up to 10% more ethanol on a cornmeal hydrolysate medium. Similar increase in ethanol accumulation was observed in the mutants resistant to the toxic inhibitors of glycolysis like 3-bromopyruvate and others. Substantial increase in fuel ethanol production will be obtained by the development of new strains of yeasts that ferment sugars of the abundant lignocellulosic feedstocks, especially xylose, a pentose sugar. We have found that xylose can be fermented under elevated temperatures by the thermotolerant yeast, Hansenula polymorpha. We combined protein engineering of the gene coding for xylose reductase (XYL1) along with overexpression of the other two genes responsible for xylose metabolism in yeast (XYL2, XYL3) and the deletion of the global transcriptional activator CAT8, with the selection of mutants defective in utilizing ethanol as a carbon source using the anticancer drug, 3-bromopyruvate. Resulted strains accumulated 20-25 times more ethanol from xylose at the elevated temperature of 45°C with up to 12.5 g L(-1) produced. Increase in ethanol yield and productivity from xylose was also achieved by overexpression of genes coding for the peroxisomal enzymes: transketolase (DAS1) and transaldolase (TAL2), and deletion of the ATG13 gene. PMID:26619255

  3. Establishment of the 1st World Health Organization international standards for human papillomavirus type 16 DNA and type 18 DNA.

    PubMed

    Wilkinson, Dianna E; Baylis, Sally A; Padley, David; Heath, Alan B; Ferguson, Morag; Pagliusi, Sonia R; Quint, Wim G; Wheeler, Cosette M

    2010-06-15

    A World Health Organization collaborative study was conducted to evaluate candidate international standards for human papillomavirus (HPV) Type 16 DNA (NIBSC code 06/202) and HPV Type 18 DNA (NIBSC code 06/206) for use in the amplification and detection steps of nucleic acid-based assays. The freeze-dried candidate international standards were prepared from bulk preparations of cloned plasmid containing full-length HPV-16 or HPV-18 genomic DNA. Nineteen laboratories from 13 countries participated in the study using a variety of commercial and in-house quantitative and qualitative assays. The data presented here indicate that, upon freeze-drying, there is no significant loss in potency for the candidate HPV-18 DNA and a slight loss in potency for the candidate HPV-16 DNA; although this is likely not scientifically relevant when assay precision is considered. In general, the individual laboratory mean estimates for each study sample were grouped +/- approximately 2 log(10) around the theoretical HPV DNA concentration of the reconstituted ampoule (1 x 10(7) HPV genome equivalents/mL). The agreement between laboratories is improved when potencies are made relative to the candidate international standards, demonstrating their utility in harmonizing amplification and detection steps of HPV-16 and -18 DNA assays. Degradation studies indicate that the candidate international standards are extremely stable and suitable for long-term use. Based on these findings, the candidate standards were established as the 1st WHO international standards for HPV-16 DNA and HPV-18 DNA, each with a potency of 5 x 10(6) international units (IU) per ampoule or 1 x 10(7) IU mL(-1) when reconstituted as directed.

  4. Cognitive-based approach in teaching 1st year Physics for Life Sciences, including Atmospheric Physics and Climate Change components

    NASA Astrophysics Data System (ADS)

    Petelina, S. V.

    2009-12-01

    Most 1st year students who take the service course in Physics - Physics for Life Sciences - in Australia encounter numerous problems caused by such factors as no previous experience with this subject; general perception that Physics is hard and only very gifted people are able to understand it; lack of knowledge of elementary mathematics; difficulties encountered by lecturers in teaching university level Physics to a class of nearly 200 students with no prior experience, diverse and sometime disadvantageous backgrounds, different majoring areas, and different learning abilities. As a result, many students either drop, or fail the subject. In addition, many of those who pass develop a huge dislike towards Physics, consider the whole experience as time wasted, and spread this opinion among their peers and friends. The above issues were addressed by introducing numerous changes to the curriculum and modifying strategies and approaches in teaching Physics for Life Sciences. Instead of a conventional approach - teaching Physics from simple to complicated, topic after topic, the students were placed in the world of Physics in the same way as a newborn child is introduced to this world - everything is seen all the time and everywhere. That created a unique environment where a bigger picture and all details were always present and interrelated. Numerous concepts of classical and modern physics were discussed, compared, and interconnected all the time with “Light” being a key component. Our primary field of research is Atmospheric Physics, in particular studying the atmospheric composition and structure using various satellite and ground-based data. With this expertise and also inspired by an increasing importance of training a scientifically educated generation who understands the challenges of the modern society and responsibilities that come with wealth, a new section on environmental physics has been developed. It included atmospheric processes and the greenhouse

  5. Teaching Astronomy in UK Schools

    ERIC Educational Resources Information Center

    Roche, Paul; Roberts, Sarah; Newsam, Andy; Barclay, Charles

    2012-01-01

    This article attempts to summarise the good, bad and (occasionally) ugly aspects of teaching astronomy in UK schools. It covers the most common problems reported by teachers when asked about covering the astronomy/space topics in school. Particular focus is given to the GCSE Astronomy qualification offered by Edexcel (which is currently the…

  6. Purification and Properties of a Protein Which Binds Cytokinin-active 6-Substituted Purines 1

    PubMed Central

    Erion, Jack L.; Fox, J. Eugene

    1981-01-01

    A protein which binds 6-substituted purines of the cytokinin type with relatively high affinity has been extensively purified from wheat germ. Conventional chromatographic techniques, as well as an affinity matrix to which a cytokinin was covalently coupled, were used in the purification. The wheat germ cytokinin-binding protein (CBF-1) has four unlike subunits and an apparent molecular weight of 183,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. CBF-1 is saturated at one cytokinin molecule per tetramer with a Kd for 6-benzylaminopurine of 5 × 10−7 molar. The protein exists both on the native wheat germ ribosome (1 molecule CBF-1 per 80S ribosome) and free in the cytosol with approximately three copies of the latter for each of the former. Data from affinity chromatography studies and cross-linking experiments strongly suggest that a specific binding site for CBF-1 occurs on the wheat germ ribosome. Images PMID:16661618

  7. Modification of purine and pyrimidine nucleosides by direct C-H bond activation.

    PubMed

    Liang, Yong; Wnuk, Stanislaw F

    2015-03-17

    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.

  8. The ligand binding mechanism to purine nucleoside phosphorylase elucidated via molecular dynamics and machine learning

    PubMed Central

    Decherchi, Sergio; Berteotti, Anna; Bottegoni, Giovanni; Rocchia, Walter; Cavalli, Andrea

    2015-01-01

    The study of biomolecular interactions between a drug and its biological target is of paramount importance for the design of novel bioactive compounds. In this paper, we report on the use of molecular dynamics (MD) simulations and machine learning to study the binding mechanism of a transition state analogue (DADMe–immucillin-H) to the purine nucleoside phosphorylase (PNP) enzyme. Microsecond-long MD simulations allow us to observe several binding events, following different dynamical routes and reaching diverse binding configurations. These simulations are used to estimate kinetic and thermodynamic quantities, such as kon and binding free energy, obtaining a good agreement with available experimental data. In addition, we advance a hypothesis for the slow-onset inhibition mechanism of DADMe–immucillin-H against PNP. Combining extensive MD simulations with machine learning algorithms could therefore be a fruitful approach for capturing key aspects of drug–target recognition and binding. PMID:25625196

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

    SciTech Connect

    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

  10. Evaluation of capillary chromatographic supports for immobilized human purine nucleoside phosphorylase in frontal affinity chromatography studies.

    PubMed

    de Moraes, Marcela Cristina; Temporini, Caterina; Calleri, Enrica; Bruni, Giovanna; Ducati, Rodrigo Gay; Santos, Diógenes Santiago; Cardoso, Carmen Lucia; Cass, Quezia Bezerra; Massolini, Gabriella

    2014-04-18

    The aim of this work was to optimize the preparation of a capillary human purine nucleoside phosphorylase (HsPNP) immobilized enzyme reactor (IMER) for characterization and affinity screening studies of new inhibitors by frontal affinity chromatography coupled to mass spectrometry (FAC-MS). For this purpose two monolithic supports, a Chromolith Speed Rod (0.1mm I.D.×5cm) and a methacrylate-based monolithic epoxy polymeric capillary column (0.25mm I.D.×5cm) with epoxy reactive groups were considered and compared to an IMER previously developed using an open fused silica capillary. Each HsPNP-IMER was characterized in terms of catalytic activity using Inosine as standard substrate. Furthermore, they were also explored for affinity ranking experiments. Kd determination was carried out with the based fused silica HsPNP-IMER and the results are herein discussed.

  11. Novel skeleton compound Allomyrinanoid A and two purine alkaloids from the adult of Allomyrina dichotoma L.

    PubMed

    Niu, Lanlan; Gao, Jiayu; Li, Haidi; Liu, Junna; Yin, Weiping

    2016-01-15

    Three new compounds were isolated from the adult insect of Allomyrina dichotoma L. for the first time. A new skeleton compound is named as Allomyrinanoid A (1) originated from the familiar norbornane derivatives and two new compounds of purine alkaloid are named as adenine-9-methylaldehyde oxime B (2) and 6-N-methyleneimine-adenine-9-methylaldehyde oxime B (3). The compounds (2) and (3) are the tautomers of imine-enamine and creatively separated form the solvent using column chromatography method. The structures of all isolated compounds were established by spectroscopic methods including analyses of their 1D, 2D NMR and HRESI-MS data, and confirmed by comparison of the literature data. These new components displayed antibacterial activities against both Gram-positive and Gram-negative strain.

  12. Myoadenylate deaminase deficiency. Functional and metabolic abnormalities associated with disruption of the purine nucleotide cycle.

    PubMed Central

    Sabina, R L; Swain, J L; Olanow, C W; Bradley, W G; Fishbein, W N; DiMauro, S; Holmes, E W

    1984-01-01

    To assess the role of the purine nucleotide cycle in human skeletal muscle function, we evaluated 10 patients with AMP deaminase deficiency (myoadenylate deaminase deficiency; MDD). 4 MDD and 19 non-MDD controls participated in an exercise protocol. The latter group was composed of a patient cohort (n = 8) exhibiting a constellation of symptoms similar to those of the MDD patients, i.e., postexertional aches, cramps, and pains; as well as a cohort of normal, unconditioned volunteers (n = 11). The individuals with MDD fatigued after performing only 28% as much work as their non-MDD counterparts. Muscle biopsies were obtained from the four MDD patients and the eight non-MDD patients at rest and following exercise to the point of fatigue. Creatine phosphate content fell to a comparable extent in the MDD (69%) and non-MDD (52%) patients at the onset of fatigue. Following exercise the 34% decrease in ATP content of muscle from the non-MDD subjects was significantly greater than the 6% decrease in ATP noted in muscle from the MDD patients (P = 0.048). Only one of four MDD patients had a measurable drop in ATP compared with seven of eight non-MDD patients. At end-exercise the muscle content of inosine 5'-monophosphate (IMP), a product of AMP deaminase, was 13-fold greater in the non-MDD patients than that observed in the MDD group (P = 0.008). Adenosine content of muscle from the MDD patients increased 16-fold following exercise, while there was only a twofold increase in adenosine content of muscle from the non-MDD patients (P = 0.028). Those non-MDD patients in whom the decrease in ATP content following exercise was measurable exhibited a stoichiometric increase in IMP, and total purine content of the muscle did not change significantly. The one MDD patient in whom the decrease in ATP was measurable, did not exhibit a stoichiometric increase in IMP. Although the adenosine content increased 13-fold in this patient, only 48% of the ATP catabolized could be accounted for

  13. N-Benzyl-9-isopropyl-9H-purin-6-amine

    PubMed Central

    Gergela, David; Rouchal, Michal; Bartoš, Peter; Vícha, Robert

    2013-01-01

    The asymmetric unit of the title compound, C15H17N5, consists of two mol­ecules in which the dihedral angles between the best planes of the purine ring system (r.m.s. deviations = 0.0060 and 0.0190 Å) and the benzene ring are 89.21 (3) and 82.14 (4)°. The mol­ecules within the asymmetric unit are linked into dimers by pairs of N—H⋯N hydrogen bonds. Weak C—H⋯π contacts and π–π inter­actions [centroid–centroid = 3.3071 (1) Å] further connect the mol­ecules into a three-dimensional network. PMID:23795114

  14. Factors influencing the family consent rate for organ donation in the UK.

    PubMed

    Hulme, W; Allen, J; Manara, A R; Murphy, P G; Gardiner, D; Poppitt, E

    2016-09-01

    The refusal rate for organ donation in the UK is 42%, among the highest in Europe. We extracted data on every family approach for donation in UK ICUs or Emergency Departments between 1st April 2012 and 30th September 2013, and performed multiple logistic regression to identify modifiable factors associated with consent. Complete data were available for 4703 of 4899 approaches during the study period. Consent for donation after brain death was 68.9%, and for donation after circulatory death 56.5% (p < 0.0001). Patient ethnicity, knowledge of a patient's wishes and involvement of a specialist nurse in organ donation in the approach were strongly associated with consent (p < 0.0001). The impact of the specialist nurse was stronger for donation after circulatory death than for donation after brain death, even after accounting for the impact of prior knowledge of patients' wishes. Involvement of the specialist nurse in the approach, encouraging family discussions about donation wishes and promotion of the organ donor register are key strategies to increase UK consent rates, and are supported by this study.

  15. Factors influencing the family consent rate for organ donation in the UK.

    PubMed

    Hulme, W; Allen, J; Manara, A R; Murphy, P G; Gardiner, D; Poppitt, E

    2016-09-01

    The refusal rate for organ donation in the UK is 42%, among the highest in Europe. We extracted data on every family approach for donation in UK ICUs or Emergency Departments between 1st April 2012 and 30th September 2013, and performed multiple logistic regression to identify modifiable factors associated with consent. Complete data were available for 4703 of 4899 approaches during the study period. Consent for donation after brain death was 68.9%, and for donation after circulatory death 56.5% (p < 0.0001). Patient ethnicity, knowledge of a patient's wishes and involvement of a specialist nurse in organ donation in the approach were strongly associated with consent (p < 0.0001). The impact of the specialist nurse was stronger for donation after circulatory death than for donation after brain death, even after accounting for the impact of prior knowledge of patients' wishes. Involvement of the specialist nurse in the approach, encouraging family discussions about donation wishes and promotion of the organ donor register are key strategies to increase UK consent rates, and are supported by this study. PMID:27440055

  16. Controlled transcriptional regulation in eukaryotes by a novel transcription factor derived from Escherichia coli purine repressor.

    PubMed

    Yeon, Eun-Hee; Noh, Ju-Young; Kim, Jong-Min; Lee, Min-Young; Yoon, Sarah; Park, Sang-Kyu; Choi, Kang-Yell; Kim, Kyung-Sup

    2004-06-25

    Unlike the DNA-binding domains (DBD) of most eukaryotic transcription factors, Escherichia coli LacI family transcription factors are unable to bind to specific target DNA sequences without a cofactor-binding domain. In the present study, we reconstructed a novel DBD designated as PurHG, which binds constitutively to a 16bp purine repressor operator, by fusion of the purine repressor (PurR) DBD (residues 1-57) and the GAL4 dimerization domain (DD, residues 42-148). Binding of PurHG to DNA requires the dimerization and a hinge helix of PurR DBD. When the PurHG was expressed as a fusion protein in a form of a transcription activator (PurAD) or an artificial nuclear receptor (PurAPR or PurAER) responding to ligand, such as RU486 or beta-estradiol, it could regulate the expression of the reporter genes in NIH3T3 cells. The prerequisite region of the GAL4 DD for DNA-binding was amino acid residues from 42 to 98 in the form of PurAD, while the amino acid residues from 42 to 75 were sufficient for ligand-dependent regulation in the form of PurAPR. These results suggest that the dimerization function of the progesterone ligand-binding domain could be substituted for region 76-98 of the GAL4 DD. In summary, the fusion of the PurR DBD and the GAL4 DD generates fully active DNA-binding protein, PurHG, in vitro and in vivo, and these results provide the direct evidence of structural predictions that the proximate positioning of PurR hinge helical regions is critical for DNA-binding.

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

    PubMed

    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. PMID:24856135

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

    PubMed

    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.

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

    PubMed Central

    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

  20. Vascular actions of purines in the foetal circulation of the human placenta.

    PubMed Central

    Read, M. A.; Boura, A. L.; Walters, W. A.

    1993-01-01

    1. The vasoactive effects of adenosine triphosphate (ATP), adenosine and other purines in the foetal circulation of the human placenta were examined. Single lobules of the placenta were bilaterally perfused in vitro with Krebs buffer (maternal and foetal sides 5 ml min-1 each, 95% O2:5% CO2, 37 degrees C). Changes in foetal vascular tone were assessed by recording perfusion pressure during constant infusion of each purine. To allow recording of the vasodilator effects, submaximal vasoconstriction was induced by concomitant infusion of prostaglandin F2 alpha (0.7-2.0 mumol l-1). 2. ATP (1.0-100 mumol l-1) usually caused concentration-dependent reductions in perfusion pressure. However, biphasic with initial transient increases, or only increases in pressure were sometimes observed. Falls in pressure caused by ATP were significantly reduced by addition to the perfusate of NG-nitro-L-arginine (L-NOARG) (100 mumol l-1) but not NG-nitro-D-arginine (D-NOARG) (100 mumol l-1). They were not influenced by addition of indomethacin (10 mumol l-1) or L-arginine (100 mumol l-1). 3. Adenosine (0.01-1.0 mmol l-1) consistently caused concentration-dependent reductions in perfusion pressure, this effect not being influenced by indomethacin. L-NOARG, but not D-NOARG, reduced the potency of adenosine approximately three fold. L-Arginine, but not D-arginine enhanced its potency by a similar amount. 4. 2-Methylthio-ATP, a selective P2 gamma agonist was approximately 50 times more potent than ATP as a vasodilator agent, always causing decreases in perfusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8220907

  1. Purine metabolism in response to hypoxic conditions associated with breath-hold diving and exercise in erythrocytes and plasma from bottlenose dolphins (Tursiops truncatus).

    PubMed

    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.

  2. Creating Research-Rich Learning Experiences and Quantitative Skills in a 1st Year Earth Systems Course

    NASA Astrophysics Data System (ADS)

    King, P. L.; Eggins, S.; Jones, S.

    2014-12-01

    We are creating a 1st year Earth Systems course at the Australian National University that is built around research-rich learning experiences and quantitative skills. The course has top students including ≤20% indigenous/foreign students; nonetheless, students' backgrounds in math and science vary considerably posing challenges for learning. We are addressing this issue and aiming to improve knowledge retention and deep learning by changing our teaching approach. In 2013-2014, we modified the weekly course structure to a 1hr lecture; a 2hr workshop with hands-on activities; a 2hr lab; an assessment piece covering all face-to-face activities; and a 1hr tutorial. Our new approach was aimed at: 1) building student confidence with data analysis and quantitative skills through increasingly difficult tasks in science, math, physics, chemistry, climate science and biology; 2) creating effective learning groups using name tags and a classroom with 8-person tiered tables; 3) requiring students to apply new knowledge to new situations in group activities, two 1-day field trips and assessment items; 4) using pre-lab and pre-workshop exercises to promote prior engagement with key concepts; 5) adding open-ended experiments to foster structured 'scientific play' or enquiry and creativity; and 6) aligning the assessment with the learning outcomes and ensuring that it contains authentic and challenging southern hemisphere problems. Students were asked to design their own ocean current experiment in the lab and we were astounded by their ingenuity: they simulated the ocean currents off Antarctica; varied water density to verify an equation; and examined the effect of wind and seafloor topography on currents. To evaluate changes in student learning, we conducted surveys in 2013 and 2014. In 2014, we found higher levels of student engagement with the course: >~80% attendance rates and >~70% satisfaction (20% neutral). The 2014 cohort felt that they were more competent in writing

  3. PREFACE: 1st International School and Conference "Saint Petersburg OPEN 2014" on Optoelectronics, Photonics, Engineering and Nanostructures

    NASA Astrophysics Data System (ADS)

    2014-09-01

    Dear Colleagues, 1st International School and Conference "Saint Petersburg OPEN 2014" on Optoelectronics, Photonics, Engineering and Nanostructures was held on March 25 - 27, 2014 at St. Petersburg Academic University - Nanotechnology Research and Education Centre of the Russian Academy of Sciences. The School and Conference included a series of invited talks given by leading professors with the aim to introduce young scientists with actual problems and major advances in physics and technology. The keynote speakers were: Mikhail Glazov (Ioffe Physico-Technical Institute RAS, Russia) Vladimir Dubrovskii (Saint Petersburg Academic University RAS, Russia) Alexey Kavokin (University of Southampton, United Kingdom and St. Petersburg State University, Russia) Vladimir Korenev (Ioffe Physico-Technical Institute RAS, Russia) Sergey Kukushkin (Institute of Problems of Mechanical Engineering RAS, Russia) Nikita Pikhtin (Ioffe Physico-Technical Institute RAS, Russia and "Elfolum" Ltd., Russia) Dmitry Firsov (Saint Petersburg State Polytechnical University, Russia) During the poster session all undergraduate and graduate students attending the conference presented their works. Sufficiently large number of participants with more than 160 student attendees from all over the world allowed the Conference to provide a fertile ground for the fruitful discussions between the young scientists as well as to become a perfect platform for the valuable discussions between student authors and highly experienced scientists. The best student papers, which were selected by the Program Committee and by the invited speakers basing on the theses and their poster presentation, were awarded with diplomas of the conference - see the photos. This year's School and Conference is supported by SPIE (The International Society for Optics and Photonics), OSA (The Optical Society), St. Petersburg State Polytechnical University and by Skolkovo Foundation. It is a continuation of the annual schools and

  4. 1st Guidelines of the Brazilian Society of Cardiology on processes and skills for education in cardiology in Brazil--executive summary.

    PubMed

    Sousa, Marcos Roberto de; Mourilhe-Rocha, Ricardo; Paola, Angelo Amato Vincenzo de; Köhler, Ilmar; Feitosa, Gilson Soares; Schneider, Jamil Cherem; Feitosa-Filho, Gilson Soares; Nicolau, José Carlos; Ferreira, João Fernando Monteiro; Morais, Nelson Siqueira de

    2012-02-01

    This article summarizes the "1st Guidelines of the Brazilian Society of Cardiology on Processes and Skills for Education in Cardiology in Brazil," which can be found in full at: . The guideline establishes the education time required in Internal Medicine and Cardiology with Specialization through theoretical and practical training. These requirements must be available at the center forming Specialists in Cardiology and the Cardiology contents.

  5. The 1st European Summer School on 'proteomic basics'--the students view. 12-18 August, 2007 Kloster Neustift, Brixen/Bressanone, South Tyrol, Italy.

    PubMed

    Collins, Emily S; Little, Samantha J

    2008-01-01

    Fifty postgraduate and postdoctoral delegates from all over Europe attended the week-long '1st European Summer School on Proteomic Basics' in Kloster Neustift in the Italian South Tyrol in August 2007. Invited proteomics experts gave tutorial lectures on Proteomics techniques with an emphasis on sample preparation, protein separation and purification in the first of an annual series of Proteomics Summer Schools funded by the EU and the Volkswagen Stiftung.

  6. The 1st European Summer School on 'proteomic basics'--the students view. 12-18 August, 2007 Kloster Neustift, Brixen/Bressanone, South Tyrol, Italy.

    PubMed

    Collins, Emily S; Little, Samantha J

    2008-01-01

    Fifty postgraduate and postdoctoral delegates from all over Europe attended the week-long '1st European Summer School on Proteomic Basics' in Kloster Neustift in the Italian South Tyrol in August 2007. Invited proteomics experts gave tutorial lectures on Proteomics techniques with an emphasis on sample preparation, protein separation and purification in the first of an annual series of Proteomics Summer Schools funded by the EU and the Volkswagen Stiftung. PMID:18203275

  7. All-optical 1st- and 2nd-order differential equation solvers with large tuning ranges using Fabry-Pérot semiconductor optical amplifiers.

    PubMed

    Chen, Kaisheng; Hou, Jie; Huang, Zhuyang; Cao, Tong; Zhang, Jihua; Yu, Yuan; Zhang, Xinliang

    2015-02-01

    We experimentally demonstrate an all-optical temporal computation scheme for solving 1st- and 2nd-order linear ordinary differential equations (ODEs) with tunable constant coefficients by using Fabry-Pérot semiconductor optical amplifiers (FP-SOAs). By changing the injection currents of FP-SOAs, the constant coefficients of the differential equations are practically tuned. A quite large constant coefficient tunable range from 0.0026/ps to 0.085/ps is achieved for the 1st-order differential equation. Moreover, the constant coefficient p of the 2nd-order ODE solver can be continuously tuned from 0.0216/ps to 0.158/ps, correspondingly with the constant coefficient q varying from 0.0000494/ps(2) to 0.006205/ps(2). Additionally, a theoretical model that combining the carrier density rate equation of the semiconductor optical amplifier (SOA) with the transfer function of the Fabry-Pérot (FP) cavity is exploited to analyze the solving processes. For both 1st- and 2nd-order solvers, excellent agreements between the numerical simulations and the experimental results are obtained. The FP-SOAs based all-optical differential-equation solvers can be easily integrated with other optical components based on InP/InGaAsP materials, such as laser, modulator, photodetector and waveguide, which can motivate the realization of the complicated optical computing on a single integrated chip.

  8. UK report on waste management

    SciTech Connect

    Ferguson, J.

