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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. 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.

  3. "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…

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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 ...

  9. 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.

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

    NASA Video Gallery

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

  11. 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.

  12. 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 ...

  13. 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.

  14. 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.

  15. A New HPLC Purine Assay for Quantifying Microbial Flow

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. 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.

  17. ["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.

  18. [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.

  19. 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

  20. 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.

  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. 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.

  3. 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).

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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

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

    SciTech Connect

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

    2004-05-19

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

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

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

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

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

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

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

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

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

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

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

  15. 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

  16. 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

  17. 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 ...

  18. 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

  19. 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.

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. "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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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…

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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…

  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. 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…

  5. 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…

  6. 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...

  7. 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

  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. 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…

  10. 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.

  11. Evaluation of Purine Salvage as a Chemotherapeutic Target in the Plasmodium yoelii Rodent Model

    DTIC Science & Technology

    2008-03-01

    modification machinery to control gene expression. The sexual cycle of Plasmodium is a critical process required for transmission of malaria via the...for RNA and DNA and must salvage purines from their host. We are investigating whether the malaria purine salvage pathway can be exploited to develop...chemotherapy are needed to protect military personnel stationed in developing countries. Malaria parasites cannot make purines needed for RNA and DNA and

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

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

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

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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. [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.

  2. 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.

  3. 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)

  4. 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.

  5. [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.

  6. 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.

  7. 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.

  8. 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.

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

    PubMed Central

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

    2015-01-01

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

  10. 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.

  11. 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.

  12. 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.

  13. 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).

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. [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.

  20. 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

  1. A link between impaired purine nucleotide synthesis and apoptosis in Drosophila melanogaster.

    PubMed

    Holland, Catherine; Lipsett, David B; Clark, Denise V

    2011-06-01

    The biosynthetic pathways and multiple functions of purine nucleotides are well known. However, the pathways that respond to alterations in purine nucleotide synthesis in vivo in an animal model organism have not been identified. We examined the effects of inhibiting purine de novo synthesis in vivo and in cultured cells of Drosophila melanogaster. The purine de novo synthesis gene ade2 encodes phosphoribosylformylglycinamidine synthase (EC 6.3.5.3). An ade2 deletion, generated by P-element transposon excision, causes lethality in early pupal development, with darkening, or necrosis, of leg and wing imaginal disc tissue upon disc eversion. Together with analysis of a previously isolated weaker allele, ade2(4), and an allele of the Prat gene, which encodes an enzyme for the first step in the pathway, we determined that the lethal arrest and imaginal disc phenotypes involve apoptosis. A transgene expressing the baculovirus caspase inhibitor p35, which suppresses apoptosis caused by other stresses such as DNA damage, suppresses both the imaginal disc tissue darkening and the pupal lethality of all three purine de novo synthesis mutants. Furthermore, we showed the presence of apoptosis at the cellular level in both ade2 and Prat mutants by detecting TUNEL-positive nuclei in wing imaginal discs. Purine de novo synthesis inhibition was also examined in tissue culture by ade2 RNA interference followed by analysis of genome-wide changes in transcript levels. Among the upregulated genes was HtrA2, which encodes an apoptosis effector and is thus a candidate for initiating apoptosis in response to purine depletion.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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…

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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…

  6. 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

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-04

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

  9. 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…

  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. 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.

  12. 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

  13. 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.

  14. 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).

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Dippold, Vance F., III

    2014-01-01

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

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

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

    SciTech Connect

    DeMoll, E.

    1998-11-01

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

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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…

  14. 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…

  15. CO2 dynamics in nested catchments: a longitudinal perspective from soil to 1st and 2nd order streams

    NASA Astrophysics Data System (ADS)

    Johnson, M. S.; Lehmann, J.; Riha, S. J.; Couto, E. G.

    2005-12-01

    Fluxes of CO2 from terrestrial to aquatic environments were investigated in a nested catchment study in the seasonally-dry southern Amazon. Dissolved CO2 concentrations in groundwater springs, four 1st order streams and one 2nd order stream were determined via routine sampling and in-situ monitoring. CO2 concentrations were monitored in the soil atmosphere to 8m. Belowground, the seasonal trend in soil CO2 concentrations at depth lagged that of seasonal water table dynamics, with peak concentrations (8.7% CO2 vol/vol at 4m) occurring one month after maximum water table height, indicating a shift in root respiration and plant water uptake to deeper soil layers during the dry season. Peak dissolved CO2 concentrations in springs and streams lagged the soil CO2 maximum by an additional month. During storm events, streamflow CO2 concentrations were found to decrease initially, reflecting the initial contribution of low-CO2 direct precipitation and surface runoff. Streamwater CO2 then increased as the contribution of pre-event water to storm flow increased. Dissolved CO2 in springs was also found to increase during storm events. Diurnal fluctuations in dissolved CO2 of springs were also observed, indicating the connectivity of the biosphere, pedosphere and hydrosphere for headwater catchments. The dissolved CO2 concentration within 1st order streams decreases rapidly downstream from stream sources, with spring CO2 concentration 3.3 times that at headwater catchment outlets. This initial outgassing of CO2 within 1st order streams was found to be accompanied by a corresponding increase in the pH of stream water. However, dissolved CO2 concentrations were not found to be significantly different between 1st and 2nd order streams. This suggests a discontinuity between some processes at the terrestrial-aquatic interface in headwater catchments and those of larger-order watersheds.

  16. 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

  17. 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.

  18. 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

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

    ERIC Educational Resources Information Center

    Marini, Isabella; Ipata, Piero Luigi

    2007-01-01

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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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],...

  5. 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.

  6. 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

  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. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

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

    PubMed

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

    2017-03-20

    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.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

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

    SciTech Connect

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

    2008-01-01

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

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

    PubMed

    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.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  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. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

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

    NASA Astrophysics Data System (ADS)

    Wagner, Sebastian; Zorita, Eduardo

    2015-04-01

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

  10. 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.

  11. 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.

  12. 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.

  13. 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…

  14. 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.

  15. [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.

  16. 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.

  17. 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

  18. 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.

  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. 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

  1. 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

  2. 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.

  3. 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.

  4. 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

  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. 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

  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. UK policy: A success story?

    PubMed Central

    Bradshaw, Jonathan

    2007-01-01

    Child poverty is at the heart of the United Kingdom (UK) government’s social policy agenda. Child poverty rose rapidly in the 1980s; the child poverty rate was one of the highest in Europe by 2000. In 1999, the government’s objective was to reduce child poverty by 50% by 2004/2005, which it narrowly failed to meet. In 2005/2006, there was an increase in child poverty. An index of child well-being found that the UK was 21st out of the 25 European Union countries. Overall, the UK came in last in the UNICEF well-being index. The government’s child poverty strategy has been to manage the economy to maximize employment and to improve in-work incomes. Both have been successful in reducing child poverty. Out-of-work incomes have also been improved, but not enough to lift many children out of poverty. Public expenditure on services, especially health, education and childcare, has also increased; although there are questions about how much of this extra spending has focused on children and child poverty. The comprehensive spending review, reporting later in 2007, is likely to be tight, and it is now unlikely that the government will succeed in its aim of reducing child poverty by 50% by 2010 unless there are radical changes in policy. Constraints on the government’s ability to do this include the structural inequalities in British society and public attitudes toward people in poverty. PMID:19030446

  10. Nutritional knowledge of UK coaches.

    PubMed

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

    2014-04-10

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

  11. Equine uveitis: a UK perspective.

    PubMed

    Lowe, R C

    2010-03-01

    Uveitis in the equine population of the UK does not appear to be as prevalent or disastrous as seen across regions of Europe and the USA. Some cases perceived to be recurrent uveitis may be poorly resolved single episodes of uveitis and care should be taken not to make the diagnosis of recurrence without ensuring effective control of the initial episode. Leptospira spp. appear to play only a minor role ERU in the UK which is probably the main reason for the prevalence of the disease being much lower compared to the USA and mainland Europe. Actual data are relatively few on the ground as far as disease surveillance in concerned. This has 2 implications. Firstly unless we are able to effectively monitor the levels of uveitic disease, it will be difficult to pick up early changes in the trend which may allow quicker intervention. Secondly, it is difficult to secure funding for further research if the prevalence of the problem is poorly defined. This may leave the UK equine population at risk should the disease profile suddenly alter for the worse.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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…

  13. 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.

  14. 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…

  15. 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…

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. Uveal Melanoma UK National Guidelines.

    PubMed

    Nathan, P; Cohen, V; Coupland, S; Curtis, K; Damato, B; Evans, J; Fenwick, S; Kirkpatrick, L; Li, O; Marshall, E; McGuirk, K; Ottensmeier, C; Pearce, N; Salvi, S; Stedman, B; Szlosarek, P; Turnbull, N

    2015-11-01

    The United Kingdom (UK) uveal melanoma guideline development group used an evidence based systematic approach (Scottish Intercollegiate Guidelines Network (SIGN)) to make recommendations in key areas of uncertainty in the field including: the use and effectiveness of new technologies for prognostication, the appropriate pathway for the surveillance of patients following treatment for primary uveal melanoma, the use and effectiveness of new technologies in the treatment of hepatic recurrence and the use of systemic treatments. The guidelines were sent for international peer review and have been accredited by NICE. A summary of key recommendations is presented. The full documents are available on the Melanoma Focus website.

  1. UK mining invests, suppliers profit

    SciTech Connect

    2009-04-15

    In the midst of a major economic crisis in the United Kingdom, equipment suppliers have been reporting a number of considerable purchases by British coal mining companies. In December 2008, Liebherr-Great Britain delivered the first two of four Rq350 Litronic hydraulic excavators for use at the Broken Cross opencast coal site in Lanarkshire, Scotland. Ten Terex TR100 rigid haulers were delivered to the site in late 2008. Hatfield Colliery at Stainforth, South Yorkshire, has been reopened by PowerFuel. The main equipment for two longwall faces was supplied by Joy Mining Machinery UK Ltd. 2 photos.

  2. 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

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

    PubMed

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

    2010-06-15

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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

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

    PubMed

    Schimpl, Flávia Camila; Kiyota, Eduardo; Mayer, Juliana Lischka Sampaio; Gonçalves, José Francisco de Carvalho; da Silva, José Ferreira; Mazzafera, Paulo

    2014-09-01

    Guarana seeds have the highest caffeine concentration among plants accumulating purine alkaloids, but in contrast with coffee and tea, practically nothing is known about caffeine metabolism in this Amazonian plant. In this study, the levels of purine alkaloids in tissues of five guarana cultivars were determined. Theobromine was the main alkaloid that accumulated in leaves, stems, inflorescences and pericarps of fruit, while caffeine accumulated in the seeds and reached levels from 3.3% to 5.8%. In all tissues analysed, the alkaloid concentration, whether theobromine or caffeine, was higher in young/immature tissues, then decreasing with plant development/maturation. Caffeine synthase activity was highest in seeds of immature fruit. A nucleotide sequence (PcCS) was assembled with sequences retrieved from the EST database REALGENE using sequences of caffeine synthase from coffee and tea, whose expression was also highest in seeds from immature fruit. The PcCS has 1083bp and the protein sequence has greater similarity and identity with the caffeine synthase from cocoa (BTS1) and tea (TCS1). A recombinant PcCS allowed functional characterization of the enzyme as a bifunctional CS, able to catalyse the methylation of 7-methylxanthine to theobromine (3,7-dimethylxanthine), and theobromine to caffeine (1,3,7-trimethylxanthine), respectively. Among several substrates tested, PcCS showed higher affinity for theobromine, differing from all other caffeine synthases described so far, which have higher affinity for paraxanthine. When compared to previous knowledge on the protein structure of coffee caffeine synthase, the unique substrate affinity of PcCS is probably explained by the amino acid residues found in the active site of the predicted protein.

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

    PubMed

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

    2012-05-09

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

  14. 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.

  15. An Introduction to ESERO-UK, the UK Space Education Office

    ERIC Educational Resources Information Center

    Clements, Allan; Mather, Edward

    2012-01-01

    This article introduces the UK branch of the European Space Education Resource Office (ESERO-UK), also known as the UK Space Education Office. It is a teaching project designed to use space to enthuse primary and secondary students to study science, technology, engineering and mathematics (STEM) subjects. The office is funded by the European Space…

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

    PubMed

    del Castillo Velasco-Martínez, Iris; Hernández-Camacho, Claudia J; Méndez-Rodríguez, Lía C; Zenteno-Savín, Tania

    2016-01-01

    In mammalian tissues under hypoxic conditions, ATP degradation results in accumulation of purine metabolites. During exercise, muscle energetic demand increases and oxygen consumption can exceed its supply. During breath-hold diving, oxygen supply is reduced and, although oxygen utilization is regulated by bradycardia (low heart rate) and peripheral vasoconstriction, tissues with low blood flow (ischemia) may become hypoxic. The goal of this study was to evaluate potential differences in the circulating levels of purine metabolism components between diving and exercise in bottlenose dolphins (Tursiops truncatus). Blood samples were taken from captive dolphins following a swimming routine (n=8) and after a 2min dive (n=8). Activity of enzymes involved in purine metabolism (hypoxanthine guanine phosphoribosyl transferase (HGPRT), inosine monophosphate deshydrogenase (IMPDH), xanthine oxidase (XO), purine nucleoside phosphorylase (PNP)), and purine metabolite (hypoxanthine (HX), xanthine (X), uric acid (UA), inosine monophosphate (IMP), inosine, nicotinamide adenine dinucleotide (NAD(+)), adenosine, adenosine monophosphate (AMP), adenosine diphosphate (ADP), ATP, guanosine diphosphate (GDP), guanosine triphosphate (GTP)) concentrations were quantified in erythrocyte and plasma samples. Enzymatic activity and purine metabolite concentrations involved in purine synthesis and degradation, were not significantly different between diving and exercise. Plasma adenosine concentration was higher after diving than exercise (p=0.03); this may be related to dive-induced ischemia. In erythrocytes, HGPRT activity was higher after diving than exercise (p=0.007), suggesting an increased capacity for purine recycling and ATP synthesis from IMP in ischemic tissues of bottlenose dolphins during diving. Purine recycling and physiological adaptations may maintain the ATP concentrations in bottlenose dolphins after diving and exercise.

  17. 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

  18. 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

  19. Science education reforms in the UK.

    PubMed

    2012-10-01

    As children return to school at the end of the summer in the UK, planned reforms aim to increase their science and maths literacy. A comprehensive foundation in these essential subjects is necessary to ensure that the UK remains at the forefront of science and technology for decades to come.

  20. Leadership Practices in German and UK Organisations

    ERIC Educational Resources Information Center

    McCarthy, Grace

    2005-01-01

    Purpose: The aim of this research was to determine whether leadership practices vary between German and UK organisations. Design/methodology/approach: The author used self-assessment documents submitted by German and UK organisations to the European Foundation for Quality Management (EFQM), to identify leadership practices in both countries. A…

  1. UK Policy on Folate Fortification of Foods

    ERIC Educational Resources Information Center

    Malcolm, Alan

    2004-01-01

    The UK Food Standards Agency has decided not to recommend fortification of foods with folate, the family of vitamins associated with the prevention of neural tube defects in babies. This is a change in attitude from previous recommendations made by a series of committees and reports in the UK. Notably, it differs from US policy on the matter. The…

  2. Proceedings of the IEEE International Workshop on Safety of Systems (1st) held in Monterey, California on 15-16 Mar 2007

    DTIC Science & Technology

    2007-03-01

    Programming: Concurrency Page 36© 2005 by Andrew Kornecki and Janusz Zalewski • An informal scan of the real-time (embedded, dedicated, safety...Press, pp. 40-47. 8. R. Sterritt, D.F. Bantz, “PAC-MEN: Personal Autonomic Computing Monitoring Environments,” In Proceedings of IEEE DEXA 2004...Autonomic Computing Environment,” In Proceedings of IEEE DEXA 2003 Workshops - 1st International Workshop on Autonomic Computing Systems, Prague, Czech

  3. Injuries and Physical Fitness Before and After Deployments of the 10th Mountain Division to Afghanistan and the 1st Cavalry Division to Iraq, September 2005 - October 2008

    DTIC Science & Technology

    2008-10-01

    determined using the McNemar Test. The McNemar Test allows comparison of frequency data involving repeated measures on the same individuals.(71) (3...and After Deployment of the 10thMt Cohort (n=505 Men) Injury Index Injury Incidence p-value ( McNemar Test) Predeployment Postdeployment Period 1...Injury Incidence Before and After Deployment of the 1stCav Cohort – Men (n=3242) Injury Index Injury Incidence p-value ( McNemar Test) Predeployment

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

    PubMed

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

    2015-02-09

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

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

    PubMed

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

    2014-07-23

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

  6. Synthesis of 9,9'-[1,2-ethanediylbis(oxymethylene)]bis-2-amino-1,9-dihydro-6H-purin-6-one, an impurity of acyclovir.

    PubMed

    Suárez, Rosa M; Matía, Maria Paz; Novella, José Luis; Molina, Andres; Cosme, Antonio; Vaquero, Juan José; Alvarez-Builla, Julio

    2012-07-25

    The synthesis of 9,9'-[1,2-ethanediylbis(oxymethylene)]bis-2-amino-1,9-dihydro-6H-purin-6-one, a minor impurity of acyclovir, is described. Starting with commercial N-(9-acetyl-6-oxo-1H-purin-2-yl)acetamide, the process uses an acid catalysed phase transfer catalysis (PTC) process to produce the selective alkylation at the 9 position of the guanine ring.

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

    NASA Astrophysics Data System (ADS)

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

    2012-07-01

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

  8. Theacrine, a special purine alkaloid with sedative and hypnotic properties from Cammelia assamica var. kucha in mice.

    PubMed

    Xu, Jie-Kun; Kurihara, Hiroshi; Zhao, Liang; Yao, Xin-Sheng

    2007-01-01

    The central nervous system activities of theacrine (1,3,7,9-tetramethyluric acid), a purine alkaloid which is abundantly present in Camellia assamica var. kucha, were investigated in ambulatory activity, pentobarbital-induced sleep and forced swimming test in mice, compared with two other purine alkaloids, caffeine and theobromine. Caffeine treatment led to a marked increase in the ambulatory activity accompanied with decreasing of the immobility time in forced swimming test at both 10 and 30 mg/kg. Under the same conditions, neither theacrine nor theobromine showed obvious excited efficacy. Both doses of theacrine could significantly prolong the sleeping time induced by pentobarbital, while caffeine and theobromine exhibited an inverted effect. These results indicated that theacrine possessed potent sedative and hypnotic properties and its central nervous system effects were different from those of caffeine and theobromine.

  9. Isolation and Characterization of a Slowly Milk-Coagulating Variant of Lactobacillus helveticus Deficient in Purine Biosynthesis

    PubMed Central

    Hebert, Elvira M.; De Giori, Graciela S.; Raya, Raul R.

    2001-01-01

    A slowly milk-coagulating variant (Fmc−) of Lactobacillus helveticus CRL 1062, designated S1, was isolated and characterized. Strain S1 possessed all the known essential components required to utilize casein as a nitrogen source, which include functional proteinase and peptidase activities as well as functional amino acid, di- and tripeptide, and oligopeptide transport systems. The amino acid requirements of strain S1 were similar to those of the parental strain. However, on a purine-free, chemically defined medium, the growth rate of the Fmc− strain was threefold lower than that of the wild-type strain. L. helveticus S1 was found to be defective in IMP dehydrogenase activity and therefore was deficient in the ability to synthesize XMP and GMP. This conclusion was further supported by the observation that the addition of guanine or xanthine to milk, a substrate poor in purine compounds, restored the Fmc+ phenotype of L. helveticus S1. PMID:11282642

  10. Experiences of non-UK-qualified doctors working within the UK regulatory framework: a qualitative study

    PubMed Central

    Slowther, A; Lewando Hundt, GA; Purkis, J; Taylor, R

    2012-01-01

    Objective To explore the experience of non-UK-qualified doctors in working within the regulatory framework of the General Medical Council (GMC) document Good Medical Practice. Design Individual interviews and focus groups. Setting United Kingdom. Participants Non-UK-qualified doctors who had registered with the GMC between 1 April 2006 and 31 March 2008, doctors attending training/induction programmes for non-UK-qualified doctors, and key informants involved in training and support for non-UK-qualified doctors. Main outcome measures Themes identified from analysis of interview and focus group transcripts. Results Information and support for non-UK qualified doctors who apply to register to work in the UK has little reference to the ethical and professional standards required of doctors working in the UK. Recognition of the ethical, legal and cultural context of UK healthcare occurs once doctors are working in practice. Non-UK qualified doctors reported clear differences in the ethical and legal framework for practising medicine between the UK and their country of qualification, particularly in the model of the doctor–patient relationship. The degree of support for non-UK-qualified doctors in dealing with ethical concerns is related to the type of post they work in. European doctors describe similar difficulties with working in an unfamiliar regulatory framework to their non-European colleagues. Conclusions Non-UK-qualified doctors experience a number of difficulties related to practising within a different ethical and professional regulatory framework. Provision of information and educational resources before registration, together with in-practice support would help to develop a more effective understanding of GMP and its implications for practice in the UK. PMID:22408082

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

    NASA Astrophysics Data System (ADS)

    Korenman, Ya. I.; Krivosheeva, O. A.; Mokshina, N. Ya.

    2012-12-01

    The distribution of purine alkaloids (caffeine, theobromine, theophylline) was studied in the systems: alkyl acetates-dialkyl phtalate-salting-out agent (ammonium sulfate). The quantitative characteristics of the extraction-distribution coefficients ( D) and the degree of extraction ( R, %) are calculated. The relationships between the distribution coefficients of alkaloids and the length of the hydrocarbon radical in the molecule of alkyl acetate (dialkyl phtalate) are determined. The possibility of predicting the distribution coefficients is demonstrated.

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

    Dangoudoubiyam, Sriveny; Zhang, Zijing; Howe, Daniel K

    2014-09-01

    Sarcocystis neurona is an apicomplexan parasite that causes severe neurological disease in horses and marine mammals. The Apicomplexa are all obligate intracellular parasites that lack purine biosynthesis pathways and rely on the host cell for their purine requirements. Hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT) and adenosine kinase (AK) are key enzymes that function in two complementary purine salvage pathways in apicomplexans. Bioinformatic searches of the S. neurona genome revealed genes encoding HXGPRT, AK and all of the major purine salvage enzymes except purine nucleoside phosphorylase. Wild-type S. neurona were able to grow in the presence of mycophenolic acid (MPA) but were inhibited by 6-thioxanthine (6-TX), suggesting that the pathways involving either HXGPRT or AK are functional in this parasite. Prior work with Toxoplasma gondii demonstrated the utility of HXGPRT as a positive-negative selection marker. To enable the use of HXGPRT in S. neurona, the SnHXGPRT gene sequence was determined and a gene-targeting plasmid was transfected into S. neurona. SnHXGPRT-deficient mutants were selected with 6-TX, and single-cell clones were obtained. These Sn∆HXG parasites were susceptible to MPA and could be complemented using the heterologous T. gondii HXGPRT gene. In summary, S. neurona possesses both purine salvage pathways described in apicomplexans, thus allowing the use of HXGPRT as a positive-negative drug selection marker in this parasite.

  14. Lipoedema: the first UK patient survey.

    PubMed

    Evans, Suzanne

    2013-04-01

    Lipoedema UK was founded in 2012 by women with lipoedema and clinicians working in the Lymphoedema Service at St George's Hospital in London. Its patron is Professor Peter Mortimer, the UK's leading Lipoedema expert, and its nurse consultant is Sandy Ellis, who diagnoses and treats many women with Lipoedema in the UK and is also the nurse consultant in the St George's team. The charity's objectives are to educate doctors, health professionals and the public about lipoedema and its symptoms, so it may be diagnosed and treated earlier.

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

    PubMed

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

    2014-03-01

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

  16. Altered Mitochondria, Protein Synthesis Machinery, and Purine Metabolism Are Molecular Contributors to the Pathogenesis of Creutzfeldt-Jakob Disease.

    PubMed

    Ansoleaga, Belén; Garcia-Esparcia, Paula; Llorens, Franc; Hernández-Ortega, Karina; Carmona Tech, Margarita; Antonio Del Rio, José; Zerr, Inga; Ferrer, Isidro

    2016-06-12

    Neuron loss, synaptic decline, and spongiform change are the hallmarks of sporadic Creutzfeldt-Jakob disease (sCJD), and may be related to deficiencies in mitochondria, energy metabolism, and protein synthesis. To investigate these relationships, we determined the expression levels of genes encoding subunits of the 5 protein complexes of the electron transport chain, proteins involved in energy metabolism, nucleolar and ribosomal proteins, and enzymes of purine metabolism in frontal cortex samples from 15 cases of sCJD MM1 and age-matched controls. We also assessed the protein expression levels of subunits of the respiratory chain, initiation and elongation translation factors of protein synthesis, and localization of selected mitochondrial components. We identified marked, generalized alterations of mRNA and protein expression of most subunits of all 5 mitochondrial respiratory chain complexes in sCJD cases. Expression of molecules involved in protein synthesis and purine metabolism were also altered in sCJD. These findings point to altered mRNA and protein expression of components of mitochondria, protein synthesis machinery, and purine metabolism as components of the pathogenesis of CJD.

  17. Molecular and Genetic Analyses of Drosophila Prat, Which Encodes the First Enzyme of De Novo Purine Biosynthesis

    PubMed Central

    Clark, D. V.

    1994-01-01

    The Drosophila Prat gene encodes phosphoribosylamidotransferase (PRAT), the enzyme that performs the first committed step of the de novo purine nucleotide biosynthesis pathway. Using information from amino acid sequence alignments of PRAT from other organisms, a polymerase chain reaction-based approach was employed to clone Prat. Amino acid sequence alignment of Drosophila PRAT with PRAT from bacteria, yeast, and vertebrates indicates that it is most identical (at least 60%) to the vertebrate PRATs. It shares putative amino-terminal propeptide and ironbinding domains seen only in Bacillus subtilis and vertebrate PRATs. Prat was localized to the right arm of chromosome 3 at polytene band 84E1-2. Owing to the fact that this region had been well characterized previously, Prat was localized to a 30-kilobase region between two deficiency break-points. By making the prediction that Prat would have a similar ``purine syndrome'' phenotype as mutations in the genes ade2 and ade3, which encode enzymes downstream in the pathway, five alleles of Prat were isolated. Three of the alleles were identified as missense mutations. A comparison of PRAT enzyme activity with phenotype in three of the mutants indicates that a reduction to 40% of the wild-type allele's activity is sufficient to cause the purine syndrome, suggesting that PRAT activity is limiting in Drosophila. PMID:8150282

  18. Profiles of phenolic compounds and purine alkaloids during the development of seeds of Theobroma cacao cv. Trinitario.

