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Sample records for 1st uk purine

  1. Highlights of the 1st Student Symposium of the ISCB RSG UK

    PubMed Central

    Rahman, Farzana; Farmer, Rohit; Das, Sayoni; Vayani, Fatima; Hassan, Mehedi

    2015-01-01

    This short report summarises the scientific content and activities of a student-led event, the 1st student symposium by the UK Regional Student Group of the International Society for Computational Biology. The event took place on the 8th of October 2014. PMID:26998223

  2. Validation of the Edinburgh Claudication Questionnaire in 1st generation Black African-Caribbean and South Asian UK migrants: A sub-study to the Ethnic-Echocardiographic Heart of England Screening (E-ECHOES) study

    PubMed Central

    2011-01-01

    Background We determined the diagnostic accuracy of the Edinburgh Claudication Questionnaire (ECQ) in 1st generation Black African-Caribbean UK migrants as previous diagnostic questionnaires have been found to be less accurate in this population. We also determined the diagnostic accuracy of translated versions of the ECQ in 1st generation South Asian UK migrants, as this has not been investigated before. Methods Subjects were recruited from the Ethnic-Echocardiographic Heart of England Screening (E-ECHOES) study, a community based screening survey for heart failure in minority ethnic groups. Translated versions of the ECQ were prepared following a recognised protocol. All participants attending screening between October 2007 and February 2009 were asked to complete the ECQ in the language of their choice (English, Punjabi, Bengali, Urdu, Hindi or Gujarati). Subjects answering positively to experiencing leg pain or discomfort on walking were asked to return to have Ankle Brachial Pressure Index (ABPI) measured. Results 154 out of 2831 subjects participating in E-ECHOES (5.4%) were eligible to participate in this sub-study, for which 74.3% returned for ABPI assessment. Non-responders were younger than participants (59[9] vs. 65[11] years; p = 0.015). Punjabi, English and Bengali questionnaires identified participants with Intermittent Claudication, so these questionnaires were assessed. The sensitivities (SN), specificities (SP), positive (PPV) and negative (NPV) predictive values were calculated. English: SN: 50%; SP: 68%; PPV: 43%; NPV: 74%. Punjabi: SN: 50%; SP: 87%; PPV: 43%; NPV: 90%. Bengali: SN: 33%; SP: 50%; PPV: 13%; NPV: 73%. There were significant differences in diagnostic accuracy between the 3 versions (Punjabi: 83.8%; Bengali: 45%; English: 62.2%; p < 0.0001). No significant differences were found in sensitivity and specificity between illiterate and literate participants in any of the questionnaires and there was no significant different difference

  3. Purine and pyrimidine metabolism.

    PubMed

    Zöllner, N

    1982-09-01

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

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

    PubMed

    Colling, M; Wolfram, G

    1987-10-01

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

  5. 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.

  6. "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…

  7. "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…

  8. Purine and pyrimidine metabolism in man V

    SciTech Connect

    Nyhan, W.L.; Thompson, L.F.; Watts, R.W.E.

    1986-01-01

    This book comprises the proceedings of the Fifth International Symposium on Human Purine and Pyrimidine Metabolism. Its papers are organized under the following categories: adenosine receptors; purine receptors and the central nervous system; nucleoside and base transport; studies with antimetabolites; deoxynucleotide and nucleoside toxicity and metabolism; enzymes; purine and pyrimidine metabolism during lymphocyte differentiation; purine metabolism in skeletal muscle; purine nucleotide metabolism in the heart; purine and pyrimidine metabolism in primary cell cultures and in parasites; nucleoside kinases and drug activation; phosphoribosylpyrophosphate; S-adenosylmethionine metabolism; and the metabolic effects of interferon.

  9. Purine metabolism in Toxoplasma gondii

    SciTech Connect

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

    1989-06-25

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

  10. Was adenine the first purine?

    NASA Technical Reports Server (NTRS)

    Schwartz, Alan W.; Bakker, C. G.

    1989-01-01

    Oligomerization of HCN (1 molar) in the presence of added formaldehyde (0.5 molar) produced an order of magnitude more 8-hydroxymethyladenine than adenine or any other biologically significant purine. This result suggests that on the prebiotic earth, nucleoside analogs may have been synthesized directly in more complex mixtures of HCN with other aldehydes.

  11. Was adenine the first purine?

    NASA Technical Reports Server (NTRS)

    Schwartz, Alan W.; Bakker, C. G.

    1989-01-01

    Oligomerization of HCN (1 molar) in the presence of added formaldehyde (0.5 molar) produced an order of magnitude more 8-hydroxymethyladenine than adenine or any other biologically significant purine. This result suggests that on the prebiotic earth, nucleoside analogs may have been synthesized directly in more complex mixtures of HCN with other aldehydes.

  12. The interaction of aflatoxins with purines and purine nucleosides

    PubMed Central

    Clifford, Janet I.; Rees, K. R.

    1967-01-01

    From measurements of thermal hyperchromicity and the behaviour of an aflatoxin–DNA mixture on a Sephadex column it was concluded that aflatoxin B1 is capable of weak binding to single-stranded DNA. The interactions of the aflatoxins (B1, G1 and G2) with nucleosides result in difference spectra and suggest that the purine bases and the amino group play a role in the binding of all the aflatoxins to DNA. PMID:6032981

  13. Mechanism of purine antimetabolites and purine nucleodise imbalance

    SciTech Connect

    Duan, D.S.

    1989-01-01

    Purine starvation is responsible for the cytotoxic effects of many purine antimetabolites. Guanine nucleotide depletion leads to a drastic DNA synthesis inhibition while adenine nucleotide depletion interferes with other vital functions before inhibiting DNA synthesis. To investigate the mechanism of these distinct effects, kinetics studies of adenine and guanine tracer incorporation into nucleotide pools and DNA were performed in S-49 cells. To address the question whether the cellular dGTP pool is compartmentalized, ({sup 14}C)Gua and ({sup 3}H)Guo tracer experiments were performed in a double mutant S-49 cell line, dGuo-L, with purine nucleoside phosphorylase (PNP) deficiency and dGTP feedback resistant ribonucleotide reductase (RR). While RR inhibition by dGTP was proposed as the cytotoxic mechanism in PNP immunodeficiency, additional effects of dGuo were studied in S-49 cells and human peripheral blood T lymphocytes (PBTL). RNA synthesis but not DNA synthesis was among the earliest targets of dGuo toxicity, and dGuo exerted cytotoxicity in resting PBTL before DNA synthesis. Three transformed T cells lines, PEER, HPB-ALL and HPB-MLT, were selected and characterized for cell surface markers and their sensitivities to dAdo and deoxycoformycin, an ADA inhibitor.

  14. Case study: a case of debilitating gout in the 1st metatarsophalangeal joint.

    PubMed

    Tanner, Natalie; Diaper, Ross; King, Mathew; Metcalfe, Stuart A

    2015-03-01

    Gout is a painful arthritic condition that affects many people worldwide. The disease has been associated with hyperuricaemia and life style risk factors such as obesity, alcohol intake, meat and seafood consumption. We present a case of a 67-year-old male with a history of gout, who attended the clinic with a painful 1st metatarsophalangeal joint, which had progressively worsened in pain, mobility and deformity in the last 20 years. Although lifestyle changes had been advised by the GP some years earlier such as a low purine based diet, management had only consisted of NSAID's, which had not significantly improved symptoms. Surgical excision of chalky white material from around the 1st metatarsophalangeal joint rendered the patient symptom free with increased mobility after 6 weeks. Histopathology confirmed the excised tissue as gouty tophus. Following this, the patient was placed on allopurinol, a xanthine oxidase inhibitor to prevent recurrent attacks. This case study highlights the importance of early recognition and prophylactic management in gout sufferers. In joints where the disease process is well-established surgical excision of the gouty tophus may help mitigate further disease progression, and restore quality of life to individuals.

  15. [Total purine content in selected foods].

    PubMed

    Wolfram, G; Colling, M

    1987-12-01

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

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

    PubMed

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

    2012-01-01

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

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

    NASA Image and Video Library

    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...

  18. 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.

  19. 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.

  20. Electronic Health Records Place 1st at Indy 500

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues EHR Electronic Health Records Place 1st at Indy 500 Past ... last May's Indy 500 had thousands of personal Electronic Health Records on hand for those attending—and ...

  1. Avascular necrosis of the 1st metatarsal head.

    PubMed

    Gurevich, M; Bialik, V; Eidelman, M; Katzman, A

    2008-10-01

    Idiopathic avascular necrosis of first metatarsophalangeal head in child is unique condition not described in literature in past exlude one case. It seems to be part of avascular bone necrosis syndromes, like Freiberg disease, Sever disease etc. and the same principles of treatment are appropriate in AVN of 1st MTT head. We describe the case of bilateral AVN of 1st MTT head treated conservatively with complete cure.

  2. Kinetics of luminol sonochemiluminescence quenched by purines.

    PubMed

    Wang, Jian; Lai, Yongquan; Chen, Meili; Jiang, Zhou; Chen, Guonan

    2013-01-01

    A homogeneous chemiluminescence (CL) reaction was initiated by ultrasound irradiation. Luminol sonochemiluminescence (SCL) reaction kinetics were determined under pseudo-first-order conditions, and the reaction followed the model for simple rise-fall kinetics. In addition, SCL quenching reactions induced by purines were also investigated in which the interactions between luminol and purines were analysed using the Stern-Volmer (S-V) mechanism. The results implied that the high rate constant of luminol CL quenched by purines may be attributed to ground state interactions originating from hydrogen bonding. Copyright © 2012 John Wiley & Sons, Ltd.

  3. Genetics Home Reference: purine nucleoside phosphorylase deficiency

    MedlinePlus

    ... patients with purine nucleoside phosphorylase deficiency. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1411-5. Erratum in: Nucleosides Nucleotides Nucleic Acids. 2005;24(4):303. Citation on PubMed Nyhan ...

  4. Dietary purines in vegetarian meat analogues.

    PubMed

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

    2010-11-01

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

  5. Prebiotic syntheses of purines and pyrimidines.

    PubMed

    Basile, B; Lazcano, A; Oró, J

    1984-01-01

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

  6. 1st Major Astronomy Convention in the Philippines - A Success!

    NASA Astrophysics Data System (ADS)

    Ty, J. K.

    2009-03-01

    February 15, 2009. The 1st Philippine Astronomy Convention was held at the Plenary Hall of the Rizal Technological University (RTU) in Boni Avenue, Mandaluyong City, Philippines. The event was organized by the Astronomical League of the Philippines as part of the International Year of Astronomy 2009 celebrations.

  7. 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.

  8. 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.

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

    PubMed

    Colling, M; Wolfram, G

    1987-12-01

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

  10. A New HPLC Purine Assay for Quantifying Microbial Flow

    USDA-ARS?s Scientific Manuscript database

    A HPLC method was developed to quantify the purines adenine and guanine and their metabolites xanthine and hypoxanthine in hydrolysates of isolated bacteria and omasal digesta and to assess the effect of using either purines only, or purines plus metabolites, as microbial markers for estimating micr...

  11. Isolation of fast purine nucleotide synthase ribozymes.

    PubMed

    Lau, Matthew W L; Cadieux, Kelly E C; Unrau, Peter J

    2004-12-08

    Here we report the in vitro selection of fast ribozymes capable of promoting the synthesis of a purine nucleotide (6-thioguanosine monophosphate) from tethered 5-phosphoribosyl 1-pyrophosphate (PRPP) and 6-thioguanine ((6S)Gua). The two most proficient purine synthases have apparent efficiencies of 284 and 230 M(-1) min(-1) and are both significantly more efficient than pyrimidine nucleotide synthase ribozymes selected previously by a similar approach. Interestingly, while both ribozymes showed good substrate discrimination, one ribozyme had no detectable affinity for 6-thioguanine while the second had a K(m) of approximately 80 muM, indicating that these ribozymes use considerably different modes of substrate recognition. The purine synthases were isolated after 10 rounds of selection from two high-diversity RNA pools. The first pool contained a long random sequence region. The second pool contained random sequence elements interspersed with the mutagenized helical elements of a previously characterized 4-thiouridine synthase ribozyme. While nearly all of the ribozymes isolated from this biased pool population appeared to have benefited from utilizing one of the progenitor's helical elements, little evidence for more complicated secondary structure preservation was evident. The discovery of purine synthases, in addition to pyrimidine synthases, demonstrates the potential for nucleotide synthesis in an 'RNA World' and provides a context from which to study small molecule RNA catalysis.

  12. ["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.

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

    PubMed

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

    2014-01-01

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

  14. [Granuloma Gravidarum in a 37-year-old 1st Gravida, 1st Para--A Case Report].

    PubMed

    Findeklee, S

    2015-10-01

    The granuloma gravidarum is a rare benign tumour with gingival origin. It occurs in circa 0.2% of pregnancies. Mostly we see an asymptomatic course of disease terminated by hormonal changes after delivery. If the granuloma is associated with complaints of the pregnant woman, for example masticational pain or recurrent bleedings, therapeutic options are conservative therapy, surgery or delivery. We report the case of a 37-year-old 1st gravida, 1st para who had an induced delivery in the 39+2 gestational week because of a symptomatic granuloma gravidarum. We saw a spontaneous remission of the granuloma within 3 months post partum. The case report underlines the importance of suitable information for pregnant women about oral hygiene and the necessity of regular dental controls during pregnancy for prophylaxis of granuloma gravidarum.

  15. De novo purine nucleotide synthesis in the rat small and large intestine: effect of dietary protein and purines.

    PubMed

    LeLeiko, N S; Bronstein, A D; Baliga, B S; Munro, H N

    1983-05-01

    This study assessed the pathway for de novo purine nucleotide synthesis in rat small intestinal and colonic mucosal cells, and determined the effects of dietary purines and protein on de novo purine nucleotide synthetic activity in the small intestine in vitro. Incubation of small intestinal mucosal scrapings with [14C]glycine failed to show an active pathway of de novo synthesis; in contrast, the colon showed incorporation of [14C]glycine into RNA. Rats fed a diet deficient in purines demonstrated increased incorporation of [14C]glycine into RNA-adrenine in small intestinal mucosal cells. Measurement of glutamine-amidophosphoribosyltransferase demonstrated that, regardless of the purine content of the diet, enzyme activity in the small intestine is significantly lower than in the colon or liver. The results indicate that, in the small intestine of the rat, there is an inactive de novo pathway of purine nucleotide biosynthesis that can be stimulated when purines are omitted from the diet.

  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. Joint Force Quarterly. Issue 64, 1st Quarter 2012

    DTIC Science & Technology

    2012-01-01

    JF Q J O I N T F O R C E Q U A R T E R L Y ISSU E SIx T Y -F O U R , 1 ST Q U A R T E R 2012 NEW SECURITY CHALLENGESAre you a professional...will pass this test, and we will do it by focusing our efforts in four areas. I will soon publish a pamphlet on these key efforts and encourage you ...to read, discuss, and debate them. I need your support, and I challenge you to do what you can in your corner of our wonderful profession to

  18. Structural Biology of the Purine Biosynthetic Pathway

    PubMed Central

    Zhang, Yang; Morar, Mariya; Ealick, Steven E.

    2008-01-01

    Purine biosynthesis requires ten enzymatic transformations to generate inosine monophosphate. PurF, PurD, PurL, PurM, PurC, and PurB are common to all pathways, while PurN or PurT, PurK/PurE-I or PurE-II, PurH or PurP, and PurJ or PurO catalyze the same steps in different organisms. X-ray crystal structures are available for all 15 purine biosynthetic enzymes, including seven ATP-dependent enzymes, two amidotransferases and two tetrahydrofolate-dependent enzymes. Here we summarize the structures of the purine biosynthetic enzymes, discuss similarities and differences, and present arguments for pathway evolution. Four of the ATP-dependent enzymes belong to the ATP-grasp superfamily and two to the PurM superfamily. The amidotransferases are unrelated with one utilizing an NTN-glutaminase and the other utilizing a triad glutaminase. Likewise the tetrahydrofolate-dependent enzymes are unrelated. Ancestral proteins may have included a broad specificity enzyme instead of PurD, PurT, PurK, PurC, and PurP, and a separate enzyme instead of PurM and PurL. PMID:18712276

  19. Purines: forgotten mediators in traumatic brain injury.

    PubMed

    Jackson, Edwin K; Boison, Detlev; Schwarzschild, Michael A; Kochanek, Patrick M

    2016-04-01

    Recently, the topic of traumatic brain injury has gained attention in both the scientific community and lay press. Similarly, there have been exciting developments on multiple fronts in the area of neurochemistry specifically related to purine biology that are relevant to both neuroprotection and neurodegeneration. At the 2105 meeting of the National Neurotrauma Society, a session sponsored by the International Society for Neurochemistry featured three experts in the field of purine biology who discussed new developments that are germane to both the pathomechanisms of secondary injury and development of therapies for traumatic brain injury. This included presentations by Drs. Edwin Jackson on the novel 2',3'-cAMP pathway in neuroprotection, Detlev Boison on adenosine in post-traumatic seizures and epilepsy, and Michael Schwarzschild on the potential of urate to treat central nervous system injury. This mini review summarizes the important findings in these three areas and outlines future directions for the development of new purine-related therapies for traumatic brain injury and other forms of central nervous system injury. In this review, novel therapies based on three emerging areas of adenosine-related pathobiology in traumatic brain injury (TBI) were proposed, namely, therapies targeting 1) the 2',3'-cyclic adenosine monophosphate (cAMP) pathway, 2) adenosine deficiency after TBI, and 3) augmentation of urate after TBI. © 2016 International Society for Neurochemistry.

  20. AIDS. 1st annual George H. Gallup Memorial Survey.

    PubMed

    1988-06-01

    Acquired immunodeficiency syndrome (AIDS) was selected as the subject for the 1st annual George H Gallup Memorial Survey. This survey, conducted in August 1987-April 1988 in 35 countries, measured the level of awareness of AIDS, the extent of concern about AIDS, knowledge, changes in behavior resulting form the AIDS epidemic, and attitudes toward people with AIDS. Overall, the poll's findings attest to the effectiveness of the health education efforts of governmental and nongovernmental organizations. Awareness that AIDS poses an urgent international health problem was almost universal in the 35 samples. In about half of these countries, AIDS was identified as the most important national health problem; in the remaining countries, AIDS was ranked 2nd to cancer. The proportion of respondents expressing a fear of personally contracting the AIDS virus ranged from lows of under 10% in most of Europe to a high of 45% among South African blacks. A majority of respondents in the US, Colombia, the Philippines, Brazil, Nigeria, Ecuador, El Salvador, and Chile believed that AIDS will soon spread beyond current risk groups to the general population. Despite widespread awareness of the grave threat posed by AIDS, insufficient numbers of respondents reported that they had made specific behavioral changes intended to protect themselves form HIV infection. Overall, about half of those interviewed indicated they are now more cautious in their choice of sexual partners; similarly, about half are using condoms more or for the 1st time.

  1. The Effects of Azathioprine (Imuran) on Purine Synthesis in Clinical Disorders of Purine Metabolism*

    PubMed Central

    Kelley, William N.; Rosenbloom, Frederick M.; Seegmiller, J. Edwin

    1967-01-01

    Azathioprine, a purine analogue, significantly suppressed the purine synthesis de novo of two gouty patients manifesting overproduction of uric acid, as well as three of four gouty patients who showed normal uric acid production. This suppression is taken as evidence that phosphoribosyl-pyrophosphate amidotransferase, the rate-controlling step in purine synthesis de novo, has a normal sensitivity to feedback inhibitors in the patients who responded to the drug. Two children afflicted with the familial disorder of hyperuricemia, choreo-athetosis, and self-mutilation described by Lesch and Nyhan showed no reduction in the activity of the biosynthetic pathway in response to azathioprine. This inability to respond to azathioprine can be directly related to the absence in these patients of the enzyme hypoxanthine-guanine phosphoribosyltransferase which is required for conversion of the drug or its metabolites to the biochemically active ribonucleotide form. PMID:16695929

  2. Purines 2010: Adenine Nucleosides and Nucleotides in Biomedicine.

    PubMed

    Sereda, Michal J

    2010-08-01

    The Purines 2010: Adenine Nucleosides and Nucleotides in Biomedicine meeting, held in Tarragona, Spain, included topics covering new findings in the field of purinergic signaling and the development of purine-based drugs. This conference report highlights selected presentations on developments in purinerigic signaling, medicinal chemistry, the therapeutic potential of purine-based drugs, and the role of purines and adenosine receptors in neurodegenerative disorders, sickle cell disease, bone homeostasis, pulmonary fibrosis and pain. Investigational drugs discussed include CF-101 (Can-Fite BioPharma Ltd/NIH/Kwang Dong Pharmaceutical Co Ltd/Seikagaku Corp) and denufosol tetrasodium (Cystic Fibrosis Foundation Therapeutics Inc/Inspire Pharmaceuticals Inc).

  3. Exclusion of RNA strands from a purine motif triple helix.

    PubMed Central

    Semerad, C L; Maher, L J

    1994-01-01

    Research concerning oligonucleotide-directed triple helix formation has mainly focused on the binding of DNA oligonucleotides to duplex DNA. The participation of RNA strands in triple helices is also of interest. For the pyrimidine motif (pyrimidine.purine.pyrimidine triplets), systematic substitution of RNA for DNA in one, two, or all three triplex strands has previously been reported. For the purine motif (purine.purine.pyrimidine triplets), studies have shown only that RNA cannot bind to duplex DNA. To extend this result, we created a DNA triple helix in the purine motif and systematically replaced one, two, or all three strands with RNA. In dramatic contrast to the general accommodation of RNA strands in the pyrimidine triple helix motif, a stable triplex forms in the purine motif only when all three of the substituent strands are DNA. The lack of triplex formation among any of the other seven possible strand combinations involving RNA suggests that: (i) duplex structures containing RNA cannot be targeted by DNA oligonucleotides in the purine motif; (ii) RNA strands cannot be employed to recognize duplex DNA in the purine motif; and (iii) RNA tertiary structures are likely to contain only isolated base triplets in the purine motif. Images PMID:7529405

  4. 1st Workshop of the Canadian Society for Virology

    PubMed Central

    McCormick, Craig; Grandvaux, Nathalie

    2017-01-01

    The 1st Workshop of the Canadian Society for Virology (CSV2016) was a Special Workshop of the 35th Annual Meeting for the American Society for Virology, held on 18 June 2016 on the beautiful Virginia Tech campus in Blacksburg, Virginia. The workshop provided a forum for discussion of recent advances in the field, in an informal setting conducive to interaction with colleagues. CSV2016 featured two internationally-renowned Canadian keynote speakers who discussed translational virology research; American Society for Virology President Grant McFadden (then from University of Florida, now relocated to Arizona State University) who presented his studies of oncolytic poxviruses, while Matthew Miller (McMaster University) reviewed the prospects for a universal influenza vaccine. The workshop also featured a variety of trainee oral and poster presentations, and a panel discussion on the topic of the future of the CSV and virus research in Canada. PMID:28335511

  5. 1st Workshop of the Canadian Society for Virology.

    PubMed

    McCormick, Craig; Grandvaux, Nathalie

    2017-03-20

    The 1st Workshop of the Canadian Society for Virology (CSV2016) was a Special Workshop of the 35th Annual Meeting for the American Society for Virology, held on 18 June 2016 on the beautiful Virginia Tech campus in Blacksburg, Virginia. The workshop provided a forum for discussion of recent advances in the field, in an informal setting conducive to interaction with colleagues. CSV2016 featured two internationally-renowned Canadian keynote speakers who discussed translational virology research; American Society for Virology President Grant McFadden (then from University of Florida, now relocated to Arizona State University) who presented his studies of oncolytic poxviruses, while Matthew Miller (McMaster University) reviewed the prospects for a universal influenza vaccine. The workshop also featured a variety of trainee oral and poster presentations, and a panel discussion on the topic of the future of the CSV and virus research in Canada.

  6. Structure of grouper iridovirus purine nucleoside phosphorylase

    SciTech Connect

    Kang, You-Na; Zhang, Yang; Allan, Paula W.; Parker, William B.; Ting, Jing-Wen; Chang, Chi-Yao; Ealick, Steven E.

    2010-02-01

    The crystal structure of purine nucleoside phosphorylase from grouper iridovirus was solved at 2.38 Å resolution. Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of purine ribonucleosides to the corresponding free bases and ribose 1-phosphate. The crystal structure of grouper iridovirus PNP (givPNP), corresponding to the first PNP gene to be found in a virus, was determined at 2.4 Å resolution. The crystals belonged to space group R3, with unit-cell parameters a = 193.0, c = 105.6 Å, and contained four protomers per asymmetric unit. The overall structure of givPNP shows high similarity to mammalian PNPs, having an α/β structure with a nine-stranded mixed β-barrel flanked by a total of nine α-helices. The predicted phosphate-binding and ribose-binding sites are occupied by a phosphate ion and a Tris molecule, respectively. The geometrical arrangement and hydrogen-bonding patterns of the phosphate-binding site are similar to those found in the human and bovine PNP structures. The enzymatic activity assay of givPNP on various substrates revealed that givPNP can only accept 6-oxopurine nucleosides as substrates, which is also suggested by its amino-acid composition and active-site architecture. All these results suggest that givPNP is a homologue of mammalian PNPs in terms of amino-acid sequence, molecular mass, substrate specificity and overall structure, as well as in the composition of the active site.

  7. 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

  8. Structure, stability, and thermodynamics of a short intermolecular purine-purine-pyrimidine triple helix

    SciTech Connect

    Pilch, D.S.; Shafer, R.H. ); Levenson, C. )

    1991-06-25

    The authors have investigated the structure and physical chemistry of the d(C{sub 3}T{sub 4}C{sub 3}){center dot}2(d(G{sub 3}A{sub 4}G{sub 3})) triple helix by polyacrylamide gel electrophoresis (PAGE), {sup 1}H NMR, and ultraviolet (UV) absorption spectroscopy. The triplex was stabilized with MgCl{sub 2} at neutral pH. PAGE studies verify the stoichiometry of the strands comprising the triplex and indicate that the orientation of the third strand in purine-purine-pyrimidine (pur-pur-pyr) triplexes is antiparallel with respect to the purine strand of the underlying duplex. Imino proton NMR spectra provide evidence for the existence of new purine-purine (pur{center dot}pur) hydrogen bonds, in addition to those of the Watson-Crick (W-C) base pairs, in the triplex structure. These new hydrogen bonds are likely to correspond to the interaction between third-strand guanine NH1 imino protons and the N7 atoms of guanine residues on the puring strand of the underlying duplex. Thermal denaturation of the triplex proceeds to single strands in one step, under the conditions used in this study. Binding of the third strand appears to enhance the thermal stability of the duplex by 1-3 C, depending on the DNA concentration. This marked enhancement in stability, coupled with the lack of an acidic pH requirement, suggests that pur-pur-pyr triplexes are appealing choices for use in applications involving oligonucleotide targeting of duplex DNA in vitro and in vivo.

  9. Chance UK

    ERIC Educational Resources Information Center

    McGrath, Gracia

    2003-01-01

    Chance UK is a unique charity in the UK that specialises in mentoring programmes for primary schoolchildren with behavioural problems. It was founded in 1995 by a policeman, Chief Superintendent Paul Mathias, who believed that by stepping in early, young children with behavioural difficulties could be given the chance to develop the necessary…

  10. 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.

  11. Extracellular purines, purinergic receptors and tumor growth

    PubMed Central

    Di Virgilio, F; Adinolfi, E

    2017-01-01

    Virtually, all tumor cells as well as all immune cells express plasma membrane receptors for extracellular nucleosides (adenosine) and nucleotides (ATP, ADP, UTP, UDP and sugar UDP). The tumor microenvironment is characterized by an unusually high concentration of ATP and adenosine. Adenosine is a major determinant of the immunosuppressive tumor milieu. Sequential hydrolysis of extracellular ATP catalyzed by CD39 and CD73 is the main pathway for the generation of adenosine in the tumor interstitium. Extracellular ATP and adenosine mold both host and tumor responses. Depending on the specific receptor activated, extracellular purines mediate immunosuppression or immunostimulation on the host side, and growth stimulation or cytotoxicity on the tumor side. Recent progress in this field is providing the key to decode this complex scenario and to lay the basis to harness the potential benefits for therapy. Preclinical data show that targeting the adenosine-generating pathway (that is, CD73) or adenosinergic receptors (that is, A2A) relieves immunosuppresion and potently inhibits tumor growth. On the other hand, growth of experimental tumors is strongly inhibited by targeting the P2X7 ATP-selective receptor of cancer and immune cells. This review summarizes the recent data on the role played by extracellular purines (purinergic signaling) in host–tumor interaction and highlights novel therapeutic options stemming from recent advances in this field. PMID:27321181

  12. 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

  13. Structure and mechanism of purine binding riboswitches

    PubMed Central

    Batey, Robert T.

    2013-01-01

    A riboswitch is a non-protein coding sequence capable of directly binding a small molecule effector without the assistance of accessory proteins to regulate expression of the mRNA in which it is embedded. Currently, over 20 different classes of riboswitches have been validated in bacteria with the promise of many more to come, making them an important means of regulation of the genome in the bacterial kingdom. Strikingly, half of the known riboswitches recognize effector compounds that contain a purine or related moiety. In the last decade significant progress has been made to determine how riboswitches specifically recognize these compounds against the background of many other similar cellular metabolites and transduce this signal into a regulatory response. Of the known riboswitches, the purine family containing guanine, adenine, and 2’-deoxyguanosine binding classes are the most extensively studied, serving as a simple and useful paradigm for understanding how these regulatory RNAs function. This review provides a comprehensive summary of the current state of knowledge regarding the structure and mechanism of these riboswitches, as well as insights into how they might be exploited as therapeutic targets and novel biosensors. PMID:22850604

  14. T1/ST2 promotes T helper 2 cell activation and polyfunctionality in bronchopulmonary mycosis.

    PubMed

    Piehler, D; Grahnert, A; Eschke, M; Richter, T; Köhler, G; Stenzel, W; Alber, G

    2013-03-01

    Interleukin (IL)-33 enhances T helper (Th)2 immunity via its receptor T1/ST2. Infection with the yeast-like pathogen Cryptococcus neoformans is usually controlled by a Th1-mediated immune response. The mechanisms responsible for nonprotective Th2 immunity leading to allergic inflammation in pulmonary cryptococcosis are still not fully understood. Using a murine pulmonary model of C. neoformans infection, we report that T1/ST2 expression correlates with the intensity of Th2 activation, as demonstrated by the expression of CD25 and CD44 and downregulation of CD62L. Antigen-specific T1/ST2(+) Th cells are the primary source of the Th2 cytokines IL-5 and IL-13 as compared with wild-type T1/ST2(-) Th cells or Th cells from T1/ST2(-/-) mice. In addition, T1/ST2(+) Th cells almost exclusively contain bi- and trifunctional Th2 cytokine-producing Th cells compared with T1/ST2(-) Th cells or Th cells from T1/ST2(-/-) mice. Finally, T1/ST2-driven Th2 development resulted in defective pulmonary fungal control. These data demonstrate that T1/ST2 directs Th2 cell activation and polyfunctionality in allergic bronchopulmonary mycosis.

  15. 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.

  16. Conference report: 1st Medicon Valley Inhalation Symposium.

    PubMed

    Lastow, Orest

    2013-02-01

    The 1st Medicon Valley Inhalation Symposium was arranged by the Medicon Valley Inhalation Consortium. It was held at the Medicon Village site, which is the former AstraZeneca site in Lund, Sweden. It was a 1-day symposium focused on inhaled drug delivery and inhalation product development. A total of 90 delegates listened to 15 speakers. The program was organized to follow the value chain of an inhalation product development. The benefits and future opportunities of inhaled drug delivery were discussed together with some new disease areas that can be targeted with inhalation. The pros and cons of the two main formulation types; dry powder and liquid formulations, were discussed by a panel. The different requirements of the drug molecules from a pharmacology, chemical and physical perspective were explained. The modeling of the physics inside an inhaler was demonstrated and the potential strategic benefits of device design were highlighted together with the many challenges of formulation manufacturing. Lung deposition mechanisms and the difficulties of the generic bioequivalence concept were discussed. Using an anatomically correct impactor inlet is a valuable tool in lung deposition predictions and the planning of clinical trials. The management of the biological material generated in clinical studies is key to successful studies.

  17. 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

  18. Purine Salvage in Two Halophilic Archaea: Characterization of Salvage Pathways and Isolation of Mutants Resistant to Purine Analogs

    PubMed Central

    Stuer-Lauridsen, Birgitte; Nygaard, Per

    1998-01-01

    In exponentially growing cultures of the extreme halophile Halobacterium halobium and the moderate halophile Haloferax volcanii, growth characteristics including intracellular protein levels, RNA content, and nucleotide pool sizes were analyzed. This is the first report on pool sizes of nucleoside triphosphates, NAD, and PRPP (5-phosphoribosyl-α-1-pyrophosphate) in archaea. The presence of a number of salvage and interconversion enzymes was determined by enzymatic assays. The levels varied significantly between the two organisms. The most significant difference was the absence of GMP reductase activity in H. halobium. The metabolism of exogenous purines was investigated in growing cultures. Both purine bases and nucleosides were readily taken up and were incorporated into nucleic acids. Growth of both organisms was affected by a number of inhibitors of nucleotide synthesis. H. volcanii was more sensitive than H. halobium, and purine base analogs were more toxic than nucleoside analogs. Growth of H. volcanii was inhibited by trimethoprim and sulfathiazole, while these compounds had no effect on the growth of H. halobium. Spontaneous mutants resistant to purine analogs were isolated. The most frequent cause of resistance was a defect in purine phosphoribosyltransferase activity coupled with reduced purine uptake. A single phosphoribosyltransferase seemed to convert guanine as well as hypoxanthine to nucleoside monophosphates, and another phosphoribosyltransferase had specificity towards adenine. The differences in the metabolism of purine bases and nucleosides and the sensitivity to purine analogs between the two halobacteria were reflected in differences in purine enzyme levels. Based on our results, we conclude that purine salvage and interconversion pathways differ just as much between the two archaeal species as among archaea, bacteria, and eukarya. PMID:9457844

  19. 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.

  20. 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

  1. VIEW WEST, 1ST FLOOR, EAST ROOM, HYDRAULIC COTTON PRESS, DETAIL, ...

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

    VIEW WEST, 1ST FLOOR, EAST ROOM, HYDRAULIC COTTON PRESS, DETAIL, CONTINENTAL GIN COMPANY HYDRAULIC TANK - Magnolia Plantation, Cotton Gins & Presses, LA Route 119, Natchitoches, Natchitoches Parish, LA

  2. 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

  3. 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.

  4. 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.

  5. Proceedings of the 1st Puerto Rico Biobanking Workshop.

    PubMed

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

    2014-01-01

    The 1st Puerto Rico Biobanking Workshop took place on August 20st, 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

  6. 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

  7. 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

  8. 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…

  9. Trophic effects of purines in neurons and glial cells.

    PubMed

    Rathbone, M P; Middlemiss, P J; Gysbers, J W; Andrew, C; Herman, M A; Reed, J K; Ciccarelli, R; Di Iorio, P; Caciagli, F

    1999-12-01

    In addition to their well known roles within cells, purine nucleotides such as adenosine 5' triphosphate (ATP) and guanosine 5' triphosphate (GTP), nucleosides such as adenosine and guanosine and bases, such as adenine and guanine and their metabolic products xanthine and hypoxanthine are released into the extracellular space where they act as intercellular signaling molecules. In the nervous system they mediate both immediate effects, such as neurotransmission, and trophic effects which induce changes in cell metabolism, structure and function and therefore have a longer time course. Some trophic effects of purines are mediated via purinergic cell surface receptors, whereas others require uptake of purines by the target cells. Purine nucleosides and nucleotides, especially guanosine, ATP and GTP stimulate incorporation of [3H]thymidine into DNA of astrocytes and microglia and concomitant mitosis in vitro. High concentrations of adenosine also induce apoptosis, through both activation of cell-surface A3 receptors and through a mechanism requiring uptake into the cells. Extracellular purines also stimulate the synthesis and release of protein trophic factors by astrocytes, including bFGF (basic fibroblast growth factor), nerve growth factor (NGF), neurotrophin-3, ciliary neurotrophic factor and S-100beta protein. In vivo infusion into brain of adenosine analogs stimulates reactive gliosis. Purine nucleosides and nucleotides also stimulate the differentiation and process outgrowth from various neurons including primary cultures of hippocampal neurons and pheochromocytoma cells. A tonic release of ATP from neurons, its hydrolysis by ecto-nucleotidases and subsequent re-uptake by axons appears crucial for normal axonal growth. Guanosine and GTP, through apparently different mechanisms, are also potent stimulators of axonal growth in vitro. In vivo the extracellular concentration of purines depends on a balance between the release of purines from cells and their re

  10. Potential chemotherapeutic targets in the purine metabolism of parasites.

    PubMed

    el Kouni, Mahmoud H

    2003-09-01

    Parasites are responsible for a wide variety of infectious diseases in human as well as in domestic and wild animals, causing an enormous health and economical blight. Current containment strategies are not entirely successful and parasitic infections are on the rise. In the absence of availability of antiparasitic vaccines, chemotherapy remains the mainstay for the treatment of most parasitic diseases. However, there is an urgent need for new drugs to prevent or combat some major parasitic infections because of lack of a single effective approach for controlling the parasites (e.g., trypanosomiasis) or because some serious parasitic infections developed resistance to presently available drugs (e.g., malaria). The rational design of a drug is usually based on biochemical and physiological differences between pathogens and host. Some of the most striking differences between parasites and their mammalian host are found in purine metabolism. Purine nucleotides can be synthesized by the de novo and/or the so-called "salvage" pathways. Unlike their mammalian host, most parasites studied lack the pathways for de novo purine biosynthesis and rely on the salvage pathways to meet their purine demands. Moreover, because of the great phylogenic separation between the host and the parasite, there are in some cases sufficient distinctions between corresponding enzymes of the purine salvage from the host and the parasite that can be exploited to design specific inhibitors or "subversive substrates" for the parasitic enzymes. Furthermore, the specificities of purine transport, the first step in purine salvage, diverge significantly between parasites and their mammalian host. This review highlights the unique transporters and enzymes responsible for the salvage of purines in parasites that could constitute excellent potential targets for the design of safe and effective antiparasitic drugs.