    1995-09-01

    Arising jointly from the National and European Union requirements for more intensive attention to be paid to the environment, the United Kingdom (UK) has taken many strides forward in protecting the environment from pollution and preventing harm to human health arising from the handling, transport and disposal of wastes. Major adjustments are taking place in Europe following the opening up of the Eastern European countries. The consequences of the illegal movement of wastes and its mistreatment and disposal are now recognised within the European Union. The UK as a member State is well aware of the consequences which arise from the lack of proper waste management. This paper discusses waste management and legislation pertaining to waste management in the United Kingdom.

  9. Nutritional knowledge of UK coaches.

    PubMed

    Cockburn, Emma; Fortune, Alistair; Briggs, Marc; Rumbold, Penny

    2014-04-10

    Athletes obtain nutritional information from their coaches, yet their competency in this area is lacking. Currently, no research exists in the UK which has a different coach education system to many other countries. Therefore, the aim of this study was to evaluate the sports nutrition knowledge of UK coaching certificate (UKCC) level 2 and 3, hockey and netball qualified coaches. All coaches (n = 163) completed a sports nutrition questionnaire to identify: (a) if they provided nutritional advice; (b) their level of sport nutrition knowledge; and (c) factors that may have contributed to their level of knowledge. Over half the coaches provided advice to their athletes (n = 93, 57.1%), even though they were not competent to do so. Coaches responded correctly to 60.3 ± 10.5% of all knowledge questions with no differences between those providing advice and those who did not (p > 0.05). Those coaches who had undertaken formal nutrition training achieved higher scores than those who had not (p < 0.05). In conclusion, UK sports coaches would benefit from continued professional development in sports nutrition to enhance their coaching practice.

  10. The PurR mutation of Drosophila melanogaster confers resistance to purine and 2,6-diaminopurine by elevating adenosine deaminase activity.

    PubMed

    Dutton, F L; Chovnick, A

    1990-01-01

    Media supplemented with purine (7H-imidazo[4,5-d]pyrimidine) or the purine analogue 2,6-diaminopurine (DAP) can be employed to select several classes of purine-resistant variants from mutagenized cultures of Drosophila. One class results in elevated resistance to purine and diaminopurine which is correlated with elevated activity of the enzyme adenosine deaminase (adenosine aminohydrolase = EC 3.5.4.4). The first member of this class, Pur R, maps to position 82 +/- in the right arm of the second chromosome. The Pur R mutation causes an elevation of adenosine deaminase (ADA) enzyme activity, apparently by altering a thermolabile, ADA-specific repressor. Pur R may thus encode a negative regulator of adenosine deaminase activity similar to the ADA-binding protein found in mammalian systems.

  11. PREFACE: 1st Nano-IBCT Conference 2011 - Radiation Damage of Biomolecular Systems: Nanoscale Insights into Ion Beam Cancer Therapy

    NASA Astrophysics Data System (ADS)

    Huber, Bernd A.; Malot, Christiane; Domaracka, Alicja; Solov'yov, Andrey V.

    2012-07-01

    The 1st Nano-IBCT Conference entitled 'Radiation Damage in Biomolecular Systems: Nanoscale Insights into Ion Beam Cancer Therapy' was held in Caen, France, in October 2011. The Meeting was organised in the framework of the COST Action MP1002 (Nano-IBCT) which was launched in December 2010 (http://fias.uni-frankfurt.de/nano-ibct). This action aims to promote the understanding of mechanisms and processes underlying the radiation damage of biomolecular systems at the molecular and nanoscopic level and to use the findings to improve the strategy of Ion Beam Cancer Therapy. In the hope of achieving this, participants from different disciplines were invited to represent the fields of physics, biology, medicine and chemistry, and also included those from industry and the operators of hadron therapy centres. Ion beam therapy offers the possibility of excellent dose localization for treatment of malignant tumours, minimizing radiation damage in normal healthy tissue, while maximizing cell killing within the tumour. Several ion beam cancer therapy clinical centres are now operating in Europe and elsewhere. However, the full potential of such therapy can only be exploited by better understanding the physical, chemical and biological mechanisms that lead to cell death under ion irradiation. Considering a range of spatio-temporal scales, the proposed action therefore aims to combine the unique experimental and theoretical expertise available within Europe to acquire greater insight at the nanoscopic and molecular level into radiation damage induced by ion impact. Success in this endeavour will be both an important scientific breakthrough and give great impetus to the practical improvement of this innovative therapeutic technique. Ion therapy potentially provides an important advance in cancer therapy and the COST action MP1002 will be very significant in ensuring Europe's leadership in this field, providing the scientific background, required data and mechanistic insight which

  12. Microwave-assisted synthesis of C-8 aryl and heteroaryl inosines and determination of their inhibitory activities against Plasmodium falciparum purine nucleoside phosphorylase.

    PubMed

    Gigante, Alba; Priego, Eva-María; Sánchez-Carrasco, Paula; Ruiz-Pérez, Luis Miguel; Vande Voorde, Johan; Camarasa, María-José; Balzarini, Jan; González-Pacanowska, Dolores; Pérez-Pérez, María-Jesús

    2014-07-23

    8-Arylinosines have been scarcely studied for therapeutic purposes, probably due to difficulties in their synthesis. The recently described direct arylation reaction at position 8 of purine nucleosides has been employed to synthesize a series of 8-aryl and 8-pyridylinosines. These compounds have been studied for hydrolytic stability and subjected to biological evaluation. Three compounds have shown a pronounced specific inhibition of Plasmodium falciparum-encoded purine nucleoside phosphorylase, an important target for antimalarial chemotherapy. PMID:24929343

  13. Identification of unprecedented purine-containing compounds, the zingerines, from ginger rhizomes (Zingiber officinale Roscoe) using a phase-trafficking approach.

    PubMed

    Araya, Juan J; Zhang, Huaping; Prisinzano, Thomas E; Mitscher, Lester A; Timmermann, Barbara N

    2011-06-01

    Three unprecedented purine-containing compounds, named [6]-, [8]-, and [10]-zingerines as they are 5-(6-amino-9H-purin-9-yl) analogs of [6]-, [8]-, and [10]-gingerols, respectively, were isolated from a methanolic extract of ginger rhizomes using a phase trafficking-based method that utilizes solid phase reagents allowing for fast and selective simultaneous separation of basic, acidic, and neutral components of natural products extracts.

  14. Identification of unprecedented purine-containing compounds, the zingerines, from ginger rhizomes (Zingiber officinale Roscoe) using a phase-trafficking approach.

    PubMed

    Araya, Juan J; Zhang, Huaping; Prisinzano, Thomas E; Mitscher, Lester A; Timmermann, Barbara N

    2011-06-01

    Three unprecedented purine-containing compounds, named [6]-, [8]-, and [10]-zingerines as they are 5-(6-amino-9H-purin-9-yl) analogs of [6]-, [8]-, and [10]-gingerols, respectively, were isolated from a methanolic extract of ginger rhizomes using a phase trafficking-based method that utilizes solid phase reagents allowing for fast and selective simultaneous separation of basic, acidic, and neutral components of natural products extracts. PMID:21497863

  15. Regulation of Escherichia coli purA by purine repressor, one component of a dual control mechanism.

    PubMed

    He, B; Zalkin, H

    1994-02-01

    Escherichia coli purA encodes adenylosuccinate synthetase, one of two enzymes required for synthesis of AMP from IMP. purA is subject to two- to threefold regulation by purR and about twofold regulation by a purR-independent mechanism. The 5'-flanking region of purA confers purR-dependent transcriptional regulation of purA but not the purR-independent regulation. Two operator sites in the 5'-flanking region which bind purine repressor in vitro and are required for in vivo regulation were identified. The purR-independent regulation may be posttranscriptional. It is now established that all transcription units involved in de novo synthesis of purine nucleotides, nine pur operons, as well as purR itself and guaBA, are subject to purR control.

  16. Kinetic properties of Cellulomonas sp. purine nucleoside phosphorylase with typical and non-typical substrates: implications for the reaction mechanism.

    PubMed

    Wielgus-Kutrowska, Beata; Bzowska, Agnieszka

    2005-01-01

    Phosphorolysis catalyzed by Cellulomonas sp. PNP with typical nucleoside substrate, inosine (Ino), and non-typical 7-methylguanosine (m7Guo), with either nucleoside or phosphate (Pd) as the varied substrate, kinetics of the reverse synthetic reaction with guanine (Gua) and ribose-1-phosphate (R1P) as the varied substrates, and product inhibition patterns of synthetic and phosphorolytic reaction pathways were studied by steady-state kinetic methods. It is concluded that, like for mammalian trimeric PNP, complex kinetic characteristics observed for Cellulomonas enzyme results from simultaneous occurrence of three phenomena. These are sequential but random, not ordered binding of substrates, tight binding of one substrate purine bases, leading to the circumstances that for such substrates (products) rapid-equilibrium assumptions do not hold, and a dual role of Pi, a substrate, and also a reaction modifier that helps to release a tightly bound purine base.

  17. N-(2-Meth­oxy­benz­yl)-9-(oxolan-2-yl)-9H-purin-6-amine

    PubMed Central

    Trávníček, Zdeněk; Popa, Igor; Dvořák, Zdeněk; Štarha, Pavel

    2013-01-01

    The title compound, C17H19N5O2, features an almost planar purine skeleton (r.m.s. deviation = 0.009 Å) substituted by a tetra­hydro­furan ring, which adopts an envelope conformation. The purine and benzene rings subtend a dihedral angle of 66.70 (3)°. In the crystal, pairs of N—H⋯N hydrogen bonds connect adjacent mol­ecules into inversion dimers. C—H⋯N, C—H⋯O, C—H⋯π and π–π inter­actions [pyrimidine ring centroid–centroid distance = 3.3909 (1) Å] connect the dimers into a three-dimensional architecture. PMID:23634119

  18. N-(2-Meth-oxy-benz-yl)-9-(oxolan-2-yl)-9H-purin-6-amine.

    PubMed

    Trávníček, Zdeněk; Popa, Igor; Dvořák, Zdeněk; Starha, Pavel

    2013-04-01

    The title compound, C17H19N5O2, features an almost planar purine skeleton (r.m.s. deviation = 0.009 Å) substituted by a tetra-hydro-furan ring, which adopts an envelope conformation. The purine and benzene rings subtend a dihedral angle of 66.70 (3)°. In the crystal, pairs of N-H⋯N hydrogen bonds connect adjacent mol-ecules into inversion dimers. C-H⋯N, C-H⋯O, C-H⋯π and π-π inter-actions [pyrimidine ring centroid-centroid distance = 3.3909 (1) Å] connect the dimers into a three-dimensional architecture. PMID:23634119

  19. Effects of different lipid sources on intake, digestibility and purine derivatives in hair lambs.

    PubMed

    Pereira, E S; Pereira, M W F; Arruda, P C L; Cabral, L S; Oliveira, R L; Mizubuti, I Y; Pinto, A P; Campos, A C N; Gadelha, C R F; Carneiro, M S S

    2016-08-01

    An experiment was conducted to evaluate the effects of different lipid sources on the nutrient intake, digestibility and purine derivative excretion of lambs. Thirty-five 60-day-old, male, non-castrated Santa Ines lambs with an initial average body weight (BW) of 13.00 ± 1.80 kg were used in a randomized complete block design with seven blocks and five treatments. The experimental treatments consisted of a control diet without supplemental lipids and four test diets with different lipid supplements, selected according to the degree of ruminal protection from hydrogenation: supplementation, being supplementation with whole cottonseed (WC), supplementation with cashew nut meal (CNM), supplementation with both cottonseed and cashew nut meal (WC-CNM) and supplementation with calcium salts of long-chain fatty acids (Ca-LCFA). The lambs were slaughtered after reaching 28 kg average BW for each treatment. The ether extract intake (EEI) was higher (p < 0.01) for the lipid supplemented compared to control diet lambs. Supplementation with WC decreased the digestibility of dry matter (DM), organic matter (OM), neutral detergent fibre (NDF) and total carbohydrate (TC) (p < 0.01), whereas supplementation with CNM, WC-CNM and Ca-LCFA reduced non-fibrous carbohydrate (NFC) digestibility (p < 0.01). The ether extract (EE) digestibility coefficient was higher with CNM, followed by Ca-LCFA and WC, when compared to WC-CNM and control diets. Nitrogen balance (NB) was not influenced (p > 0.05) by the different lipid sources. A lower purine derivative (PD) excretion and thus lower microbial protein supply (MPS) was observed for animals supplemented with Ca-LCFA (p < 0.01) compared to the WC-CNM and control diets. In conclusion, WC, CNM and WC-CNM supplementation did not have negative effects on MPS, although negative effects have been observed on nutrient digestibility. PMID:26854276

  20. Purine salvage in the apicomplexan Sarcocystis neurona, and generation of hypoxanthine-xanthine-guanine phosphoribosyltransferase-deficient clones for positive-negative selection of transgenic parasites.

    PubMed

    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.

  1. UK photonics in defence and security

    NASA Astrophysics Data System (ADS)

    Gracie, C.; Tooley, I.; Wilson, A.

    2008-10-01

    The UK is globally recognised as strong in Photonics. However its Photonics sector is fragmented and the size and sectors of interest have not previously been established. The UK government has instigated the formation of the Photonics Knowledge Transfer Network (PKTN) to bring the Photonics community together. The UK features in Defence & Security; Communications; Measurement; Medical Technology; Lighting; Solar Energy; Information Technology and Flat Panels. This expertise is scattered through out the UK in geographic areas each with a breadth of Photonic interests. The PKTN has mapped the UK capability in all Photonics sectors. This paper will present the capability of the Companies, Research Institutions and Infrastructure making up the Defence & Security Photonics scene in the UK. Large Defence companies in the UK are well known throughout the world. However, there are a large number of SMEs, which may not be as well known in the supply chain. These are being actively encouraged by the UK MoD to engage with the Defence & Security Market and shall be discussed here. The presentation will reference a number of organisations which help to fund and network the community, such as the Defence Technology Centres. In addition the Roadmap for Defence & Security in the UK, produced for the UK Photonics Strategy (July 2006) by the Scottish Optoelectronics Association will be described and the plans in taking it forward under the PKTN will be revealed.

  2. Asymmetric Hydrogenation of α-Purine Nucleobase-Substituted Acrylates with Rhodium Diphosphine Complexes: Access to Tenofovir Analogues.

    PubMed

    Sun, Huan-Li; Chen, Fei; Xie, Ming-Sheng; Guo, Hai-Ming; Qu, Gui-Rong; He, Yan-Mei; Fan, Qing-Hua

    2016-05-01

    The first asymmetric hydrogenation of α-purine nucleobase-substituted α,β-unsaturated esters, catalyzed by a chiral rhodium (R)-Synphos catalyst, has been developed. A wide range of mono- and disubstituted acrylates were successfully hydrogenated under very mild conditions in high yields with good to excellent enantioselectivities (up to 99% ee). This method provides a convenient approach to the synthesis of a new kind of optically pure acyclic nucleoside and Tenofovir analogues. PMID:27112983

  3. Distribution coefficients of purine alkaloids in water-ammonium sulfate-alkyl acetate-dialkyl phthalate systems

    NASA Astrophysics Data System (ADS)

    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.

  4. Synthesis of some glycoside analogs and related compounds from 9-amino-6-(methylthio)-9H-purine.

    PubMed

    Temple, C; Kussner, C L; Montgomery, J A

    1975-12-01

    Additional information on the anticancer activity of 9-amino-9H-purine-6(1H)-thione and its derivatives was sought by the synthesis of some 9-(substituted amino)-6-(methylthio)-9H-purines in which the 9-substituent contained functional groups capable of either reversible or irreversible binding with an enzymatic site. Condensation of 9-amino-6-(methylthio)-9H-purine (1) with some carbonyl compounds followed by hydride reduction of the azomethine linkage in the intermediates leads to the 2-pyrrolylmethyl (8), 2,3,4-trihydroxybutyl (10), and the 1,5-dihydroxy-2- and 3-pentyl (11 and 12) compounds. A 4-hydroxybutyl derivative (13) was obtained by alkylation of 18, the 9-acetyl derivative of 1, with 4-chlorobutyl acetate followed by saponification. The cyclization of 13 and 11 with a sulfonyl chloride gave the 9-pyrrolidin-1-yl (27) and the 9-[2-(tosyloxymethyl)pyrrolidin-1-yl] (28), respectively. Acylation of 1 with ethyl L-2-pyrrolidine-5-carboxylate and ethyl 1-methyl-5-pyrrolidone-3-carboxylate, respectively, in Me2SO containing NaH gave the corresponding amides 15 and 17. Alkylation of 18 with 1-bromo-2-chloroethane and epichlorohydrin gave the N-(2-chloroethyl) and N-(1,2-epoxy-3-propyl) derivatives 19 and 20. The chloro group of the chlorobutyl derivative of 18 was displaced with KSCN and NaN3, respectively, to give the thiocyanate and azido derivatives 23 and 24. Hydrogenation of the latter gave the amine (25), which was acylated with ethyl chloroformate to give the (ethoxycarbonyl)amino compound 26. None of these compounds showed activity against L1210 leukemia cells implanted ip in mice on a single-dose schedule, suggesting that the activity observed in the simpler 9-aminopurines resulted from cleavage of the hydrazino linkage to give pH-purine-6(1H)-thione. PMID:1195279

  5. CuBr catalyzed C-N cross coupling reaction of purines and diaryliodonium salts to 9-arylpurines.

    PubMed

    Niu, Hong-Ying; Xia, Chao; Qu, Gui-Rong; Zhang, Qian; Jiang, Yi; Mao, Run-Ze; Li, De-Yang; Guo, Hai-Ming

    2011-07-21

    CuBr was found to be an efficient catalyst for the C-N cross coupling reaction of purine and diaryliodonium salts. 9-Arylpurines were synthesized in excellent yields with short reaction times (2.5 h). The method represents an alternative to the synthesis of 9-arylpurines via Cu(II) catalyzed C-N coupling reaction with arylboronic acids as arylating agents. PMID:21660365

  6. 2-Chloro-6-[(2,4-dimeth-oxy-benz-yl)amino]-9-isopropyl-9H-purine.

    PubMed

    Novotná, Radka; Trávníček, Zdeněk

    2013-03-01

    In the title compound, C17H20ClN5O2, the benzene ring and the purine ring system make a dihedral angle of 78.56 (4)°. In the crystal, mol-ecules are linked by pairs of N-H⋯N hydrogen bonds, forming inversion dimers. C-H⋯O and C-H⋯Cl contacts further link the mol-ecules, forming a three-dimensional network. PMID:23476575

  7. Purine analog substitution of the HIV-1 polypurine tract primer defines regions controlling initiation of plus-strand DNA synthesis

    PubMed Central

    Rausch, Jason W.; Le Grice, Stuart F. J.

    2007-01-01

    Despite extensive study, the mechanism by which retroviral reverse transciptases (RTs) specifically utilize polypurine tract (PPT) RNA for initiation of plus-strand DNA synthesis remains unclear. Three sequence motifs within or adjacent to the purine-rich elements are highly conserved, namely, a rU:dA tract region immediately 5′ to the PPT, an rA:dT-rich sequence constituting the upstream portion of the PPT and a downstream rG:dC tract. Using an in vitro HIV-1 model system, we determined that the former two elements define the 5′ terminus of the (+)-strand primer, whereas the rG:dC tract serves as the primary determinant of initiation specificity. Subsequent analysis demonstrated that G→A or A→G substitution at PPT positions −2, −4 and +1 (relative to the scissile phosphate) substantially reduces (+)-strand priming. We explored this observation further using PPT substrates substituted with a variety of nucleoside analogs [inosine (I), purine riboside (PR), 2-aminopurine (2-AP), 2,6-diaminopurine (2,6-DAP), isoguanine (iG)], or one of the naturally occurring bases at these positions. Our results demonstrate that for PPT positions −2 or +1, substituting position 2 of the purine was an important determinant of cleavage specificity. In addition, cleavage specificity was greatly affected by substituting −4G with an analog containing a 6-NH2 moiety. PMID:17164285

  8. Role and regulation of coordinately expressed de novo purine biosynthetic enzymes PPAT and PAICS in lung cancer.

    PubMed

    Goswami, Moloy T; Chen, Guoan; Chakravarthi, Balabhadrapatruni V S K; Pathi, Satya S; Anand, Sharath K; Carskadon, Shannon L; Giordano, Thomas J; Chinnaiyan, Arul M; Thomas, Dafydd G; Palanisamy, Nallasivam; Beer, David G; Varambally, Sooryanarayana

    2015-09-15

    Cancer cells exhibit altered metabolism including aerobic glycolysis that channels several glycolytic intermediates into de novo purine biosynthetic pathway. We discovered increased expression of phosphoribosyl amidotransferase (PPAT) and phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) enzymes of de novo purine biosynthetic pathway in lung adenocarcinomas. Transcript analyses from next-generation RNA sequencing and gene expression profiling studies suggested that PPAT and PAICS can serve as prognostic biomarkers for aggressive lung adenocarcinoma. Immunohistochemical analysis of PAICS performed on tissue microarrays showed increased expression with disease progression and was significantly associated with poor prognosis. Through gene knockdown and over-expression studies we demonstrate that altering PPAT and PAICS expression modulates pyruvate kinase activity, cell proliferation and invasion. Furthermore we identified genomic amplification and aneuploidy of the divergently transcribed PPAT-PAICS genomic region in a subset of lung cancers. We also present evidence for regulation of both PPAT and PAICS and pyruvate kinase activity by L-glutamine, a co-substrate for PPAT. A glutamine antagonist, 6-Diazo-5-oxo-L-norleucine (DON) blocked glutamine mediated induction of PPAT and PAICS as well as reduced pyruvate kinase activity. In summary, this study reveals the regulatory mechanisms by which purine biosynthetic pathway enzymes PPAT and PAICS, and pyruvate kinase activity is increased and exposes an existing metabolic vulnerability in lung cancer cells that can be explored for pharmacological intervention. PMID:26140362

  9. Role and regulation of coordinately expressed de novo purine biosynthetic enzymes PPAT and PAICS in lung cancer

    PubMed Central

    Pathi, Satya S.; Anand, Sharath K.; Carskadon, Shannon L.; Giordano, Thomas J.; Chinnaiyan, Arul M.; Thomas, Dafydd G.; Palanisamy, Nallasivam; Beer, David G.; Varambally, Sooryanarayana

    2015-01-01

    Cancer cells exhibit altered metabolism including aerobic glycolysis that channels several glycolytic intermediates into de novo purine biosynthetic pathway. We discovered increased expression of phosphoribosyl amidotransferase (PPAT) and phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) enzymes of de novo purine biosynthetic pathway in lung adenocarcinomas. Transcript analyses from next-generation RNA sequencing and gene expression profiling studies suggested that PPAT and PAICS can serve as prognostic biomarkers for aggressive lung adenocarcinoma. Immunohistochemical analysis of PAICS performed on tissue microarrays showed increased expression with disease progression and was significantly associated with poor prognosis. Through gene knockdown and over-expression studies we demonstrate that altering PPAT and PAICS expression modulates pyruvate kinase activity, cell proliferation and invasion. Furthermore we identified genomic amplification and aneuploidy of the divergently transcribed PPAT-PAICS genomic region in a subset of lung cancers. We also present evidence for regulation of both PPAT and PAICS and pyruvate kinase activity by L-glutamine, a co-substrate for PPAT. A glutamine antagonist, 6-Diazo-5-oxo-L-norleucine (DON) blocked glutamine mediated induction of PPAT and PAICS as well as reduced pyruvate kinase activity. In summary, this study reveals the regulatory mechanisms by which purine biosynthetic pathway enzymes PPAT and PAICS, and pyruvate kinase activity is increased and exposes an existing metabolic vulnerability in lung cancer cells that can be explored for pharmacological intervention. PMID:26140362

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

    PubMed Central

    2012-01-01

    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. PMID:23092390

  11. Profiles of phenolic compounds and purine alkaloids during the development of seeds of Theobroma cacao cv. Trinitario.

    PubMed

    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.

  12. Dependence of gamma-aminobutyric acid modulation of cholinergic transmission on nitric oxide and purines in cat terminal ileum.

    PubMed

    Pencheva, N

    1997-11-27

    The possible involvement of purines and/or nitric oxide (NO) in the gamma-aminobutyric acid (GABA)A receptor-mediated effects on the spontaneous activity of isolated preparations from longitudinal and circular muscles of cat terminal ileum was investigated. GABA had biphasic effects, which were neurogenic and muscarinic. ATP and adenosine dose dependently inhibited the activity of the muscles. A contractile response evoked by the nucleotide only was also observed. The effects of the purines were equipotent and resistant to Nomega-nitro-L-arginine (L-NNA), tetrodotoxin and to desensitization by alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-meATP), except for the contractile effect of ATP, which was abolished by alpha,beta-meATP. Pretreatment of the preparations with ATP or adenosine produced: (i) desensitization to the effects of the respective purinoceptor agonist only; and (ii) suppression of the GABA-induced responses of longitudinal and circular muscles. Hemoglobin and L-NNA greatly reduced or completely blocked the GABA(A)-induced relaxation and decreased the GABA(A)-induced contraction. Our results indicate that purines and NO, to a different extent, mediate the relaxant phase of the GABA effects in both layers. Interactions between muscarinic cholinoceptors and GABA-nitrergic pathway and a concomitant activation of postjunctional P1 and P2y purinoceptors are suggested to explain the prejunctional biphasic effects of GABA.