    PubMed

    Pereira-Caro, Gema; Borges, Gina; Nagai, Chifumi; Jackson, Mel C; Yokota, Takao; Crozier, Alan; Ashihara, Hiroshi

    2013-01-16

    Changes occurring in phenolic compounds and purine alkaloids, during the growth of seeds of cacao (Theobroma cacao) cv. Trinitario, were investigated using HPLC-MS/MS. Extracts of seeds with a fresh weight of 125, 700, 1550, and 2050 mg (stages 1-4, respectively) were analyzed. The phenolic compounds present in highest concentrations in developing and mature seeds (stages 3 and 4) were flavonols and flavan-3-ols. Flavan-3-ols existed as monomers of epicatechin and catechin and as procyanidins. Type B procyanidins were major components and varied from dimers to pentadecamer. Two anthocyanins, cyanidin-3-O-arabinoside and cyanidin-3-O-galactoside, along with the N-phenylpropernoyl-l-amino acids, N-caffeoyl-l-aspartate, N-coumaroyl-l-aspartate, N-coumaroyl-3-hydroxytyrosine (clovamide), and N-coumaroyltyrosine (deoxyclovamide), and the purine alkaloids theobromine and caffeine, were present in stage 3 and 4 seeds. Other purine alkaloids, such as theophylline and additional methylxanthines, did not occur in detectable quantities. Flavan-3-ols were the only components to accumulate in detectable quantities in young seeds at developmental stages 1 and 2.

  19. Purine nucleoside phosphorylase from Pseudoalteromonas sp. Bsi590: molecular cloning, gene expression and characterization of the recombinant protein.

    PubMed

    Li, Xiaohui; Jiang, Xinyin; Li, Huirong; Ren, Daming

    2008-05-01

    The gene encoding purine nucleoside phosphorylase (PNP) from the cold-adapted marine bacterium Pseudoalteromonas sp. Bsi590 was identified, cloned and expressed in Escherichia coli. The gene encodes a polypeptide of 233 amino acids with a calculated molecular weight of 25,018 Da. Pseudoalteromonas sp. Bsi590 PNP (PiPNP) shares 60% amino sequence identity and conservation of amino acid residues involved in catalysis with mesophilic Escherichia coli deoD-encoded purine nucleoside phosphorylase (EcPNP). N-terminal his-tagged PiPNP and EcPNP were purified to apparent homogeneity using Ni2+-chelating column. Compared with EcPNP, PiPNP possessed a lower temperature optimum and thermal stability. As for PNP enzymes in general, PiPNP and EcPNP displayed complicated kinetic properties; PiPNP possessed higher Km and catalytic efficiency (kcat/Km) compared to EcPNP at 37 degrees C. Substrate specificity results showed PiPNP catalyzed the phosphorolytic cleavage of 6-oxopurine and 6-aminopurine nucleosides (or 2-deoxynucleosides), and to a lesser extent purine arabinosides. PiPNP showed a better activity with inosine while no activity toward pyrimidine nucleosides. The protein conformation was analyzed by temperature perturbation difference spectrum. Results showed that PiPNP had lower conformation transition point temperature than EcPNP; phosphate buffer and KCl had significant influence on PiPNP protein conformation stability and thermostability.

  20. [Genetic control of metabolism of mutagenic purine base analogs 6-hydroxylaminopurine and 2-amino-6-hydroxylaminopurine in yeast Saccharomyces cerevisiae].

    PubMed

    Stepchenkova, E I; Koz'min, S G; Alenin, V V; Pavlov, Iu I

    2009-04-01

    The influence of inactivation of genes, which control biosynthesis of inosine monophosphate (IMP) de novo and the purine utilization and interconversion pathway, on sensitivity of yeast Saccharomyces cerevisiae cells to the mutagenic and toxic action of 6-hydroxylaminopurine (HAP) and 2-amino-6-hydroxylaminopurine (AHA) was studied. It was shown that the manifestation of HAP and AHA mutagenic properties involves the action of enzyme adenine phosphoribosyltransferase encoded in yeast by APT1 gene. A blockade of each stage of IMP biosynthesis, with the exception of the block mediated by inactivation of genes ADE16 and ADE17 leading to the accumulation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), was shown to enhance yeast cell sensitivity to the HAP mutagenic effect; however, it does not affect the sensitivity to AHA. A blockade of conversion of IMP into adenosine monophosphate (AMP) causes hypersensitivity of yeast cells to the mutagenic action of HAP and to the toxic effect of HAP, AHA, and hypoxanthine. It is fully probable that this enhancement of sensitivity to HAP and AHA is conditioned by changes in the pool of purines. This indicates that genes ADE12, ADE13, AAH1, and HAM1 controlling processes of purine utilization and interconversion in yeast make the greatest contribution to the system of protection against the toxic and mutagenic action of the examined analogs. Possible mechanisms of HAP detoxication in bacteria, yeast, and humans are considered.

  1. Heavens Open Up for UK Astronomers

    NASA Astrophysics Data System (ADS)

    2002-07-01

    A significant milestone for British and European science occurred today (July 8, 2002) when the Council of the European Southern Observatory (ESO) met in London. At this historical meeting, the United Kingdom was formally welcomed into ESO by the nine other member states. The UK, one of the leading nations in astronomical research, now joins one of the world's major astronomical organisations. UK astronomers will now be able to use the four 8.2-metre and several 1.8-metre telescopes that comprise the Very Large Telescope (VLT) facility located at the Paranal Observatory in the northern part of the Atacama desert in Chile, as well as two 4-m class telescopes and several smaller ones at the ESO La Silla Observatory further south. The UK will also benefit from increased involvement in the design and construction of the Atacama Large Millimetre Array (ALMA), a network of 64 twelve-metre telescopes also sited in Chile, and play a defining role in ESO's 100-metre Overwhelmingly Large Telescope (OWL). Sir Martin Rees , The Astronomer Royal, said, "Joining ESO is good for UK science, and I think good for Europe as well. It offers us access to the VLT's 8-m class telescopes and restores the UK's full competitiveness in optical astronomy. We're now guaranteed full involvement in ALMA and in the next generation of giant optical instruments - projects that will be at the forefront of the research in the next decade and beyond. Moreover, our commitment to ESO should enhance its chances of forging ahead of the US in these technically challenging and high profile scientific projects. UK membership of ESO is a significant and welcome outcome of this government's increasing investment in science". Prof. Ian Halliday , Chief Executive of the Particle Physics and Astronomy Research Council (PPARC), the UK's strategic science investment agency said, "The United Kingdom already participates in Europe's flagship particle physics research and the space science research programmes through

  2. Learning from UK primary care.

    PubMed

    Hays, Richard

    2009-03-01

    The Australian Government is wise to examine other health care systems as it strives to improve the quality of care and address rising costs to both governments and individuals. Focus is currently on the United Kingdom, whose National Health Service (NHS) stands out as one that delivers good care at a reasonable price to all who need it. The Australian and UK systems have many similarities: universal access, tax payer support, no or low cost at point of delivery, and good population health outcomes. They also face similar pressures on services from aging, increasingly unwell yet expectant populations.However, there are also differences, largely in the way that health care is funded, organised and delivered. The NHS is a huge system for 60 million people in four home countries with diverging policies. Within England, the system is managed through 10 strategic health authorities, each responsible for about 5 million people and having the right to interpret national policy. Population based health care, including tertiary care, is funded locally via primary care trusts.

  3. UK organisation of access care.

    PubMed

    Wilmink, Teun; Powers, Sarah; Baharani, Jyoti

    2015-01-01

    National UK audits show that 73% of patients start renal replacement therapy (RRT) with haemodialysis (HD). However, 59% of those start HD on non-permanent access in the form of a tunnelled line (TL) or a non-tunnelled line (NTL), 40% on an arteriovenous fistula (AVF) and 1% on an arteriovenous graft (AVG). After 3 months, the number of patients dialysing on AVF was only 41%. Late referrals, within 90 days of starting dialysis to the renal service, occur in one-fifth of all incident HD patients. Referral to a surgeon was an important determinant of mode of access at first dialysis. However, referral to a surgeon occurred in 67% of patients who were known to the nephrologist for over a year and in 46% of patients who were known to nephrology less than a year but more than 90 days. Best practice tariffs of the National Health Service (NHS) payment by results program have set a target of 75% of prevalent HD occurring via an AVF or AVG in 2011/2012, rising to 85% in 2013/2014. We suggest that this target is best achieved by increasing timely referral to a surgeon for creation of access before HD is needed.

  4. An Unusual Protector-Protégé Strategy for the Biosynthesis of Purine Nucleoside Antibiotics.

    PubMed

    Wu, Pan; Wan, Dan; Xu, Gudan; Wang, Gui; Ma, Hongmin; Wang, Tingting; Gao, Yaojie; Qi, Jianzhao; Chen, Xiaoxia; Zhu, Jian; Li, Yong-Quan; Deng, Zixin; Chen, Wenqing

    2017-02-16

    Pentostatin (PTN, deoxycoformycin) and arabinofuranosyladenine (Ara-A, vidarabine) are purine nucleoside antibiotics used clinically to treat hematological cancers and human DNA virus infections, respectively. PTN has a 1,3-diazepine ring, and Ara-A is an adenosine analog with an intriguing epimerization at the C-2' hydroxyl group. However, the logic underlying the biosynthesis of these interesting molecules has long remained elusive. Here, we report that the biosynthesis of PTN and Ara-A employs an unusual protector-protégé strategy. To our surprise, we determined that a single gene cluster governs PTN and Ara-A biosynthesis via two independent pathways. Moreover, we verified that PenB functions as a reversible oxidoreductase for the final step of PTN. Remarkably, we provided the first direct biochemical evidence that PTN can protect Ara-A from deamination by selective inhibition of the host adenosine deaminase. These findings expand our knowledge of natural product biosynthesis and open the way for target-directed genome mining of Ara-A/PTN-related antibiotics.

  5. Activities of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) on undernourished and renourished rats' thymus.

    PubMed

    Feliu, M S.; Slobodianik, N H.

    2001-02-01

    We studied the effect of administration of a low quality dietary protein, from weaning onwards, on the thymus of undernourished rats and the posterior effect of refeeding with a high quality dietary protein. Changes in thymus weight and the activity of Adenosine Deaminase (ADA) and Purine Nucleoside Phosphorylase (PNP) on thymus, were determined. Wistar rats were suckled in groups of 14-16 per dam since birth to weaning (23 days) to obtain undernutrition. At weaning, a group of 14-16 rats received pre-cooked maize flour (Protein content: 6.5%) for 18 days. One group was sacrificed (M) and the other rats were refed with the casein diet (Protein content: 20%) during 20 days (R). The age-matched control groups were fed stock diet since 40 (C40) and 60 (C60) days of age, respectively. At the end of the experimental period, body (Bw) and thymus weight were determined. ADA and PNP activities were determined in thymocyte suspensions. Highly significant differences in thymus weight-expressed as mg or mg/Bw(0.75)-and the activity of ADA and PNP were observed in rats fed the experimental diet containing maize flour, when compared to the respective age-matched control. No statistical differences were observed between R and C60.The administration of a high quality dietary protein to undernourished weanling rats is capable to reverse the damage produced by the low quality dietary protein on thymus weight and ADA and PNP thymus activities.

  6. The role of a purine-specific nucleoside hydrolase in spore germination of Bacillus thuringiensis.

    PubMed

    Liang, Liang; He, Xihong; Liu, Gang; Tan, Huarong

    2008-05-01

    A homologous gene (iunH) of a putative nucleoside hydrolase (NH), which had been identified from the exosporia of Bacillus cereus and Bacillus anthracis spores, was cloned from Bacillus thuringiensis subsp. kurstaki. Disruption of iunH did not affect the vegetative growth and sporulation of Bacillus thuringiensis, but promoted both inosine- and adenosine-induced spore germination. The inosine- or adenosine-induced germination rate decreased when the wild-type iunH gene was overexpressed in Bacillus thuringiensis. The iunH gene product was characterized as a purine-specific NH. The kinetic parameters of IunH with inosine as substrate were K(m)=399+/-115 microM, k(cat)=48.9+/-8.5 s(-1) and k(cat)/K(m)=1.23 x 10(5) M(-1) s(-1). The optimal pH and temperature for IunH were found to be pH 6 and 80 degrees C. Meanwhile, the specific activity of inosine hydrolase in intact spores of the wild-type strain with inosine as substrate was 2.89+/-0.23x10(-2) micromol min(-1) (mg dry wt)(-1). These results indicate that IunH is important in moderating inosine- or adenosine-induced germination of Bacillus thuringiensis spores.

  7. Solvent effects on the photochemistry of 4-aminoimidazole-5-carbonitrile, a prebiotically plausible precursor of purines.

    PubMed

    Szabla, Rafał; Sponer, Judit E; Sponer, Jiří; Sobolewski, Andrzej L; Góra, Robert W

    2014-09-07

    4-Aminoimidazole-5-carbonitrile (AICN) was suggested as a prebiotically plausible precursor of purine nucleobases and nucleotides. Although it can be formed in a sequence of photoreactions, AICN is immune to further irradiation with UV-light. We present state-of-the-art multi-reference quantum-chemical calculations of potential energy surface cuts and conical intersection optimizations to explain the molecular mechanisms underlying the photostability of this compound. We have identified the N-H bond stretching and ring-puckering mechanisms that should be responsible for the photochemistry of AICN in the gas phase. We have further considered the photochemistry of AICN-water clusters, while including up to six explicit water molecules. The calculations reveal charge transfer to solvent followed by formation of an H3O(+) cation, both of which occur on the (1)πσ* hypersurface. Interestingly, a second proton transfer to an adjacent water molecule leads to a (1)πσ*/S0 conical intersection. We suggest that this electron-driven proton relay might be characteristic of low-lying (1)πσ* states in chromophore-water clusters. Owing to its nature, this mechanism might also be responsible for the photostability of analogous organic molecules in bulk water.

  8. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine

    PubMed Central

    Hirka, Gábor; Glávits, Róbert; Palmer, Philip A.; Endres, John R.; Pasics Szakonyiné, Ilona

    2016-01-01

    A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals. PMID:27635133

  9. Effect of ethanol on metabolism of purine bases (hypoxanthine, xanthine, and uric acid).

    PubMed

    Yamamoto, Tetsuya; Moriwaki, Yuji; Takahashi, Sumio

    2005-06-01

    There are many factors that contribute to hyperuricemia, including obesity, insulin resistance, alcohol consumption, diuretic use, hypertension, renal insufficiency, genetic makeup, etc. Of these, alcohol (ethanol) is the most important. Ethanol enhances adenine nucleotide degradation and increases lactic acid level in blood, leading to hyperuricemia. In beer, purines also contribute to an increase in plasma uric acid. Although rare, dehydration and ketoacidosis (due to ethanol ingestion) are associated with the ethanol-induced increase in serum uric acid levels. Ethanol also increases the plasma concentrations and urinary excretion of hypoxanthine and xanthine via the acceleration of adenine nucleotide degradation and a possible weak inhibition of xanthine dehydrogenase activity. Since many factors such as the ALDH2*1 gene and ADH2*2 gene, daily drinking habits, exercise, and dehydration enhance the increase in plasma concentration of uric acid induced by ethanol, it is important to pay attention to these factors, as well as ingested ethanol volume, type of alcoholic beverage, and the administration of anti-hyperuricemic agents, to prevent and treat ethanol-induced hyperuricemia.

  10. The antibacterial activity and toxicity of enrofloxacin are decreased by nanocellulose conjugated with aminobenzyl purin.

    PubMed

    Yasini, Seyed Ali; Zadeh, Mohammad Hossein Balal; Shahdadi, Hossein

    2015-11-01

    The first aim of this study was to synthesize nanocellulose conjugated with aminobenzyl purin (NCABP), and the second aim was to evaluate the effect of NCABP on both toxicity and antibacterial activity of enrofloxacin. Here, the adsorption of enrofloxacin by NCABP was first modeled by molecular dynamic (MD) simulation. In the next step, NCABP was synthesized, and was exposed to enrofloxacin, 1000 μg mL(-1), at various conditions. Then, the quantity of adsorption and release was separately measured. Furthermore, both toxicity and antibacterial activity of NCABP, enrofloxacin, and (NCABP+enrofloxacin) were separately evaluated. In this study, MD simulation clearly showed the adsorption after 50 picoseconds. The adsorption tests revealed that the increase of incubation time and NCABP concentration, at range of 50-200 μg mL(-1), led to increase of adsorption. Moreover, the decrease of pH led to increase of adsorption. Interestingly, NCABP could adsorb enrofloxacin, up to 1000 μg mL(-1), in different types of meat. Moreover, the increase of incubation time and temperature did not release enrofloxacin, but the increase of pH increased release. This study showed that both toxicity and antibacterial activity of enrofloxacin were decreased when exposed together with NCABP.

  11. Influence of sprint training on human skeletal muscle purine nucleotide metabolism.

    PubMed

    Stathis, C G; Febbraio, M A; Carey, M F; Snow, R J

    1994-04-01

    To examine the effect of sprint training on human skeletal muscle purine nucleotide metabolism, eight active untrained subjects completed a maximal 30-s sprint bout on a cycle ergometer before and after 7 wk of sprint training. Resting muscle ATP and total adenine nucleotide content were reduced (P < 0.05) by 19 and 18%, respectively, after training. Training resulted in a 52% attenuation (P < 0.05) in the magnitude of ATP depletion after exercise and a similar reduction (P < 0.05) in the accumulation of inosine 5'-monophosphate and ammonia. During recovery, muscle inosine 5'-monophosphate (P < 0.05) and inosine (P < 0.01) content were reduced after training, as was the accumulation of inosine (P < 0.05). Plasma ammonia was higher (P < 0.05) after training early in recovery; in contrast, plasma hypoxanthine concentrations were reduced (P < 0.05) during the latter stages of recovery. The attenuated resting ATP and total adenine nucleotide contents after training probably result from the acute effects of prior training sessions. The reduction in the magnitude of ATP depletion during a 30-s sprint bout after training must reflect an improved balance between ATP hydrolysis and resynthesis. It is unclear which mechanism(s) is responsible for the reduction in the magnitude of ATP degradation after training.

  12. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine.

    PubMed

    Clewell, Amy; Hirka, Gábor; Glávits, Róbert; Palmer, Philip A; Endres, John R; Murbach, Timothy S; Marx, Tennille; Pasics Szakonyiné, Ilona

    2016-01-01

    A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals.

  13. Cloning of three human multifunctional de novo purine biosynthetic genes by functional complementation of yeast mutations.

    PubMed Central

    Schild, D; Brake, A J; Kiefer, M C; Young, D; Barr, P J

    1990-01-01

    Functional complementation of mutations in the yeast Saccharomyces cerevisiae has been used to clone three multifunctional human genes involved in de novo purine biosynthesis. A HepG2 cDNA library constructed in a yeast expression vector was used to transform yeast strains with mutations in adenine biosynthetic genes. Clones were isolated that complement mutations in the yeast ADE2, ADE3, and ADE8 genes. The cDNA that complemented the ade8 (phosphoribosylglycinamide formyltransferase, GART) mutation, also complemented the ade5 (phosphoribosylglycinamide synthetase) and ade7 [phosphoribosylaminoimidazole synthetase (AIRS; also known as PAIS)] mutations, indicating that it is the human trifunctional GART gene. Supporting data include homology between the AIRS and GART domains of this gene and the published sequence of these domains from other organisms, and localization of the cloned gene to human chromosome 21, where the GART gene has been shown to map. The cDNA that complemented ade2 (phosphoribosylaminoimidazole carboxylase) also complemented ade1 (phosphoribosylaminoimidazole succinocarboxamide synthetase), supporting earlier data suggesting that in some organisms these functions are part of a bifunctional protein. The cDNA that complemented ade3 (formyltetrahydrofolate synthetase) is different from the recently isolated human cDNA encoding this enzyme and instead appears to encode a related mitochondrial enzyme. Images PMID:2183217

  14. Analysis of abnormalities in purine metabolism leading to gout and to neurological dysfunctions in man.

    PubMed Central

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

    1998-01-01

    A modelling approach is used to analyse diseases associated with purine metabolism in man. The specific focus is on deficiencies in two enzymes, hypoxanthine:guanine phosphoribosyltransferase and adenylosuccinate lyase. These deficiencies can lead to a number of symptoms, including neurological dysfunctions and mental retardation. Although the biochemical mechanisms of dysfunctions associated with adenylosuccinate lyase deficiency are not completely understood, there is at least general agreement in the literature about possible causes. Simulations with our model confirm that accumulation of the two substrates of the enzyme can lead to significant biochemical imbalance. In hypoxanthine:guanine phosphoribosyltransferase deficiency the biochemical mechanisms associated with neurological dysfunctions are less clear. Model analyses support some old hypotheses but also suggest new indicators for possible causes of neurological dysfunctions associated with this deficiency. Hypoxanthine:guanine phosphoribosyltransferase deficiency is known to cause hyperuricaemia and gout. We compare the relative importance of this deficiency with other known causes of gout in humans. The analysis suggests that defects in the excretion of uric acid are more consequential than defects in uric acid synthesis such as hypoxanthine:guanine phosphoribosyltransferase deficiency. PMID:9445373

  15. A complex of nuclear proteins mediates SR protein binding to a purine-rich splicing enhancer.

    PubMed Central

    Yeakley, J M; Morfin, J P; Rosenfeld, M G; Fu, X D

    1996-01-01

    A purine-rich splicing enhancer from a constitutive exon has been shown to shift the alternative splicing of calcitonin/CGRP pre-mRNA in vivo. Here, we demonstrate that the native repetitive GAA sequence comprises the optimal enhancer element and specifically binds a saturable complex of proteins required for general splicing in vitro. This complex contains a 37-kDa protein that directly binds the repetitive GAA sequence and SRp40, a member of the SR family of non-snRNP splicing factors. While purified SR proteins do not stably bind the repetitive GAA element, exogenous SR proteins become associated with the GAA element in the presence of nuclear extracts and stimulate GAA-dependent splicing. These results suggest that repetitive GAA sequences enhance splicing by binding a protein complex containing a sequence-specific RNA binding protein and a general splicing activator that, in turn, recruit additional SR proteins. This type of mechanism resembles the tra/tra-2-dependent recruitment of SR proteins to the Drosophila doublesex alternative splicing regulatory element. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8755518

  16. Solution-phase parallel synthesis of acyclic nucleoside libraries of purine, pyrimidine, and triazole acetamides.

    PubMed

    Pathak, Ashish K; Pathak, Vibha; Reynolds, Robert C

    2014-09-08

    Molecular diversity plays a pivotal role in modern drug discovery against phenotypic or enzyme-based targets using high throughput screening technology. Under the auspices of the Pilot Scale Library Program of the NIH Roadmap Initiative, we produced and report herein a diverse library of 181 purine, pyrimidine, and 1,2,4-triazole-N-acetamide analogues which were prepared in a parallel high throughput solution-phase reaction format. A set of assorted amines were reacted with several nucleic acid N-acetic acids utilizing HATU as the coupling reagent to produce diverse acyclic nucleoside N-acetamide analogues. These reactions were performed using 24 well reaction blocks and an automatic reagent-dispensing platform under inert atmosphere. The targeted compounds were purified on an automated purification system using solid sample loading prepacked cartridges and prepacked silica gel columns. All compounds were characterized by NMR and HRMS, and were analyzed for purity by HPLC before submission to the Molecular Libraries Small Molecule Repository (MLSMR) at NIH. Initial screening through the Molecular Libraries Probe Production Centers Network (MLPCN) program, indicates that several analogues showed diverse and interesting biological activities.

  17. Factors associated with a purine-rich exonic splicing enhancer sequence in Xenopus oocyte nucleus

    SciTech Connect

    Masuyama, Kaoru; Taniguchi, Ichiro; Okawa, Katsuya; Ohno, Mutsuhito . E-mail: hitoohno@virus.kyoto-u.ac.jp

    2007-08-03

    Purine-rich exonic splicing enhancers (ESEs) stimulate splicing of the adjacent introns with suboptimal splice sites. To elucidate the mechanism regarding ESEs, factors specifically associated with ESEs in HeLa cell nuclear extracts were previously investigated, and shown to include SR (serine/arginine-rich) proteins. However, factors associated with ESEs in vivo have not yet been explored. Here we show that a GAA repeat RNA sequence, a typical ESE, is associated in Xenopus oocyte nuclei with at least one SR protein, SF2/ASF, as was expected. Moreover, components of SF3a/b complexes, U2 snRNA, and U2AF{sup 65} were also found to be associated with the ESE in the nucleus. Since SF3a/b complexes are the constituents of the 17S U2 snRNP, these results suggest that the 17S U2 snRNP is associated with the ESE in the nucleus, probably through bridging interactions of U2AF and SR proteins. The identified factors may represent a functional splicing enhancer complex in vivo.

  18. UK Announces Intention to Join ESO

    NASA Astrophysics Data System (ADS)

    2000-11-01

    Summary The Particle Physics and Astronomy Research Council (PPARC) , the UK's strategic science investment agency, today announced that the government of the United Kingdom is making funds available that provide a baseline for this country to join the European Southern Observatory (ESO) . The ESO Director General, Dr. Catherine Cesarsky , and the ESO Community warmly welcome this move towards fuller integration in European astronomy. "With the UK as a potential member country of ESO, our joint opportunities for front-line research and technology will grow significantly", she said. "This announcement is a clear sign of confidence in ESO's abilities, most recently demonstrated with the construction and operation of the unique Very Large Telescope (VLT) on Paranal. Together we will look forward with confidence towards new, exciting projects in ground-based astronomy." It was decided earlier this year to place the 4-m UK Visible and Infrared Survey Telescope (VISTA) at Paranal, cf. ESO Press Release 03/00. Following negotiations between ESO and PPARC, a detailed proposal for the associated UK/ESO Agreement with the various entry modalities will now be presented to the ESO Council for approval. Before this Agreement can enter into force, the ESO Convention and associated protocols must also be ratified by the UK Parliament. Research and key technologies According to the PPARC press release, increased funding for science, announced by the UK government today, will enable UK astronomers to prepare for the next generation of telescopes and expand their current telescope portfolio through membership of the European Southern Observatory (ESO). The uplift to its baseline budget will enable PPARC to enter into final negotiations for UK membership of the ESO. This will ensure that UK astronomers, together with their colleagues in the ESO member states, are actively involved in global scale preparations for the next generation of astronomy facilities. among these are ALMA

  19. The licensing of medicines in the UK.

    PubMed

    2009-04-01

    Before a medicinal product* can be marketed in the UK, a marketing authorisation (formerly called a 'product licence') is needed. Such an authorisation can be granted in the European Union (EU), via the European Medicines Agency (EMEA), European Commission (EC) and member state's competent authorities or, specifically in the UK, via the Medicines and Healthcare product Regulatory Agency (MHRA) on behalf of the UK licensing authority.2(-)4 Also, a change to the authorisation is needed if the licensing status of a medicine is changed; for example, from a prescription-only medicine (POM) to a pharmacy medicine (P). Here we look at the procedures involved in the licensing of medicines (including herbal and homoeopathic products) for use in the UK.