  11. Biosensor measurement of purine release from cerebellar cultures and slices.

    PubMed

    Wall, Mark; Eason, Robert; Dale, Nicholas

    2010-09-01

    We have previously described an action-potential and Ca(2+)-dependent form of adenosine release in the molecular layer of cerebellar slices. The most likely source of the adenosine is the parallel fibres, the axons of granule cells. Using microelectrode biosensors, we have therefore investigated whether cultured granule cells (from postnatal day 7-8 rats) can release adenosine. Although no purine release could be detected in response to focal electrical stimulation, purine (adenosine, inosine or hypoxanthine) release occurred in response to an increase in extracellular K(+) concentration from 3 to 25 mM coupled with addition of 1 mM glutamate. The mechanism of purine release was transport from the cytoplasm via an ENT transporter. This process did not require action-potential firing but was Ca(2+)dependent. The major purine released was not adenosine, but was either inosine or hypoxanthine. In order for inosine/hypoxanthine release to occur, cultures had to contain both granule cells and glial cells; neither cellular component was sufficient alone. Using the same stimulus in cerebellar slices (postnatal day 7-25), it was possible to release purines. The release however was not blocked by ENT blockers and there was a shift in the Ca(2+) dependence during development. This data from cultures and slices further illustrates the complexities of purine release, which is dependent on cellular composition and developmental stage.

  12. 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.

  13. Metabolic Reprogramming during Purine Stress in the Protozoan Pathogen Leishmania donovani

    PubMed Central

    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.

    2014-01-01

    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. PMID:24586154

  14. Characterizing substrate properties of purine-related compounds with purine metabolism enzymes for enzymatic peak-shift HPLC method.

    PubMed

    Fukuuchi, T; Morimura, A; Kawatani, M; Yamamoto, K; Yamaoka, N; Kaneko, K

    2014-01-01

    We have extended peak-shift method for measuring purine bases to make it suitable for other purine-related compounds. We optimized the reactions of the purine metabolism enzymes 5'-nucleotidase (EC 3.1.3.5), purine nucleoside phosphorylase (PNP) (EC 2.4.2.1), xanthine oxidase (XO) (EC 1.17.3.2), urate hydroxylase (EC 1.7.3.3), adenosine deaminase (ADA) (EC 3.5.4.4), and guanine deaminase (EC 3.5.4.3) by determining their substrate specificity and reaction kinetics. These enzymes eliminate the five purine base peaks (adenine, guanine, hypoxanthine, xanthine, and uric acid) and four nucleosides (adenosine, guanosine, inosine, and xanthosine). The bases and nucleosides can be identified and accurately quantified by comparing the chromatograms before and after treatment with the enzymes. Elimination of the individual purine compound peaks was complete in a few minutes. However, when there were multiple substrates, such as for XO, and when the metabolites were purine compounds, such as for PNP and ADA, it took longer to eliminate the peaks. The optimum reaction conditions for the peak-shift assay methods were an assay mixture containing the substrate (10 μL, 0.1 mg/mL), the combined enzyme solution (10 μL each, optimum concentration), and 50 mM sodium phosphate (up to 120 μL, pH 7.4). The mixture was incubated for 60 minutes at 37°C. This method should be suitable for determining the purine content of a variety of samples, without interference from impurities.

  15. Indirect Readout of DNA Sequence at the Primary-kink Site in the CAP-DNA Complex: Recognition of Pyrimidine-Purine and Purine-Purine Steps

    SciTech Connect

    Napoli,A.; Lawson, C.; Ebright, R.; Berman, H.

    2006-01-01

    The catabolite activator protein (CAP) bends DNA in the CAP-DNA complex, typically introducing a sharp DNA kink, with a roll angle of {approx}40 deg and a twist angle of {approx}20 deg, between positions 6 and 7 of the DNA half-site, 5'-A1A2A3T4G5T6G7A8T9C10T11-3' ('primary kink'). In previous work, we showed that CAP recognizes the nucleotide immediately 5' to the primary-kink site, T6, through an 'indirect-readout' mechanism involving sequence effects on energetics of primary-kink formation. Here, to understand further this example of indirect readout, we have determined crystal structures of CAP-DNA complexes containing each possible nucleotide at position 6. The structures show that CAP can introduce a DNA kink at the primary-kink site with any nucleotide at position 6. The DNA kink is sharp with the consensus pyrimidine-purine step T{sub 6}G{sub 7}, and the non-consensus pyrimidine-purine step C{sub 6}G{sub 7} (roll angles of {approx}42 deg, twist angles of {approx}16 deg), but is much less sharp with the non-consensus purine-purine steps A{sub 6}G{sub 7} and G{sub 6}G{sub 7} (roll angles of {approx}20 deg, twist angles of {approx}17 deg). We infer that CAP discriminates between consensus and non-consensus pyrimidine-purine steps at positions 6-7 solely based on differences in the energetics of DNA deformation, but that CAP discriminates between the consensus pyrimidine-purine step and non-consensus purine-purine steps at positions 6-7 both based on differences in the energetics of DNA deformation and based on qualitative differences in DNA deformation. The structures further show that CAP can achieve a similar, {approx}46 deg per DNA half-site, overall DNA bend through a sharp DNA kink, a less sharp DNA kink, or a smooth DNA bend. Analysis of these and other crystal structures of CAP-DNA complexes indicates that there is a large, {approx}28 deg per DNA half-site, out-of-plane component of CAP-induced DNA bending in structures not constrained by end-to-end DNA

  16. 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.

  17. A role for adenine nucleotides in the sensing mechanism to purine starvation in Leishmania donovani.

    PubMed

    Martin, Jessica L; Yates, Phillip A; Boitz, Jan M; Koop, Dennis R; Fulwiler, Audrey L; Cassera, Maria Belen; Ullman, Buddy; Carter, Nicola S

    2016-07-01

    Purine salvage by Leishmania is an obligatory nutritional process that impacts both cell viability and growth. Previously, we have demonstrated that the removal of purines in culture provokes significant metabolic changes that enable Leishmania to survive prolonged periods of purine starvation. In order to understand how Leishmania sense and respond to changes in their purine environment, we have exploited several purine pathway mutants, some in which adenine and guanine nucleotide metabolism is uncoupled. While wild type parasites grow in any one of a variety of naturally occurring purines, the proliferation of these purine pathway mutants requires specific types or combinations of exogenous purines. By culturing purine pathway mutants in high levels of extracellular purines that are either permissive or non-permissive for growth and monitoring for previously defined markers of the adaptive response to purine starvation, we determined that adaptation arises from a surveillance of intracellular purine nucleotide pools rather than from a direct sensing of the extracellular purine content of the environment. Specifically, our data suggest that perturbation of intracellular adenine-containing nucleotide pools provides a crucial signal for inducing the metabolic changes necessary for the long-term survival of Leishmania in a purine-scarce environment. © 2016 John Wiley & Sons Ltd.

  18. Purine-rich foods intake and recurrent gout attacks

    PubMed Central

    Zhang, Yuqing; Chen, Clara; Choi, Hyon; Chaisson, Christine; Hunter, David; Niu, Jingbo; Neogi, Tuhina

    2014-01-01

    Objective To examine and quantify the relation between purine intake and the risk of recurrent gout attacks among gout patients. Methods The authors conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for 1 year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, clinical symptoms and signs, medications (including antigout medications), and presence of potential risk factors (including daily intake of various purine-containing food items) during the 2-day period prior to the gout attack. The same exposure information was also assessed over 2-day control periods. Results This study included 633 participants with gout. Compared with the lowest quintile of total purine intake over a 2-day period, OR of recurrent gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and 2.41 for increasing quintiles of purine intake from animal sources (p for trend <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively. The effect of purine intake persisted across subgroups by sex, use of alcohol, diuretics, allopurinol, NSAIDs and colchicine. Conclusions The study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost fivefold among gout patients. Avoiding or reducing amount of purine-rich foods intake, especially of animal origin, may help reduce the risk of gout attacks. PMID:22648933

  19. Ophidian envenomation strategies and the role of purines.

    PubMed

    Aird, Steven D

    2002-04-01

    Snake envenomation employs three well integrated strategies: prey immobilization via hypotension, prey immobilization via paralysis, and prey digestion. Purines (adenosine, guanosine and inosine) evidently play a central role in the envenomation strategies of most advanced snakes. Purines constitute the perfect multifunctional toxins, participating simultaneously in all three envenomation strategies. Because they are endogenous regulatory compounds in all vertebrates, it is impossible for any prey organism to develop resistance to them. Purine generation from endogenous precursors in the prey explains the presence of many hitherto unexplained enzyme activities in snake venoms: 5'-nucleotidase, endonucleases (including ribonuclease), phosphodiesterase, ATPase, ADPase, phosphomonoesterase, and NADase. Phospholipases A(2), cytotoxins, myotoxins, and heparinase also participate in purine liberation, in addition to their better known functions. Adenosine contributes to prey immobilization by activation of neuronal adenosine A(1) receptors, suppressing acetylcholine release from motor neurons and excitatory neurotransmitters from central sites. It also exacerbates venom-induced hypotension by activating A(2) receptors in the vasculature. Adenosine and inosine both activate mast cell A(3) receptors, liberating vasoactive substances and increasing vascular permeability. Guanosine probably contributes to hypotension, by augmenting vascular endothelial cGMP levels via an unknown mechanism. Novel functions are suggested for toxins that act upon blood coagulation factors, including nitric oxide production, using the prey's carboxypeptidases. Leucine aminopeptidase may link venom hemorrhagic metalloproteases and endogenous chymotrypsin-like proteases with venom L-amino acid oxidase (LAO), accelerating the latter. The primary function of LAO is probably to promote prey hypotension by activating soluble guanylate cyclase in the presence of superoxide dismutase. LAO's apoptotic

  20. 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

  1. Introduction to the 1st International Symposium on Phytochemicals in Medicine and Food (ISPMF 2015).

    PubMed

    Zheng, Yafeng; Jassbi, Amir Reza; Xiao, Jianbo

    2016-03-30

    The 1st International Symposium on Phytochemicals in Medicine and Food (ISPMF 2015) was held in Shanghai, China, from June 26th to 29th, 2015. The 1st ISPMF was organized by the Phytochemical Society of Europe (PSE) and the Phytochemical Society of Asia (PSA). More than 270 scientists from 48 countries attended this meeting. The program of ISPMF 2015 consisted of 12 plenary lectures, 20 invited talks, and 55 short oral presentations in 16 sessions, including phytochemistry, phytomedicine, pharmacology, and application of phytochemicals in medicine and food. The 1st ISPMF has obtained support from Critical Reviews in Food Science and Nutrition, Food Chemistry, Phytochemistry Reviews, and Nutrients. As supported by Prof. Thomas F. Hofmann, a special issue on Journal of Agricultural and Food Chemistry (ACS) for the 1st ISPMF was initiated in January 2015.

  2. 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

  3. FDA Approves 1st Direct-to-Consumer Genetic Risk Tests

    MedlinePlus

    ... 164507.html FDA Approves 1st Direct-to-Consumer Genetic Risk Tests They screen for gene variants linked ... on Thursday approved the first direct-to-consumer genetic health risk tests. Known as the 23andMe Personal ...

  4. 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

  5. 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

  6. 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

  7. 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

  8. 15. Building 105, Facilities Engineering Building, 1830, interior, 1st floor, ...

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

    15. Building 105, Facilities Engineering Building, 1830, interior, 1st floor, piping for sprinkler system, S end of building, E wall. - Watervliet Arsenal, Building 105, South Broadway, on Hudson River, Watervliet, Albany County, NY

  9. 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

  10. 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

  11. 24. Interior, 1st floor, hewn timber braced framing for interior ...

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

    24. Interior, 1st floor, hewn timber braced framing for interior wall between northeast and northwest "kitchen" rooms in older section, looking west - Brawner Farmhouse, Lee Highway/Route 29, Manassas, Manassas, VA

  12. 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

  13. Purine receptor mediated actin cytoskeleton remodeling of human fibroblasts

    PubMed Central

    Goldman, Nanna; Chandler-Militello, Devin; Langevin, Helene; Nedergaard, Maiken; Takano, Takahiro

    2013-01-01

    Earlier studies have shown that activation of adenosine A1 receptors on peripheral pain fibers contributes to acupuncture-induced suppression of painful input. In addition to adenosine, acupuncture triggers the release of other purines, including ATP and ADP that may bind to purine receptors on nearby fibroblasts. We here show that purine agonists trigger increase in cytosolic Ca 2+ signaling in a cultured human fibroblasts cell line. The profile of agonist-induced Ca2+ increases indicates that the cells express functional P2yR2 and P2yR4 receptors, as well as P2yR1 and P2xR7 receptors. Unexpectedly, purine-induced Ca2+ signaling was associated with a remodeling of the actin cytoskeleton. ATP induced a transient loss in F-actin stress fiber. The changes of actin cytoskeleton occurred slowly and peaked at 10 min after agonist exposure. Inhibition of ATP-induced increases in Ca2+ by cyclopiazonic acid blocked receptor-mediated cytoskeleton remodeling. The Ca2+ ionophore failed to induce cytoskeletal remodeling despite triggering robust increases in cytosolic Ca2+. These observations indicate that purine signaling induces transient changes in fibroblast cytoarchitecture that could be related to the beneficial effects of acupuncture. PMID:23462235

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 8-Phosphorus substituted isosteres of purine and deazapurines.

    PubMed Central

    Khwaja, T A; Pande, H

    1979-01-01

    Synthesis of 8-phosphorus substituted isosteres of purine [pyrimidino (4,5-d)-1,3,2-diazaphosphole], 1-deazapurine [pyridino (2,3-d)-1,3,2-diazaphosphole] and 3-deazapurine [pyridino (4,5-d)-1,3,2-diazaphosphole] has been achieved by the reaction of equimolar amounts of triphenylphosphite and 4,5-diaminopyrimidine, 2,3-diaminopyridine and 3,4-diaminopyridine, respectively. These compounds hydrolyzed (cleavage of the phosphorus-nitrogen bounds) in aqueous solutions to provide the corresponding diaminopyrimidine or diaminopyridines. These three new basic ring systems constitute the first reported synthesis of purines in which ring carbon atom is substituted with a phosphorus atom. 8-Phosphorus substituted purine at a concentration of 4 X 10(-4)M caused a 50% inhibition in the growth of leukemia L1210 cells in culture. The biochemical rationale for the synthesis of these compounds is discussed. PMID:493140

  19. 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.

  20. Arthrobacter oxydans as a biocatalyst for purine deamination.

    PubMed

    Médici, Rosario; Lewkowicz, Elizabeth S; Iribarren, Adolfo M

    2008-12-01

    Deaminases are enzymes that catalyze the hydrolysis of amino groups of nucleosides or their bases. Because these enzymes play important roles in nucleotide metabolism, they are relevant targets in anticancer and antibacterial therapies. Mammalian deaminases are commercially available but the use of bacterial whole cells, especially as biocatalysts, is continuously growing because of their economical benefits. Moreover, deaminases are useful for the preparative chemoenzymatic transformation of nucleoside and base analogues into a variety of derivatives. The purine deaminase activities of Arthrobacter oxydans, a gram-positive bacterium utilized widely in bioremediation, were studied. The presence of adenosine, adenine and guanine deaminases was demonstrated and some purine bases and nucleosides were analyzed as substrates. Using A. oxydans whole cells as the biocatalyst, different purine compounds such as the anti-HIV, 2',3'-dideoxyinosine (73%, 2 h) were obtained.

  1. Gene expression control by Bacillus anthracis purine riboswitches.

    PubMed

    Kirchner, Marion; Schneider, Sabine

    2017-02-16

    In all kingdoms of life, cellular replication relies on the presence of nucleosides and nucleotides, the building blocks of nucleic acids and the main source of energy. In bacteria, the availability of metabolites sometimes directly regulates the expression of enzymes and proteins involved in purine salvage, biosynthesis and uptake through riboswitches. Riboswitches are located in bacterial mRNAs and can control gene expression by conformational changes in response to ligand binding. We have established an inverse reporter gene system in Bacillus subtilis that allows us to monitor riboswitch-controlled gene expression. We used it to investigate the activity of five potential purine riboswitches from B. anthracis in response to different purines and pyrimidines. Furthermore, in vitro studies on the aptamer domains of the riboswitches reveal their variation in guanine binding affinity ranging from nM to µM. These data do not only provide insight into metabolite sensing but can also aid to engineer artificial cell regulatory systems.

  2. Recombinant purine nucleoside phosphorylases from thermophiles: preparation, properties and activity towards purine and pyrimidine nucleosides.

    PubMed

    Zhou, Xinrui; Szeker, Kathleen; Janocha, Bernd; Böhme, Thomas; Albrecht, Dirk; Mikhailopulo, Igor A; Neubauer, Peter

    2013-03-01

    Thermostable nucleoside phosphorylases are attractive biocatalysts for the synthesis of modified nucleosides. Hence we report on the recombinant expression of three 'high molecular mass' purine nucleoside phosphorylases (PNPs) derived from the thermophilic bacteria Deinococcus geothermalis, Geobacillus thermoglucosidasius and from the hyperthermophilic archaeon Aeropyrum pernix (5'-methythioadenosine phosphorylase; ApMTAP). Thermostability studies, kinetic analysis and substrate specificities are reported. The PNPs were stable at their optimal temperatures (DgPNP, 55 °C; GtPNP, 70 °C; ApMTAP, activity rising to 99 °C). Substrate properties were investigated for natural purine nucleosides [adenosine, inosine and their C2'-deoxy counterparts (activity within 50-500 U·mg(-1))], analogues with 2'-amino modified 2'-deoxy-adenosine and -inosine (within 0.1-3 U·mg(-1)) as well as 2'-deoxy-2'-fluoroadenosine (9) and its C2'-arabino diastereomer (10, within 0.01-0.03 U·mg(-1)). Our results reveal that the structure of the heterocyclic base (e.g. adenine or hypoxanthine) can play a critical role in the phosphorolysis reaction. The implications of this finding may be helpful for reaction mechanism studies or optimization of reaction conditions. Unexpectedly, the diastereomeric 2'-deoxyfluoro adenine ribo- and arabino-nucleosides displayed similar substrate properties. Moreover, cytidine and 2'-deoxycytidine were found to be moderate substrates of the prepared PNPs, with substrate activities in a range similar to those determined for 2'-deoxyfluoro adenine nucleosides 9 and 10. C2'-modified nucleosides are accepted as substrates by all recombinant enzymes studied, making these enzymes promising biocatalysts for the synthesis of modified nucleosides. Indeed, the prepared PNPs performed well in preliminary transglycosylation reactions resulting in the synthesis of 2'-deoxyfluoro adenine ribo- and arabino- nucleosides in moderate yield (24%). © 2013 The Authors Journal

  3. Advances in purine and pyrimidine metabolism in health and diseases.

    PubMed

    Hirano, Michio; Peters, Godefridus J

    2016-12-01

    In June, 2015, the Purine and Pyrimidine Society organized the 16th biennial symposium on Purine and Pyrimidine metabolism at the Faculty House of Columbia University, New York City. This exciting meeting focused on these important molecules, new developments in inborn errors of metabolism; therapeutic analogs. In addition, the biochemistry of mammalian and non-mammalian systems were discussed. Due to significant advances in molecular medicine, the boundaries between clinical and basic sciences have merged into exciting translational research, of which a small portion was highlighted in the presymposium.

  4. 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 the...

  5. 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 the...

  6. 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 the...

  7. 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 the...

  8. 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 the...

  9. Statistical analysis plan for the Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial (LiGHT): a multi-centre randomised controlled trial.

    PubMed

    Vickerstaff, Victoria; Ambler, Gareth; Bunce, Catey; Xing, Wen; Gazzard, Gus

    2015-11-11

    The LiGHT trial (Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial) is a multicentre randomised controlled trial of two treatment pathways for patients who are newly diagnosed with open-angle glaucoma (OAG) and ocular hypertension (OHT). The main hypothesis for the trial is that lowering intraocular pressure (IOP) with selective laser trabeculoplasty (SLT) as the primary treatment ('Laser-1st') leads to a better health-related quality of life than for those started on IOP-lowering drops as their primary treatment ('Medicine-1st') and that this is associated with reduced costs and improved tolerability of treatment. This paper describes the statistical analysis plan for the study. The LiGHT trial is an unmasked, multi-centre randomised controlled trial. A total of 718 patients (359 per arm) are being randomised to two groups: medicine-first or laser-first treatment. Outcomes are recorded at baseline and at 6-month intervals up to 36 months. The primary outcome measure is health-related quality of life (HRQL) at 36 months measured using the EQ-5D-5L. The main secondary outcome is the Glaucoma Utility Index. We plan to analyse the patient outcome data according to the group to which the patient was originally assigned. Methods of statistical analysis are described, including the handling of missing data, the covariates used in the adjusted analyses and the planned sensitivity analyses. The trial was registered with the ISRCTN register on 23/07/2012, number ISRCTN32038223 .

  10. 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

  11. 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.

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

    PubMed Central

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

    2011-01-01

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

  13. 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.

  14. 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.

  15. Purine nucleoside transport and metabolism in isolated rat jejunum.

    PubMed Central

    Stow, R A; Bronk, J R

    1993-01-01

    1. The absorption and metabolism of purine nucleosides and their constituent bases has been investigated by perfusion through the lumen of isolated loops of rat jejunum. In control perfusions and those with luminal purines or purine nucleosides, high-performance liquid chromatography (HPLC) revealed uric acid as the only detectable purine in the mucosal epithelial layer and the serosal secretions unless the xanthine oxidase inhibitor allopurinol was present. 2. Adenosine (0.5 mM) was quantitatively deaminated to inosine in the lumen after perfusion for 30 min. 3. Luminal inosine and hypoxanthine (0.15-1.0 mM) increased the serosal uric acid concentration significantly (P < 0.001); at 0.5 and 1.0 mM the nucleoside gave a significantly greater (P < 0.01) rate of serosal uric acid appearance than the base. 4. Luminal guanosine (0.05-0.50 mM) and guanine (0.05-0.15 mM) increased the serosal uric acid concentration significantly (P < 0.001); with 0.15 mM nucleoside the serosal uric acid appeared significantly faster (P < 0.01) than it did from the base. 5. Luminal allopurinol (0.3 mM) inhibited xanthine oxidase by 80% and reduced serosal purine appearance significantly (P < 0.01) from luminal guanine, hypoxanthine and inosine. With allopurinol, guanosine (0.1 and 0.15 mM) and inosine (0.1-1.0 mM) gave significantly higher (P < 0.01) total serosal purine concentrations than their respective bases. 6. Inosine and guanosine were cleaved to their respective bases plus ribose phosphate by the action of a cytoplasmic nucleoside phosphorylase, which was found to have widely different Michaelis constants (Km; 318 +/- 45 and 41.4 +/- 3.6 microM for inosine and guanosine, respectively) and maximum velocities (Vmax; 79.3 +/- 4.0 and 20.5 +/- 0.05 mumol min-1 (mg protein)-1 for inosine and guanosine, respectively). 7. We conclude that hypoxanthine and guanine absorbed by rat small intestine are oxidized to uric acid which is released in the serosa. The corresponding nucleosides are

  16. Purine metabolism is dysregulated in patients with major depressive disorder.

    PubMed

    Ali-Sisto, Toni; Tolmunen, Tommi; Toffol, Elena; Viinamäki, Heimo; Mäntyselkä, Pekka; Valkonen-Korhonen, Minna; Honkalampi, Kirsi; Ruusunen, Anu; Velagapudi, Vidya; Lehto, Soili M

    2016-08-01

    The purine cycle and altered purinergic signaling have been suggested to play a role in major depressive disorder (MDD). Nevertheless, data on this topic are scarce. Based on previous studies, we hypothesized that compared with non-depressed controls, MDD patients have distinct purine metabolite profiles. The samples comprised 99 MDD patients and 253 non-depressed controls, aged 20-71 years. Background data were collected with questionnaires. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) to determine seven purine cycle metabolites belonging to the purine cycle. We investigated the levels of these metabolites in three settings: (1) MDD patients vs. non-depressed controls and (2) remitted vs. non-remitted MDD patients, and also (3) within-group changes in metabolite levels during the follow-up period. In logistic regression adjusted for age, gender, smoking, alcohol use, physical exercise, glycosylated hemoglobin, and high-density lipoprotein cholesterol, lower levels of inosine (OR 0.89, 95% CI 0.82-0.97) and guanosine (OR 0.32, 95% CI 0.17-0.59), and higher levels of xanthine (OR 2.21, 95% CI 1.30-3.75) were associated with MDD vs. the non-depressed group. Levels of several metabolites changed significantly during the follow-up period in the MDD group, but there were no differences between remitted and non-remitted groups. We observed altered purine metabolism in MDD patients compared with non-depressed controls. Furthermore, our observations suggest that circulating xanthine may accumulate in MDD patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Allied Forces. 1st Airborne Task Force. Field Order Number 1

    DTIC Science & Technology

    1944-08-05

    D761 ALLIED FORCES. 1st . AIRBORNE TASK FORCE. FIELD ORDER W6> 1 D 761 .A63 Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting...Allied Forces. 1st . Airborne Task Force. Field Order No. 1 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...34 .83d Cml B n CO, jCo "A" 2d Cml Bn CO,,’AT CO, /:/•"’""a| Regt CO I 5"L?’ih ’j 67^’th Med Co "Oet, 3d Ord 1 1st ABTF 5, PSTF G3,. ABTF ACofS

  18. "European Resuscitation Council 2015 burn 1st Aid recommendations-concerns and issues for first responders".

    PubMed

    Goodwin, Nicholas S

    2016-08-01

    As the lead author of a recently published systematic review on hydrogel burn dressings in pre-hospital, I was alarmed to read the claim by the authors to the effect no one method of burn wound cooling was superior to any other; "There is no evidence to recommend a specific temperature or method of cooling". The reputation and prominence of the ERC within the circle of resuscitation councils now delving into 1st Aid recommendations leads to the conclusion that misguided recommendations may cause confusion amongst first responders, may falsely misdirect 1st Aid providers to unsupported practices or alternatively create a window of opportunity for marketers or sellers of alternative burn 1st Aid technologies to make unsupported claims in respect of comparable efficacy of their own product versus "traditional" methods. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  19. 25. PRIMARY POWER TRANSMISSION BELT HOLES IN 1st FLOOR MILL ...

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

    25. PRIMARY POWER TRANSMISSION BELT HOLES IN 1st FLOOR MILL NO. 1 CEILING. WATER-POWERED MACHINERY LOCATED IN BASEMENT RAN LEATHER BELTS THROUGH THESE HOLES. POWER WAS THEN TRANSMITTED TO SHAFTS AND PULLEYS TO RUN MACHINERY ON MILL FLOORS. - Prattville Manufacturing Company, Number One, 242 South Court Street, Prattville, Autauga County, AL

  20. 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…

  1. 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…

  2. 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…

  3. 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...

  4. 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…

  5. Breaking Down Barriers for 1st-Year Teachers: What Teacher Preparation Programs Can Do

    ERIC Educational Resources Information Center

    Brashier, Allison; Norris, Elizabeth

    2008-01-01

    A developmentally appropriate learning environment for young children is vital for successful learning. However, implementing developmentally appropriate practices can be a challenge for 1st-year teachers because of the pressures of standardized testing. The purpose of this study was to examine the struggles teachers encounter in implementing…

  6. 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

  7. 75 FR 12544 - Filing Dates for the Hawaii Special Election In the 1st Congressional District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-16

    ... Filing Dates for the Hawaii Special Election In the 1st Congressional District AGENCY: Federal Election Commission. ACTION: Notice of filing dates for special election. SUMMARY: Hawaii has scheduled a Special... Campaign Committees All principal campaign committees of candidates who participate in the Hawaii Special...

  8. 26. Photograph of original Fresnel lens a 1st order fixed ...

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

    26. Photograph of original Fresnel lens a 1st order fixed white light. (Installed 1874 and first illuminated Feb. 1, 1875. This is the only known photograph of this lens - - removed in 1929.)ca. 1918. - Block Island Southeast Light, Spring Street & Mohegan Trail at Mohegan Bluffs, New Shoreham, Washington County, RI

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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…

  14. 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

  15. 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…

  16. Aedes aegypti pharate 1st instar quiescence: a case for anticipatory reproductive plasticity.

    PubMed

    Perez, Mario H; Noriega, Fernando G

    2013-03-01

    Aedes aegypti mosquitoes use pharate 1st instar quiescence to cope with fluctuations in water availability hosting a fully developed 1st instar larvae within the chorion. The duration of this quiescence has been shown to affect larval fitness. This study sought to determine if an extended egg quiescence can elicit a plastic response resulting in an adult phenotype distinct from adults reared from short quiescence eggs. Our findings indicate that extended pharate 1st instar quiescence affects the performance and reproductive fitness of the adult female mosquito as well as the nutritional status of its progeny via maternal effects in an adaptive manner. This study demonstrates that phenotypic plasticity results as a consequence of the duration of pharate 1st instar quiescence and alternative phenotypes may exist for this mosquito with quiescence serving as a cue possibly signaling the environmental conditions that follow a dry period. These findings have implications for A. aegypti's success as a vector, geographic distribution, vector capacity and control.

  17. 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…

  18. Plasmodium falciparum malaria in 1(st)-2(nd) century CE southern Italy.

    PubMed

    Marciniak, Stephanie; Prowse, Tracy L; Herring, D Ann; Klunk, Jennifer; Kuch, Melanie; Duggan, Ana T; Bondioli, Luca; Holmes, Edward C; Poinar, Hendrik N

    2016-12-05

    The historical record attests to the devastation malaria exacted on ancient civilizations, particularly the Roman Empire [1]. However, evidence for the presence of malaria during the Imperial period in Italy (1st-5th century CE) is based on indirect sources, such as historical, epigraphic, or skeletal evidence. Although these sources are crucial for revealing the context of this disease, they cannot establish the causative species of Plasmodium. Importantly, definitive evidence for the presence of malaria is now possible through the implementation of ancient DNA technology. As malaria is presumed to have been at its zenith during the Imperial period [1], we selected first or second molars from 58 adults from three cemeteries from this time: Isola Sacra (associated with Portus Romae, 1st-3rd century CE), Velia (1st-2nd century CE), and Vagnari (1st-4th century CE). We performed hybridization capture using baits designed from the mitochondrial (mtDNA) genomes of Plasmodium spp. on a prioritized subset of 11 adults (informed by metagenomic sequencing). The mtDNA sequences generated provided compelling phylogenetic evidence for the presence of P. falciparum in two individuals. This is the first genomic data directly implicating P. falciparum in Imperial period southern Italy in adults.

  19. Purification and characterization of purine nucleoside phosphorylase from Proteus vulgaris.

    PubMed Central

    Surette, M; Gill, T; MacLean, S

    1990-01-01

    Purine nucleoside phosphorylase was isolated and purified from cell extracts of Proteus vulgaris recovered from spoiling cod fish (Gadus morhua). The molecular weight and isoelectric point of the enzyme were 120,000 +/- 2,000 and pH 6.8. The Michaelis constant for inosine as substrate was 3.9 x 10(-5). Guanosine also served as a substrate (Km = 2.9 x 10(-5). However, the enzyme was incapable of phosphorylizing adenosine. Adenosine proved to be useful as a competitive inhibitor and was used as a ligand for affinity chromatography of purine nucleoside phosphorylase following initial purification steps of gel filtration and ion-exchange chromatography. PMID:2111121

  20. 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.

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

    PubMed

    Ribeiro, José M C; Valenzuela, Jesus G

    2003-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

    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.

  3. Fine targeting of purine salvage in Cryptosporidium parasites.

    PubMed

    Hyde, John E

    2008-08-01

    The apicomplexan pathogen Cryptosporidium parvum poses major logistical problems in the search for effective drug treatments. These treatments are required urgently because this parasite can cause severe disease and death in immunocompromised individuals and young children. In a recent study, the dependence of Cryptosporidium parasites on a single salvage pathway that leads to essential purine derivatives has been exploited and inhibitors have been identified that selectively target a key enzyme in this salvage process, inosine 5'-monophosphate dehydrogenase.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    The purine degradation pathway in humans ends with uric acid, which has low water solubility. When the production of uric acid is increased either by elevated purine intake or by impaired kidney function, uric acid will accumulate in the blood (hyperuricemia). This increases the risk of gout, a disease described in humans for at least 1000 years. Many lower organisms, such as the yeast Arxula adeninivorans, possess the enzyme, urate oxidase that converts uric acid to 5-hydroxyisourate, thus preventing uric acid accumulation. We have examined the complete purine degradation pathway in A. adeninivorans and analyzed enzymes involved. Recombinant adenine deaminase, guanine deaminase, urate oxidase and endogenous xanthine oxidoreductase have been investigated as potential additives to degrade purines in the food. Here, we review the current model of the purine degradation pathway of A. adeninivorans and present an overview of proposed enzyme system with perspectives for its further development. PMID:25513995

  6. T.C.G triplet in an antiparallel purine.purine.pyrimidine DNA triplex. Conformational studies by NMR.

    PubMed

    Dittrich, K; Gu, J; Tinder, R; Hogan, M; Gao, X

    1994-04-12

    The antiparallel purine.purine.pyrimidine DNA triplex, RRY6, which contains a T.C.G inverted triplet in the center of the sequence, was examined by proton and phosphorous two-dimensional NMR spectroscopy. The local conformation of the T.C.G triplet (T4.C11.G18) and the effect of this triplet on the global helical structure were analyzed in detail. The formation of the T.C.G triplet is confirmed by a set of cross-strand NOEs, including unusual cross-strand NOEs between the third strand and the pyrimidine strand as opposed to the purine strand of the duplex. NMR data suggest that the T.C.G triplet may be present in an equilibrium between a non-hydrogen-bonded form and a T(O4)-C(NH2) hydrogen-bonded form and that there is a distortion of the in-plane alignment of the three bases. The flanking G.G.C base triplets are well-defined on the 5'-side of T4, but somewhat interrupted on the 3'-side of T4. The effect of the third strand binding on the Watson-Crick duplex was probed by an NMR study of the free duplex RY6. NMR parameters are affected mostly around the T.C.G inversion site. The perturbations extend to at least two adjacent base triplets on either side. The binding of the third purine strand and the accommodation of a central T.C.G inversion in RRY6 does not require a readjustment in sugar pucker, which remains in the range of C2'-endo. 31P resonances of RRY6 distribute over a range of 2.2 ppm. The H-P coupling patterns of the third strand differ from those of the duplex. General spectral patterns defined by the marker protons of the RRY and YRY triplexes are compared.

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

    PubMed

    Thieme, Niels; Breit, Bernhard

    2017-02-01

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

  8. 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.

  9. The 1st of April 2470 BC Total Solar Eclipse Seen by the Prophet Ibraheem

    NASA Astrophysics Data System (ADS)

    Yousef, S. M.

    The Holy Quran describes a phenomenon seen by young Abraham that can only fit a solar eclipse. Two criteria were given for this particular eclipse; first only one planet was seen as soon as it got dark and second no corona was seen. In order to justify the first selection rule, examinations of solar and planetary longitudes for total solar eclipses passing over Babel were carried out. Only the eclipse of the 1st of April 2470 BC meets this condition, as it was only Venus that was seen at that eclipse. The second selection rule was also naturally fulfilled, as Babel happened to be on the border of the totality zone hence no corona was seen, however all the time the moon glistened as Baily's beads. There is no doubt that the prophet Abraham witnessed the 1st of April total solar eclipse that passed over Babel. This will put him about 470 years backward than it was previously anticipated.

  10. 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

  11. 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

  12. 1st Central and Eastern European Proteomic Conference and 3rd Czech Proteomic Conference.

    PubMed

    Kovarova, Hana; Gadher, Suresh Jivan; Archakov, Alexander

    2008-02-01

    The 1st Central and Eastern European Proteomic Conference was organized together with the 3rd Czech Proteomic Conference in the TOP Hotel, Prague in the Czech Republic from the 29th to the 31st October, 2007. The aim was to strengthen links with scientists from Central and Eastern Europe including Russia, which until now have been weak or nonexistent, and to highlight the emergence of excellent proteomic studies from various countries, which until now were not visible.

  13. 1st Cavalry Division’s Effectiveness In Conducting Airmobile Operations During Operation Pegasus

    DTIC Science & Technology

    2016-05-26

    company movements, to complex movements of entire divisions. From April 1 to April 15, 1968, 1st Cavalry Division successfully conducted Operation Pegasus...Siege of Khe Sanh (Boston, MA: Houghton Mifflin Company , 1991), 418-419. 13 Ibid., 417. 5...Tokyo, Japan: Dai Nippon Printing Company , 1968), 9. 34 John Galvin Air Assault: the development of airmobile warfare (New York, NY: Hawthorn Books, 1969

  14. Development of repair mechanism of FSX-414 based 1st stage nozzle of gas turbine

    NASA Astrophysics Data System (ADS)

    Rahman, Md. Tawfiqur

    2017-06-01

    This paper describes the failure mechanism and repair technology of 1st stage nozzle or vane of industrial gas turbine which is made of cobalt based super alloy FSX-414. 1st stage nozzles or vanes are important stationery components of gas turbine based power plant. Those are the parts of hot gas path components of gas turbine and their manufacturing process is casting. At present, it is widely accepted that gas turbine based combined cycle power plant is the most efficient and cost effective solution to generate electricity. One of the factors of high efficiency of this type of gas turbine is the increase of its turbine inlet temperature. As an effect of this factor and in conjunction with some other factors, the 1st stage nozzle of gas turbine operates under extremely high temperature and thermal stresses. As a result, the design lifetime of these components becomes limited. Furthermore, attention on nozzles or vanes is required in order to achieve their design lifetime. However, due to unfriendly operational condition and environmental effect, anytime failure can occur on these heat resistant alloy based components which may lead to severe damage of gas turbine. To mitigate these adverse effects, schedule maintenance is performed on a predetermined time interval of hot gas path components of gas turbine based power plant. This paper addresses common failures in gas turbine's 1st stage nozzles or vanes. Usually these are repaired by using ADH process but for several reasons ADH process is not used here. Hence the challenging task is performed using gas tungsten arc welding which is presented in this article systematically.