  13. Plant Purine Nucleoside Catabolism Employs a Guanosine Deaminase Required for the Generation of Xanthosine in Arabidopsis[W

    PubMed Central

    Dahncke, Kathleen; Witte, Claus-Peter

    2013-01-01

    Purine nucleotide catabolism is common to most organisms and involves a guanine deaminase to convert guanine to xanthine in animals, invertebrates, and microorganisms. Using metabolomic analysis of mutants, we demonstrate that Arabidopsis thaliana uses an alternative catabolic route employing a highly specific guanosine deaminase (GSDA) not reported from any organism so far. The enzyme is ubiquitously expressed and deaminates exclusively guanosine and 2’-deoxyguanosine but no other aminated purines, pyrimidines, or pterines. GSDA belongs to the cytidine/deoxycytidylate deaminase family of proteins together with a deaminase involved in riboflavin biosynthesis, the chloroplastic tRNA adenosine deaminase Arg and a predicted tRNA-specific adenosine deaminase 2 in A. thaliana. GSDA is conserved in plants, including the moss Physcomitrella patens, but is absent in the algae and outside the plant kingdom. Our data show that xanthosine is exclusively generated through the deamination of guanosine by GSDA in A. thaliana, excluding other possible sources like the dephosphorylation of xanthosine monophosphate. Like the nucleoside hydrolases NUCLEOSIDE HYDROLASE1 (NSH1) and NSH2, GSDA is located in the cytosol, indicating that GMP catabolism to xanthine proceeds in a mostly cytosolic pathway via guanosine and xanthosine. Possible implications for the biosynthetic route of purine alkaloids (caffeine and theobromine) and ureides in other plants are discussed. PMID:24130159

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

    PubMed

    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.

  15. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine

    PubMed Central

    Hirka, Gábor; Glávits, Róbert; Palmer, Philip A.; Endres, John R.; Pasics Szakonyiné, Ilona

    2016-01-01

    A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals. PMID:27635133

  16. Kinetic and thermodynamic studies of purine repressor binding to corepressor and operator DNA.

    PubMed

    Xu, H; Moraitis, M; Reedstrom, R J; Matthews, K S

    1998-04-10

    The kinetic and thermodynamic parameters for purine repressor (PurR)-operator and PurR-guanine binding were determined using fluorescence spectroscopy and nitrocellulose filter binding. Operator binding affinity was increased by the presence of guanine as demonstrated previously (Choi, K. Y., Lu, F., and Zalkin, H. (1994) J. Biol. Chem. 269, 24066-24072; Rolfes, R. J., and Zalkin, H. (1990) J. Bacteriol. 172, 5637-5642), and conversely guanine binding affinity was increased by the presence of operator. Guanine enhanced operator affinity by increasing the association rate constant and decreasing the dissociation rate constant for binding. Operator had minimal effect on the association rate constant for guanine binding; however, this DNA decreased the dissociation rate constant for corepressor by approximately 10-fold. Despite significant sequence and structural similarity between PurR and LacI proteins, PurR binds to its corepressor ligand with a lower association rate constant than LacI binds to its inducer ligand. However, the rate constant for PurR-guanine binding to operator is approximately 3-fold higher than for LacI binding to its cognate operator under the same solution conditions. The distinct metabolic roles of the enzymes under regulation by these two repressor proteins provide a rationale for the observed functional differences.

  17. Purine nucleoside metabolism in the erythrocytes of patients with adenosine deaminase deficiency and severe combined immunodeficiency.

    PubMed Central

    Agarwal, R P; Crabtree, G W; Parks, R E; Nelson, J A; Keightley, R; Parkman, R; Rosen, F S; Stern, R C; Polmar, S H

    1976-01-01

    Deficiency of erythrocytic and lymphocytic adenosine deaminase (ADA) occurs in some patients with severe combined immunodeficiency disease (SCID). SCID with ADA deficiency is inherited as an autosomal recessive trait. ADA is markedly reduced or undetectable in affected patients (homozygotes), and approximately one-half normal levels are found in individuals heterozygous for ADA deficiency. The metabolism of purine nucleosides was studied in erythrocytes from normal individuals, four ADA-deficiency patients, and two heterozygous individuals. ADA deficiency in intake erythrocytes was confirmed by a very sensitive ammonia-liberation technique. Erythrocytic ADA activity in three heterozygous individuals (0.07,0.08, and 0.14 mumolar units/ml of packed cells) was between that of the four normal controls (0.20-0.37 mumol/ml) and the ADA-deficient patients (no activity). In vitro, adenosine was incorporated principally into IMP in the heterozygous and normal individuals but into the adenosine nucleotides in the ADa-deficient patients. Coformycin (3-beta-D-ribofuranosyl-6,7,8-trihydroimidazo[4,5-4] [1,3] diazepin-8 (R)-ol), a potent inhibitor of ADA, made possible incorporation of adenosine nucleotides in the ADA-deficient patients... PMID:947948

  18. Analysis of abnormalities in purine metabolism leading to gout and to neurological dysfunctions in man.

    PubMed Central

    Curto, R; Voit, E O; Cascante, M

    1998-01-01

    A modelling approach is used to analyse diseases associated with purine metabolism in man. The specific focus is on deficiencies in two enzymes, hypoxanthine:guanine phosphoribosyltransferase and adenylosuccinate lyase. These deficiencies can lead to a number of symptoms, including neurological dysfunctions and mental retardation. Although the biochemical mechanisms of dysfunctions associated with adenylosuccinate lyase deficiency are not completely understood, there is at least general agreement in the literature about possible causes. Simulations with our model confirm that accumulation of the two substrates of the enzyme can lead to significant biochemical imbalance. In hypoxanthine:guanine phosphoribosyltransferase deficiency the biochemical mechanisms associated with neurological dysfunctions are less clear. Model analyses support some old hypotheses but also suggest new indicators for possible causes of neurological dysfunctions associated with this deficiency. Hypoxanthine:guanine phosphoribosyltransferase deficiency is known to cause hyperuricaemia and gout. We compare the relative importance of this deficiency with other known causes of gout in humans. The analysis suggests that defects in the excretion of uric acid are more consequential than defects in uric acid synthesis such as hypoxanthine:guanine phosphoribosyltransferase deficiency. PMID:9445373

  19. Solvent effects on the photochemistry of 4-aminoimidazole-5-carbonitrile, a prebiotically plausible precursor of purines.

    PubMed

    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.

  20. Oscillating response to a purine nucleotide disrupted by mutation in Paramecium tetraurelia.

    PubMed Central

    Mimikakis, J L; Nelson, D L; Preston, R R

    1998-01-01

    The purine nucleotide GTP, when added extracellularly, induces oscillations in the swimming behaviour of the protist Paramecium tetraurelia. For periods as long as 10 min the cell swims backwards and forwards repetitively. The oscillations in swimming behaviour are driven by changes in membrane potential of the cell, which in turn are caused by periodic activation of inward Mg2+- and Na+-specific currents. We screened for and isolated mutants that are defective in this response, exploiting the fact that the net result of GTP on a population of cells is repulsion. One mutant, GTP-insensitive (gin A), is not repelled by GTP. In addition, GTP fails to induce repetitive backwards swimming in gin A mutants, although they swim backwards normally in response to other stimuli. GTP fails to evoke oscillations in membrane potential or Mg2+ and Na+ currents in the mutant, although the Mg2+ and Na+ conductances are not themselves measurably affected. A small, oscillating Ca2+ current induced by GTP in the wild type, which might be part of the mechanism that generates oscillations, is also missing from gin A cells. To our knowledge, gin A is the first example of a mutant defective in a purinergic response. We discuss the possibility that the gin A lesion affects the oscillator itself. PMID:9461502

  1. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine.

    PubMed

    Clewell, Amy; Hirka, Gábor; Glávits, Róbert; Palmer, Philip A; Endres, John R; Murbach, Timothy S; Marx, Tennille; Pasics Szakonyiné, Ilona

    2016-01-01

    A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals. PMID:27635133

  2. A defect in the p53 response pathway induced by de novo purine synthesis inhibition.

    PubMed

    Bronder, Julie L; Moran, Richard G

    2003-12-01

    p53 is believed to sense cellular ribonucleotide depletion in the absence of DNA strand breaks and to respond by imposition of a p21-dependent G1 cell cycle arrest. We now report that the p53-dependent G1 checkpoint is blocked in human carcinoma cell lines after inhibition of de novo purine synthesis by folate analogs inhibitory to glycinamide ribonucleotide formyltransferase (GART). p53 accumulated in HCT116, MCF7, or A549 carcinoma cells upon GART inhibition, but, surprisingly, transcription of several p53 targets, including p21cip1/waf1, was impaired. The mechanism of this defect was examined. The p53 accumulating in these cells was nuclear but was not phosphorylated at serines 6, 15, and 20, nor was it acetylated at lysines 373 or 382. The DDATHF-stabilized p53 bound to the p21 promoter in vitro and in vivo but did not activate histone acetylation over the p53 binding sites in the p21 promoter that is an integral part of the transcriptional response mediated by the DNA damage pathway. We concluded that the robust initial response of the p53 pathway to GART inhibitors is not transcriptionally propagated to target genes due to a defect in p53 post-translational modifications and a failure to open chromatin structure despite promoter binding of this unmodified p53. PMID:14517211

  3. Solution-Phase Parallel Synthesis of Acyclic Nucleoside Libraries of Purine, Pyrimidine, and Triazole Acetamides

    PubMed Central

    2015-01-01

    Molecular diversity plays a pivotal role in modern drug discovery against phenotypic or enzyme-based targets using high throughput screening technology. Under the auspices of the Pilot Scale Library Program of the NIH Roadmap Initiative, we produced and report herein a diverse library of 181 purine, pyrimidine, and 1,2,4-triazole-N-acetamide analogues which were prepared in a parallel high throughput solution-phase reaction format. A set of assorted amines were reacted with several nucleic acid N-acetic acids utilizing HATU as the coupling reagent to produce diverse acyclic nucleoside N-acetamide analogues. These reactions were performed using 24 well reaction blocks and an automatic reagent-dispensing platform under inert atmosphere. The targeted compounds were purified on an automated purification system using solid sample loading prepacked cartridges and prepacked silica gel columns. All compounds were characterized by NMR and HRMS, and were analyzed for purity by HPLC before submission to the Molecular Libraries Small Molecule Repository (MLSMR) at NIH. Initial screening through the Molecular Libraries Probe Production Centers Network (MLPCN) program, indicates that several analogues showed diverse and interesting biological activities. PMID:24933643

  4. Central nervous system dysfunction and erythrocyte guanosine triphosphate depletion in purine nucleoside phosphorylase deficiency.

    PubMed Central

    Simmonds, H A; Fairbanks, L D; Morris, G S; Morgan, G; Watson, A R; Timms, P; Singh, B

    1987-01-01

    Developmental retardation was a prominent clinical feature in six infants from three kindreds deficient in the enzyme purine nucleoside phosphorylase (PNP) and was present before development of T cell immunodeficiency. Guanosine triphosphate (GTP) depletion was noted in the erythrocytes of all surviving homozygotes and was of equivalent magnitude to that found in the Lesch-Nyhan syndrome (complete hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency). The similarity between the neurological complications in both disorders indicates that the two major clinical consequences of complete PNP deficiency have differing aetiologies: neurological effects resulting from deficiency of the PNP enzyme products, which are the substrates for HGPRT, leading to functional deficiency of this enzyme. immunodeficiency caused by accumulation of the PNP enzyme substrates, one of which, deoxyguanosine, is toxic to T cells. These studies show the need to consider PNP deficiency (suggested by the finding of hypouricaemia) in patients with neurological dysfunction, as well as in T cell immunodeficiency. They suggest an important role for GTP in normal central nervous system function. PMID:2439024

  5. Effect of root application of 6-benzylamine purine on auxin transport in Malus domestica

    SciTech Connect

    Stutte, G.

    1987-04-01

    The effect of 6-benzylamine purine (BA) on movement of napthalene acetic acid (NAA) applied to the shoot was investigated. Three-month-old York apple seedlings in sand culture were placed under mercury halide lamps (285 ..mu..mol m/sup -2/ s/sup -1/) at 22/sup 0/C for 24 hours; then 13.8, 27.5 or 55 ..mu..Mol of BA was applied as a soil drench. (/sup 14/C)-NAA was injected into the shoot at petiole base of 4th mature leaf. After 24 hours plants were harvested and movement of label acropetally to new shoot growth and basipetally to old shoot growth or roots determined. Seventeen (S.E. 3.3) percent of applied label was recovered away from application site. In controls, 67% of /sup 14/C that moved was recovered from new shoot growth, 9% in roots and 24% in old shoot tissue. The 13.8 ..mu..Mol treatment resulted in 37% of label being recovered in root tissue and 48% in new growth. The 27.5 and 55 ..mu..Mol applications increased the amount recovered in old shoot tissue but did not increase labelling of root tissues.

  6. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine

    PubMed Central

    Hirka, Gábor; Glávits, Róbert; Palmer, Philip A.; Endres, John R.; Pasics Szakonyiné, Ilona

    2016-01-01

    A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals.

  7. The antibacterial activity and toxicity of enrofloxacin are decreased by nanocellulose conjugated with aminobenzyl purin.

    PubMed

    Yasini, Seyed Ali; Zadeh, Mohammad Hossein Balal; Shahdadi, Hossein

    2015-11-01

    The first aim of this study was to synthesize nanocellulose conjugated with aminobenzyl purin (NCABP), and the second aim was to evaluate the effect of NCABP on both toxicity and antibacterial activity of enrofloxacin. Here, the adsorption of enrofloxacin by NCABP was first modeled by molecular dynamic (MD) simulation. In the next step, NCABP was synthesized, and was exposed to enrofloxacin, 1000 μg mL(-1), at various conditions. Then, the quantity of adsorption and release was separately measured. Furthermore, both toxicity and antibacterial activity of NCABP, enrofloxacin, and (NCABP+enrofloxacin) were separately evaluated. In this study, MD simulation clearly showed the adsorption after 50 picoseconds. The adsorption tests revealed that the increase of incubation time and NCABP concentration, at range of 50-200 μg mL(-1), led to increase of adsorption. Moreover, the decrease of pH led to increase of adsorption. Interestingly, NCABP could adsorb enrofloxacin, up to 1000 μg mL(-1), in different types of meat. Moreover, the increase of incubation time and temperature did not release enrofloxacin, but the increase of pH increased release. This study showed that both toxicity and antibacterial activity of enrofloxacin were decreased when exposed together with NCABP. PMID:26295691

  8. Elucidation of Different Binding Modes of Purine Nucleosides to Human Deoxycytidine Kinase

    SciTech Connect

    Sabini, Elisabetta; Hazra, Saugata; Konrad, Manfred; Lavie, Arnon

    2008-07-30

    Purine nucleoside analogues of medicinal importance, such as cladribine, require phosphorylation by deoxycytidine kinase (dCK) for pharmacological activity. Structural studies of ternary complexes of human dCK show that the enzyme conformation adjusts to the different hydrogen-bonding properties between dA and dG and to the presence of substituent at the 2-position present in dG and cladribine. Specifically, the carbonyl group in dG elicits a previously unseen conformational adjustment of the active site residues Arg104 and Asp133. In addition, dG and cladribine adopt the anti conformation, in contrast to the syn conformation observed with dA. Kinetic analysis reveals that cladribine is phosphorylated at the highest efficiency with UTP as donor. We attribute this to the ability of cladribine to combine advantageous properties from dA (favorable hydrogen-bonding pattern) and dG (propensity to bind to the enzyme in its anti conformation), suggesting that dA analogues with a substituent at the 2-position are likely to be better activated by human dCK.

  9. Crystal structure and molecular dynamics studies of human purine nucleoside phosphorylase complexed with 7-deazaguanine.

    PubMed

    Caceres, Rafael Andrade; Timmers, Luis Fernando Saraiva Macedo; Pauli, Ivani; Gava, Lisandra Marques; Ducati, Rodrigo Gay; Basso, Luiz Augusto; Santos, Diógenes Santiago; de Azevedo, Walter Filgueira

    2010-03-01

    In humans, purine nucleoside phosphorylase (HsPNP) is responsible for degradation of deoxyguanosine, and genetic deficiency of this enzyme leads to profound T-cell mediated immunosuppression. HsPNP is a target for inhibitor development aiming at T-cell immune response modulation. Here we report the crystal structure of HsPNP in complex with 7-deazaguanine (HsPNP:7DG) at 2.75 A. Molecular dynamics simulations were employed to assess the structural features of HsPNP in both free form and in complex with 7DG. Our results show that some regions, responsible for entrance and exit of substrate, present a conformational variability, which is dissected by dynamics simulation analysis. Enzymatic assays were also carried out and revealed that 7-deazaguanine presents a lower inhibitory activity against HsPNP (K(i)=200 microM). The present structure may be employed in both structure-based design of PNP inhibitors and in development of specific empirical scoring functions.

  10. Substrate specificity and kinetic mechanism of purine nucleoside phosphorylase from Mycobacterium tuberculosis.

    PubMed

    Ducati, Rodrigo G; Santos, Diógenes S; Basso, Luiz A

    2009-06-15

    Purine nucleoside phosphorylase from Mycobacterium tuberculosis (MtPNP) is numbered among targets for persistence of the causative agent of tuberculosis. Here, it is shown that MtPNP is more specific to natural 6-oxopurine nucleosides and synthetic compounds, and does not catalyze the phosphorolysis of adenosine. Initial velocity, product inhibition and equilibrium binding data suggest that MtPNP catalyzes 2'-deoxyguanosine (2dGuo) phosphorolysis by a steady-state ordered bi bi kinetic mechanism, in which inorganic phosphate (P(i)) binds first followed by 2dGuo, and ribose 1-phosphate dissociates first followed by guanine. pH-rate profiles indicated a general acid as being essential for both catalysis and 2dGuo binding, and that deprotonation of a group abolishes P(i) binding. Proton inventory and solvent deuterium isotope effects indicate that a single solvent proton transfer makes a modest contribution to the rate-limiting step. Pre-steady-state kinetic data indicate that product release appears to contribute to the rate-limiting step for MtPNP-catalyzed reaction.

  11. Capillary bioreactors based on human purine nucleoside phosphorylase: a new approach for ligands identification and characterization.

    PubMed

    de Moraes, Marcela Cristina; Ducati, Rodrigo Gay; Donato, Augusto José; Basso, Luiz Augusto; Santos, Diógenes Santiago; Cardoso, Carmen Lucia; Cass, Quezia Bezerra

    2012-04-01

    The enzyme purine nucleoside phosphorylase (PNP) is a target for the discovery of new lead compounds employed on the treatment severe T-cell mediated disorders. Within this context, the development of new, direct, and reliable methods for ligands screening is an important task. This paper describes the preparation of fused silica capillaries human PNP (HsPNP) immobilized enzyme reactor (IMER). The activity of the obtained IMER is monitored on line in a multidimensional liquid chromatography system, by the quantification of the product formed throughout the enzymatic reaction. The K(M) value for the immobilized enzyme was about twofold higher than that measured for the enzyme in solution (255 ± 29.2 μM and 133 ± 14.9 μM, respectively). A new fourth-generation immucillin derivative (DI4G; IC(50)=40.6 ± 0.36 nM), previously identified and characterized in HsPNP free enzyme assays, was used to validate the IMER as a screening method for HsPNP ligands. The validated method was also used for mechanistic studies with this inhibitor. This new approach is a valuable tool to PNP ligand screening, since it directly measures the hypoxanthine released by inosine phosphorolysis, thus furnishing more reliable results than those one used in a coupled enzymatic spectrophotometric assay.

  12. Structural studies of human purine nucleoside phosphorylase: towards a new specific empirical scoring function.

    PubMed

    Timmers, Luis Fernando Saraiva Macedo; Caceres, Rafael Andrade; Vivan, Ana Luiza; Gava, Lisandra Marques; Dias, Raquel; Ducati, Rodrigo Gay; Basso, Luiz Augusto; Santos, Diogenes Santiago; de Azevedo, Walter Filgueira

    2008-11-01

    Human purine nucleoside phosphorylase (HsPNP) is a target for inhibitor development aiming at T-cell immune response modulation. In this work, we report the development of a new set of empirical scoring functions and its application to evaluate binding affinities and docking results. To test these new functions, we solved the structure of HsPNP and 2-mercapto-4(3H)-quinazolinone (HsPNP:MQU) binary complex at 2.7A resolution using synchrotron radiation, and used these functions to predict ligand position obtained in docking simulations. We also employed molecular dynamics simulations to analyze HsPNP in two conditions, as apoenzyme and in the binary complex form, in order to assess the structural features responsible for stability. Analysis of the structural differences between systems provides explanation for inhibitor binding. The use of these scoring functions to evaluate binding affinities and molecular docking results may be used to guide future efforts on virtual screening focused on HsPNP.

  13. UK mining invests, suppliers profit

    SciTech Connect

    2009-04-15

    In the midst of a major economic crisis in the United Kingdom, equipment suppliers have been reporting a number of considerable purchases by British coal mining companies. In December 2008, Liebherr-Great Britain delivered the first two of four Rq350 Litronic hydraulic excavators for use at the Broken Cross opencast coal site in Lanarkshire, Scotland. Ten Terex TR100 rigid haulers were delivered to the site in late 2008. Hatfield Colliery at Stainforth, South Yorkshire, has been reopened by PowerFuel. The main equipment for two longwall faces was supplied by Joy Mining Machinery UK Ltd. 2 photos.

  14. A novel bis(pinacolato)diboron-mediated N-O bond deoxygenative route to C6 benzotriazolyl purine nucleoside derivatives.

    PubMed

    Basava, Vikram; Yang, Lijia; Pradhan, Padmanava; Lakshman, Mahesh K

    2016-08-01

    Reaction of amide bonds in t-butyldimethylsilyl-protected inosine, 2'-deoxyinosine, guanosine, 2'-deoxyguanosine, and 2-phenylinosine with commercially available peptide-coupling agents (benzotriazol-1H-yloxy)tris(dimethylaminophosphonium) hexafluorophosphate (BOP), (6-chloro-benzotriazol-1H-yloxy)trispyrrolidinophosphonium hexafluorophosphate (PyClocK), and (7-azabenzotriazol-1H-yloxy)trispyrrolidinophosphonium hexafluorophospate (PyAOP) gave the corresponding O(6)-(benzotriazol-1-yl) nucleoside analogues containing a C-O-N bond. Upon exposure to bis(pinacolato)diboron and base, the O(6)-(benzotriazol-1-yl) and O(6)-(6-chlorobenzotriazol-1-yl) purine nucleoside derivatives obtained from BOP and PyClocK, respectively, underwent N-O bond reduction and C-N bond formation, leading to the corresponding C6 benzotriazolyl purine nucleoside analogues. In contrast, the 7-azabenzotriazolyloxy purine nucleoside derivatives did not undergo efficient deoxygenation, but gave unsymmetrical nucleoside dimers instead. This is consistent with a prior report on the slow reduction of 1-hydroxy-1H-4-aza and 1-hydroxy-1H-7-azabenzotriazoles. Because of the limited number of commercial benzotriazole-based peptide coupling agents, and to show the applicability of the method when such coupling agents are unavailable, 1-hydroxy-1H-5,6-dichlorobenzotriazole was synthesized. Using this compound, silyl-protected inosine and 2'-deoxyinosine were converted to the O(6)-(5,6-dichlorobenzotriazol-1-yl) derivatives via in situ amide activation with PyBroP. The O(6)-(5,6-dichlorobenzotriazol-1-yl) purine nucleosides so obtained also underwent smooth reduction to afford the corresponding C6 5,6-dichlorobenzotriazolyl purine nucleoside derivatives. A total of 13 examples were studied with successful reactions occurring in 11 cases (the azabenzotriazole derivatives, mentioned above, being the only unreactive entities). To understand whether these reactions are intra or intermolecular processes, a

  15. Three-dimensional analysis of the distal movement of maxillary 1st molars in patients fitted with mini-implant-aided trans-palatal arches

    PubMed Central

    Miresmaeili, Amirfarhang; Sajedi, Ahmad; Moghimbeigi, Abbas

    2015-01-01

    Objective The aim of this study was to investigate three-dimensional molar displacement after distalization via miniscrews and a horizontal modification of the trans-palatal-arch (TPA). Methods The subjects in this clinical trial were 26 Class II patients. After the preparation of a complete set of diagnostic records, miniscrews were inserted between the maxillary 2nd premolar and 1st molar on the palatal side. Elastic modules connected to the TPA exerting an average force of 150-200 g/side parallel to the occlusal plane were applied. Cone-beam computed tomography was utilized to evaluate the position of the miniscrews relative to the adjacent teeth and maxillary sinus, and the direction of force relative to molar furcation. The distances from the central point of the incisive papilla to the mesiopalatal cusps of the 1st maxillary molars and the distances between the mesiopalatal cusps of the left and right molars were measured to evaluate displacement of the maxillary molars on the horizontal plane. Interocclusal space was used to evaluate vertical changes. Results Mean maxillary 1st molar distalization was 2.3 ± 1.1 mm, at a rate of 0.4 ± 0.2 mm/month, and rotation was not significant. Intermolar width increased by 2.9 ± 1.8 mm. Molars were intruded relative to the neighboring teeth, from 0.1 to 0.8 mm. Conclusions Distalization of molars was possible without extrusion, using the appliance investigated. The intrusive component of force reduced the rate of distal movement. PMID:26445718

  16. An Introduction to ESERO-UK, the UK Space Education Office

    ERIC Educational Resources Information Center

    Clements, Allan; Mather, Edward

    2012-01-01

    This article introduces the UK branch of the European Space Education Resource Office (ESERO-UK), also known as the UK Space Education Office. It is a teaching project designed to use space to enthuse primary and secondary students to study science, technology, engineering and mathematics (STEM) subjects. The office is funded by the European Space…

  17. Incidence of Myelodysplastic Syndrome in UK Petroleum Distribution and Oil Refinery Workers, 1995-2011.

    PubMed

    Sorahan, Tom; Mohammed, Nuredin

    2016-05-06

    The incidence of myelodysplastic syndrome (MDS) experienced by cohorts of 16,467 petroleum distribution workers and 28,554 oil refinery workers has been investigated. Study subjects were all those male employees first employed at one of 476 UK petroleum distribution centres or eight UK oil refineries in the period 1946-1974; all subjects had a minimum of twelve months employment with some employment after 1st January, 1951. Observed numbers (Obs) of MDS cases were compared with expectations based on national incidence rates for the period 1995-2011. The overall standardised registration ratio (SRR) was 73 (Obs = 17) in petroleum distribution workers for the age-range 15-84 years, and 77 (Obs = 21) for the age-range 15-99 years. The overall SRR was 81 (Obs = 29) in oil refinery workers for the age-range 15-84 years, and 83 (Obs = 36) for the age-range 15-99 years. More detailed analyses were carried out in terms of year of registration, period from hire, decade of hire, and duration of employment. The overall SRR findings did not provide clear evidence for the presence of an occupational cancer hazard, and provide no support for the hypothesis that low-level benzene exposure has an important effect on the risks of MDS.