  20. The UK pharmaceutical market. An overview.

    PubMed

    Towse, A

    1996-01-01

    The National Health Service (NHS) accounts for more than 98% of the UK prescription medicines market, which is the sixth largest pharmaceutical market in the world. Most of this market is driven by the UK's approximately 35,000 general practitioners (GPs). It is an open market, with most leading foreign pharmaceutical companies having a strong presence. While the growth rate of this market has been decelerating, it remains one of the fastest growing components of NHS expenditure. The NHS does not operate any kind of national reimbursement list, but the UK government has adopted several means to keep medicines expenditure under control. These include cash incentives and constraints for GPs relating to expenditure on medicines, individual quarterly updates on GP prescribing, the publication of a list of medicines that cannot be prescribed by GPs, the switching of some prescription-only medicines to over-the-counter medicines, and a co-payment system. The main form of economic regulation in the UK, however, remains the Pharmaceutical Price Regulation Scheme (PPRS). This limits the rate-of-return on capital attributable to medicines sales to the NHS, with the intended rate-of-return being equal to that of UK industry overall. The pharmaceutical industry has generally performed relatively well in the UK market, managing to preserve incentives to innovation. This reflects the fact that UK GPs have been able to maintain their clinical freedom, as well as government recognition of the economic contribution made by the pharmaceutical industry. Current issues of interest in the UK pharmaceutical market context include the future of the PPRS, the debates over the imposition of a national formulary and generic substitution, and over parallel trade, the potential impact of managed-care protocols and computer-based prescribing on pharmaceutical expenditures, and possible political changes.

  1. Vocational Qualifications for the UK Explosives Industry

    DTIC Science & Technology

    2010-07-15

    possible consequences of a lack of competence when working with munitions or explosives can be devastating and the UK has long held concerns over these...their workforces; • activities with significant, or indeed, perceived health and safety and public safety risks are subject to increasingly...www.homelandsecurityqualifications.co.uk 4 National Occupational Standards (NOS) for Explosives Substances and Articles (ESA). The Health and Safety Executive (HSE) has

  2. Future perspectives in melanoma research : Meeting report from the "Melanoma Bridge". Napoli, December 1st-4th 2015.

    PubMed

    Ascierto, Paolo A; Agarwala, Sanjiv; Botti, Gerardo; Cesano, Alessandra; Ciliberto, Gennaro; Davies, Michael A; Demaria, Sandra; Dummer, Reinhard; Eggermont, Alexander M; Ferrone, Soldano; Fu, Yang Xin; Gajewski, Thomas F; Garbe, Claus; Huber, Veronica; Khleif, Samir; Krauthammer, Michael; Lo, Roger S; Masucci, Giuseppe; Palmieri, Giuseppe; Postow, Michael; Puzanov, Igor; Silk, Ann; Spranger, Stefani; Stroncek, David F; Tarhini, Ahmad; Taube, Janis M; Testori, Alessandro; Wang, Ena; Wargo, Jennifer A; Yee, Cassian; Zarour, Hassane; Zitvogel, Laurence; Fox, Bernard A; Mozzillo, Nicola; Marincola, Francesco M; Thurin, Magdalena

    2016-11-15

    The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's disease. Specifically, many clinical successes have been using checkpoint receptor blockade, including T cell inhibitory receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death-1 (PD-1) and its ligand PD-L1. Despite demonstrated successes, responses to immunotherapy interventions occur only in a minority of patients. Attempts are being made to improve responses to immunotherapy by developing biomarkers. Optimizing biomarkers for immunotherapy could help properly select patients for treatment and help to monitor response, progression and resistance that are critical challenges for the immuno-oncology (IO) field. Importantly, biomarkers could help to design rational combination therapies. In addition, biomarkers may help to define mechanism of action of different agents, dose selection and to sequence drug combinations. However, biomarkers and assays development to guide cancer immunotherapy is highly challenging for several reasons: (i) multiplicity of immunotherapy agents with different mechanisms of action including immunotherapies that target activating and inhibitory T cell receptors (e.g., CTLA-4, PD-1, etc.); adoptive T cell therapies that include tissue infiltrating lymphocytes (TILs), chimeric antigen receptors (CARs), and

  3. Three-dimensional analysis of the distal movement of maxillary 1st molars in patients fitted with mini-implant-aided trans-palatal arches

    PubMed Central

    Miresmaeili, Amirfarhang; Sajedi, Ahmad; Moghimbeigi, Abbas

    2015-01-01

    Objective The aim of this study was to investigate three-dimensional molar displacement after distalization via miniscrews and a horizontal modification of the trans-palatal-arch (TPA). Methods The subjects in this clinical trial were 26 Class II patients. After the preparation of a complete set of diagnostic records, miniscrews were inserted between the maxillary 2nd premolar and 1st molar on the palatal side. Elastic modules connected to the TPA exerting an average force of 150-200 g/side parallel to the occlusal plane were applied. Cone-beam computed tomography was utilized to evaluate the position of the miniscrews relative to the adjacent teeth and maxillary sinus, and the direction of force relative to molar furcation. The distances from the central point of the incisive papilla to the mesiopalatal cusps of the 1st maxillary molars and the distances between the mesiopalatal cusps of the left and right molars were measured to evaluate displacement of the maxillary molars on the horizontal plane. Interocclusal space was used to evaluate vertical changes. Results Mean maxillary 1st molar distalization was 2.3 ± 1.1 mm, at a rate of 0.4 ± 0.2 mm/month, and rotation was not significant. Intermolar width increased by 2.9 ± 1.8 mm. Molars were intruded relative to the neighboring teeth, from 0.1 to 0.8 mm. Conclusions Distalization of molars was possible without extrusion, using the appliance investigated. The intrusive component of force reduced the rate of distal movement. PMID:26445718

  4. Characterization of the 1st and 2nd EF-hands of NADPH oxidase 5 by fluorescence, isothermal titration calorimetry, and circular dichroism

    PubMed Central

    2012-01-01

    Background Superoxide generated by non-phagocytic NADPH oxidases (NOXs) is of growing importance for physiology and pathobiology. The calcium binding domain (CaBD) of NOX5 contains four EF-hands, each binding one calcium ion. To better understand the metal binding properties of the 1st and 2nd EF-hands, we characterized the N-terminal half of CaBD (NCaBD) and its calcium-binding knockout mutants. Results The isothermal titration calorimetry measurement for NCaBD reveals that the calcium binding of two EF-hands are loosely associated with each other and can be treated as independent binding events. However, the Ca2+ binding studies on NCaBD(E31Q) and NCaBD(E63Q) showed their binding constants to be 6.5 × 105 and 5.0 × 102 M-1 with ΔHs of -14 and -4 kJ/mol, respectively, suggesting that intrinsic calcium binding for the 1st non-canonical EF-hand is largely enhanced by the binding of Ca2+ to the 2nd canonical EF-hand. The fluorescence quenching and CD spectra support a conformational change upon Ca2+ binding, which changes Trp residues toward a more non-polar and exposed environment and also increases its α-helix secondary structure content. All measurements exclude Mg2+-binding in NCaBD. Conclusions We demonstrated that the 1st non-canonical EF-hand of NOX5 has very weak Ca2+ binding affinity compared with the 2nd canonical EF-hand. Both EF-hands interact with each other in a cooperative manner to enhance their Ca2+ binding affinity. Our characterization reveals that the two EF-hands in the N-terminal NOX5 are Ca2+ specific. Graphical abstract PMID:22490336

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

    PubMed

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

    1997-01-15

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

  6. Hydrogen bond donors accelerate vibrational cooling of hot purine derivatives in heavy water.

    PubMed

    Zhang, Yuyuan; Chen, Jinquan; Kohler, Bern

    2013-08-08

    Natural nucleobases and many of their derivatives have ultrashort excited state lifetimes that make them excellent model systems for studying intermolecular energy flow from a hot solute molecule to the solvent. UV-pump/broadband-mid-IR-probe transient absorption spectra of canonical purine nucleobases and several xanthine derivatives were acquired in D2O and acetonitrile in the probe frequency range of 1500-1750 cm(-1). The spectra reveal that vibrationally hot ground state molecules created by ultrafast internal conversion return to thermal equilibrium in several picoseconds by dissipating their excess energy to solvent molecules. In acetonitrile solution, where hydrogen bonding is minimal, vibrational cooling (VC) occurs with the same time constant of 10 ± 3 ps for paraxanthine, theophylline, and caffeine within experimental uncertainty. In D2O, VC by these molecules occurs more rapidly and at different rates that are correlated with the number of N-D bonds. Hypoxanthine has a VC time constant of 3 ± 1 ps, while similar lifetimes of 2.3 ± 0.8 ps and 3.1 ± 0.3 ps are seen for 5'-adenosine monophosphate and 5'-guanosine monophosphate, respectively. All three molecules have at least two N-D bonds. Slightly slower VC time constants are measured for paraxanthine (4 ± 1 ps) and theophylline (5.1 ± 0.8 ps), dimethylated xanthines that have only one N-D bond. Caffeine, a trimethylated xanthine with no N-D bonds, has a VC time constant of 7.7 ± 0.9 ps, the longest ever observed for any nucleobase in aqueous solution. Hydrogen bond donation by solute molecules is proposed to enable rapid energy disposal to water via direct coupling of high frequency solute-solvent modes.

  7. Polymerase recognition of synthetic oligodeoxyribonucleotides incorporating degenerate pyrimidine and purine bases

    PubMed Central

    Hill, F.; Loakes, D.; Brown, D. M.

    1998-01-01

    A universal base that is capable of substituting for any of the four natural bases in DNA would be of great utility in both mutagenesis and recombinant DNA experiments. This paper describes the properties of oligonucleotides incorporating two degenerate bases, the pyrimidine base 6H,8H-3,4-dihydropyrimido[4,5-c][1,2]oxazin-7-one and the purine base N6-methoxy-2,6-diaminopurine, designated P and K, respectively. An equimolar mixture of the analogues P and K (called M) acts, in primers, as a universal base. The thermal stability of oligonucleotide duplexes were only slightly reduced when natural bases were replaced by P or K. Templates containing the modified bases were copied by Taq polymerase; P behaved as thymine in 60% of copying events and as cytosine in 40%, whereas K behaved as if it were guanine (13%) or adenine (87%). The dUTPase gene of Caenorhabditis elegans, which we have found to contain three nonidentical homologous repeats, was used as a model system to test the use of these bases in primers for DNA synthesis. A pair of oligodeoxyribonucleotides, each 20 residues long and containing an equimolar mixture of P and K at six positions, primed with high specificity both T7 DNA polymerase in sequencing reactions and Taq polymerase in PCRs; no nonspecific amplification was obtained on genomic DNA of C. elegans. Use of P and K can significantly reduce the complexity of degenerate oligonucleotide mixtures, and when used together, P and K can act as a universal base. PMID:9539724

  8. The Evolutionary Fate of the Genes Encoding the Purine Catabolic Enzymes in Hominoids, Birds, and Reptiles

    PubMed Central

    Keebaugh, Alaine C.; Thomas, James W.

    2010-01-01

    Gene loss has been proposed to play a major role in adaptive evolution, and recent studies are beginning to reveal its importance in human evolution. However, the potential consequence of a single gene-loss event upon the fates of functionally interrelated genes is poorly understood. Here, we use the purine metabolic pathway as a model system in which to explore this important question. The loss of urate oxidase (UOX) activity, a necessary step in this pathway, has occurred independently in the hominoid and bird/reptile lineages. Because the loss of UOX would have removed the functional constraint upon downstream genes in this pathway, these downstream genes are generally assumed to have subsequently deteriorated. In this study, we used a comparative genomics approach to empirically determine the fate of UOX itself and the downstream genes in five hominoids, two birds, and a reptile. Although we found that the loss of UOX likely triggered the genetic deterioration of the immediate downstream genes in the hominoids, surprisingly in the birds and reptiles, the UOX locus itself and some of the downstream genes were present in the genome and predicted to encode proteins. To account for the variable pattern of gene retention and loss after the inactivation of UOX, we hypothesize that although gene loss is a common fate for genes that have been rendered obsolete due to the upstream loss of an enzyme a metabolic pathway, it is also possible that same lack of constraint will foster the evolution of new functions or allow the optimization of preexisting alternative functions in the downstream genes, thereby resulting in gene retention. Thus, adaptive single-gene losses have the potential to influence the long-term evolutionary fate of functionally interrelated genes. PMID:20106906

  9. Thermodynamics of the Purine Nucleoside Phosphorylase Reaction Revealed by Computer Simulations.

    PubMed

    Isaksen, Geir Villy; Åqvist, Johan; Brandsdal, Bjørn Olav

    2017-01-10

    Enzymes are able to catalyze chemical reactions by reducing the activation free energy, yielding significant increases in the reaction rates. This can thermodynamically be accomplished by either reducing the activation enthalpy or increasing the activation entropy. The effect of remote mutations on the thermodynamic activation parameters of human purine nucleoside phosphorylase is examined using extensive molecular dynamics and free energy simulations. More than 2700 independent reaction free energy profiles for six different temperatures have been calculated to obtain high-precision computational Arrhenius plots. On the basis of these, the activation enthalpies and entropies were computed from linear regression of the plots with ΔG(⧧) as a function of 1/T, and the obtained thermodynamic activation parameters are in very good agreement with those from experiments. The Arrhenius plots immediately show that the 6-oxopurines (INO and GUO) have identical slopes, whereas the 6-aminopurine (ADO) has a significantly different slope, indicating that the substrate specificity is related to the difference in thermodynamic activation parameters. Furthermore, the calculations show that the human PNP specificity for 6-oxopurines over 6-aminopurines originates from significant differences in electrostatic preorganization. The effect of the remote double mutation, K22E and H104R (E:R), has also been examined, as it alters human PNP toward the bovine PNP. These residues are situated on the protein surface, 28-35 Å from the active site, and the mutation alters the enthalpy-entropy balance with little effect on the catalytic rates. It is thus quite remarkable that the empirical valence bond method can reproduce the enthalpies and entropies induced by these long-range mutations.

  10. Four Generations of Transition State Analogues for Human Purine Nucleoside Phosphorylase

    SciTech Connect

    Ho, M.; Shi, W; Rinaldo-Mathis, A; Tyler, P; Evans, G; Almo, S; Schramm, V

    2010-01-01

    Inhibition of human purine nucleoside phosphorylase (PNP) stops growth of activated T-cells and the formation of 6-oxypurine bases, making it a target for leukemia, autoimmune disorders, and gout. Four generations of ribocation transition-state mimics bound to PNP are structurally characterized. Immucillin-H (K*{sub i} = 58 pM, first-generation) contains an iminoribitol cation with four asymmetric carbons. DADMe-Immucillin-H (K*{sub i} = 9 pM, second-generation), uses a methylene-bridged dihydroxypyrrolidine cation with two asymmetric centers. DATMe-Immucillin-H (K*{sub i} = 9 pM, third-generation) contains an open-chain amino alcohol cation with two asymmetric carbons. SerMe-ImmH (K*{sub i} = 5 pM, fourth-generation) uses achiral dihydroxyaminoalcohol seramide as the ribocation mimic. Crystal structures of PNPs establish features of tight binding to be; (1) ion-pair formation between bound phosphate (or its mimic) and inhibitor cation, (2) leaving-group interactions to N1, O6, and N7 of 9-deazahypoxanthine, (3) interaction between phosphate and inhibitor hydroxyl groups, and (4) His257 interacting with the 5{prime}-hydroxyl group. The first generation analogue is an imperfect fit to the catalytic site with a long ion pair distance between the iminoribitol and bound phosphate and weaker interactions to the leaving group. Increasing the ribocation to leaving-group distance in the second- to fourth-generation analogues provides powerful binding interactions and a facile synthetic route to powerful inhibitors. Despite chemical diversity in the four generations of transition-state analogues, the catalytic site geometry is almost the same for all analogues. Multiple solutions in transition-state analogue design are available to convert the energy of catalytic rate enhancement to binding energy in human PNP.

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

    PubMed Central

    Bagshaw, Andrew TM; Pitt, Joel PW; Gemmell, Neil J

    2006-01-01

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

  12. UK malaria treatment guidelines 2016.

    PubMed

    Lalloo, David G; Shingadia, Delane; Bell, David J; Beeching, Nicholas J; Whitty, Christopher J M; Chiodini, Peter L

    2016-06-01

    1.Malaria is the tropical disease most commonly imported into the UK, with 1300-1800 cases reported each year, and 2-11 deaths. 2. Approximately three quarters of reported malaria cases in the UK are caused by Plasmodium falciparum, which is capable of invading a high proportion of red blood cells and rapidly leading to severe or life-threatening multi-organ disease. 3. Most non-falciparum malaria cases are caused by Plasmodium vivax; a few cases are caused by the other species of plasmodium: Plasmodium ovale, Plasmodium malariae or Plasmodium knowlesi. 4. Mixed infections with more than one species of parasite can occur; they commonly involve P. falciparum with the attendant risks of severe malaria. 5. There are no typical clinical features of malaria; even fever is not invariably present. Malaria in children (and sometimes in adults) may present with misleading symptoms such as gastrointestinal features, sore throat or lower respiratory complaints. 6. A diagnosis of malaria must always be sought in a feverish or sick child or adult who has visited malaria-endemic areas. Specific country information on malaria can be found at http://travelhealthpro.org.uk/. P. falciparum infection rarely presents more than six months after exposure but presentation of other species can occur more than a year after exposure. 7. Management of malaria depends on awareness of the diagnosis and on performing the correct diagnostic tests: the diagnosis cannot be excluded until more than one blood specimen has been examined. Other travel related infections, especially viral haemorrhagic fevers, should also be considered. 8. The optimum diagnostic procedure is examination of thick and thin blood films by an expert to detect and speciate the malarial parasites. P. falciparum and P. vivax (depending upon the product) malaria can be diagnosed almost as accurately using rapid diagnostic tests (RDTs) which detect plasmodial antigens. RDTs for other Plasmodium species are not as reliable. 9

  13. Purines in the eye: recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Müller cells, lens, trabecular meshwork, cornea and lacrimal gland.

    PubMed

    Sanderson, Julie; Dartt, Darlene A; Trinkaus-Randall, Vickery; Pintor, Jesus; Civan, Mortimer M; Delamere, Nicholas A; Fletcher, Erica L; Salt, Thomas E; Grosche, Antje; Mitchell, Claire H

    2014-10-01

    This review highlights recent findings that describ how purines modulate the physiological and pathophysiological responses of ocular tissues. For example, in lacrimal glands the cross-talk between P2X7 receptors and both M3 muscarinic receptors and α1D-adrenergic receptors can influence tear secretion. In the cornea, purines lead to post-translational modification of EGFR and structural proteins that participate in wound repair in the epithelium and influence the expression of matrix proteins in the stroma. Purines act at receptors on both the trabecular meshwork and ciliary epithelium to modulate intraocular pressure (IOP); ATP-release pathways of inflow and outflow cells differ, possibly permitting differential modulation of adenosine delivery. Modulators of trabecular meshwork cell ATP release include cell volume, stretch, extracellular Ca(2+) concentration, oxidation state, actin remodeling and possibly endogenous cardiotonic steroids. In the lens, osmotic stress leads to ATP release following TRPV4 activation upstream of hemichannel opening. In the anterior eye, diadenosine polyphosphates such as Ap4A act at P2 receptors to modulate the rate and composition of tear secretion, impact corneal wound healing and lower IOP. The Gq11-coupled P2Y1-receptor contributes to volume control in Müller cells and thus the retina. P2X receptors are expressed in neurons in the inner and outer retina and contribute to visual processing as well as the demise of retinal ganglion cells. In RPE cells, the balance between extracellular ATP and adenosine may modulate lysosomal pH and the rate of lipofuscin formation. In optic nerve head astrocytes, mechanosensitive ATP release via pannexin hemichannels, coupled with stretch-dependent upregulation of pannexins, provides a mechanism for ATP signaling in chronic glaucoma. With so many receptors linked to divergent functions throughout the eye, ensuring the transmitters remain local and stimulation is restricted to the intended target

  14. Design of an adenosine phosphorylase by active-site modification of murine purine nucleoside phosphorylase. Enzyme kinetics and molecular dynamics simulation of Asn-243 and Lys-244 substitutions of purine nucleoside phosphorylase.

    PubMed

    Maynes, J T; Yam, W; Jenuth, J P; Gang Yuan, R; Litster, S A; Phipps, B M; Snyder, F F

    1999-12-01

    Our objective was to alter the substrate specificity of purine nucleoside phosphorylase such that it would catalyse the phosphorolysis of 6-aminopurine nucleosides. We modified both Asn-243 and Lys-244 in order to promote the acceptance of the C6-amino group of adenosine. The Asn-243-Asp substitution resulted in an 8-fold increase in K(m) for inosine from 58 to 484 microM and a 1000-fold decrease in k(cat)/K(m). The Asn-243-Asp construct catalysed the phosphorolysis of adenosine with a K(m) of 45 microM and a k(cat)/K(m) 8-fold that with inosine. The Lys-244-Gln construct showed only marginal reduction in k(cat)/K(m), 83% of wild type, but had no activity with adenosine. The Asn-243-Asp;Lys-244-Gln construct had a 14-fold increase in K(m) with inosine and 7-fold decrease in k(cat)/K(m) as compared to wild type. This double substitution catalysed the phosphorolysis of adenosine with a K(m) of 42 microM and a k(cat)/K(m) twice that of the single Asn-243-Asp substitution. Molecular dynamics simulation of the engineered proteins with adenine as substrate revealed favourable hydrogen bond distances between N7 of the purine ring and the Asp-243 carboxylate at 2.93 and 2.88 A, for Asn-243-Asp and the Asn-243-Asp;Lys-244-Gln constructs respectively. Simulation also supported a favourable hydrogen bond distance between the purine C6-amino group and Asp-243 at 2.83 and 2.88 A for each construct respectively. The Asn-243-Thr substitution did not yield activity with adenosine and simulation gave unfavourable hydrogen bond distances between Thr-243 and both the C6-amino group and N7 of the purine ring. The substitutions were not in the region of phosphate binding and the apparent S(0.5) for phosphate with wild type and the Asn-243-Asp enzymes were 1.35+/-0.01 and 1.84+/-0.06 mM, respectively. Both proteins exhibited positive co-operativity with phosphate giving Hill coefficients of 7.9 and 3.8 respectively.

  15. Design of an adenosine phosphorylase by active-site modification of murine purine nucleoside phosphorylase. Enzyme kinetics and molecular dynamics simulation of Asn-243 and Lys-244 substitutions of purine nucleoside phosphorylase.

    PubMed Central

    Maynes, J T; Yam, W; Jenuth, J P; Gang Yuan, R; Litster, S A; Phipps, B M; Snyder, F F

    1999-01-01

    Our objective was to alter the substrate specificity of purine nucleoside phosphorylase such that it would catalyse the phosphorolysis of 6-aminopurine nucleosides. We modified both Asn-243 and Lys-244 in order to promote the acceptance of the C6-amino group of adenosine. The Asn-243-Asp substitution resulted in an 8-fold increase in K(m) for inosine from 58 to 484 microM and a 1000-fold decrease in k(cat)/K(m). The Asn-243-Asp construct catalysed the phosphorolysis of adenosine with a K(m) of 45 microM and a k(cat)/K(m) 8-fold that with inosine. The Lys-244-Gln construct showed only marginal reduction in k(cat)/K(m), 83% of wild type, but had no activity with adenosine. The Asn-243-Asp;Lys-244-Gln construct had a 14-fold increase in K(m) with inosine and 7-fold decrease in k(cat)/K(m) as compared to wild type. This double substitution catalysed the phosphorolysis of adenosine with a K(m) of 42 microM and a k(cat)/K(m) twice that of the single Asn-243-Asp substitution. Molecular dynamics simulation of the engineered proteins with adenine as substrate revealed favourable hydrogen bond distances between N7 of the purine ring and the Asp-243 carboxylate at 2.93 and 2.88 A, for Asn-243-Asp and the Asn-243-Asp;Lys-244-Gln constructs respectively. Simulation also supported a favourable hydrogen bond distance between the purine C6-amino group and Asp-243 at 2.83 and 2.88 A for each construct respectively. The Asn-243-Thr substitution did not yield activity with adenosine and simulation gave unfavourable hydrogen bond distances between Thr-243 and both the C6-amino group and N7 of the purine ring. The substitutions were not in the region of phosphate binding and the apparent S(0.5) for phosphate with wild type and the Asn-243-Asp enzymes were 1.35+/-0.01 and 1.84+/-0.06 mM, respectively. Both proteins exhibited positive co-operativity with phosphate giving Hill coefficients of 7.9 and 3.8 respectively. PMID:10567244

  16. Biofortification of UK food crops with selenium.

    PubMed

    Broadley, Martin R; White, Philip J; Bryson, Rosie J; Meacham, Mark C; Bowen, Helen C; Johnson, Sarah E; Hawkesford, Malcolm J; McGrath, Steve P; Zhao, Fang-Jie; Breward, Neil; Harriman, Miles; Tucker, Mark

    2006-05-01

    Se is an essential element for animals. In man low dietary Se intakes are associated with health disorders including oxidative stress-related conditions, reduced fertility and immune functions and an increased risk of cancers. Although the reference nutrient intakes for adult females and males in the UK are 60 and 75 microg Se/d respectively, dietary Se intakes in the UK have declined from >60 microg Se/d in the 1970s to 35 microg Se/d in the 1990s, with a concomitant decline in human Se status. This decline in Se intake and status has been attributed primarily to the replacement of milling wheat having high levels of grain Se and grown on high-Se soils in North America with UK-sourced wheat having low levels of grain Se and grown on low-Se soils. An immediate solution to low dietary Se intake and status is to enrich UK-grown food crops using Se fertilisers (agronomic biofortification). Such a strategy has been adopted with success in Finland. It may also be possible to enrich food crops in the longer term by selecting or breeding crop varieties with enhanced Se-accumulation characteristics (genetic biofortification). The present paper will review the potential for biofortification of UK food crops with Se.

  17. The effects of morphine and methionine-enkephalin on the release of purines from cerebral cortex slices of rats and mice.

    PubMed Central

    Stone, T. W.

    1981-01-01

    1 Slices of cerebral cortex from Wistar rats, TO mice or C57 mice were preincubated with [3H]-adenosine, and labelled purines were subsequently releases by electrical stimulation or by perfusing with ouabain, 100 micro M. 2 Electrically-evoked purine release was substantially reduced when the Ca2+ concentration in the medium was lowered from 2.4 to 0.1 mM. In both rats and mice, the electrically-evoked release was increased by morphine and methionine-enkephalin (Met-enkephalin), 10 micro M, and in rats and TO mice by morphine 1 micro M, both drug effects being prevented by naloxone. 3 Purine release evoked by ouabain was also increased by morphine 1 and 10 micro M, though not by Met-enkephalin, from slices of rat cortex. Ouabain-induced release from TO mice was reduced by morphine, and from C57 mice was unchanged. 4 The enhancement by morphine of electrically-evoked purine release may indicate that purines mediate some effects of morphine in the CNS. PMID:7272599

  18. Structure and Function of Nucleoside Hydrolases from Physcomitrella patens and Maize Catalyzing the Hydrolysis of Purine, Pyrimidine, and Cytokinin Ribosides1[W

    PubMed Central

    Kopečná, Martina; Blaschke, Hanna; Kopečný, David; Vigouroux, Armelle; Končitíková, Radka; Novák, Ondřej; Kotland, Ondřej; Strnad, Miroslav; Moréra, Solange; von Schwartzenberg, Klaus

    2013-01-01

    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. PMID:24170203

  19. Identification of genes containing expanded purine repeats in the human genome and their apparent protective role against cancer.