  15. Aedes aegypti pharate 1st instar quiescence affects larval fitness and metal tolerance.

    PubMed

    Perez, Mario H; Noriega, Fernando G

    2012-06-01

    The eggs of the mosquito Aedes aegypti possess the ability to undergo an extended quiescence hosting a fully developed 1st instar larvae within the chorion. As a result of this life history trait pharate larvae can withstand months of quiescence inside the egg where they depend on stored maternal reserves. A. aegypti mosquitoes are frequently associated with urban habitats that may contain significant metal pollution. Therefore, the duration of quiescence and extent of nutritional depletion may affect the physiology and survival of larvae that hatch in a suboptimal habitat. The aim of this study was to determine the effect of an extended quiescence on larval nutrient reserves and the subsequent effects of metal exposure on larval fitness, survival and development. We hypothesized that an extended quiescence would reduce nutritional reserves and alter the molecular response to metal exposure thereby reducing larval survival and altering larval development. As a molecular marker for metal stress responses, we evaluated transcriptional changes in the metallothionein gene (AaMtn) in response to quiescence and metal exposure. Extended 1st instar quiescence resulted in a significant decrease in lipid reserves and negatively affected larval fitness and development. AaMtn transcription and metal tolerance were compromised in first instars emerged from eggs that had undergone an extended quiescence. These findings suggest that newly emerged mosquito larvae that had survived a relatively long pharate 1st instar quiescence (as might occur during a dry season) are more vulnerable to environmental stress. Pharate 1st instar quiescence could have implications for vector control strategies. Newly emerged mosquito larvae at the end of the dry season or start of the wet season are physiologically compromised, and therefore potentially more susceptible to vector control strategies than mosquito larvae hatched subsequently throughout the wet season. Published by Elsevier Ltd.

  16. 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

  17. 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

  18. 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

  19. Determination of purine contents of alcoholic beverages using high performance liquid chromatography.

    PubMed

    Kaneko, Kiyoko; Yamanobe, Tomoyo; Fujimori, Shin

    2009-08-01

    The purine contents of alcoholic beverages were determined in order to utilize them in the dietary care of gout and hyperuricemia. In the management of these diseases, restriction of both alcohol and purine intake are important. The method employed in this study is a quantitative determination of purine contents by HPLC. Alcoholic beverages were hydrolyzed to corresponding purine bases, which were then separated by HPLC, and base peaks were identified using an enzymatic peak-shift technique. This method is sufficiently accurate and reproducible to examine the purine contents of various alcoholic beverages that patients consume. Purine contents were as follows: spirits, 0.7-26.4 micromol/L; regular beer, 225.0-580.2 micromol/L; low-malt beer, 193.4-267.9 micromol/L; low-malt and low-purine beer, 13.3 micromol/L; other liquors, 13.1-818.3 micromol/L. Some local and low-alcohol beers were found to contain about 2.5 times more purines than regular beer. As some alcoholic beverages contain considerable amounts of purines, we recommend that excess consumption of these beverages be avoided. These data should be useful in the management of hyperuricemia and gout, not only for patients but also for physicians. (c) 2009 John Wiley & Sons, Ltd.

  20. 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.

  1. Magnetic field induced 1st order transitions: Recent studies, and some new concepts

    NASA Astrophysics Data System (ADS)

    Chaddah, P.

    2015-05-01

    Phase transitions are caused by varying temperature, or pressure, or magnetic field. The observation of 1st order magneto-structural transitions has created application possibilities based on magnetoresistance, magnetocaloric effect, magnetic shape memory effect, and magneto-dielectric effect. Magnetic field induced transitions, and phase coexistence of competing magnetic phases down to the lowest temperature, gained prominence over a decade ago with theoretical models suggesting that the ground state is not homogeneous. Researchers at Indore pushed an alternative view that this phase coexistence could be due to glasslike "kinetic arrest" of a disorder-broadened first-order magnetic transition between two states with long-range magnetic order, resulting in phase coexistence down to the lowest temperatures. The CHUF (cooling and heating in unequal field) protocol created at Indore allows the observation of `devitrification', followed by `melting'. I show examples of measurements establishing kinetic arrest in various materials, emphasizing that glasslike arrest of 1st order magnetic transitions may be as ubiquitous as glass formation following the arrest of 1st order structural transitions.

  2. Gene set analysis of purine and pyrimidine antimetabolites cancer therapies.

    PubMed

    Fridley, Brooke L; Batzler, Anthony; Li, Liang; Li, Fang; Matimba, Alice; Jenkins, Gregory D; Ji, Yuan; Wang, Liewei; Weinshilboum, Richard M

    2011-11-01

    Responses to therapies, either with regard to toxicities or efficacy, are expected to involve complex relationships of gene products within the same molecular pathway or functional gene set. Therefore, pathways or gene sets, as opposed to single genes, may better reflect the true underlying biology and may be more appropriate units for analysis of pharmacogenomic studies. Application of such methods to pharmacogenomic studies may enable the detection of more subtle effects of multiple genes in the same pathway that may be missed by assessing each gene individually. A gene set analysis of 3821 gene sets is presented assessing the association between basal messenger RNA expression and drug cytotoxicity using ethnically defined human lymphoblastoid cell lines for two classes of drugs: pyrimidines [gemcitabine (dFdC) and arabinoside] and purines [6-thioguanine and 6-mercaptopurine]. The gene set nucleoside-diphosphatase activity was found to be significantly associated with both dFdC and arabinoside, whereas gene set γ-aminobutyric acid catabolic process was associated with dFdC and 6-thioguanine. These gene sets were significantly associated with the phenotype even after adjusting for multiple testing. In addition, five associated gene sets were found in common between the pyrimidines and two gene sets for the purines (3',5'-cyclic-AMP phosphodiesterase activity and γ-aminobutyric acid catabolic process) with a P value of less than 0.0001. Functional validation was attempted with four genes each in gene sets for thiopurine and pyrimidine antimetabolites. All four genes selected from the pyrimidine gene sets (PSME3, CANT1, ENTPD6, ADRM1) were validated, but only one (PDE4D) was validated for the thiopurine gene sets. In summary, results from the gene set analysis of pyrimidine and purine therapies, used often in the treatment of various cancers, provide novel insight into the relationship between genomic variation and drug response.

  3. Gene set analysis of purine and pyrimidine antimetabolites cancer therapies

    PubMed Central

    Fridley, Brooke L.; Batzler, Anthony; Li, Liang; Li, Fang; Matimba, Alice; Jenkins, Gregory D.; Ji, Yuan; Wang, Liewei; Weinshilboum, Richard M.

    2011-01-01

    Objective Responses to therapies, either with regards to toxicities or efficacy, are expected to involve complex relationships of gene products within the same molecular pathway or functional gene set. Therefore, pathways or gene sets, as opposed to single genes, may better reflect the true underlying biology and may be more appropriate units for analysis of pharmacogenomic studies. Application of such methods to pharmacogenomic studies may enable the detection of more subtle effects of multiple genes in the same pathway that may be missed by assessing each gene individually. Methods A gene set analysis of 3,821 gene sets is presented assessing the association between basal mRNA expression and drug cytotoxicity using ethnically defined human lymphoblastoid cell lines for two classes of drugs: pyrimidines (dFdC and AraC) and purines (6-TG and 6-MP). Results The gene set nucleoside-diphosphatase activity was found to be significantly associated with both dFdC and AraC, while gene set gamma-aminobutyric acid catabolic process was associated with dFdC and 6-TG. These gene sets were significantly associated with the phenotype even after adjusting for multiple testing. In addition, five associated gene sets were found in common between the pyrimidines and two gene sets for the purines (3′,5′-cyclic-AMP phosphodiesterase activity and gamma-aminobutyric acid catabolic process) with p < 0.0001. Functional validation was attempted with 4 genes each in gene sets for thiopurine and pyrimidine anti-metabolites. All four genes selected from the pyrimidine gene sets (PSME3, CANT1, ENTPD6, ADRM1) were validated, but only one (PDE4D) was validated for the thiopurine gene sets. Conclusions In summary, results from the gene set analysis of pyrimidine and purine therapies, used often in the treatment of various cancers, provide novel insight into the relationship between genomic variation and drug response. PMID:21869733

  4. 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.

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

    PubMed

    PULLMAN, B; CLAVERIE, P; CAILLET, J

    1965-03-12

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

  6. 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.

  7. Associations between purine metabolites and monoamine neurotransmitters in first-episode psychosis

    PubMed Central

    Yao, Jeffrey K.; Dougherty, George G.; Reddy, Ravinder D.; Matson, Wayne R.; Kaddurah-Daouk, Rima; Keshavan, Matcheri S.

    2013-01-01

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

  8. 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.

  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. Purine import into malaria parasites as a target for antimalarial drug development.

    PubMed

    Frame, I J; Deniskin, Roman; Arora, Avish; Akabas, Myles H

    2015-04-01

    Infection with Plasmodium species parasites causes malaria. Plasmodium parasites are purine auxotrophs. In all life cycle stages, they require purines for RNA and DNA synthesis and other cellular metabolic processes. Purines are imported from the host erythrocyte by equilibrative nucleoside transporters (ENTs). They are processed via purine salvage pathway enzymes to form the required purine nucleotides. The Plasmodium falciparum genome encodes four putative ENTs (PfENT1-4). Genetic, biochemical, and physiologic evidence suggest that PfENT1 is the primary purine transporter supplying the purine salvage pathway. Protein mass spectrometry shows that PfENT1 is expressed in all parasite stages. PfENT1 knockout parasites are not viable in culture at purine concentrations found in human blood (<10 μM). Thus, PfENT1 is a potential target for novel antimalarial drugs, but no PfENT1 inhibitors have been identified to test the hypothesis. Identifying inhibitors of PfENT1 is an essential step to validate PfENT1 as a potential antimalarial drug target.

  11. 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.

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

    PubMed

    Bednářová, Martina; Borkovcová, Marie; Komprda, Tomáš

    2014-01-15

    Considering their high content of protein, insects are a valuable alternative protein source. However, no evaluation of their purine content has so far been done. High content of purine derivates may lead to the exclusion of such food from the diet of people with specific diseases. The aim of this study was to analyse the content of selected purine derivates and amino acid profile in the three insect species most often used for entomophagy in Europe and compare them with the purine content in egg white and chicken breast. The content of individual purine derivates and their total content were significantly dependent on insect species. The purine content in all three species was significantly higher (P < 0.05) than in egg white, but some values were significantly lower (P < 0.05) than in chicken breast. The total protein content was 548.9 g kg(-1) dry matter (DM) in mealworm (Tenebrio molitor), 551.6 g kg(-1) DM in superworm (Zophobas atratus) and 564.9 g kg(-1) DM in cricket (Gryllus assimilis). Larvae of mealworm and superworm are protein-rich and purine-low meat alternatives. In contrast, cricket nymphs are protein-rich and purine-rich and cannot be recommended for people with hyperuricemia or gout. © 2013 Society of Chemical Industry.

  13. Effect of dietary purines on the pharmacokinetics of orally administered ribavirin.

    PubMed

    Li, Linghui; Koo, Seok Hwee; Limenta, Lie Michael George; Han, Li; Hashim, Khadijah Binte; Quek, Hung Hiang; Lee, Edmund Jon Deoon

    2009-06-01

    Ribavirin is found to be absorbed in the intestine through the human concentrative nucleoside transporter 2 (hCNT2). Cellular uptake of ribavirin was strongly inhibited by purine nucleoside in an in vitro study. This study aims to examine the effects of dietary purine on the pharmacokinetics of orally administered ribavirin in vivo. Twenty healthy participants were enrolled in a randomized, 2-period crossover study. Participants were administered a single 600-mg oral dose of ribavirin after either a high-purine meal or a low-purine meal. Serial blood samples were collected predose and over 144 hours after dosing. Ribavirin concentrations were measured by liquid chromatography/tandem mass spectrometry. In comparison with corresponding plasma values of ribavirin following a high-purine meal, C(max), AUC(0-144) and AUC(0-infinity) of ribavirin following a low-purine meal were 136% (90% confidence internal [CI]: 120%-155%), 134% (90% CI: 118%-153%), and 139% (90% CI: 120%-159%), respectively. This study indicates that dietary purines have an effect on ribavirin absorption. Dosage regimens of ribavirin might need to be adjusted according to the purine content of the meal.

  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. 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.

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

    SciTech Connect

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

    2009-01-01

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

  17. 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.

  18. B Family DNA Polymerases Asymmetrically Recognize Pyrimidines and Purines

    PubMed Central

    Lund, Travis J.; Cavanaugh, Nisha A.; Joubert, Nicolas; Urban, Milan; Patro, Jennifer N.; Hocek, Michal; Kuchta, Robert D.

    2011-01-01

    We utilized a series of pyrimidine analogues modified at O2, N-3, and N4/O4 to determine if two B family DNA polymerases, human DNA polymerase α and herpes simplex virus I DNA polymerase, choose whether or not to polymerize pyrimidine dNTPs using the same mechanisms they use for purine dNTPs. Removing O2 of a pyrimidine dNTP vastly decreased incorporation by these enzymes and also compromised fidelity in the case of C analogues, while removing O2 from the templating base had more modest effects. Removing the Watson-Crick hydrogen bonding groups of N-3 and N4/O4 greatly impaired polymerization, both of the resulting dNTP analogues as well as polymerization of natural dNTPs opposite these pyrimidine analogues when present in the template strand. Thus, the Watson-Crick hydrogen bonding groups of a pyrimidine clearly play an important role in enhancing correct dNTP polymerization, but are not essential for preventing misincorporation. These studies also indicate that DNA polymerases recognize bases extremely asymmetrically, both in terms of whether they are a purine or pyrimidine and whether they are in the template or are the incoming dNTP. The mechanistic implications of these results regarding how polymerases discriminate between right and wrong dNTPs are discussed. PMID:21761848

  19. 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

  20. 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

  1. A Preliminary to War: The 1st Aero Squadron and the Mexican Punitive Expedition of 1916

    DTIC Science & Technology

    2003-01-01

    ordered a reconnaissance along the Mexican Northwestern railroad south toward Cumbre Pass in the Sierra Madre mountains. Dodd and Foulois flew this...Casas Grandes and Galeana Valleys ranged between 6,000 and 7,000 feet, and that Cumbre Pass lay at about 9,000 feet. All of these altitudes were higher...of the Cumbre Pass tunnel, but could go no farther. For two hours, 25 The 1st Aero Squadron in Mexico; probably following a mission by Signal Corps No

  2. Absorption and intermediary metabolism of purines and pyrimidines in lactating dairy cows.

    PubMed

    Stentoft, Charlotte; Røjen, Betina Amdisen; Jensen, Søren Krogh; Kristensen, Niels B; Vestergaard, Mogens; Larsen, Mogens

    2015-02-28

    About 20 % of ruminal microbial N in dairy cows derives from purines and pyrimidines; however, their intermediary metabolism and contribution to the overall N metabolism has sparsely been described. In the present study, the postprandial patterns of net portal-drained viscera (PDV) and hepatic metabolism were assessed to evaluate purine and pyrimidine N in dairy cows. Blood was sampled simultaneously from four veins with eight hourly samples from four multi-catheterised Holstein cows. Quantification of twenty purines and pyrimidines was performed with HPLC-MS/MS, and net fluxes were estimated across the PDV, hepatic tissue and total splanchnic tissue (TSP). Concentration differences between veins of fifteen purine and pyrimidine nucleosides (NS), bases (BS) and degradation products (DP) were different from zero (P≤ 0·05), resulting in the net PDV releases of purine NS (0·33-1·3 mmol/h), purine BS (0·0023-0·018 mmol/h), purine DP (7·0-7·8 mmol/h), pyrimidine NS (0·30-2·8 mmol/h) and pyrimidine DP (0·047-0·77 mmol/h). The hepatic removal of purine and pyrimidine was almost equivalent to the net PDV release, resulting in no net TSP release. One exception was uric acid (7·9 mmol/h) from which a large net TSP release originated from the degradation of purine NS and BS. A small net TSP release of the pyrimidine DP β-alanine and β-aminoisobutyric acid (-0·032 to 0·37 mmol/h) demonstrated an outlet of N into the circulating N pool. No effect of time relative to feeding was observed (P>0·05). These data indicate that considerable amounts of N are lost in the dairy cow due to prominent intermediary degradation of purines, but that pyrimidine N is reusable to a larger extent.

  3. PRESENCE OF PURINE METABOLITES IN OMASAL DIGESTA AND BACTERIA: NEW ANALYTICAL METHOD AND EFFECTS ON MICROBIAL FLOWS

    USDA-ARS?s Scientific Manuscript database

    A new HPLC method was developed to determine concentrations of purines [adenine (A) and guanine (G)], and their metabolites [xanthine (X) and hypoxanthine (HX)] in omasal digesta and bacterial samples and to assess the effect of using either purines (TP) or purines plus their metabolites (PM) as mic...

  4. Autopsy as a tool for learning gross anatomy during 1(st) year MBBS.

    PubMed

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

    2016-01-01

    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 1(st) year MBBS students, and their perception was noted. 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. 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. Visualizing single fresh body dissection during 1(st) year professional MBBS is recommended either on medicolegal autopsy or on voluntarily-donated bodies.

  5. 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.

  6. Synthesis and cytostatic activity of purine nucleosides derivatives of allofuranose.

    PubMed

    Besada, Pedro; Costas, Tamara; Teijeira, Marta; Terán, Carmen

    2010-12-01

    Several new purine nucleosides derivatives of allofuranose were prepared according to Vorbrüggen method, starting from 1,2,5,6-di-O-isopropylidene-α-D-allofuranose and using 1,2,3,5,6-pentaacetoxy-β-D-allofuranose as key intermediate. The synthesized allofuranosyl nucleosides, as well as some acetyl derivatives, were evaluated for their cytotoxicity in vitro in three human cancer cell lines (MCF-7, Hela-229 and HL-60). Among the studied compounds the 9-(2,3,5,6-tetra-O-acetyl-β-D-allofuranosyl)-2,6-dichloropurine (9) was the most potent one on the three cell lines evaluated, being its activity against HL-60 cells similar to cisplatin.

  7. [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.

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

    PubMed

    Jorda, Radek; Paruch, Kamil; Krystof, Vladimír

    2012-01-01

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

  9. Antimalarial activity of thiosemicarbazones and purine derived nitriles

    PubMed Central

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

    2009-01-01

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

  10. The Attachment of Amino Fragment to Purine: Inner-Shell Structures And Spectra

    SciTech Connect

    Saha, Saumitra; Wang, Feng; MacNaughton, Janay B.; Moewes, Alex; Chong, Denalo P.; /British Columbia U.

    2009-05-11

    The impact of the amino fragment (-NH{sub 2}) attachment on the inner-shell structures and spectra of unsubstituted purine and the purine ring of adenine are studied. Density functional theory calculations, using the LB94/TZ2P//B3LYP/TZVP model, reveal significant site-dependent electronic structural changes in the inner shell of the species. A condensed Fukui function indicates that all of the N and C sites, except for N{sub (1)} and C{sub (5)}, demonstrate significant electrophilic reactivity (f > 0.5 in |e|) in the unsubstituted purine. Once the amino fragment binds to the C{sub (6)} position of purine to form adenine, the electrophilic reactivity of these N and C sites is greatly reduced. As expected, the C{sub (6)} position experiences substantial changes in energy and charge transfer, owing to the formation of the C-NH{sub 2} bond in adenine. The present study reveals that the N1s spectra of adenine inherit the N1s spectra of the unsubstituted purine, whereas the C1s spectra experience significant changes although purine and adenine have geometrically similar carbon frames. The findings also indicate that the attachment of the NH{sub 2} fragment to purine exhibits deeply rooted influences to the inner-shell structures of DNA/RNA bases. The present study suggests that some fragment-based methods may not be applicable to spectral analyses in the inner shell.

  11. 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

  12. Evidence for purine nucleoside phosphorylase (PNP) release from rat C6 glioma cells.

    PubMed

    Giuliani, Patricia; Zuccarini, Mariachiara; Buccella, Silvana; Peña-Altamira, Luis Emiliano; Polazzi, Elisabetta; Virgili, Marco; Monti, Barbara; Poli, Alessandro; Rathbone, Michel P; Di Iorio, Patrizia; Ciccarelli, Renata; Caciagli, Francesco

    2017-04-01

    Intracellular purine turnover is mainly oriented to preserving the level of triphosphate nucleotides, fundamental molecules in vital cell functions that, when released outside cells, act as receptor signals. Conversely, high levels of purine bases and uric acid are found in the extracellular milieu, even in resting conditions. These compounds could derive from nucleosides/bases that, having escaped to cell reuptake, are metabolized by extracellular enzymes similar to the cytosolic ones. Focusing on purine nucleoside phosphorylase (PNP) that catalyzes the reversible phosphorolysis of purine (deoxy)-nucleosides/bases, we found that it is constitutively released from cultured rat C6 glioma cells into the medium, and has a molecular weight and enzyme activity similar to the cytosolic enzyme. Cell exposure to 10 μM ATP or guanosine triphosphate (GTP) increased the extracellular amount of all corresponding purines without modifying the levels/activity of released PNP, whereas selective activation of ATP P2Y1 or adenosine A2A metabotropic receptors increased PNP release and purine base formation. The reduction to 1% in oxygen supply (2 h) to cells decreased the levels of released PNP, leading to an increased presence of extracellular nucleosides and to a reduced formation of xanthine and uric acid. Conversely, 2 h cell re-oxygenation enhanced the extracellular amounts of both PNP and purine bases. Thus, hypoxia and re-oxygenation modulated in opposite manner the PNP release/activity and, thereby, the extracellular formation of purine metabolism end-products. In conclusion, extracellular PNP and likely other enzymes deputed to purine base metabolism are released from cells, contributing to the purinergic system homeostasis and exhibiting an important pathophysiological role. © 2017 International Society for Neurochemistry.

  13. Blood purine measurements as a rapid real-time indicator of reversible brain ischaemia.

    PubMed

    Tian, Faming; Bibi, Fakhra; Dale, Nicholas; Imray, Christopher H E

    2017-08-12

    To preserve the disequilibrium between ATP and ADP necessary to drive cellular metabolism, enzymatic pathways rapidly convert ADP to adenosine and the downstream purines inosine and hypoxanthine. During ischaemia, these same pathways result in the production of purines. We performed a prospective observational study to test whether purine levels in arterial blood might correlate with brain ischaemia. We made real-time perioperative measurements, via microelectrode biosensors, of the purine levels in untreated arterial blood from 18 patients undergoing regional anaesthetic carotid endarterectomy. Pre-operatively, the median purine level was 2.4 μM (95% CI 1.3-4.0 μM); during the cross-clamp phase, the purines rose to 6.7 μM (95% CI 4.7-11.5 μM) and fell back to 1.9 μM (95% CI 1.4-2.7 μM) in recovery. Three patients became unconscious during carotid clamping, necessitating insertion of a temporary carotid shunt to restore cerebral blood flow. In these, the pre-operative median purine level was 5.4 μM (range 4.7-6.1 μM), on clamping, 9.6 μM (range 9.4-16.1 μM); during shunting, purines fell to below the pre-operative level (1.4 μM, range 0.4-2.9 μM) and in recovery 1.8 μM (range 1.8-2.6 μM). Our results suggest that blood purines may be a sensitive real-time and rapidly produced indicator of brain ischaemia, even when there is no accompanying neurological obtundation.

  14. Comparison of nitrogen-15 and purines as microbial markers in continuous culture.

    PubMed

    Calsamiglia, S; Stern, M D; Firkins, J L

    1996-06-01

    Eight dual-flow continuous-culture fermenters were used in four replicated periods to compare the effects of diet and microbial marker on estimates of N metabolism in continuous culture of ruminal microorganisms. A basal diet was supplemented with urea and tryptone, soybean meal (SBM), lignosulfonate-treated SBM, corn gluten meal, blood meal (BM), hydrolyzed feather meal, fish meal (FM), or meat and bone meal (MBM). Microbial protein flow and protein degradation in fermenters were estimated using purines, purine N, and 15N in bacteria obtained from fermenter flasks or from the effluent. The ratio of purine N to total N in bacteria averaged .083 and was not affected (P > .05) by treatment. Dietary purine content (percentage of DM) ranged from .033 in BM to .084 in FM. Escape of feed purine N (percentage of total purine N flow) averaged 1.7% (SE = 2.9) and was not different (P > .05) among treatments. Bacterial N flows obtained using purines were more variable than estimates obtained using 15N. Bacterial N flows calculated using 15N in bacteria isolated from fermenters were more variable than those obtained using bacteria isolated from the effluent. The use of purines as a microbial marker resulted in lower estimates of protein degradation and smaller differences among treatments compared with use of 15N. Data suggest that escape of feed purine N seems to be a minor factor affecting calculation of bacterial N flow and that the use of 15N in effluent bacteria may be a more accurate procedure when using continuous-culture fermenters.

  15. Use of Analogues and the Substrate-Sensitivity of Mutants in Analysis of Purine Uptake and Breakdown in Aspergillus nidulans

    PubMed Central

    Darlington, A. J.; Scazzocchio, C.

    1967-01-01

    Aspergillus mutants resistant to various purine analogues (purine, 8-azaguanine, 2-thioxanthine, and 2-thiouric acid) are defective in at least one step of purine uptake or breakdown. The properties of these mutants show that there are two uptake systems for purines, one which mediates the uptake of hypoxanthine, guanine, and adenine, and the other, xanthine and uric acid. Allantoinase-less strains are sensitive to the toxic effects of allantoin accumulation. They are severely inhibited when grown in the presence of naturally occurring purines. Mutant strains derived from these, resistant to naturally occurring purines, may be isolated. These are either wild-type revertants, or carry a second metabolic block in the uptake or breakdown of purines. The properties of these double mutants confirm the interpretation of the nature of the analogue-resistant mutants. PMID:6025432

  16. 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

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

    PubMed

    Brovarets', O O; Govorun D M

    2010-01-01

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

  18. Novel N9-arenethenyl purines as potent dual Src/Abl tyrosine kinase inhibitors.

    PubMed

    Wang, Yihan; Shakespeare, William C; Huang, Wei-Sheng; Sundaramoorthi, Raji; Lentini, Scott; Das, Sasmita; Liu, Shuangying; Banda, Geeta; Wen, David; Zhu, Xiaotian; Xu, Qihong; Keats, Jeffrey; Wang, Frank; Wardwell, Scott; Ning, Yaoyu; Snodgrass, Joseph T; Broudy, Mark I; Russian, Karin; Dalgarno, David; Clackson, Tim; Sawyer, Tomi K

    2008-09-01

    Novel N(9)-arenethenyl purines, optimized potent dual Src/Abl tyrosine kinase inhibitors, are described. The key structural feature is a trans vinyl linkage at N(9) on the purine core which projects hydrophobic substituents into the selectivity pocket at the rear of the ATP site. Their synthesis was achieved through a Horner-Wadsworth-Emmons reaction of N(9)-phosphorylmethylpurines and substituted benzaldehydes or Heck reactions between 9-vinyl purines and aryl halides. Most compounds are potent inhibitors of both Src and Abl kinase, and several possess good oral bioavailability.

  19. Novel developments in metabolic disorders of purine and pyrimidine metabolism and therapeutic applications of their analogs.

    PubMed

    Torres, Rosa J; Peters, Godefridus J; Puig, Juan G

    2014-01-01

    The biennial 15th symposium on Purine and Pyrimidine metabolism was held in Madrid, June 2013 (PP13). During the meeting, several novel developments on the diagnosis, pathophysiology, and treatment of several inborn errors of purine and pyrimidine metabolism were presented. These ranged from new drugs for gout to enzyme replacement therapies for mitochondrial diseases. A relatively novel aspect in this meeting was the interest in purine and pyrimidine metabolism in nonmammalian systems, such as parasites, mycoplasms, and bacteria. Development of novel analogs for parasite infections, cardiovascular diseases, inflammatory diseases, and cancer were also discussed.

  20. 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)

  1. 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.

  2. Idaho National Laboratory Quarterly Occurrence Analysis for the 1st Quarter FY2017

    SciTech Connect

    Mitchell, Lisbeth Ann

    2017-01-01

    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 82 reportable events (13 from the 1st quarter (Qtr) of fiscal year (FY) 2017 and 68 from the prior three reporting quarters), as well as 31 other issue reports (including events found to be not reportable and Significant Category A and B conditions) identified at INL during the past 12 months (seven from this quarter and 24 from the prior three quarters).

  3. Correlates and Phenomenology of 1st and 3rd Person Memories

    PubMed Central

    Sutin, Angelina R.; Robins, Richard W.

    2010-01-01

    The present research addressed fundamental questions about the visual perspective of autobiographical memories: Are stable personality characteristics associated with visual perspective? Does visual perspective influence the memory's phenomenological qualities? Participants in Study 1 (N = 1,684) completed individual-difference measures and indicated the perspective from which they generally retrieve memories. Participants in Study 2 (N = 706) retrieved a memory from their natural or manipulated perspective, rated its phenomenology, and completed the same individual-difference measures. Dissociation and anxiety were associated with 3rd person retrieval style; the Big Five personality traits were primarily unrelated to perspective. Compared to 3rd person memories, naturally-occurring 1st person memories were higher on Vividness, Coherence, Accessibility, Sensory Detail, Emotional Intensity, and Time Perspective and lower on Distancing; manipulating perspective eliminated these differences. Visual perspective is associated with clinically-relevant constructs and, although associated with the memory's phenomenology, perspective does not shape it. PMID:20665336

  4. Validation of the corrective optics on the Hubble Space Telescope 1st Servicing Mission

    NASA Astrophysics Data System (ADS)

    Thompson, Kevin P.; Kestner, Robert; Rodgers, J. Michael; Bajuk, Dan

    2016-07-01

    The Hubble Space Telescope 1st Servicing Mission carried with it a total of 14 corrective mirrors, four in wide field (WF) 2 and the planetary (PC) 2 (three WF and one PC), two each for the three axial SIs (FOS red and blue), faint object camera (f48 and f/96), and Goddard high resolution spectrograph, which were packaged in a single module, corrective optics space telescope axial replacement (COSTAR). This paper presents the fabrication and validation of these mirrors that were the cornerstone of strategy to recover the telescope performance. The COSTAR optics were particularly challenging and represented one of the earliest examples of anamorphic aspheric mirrors fabricated to <0.005 waves RMS of surface figure residual. Other firsts included one of the earliest applications of phase stepping interferometry, now an industry standard. Insights into the corrective designs, the mirror figure shapes, and the technology used in the validation of the mirrors are presented.

  5. Summary of the 1st International Workshop on Environmental, Safety and Economic Aspects of Fusion Power

    NASA Astrophysics Data System (ADS)

    Wu, Y.; Stevens, E.; Kim, K.; Maisonnier, D.; Kalashnikov, A.; Tobita, K.; Jackson, D.; Alejaldre, C.; Perrault, D.; Panayotov, D.; Merrill, B.; Grisolia, C.; Zucchetti, M.; Pinna, T.; van Houtte, D.; Konishi, S.; Kolbasov, B.

    2016-12-01

    The 1st International workshop on Environmental, Safety and Economic Aspects of Fusion Power (ESEFP) was held on 13 September 2015 at Jeju Island, South Korea. The workshop was initiated by the International Energy Agency Implementing Agreement on a Co-operative Program on ESEFP. The workshop was well attended with about forty participants representing twelve institutions in ten countries. The presentations covered safety issues and environmental impacts, availability improvement and risk control and socio-economic aspects of fusion power. Safety and licensing gaps between DEMO and ITER were discussed in depth with the consensus output presented as a plenary presentation at the 12th International Symposium on Fusion Nuclear Technology (ISFNT-12). The next workshop is planned to be held in conjunction with the ISFNT-13 in 2017.

  6. 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.

  7. Idaho National Laboratory Quarterly Occurrence Analysis - 1st Quarter FY 2016

    SciTech Connect

    Mitchell, Lisbeth Ann

    2016-03-01

    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 74 reportable events (16 from the 1st Qtr FY-16 and 58 from the prior three reporting quarters), as well as 35 other issue reports (including events found to be not reportable and Significant Category A and B conditions) identified at INL during the past 12 months (15 from this quarter and 20 from the prior three quarters).

  8. 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.

  9. 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.

  10. 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.

  11. Long-term follow-up after purine analogue therapy in hairy cell leukaemia.

    PubMed

    Else, Monica; Dearden, Claire E; Catovsky, Daniel

    2015-12-01

    Since 2006 when we last reviewed the literature concerning the use of purine analogues in hairy cell leukaemia (HCL), results from several new and updated series have been published. Here we examine these reports and consider their implications for patient management. The two purine analogues pentostatin and cladribine remain the first-line treatments of choice for all patients with HCL. Although they have not been compared in randomised trials, they appear to be equally effective. A complete response is important for the long-term outcome and we look at how best this can be achieved. Evidence is emerging which supports the use of either purine analogue plus an anti-CD20 monoclonal antibody after relapse, though questions remain concerning the scheduling of the monoclonal antibody. Patients refractory to the purine analogues may require alternative agents. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Complete genome sequence of Bacillus amyloliquefaciens XH7, which exhibits production of purine nucleosides.

    PubMed

    Yang, Huilin; Liao, Yuling; Wang, Bin; Lin, Ying; Pan, Li

    2011-10-01

    Here, we report the complete annotated genome sequence of Bacillus amyloliquefaciens XH7, which is used to produce purine nucleosides in industry. The genome sequence will allow for the characterization of the molecular mechanisms underlying its beneficial properties.

  13. 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

  14. 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.

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

    PubMed

    Reem, G H

    1972-05-01

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

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

    PubMed

    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

  17. 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

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

    PubMed Central

    Ardente, AJ; Garrett, TJ; Wells, RS; Walsh, M; Smith, CR; Colee, J; Hill, RC

    2016-01-01

    Bottlenose dolphins managed under human care, human beings and Dalmatian dogs are prone to forming urate uroliths. Limiting dietary purine intake limits urate urolith formation in people and dogs because purines are metabolized to uric acid, which is excreted in urine. Managed dolphins develop ammonium urate nephroliths, whereas free-ranging dolphins do not. Free-ranging dolphins consume live fish, whereas managed dolphins consume different species that have been stored frozen and thawed. Differences in the purine content of fish consumed by dolphins under human care versus in the wild may be responsible for the difference in urolith prevalence. Commercially available purine assays measure only four purines, but reported changes in purines during frozen storage suggest that a wider range of metabolites should be measured when comparing fresh and stored fish. A method using high performance liquid chromatography with tandem mass spectrometry was developed to quantify eight purine metabolites in whole fish and squid commonly consumed by dolphins. The coefficient of variation within and among days was sometimes high for purines present in small amounts but was acceptable (≤ 25%) for guanine, hypoxanthine, and inosine, which were present in high concentrations. This expanded assay identified a total purine content up to 2.5 times greater than the total that would be quantified if only four purines were measured. Assuming additional purines are absorbed, these results suggest that additional purine metabolites should be measured to better understand the associated risk when fish or other purine-rich foods are consumed by people or animals prone to developing uroliths. PMID:27904786

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

    PubMed

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

    2016-10-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2017-05-01

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

  1. The Role of Gene Duplication in the Evolution of Purine Nucleotide Salvage Pathways

    NASA Astrophysics Data System (ADS)

    Becerra, Arturo; Lazcano, Antonio

    1998-10-01

    Purine nucleotides are formed de novo by a widespread biochemical route that may be of monophyletic origin, or are synthesized from preformed purine bases and nucleosides through different salvage pathways. Three monophyletic sets of purine salvage enzymes, each of which catalyzes mechanistically similar reactions, can be identified: (a) adenine-, xanthine-, hypoxanthine- and guanine-phosphoribosyltransferases, which are all homologous among themselves, as well as to nucleoside phosphorylases; (b) adenine deaminase, adenosine deaminase, and adenosine monophophate deaminase; and (c) guanine reductase and inosine monophosphate dehydrogenase. These homologies support the idea that substrate specificity is the outcome of gene duplication, and that the purine nucleotide salvage pathways were assembled by a patchwork process that probably took place before the divergence of the three cell domains (Bacteria, Archaea, and Eucarya). Based on the ability of adenine PRTase to catalyze the condensation of PRPP with 4-aminoimidazole-5-carboxamide (AICA), a simpler scheme of purine nucleotide biosynthesis is presented. This hypothetical route requires the prior evolution of PRPP biosynthesis. Since it has been argued that PRPP, nucleosides, and nucleotides are susceptible to hydrolysis, they are very unlikely prebiotic compounds. If this is the case, it implies that many purine salvage pathways appeared only after the evolution of phosphorylated sugar biosynthetic pathways made ribosides available.

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

    PubMed

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

    2013-09-01

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

  3. 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

  4. [Prevalence and causes of pain after cataract surgery: Comparison of 1st and 2nd eyes].