  18. Science education reforms in the UK.

    PubMed

    2012-10-01

    As children return to school at the end of the summer in the UK, planned reforms aim to increase their science and maths literacy. A comprehensive foundation in these essential subjects is necessary to ensure that the UK remains at the forefront of science and technology for decades to come.

  19. Leadership Practices in German and UK Organisations

    ERIC Educational Resources Information Center

    McCarthy, Grace

    2005-01-01

    Purpose: The aim of this research was to determine whether leadership practices vary between German and UK organisations. Design/methodology/approach: The author used self-assessment documents submitted by German and UK organisations to the European Foundation for Quality Management (EFQM), to identify leadership practices in both countries. A…

  20. The Geomatics.org.UK Project

    ERIC Educational Resources Information Center

    Bramald, Tom; Powell, Jonathan

    2006-01-01

    In this article, the authors describe how pupils can benefit from some unusual and exciting free resources of geomatics.org.uk. Geomatics.org.uk is a project that provides free resources to support teaching and learning in a variety of subjects including maths and geography, often in a cross-curricular way. Via the project website, it is possible,…

  1. An IT Revolution in UK Schools?

    ERIC Educational Resources Information Center

    Watson, Deryn M.

    Evidence indicates that the anticipated Information Technology (IT) revolution in United Kingdom (UK) schools has not occurred. The ImpacT study evaluated the effect of IT on children's achievements in UK primary and secondary schools. The research revealed that IT can make significant contributions to teaching and learning, but a variety of…

  2. UK Policy on Folate Fortification of Foods

    ERIC Educational Resources Information Center

    Malcolm, Alan

    2004-01-01

    The UK Food Standards Agency has decided not to recommend fortification of foods with folate, the family of vitamins associated with the prevention of neural tube defects in babies. This is a change in attitude from previous recommendations made by a series of committees and reports in the UK. Notably, it differs from US policy on the matter. The…

  3. Four Generations of Transition State Analogues for Human Purine Nucleoside Phosphorylase

    SciTech Connect

    Ho, M.; Shi, W; Rinaldo-Mathis, A; Tyler, P; Evans, G; Almo, S; Schramm, V

    2010-01-01

    Inhibition of human purine nucleoside phosphorylase (PNP) stops growth of activated T-cells and the formation of 6-oxypurine bases, making it a target for leukemia, autoimmune disorders, and gout. Four generations of ribocation transition-state mimics bound to PNP are structurally characterized. Immucillin-H (K*{sub i} = 58 pM, first-generation) contains an iminoribitol cation with four asymmetric carbons. DADMe-Immucillin-H (K*{sub i} = 9 pM, second-generation), uses a methylene-bridged dihydroxypyrrolidine cation with two asymmetric centers. DATMe-Immucillin-H (K*{sub i} = 9 pM, third-generation) contains an open-chain amino alcohol cation with two asymmetric carbons. SerMe-ImmH (K*{sub i} = 5 pM, fourth-generation) uses achiral dihydroxyaminoalcohol seramide as the ribocation mimic. Crystal structures of PNPs establish features of tight binding to be; (1) ion-pair formation between bound phosphate (or its mimic) and inhibitor cation, (2) leaving-group interactions to N1, O6, and N7 of 9-deazahypoxanthine, (3) interaction between phosphate and inhibitor hydroxyl groups, and (4) His257 interacting with the 5{prime}-hydroxyl group. The first generation analogue is an imperfect fit to the catalytic site with a long ion pair distance between the iminoribitol and bound phosphate and weaker interactions to the leaving group. Increasing the ribocation to leaving-group distance in the second- to fourth-generation analogues provides powerful binding interactions and a facile synthetic route to powerful inhibitors. Despite chemical diversity in the four generations of transition-state analogues, the catalytic site geometry is almost the same for all analogues. Multiple solutions in transition-state analogue design are available to convert the energy of catalytic rate enhancement to binding energy in human PNP.

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

    PubMed Central

    Bagshaw, Andrew TM; Pitt, Joel PW; Gemmell, Neil J

    2006-01-01

    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 recombination hot spots

  5. Conformational States of Human Purine Nucleoside Phosphorylase at Rest, at Work and with Transition State Analogues†

    PubMed Central

    Edwards, Achelle A.; Tipton, Jeremiah D.; Brenowitz, Michael D.; Emmett, Mark R.; Marshall, Alan G.; Evans, Gary B.; Tyler, Peter C.; Schramm, Vern L.

    2010-01-01

    Human purine nucleoside phosphorylase (PNP) is a homotrimer binding tightly to the transition state analogues Immucillin-H (ImmH, Kd = 56 pM) and DATMe-ImmH-Immucillin-H (DATMe-ImmH, Kd = 8.6 pM). ImmH binds with a larger entropic penalty than DATMe-ImmH, a chemically more flexible inhibitor. The testable hypothesis is that PNP conformational states are more relaxed (dynamic) with DATMe-ImmH, despite tighter binding than with ImmH. PNP conformations are probed by peptide amide deuterium exchange (HDX) using liquid chromatography high-resolution Fourier transform ion cyclotron resonance mass spectrometry and by sedimentation rates. Catalytically equilibrating Michaelis complexes (PNP•PO4•Inosine ↔ PNP•Hx•R-1-P) and inhibited complexes (PNP•PO4•DATMe-ImmH and PNP•PO4•ImmH) show protection from HDX at 9, 13 and 15 sites per subunit relative to resting PNP (PNP•PO4) in extended incubations. The PNP•PO4•ImmH complex is more compact (by sedimentation rate) than the other complexes. HDX kinetic analysis of ligand-protected sites corresponds to peptides near the catalytic sites. HDX and sedimentation results establish that PNP protein conformation (dynamic motion) correlates more closely to entropy of binding than to affinity. Catalytically active turnover with saturated substrate sites causes less change in HDX and sedimentation rates than binding of transition state analogues. DATMe-ImmH more closely mimics the transition of human PNP than does ImmH, and achieves strong binding interactions at the catalytic site while causing relatively modest alterations of the protein dynamic motion. Transition state analogues causing the most rigid, closed protein conformation are therefore not necessarily the most tightly bound. Close mimics of the transition state are hypothesized to retain enzymatic dynamic motions related to transition state formation. PMID:20108972

  6. Hydrogen bond donors accelerate vibrational cooling of hot purine derivatives in heavy water.

    PubMed

    Zhang, Yuyuan; Chen, Jinquan; Kohler, Bern

    2013-08-01

    Natural nucleobases and many of their derivatives have ultrashort excited state lifetimes that make them excellent model systems for studying intermolecular energy flow from a hot solute molecule to the solvent. UV-pump/broadband-mid-IR-probe transient absorption spectra of canonical purine nucleobases and several xanthine derivatives were acquired in D2O and acetonitrile in the probe frequency range of 1500-1750 cm(-1). The spectra reveal that vibrationally hot ground state molecules created by ultrafast internal conversion return to thermal equilibrium in several picoseconds by dissipating their excess energy to solvent molecules. In acetonitrile solution, where hydrogen bonding is minimal, vibrational cooling (VC) occurs with the same time constant of 10 ± 3 ps for paraxanthine, theophylline, and caffeine within experimental uncertainty. In D2O, VC by these molecules occurs more rapidly and at different rates that are correlated with the number of N-D bonds. Hypoxanthine has a VC time constant of 3 ± 1 ps, while similar lifetimes of 2.3 ± 0.8 ps and 3.1 ± 0.3 ps are seen for 5'-adenosine monophosphate and 5'-guanosine monophosphate, respectively. All three molecules have at least two N-D bonds. Slightly slower VC time constants are measured for paraxanthine (4 ± 1 ps) and theophylline (5.1 ± 0.8 ps), dimethylated xanthines that have only one N-D bond. Caffeine, a trimethylated xanthine with no N-D bonds, has a VC time constant of 7.7 ± 0.9 ps, the longest ever observed for any nucleobase in aqueous solution. Hydrogen bond donation by solute molecules is proposed to enable rapid energy disposal to water via direct coupling of high frequency solute-solvent modes.

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

    PubMed Central

    Chène, Patrick; Rudloff, Joëlle; Schoepfer, Joseph; Furet, Pascal; Meier, Peter; Qian, Zhiyan; Schlaeppi, Jean-Marc; Schmitz, Rita; Radimerski, Thomas

    2009-01-01

    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. PMID:19128485

  8. Effect of thrombin on purine metabolism in the guinea pig heart

    SciTech Connect

    Whelton, B.K.; Thompson, C.I.; Sparks, H.V.

    1986-03-01

    In vitro coronary endothelial cells (EC) release adenosine (ADO) in response to thrombin (THR). The authors tested the hypothesis that THR causes the release of ADO from in situ EC of isolated guinea pig hearts. The authors preferentially labelled the EC by infusing 2,8-/sup 3/H-ADO (ADO; 5 x 10/sup -8/ M) into the heart for 30 minutes. Then THR (1 U/ml) or THR plus allopurinol (2.4 x 10-/sup 4M) was infused into the heart. Venous effluent samples analyzed for ADO, ADO and /sup 3/H-H/sub 2/O. THR increased the release of ADO from 32 +/- 11 pm/min/g to 175 +/- 47 after 4 minutes (p < 0.02, n = 5). Despite the increase in total ADO release, ADO did not increase. Release of H/sub 2/O increased from 10.1 +/- 10/sup 3/ dpm/min/g to 23.5 +/- 5.7 x 10/sup 3/ at 4 minutes. In the presence of the xanthine oxidase/dehydrogenase inhibitor allopurinol, H/sub 2/O release in response to THR fell to 3.6 +/- 1.2 x 10 dpm/min/gm. The authors conclude that the labelled EC are not the source of ADO released in response to THR. Instead the ADO released by THR comes from an unlabelled compartment, most likely the myocytes. This suggests that ADO release from myocytes may be a mechanism to regulate thrombogenesis. The THR-induced increase in H/sub 2/O release and it's inhibition by allopurinol indicates that THR enhances purine catabolism in EC.

  9. High-Frequency Variation of Purine Biosynthesis Genes Is a Mechanism of Success in Campylobacter jejuni

    PubMed Central

    Cameron, Andrew; Huynh, Steven; Scott, Nichollas E.; Frirdich, Emilisa; Apel, Dmitry; Foster, Leonard J.; Parker, Craig T.

    2015-01-01

    ABSTRACT Phenotypic variation is prevalent in the zoonotic pathogen Campylobacter jejuni, the leading agent of enterocolitis in the developed world. Heterogeneity enhances the survival and adaptive malleability of bacterial populations because variable phenotypes may allow some cells to be protected against future stress. Exposure to hyperosmotic stress previously revealed prevalent differences in growth between C. jejuni strain 81-176 colonies due to resistant or sensitive phenotypes, and these isolated colonies continued to produce progeny with differential phenotypes. In this study, whole-genome sequencing of isolated colonies identified allelic variants of two purine biosynthesis genes, purF and apt, encoding phosphoribosyltransferases that utilize a shared substrate. Genetic analyses determined that purF was essential for fitness, while apt was critical. Traditional and high-depth amplicon-sequencing analyses confirmed extensive intrapopulation genetic variation of purF and apt that resulted in viable strains bearing alleles with in-frame insertion duplications, deletions, or missense polymorphisms. Different purF and apt alleles were associated with various stress survival capabilities under several niche-relevant conditions and contributed to differential intracellular survival in an epithelial cell infection model. Amplicon sequencing revealed that intracellular survival selected for stress-fit purF and apt alleles, as did exposure to oxygen and hyperosmotic stress. Putative protein recognition direct repeat sequences were identified in purF and apt, and a DNA-protein affinity screen captured a predicted exonuclease that promoted the global spontaneous mutation rate. This work illustrates the adaptive properties of high-frequency genetic variation in two housekeeping genes, which influences C. jejuni survival under stress and promotes its success as a pathogen. PMID:26419875

  10. Understanding abnormal potential behaviors at the 1st charge in Li2S cathode material for rechargeable Li-S batteries.

    PubMed

    Jung, Yongjo; Kang, Byoungwoo

    2016-08-01

    In this study, electrochemical behaviors of Li2S such as a large potential barrier at the beginning of the 1st charging process and a continuous increase in potential to ∼4 V during the rest of this process were understood through X-ray photoelectron spectroscopy measurements and electrochemical evaluations for a full utilization of Li2S. The large potential barrier to the 1st charge in Li2S can be caused by the presence of insulating oxidized products (Li2SO3 or Li2SO4-like structures) on the surface; simple surface etching can remove them and thereby reduce the potential barrier. Even though the potential barrier was substantially reduced, the electrochemical activity of Li2S might not be improved due to the continuous increase in potential. This increase in potential was related to the polarization caused by the Li2S-conversion reaction; the polarization can affect the utilization of Li2S in subsequent cycles. We speculate that the increase in potential is related to the decomposition of oxidized products such as Li2CO3-like or Li2O-like structures on the surface of the Li2S particles. These findings indicate that the full utilization of Li2S can be achieved by controlling their surface characteristics, especially the surface oxidation products. PMID:27426215

  11. Purines in the eye: recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Müller cells, lens, trabecular meshwork, cornea and lacrimal gland.

    PubMed

    Sanderson, Julie; Dartt, Darlene A; Trinkaus-Randall, Vickery; Pintor, Jesus; Civan, Mortimer M; Delamere, Nicholas A; Fletcher, Erica L; Salt, Thomas E; Grosche, Antje; Mitchell, Claire H

    2014-10-01

    This review highlights recent findings that describ how purines modulate the physiological and pathophysiological responses of ocular tissues. For example, in lacrimal glands the cross-talk between P2X7 receptors and both M3 muscarinic receptors and α1D-adrenergic receptors can influence tear secretion. In the cornea, purines lead to post-translational modification of EGFR and structural proteins that participate in wound repair in the epithelium and influence the expression of matrix proteins in the stroma. Purines act at receptors on both the trabecular meshwork and ciliary epithelium to modulate intraocular pressure (IOP); ATP-release pathways of inflow and outflow cells differ, possibly permitting differential modulation of adenosine delivery. Modulators of trabecular meshwork cell ATP release include cell volume, stretch, extracellular Ca(2+) concentration, oxidation state, actin remodeling and possibly endogenous cardiotonic steroids. In the lens, osmotic stress leads to ATP release following TRPV4 activation upstream of hemichannel opening. In the anterior eye, diadenosine polyphosphates such as Ap4A act at P2 receptors to modulate the rate and composition of tear secretion, impact corneal wound healing and lower IOP. The Gq11-coupled P2Y1-receptor contributes to volume control in Müller cells and thus the retina. P2X receptors are expressed in neurons in the inner and outer retina and contribute to visual processing as well as the demise of retinal ganglion cells. In RPE cells, the balance between extracellular ATP and adenosine may modulate lysosomal pH and the rate of lipofuscin formation. In optic nerve head astrocytes, mechanosensitive ATP release via pannexin hemichannels, coupled with stretch-dependent upregulation of pannexins, provides a mechanism for ATP signaling in chronic glaucoma. With so many receptors linked to divergent functions throughout the eye, ensuring the transmitters remain local and stimulation is restricted to the intended target

  12. Purines in the eye: recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Müller cells, lens, trabecular meshwork, cornea and lacrimal gland

    PubMed Central

    Sanderson, Julie; Dartt, Darlene A.; Trinkaus-Randall, Vickery; Pintor, Jesus; Civan, Mortimer M.; Delamere, Nicholas A.; Fletcher, Erica L.; Salt, Thomas E.; Grosche, Antje; Mitchell, Claire H.

    2014-01-01

    This review highlights recent findings that describe how purines modulate the physiological and pathophysiological responses of ocular tissues. For example, in lacrimal glands the cross-talk between P2X7 receptors and both M3 muscarinic receptors and α1D-adrenergic receptors can influence tear secretion. In the cornea, purines lead to post-translational modification of EGFR and structural proteins that participate in wound repair in the epithelium and influence the expression of matrix proteins in the stroma. Purines act at receptors on both the trabecular meshwork and ciliary epithelium to modulate intraocular pressure (IOP); ATP-release pathways of inflow and outflow cells differ, possibly permitting differential modulation of adenosine delivery. Modulators of trabecular meshwork cell ATP release include cell volume, stretch, extracellular Ca2+ concentration, oxidation state, actin remodeling and possibly endogenous cardiotonic steroids. In the lens, osmotic stress leads to ATP release following TRPV4 activation upstream of hemichannel opening. In the anterior eye, diadenosine polyphosphates such as Ap4A act at P2 receptors to modulate the rate and composition of tear secretion, impact corneal wound healing and lower IOP. The Gq11-coupled P2Y1-receptor contributes to volume control in Müller cells and thus the retina. P2X receptors are expressed in neurons in the inner and outer retina and contribute to visual processing as well as the demise of retinal ganglion cells. In RPE cells, the balance between extracellular ATP and adenosine may modulate lysosomal pH and the rate of lipofuscin formation. In optic nerve head astrocytes, mechanosensitive ATP release via pannexin hemichannels, coupled with stretch-dependent upregulation of pannexins, provides a mechanism for ATP signaling in chronic glaucoma. With so many receptors linked to divergent functions throughout the eye, ensuring the transmitters remain local and stimulation is restricted to the intended target

  13. Fluoride in the UK diet.

    PubMed

    Ruxton, Carrie

    2014-08-12

    Fluoride is a naturally occurring mineral that can be obtained from foods and fluids originating from soils containing fluoride, as well as by drinking water that has been fluoridated. While consuming adequate fluoride intake can deliver benefits for dental and bone health, there have been concerns that excessive fluoride intake could lead to dental fluorosis, or even cause harm to bones. This article considers the balance of evidence in this area, and discusses the benefits and potential risks of fluoride in the UK diet. The role of tea as a major contributor to normal fluoride intake is highlighted, alongside some positive implications of this. Information is also provided to help nurses and midwives communicate the latest advice and guidance on fluoride to their patients. PMID:25095960

  14. Fluoride in the UK diet.

    PubMed

    Ruxton, Carrie

    2014-08-12

    Fluoride is a naturally occurring mineral that can be obtained from foods and fluids originating from soils containing fluoride, as well as by drinking water that has been fluoridated. While consuming adequate fluoride intake can deliver benefits for dental and bone health, there have been concerns that excessive fluoride intake could lead to dental fluorosis, or even cause harm to bones. This article considers the balance of evidence in this area, and discusses the benefits and potential risks of fluoride in the UK diet. The role of tea as a major contributor to normal fluoride intake is highlighted, alongside some positive implications of this. Information is also provided to help nurses and midwives communicate the latest advice and guidance on fluoride to their patients.

  15. Sustainable psychiatry in the UK

    PubMed Central

    Yarlagadda, Sucharita; Maughan, Daniel; Lingwood, Susie; Davison, Phil

    2014-01-01

    Demands on our mental health services are growing as financial pressures increase. In addition, there are regular changes to service design and commissioning. The current political mantra is ‘more and more, of better quality, for less and less, please’. We suggest that mental health services need to actively respond to these constraints and that clinical transformation is needed to move towards a more sustainable system of healthcare. Emphasis on prevention, patient empowerment and leaner, greener services is required alongside more extensive use of technologies. Focusing on these areas will make mental health services more responsive to the challenges we face and serve to future-proof psychiatry in the UK. Services need to be delivered to provide maximum benefit to the health of our patients, but also to our society and the environment. PMID:25505629

  16. Homochiral Selectivity in RNA Synthesis: Montmorillonite-catalyzed Quaternary Reactions of D, L-Purine with D, L- Pyrimidine Nucleotides

    NASA Astrophysics Data System (ADS)

    Joshi, Prakash C.; Aldersley, Michael F.; Ferris, James P.

    2011-06-01

    Selective adsorption of D, L-ImpA with D, L-ImpU on the platelets of montmorillonite demonstrates an important reaction pathway for the origin of homochirality in RNA synthesis. Our earlier studies have shown that the individual reactions of D, L-ImpA or D, L-ImpU on montmorillonite catalyst produced oligomers which were only partially inhibited by the incorporation of both D- and L-enantiomers. Homochirality in these reactions was largely due to the formation of cyclic dimers that cannot elongate. We investigated the quaternary reactions of D, L-ImpA with D, L-ImpU on montmorillonite. The chain length of these oligomers increased from 9-mer to 11-mer as observed by HPLC, with a concominant increase in the yield of linear dimers and higher oligomers in the reactions involving D, L-ImpA with D, L-ImpU as compared to the similar reactions carried out with D-enantiomers only. The formation of cyclic dimers of U was completely inhibited in the quaternary reactions. The yield of cyclic dimers of A was reduced from 60% to 10% within the dimer fraction. 12 linear dimers and 3 cyclic dimers were isolated and characterized from the quaternary reaction. The homochirality and regioselectivity of dimers were 64.1% and 71.7%, respectively. Their sequence selectivity was shown by the formation of purine-pyrimidine (54-59%) linkages, followed by purine-purine (29-32%) linkages and pyrimidine-pyrimidine (9-13%) linkages. Of the 16 trimers detected, 10 were homochiral with an overall homochirality of 73-76%. In view of the greater homochirality, sequence- and regio- selectivity, the quaternary reactions on montmorillonite demonstrate an unexpectedly favorable route for the prebiotic synthesis of homochiral RNA compared with the separate reactions of enantiomeric activated mononucleotides.

  17. [Separation of purines, pyrimidines, pterins and flavonoids on magnolol-bonded silica gel stationary phase by high performance liquid chromatography].

    PubMed

    Chen, Hong; Li, Laishen; Zhang, Yang; Zhou, Rendan

    2012-10-01

    A new magnolol-bonded silica gel stationary phase (MSP) was used to separate the basic drugs including four purines, eight pyrimidines, four pterins and five flavonoids as polar representative samples by high performance liquid chromatography (HPLC). To clarify the separation mechanism, a commercial ODS column was also tested under the same chromatographic conditions. The high selectivities and fast baseline separations of the above drugs were achieved by using simple mobile phases on MSP. Although there is no end-caped treatment, the peak shapes of basic drugs containing nitrogen such as purines, pyrimidines and pterins were rather symmetrical on MSP, which indicated the the magnolol as ligand with multi-sites could shield the side effect of residual silanol groups on the surface of silica gel. Although somewhat different in the separation resolution, it was found that the elution orders of some drugs were generally similar on both MSP and ODS. The hydrophobic interaction should play a significant role in the separations of the above basic drugs, which was attributed to their reversed-phase property in the nature. However, MSP could provide the additional sites for many polar solutes, which was a rational explanation for the high selectivity of MSP. For example, in the separation of purines, pyrimidines and pterins on MSP, hydrogen-bonding and dipole-dipole interactions played leading roles besides hydrophobic interaction. Some solute molecules (such as mercaptopurine, vitexicarpin) and MSP can form the strong pi-pi stacking in the separation process. All enhanced the retention and improved the separation selectivity of MSP, which facilitated the separation of the basic drugs.

  18. Methanocarba ring as a ribose modification in ligands of G protein-coupled purine and pyrimidine receptors: synthetic approaches

    PubMed Central

    Tosh, Dilip K.

    2015-01-01

    Adenosine receptors (ARs) and P2Y receptors for purine and pyrimidine nucleotides have widespread distribution and regulate countless physiological processes. Various synthetic ligands are in clinical trials for treatment of inflammatory diseases, pain, cancer, thrombosis, ischemia, and other conditions. The methanocarba (bicyclo[3.1.0]hexane) ring system as a rigid substitution for ribose, which maintains either a North (N) or South (S) conformation, tends to preserve or enhance the potency and/or selectivity for certain receptor subtypes. This review summarizes recent developments in the synthetic approaches to these biologically important nucleoside and nucleotide analogues. PMID:26161251

  19. Exploring human adenosine A3 receptor complementarity and activity for adenosine analogues modified in the ribose and purine moiety

    PubMed Central

    Van Rompaey, Philippe; Jacobson, Kenneth A.; Gross, Ariel S.; Gao, Zhan-Guo; Van Calenbergh, Serge

    2012-01-01

    In this paper we investigated the influence on affinity, selectivity and intrinsic activity upon modification of the adenosine agonist scaffold at the 3′- and 5′-positions of the ribofuranosyl moiety and the 2- and N6-positions of the purine base. This resulted in the synthesis of various analogues, that is, 3–12 and 24–33, with good hA3AR selectivity and moderate-to-high affinities (as in 32, Ki = 27 nM). Interesting was the ability to tune the intrinsic activity depending on the substituent introduced at the 3′-position. PMID:15670905

  20. New synthetic routes to protected purine 2'-O-methylriboside-3'-O-phosphoramidites using a novel alkylation procedure.