    PubMed

    Singh, Himanshu Narayan; Rajeswari, Moganty R

    2016-01-01

    Purine repeat sequences present in a gene are unique as they have high propensity to form unusual DNA-triple helix structures. Friedreich's ataxia is the only human disease that is well known to be associated with DNA-triplexes formed by purine repeats. The purpose of this study was to recognize the expanded purine repeats (EPRs) in human genome and find their correlation with cancer pathogenesis. We developed "PuRepeatFinder.pl" algorithm to identify non-overlapping EPRs without pyrimidine interruptions in the human genome and customized for searching repeat lengths, n ≥ 200. A total of 1158 EPRs were identified in the genome which followed Wakeby distribution. Two hundred and ninety-six EPRs were found in geneic regions of 282 genes (EPR-genes). Gene clustering of EPR-genes was done based on their cellular function and a large number of EPR-genes were found to be enzymes/enzyme modulators. Meta-analysis of 282 EPR-genes identified only 63 EPR-genes in association with cancer, mostly in breast, lung, and blood cancers. Protein-protein interaction network analysis of all 282 EPR-genes identified proteins including those in cadherins and VEGF. The two observations, that EPRs can induce mutations under malignant conditions and that identification of some EPR-gene products in vital cell signaling-mediated pathways, together suggest the crucial role of EPRs in carcinogenesis. The new link between EPR-genes and their functionally interacting proteins throws a new dimension in the present understanding of cancer pathogenesis and can help in planning therapeutic strategies. Validation of present results using techniques like NGS is required to establish the role of the EPR genes in cancer pathology.

  20. Homochiral Selectivity in RNA Synthesis: Montmorillonite-catalyzed Quaternary Reactions of D, L-Purine with D, L- Pyrimidine Nucleotides

    NASA Astrophysics Data System (ADS)

    Joshi, Prakash C.; Aldersley, Michael F.; Ferris, James P.

    2011-06-01

    Selective adsorption of D, L-ImpA with D, L-ImpU on the platelets of montmorillonite demonstrates an important reaction pathway for the origin of homochirality in RNA synthesis. Our earlier studies have shown that the individual reactions of D, L-ImpA or D, L-ImpU on montmorillonite catalyst produced oligomers which were only partially inhibited by the incorporation of both D- and L-enantiomers. Homochirality in these reactions was largely due to the formation of cyclic dimers that cannot elongate. We investigated the quaternary reactions of D, L-ImpA with D, L-ImpU on montmorillonite. The chain length of these oligomers increased from 9-mer to 11-mer as observed by HPLC, with a concominant increase in the yield of linear dimers and higher oligomers in the reactions involving D, L-ImpA with D, L-ImpU as compared to the similar reactions carried out with D-enantiomers only. The formation of cyclic dimers of U was completely inhibited in the quaternary reactions. The yield of cyclic dimers of A was reduced from 60% to 10% within the dimer fraction. 12 linear dimers and 3 cyclic dimers were isolated and characterized from the quaternary reaction. The homochirality and regioselectivity of dimers were 64.1% and 71.7%, respectively. Their sequence selectivity was shown by the formation of purine-pyrimidine (54-59%) linkages, followed by purine-purine (29-32%) linkages and pyrimidine-pyrimidine (9-13%) linkages. Of the 16 trimers detected, 10 were homochiral with an overall homochirality of 73-76%. In view of the greater homochirality, sequence- and regio- selectivity, the quaternary reactions on montmorillonite demonstrate an unexpectedly favorable route for the prebiotic synthesis of homochiral RNA compared with the separate reactions of enantiomeric activated mononucleotides.

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2008-01-24

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

  3. [Separation of purines, pyrimidines, pterins and flavonoids on magnolol-bonded silica gel stationary phase by high performance liquid chromatography].

    PubMed

    Chen, Hong; Li, Laishen; Zhang, Yang; Zhou, Rendan

    2012-10-01

    A new magnolol-bonded silica gel stationary phase (MSP) was used to separate the basic drugs including four purines, eight pyrimidines, four pterins and five flavonoids as polar representative samples by high performance liquid chromatography (HPLC). To clarify the separation mechanism, a commercial ODS column was also tested under the same chromatographic conditions. The high selectivities and fast baseline separations of the above drugs were achieved by using simple mobile phases on MSP. Although there is no end-caped treatment, the peak shapes of basic drugs containing nitrogen such as purines, pyrimidines and pterins were rather symmetrical on MSP, which indicated the the magnolol as ligand with multi-sites could shield the side effect of residual silanol groups on the surface of silica gel. Although somewhat different in the separation resolution, it was found that the elution orders of some drugs were generally similar on both MSP and ODS. The hydrophobic interaction should play a significant role in the separations of the above basic drugs, which was attributed to their reversed-phase property in the nature. However, MSP could provide the additional sites for many polar solutes, which was a rational explanation for the high selectivity of MSP. For example, in the separation of purines, pyrimidines and pterins on MSP, hydrogen-bonding and dipole-dipole interactions played leading roles besides hydrophobic interaction. Some solute molecules (such as mercaptopurine, vitexicarpin) and MSP can form the strong pi-pi stacking in the separation process. All enhanced the retention and improved the separation selectivity of MSP, which facilitated the separation of the basic drugs.

  4. Hetero-ring-expansion design for purine analogs: A theoretical study on the structural, electronic, and excited-state properties

    NASA Astrophysics Data System (ADS)

    Zhang, Laibin; Zhou, Liuzhu; Tian, Jianxiang; Li, Xiaoming

    2014-03-01

    A series of hetero-ring-expanded purine analogs are designed and their structural, electronic and excited-state properties are investigated by DFT calculations. The results indicate that the designed analogs can form stable base pairs with natural counterparts. Compared with natural ones, these size-expanded analogs and corresponding base pairs have smaller ionization potentials and HOMO-LUMO gaps. Furthermore, the A-analogs have ionization potentials even lower than natural G. Finally, the electronic absorption spectra are calculated and the nature of the low-lying excited states is discussed. These observations imply their promising applications as molecular wires and new DNA motifs.

  5. Methanocarba ring as a ribose modification in ligands of G protein-coupled purine and pyrimidine receptors: synthetic approaches

    PubMed Central

    Tosh, Dilip K.

    2015-01-01

    Adenosine receptors (ARs) and P2Y receptors for purine and pyrimidine nucleotides have widespread distribution and regulate countless physiological processes. Various synthetic ligands are in clinical trials for treatment of inflammatory diseases, pain, cancer, thrombosis, ischemia, and other conditions. The methanocarba (bicyclo[3.1.0]hexane) ring system as a rigid substitution for ribose, which maintains either a North (N) or South (S) conformation, tends to preserve or enhance the potency and/or selectivity for certain receptor subtypes. This review summarizes recent developments in the synthetic approaches to these biologically important nucleoside and nucleotide analogues. PMID:26161251

  6. Tobacco imagery on prime time UK television

    PubMed Central

    Lyons, Ailsa; McNeill, Ann; Britton, John

    2014-01-01

    Background Smoking in films is a common and well documented cause of youth smoking experimentation and uptake and hence a significant health hazard. The extent of exposure of young people to tobacco imagery in television programming has to date been far less investigated. We have therefore measured the extent to which tobacco content occurs in prime time UK television, and estimated exposure of UK youth. Methods The occurrence of tobacco, categorised as actual tobacco use, implied tobacco use, tobacco paraphernalia, other reference to tobacco, tobacco brand appearances or any of these, occurring in all prime time broadcasting on the five most popularly viewed UK television stations during 3 separate weeks in 2010 were measured by 1-minute interval coding. Youth exposure to tobacco content in the UK was estimated using media viewing figures. Findings Actual tobacco use, predominantly cigarette smoking, occurred in 73 of 613 (12%) programmes, particularly in feature films and reality TV. Brand appearances were rare, occurring in only 18 programmes, of which 12 were news or other factual genres, and 6 were episodes of the same British soap opera. Tobacco occurred with similar frequency before as after 21:00, the UK watershed for programmes suitable for youth. The estimated number of incidences of exposure of the audience aged less than 18 years for any tobacco, actual tobacco use and tobacco branding were 59 million, 16 million and 3 million, respectively on average per week. Conclusions Television programming is a source of significant exposure of youth to tobacco imagery, before and after the watershed. Tobacco branding is particularly common in Coronation Street, a soap opera popular among youth audiences. More stringent controls on tobacco in prime time television therefore have the potential to reduce the uptake of youth smoking in the UK. PMID:23479113

  7. Health Technology Assessment in the UK.

    PubMed

    Raftery, James; Powell, John

    2013-10-12

    In this Review, we discuss the UK's Health Technology Assessment programme, which is 20 years old in 2013. We situate the programme in the context of the UK landscape for evidence-based medicine, including in relation to the National Institute for Health and Care Excellence and as guidance to the National Health Service. We identify features that might be of value to other health systems as they confront the challenges of rapid innovation and rising costs. We use examples of recent studies to show the strengths and weaknesses of the programme.

  8. Bullying and the UK Armed Forces.

    PubMed

    Coetzee, R H; Atkins, S; Gould, M

    2012-06-01

    There are certain characteristics of the culture and environment in the Armed Forces that may be conducive to bullying. In this article we examine the cultural and environmental factors that may encourage such behaviour and those that act as deterrents for victims to come forward. We will look at the scope of this problem within the UK Armed Forces specifically, before more generally considering the psychological impact of bullying. There appears to be an overall downward trend in bullying within the UK Armed Forces and a positive increase in complaints as more victims step forward. We conclude by highlighting some areas for further development.

  9. Nitrogen K-edge X-ray absorption near edge structure (XANES) spectra of purine-containing nucleotides in aqueous solution.

    PubMed

    Shimada, Hiroyuki; Fukao, Taishi; Minami, Hirotake; Ukai, Masatoshi; Fujii, Kentaro; Yokoya, Akinari; Fukuda, Yoshihiro; Saitoh, Yuji

    2014-08-07

    The N K-edge X-ray absorption near edge structure (XANES) spectra of the purine-containing nucleotide, guanosine 5'-monophosphate (GMP), in aqueous solution are measured under various pH conditions. The spectra show characteristic peaks, which originate from resonant excitations of N 1s electrons to π* orbitals inside the guanine moiety of GMP. The relative intensities of these peaks depend on the pH values of the solution. The pH dependence is explained by the core-level shift of N atoms at specific sites caused by protonation and deprotonation. The experimental spectra are compared with theoretical spectra calculated by using density functional theory for GMP and the other purine-containing nucleotides, adenosine 5'-monophosphate, and adenosine 5'-triphosphate. The N K-edge XANES spectra for all of these nucleotides are classified by the numbers of N atoms with particular chemical bonding characteristics in the purine moiety.

  10. Complex coordinated extracellular metabolism: Acid phosphatases activate diluted human leukocyte proteins to generate energy flow as NADPH from purine nucleotide ribose

    PubMed Central

    Hibbs, John B.; Vavrin, Zdenek; Cox, James E.

    2016-01-01

    Complex metabolism is thought to occur exclusively in the crowded intracellular environment. Here we report that diluted enzymes from lysed human leukocytes produce extracellular energy. Our findings involve two pathways: the purine nucleotide catabolic pathway and the pentose phosphate pathway, which function together to generate energy as NADPH. Glucose6P fuel for NADPH production is generated from structural ribose of purine ribonucleoside monophosphates, ADP, and ADP-ribose. NADPH drives glutathione reductase to reduce an oxidized glutathione disulfide-glutathione redox couple. Acid phosphatases initiate ribose5P salvage from purine ribonucleoside monophosphates, and transaldolase controls the direction of carbon chain flow through the nonoxidative branch of the pentose phosphate pathway. These metabolic control points are regulated by pH. Biologically, this energy conserving metabolism could function in perturbed extracellular spaces. PMID:26895212

  11. Effect of milk feed source, frequency of feeding and age at turnout on calf performance, live-weight at mating and 1st lactation milk production

    PubMed Central

    2012-01-01

    Female calves (n = 108) were assigned to 6 cold milk feeding treatments in two experiments for a 70-day period. Live-weight (LW) was measured weekly, with an additional LW taken at day 410 and post-calving for animals in experiment 1. In Experiment 1, the effect of feeding frequency and age of turnout to pasture on calf performance and 1st lactation milk yields were evaluated. The whole milk (WM) feeding treatments applied were (i) once daily feeding (OD), (ii) twice daily feeding (TD), (iii) OD feeding, outdoors at 38 days (ODO). In Experiment 2, the effects of feeding milk replacer (MR) as opposed to WM and age of turnout to pasture on calf performance were evaluated. The treatments applied were (i) OD feeding with WM (OD), (ii) OD feeding with milk replacer (MR) (ODMR), (iii) OD feeding with MR, outdoors at 38 days (ODMRO). Experiment 1: There were no differences (P > 0.05) in LW or average daily gain between TD and OD calves at day 80 or 410. ODO calves had lower LW at day 80 as compared to OD or TD (P < 0.001). Calf LW at day 80 was 86, 89 and 85 kg and at day 410 was 304, 309 and 316 kg for OD, TD and ODO, respectively. Milk feeding frequency or time of calf turnout had no effect on LW post calving, milk composition or 1st lactation milk yields. Experiment 2: Total LW at day 80 was higher (P < 0.05) for ODMR compared to OD or ODMRO calves. Calf LW was 87, 95, and 88 kg for OD, ODMR and ODMRO, respectively. However, LW at day 410 did not differ between treatments. This study showed that while some differences were observed in calf LW at day 80, these differences had no effect on LW at day 410 or 1st lactation milk yield. It can be concluded that calves can be successfully reared when fed OD with WM or MR, indoors and when turned out to pasture at 38 days of age. PMID:23078871

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

    PubMed

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

    2015-01-01

    This study investigated the response of urinary purine derivatives (PD) excretion to increasing levels of intraruminal glucose infusion to evaluate how well this indicator reflects induced changes in microbial crude protein flow. Four rumen-cannulated heifers (482 ± 25 kg body weight) were fed at maintenance energy level with a basal diet (on fresh matter basis) of 4 kg/d hay, 1.5 kg/d concentrate and 60 g/d minerals in two equal meals. The trial comprised a control period (Control I) without glucose infusion followed by four consecutive periods in which all animals received 125 g, 250 g, 500 g or 1000 g/d of glucose, respectively. For this, daily dosages of glucose and urea (90 g/d during all periods) were divided into three portions that were dissolved in water and directly administered into the rumen during morning and afternoon feedings and once during noon. After the highest glucose dosage, a second control period was carried out (Control II). Urinary PD excretion increased with glucose infusion of 125 g/d (71.4 mmol/d) and 1000 g/d (74.2 mmol/d) over the level at Control I (53.9 mmol/d (standard error of the mean (SEM) 3.4; p = 0.012). After withdrawing glucose infusion, PD excretion (79.0 mmol/d) did not return to Control I level (p = 0.001). In contrast, faecal nitrogen (N) excretions linearly increased with incremental glucose infusion (p < 0.001) from 33.9 g/d at Control I to 39.7 g/d (SEM 0.5) at 1000 g/d of glucose and were similar in Control I and II (p = 0.086). The contradicting responses in the excretions of faecal N and urinary PD to increasing glucose infusions highlight the limited accuracy of the PD excretion as a non-invasive indicator when incremental dosages of rapidly fermentable carbohydrates are supplied.

  13. Novel, Highly Specific N-Demethylases Enable Bacteria To Live on Caffeine and Related Purine Alkaloids

    PubMed Central

    Summers, Ryan M.; Louie, Tai Man; Yu, Chi-Li; Gakhar, Lokesh; Louie, Kailin C.

    2012-01-01

    The molecular basis for the ability of bacteria to live on caffeine as a sole carbon and nitrogen source is unknown. Pseudomonas putida CBB5, which grows on several purine alkaloids, metabolizes caffeine and related methylxanthines via sequential N-demethylation to xanthine. Metabolism of caffeine by CBB5 was previously attributed to one broad-specificity methylxanthine N-demethylase composed of two subunits, NdmA and NdmB. Here, we report that NdmA and NdmB are actually two independent Rieske nonheme iron monooxygenases with N1- and N3-specific N-demethylation activity, respectively. Activity for both enzymes is dependent on electron transfer from NADH via a redox-center-dense Rieske reductase, NdmD. NdmD itself is a novel protein with one Rieske [2Fe-2S] cluster, one plant-type [2Fe-2S] cluster, and one flavin mononucleotide (FMN) per enzyme. All ndm genes are located in a 13.2-kb genomic DNA fragment which also contained a formaldehyde dehydrogenase. ndmA, ndmB, and ndmD were cloned as His6 fusion genes, expressed in Escherichia coli, and purified using a Ni-NTA column. NdmA-His6 plus His6-NdmD catalyzed N1-demethylation of caffeine, theophylline, paraxanthine, and 1-methylxanthine to theobromine, 3-methylxanthine, 7-methylxanthine, and xanthine, respectively. NdmB-His6 plus His6-NdmD catalyzed N3-demethylation of theobromine, 3-methylxanthine, caffeine, and theophylline to 7-methylxanthine, xanthine, paraxanthine, and 1-methylxanthine, respectively. One formaldehyde was produced from each methyl group removed. Activity of an N7-specific N-demethylase, NdmC, has been confirmed biochemically. This is the first report of bacterial N-demethylase genes that enable bacteria to live on caffeine. These genes represent a new class of Rieske oxygenases and have the potential to produce biofuels, animal feed, and pharmaceuticals from coffee and tea waste. PMID:22328667

  14. Simultaneous determination of purine metabolites, creatinine and pseudouridine in ruminant urine by reversed-phase high-performance liquid chromatography.

    PubMed

    Shingfield, K J; Offer, N W

    1999-02-19

    Determination of purine metabolites, pseudouridine and creatinine in both bovine and ovine urine using high-performance liquid chromatography (HPLC) is described. Following dilution and filtration, urine samples were analysed directly. Separation and quantification was achieved using a Spherisorb ODS II C18 column (250x4.6 mm I.D.) under isocratic conditions. The mobile phase contained 7.5 mM ammonium dihydrogen phosphate, 10 mM sodium 1-heptane sulphonic acid and 1.0 mM triethylamine at pH 3.0. Chromatography was achieved at a flow-rate of 1.0 ml/min and monitoring column effluent at 218 nm. Total analysis time was 60 min. Recovery of all compound standards added to urine was above 96%. In all cases, close spectral matches of compound standards and corresponding identified peaks in ovine and bovine urine were obtained. Lowest detectable concentrations of allantoin, uric acid, xanthine, hypoxanthine, creatinine and pseudouridine were 1.1, 1.0, 1.0, 3.0 and 0.4 micromol/l, respectively. Advantages of simultaneous determination of purine metabolites, creatinine and pseudouridine in ruminant urine collected from both sheep and cattle exist over current methods.

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

    PubMed Central

    Kelemen, Linda E.; Terry, Kathryn L.; Goodman, Marc T.; Webb, Penelope M.; Bandera, Elisa V.; McGuire, Valerie; Rossing, Mary Anne; Wang, Qinggang; Dicks, Ed; Tyrer, Jonathan P.; Song, Honglin; Kupryjanczyk, Jolanta; Dansonka-Mieszkowska, Agnieszka; Plisiecka-Halasa, Joanna; Timorek, Agnieszka; Menon, Usha; Gentry-Maharaj, Aleksandra; Gayther, Simon A.; Ramus, Susan J.; Narod, Steven A.; Risch, Harvey A.; McLaughlin, John R.; Siddiqui, Nadeem; Glasspool, Rosalind; Paul, James; Carty, Karen; Gronwald, Jacek; Lubiński, Jan; Jakubowska, Anna; Cybulski, Cezary; Kiemeney, Lambertus A.; Massuger, Leon F. A. G.; van Altena, Anne M.; Aben, Katja K. H.; Olson, Sara H.; Orlow, Irene; Cramer, Daniel W.; Levine, Douglas A.; Bisogna, Maria; Giles, Graham G.; Southey, Melissa C.; Bruinsma, Fiona; Kjær, Susanne Krüger; Høgdall, Estrid; Jensen, Allan; Høgdall, Claus K.; Lundvall, Lene; Engelholm, Svend-Aage; Heitz, Florian; du Bois, Andreas; Harter, Philipp; Schwaab, Ira; Butzow, Ralf; Nevanlinna, Heli; Pelttari, Liisa M.; Leminen, Arto; Thompson, Pamela J.; Lurie, Galina; Wilkens, Lynne R.; Lambrechts, Diether; Van Nieuwenhuysen, Els; Lambrechts, Sandrina; Vergote, Ignace; Beesley, Jonathan; Fasching, Peter A.; Beckmann, Matthias W.; Hein, Alexander; Ekici, Arif B.; Doherty, Jennifer A.; Wu, Anna H.; Pearce, Celeste L.; Pike, Malcolm C.; Stram, Daniel; Chang-Claude, Jenny; Rudolph, Anja; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B.; Bogdanova, Natalia; Antonenkova, Natalia; Odunsi, Kunle; Edwards, Robert P.; Kelley, Joseph L.; Modugno, Francesmary; Ness, Roberta B.; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; Orsulic, Sandra; Fridley, Brooke L.; Vierkant, Robert A.; Cunningham, Julie M.; Wu, Xifeng; Lu, Karen; Liang, Dong; Hildebrandt, Michelle A.T.; Weber, Rachel Palmieri; Iversen, Edwin S.; Tworoger, Shelley S.; Poole, Elizabeth M.; Salvesen, Helga B.; Krakstad, Camilla; Bjorge, Line; Tangen, Ingvild L.; Pejovic, Tanja; Bean, Yukie; Kellar, Melissa; Wentzensen, Nicolas; Brinton, Louise A.; Lissowska, Jolanta; Garcia-Closas, Montserrat; Campbell, Ian G.; Eccles, Diana; Whittemore, Alice S.; Sieh, Weiva; Rothstein, Joseph H.; Anton-Culver, Hoda; Ziogas, Argyrios; Phelan, Catherine M.; Moysich, Kirsten B.; Goode, Ellen L.; Schildkraut, Joellen M.; Berchuck, Andrew; Pharoah, Paul D.P.; Sellers, Thomas A.; Brooks-Wilson, Angela; Cook, Linda S.; Le, Nhu D.

    2014-01-01

    Scope We re-evaluated previously reported associations between variants in pathways of one-carbon (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake. Methods and Results Odds ratios (OR) for 446 genetic variants were estimated among 13,410 OC cases and 22,635 controls and among 2,281 cases and 3,444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for DPYD variants rs11587873 (OR=0.92, P=6x10−5) and rs828054 (OR=1.06, P=1x10−4). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT and TYMS, also interacted significantly with folate in a multi-variant analysis (corrected P=9.9x10−6) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in SHMT1 in one-carbon transfer, previously reported with OC, suggested lower risk at higher folate (Pinteraction=0.03-0.006). Conclusions Variation in pyrimidine metabolism genes, particularly DPYD, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. SHMT1 SNP-byfolate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC. PMID:25066213

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

    PubMed

    Ishikawa, Toshihisa; Aw, Wanping; Kaneko, Kiyoko

    2013-11-04

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

  17. Structure of nucleoside diphosphate kinase from pacific shrimp (Litopenaeus vannamei) in binary complexes with purine and pyrimidine nucleoside diphosphates.

    PubMed

    López-Zavala, Alonso A; Quintero-Reyes, Idania E; Carrasco-Miranda, Jesús S; Stojanoff, Vivian; Weichsel, Andrzej; Rudiño-Piñera, Enrique; Sotelo-Mundo, Rogerio R

    2014-09-01

    Nucleoside diphosphate kinase (NDK; EC 2.7.4.6) is an enzyme that catalyzes the third phosphorylation of nucleoside diphosphates, leading to nucleoside triphosphates for DNA replication. Expression of the NDK from Litopenaeus vannamei (LvNDK) is known to be regulated under viral infection. Also, as determined by isothermal titration calorimetry, LvNDK binds both purine and pyrimidine deoxynucleoside diphosphates with high binding affinity for dGDP and dADP and with no heat of binding interaction for dCDP [Quintero-Reyes et al. (2012), J. Bioenerg. Biomembr. 44, 325-331]. In order to investigate the differences in selectivity, LvNDK was crystallized as binary complexes with both acceptor (dADP and dCDP) and donor (ADP) phosphate-group nucleoside diphosphate substrates and their structures were determined. The three structures with purine or pyrimidine nucleotide ligands are all hexameric. Also, the binding of deoxy or ribonucleotides is similar, as in the former a water molecule replaces the hydrogen bond made by Lys11 to the 2'-hydroxyl group of the ribose moiety. This allows Lys11 to maintain a catalytically favourable conformation independently of the kind of sugar found in the nucleotide. Because of this, shrimp NDK may phosphorylate nucleotide analogues to inhibit the viral infections that attack this organism.

  18. The pharmacological role of phosphatases (acid and alkaline phosphomonoesterases) in snake venoms related to release of purines - a multitoxin.

    PubMed

    Dhananjaya, Bhadrapura L; D'Souza, Cletus J M

    2011-02-01

    Snake venom components, acting in concert in the prey, cause their immobilization and initiate digestion. To achieve this, several hydrolytic enzymes of snake venom have evolved to interfere in various physiological processes, which are well defined. However, hydrolytic enzymes such as phosphatases (acid and alkaline phosphomonoesterases) are less studied and their pharmacological role in venoms is not clearly defined. Also, they show overlapping substrate specificities and have other common biochemical properties causing uncertainty about their identity in venoms. The near-ubiquitous distribution of these enzymes in venoms, suggests a significant role for these enzymes in envenomation. It appears that these enzymes may play a central role in liberating purines (mainly adenosine) - a multitoxin and through the action of purines help in prey immobilization. However, apart from this, these enzymes could also possess other pharmacological activities as venom enzymes have been evolved to interfere in diverse physiological processes. This has not been verified by pharmacological studies using purified enzymes. Further research is needed to biologically characterize these enzymes in snake venoms, such that their role in venom is clearly established.

  19. Structure of nucleoside diphosphate kinase from pacific shrimp (Litopenaeus vannamei) in binary complexes with purine and pyrimidine nucleoside diphosphates

    PubMed Central

    López-Zavala, Alonso A.; Quintero-Reyes, Idania E.; Carrasco-Miranda, Jesús S.; Stojanoff, Vivian; Weichsel, Andrzej; Rudiño-Piñera, Enrique; Sotelo-Mundo, Rogerio R.