    PubMed

    Gayadine-Harricham, Y; Amzallag, T

    2017-06-01

    In our practice, patients undergoing bilateral cataract surgery complain of more significant pain after the 2nd eye surgery. The goal of this study was to compare postoperative pain between the 1st and 2nd eyes with cataract surgery under topical anesthesia and to identify the causes of this pain. We conducted a prospective observational study between May and September 2015. We included 69 consecutive adults scheduled for bilateral cataract surgery under topical anesthesia within 2 months by the same surgeon. A self-assessment questionnaire of anxiety (the Amsterdam Preoperative Anxiety and Information Scale [APAIS]) was completed before each procedure. Postoperative pain was assessed by the visual analogue scale (VAS) in the recovery room. Among the 69 included patients (mean age: 70±1.3 years), 13 (19%) experienced more pain after the 2nd eye procedure. The median VAS was 0 (EI: 0-1) after the first eye versus 0 (EI: 0-2) after the second eye (P=0.836). The patients with the most pain after the second eye surgery had a median anxiety score of 5 (EI: 4 to 9.5), which was comparable to those without pain (P=0.589). On bivariate analysis, women had more pain after second eye surgery (27%) than men (4%) (P=0.026). However, this association lost its significance when the analysis was adjusted for the level of anxiety (adjusted OR 7.7, 95% CI [0.91; 64.6]). In fact, women were more anxious [median anxiety score of 6 (EI: 4 to 8.5)] before 2nd eye surgery than men [median score: 4 (EI: 4-6); P=0.013]. Pain levels appeared to be very moderate on both sides when measured postoperatively, as opposed to statements often made in the immediate postoperative period. There is a discrepancy with the literature data. However, each study had small sample sizes. We did not find any significant difference in pain between 1st and 2nd eye cataract surgery under topical local anesthesia. While postoperative pain appeared greater among women, we have noted the possible influence of

  5. 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

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

    PubMed

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

    1989-04-01

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

  7. Purines, a new class of agonists in salivary glands?

    PubMed

    Dehaye, J P; Moran, A; Marino, A

    1999-05-01

    The response of rat submandibular glands to extracellular purines was tested. In crude cellular suspensions, ATP increased the [Ca2+]i mostly by promoting uptake of extracellular calcium. ATP caused the pHi to drop, a response blocked by chloride channel inhibitors. ATP also inhibited the basal and isoproterenol-stimulated activity of the Na+ -K+ -2Cl-cotransporter. These effects were reproduced by benzoyl-ATP, an agonist of ionotropic purinoceptors. In pure ductal suspensions, ATP activated a metabotropic P2Y1 purinergic receptor coupled to phospholipase C and opened a non-specific cation channel coupled to a P2X7 receptor. Activation of these receptors stimulated a Ca2+ -dependent and a Ca2+ -independent phospholipase A2, the latter resulting in kallikrein secretion. We conclude that purinergic agonists can modulate the activity of both acinar and ductal phases of secretion. Activation of metabotropic receptors coupled to phospholipase C could lead to responses resembling those to muscarinic or adrenergic agonists. Activation of ionotropic receptors could stimulate new intracellular responses also involved in secretory function.

  8. Pathophysiological roles for purines: adenosine, caffeine and urate

    PubMed Central

    Morelli, Micaela; Carta, Anna R; Kachroo, Anil; Schwarzschild, Michael A.

    2011-01-01

    The motor symptoms of Parkinson's disease (PD) are due primarily to the degeneration of the dopaminergic neurons in the nigrostriatal pathway. However, several other brain areas and neurotransmitters other than dopamine such as noradrenaline, 5-hydroxytryptamine and acetylcholine are affected in the disease. Moreover, adenosine because of the extensive interaction of its receptors with the dopaminergic system has been implicated in the in the pathophysiology of the disease. Based on the involvement of these nondopaminergic neurotransmitters in PD and the sometimes severe adverse effects that limit the mainstay use of dopamine-based antiparkinsonian treatments, recent assessments have called for a broadening of therapeutic options beyond the traditional dopaminergic drug arsenal. In this review we describe the interactions between dopamine and adenosine receptors that underpin the preclinical and clinical rationale for pursuing adenosine A2A receptor antagonists as symptomatic and potentially neuroprotective treatment of PD. The review will pay particular attention to recent results regarding specific A2A receptor-receptor interactions and recent findings identifying urate, the end product of purine metabolism, as a novel prognostic biomarker and candidate neuroprotectant in PD. PMID:20696321

  9. From formamide to purine: an energetically viable mechanistic reaction pathway.

    PubMed

    Wang, Jing; Gu, Jiande; Nguyen, Minh Tho; Springsteen, Greg; Leszczynski, Jerzy

    2013-02-28

    A step-by-step mechanistic pathway following the transformation of formamide to purine through a five-membered ring intermediate has been explored by density functional theory computations. The highlight of the mechanistic route detailed here is that the proposed pathway represents the simplest reaction pathway. All necessary reactants are generated from a single starting compound, formamide, through energetically viable reactions. Several important reaction steps are involved in this mechanistic route: formylation-dehydration, Leuckart reduction, five- and six-membered ring-closure, and deamination. On the basis of the study of noncatalytic pathways, catalytic water has been found to provide energetically viable step-by-step mechanistic pathways. Among these reaction steps, five-member ring-closure is the rate-determining step. The energy barrier (ca. 42 kcal/mol) of this rate-control step is somewhat lower than the rate-determining step (ca. 44 kcal/mol) for a pyrimidine-based pathway reported previously. The mechanistic pathway reported herein is less energetically demanding than for previously proposed routes to adenine.

  10. 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.

  11. 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.

  12. 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.

  13. Preventive medicine in Task Force 1st Armored Division during Operation Iraqi Freedom.

    PubMed

    Harris, Mark D; Johnson, Christopher R

    2006-09-01

    Task Force 1st Armored Division (TF1AD) deployed to Baghdad and South Central Iraq from April 2003 through July 2004. TF1AD preventive medicine had responsibility for ensuring divisional force health protection, including soldier health, disease and nonbattle injury mitigation, health promotion, and civil affairs operations. Heat injury, diarrheal disease, skin and respiratory disease, and eye and musculoskeletal injury rates were high. Command emphasis and preventive medicine action resulted in better living conditions and personal sanitation. To counter the threat, the TF1AD preventive medicine/ division surgeon team used a "spiraling out" approach that focused attention first on hand-washing, potable water, vector control, waste disposal, and food sanitation and later on noise, asbestos, environmental contamination, and radiation. In April 2004, TF1AD shifted focus to the Multinational Division Central-South region of Iraq and many similar problems occurred as in May 2003, although they were less severe, in part because of the lessons learned in Baghdad.

  14. Establishing the 1st Chinese National Standard for inactivated hepatitis A vaccine.

    PubMed

    Gao, Fan; Mao, Qun-Ying; Wang, Yi-Ping; Chen, Pan; Liang, Zheng-Lun

    2016-07-01

    A reference standard calibrated in the International Units is needed for the quality control of hepatitis A vaccine. Thus, National Institutes for Food and Drug Control launched a project to establish a non-adsorbed inactivated hepatitis A vaccine reference as the working standard calibrated against the 1st International Standard (IS). Two national standard candidates (NSCs) were obtained from two manufacturers, and designated as NSC A (lyophilized form) and NSC B (liquid form). Six laboratories participated in the collaborative study and were asked to use their in-house validated enzyme-linked immunosorbent assay methods to detect hepatitis A vaccine antigen content. Although both exhibited good parallelism and linear relationship with IS, NSC B showed a better agreement among laboratories than NSC A. And based on suitability of the candidates, NSC B was selected. The accelerated degradation study showed that NSC B was stable at the storage temperature (≤-70 °C). Therefore NSC B was approved as the first Chinese national antigen standard for inactivated hepatitis A vaccine, with an assigned antigen content of 70 IU/ml.

  15. 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.

  16. 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.

  17. 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.

  18. 1st ACT global trajectory optimisation competition: Results found at the Jet Propulsion Laboratory

    NASA Astrophysics Data System (ADS)

    Petropoulos, Anastassios E.; Kowalkowski, Theresa D.; Vavrina, Matthew A.; Parcher, Daniel W.; Finlayson, Paul A.; Whiffen, Gregory J.; Sims, Jon A.

    2007-11-01

    Results obtained at the Jet Propulsion Laboratory for the 1st ACT global trajectory optimisation competition are presented and the methods used to obtain them are described. The search for the globally optimal, low-thrust, gravity-assist trajectory for maximally deflecting an asteroid is performed in two steps. The first step involves a rough global search of the global search space, which has, however, been somewhat bounded based on prior mission-design experience, intuition, and energy arguments. A shape-based method is used to represent the low-thrust arcs, while the ballistic portions are searched almost exhaustively. The second step involves local optimisation of trajectories which stand out from the rough global search. The low-thrust optimisation problem is turned into a parameter optimisation problem by approximating the continuous thrusting as a series of impulsive manoeuvres. Of the many trajectories found, three optimal trajectories are reported and compared, including the one submitted for the competition. The best one employed a double-Venus, quadruple-Earth, Jupiter Saturn Jupiter gravity-assist sequence. The trajectory submitted for the competition used one less Venus flyby and one less Earth flyby.

  19. Parenting and Preschool Self-Regulation as Predictors of Social Emotional Competence in 1st Grade

    PubMed Central

    Russell, Beth S.; Lee, Jungeun Olivia; Spieker, Susan; Oxford, Monica L.

    2016-01-01

    The current longitudinal study used data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care and Youth Development (SECCYD) to examine a model of development that emphasizes early caregiving environments as predictors of social emotional competence (including classroom competence). This path analysis model included features of parenting, emotion regulation, preschool language skills, and attention to predict child outcomes in 1st grade. Early caregiving environments were directly predictive of peer relationship satisfaction, oppositional behavior, social skills, and classroom competence over and above significant mediated effects through preschool self regulation (language, inattention, and anger/frustration). These results suggest that the characteristics of supportive and stimulating caregiving shift in valence over time, such that qualities of the infant-child relationship that are significant in predicting early childhood outcomes are not the same as the caregiving qualities that move to the foreground in predicting primary school outcomes. Implications for school-readiness programming are discussed, including interventions in the early caregiving system to encourage sensitive and supportive parent child interactions to bolster school readiness via the development of social-emotional competence. PMID:27616805

  20. Providing simulation experiences for large cohorts of 1st year nursing students: evaluating quality and impact.

    PubMed

    Rochester, Suzanne; Kelly, Michelle; Disler, Rebecca; White, Haidee; Forber, Jan; Matiuk, Sonia

    2012-01-01

    To provide each student within a large cohort the opportunity to participate in a small group simulation that meets recognised quality indicators is a challenge for Bachelor of Nursing programmes in Australia. This paper, as part of a larger longitudinal study, describes one approach used to manage a simulation for 375 1st year nursing students and to report on the quality of the experience from the student's perspective. To ensure quality was maintained within the large cohort, aspects of the simulation were assessed against the following indicators: alignment with curriculum pedagogy and goals; preparation of students and staff; fidelity; and debriefing. Data obtained from a student focus group were analysed in the context of the quality indicators. The following themes emerged from the data: knowing what to expect; assuming roles for the simulation; authenticity and thinking on your feet; feeling the RN role; and, preparation for clinical practice. This paper demonstrates it is possible to provide students in large cohorts with active participatory roles in simulations whilst maintaining quality indicators.

  1. The Current Status of the 1st Electromagnetism Satellite Mission in China

    NASA Astrophysics Data System (ADS)

    Shen, Xuhui; Wang, Lanwei; Zhang, Xuemin; Yuan, Shigeng

    2014-05-01

    The 1st China Electromagnetism Satellite now is on its Phase C for Electrical Mode and Qualification mode. And according to the developing schedule, the satellite is due to be launched before the end of 2016. The first electromagnetism satellite is defined as an experiment satellite with it's major scientific objectives to monitor the global electromagnetic fields as well as plasma distribution in ionosphere, to provide seismo-eletromagnetic information for studying earthquake mechanism and short-term prediction of large earthquakes, and to share the data with earthquake sciences and space sciences. The satellite will work on Sun synchronous orbit with the attitude of about 500km and descending node 14:00LT. The payload assembly are as following: Search Coil Magnetometer, Electric Field Detector, Flux-Gate Magnetometer, Plasma Analyser, Langmuir Probe, GNSS Two-frequency Receiver, Three-frequency Transmitter, Energetic Particle Detector. The main physical parameters and products of the mission are electromagnetic field and electromagnetic wave, plasma density, temperature, and tomography in ionosphere, high energy particle disturbance, etc. The Chinese work team is ready to open the data and jointly research on common topics with international colleagues.

  2. Calibration and commutability assessment of the 1st International Standard for Diphtheria Antitoxin Human.

    PubMed

    Stickings, Paul; Rigsby, Peter; Coombes, Laura; von Hunolstein, Christina; Ralli, Luisa; Pinto, Antonella; Sesardic, Dorothea

    2013-11-01

    The 1st International Standard for Diphtheria Antitoxin Human (coded 10/262) was established by the World Health Organization Expert Committee on Biological Standardization in 2012. This paper describes the production, characterization and calibration of the new standard which is intended for use in the standardization of assays used to measure diphtheria antibody responses in human serum. The new standard was calibrated in terms of the International Standard for Diphtheria Antitoxin Equine in an international collaborative study. A total of 8 participants from 8 different countries performed in vivo and/or in vitro toxin neutralization tests and returned data that was used to assign units to the proposed new standard. The new standard has a diphtheria antitoxin potency of 2 IU/ampoule and is predicted to be stable. A follow up study was performed to assess commutability of the new standard. The follow up study was an existing external quality assessment, modified to include the new standard. Results obtained suggest that the new standard is commutable, showing comparable behaviour to native human serum samples in the majority of the assays compared, and is therefore suitable for use as a reference preparation in assays used to measure the level of anti-diphtheria antibodies in human serum.

  3. 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.

  4. 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…

  5. 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…

  6. 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...

  7. 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…

  8. 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…

  9. Comparative analysis of 1st, 2nd, and 4th year MD students' attitudes toward Complementary Alternative Medicine (CAM)

    PubMed Central

    Riccard, Christopher P; Skelton, Michele

    2008-01-01

    Background To identify and report the attitudes and beliefs of 1st, 2nd, and 4th year medical students toward complementary alternative medicine (CAM). Methods The previously validated and reliability tested CHBQ was administered to medical students attending the University of South Florida School of Medicine. Results Significant changes were found between both 1st (46.0 ± 7.7) and 4th (37.8 ± 15.7) year students and 2nd (48.3 ± 7.8) and 4th (37.8 ± 15.7) year students. No significant difference was found between 1st (46.0 ± 7.7) and 2nd (48.3 ± 7.8) year students. When comparing scores based on gender, a significant difference was present between males (41.2 ± 12.2) and females (46.1 ± 11.0). Conclusion CHBQ scores were significantly more positive in both 1st and 2nd year medical students in comparison with 4th year student's scores. These findings suggest that as student exposure to allopathic techniques and procedures increases during the last year of medical school, their attitudes toward CAM decrease. Females were also significantly more likely to have stronger positive attitudes toward CAM than males, though both genders represented an overall positive attitude toward CAM. PMID:18799010

  10. 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…

  11. Reselecting 1st grade area of Environmental Conservation Value Assessment Map by Using Frequency ratio and Regression model

    NASA Astrophysics Data System (ADS)

    Park, Y.

    2016-12-01

    Environmental Conservation Value Assessment Map (ECVAM) is a five grade assessment map divides country 5 grade by superposition various maps to comprehensive assessment of environmental information of land use. The equivalent-weighting method and least-index method is typical features of this map. Prior makes it possible to maintain objectivity When assigning value to each item and latter assigns the highest grade to a conservation zone if it has received multiple grades. There has been relatively steady research of Environmental Conservation Value Assessment Map (ECVAM) in the country. In particular, the studies most focus on the research of improving or introducing new criteria filling. But there are few research on the over-allocation of 1st grade area of map. The 1st grade of the map is development impossible area which amounts 40% of the map. But it is often questionable whether an appropriate part of the value to be given as a class. Therefore in this research, frequency ratio analysis and logistic regression model are used to reselect 1st grade of Environmental Conservation Value Assessment Map (ECVAM). Results show that current map of 1st grade is overestimated. This research will contribute when renewal Environmental Conservation Value Assessment Map (ECVAM).

  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. A 1st-Grade Teacher's Survival Guide to the Implementation and Management of Literacy Centers During Guided Reading

    ERIC Educational Resources Information Center

    Kieff, Judith

    2005-01-01

    This Classroom Idea Sparker was submitted by Pandora Zook, a 1st-grade teacher at Guilford Elementary School in Sterling, Virginia. She shares her experiences in creating self-guided literacy centers that run smoothly and encourage children to be constructively engaged in learning activities that do not require constant direct supervision.

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

    PubMed

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

    2005-06-01

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

  15. Helicobacter pylori Salvages Purines from Extracellular Host Cell DNA Utilizing the Outer Membrane-Associated Nuclease NucT

    PubMed Central

    Liechti, George W.

    2013-01-01

    Helicobacter pylori is a bacterial pathogen that establishes life-long infections in humans, and its presence in the gastric epithelium is strongly associated with gastritis, peptic ulcer disease, and gastric cancer. Having evolved in this specific gastric niche for hundreds of thousands of years, this microbe has become dependent on its human host. Bioinformatic analysis reveals that H. pylori has lost several genes involved in the de novo synthesis of purine nucleotides, and without this pathway present, H. pylori must salvage purines from its environment in order to grow. While the presence and abundance of free purines in various mammalian tissues has been loosely quantified, the concentration of purines present within the gastric mucosa remains unknown. There is evidence, however, that a significant amount of extracellular DNA is present in the human gastric mucosal layer as a result of epithelial cell turnover, and this DNA has the potential to serve as an adequate purine source for gastric purine auxotrophs. In this study, we characterize the ability of H. pylori to grow utilizing only DNA as a purine source. We show that this ability is independent of the ComB DNA uptake system, and that H. pylori utilization of DNA as a purine source is largely influenced by the presence of an outer membrane-associated nuclease (NucT). A ΔnucT mutant exhibits significantly reduced extracellular nuclease activity and is deficient in growth when DNA is provided as the sole purine source in laboratory growth media. These growth defects are also evident when this nuclease mutant is grown in the presence of AGS cells or in purine-free tissue culture medium that has been conditioned by AGS cells in the absence of fetal bovine serum. Taken together, these results indicate that the salvage of purines from exogenous host cell DNA plays an important role in allowing H. pylori to meet its purine requirements for growth. PMID:23893109

  16. Lactobacillus gasseri PA-3 Uses the Purines IMP, Inosine and Hypoxanthine and Reduces their Absorption in Rats.

    PubMed

    Yamada, Naruomi; Saito-Iwamoto, Chizuru; Nakamura, Marie; Soeda, Misato; Chiba, Yoshika; Kano, Hiroshi; Asami, Yukio

    2017-03-08

    Excessive intake of purine-rich foods elevates serum levels of uric acid. Animal and fish meats contain high amounts of inosine and its related purines, and the reduction of taking those purines is crucial for the improvement of serum uric acid levels. We previously showed that Lactobacillus gasseri PA-3 (PA-3) incorporates adenosine and its related purines and that oral treatment with PA-3 reduced adenosine absorption in rats. This study investigated whether PA-3 also incorporates IMP (inosine 5'-monophosphate), inosine, and hypoxanthine, and whether it reduces their absorption in rats. PA-3 was incubated in vitro with radioisotope (RI)-labeled IMP, inosine, and hypoxanthine, and the incorporation of these compounds by PA-3 was evaluated. In addition, rats were orally administered PA-3 along with RI-labeled inosine 5'-monophosphate, inosine, or hypoxanthine, and the ability of PA-3 to attenuate the absorption of these purines was determined. PA-3 incorporated all three purines and displayed greater proliferation in the presence than in the absence of these purines. Oral administration of PA-3 to rats reduced the absorption of IMP, inosine, and hypoxanthine. These results indicate that PA-3 reduces the absorption of purines contained in foods and it is expected that PA-3 contributes attenuation of the excessive intake of dietary purines.

  17. Lactobacillus gasseri PA-3 Uses the Purines IMP, Inosine and Hypoxanthine and Reduces Their Absorption in Rats

    PubMed Central

    Yamada, Naruomi; Saito-Iwamoto, Chizuru; Nakamura, Marie; Soeda, Misato; Chiba, Yoshika; Kano, Hiroshi; Asami, Yukio

    2017-01-01

    Excessive intake of purine-rich foods elevates serum levels of uric acid. Animal and fish meats contain high amounts of inosine and its related purines, and the reduction of taking those purines is crucial for the improvement of serum uric acid levels. We previously showed that Lactobacillus gasseri PA-3 (PA-3) incorporates adenosine and its related purines and that oral treatment with PA-3 reduced adenosine absorption in rats. This study investigated whether PA-3 also incorporates IMP (inosine 5′-monophosphate), inosine, and hypoxanthine, and whether it reduces their absorption in rats. PA-3 was incubated in vitro with radioisotope (RI)-labeled IMP, inosine, and hypoxanthine, and the incorporation of these compounds by PA-3 was evaluated. In addition, rats were orally administered PA-3 along with RI-labeled inosine 5′-monophosphate, inosine, or hypoxanthine, and the ability of PA-3 to attenuate the absorption of these purines was determined. PA-3 incorporated all three purines and displayed greater proliferation in the presence than in the absence of these purines. Oral administration of PA-3 to rats reduced the absorption of IMP, inosine, and hypoxanthine. These results indicate that PA-3 reduces the absorption of purines contained in foods and it is expected that PA-3 contributes attenuation of the excessive intake of dietary purines. PMID:28282902

  18. Autoimmune dysregulation and purine metabolism in adenosine deaminase deficiency.

    PubMed

    Sauer, Aisha Vanessa; Brigida, Immacolata; Carriglio, Nicola; Aiuti, Alessandro

    2012-01-01

    Genetic defects in the adenosine deaminase (ADA) gene are among the most common causes for severe combined immunodeficiency (SCID). ADA-SCID patients suffer from lymphopenia, severely impaired cellular and humoral immunity, failure to thrive, and recurrent infections. Currently available therapeutic options for this otherwise fatal disorder include bone marrow transplantation (BMT), enzyme replacement therapy with bovine ADA (PEG-ADA), or hematopoietic stem cell gene therapy (HSC-GT). Although varying degrees of immune reconstitution can be achieved by these treatments, breakdown of tolerance is a major concern in ADA-SCID. Immune dysregulation such as autoimmune hypothyroidism, diabetes mellitus, hemolytic anemia, and immune thrombocytopenia are frequently observed in milder forms of the disease. However, several reports document similar complications also in patients on long-term PEG-ADA and after BMT or GT treatment. A skewed repertoire and decreased immune functions have been implicated in autoimmunity observed in certain B-cell and/or T-cell immunodeficiencies, but it remains unclear to what extent specific mechanisms of tolerance are affected in ADA deficiency. Herein we provide an overview about ADA-SCID and the autoimmune manifestations reported in these patients before and after treatment. We also assess the value of the ADA-deficient mouse model as a useful tool to study both immune and metabolic disease mechanisms. With focus on regulatory T- and B-cells we discuss the lymphocyte subpopulations particularly prone to contribute to the loss of self-tolerance and onset of autoimmunity in ADA deficiency. Moreover we address which aspects of immune dysregulation are specifically related to alterations in purine metabolism caused by the lack of ADA and the subsequent accumulation of metabolites with immunomodulatory properties.

  19. Effects of NAD at purine receptors in isolated blood vessels.

    PubMed

    Alefishat, E; Alexander, S P H; Ralevic, V

    2015-03-01

    Nicotinamide adenine dinucleotide (NAD) belongs to the family of naturally occurring adenine dinucleotides, best known for their various intracellular roles. However, there is evidence that they can also be released from cells to act as novel extracellular signalling molecules. Relatively little is known about the extracellular actions of NAD, especially in the cardiovascular system. The present study investigated the actions of NAD in the rat thoracic aorta, porcine coronary artery and porcine mesenteric arteries, mounted in organ baths for isometric tension recording. In the rat thoracic aorta and porcine coronary artery, NAD caused endothelium-independent concentration-dependent vasorelaxations which were unaffected by palmitoylCoA, a P2Y1 receptor antagonist, but which were blocked by CGS15943, a non-selective adenosine receptor antagonist. In the porcine coronary artery, NAD-evoked relaxations were abolished by SCH58261, a selective A2A receptor antagonist. In the rat thoracic aorta, NAD-evoked relaxations were attenuated by A2A receptor antagonism with SCH58261 but were unaffected by an A2B receptor antagonist, MRS1754. In contrast, in the porcine mesenteric artery, NAD-evoked endothelium-independent contractions, which were unaffected by a P2 receptor antagonist, suramin, or by NF449, a P2X1 receptor antagonist, but were attenuated following P2X receptor desensitisation with αβ-meATP. In conclusion, the present results show that NAD can alter vascular tone through actions at purine receptors in three different arteries from two species; its molecular targets differ according to the type of blood vessel.

  20. 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

  1. Prevalence of injuries in Wushu competition during the 1st Asian Martial Arts Games 2009.

    PubMed

    Yiemsiri, Pichet; Wanawan, Amarin

    2014-02-01

    To determine the prevalence and characteristic of injuries in Wushu Competition during the IP' Asian MartialArts Games 2009. Sixty international athletes (38 males) participating in Wushu Competition during the 1st Asian Martial Arts Games 2009. Injuries were recorded on injury report forms to document any injuries seen and treatment provided by tournament physician during competitions. The injury forms described the athlete s causes, type, site, and severity of the injuries. There were 60 international athletes the average age were 22.49 +/- 3.75 years. The prevalence ofinjuries was 228.07/ 1000 athlete exposure (AE). The prevalence in males andfemales was 161.76/1000 AE and 326.09/1000 AE, respectively. The most common injured body parts in males were lower extremities 102.94/1000 AE, followed by head and face injuries 58.82/1000 AE. The most common injured body parts in females were lower extremities 282.61/1000 AE. The most common types of injuries in males were contusions 58.82/1000 AE, concussion 29.41/1000 AE and strain-sprain 29.41/1000 AE. In females the most common type of injury were contusion 195.65/1000 AEfollowed by strain-sprain 130.43/1000 AE. The most common mechanism of injury in males werereceiving a punch 58.82/1000 AE, receiving a kick 44.12/1000 AE and delivering a kick 44.12/1000 AE. Meanwhile, in females common mechanisms were receiving a kick 152.17/1000 AE followed by delivering a kick 130.43/1000 AE. High prevalence of injuries in Wushu competition during the 1" Asian MartialArts Games 2009 revealedfemale injuries were higher than male and had a higher prevalence compared with Muay Thai or Taekwondo competitions.

  2. Meteorological features associated with unprecedented precipitation over India during 1st week of March 2015

    NASA Astrophysics Data System (ADS)

    Kumar, Naresh; Mohapatra, M.; Jaswal, A. K.

    2017-07-01

    Unprecedented precipitation along with heavy falls occurred over many parts of India from 28th February to 2nd March 2015. Many of the stations of northwest and central India received an all time high 24 hr cumulative precipitation of March during this period. Even the national capital, New Delhi, broke all the previous historical 24 hr rainfall records of the last 100 years to the rainfall record in March 2015. Due to this event, huge loss to agricultural and horticultural crops occurred in several parts of India. In the present study, an attempt is made to understand the various meteorological features associated with this unprecedented precipitation event over India. It occurred due to the presence of an intense western disturbance (WD) over Afghanistan and neighbouring areas in the form of north-south oriented deep trough in westerlies in middle and upper tropospheric levels with its southern end deep in the Arabian Sea, which pumped huge moisture feed over Indian region. Also, there was a jet stream with core wind speed up to 160 knots that generated high positive divergence at upper tropospheric level over Indian region; along with this there was high magnitude of negative vertical velocity and velocity convergence were there at middle tropospheric level. It caused intense upward motion and forced lower levels air to rise and strengthen the lower levels cyclonic circulations (CCs)/Lows. Moreover, the induced CCs/Lows at lower tropospheric levels associated with WD were more towards south of its normal position. Additionally, there was wind confluence over central parts of India due to westerlies in association with WD and easterlies from anticyclone over north Bay of Bengal. Thus, intense WD along with wind confluence between westerlies and easterlies caused unprecedented precipitation over India during the 1st week of March 2015.

  3. 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

  4. 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.

  5. Information and Productivity--Implications for Education and Training. Report of a Joint UK/US Seminar (1st Cranfield, England, July 27-30, 1984).

    ERIC Educational Resources Information Center

    National Commission on Libraries and Information Science, Washington, DC.

    A small group of top-level experts on information and productivity and other key decision makers met to discuss information and productivity and its implications for education. The meeting was the first in a proposed series of bilateral meetings between individuals in the library/information field in the United States (US) and the United Kingdom…

  6. 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

  7. Coordinate developmental regulation of purine catabolic enzyme expression in gastrointestinal and postimplantation reproductive tracts

    PubMed Central

    1991-01-01

    Using histochemical detection, we have visualized in situ the complete metabolic pathway for the degradation of purine nucleotides. From the tongue to the ileum, diverse epithelial cell types lining the lumen of the mouse gastrointestinal (GI) tract strongly coexpress each of the five key purine catabolic enzymes. Dramatic increases in the expression of each enzyme occurred during postnatal maturation of the GI tract. Using in situ hybridization, an intense accumulation of adenosine deaminase (ADA) mRNA was detected only within GI epithelial cells undergoing postmitotic differentiation. In a similar manner, at the developing maternal-fetal interface, high level expression of the purine catabolic pathway also occurred in a unique subset of maternal decidual cells previously known to express high levels of alkaline phosphatase and ADA. This induction occurred almost immediately after implantation in the periembryonic maternal decidual cells, shortly thereafter in antimesometrial decidual cells, and later in cells of the placental decidua basalis: all of which contain cell types thought to be undergoing programmed cell death. The expression of the pathway at the site of embryo implantation appears to be critical because its pharmacologic inhibition during pregnancy has been found to be embryolethal or teratogenic. Purine destruction at these nutritional interfaces (placenta and gastrointestinal tract) seem to override any potential economy of purine salvage, and may represent biochemical adaptation to nucleic acid breakdown occurring in the context of dietary digestion or extensive programmed cell death. PMID:1918135

  8. Extracellular conversion of guanine-based purines to guanosine specifically enhances astrocyte glutamate uptake.

    PubMed

    Frizzo, Marcos Emílio dos Santos; Antunes Soares, Félix Alexandre; Dall'Onder, Leonara Patrícia; Lara, Diogo Rizzato; Swanson, Raymond A; Souza, Diogo Onofre

    2003-05-16

    Guanosine (GUO) has been shown to stimulate glutamate uptake in primary astrocyte cultures. The purpose of this study was to determine the effect and specificity of guanine- or adenine-based purines on glutamate and GABA uptake in cultured astrocytes. Stimulatory effect on glutamate uptake was observed with GUO, GMP or GTP. Simultaneous exposure with these guanine-based purines did not show an additive effect. We also investigated a possible interconversion of guanine-based purines during incubation time. Action by GTP was excluded since the hydrolysis resistant GTP analog, GMP-PNP did not stimulate glutamate uptake. Addition of an ecto-5'-nucleotidase inhibitor abolished GMP-stimulatory effect on glutamate uptake, without affecting GUO action. Taken together, these results suggest that GUO is the guanine-based purines responsible for glutamate uptake activation. In addition, the stimulatory effect on glutamate uptake was not observed with adenine-based purines. Moreover, GABA uptake was not activated by GUO. These results point to specificity in the interaction between GUO and the astrocyte glutamate uptake system.

  9. 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.

  10. 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.

  11. Purine nucleoside phosphorylase deficiency in a patient with spastic paraplegia and recurrent infections.

    PubMed

    Ozkinay, Ferda; Pehlivan, Sacide; Onay, Huseyin; van den Berg, Paul; Vardar, Fadil; Koturoglu, Guldane; Aksu, Guzide; Unal, Durisehvar; Tekgul, Hasan; Can, Sema; Ozkinay, Cihangir

    2007-06-01

    Purine nucleoside phosphorylase deficiency is a rare autosomal recessive immunodeficiency disease. The characteristic features of the disease include severe T cell immune defects with recurrent infections, a failure to thrive, and progressive neurological findings. To date, 35 cases of purine nucleosidase phosphorylase deficiency have been reported worldwide. A 2-year-old female patient was hospitalized due to recurrent infections starting from 6 months and a fever that had continued for a month. The parents were first cousins. Physical examination showed a failure to thrive, herpetic lesions around the lips, painful lesions on the tongue and the buccal mucosa, lung infection, and spastic paraparesis in the lower extremities. She had motor and mental retardation. Laboratory tests revealed lymphopenia; low CD3, CD4, and CD8 counts; normal immunoglobulin levels; low uric acid; and very low purine nucleoside phosphorylase enzyme activity (1.4 nmol/h/mg; normal range, 490-1530). DNA sequencing of the purine nucleosidase phosphorylase gene revealed a missense homozygous mutation, a G to A transition at exon 4 position 64 (349G>A transition), which led to a substitution of alanine by threonine at codon 117 (Ala117Thr). Both parents were heterozygous for the mutation. This is the second purine nucleosidase phosphorylase deficient case to have been presented and carrying this mutation worldwide. Various antibiotics, antifungal drugs, and intravenous immunoglobulin were used to treat the infections during her 3 months. This form of treatment proved to be unresponsive, resulting in her subsequent death at 26 months of age.

  12. Drosophila melanogaster Prat, a Purine de Novo Synthesis Gene, Has a Pleiotropic Maternal-Effect Phenotype

    PubMed Central

    Malmanche, Nicolas; Clark, Denise V.

    2004-01-01

    In Drosophila melanogaster, two genes, Prat and Prat2, encode the enzyme, amidophosphoribosyltransferase, that performs the first and limiting step in purine de novo synthesis. Only Prat mRNA is present in the female germline and 0- to 2-hr embryos prior to the onset of zygotic transcription. We studied the maternal-effect phenotype caused by Prat loss-of-function mutations, allowing us to examine the effects of decreased purine de novo synthesis during oogenesis and the early stages of embryonic development. In addition to the purine syndrome previously characterized, we found that Prat mutant adult females have a significantly shorter life span and are conditionally semisterile. The semisterility is associated with a pleiotropic phenotype, including egg chamber defects and later effects on embryonic and larval viability. Embryos show mitotic synchrony and/or nuclear content defects at the syncytial blastoderm stages and segmentation defects at later stages. The semisterility is partially rescued by providing Prat mutant females with an RNA-enriched diet as a source of purines. Our results suggest that purine de novo synthesis is a limiting factor during the processes of cellular or nuclear proliferation that take place during egg chamber and embryonic development. PMID:15611171

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

    PubMed

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

    2015-03-01

    Determination of adenine, hypoxanthine, guanine and xanthine in different parts of pork and beef using high performance liquid chromatography was described. Chromatographic separation was carried out on Waters Atlantis T3 column (4.6 mm × 250 mm × 5 μm) with column temperature at 30 °C. The mobile phase contained 99% 10.0 mmol/L ammonium formate solution at pH 3.6 and 1.0% methanol. Chromatography was achieved at a flow rate of 1.0 mL/min and detection wavelength at 254 nm. The results indicated that total purine amounts in pork rump and beef sirloin were higher than those in other parts (P<0.05). The principal purine bases were hypoxanthine and adenine, and hypoxanthine content was the most highest in all samples (P<0.05). As pork rump and beef sirloin contain considerable amounts of total purine and uricogenic purine base, we suggest that excess consumption of them be avoid, whereas pork loin chop and beef rib eye are more suitable for a low-purine diet. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. SU-E-T-188: Commission of World 1st Commercial Compact PBS Proton System

    SciTech Connect

    Ding, X; Patel, B; Song, X; Syh, J; Syh, J; Zhang, J; Freund, D; Rosen, L; Wu, H

    2015-06-15

    Purpose: ProteusONE is the 1st commercial compact PBS proton system with an upstream scanning gantry and C230 cyclotron. We commissioned XiO and Raystation TPS simultaneously. This is a summary of beam data collection, modeling, and verification and comparison without range shiter for this unique system with both TPS. Methods: Both Raystation and XiO requires the same measurements data: (i) integral depth dose(IDDs) of single central spot measured in water tank; (ii) absolute dose calibration measured at 2cm depth of water with mono-energetic 10×10 cm2 field with spot spacing 4mm, 1MU per spot; and (iii) beam spot characteristics in air at 0cm and ± 20cm away from ISO. To verify the beam model for both TPS, same 15 cube plans were created to simulate different treatment sites, target volumes and positions. PDDs of each plan were measured using a Multi-layer Ionization Chamber(MLIC), absolute point dose verification were measured using PPC05 in water tank and patient-specific QA were measured using MatriXX PT, a 2D ion chamber array. Results: All the point dose measurements at midSOBP were within 2% for both XiO and Raystation. However, up to 5% deviations were observed in XiO’s plans at shallow depth while within 2% in Raystation plans. 100% of the ranges measured were within 1 mm with maximum deviation of 0.5 mm. 20 patient specific plan were generated and measured in 3 planes (distal, proximal and midSOBP) in Raystation. The average of gamma index is 98.7%±3% with minimum 94% Conclusions: Both TPS were successfully commissioned and can be safely deployed for clinical use for ProteusONE. Based on our clinical experience in PBS planning, user interface, function and workflow, we preferably use Raystation as our main clinical TPS. Gamma Index >95% at 3%/3 mm criteria is our institution action level for patient specific plan QAs.

  15. 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

  16. PREFACE: 1st-2nd Young Researchers Meetings in Rome - Proceedings

    NASA Astrophysics Data System (ADS)

    YRMR Organizing Committee; Cannuccia, E.; Mazzaferro, L.; Migliaccio, M.; Pietrobon, D.; Stellato, F.; Veneziani, M.