    PubMed Central

    Sproat, B S; Beijer, B; Iribarren, A

    1990-01-01

    A highly selective alkylation procedure has been developed enabling new synthetic routes to be established for protected purine 2'-O-methylriboside-3'-O-phosphoramidites; building blocks for the assembly of 2'-O-methyloligoribonucleotides. The new procedure avoids the use of the highly toxic and potentially explosive reagent diazomethane and is far superior to the use of silver oxide/methyl iodide. Moreover, the use of highly versatile key intermediates will enable the synthesis of a wide variety of base modified analogues as well as other 2'-O-alkylriboside derivatives. PMID:2308835

  1. 4-(1-Adamantylmeth­yl)-N-(2-chloro-9-isopropyl-9H-purin-6-yl)aniline

    PubMed Central

    Rouchal, Michal; Nečas, Marek; Vícha, Robert

    2009-01-01

    The asymmetric unit of the title compound, C25H30ClN5, consists of two mol­ecules with slightly different geometrical parameters. The dihedral angles between the purine and benzene rings are 39.54 (5) and 23.69 (5)° in the two mol­ecules. The adamantane cages consist of three fused cyclo­hexane rings in classical chair conformations, with C—C—C angles in the range 108 (2)–111 (2)°. In the crystal, mol­ecules are linked into dimers via two N—H⋯N hydrogen bonds. PMID:21582935

  2. Specialty preferences of 1st year medical students in a Saudi Medical School – Factors affecting these choices and the influence of gender

    PubMed Central

    Kaliyadan, Feroze; Amin, Tarek Tawfik; Qureshi, Habib; Al Wadani, Fahad

    2015-01-01

    Background and Aims: In recent years there has been a growing appreciation of the issues of career preference in medicine as it affects student learning and academic performance. Various factors influence the specialty choices of medical students. Some specialties tend to attract students more than others. One possible consequence of this would be a mismatch between health needs and specialist numbers in the region. This study investigated the career preferences of 1st year medical students in a Saudi medical school and to assess factors affecting these choices. Materials and Methods: The study was a cross-sectional survey carried out on the 1st year undergraduate students in the college of medicine, King Faisal University, Saudi Arabia. A total of 109 students (57 female and 52 males) responded to the questionnaire which was initially administered to all the students of the 1st year – A total of 120 students (response rate was 90.8%). A mixed method approach was used and qualitative data from open-ended questions were analyzed based on thematic analysis. Results: The top choices were general surgery, internal medicine, and pediatrics. Among female students; the top specialty choices were: General surgery (23%), pediatrics (18%), and dermatology (15%). Among the male students; the top choices were: General surgery (54%) and internal medicine (23%). Of the total, 57% of the students agreed or strongly agreed that primary aptitude was the main factor affecting the choice. Only 31% felt that there was a significant influence of role model, 48% felt that the advice of others – peers and family, would be a factor influencing their choices, and 53% agreed that specialty choice would influence their future learning patterns. Males were more likely to choose a specialty based on actual aptitude for the specialty, financial rewards, and scope for research; and this gender difference was statistically significant. Conclusion: Surgery was the top-choice in both genders

  3. Effect of milk feed source, frequency of feeding and age at turnout on calf performance, live-weight at mating and 1st lactation milk production

    PubMed Central

    2012-01-01

    Female calves (n = 108) were assigned to 6 cold milk feeding treatments in two experiments for a 70-day period. Live-weight (LW) was measured weekly, with an additional LW taken at day 410 and post-calving for animals in experiment 1. In Experiment 1, the effect of feeding frequency and age of turnout to pasture on calf performance and 1st lactation milk yields were evaluated. The whole milk (WM) feeding treatments applied were (i) once daily feeding (OD), (ii) twice daily feeding (TD), (iii) OD feeding, outdoors at 38 days (ODO). In Experiment 2, the effects of feeding milk replacer (MR) as opposed to WM and age of turnout to pasture on calf performance were evaluated. The treatments applied were (i) OD feeding with WM (OD), (ii) OD feeding with milk replacer (MR) (ODMR), (iii) OD feeding with MR, outdoors at 38 days (ODMRO). Experiment 1: There were no differences (P > 0.05) in LW or average daily gain between TD and OD calves at day 80 or 410. ODO calves had lower LW at day 80 as compared to OD or TD (P < 0.001). Calf LW at day 80 was 86, 89 and 85 kg and at day 410 was 304, 309 and 316 kg for OD, TD and ODO, respectively. Milk feeding frequency or time of calf turnout had no effect on LW post calving, milk composition or 1st lactation milk yields. Experiment 2: Total LW at day 80 was higher (P < 0.05) for ODMR compared to OD or ODMRO calves. Calf LW was 87, 95, and 88 kg for OD, ODMR and ODMRO, respectively. However, LW at day 410 did not differ between treatments. This study showed that while some differences were observed in calf LW at day 80, these differences had no effect on LW at day 410 or 1st lactation milk yield. It can be concluded that calves can be successfully reared when fed OD with WM or MR, indoors and when turned out to pasture at 38 days of age. PMID:23078871

  4. Complex coordinated extracellular metabolism: Acid phosphatases activate diluted human leukocyte proteins to generate energy flow as NADPH from purine nucleotide ribose

    PubMed Central

    Hibbs, John B.; Vavrin, Zdenek; Cox, James E.

    2016-01-01

    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. PMID:26895212

  5. Complex coordinated extracellular metabolism: Acid phosphatases activate diluted human leukocyte proteins to generate energy flow as NADPH from purine nucleotide ribose.

    PubMed

    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.

  6. Nitrogen K-edge X-ray absorption near edge structure (XANES) spectra of purine-containing nucleotides in aqueous solution

    NASA Astrophysics Data System (ADS)

    Shimada, Hiroyuki; Fukao, Taishi; Minami, Hirotake; Ukai, Masatoshi; Fujii, Kentaro; Yokoya, Akinari; Fukuda, Yoshihiro; Saitoh, Yuji

    2014-08-01

    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.

  7. Experiences of non-UK-qualified doctors working within the UK regulatory framework: a qualitative study

    PubMed Central

    Slowther, A; Lewando Hundt, GA; Purkis, J; Taylor, R

    2012-01-01

    Objective To explore the experience of non-UK-qualified doctors in working within the regulatory framework of the General Medical Council (GMC) document Good Medical Practice. Design Individual interviews and focus groups. Setting United Kingdom. Participants Non-UK-qualified doctors who had registered with the GMC between 1 April 2006 and 31 March 2008, doctors attending training/induction programmes for non-UK-qualified doctors, and key informants involved in training and support for non-UK-qualified doctors. Main outcome measures Themes identified from analysis of interview and focus group transcripts. Results Information and support for non-UK qualified doctors who apply to register to work in the UK has little reference to the ethical and professional standards required of doctors working in the UK. Recognition of the ethical, legal and cultural context of UK healthcare occurs once doctors are working in practice. Non-UK qualified doctors reported clear differences in the ethical and legal framework for practising medicine between the UK and their country of qualification, particularly in the model of the doctor–patient relationship. The degree of support for non-UK-qualified doctors in dealing with ethical concerns is related to the type of post they work in. European doctors describe similar difficulties with working in an unfamiliar regulatory framework to their non-European colleagues. Conclusions Non-UK-qualified doctors experience a number of difficulties related to practising within a different ethical and professional regulatory framework. Provision of information and educational resources before registration, together with in-practice support would help to develop a more effective understanding of GMP and its implications for practice in the UK. PMID:22408082

  8. The Formamidopyrimidines: Purine Lesions Formed in Competition With 8-Oxopurines From Oxidative Stress

    PubMed Central

    Greenberg, Marc M.

    2011-01-01

    Conspectus DNA is constantly exposed to agents that induce structural damage, from sources both internal and external to an organism. Endogenous species, such as oxidizing chemicals, and exogenous agents, such as ultraviolet rays in sunlight, together produce more than 70 distinct chemical modifications of native nucleotides. Of these, about 15 of the lesions have been detected in cellular DNA. This kind of structural DNA damage can be cytotoxic, carcinogenic, or both, and is being linked to an increasingly lengthy list of diseases. The formamidopyrimidine (Fapy) lesions are a family of DNA lesions that result after purines undergo oxidative stress. The Fapy lesions are produced in yields comparable to the 8-oxopurines, which, owing in part to a perception of mutagenicity in some quarters, have been subjected to intense research scrutiny. But despite the comparable abundance of the formamidopyrimidines and the 8-oxopurines, until recently very little was known about the effects of Fapy lesions on biochemical processes involving DNA or on the structure and stability of the genomic material. In this Account, we discuss the detection of Fapy lesions in DNA and the mechanism proposed for their formation. We also describe methods for the chemical synthesis of oligonucleotides containing Fapy•dA or Fapy•dG and the outcomes of chemical and biochemical studies utilizing these compounds. These experiments reveal that the formamidopyrimidines decrease the fidelity of polymerases and are substrates for DNA repair enzymes. The mutation frequency of Fapy•dG in mammals is even greater than that of 8-oxodGuo (8-oxo-7,8-dihydro-2′-deoxyguanosine, one of the 8-oxopurines), suggesting that this lesion could be a useful biomarker and biologically significant. Despite clear similarities, the formamidopyrimidines have lived in the shadow of the corresponding 8-oxopurine lesions. But the recent development of methods for synthesizing oligonucleotides containing Fapy•dA or

  9. Heavens Open Up for UK Astronomers

    NASA Astrophysics Data System (ADS)

    2002-07-01

    A significant milestone for British and European science occurred today (July 8, 2002) when the Council of the European Southern Observatory (ESO) met in London. At this historical meeting, the United Kingdom was formally welcomed into ESO by the nine other member states. The UK, one of the leading nations in astronomical research, now joins one of the world's major astronomical organisations. UK astronomers will now be able to use the four 8.2-metre and several 1.8-metre telescopes that comprise the Very Large Telescope (VLT) facility located at the Paranal Observatory in the northern part of the Atacama desert in Chile, as well as two 4-m class telescopes and several smaller ones at the ESO La Silla Observatory further south. The UK will also benefit from increased involvement in the design and construction of the Atacama Large Millimetre Array (ALMA), a network of 64 twelve-metre telescopes also sited in Chile, and play a defining role in ESO's 100-metre Overwhelmingly Large Telescope (OWL). Sir Martin Rees , The Astronomer Royal, said, "Joining ESO is good for UK science, and I think good for Europe as well. It offers us access to the VLT's 8-m class telescopes and restores the UK's full competitiveness in optical astronomy. We're now guaranteed full involvement in ALMA and in the next generation of giant optical instruments - projects that will be at the forefront of the research in the next decade and beyond. Moreover, our commitment to ESO should enhance its chances of forging ahead of the US in these technically challenging and high profile scientific projects. UK membership of ESO is a significant and welcome outcome of this government's increasing investment in science". Prof. Ian Halliday , Chief Executive of the Particle Physics and Astronomy Research Council (PPARC), the UK's strategic science investment agency said, "The United Kingdom already participates in Europe's flagship particle physics research and the space science research programmes through

  10. Spatial epidemiology in zoonotic parasitic diseases: insights gained at the 1st International Symposium on Geospatial Health in Lijiang, China, 2007

    PubMed Central

    Zhou, Xiao-Nong; Lv, Shan; Yang, Guo-Jing; Kristensen, Thomas K; Bergquist, N Robert; Utzinger, Jürg; Malone, John B

    2009-01-01

    The 1st International Symposium on Geospatial Health was convened in Lijiang, Yunnan province, People's Republic of China from 8 to 9 September, 2007. The objective was to review progress made with the application of spatial techniques on zoonotic parasitic diseases, particularly in Southeast Asia. The symposium featured 71 presentations covering soil-transmitted and water-borne helminth infections, as well as arthropod-borne diseases such as leishmaniasis, malaria and lymphatic filariasis. The work made public at this occasion is briefly summarized here to highlight the advances made and to put forth research priorities in this area. Approaches such as geographical information systems (GIS), global positioning systems (GPS) and remote sensing (RS), including spatial statistics, web-based GIS and map visualization of field investigations, figured prominently in the presentation. PMID:19193214

  11. JANNAF 25th Airbreathing Propulsion Subcommittee, 37th Combustion Subcommittee and 1st Modeling and Simulation Subcommittee Joint Meeting. Volume 1

    NASA Technical Reports Server (NTRS)

    Fry, Ronald S.; Becker, Dorothy L.

    2000-01-01

    Volume I, the first of three volumes, is a compilation of 24 unclassified/unlimited-distribution technical papers presented at the Joint Army-Navy-NASA-Air Force (JANNAF) 25th Airbreathing Propulsion Subcommittee, 37th Combustion Subcommittee and 1st Modeling and Simulation Subcommittee (MSS) meeting held jointly with the 19th Propulsion Systems Hazards Subcommittee. The meeting was held 13-17 November 2000 at the Naval Postgraduate School and Hyatt Regency Hotel, Monterey, California. Topics covered include: a Keynote Address on Future Combat Systems, a review of the new JANNAF Modeling and Simulation Subcommittee, and technical papers on Hyper-X propulsion development and verification; GTX airbreathing launch vehicles; Hypersonic technology development, including program overviews, fuels for advanced propulsion, ramjet and scramjet research, hypersonic test medium effects; and RBCC engine design and performance, and PDE and UCAV advanced and combined cycle engine technologies.

  12. [State of the reproductive systemin in male rats of 1st generation obtained from irradiated parents and exposed to electromagnetic radiation (897 MHz) during embryogenesis and postnatal development].

    PubMed

    Vereshchako, G G; Chueshova, N V; Gorokh, G A; Naumov, A D

    2014-01-01

    The consequences of prolonged exposure to electromagnetic radiation from cellular phone (897 MHz, daily 8 h/day) in male rats of the 1st generation obtained from irradiated parents and subjected to prolonged exposure to electromagnetic radiation of the range of mobile communications during ontogeny and postnatal development were studied. It has been found that irradiation causes a decrease in the number of births of animals, changing the sex ratio towards the increase in the number of males. It had a significant impact on the reproductive system of males, accelerating their sexual development, revealed at the age of two months. Radiation from cell phones led to significant disproportions in the cell number at different stages of spermatogenesis. It increased the number of mature spermatozoa which decreased viability.

  13. [State of the reproductive systemin in male rats of 1st generation obtained from irradiated parents and exposed to electromagnetic radiation (897 MHz) during embryogenesis and postnatal development].

    PubMed

    Vereshchako, G G; Chueshova, N V; Gorokh, G A; Naumov, A D

    2014-01-01

    The consequences of prolonged exposure to electromagnetic radiation from cellular phone (897 MHz, daily 8 h/day) in male rats of the 1st generation obtained from irradiated parents and subjected to prolonged exposure to electromagnetic radiation of the range of mobile communications during ontogeny and postnatal development were studied. It has been found that irradiation causes a decrease in the number of births of animals, changing the sex ratio towards the increase in the number of males. It had a significant impact on the reproductive system of males, accelerating their sexual development, revealed at the age of two months. Radiation from cell phones led to significant disproportions in the cell number at different stages of spermatogenesis. It increased the number of mature spermatozoa which decreased viability. PMID:25764821

  14. Understanding Stress-Related Behavioral Phenotypes: Report from the 1st International Neuroscience Summer School and the 11th International “Stress and Behavior” Conference

    PubMed Central

    LaPorte, J. L.; Klimenko, V. M.; Kalueff, A. V.

    2008-01-01

    The 1st International Neuroscience Summer School and the 11th International Multidisciplinary Neuroscience and Biopsychiatry Conference on Stress and Behavior were held in St. Petersburg, Russia, during May 9–20, 2008. The summer school gathered 30 talented young scientists from 15 countries worldwide, and was dedicated to different topics of behavioral neuroscience. Many interactive courses were provided on neuropharmacology, animal phenotyping, and biopsychology. The conference's excellent scientific and social program attracted almost 500 delegates from 40 countries from many areas of stress research. The eclectic interaction between medical doctors, basic scientists, psychologists, and students made for a productive and collaborative environment, which contributed greatly to the success of the school and conference.

  15. The UK silicon photonics project

    NASA Astrophysics Data System (ADS)

    Reed, G. T.; Wright, N.; Mashanovich, G. Z.; Timotijevic, B.; Krauss, T. F.; White, T. P.; O'Faolain, L.; Kelsall, R. W.; Lever, L.; Ikonic, Z.; Valvanis, A.; Leadley, D.; Findlayson, E.; Jenkins, R. M.

    2010-05-01

    The project is a consortium based activity involving researchers from the UK institutions of the Universities of Surrey, St. Andrews, Leeds, Warwick, and Southampton, as well as the commercial research institution QinetiQ. The aims of the project are to progress the state of the art in Silicon Photonics, in the areas of waveguides, modulators, couplers, detectors, Raman processes, and integration with electronics. Thus the field is vast, and impossible to cover comprehensively in one project, nor indeed in one paper. The programme is run on a truly collaborative basis, with members from each institution running one or more work packages within the project, each co-ordinating work from their own plus other institutions. To date, the most well developed work has emerged from the activity on basic waveguides and their characteristics, the modulator activity, optical filters, and work on Raman Amplifiers. This work will be the main focus of this paper, but an attempt will be made to update the audience on the remaining activities within the project. By the nature of the project, much of the work is medium term, and hence some activities are not expected to yield viable results until at least next year, hence the concentration on some activities rather than all activities at this stage.

  16. Learning from UK primary care.

    PubMed

    Hays, Richard

    2009-03-01

    The Australian Government is wise to examine other health care systems as it strives to improve the quality of care and address rising costs to both governments and individuals. Focus is currently on the United Kingdom, whose National Health Service (NHS) stands out as one that delivers good care at a reasonable price to all who need it. The Australian and UK systems have many similarities: universal access, tax payer support, no or low cost at point of delivery, and good population health outcomes. They also face similar pressures on services from aging, increasingly unwell yet expectant populations.However, there are also differences, largely in the way that health care is funded, organised and delivered. The NHS is a huge system for 60 million people in four home countries with diverging policies. Within England, the system is managed through 10 strategic health authorities, each responsible for about 5 million people and having the right to interpret national policy. Population based health care, including tertiary care, is funded locally via primary care trusts. PMID:19283244

  17. Lengthening osteotomy of the calcaneus and flexor digitorum longus tendon transfer in flexible flatfoot deformity improves talo-1st metatarsal-Index, clinical outcome and pedographic parameter.

    PubMed

    Richter, Martinus; Zech, Stefan

    2013-03-01

    Lengthening osteotomy of the calcaneus (LO) and flexor digitorum longus tendon (FDL) transfer to the navicular is one option for the treatment of flexible flatfoot deformity (FD). The aim of the study was to analyse the amount of correction and clinical outcome including pedographic assessment. In a prospective consecutive non-controlled clinical followup study, all patients with FD that were treated with LO and FDL from September 1st 2006 to August 31st, 2009 were included. Assessment was performed before surgery and at 2-year-followup including clinical examination (with staging of posterior tibialis insufficiency) weight bearing radiographs (Talo-1st metatarsal angles (TMT)), pedography (increased midfoot contact area and force) and Visual Analogue Scale Foot and Ankle (VAS FA). 112 feet in 102 patients were analysed (age, 57.6 (13-82), 42% male). In 12 feet (9%) wound healing delay without further surgical measures was registered. All patients achieved full weight bearing during the 7th postoperative week. Until followup, revision surgery was done in 3 patients (fusion calcaneocuboid joint (n=2), correction triple arthrodesis (n=1)). 101 feet (90%) completed 2-year-followup. TMT dorsoplantar/lateral/Index and VAS FA scores were increased, and posterior tibialis insufficiency stage, pedographic midfoot contact area and force percentage were decreased (each p<.05). All relevant parameters (stage of posterior tibialis insufficiency, TMT angles and Index, pedographic midfoot contact area and force percentage, VAS FA) were improved 2 years after LO and FDL transfer to the navicular in FD. The complication rate was low. This method allows safe and predictable correction.

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

    PubMed

    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.

  19. Short-term effect of caffeine on purine, pyrimidine and pyridine metabolism in rice (Oryza sativa) seedlings.

    PubMed

    Deng, Wei-Wei; Katahira, Riko; Ashihara, Hiroshi

    2015-05-01

    As part of our studies on the physiological and ecological function of caffeine, we investigated the effect of exogenously supplied caffeine on purine, pyrimidine and pyridine metabolism in rice seedlings. We examined the effect of 1 mM caffeine on the in situ metabolism of 14C-labelled adenine, guanine, inosine, uridine, uracil, nicotinamide and nicotinic acid. The segments of 4-day-old dark-grown seedlings were incubated with these labelled compounds for 6 h. For purines, the incorporation of radioactivity from [8-(14)C]adenine and [8-(14)C]guanine into nucleotides was enhanced by caffeine; in contrast, incorporation into CO2 were reduced. The radioactivity in ureides (allantoin and allantoic acid) from [8-(14)C]guanine and [8-(14)C]inosine was increased by caffeine. For pyrimidines, caffeine enhanced the incorporation of radioactivity from [2-(14)C]uridine into nucleotides, which was accompanied by a decrease in pyrimidine catabolism. Such difference was not found in the metabolism of [2-(14)C]uracil. Caffeine did not influence the pyridine metabolism of [carbonyl-14C]- nicotinamide and [2-(14)C]nicotinic acid. The possible control steps of caffeine on nucleotide metabolism in rice are discussed.

  20. Structure of nucleoside diphosphate kinase from pacific shrimp (Litopenaeus vannamei) in binary complexes with purine and pyrimidine nucleoside diphosphates.

    PubMed

    López-Zavala, Alonso A; Quintero-Reyes, Idania E; Carrasco-Miranda, Jesús S; Stojanoff, Vivian; Weichsel, Andrzej; Rudiño-Piñera, Enrique; Sotelo-Mundo, Rogerio R

    2014-09-01

    Nucleoside diphosphate kinase (NDK; EC 2.7.4.6) is an enzyme that catalyzes the third phosphorylation of nucleoside diphosphates, leading to nucleoside triphosphates for DNA replication. Expression of the NDK from Litopenaeus vannamei (LvNDK) is known to be regulated under viral infection. Also, as determined by isothermal titration calorimetry, LvNDK binds both purine and pyrimidine deoxynucleoside diphosphates with high binding affinity for dGDP and dADP and with no heat of binding interaction for dCDP [Quintero-Reyes et al. (2012), J. Bioenerg. Biomembr. 44, 325-331]. In order to investigate the differences in selectivity, LvNDK was crystallized as binary complexes with both acceptor (dADP and dCDP) and donor (ADP) phosphate-group nucleoside diphosphate substrates and their structures were determined. The three structures with purine or pyrimidine nucleotide ligands are all hexameric. Also, the binding of deoxy or ribonucleotides is similar, as in the former a water molecule replaces the hydrogen bond made by Lys11 to the 2'-hydroxyl group of the ribose moiety. This allows Lys11 to maintain a catalytically favourable conformation independently of the kind of sugar found in the nucleotide. Because of this, shrimp NDK may phosphorylate nucleotide analogues to inhibit the viral infections that attack this organism.

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

    PubMed Central

    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

  2. Loss of DNA polymerase beta stacking interactions with templating purines, but not pyrimidines, alters catalytic efficiency and fidelity.

    PubMed

    Beard, William A; Shock, David D; Yang, Xiao-Ping; DeLauder, Saundra F; Wilson, Samuel H

    2002-03-01

    Structures of DNA polymerases bound with DNA reveal that the 5'-trajectory of the template strand is dramatically altered as it exits the polymerase active site. This distortion provides the polymerase access to the nascent base pair to interrogate proper Watson-Crick geometry. Upon binding a correct deoxynucleoside triphosphate, alpha-helix N of DNA polymerase beta is observed to form one face of the binding pocket for the new base pair. Asp-276 and Lys-280 stack with the bases of the incoming nucleotide and template, respectively. To determine the role of Lys-280, site-directed mutants were constructed at this position, and the proteins were expressed and purified, and their catalytic efficiency and fidelity were assessed. The catalytic efficiency for single-nucleotide gap filling with the glycine mutant (K280G) was strongly diminished relative to wild type for templating purines (>15-fold) due to a decreased binding affinity for the incoming nucleotide. In contrast, catalytic efficiency was hardly affected by glycine substitution for templating pyrimidines (<4-fold). The fidelity of the glycine mutant was identical to the wild type enzyme for misinsertion opposite a template thymidine, whereas the fidelity of misinsertion opposite a template guanine was modestly altered. The nature of the Lys-280 side-chain substitution for thymidine triphosphate insertion (templating adenine) indicates that Lys-280 "stabilizes" templating purines through van der Waals interactions. PMID:11756435

  3. Disturbance of Antioxidant Enzymes and Purine Metabolism in the Ejaculate of Men Living in Disadvantaged Areas of Kyzylorda Region

    PubMed Central

    Kislitskaya, Valentihna N.; Kenzhin, Zhandos D.; Kultanov, Berikbay Zh.; Dosmagambetova, Raushan S.; Turmuhambetova, Anar A.