    2014-01-01

    Nucleoside diphosphate kinase (NDK; EC 2.7.4.6) is an enzyme that catalyzes the third phosphorylation of nucleoside diphosphates, leading to nucleoside triphosphates for DNA replication. Expression of the NDK from Litopenaeus vannamei (LvNDK) is known to be regulated under viral infection. Also, as determined by isothermal titration calorimetry, LvNDK binds both purine and pyrimidine deoxynucleoside diphosphates with high binding affinity for dGDP and dADP and with no heat of binding interaction for dCDP [Quintero-Reyes et al. (2012 ▶), J. Bioenerg. Biomembr. 44, 325–331]. In order to investigate the differences in selectivity, LvNDK was crystallized as binary complexes with both acceptor (dADP and dCDP) and donor (ADP) phosphate-group nucleoside diphosphate substrates and their structures were determined. The three structures with purine or pyrimidine nucleotide ligands are all hexameric. Also, the binding of deoxy or ribonucleotides is similar, as in the former a water molecule replaces the hydrogen bond made by Lys11 to the 2′-hydroxyl group of the ribose moiety. This allows Lys11 to maintain a catalytically favourable conformation independently of the kind of sugar found in the nucleotide. Because of this, shrimp NDK may phosphorylate nucleotide analogues to inhibit the viral infections that attack this organism. PMID:25195883

  20. Spatial epidemiology in zoonotic parasitic diseases: insights gained at the 1st International Symposium on Geospatial Health in Lijiang, China, 2007

    PubMed Central

    Zhou, Xiao-Nong; Lv, Shan; Yang, Guo-Jing; Kristensen, Thomas K; Bergquist, N Robert; Utzinger, Jürg; Malone, John B

    2009-01-01

    The 1st International Symposium on Geospatial Health was convened in Lijiang, Yunnan province, People's Republic of China from 8 to 9 September, 2007. The objective was to review progress made with the application of spatial techniques on zoonotic parasitic diseases, particularly in Southeast Asia. The symposium featured 71 presentations covering soil-transmitted and water-borne helminth infections, as well as arthropod-borne diseases such as leishmaniasis, malaria and lymphatic filariasis. The work made public at this occasion is briefly summarized here to highlight the advances made and to put forth research priorities in this area. Approaches such as geographical information systems (GIS), global positioning systems (GPS) and remote sensing (RS), including spatial statistics, web-based GIS and map visualization of field investigations, figured prominently in the presentation. PMID:19193214

  1. JANNAF 25th Airbreathing Propulsion Subcommittee, 37th Combustion Subcommittee and 1st Modeling and Simulation Subcommittee Joint Meeting. Volume 1

    NASA Technical Reports Server (NTRS)

    Fry, Ronald S.; Becker, Dorothy L.

    2000-01-01

    Volume I, the first of three volumes, is a compilation of 24 unclassified/unlimited-distribution technical papers presented at the Joint Army-Navy-NASA-Air Force (JANNAF) 25th Airbreathing Propulsion Subcommittee, 37th Combustion Subcommittee and 1st Modeling and Simulation Subcommittee (MSS) meeting held jointly with the 19th Propulsion Systems Hazards Subcommittee. The meeting was held 13-17 November 2000 at the Naval Postgraduate School and Hyatt Regency Hotel, Monterey, California. Topics covered include: a Keynote Address on Future Combat Systems, a review of the new JANNAF Modeling and Simulation Subcommittee, and technical papers on Hyper-X propulsion development and verification; GTX airbreathing launch vehicles; Hypersonic technology development, including program overviews, fuels for advanced propulsion, ramjet and scramjet research, hypersonic test medium effects; and RBCC engine design and performance, and PDE and UCAV advanced and combined cycle engine technologies.

  2. 1(st) EMBL/DFG Women in Science Network Conference Heidelberg 2016: From Genes, Cells and the Immune System towards Therapies - Meeting Report.

    PubMed

    Stripecke, Renata; Gouttefangeas, Cécile; Förster, Irmgard

    2016-11-01

    The 1(st) EMBL/DFG Women in Science (WiS) Conference "From Genes, Cells and the Immune System towards Therapies" was held on 19(th) - 20(th) September 2016 in Heidelberg, Germany. The WiS conference was funded by nine Collaborative Research Centers (CRCs) of the German Research Council (Deutsche Forschungsgemeinschaft, DFG; Table 1) and benefited from an outstanding hosting environment at the Advanced Training Center of the European Molecular Biology Laboratory (EMBL). Scientific talks focused at genetic, cellular and immunologic mechanisms, and immune therapy, and progress from all stages of development covering basic research to clinical developments was described. The presentations were embedded between structured networking sessions and a round table discussion with representatives of the DFG, EMBL, European Molecular Biology Organisation (EMBO), and the German Society of Immunology (DGfI).

  3. [State of the reproductive systemin in male rats of 1st generation obtained from irradiated parents and exposed to electromagnetic radiation (897 MHz) during embryogenesis and postnatal development].

    PubMed

    Vereshchako, G G; Chueshova, N V; Gorokh, G A; Naumov, A D

    2014-01-01

    The consequences of prolonged exposure to electromagnetic radiation from cellular phone (897 MHz, daily 8 h/day) in male rats of the 1st generation obtained from irradiated parents and subjected to prolonged exposure to electromagnetic radiation of the range of mobile communications during ontogeny and postnatal development were studied. It has been found that irradiation causes a decrease in the number of births of animals, changing the sex ratio towards the increase in the number of males. It had a significant impact on the reproductive system of males, accelerating their sexual development, revealed at the age of two months. Radiation from cell phones led to significant disproportions in the cell number at different stages of spermatogenesis. It increased the number of mature spermatozoa which decreased viability.

  4. 1st International Symposium on Gait and Balance in MS: Gait and Balance Measures in the Evaluation of People with MS

    PubMed Central

    Cameron, Michelle; Wagner, Joanne; Zackowski, Kathleen; Spain, Rebecca

    2012-01-01

    Gait and balance measures have particular potential as outcome measures in Multiple Sclerosis (MS) because, of the many hallmarks of MS disability, gait and balance dysfunction are present throughout the course of the disease, impact many aspects of a person's life, and progress over time. To highlight the importance and relevance of gait and balance measures in MS, explore novel measurements of gait and balance in MS, and discuss how gait, balance, and fall measures can best be used and developed in clinical and research settings, the 1st International Symposium on Gait and Balance in Multiple Sclerosis was held in Portland, Oregon, USA on October 1, 2011. This meeting brought together nearly 100 neurologists, physiatrists, physical therapists, occupational therapists, nurses, engineers, and others to discuss the current status and recent advances in the measurement of gait and balance in MS. Presentations focused on clinician-administered, self-administered, and instrumented measures of gait, balance, and falls in MS. PMID:22762000

  5. Progressing Professional Careers in UK Higher Education

    ERIC Educational Resources Information Center

    Whitchurch, Celia

    2009-01-01

    This paper arises out of a study conducted for the Leadership Foundation for Higher Education on "Professional Managers in UK Higher Education: Preparing for Complex Futures," and focuses on those aspects relating to professional and career development. The author reviewed understandings in the literature about the roles and identities…

  6. Single heterostructure lasers: a UK perspective

    NASA Astrophysics Data System (ADS)

    Selway, Peter

    2012-09-01

    The gallium-aluminium-arsenide single heterostructure laser was the first commercially successful semiconductor laser produced in the UK. This paper presents a personal perspective on the events leading up to volume production and highlights the fascinating physics involved in this device and the impact of this on the task of engineering a robust component which was eventually manufactured for over 20 years.

  7. Globalisation and MATESOL Programmes in the UK

    ERIC Educational Resources Information Center

    Hasrati, Mostafa; Tavakoli, Parvaneh

    2015-01-01

    This article reports the results of a mixed-methods approach to investigating the association between globalisation and MATESOL in UK universities. Qualitative and quantitative data collected from academic staff through eight emails, four interviews and 41 questionnaires indicate that the globalised context of higher education has affected these…

  8. Accelerated technology transfer: the UK quantum initiative

    NASA Astrophysics Data System (ADS)

    Bennett, Simon D.

    2016-10-01

    A new generation of quantum technology based systems, exploiting effects such as superposition and entanglement, will enable widespread, highly disruptive applications which are expected to be of great economic significance. However, the technology is only just emerging from the physics laboratory and generally remains at low TRLs. The question is: where, and when, will this impact be first manifest? The UK, with substantial Government backing, has embarked on an ambitious national program to accelerate the process of technology transfer with the objective of seizing a significant and sustainable share of the future economic benefit for the UK. Many challenges and uncertainties remain but the combined and co-ordinated efforts of Government, Industry and Academia are making great progress. The level of collaboration is unusually high and the goal of embedding a "QT Ecosystem" in the UK looks to be attainable. This paper describes the UK national programme, its key players, and their respective roles. It will illustrate some of the likely first commercial applications and provide a status update. Some of the challenges that might prevent realisation of the goal will be highlighted.

  9. Cohort profile: UK Millennium Cohort Study (MCS).

    PubMed

    Connelly, Roxanne; Platt, Lucinda

    2014-12-01

    The UK Millennium Cohort Study (MCS) is an observational, multidisciplinary cohort study that was set up to follow the lives of children born at the turn of the new century. The MCS is nationally representative and 18 552 families (18 827 children) were recruited to the cohort in the first sweep. There have currently been five main sweeps of data collection, at ages 9 months and 3, 5, 7 and 11 years. A further sweep of data collection is planned for age 14 years. A range of health-related data have been collected as well as measures concerning child development, cognitive ability and educational attainment. The data also include a wealth of information describing the social, economic and demographic characteristics of the cohort members and their families. In addition, the MCS data have been linked to administrative data resources including health records. The MCS provides a unique and valuable resource for the analysis of health outcomes and health inequalities. The MCS data are freely available to bona fide researchers under standard access conditions via the UK Data Service (http://ukdataservice.ac.uk) and the MCS website provides detailed information on the study (http://www.cls.ioe.ac.uk/mcs).

  10. Challenges for Academic Accreditation: The UK Experience

    ERIC Educational Resources Information Center

    Shearman, Richard; Seddon, Deborah

    2010-01-01

    Several factors (government policy, demographic trends, employer pressure) are leading to new forms of degree programmes in UK universities. The government is strongly encouraging engagement between universities and employers. Work-based learning is increasingly found in first and second cycle programmes, along with modules designed by employers…

  11. Subject Choice and Earnings of UK Graduates

    ERIC Educational Resources Information Center

    Chevalier, Arnaud

    2011-01-01

    Using a survey of a cohort of UK graduates, linked to administrative data on higher education participation, this paper investigates the labour market attainment of recent graduates by subject of study. We document a large heterogeneity in the mean wages of graduates from different subjects and a considerably larger one within subject with…

  12. After Brexit: nursing a divided UK.

    PubMed

    Trueland, Jennifer

    2016-09-14

    Back in September 2014, the people of Scotland voted by 55% to 45% to stay part of the UK. Billed as a once in a generation event, the referendum appeared to put paid to the idea of an independent Scotland for the foreseeable future.

  13. Disability in the UK: Measuring Equality

    ERIC Educational Resources Information Center

    Purdam, Kingsley; Afkhami, Reza; Olsen, Wendy; Thornton, Patricia

    2008-01-01

    In this article we identify the key survey data for examining the issue of equality in the lives of disabled people in the UK. Such data is essential for assessing change in quality of life over time and for the evaluation of the impact of policy initiatives. For each data source we consider definitions, data collection, issue coverage, sample…

  14. Sunday Opening in UK Public Libraries

    ERIC Educational Resources Information Center

    Moore, Chris; Creaser, Claire

    2010-01-01

    This paper presents a summary of the first survey of public library authorities in the UK to explore Sunday opening, undertaken in 2007 as part of the Clore Leadership Programme. It provides a snapshot of Sunday opening practice, set against a context of societal, economic, and policy developments, and examines whether Sunday opening furthers the…

  15. Resources for Teaching Astronomy in UK Schools

    ERIC Educational Resources Information Center

    Roche, Paul; Newsam, Andy; Roberts, Sarah; Mason, Tom; Baruch, John

    2012-01-01

    This article looks at a selection of resources currently available for use in the teaching of astronomy in UK schools. It is by no means an exhaustive list but it highlights a variety of free resources that can be used in the classroom to help engage students of all ages with astronomy and space science. It also lists several facilities with a…

  16. Quality assurance in UK higher education

    NASA Astrophysics Data System (ADS)

    Shrimplin, Valerie

    Quality Assurance methods are becoming increasingly well known as systems applicable in business, commerce and industry. In modified form, such concepts can be applied to higher education and, in the UK, quality systems are utilized in universities in order to ensure the quality of provision and standards of awards. Similar principles may also be applied to the evaluation of quality in research.

  17. Ammonia emission factors for UK agriculture

    NASA Astrophysics Data System (ADS)

    Misselbrook, T. H.; Van Der Weerden, T. J.; Pain, B. F.; Jarvis, S. C.; Chambers, B. J.; Smith, K. A.; Phillips, V. R.; Demmers, T. G. M.

    Ammonia (NH 3) emission inventories are required for modelling atmospheric NH 3 transport and estimating downwind deposition. A recent inventory for UK agriculture, estimating emission as 197 kt NH 3-N yr -1, was constructed using 1993 statistical and census data for the UK. This paper describes the derivation of the UK-based emission factors used in the calculation of that emission for a range of livestock classes, farm practices and fertiliser applications to agricultural land. Some emission factors have been updated where more recent information has become available. Some of the largest emission factors derived for each farming practice include 16.9 g NH 3-N dairy cow -1 d -1 for grazing, 148.8 g NH 3-N liveweight unit -1 yr -1 for housed broilers and 4.8 g NH 3-N m -2 d -1 for storage of solid pig and poultry waste as manure heaps. Emissions for land spreading of all livestock waste were 59% of the total ammoniacal nitrogen (TAN) applied as a high dry matter content slurry and 76% of TAN applied as farm yard manure. An updated estimate of emission from UK agriculture, using updated emission factors together with 1997 statistical and census data, is presented, giving a total of 226 kt NH 3-N per year.

  18. Migrant cap 'may damage' UK physics

    NASA Astrophysics Data System (ADS)

    Harris, Margaret

    2011-01-01

    Scientists have expressed concern that changes to UK immigration rules - including a sharp drop in the number of visas available for the most highly skilled migrants - could make it more difficult for universities and other institutions to recruit talented researchers from overseas.

  19. IS Curriculum Career Tracks: A UK Study

    ERIC Educational Resources Information Center

    Stefanidis, Angelos; Fitzgerald, Guy; Counsell, Steve

    2013-01-01

    Purpose: The purpose of this paper is to present the results of a comprehensive study on the specialisations or career tracks supported by the Information Systems (IS) curriculum in the UK. Design/methodology/approach: The study utilises the recently published IS curriculum guidelines (IS 2010) to develop a method for ranking the career tracks of…

  20. Metaphor Use in Three UK University Lectures

    ERIC Educational Resources Information Center

    Low, Graham; Littlemore, Jeannette; Koester, Almut

    2008-01-01

    It has been claimed in recent years that, on the one hand, metaphor occurs in UK university lectures in ways that are likely to confuse ESL learners (Littlemore 2001, 2003) and on the other hand that US lecturers use it in highly structured ways, particularly involving linked clusters, to help organize the lecture and indicate the opinions of the…

  1. Lengthening osteotomy of the calcaneus and flexor digitorum longus tendon transfer in flexible flatfoot deformity improves talo-1st metatarsal-Index, clinical outcome and pedographic parameter.

    PubMed

    Richter, Martinus; Zech, Stefan

    2013-03-01

    Lengthening osteotomy of the calcaneus (LO) and flexor digitorum longus tendon (FDL) transfer to the navicular is one option for the treatment of flexible flatfoot deformity (FD). The aim of the study was to analyse the amount of correction and clinical outcome including pedographic assessment. In a prospective consecutive non-controlled clinical followup study, all patients with FD that were treated with LO and FDL from September 1st 2006 to August 31st, 2009 were included. Assessment was performed before surgery and at 2-year-followup including clinical examination (with staging of posterior tibialis insufficiency) weight bearing radiographs (Talo-1st metatarsal angles (TMT)), pedography (increased midfoot contact area and force) and Visual Analogue Scale Foot and Ankle (VAS FA). 112 feet in 102 patients were analysed (age, 57.6 (13-82), 42% male). In 12 feet (9%) wound healing delay without further surgical measures was registered. All patients achieved full weight bearing during the 7th postoperative week. Until followup, revision surgery was done in 3 patients (fusion calcaneocuboid joint (n=2), correction triple arthrodesis (n=1)). 101 feet (90%) completed 2-year-followup. TMT dorsoplantar/lateral/Index and VAS FA scores were increased, and posterior tibialis insufficiency stage, pedographic midfoot contact area and force percentage were decreased (each p<.05). All relevant parameters (stage of posterior tibialis insufficiency, TMT angles and Index, pedographic midfoot contact area and force percentage, VAS FA) were improved 2 years after LO and FDL transfer to the navicular in FD. The complication rate was low. This method allows safe and predictable correction.

  2. Higher Cord C-Peptide Concentrations Are Associated With Slower Growth Rate in the 1st Year of Life in Girls but Not in Boys

    PubMed Central

    Regnault, Nolwenn; Botton, Jérémie; Heude, Barbara; Forhan, Anne; Hankard, Régis; Foliguet, Bernard; Hillier, Teresa A.; Souberbielle, Jean-Claude; Dargent-Molina, Patricia; Charles, Marie-Aline

    2011-01-01

    OBJECTIVE To understand the relationships between maternal glycemia during pregnancy and prenatal and early postnatal growth by evaluating cord C-peptide and IGF-I as mediating biomarkers in boys and girls separately. RESEARCH DESIGN AND METHODS We evaluated 342 neonates within the EDEN mother-child cohort study born to mothers without diabetes diagnosis before pregnancy. We measured maternal glycemia at 24–28 weeks of gestation and neonates’ cord blood C-peptide (used as a proxy for fetal insulin) and IGF-I at birth. Reported maternal prepregnancy BMI and all measured infant weights and lengths in the 1st year were recorded. Growth modeling was used to obtain an individual growth curve for each infant in the 1st year. Path models, a type of structural equation modeling, were used for statistical analysis. Path analysis is a multivariate method associated with a graphical display that allows evaluation of mediating factors and distinguishes direct, indirect, and total effects. RESULTS Cord C-peptide at birth was positively correlated with maternal prepregnancy BMI and maternal glycemia and was higher in girls. In a path model that represented prenatal growth, there was no significant direct effect of maternal glycemia on birth weight, but the effect of maternal glycemia on birth weight was mediated by fetal insulin and IGF-I in both girls and boys. However, in girls only, higher concentrations of cord C-peptide (but not cord IGF-I or maternal glucose) were associated with slower weight growth in the first 3 months of life. CONCLUSIONS Our study underlines the role of the fetal insulin–IGF-I axis in the relationship between maternal glycemia during pregnancy and birth weight. We also show for the first time that high insulin concentration in female fetuses is associated with slower early postnatal growth. This slow, early growth pattern may be programmed by fetal hyperinsulinemia, and girls may be more susceptible than boys to its consequences. PMID:21700880

  3. Effect of maternal dietary counselling during the 1st year of life on glucose profile and insulin resistance at the age of 8 years: a randomised field trial.

    PubMed

    Costa, Cintia S; Campagnolo, Paula D B; Lumey, L H; Vitolo, Marcia R

    2017-01-01

    Education interventions that stimulate complementary feeding practices can improve the nutritional status of children and may protect against future chronic diseases. We assessed the long-term effectiveness of dietary intervention during the 1st year of life on insulin resistance levels, and investigated the relationship between insulin resistance and weight changes over time. A randomised field trial was conducted among 500 mothers who gave birth to full-term infants between October 2001 and June 2002 in a low-income area in São Leopoldo, Brazil. Mother-child pairs were randomly assigned to intervention (n 200) and control groups (n 300), and the mothers in the intervention group received dietary counselling on breast-feeding and complementary feeding of their children during the 1st year of life. Fieldworkers blinded to assignment assessed socio-demographic, dietary and anthropometric data during follow-up at ages 1, 4 and 8 years. Blood tests were performed in 305 children aged 8 years to measure fasting serum glucose and insulin concentrations and the homoeostasis model assessment index of insulin resistance (HOMA-IR). At the age of 8 years, the intervention group showed no changes in glucose and insulin concentrations or HOMA-IR values (change 0·07; 95 % CI -0·06, 0·21 for girls; and change -0·07; 95 % CI -0·19, 0·04 for boys) compared with study controls. Insulin resistance was highly correlated, however, with increases in BMI between birth and 8 years of age. Although this dietary intervention had no impact on glucose profile at age 8 years, our findings suggest that BMI changes in early childhood can serve as an effective marker of insulin resistance.

  4. Finding a VOICE for UK clinical pharmacology

    PubMed Central

    Aronson, Jeffrey K

    2012-01-01

    At a James Black Conference held in Oxford on 20–22 June 2011, a group of senior clinical pharmacologists and their junior colleagues, other medical specialists, and pharmacists discussed an agenda for UK clinical pharmacology for the next 5 years, addressing the following broad questions. How should UK clinical pharmacology be further developed and delivered as a discipline in universities, the NHS, pharmaceutical companies, and regulatory authorities? How should teaching and training in UK clinical pharmacology and therapeutics be delivered and assessed? What topics should be priorities for research in UK academic clinical pharmacology? How should clinical pharmacology contribute to UK drugs policy? How should pharmacology and clinical pharmacology be further integrated, to the benefit of both? Numerous recommendations emerged, under the collective acronym VOICE, standing for Visibility, Outreach, Integration, Coverage and Emissaries. Visibility The visibility of the discipline needs to be increased. This could be done, for example, by increased activities in acute general medicine/toxicology, through activities of Medicines and Therapeutics Committees, participation in grand rounds, teaching and training, and monitoring therapeutic interventions, and by offering bolt-on training for other specialists (for example, short courses, MSc courses, and training programmes). Outreach Methods of increasing outreach include roadshows in schools/medical schools, national special study modules, public education, press coverage, and social marketing. Integration Closer collaborations with pharmacologists, clinical pharmacists, other prescribers, and pharmaceutical companies (e.g. through joint training programmes) are desirable. Coverage Attention to neglected areas, such as general practice, paediatrics, obstetrics, geriatrics, anaesthetics, cancer, and immunology. Emissaries Trainees to spread the word. PMID:22360150

  5. Finding a VOICE for UK clinical pharmacology.

    PubMed

    Aronson, Jeffrey K

    2012-06-01

    At a James Black Conference held in Oxford on 20-22 June 2011, a group of senior clinical pharmacologists and their junior colleagues, other medical specialists, and pharmacists discussed an agenda for UK clinical pharmacology for the next 5 years, addressing the following broad questions. How should UK clinical pharmacology be further developed and delivered as a discipline in universities, the NHS, pharmaceutical companies, and regulatory authorities? How should teaching and training in UK clinical pharmacology and therapeutics be delivered and assessed? What topics should be priorities for research in UK academic clinical pharmacology? How should clinical pharmacology contribute to UK drugs policy? How should pharmacology and clinical pharmacology be further integrated, to the benefit of both? Numerous recommendations emerged, under the collective acronym VOICE, standing for Visibility, Outreach, Integration, Coverage and Emissaries. VISIBILITY: The visibility of the discipline needs to be increased. This could be done, for example, by increased activities in acute general medicine/toxicology, through activities of Medicines and Therapeutics Committees, participation in grand rounds, teaching and training, and monitoring therapeutic interventions, and by offering bolt-on training for other specialists (for example, short courses, MSc courses, and training programmes). OUTREACH: Methods of increasing outreach include roadshows in schools/medical schools, national special study modules, public education, press coverage, and social marketing. INTEGRATION: Closer collaborations with pharmacologists, clinical pharmacists, other prescribers, and pharmaceutical companies (e.g. through joint training programmes) are desirable. COVERAGE: Attention to neglected areas, such as general practice, paediatrics, obstetrics, geriatrics, anaesthetics, cancer, and immunology. EMISSARIES: Trainees to spread the word.

  6. The future of learning disabilities nursing in the UK.

    PubMed

    Clapham, Anthony

    2014-07-02

    This article appraises the report Strengthening the Commitment, which is a UK-wide review of learning disabilities nursing by the UK's four chief nursing officers. Strengthening the Commitment has strategic importance in reviewing progress in the care of people with learning disabilities in the UK. It also has a role in helping to guide future strategies and initiatives addressing the continuing health inequalities experienced by people with learning disabilities throughout the UK.

  7. Patterns of Higher Education Institutions in the UK. Tenth Report

    ERIC Educational Resources Information Center

    Ramsden, Brian

    2010-01-01

    This report is the tenth in a series published annually by Universities UK, with the support of GuildHE, updating and expanding a rich variety of data which help us to understand higher education in the UK. Since its first report in 2001, the "Patterns" series has examined the trends in UK higher education at both the sector and…

  8. UK Schools, CCTV and the Data Protection Act 1998

    ERIC Educational Resources Information Center

    Taylor, Emmeline

    2011-01-01

    The use of CCTV in schools is now commonplace in the UK. It is estimated that 85% of all UK secondary schools currently have CCTV systems in operation. The introduction of the Data Protection Act 1998 (DPA) (enacted in March 2000) meant that for the first time CCTV had direct legislation governing its use in the UK. This paper attempts to apply…

  9. Separation and identification of purine nucleosides in the urine of patients with malignant cancer by reverse phase liquid chromatography/electrospray tandem mass spectrometry.

    PubMed

    Li, Hua-Yu; Wang, Shao-Min; Liu, Hong-Min; Bu, Shan-Shan; Li, Juan; Han, Dong; Zhang, Ming-zhi; Wu, Guang-Yin

    2009-05-01

    Urinary-modified nucleosides have a potential role as cancer biomarkers for a number of malignant diseases. High performance liquid chromatography (HPLC) was combined with full-scan mass spectrometry, MS/MS analysis and accurate mass measurements in order to identify purine nucleosides purified from urine. Potential purine nucleosides were assessed by their evident UV absorbance in the HPLC chromatogram and then further examined by the mass spectrometric techniques. In this manner, numerous modified purine nucleosides were identified in the urine samples from cancer patients including xanthine, adenosine, N1-methyladenosine, 5'-deoxy-5'-methylthioadenosine, 2-methyladenosine, N6-threonylcarbamoyladenosine, inosine, N1-methylinosine, guanosine, N1-methylguanosine, N7-methylguanine, N2-methylguanosine, N2,N2-dimethyguanosine, N2,N2,N7-trimethylguanosine. Furthermore, a number of novel purine nucleosides were tentatively identified via critical interpretation of the combined mass spectrometric data including N3-methyladenosine, N7-methyladenine, 5'-dehydro-2'-deoxyinosine, N3-methylguanine, O6-methylguanosine, N1,N2,N7-trimethylguanosine, N1-methyl-N2-ethylguanosine and N7-methyl-N1-ethylguanosine.

  10. Integrative Analysis of Circadian Transcriptome and Metabolic Network Reveals the Role of De Novo Purine Synthesis in Circadian Control of Cell Cycle

    PubMed Central

    Li, Ying; Li, Guang; Görling, Benjamin; Luy, Burkhard; Du, Jiulin; Yan, Jun

    2015-01-01

    Metabolism is the major output of the circadian clock in many organisms. We developed a computational method to integrate both circadian gene expression and metabolic network. Applying this method to zebrafish circadian transcriptome, we have identified large clusters of metabolic genes containing mostly genes in purine and pyrimidine metabolism in the metabolic network showing similar circadian phases. Our metabolomics analysis found that the level of inosine 5'-monophosphate (IMP), an intermediate metabolite in de novo purine synthesis, showed significant circadian oscillation in larval zebrafish. We focused on IMP dehydrogenase (impdh), a rate-limiting enzyme in de novo purine synthesis, with three circadian oscillating gene homologs: impdh1a, impdh1b and impdh2. Functional analysis revealed that impdh2 contributes to the daily rhythm of S phase in the cell cycle while impdh1a contributes to ocular development and pigment synthesis. The three zebrafish homologs of impdh are likely regulated by different circadian transcription factors. We propose that the circadian regulation of de novo purine synthesis that supplies crucial building blocks for DNA replication is an important mechanism conferring circadian rhythmicity on the cell cycle. Our method is widely applicable to study the impact of circadian transcriptome on metabolism in complex organisms. PMID:25714999

  11. Complete assignment of the (1)H and (13)C NMR spectra of cis and trans isonucleoside derivatives of purine with a tetrahydropyran ring.