    2011-03-01

    Students in science, particularly in physics, face a fascinating and challenging future. Scientists have proposed very interesting theories, which describe the microscopic and macroscopic world fairly well, trying to match the quantum regime with cosmological scales. Between the extremes of this scenario, biological phenomena in all their complexity take place, challenging the laws we observe in the atomic and sub-atomic world. More and more accurate and complex experiments have been devised and these are now going to test the paradigms of physics. Notable experiments include: the Large Hadronic Collider (LHC), which is going to shed light on the physics of the Standard Model of Particles and its extensions; the Planck-Herschel satellites, which target a very precise measurement of the properties of our Universe; and the Free Electron Lasers facilities, which produce high-brilliance, ultrafast X-ray pulses, allowing the investigation of the fundamental processes of solid state physics, chemistry, and biology. These projects are the result of huge collaborations spread across the world, involving scientists belonging to different and complementary research fields: physicists, chemists, biologists and others, keen to make the best of these extraordinary laboratories. Even though each branch of science is experiencing a process of growing specialization, it is very important to keep an eye on the global picture, remaining aware of the deep interconnections between inherent fields. This is even more crucial for students who are beginning their research careers. These considerations motivated PhD students and young post-docs connected to the Roman scientific research area to organize a conference, to establish the background and the network for interactions and collaborations. This resulted in the 1st and 2nd Young Researchers Meetings in Rome (http://ryrm.roma2.infn.it), one day conferences aimed primarily at graduate students and post-docs, working in physics in Italy

  17. 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

  18. The Formation of Nucleobases from the Ultraviolet Photoirradiation of Purine in Simple Astrophysical Ice Analogues

    NASA Astrophysics Data System (ADS)

    Materese, Christopher K.; Nuevo, Michel; Sandford, Scott A.

    2017-08-01

    Nucleobases are the informational subunits of RNA and DNA and are essential to all known forms of life. The nucleobases can be divided into two groups of molecules: the pyrimidine-based compounds that include uracil, cytosine, and thymine, and the purine-based compounds that include adenine and guanine. Previous work in our laboratory has demonstrated that uracil, cytosine, thymine, and other nonbiological, less common nucleobases can form abiotically from the UV photoirradiation of pyrimidine in simple astrophysical ice analogues containing combinations of H2O, NH3, and CH4. In this work, we focused on the UV photoirradiation of purine mixed with combinations of H2O and NH3 ices to determine whether or not the full complement of biological nucleobases can be formed abiotically under astrophysical conditions. Room-temperature analyses of the resulting photoproducts resulted in the detection of adenine, guanine, and numerous other functionalized purine derivatives.

  19. 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

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

    PubMed

    Scheffler, P; Haghchenas, D; Wigand, R

    1975-04-01

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

  1. Dephosphorylation of purine mononucleotides by alkaline phosphatases. Substrate specificity and inhibition patterns.

    PubMed

    Jensen, M H

    1979-11-09

    Three purine mononucleotides, adenosine-, inosine- and guanosine monophosphate, were used as substrates at pH 7.4 and at 10.4 for three alkaline phosphatases (orthophosphoric-monoester phosphohydrolase (acid optimum), EC 3.1.3.1) containing similar phosphate-binding serine groups at their esteratic sites. Substrate specificity was found for the enzymes from calf intestine and bovine liver. Alkaline phosphatase from Escherichia coli was nonspecific. A substrate-dependent and pronounced inhibition with the purine analogue 1,3-dimethyl xanthine was found for the enzymes from intestine and liver, but not for alkaline phosphatase from E. coli. A substrate-independent and pronounced inhibition was found for all three enzymes with the phosphomonoester p-nitrophenol phosphate as the inhibitor. Alkaline phosphatases may play an important role in the regulation of the intracellular content of purine mononucleotides.

  2. Analysis of mixtures of purines and pyrimidines by first- and second-derivative ultraviolet spectrometry.

    PubMed

    Aaron, J J; Gaye, M D

    1988-07-01

    Zero-order, first-derivative and second-derivative ultraviolet absorption spectra of a series of purines, pyrimidines and their binary mixtures in aqueous solution have been recorded at 298 K. It is shown that second-derivative spectra can be used for the identification of eight mixtures of purines and pyrimidines. Several graphical procedures are tested for evaluating derivative spectra in quantitative measurements of single compounds and mixtures. Linear log-log calibration plots are obtained with correlation coefficients generally larger than 0.99. Second-derivative spectra appear to provide a precise and simple method for determination of purines and pyrimidines, at concentrations ranging between 5 x 10(-6) and 5 x 10(-4)M.

  3. 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).

  4. Purine enzyme activities in recent onset rheumatoid arthritis: are there differences between patients and healthy controls?

    PubMed Central

    Stolk, J N; Boerbooms, A M; De Abreu, R A; Kerstens, P J; de Koning, D G; de Graaf, R; Mulder, J; van de Putte, L B

    1996-01-01

    OBJECTIVE: Purine enzyme activities may predict the effectiveness of azathioprine treatment and be associated with increased deaths from infectious diseases. In rheumatoid arthritis, patients show variable responses to azathioprine and a higher percentage of death is caused by infections. The aim of the study was to investigate possible rheumatoid arthritis associated abnormalities of purine enzyme activities by measuring several of these enzymes in patients with recent onset rheumatoid arthritis before treatment with disease modifying antirheumatic drugs or prednisone. METHODS: 23 patients with recent onset rheumatoid arthritis and 28 healthy controls were studied. Activities of the enzymes 5'-nucleotidase, purine nucleoside phosphorylase (PNP), hypoxanthine guanine phosphoribosyltransferase (HGPRT), and thiopurine methyltransferase (TPMT) were measured. Assessment of disease activity and blood sampling for routine measurements and HLA typing were done simultaneously. RESULTS: Purine enzyme activities did not differ between patients and healthy controls. Enzyme activities had no significant relations with indices of disease activity or rheumatoid factor titre or with the rheumatoid arthritis associated HLA types. Activity of 5'nucleotidase decreased with age (P < or = 0.05) and was lower by about 27% (P = 0.007) in males than in females. CONCLUSIONS: In rheumatoid arthritis patients, neither the variability in azathioprine effectiveness nor the increased death rate from infections can be explained by pre-existing abnormalities in the activities of the purine enzymes 5'-nucleotidase, PNP, HGPRT, or TPMT at an early stage of the disease, before disease modifying antirheumatic drugs or prednisone treatment. Besides adjustment for age, results of studies involving purine 5' nucleotidase activity should also be adjusted for sex. PMID:8984938

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

    PubMed

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

    2016-11-01

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

  6. Inhibitors of the purine salvage pathway: a valuable approach for antiprotozoal chemotherapy?

    PubMed

    Berg, M; Van der Veken, P; Goeminne, A; Haemers, A; Augustyns, K

    2010-01-01

    For many years, the purine salvage pathway of parasitic protozoa has been regarded as an attractive chemotherapeutic target. Parasitic protozoa lack de novo synthesis and rely entirely on the purine salvage pathway to meet their purine demands. Because of the great phylogenetic difference between parasite and host, there are often sufficient distinctions that can be exploited to design specific inhibitors for the parasitic enzymes. As a result, this pathway has been thoroughly investigated over the last twenty years. It is only quite recently that the genome studies of Trypanosoma, Leishmania and Plasmodium have been published. Based on these genomic data however, the existence of by-pass mechanisms by other enzymes and transporter systems could be suggested. Taking into account such proposition, the question might arise as to whether inhibition of a single salvage enzyme will be able or not to cause parasite death or growth arrest. In this paper, the key enzymes in the purine salvage pathways of relevant pathogenic species from the genera Trypanosoma, Leishmania and Plasmodium are reviewed. Their potential as drug targets is critically evaluated and where possible, correlated to literature data on antiparasitic activity of their inhibitors. While many studies over the past ten years have yielded contradictory results, this review attempts to clarify these findings by discussing the latest elements of progress in the field. Additionally, as part of a broader discussion on substrate analogue types of inhibitors, special attention is paid to iminoribitol derivatives, serving as transition state analogues of nucleoside-processing enzymes and comprising the most potent inhibitors reported for purine salvage enzymes. More specifically, the development of three generations of immucillins and a newer series of N-(arylmethyl-) substituted iminoribitol derivatives will be discussed. Finally, this review also covers subversive substrates of salvage enzymes: compounds that

  7. Killing Two Birds with One Stone: Improving 4th Year Student Teachers' Teaching Skills and Preparing 1st Year Student Teachers for Teaching Practice

    ERIC Educational Resources Information Center

    Saka, Ahmet Zeki; Saka, Arzu

    2004-01-01

    The aim of this study is to develop a new approach to help both 4th year students and 1st year students to get the utmost benefit from application activities. This new approach will provide 4th year students with an experience of teaching practice and also preparation of 1st student teachers to teaching practice process before they start their…

  8. Adaptive and Effortful Control and Academic Self-Efficacy Beliefs on Achievement: A Longitudinal Study of 1st through 3rd Graders

    ERIC Educational Resources Information Center

    Liew, Jeffrey; McTigue, Erin M.; Barrois, Lisa; Hughes, Jan N.

    2008-01-01

    The linkages between self-regulatory processes and achievement were examined across 3 years in 733 children beginning at 1st grade (M = 6.57 years, S.D. = 0.39 at 1st grade) who were identified as lower achieving in literacy. Accounting for consistencies in measures (from 1 year prior) and for influences of child's age, gender, IQ, ethnicity and…

  9. Enhancement of the therapeutic effectiveness of methotrexate and protection of normal proliferating tissues with purines and pyrimidines.

    PubMed

    Harrap, K R; Taylor, G A; Browman, G P

    1977-07-01

    Mice can be protected against the toxicity arising from lethal doses of methotrexate with purine and pyrimidine combinations, but not with pyrimidine alone. Furthermore, methotrexate treatment of tumour-bearing mice, conjunction with purine/pyrimidine protection, can be more effective than conventional metotrexate/folinic acid treatment.

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

    PubMed

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

    2017-01-01

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

  11. Genetic and proteomic analyses of a Xanthomonas campestris pv. campestris purC mutant deficient in purine biosynthesis and virulence.

    PubMed

    Yuan, Zhihui; Wang, Li; Sun, Shutao; Wu, Yao; Qian, Wei

    2013-09-20

    Bacterial proliferation in hosts requires activation of a number of housekeeping pathways, including purine de novo biosynthesis. Although inactivation of purine biosynthesis genes can attenuate virulence, it is unclear which biochemical or virulence factors are associated with the purine biosynthesis pathway in vivo. We report that inactivation of purC, a gene encoding phosphoribosylaminoimidazole-succinocarboxamide synthase, caused complete loss of virulence in Xanthomonas campestris pv. campestris, the causal agent of black rot disease of cruciferous plants. The purC mutant was a purine auxotroph; it could not grow on minimal medium, whereas addition of purine derivatives, such as hypoxanthine or adenine plus guanine, restored growth of the mutant. The purC mutation also significantly enhanced the production of an unknown purine synthesis associated pigment and extracellular polysaccharides by the bacterium. In addition, comparative proteomic analyses of bacteria grown on rich and minimal media revealed that the purC mutation affected the expression levels of diverse proteins involved in purine and pyrimidine synthesis, carbon and energy metabolisms, iron uptake, proteolysis, protein secretion, and signal transduction. These results provided clues to understanding the contributions of purine synthesis to bacterial virulence and interactions with host immune systems.

  12. Purine salvage pathways of Bacillus subtilis and effect of guanine on growth of GMP reductase mutants.

    PubMed Central

    Endo, T; Uratani, B; Freese, E

    1983-01-01

    We have isolated numerous mutants containing mutations in the salvage pathways of purine synthesis. The mutations cause deficiencies in adenine phosphoribosyltransferase (adeF), in hypoxanthine-guanine phosphoribosyltransferase (guaF), in adenine deaminase (adeC), in inosine-guanosine phosphorylase, (guaP), and in GMP reductase (guaC). The physiological properties of mutants containing one or more of these mutations and corresponding enzyme measurements have been used to derive a metabolic chart of the purine salvage pathway of Bacillus subtilis. PMID:6408059

  13. 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.

  14. Synthesis of cycloalkyl substituted purine nucleosides via a metal-free radical route.

    PubMed

    Wang, Dong-Chao; Xia, Ran; Xie, Ming-Sheng; Qu, Gui-Rong; Guo, Hai-Ming

    2016-05-04

    An efficient route to synthesize cycloalkyl substituted purine nucleosides was developed. This metal-free C-H activation was accomplished by a tBuOOtBu initiated radical reaction. By adjusting the amount of tBuOOtBu and reaction time, the selective synthesis of C6-monocycloalkyl or C6,C8-dicycloalkyl substituted purine nucleosides could be realized. Furthermore, uracil and related nucleosides were also suitable substrates, giving the C5-cyclohexyl substituted uracil derivatives in good yields with excellent regioselectivities.

  15. meta-C-H Bromination on Purine Bases by Heterogeneous Ruthenium Catalysis.

    PubMed

    Warratz, Svenja; Burns, David J; Zhu, Cuiju; Korvorapun, Korkit; Rogge, Torben; Scholz, Julius; Jooss, Christian; Gelman, Dmitri; Ackermann, Lutz

    2017-02-01

    Methods for positionally selective remote C-H functionalizations are in high demand. Herein, we disclose the first heterogeneous ruthenium catalyst for meta-selective C-H functionalizations, which enabled remote halogenations with excellent site selectivity and ample scope. The versatile heterogeneous Ru@SiO2 catalyst was broadly applicable and could be easily recovered and reused, which set the stage for the direct fluorescent labeling of purines. In contrast to palladium, rhodium, iridium, or cobalt complexes, solely the ruthenium catalysis manifold provided access to meta-halogenated purine derivatives, illustrating the unique power of ruthenium C-H activation catalysis.

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

    PubMed

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

    2014-02-03

    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.

  17. 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…

  18. 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…

  19. Uncertainty Requirement Analysis for the Orbit, Attitude, and Burn Performance of the 1st Lunar Orbit Insertion Maneuver

    NASA Astrophysics Data System (ADS)

    Song, Young-Joo; Bae, Jonghee; Kim, Young-Rok; Kim, Bang-Yeop

    2016-12-01

    In this study, the uncertainty requirements for orbit, attitude, and burn performance were estimated and analyzed for the execution of the 1st lunar orbit insertion (LOI) maneuver of the Korea Pathfinder Lunar Orbiter (KPLO) mission. During the early design phase of the system, associate analysis is an essential design factor as the 1st LOI maneuver is the largest burn that utilizes the onboard propulsion system; the success of the lunar capture is directly affected by the performance achieved. For the analysis, the spacecraft is assumed to have already approached the periselene with a hyperbolic arrival trajectory around the moon. In addition, diverse arrival conditions and mission constraints were considered, such as varying periselene approach velocity, altitude, and orbital period of the capture orbit after execution of the 1st LOI maneuver. The current analysis assumed an impulsive LOI maneuver, and two-body equations of motion were adapted to simplify the problem for a preliminary analysis. Monte Carlo simulations were performed for the statistical analysis to analyze diverse uncertainties that might arise at the moment when the maneuver is executed. As a result, three major requirements were analyzed and estimated for the early design phase. First, the minimum requirements were estimated for the burn performance to be captured around the moon. Second, the requirements for orbit, attitude, and maneuver burn performances were simultaneously estimated and analyzed to maintain the 1st elliptical orbit achieved around the moon within the specified orbital period. Finally, the dispersion requirements on the B-plane aiming at target points to meet the target insertion goal were analyzed and can be utilized as reference target guidelines for a mid-course correction (MCC) maneuver during the transfer. More detailed system requirements for the KPLO mission, particularly for the spacecraft bus itself and for the flight dynamics subsystem at the ground control center

  20. 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

  1. [Indicators of the risk of death during the 1st year of life in rural areas of Guatemala].

    PubMed

    Lechtig, A; Ibarra, A; Gupta, M; Klein, R E

    1980-12-01

    These data were collected as part of the longitudinal study on nutrition and mental development promoted by INCAP in rural areas of Guatemala to investigate indicators of risk of moratlity during the 1st year of life. 1384 children born between January 1968-September 1976 were observed. Of these only 578 were measured before the 15th day of life; in this group there were 18 deaths, or 3.11%, within the 1st year of life. Of the remaining 764 children whose anthrompometric measures had not been taken, 29, or 3.79% died within the 1st year of life. Measures investigated were weight, height, arm circumference and head circumference. High risk infants were those with weight less than 3 kg, height equal or less than 48 cm, head circumference equal or less than 35 mm, and arm circumference equal or less than 9.9 mm. These variables can easily be used as simple indicators of risk of death in infant health care centers in both urban and rural areas.

  2. 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.

  3. 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

  4. The 1st October 2009 Messina debris flows: first analysis for a susceptibility model

    NASA Astrophysics Data System (ADS)

    Agnesi, Valerio; Cappadonia, Chiara; Conoscenti, Christian; Costanzo, Dario; Pino, Paolo; Puglisi, Claudio; Rotigliano, Edoardo

    2010-05-01

    In the evening of the 1st of October 2009, a sector of the Messina district (Sicily, Italy) was struck by a number of debris flows, triggered by extraordinary intense rainfall that, from 2 pm to 10 pm, discharged an amount of more than 160 mm and that followed the ones of September 23-24 (more than 200 mm in 10 hours). A number of villages (Altolia, Briga, Giampilieri, Guidomandri, Itala, Molino, Pezzolo, Scaletta), suffered for severe damages, including the destruction of houses and small buildings and more of 30 deaths. The area is located South from the city of Messina and mainly includes five short fluvial basins, that from the Peloritanian chain drain south-eastward for some kilometres to the Ionian sea. The area is characterized by the outcropping of metamorphic rocks and, due to the closeness of the chain (ranging up to 1200 meters a.s.l.) to the sea, the steepness of the slopes is typically very high. The debris flows involved the shallow layer made up of colluvial/eluvial and landslide deposits, having a thickness of some decimetres; both pure debris flow and debris slide movements have been inferred at the initiation zones, in light of the morphologic features of the source area (scarps). Also, according to the specific patterns recognized for the flow track zone, four typologies have been distinguished: ribbon-shaped, triangular, arch-shaped and multi-lobed debris flow. The landslides moved fast, as single or multiple/successive confluent style, so that already at the medium sector of the slopes, where the villages are, huge volumes of the debris flowed. Due to the shallowness of the failure zone, the high water content and velocity, the tracks of the debris flows have been highly controlled by hydrography, reaching, where no obstacles were present, the valley floor, with kilometric run-out distances. To each of the 379 recognized debris flows, which produced a total landslide area of about 7 km2, a landslide identification point (LIP) has been assigned

  5. The theoretical simulation on electrostatic distribution of 1st proximity region in proximity focusing low-light-level image intensifier

    NASA Astrophysics Data System (ADS)

    Zhang, Liandong; Bai, Xiaofeng; Song, De; Fu, Shencheng; Li, Ye; Duanmu, Qingduo

    2015-03-01

    Low-light-level night vision technology is magnifying low light level signal large enough to be seen by naked eye, which uses the photons - photoelectron as information carrier. Until the micro-channel plate was invented, it has been possibility for the realization of high performance and miniaturization of low-light-level night vision device. The device is double-proximity focusing low-light-level image intensifier which places a micro-channel plate close to photocathode and phosphor screen. The advantages of proximity focusing low-light-level night vision are small size, light weight, small power consumption, no distortion, fast response speed, wide dynamic range and so on. It is placed parallel to each other for Micro-channel plate (both sides of it with metal electrode), the photocathode and the phosphor screen are placed parallel to each other. The voltage is applied between photocathode and the input of micro-channel plate when image intensifier works. The emission electron excited by photo on the photocathode move towards to micro-channel plate under the electric field in 1st proximity focusing region, and then it is multiplied through the micro-channel. The movement locus of emission electrons can be calculated and simulated when the distributions of electrostatic field equipotential lines are determined in the 1st proximity focusing region. Furthermore the resolution of image tube can be determined. However the distributions of electrostatic fields and equipotential lines are complex due to a lot of micro-channel existing in the micro channel plate. This paper simulates electrostatic distribution of 1st proximity region in double-proximity focusing low-light-level image intensifier with the finite element simulation analysis software Ansoft maxwell 3D. The electrostatic field distributions of 1st proximity region are compared when the micro-channel plates' pore size, spacing and inclination angle ranged. We believe that the electron beam movement

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

    PubMed

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

    2017-04-21

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

  7. 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.

  8. Formation of A Novel Purine Metabolite through CYP3A4 Bioactivation and Glutathione Conjugation

    PubMed Central

    Apuy, Julius L.; Xiang, Cathie; Franc, Sarah; Hegde, Sayee G.; Hubbard, Robert; Zhao, Jingjing; Moghaddam, Mehran F.

    2016-01-01

    Background: The study of novel sites of metabolism is important in understanding new mechanisms of biotransformation of a particular moiety by metabolic enzymes. This information is valuable in designing metabolically-stable compounds with drug-like properties. It may also provide insights into the existence of active and reactive metabolites. Methods: We utilized small scale incubations to generate adequate amounts of the metabolite of interest. After purification, LC-MS/MS and Proton Nuclear Magnetic Resonance (1H-NMR) were utilized to unequivocally assign the novel site of glutathione conjugation on the purine ring system. Results: A proposed novel site of glutathione conjugation was investigated on a diaminopurine-containing molecule. It was demonstrated that the formation of the glutathione conjugate at the C-6 position of the purine ring system was due to the bioactivation of the compound to a di-imine intermediate by CYP3A4, followed by the nucleophilic addition of glutathione. Conclusion: S-glutathionylation at C-6 position of a purine was proven unequivocally. This previously unreported mechanism constitutes a novel biotransformation for purines. PMID:27165340

  9. 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.

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

    NASA Astrophysics Data System (ADS)

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

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

  11. Photogeneration of 2-deoxyribonolactone in benzophenone-purine dyads. Formation of ketyl-C1' biradicals.

    PubMed

    Paris, Cecilia; Encinas, Susana; Belmadoui, Nourreddine; Climent, María J; Miranda, Miguel Angel

    2008-10-16

    Photolysis of the title dyads under aerobic conditions leads to a 2-deoxyribonolactone derivative. Laser flash photolysis reveals that the process occurs from the short-lived benzophenone-like triplet excited state. A mechanism involving intramolecular electron transfer with the purine bases (adenine, guanine, or 8-oxoadenine) as donors is proposed.

  12. The purine metabolite allantoin enhances abiotic stress tolerance through synergistic activation of abscisic acid metabolism.

    PubMed

    Watanabe, Shunsuke; Matsumoto, Mayumi; Hakomori, Yuki; Takagi, Hiroshi; Shimada, Hiroshi; Sakamoto, Atsushi

    2014-04-01

    Purine catabolism is regarded as a housekeeping function that remobilizes nitrogen for plant growth and development. However, emerging evidence suggests that certain purine metabolites might contribute to stress protection of plants. Here, we show that in Arabidopsis, the intermediary metabolite allantoin plays a role in abiotic stress tolerance via activation of abscisic acid (ABA) metabolism. The aln loss-of-function of ALN, encoding allantoinase, results in increased allantoin accumulation, genome-wide up-regulation of stress-related genes and enhanced tolerance to drought-shock and osmotic stress in aln mutant seedlings. This phenotype is not caused by a general response to purine catabolism inhibition, but rather results from a specific effect of allantoin. Allantoin activates ABA production both through increased transcription of NCED3, encoding a key enzyme in ABA biosynthesis, and through post-translational activation via high-molecular-weight complex formation of BG1, a β-glucosidase hydrolysing glucose-conjugated ABA. Exogenous application of allantoin to wild-type plants also activates the two ABA-producing pathways that lead to ABA accumulation and stress-responsive gene expression, but this effect is abrogated in ABA-deficient and BG1-knockout mutants. We propose that purine catabolism functions not only in nitrogen metabolism, but also in stress tolerance by influencing ABA production, which is mediated by the possible regulatory action of allantoin. © 2013 John Wiley & Sons Ltd.

  13. 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…

  14. 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…

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

    PubMed

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

    2007-02-01

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

  16. Targeting DNA repair with aphidicolin sensitizes primary chronic lymphocytic leukemia cells to purine analogs

    PubMed Central

    Starczewska, Eliza; Beyaert, Maxime; Michaux, Lucienne; Vekemans, Marie-Christiane; Saussoy, Pascale; Bol, Vanesa; Echarri, Ainhoa Arana; Smal, Caroline; Van Den Neste, Eric; Bontemps, Françoise

    2016-01-01

    Purine analogs are among the most effective chemotherapeutic drugs for the treatment of chronic lymphocytic leukemia (CLL). However, chemoresistance and toxicity limit their clinical use. Here, we report that the DNA polymerase inhibitor aphidicolin, which displayed negligible cytotoxicity as a single agent in primary CLL cells, markedly synergizes with fludarabine and cladribine via enhanced apoptosis. Importantly, synergy was recorded regardless of CLL prognostic markers. At the molecular level, aphidicolin enhanced purine analog-induced phosphorylation of p53 and accumulation of γH2AX, consistent with increase in DNA damage. In addition, aphidicolin delayed γH2AX disappearance that arises after removal of purine analogs, suggesting that aphidicolin causes an increase in DNA damage by impeding DNA damage repair. Similarly, aphidicolin inhibited UV-induced DNA repair known to occur primarily through the nucleotide excision repair (NER) pathway. Finally, we showed that fludarabine induced nuclear import of XPA, an indispensable factor for NER, and that XPA silencing sensitized cell lines to undergo apoptosis in response to fludarabine. Together, our data indicate that aphidicolin potentiates the cytotoxicity of purine analogs by inhibiting a DNA repair pathway that involves DNA polymerases, most likely NER, and provide a rationale for manipulating it to therapeutic advantage. PMID:27223263

  17. Participation of purines in the modulation of inflammatory response in rats experimentally infected by Cryptococcus neoformans.

    PubMed

    de Azevedo, Maria Isabel; Ferreiro, Laerte; Da Silva, Aleksandro S; Tonin, Alexandre A; Monteiro, Danieli Urach; Casali, Emerson A; Moritz, Cesar E J; Schirmbeck, Gabriel H; Cardoso, Valesca V; Flores, Mariana M; Fighera, Rafael; Stefani, Lenita M; Santurio, Janio M

    2016-10-01

    The present study was carried out to assess the participation of purines in the activation and modulation of inflammatory response of rats experimentally infected by Cryptococcus neoformans. Twenty four Wistar rats were divided into two groups of 12 animals each: Group A - uninfected control group and Group B - infected by C. neoformans. Blood was collected 20 and 50 days post-infection (PI) from six animals of each group in order to verify purine levels (adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenosine (ADO), inosine (INO), hypoxanthine (HYPO), xanthine (XAN) and uric acid (URIC)). ATP levels were significantly increased (P < 0.05) in serum from infected animals on days 20 and 50 PI, as well as adenosine levels after 20 days PI on rats. On day 50 PI, levels of adenosine and uric acid were also reduced, but the levels of inosine and xanthine increased in animals infected by the fungus (P < 0.05). Therefore, it was possible to conclude that the purine levels in serum were altered and that these changes may be able to influence the pathogenesis of the disease caused by C. neoformans due the participation of purines (ATP and adenosine main) in the activation and modulation of inflammatory response.

  18. Metabolism of purine alkaloids and xanthine in leaves of maté (Ilex paraguariensis).

    PubMed

    Yin, Yuling; Katahira, Riko; Ashihara, Hiroshi

    2015-05-01

    Accumulation and metabolism of purine alkaloids in leaves of maté (Ilex paraguariensis) were investigated. In winter, leaves accumulated caffeine but not theobromine, indicating that caffeine is the end product of purine alkaloid synthesis in maté. To elucidate the purine alkaloid metabolism in maté leaves, the metabolic fate of [8-(14)C]theobromine, [8-(14)C]theophylline, [8-(14)C]caffeine and [8-(14)C] xanthine was investigated in the leaf disks of young and mature leaves. In young maté leaves, significant amounts of theobromine and theophylline were utilized for caffeine biosynthesis, but the conversion was not observed in mature leaves. A small amount of theophylline was converted to theobromine. Practically no caffeine catabolism was detected in maté leaves during a 24 h-incubation. Catabolism of theobromine and theophylline via 3-methylxanthine was observed mainly in mature leaves. Xanthine was catabolised extensively via ureides in both young and mature leaves, but limited amounts are also utilized for the synthesis of theobromine, theophylline and caffeine. Possible pathways for the metabolism of purine alkaloids in maté leaves are discussed.

  19. Modular Synthesis of Constrained Ethyl (cEt) Purine and Pyrimidine Nucleosides.

    PubMed

    Blade, Helen; Bradley, Derek; Diorazio, Louis; Evans, Timothy; Hayter, Barry R; Howell, Gareth P

    2015-05-15

    A modular and scalable approach to pyrimidine- and purine-containing constrained ethyl (cEt) nucleosides is demonstrated. Minimizing stereochemical adjustments and protecting group manipulations, diacetone glucose is converted to two representative cEt nucleosides via a functionalized, common intermediate. The retrosynthetic approach to this complex class of drug precursors offers clear benefits over existing routes based on step count and efficiency.

  20. Synthesis and evaluation of the substrate activity of C-6 substituted purine ribosides with E. coli purine nucleoside phosphorylase: palladium mediated cross-coupling of organozinc halides with 6-chloropurine nucleosides.

    PubMed

    Hassan, Abdalla E A; Abou-Elkhair, Reham A I; Riordan, James M; Allan, Paula W; Parker, William B; Khare, Rashmi; Waud, William R; Montgomery, John A; Secrist, John A

    2012-01-01

    A series of C-6 alkyl, cycloalkyl, and aryl-9-(β-d-ribofuranosyl)purines were synthesized and their substrate activities with Escherichia coli purine nucleoside phosphorylase (E. coli PNP) were evaluated. (Ph(3)P)(4)Pd-mediated cross-coupling reactions of 6-chloro-9-(2,3,5-tri-O-acetyl-β-d-ribofuranosyl)-purine (6) with primary alkyl (Me, Et, n-Pr, n-Bu, isoBu) zinc halides followed by treatment with NH(3)/MeOH gave the corresponding 6-alkyl-9-(β-d-ribofuranosyl)purine derivatives 7-11, respectively, in good yields. Reactions of 6 with cycloalkyl(propyl, butyl, pentyl)zinc halides and aryl (phenyl, 2-thienyl)zinc halides gave under similar conditions the corresponding 6-cyclopropyl, cyclobutyl, cyclopentyl, phenyl, and thienyl -9-(β-d-ribofuranosyl)purine derivatives 12-16, respectively in high yields. E. coli PNP showed a high tolerance to the steric and hydrophobic environment at the 6-position of the synthesized purine ribonucleosides. Significant cytotoxic activity was observed for 8, 12, 15, and 16. Evaluation of 12 and 16 against human tumor xenografts in mice did not demonstrate any selective antitumor activity. In addition, 6-methyl-9-(β-d-arabinofuranosyl)purine (18) was prepared and evaluated. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  1. High prevalence of blaCTX-M-1/IncI1/ST3 and blaCMY-2/IncI1/ST2 plasmids in healthy urban dogs in France.

    PubMed

    Haenni, Marisa; Saras, Estelle; Métayer, Véronique; Médaille, Christine; Madec, Jean-Yves

    2014-09-01

    In the community, close contacts between humans and dogs may promote the transfer of extended-spectrum beta-lactamase/plasmidic AmpC cephalosporinase (ESBL/pAmpC) genes. Large-scale prevalence studies on ESBL/pAmpC carriage in dogs are rare, and data on ESBL/pAmpC plasmids are even more limited. Here, a considerable rate of 18.5% ESBL/pAmpC carriers was found among 368 unrelated healthy dogs in Paris, France. This prevalence is much higher than the one found in healthy humans in the same city (6%) but close to that recently reported in dogs in China (24.5%). All isolates were identified as Escherichia coli, except one Salmonella enterica and one Klebsiella pneumoniae isolate. The sequence type 131 (ST131) clone was rare (2/73 isolates). Interestingly, two plasmids (blaCTX-M-1/IncI1/ST3 and blaCMY-2/IncI1/ST2) were unexpectedly highly predominant, raising the question of their successful spread. Considering that CTX-M-1 was recently found to be equally as abundant as CTX-M-15 in healthy Parisian subjects, the question of dogs being a CTX-M-1 reservoir for humans is open. Such a high prevalence of the blaCMY-2/IncI1/ST2 plasmid may result from the use of cephalexin in veterinary medicine, as previously demonstrated experimentally. In all, our study points out healthy urban dogs as a potential source of ESBL/pAmpC genes that can further disseminate to the human community.

  2. High Prevalence of blaCTX-M-1/IncI1/ST3 and blaCMY-2/IncI1/ST2 Plasmids in Healthy Urban Dogs in France

    PubMed Central

    Saras, Estelle; Métayer, Véronique; Médaille, Christine; Madec, Jean-Yves

    2014-01-01

    In the community, close contacts between humans and dogs may promote the transfer of extended-spectrum beta-lactamase/plasmidic AmpC cephalosporinase (ESBL/pAmpC) genes. Large-scale prevalence studies on ESBL/pAmpC carriage in dogs are rare, and data on ESBL/pAmpC plasmids are even more limited. Here, a considerable rate of 18.5% ESBL/pAmpC carriers was found among 368 unrelated healthy dogs in Paris, France. This prevalence is much higher than the one found in healthy humans in the same city (6%) but close to that recently reported in dogs in China (24.5%). All isolates were identified as Escherichia coli, except one Salmonella enterica and one Klebsiella pneumoniae isolate. The sequence type 131 (ST131) clone was rare (2/73 isolates). Interestingly, two plasmids (blaCTX-M-1/IncI1/ST3 and blaCMY-2/IncI1/ST2) were unexpectedly highly predominant, raising the question of their successful spread. Considering that CTX-M-1 was recently found to be equally as abundant as CTX-M-15 in healthy Parisian subjects, the question of dogs being a CTX-M-1 reservoir for humans is open. Such a high prevalence of the blaCMY-2/IncI1/ST2 plasmid may result from the use of cephalexin in veterinary medicine, as previously demonstrated experimentally. In all, our study points out healthy urban dogs as a potential source of ESBL/pAmpC genes that can further disseminate to the human community. PMID:24982072

  3. Crucial Role of the Interleukin 1 Receptor Family Member T1/St2 in T Helper Cell Type 2–Mediated Lung Mucosal Immune Responses

    PubMed Central

    Coyle, Anthony J.; Lloyd, Clare; Tian, Jane; Nguyen, Trang; Erikkson, Christina; Wang, Lin; Ottoson, Par; Persson, Per; Delaney, Tracy; Lehar, Sophie; Lin, Steve; Poisson, Louis; Meisel, Christian; Kamradt, Thomas; Bjerke, Torbjorn; Levinson, Douglas; Gutierrez-Ramos, Jose Carlos

    1999-01-01

    T1/ST2 is an orphan receptor of unknown function that is expressed on the surface of murine T helper cell type 2 (Th2), but not Th1 effector cells. In vitro blockade of T1/ST2 signaling with an immunoglobulin (Ig) fusion protein suppresses both differentiation to and activation of Th2, but not Th1 effector populations. In a nascent Th2-dominated response, anti-T1/ST2 monoclonal antibody (mAb) inhibited eosinophil infiltration, interleukin 5 secretion, and IgE production. To determine if these effects were mediated by a direct effect on Th2 cells, we next used a murine adoptive transfer model of Th1- and Th2-mediated lung mucosal immune responses. Administration of either T1/ST2 mAb or T1/ST2-Ig abrogated Th2 cytokine production in vivo and the induction of an eosinophilic inflammatory response, but failed to modify Th1-mediated inflammation. Taken together, our data demonstrate an important role of T1/ST2 in Th2-mediated inflammatory responses and suggest that T1/ST2 may prove to be a novel target for the selective suppression of Th2 immune responses. PMID:10510079

  4. Purine nucleobase transport in human erythrocytes. Reinvestigation with a novel "inhibitor-stop" assay.

    PubMed

    Domin, B A; Mahony, W B; Zimmerman, T P

    1988-07-05

    A novel "inhibitor-stop" method for the determination of initial rates of purine nucleobase transport in human erythrocytes has been developed, based on the addition of seven assay volumes of cold 19 mM papaverine to terminate influx. In view of our finding that the initial velocities of adenine, guanine, and hypoxanthine influx into human erythrocytes were linear for only 4-6 s at 37 degrees C, the present method has been used to reexamine the kinetics of purine nucleobase transport in these cells. Initial influx rates of all three purine nucleobases were shown to be the result of concurrent facilitated and nonfacilitated diffusion. The nonfacilitated influx rates could be estimated either from the linear concentration dependence of nucleobase influx at high concentrations of permeant or from residual influx rates which were not inhibited by the presence of co-permeants. Appropriate corrections for nonfacilitated diffusion were made to the influx rates observed at low nucleobase concentrations. Kinetic analyses indicated that adenine (Km = 13 +/- 1 microM, n = 7), guanine (Km = 37 +/- 2 microM, n = 5), and hypoxanthine (Km = 180 +/- 12 microM, n = 6) were mutually competitive substrates for transport. The Ki values obtained with each nucleobase as an inhibitor of the influx of the other nucleobases were similar to their respective Km values for influx. Furthermore, the transport of the purine nucleobases was not inhibited by nucleosides (uridine, inosine) or by inhibitors of nucleoside transport (6-[(4-nitrobenzyl)thio]-9-beta-D-ribofuranosylpurine, dilazep, dipyridamole). It is concluded that all three purine nucleobases share a common facilitated transport system in human erythrocytes which is functionally distinct from the nucleoside transporter.

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

    NASA Astrophysics Data System (ADS)

    Cléroux, Caroline; Fehrenbacher, Jennifer; Phipps, Steven; Rupper, Summer; Williams, Branwen; Kiefer, Thorsten

    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

  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.

  7. 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

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

    PubMed

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

    2014-01-01

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

  9. When should orthostatic blood pressure changes be evaluated in elderly: 1st, 3rd or 5th minute?

    PubMed

    Soysal, Pinar; Aydin, Ali Ekrem; Koc Okudur, Saadet; Isik, Ahmet Turan

    2016-01-01

    Detection of orthostatic hypotension (OH) is very important in geriatric practice, since OH is associated with mortality, ischemic stroke, falls, cognitive failure and depression. It was aimed to determine the most appropriate time for measuring blood pressure in transition from supine to upright position in order to diagnose OH in elderly. Comprehensive geriatric assessment (CGA) including Head up Tilt Table (HUT) test was performed in 407 geriatric patients. Orthostatic changes were assessed separately for the 1st, 3rd and 5th minutes (HUT1, HUT3 and HUT5, respectively) taking the data in supine position as the basis. The mean age, recurrent falls, presence of dementia and Parkinson's disease, number of drugs, alpha-blocker and anti-dementia drug use, and fasting blood glucose levels were significantly higher in the patients with versus without OH; whereas, albumin and 25-hydroxy vitamin D levels were significantly lower (p<0.05). However, different from HUT3 and HUT5, Charlson Comorbidity Index and the prevalence of diabetes mellitus were higher, the use of antidiabetics, antipsychotics, benzodiazepine, opioid and levodopa were more common (p<0.05). Statistical significance of the number of drugs and fasting blood glucose level was prominent in HUT1 as compared to HUT3 (p<0.01, p<0.05). Comparison of the patients that had OH only in HUT1, HUT3or HUT5 revealed no difference in terms of CGA parameters. These results suggests that orthostatic blood pressure changes determined at the 1st minute might be more important for geriatric practice. Moreover, 1st minute measurement might be more convenient in the elderly as it requires shorter time in practice.