    2015-01-01

    AIM: Objective of the study was to evaluate the state of the main indicators of antioxidant status and enzymes of purine metabolism in the germ cells of men living in the zone of ecological catastrophe Aral Sea region. METHODS: The criterion for inclusion is the stay of an adult in the Aral Sea area is not less than 5 years, employment in occupations with no more than 2 hazard class. Determination of the activity of adenosine deaminase (ADA) was conducted in semen by the method of Nemechek et al., 1993. Determination of the activity of catalase (CAT) was performed according by the method of Korolyuk et al., 1988. RESULTS: Results of the study indicate a change in the activity of catalase and adenosine deaminase, due to increased levels of oxidative stress and the development of the pathological process. 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. PMID:27275276

  4. Excretion of purine derivatives by ruminants: recycling of allantoin into the rumen via saliva and its fate in the gut.

    PubMed

    Chen, X B; Hovell, F D; Orskov, E R

    1990-03-01

    The saliva of sheep was shown to contain significant concentrations of uric acid (16(SD 4.5) mumol/l) and allantoin (120(SD 16.4) mumol/l), sufficient to recycle purine derivatives equivalent to about 0.10 of the normal urinary excretion. When allantoin was incubated in vitro in rumen fluid, it was degraded at a rate sufficient to ensure complete destruction of recycled allantoin. In a series of experiments in which allantoin was infused into the rumen of sheep fed normally, or into the rumen or abomasum of sheep and the rumen of cattle completely nourished by intragastric infusion of volatile fatty acids and casein, no additional allantoin was recovered in the urine. These losses were probably due to the degradation of allantoin by micro-organisms associated with the digestive tract. It is concluded that all allantion and uric acid recycled to the rumen via saliva will be similarly degraded. Therefore, the use of urinary excretion of purine derivatives as an estimator of the rumen microbial biomass available to ruminants will need to be corrected for such losses.

  5. Alzheimer's Research UK 2016 Conference report.

    PubMed

    Sancho, Rosa M; Cox, Carla J; Phipps, Laura E; Ridley, Simon H

    2016-01-01

    The annual Alzheimer's Research UK (ARUK) Conference was hosted by the Manchester and North West Network Centre on March 8-9, 2016. In this report, we provide a summary of the research presented. PMID:27630086

  6. UK now claims world's top discovery rate

    SciTech Connect

    Not Available

    1985-05-01

    UK explorers are a bit more cheerful these days even though no one has discovered a giant field or anything elephant-sized. The reason is a benign tax regime and a growing confidence among industry explorers. This last has resulted in discovery of many smaller fields - particularly gas, some potentially commercial. It is claimed that the UK's discovery rate is now the highest in the world.

  7. Patterns of Higher Education Institutions in the UK. Ninth Report

    ERIC Educational Resources Information Center

    Ramsden, Brian

    2009-01-01

    This report is the ninth in a series published annually by Universities UK, with the support of GuildHE and the UK Higher Education Europe Unit, updating and expanding a rich variety of data through which to understand higher education institutions in the UK. Since its first report in 2001, has examined the trends in UK higher education at both…

  8. Activity analysis of telemedicine in the UK

    PubMed Central

    Debnath, D

    2004-01-01

    Background: Telemedicine is a new way of delivering health care to people, particularly in remote areas. The UK has experienced a surge of telematic projects in recent years. However, there is little information available in the literature regarding the past and present of telemedicine in the UK. Objectives: To evaluate the state of telemedicine in the UK. Methods: All the projects that took place in UK since 1991 were considered for the study and evaluated according to the population and area served. Results: A total of 216 projects were identified. The number of projects was highest in England (172). Emergency medicine, medical specialties, and educational projects received most consideration (9.7% each). With the exception of Wales, the number of projects increased steadily with time. The projects, when correlated in accordance with the area (per 10 000 sq km) and population (per million), were found to be highest in England (49.5%) and Northern Ireland (36.2%) respectively. No dedicated educational project took place in Scotland, Northern Ireland, and Wales. Conclusions: The UK embraced telemedicine in the early 1990s and the overall growth had been steady. Scotland, in spite of being the most likely beneficiary in UK, has lagged behind in telemedicine schemes and merits more projects. The issue of tele-education needs urgent review. Multisite trials and a combined approach involving the government, health professionals, technologists, and patients' representatives would facilitate such developments and help widen the application of telemedicine. PMID:15192165

  9. Integrative Analysis of Circadian Transcriptome and Metabolic Network Reveals the Role of De Novo Purine Synthesis in Circadian Control of Cell Cycle

    PubMed Central

    Li, Ying; Li, Guang; Görling, Benjamin; Luy, Burkhard; Du, Jiulin; Yan, Jun

    2015-01-01

    Metabolism is the major output of the circadian clock in many organisms. We developed a computational method to integrate both circadian gene expression and metabolic network. Applying this method to zebrafish circadian transcriptome, we have identified large clusters of metabolic genes containing mostly genes in purine and pyrimidine metabolism in the metabolic network showing similar circadian phases. Our metabolomics analysis found that the level of inosine 5'-monophosphate (IMP), an intermediate metabolite in de novo purine synthesis, showed significant circadian oscillation in larval zebrafish. We focused on IMP dehydrogenase (impdh), a rate-limiting enzyme in de novo purine synthesis, with three circadian oscillating gene homologs: impdh1a, impdh1b and impdh2. Functional analysis revealed that impdh2 contributes to the daily rhythm of S phase in the cell cycle while impdh1a contributes to ocular development and pigment synthesis. The three zebrafish homologs of impdh are likely regulated by different circadian transcription factors. We propose that the circadian regulation of de novo purine synthesis that supplies crucial building blocks for DNA replication is an important mechanism conferring circadian rhythmicity on the cell cycle. Our method is widely applicable to study the impact of circadian transcriptome on metabolism in complex organisms. PMID:25714999

  10. Anti-proliferative activity of 2,6-dichloro-9- or 7-(ethoxycarbonylmethyl)-9H- or 7H-purines against several human solid tumour cell lines.

    PubMed

    Morales, Fátima; Ramírez, Alberto; Conejo-García, Ana; Morata, Cynthia; Marchal, Juan A; Campos, Joaquín M

    2014-04-01

    As leads we took several benzo-fused seven- and six-membered scaffolds linked to the pyrimidine or purine moieties with notable anti-proliferative activity against human breast, colon and melanoma cancerous cell lines. We then decided to maintain the double-ringed nitrogenous bases and change the other components to the ethyl acetate moiety. This way six purine and two 5-fluorouracil derivatives were obtained and evaluated against the MCF-7, HCT-116, A-375 and G-361 cancer cell lines. Two QSARs are obtained between the anti-proliferative IC₅₀ values for compounds 26-33 and the clog P against the melanoma cell lines A-375 and G-361. Our results show that two of the analogues [ethyl 2-(2,6-dichloro-9H- or 7H-purine-9- or 7-yl)acetates (30 and 33, respectively)] are potent cytotoxic agents against all the tumour cell lines assayed, showing single-digit micromolar IC₅₀ values. This exemplifies the potential of our previously reported purine compounds to qualify as lead structures for medicinal chemistry campaigns, affording simplified analogues easy to synthesize and with a noteworthy bioactivity. The selective activity of 30 and 33 against the melanoma cell line A-375, via apoptosis, supposes a great advantage for a future therapeutic use.

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

    PubMed

    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. PMID:26237090

  12. Kinetics and mechanism of electron transfer between purines and pyrimidines, their dinucleotides and polynucleotides after reaction with hydrated electrons; a pulse radiolysis study.

    PubMed

    Visscher, K J; Spoelder, H J; Loman, H; Hummel, A; Hom, M L

    1988-11-01

    The radical spectra of mixtures of thymidine 5'-monophosphate (TMP) or uridine 5'-monophosphate (UMP) with adenine 5'-monophosphate (AMP) after hydrated electron attack, measured from 5 to 3000 microsecond after pulse radiolysis, can only be described in terms of the radical spectra of the nucleotides if an electron transfer is taken into account from the purine radical anion to the pyrimidine, resulting in the formation of a pyrimidine radical anion. From analysis of the spectra of the dinucleoside phosphates ApU, dApT and dCpdA after eaq- attack it follows that the electron-donating species is the purine radical anion (A-.) rather than the protonated purine radical. The electron transfer competes with the fast protonation of the purine radical anion: A-. + py----A + py.- and A-. + H2O in equilibrium AH. respectively. The electron transfer is found to have a diffusion-controlled reaction rate constant of approximately 1.2 X 10(10) for TMP and 3.5 X 10(9) dm3 mol-1 s-1 for UMP.

  13. UK malaria treatment guidelines 2016.

    PubMed

    Lalloo, David G; Shingadia, Delane; Bell, David J; Beeching, Nicholas J; Whitty, Christopher J M; Chiodini, Peter L

    2016-06-01

    1.Malaria is the tropical disease most commonly imported into the UK, with 1300-1800 cases reported each year, and 2-11 deaths. 2. Approximately three quarters of reported malaria cases in the UK are caused by Plasmodium falciparum, which is capable of invading a high proportion of red blood cells and rapidly leading to severe or life-threatening multi-organ disease. 3. Most non-falciparum malaria cases are caused by Plasmodium vivax; a few cases are caused by the other species of plasmodium: Plasmodium ovale, Plasmodium malariae or Plasmodium knowlesi. 4. Mixed infections with more than one species of parasite can occur; they commonly involve P. falciparum with the attendant risks of severe malaria. 5. There are no typical clinical features of malaria; even fever is not invariably present. Malaria in children (and sometimes in adults) may present with misleading symptoms such as gastrointestinal features, sore throat or lower respiratory complaints. 6. A diagnosis of malaria must always be sought in a feverish or sick child or adult who has visited malaria-endemic areas. Specific country information on malaria can be found at http://travelhealthpro.org.uk/. P. falciparum infection rarely presents more than six months after exposure but presentation of other species can occur more than a year after exposure. 7. Management of malaria depends on awareness of the diagnosis and on performing the correct diagnostic tests: the diagnosis cannot be excluded until more than one blood specimen has been examined. Other travel related infections, especially viral haemorrhagic fevers, should also be considered. 8. The optimum diagnostic procedure is examination of thick and thin blood films by an expert to detect and speciate the malarial parasites. P. falciparum and P. vivax (depending upon the product) malaria can be diagnosed almost as accurately using rapid diagnostic tests (RDTs) which detect plasmodial antigens. RDTs for other Plasmodium species are not as reliable. 9

  14. Trends in UK mean sea level revisited

    NASA Astrophysics Data System (ADS)

    Woodworth, P. L.; Teferle, F. N.; Bingley, R. M.; Shennan, I.; Williams, S. D. P.

    2009-01-01

    This paper presents estimates of rates of mean sea level (MSL) change around the UK, based on a larger tide gauge data set and more accurate analysis methods than have been employed so far. The spatial variation of the trend in MSL is found to be similar to that inferred from geological information and from advanced geodetic techniques, which is a similar conclusion to that arrived at in the previous studies. The tide gauge MSL trends for 1901 onwards are estimated to be 1.4 +/- 0.2 mm yr-1 larger than those inferred from geology or geodetic methods, suggesting a regional sea level rise of climate change origin several one-tenths of mm per year lower than global estimates for the 20th century. However, UK MSL change cannot be described in terms of a simple linear increase alone but includes variations on interannual and decadal timescales. The possible sources of variation in a `UK sea level index' are explored. Air pressure is clearly one such possible source but its direct local forcing through the `inverse barometer' accounts for only one-third of the observed variability. A number of larger scale atmospheric and ocean processes must also play important roles, but modelling them satisfactorily and separating the individual contributions present a major challenge. As regards future regional UK sea level changes, we conclude that there is no basis for major modification to existing projections for the 2080s included in the 2002 UK Climate Impacts Programme studies.

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

    PubMed

    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.

  16. 6-(3,5-Dimeth-oxy-benzyl-amino)-9-(oxan-2-yl)-9H-purine.

    PubMed

    Starha, Pavel; Popa, Igor; Dvořák, Zdeněk; Trávníček, Zdeněk

    2013-04-01

    The mol-ecule of the title compound, C19H23N5O3, contains six-membered pyrimidine and five-membered imidazole rings merged into the essentially planar purine skeleton (r.m.s. deviation = 0.01 Å). In the crystal, pairs of N-H⋯N hydrogen bonds link mol-ecules into inversion dimers. The dimers are linked via C-H⋯O hydrogen bonds, forming double-stranded chains propagating along [001]. These chains are linked via C-H⋯π and parallel slipped π-π inter-actions [centroid-centroid distance = 3.467 (1) Å; slippage 0.519 Å], forming a three-dimensional network. PMID:23634074

  17. 6-(3,5-Dimeth­oxy­benzyl­amino)-9-(oxan-2-yl)-9H-purine

    PubMed Central

    Štarha, Pavel; Popa, Igor; Dvořák, Zdeněk; Trávníček, Zdeněk

    2013-01-01

    The mol­ecule of the title compound, C19H23N5O3, contains six-membered pyrimidine and five-membered imidazole rings merged into the essentially planar purine skeleton (r.m.s. deviation = 0.01 Å). In the crystal, pairs of N—H⋯N hydrogen bonds link mol­ecules into inversion dimers. The dimers are linked via C—H⋯O hydrogen bonds, forming double-stranded chains propagating along [001]. These chains are linked via C—H⋯π and parallel slipped π–π inter­actions [centroid–centroid distance = 3.467 (1) Å; slippage 0.519 Å], forming a three-dimensional network. PMID:23634074

  18. A Canonical Correlation Analysis of AIDS Restriction Genes and Metabolic Pathways Identifies Purine Metabolism as a Key Cooperator

    PubMed Central

    Ye, Hanhui; Yuan, Jinjin; Wang, Zhengwu; Huang, Aiqiong; Liu, Xiaolong; Han, Xiao; Chen, Yahong

    2016-01-01

    Human immunodeficiency virus causes a severe disease in humans, referred to as immune deficiency syndrome. Studies on the interaction between host genetic factors and the virus have revealed dozens of genes that impact diverse processes in the AIDS disease. To resolve more genetic factors related to AIDS, a canonical correlation analysis was used to determine the correlation between AIDS restriction and metabolic pathway gene expression. The results show that HIV-1 postentry cellular viral cofactors from AIDS restriction genes are coexpressed in human transcriptome microarray datasets. Further, the purine metabolism pathway comprises novel host factors that are coexpressed with AIDS restriction genes. Using a canonical correlation analysis for expression is a reliable approach to exploring the mechanism underlying AIDS. PMID:27462363

  19. The PurR regulon in Lactococcus lactis - transcriptional regulation of the purine nucleotide metabolism and translational machinery.

    PubMed

    Jendresen, Christian Bille; Martinussen, Jan; Kilstrup, Mogens

    2012-08-01

    Purine nucleotides are either synthesized de novo from 5-phosphoribosyl-1-pyrophosphate (PRPP) or salvaged from the environment. In Lactococcus lactis, transcription of the de novo synthesis operons, purCSQLF and purDEK, has genetically been shown to be activated by the PurR protein when bound to a conserved PurBox motif present on the DNA at a fixed distance from the promoter -10 element. PurR contains a PRPP-binding site, and activation occurs when the intracellular PRPP pool is high as a consequence of low exogenous purine nucleotide pools. By an iterative approach of bioinformatics searches and motif optimization, 21 PurR-regulated genes were identified and used in a redefinition of the PurBox consensus sequence. In the process a new motif, the double-PurBox, which is present in a number of promoters and contains two partly overlapping PurBox motifs, was established. Transcriptional fusions were used to analyse wild-type promoters and promoters with inactivating PurBox mutations to confirm the relevance of the PurBox motifs as PurR-binding sites. The promoters of several operons were shown to be devoid of any -35 sequence, and found to be completely dependent on PurR-mediated activation. This suggests that binding of the PurR protein to the PurBox takes over the role of the -35 sequence. The study has expanded the PurR regulon to include promoters in nucleotide metabolism, C(1) compound metabolism, phosphonate transport, pyrophosphatase activity, (p)ppGpp metabolism, and translation-related functions. Of special interest is the presence of PurBox motifs in rrn promoters, suggesting a novel connection between nucleotide availability and the translational machinery.

  20. Purine biosynthesis in L1210 leukemia cells is inhibited by 7-hydroxymethotrexate (7-OH-MTX) polyglutamates (PGS)

    SciTech Connect

    Seither, R.L.; Matherly, L.H.; Goldman, I.D.

    1986-05-01

    The biochemical basis for 7-OH-MTX cytotoxicity was examined in L1210 tumor cells. Cells were exposed to 100 ..mu..M 7-OH-MTX (approx. 50% growth inhibition) or 10 ..mu..M methotrexate (MTX) (approx. 95% growth inhibition) for 6 hrs to allow high levels of PGS to accumulate. Dihydrofolate reductase (DHFR) activity was assessed by dihydrofolate (FH/sub 2/) pools labeled with 5-formyl-(/sup 3/H)-tetrahydrofolate (5..mu..M) or /sup 3/H-folic acid (1 ..mu..M). FH/sub 2/ was not elevated above control levels in 7-OH-MTX treated cells, in contrast to MTX treated cells in which FH/sub 2/ increased 4- to 7-fold. /sup 3/H-Deoxyuridine incorporation into DNA was not inhibited in cells containing high levels (11.5 nmol/g dry wt.) of 7-OH-MTX tetraglutamate (7-OH-4-NH/sub 2/-10-CH/sub 3/-PteGlu/sub 4/), well in excess of the DHFR-binding capacity (7.3 +/- 0.9 nmol/g), indicating a normal rate of thymidylate synthesis. Although small amounts of 7-OH-MTX and its PGS were bound to DHFR in L1210 cells, as assessed by gel filtration, there was evidence for the preferential binding of 7-OH-MTX tetraglutamate. In all cases this was well below the DHFR binding capacity, consistent with normal rates of deoxyuridine metabolism and FH/sub 2/ levels in the cell. Incorporation of /sup 14/C-formate (60 min) into thymidylate and amino acids was unaffected by 7-OH-MTX, yet incorporation into purines was inhibited over 50%, supporting a block(s) in de novo purine biosynthesis.

  1. Alterations in purine metabolism in middle-aged elite, amateur, and recreational runners across a 1-year training cycle.

    PubMed

    Zieliński, Jacek; Kusy, Krzysztof; Słomińska, Ewa

    2013-03-01

    Changes in purine derivatives may be considered as signs of training-induced metabolic adaptations. The purpose of this study was to assess the effect of a 1-year training cycle on the response of hypoxanthine (Hx) concentration and Hx-guanine phosphoribosyltransferase (HGPRT) activity. Three groups of middle-aged male runners were examined: 11 elite master runners (EL; 46.0 ± 3.8 years), 9 amateur runners (AM; 45.1 ± 4.7 years), and 10 recreational runners (RE; 45.9 ± 6.1 years). Plasma Hx concentration and erythrocyte HGPRT activity were measured in three characteristic training phases of the annual cycle. Significant differences in post-exercise Hx concentration and resting HGPRT activity were demonstrated between the EL, AM, and RE groups across consecutive training phases. The EL group showed lowest Hx concentration and highest HGPRT activity compared to the AM and RE groups. Analogous differences were observed between the AM and RE groups during specific preparation. For the EL group, the changes were observed across all examinations and the lowest Hx concentration and highest HGPRT activity were found in the competition phase. Significant change was also revealed in the AM group between the general and specific preparation, but not in the competition phase. No significant changes were found in the RE runners who did not use anaerobic exercise in their training. In conclusion, a long-lasting endurance training, incorporating high-intensity exercise, results in significant changes in purine metabolism, whereas training characterized by constant low-intensity exercise does not. Plasma Hx concentration and erythrocyte HGPRT activity may be sensitive indicators of training adaptation and training status in middle-aged athletes.

  2. Calf spleen purine nucleoside phosphorylase: structure of its ternary complex with an N(7)-acycloguanosine inhibitor and a phosphate anion.

    PubMed

    Luić, M; Koellner, G; Shugar, D; Saenger, W; Bzowska, A

    2001-01-01

    The calf spleen purine nucleoside phosphorylase (PNP) ternary complex with an N(7)-acycloguanosine inhibitor and a phosphate ion has been crystallized in the cubic space group P2(1)3, with unit-cell parameter a = 94.11 A and one monomer per asymmetric unit. X-ray diffraction data were collected using synchrotron radiation (Station X31, EMBL Outstation, DESY, Hamburg). The crystal structure was refined to a resolution of 2.2 A and R and R(free) values of 17.5 and 24.5%, respectively. The acyclonucleoside inhibitor is bound in the active site in an inverted ('upside-down') orientation of the purine base compared with natural substrates. The side chain of Asp243 forms two hydrogen bonds with the base ring: N(delta) donates a hydrogen to N(3) and O(delta) accepts a hydrogen from the guanine N(2)-amino group. N(1)--H of the base is hydrogen bonded to O(epsilon) of Glu201, while N(9) accepts a hydrogen bond from Thr242 O(gamma). In addition, a water molecule (W417) bridges the N(2)-amino group of the base and O(epsilon) of Glu201. In the phosphate-binding site, a phosphate ion is bound to Ser33, His64, Arg84, His86, Ala116 and Ser220. The acyclic chain of the N(7)-acycloguanosine inhibitor is in a folded conformation and together with a water molecule (W388) occupies the pentose-binding site, with possible hydrogen bonds to Tyr88 O(eta) and His257 N(delta 1). This new binding mode fully accounts for the previously observed substrate properties of 7-beta-D-ribofuranosides of hypoxanthine and guanine. It also provides a new starting point for the design of inhibitors of PNP for therapeutic and other applications.

  3. UK Announces Intention to Join ESO

    NASA Astrophysics Data System (ADS)

    2000-11-01

    Summary The Particle Physics and Astronomy Research Council (PPARC) , the UK's strategic science investment agency, today announced that the government of the United Kingdom is making funds available that provide a baseline for this country to join the European Southern Observatory (ESO) . The ESO Director General, Dr. Catherine Cesarsky , and the ESO Community warmly welcome this move towards fuller integration in European astronomy. "With the UK as a potential member country of ESO, our joint opportunities for front-line research and technology will grow significantly", she said. "This announcement is a clear sign of confidence in ESO's abilities, most recently demonstrated with the construction and operation of the unique Very Large Telescope (VLT) on Paranal. Together we will look forward with confidence towards new, exciting projects in ground-based astronomy." It was decided earlier this year to place the 4-m UK Visible and Infrared Survey Telescope (VISTA) at Paranal, cf. ESO Press Release 03/00. Following negotiations between ESO and PPARC, a detailed proposal for the associated UK/ESO Agreement with the various entry modalities will now be presented to the ESO Council for approval. Before this Agreement can enter into force, the ESO Convention and associated protocols must also be ratified by the UK Parliament. Research and key technologies According to the PPARC press release, increased funding for science, announced by the UK government today, will enable UK astronomers to prepare for the next generation of telescopes and expand their current telescope portfolio through membership of the European Southern Observatory (ESO). The uplift to its baseline budget will enable PPARC to enter into final negotiations for UK membership of the ESO. This will ensure that UK astronomers, together with their colleagues in the ESO member states, are actively involved in global scale preparations for the next generation of astronomy facilities. among these are ALMA

  4. Molecular cloning, functional characterization and expression of potato (Solanum tuberosum) 1-deoxy-d-xylulose 5-phosphate synthase 1 (StDXS1) in response to Phytophthora infestans.

    PubMed

    Henriquez, Maria Antonia; Soliman, Atta; Li, Genyi; Hannoufa, Abdelali; Ayele, Belay T; Daayf, Fouad

    2016-02-01

    1-Deoxy-D-xylulose 5-phosphate synthase (DXS) catalyzes the initial step of the plastidial 2C-methyl-D-erythritol-4-phosphate (DOXP-MEP) pathway involved in isoprenoid biosynthesis. In this study, we cloned the complete cDNA of potato DXS gene that was designated StDXS1. StDXS1 cDNA encodes for 719 amino acid residues, with MW of 77.8 kDa, and is present in one copy in the potato genome. Phylogenetic analysis and protein sequence alignments assigned StDXS1 to a group with DXS homologues from closely related species and exhibited homodomain identity with known DXS proteins from other plant species. Late blight symptoms occurred in parallel with a reduction in StDXS1 transcript levels, which may be associated with the levels of isoprenoids that contribute to plant protection against pathogens. Subcellular localization indicated that StDXS1 targets the chloroplasts where isoprenoids are synthesized. Arabidopsis expressing StDXS1 showed a higher accumulation of carotenoids and chlorophyll as compared to wild type controls. Lower levels of ABA and GA were detected in the transgenic DXS lines as compared to control plants, which reflected on higher germination rates of the transgenic DXS lines. No changes were detected in JA or SA contents. Selected downstream genes in the DOXP-MEP pathway, especially GGPPS genes, were up-regulated in the transgenic lines.

  5. Report on: "The 1st Workshop on National Immunization Programs and Vaccine Coverage in ASEAN Countries, April 30, 2015, Pattaya, Thailand".

    PubMed

    Hattasingh, Weerawan; Pengsaa, Krisana; Thisyakorn, Usa

    2016-03-01

    The 1st Workshop on National Immunization Programs and Vaccine Coverage in Association of Southeast Asian Nations (ASEAN) Countries Group (WNIPVC-ASEAN) held a meeting on April 30, 2015, Pattaya, Thailand under the auspices of the Pediatric Infectious Diseases Society and the World Health Organization (WHO). Reports on the current status and initiatives of the national immunization program (NIP) in each ASEAN countries that attended were presented. These reports along with survey data collected from ministries of health in ASEAN countries NIPs demonstrate that good progress has been made toward the goal of the Global Vaccine Action Plan (GVAP). However, some ASEAN countries have fragile health care systems that still have insufficient vaccine coverage of some basic EPI antigens. Most ASEAN countries still do not have national coverage of some new and underused vaccines, and raising funds for the expansion of NIPs is challenging. Also, there is insufficient research into disease burden of vaccine preventable diseases and surveillance. Health care workers must advocate NIPs to government policy makers and other stakeholders as well as improve research and surveillance to achieve the goals of the GVAP.