    PubMed

    Besada, Pedro; Costas, Tamara; Terán, Carmen

    2010-06-01

    (1)H and (13)C NMR chemical shifts of cis and trans isonucleoside analogues of purine in which the furanose moiety is substituted by a tetrahydropyran ring were completely assigned using one- and two-dimensional NMR experiments that include NOE, DEPT, COSY and HSQC. The significant (1)H and (13)C NMR signals differentiating between the cis and trans stereoisomers were compared.

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

    PubMed

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

    2015-01-01

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

  13. Anti-proliferative activity of 2,6-dichloro-9- or 7-(ethoxycarbonylmethyl)-9H- or 7H-purines against several human solid tumour cell lines.

    PubMed

    Morales, Fátima; Ramírez, Alberto; Conejo-García, Ana; Morata, Cynthia; Marchal, Juan A; Campos, Joaquín M

    2014-04-09

    As leads we took several benzo-fused seven- and six-membered scaffolds linked to the pyrimidine or purine moieties with notable anti-proliferative activity against human breast, colon and melanoma cancerous cell lines. We then decided to maintain the double-ringed nitrogenous bases and change the other components to the ethyl acetate moiety. This way six purine and two 5-fluorouracil derivatives were obtained and evaluated against the MCF-7, HCT-116, A-375 and G-361 cancer cell lines. Two QSARs are obtained between the anti-proliferative IC₅₀ values for compounds 26-33 and the clog P against the melanoma cell lines A-375 and G-361. Our results show that two of the analogues [ethyl 2-(2,6-dichloro-9H- or 7H-purine-9- or 7-yl)acetates (30 and 33, respectively)] are potent cytotoxic agents against all the tumour cell lines assayed, showing single-digit micromolar IC₅₀ values. This exemplifies the potential of our previously reported purine compounds to qualify as lead structures for medicinal chemistry campaigns, affording simplified analogues easy to synthesize and with a noteworthy bioactivity. The selective activity of 30 and 33 against the melanoma cell line A-375, via apoptosis, supposes a great advantage for a future therapeutic use.

  14. Wound botulism in the UK and Ireland.

    PubMed

    Brett, Moira M; Hallas, Gill; Mpamugo, Obioma

    2004-06-01

    There are three main, naturally occurring, epidemiological types of botulism: food-borne, intestinal colonization (infant botulism) and wound botulism. The neurological signs and symptoms are the same for all three epidemiological types and may include respiratory paralysis. Wound botulism is caused by growth of cells and release of toxin in vivo, is associated with traumatic wounds and abscesses and has been reported in drug users, such as those injecting heroin or sniffing cocaine. Up to the end of 1999 there were no confirmed cases of wound botulism in the UK. Between the beginning of 2000 and the end of December 2002, there were 33 clinically diagnosed cases of wound botulism in the UK and Ireland. All cases had injected heroin into muscle or by 'skin popping'. The clinical diagnosis was confirmed by laboratory tests in 20 of these cases. Eighteen cases were caused by type A toxin and two by type B toxin.

  15. Update on dialysis economics in the UK.

    PubMed

    Sharif, Adnan; Baboolal, Keshwar

    2011-03-01

    The burgeoning population of patients requiring renal replacement therapy contributes a disproportionate strain on National Health Service resources. Although renal transplantation is the preferred treatment modality for patients with established renal failure, achieving both clinical and financial advantages, limitations to organ donation and clinical comorbidities will leave a significant proportion of patients with established renal failure requiring expensive dialysis therapy in the form of either hemodialysis or peritoneal dialysis. An understanding of dialysis economics is essential for both healthcare providers and clinical leaders to establish clinically efficient and cost-effective treatment modalities that maximize service provision. In light of changes to the provision of healthcare funds in the form of "Payment by Results," it is imperative for UK renal units to adopt clinically effective and financially accountable dialysis programs. This article explores the role of dialysis economics and implications for UK renal replacement therapy programs.

  16. The 2015 Pregnancy Summit, London, UK.

    PubMed

    Johansson, Cherynne

    2016-01-01

    Pregnancy Summit, Cineworld, The O2, London, UK, 29 September to 1 October 2015 The 2015 Pregnancy Summit was held over 3 days from 29 September to 1 October at Cineworld, The O2, London, UK. The event brings together a multidisciplinary faculty of international researchers and clinicians to discuss both scientific and clinical aspects of pregnancy-related issues in an informal setting. The goal of the meeting was to provide delegates with an update of recent advances in management of pregnancy-related conditions, to present research data and to discuss the current attitudes and practices in relevant topics. An extensive range of topics were discussed, from preeclampsia and treatment of hypertension, to the psychological impact of termination of pregnancy and feticide. This report will summarize a selection of the lectures presented.

  17. Evidence for trends in UK flooding.

    PubMed

    Robson, Alice J

    2002-07-15

    Recent major flooding in the UK has raised concern that climate change is causing increases in flood frequency and flood magnitude. This paper considers whether UK flood data provide evidence of increasing trends in fluvial floods. The analysis examines both local and national flood series and investigates the effect of climate variability on trend detection. The results suggest that there have been trends towards more protracted high flows over the last 30-50 years, but that this could be accounted for as part of climatic variation rather than climate change. There is no statistical evidence of a long-term trend in flooding over the last 80-120 years. Thus, although climate change could be influencing floods, direct analysis of flood records does not yet provide proof.

  18. History of Inclusive Design in the UK.

    PubMed

    John Clarkson, P; Coleman, Roger

    2015-01-01

    The UK Design Council describes Inclusive Design as neither a new genre of design, nor a separate specialism, but as a general approach to designing in which designers ensure that their products and services address the needs of the widest possible audience, irrespective of age or ability. Inclusive Design (also known [in Europe] as Design for All and as Universal Design in the USA) is in essence the inverse of earlier approaches to designing for disabled and elderly people as a sub-set of the population, and an integral part of a more recent international trend towards the integration of older and disabled people in the mainstream of society. This paper describes the development of Inclusive Design in the UK, from its early beginnings, through its subsequent adoption as a topic of academic research, leading to its recent emergence embodied as a framework and toolkit for design.

  19. UK-4 flight spacecraft magnetic tests

    NASA Technical Reports Server (NTRS)

    Pruett, W. E.

    1972-01-01

    Magnetic tests conducted on the UK-4 spacecraft are discussed. The objectives of the test are: (1) to determine the permanent, induced, and stray magnetic moments of the spacecraft, (2) to assess its magnetic stability, (3) to determine the dipole moment produced by energizing the magnetorquer coil, (4) to measure the despin torque due to eddy current and magnetic hysteresis, and (5) to deperm, compensate, and make other adjustments necessary to achieve satisfactory magnetic characteristics for the spacecraft.

  20. Asteroidal occultation timed by four UK observers

    NASA Astrophysics Data System (ADS)

    McGee, H.

    2000-04-01

    The occultation of a 9th magnitude star by the minor planet (49) Pales at 01.00 on Monday January 17 was the first such event to be timed by more than one observer at different locations on the track in the UK (see Figure 1). It was also seen from Hungary, and by three sets of observers in Canada and the USA, but unfortunately heavy cloud prevented observation across most of Europe.

  1. Role of Achiral Nucleobases in Multicomponent Chiral Self-Assembly: Purine-Triggered Helix and Chirality Transfer.

    PubMed

    Deng, Ming; Zhang, Li; Jiang, Yuqian; Liu, Minghua

    2016-11-21

    Chiral self-assembly is a basic process in biological systems, where many chiral biomolecules such as amino acids and sugars play important roles. Achiral nucleobases usually covalently bond to saccharides and play a significant role in the formation of the double helix structure. However, it remains unclear how the achiral nucleobases can function in chiral self-assembly without the sugar modification. Herein, we have clarified that purine nucleobases could trigger N-(9-fluorenylmethox-ycarbonyl) (Fmoc)-protected glutamic acid to self-assemble into helical nanostructures. Moreover, the helical nanostructure could serve as a matrix and transfer the chirality to an achiral fluorescence probe, thioflavin T (ThT). Upon chirality transfer, the ThT showed not only supramolecular chirality but also circular polarized fluorescence (CPL). Without the nucleobase, the self-assembly processes cannot happen, thus providing an example where achiral molecules played an essential role in the expression and transfer of the chirality.

  2. A Canonical Correlation Analysis of AIDS Restriction Genes and Metabolic Pathways Identifies Purine Metabolism as a Key Cooperator

    PubMed Central

    Ye, Hanhui; Yuan, Jinjin; Wang, Zhengwu; Huang, Aiqiong; Liu, Xiaolong; Han, Xiao; Chen, Yahong

    2016-01-01

    Human immunodeficiency virus causes a severe disease in humans, referred to as immune deficiency syndrome. Studies on the interaction between host genetic factors and the virus have revealed dozens of genes that impact diverse processes in the AIDS disease. To resolve more genetic factors related to AIDS, a canonical correlation analysis was used to determine the correlation between AIDS restriction and metabolic pathway gene expression. The results show that HIV-1 postentry cellular viral cofactors from AIDS restriction genes are coexpressed in human transcriptome microarray datasets. Further, the purine metabolism pathway comprises novel host factors that are coexpressed with AIDS restriction genes. Using a canonical correlation analysis for expression is a reliable approach to exploring the mechanism underlying AIDS. PMID:27462363

  3. HAWC 1st year catalog

    NASA Astrophysics Data System (ADS)

    Riviére, Colas; HAWC Collaboration

    2017-01-01

    The High Altitude Water Cherenkov (HAWC) Observatory was inaugurated in March 2015. With its high duty cycle and wide field of view, it observes 2/3 of the TeV sky daily. After a single year of observation, the integral sensitivity already exceeds that of the previous generation of wide field instruments by a factor of five. We will present the results of the first all sky search with a year of data of the complete HAWC detector. Some known sources as well as new TeV point and extended sources will be highlighted.

  4. Purine biosynthetic enzyme ATase2 is involved in the regulation of early chloroplast development and chloroplast gene expression in Arabidopsis.

    PubMed

    Yang, Zhipan; Shang, Zengzhen; Wang, Lei; Lu, Qingtao; Wen, Xiaogang; Chi, Wei; Zhang, Lixin; Lu, Congming

    2015-12-01

    To investigate the molecular mechanism of chloroplast biogenesis and development, we characterized an Arabidopsis mutant (dg169, delayed greening 169) which showed growth retardation and delayed greening phenotype in leaves. Newly emerged chlorotic leaves recovered gradually with leaf development in the mutant, and the mature leaves showed similar phenotype to those of wild-typewild-type plants. Compared with wild-type, the chloroplasts were oval-shaped and smaller and the thylakoid membranes were less abundant in yellow section of young leaves of dg169. In addition, the functions of photosystem II (PSII) and photosystem I (PSI) were also impaired. Furthermore, the amount of core subunits of PSII and PSI, as well as PSII and PSI complexes reduced in yellow section of young leaves of dg169. Map-based positional cloning identified that phenotype of dg169 was attributed to a point mutation of ATase2 which converts the conserved Ile-155 residue to Asn. ATase2 catalyzes the first step of de novo purine biosynthesis. This mutation resulted in impaired purine synthesis and a significant decrease in ATP, ADP, GTP and GDP contents. The analysis of ATase2-GFP protein fusion showed that ATase2 was localized to nucleoid of chloroplasts. Our results further demonstrated that the levels of PEP-dependent transcripts in yellow section of young leaves of dg169 were decreased while NEP-dependent and both PEP- and NEP-dependent transcripts and chloroplast DNA replications were increased. The results in this study suggest that ATase2 plays an essential role in early chloroplast development through maintaining PEP function.

  5. Triple helix formation with purine-rich phosphorothioate-containing oligonucleotides covalently linked to an acridine derivative.

    PubMed Central

    Lacoste, J; François, J C; Hélène, C

    1997-01-01

    Purine-rich (GA)- and (GT)-containing oligophosphorothioates were investigated for their triplex-forming potential on a 23 bp DNA duplex target. In our system, GA-containing oligophosphorothioates (23mer GA-PS) were capable of triplex formation with binding affinities lower than (GA)-containing oligophosphodiesters (23mer GA-PO). The orientation of the third strand 23mers GA-PS and GA-PO was antiparallel to the purine strand of the duplex DNA target. In contrast, (GT)-containing oligophosphorothioates (23mer GT-PS) did not support triplex formation in either orientation, whereas the 23mer GT-PO oligophosphodiester demonstrated triplex formation in the antiparallel orientation. GA-PS oligonucleotides, in contrast to GT-PS oligonucleotides, were capable of self-association, but these self-associated structures exhibited lower stabilities than those formed with GA-PO oligonucleotides, suggesting that homoduplex formation (previously described for the 23mer GA-PO sequence by Noonberg et al.) could not fully account for the decrease in triplex stability when phosphorothioate linkages were used. The 23mer GA-PS oligonucleotide was covalently linked via its 5'-end to an acridine derivative (23mer Acr-GA-PS). In the presence of potassium cations, this conjugate demonstrated triplex formation with higher binding affinity than the unmodified 23mer GA-PS oligonucleotide and even than the 23mer GA-PO oligonucleotide. A (GA)-containing oligophosphodiester with two phosphorothioate linkages at both the 5'- and 3'-ends exhibited similar binding affinity to duplex DNA compared with the unmodified GA-PO oligophosphodiester. This capped oligonucleotide was more resistant to nucleases than the GA-PO oligomer and thus represents a good alternative for ex vivo applications of (GA)-containing, triplex-forming oligonucleotides, allowing a higher binding affinity for its duplex target without rapid cellular degradation. PMID:9115367

  6. Purine biosynthesis in L1210 leukemia cells is inhibited by 7-hydroxymethotrexate (7-OH-MTX) polyglutamates (PGS)

    SciTech Connect

    Seither, R.L.; Matherly, L.H.; Goldman, I.D.

    1986-05-01

    The biochemical basis for 7-OH-MTX cytotoxicity was examined in L1210 tumor cells. Cells were exposed to 100 ..mu..M 7-OH-MTX (approx. 50% growth inhibition) or 10 ..mu..M methotrexate (MTX) (approx. 95% growth inhibition) for 6 hrs to allow high levels of PGS to accumulate. Dihydrofolate reductase (DHFR) activity was assessed by dihydrofolate (FH/sub 2/) pools labeled with 5-formyl-(/sup 3/H)-tetrahydrofolate (5..mu..M) or /sup 3/H-folic acid (1 ..mu..M). FH/sub 2/ was not elevated above control levels in 7-OH-MTX treated cells, in contrast to MTX treated cells in which FH/sub 2/ increased 4- to 7-fold. /sup 3/H-Deoxyuridine incorporation into DNA was not inhibited in cells containing high levels (11.5 nmol/g dry wt.) of 7-OH-MTX tetraglutamate (7-OH-4-NH/sub 2/-10-CH/sub 3/-PteGlu/sub 4/), well in excess of the DHFR-binding capacity (7.3 +/- 0.9 nmol/g), indicating a normal rate of thymidylate synthesis. Although small amounts of 7-OH-MTX and its PGS were bound to DHFR in L1210 cells, as assessed by gel filtration, there was evidence for the preferential binding of 7-OH-MTX tetraglutamate. In all cases this was well below the DHFR binding capacity, consistent with normal rates of deoxyuridine metabolism and FH/sub 2/ levels in the cell. Incorporation of /sup 14/C-formate (60 min) into thymidylate and amino acids was unaffected by 7-OH-MTX, yet incorporation into purines was inhibited over 50%, supporting a block(s) in de novo purine biosynthesis.

  7. Levels of Salivary Enzymes of Apolygus Lucorum (Hemiptera: Miridae), From 1st Instar Nymph to Adult, and Their Potential Relation to Bug Feeding

    PubMed Central

    Tan, Xiumei; Xu, Xiuping; Gao, Yong; Yang, Qinmin; Zhu, Yunsheng; Wang, Jiqing; Wan, Fanghao; Zhou, Hongxu

    2016-01-01

    In recent years, Apolygus lucorum has caused increasing damage to cotton and fruit trees in China. The salivary enzymes secreted by A. lucorum when sucking on host plants induce a series of biochemical reactions in plants, and the pre-oral digestion benefits the bug feeding. In this study, the food intake of A. lucorum from 1st instar nymphs to adults was measured, and the corresponding salivary activity of pectinase, amylase, cellulase, protease, polyphenol oxidase and peroxidase was determined. Daily food intake varied with developmental stage, peaking in 3rd and 4th instar nymphs. Pectinase, amylase, cellulase and protease were detected in both nymphal and adult saliva of A. lucorum, while neither polyphenol oxidase nor peroxidase was detected. Protease activity varied with food intake peaking at the 3rd-4th instar, and then slightly decreasing at the 5th instar. Levels of pectinase, amylase and cellulase increased significantly with the daily feeding level until the 3rd instar, corresponding with increasing damage to host plants. The activity of both cellulase and protease had a significant linear relationship with the average daily food intake. The increasing activity of enzymes in saliva explain stage-specific impacts of A. lucorum on the host plants, and suggest that optimal management of A. lucorum would be confined to its control threshold prior to the peak of daily feeding in the 3rd instar. PMID:28002486

  8. The August 1st, 2014 ( M w 5.3) Moderate Earthquake: Evidence for an Active Thrust Fault in the Bay of Algiers (Algeria)

    NASA Astrophysics Data System (ADS)

    Benfedda, A.; Abbes, K.; Bouziane, D.; Bouhadad, Y.; Slimani, A.; Larbes, S.; Haddouche, D.; Bezzeghoud, M.

    2017-03-01

    On August 1st, 2014, a moderate-sized earthquake struck the capital city of Algiers at 05:11:17.6 (GMT+1). The earthquake caused the death of six peoples and injured 420, mainly following a panic movement among the population. Following the main shock, we surveyed the aftershock activity using a portable seismological network (short period), installed from August 2nd, 2014 to August 21st, 2015. In this work, first, we determined the main shock epicenter using the accelerograms recorded by the Algerian accelerograph network (under the coordination of the National Center of Applied Research in Earthquake Engineering-CGS). We calculated the focal mechanism of the main shock, using the inversion of the accelerograph waveforms in displacement that provides a reverse fault with a slight right-lateral component of slip and a compression axis striking NNW-SSE. The obtained scalar seismic moment ( M o = 1.25 × 1017 Nm) corresponds to a moment magnitude of M w = 5.3. Second, the analysis of the obtained aftershock swarm, of the survey, suggests an offshore ENE-WSW, trending and NNW dipping, causative active fault in the bay of Algiers, which may likely correspond to an offshore unknown segment of the Sahel active fault.

  9. Ethylene responsive element binding protein 1 (StEREBP1) from Solanum tuberosum increases tolerance to abiotic stress in transgenic potato plants.

    PubMed

    Lee, Hye Eun; Shin, Dongjin; Park, Sang Ryeol; Han, Sang-Eun; Jeong, Mi-Jeong; Kwon, Tack-Ryun; Lee, Seong-Kon; Park, Soo-Chul; Yi, Bu Young; Kwon, Hawk-Bin; Byun, Myung-Ok

    2007-02-23

    To identify components of the plant stress signal transduction cascade and response mechanisms, we screened plant genes using reverse Northern blot analysis, and chose the ethylene responsive element binding protein 1 (StEREBP1) for further characterization. To investigate its biological function in the potato, we performed Northern blot analysis and observed enhanced levels of transcription in response to several environmental stresses including low temperature. In vivo targeting experiments using a green fluorescent protein (GFP) reporter indicated that StEREBP1 localized to the nucleus of onion epidermal cells. StEREBP1 was found to bind to GCC and DRE/CRT cis-elements and both microarray and RT-PCR analyses indicated that overexpression of StEREBP1 induced expression of several GCC box-containing stress response genes. In addition, overexpression of StEREBP1 enhanced tolerance to cold and salt stress in transgenic potato plants. The results of this study suggest that StEREBP1 is a functional transcription factor that may be involved in abiotic stress responses in plants.

  10. Excerpts from the 1st international NTNU symposium on current and future clinical biomarkers of cancer: innovation and implementation, June 16th and 17th 2016, Trondheim, Norway.

    PubMed

    Robles, Ana I; Olsen, Karina Standahl; Tsui, Dana W T; Georgoulias, Vassilis; Creaney, Jenette; Dobra, Katalin; Vyberg, Mogens; Minato, Nagahiro; Anders, Robert A; Børresen-Dale, Anne-Lise; Zhou, Jianwei; Sætrom, Pål; Nielsen, Boye Schnack; Kirschner, Michaela B; Krokan, Hans E; Papadimitrakopoulou, Vassiliki; Tsamardinos, Ioannis; Røe, Oluf D

    2016-10-19

    The goal of biomarker research is to identify clinically valid markers. Despite decades of research there has been disappointingly few molecules or techniques that are in use today. The "1st International NTNU Symposium on Current and Future Clinical Biomarkers of Cancer: Innovation and Implementation", was held June 16th and 17th 2016, at the Knowledge Center of the St. Olavs Hospital in Trondheim, Norway, under the auspices of the Norwegian University of Science and Technology (NTNU) and the HUNT biobank and research center. The Symposium attracted approximately 100 attendees and invited speakers from 12 countries and 4 continents. In this Symposium original research and overviews on diagnostic, predictive and prognostic cancer biomarkers in serum, plasma, urine, pleural fluid and tumor, circulating tumor cells and bioinformatics as well as how to implement biomarkers in clinical trials were presented. Senior researchers and young investigators presented, reviewed and vividly discussed important new developments in the field of clinical biomarkers of cancer, with the goal of accelerating biomarker research and implementation. The excerpts of this symposium aim to give a cutting-edge overview and insight on some highly important aspects of clinical cancer biomarkers to-date to connect molecular innovation with clinical implementation to eventually improve patient care.

  11. Report from the 1st Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group.

    PubMed

    Schnell, Oliver; Standl, Eberhard; Catrinoiu, Doina; Genovese, Stefano; Lalic, Nebojsa; Skra, Jan; Valensi, Paul; Ceriello, Antonio

    2016-02-18

    The 1st Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group was held during the annual meeting on 30 October 2015 in Munich. This summit was organized in light of recently published and numerous ongoing CVOTs on diabetes, which have emerged in response to the FDA and the EMA Guidelines. The CVOT Summit stands as a novel conference setup, with the aim of serving as a reference meeting for all topics related to CVOTs in diabetes. Members of the steering committee of the D&CVD EASD Study Group constitute the backbone of the summit. It included presentations of key results on DPP-4 inhibitors, GLP-1-Analogues, SGLT-2 inhibitors, acarbose and insulins. Diabetologists' and cardiologists' perspective on the potential need of new study designs were also highlighted. Furthermore, panel discussions on the design of CVOTs on diabetes were included in the program. The D&CVD EASD Study Group will continue its activity. In-depth discussions and presentations of new CVOTs like LEADER, will be resumed at the 2nd CVOT on diabetes of the D&CVD EASD Study Group, which will be held from 20-22 October 2016 in Munich ( http://www.dcvd.org).

  12. [Report of the World Federation of Neurosurgical Societies (WFNS) international course and Cameroon Neurosurgery Society Congress (CNS) Yaoundé (Cameroon), 1st--4th October 2007].

    PubMed

    Eyenga, V C; Ndoumbe, A; Eloundou, N J

    2008-04-01

    Neurosurgery remains a very marginal activity in sub-Saharan Africa. In this part of the world which counts nearly 40 countries, some do not have a single neurosurgeon, some have one to five, the number of ten neurosurgeons per country remaining an exception! In its concern of popularizing and of developing neurosurgery worldwide, the WFNS organized an international course in Africa, October 2007 2nd-3rd in Yaoundé (Cameroon). The Cameroon Neurosurgery Society (CNS) took this opportunity to organize its very first congress in the presence of the WFNS delegation from October 1st to 4th, 2007. The joint meeting with the WFNS was baptized the "African Week of Neurosurgery". This special event was a first in sub-Saharan Africa. The delegation of the WFNS, led by Professor J. Brotchi (Belgium) President of the WFNS, was made up of Professors A. Sousa (Brazil), Mr. Choux (France), N. Tribolet (Swiss), M. Arraez (Spain), A. Bricolo (Italy), A. Kamlichi (Morocco), G. Dechambenoit (France), K. Kalangu (Zimbabwe). Twenty three neurosurgeons coming from nine African countries (Cameroon, Nigeria, Gabon, Congo, Niger, Burkina Faso, Ivory Coast, Senegal, and Guinea) took an active part in work. The scientific success of this event led to the creation of the "Association of Neurological Surgeons of Africa (ANSA)" which will be the WFNS-Africa interface in order to insure the development of neurosurgery in Africa.

  13. Molecular cloning, functional characterization and expression of potato (Solanum tuberosum) 1-deoxy-d-xylulose 5-phosphate synthase 1 (StDXS1) in response to Phytophthora infestans.

    PubMed

    Henriquez, Maria Antonia; Soliman, Atta; Li, Genyi; Hannoufa, Abdelali; Ayele, Belay T; Daayf, Fouad

    2016-02-01

    1-Deoxy-D-xylulose 5-phosphate synthase (DXS) catalyzes the initial step of the plastidial 2C-methyl-D-erythritol-4-phosphate (DOXP-MEP) pathway involved in isoprenoid biosynthesis. In this study, we cloned the complete cDNA of potato DXS gene that was designated StDXS1. StDXS1 cDNA encodes for 719 amino acid residues, with MW of 77.8 kDa, and is present in one copy in the potato genome. Phylogenetic analysis and protein sequence alignments assigned StDXS1 to a group with DXS homologues from closely related species and exhibited homodomain identity with known DXS proteins from other plant species. Late blight symptoms occurred in parallel with a reduction in StDXS1 transcript levels, which may be associated with the levels of isoprenoids that contribute to plant protection against pathogens. Subcellular localization indicated that StDXS1 targets the chloroplasts where isoprenoids are synthesized. Arabidopsis expressing StDXS1 showed a higher accumulation of carotenoids and chlorophyll as compared to wild type controls. Lower levels of ABA and GA were detected in the transgenic DXS lines as compared to control plants, which reflected on higher germination rates of the transgenic DXS lines. No changes were detected in JA or SA contents. Selected downstream genes in the DOXP-MEP pathway, especially GGPPS genes, were up-regulated in the transgenic lines.

  14. Stable isotopic evidence for diet at the Imperial Roman coastal site of Velia (1st and 2nd centuries AD) in Southern Italy.