  10. 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.

  11. 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

    ... August 6, 2006 and currently abandoned ; and UK Patent Application No. 01903043.6, filed January 12, 2001 and issued as UK Patent No. 1252160 on August 16, 2006 [HHS Ref. No. E-176-1999/0-GB- 08],...

  12. 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.

  13. Radiotherapy in the UK

    SciTech Connect

    Ramsay, S.

    1993-10-09

    What is wrong with radiation treatment in the UK Is it bad practice or merely bad publicity Between 1982 and 1991, 1,000 patients receiving isocentric radiation therapy at the North Staffordshire Royal Infirmary received a substantial underdose of radiation; the clinical report on this incident was published last week. The operator had been using a correction factor for tumor-to-skin distance, unaware that this factor had already been applied by the computer system. Although the report pointed out that it is not surprising that the clinicians were not alerted to the undertreatment, is also noted that there were no resources at the hospital to audit the outcome of radiotherapy.

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

    PubMed

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

    2006-06-09

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

  15. Hypouricemic effects of novel concentrative nucleoside transporter 2 inhibitors through suppressing intestinal absorption of purine nucleosides.

    PubMed

    Hiratochi, Masahiro; Tatani, Kazuya; Shimizu, Kazuo; Kuramochi, Yu; Kikuchi, Norihiko; Kamada, Noboru; Itoh, Fumiaki; Isaji, Masayuki

    2012-09-05

    We have developed concentrative nucleoside transporter 2 (CNT2) inhibitors as a novel pharmacological approach for improving hyperuricemia by inhibiting intestinal absorption of purines. Dietary purine nucleosides are absorbed in the small intestines by CNTs expressed in the apical membrane. In humans, the absorbed purine nucleosides are rapidly degraded to their final end product, uric acid, by xanthine oxidase. Based on the expression profile of human CNTs in digestive tract tissues, we established a working hypothesis that mainly CNT2 contributes to the intestinal absorption of purine nucleosides. In order to confirm this possibility, we developed CNT2 inhibitors and found that (2R,3R,4S,5R)-2-(6-amino-8-{[3'-(3-aminopropoxy)-biphenyl-4-ylmethyl]-amino}-9H-purin-9-yl)-5-hydroxymethyl-tetrahydrofuran-3,4-diol (KGO-2142) and 1-[3-(5-{[1-((2R,3R,4S,5R)-3,4-dihydroxy-5-hydroxymethyl-tetrahydrofuran-2-yl)-1H-benzimidazol-2-ylamino]-methyl}-2-ethoxyphenoxy)-propyl]-piperidine-4-carboxylic acid amide (KGO-2173) were inhibitory. These CNT2 inhibitors had potent inhibitory activity against inosine uptake via human CNT2, but they did not potently interfere with nucleoside uptake via human CNT1, CNT3 or equilibrative nucleoside transporters (ENTs) in vitro. After oral administration of KGO-2173 along with [(14)C]-inosine, KGO-2173 significantly decreased the urinary excretion of radioactivity at 6 and 24h in rats. Since dietary purine nucleosides are not utilized in the body and are excreted into the urine rapidly, this decrease in radioactivity in the urine represented the inhibitory activity of KGO-2173 toward the absorption of [(14)C]-inosine in the small intestines. KGO-2142 almost completely inhibited dietary RNA-induced hyperuricemia and the increase in urinary excretion of uric acid in cebus monkeys. These novel CNT2 inhibitors, KGO-2142 and KGO-2173, could be useful therapeutic options for the treatment of hyperuricemia. Copyright © 2012 Elsevier B.V. All rights

  16. Iron Sappers Lead the Way: The 16th Engineer Battalion’s Support of 1st Armored Division in Southwest Asia

    DTIC Science & Technology

    1993-03-30

    limited value due to the availability of double impulse, blast resistant mines and the success of the tank plow. The GEMSS ( ground emplaced mine...34 Ironsides (Ansbach, Germany), 5 July 1991, p. 10. Headquarters, Phantom Brigade, 1st Armored Division. "DESERT SHIELD and DESERT STORM After Action...govemment agency. IRON SAPPERS LEAD THE WAY: THE 16TH ENGINEER BATTALION’S SUPPORT OF 1ST ARMORED DIVISION IN SOUTHWEST ASIA BY LIEUTENANT COLONEL

  17. The Viability of Phantom Dark Energy as a Quantum Field in 1st-Order FLRW Space

    NASA Astrophysics Data System (ADS)

    Ludwick, Kevin

    2017-01-01

    In the standard cosmological framework of the 0th-order FLRW metric and the use of perfect fluids in the stress-energy tensor, dark energy with an equation-of-state parameter w < - 1 (known as phantom dark energy) implies negative kinetic energy and vacuum instability when modeled as a scalar field. However, the accepted values for present-day w from Planck and WMAP9 include a significant range of values less than - 1 . We consider a more accurate description of the universe through the 1st-order perturbing of the isotropic and homogeneous FLRW metric and the components of the stress-energy tensor and investigate whether a field with an apparent w < - 1 may still have positive kinetic energy. Treating dark energy as a classical scalar field in this metric, we find that it is not as obvious as one might think that phantom dark energy has negative kinetic energy categorically. Analogously, we find that field models of quintessence dark energy (w > - 1) do not necessarily have positive kinetic energy categorically. We then investigate the same question treating dark energy as a quantum field in 1st-order FLRW space-time and examining the expectation value of the stress-energy tensor for w < - 1 using adiabatic expansion.

  18. Occurrence of Legionella in UK household showers.

    PubMed

    Collins, Samuel; Stevenson, David; Bennett, Allan; Walker, Jimmy

    2017-04-01

    Household water systems have been proposed as a source of sporadic, community acquired Legionnaires' disease. Showers represent a frequently used aerosol generating device in the domestic setting yet little is known about the occurrence of Legionella spp. in these systems. This study has investigated the prevalence of Legionella spp. by culture and qPCR in UK household showers. Ninety nine showers from 82 separate properties in the South of England were sampled. Clinically relevant Legionella spp. were isolated by culture in 8% of shower water samples representing 6% of households. Legionella pneumophila sg1 ST59 was isolated from two showers in one property and air sampling demonstrated its presence in the aerosol state. A further 31% of showers were positive by Legionella spp. qPCR. By multi-variable binomial regression modelling Legionella spp. qPCR positivity was associated with the age of the property (p=0.02), the age of the shower (p=0.01) and the frequency of use (p=0.09). The concentration of Legionella spp. detected by qPCR was shown to decrease with increased frequency of use (p=0.04) and more frequent showerhead cleaning (p=0.05). There was no association between Legionella spp. qPCR positivity and the cold water supply or the showerhead material (p=0.65 and p=0.71, respectively). Household showers may be important reservoirs of clinically significant Legionella and should be considered in source investigations. Simple public health advice may help to mitigate the risk of Legionella exposure in the domestic shower environment. Crown Copyright © 2016. Published by Elsevier GmbH. All rights reserved.

  19. 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

    2015-03-16

    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.

  20. Akt Phosphorylation and Regulation of Transketolase Is a Nodal Point for Amino Acid Control of Purine Synthesis

    PubMed Central

    Saha, Arindam; Connelly, Stephen; Jiang, Jingjing; Zhuang, Shunhui; Amador, Deron T.; Phan, Tony; Pilz, Renate B.; Boss, Gerry R.

    2014-01-01

    SUMMARY The phosphatidylinositol 3-kinase (PI3K)/Akt pathway integrates environmental clues to regulate cell growth and survival. We showed previously that depriving cells of a single essential amino acid rapidly and reversibly arrests purine synthesis. Here we demonstrate that amino acids via mTORC2 and IκB kinase regulate Akt activity, and Akt association and phosphorylation of transketolase (TKT), a key enzyme of the non-oxidative pentose phosphate pathway (PPP). Akt phosphorylates TKT on Thr382, markedly enhancing enzyme activity and increasing carbon flow through the non-oxidative PPP, thereby increasing purine synthesis. Mice fed a lysine-deficient diet for two days show decreased Akt activity, TKT activity, and purine synthesis in multiple organs. These results provide a new mechanism whereby Akt coordinates amino acid availability with glucose utilization, purine synthesis, and RNA and DNA synthesis. PMID:24981175

  1. Akt phosphorylation and regulation of transketolase is a nodal point for amino acid control of purine synthesis.

    PubMed

    Saha, Arindam; Connelly, Stephen; Jiang, Jingjing; Zhuang, Shunhui; Amador, Deron T; Phan, Tony; Pilz, Renate B; Boss, Gerry R

    2014-07-17

    The phosphatidylinositol 3-kinase (PI3K)/Akt pathway integrates environmental clues to regulate cell growth and survival. We showed previously that depriving cells of a single essential amino acid rapidly and reversibly arrests purine synthesis. Here we demonstrate that amino acids via mammalian target of rapamycin 2 and IκB kinase regulate Akt activity and Akt association and phosphorylation of transketolase (TKT), a key enzyme of the nonoxidative pentose phosphate pathway (PPP). Akt phosphorylates TKT on Thr382, markedly enhancing enzyme activity and increasing carbon flow through the nonoxidative PPP, thereby increasing purine synthesis. Mice fed a lysine-deficient diet for 2 days show decreased Akt activity, TKT activity, and purine synthesis in multiple organs. These results provide a mechanism whereby Akt coordinates amino acid availability with glucose utilization, purine synthesis, and RNA and DNA synthesis. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. 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.

  3. 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.

  4. 9H-Purine Scaffold Reveals Induced-Fit Pocket Plasticity of the BRD9 Bromodomain

    PubMed Central

    2015-01-01

    The 2-amine-9H-purine scaffold was identified as a weak bromodomain template and was developed via iterative structure based design into a potent nanomolar ligand for the bromodomain of human BRD9 with small residual micromolar affinity toward the bromodomain of BRD4. Binding of the lead compound 11 to the bromodomain of BRD9 results in an unprecedented rearrangement of residues forming the acetyllysine recognition site, affecting plasticity of the protein in an induced-fit pocket. The compound does not exhibit any cytotoxic effect in HEK293 cells and displaces the BRD9 bromodomain from chromatin in bioluminescence proximity assays without affecting the BRD4/histone complex. The 2-amine-9H-purine scaffold represents a novel template that can be further modified to yield highly potent and selective tool compounds to interrogate the biological role of BRD9 in diverse cellular systems. PMID:25703523

  5. 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.

  6. Purine derivatives as potent Bruton’s tyrosine kinase (BTK) inhibitors for autoimmune diseases

    SciTech Connect

    Shi, Qing; Tebben, Andrew; Dyckman, Alaric J.; Li, Hedy; Liu, Chunjian; Lin, James; Spergel, Steve; Burke, James R.; McIntyre, Kim W.; Olini, Gilbert C.; Strnad, Joann; Surti, Neha; Muckelbauer, Jodi K.; Chang, Chiehying; An, Yongmi; Cheng, Lin; Ruan, Qian; Leftheris, Katerina; Carter, Percy H.; Tino, Joseph; De Lucca, George V.

    2014-05-01

    Investigation of various heterocyclic core isosteres of imidazopyrazines 1 & 2 yielded purine derivatives 3 & 8 as potent and selective BTK inhibitors. Subsequent SAR studies of the purine series led to the discovery of 20 as a leading compound. Compound 20 is very selective when screened against a panel of 400 kinases and is a potent inhibitor in cellular assays of human B cell function including B-Cell proliferation and CD86 cell surface expression and exhibited in vivo efficacy in a mouse PCA model. Its X-ray co-crystal structure with BTK shows that the high selectivity is gained from filling a BTK specific lipophilic pocket. However, physical and ADME properties leading to low oral exposure hindered further development.

  7. 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.

  8. Synthesis of Novel N9-Substituted Purine Derivatives from Polymer Supported α-Amino Acids.

    PubMed

    Vanda, David; Jorda, Radek; Lemrová, Barbora; Volná, Tereza; Kryštof, Vladimír; McMaster, Claire; Soural, Miroslav

    2015-07-13

    Solid-phase synthesis of purine derivatives bearing an α-amino acid motif in position 9 is described herein. Polymer supported amines were acylated with various Fmoc-α-amino acids and, after cleavage of the protecting group, arylation with 4,6-dichloro-5-nitropyrimidine or 2,4-dichloro-5-nitropyrimidine was performed. The second chlorine atom was replaced with various amines. Subsequent reduction of the nitro group, followed by reaction with aldehydes, afforded the purine scaffold. After cleavage from the polymer support, the target compounds were obtained in very good crude purity, good overall yields, and excellent enantiomeric purity. The anticancer activity of prepared compounds was tested in vitro against human cancer cell lines MCF7 and K562, and they were found to have mild, but clear dose-dependent effects.

  9. 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. Copyright © 2016, American Association for the Advancement of Science.

  10. 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.

  11. 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

  12. 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.

  13. Purine Pathway Implicated in Mechanism of Resistance to Aspirin Therapy: Pharmacometabolomics-Informed-Pharmacogenomics

    PubMed Central

    Yerges-Armstrong, Laura M.; Ellero-Simatos, Sandrine; Georgiades, Anastasia; Zhu, Hongjie; Lewis, Joshua; Horenstein, Richard B.; Beitelshees, Amber L.; Dane, Adrie; Reijmers, Theo; Hankemeier, Thomas; Fiehn, Oliver; Shuldiner, Alan R.; Kaddurah-Daouk, Rima

    2014-01-01

    Though 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 (HAPI) Heart Study. Many metabolites, including known aspirin catabolites, changed upon exposure to aspirin and pathway enrichment analysis identified purine metabolism as significantly affected by drug exposure. Further, purines were associated with aspirin response and poor responders had higher post-aspirin adenosine and inosine than good responders (N=76;p<4×10-3 both). Using our established “pharmacometabolomics-informs-pharmacogenomics” approach we identified genetic variants in adenosine kinase (ADK) 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

  14. 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.

  15. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

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

    PubMed

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

    2017-08-01

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

  18. The influence of exocyclic substituents of purine bases on DNA curvature.

    PubMed Central

    Diekmann, S; von Kitzing, E; McLaughlin, L; Ott, J; Eckstein, F

    1987-01-01

    Complementary oligonucleotides with 5' overhanging deoxyguanosine or deoxycytidine stretches, respectively, of the general form 5'-d(GGGCAARAAC).5'-d(CCCGTTYTTG), where R represents the bases adenine (A), hypoxanthine (base of inosine nucleoside, I), purine (R), 2-aminopurine (n2R), or 2,6-diaminopurine (n2,6(2)R) and where Y represents the pyrimidine bases thymine (T) or cytosine (C), have been chemically synthesized. After hybridization of complementary fragments, they were ligated to form multimers and analyzed by polyacrylamide gel electrophoresis. Anomalous gel migration was observed for the sequences 5'-d(AARAA) when the R.Y base pair was dA.dT, dI.dC, or dR.dT. All of these base pairs lack at least the amino group at position 2 of the purine base. The degree of anomalous gel migration was also related to the substituent at position 6 of the purine base. An amino group at position 6 was more effective than a carbonyl or a hydrogen in inducing anomalous gel migration. Additionally, the fragments 5'-d(GGGCAIAIAC).5'-d(CCCGTCTCTG), 5'-d(GGGCAIIIAC).5'-d(CCCGTCCCTG), and 5'-d(GGGCIIAIIC).5'-d(CCCGCCTCCG) were prepared in which increasing numbers of dA.dT base pairs are replaced by dI.dC base pairs. The degree of gel-migration anomaly of these sequences correlates with the number of dA.dT base pairs left in the five-base purine block. The data support the hypothesis that within the deoxyadenosine tracts, the base pairs fold into the minor groove at position 2 of the base to balance for the NH2 groups at position 6. This hypothesis explains the formation of a B'-form DNA structure for the deoxyadenosine tracts as well as DNA curvature. Images PMID:3479789

  19. Evidence for incorporation of intact dietary pyrimidine (but not purine) nucleosides into hepatic RNA.

    PubMed Central

    Berthold, H K; Crain, P F; Gouni, I; Reeds, P J; Klein, P D

    1995-01-01

    The absorption and metabolism of dietary nucleic acids have received less attention than those of other organic nutrients, largely because of methodological difficulties. We supplemented the rations of poultry and mice with the edible alga Spirulina platensis, which had been uniformly labeled with 13C by hydroponic culture in 13CO2. The rations were ingested by a hen for 4 wk and by four mice for 6 days; two mice were fed a normal diet and two were fed a nucleic acid-deficient diet. The animals were killed and nucleosides were isolated from hepatic RNA. The isotopic enrichment of all mass isotopomers of the nucleosides was analyzed by selected ion monitoring of the negative chemical ionization mass spectrum and the labeling pattern was deconvoluted by reference to the enrichment pattern of the tracer material. We found a distinct difference in the 13C enrichment pattern between pyrimidine and purine nucleosides; the isotopic enrichment of uniformly labeled [M + 9] isotopomers of pyrimidines exceeded that of purines [M + 10] by > 2 orders of magnitude in the avian nucleic acids and by 7- and 14-fold in the murine nucleic acids. The purines were more enriched in lower mass isotopomers, those less than [M + 3], than the pyrimidines. Our results suggest that large quantities of dietary pyrimidine nucleosides and almost no dietary purine nucleosides are incorporated into hepatic nucleic acids without hydrolytic removal of the ribose moiety. In addition, our results support a potential nutritional role for nucleosides and suggest that pyrimidines are conditionally essential organic nutrients. PMID:7479738

  20. 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

  1. 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. © 2015 Strom et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  2. Electronic and structural elements that regulate the excited-state dynamics in purine nucleobase derivatives.

    PubMed

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

    2015-04-08

    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 (1)nπ* state. Following vibrational and conformational relaxation, the (1)nπ* 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 (1)nπ* state while simultaneously facilitating access to the (1)ππ*(La)/S0 conical intersection, such that population of the (1)nπ* state cannot compete with the relaxation pathways to the ground state involving ring puckering at the C2 position.

  3. [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.

  4. 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

  5. [Measurement of purines and uric acid simultaneous in meat with high performance liquid chromatographys].

    PubMed

    Yang, Haibin; Zhang, Jialing; Liu, Guiying; Zhang, Ping

    2012-03-01

    To determinate adenine, guanine, hypoxanthine, xanthine and uric acid simultaneously in meat, a reversed-phase high performance liquid chromatography (HPLC) was developed. The meat were hydrolyzed with perchloric acid 10% (v/v) in boiling water for 60 mm. After the hydrolysate was adjusted to pH 4, centrifuge , and filtrated with a 0.45 mirom membrane, the supernatants were separated on an Agilent ZORBAX Eclipse XDB-C18 column (250 mm x 4.6 mm i.d., 5 microm) at 25 degrees C with a mobile phase of 7 x 10(-3) mol/L KH2PO4-H3P04(pH 4.0) ,a flow rate of 1.0 ml/ mm, and UV detection at 254 nm. Each component in the corresponding concentration range showed a good linear relation with its peak area, correlation coefficient r > 0.9999, recovery was 90.0%-107. 5%, RSD was 1.7%-13.3%. In addition to containing four kinds of purines, there was quite amount of uric acid (about 133.7 -86.2 pug/g) in the mentioned meat. The ratio of uric acid to total purine and uric acid was about 7%. The content of total purine in chicken was (1759.3 +/- 64.6) microg/g higher than in rabbit, mutton, pork and beef (1440-1000 microg/g). The validated method is simple, rapid, accurate and reliable to the determination of purines and uric acid in meat.

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

    PubMed

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

    2012-05-01

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

  7. 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.

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

    PubMed Central

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

    2012-01-01

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

  9. 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.

  10. Proline metabolism in N2-fixing root nodules: energy transfer and regulation of purine synthesis.

    PubMed Central

    Kohl, D H; Schubert, K R; Carter, M B; Hagedorn, C H; Shearer, G

    1988-01-01

    N2-fixing root nodules of soybean (Glycine max L. Merr.) convert atmospheric N2 to ammonia(um) in an energy-intensive enzymatic reaction. These nodules synthesize large quantities of purines because nitrogen fixed by bacteria contained within this tissue is transferred to the shoots in the form of ureides, which are degradation products of purines. In animal systems, it has been proposed that proline biosynthesis by pyrroline-5-carboxylate reductase (P5CR) is used to generate the NADP+ required for the synthesis of the purine precursor ribose 5-phosphate. We have examined the levels, properties, and location of P5CR and proline dehydrogenase (ProDH) in soybean nodules. Nodule P5CR was found in the plant cytosol. Its activity was substantially higher than that reported for other animal and plant tissues and is 4-fold higher than in pea (Pisum sativum) nodules (which export amides). The Km for NADPH was lower by a factor of 25 than the Km for NADH, while the Vmax with NADPH was one-third of that with NADH. P5CR activity was diminished by NADP+ but not by proline. These characteristics are consistent with a role for P5CR in supporting nodule purine biosynthesis rather than in producing proline for incorporation into protein. ProDH activity was divided between the bacteroids and plant cytosol, but less than 2% was in the mitochondria-rich fractions. The specific activity of ProDH in soybean nodule bacteroids was comparable to that in rat liver mitochondria. In addition, we propose that some of the proline synthesized in the plant cytosol by P5CR is catabolized within the bacteroids by ProDH and that this represents a novel mechanism for transferring energy from the plant to its endosymbiont. PMID:3353366

  11. 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…

  12. 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…

  13. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. 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

  15. 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.

  16. 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

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

    PubMed

    Díaz-Muñoz, M; Salín-Pascual, R

    2010-12-01

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

  18. GPCRs regulate the assembly of a multienzyme complex for purine biosynthesis

    PubMed Central

    Verrier, Florence; An, Songon; Ferrie, Ann M.; Sun, Haiyan; Kyoung, Minjoung; Deng, Huayun; Fang, Ye; Benkovic, Stephen J.

    2011-01-01

    G protein-coupled receptors (GPCRs) transmit exogenous signals to the nucleus, promoting a myriad of biological responses via multiple signaling pathways in both normal and cancer cells. However, little is known about the response in cytosolic metabolic pathways to GPCR-mediated signaling. Here, we applied fluorescent live-cell imaging and label-free dynamic mass redistribution assays to study whether purine metabolism is associated with GPCR signaling. By screening a library of GPCR ligands in conjunction with live-cell imaging of a metabolic multienzyme complex for de novo purine biosynthesis, the purinosome, we demonstrated that the activation of endogenous Gαi-coupled receptors correlates with purinosome assembly/disassembly in native HeLa cells. Given the implications of GPCRs in mitogenic signaling as well as the purinosome in controlling metabolic flux via de novo purine biosynthesis, we hypothesize that regulation of purinosome assembly/disassembly may represent one of downstream events of mitogenic GPCR signaling in human cancer cells. PMID:22020552

  19. GPCRs regulate the assembly of a multienzyme complex for purine biosynthesis.

    PubMed

    Verrier, Florence; An, Songon; Ferrie, Ann M; Sun, Haiyan; Kyoung, Minjoung; Deng, Huayun; Fang, Ye; Benkovic, Stephen J

    2011-10-23

    G protein-coupled receptors (GPCRs) transmit exogenous signals to the nucleus, promoting a myriad of biological responses via multiple signaling pathways in both healthy and cancerous cells. However, little is known about the response of cytosolic metabolic pathways to GPCR-mediated signaling. Here we applied fluorescent live-cell imaging and label-free dynamic mass redistribution assays to study whether purine metabolism is associated with GPCR signaling. Through a library screen of GPCR ligands in conjunction with live-cell imaging of a metabolic multienzyme complex for de novo purine biosynthesis, the purinosome, we demonstrated that the activation of endogenous Gα(i)-coupled receptors correlates with purinosome assembly and disassembly in native HeLa cells. Given the implications of GPCRs in mitogenic signaling and of the purinosome in controlling metabolic flux via de novo purine biosynthesis, we hypothesize that regulation of purinosome assembly and disassembly may be one of the downstream events of mitogenic GPCR signaling in human cancer cells.

  20. 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.

  1. Effects of allopurinol and oxipurinol on purine synthesis in cultured human cells

    PubMed Central

    Kelley, William N.; Wyngaarden, James B.

    1970-01-01

    In the present study we have examined the effects of allopurinol and oxipurinol on the de novo synthesis of purines in cultured human fibroblasts. Allopurinol inhibits de novo purine synthesis in the absence of xanthine oxidase. Inhibition at lower concentrations of the drug requires the presence of hypoxanthine-guanine phosphoribosyltransferase as it does in vivo. Although this suggests that the inhibitory effect of allopurinol at least at the lower concentrations tested is a consequence of its conversion to the ribonucleotide form in human cells, the nucleotide derivative could not be demonstrated. Several possible indirect consequences of such a conversion were also sought. There was no evidence that allopurinol was further utilized in the synthesis of nucleic acids in these cultured human cells and no effect of either allopurinol or oxipurinol on the long-term survival of human cells in vitro could be demonstrated. At higher concentrations, both allopurinol and oxipurinol inhibit the early steps of de novo purine synthesis in the absence of either xanthine oxidase or hypoxanthine-guanine phosphoribosyltransferase. This indicates that at higher drug concentrations, inhibition is occurring by some mechanism other than those previously postulated. PMID:5415686

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

    PubMed

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

    2002-01-08

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

  3. 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.

  4. 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

  5. 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.

  6. Enzymic cleavage of purine ultraviolet photoproducts formed at biologically significant wavelengths

    SciTech Connect

    Gallagher, P.E.; Duker, N.J.

    1986-05-01

    A paradox of ultraviolet carcinogenesis research has been that maximal absorption and mutagenesis occurs at 254 nm irradiation, while the greatest tumor yield in irradiated animals has been at wavelengths between 275 and 300 nm. Ambient actinic radiation contains mostly wavelengths above 280 nm with no substantial 254 nm component. Therefore, the authors investigated formation of DNA damage by 250-400 nm irradiation. Irradiated, 3'-end-labeled, 92 base pair sequence of the human alphoid segment was incubated with endonuclease v, purified from T4-infected E. coli, or with a crude extract of M. luteus. Analysis by gel electrophoresis showed that besides pyrimidine photodimers, previously unreported photoproducts were incised. These are not 6-4'(pyrimidin-2'-one)-pyrimidines, apurinic or apyrimidinic sites, or ring-opened purines. The new products are at specific purine loci and are formed in quantities similar to pyridimine dimers. The optimal wavelengths for their formation are 275-295 nm, similar to the maximum peak of actinic carcinogenesis. The enzyme incising these products is inactivated by different heating conditions than the pyrimidine dimer-DNA glycosylase, and they appear to be separable by column chromatography. The authors propose that a novel family of photoproducts, possibly purine-containing dimers, are incised by previously uncharacterized DNA repair enzymes.

  7. Levels of purine, kynurenine and lipid peroxidation products in patients with inflammatory bowel disease.

    PubMed

    Forrest, Caroline M; Gould, Stuart R; Darlington, L Gail; Stone, Trevor W

    2003-01-01

    The factors affecting gut activity in inflammatory bowel disease are unclear, but purines and kynurenines may be involved in the regulation of neuronal activity and therefore gut motility and secretion. We have measured the serum levels of these compounds in patients and in sex- and age-matched controls. Purines and kynurenines were analysed using HPLC. The levels of tryptophan and its metabolites 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid were unchanged in all patients. However, the levels of kynurenine and kynurenic acid were significantly elevated in patients with inflammatory bowel disease when compared to control subjects. There were no significant differences between patients and controls for any of the purines analysed or for neopterin. In the inflammatory bowel disease patients serum lipid peroxidation products were significantly elevated when compared to control subjects, suggesting the presence of increased oxidative stress consistent with inflammatory activity. The elevated level of kynurenic acid may represent either a compensatory response to elevated activation of enteric neurones, or a primary abnormality, which induces a compensatory increase in gut activity, but may indicate a role for kynurenine modulation of glutamate receptors in the symptoms of inflammatory bowel disease.

  8. Hypercrosslinked strong cation-exchange polymers for selective extraction of serum purine metabolites associated with gout.

    PubMed

    Xu, Yating; Liu, Ju; Zhang, Hongyang; Jiang, Min; Cao, Lingling; Zhang, Min; Sun, Wei; Ruan, Shengli; Hu, Ping

    2016-05-01

    In this study, hypercrosslinked strong cation-exchange polymer resins (HXLPP-SCX) were synthesized and employed as selective sorbents for the solid-phase extraction (SPE) of basic purine metabolites associated with gout. The HXLPP-SCX material was prepared based on hypercrosslinking reactions and sulfonated with concentrated H2SO4. This synthetic procedure is facile and efficient without using highly toxic reagent. The resulting resins were characterized in the form of monodisperse microspheres (mean diameters of 3‒5μm) with narrow pore size (2.1nm) and relatively high specific surface areas (801m(2)/g). The polymers also possess high ion-exchange capacity (IEC, 2.22mmol/g) and good adsorption and selectivity performances for basic compounds. The resins used as SPE sorbents permit the selective enrichment of three pivotal purine metabolites (hypoxanthine, xanthine and inosine) in human serum followed by HPLC analysis. Method validation including linearity range, sensitivity, accuracy and reproducibility were evaluated. This method was exemplarily applied in the analysis of serum purines in gout patients and healthy controls. The present results demonstrate a promising potential of this HXLPP-SCX material for the clinical sample pretreatment.

  9. [Purine and pyrimidine nucleoside phosphorylases - remarkable enzymes still not fully understood].

    PubMed

    Bzowska, Agnieszka

    2015-01-01

    Purine and pyrimidine nucleoside phosphorylases catalyze the reversible phosphorolytic cleavage of the glycosidic bond of purine and pyrimidine nucleosides, and are key enzymes of the nucleoside salvage pathway. This metabolic route is the less costly alternative to the de novo synthesis of nucleosides and nucleotides, supplying cells with these important building blocks. Interest in nucleoside phosphorylases is not only due to their important role in metabolism of nucleosides and nucleotides, but also due to the potential medical use of the enzymes (all phosphorylases in activating prodrugs - nucleoside and nucleic base analogs, high-molecular mass purine nucleoside phosphorylases in gene therapy of some solid tumors) and their inhibitors (as selective immunosuppressive, anticancer and antiparasitic agents, and preventing inactivation of other nucleoside drugs). Phosphorylases are also convenient tools for efficient enzymatic synthesis of otherwise inaccessible nucleoside analogues. In this paper the contribution of Professor David Shugar and some of his colleagues and coworkers in studies of these remarkable enzymes carried out over nearly 40 years is discussed on the background of global research in this field.

  10. Novel anomeric sugar phosphodiesters synthesis, hydrolytic mechanism, structure and interaction with purine nucleoside phosphorylase

    SciTech Connect

    Fathi, R.

    1988-01-01

    Some five-membered ring ribofuranosyl-1,2-cyclic phosphates were synthesized, purified, and characterized for the purpose of employing them as stereoselective electrophilic substrate analogs with a potential to trap enzymic nucleophiles on the purine salvage pathway. The purine salvage enzyme purine nucleoside phosphorylase from mammalian sources was irreversibly inactivated at its catalytic center by ..cap alpha..-D-ribofuranosyl-1,2-cyclic monophosphate. The product distribution and kinetics of hydronium and hydroxide catalyzed hydrolysis of cyclic phosphates were monitored by /sup 31/P NMR. Alkaline hydrolysis was demonstrated to proceed exclusively by O-P bond cleavage by employing a specifically /sup 18/O-labelled substrate. Acid hydrolysis proceeded by C-O bond cleavage. The high rates of alkaline hydrolysis were similar to those reported for ethylene phosphate, presumably due to the presence of a strained cyclic phosphate ring. Extensive NMR (/sup 1/H, /sup 13/C, and /sup 31/P) data on the cyclic phosphates were consistent with a C3-endo ribofuranosyl conformation.

  11. UK goes to the Planets

    NASA Astrophysics Data System (ADS)

    Heward, A.

    UK goes to the Planets Anita Heward UK Goes to the Planets Co-ordinator (anitaheward@btinternet.com) "UK goes to the Planets" is a campaign to promote the UK's involvement in missions to explore the Solar System. The campaign is run by a consortium of representatives from the research institutions and commercial companies that are involved in these missions. Since the end of 2002, the consortium has met every few months to discuss how to capitalise on the promotional opportunity offered by this busy time in planetary exploration. The main aim is to encourage collaboration between organisations in order to produce the most comprehensive and cost-effective outreach activities and highlight the UK-wide involvement in planetary science. Activities to date have included press and media events, as well as the development of a website, publications, educational materials and exhibitions. This talk will review the achievements of the past four years and look ahead to future plans.

  12. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Explicit and asymptotic solutions of simultaneous 1st-order and Riccati equations for a gas reaction system

    NASA Astrophysics Data System (ADS)

    Gilliam, Ashley E.; Wunsch, Jared; Lerman, Abraham

    2017-09-01

    Systems of simultaneous or parallel chemical reactions of the type A → B → C → Other products are often treated as first order or pseudo-first order. For a system of simultaneous first and second order reactions — dB/dt = kABA - kBCB2 and dC/dt = kBCB2 - kCC, where A, B, and C are concentrations, t is time, and the reaction rate parameters kAB and kC in yr-1 are 1st-order and kBC in cm3 molecule-1 yr-1 is 2nd-order — no explicit solution is available, as far as we are aware. This paper presents explicit and asymptotic solutions of simultaneous 1st- and 2nd order Riccati equations and applies them to a simplified sequence of gas reactions in the atmosphere of Titan, the largest satellite of Saturn: CH4 methane (1st order, k12) → CH3 methyl (2nd order, k23) → C2H6 ethane (1st order, k3) → Other products. The Titan's atmosphere contains methane (CH4) at the present-day partial pressure of 0.1 bar, out of a total atmospheric pressure made up by nitrogen (N2) of 1.5 bar, comparable to Earth's. Methyl CH3 and ethane C2H6 are minor components. On Titan, methyl (CH3) is an intermediate product from methane to ethane, the latter raining out as liquid on Titan's surface. The main points of this paper are: (1) the asymptotic solutions that approximate near-steady state of Titan's atmosphere about 4.5 billion years after its accretion; (2) the computed present-day concentrations of the three gases in Titan's scale atmosphere (i.e., scale atmosphere is a model of an isothermal well mixed reservoir); and (3) the agreement between Titan's reported and computed atmospheric concentrations of CH4, CH3, and C2H6. The reaction rate parameters of the species are constants representative of their mean values during the satellite's cooling history. The present-day concentrations of methyl (CH3) and ethane (C2H6) are several orders of magnitude lower than the concentration of methane (CH4). Since Titan's accretion about 4.5 billion years B.P., steady-state concentrations

  14. A compositional study of a museum jewellery collection (7th-1st BC) by means of a portable XRF spectrometer

    NASA Astrophysics Data System (ADS)

    Karydas, A. G.; Kotzamani, D.; Bernard, R.; Barrandon, J. N.; Zarkadas, Ch.

    2004-11-01

    Within the framework of the project "Jewelmed" (ICA3-1999-10020), the chemical composition of 34 gold and four silver jewels was examined. These jewels belong to the Benaki museum's collection in Athens, Greece and are dating from the 7th to the 1st century BC. The compositional analysis of the jewels was performed by means of a "home-made" portable X-ray fluorescence (XRF) spectrometer. The XRF results have shown that the gold jewels can be categorized in two groups, which include artifacts made by native and by high purity gold, respectively. For the silver jewels the results have provided interesting information regarding the manufacturing technology, the authenticity of the jewels and the raw materials used. The potential and the limitations of the XRF technique, applied in the chemical analysis of archaeological metal artifacts, are also discussed.

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

    PubMed

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

    2013-05-01

    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.

  16. [Effectiveness of teaching gerontology and geriatrics in students of the 1st Faculty of Medicine, Charles University in Prague].

    PubMed

    Mádlová, P; Neuwirth, J; Topinková, E

    2006-01-01

    Increasing number of seniors in the society requires more university-degree educated professionals--health care professionals, social care workers and managers with basic exposure to and knowledge of gerontology and geriatrics. The aim of our paper was to evaluate the effectiveness of undergraduate training of gerontology and geriatrics among students of the 1st Faculty of Medicine, Charles University in Prague. To get information about knowledge of medical students and students of ergotherapy and physiotherapy and about their attitudes towards senior citizens we conducted a survey using two anonymous questionnaires prepared in our department and piloted earlier. The survey ran during the academic year 2004/2005. Students completed identical questionnaires twice, first time before the start of the clinical rotation and second time after the training end (n=134). Evaluation of knowledge and attitudes confirmed that one to two weeks clinical rotation at Department of Geriatrics was effective and increased knowledge of students in the topic trained. The percentage of correct answers in all three evaluated training programmes increased after the completion of the clinical rotation and reached 83% and more. From 134 participating students, 54.5 % appreciated life experience and wisdom of seniors they met, 98.4 % of students were satisfied with the training programme and 67.2 % of students reported that after training they changed their attitude towards senior population. Our survey confirmed that clinical training in geriatric medicine at 1st Faculty of Medicine, Charles University in Prague, prepared in agreement with current European recommendations is sufficiently effective and well accepted by the students. Therefore we recommend introduction of formal geriatric training for students in all medical faculties in the Czech Republic.

  17. Evaluation of a modified team based learning method for teaching general embryology to 1st year medical graduate students.