  6. Spectroscopic Classification of ASASSN-15uk

    NASA Astrophysics Data System (ADS)

    Wang, Chun; Liu, X.-W.; Dong, S.; Prieto, J. L.

    2015-12-01

    We obtained a low-resolution optical spectrum of ASASSN-15uk (ATel #8461) on 2015 December 25.9 with the 2.16-m telescope at Xinglong Station of NAOC. Cross-correlation with a library of SN spectra using SNID (Blondin & Tonry 2007, ApJ, 666, 1024) shows that ASASSN-15uk is a Type Ia and matches best the normal SN 1999ef and the SN 1991T-like SN 2003fa at 7-9 days after maximum.

  7. UK medical selection: lottery or meritocracy?

    PubMed

    Harris, Benjamin H L; Walsh, Jason L; Lammy, Simon

    2015-02-01

    From senior school through to consultancy, a plethora of assessments shape medical careers. Multiple methods of assessment are used to discriminate between applicants. Medical selection in the UK appears to be moving increasingly towards non-knowledge-based testing at all career stages. We review the evidence for non-knowledge-based tests and discuss their perceived benefits. We raise the question: is the current use of non-knowledge-based tests within the UK at risk of undermining more robust measures of medical school and postgraduate performance?

  8. Under pressure: homeopathy UK and its detractors.

    PubMed

    Milgrom, Lionel R

    2009-08-01

    Though homeopathy has been in successful and continuous use for well over 200 years, in the United Kingdom it is under growing pressure, from scientific detractors and sections of the media. As such, homeopathy's free National Health Service provision is threatened because it is derided as 'unproven', 'unscientific', and even 'deadly'. While refuting these and other detractions, this paper considers possible reasons for the current plight of homeopathy UK. Thus, the current attacks against homeopathy should be viewed more in the context of the globalised pharmaceutical industry which is itself in crisis, and a succession of UK governments seemingly supine in the face of legislation originating from the European Union.

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

    PubMed

    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

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

    PubMed Central

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

    2014-01-01

    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

  11. Challenges for Academic Accreditation: The UK Experience

    ERIC Educational Resources Information Center

    Shearman, Richard; Seddon, Deborah

    2010-01-01

    Several factors (government policy, demographic trends, employer pressure) are leading to new forms of degree programmes in UK universities. The government is strongly encouraging engagement between universities and employers. Work-based learning is increasingly found in first and second cycle programmes, along with modules designed by employers…

  12. Sunday Opening in UK Public Libraries

    ERIC Educational Resources Information Center

    Moore, Chris; Creaser, Claire

    2010-01-01

    This paper presents a summary of the first survey of public library authorities in the UK to explore Sunday opening, undertaken in 2007 as part of the Clore Leadership Programme. It provides a snapshot of Sunday opening practice, set against a context of societal, economic, and policy developments, and examines whether Sunday opening furthers the…

  13. Universities UK: Manifesto for Higher Education

    ERIC Educational Resources Information Center

    Universities UK, 2010

    2010-01-01

    The challenges that the UK faces today are global and they require world-class solutions. With continued support and investment from the Government, higher education will play a central role in meeting those challenges. Tomorrow's knowledge-based economy will demand a flexible, diverse and well educated workforce. Climate change and rapid…

  14. Metaphor Use in Three UK University Lectures

    ERIC Educational Resources Information Center

    Low, Graham; Littlemore, Jeannette; Koester, Almut

    2008-01-01

    It has been claimed in recent years that, on the one hand, metaphor occurs in UK university lectures in ways that are likely to confuse ESL learners (Littlemore 2001, 2003) and on the other hand that US lecturers use it in highly structured ways, particularly involving linked clusters, to help organize the lecture and indicate the opinions of the…

  15. Resources for Teaching Astronomy in UK Schools

    ERIC Educational Resources Information Center

    Roche, Paul; Newsam, Andy; Roberts, Sarah; Mason, Tom; Baruch, John

    2012-01-01

    This article looks at a selection of resources currently available for use in the teaching of astronomy in UK schools. It is by no means an exhaustive list but it highlights a variety of free resources that can be used in the classroom to help engage students of all ages with astronomy and space science. It also lists several facilities with a…

  16. Disability in the UK: Measuring Equality

    ERIC Educational Resources Information Center

    Purdam, Kingsley; Afkhami, Reza; Olsen, Wendy; Thornton, Patricia

    2008-01-01

    In this article we identify the key survey data for examining the issue of equality in the lives of disabled people in the UK. Such data is essential for assessing change in quality of life over time and for the evaluation of the impact of policy initiatives. For each data source we consider definitions, data collection, issue coverage, sample…

  17. Globalisation and MATESOL Programmes in the UK

    ERIC Educational Resources Information Center

    Hasrati, Mostafa; Tavakoli, Parvaneh

    2015-01-01

    This article reports the results of a mixed-methods approach to investigating the association between globalisation and MATESOL in UK universities. Qualitative and quantitative data collected from academic staff through eight emails, four interviews and 41 questionnaires indicate that the globalised context of higher education has affected these…

  18. Economic Cost of Autism in the UK

    ERIC Educational Resources Information Center

    Knapp, Martin; Romeo, Renee; Beecham, Jennifer

    2009-01-01

    Autism has lifetime consequences, with potentially a range of impacts on the health, wellbeing, social integration and quality of life of individuals and families. Many of those impacts are economic. This study estimated the costs of autism spectrum disorders (ASDs) in the UK. Data on prevalence, level of intellectual disability and place of…

  19. Subject Choice and Earnings of UK Graduates

    ERIC Educational Resources Information Center

    Chevalier, Arnaud

    2011-01-01

    Using a survey of a cohort of UK graduates, linked to administrative data on higher education participation, this paper investigates the labour market attainment of recent graduates by subject of study. We document a large heterogeneity in the mean wages of graduates from different subjects and a considerably larger one within subject with…

  20. Leptospirosis and Weil's disease in the UK.

    PubMed

    Forbes, A E; Zochowski, W J; Dubrey, S W; Sivaprakasam, V

    2012-12-01

    The recent high-profile death of a British Olympic rower from leptospirosis has raised awareness to this uncommon but potentially fatal disease. The re-emergence of the disease abroad is well documented in the literature, but less is known about cases in the UK. The increase in participation in water sports, foreign travel and often a combination of the two, has increased the exposure of tourists subsequently returning to the UK from areas of high prevalence. Leptospirosis is a zoonotic infection. The bacteria are shed in the urine of animals to the environment from where humans are infected by incidental hosts. There is a wide spectrum of severity of symptoms, from a self-limiting febrile illness to fatal pulmonary haemorrhage, renal or liver failure. It is thought that cases remain unrecognized every year in the UK, largely due to the mild nature of symptoms and the wide differential for febrile illness and partly due to lack of awareness among clinicians. This review examines the epidemiology of leptospirosis in the UK, over the period 2006-10, the clinical features, diagnostic techniques and treatment. PMID:22843698

  1. Migrant cap 'may damage' UK physics

    NASA Astrophysics Data System (ADS)

    Harris, Margaret

    2011-01-01

    Scientists have expressed concern that changes to UK immigration rules - including a sharp drop in the number of visas available for the most highly skilled migrants - could make it more difficult for universities and other institutions to recruit talented researchers from overseas.

  2. UK Work Placements: A Choice Too Far?

    ERIC Educational Resources Information Center

    Little, Brenda; Harvey, Lee

    2007-01-01

    Increasing expectations are being placed on higher education institutions to ensure the economic relevance of research and knowledge creation as well as developing the skill needs of workers in modern knowledge-based societies. In the UK, workplace learning has long been a feature of higher education in certain subject areas, and in the late 1990s…

  3. Source Process of the Solomon Islands Earthquake of April 1st, 2007 (Mw8.1) Based on SAR Data and its Tectonic Implications

    NASA Astrophysics Data System (ADS)

    Mori, M.; Kato, T.; Furuya, M.; Ochi, T.; Miyazaki, S.; Aoki, Y.

    2008-12-01

    We analyzed SAR (Synthetic Aperture Radar) data to derive the crustal deformation due to the Solomon Islands earthquake (Mw8.1) that occurred on April 1st, 2007. Three tracks that cover the source areas were used and the image data taken before and after the earthquake were processed to make interferograms. Then, we examined the obtained interferograms if the previous two source models that were obtained by seismic wave form inversion analyses could reproduce them. However, none of the models were able to reproduce the crustal deformations derived from the SAR data analysis. Then, we tried to construct a source model that explains the observed crustal deformations well. We considered some geophysical data to constrain the source geometry; the multichannel reflection data and observed vertical deformations using coral reef survey. Considering these lines of evidence, we introduced two possible source geometries; one is single-segment model that assumes only shallow-dipping (10 deg.) main thrust ruptured, and the other is two-segment model that assumes both a high angle spray fault of 30 degree dip and the main thrust fault slipped. The comparison of models based on inversion analyses suggested that the two-segment model would be preferable. This result suggests that the Solomon Islands earthquake would be the first observed earthquake on a steeply dipping splay fault that ruptured off the main converging plate boundary. If this is the case, this earthquake might provide us with an important clue for understanding the mechanisms of land formation such as landward titling of the coastal terraces.

  4. Establishment of the 1st World Health Organization International Standard for Plasmodium falciparum DNA for nucleic acid amplification technique (NAT)-based assays

    PubMed Central

    Padley, David J; Heath, Alan B; Sutherland, Colin; Chiodini, Peter L; Baylis, Sally A

    2008-01-01

    Background In order to harmonize results for the detection and quantification of Plasmodium falciparum DNA by nucleic acid amplification technique (NAT)-based assays, a World Health Organization (WHO) collaborative study was performed, evaluating a series of candidate standard preparations. Methods Fourteen laboratories from 10 different countries participated in the collaborative study. Four candidate preparations based upon blood samples parasitaemic for P. falciparum were evaluated in the study. Sample AA was lyophilized, whilst samples BB, CC and DD were liquid/frozen preparations. The candidate standards were tested by each laboratory at a range of dilutions in four independent assays, using both qualitative and quantitative NAT-based assays. The results were collated and analysed statistically. Results Twenty sets of data were returned from the participating laboratories and used to determine the mean P. falciparum DNA content for each sample. The mean log10 "equivalents"/ml were 8.51 for sample AA, 8.45 for sample BB, 8.35 for sample CC, and 5.51 for sample DD. The freeze-dried preparation AA, was examined by accelerated thermal degradation studies and found to be highly stable. Conclusion On the basis of the collaborative study, the freeze-dried material, AA (NIBSC code No. 04/176) was established as the 1st WHO International Standard for P. falciparum DNA NAT-based assays and has been assigned a potency of 109 International Units (IU) per ml. Each vial contains 5 × 108 IU, equivalent to 0.5 ml of material after reconstitution. PMID:18652656

  5. PREFACE: 1st International Workshop on Theoretical and Computational Physics: Condensed Matter, Soft Matter and Materials Physics & 38th National Conference on Theoretical Physics

    NASA Astrophysics Data System (ADS)

    2014-09-01

    This volume contains selected papers presented at the 38th National Conference on Theoretical Physics (NCTP-38) and the 1st International Workshop on Theoretical and Computational Physics: Condensed Matter, Soft Matter and Materials Physics (IWTCP-1). Both the conference and the workshop were held from 29 July to 1 August 2013 in Pullman hotel, Da Nang, Vietnam. The IWTCP-1 was a new activity of the Vietnamese Theoretical Physics Society (VTPS) organized in association with the 38th National Conference on Theoretical Physics (NCTP-38), the most well-known annual scientific forum dedicated to the dissemination of the latest development in the field of theoretical physics within the country. The IWTCP-1 was also an External Activity of the Asia Pacific Center for Theoretical Physics (APCTP). The overriding goal of the IWTCP is to provide an international forum for scientists and engineers from academia to share ideas, problems and solution relating to the recent advances in theoretical physics as well as in computational physics. The main IWTCP motivation is to foster scientific exchanges between the Vietnamese theoretical and computational physics community and world-wide scientists as well as to promote high-standard level of research and education activities for young physicists in the country. About 110 participants coming from 10 countries participated in the conference and the workshop. 4 invited talks, 18 oral contributions and 46 posters were presented at the conference. In the workshop we had one keynote lecture and 9 invited talks presented by international experts in the fields of theoretical and computational physics, together with 14 oral and 33 poster contributions. The proceedings were edited by Nguyen Tri Lan, Trinh Xuan Hoang, and Nguyen Ai Viet. We would like to thank all invited speakers, participants and sponsors for making the conference and the workshop successful. Nguyen Ai Viet Chair of NCTP-38 and IWTCP-1

  6. FOREWORD: 13th International Workshop on Plasma-Facing Materials and Components for Fusion Applications/1st International Conference on Fusion Energy Materials Science 13th International Workshop on Plasma-Facing Materials and Components for Fusion Applications/1st International Conference on Fusion Energy Materials Science

    NASA Astrophysics Data System (ADS)

    Jacob, Wolfgang; Linsmeier, Christian; Rubel, Marek

    2011-12-01

    The 13th International Workshop on Plasma-Facing Materials and Components (PFMC-13) jointly organized with the 1st International Conference on Fusion Energy Materials Science (FEMaS-1) was held in Rosenheim (Germany) on 9-13 May 2011. PFMC-13 is a successor of the International Workshop on Carbon Materials for Fusion Applications series. Between 1985 and 2003 ten 'Carbon Workshops' were organized in Jülich, Stockholm and Hohenkammer. Then it was time for a change and redefinition of the scope of the symposium to reflect the new requirements of ITER and the ongoing evolution in the field. Under the new name (PFMC-11), the workshop was first organized in 2006 in Greifswald, Germany and PFMC-12 took place in Jülich in 2009. Initially starting in 1985 with about 40 participants as a 1.5 day workshop, the event has continuously grown to about 220 participants at PFMC-12. Due to the joint organization with FEMaS-1, PFMC-13 set a new record with more than 280 participants. The European project Fusion Energy Materials Science, FEMaS, coordinated by the Max-Planck-Institut für Plasmaphysik (IPP), organizes and stimulates cooperative research activities which involve large-scale research facilities as well as other top-level materials characterization laboratories. Five different fields are addressed: benchmarking experiments for radiation damage modelling, the application of micro-mechanical characterization methods, synchrotron and neutron radiation-based techniques and advanced nanoscopic analysis based on transmission electron microscopy. All these fields need to be exploited further by the fusion materials community for timely materials solutions for a DEMO reactor. In order to integrate these materials research fields, FEMaS acted as a co-organizer for the 2011 workshop and successfully introduced a number of participants from research labs and universities into the PFMC community. Plasma-facing materials experience particularly hostile conditions as they are

  7. Finding a VOICE for UK clinical pharmacology.

    PubMed

    Aronson, Jeffrey K

    2012-06-01

    At a James Black Conference held in Oxford on 20-22 June 2011, a group of senior clinical pharmacologists and their junior colleagues, other medical specialists, and pharmacists discussed an agenda for UK clinical pharmacology for the next 5 years, addressing the following broad questions. How should UK clinical pharmacology be further developed and delivered as a discipline in universities, the NHS, pharmaceutical companies, and regulatory authorities? How should teaching and training in UK clinical pharmacology and therapeutics be delivered and assessed? What topics should be priorities for research in UK academic clinical pharmacology? How should clinical pharmacology contribute to UK drugs policy? How should pharmacology and clinical pharmacology be further integrated, to the benefit of both? Numerous recommendations emerged, under the collective acronym VOICE, standing for Visibility, Outreach, Integration, Coverage and Emissaries. VISIBILITY: The visibility of the discipline needs to be increased. This could be done, for example, by increased activities in acute general medicine/toxicology, through activities of Medicines and Therapeutics Committees, participation in grand rounds, teaching and training, and monitoring therapeutic interventions, and by offering bolt-on training for other specialists (for example, short courses, MSc courses, and training programmes). OUTREACH: Methods of increasing outreach include roadshows in schools/medical schools, national special study modules, public education, press coverage, and social marketing. INTEGRATION: Closer collaborations with pharmacologists, clinical pharmacists, other prescribers, and pharmaceutical companies (e.g. through joint training programmes) are desirable. COVERAGE: Attention to neglected areas, such as general practice, paediatrics, obstetrics, geriatrics, anaesthetics, cancer, and immunology. EMISSARIES: Trainees to spread the word. PMID:22360150

  8. Finding a VOICE for UK clinical pharmacology.

    PubMed

    Aronson, Jeffrey K

    2012-06-01

    At a James Black Conference held in Oxford on 20-22 June 2011, a group of senior clinical pharmacologists and their junior colleagues, other medical specialists, and pharmacists discussed an agenda for UK clinical pharmacology for the next 5 years, addressing the following broad questions. How should UK clinical pharmacology be further developed and delivered as a discipline in universities, the NHS, pharmaceutical companies, and regulatory authorities? How should teaching and training in UK clinical pharmacology and therapeutics be delivered and assessed? What topics should be priorities for research in UK academic clinical pharmacology? How should clinical pharmacology contribute to UK drugs policy? How should pharmacology and clinical pharmacology be further integrated, to the benefit of both? Numerous recommendations emerged, under the collective acronym VOICE, standing for Visibility, Outreach, Integration, Coverage and Emissaries. VISIBILITY: The visibility of the discipline needs to be increased. This could be done, for example, by increased activities in acute general medicine/toxicology, through activities of Medicines and Therapeutics Committees, participation in grand rounds, teaching and training, and monitoring therapeutic interventions, and by offering bolt-on training for other specialists (for example, short courses, MSc courses, and training programmes). OUTREACH: Methods of increasing outreach include roadshows in schools/medical schools, national special study modules, public education, press coverage, and social marketing. INTEGRATION: Closer collaborations with pharmacologists, clinical pharmacists, other prescribers, and pharmaceutical companies (e.g. through joint training programmes) are desirable. COVERAGE: Attention to neglected areas, such as general practice, paediatrics, obstetrics, geriatrics, anaesthetics, cancer, and immunology. EMISSARIES: Trainees to spread the word.

  9. The future of learning disabilities nursing in the UK.

    PubMed

    Clapham, Anthony

    2014-07-01

    This article appraises the report Strengthening the Commitment, which is a UK-wide review of learning disabilities nursing by the UK's four chief nursing officers. Strengthening the Commitment has strategic importance in reviewing progress in the care of people with learning disabilities in the UK. It also has a role in helping to guide future strategies and initiatives addressing the continuing health inequalities experienced by people with learning disabilities throughout the UK.

  10. Global health in the UK government and university sector.

    PubMed

    Coltart, Cordelia E M; Black, Mary E; Easterbrook, Philippa J

    2011-09-01

    In this article, the authors review recent global health activities in the United Kingdom by key organisations in several defined areas:- UK government (international aid and global health strategy); UK research funding agencies (overseas research units); non-governmental organisations; UK universities and hospitals and academic/clinical international partnerships;professional societies; UK undergraduate and postgraduate training opportunities in global health; and opportunities for international medical graduates.

  11. PLAB and UK graduates’ performance on MRCP(UK) and MRCGP examinations: data linkage study

    PubMed Central

    Wakeford, Richard

    2014-01-01

    Objectives To assess whether international medical graduates passing the two examinations set by the Professional and Linguistic Assessments Board (PLAB1 and PLAB2) of the General Medical Council (GMC) are equivalent to UK graduates at the end of the first foundation year of medical training (F1), as the GMC requires, and if not, to assess what changes in the PLAB pass marks might produce equivalence. Design Data linkage of GMC PLAB performance data with data from the Royal Colleges of Physicians and the Royal College of General Practitioners on performance of PLAB graduates and UK graduates at the MRCP(UK) and MRCGP examinations. Setting Doctors in training for internal medicine or general practice in the United Kingdom. Participants 7829, 5135, and 4387 PLAB graduates on their first attempt at MRCP(UK) Part 1, Part 2, and PACES assessments from 2001 to 2012 compared with 18 532, 14 094, and 14 376 UK graduates taking the same assessments; 3160 PLAB1 graduates making their first attempt at the MRCGP AKT during 2007-12 compared with 14 235 UK graduates; and 1411 PLAB2 graduates making their first attempt at the MRCGP CSA during 2010-12 compared with 6935 UK graduates. Main outcome measures Performance at MRCP(UK) Part 1, Part 2, and PACES assessments, and MRCGP AKT and CSA assessments in relation to performance on PLAB1 and PLAB2 assessments, as well as to International English Language Testing System (IELTS) scores. MRCP(UK), MRCGP, and PLAB results were analysed as marks relative to the pass mark at the first attempt. Results PLAB1 marks were a valid predictor of MRCP(UK) Part 1, MRCP(UK) Part 2, and MRCGP AKT (r=0.521, 0.390, and 0.490; all P<0.001). PLAB2 marks correlated with MRCP(UK) PACES and MRCGP CSA (r=0.274, 0.321; both P<0.001). PLAB graduates had significantly lower MRCP(UK) and MRCGP assessments (Glass’s Δ=0.94, 0.91, 1.40, 1.01, and 1.82 for MRCP(UK) Part 1, Part 2, and PACES and MRCGP AKT and CSA), and were more likely to fail assessments

  12. UK Schools, CCTV and the Data Protection Act 1998

    ERIC Educational Resources Information Center

    Taylor, Emmeline

    2011-01-01

    The use of CCTV in schools is now commonplace in the UK. It is estimated that 85% of all UK secondary schools currently have CCTV systems in operation. The introduction of the Data Protection Act 1998 (DPA) (enacted in March 2000) meant that for the first time CCTV had direct legislation governing its use in the UK. This paper attempts to apply…

  13. Patterns and Trends in UK Higher Education, 2011

    ERIC Educational Resources Information Center

    Universities UK, 2011

    2011-01-01

    This report builds on the time series data produced annually since 2001 under the title "Patterns of higher education institutions in the UK." It offers a unique overview of provision at publicly-funded higher education institutions in the UK. All charts and tables in the report are now also available to download from the Universities UK website.…

  14. Predictors of the timing of initiation of antenatal care in an ethnically diverse urban cohort in the UK

    PubMed Central

    2013-01-01

    Background In the UK, women are recommended to engage with maternity services and establish a plan of care prior to the 12th completed week of pregnancy. The aim of this study was to identify predictors for late initiation of antenatal care within an ethnically diverse cohort in East London. Methods Cross-sectional analysis of routinely collected electronic patient record data from Newham University Hospital NHS Trust (NUHT). All women who attended their antenatal booking appointment within NUHT between 1st January 2008 and 24th January 2011 were included in this study. The main outcome measure was late antenatal booking, defined as attendance at the antenatal booking appointment after 12 weeks (+6 days) gestation. Data were analysed using multivariable logistic regression with robust standard errors. Results Late initiation of antenatal care was independently associated with non-British (White) ethnicity, inability to speak English, and non-UK maternal birthplace in the multivariable model. However, among those women who both spoke English and were born in the UK, the only ethnic group at increased risk of late booking were women who identified as African/Caribbean (aOR: 1.40: 95% CI: 1.11, 1.76) relative to British (White). Other predictors identified include maternal age younger than 20 years (aOR: 1.32; 95% CI: 1.13-1.54), high parity (aOR: 2.09; 95% CI: 1.77-2.46) and living in temporary accommodation (aOR: 1.71; 95% CI: 1.35-2.16). Conclusions Socio-cultural factors in addition to poor English ability or assimilation may play an important role in determining early initiation of antenatal care. Future research should focus on effective interventions to encourage and enable these minority groups to engage with the maternity services. PMID:23642084

  15. Calf spleen purine nucleoside phosphorylase: complex kinetic mechanism, hydrolysis of 7-methylguanosine, and oligomeric state in solution.

    PubMed

    Bzowska, Agnieszka

    2002-04-29

    The active enzyme form was found to be a homotrimer, no active monomers were observed. Only in the presence of an extremely high orthophosphate concentration (0.5 M) or at a low enzyme concentration (0.2 microg/ml) with no ligands present a small fraction of the enzyme is probably in a dissociated and/or non-active form. The specific activity is invariant over a broad enzyme concentration range (0.017 microg/ml-0.29 mg/ml). At concentrations below 0.9 microg/ml and in the absence of ligands the enzyme tends to loose its catalytic activity, while in the presence of any substrate or at higher concentrations it was found to be active as a trimer. In the absence of phosphate the enzyme catalyses the hydrolysis of 7-methylguanosine (m7Guo) with a catalytic rate constant 1.3x10(-3) x s(-1) as compared with the rate of 38 s(-1) for the phosphorolysis of this nucleoside. The initial pre-steady-state phase of the phosphorolysis of m7Guo, 70 s(-1), is almost twice faster than the steady-state rate and indicates that the rate-limiting step is subsequent to the glycosidic bond cleavage. Complex kinetic behaviour with substrates of phosphorolytic direction (various nucleosides and orthophosphate) was observed; data for phosphate as the variable substrate with inosine and guanosine, but not with their 7-methyl counterparts, might be interpreted as two binding sites with different affinities, or as a negative cooperativity. However, the titration of the enzyme intrinsic fluorescence with 0.2 microM-30 mM phosphate is consistent with only one dissociation constant for phosphate, K(d)=220+/-120 microM. Protective effects of ligands on the thermal inactivation of the enzyme indicate that all substrates of the phosphorolytic and the synthetic reactions are able to form binary complexes with the calf spleen purine nucleoside phosphorylase. The purine bases, guanine and hypoxanthine, bind strongly with dissociation constants of about 0.1 microM, while all other ligands studied

  16. X-ray structure, NMR and stability-in-solution study of 6-(furfurylamino)-9-(tetrahydropyran-2-yl)purine - A new active compound for cosmetology

    NASA Astrophysics Data System (ADS)

    Walla, Jan; Szüčová, Lucie; Císařová, Ivana; Gucký, Tomáš; Zatloukal, Marek; Doležal, Karel; Greplová, Jarmila; Massino, Frank J.; Strnad, Miroslav

    2010-06-01

    The crystal and molecular structure of 6-(furfurylamino)-9-(tetrahydropyran-2-yl)purine ( 1) was determined at 150(2) K. The compound crystallizes in monoclinic P2 1/ c space group with a = 10.5642(2), b = 13.6174(3), c = 10.3742(2) Å, V = 1460.78(5) Å 3, Z = 4, R( F) = for 3344 unique reflections. The purine moiety and furfuryl ring are planar and the tetrahydropyran-2-yl is disordered in the ratio 1:3, probably due to the chiral carbon atom C(17). The individual 1H and 13C NMR signals were assigned by 2D correlation experiments such as 1H- 1H COSY and ge-2D HSQC. Stability-in-solution was determined in methanol/water in acidic pH (3-7).