    PubMed

    Craig, Oliver E; Biazzo, Marco; O'Connell, Tamsin C; Garnsey, Peter; Martinez-Labarga, Cristina; Lelli, Roberta; Salvadei, Loretana; Tartaglia, Gianna; Nava, Alessia; Renò, Lorena; Fiammenghi, Antonella; Rickards, Olga; Bondioli, Luca

    2009-08-01

    Here we report on a stable isotope palaeodietary study of a Imperial Roman population interred near the port of Velia in Southern Italy during the 1st and 2nd centuries AD. Carbon and nitrogen stable isotope analyses were performed on collagen extracted from 117 adult humans as well as a range of fauna to reconstruct individual dietary histories. For the majority of individuals, we found that stable isotope data were consistent with a diet high in cereals, with relatively modest contributions of meat and only minor contributions of marine fish. However, substantial isotopic variation was found within the population, indicating that diets were not uniform. We suggest that a number of individuals, mainly but not exclusively males, had greater access to marine resources, especially high trophic level fish. However, the observed dietary variation did not correlate with burial type, number of grave goods, nor age at death. Also, individuals buried at the necropolis at Velia ate much less fish overall compared with the contemporaneous population from the necropolis of Portus at Isola Sacra, located on the coast close to Rome. Marine and riverine transport and commerce dominated the economy of Portus, and its people were in a position to supplement their own stocks of fish with imported goods in transit to Rome, whereas at Velia marine exploitation existed side-by-side with land-based economic activities.

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

    PubMed

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

    2014-09-01

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

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

    PubMed Central

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

    2014-01-01

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

  17. Bring UK data to the web

    SciTech Connect

    Roberts, M.

    1995-11-01

    As part of its ongoing {open_quotes}Right to know{close_quotes}campaign friends of the Earth has made the U.K.`s new Chemical Release Inventory (CRI) significantly more accessible via a new Internet web site. Users enter a postal code, get a map of major industrial sites within a certain radius, and then look up the recent authorized and unauthorized releases of each site. {open_quotes}We fully support this,{close_quotes} says the U.K.`s HM Inspectorate of Pollution (HMIP), which is in charge of CRI. HMIP launched CRI last September, but FOE attacked it as {open_quote}fundamentally flawed... a pale shadow of the U.S. Toxics Release Inventory [TRI].{close_quotes} The CRI report, covering 1992 and 1993, contains only broad aggregate data-for example, total emissions from industry sectors in geographic areas. FOE says it should list emissions by site or by total emissions of companies. HMIP says the report is {open_quotes}only the beginning{close_quote} and will improve. It adds that it is meant to show general trends and that people interested in site-by-site data can call an HMIP information hotline. CRI includes emissions to air, land, and water from industrial processes regulated by the U.K.`s Integrated Pollution Control (IPC) regulations. HMIP says CRI will improve in two to three years, when IPC-which started up in 1991-is fully implemented. The FOE web site is based on the full HMIP database of emissions reported under IPC regulations, though some commercially sensitive information has been omitted, HMIP says.

  18. A Water Grid for the UK

    NASA Astrophysics Data System (ADS)

    Leathard, A.; Fowler, H. J.; Kilsby, C. G.

    2009-12-01

    Anthropogenically aggravated climate change associated with intensive expansion of the global economy has increased the demand for water whilst simultaneously altering natural variability in its distribution, straining water resources unsustainably and inequitably in many parts of the world, increasing drought risk, and encouraging decision-makers to reconsider the security of water supply. Indeed, in the absence of additional resource development, contemporary planning forecasts imply increased water stress across much of the United Kingdom. Until recently the regulatory authorities of the UK promoted increased efficiency of water delivery and consumption combined with a portfolio of financial instruments as a means of reducing water stress, maintaining present levels of consumer service without significant further exploitation of the environment. However, despite an increasingly sophisticated understanding of climate change and its effects, significant uncertainty remains in the quantification of its impacts on the water sector, and questions persist as to the effectiveness of such demand management measures compared to that of more traditional infrastructure improvements. Faced with possible futures provided for by detrimentally over-stressed resources, what opportunities remain for future strategic development in the UK? Is there a single national strategy that is both politically and socially acceptable? Do the benefits of national water infrastructure projects outweigh their costs? This ongoing study aims to evolve robust national adaptation strategies by quantifying the projected impacts of climate change across mainland UK using multi-model and perturbed-physics ensembles of projected future climate, encapsulating uncertainties in a scenario-driven integrated water resources model incorporating socio-economic elements.

  19. UK: impact of European human rights law.

    PubMed

    Brahams, D

    2000-10-21

    The UK's Human Rights Act 1998, which incorporates into that country's law the European Convention on Rights and Freedoms, came into full operation on Oct 2, 2000. The Act imposes duties on public authorities, who must now justify their position if that is in conflict with a Convention right. Four Articles in the Convention are potential flashpoints in respect of health cases, examples being patients' rights to receive expensive life-saving treatment and disciplinary procedures, including those of the General Medical Council and National Health Service trusts.

  20. Resuscitation of general paediatrics in the UK.

    PubMed

    Wacogne, I; Scott-Jupp, R; Chambers, T

    2006-12-01

    "The report of my death was an exaggeration", said Mark Twain. For a dying specialty, general paediatrics has certainly been looking very healthy recently. It is timely to examine why our specialty was thought to be at such risk, and to explore why, although in many cases shocked and confused, it is well on the way to recovery. This article explores what is needed to keep it healthy to ensure that the general paediatrician is at the centre of the delivery of paediatrics in the UK.

  1. Starlink: Software and sociology in UK astronomy

    NASA Astrophysics Data System (ADS)

    Pimbblet, Kevin A.

    2002-02-01

    Why don't people use Starlink software? Kevin A Pimbblet outlines the problem and some possible solutions. I discuss the remit of Starlink's software strategy groups and an item on the agenda of one group's meeting on 26 January 2001: ``Why don't people use Starlink software?'' The answer was thought to be primarily a sociological effect: most people supervising UK astronomy PhD students learnt their trade when Starlink had a less than perfect reputation. I report on recommendations made to counter this effect.

  2. Well integrity failure in the UK

    NASA Astrophysics Data System (ADS)

    Worrall, F.

    2015-12-01

    The aim of this study was to consider the potential legacy of increased onshore, unconventional gas production by examining the integrity of decommissioned, onshore, oil and gas wells in the UK. In the absence of a history of unconventional hydrocarbon exploitation in the UK, conventional onshore sites were considered and an examination of pollution incidents records had suggested that only a small fraction of operational, onshore wells could show integrity failures. A consideration of groundwater and surface water quality monitoring could find no regional impact of historic or current conventional oil and gas exploitation in the UK. As a more direct measure of well legacy this study considered the fugitive emissions of methane from former oil and gas wells onshore in the UK as a measure of well integrity. The survey considered 102 decommissioned (abandoned) wells from 4 different basins that were between 8 and 78 years old; all but one of these wells would be considered as having been decommissioned properly, i.e. wells cut, sealed and buried by soil cover to the extent that the well sites were being used for agriculture. For each well site the soil gas methane was analysed multiple times and assessed relative to a nearby control site of similar land-use and soil type. The results showed that of the 102 wells surveyed, 30% had soil gas CH4 at the soil surface that was significantly greater than their respective control. Conversely, 39% of well sites had significant lower surface soil gas CH4 concentrations than their respective control. We interpret elevated soil gas CH4 concentrations to be the result of well integrity failure, but do not know the source of the gas nor the route to the surface. Where elevated CH4 was detected it appears to have occurred within a decade of the well being decommissioned. The flux of CH4 from wells was 364 ± 677 kg CO2eq/well/yr with a 27% chance that any well would be a net sink of CH4 independent of well age. This flux is low

  3. Agricultural biotechnology and the UK public.

    PubMed

    Moses, Vivian

    2002-09-01

    It might be an exaggeration to claim that UK agriculture is in a state of crisis, but it is certainly a time for decisions. Uncertainties abound: the implications of growing free trade; a steady reduction in subsidies; the ongoing drift of people to towns and what some regard as the stranglehold of retailers both on food prices and on what the farmer gets. To all of this has to be added the backwash of bovine spongiform encephalopathy (BSE) and foot-and-mouth disease (FMD), and the advent of new technologies, especially those based on modern genetics.

  4. Implications for alcohol minimum unit pricing advocacy: what can we learn for public health from UK newsprint coverage of key claim-makers in the policy debate?

    PubMed

    Hilton, Shona; Wood, Karen; Patterson, Chris; Katikireddi, Srinivasa Vittal

    2014-02-01

    On May 24th 2012, Scotland passed the Alcohol (Minimum Pricing) Bill. Minimum unit pricing (MUP) is an intervention that raises the price of the cheapest alcohol to reduce alcohol consumption and related harms. There is a growing literature on industry's influence in policymaking and media representations of policies, but relatively little about frames used by key claim-makers in the public MUP policy debate. This study elucidates the dynamic interplay between key claim-makers to identify lessons for policy advocacy in the media in the UK and internationally. Content analysis was conducted on 262 articles from seven UK and three Scottish national newspapers between 1st May 2011 and 31st May 2012, retrieved from electronic databases. Advocates' and critics' constructions of the alcohol problem and MUP were examined. Advocates depicted the problem as primarily driven by cheap alcohol and marketing, while critics' constructions focused on youth binge drinkers and dependent drinkers. Advocates justified support by citing the intervention's targeted design, but critics denounced the policy as illegal, likely to encourage illicit trade, unsupported by evidence and likely to be ineffective, while harming the responsible majority, low-income consumers and businesses. Critics' arguments were consistent over time, and single statements often encompassed multiple rationales. This study presents advocates with several important lessons for promoting policies in the media. Firstly, it may be useful to shift focus away from young binge drinkers and heavy drinkers, towards population-level over-consumption. Secondly, advocates might focus on presenting the policy as part of a wider package of alcohol policies. Thirdly, emphasis on the success of recent public health policies could help portray the UK and Scotland as world leaders in tackling culturally embedded health and social problems through policy; highlighting past successes when presenting future policies may be a valuable

  5. Implications for alcohol minimum unit pricing advocacy: What can we learn for public health from UK newsprint coverage of key claim-makers in the policy debate?

    PubMed Central

    Hilton, Shona; Wood, Karen; Patterson, Chris; Katikireddi, Srinivasa Vittal

    2014-01-01

    On May 24th 2012, Scotland passed the Alcohol (Minimum Pricing) Bill. Minimum unit pricing (MUP) is an intervention that raises the price of the cheapest alcohol to reduce alcohol consumption and related harms. There is a growing literature on industry's influence in policymaking and media representations of policies, but relatively little about frames used by key claim-makers in the public MUP policy debate. This study elucidates the dynamic interplay between key claim-makers to identify lessons for policy advocacy in the media in the UK and internationally. Content analysis was conducted on 262 articles from seven UK and three Scottish national newspapers between 1st May 2011 and 31st May 2012, retrieved from electronic databases. Advocates' and critics' constructions of the alcohol problem and MUP were examined. Advocates depicted the problem as primarily driven by cheap alcohol and marketing, while critics' constructions focused on youth binge drinkers and dependent drinkers. Advocates justified support by citing the intervention's targeted design, but critics denounced the policy as illegal, likely to encourage illicit trade, unsupported by evidence and likely to be ineffective, while harming the responsible majority, low-income consumers and businesses. Critics' arguments were consistent over time, and single statements often encompassed multiple rationales. This study presents advocates with several important lessons for promoting policies in the media. Firstly, it may be useful to shift focus away from young binge drinkers and heavy drinkers, towards population-level over-consumption. Secondly, advocates might focus on presenting the policy as part of a wider package of alcohol policies. Thirdly, emphasis on the success of recent public health policies could help portray the UK and Scotland as world leaders in tackling culturally embedded health and social problems through policy; highlighting past successes when presenting future policies may be a valuable

  6. FOREWORD: 13th International Workshop on Plasma-Facing Materials and Components for Fusion Applications/1st International Conference on Fusion Energy Materials Science 13th International Workshop on Plasma-Facing Materials and Components for Fusion Applications/1st International Conference on Fusion Energy Materials Science

    NASA Astrophysics Data System (ADS)

    Jacob, Wolfgang; Linsmeier, Christian; Rubel, Marek

    2011-12-01

    The 13th International Workshop on Plasma-Facing Materials and Components (PFMC-13) jointly organized with the 1st International Conference on Fusion Energy Materials Science (FEMaS-1) was held in Rosenheim (Germany) on 9-13 May 2011. PFMC-13 is a successor of the International Workshop on Carbon Materials for Fusion Applications series. Between 1985 and 2003 ten 'Carbon Workshops' were organized in Jülich, Stockholm and Hohenkammer. Then it was time for a change and redefinition of the scope of the symposium to reflect the new requirements of ITER and the ongoing evolution in the field. Under the new name (PFMC-11), the workshop was first organized in 2006 in Greifswald, Germany and PFMC-12 took place in Jülich in 2009. Initially starting in 1985 with about 40 participants as a 1.5 day workshop, the event has continuously grown to about 220 participants at PFMC-12. Due to the joint organization with FEMaS-1, PFMC-13 set a new record with more than 280 participants. The European project Fusion Energy Materials Science, FEMaS, coordinated by the Max-Planck-Institut für Plasmaphysik (IPP), organizes and stimulates cooperative research activities which involve large-scale research facilities as well as other top-level materials characterization laboratories. Five different fields are addressed: benchmarking experiments for radiation damage modelling, the application of micro-mechanical characterization methods, synchrotron and neutron radiation-based techniques and advanced nanoscopic analysis based on transmission electron microscopy. All these fields need to be exploited further by the fusion materials community for timely materials solutions for a DEMO reactor. In order to integrate these materials research fields, FEMaS acted as a co-organizer for the 2011 workshop and successfully introduced a number of participants from research labs and universities into the PFMC community. Plasma-facing materials experience particularly hostile conditions as they are

  7. Interpreting in the UK Community: Some Reflections on Public Service Interpreting in the UK

    ERIC Educational Resources Information Center

    Townsley, Brooke

    2007-01-01

    Starting with the question "why do we need professional public service interpreters?" this paper offers an overview of the present situation regarding the provision of public service interpreters (PSIs) in the UK to public service clients and touches on the main obstacles to the professionalisation of public service interpreting so far…

  8. The 1st and the 2nd Italian Consensus Conferences on low-density lipoprotein-apheresis. A practical synopsis and update

    PubMed Central

    Stefanutti, Claudia

    2017-01-01

    The clinical indications and guidelines for low-density lipoprotein (LDL)-apheresis set by the 1st Italian Consensus Conference held in Ostuni in 1990 and completed in 1992, but never published, are reported schematically. In 1994, within the Project “Prevention and control of the factors of the disease (FATMA)” by the Italian National Research Council, subproject 8 “Control of cardiovascular disease”, a “Hearing on therapeutic apheresis: need for a target-oriented project” was organised. The meeting was the last scientific initiative on LDL-apheresis supported by public funds in Italy. After roughly two decades of use of LDL-apheresis, new guidelines were required based on the latest scientific evidence. In 2006, the Italian multicentre study on LDL-apheresis Working Group (IMSLDLa-WP), a scientific initiative at national level, was developed. It initially gathered together 19 Italian centres qualified for the application of lipid apheresis and LDL-apheresis (2007–2008), then 23 in 2010, located in the north, south, centre of Italy and in Sicily and Sardinia. The multicentre study aimed to validate the protocol for selecting patients and to create a network between the Italian centres. A secondary objective was the creation of a database of patients with familial hypercholesterolaemia and other severe forms of dyslipidaemia undergoing treatment with LDL-apheresis using the available techniques. Since LDL-apheresis has multidisciplinary treatment indications, the agreement on the new guidelines was reached through a panel of experts, of different medical and surgical specialties, with scientific and medical interest in the treatment indications, application and development of LDL-apheresis. The initiatives of the IMSLDLa-WP led to the 2nd Italian Consensus Conference on LDL-apheresis held in Rome in 2009. The previous and most recent guidelines are reported here synoptically. PMID:27416576

  9. Establishment of the 1st World Health Organization International Standard for Plasmodium falciparum DNA for nucleic acid amplification technique (NAT)-based assays

    PubMed Central

    Padley, David J; Heath, Alan B; Sutherland, Colin; Chiodini, Peter L; Baylis, Sally A

    2008-01-01

    Background In order to harmonize results for the detection and quantification of Plasmodium falciparum DNA by nucleic acid amplification technique (NAT)-based assays, a World Health Organization (WHO) collaborative study was performed, evaluating a series of candidate standard preparations. Methods Fourteen laboratories from 10 different countries participated in the collaborative study. Four candidate preparations based upon blood samples parasitaemic for P. falciparum were evaluated in the study. Sample AA was lyophilized, whilst samples BB, CC and DD were liquid/frozen preparations. The candidate standards were tested by each laboratory at a range of dilutions in four independent assays, using both qualitative and quantitative NAT-based assays. The results were collated and analysed statistically. Results Twenty sets of data were returned from the participating laboratories and used to determine the mean P. falciparum DNA content for each sample. The mean log10 "equivalents"/ml were 8.51 for sample AA, 8.45 for sample BB, 8.35 for sample CC, and 5.51 for sample DD. The freeze-dried preparation AA, was examined by accelerated thermal degradation studies and found to be highly stable. Conclusion On the basis of the collaborative study, the freeze-dried material, AA (NIBSC code No. 04/176) was established as the 1st WHO International Standard for P. falciparum DNA NAT-based assays and has been assigned a potency of 109 International Units (IU) per ml. Each vial contains 5 × 108 IU, equivalent to 0.5 ml of material after reconstitution. PMID:18652656

  10. Practice of use of antiemetic in patients for laparoscopic gynaecological surgery and its impact on the early (1st two hrs) postoperative period.

    PubMed

    Ismail, Samina

    2008-04-01

    There is no agreed technique for minimizing PONV (Postoperative Nausea and Vomiting) although some techniques are associated with low rate. Best practice involves identifying high risk patients and surgeries and use of prophylactic antiemetic where appropriate. Laparoscopic gynaecological surgery has high incidence of PONV (54-92%). An audit on the practice of antiemetic use in diagnostic laparoscopic gynaecological surgery was done in the department of anaesthesia of Aga Khan University Hospital from 1st January to 30th June 2006. We included all the patients scheduled for this procedure lasting less than 90 minutes. Anaesthetist involved in the audit identified the patient falling into the predetermined risk factors. The following facts about antiemetic were noted; whether the patients received any antiemetics or not, if it was prophylactic or rescue, type, dose route and timing of antiemetic. Patients were rated for any signs of nausea and vomiting (retching) after extubation in the operating room by the anaesthetist and in the recovery room or surgical day care unit (SDC) by the nurse who was briefed about it and was cross checked by the anaesthetist involved in the audit. This was done for two hours postoperatively. Our results showed that only 75% of patients with risk factors received an antiemetic. The most commonly used antiemetic was Metoclopramide. Eight percent of the patients had vomiting and all of them had received a prophylactic antiemetic. They received the same rescue antiemetic. This audit recommended institutional guidelines for the management of PONV. These should be based on evidence obtained from the published peer-reviewed studies. These guidelines could be communicated to health care workers involved in postoperative management of patients to help them achieve an optimal management strategy for this uncomfortable postoperative complication.

  11. PREFACE: 1st International Workshop on Theoretical and Computational Physics: Condensed Matter, Soft Matter and Materials Physics & 38th National Conference on Theoretical Physics

    NASA Astrophysics Data System (ADS)

    2014-09-01

    This volume contains selected papers presented at the 38th National Conference on Theoretical Physics (NCTP-38) and the 1st International Workshop on Theoretical and Computational Physics: Condensed Matter, Soft Matter and Materials Physics (IWTCP-1). Both the conference and the workshop were held from 29 July to 1 August 2013 in Pullman hotel, Da Nang, Vietnam. The IWTCP-1 was a new activity of the Vietnamese Theoretical Physics Society (VTPS) organized in association with the 38th National Conference on Theoretical Physics (NCTP-38), the most well-known annual scientific forum dedicated to the dissemination of the latest development in the field of theoretical physics within the country. The IWTCP-1 was also an External Activity of the Asia Pacific Center for Theoretical Physics (APCTP). The overriding goal of the IWTCP is to provide an international forum for scientists and engineers from academia to share ideas, problems and solution relating to the recent advances in theoretical physics as well as in computational physics. The main IWTCP motivation is to foster scientific exchanges between the Vietnamese theoretical and computational physics community and world-wide scientists as well as to promote high-standard level of research and education activities for young physicists in the country. About 110 participants coming from 10 countries participated in the conference and the workshop. 4 invited talks, 18 oral contributions and 46 posters were presented at the conference. In the workshop we had one keynote lecture and 9 invited talks presented by international experts in the fields of theoretical and computational physics, together with 14 oral and 33 poster contributions. The proceedings were edited by Nguyen Tri Lan, Trinh Xuan Hoang, and Nguyen Ai Viet. We would like to thank all invited speakers, participants and sponsors for making the conference and the workshop successful. Nguyen Ai Viet Chair of NCTP-38 and IWTCP-1

  12. Supporting UK adaptation: building services for the next set of UK climate projections

    NASA Astrophysics Data System (ADS)

    Fung, Fai; Lowe, Jason

    2016-04-01

    As part of the Climate Change Act 2008, the UK Government sets out a national adaptation programme to address the risks and opportunities identified in a national climate change risk assessment (CCRA) every five years. The last risk assessment in 2012 was based on the probabilistic projections for the UK published in 2009 (UKCP09). The second risk assessment will also use information from UKCP09 alongside other evidence on climate projections. However, developments in the science of climate projeciton, and evolving user needs (based partly on what has been learnt about the diverse user requirements of the UK adaptation community from the seven years of delivering and managing UKCP09 products, market research and the peer-reviewed literature) suggest now is an appropriate time to update the projections and how they are delivered. A new set of UK climate projections are now being produced to upgrade UKCP09 to reflect the latest developments in climate science, the first phase of which will be delivered in 2018 to support the third CCRA. A major component of the work is the building of a tailored service to support users of the new projections during their development and to involve users in key decisions so that the projections are of most use. We will set out the plan for the new climate projections that seek to address the evolving user need. We will also present a framework which aims to (i) facilitate the dialogue between users, boundary organisations and producers, reflecting their different decision-making roles (ii) produce scientifically robust, user-relevant climate information (iii) provide the building blocks for developing further climate services to support adaptation activities in the UK.

  13. Characterising Cold Weather for the UK mainland

    NASA Astrophysics Data System (ADS)

    Fradley, Kate; Dacre, Helen; Ambaum, Maarten

    2016-04-01

    Excess Winter Mortality is a peak in the population's mortality rate during winter months and is correlated with low outdoor temperatures. Excess Winter Mortality has adverse impacts, including increased demand on health services. The management of resources for such increased demands maybe improved through incorporation of weather forecasting information to advanced warnings. For the UK, prolonged cold periods are associated with easterly advection, and high pressure systems. Characterisation of the synoptic conditions associated with cold periods is important to understand forecast performance. Principal Component Analysis has been used with mean sea level pressure from 35 years of ERA interim reanalysis to capture synoptic variability on a continuous scale. Cold events in the North and South of the UK mainland have been identified as having different synoptic variability using this method. Furthermore extending the Principal Component Analysis to investigate the skill of forecasts has identified systematic under prediction of some cold weather synoptic conditions. Ensemble forecasts are used to quantify the uncertainty associated with these cold weather synoptic conditions. This information maybe be used to improve the value of existing weather warnings.

  14. Underwater noise levels in UK waters

    NASA Astrophysics Data System (ADS)

    Merchant, Nathan D.; Brookes, Kate L.; Faulkner, Rebecca C.; Bicknell, Anthony W. J.; Godley, Brendan J.; Witt, Matthew J.

    2016-11-01

    Underwater noise from human activities appears to be rising, with ramifications for acoustically sensitive marine organisms and the functioning of marine ecosystems. Policymakers are beginning to address the risk of ecological impact, but are constrained by a lack of data on current and historic noise levels. Here, we present the first nationally coordinated effort to quantify underwater noise levels, in support of UK policy objectives under the EU Marine Strategy Framework Directive (MSFD). Field measurements were made during 2013–2014 at twelve sites around the UK. Median noise levels ranged from 81.5–95.5 dB re 1 μPa for one-third octave bands from 63–500 Hz. Noise exposure varied considerably, with little anthropogenic influence at the Celtic Sea site, to several North Sea sites with persistent vessel noise. Comparison of acoustic metrics found that the RMS level (conventionally used to represent the mean) was highly skewed by outliers, exceeding the 97th percentile at some frequencies. We conclude that environmental indicators of anthropogenic noise should instead use percentiles, to ensure statistical robustness. Power analysis indicated that at least three decades of continuous monitoring would be required to detect trends of similar magnitude to historic rises in noise levels observed in the Northeast Pacific.

  15. Refugee blues: a UK and European perspective

    PubMed Central

    Turner, Stuart

    2015-01-01

    In this paper, the numbers of refugees travelling to the European Union are set in a global context. It is argued that the increasing restrictions placed on asylum seekers from the 1980s onwards in the UK and the associated culture of deterrence and prohibition have had the perverse effect of supporting the economic market for people smuggling. It appears that these restrictions were initially designed to deter people, most of whom would have been granted humanitarian assistance had they managed to arrive in the UK, so as to prevent them from accessing the decision-making process on asylum. Policy changes concerning travel, benefits, and other pressures on asylum seekers are also considered in the context of deterrence. The problems facing asylum seekers do not end with their arrival in a safe country. The current methods of determining refugee status are alarmingly weak. Indeed there is evidence suggesting that those who are most traumatised before arrival face systematic disadvantage. The focus of this paper is on the United Kingdom but its conclusions apply to most Western European countries. The paper concludes with some tentative suggestions for change. PMID:26514159

  16. Teaching fellowships for UK foundation doctors.

    PubMed

    Qureshi, Shaun

    2015-01-01

    Teaching Fellowships for junior doctors in their second post-graduate (FY2) year should be considered by medical students and junior doctors in UK. FY2 Teaching Fellowships are available in many foundation schools as part of the UK Academic Foundation Programme. Although programme structures differ between schools, they are designed to allow junior trainees to take time out from clinical practice to develop their teaching skills and gain insights into medication education careers. The advantages of an FY2 teaching fellowship include valuable experience of teaching and formal feedback not available to other trainees; the opportunity to further develop your portfolio; further development of the trainee's own knowledge and skills; the stimulation of working with students. Potential drawbacks to be considered are reduced direct clinical contact; reduced salary; difficulty carrying out education research in the allocated time frame; occasional difficulties establishing the teacher-student relationship while the trainee is at a relatively junior level. Experience of medical education as an FY2 trainee provides a helpful stepping stone whether or not the trainee further pursues education as a career, because the teaching skills are transferable to any specialty, and the unique experience enhances the trainee's confidence as a role model for junior colleagues.