    PubMed

    Shankar, Nachiket; Roopa, R

    2009-01-01

    To encourage student participation in the learning process, the authors introduced a modified team based learning (TBL) method to cover two general embryology topics in the 1st year MBBS curriculum. The aim of this study was to evaluate students' perception of this method vis-à-vis the lecture method of teaching. A questionnaire was used to survey and evaluate the perceptions of 1st year MBBS students at the Department of Anatomy at our medical college in India. A total of eight classes were allotted to cover General Embryology. Six of these classes were conducted using the traditional didactic lecture method. Two topics were covered using the modified TBL method. Five teams of students were constituted, and each team was given handouts which contained basic factual material, four clinical case histories, and previous university exam questions from the topic. On the day of the session, these were discussed in the presence of the faculty facilitator. Students evaluated these sessions through a questionnaire. A majority of students felt that the modified TBL sessions were better at fulfilling learning objectives (46 students, 85%), enabled better understanding (43 students, 79%), were more interesting (43 students, 81%), ensured greater student participation (51 students, 94%) and involved greater effort on the part of students (53 students, 98%), as compared to traditional teaching methods. Most of the students (43 students, 79%) opined that more such sessions should be organized in the future. Responses from students show that the modified TBL classes could be utilized judiciously along with the traditional didactic lectures for teaching embryology.

  18. [Evaluation of the higher brain functions in 1st and 7th grade schoolchildren belonging to two different socioeconomic groups].

    PubMed

    Nogueira, G J; Castro, A; Naveira, L; Nogueira-Antuñano, F; Natinzon, A; Gigli, S L; Grossi, M C; Frugone, M; Leofanti, H; Marchesi, M

    The higher brain functions, together with the devices that sustain them, are essential assets belonging to human beings which are used to situate themselves in the world. They can be studied by conducting neuropsychological tests, the results of which vary according to demographic factors, such as age, sex, hand dominance, culture and level of schooling. The socioeconomic level (SEL) is another factor to be taken into account and must also be evaluated. Our objective was to evaluate and analyse the influence of SEL on the results obtained from neuropsychological tests carried out in normal school-age children. We studied 401 normal children, of both sexes, taken at random, at the beginning (1st grade, 6 years old) and at the end (7th grade, 12 years old) of elementary school and belonging to two different SEL: high and low. Schools belonging to different categories were selected: public, private, urban and suburban. A battery of tests that is commonly used in Neuropsychology was utilised to evaluate laterality, spatial orientation, integration (Bender's test and the Rey figure test), attention, memory and the areas of language, gnosis and praxis. Significant differences were found in relation to the SEL in the 1st and 7th grade tests: 20/27 (74%) and 17/27 (62%), respectively. These always meant lower results in the low SEL, except body scheme, ideomotor praxis and phonological coding, which in the 7th grade run in the opposite direction. Results were not related to the type of school (urban-suburban, public-private), sex, laterality or teachers' characteristics. Differences were more striking in the area of language, basic devices (attention, memory) and in the tests that integrate several different functions (Bender's test, Rey figure test). SEL is linked to the results obtained in neuropsychological evaluation tests. There is a direct relationship with low results in the low level. There is also a correlation between certain family characteristics associated to

  19. UK malaria treatment guidelines.

    PubMed

    Lalloo, David G; Shingadia, Delane; Pasvol, Geoffrey; Chiodini, Peter L; Whitty, Christopher J; Beeching, Nicholas J; Hill, David R; Warrell, David A; Bannister, Barbara A

    2007-02-01

    Malaria is the tropical disease most commonly imported into the UK, with 1500-2000 cases reported each year, and 10-20 deaths. 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. Most non-falciparum malaria cases are caused by Plasmodium vivax; a few cases are caused by the other two species of Plasmodium: Plasmodium ovale or Plasmodium malariae. Mixed infections with more than 1 species of parasite can occur; they commonly involve P. falciparum with the attendant risks of severe malaria. Management of malaria depends on awareness of the diagnosis and on performing the correct diagnostic tests: the diagnosis cannot be excluded until 3 blood specimens have been examined by an experienced microscopist. There are no typical clinical features of malaria, even fever is not invariably present. The optimum diagnostic procedure is examination of thick and thin blood films by an expert to detect and speciate the malarial parasites; P. falciparum malaria can be diagnosed almost as accurately using rapid diagnostic tests (RDTs) which detect plasmodial antigens or enzymes, although RDTs for other Plasmodium species are not as reliable. The treatment of choice for non-falciparum malaria is a 3-day course of oral chloroquine, to which only a limited proportion of P. vivax strains have gained resistance. Dormant parasites (hypnozoites) persist in the liver after treatment of P. vivax or P. ovale infection: the only currently effective drug for eradication of hypnozoites is primaquine. This must be avoided or given with caution under expert supervision in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), in whom it may cause severe haemolysis. Uncomplicated P. falciparum malaria can be treated orally with quinine, atovaquone plus proguanil (Malarone) or co-artemether (Riamet

  20. Analysis of Intra- and Extracellular Levels of Purine Bases, Nucleosides, and Nucleotides in HepG2 Cells by High-performance Liquid Chromatography.

    PubMed

    Fukuuchi, Tomoko; Yamaoka, Noriko; Kaneko, Kiyoko

    2015-01-01

    To evaluate cellular uptake and purine transport, we developed a high-performance liquid chromatography method for intra- and extracellular purine quantification. Our aim was to develop an effective method for simultaneously quantifying the substrate and metabolites with high sensitivity. C18 columns from different manufacturers were tested for simultaneous quantification of 22 different purine bases, nucleosides, and nucleotides. We used a YMC-Triart C18 column. The analysis conditions, including extraction solutions for the cells and cell culture medium, were optimized to achieve good quantification. Linearity, accuracy, determination limits, and recovery were assessed and showed good performance. The developed HPLC method was successfully applied to the qualitative analysis of 22 different intra- and extracellular purines, demonstrating that it is useful for studying the overall pattern of purine metabolism. This method could also be useful for evaluating metabolic dynamics of purines under a variety of stimulatory conditions of culture cells.

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

    PubMed

    Herbel, W; Montag, A

    1987-01-01

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

  2. A population study of Lesch-Nyhan disease in the UK.

    PubMed

    McCarthy, Gillian T; Green, Elizabeth M; Ogunbona, Oluwafemi; Simmonds, H Anne; Fairbanks, Lynette; Pountney, Terry; Bryant, Elizabeth

    2011-01-01

    The aims of this study were to identify all people with Lesch-Nyhan disease (LND) born in the UK between 1988 and 2008, and to obtain a clinical profile including age at diagnosis, genetic background, family history, neurological signs, and medications. Potential participants were contacted through the British Paediatric Neurology Surveillance Unit. Questionnaires were sent to each child's paediatric neurologist or primary consultant. Two purine laboratories provided metabolic information. Twenty-three live males with LND in the 0- to 20-year age band and eight live males over the age of 20 years were identified. Thirty-one live people with LND were identified in the UK in 2008, giving a prevalence of 1 in 2 million people. Over the 20 years of study, there was a mean incidence rate of 0.18 per 100 000 live births, range 0 to 0.5. To our knowledge, this study is the first to provide details of the prevalence and incidence of LND in the UK. The data highlight that clinical profiles, at the time of diagnosis, and management of the disease are variable. There is the need for ongoing monitoring of allopurinol dosage and metabolic screening. © The Authors. Journal compilation © Mac Keith Press 2010.

  3. Adaptive and Effortful Control and Academic Self-efficacy Beliefs on Achievement: A Longitudinal Study of 1st through 3rd Graders

    PubMed Central

    Liew, Jeffrey; McTigue, Erin; Barrois, Lisa; Hughes, Jan

    2009-01-01

    The linkages between self-regulatory processes and achievement were examined across three years in 733 children beginning at 1st grade (M = 6.57 years, SD = .39 at 1st grade) who were identified as lower achieving in literacy. Accounting for consistencies in measures (from one year prior) and for influences of child’s age, gender, IQ, ethnicity and economic adversity on achievement, results indicate that adaptive/effortful control at 1st grade contributed to both academic self-efficacy beliefs at 2nd grade, and reading (but not math) achievement at 3rd grade. Although academic self-efficacy did not partially mediate the linkage between adaptive/effortful control and achievement, academic self-efficacy beliefs were positively correlated with reading and math. Results support the notion that early efforts to promote children’s self-regulatory skills would enhance future academic self-beliefs and achievement, particularly in literacy. PMID:19169387

  4. 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.

  5. UK to support open access

    NASA Astrophysics Data System (ADS)

    Banks, Michael

    2012-08-01

    The UK government has "widely accepted" the recommendations of a major report into open-access publishing that was released in June by a 15-strong working group led by the British sociologist Janet Finch.

  6. MPs consider UK engineering's future.

    PubMed

    Long, John

    2008-08-01

    The Government's Parliamentary Innovation, Universities, Science and Skills Committee (IUSSC), which in January launched an enquiry into the current "state" of the UK engineering sector, recently held a session in Westminster to hear evidence on the topic from expert bodies. IHEEM chief executive John Long was among those to draft written evidence for the Committee that not only provides an overview of the current UK engineering sector and its major challenges, but also recommends ways to maximise engineers' contribution in the future.

  7. Detection of 1st- and 2nd-order temporal-envelope cues in a patient with left superior cortical damage.

    PubMed

    Füllgrabe, Christian; Maillet, Didier; Moroni, Christine; Belin, Catherine; Lorenzi, Christian

    2004-06-01

    This psychophysical study explores the extent to which the auditory cortex is necessary for various aspects of temporal-envelope perception, that is, perception of the slow temporal modulations in amplitude known to be crucial for sound identification. The ability to detect 1st- and 2nd-order sinusoidal amplitude modulation (AM) is evaluated in a single patient showing left-hemisphere damage encroaching the primary and secondary auditory cortices. Here, 1st- and 2nd-order AM refer to (1) sinusoidal variation in the amplitude of a 2 kHz pure tone, and (2) sinusoidal variation in the depth of a 64 Hz AM applied to the 2 kHz pure tone, respectively. The results replicate previous findings by showing that damage to the left auditory cortex results in a selective deficit in auditory sensitivity to the lowest 1St-order AM (i.e., 1st-order AM frequencies < 16 Hz). Moreover, a dissociation is apparent between the ability to detect 1st- and 2nd-order temporal-envelope cues. The patient shows poorer than normal ability to detect 2nd-order AM at low frequencies ranging from 4-23 Hz, but normal ability to detect the high (64 Hz) 1st-order AM carrying these 2nd-order modulations. This result indicates that damage to the left primary and secondary auditory cortices affects the ability to detect temporal variations in the local properties of sounds(such as AM depth). It is also consistent with the idea that, as in vision, central nonlinear mechanisms are involved in the computation of such local (or 2nd-order) temporal properties.

  8. U.S. Army Chemical Corps Historical Studies, Gas Warfare in World War I: The 1st Division in the Meuse-Argonne 1-12 October 1918

    DTIC Science & Technology

    1957-08-01

    October, instead of 30 September-I October 0 On the night of the relief the .Jnemy began shelling at 10s00 porn October 1st and continued until 4s00... Juvin and Landre, out off the Argoure front, and attack in rear of the Brunhild position to effect decisive action on the Group -Argonnej." 8 7 At...attack, fired on the Son’.erance area and north of St Georges et Landres, Juvin , Marcq, and Champigxeulle. 93 Company C, 1st Gas Regiment, was ordered

  9. [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.

  10. 1,3,5-Triazine-based analogues of purine: from isosteres to privileged scaffolds in medicinal chemistry.

    PubMed

    Lim, Felicia Phei Lin; Dolzhenko, Anton V

    2014-10-06

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

  11. Consequences of Impaired Purine Recycling on the Proteome in a Cellular Model of Lesch-Nyhan Disease

    PubMed Central

    Duong, Duc M.; Hanfelt, John; Seyfried, Nicholas T.; Jinnah, H. A.

    2015-01-01

    The importance of specific pathways of purine metabolism for normal brain function is highlighted by several inherited disorders, such as Lesch-Nyhan disease (LND). In this disorder, deficiency of the purine recycling enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt), causes severe neurological and behavioral abnormalities. Despite many years of research, the mechanisms linking the defect in purine recycling to the neurobehavioral abnormalities remain unclear. In the current studies, an unbiased approach to the identification of potential mechanisms was undertaken by examining changes in protein expression in a model of HGprt deficiency based on the dopaminergic rat PC6-3 line, before and after differentiation with nerve growth factor (NGF). Protein expression profiles of 5 mutant sublines carrying different mutations affecting HGprt enzyme activity were compared to the HGprt-competent parent line using the method of stable isotopic labeling by amino acids in cell culture (SILAC) followed by denaturing gel electrophoresis with liquid chromatography and tandem mass spectrometry (LC-MS/MS) of tryptic digests, and subsequent identification of affected biochemical pathways using the Database for Annotation, Visualization and Integrated Discovery (DAVID) functional annotation chart analysis. The results demonstrate that HGprt deficiency causes broad changes in protein expression that depend on whether the cells are differentiated or not. Several of the pathways identified reflect predictable consequences of defective purine recycling. Other pathways were not anticipated, disclosing previously unknown connections with purine metabolism and novel insights into the pathogenesis of LND. PMID:25769394

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

    PubMed

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

    2015-04-01

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

  13. 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.

  14. 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

  15. 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. © 2015 Phycological Society of America.

  16. The Purine-Utilizing Bacterium Clostridium acidurici 9a: A Genome-Guided Metabolic Reconsideration

    PubMed Central

    Hartwich, Katrin; Poehlein, Anja; Daniel, Rolf

    2012-01-01

    Clostridium acidurici is an anaerobic, homoacetogenic bacterium, which is able to use purines such as uric acid as sole carbon, nitrogen, and energy source. Together with the two other known purinolytic clostridia C. cylindrosporum and C. purinilyticum, C. acidurici serves as a model organism for investigation of purine fermentation. Here, we present the first complete sequence and analysis of a genome derived from a purinolytic Clostridium. The genome of C. acidurici 9a consists of one chromosome (3,105,335 bp) and one small circular plasmid (2,913 bp). The lack of candidate genes encoding glycine reductase indicates that C. acidurici 9a uses the energetically less favorable glycine-serine-pyruvate pathway for glycine degradation. In accordance with the specialized lifestyle and the corresponding narrow substrate spectrum of C. acidurici 9a, the number of genes involved in carbohydrate transport and metabolism is significantly lower than in other clostridia such as C. acetobutylicum, C. saccharolyticum, and C. beijerinckii. The only amino acid that can be degraded by C. acidurici is glycine but growth on glycine only occurs in the presence of a fermentable purine. Nevertheless, the addition of glycine resulted in increased transcription levels of genes encoding enzymes involved in the glycine-serine-pyruvate pathway such as serine hydroxymethyltransferase and acetate kinase, whereas the transcription levels of formate dehydrogenase-encoding genes decreased. Sugars could not be utilized by C. acidurici but the full genetic repertoire for glycolysis was detected. In addition, genes encoding enzymes that mediate resistance against several antimicrobials and metals were identified. High resistance of C. acidurici towards bacitracin, acriflavine and azaleucine was experimentally confirmed. PMID:23240052

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

    PubMed

    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.

  18. Construction and Characterization of an Attenuated Purine Auxotroph in a Francisella tularensis Live Vaccine Strain

    PubMed Central

    Pechous, Roger; Celli, Jean; Penoske, Renee; Hayes, Stanley F.; Frank, Dara W.; Zahrt, Thomas C.

    2006-01-01

    Francisella tularensis is a facultative intracellular pathogen and is the etiological agent of tularemia. It is capable of escaping from the phagosome, replicating to high numbers in the cytosol, and inducing apoptosis in macrophages of a variety of hosts. F. tularensis has received significant attention recently due to its potential use as a bioweapon. Currently, there is no licensed vaccine against F. tularensis, although a partially protective live vaccine strain (LVS) that is attenuated in humans but remains fully virulent for mice was previously developed. An F. tularensis LVS mutant deleted in the purMCD purine biosynthetic locus was constructed and partially characterized by using an allelic exchange strategy. The F. tularensis LVS ΔpurMCD mutant was auxotrophic for purines when grown in defined medium and exhibited significant attenuation in virulence when assayed in murine macrophages in vitro or in BALB/c mice. Growth and virulence defects were complemented by the addition of the purine precursor hypoxanthine or by introduction of purMCDN in trans. The F. tularensis LVS ΔpurMCD mutant escaped from the phagosome but failed to replicate in the cytosol or induce apoptotic and cytopathic responses in infected cells. Importantly, mice vaccinated with a low dose of the F. tularensis LVS ΔpurMCD mutant were fully protected against subsequent lethal challenge with the LVS parental strain. Collectively, these results suggest that F. tularensis mutants deleted in the purMCD biosynthetic locus exhibit characteristics that may warrant further investigation of their use as potential live vaccine candidates. PMID:16861631

  19. Purine utilization by Klebsiella oxytoca M5al: genes for ring-oxidizing and -opening enzymes.

    PubMed

    Pope, Scott D; Chen, Li-Ling; Stewart, Valley

    2009-02-01

    The enterobacterium Klebsiella oxytoca uses a variety of inorganic and organic nitrogen sources, including purines, nitrogen-rich compounds that are widespread in the biosphere. We have identified a 23-gene cluster that encodes the enzymes for utilizing purines as the sole nitrogen source. Growth and complementation tests with insertion mutants, combined with sequence comparisons, reveal functions for the products of these genes. Here, we report our characterization of 12 genes, one encoding guanine deaminase and the others encoding enzymes for converting (hypo)xanthine to allantoate. Conventionally, xanthine dehydrogenase, a broadly distributed molybdoflavoenzyme, catalyzes sequential hydroxylation reactions to convert hypoxanthine via xanthine to urate. Our results show that these reactions in K. oxytoca are catalyzed by a two-component oxygenase (HpxE-HpxD enzyme) homologous to Rieske nonheme iron aromatic-ring-hydroxylating systems, such as phthalate dioxygenase. Our results also reveal previously undescribed enzymes involved in urate oxidation to allantoin, catalyzed by a flavoprotein monooxygenase (HpxO enzyme), and in allantoin conversion to allantoate, which involves allantoin racemase (HpxA enzyme). The pathway also includes the recently described PuuE allantoinase (HpxB enzyme). The HpxE-HpxD and HpxO enzymes were discovered independently by de la Riva et al. (L. de la Riva, J. Badia, J. Aguilar, R. A. Bender, and L. Baldoma, J. Bacteriol. 190:7892-7903, 2008). Thus, several enzymes in this K. oxytoca purine utilization pathway differ from those in other microorganisms. Isofunctional homologs of these enzymes apparently are encoded by other species, including Acinetobacter, Burkholderia, Pseudomonas, Saccharomyces, and Xanthomonas.

  20. Endophytic bacteria from Pinellia ternata, a new source of purine alkaloids and bacterial manure.

    PubMed

    Liu, Yonghong; Liu, Wenting; Liang, Zongsuo

    2015-01-01

    Pinellia ternata (Thunb.) Berit., a perennial herb belonging to Araceae, is one of the few medicinal plants to produce purine alkaloids. It is speculated that endophytic bacteria from P. ternata may produce guanosine or inosine. However, there is no report about endophytic bacteria in P. ternata. In this study, endophytic bacteria were isolated from P. ternata and examined for the first time. This study finds a novel way to increase the yield of P. ternata herb, and to provide some new alkaloid producers. Plant material includes leaves, tubers, and roots of cultivated and wild P. ternata. The dilutions were smeared onto beef extract-peptone medium and cultured at 28 °C in darkness for 48-72 h. Co-culture treatments were prepared by inoculating 100 mL liquid 1/2 MS medium with bacterial culture broth at concentrations of 0 (control), 0.5%, and 1.5% (v/v). Of the 34 endophytic bacterial colonies isolated from P. ternata leaves, roots, and tubers, five strains were able to produce purine alkaloids. Results from 16s rDNA sequence analysis indicated that the bacteria belonged to Bacillus cereus, Aranicola proteolyticus, Serratia liquefaciens, Bacillus thuringiensis, and Bacillus licheniformis. Co-culture with living Serratia liquefaciens cells increased PLB growth by 58-71%. Co-culture with living Bacillus licheniformis cells increased PLB growth by 4-11%. This study provides a novel way for improving the yield of P. ternata herb, and for the production of purine alkaloids by the fermentation industry.

  1. Effects of extracellular purines on ion transport across the integument of Hirudo medicinalis.

    PubMed

    Schnizler, Mikael; Buss, Mirjam; Clauss, Wolfgang

    2002-09-01

    Little is known about the long-term regulation of epithelial ion transport in invertebrates and the specific mediators involved. For some years, we have been investigating the short-term regulation of transepithelial ion transport across the dorsal integument of the leech Hirudo medicinalis, and we have established a model of Na+ uptake. In the present study, we investigated the effect of long-term acclimation on transintegumental ion transport by adapting leeches to high-salinity conditions. We dissected segments of dorsal integument and measured ion currents in Ussing chamber experiments. Electrophysiological variables, such as transepithelial potential (V(T)) and short-circuit-current (I(sc)), were profoundly affected by adaptation to high-salinity conditions. The total transepithelial Na+ current (I(Na)) decreased from 7.66+/-0.82 to 4.6+/-0.54 microA cm(-2) in preparations adapted to high salinity. The involvement of epithelial Na+ channels was determined as current inhibition (I(ami)) by apical application of amiloride; Na+ channels were equally active in control epithelia and epithelia from leeches adapted to high salinity. Removal of Ca2+ from the apical solutions, which is believed to reduce intracellular Ca2+ concentrations, equalized transepithelial variables between high-salt-adapted integuments and control integuments. Extracellular purines regulate transepithelial Cl- secretion and Na+ absorption. In a variety of tissues we tested ATP and adenosine for their effects on epithelial transport. Examination of integuments from pondwater- and high-salinity-adapted leeches revealed different sensitivities for these purines. Apical and basolateral application of ATP both stimulated transepithelial Na+ uptake and I(ami). Adenosine upregulated non-Na+ currents and acted from the basolateral side only. Apical Ca2+-free conditions attenuated these effects of purines on transepithelial currents. Extracellular UTP had no effect on ion transport.

  2. 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

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

    PubMed

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

    2001-10-01

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

  4. [Fitness by cold stimulation of various intensity: effects on metabolism of purines and free radicals].

    PubMed

    Brenke, R; Siems, W; Maass, R

    1994-01-01

    Whole-body cold stimuli lead to a dosage-depended decrease of uric acid level in blood plasma. This could be observed in own studies on winter-swimming and cold shower application and in studies on patients treated by cold-chamber-therapy. This uric acid decrease is due to an accelerated oxygen radical formation during cold exposition rather than to an inhibition of purine metabolism. The acute oxidative loading due to cold exposure and the long-term antioxidative adaptation may be interpreted as a new molecular mechanism resulting in body hardening.

  5. Asymmetric purine-pyrimidine distribution in cellular small RNA population of papaya

    PubMed Central

    2012-01-01

    Background The small RNAs (sRNA) are a regulatory class of RNA mainly represented by the 21 and 24-nucleotide size classes. The cellular sRNAs are processed by RNase III family enzyme dicer (Dicer like in plant) from a self-complementary hairpin loop or other type of RNA duplexes. The papaya genome has been sequenced, but its microRNAs and other regulatory RNAs are yet to be analyzed. Results We analyzed the genomic features of the papaya sRNA population from three sRNA deep sequencing libraries made from leaves, flowers, and leaves infected with Papaya Ringspot Virus (PRSV). We also used the deep sequencing data to annotate the micro RNA (miRNA) in papaya. We identified 60 miRNAs, 24 of which were conserved in other species, and 36 of which were novel miRNAs specific to papaya. In contrast to the Chargaff’s purine-pyrimidine equilibrium, cellular sRNA was significantly biased towards a purine rich population. Of the two purine bases, higher frequency of adenine was present in 23nt or longer sRNAs, while 22nt or shorter sRNAs were over represented by guanine bases. However, this bias was not observed in the annotated miRNAs in plants. The 21nt species were expressed from fewer loci but expressed at higher levels relative to the 24nt species. The highly expressed 21nt species were clustered in a few isolated locations of the genome. The PRSV infected leaves showed higher accumulation of 21 and 22nt sRNA compared to uninfected leaves. We observed higher accumulation of miRNA* of seven annotated miRNAs in virus-infected tissue, indicating the potential function of miRNA* under stressed conditions. Conclusions We have identified 60 miRNAs in papaya. Our study revealed the asymmetric purine-pyrimidine distribution in cellular sRNA population. The 21nt species of sRNAs have higher expression levels than 24nt sRNA. The miRNA* of some miRNAs shows higher accumulation in PRSV infected tissues, suggesting that these strands are not totally functionally redundant. The

  6. 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.

  7. 9-Benzyl-6-benzyl­sulfanyl-9H-purin-2-amine

    PubMed Central

    Hariono, Maywan; Wahab, Habibah A.; Tan, Mei Lan; Rosli, Mohd Mustaqim; Razak, Ibrahim Abdul

    2014-01-01

    In the title compound, C19H17N5S, the dihedral angles between the purine ring system (r.m.s. deviation = 0.009 Å) and the S-bound and methyl­ene-bound phenyl rings are 74.67 (8) and 71.28 (7)°, respectively. In the crystal, inversion dimers linked by pairs of N—H⋯N hydrogen bonds generate R 2 2(8) loops. C—H⋯N inter­actions link the dimers into (100) sheets. PMID:24764997

  8. 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.

  9. Synthesis and anticancer activity of novel C6-piperazine substituted purine steroid-nucleosides analogues.

    PubMed

    Huang, Li-Hua; Xu, Hong-De; Yang, Zhuo-Ya; Zheng, Yong-Fei; Liu, Hong-Min

    2014-04-01

    Novel C6-piperazine substituted purine nucleoside analogues (2-9) bearing a modified pyranose-like D ring of the 4-azasteroid moiety were efficiently synthesized through nucleophilic substitution at C6 position of the steroid-nucleoside precursors (1) with versatile piperazines. All newly-synthesized compounds were evaluated for their anticancer activity in vitro against Hela, PC-3 and MCF-7 cell lines. Among them, compounds 8b and 9b exhibited significant cytotoxicity on PC-3 cell lines. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Transversion-specific purine analogue mutagens and the mechanism of hydroxylaminopurine mutagenesis.

    PubMed

    Murray, V

    1987-04-01

    The tryptophan synthetase gene A series of mutants in E. coli has been used to examine the mutational specificity of over 80 purine base analogues. 4 purine analogues have been discovered that solely cause transversions. Evidence is presented that hydroxylaminopurine mutagenesis is caused by a covalent reaction of these compounds with DNA. The transversion-causing purine analogues are derivatives of 2-aminopurine (2AP) and 2,6-diaminopurine (2,6DAP). They stimulate the full reversion frequency of those trp A which can revert through an AT----CG transversion. 8 purine base analogues have been found that induce the AT----CG transversion at the trp A88 site; and 2-amino-6-methylaminopurine (2A6MAP) stimulates by 124-fold, 2-amino-6-ethylaminopurine by 20-fold, 2-methylaminopurine (2MAP) by 9.4-fold, 2,6-bismethylaminopurine by 25-fold, 2AP by 230-fold, 2,6DAP by 15-fold, 2.6-diaminopurine riboside by 5-fold, and 2-hydroxylaminopurine by 11-fold. The last 4 analogues also cause transitions. 2A6MAP, 2-amino-6-ethylaminopurine and 2,6-bismethylaminopurine stimulate only the AT----CG transversion while 2MAP additionally gives rise to AT----TA transversions. By testing other negative 2AP derivatives, the structural requirements necessary for AT----CG transversion mutagenesis have been determined. All 12 hydroxylaminopurine base analogues tested, 2,6-dimethoxyaminopurine and 2-hydrazinopurine were found to cause transition mutations. All of the compounds stimulated the AT----GC transition (by up to 1000-fold) and 11 of the 14 base analogues raised the GT----AT transition (by up to 450-fold). On increasing the hydroxylaminopurine concentration, the mutation frequency also increased concomitantly. Since 6-hydroxylamino-9-methylpurine and 6-methylhydroxylaminopurine cause transitions, the mechanism of hydroxylaminopurine mutagenesis cannot be entirely due to an alteration in tautomeric equilibria or "wobble" type base mispairing. It is proposed that a major mechanism for

  11. Fluorescence and electrochemical detection of pyrimidine/purine transversion by a ferrocenyl aminonaphthyridine derivative.

    PubMed

    Morita, Kotaro; Sato, Yusuke; Seino, Takehiro; Nishizawa, Seiichi; Teramae, Norio

    2008-01-21

    A novel hydrogen bond-forming ligand for pyrimidine/purine transversion, which contains both a fluorescent naphthyridine moiety and a ferrocenyl group as an electrochemical indicator, is described. Hydrogen bond-mediated recognition for a target nucleobase at an abasic site in a DNA duplex is confirmed by both fluorescence and electrochemical measurements. The analysis by fluorescence titration reveals that the ligand shows significant fluorescent quenching upon formation of a 1 : 1 complex with the target nucleobase opposite the abasic site, and the selectivity is in the order of cytosine > thymine > adenine, guanine, reflecting the stability of the hydrogen bond formation.

  12. 1st International Conference on Panic Attacks: diversity of theories and treatments. september 5-8, 2003, London.

    PubMed

    Perry, David

    2004-04-01

    The 1st International Conference on Psychophysiology of Panic Attacks focused on the diversity of treatments and theories in this complex condition. Experimental research topics were featured, as well as treatment strategies, case studies and patient perspectives. The conference aimed to create a strong multi-cultural emphasis through international, interdisciplinary and patient-professional interaction. The experimental techniques of lactate provocation of panic, carbon dioxide provocation, respiratory measures and cholecystokinin tetrapeptide infusion were used in various ongoing studies aimed at investigating familial markers, protocols for inducing panic in subjects (including opioid-receptor blockade), brain stem mechanisms involved in mediating anxiety and correlation of respiratory variability with panic severity and treatment outcome. Internet-based questionnaire surveys of panic attack (PA) in subjects that had been sexually abused and of subjective feelings about PAs in patients undergoing fertility treatment were presented, as was a survey of panic epidemiology in Iranian students. Some novel treatment modes were discussed, including non-verbal imagery and art therapy and a telephone-conferencing delivery of cognitive-behavioural therapy. Several case studies were used to illustrate treatments and a personal account of panic disorder combined some time after onset with post-traumatic stress disorder highlighted the different responses of the two disorders to psychotherapies.

  13. 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.

  14. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. User satisfaction with primary health care by region in Brazil: 1st cycle of external evaluation from PMAQ-AB.

    PubMed

    Protasio, Ane Polline Lacerda; Gomes, Luciano Bezerra; Machado, Liliane Dos Santos; Valença, Ana Maria Gondim

    2017-06-01

    The National Program for Access and Quality Improvement in Primary Care (Programa Nacional de Melhoria do Acesso e da Qualidade da Atenção Básica, PMAQ-AB) aimed to improve healthcare public service quality and satisfaction of health service users. This study's objective was to identify the main factors influencing user satisfaction with primary care (PC) services by region in Brazil. Using secondary data from the 1st Cycle of PMAQ-AB, logistic regression models were developed by region, with user satisfaction as the dependent variable, as defined by cluster analysis. Based on the obtained models, the health unit's ability to solve users' problems and feeling respected by the health providers were the most important factors for user satisfaction in all regions in Brazil. However, other important factors by region included the following: the health unit's hours of operation meeting the user's needs (Northeast); providers asking about family members (North); providers asking about other health needs (Midwest); users being seen without an appointment (South); and users asking questions after the appointment (Southeast). In conclusion, the factors influencing user satisfaction with PC vary according to region and are mainly associated with access quality, meeting users' needs, and work process organization.

  1. 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

  2. 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…

  3. 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.

  4. 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…

  5. Experimental observations on the response of 1(st) and 2(nd) order fibre optic long period grating coupling bands to the deposition of nanostructured coatings.

    PubMed

    James, Stephen W; Cheung, C S; Tatam, Ralph P

    2007-10-01

    The sensitivity of attenuation bands corresponding to the 2(nd) order coupling to cladding modes by a fibre optic long period grating (LPG) to the deposition of nanostructured coatings is investigated and compared with that of the 1(st) order coupling. The experimental observations support previously reported theoretical descriptions of LPGs with nanoscale coatings.

  6. New Emphasis: Making Staff Development Happen. Proceedings of (the) 1st Annual Staff Development Workshop, Asheville, North Carolina, April 24-25, 1975.

    ERIC Educational Resources Information Center

    Western North Carolina Consortium, Inc.

    This document compiles the addresses presented at the 1st Annual Staff Development Workshop sponsored by the Western North Carolina Consortium. Presentations include: (l) "Staff Development--Why?" by Louis W. Bender; (2) "Staff Development--The State of the Art" by W. Robert Sullins; (3) "State Resources" by Hazel…

  7. 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…

  8. 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…

  9. Prolonged effect of a mother-child caries preventive program on dental caries in the permanent 1st molars in 9 to 10-year-old children.

    PubMed

    Gomez, Santiago S; Emilson, Claes-Göran; Weber, Adriana A; Uribe, Sergio

    2007-10-01

    To evaluate the prevalence of caries in the permanent 1st molars of a group of 9 to 10-year-old children, and to determine the long-term effect of a mother-child preventive dental program (PDP) that started when the women were pregnant and continued until the children were 6 years of age. The permanent 1st molars of 37 children in the PDP group were evaluated for caries, both clinically and radiographically, and compared with those of a control group of 42 children who had not participated in the PDP. Of children in the PDP group, 70% were caries free compared to 33% in the control group (p<0.001). Of permanent 1st molars in the PDP group, 87% were caries-free compared to 61% in the control group (p<0.001). The mean DFS of the PDP children 10 years of age was 0.519+/-0.93 versus 1.57+/-1.38 for the control children (p=0.002). Examination of children 4 years after discontinuation of a caries preventive program reflected a long-term reduction in the DFS score of permanent 1st molars.

  10. Importance of specific purine amino and hydroxyl groups for efficient cleavage by a hammerhead ribozyme.

    PubMed Central

    Fu, D J; McLaughlin, L W

    1992-01-01

    Eight modified ribozymes of 19 residues have been prepared with individual purine amino or hydroxyl groups excised. The modified ribozymes were chemically synthesized with the substitution of a single 2'-deoxyadenosine, 2'-deoxyguanosine, inosine, or purine riboside for residues G10, A11, G13, or A14. Five of the modified ribozymes cleaved the 24-mer substrate with little change in rate as monitored by simple first-order kinetics. However, deletion of the 2-amino group at G10 (replacement with inosine) or deletion of either of the 2'-hydroxyls at G10 or G13 (replacement with 2'-deoxyguanosine) resulted in ribozymes with a drastic decrease in cleavage efficiency. Increasing the concentration of the Mg2+ cofactor from 10 mM to 50 mM significantly enhanced cleavage efficiency by these three derivatives. Steady-state kinetic assays for these three ribozymes indicated that the modifications result in both an increase in Km and a decrease in kcat. These results suggest that the exocyclic amino group at-G10 and the hydroxyls at G10 and G13 are important both for ribozyme-substrate binding and for the Mg(2+)-catalyzed cleavage reaction. PMID:1570323

  11. 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

  12. Single tryptophan of disordered loop from Plasmodium falciparum purine nucleoside phosphorylase: involvement in catalysis and microenvironment.

    PubMed

    Suthar, Manish Kumar; Verma, Anita; Doharey, Pawan Kumar; Singh, Shiv Vardan; Saxena, Jitendra Kumar

    2013-06-01

    Among various tropical diseases, malaria is a major life-threatening disease caused by Plasmodium parasite. Plasmodium falciparum is responsible for the deadliest form of malaria, so-called cerebral malaria. Purine nucleoside phosphorylase from P. falciparum is a homohexamer containing single tryptophan residue per subunit that accepts inosine and guanosine but not adenosine for its activity. This enzyme has been exploited as drug target against malaria disease. It is important to draw together significant knowledge about inherent properties of this enzyme which will be helpful in better understanding of this drug target. The enzyme shows disorder to order transition during catalysis. The single tryptophan residue residing in conserved region of transition loop is present in purine nucleoside phosphorylases throughout the Plasmodium genus. This active site loop motif is conserved among nucleoside phosphorylases from apicomplexan parasites. Modification of tryptophan residue by N-bromosuccinamide resulted in complete loss of activity showing its importance in catalysis. Inosine was not able to protect enzyme against N-bromosuccinamide modification. Extrinsic fluorescence studies revealed that tryptophan might not be involved in substrate binding. The tryptophan residue localised in electronegative environment showed collisional and static quenching in the presence of quenchers of different polarities.

  13. Microwave-assisted synthesis of novel purine nucleosides as selective cholinesterase inhibitors.

    PubMed

    Schwarz, S; Csuk, R; Rauter, A P

    2014-04-21

    Alzheimer's disease (AD), the most common form of senile dementia, is characterized by high butyrylcholinesterase (BChE) levels in the brain in later AD stages, for which no treatment is available. Pursuing our studies on selective BChE inhibitors, that may contribute to understand the role of this enzyme in disease progression, we present now microwave-assisted synthesis and anticholinesterase activity of a new nucleoside series embodying 6-chloropurine or 2-acetamido-6-chloropurine linked to D-glucosyl, D-galactosyl and D-mannosyl residues. It was designed to assess the contribution of sugar stereochemistry, purine structure and linkage to the sugar for cholinesterase inhibition efficiency and selectivity. Compounds were subjected to Ellman's assay and their inhibition constants determined. The α-anomers were the most active compounds, while selectivity for BChE or acetylcholinesterase (AChE) inhibition could be tuned by the purine base, by the glycosyl moiety and by N(7)-ligation. Some of the nucleosides were far more potent than the drug galantamine, and the most promising competitive and selective BChE inhibitor, the N(7)-linked 2-acetamido-α-D-mannosylpurine, showed a Ki of 50 nM and a selectivity factor of 340 fold for BChE over AChE.