  17. 2,6-Di-chloro-9-(2',3',5'-tri-O-acetyl-β-d-ribo-furanos-yl)-9H-purine.

    PubMed

    Novosjolova, Irina; Stepanovs, Dmitrijs; Bizdēna, Erika; Mishnev, Anatoly; Turks, Māris

    2014-02-01

    The title synthetic analog of purine nucleosides, C16H16Cl2N4O7, has its acetyl-ated β-furan-ose ring in a 3'β-envelope conformation, with the corresponding C atom deviating by 0.602 (5) Å from the rest of the ring. The planar part of the furan-ose ring forms a dihedral angle of 65.0 (1)° with the mean plane of the purine bicycle. In the crystal, mol-ecules form a three-dimensional network through multiple C-H⋯O and C-H⋯N hydrogen bonds and C-H⋯π interactions.

  18. Pur-1, a zinc-finger protein that binds to purine-rich sequences, transactivates an insulin promoter in heterologous cells.

    PubMed Central

    Kennedy, G C; Rutter, W J

    1992-01-01

    Purine-rich stretches of nucleotides (GAGA boxes) are often found just upstream of transcription start sites in many genes, including insulin. Mutational analysis suggests that the GAGA box plays an important role in transcription of the rat insulin I gene. We identify here at least four different proteins that bind specifically to the insulin GAGA box. Using a GAGA oligonucleotide, we have isolated a cDNA encoding a sequence-specific protein from a HIT (hamster insulinoma cell line) lambda gt11 library. This protein, which we designate Pur-1 (for purine binding), binds to the GAGA boxes of the rat insulin I and II genes and the human islet amyloid polypeptide gene. Pur-1 is a potent transactivator in both pancreatic and nonpancreatic cells. Furthermore, Pur-1 is able to activate an intact insulin promoter in HeLa cells, where it is normally inactive. Images PMID:1454839

  19. trans-Dichloridobis{2-chloro-6-[(3-fluoro-benz-yl)amino]-9-isopropyl-9H-purine-κN (7)}platinum(II).

    PubMed

    Trávníček, Zdeněk; Starha, Pavel

    2013-06-01

    In the title compound, trans-[PtCl2(C15H15ClFN5)2], the Pt(II) atom, located on an inversion centre, is coordinated by the purine N atoms of the 2-chloro-6-[(3-fluoro-benz-yl)amino]-9-isopropyl-9H-purine ligands and two Cl atoms in a slightly distorted trans-square-planar coordination geometry [N-Pt-Cl angles = 89.91 (5) and 90.09 (5)°]. Weak intra-molecular N-H⋯Cl contacts occur. In the crystal, C-H⋯Cl and C-H⋯F contacts, as well as weak π-π stacking inter-actions [centroid-centroid distances = 3.5000 (11) and 3.6495 (12) Å] connect the mol-ecules into a three-dimensional architecture. PMID:23794993

  20. trans-Dichloridobis{2-chloro-6-[(3-fluoro­benz­yl)amino]-9-isopropyl-9H-purine-κN 7}platinum(II)

    PubMed Central

    Trávníček, Zdeněk; Štarha, Pavel

    2013-01-01

    In the title compound, trans-[PtCl2(C15H15ClFN5)2], the PtII atom, located on an inversion centre, is coordinated by the purine N atoms of the 2-chloro-6-[(3-fluoro­benz­yl)amino]-9-isopropyl-9H-purine ligands and two Cl atoms in a slightly distorted trans-square-planar coordination geometry [N—Pt—Cl angles = 89.91 (5) and 90.09 (5)°]. Weak intra­molecular N—H⋯Cl contacts occur. In the crystal, C—H⋯Cl and C—H⋯F contacts, as well as weak π–π stacking inter­actions [centroid–centroid distances = 3.5000 (11) and 3.6495 (12) Å] connect the mol­ecules into a three-dimensional architecture. PMID:23794993

  1. Purine and pyrimidine-specific repression of the Escherichia coli carAB operon are functionally and structurally coupled.

    PubMed

    Devroede, Neel; Thia-Toong, Thia-Lin; Gigot, Daniel; Maes, Dominique; Charlier, Daniel

    2004-02-01

    Transcription of the carAB operon encoding the sole carbamoylphosphate synthetase of Escherichia coli proceeds from a tandem pair of promoters. P2, downstream, is repressed by arginine and the ArgR protein, whereas P1 is submitted to pyrimidine-specific regulation and as shown here to purine-specific control exerted by binding of the PurR protein to a PUR box sequence centered around nucleotide -128.5 with respect to the start of P1 transcription. In vivo analyses of the effects of trans and cis-acting mutations on the regulatory responses and single round in vitro transcription assays indicated that ligand-bound PurR is by itself unable to inhibit P1 promoter activity. To exert its effect PurR relies on the elaborated nucleoprotein complex that governs P1 activity in a pyrimidine-specific manner. Thus we reveal the existence of an unprecedented functional and structural coupling between the modulation of P1 activity by purine and pyrimidine residues that appears to result from the unique position of the PUR box in the carAB control region, far upstream of the promoter. Missing contact and premethylation binding interference studies revealed the importance of base-specific groups and of structural aspects of the PUR box sequence in complex formation. Permutation assays indicated that the overall PurR-induced bending of the carAB control region is slightly less pronounced than that of the purF operator. The PUR boxes of the carAB operon of E.coli and Salmonella typhimurium are unique in that they have a guanine residue at position eight. Interestingly, guanine at this position has been proposed to be extremely unfavorable on the basis of modeling and binding studies, as its exocyclic amino group would enter into a steric clash with the side-chain of lysine 55. To analyze the effect of guanine at position eight in the upstream half-site of the carAB operator we constructed the adenine derivative and assayed in vivo repressibility of P1 promoter activity and in vitro

  2. Effects of salicylic acid on post-ischaemic ventricular function and purine efflux in isolated mouse hearts.

    PubMed

    Farthing, Don; Gehr, Lynne; Karnes, H Thomas; Sica, Domenic; Gehr, Todd; Larus, Terri; Farthing, Christine; Xi, Lei

    2007-01-01

    Acetyl salicylic acid (aspirin) is one of the most widely used drugs in the world. Various plasma concentrations of aspirin and its predominant metabolite, salicylic acid, are required for its antiarthritic (1.5-2.5 mM), anti-inflammatory (0.5-5.0 mM) or antiplatelet (0.18-0.36 mM) actions. A recent study demonstrated the inhibitory effects of both aspirin and salicylic acid on oxidative phosphorylation and ATP synthesis in isolated rat cardiac mitochondria in a dose-dependent manner (0-10 mM concentration range). In this context, the present study was conducted to determine the effects of salicylic acid on inosine efflux (a potential biomarker of acute cardiac ischaemia) as well as cardiac contractile function in the isolated mouse heart following 20 min of zero-flow global ischaemia. Inosine efflux was found at significantly higher concentrations in ischaemic hearts perfused with Krebs buffer fortified with 1.0 mM salicylic acid compared with those without salicylic acid (12575+/-3319 vs. 1437+/-348 ng ml(-1) min(-1), mean+/-SEM, n=6 per group, p<0.01). These results indicate that 1.0 mM salicylic acid potentiates 8.8-fold ATP nucleotide purine catabolism into its metabolites (e.g. inosine, hypoxanthine). Salicylic acid (0.1 or 1.0 mM) did not appreciably inhibit purine nucleoside phosphorylase (the enzyme converts inosine to hypoxanthine) suggesting the augmented inosine efflux was due to the salicylic acid effect on upstream elements of cellular respiration. Whereas post-ischaemic cardiac function was further depressed by 1.0 mM salicylic acid, perfusion with 0.1 mM salicylic acid led to a remarkable functional improvement despite moderately increased inosine efflux (2.7-fold). We conclude that inosine is a sensitive biomarker for detecting cardiac ischaemia and salicylic acid-induced effects on cellular respiration. However, the inosine efflux level appears to be a poor predictor of the individual post-ischaemic cardiac functional recovery in this ex vivo

  3. Effects of salicylic acid on post-ischaemic ventricular function and purine efflux in isolated mouse hearts.

    PubMed

    Farthing, Don; Gehr, Lynne; Karnes, H Thomas; Sica, Domenic; Gehr, Todd; Larus, Terri; Farthing, Christine; Xi, Lei

    2007-01-01

    Acetyl salicylic acid (aspirin) is one of the most widely used drugs in the world. Various plasma concentrations of aspirin and its predominant metabolite, salicylic acid, are required for its antiarthritic (1.5-2.5 mM), anti-inflammatory (0.5-5.0 mM) or antiplatelet (0.18-0.36 mM) actions. A recent study demonstrated the inhibitory effects of both aspirin and salicylic acid on oxidative phosphorylation and ATP synthesis in isolated rat cardiac mitochondria in a dose-dependent manner (0-10 mM concentration range). In this context, the present study was conducted to determine the effects of salicylic acid on inosine efflux (a potential biomarker of acute cardiac ischaemia) as well as cardiac contractile function in the isolated mouse heart following 20 min of zero-flow global ischaemia. Inosine efflux was found at significantly higher concentrations in ischaemic hearts perfused with Krebs buffer fortified with 1.0 mM salicylic acid compared with those without salicylic acid (12575+/-3319 vs. 1437+/-348 ng ml(-1) min(-1), mean+/-SEM, n=6 per group, p<0.01). These results indicate that 1.0 mM salicylic acid potentiates 8.8-fold ATP nucleotide purine catabolism into its metabolites (e.g. inosine, hypoxanthine). Salicylic acid (0.1 or 1.0 mM) did not appreciably inhibit purine nucleoside phosphorylase (the enzyme converts inosine to hypoxanthine) suggesting the augmented inosine efflux was due to the salicylic acid effect on upstream elements of cellular respiration. Whereas post-ischaemic cardiac function was further depressed by 1.0 mM salicylic acid, perfusion with 0.1 mM salicylic acid led to a remarkable functional improvement despite moderately increased inosine efflux (2.7-fold). We conclude that inosine is a sensitive biomarker for detecting cardiac ischaemia and salicylic acid-induced effects on cellular respiration. However, the inosine efflux level appears to be a poor predictor of the individual post-ischaemic cardiac functional recovery in this ex vivo

  4. Theoretical and experimental studies on the corrosion inhibition potentials of some purines for aluminum in 0.1 M HCl

    PubMed Central

    Eddy, Nnabuk O.; Momoh-Yahaya, H.; Oguzie, Emeka E.

    2014-01-01

    Experimental aspect of the corrosion inhibition potential of adenine (AD), guanine (GU) and, hypoxanthine (HYP) was carried out using weight loss, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) methods while the theoretical aspect of the work was carried out by calculations of semi-empirical parameters (for AM1, MNDO, CNDO, PM3 and RM1 Hamiltonians), Fukui functions and inhibitor–metal interaction energies. Results obtained from the experimental studies were in good agreement and indicated that adenine (AD), guanine (GU) and hypoxanthine (HYP) are good adsorption inhibitors for the corrosion of aluminum in solutions of HCl. Data obtained from electrochemical experiment revealed that the studied purines functioned by adsorption on the aluminum/HCl interface and inhibited the cathodic half reaction to a greater extent and anodic half reaction to a lesser extent. The adsorption of the purines on the metal surface was found to be exothermic and spontaneous. Deviation of the adsorption characteristics of the studied purines from the Langmuir adsorption model was compensated by the fitness of Flory Huggins and El Awardy et al. adsorption models. Quantum chemical studies revealed that the experimental inhibition efficiencies of the studied purines are functions of some quantum chemical parameters including total energy of the molecules (TE), energy gap (EL–H), electronic energy of the molecule (EE), dipole moment and core–core repulsion energy (CCR). Fukui functions analysis through DFT and MP2 theories indicated slight complications and unphysical results. However, results obtained from calculated Huckel charges, molecular orbital and interaction energies, the adsorption of the inhibitors proceeded through the imine nitrogen (N5) in GU, emanine nitrogen (N7) in AD and the pyridine nitrogen (N5) in HPY. PMID:25750754

  5. Theoretical and experimental studies on the corrosion inhibition potentials of some purines for aluminum in 0.1 M HCl.

    PubMed

    Eddy, Nnabuk O; Momoh-Yahaya, H; Oguzie, Emeka E

    2015-03-01

    Experimental aspect of the corrosion inhibition potential of adenine (AD), guanine (GU) and, hypoxanthine (HYP) was carried out using weight loss, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) methods while the theoretical aspect of the work was carried out by calculations of semi-empirical parameters (for AM1, MNDO, CNDO, PM3 and RM1 Hamiltonians), Fukui functions and inhibitor-metal interaction energies. Results obtained from the experimental studies were in good agreement and indicated that adenine (AD), guanine (GU) and hypoxanthine (HYP) are good adsorption inhibitors for the corrosion of aluminum in solutions of HCl. Data obtained from electrochemical experiment revealed that the studied purines functioned by adsorption on the aluminum/HCl interface and inhibited the cathodic half reaction to a greater extent and anodic half reaction to a lesser extent. The adsorption of the purines on the metal surface was found to be exothermic and spontaneous. Deviation of the adsorption characteristics of the studied purines from the Langmuir adsorption model was compensated by the fitness of Flory Huggins and El Awardy et al. adsorption models. Quantum chemical studies revealed that the experimental inhibition efficiencies of the studied purines are functions of some quantum chemical parameters including total energy of the molecules (TE), energy gap (E L-H), electronic energy of the molecule (EE), dipole moment and core-core repulsion energy (CCR). Fukui functions analysis through DFT and MP2 theories indicated slight complications and unphysical results. However, results obtained from calculated Huckel charges, molecular orbital and interaction energies, the adsorption of the inhibitors proceeded through the imine nitrogen (N5) in GU, emanine nitrogen (N7) in AD and the pyridine nitrogen (N5) in HPY.

  6. 2-Chloro-6-[(2,4-dimeth­oxy­benz­yl)amino]-9-isopropyl-9H-purine

    PubMed Central

    Novotná, Radka; Trávníček, Zdeněk

    2013-01-01

    In the title compound, C17H20ClN5O2, the benzene ring and the purine ring system make a dihedral angle of 78.56 (4)°. In the crystal, mol­ecules are linked by pairs of N—H⋯N hydrogen bonds, forming inversion dimers. C—H⋯O and C—H⋯Cl contacts further link the mol­ecules, forming a three-dimensional network. PMID:23476575

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

    PubMed

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

    2009-01-01

    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. PMID:19001417

  8. Nitrogen K-edge X-ray absorption near edge structure (XANES) spectra of purine-containing nucleotides in aqueous solution

    SciTech Connect

    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{sup ′}-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{sup ′}-monophosphate, and adenosine 5{sup ′}-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.

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

    PubMed

    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.

  10. 1st principle simulations of ions in water solutions: Bond structure and chemistry in the hydration shells of highly charged ions

    NASA Astrophysics Data System (ADS)

    Weare, John

    2012-02-01

    Methods of direct simulation (Monte Carlo and molecular dynamics) have provided new insights into the structure and dynamics of electrolyte solutions. However, these methods are limited by the difficulty of developing reliable ion-solvent and solvent-solvent potential interactions in the highly perturbed hydration region. To model the interactions in this region methods of simulation that are based on the direct on the fly solution to the electronic Schr"odinger equation (ab-initio molecular dynamics, AIMD) are being developed. However, 1st principle methods have their own problems because the solution to the electronic structure problem is intractable unless rather uncontrolled approximations are made (e.g. density functional theory, DFT) and there is high computational cost to the solution to the Schr"odinger equation. To test the accuracy of AIMD methods we have directly simulated the XAFS spectra for a series of transition metal ions Ca^2+, Cr^3+, Mn^2+, Fe^3+, Co^2+, Ni^2+, Cu^2+, and Zn^2+. Despite DFT's well know deficiencies, the agreement between the calculated XAFS spectra and the data is almost quantitative for these test ions. This agreement supports the extension of the interpretation well beyond that of the usual XAFS analysis to include higher-order multiple scattering signals in the XAFS spectra, which provide a rigorous probe of the first shell distances and disorders. Less well resolved features of the spectra can still be analyzed and are related to 2nd shell structure. The combination of XAFS measurements and the parameter free AIMD method leads to new insights into the hydration structure of these ions. While strictly local DFT +gga provides excellent agreement with data, the addition of exact exchange seems to provide slightly better structural agreement. The computational complexity of these calculations requires the development of simulation tools that scale to high processor number on massively parallel supercomputers. Our present algorithm

  11. Update on dialysis economics in the UK.

    PubMed

    Sharif, Adnan; Baboolal, Keshwar

    2011-03-01

    The burgeoning population of patients requiring renal replacement therapy contributes a disproportionate strain on National Health Service resources. Although renal transplantation is the preferred treatment modality for patients with established renal failure, achieving both clinical and financial advantages, limitations to organ donation and clinical comorbidities will leave a significant proportion of patients with established renal failure requiring expensive dialysis therapy in the form of either hemodialysis or peritoneal dialysis. An understanding of dialysis economics is essential for both healthcare providers and clinical leaders to establish clinically efficient and cost-effective treatment modalities that maximize service provision. In light of changes to the provision of healthcare funds in the form of "Payment by Results," it is imperative for UK renal units to adopt clinically effective and financially accountable dialysis programs. This article explores the role of dialysis economics and implications for UK renal replacement therapy programs. PMID:21364210

  12. The 2015 Pregnancy Summit, London, UK.

    PubMed

    Johansson, Cherynne

    2016-01-01

    Pregnancy Summit, Cineworld, The O2, London, UK, 29 September to 1 October 2015 The 2015 Pregnancy Summit was held over 3 days from 29 September to 1 October at Cineworld, The O2, London, UK. The event brings together a multidisciplinary faculty of international researchers and clinicians to discuss both scientific and clinical aspects of pregnancy-related issues in an informal setting. The goal of the meeting was to provide delegates with an update of recent advances in management of pregnancy-related conditions, to present research data and to discuss the current attitudes and practices in relevant topics. An extensive range of topics were discussed, from preeclampsia and treatment of hypertension, to the psychological impact of termination of pregnancy and feticide. This report will summarize a selection of the lectures presented.

  13. The UK Earth System Model project

    NASA Astrophysics Data System (ADS)

    Tang, Yongming

    2016-04-01

    In this talk we will describe the development and current status of the UK Earth System Model (UKESM). This project is a NERC/Met Office collaboration and has two objectives; to develop and apply a world-leading Earth System Model, and to grow a community of UK Earth System Model scientists. We are building numerical models that include all the key components of the global climate system, and contain the important process interactions between global biogeochemistry, atmospheric chemistry and the physical climate system. UKESM will be used to make key CMIP6 simulations as well as long-time (e.g. millennium) simulations, large ensemble experiments and investigating a range of future carbon emission scenarios.

  14. Update on dialysis economics in the UK.

    PubMed

    Sharif, Adnan; Baboolal, Keshwar

    2011-03-01

    The burgeoning population of patients requiring renal replacement therapy contributes a disproportionate strain on National Health Service resources. Although renal transplantation is the preferred treatment modality for patients with established renal failure, achieving both clinical and financial advantages, limitations to organ donation and clinical comorbidities will leave a significant proportion of patients with established renal failure requiring expensive dialysis therapy in the form of either hemodialysis or peritoneal dialysis. An understanding of dialysis economics is essential for both healthcare providers and clinical leaders to establish clinically efficient and cost-effective treatment modalities that maximize service provision. In light of changes to the provision of healthcare funds in the form of "Payment by Results," it is imperative for UK renal units to adopt clinically effective and financially accountable dialysis programs. This article explores the role of dialysis economics and implications for UK renal replacement therapy programs.

  15. The UK sugar tax - a healthy start?

    PubMed

    Jones, C M

    2016-07-22

    The unexpected announcement by the UK Chancellor of the Exchequer of a levy on sugar sweetened beverages (SSBs) on the 16 March 2016, should be welcomed by all health professionals. This population based, structural intervention sends a strong message that there is no place for carbonated drinks, neither sugared nor sugar-free, in a healthy diet and the proposed levy has the potential to contribute to both general and dental health. The sugar content of drinks exempt from the proposed sugar levy will still cause tooth decay. Improving the proposed tax could involve a change to a scaled volumetric tax of added sugar with a lower exemption threshold. External influences such as the Common Agricultural Policy and the Transatlantic Trade and Investment Partnership may negate the benefits of the sugar levy unless it is improved. However, the proposed UK sugar tax should be considered as a start in improving the nation's diet.

  16. The UK sugar tax - a healthy start?

    PubMed

    Jones, C M

    2016-07-22

    The unexpected announcement by the UK Chancellor of the Exchequer of a levy on sugar sweetened beverages (SSBs) on the 16 March 2016, should be welcomed by all health professionals. This population based, structural intervention sends a strong message that there is no place for carbonated drinks, neither sugared nor sugar-free, in a healthy diet and the proposed levy has the potential to contribute to both general and dental health. The sugar content of drinks exempt from the proposed sugar levy will still cause tooth decay. Improving the proposed tax could involve a change to a scaled volumetric tax of added sugar with a lower exemption threshold. External influences such as the Common Agricultural Policy and the Transatlantic Trade and Investment Partnership may negate the benefits of the sugar levy unless it is improved. However, the proposed UK sugar tax should be considered as a start in improving the nation's diet. PMID:27444594

  17. History of Inclusive Design in the UK.

    PubMed

    John Clarkson, P; Coleman, Roger

    2015-01-01

    The UK Design Council describes Inclusive Design as neither a new genre of design, nor a separate specialism, but as a general approach to designing in which designers ensure that their products and services address the needs of the widest possible audience, irrespective of age or ability. Inclusive Design (also known [in Europe] as Design for All and as Universal Design in the USA) is in essence the inverse of earlier approaches to designing for disabled and elderly people as a sub-set of the population, and an integral part of a more recent international trend towards the integration of older and disabled people in the mainstream of society. This paper describes the development of Inclusive Design in the UK, from its early beginnings, through its subsequent adoption as a topic of academic research, leading to its recent emergence embodied as a framework and toolkit for design.

  18. Structure of eukaryotic purine/H(+) symporter UapA suggests a role for homodimerization in transport activity.

    PubMed

    Alguel, Yilmaz; Amillis, Sotiris; Leung, James; Lambrinidis, George; Capaldi, Stefano; Scull, Nicola J; Craven, Gregory; Iwata, So; Armstrong, Alan; Mikros, Emmanuel; Diallinas, George; Cameron, Alexander D; Byrne, Bernadette

    2016-04-18

    The uric acid/xanthine H(+) symporter, UapA, is a high-affinity purine transporter from the filamentous fungus Aspergillus nidulans. Here we present the crystal structure of a genetically stabilized version of UapA (UapA-G411VΔ1-11) in complex with xanthine. UapA is formed from two domains, a core domain and a gate domain, similar to the previously solved uracil transporter UraA, which belongs to the same family. The structure shows UapA in an inward-facing conformation with xanthine bound to residues in the core domain. Unlike UraA, which was observed to be a monomer, UapA forms a dimer in the crystals with dimer interactions formed exclusively through the gate domain. Analysis of dominant negative mutants is consistent with dimerization playing a key role in transport. We postulate that UapA uses an elevator transport mechanism likely to be shared with other structurally homologous transporters including anion exchangers and prestin.

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

    PubMed

    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.

  20. Development of a capillary electrophoresis method for analyzing adenosine deaminase and purine nucleoside phosphorylase and its application in inhibitor screening.

    PubMed

    Qi, Yanfei; Li, Youxin; Bao, James J

    2016-08-01

    A novel capillary electrophoresis (CE) method was developed for simultaneous analysis of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) in red blood cells (RBCs). The developed method considered and took advantage of the natural conversion from the ADA product, inosine to hypoxanthine. The transformation ratio was introduced for ADA and PNP analysis to obtain more reliable results. After optimizing the enzymatic incubation and electrophoresis separation conditions, the determined activities of ADA and PNP in 12 human RBCs were 0.237-0.833 U/ml and 9.013-10.453 U/ml packed cells, respectively. The analysis of ADA in mice RBCs indicated that there was an apparent activity difference between healthy and hepatoma mice. In addition, the proposed method was also successfully applied in the inhibitor screening from nine traditional Chinese medicines, and data showed that ADA activities were strongly inhibited by Rhizoma Chuanxiong and Angelica sinensis. The inhibition effect of Angelica sinensis on ADA is first reported here and could also inhibit PNP activity. PMID:27173606