  14. Myc-dependent purine biosynthesis affects nucleolar stress and therapy response in prostate cancer

    PubMed Central

    Barfeld, Stefan J.; Fazli, Ladan; Persson, Margareta; Marjavaara, Lisette; Urbanucci, Alfonso; Kaukoniemi, Kirsi M.; Rennie, Paul S.; Ceder, Yvonne; Chabes, Andrei; Visakorpi, Tapio; Mills, Ian G.

    2015-01-01

    The androgen receptor is a key transcription factor contributing to the development of all stages of prostate cancer (PCa). In addition, other transcription factors have been associated with poor prognosis in PCa, amongst which c-Myc (MYC) is a well-established oncogene in many other cancers. We have previously reported that the AR promotes glycolysis and anabolic metabolism; many of these metabolic pathways are also MYC-regulated in other cancers. In this study, we report that in PCa cells de novo purine biosynthesis and the subsequent conversion to XMP is tightly regulated by MYC and independent of AR activity. We characterized two enzymes, PAICS and IMPDH2, within the pathway as PCa biomarkers in tissue samples and report increased efficacy of established anti-androgens in combination with a clinically approved IMPDH inhibitor, mycophenolic acid (MPA). Treatment with MPA led to a significant reduction in cellular guanosine triphosphate (GTP) levels accompanied by nucleolar stress and p53 stabilization. In conclusion, targeting purine biosynthesis provides an opportunity to perturb PCa metabolism and enhance tumour suppressive stress responses. PMID:25869206

  15. New bis-N9-(methylphenylmethyl)purine derivatives: synthesis and antitumor activity.

    PubMed

    Kode, Nageswara; Chen, Liying; Murthy, Devangachinta; Adewumi, Dare; Phadtare, Shashikant

    2007-03-01

    A series of ortho-, meta- and para-bis-N9-(methylphenylmethyl)purine derivatives 4-15 were obtained by two-step synthesis from various substituted chloropurines with alpha,alpha'-dichloroxylenes. These bis-N9-(methylphenylmethyl)purines 4-15 were evaluated for the primary cytotoxic activity against a panel of NCI-H460 (lung), MCF-7 (breast) and SF-268 (CNS) cancer cell lines. The 'active' compounds which reduced growth of cancer cells to ca. 32% or less, have been evaluated in a full panel of 60 human cancer cell lines over a 5-log dose range at the National Cancer Institute, Bethesda, MD. In this series, the most activity is correlated to the compounds derived from the 2,6-dichloropurines such as bis-9-[o-(methylphenylmethyl)]2,6-dichloropurine (5), bis-9-[m-(methylphenylmethyl)]2,6-dichloropurine (8), and bis-9-[p-(methylphenylmethyl)]2,6-dichloropurine (11). In particular compound 8 exhibited high sensitivity in leukemia cell lines and compounds 5, 8 and 11 exhibited consistent high sensitivity in many breast cancer cell lines. Compound 11 was the most potent in this series and exhibited GI(50)<0.01 microM sensitivity against non-small lung cancer EKVX, colon cancer HT-29, melanoma SK-MEL-28, renal cancer RXF 393, prostate cancer DU-145 and several breast cancer HS 578T and BT-549 cell lines.

  16. Separation of purine and pyrimidine bases and nucleosides by hydrophilic interaction chromatography.

    PubMed

    Marrubini, Giorgio; Mendoza, Bolivar Enrique Castillo; Massolini, Gabriella

    2010-03-01

    The separation of 12 model compounds chosen among purine and pyrimidine bases and nucleosides was studied by using hydrophilic interaction chromatography (HILIC). The compounds investigated were small molecules with relevant properties for biomedical and pharmaceutical studies. The mixture of pyrimidines and purines was applied on a ZIC-HILIC 150 x 2.1 mm, 5 microm, and two TSKgel Amide-80 150 x 2.0 mm, 5 microm and 3 microm particle size columns. The retention of the analytes was studied by varying ACN%, ammonium formate concentration, pH, and column temperature. The results obtained confirmed the elution order of nucleobases, nucleosides, and nucleotides based on their hydrophobicity. The retention mechanism of the columns was studied considering the models used for describing partitioning and surface adsorption. The influence on retention of chromatographic conditions (ACN%, salt concentration, pH, and temperature) was described and discussed for both columns. The optimization of the conditions studied allowed to assess a gradient method for the separation of the 12 analytes. The developed method is a valuable alternative to existing methods for the separation of the compounds concerned.

  17. Roles of the amino group of purine bases in the thermodynamic stability of DNA base pairing.

    PubMed

    Nakano, Shu-ichi; Sugimoto, Naoki

    2014-08-05

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

  18. Imbalance of purine nucleotides in alanosine-resistant baby hamster kidney cells.

    PubMed

    Pang, J C; Du, R P; Bingham, H; Juranka, P; Chan, V L

    1989-03-01

    Human DNA was used to transform adenosine kinase (AK)-deficient BHK cells followed by selection of AK+ cells in medium containing alanosine, adenosine, and uridine (AAU medium). Twenty AAUr isolates were analyzed, and none of them contained AK activity. Several purine salvage enzymes were, however, found to be affected in these cells. The levels of hypoxanthine-guanine phosphoribosyltransferase and adenylosuccinate synthetase activities were elevated, while the adenylosuccinase activity was reduced. AAU-resistance may be explained by elevated activity of adenylosuccinate synthetase to overcome the alanosine block; thus AAUr cells were able to convert exogenous adenosine----inosine----hypoxanthine----IMP----AMPS----AMP. Moreover, these AAUr cells required exogenous purines for growth. HPLC analyses of endogenous nucleotide pools of AAUr cells showed that the levels of adenine nucleotides have diminished to less than 10% of the parental levels. These results suggest that the AAU-resistant mutation, which elicits pleiotropic phenotypes in BHK cells, affects an important component in the regulation of adenine nucleotide synthesis. By including erthyro-9-(2-hydroxy-3-nonyl)adenine in the AAU medium (renamed as AAUE medium) to block deamination of adenosine, AK+ BHK cells were isolated.

  19. An Investigation of Prebiotic Purine Synthesis from the Hydrolysis of HCN Polymers

    NASA Astrophysics Data System (ADS)

    Borquez, Eduardo; Cleaves, H. James; Lazcano, Antonio; Miller, Stanley L.

    2005-04-01

    The polymerization of concentrated NH4CN solutions has been studied at various temperatures and ammonia concentrations. The products of the oligomerization of ammonium cyanide include adenine and guanine, as well as trace amounts of 2,6-diaminopurine. Our results indicate that the adenine yield is not strongly dependent on temperature. Guanine is produced in lower yield. The original studies by Oró and Kimball (1961) showed that the 6 N HCl hydrolysis of the NH4CN polymerization supernatant greatly increased the adenine yield. However, this hydrolysis also decomposes adenine and other purines. Therefore, we have measured the yields from an NH4CN polymerization as a function of hydrolysis time, and found that shorter hydrolytic periods give higher yields of adenine.We have also investigated the hydrolysis of the supernatant at pH 8, which is a more reasonable model of primitive oceanic conditions, and found that the adenine yield is comparable to that obtained with acid hydrolysis (approximately 0.1%). The yield of adenine does not decline at longer hydrolysis times because of the greater stability of adenine at pH 8. The insoluble black polymer formed from NH4CN has been analyzed by both acid and neutral hydrolysis. In both cases adenine yields of approximately 0.05% were obtained. This suggests that the polymer may have been as important a prebiotic source of purines as the usually analyzed supernatant.

  20. Sustainable synthesis and automated deposition: an accessible discovery screening library of fragment-like purines.

    PubMed

    Kamper, Christoph; Korpis, Katharina; Specker, Edgar; Anger, Lennart; Neuenschwander, Martin; Bednarski, Patrick J; Link, Andreas

    2012-08-01

    A sub-library of 88 information-rich lead-like purine derivatives were prepared and deposited in an open access academic screening facility. The rationale for the synthesis of these rigid low complexity structures was the privileged character of the purine heterocycle associated with its inherent probability of interactions with multiple adenine-related targets. Although generally expected to be weak binders in many assays, such fragment-like compounds are estimated to match diverse binding sites. It is suggested that heterocycles with many anchor points for hydrogen bonds can be anticipated to undergo very specific interactions to produce more negative enthalpies and thus provide superior starting points for lead optimization than compounds that owe their activity to entropic effects. The in vitro cytotoxicity of the small compounds on a panel of human cancer cell lines has been investigated and some of them showed marked unselective or selective toxicity. This data may be useful if these fragments are to be incorporated into drug-like structures via metabolically cleavable connections. The sub-library will be implemented as part of the ChemBioNet ( www.chembionet.info ) library, and it is open to screening campaigns of academic research groups striving for a fragment-based approach in their biological assays.

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

    PubMed

    Sharma, Alka; Luxami, Vijay; Paul, Kamaldeep

    2015-03-26

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

  2. 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

  3. N-Arylmethyl substituted iminoribitol derivatives as inhibitors of a purine specific nucleoside hydrolase.

    PubMed

    Goeminne, Annelies; Berg, Maya; McNaughton, Michael; Bal, Gunther; Surpateanu, Georgiana; Van der Veken, Pieter; De Prol, Stijn; Versées, Wim; Steyaert, Jan; Haemers, Achiel; Augustyns, Koen

    2008-07-15

    A key enzyme within the purine salvage pathway of parasites, nucleoside hydrolase, is proposed as a good target for new antiparasitic drugs. We have developed N-arylmethyl-iminoribitol derivatives as a novel class of inhibitors against a purine specific nucleoside hydrolase from Trypanosoma vivax. Several of our inhibitors exhibited low nanomolar activity, with 1,4-dideoxy-1,4-imino-N-(8-quinolinyl)methyl-d-ribitol (UAMC-00115, K(i) 10.8nM), N-(9-deaza-adenin-9-yl)methyl-1,4-dideoxy-1,4-imino-d-ribitol (K(i) 4.1nM), and N-(9-deazahypoxanthin-9-yl)methyl-1,4-dideoxy-1,4-imino-d-ribitol (K(i) 4.4nM) being the three most active compounds. Docking studies of the most active inhibitors revealed several important interactions with the enzyme. Among these interactions are aromatic stacking of the nucleobase mimic with two Trp-residues, and hydrogen bonds between the hydroxyl groups of the inhibitors and amino acid residues in the active site. During the course of these docking studies we also identified a strong interaction between the Asp40 residue from the enzyme and the inhibitor. This is an interaction which has not previously been considered as being important.

  4. An expanding role for purine uptake permease-like transporters in plant secondary metabolism

    PubMed Central

    Jelesko, John G.

    2012-01-01

    For the past decade, our understanding of the plant purine uptake permease (PUP) transporter family was primarily oriented on purine nucleobase substrates and their tissue-specific expression patterns in Arabidopsis. However, a tobacco PUP-like homolog demonstrating nicotine uptake permease activity was recently shown to affect both nicotine metabolism and root cell growth. These new findings expand the physiological role for PUP-like transporters to include plant secondary metabolism. Molecular evolution analyses of PUP-like transporters indicate they are distinct group within an ancient super family of drug and metabolite transporters (DMTs). The PUP-like family originated during terrestrial plant evolution sometime between the bryophytes and the lycophytes. A phylogenetic analysis indicates that the PUP-like transporters were likely derived from a pre-existing nucleotide-sugar transporter family within the DMT super family. Within the lycophyte Selaginella, there are three paralogous groups of PUP-like transporters. One of the three PUP-like paralogous groups showed an extensive pattern of gene duplication and diversification within the angiosperm lineage, whereas the more ancestral PUP-like paralogous groups did not. Biochemical characterization of four closely related PUP-like paralogs together with model-based phylogenetic analyses indicate both subfunctionalization and neofunctionalization during the molecular evolution of angiosperm PUP-like transporters. These findings suggest that members of the PUP-like family of DMT transporters are likely involved in diverse primary and secondary plant metabolic pathways. PMID:22639664

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  6. Structural Phylogenomics Reveals Gradual Evolutionary Replacement of Abiotic Chemistries by Protein Enzymes in Purine Metabolism

    PubMed Central

    Caetano-Anollés, Kelsey; Caetano-Anollés, Gustavo

    2013-01-01

    The origin of metabolism has been linked to abiotic chemistries that existed in our planet at the beginning of life. While plausible chemical pathways have been proposed, including the synthesis of nucleobases, ribose and ribonucleotides, the cooption of these reactions by modern enzymes remains shrouded in mystery. Here we study the emergence of purine metabolism. The ages of protein domains derived from a census of fold family structure in hundreds of genomes were mapped onto enzymes in metabolic diagrams. We find that the origin of the nucleotide interconversion pathway benefited most parsimoniously from the prebiotic formation of adenine nucleosides. In turn, pathways of nucleotide biosynthesis, catabolism and salvage originated ∼300 million years later by concerted enzymatic recruitments and gradual replacement of abiotic chemistries. Remarkably, this process led to the emergence of the fully enzymatic biosynthetic pathway ∼3 billion years ago, concurrently with the appearance of a functional ribosome. The simultaneous appearance of purine biosynthesis and the ribosome probably fulfilled the expanding matter-energy and processing needs of genomic information. PMID:23516625

  7. Action of purine and pyrimidine nucleotides on the rat superior cervical ganglion.

    PubMed

    Connolly, G P; Harrison, P J; Stone, T W

    1993-12-01

    1. Using a grease-gap technique, we have investigated the effects of purine and pyrimidine nucleotides on the d.c. potential of the rat isolated superior cervical ganglion (SCG). 2. Of the purines tested, adenosine, adenosine 5'-triphosphate (ATP), beta,gamma-methylene-adenosine 5'-triphosphate (beta,gamma-MeATP) at up to 300 microM produced concentration-dependent hyperpolarizations, whereas 2-methyl-thio-ATP (2-Me.S.ATP) and alpha,beta-methylene-ATP (alpha,beta-MeATP) depolarized ganglia. Of the pyrimidines tested, uridine 5'-triphosphate (UTP) produced concentration-dependent depolarizations and cytosine 5'-triphosphate (CTP) at 1000 microM produced considerably smaller but significant depolarizations. In contrast uridine 5'-monophosphate (UMP) at 1000 microM hyperpolarized ganglia. The relative order of potency of purines and pyrimidines to depolarize ganglia was: UTP > alpha,beta-MeATP > CTP > 2-Me.S.ATP and to hyperpolarize ganglia was: adenosine = beta,gamma-MeATP > ATP > UMP. 3. The ability of purines and pyrimidines to alter the depolarizing response caused by muscarine and of purines to alter depolarization induced by gamma-aminobutyric acid (GABA) was determined. The relative order of potency of nucleotides in depressing submaximal depolarization caused by muscarine (100 nM) was: adenosine = ATP > beta,gamma-MeATP whereas 2-Me.S.ATP, alpha,beta-MeATP and UTP did not significantly alter depolarization caused by muscarine. At 100 microM beta,gamma-MeATP and adenosine but not ATP potentiated GABA-induced depolarizations. 4. Hyperpolarizations caused by adenosine, ATP, beta,gamma-MeATP and UMP and depolarizations caused by alpha,beta-MeATP were enhanced in medium containing reduced concentrations of calcium (0.1 mM) and potassium (2 mM). In this medium 8-phenyltheophylline abolished hyperpolarizations caused by adenosine and reversed hyperpolarizations caused by ATP into depolarizations. Suramin (300 microM), a P2-purinoceptor antagonist, significantly

  8. The UK free electron laser

    NASA Astrophysics Data System (ADS)

    Laing, E. W.

    1985-12-01

    The basic operating principles of a free electron laser (FEL) are reviewed. A description of a British research program to develop a pulsed relativistic electron beam and laser cavity for infrared and optical operation, the UK FEL program, is given. The tunable energy of the UK FEL is in the range 50-125 MeV, and the current is greater than or equal to 200 mA. The FEL Wiggler field consists of a periodic structure of permanent magnets made up of four sections each. The main goals of the UK FEL program are to study the spontaneous emission of the electron beam, as well as the amplification characteristics of the CO2 laser beam. Some of the prospective applications of infrared FELs include: single or multiphoton excitation; molecular dissociation; excitation of charge carriers over the infrared range; and optical bistable switching.

  9. [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.

  10. Residual effects of TMOF-Bti formulations against 1st instar Aedes aegypti Linnaeus larvae outside laboratory

    PubMed Central

    Saiful, AN; Lau, MS; Sulaiman, S; Hidayatulfathi, O

    2012-01-01

    Objective To evaluate the effectiveness and residual effects of trypsin modulating oostatic factor-Bacillus thuringiensis israeliensis (TMOF-Bti) formulations against Aedes aegypti (Ae. aegypti) (L.) larvae at UKM Campus Kuala Lumpur. Methods Twenty first instar Ae. aegypti larvae were added in each bucket containing 4 L of water supplied with crushed dried leaf powder as their source of food. Combination of TMOF-Bti in rice husk formulation with the following weights viz 10, 25, 50 and 100 mg, respectively in duplicate was distributed in the buckets; while TMOF-Bti in wettable powder formulation each weighing viz 2, 5, 10 and 20 mg, respectively in duplicate was also placed in the buckets. The control buckets run in duplicate with 4 L of water and 20 first instar Ae. aegypti larvae. All buckets were covered with mosquito netting. Larval mortality was recorded after 24 hours and weekly for five weeks. A new batch of 20 1st instar larvae Ae. aegypti was introduced into each bucket weekly without additional TMOF-Bti rice husk formulation or wettable powder. The experiment was repeated for four times. Results The result of the study showed that all formulations were very effective on the first two weeks by giving 100% larval mortality for all concentrations applied. The TMOF (2%) + Bti (2%) had a good residual effect until the end of 3rd week, TMOF (4%) + Bti (4%) until 4th week, wettable powder TMOF (20%) + Bti (20%) until the third week. Conclusions From the results it can be concluded that the TMOF-Bti formulations can be utilized in dengue vector control. PMID:23569922

  11. 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.

  12. Early psychosis intervention outpatient service of the 1st Psychiatric University Clinic in Athens: 3 Years of experience.

    PubMed

    Kollias, Constantinos; Xenaki, Lida-Alkisti; Dimitrakopoulos, Stefanos; Kosteletos, Ioannis; Kontaxakis, Vassilis; Stefanis, Nikos; Papageorgiou, Charalampos

    2016-11-09

    To present the 3-year experience of the early intervention in psychosis (EIP) service implementation of the 1st Psychiatric University Clinic in Athens. An overview of: (1) the purpose of our service, (2) the referral network, (3) the selection criteria, (4) the diagnostic procedures, (5) the therapeutic interventions and (6) the research activities. The service was established in 2012 and developed gradually aiming to provide information, early detection, treatment and support to people aged 15 to 40 years with psychotic manifestations, who are either at increased risk of developing psychosis (at-risk mental state [ARMS]) or with first episode psychosis (FEP). In order to assess individuals with ARMS, we used the comprehensive assessment of at-risk mental states interview and the Social and Occupational Functioning Assessment Scale The duration of untreated psychosis was estimated by using the Nottingham Onset Schedule. So far we have had 65 referrals, of which 26 were ARMS and 17 FEP. Based on the individual needs, they were offered psychotherapeutic and/or pharmacological treatment. After 3 years, the rate of transition to psychosis was 19.2% and the rate of psychosis relapse was 11.7%. The implementation of our service has had positive results, enabling young people with early psychosis to receive prompt and effective care. The rates of transition to psychosis are the first to be published from a Greek EIP service. Further development of our referral network and inter-hospital collaboration will allow us to address the needs of a wider part of the population. © 2016 John Wiley & Sons Australia, Ltd.

  13. Small airway dysfunction by impulse oscillometry in asthmatic patients with normal forced expiratory volume in the 1st second values.

    PubMed

    Pisi, Roberta; Tzani, Panagiota; Aiello, Marina; Martinelli, Enrico; Marangio, Emilio; Nicolini, Gabriele; Olivieri, Dario; Chetta, Alfredo

    2013-01-01

    Small airways are relevant to the pathophysiology of asthma. We investigated whether in asthmatic patients with normal forced expiratory volume in the 1st second (FEV(1)) values, impulse oscillometry system (IOS), as a measure of small airway function, contributed additional information to spirometry either at baseline or after bronchodilator, and whether it was related to the disease control. The fall in resistance from 5 to 20 Hz (R5-R20) and reactance at 5 Hz (X5) by IOS and spirometry measures of small airway function (forced expiratory flow at 25-75% [FEF(25-75)] and forced vital capacity/slow inspiratory vital capacity [FVC/SVC]) at baseline and after 400 micrograms of salbutamol were prospectively measured in 33 asthmatic patients (18 women; age range, 18-66 years). Disease control was assessed by the Asthma Control Test (ACT). R5-R20 but not X5 values were significantly related to FEF(25-75) and FVC/SVC values (p < 0.05 for both correlations). When the bronchodilator response was assessed, no correlation was found among IOS and spirometry changes. ACT scores were related to R5-R20, FEF(25-75), and FVC/SVC values (p < 0.01 for all correlations). In asthmatic patients with normal FEV(1) values, R5-R20 values were related to spirometry measures of small airway function. However, when the bronchodilator response was assessed, IOS and spirometry provided quite different results. Moreover, small airway dysfunction, as assessed by IOS and spirometry, was associated with poor disease control and history of asthma exacerbations. The results of this study confirm the value of IOS, as an investigative tool, and suggest that in asthmatic patients with normal FEV(1) values and poor disease control, small airway function should be investigated.

  14. 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.

  15. 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

  16. 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…

  17. 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…

  18. Urinary purine derivatives as a tool to estimate dry matter intake in cattle: a meta-analysis

    USDA-ARS?s Scientific Manuscript database

    The objectives of this study were: 1) to investigate the relationship between dry matter intake (DMI) and urinary purine derivatives (PD) excretion in order to develop equations to predict DMI, and 2) to determine the endogenous excretion of PD for beef and dairy cattle using a meta-analytic approac...

  19. 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.

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

    PubMed

    Shimada, Tomohiro; Kori, Ayako; Ishihama, Akira

    2013-07-01

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

  1. Plasmodium falciparum Parasites Are Killed by a Transition State Analogue of Purine Nucleoside Phosphorylase in a Primate Animal Model

    PubMed Central

    Cassera, María B.; Hazleton, Keith Z.; Merino, Emilio F.; Obaldia, Nicanor; Ho, Meng-Chiao; Murkin, Andrew S.; DePinto, Richard; Gutierrez, Jemy A.; Almo, Steven C.; Evans, Gary B.; Babu, Yarlagadda S.; Schramm, Vern L.

    2011-01-01

    Plasmodium falciparum causes most of the one million annual deaths from malaria. Drug resistance is widespread and novel agents against new targets are needed to support combination-therapy approaches promoted by the World Health Organization. Plasmodium species are purine auxotrophs. Blocking purine nucleoside phosphorylase (PNP) kills cultured parasites by purine starvation. DADMe-Immucillin-G (BCX4945) is a transition state analogue of human and Plasmodium PNPs, binding with picomolar affinity. Here, we test BCX4945 in Aotus primates, an animal model for Plasmodium falciparum infections. Oral administration of BCX4945 for seven days results in parasite clearance and recrudescence in otherwise lethal infections of P. falciparum in Aotus monkeys. The molecular action of BCX4945 is demonstrated in crystal structures of human and P. falciparum PNPs. Metabolite analysis demonstrates that PNP blockade inhibits purine salvage and polyamine synthesis in the parasites. The efficacy, oral availability, chemical stability, unique mechanism of action and low toxicity of BCX4945 demonstrate potential for combination therapies with this novel antimalarial agent. PMID:22096507

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

    PubMed

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

    2017-04-01

    Background: Formate provides one-carbon units for de novo purine and thymidylate (dTMP) synthesis and is produced via both folate-dependent and folate-independent pathways. Folate-independent pathways are mediated by cytosolic alcohol dehydrogenase 5 (ADH5) and mitochondrial aldehyde dehydrogenase 2 (ALDH2), which generate formate by oxidizing formaldehyde. Formate is a potential biomarker of B-vitamin-dependent one-carbon metabolism.Objective: This study investigated the contributions of ADH5 and ALDH2 to formate production and folate-dependent de novo purine and dTMP synthesis in HepG2 cells.Methods:ADH5 knockout and ALDH2 knockdown HepG2 cells were cultured in folate-deficient [0 nM (6S) 5-formyltetrahydrofolate] or folate-sufficient [25 nM (6S) 5-formyltetrahydrofolate] medium. Purine biosynthesis was quantified as the ratio of [(14)C]-formate to [(3)H]-hypoxanthine incorporated into genomic DNA, which indicates the contribution of the de novo purine synthesis pathway relative to salvage synthesis. dTMP synthesis was quantified as the ratio of [(14)C]-deoxyuridine to [(3)H]-thymidine incorporation into genomic DNA, which indicates the capacity of de novo dTMP synthesis relative to salvage synthesis.Results: The [(14)C]-formate-to-[(3)H]-hypoxanthine ratio was greater in ADH5 knockout than in wild-type HepG2 cells, under conditions of both folate deficiency (+30%; P < 0.001) and folate sufficiency (+22%; P = 0.02). These data indicate that ADH5 deficiency increases the use of exogenous formate for de novo purine biosynthesis. The [(14)C]-deoxyuridine-to-[(3)H]-thymidine ratio did not differ between ADH5 knockout and wild-type cells, indicating that ADH5 deficiency does not affect de novo dTMP synthesis capacity relative to salvage synthesis. Under folate deficiency, ALDH2 knockdown cells exhibited a 37% lower ratio of [(14)C]-formate to [(3)H]-hypoxanthine (P < 0.001) compared with wild-type HepG2 cells, indicating decreased use of exogenous formate, or

  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. 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

  5. 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.

  6. Comparative Review of Selected Educational Policies of 1st and 2nd Cycle Institutions in Ghana and Burkina Faso, and That of United Kingdom and United States

    ERIC Educational Resources Information Center

    Kumi, Asamoah Moses; Seidu, Abarichie Adamu

    2017-01-01

    This article examines some selected Educational Policies of First and Second Cycle Institutions in Ghana and Burkina Faso, in comparison with that of the UK and US. The purpose of the study is to itemise the commonalities and differences in Educational Policies of both developed (UK and US) and developing countries (Ghana and Burkina Faso) in…

  7. HPLC separation of some purine and pyrimidine derivatives on Chromolith Performance Si monolithic column.

    PubMed

    Kazoka, H

    2007-02-23

    The chromatographic behavior of some purines and pyrimidines on a monolithic Chromolith Performance Si column under normal-phase high-performance liquid chromatography mode has been studied. Column pressure, column efficiency and selectivity of Chromolith Performance Si column were compared to those of conventional spherical 5 microm silica packed columns Econosphere Silica and Zorbax Rx-SIL. The investigation has shown that application of Chromolith Performance Si column for analysis of polar solutes can reduce the separation time without sacrificing column efficiency and selectivity. Improvement of the monolithic silica column efficiency for polar solutes is observed when ternary mobile phases (mixtures of hexane-isopropanol with ethylene glycol, water or acetonitrile) are applied.

  8. 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

  9. Theacrine, a purine alkaloid with anti-inflammatory and analgesic activities.

    PubMed

    Wang, Yuanyuan; Yang, Xiaorong; Zheng, Xinqiang; Li, Jing; Ye, Chuangxing; Song, Xiaohong

    2010-09-01

    The anti-inflammatory and analgesic effects of theacrine (1, 3, 7, 9-tetramethyluric acid), a purine alkaloid which is abundantly present in Camellia kucha, were investigated. Xylene-induced ear edema, acetic acid-induced vascular permeability and lambda-carrageenan-induced paw edema were used to investigate anti-inflammatory activity, and acetic acid-induced writhing and hot-plate tests were used to determine analgesic effect. Oral administration of theacrine (8-32 mg/kg) induced dose-related anti-inflammatory and analgesic effects. On the other hand, oral caffeine administration (8-32 mg/kg) did not show an inhibitory effect on the inhibition of inflammatory response or cause analgesia. Additionally, the result of the acute toxicity test showed that the LD(50) of theacrine was 810.6 mg/kg (769.5-858.0mg/kg). The data obtained suggest theacrine possessed analgesic and anti-inflammatory activities.

  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. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. De novo synthesis of purine nucleotides in different fiber types of rat skeletal muscle

    SciTech Connect

    Tullson, P.C.; John-Alder, H.; Hood, D.A.; Terjung, R.L.

    1986-03-01

    The contribution of de novo purine nucleotide synthesis to nucleotide metabolism in skeletal muscles is not known. The authors have determined rates of de novo synthesis in soleus (slow-twitch red), red gastrocnemius (fast-twitch red), and white gastrocnemius (fast-twitch white) using the perfused rat hindquarter. /sup 14/C glycine incorporation into ATP was linear after 1 and 2 hours of perfusion with 0.2 mM added glycine. The intracellular (I) and extracellular (E) specific activity of /sup 14/C glycine was determined by HPLC of phenylisothiocyanate derivatives of neutralized PCA extracts. The rates of de novo synthesis when expressed relative to muscle ATP content show slow and fast-twitch red muscles to be similar and about twice as great as fast-twitch white muscles. This could represent a greater turnover of the adenine nucleotide pool in more oxidative red muscle types.

  12. Antifolate-Induced Depletion of Intracellular Glycine and Purines Inhibits Thymineless Death in E. coli

    PubMed Central

    Kwon, Yun Kyung; Higgins, Meytal B.; Rabinowitz, Joshua D.

    2010-01-01

    Despite the therapeutic importance of antifolates, the links between their direct antimetabolite activity and downstream consequences remain incompletely understood. Here we employ metabolomics to examine the complete metabolic effects of the antibiotic trimethoprim in E. coli. In rich media, trimethoprim treatment causes thymineless death. In minimal media, in contrast, trimethoprim addition results in rapid stoppage of cell growth and stable cell stasis. We show that initial impairment of cell growth is due to rapid depletion of glycine and associated activation of the stringent response. Long-term stasis is due to purine insufficiency. Thus, E. coli has dual systems for surviving folate depletion and avoiding thymineless death: a short-term response based on sensing of amino acids and a long-term response based on sensing of nucleotides. PMID:20553049

  13. Novel Ligands for a Purine Riboswitch Discovered by RNA-Ligand Docking

    PubMed Central

    Daldrop, Peter; Reyes, Francis E.; Robinson, David A.; Hammond, Colin M.; Lilley, David M.; Batey, Robert T.; Brenk, Ruth

    2011-01-01

    Summary The increasing number of RNA crystal structures enables a structure-based approach to the discovery of new RNA-binding ligands. To develop the poorly explored area of RNA-ligand docking, we have conducted a virtual screening exercise for a purine riboswitch to probe the strengths and weaknesses of RNA-ligand docking. Using a standard protein-ligand docking program with only minor modifications, four new ligands with binding affinities in the micromolar range were identified, including two compounds based on molecular scaffolds not resembling known ligands. RNA-ligand docking performed comparably to protein-ligand docking indicating that this approach is a promising option to explore the wealth of RNA structures for structure-based ligand design. PMID:21439477

  14. Release of extracellular purines from plant roots and effect on ion fluxes.

    PubMed

    Dark, Adeeba; Demidchik, Vadim; Richards, Siân L; Shabala, Sergey; Davies, Julia M

    2011-11-01

    Extracellular purine nucleotides appear capable of regulating plant development, defence and stress responses by acting in part as agonists of plasma membrane calcium channels. Factors stimulating ATP release include wounding, osmotic stress and elicitors. Here we show that exogenous abscisic acid and L-glutamate can also cause ATP accumulation around Arabidopsis thaliana roots. Release of ADP from root epidermis would trigger ionotropic receptor-like activity in the plasma membrane, resulting in transient elevation of cytosolic free calcium. Root epidermal protoplasts (expressing aequorin as a cytosolic free calcium reporter) can support an extracellular ADP-induced cytosolic calcium elevation in the presence of an extracellular reductant. This confirms that ADP could elicit calcium-based responses distinct to those of ATP, which have been shown previously to involve production of extracellular reactive oxygen species.

  15. 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

  16. The effect of cyclophosphamide and gamma irradiation on adenosine deaminase and purine nucleoside phosphorylase in mice

    SciTech Connect

    Hosek, B.; Bohaecek, J.; Sikulova, J. )

    1991-01-01

    Changes in ADA and PNP activities in the spleens and thymuses of mice were studied after a single administration of cyclophosphamide and after whole-body gamma irradiation, applied alone or three days after CY application, In the first days after the treatment the enzyme activities were significantly depressed with the exception of ADA in the spleen, where a high elevation in relation to controls was observed. During the regeneration period a pronounced rise of PNP activity in the spleen occurred mainly after a combined application of CY and irradiation. In the thymus the regeneration was manifested by a mild increase of both ADA and PNP activities towards control values. The findings suggest that the expressive changes of ADA and PNP activities, participating in the purine salvage pathway, may, after a cytotoxic treatment, influence the nucleotide pool and DNA synthesis in lymphoid organs.

  17. Effects of dairy cow diet forage proportion on duodenal nutrient supply and urinary purine derivative excretion.

    PubMed

    Moorby, J M; Dewhurst, R J; Evans, R T; Danelón, J L

    2006-09-01

    Four mature Holstein-Friesian dairy cows were used in a 4 x 4 Latin square change-over design experiment made up of four 4-wk periods to investigate the relationship between microbial protein flow to the duodenum and excretion of purine derivatives (PD) in the urine. Four dietary treatments based on ad libitum access to ryegrass silage were offered, with a standard dairy concentrate included at different forage:concentrate (F:C) ratios, calculated on a dry matter basis: 80:20, 65:35, 50:50, and 35:65. Feed intakes increased as the proportion of concentrate in the diet increased, despite a concurrent decrease in silage intake. Increased feed intake led to increased nutrient flow to the duodenum. Milk yields increased as the diet F:C ratio decreased, with cows offered the 35:65 diet yielding nearly 8 kg/d more milk than cows offered the 80:20 diet; the concentrations of milk fat decreased and milk protein increased with a decreasing F:C ratio. Purine derivative excretion in the urine increased with an increasing proportion of concentrate in the diet, and there was a strong linear relationship between total PD excretion (allantoin and uric acid) and microbial N flow to the duodenum: microbial N (g/d) = 19.9 + 0.689 x total PD (mmol/d); R = 0.887. This strengthens the case for using PD excretion as a noninvasive marker of microbial protein flow from the rumen in dairy cows.

  18. One-electron oxidation reactions of purine and pyrimidine bases in cellular DNA

    PubMed Central

    Cadet, Jean; Wagner, J. Richard; Shafirovich, Vladimir; Geacintov, Nicholas E.

    2014-01-01

    Purpose The aim of this survey is to critically review the available information on one-electron oxidation reactions of nucleobases in cellular DNA with emphasis on damage induced through the transient generation of purine and pyrimidine radical cations. Since the indirect effect of ionizing radiation mediated by hydroxyl radical is predominant in cells, efforts have been made to selectively ionize bases using suitable one-electron oxidants that consist among others of high intensity UVC laser pulses. Thus, the main oxidation product in cellular DNA was found to be 8-oxo-7,8-dihydroguanine as a result of direct bi-photonic ionization of guanine bases and indirect formation of guanine radical cations through hole transfer reactions from other base radical cations. The formation of 8-oxo-7,8-dihydroguanine and other purine and pyrimidine degradation products was rationalized in terms of the initial generation of related radical cations followed by either hydration or deprotonation reactions in agreement with mechanistic pathways inferred from detailed mechanistic studies. The guanine radical cation has been shown to be implicated in three other nucleophilic additions that give rise to DNA-protein and DNA-DNA cross-links in model systems. Evidence was recently provided for the occurrence of these three reactions in cellular DNA. Conclusion There is growing evidence that one-electron oxidation reactions of nucleobases whose mechanisms have been characterized in model studies involving aqueous solutions take place in a similar way in cells. It may also be pointed out that the above cross-linked lesions are only produced from the guanine radical cation and may be considered as diagnostic products of the direct effect of ionizing radiation. PMID:24369822

  19. Octameric structure of the human bifunctional enzyme PAICS in purine biosynthesis.

    PubMed

    Li, Shu-Xing; Tong, Yong-Ping; Xie, Xiao-Cong; Wang, Qi-Hai; Zhou, Hui-Na; Han, Yi; Zhang, Zhan-Yu; Gao, Wei; Li, Sheng-Guang; Zhang, Xuejun C; Bi, Ru-Chang

    2007-03-09

    Phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) is an important bifunctional enzyme in de novo purine biosynthesis in vertebrate with both 5-aminoimidazole ribonucleotide carboxylase (AIRc) and 4-(N-succinylcarboxamide)-5-aminoimidazole ribonucleotide synthetase (SAICARs) activities. It becomes an attractive target for rational anticancer drug design, since rapidly dividing cancer cells rely heavily on the purine de novo pathway for synthesis of adenine and guanine, whereas normal cells favor the salvage pathway. Here, we report the crystal structure of human PAICS, the first in the entire PAICS family, at 2.8 A resolution. It revealed that eight PAICS subunits, each composed of distinct AIRc and SAICARs domains, assemble a compact homo-octamer with an octameric-carboxylase core and four symmetric periphery dimers formed by synthetase domains. Based on structural comparison and functional complementation analyses, the active sites of SAICARs and AIRc were identified, including a putative substrate CO(2)-binding site. Furthermore, four symmetry-related, separate tunnel systems in the PAICS octamer were found that connect the active sites of AIRc and SAICARs. This study illustrated the octameric nature of the bifunctional enzyme. Each carboxylase active site is formed by structural elements from three AIRc domains, demonstrating that the octamer structure is essential for the carboxylation activity. Furthermore, the existence of the tunnel system implies a mechanism of intermediate channeling and suggests that the quaternary structure arrangement is crucial for effectively executing the sequential reactions. In addition, this study provides essential structural information for designing PAICS-specific inhibitors for use in cancer chemotherapy.

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

    PubMed

    Villalobos-García, Daniel; Hernández-Muñoz, Rolando

    2017-08-01

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