  17. Low background screening capability in the UK

    SciTech Connect

    Ghag, Chamkaur

    2015-08-17

    Low background rare event searches in underground laboratories seeking observation of direct dark matter interactions or neutrino-less double beta decay have the potential to profoundly advance our understanding of the physical universe. Successful results from these experiments depend critically on construction from extremely radiologically clean materials and accurate knowledge of subsequent low levels of expected background. The experiments must conduct comprehensive screening campaigns to reduce radioactivity from detector components, and these measurements also inform detailed characterisation and quantification of background sources and their impact, necessary to assign statistical significance to any potential discovery. To provide requisite sensitivity for material screening and characterisation in the UK to support our rare event search activities, we have re-developed our infrastructure to add ultra-low background capability across a range of complementary techniques that collectively allow complete radioactivity measurements. Ultra-low background HPGe and BEGe detectors have been installed at the Boulby Underground Laboratory, itself undergoing substantial facility re-furbishment, to provide high sensitivity gamma spectroscopy in particular for measuring the uranium and thorium decay series products. Dedicated low-activity mass spectrometry instrumentation has been developed at UCL for part per trillion level contaminant identification to complement underground screening with direct U and Th measurements, and meet throughput demands. Finally, radon emanation screening at UCL measures radon background inaccessible to gamma or mass spectrometry techniques. With this new capability the UK is delivering half of the radioactivity screening for the LZ dark matter search experiment.

  18. Underwater noise levels in UK waters.

    PubMed

    Merchant, Nathan D; Brookes, Kate L; Faulkner, Rebecca C; Bicknell, Anthony W J; Godley, Brendan J; Witt, Matthew J

    2016-11-10

    Underwater noise from human activities appears to be rising, with ramifications for acoustically sensitive marine organisms and the functioning of marine ecosystems. Policymakers are beginning to address the risk of ecological impact, but are constrained by a lack of data on current and historic noise levels. Here, we present the first nationally coordinated effort to quantify underwater noise levels, in support of UK policy objectives under the EU Marine Strategy Framework Directive (MSFD). Field measurements were made during 2013-2014 at twelve sites around the UK. Median noise levels ranged from 81.5-95.5 dB re 1 μPa for one-third octave bands from 63-500 Hz. Noise exposure varied considerably, with little anthropogenic influence at the Celtic Sea site, to several North Sea sites with persistent vessel noise. Comparison of acoustic metrics found that the RMS level (conventionally used to represent the mean) was highly skewed by outliers, exceeding the 97(th) percentile at some frequencies. We conclude that environmental indicators of anthropogenic noise should instead use percentiles, to ensure statistical robustness. Power analysis indicated that at least three decades of continuous monitoring would be required to detect trends of similar magnitude to historic rises in noise levels observed in the Northeast Pacific.

  19. Assisted reproductive travel: UK patient trajectories.

    PubMed

    Hudson, Nicky; Culley, Lorraine

    2011-11-01

    Media reporting of 'fertility tourism' tends to portray those who travel as a cohesive group, marked by their desperation and/or selfishness and propensity towards morally questionable behaviour. However, to date little has been known about the profile of those leaving the UK for treatment. This paper discusses the first UK-based study of patient assisted reproduction travel that was designed to explore individual travel trajectories. It is argued that existing ways of conceptualizing cross-border reproductive care as 'fertility or reproductive tourism' are in danger of essentializing what the data suggest are diverse, complex and often ambiguous motivations for reproductive travel. The concept of seriality is used to suggest that, whilst 'reproductive tourists' share some characteristics, they also differ in significant ways. This paper argues that, through an examination of the personal landscapes of fertility travel, the diverse processes involved in reproductive travel can be better understood and policymakers can be assisted to avoid what might be regarded as simplistic responses to cross-border reproductive care.

  20. Strategic marketing in the UK tobacco industry.

    PubMed

    Anderson, Susan; Hastings, Gerard; MacFadyen, Lynn

    2002-08-01

    Tobacco-industry marketing has played a central part in the global spread of tobacco use and addiction. Although the absolute size of the tobacco market has dwindled, the industry is still immensely successful, largely due to sophisticated and manipulative marketing strategies. The UK tobacco industry identifies target groups and builds enduring relationships based on careful brand management. Potential customers are exposed to brands which are likely to appeal to them most. Tobacco companies tailor their products to target markets by altering the content of tar and nicotine, and by adding flavourings to produce a distinctive taste. Marketing strategies ensure that the products are promoted heavily at the point of sale, and directed advertising and sponsorship agreements are used to increase the visibility of the brand and strengthen its image. Tobacco companies also target non-consumer organisations such as retailers and policy makers with the aim of creating the best possible business environment for tobacco sales. We review published evidence, internal-advertising-agency documents, and observational data about tobacco promotion, and discuss the use of targeted marketing strategies in the UK.

  1. Underwater noise levels in UK waters

    PubMed Central

    Merchant, Nathan D.; Brookes, Kate L.; Faulkner, Rebecca C.; Bicknell, Anthony W. J.; Godley, Brendan J.; Witt, Matthew J.

    2016-01-01

    Underwater noise from human activities appears to be rising, with ramifications for acoustically sensitive marine organisms and the functioning of marine ecosystems. Policymakers are beginning to address the risk of ecological impact, but are constrained by a lack of data on current and historic noise levels. Here, we present the first nationally coordinated effort to quantify underwater noise levels, in support of UK policy objectives under the EU Marine Strategy Framework Directive (MSFD). Field measurements were made during 2013–2014 at twelve sites around the UK. Median noise levels ranged from 81.5–95.5 dB re 1 μPa for one-third octave bands from 63–500 Hz. Noise exposure varied considerably, with little anthropogenic influence at the Celtic Sea site, to several North Sea sites with persistent vessel noise. Comparison of acoustic metrics found that the RMS level (conventionally used to represent the mean) was highly skewed by outliers, exceeding the 97th percentile at some frequencies. We conclude that environmental indicators of anthropogenic noise should instead use percentiles, to ensure statistical robustness. Power analysis indicated that at least three decades of continuous monitoring would be required to detect trends of similar magnitude to historic rises in noise levels observed in the Northeast Pacific. PMID:27830837

  2. Refugee blues: a UK and European perspective.

    PubMed

    Turner, Stuart

    2015-01-01

    In this paper, the numbers of refugees travelling to the European Union are set in a global context. It is argued that the increasing restrictions placed on asylum seekers from the 1980s onwards in the UK and the associated culture of deterrence and prohibition have had the perverse effect of supporting the economic market for people smuggling. It appears that these restrictions were initially designed to deter people, most of whom would have been granted humanitarian assistance had they managed to arrive in the UK, so as to prevent them from accessing the decision-making process on asylum. Policy changes concerning travel, benefits, and other pressures on asylum seekers are also considered in the context of deterrence. The problems facing asylum seekers do not end with their arrival in a safe country. The current methods of determining refugee status are alarmingly weak. Indeed there is evidence suggesting that those who are most traumatised before arrival face systematic disadvantage. The focus of this paper is on the United Kingdom but its conclusions apply to most Western European countries. The paper concludes with some tentative suggestions for change.

  3. Customer privacy on UK healthcare websites.

    PubMed

    Mundy, Darren P

    2006-09-01

    Privacy has been and continues to be one of the key challenges of an age devoted to the accumulation, processing, and mining of electronic information. In particular, privacy of healthcare-related information is seen as a key issue as health organizations move towards the electronic provision of services. The aim of the research detailed in this paper has been to analyse privacy policies on popular UK healthcare-related websites to determine the extent to which consumer privacy is protected. The author has combined approaches (such as approaches focused on usability, policy content, and policy quality) used in studies by other researchers on e-commerce and US healthcare websites to provide a comprehensive analysis of UK healthcare privacy policies. The author identifies a wide range of issues related to the protection of consumer privacy through his research analysis using quantitative results. The main outcomes from the author's research are that only 61% of healthcare-related websites in their sample group posted privacy policies. In addition, most of the posted privacy policies had poor readability standards and included a variety of privacy vulnerability statements. Overall, the author's findings represent significant current issues in relation to healthcare information protection on the Internet. The hope is that raising awareness of these results will drive forward changes in the industry, similar to those experienced with information quality.

  4. Synthesis and structure-activity relationships of 2-substituted-6-(dimethylamino)-9-(4-methylbenzyl)-9H-purines with antirhinovirus activity.

    PubMed

    Kelley, J L; Linn, J A; Selway, J W

    1989-01-01

    A series of 2-substituted-6-(dimethylamino)-9-(4-methylbenzyl)-9H-purines where the 2-substituent was H, F, Cl, CF3, CH3, CH2CH3, NH2, NHCH3, N(CH3)2, SCH3, or SO2CH3 was synthesized and tested for antirhinovirus activity to evaluate the effect of 2-substituents on antiviral activity. Intuitive and quantitative structure-activity relationship (QSAR) analysis showed that optimum antirhinovirus serotype 1B activity was associated with 9-benzylpurines that contained a C-2 lipophilic, electron-withdrawing substituent. The most active compound, 6-(dimethylamino)-9-(4-methylbenzyl)-2-(trifluoromethyl)-9H-purine (14), had an IC50 = 0.03 microM against serotype 1B, but its activity against 18 other serotypes was not uniform; the IC50s ranged over 260-fold.

  5. The immunosuppressives FK 506 and cyclosporin A inhibit the generation of protein factors binding to the two purine boxes of the interleukin 2 enhancer.

    PubMed Central

    Brabletz, T; Pietrowski, I; Serfling, E

    1991-01-01

    Like Cyclosporin A (CsA), the macrolide FK 506 is a potent immunosuppressive that inhibits early steps of T cell activation, including the synthesis of Interleukin 2 (II-2) and numerous other lymphokines. The block of II-2 synthesis occurs at the transcriptional level. At concentrations that block T cell activation, FK 506 and CsA inhibit the proto-enhancer activity of Purine boxes of the II-2 promoter and the generation of lymphocyte-specific factors binding to the Purine boxes. Under the same conditions, the DNA binding of other II-2 enhancer factors remains unaffected by both compounds. These results support the view that FK 506 and CsA, which both inhibit the activity of peptidylprolyl cis/trans isomerases, suppress T cell activation by a similar, if not identical mechanism. Images PMID:1707162

  6. X-ray structure, NMR and stability-in-solution study of 6-(furfurylamino)-9-(tetrahydropyran-2-yl)purine - A new active compound for cosmetology

    NASA Astrophysics Data System (ADS)

    Walla, Jan; Szüčová, Lucie; Císařová, Ivana; Gucký, Tomáš; Zatloukal, Marek; Doležal, Karel; Greplová, Jarmila; Massino, Frank J.; Strnad, Miroslav

    2010-06-01

    The crystal and molecular structure of 6-(furfurylamino)-9-(tetrahydropyran-2-yl)purine ( 1) was determined at 150(2) K. The compound crystallizes in monoclinic P2 1/ c space group with a = 10.5642(2), b = 13.6174(3), c = 10.3742(2) Å, V = 1460.78(5) Å 3, Z = 4, R( F) = for 3344 unique reflections. The purine moiety and furfuryl ring are planar and the tetrahydropyran-2-yl is disordered in the ratio 1:3, probably due to the chiral carbon atom C(17). The individual 1H and 13C NMR signals were assigned by 2D correlation experiments such as 1H- 1H COSY and ge-2D HSQC. Stability-in-solution was determined in methanol/water in acidic pH (3-7).

  7. Crystal structure of disodium 2-amino-6-oxo-6,7-di-hydro-1H-purine-1,7-diide hepta-hydrate.

    PubMed

    Gur, Dvir; Shimon, Linda J W

    2015-03-01

    In the title compound, disodium 2-amino-6-oxo-6,7-di-hydro-1H-purine-1,7-diide hepta-hydrate, 2Na(+)·C5H3N5O(2-)·7H2O, the structure is composed of alternating (100) layers of guanine mol-ecules and hydrated Na(+) ions. Within the guanine layer, the mol-ecules are arranged in centrosymmetric pairs, with a partial overlap between the guanine rings. In this compound, guanine exists as the amino-keto tautomer from which deprotonation from N1 and N7 has occurred (purine numbering). There are no direct inter-actions between the Na(+) cations and the guanine anions. Guanine mol-ecules are linked to neighboring water mol-ecules by O-H⋯N and O-H⋯O hydrogen bonds into a network structure.

  8. Purine and folate metabolism as a potential target of sex-specific nutrient allocation in Drosophila and its implication for lifespan-reproduction tradeoff.

    PubMed

    Bauer, Matthias; Katzenberger, Jörg D; Hamm, Anne C; Bonaus, Melanie; Zinke, Ingo; Jaekel, Jens; Pankratz, Michael J

    2006-05-16

    The reallocation of metabolic resources is important for survival during periods of limited nutrient intake. This has an influence on diverse physiological processes, including reproduction, repair, and aging. One important aspect of resource allocation is the difference between males and females in response to nutrient stress. We identified several groups of genes that are regulated in a sex-biased manner under complete or protein starvation. These range from expected differences in genes involved in reproductive physiology to those involved in amino acid utilization, sensory perception, immune response, and growth control. A striking difference was observed in purine and the tightly interconnected folate metabolism upon protein starvation. From these results, we conclude that the purine and folate metabolic pathway is a major point of transcriptional regulation during resource allocation and may have relevance for understanding the physiological basis for the observed tradeoff between reproduction and longevity.

  9. In Vitro Ligation of Oligodeoxynucleotides Containing C8-Oxidized Purine Lesions using Bacteriophage T4 DNA Ligase†

    PubMed Central

    Zhao, Xiaobei; Muller, James G.; Halasyam, Mohan; David, Sheila S.; Burrows, Cynthia J.

    2008-01-01

    Ligases conduct the final stage of repair of DNA damage by sealing a single-stranded nick after excision of damaged nucleotides and reinsertion of correct nucleotides. Depending upon the circumstances and the success of the repair process, lesions may remain at the ligation site, either in the template or at the oligomer termini to be joined. Ligation experiments using bacteriophage T4 DNA ligase were carried out with purine lesions in four positions surrounding the nick site in a total of 96 different duplexes. The oxidized lesion 8-oxo-7,8-dihydroguanosine (OG) showed, as expected, that the enzyme is most sensitive to lesions on the 3′ end of the nick compared to the 5′ end and to lesions located in the intact template strand. In general, substrates containing the OG·A mismatch were more readily ligated than OG·C. Ligations of duplexes containing the OA·T base pair (OA=8-oxo-7,8- dihydroadenosine) that could adopt an anti-anti conformation proceeded in high efficiencies. An OI·Acontaining duplex (OI = 8-oxo-7,8-dihydroinosine) behaved similarly to OG·A. Due to its low reduction potential, OG is readily oxidized to secondary oxidation products, such as the guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp) nucleosides; these lesions also contain an oxo group at the original C8 position of the purine. Ligation of oligomers containing Gh and Sp occurred when opposite A and G although the overall ligation efficiencies were much lower than most OG base pairs. Steady-state kinetic studies were carried out for representative examples of lesions in the template. Km increased by 90–100-fold for OG·C, OI·C, OI·A and OA·T containing duplexes compared to G·C. Substrates containing Gh·A, Gh·G, Sp·A and Sp·G base pairs showed Km values 20–70-fold higher than G·C while the Km value for OG·A was 5 times lower than G·C. PMID:17323928

  10. Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: involvement of adenosine and dopamine receptors.

    PubMed

    Feduccia, Allison A; Wang, Yuanyuan; Simms, Jeffrey A; Yi, Henry Y; Li, Rui; Bjeldanes, Leonard; Ye, Chuangxing; Bartlett, Selena E

    2012-08-01

    Purine compounds, such as caffeine, have many health-promoting properties and have proven to be beneficial in treating a number of different conditions. Theacrine, a purine alkaloid structurally similar to caffeine and abundantly present in Camellia kucha, has recently become of interest as a potential therapeutic compound. In the present study, theacrine was tested using a rodent behavioral model to investigate the effects of the drug on locomotor activity. Long Evans rats were injected with theacrine (24 or 48 mg/kg, i.p.) and activity levels were measured. Results showed that the highest dose of theacrine (48 mg/kg, i.p.) significantly increased locomotor activity compared to control animals and activity remained elevated throughout the duration of the session. To test for the involvement of adenosine receptors underlying theacrine's motor-activating properties, rats were administered a cocktail of the adenosine A₁ agonist, N⁶-cyclopentyladenosine (CPA; 0.1 mg/kg, i.p.) and A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680; 0.2 mg/kg, i.p.). Pre-treatment with theacrine significantly attenuated the motor depression induced by the adenosine receptor agonists, indicating that theacrine is likely acting as an adenosine receptor antagonist. Next, we examined the role of DA D₁ and D₂ receptor antagonism on theacrine-induced hyperlocomotion. Both antagonists, D₁R SCH23390 (0.1 or 0.05 mg/kg, i.p.) and D₂R eticlopride (0.1 mg/kg, i.p.), significantly reduced theacrine-stimulated activity indicating that this behavioral response, at least in part, is mediated by DA receptors. In order to investigate the brain region where theacrine may be acting, the drug (10 or 20 μg) was infused bilaterally into nucleus accumbens (NAc). Theacrine enhanced activity levels in a dose-dependent manner, implicating a role of the NAc in modulating theacrine's effects on locomotion. In addition, theacrine did not induce locomotor

  11. Synthesis and antirhinovirus activity of 8-substituted analogues of 6-(dimethylamino)-9-(4-methylbenzyl)-2-(trifluoromethyl)-9H-purine.

    PubMed

    Kelley, J L; Linn, J A; Selway, J W

    1991-01-01

    Several 8-substituted analogues of 6-(dimethylamino) -9-(4-methylbenzyl)-2-(trifluoromethyl)-9H-purine (1) were synthesized and tested for activity against rhinovirus type 1B. Among 16 8-substituted analogues, the 8-amino (3) and 8-bromo (2) analogues were most active with IC50s of 0.36 and 1.4 microM, respectively, under conditions where 1 had an IC50 of 0.03 microM.

  12. Theoretical and experimental studies on the corrosion inhibition potentials of some purines for aluminum in 0.1 M HCl

    PubMed Central

    Eddy, Nnabuk O.; Momoh-Yahaya, H.; Oguzie, Emeka E.

    2014-01-01

    Experimental aspect of the corrosion inhibition potential of adenine (AD), guanine (GU) and, hypoxanthine (HYP) was carried out using weight loss, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) methods while the theoretical aspect of the work was carried out by calculations of semi-empirical parameters (for AM1, MNDO, CNDO, PM3 and RM1 Hamiltonians), Fukui functions and inhibitor–metal interaction energies. Results obtained from the experimental studies were in good agreement and indicated that adenine (AD), guanine (GU) and hypoxanthine (HYP) are good adsorption inhibitors for the corrosion of aluminum in solutions of HCl. Data obtained from electrochemical experiment revealed that the studied purines functioned by adsorption on the aluminum/HCl interface and inhibited the cathodic half reaction to a greater extent and anodic half reaction to a lesser extent. The adsorption of the purines on the metal surface was found to be exothermic and spontaneous. Deviation of the adsorption characteristics of the studied purines from the Langmuir adsorption model was compensated by the fitness of Flory Huggins and El Awardy et al. adsorption models. Quantum chemical studies revealed that the experimental inhibition efficiencies of the studied purines are functions of some quantum chemical parameters including total energy of the molecules (TE), energy gap (EL–H), electronic energy of the molecule (EE), dipole moment and core–core repulsion energy (CCR). Fukui functions analysis through DFT and MP2 theories indicated slight complications and unphysical results. However, results obtained from calculated Huckel charges, molecular orbital and interaction energies, the adsorption of the inhibitors proceeded through the imine nitrogen (N5) in GU, emanine nitrogen (N7) in AD and the pyridine nitrogen (N5) in HPY. PMID:25750754

  13. Theoretical and experimental studies on the corrosion inhibition potentials of some purines for aluminum in 0.1 M HCl.

    PubMed

    Eddy, Nnabuk O; Momoh-Yahaya, H; Oguzie, Emeka E

    2015-03-01

    Experimental aspect of the corrosion inhibition potential of adenine (AD), guanine (GU) and, hypoxanthine (HYP) was carried out using weight loss, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) methods while the theoretical aspect of the work was carried out by calculations of semi-empirical parameters (for AM1, MNDO, CNDO, PM3 and RM1 Hamiltonians), Fukui functions and inhibitor-metal interaction energies. Results obtained from the experimental studies were in good agreement and indicated that adenine (AD), guanine (GU) and hypoxanthine (HYP) are good adsorption inhibitors for the corrosion of aluminum in solutions of HCl. Data obtained from electrochemical experiment revealed that the studied purines functioned by adsorption on the aluminum/HCl interface and inhibited the cathodic half reaction to a greater extent and anodic half reaction to a lesser extent. The adsorption of the purines on the metal surface was found to be exothermic and spontaneous. Deviation of the adsorption characteristics of the studied purines from the Langmuir adsorption model was compensated by the fitness of Flory Huggins and El Awardy et al. adsorption models. Quantum chemical studies revealed that the experimental inhibition efficiencies of the studied purines are functions of some quantum chemical parameters including total energy of the molecules (TE), energy gap (E L-H), electronic energy of the molecule (EE), dipole moment and core-core repulsion energy (CCR). Fukui functions analysis through DFT and MP2 theories indicated slight complications and unphysical results. However, results obtained from calculated Huckel charges, molecular orbital and interaction energies, the adsorption of the inhibitors proceeded through the imine nitrogen (N5) in GU, emanine nitrogen (N7) in AD and the pyridine nitrogen (N5) in HPY.

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

    PubMed

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

    2009-01-02

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

  15. Evaluation of effects of bivalent cations on the formation of purine-rich triple-helix DNA by ESI-FT-MS.

    PubMed

    Wan, Cuihong; Cui, Meng; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

    2009-07-01

    The GGA triplet repeats are widely dispersed throughout eukaryotic genomes. (GGA)n or (GGT)n oligonucleotides can interact with double-stranded DNA containing (GGA:CCT)n to form triple-stranded DNA. The effects of 8 divalent metal ions (3 alkaline-earth metals and 5 transition metals) on formation of these purine-rich triple-helix DNA were investigated by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FT-MS). In the absence of metal ions, no triplex but single-strand, duplex, and purine homodimer ions were observed in mass spectra. The triple-helix DNA complexes were observed only in the presence of certain divalent ions. The effects of different divalent cations on the formation of purine-rich triplexes were compared. Transition-metal ions, especially Co(2+) and Ni(2+), significantly boost the formation of triple-helix DNA, whereas alkaline-earth metal ions have no positive effects on triplex formation. In addition, Ba(2+) is notably beneficial to the formation of homodimer instead of triplex.

  16. A nuclear factor that binds purine-rich, single-stranded oligonucleotides derived from S1-sensitive elements upstream of the CFTR gene and the MUC1 gene.

    PubMed Central

    Hollingsworth, M A; Closken, C; Harris, A; McDonald, C D; Pahwa, G S; Maher, L J

    1994-01-01

    We have identified two regions of non-random purine/pyrimidine strand asymmetry that were nearly identical in sequence in the 5' flanking (promoter) regions of the human cystic fibrosis transmembrane conductance regulator (CFTR) gene and the human MUC1 gene. These regions contain perfect mirror repeat elements, a sequence motif previously found to be associated with the formation of H-DNA conformations. In this report we demonstrate that a single-stranded non-B DNA conformation exists at low pH in supercoiled plasmids containing the similar mirror repeat elements, and that S1 nuclease digestion maps the single-stranded region to the position of the mirror repeats. In addition, we identify a nuclear protein of approximately 27 kD that binds to single-stranded oligonucleotides corresponding to the purine-rich strand of this region, but not to the pyrimidine-rich strands or to double-stranded oligonucleotides with corresponding purine/pyrimidine strand asymmetry. Images PMID:7513081

  17. Nitrogen K-edge X-ray absorption near edge structure (XANES) spectra of purine-containing nucleotides in aqueous solution

    SciTech Connect

    Shimada, Hiroyuki; Fukao, Taishi; Minami, Hirotake; Ukai, Masatoshi; Fujii, Kentaro; Yokoya, Akinari; Fukuda, Yoshihiro; Saitoh, Yuji

    2014-08-07

    The N K-edge X-ray absorption near edge structure (XANES) spectra of the purine-containing nucleotide, guanosine 5{sup ′}-monophosphate (GMP), in aqueous solution are measured under various pH conditions. The spectra show characteristic peaks, which originate from resonant excitations of N 1s electrons to π* orbitals inside the guanine moiety of GMP. The relative intensities of these peaks depend on the pH values of the solution. The pH dependence is explained by the core-level shift of N atoms at specific sites caused by protonation and deprotonation. The experimental spectra are compared with theoretical spectra calculated by using density functional theory for GMP and the other purine-containing nucleotides, adenosine 5{sup ′}-monophosphate, and adenosine 5{sup ′}-triphosphate. The N K-edge XANES spectra for all of these nucleotides are classified by the numbers of N atoms with particular chemical bonding characteristics in the purine moiety.

  18. Influence of experimental canine ehrlichiosis on the E-ADA activity and purine levels in serum and possible functional correlations with pathogenesis.

    PubMed

    Da Silva, Aleksandro S; Munhoz, Thiago D; Faria, Joice L M; Vargas-Hérnandez, Giovanni; Machado, Rosangela Z; Luz, Nathalia C; Moritz, Cesar E J; Casali, Emerson A; Bottari, Nathieli B; Stefani, Lenita M; Tinucci-Costa, Mirela

    2013-10-25

    The aim of this study was to evaluate adenosine deaminase activity and purines levels in serum of dogs experimentally infected by Ehrlichia canis. Banked serum samples of dogs divided into two groups with five animals each: healthy animals and animals infected by E. canis. The concentration of purines (adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenosine, inosine, hypoxanthine, xanthine and uric acid), and adenosine deaminase (E-ADA) activity in sera were evaluated. Samples were collected on days 12 and 30 post-infection (PI). The E-ADA activity showed a significant reduction on day 12 PI, and increased on day 30 PI in dogs infected with E. canis. On day 12, an increase in seric concentration of ATP, ADP and adenosine was verified, and different levels of hypoxanthine, xanthine and uric acid had a drastic reduction in infected compared healthy dogs (P<0.05). However, on day 30 PI, the levels of seric ADP and AMP decreased, unlike the concentration of xanthine and uric acid that increased significantly in infected dogs (P<0.05). Therefore, the activity of E-ADA and purine levels are altered in experimental canine ehrlichiosis, probably with the purpose of modulating the pathogenesis of the disease related to immune response, oxidative stress and coagulation disorders in acute phase.

  19. Purine analogs sensitize the multidrug resistant cell line (NCI-H460/R) to doxorubicin and stimulate the cell growth inhibitory effect of verapamil.

    PubMed

    Pesić, Milica; Podolski, Ana; Rakić, Ljubisa; Ruzdijić, Sabera

    2010-08-01

    The resistant cell line NCI-H460/R and its counterpart NCI-H460 were used to investigate the ability of purine analogs to overcome multidrug resistance (MDR) that seriously limit the efficacy of lung cancer regimens with chemotherapeutic agents. Two purine analogs, sulfinosine (SF) and 8-Cl-cAMP, exerted dose-dependent effects on cell growth in both parental and resistant cell lines. They significantly decreased mdr1 expression in NCI-H460/R cells. Low concentrations (1 microM) of SF and 8-Cl-cAMP in combination with doxorubicin (DOX) exerted synergistic growth inhibition in both cell lines. Pretreatment with SF and 8-Cl-cAMP improved the sensitivity to DOX more than verapamil (VER), the standard modulator of MDR. The increased accumulation of DOX observed after the treatment with SF and 8-Cl-cAMP was consistent with the results obtained with VER. VER stimulated the effect of 8-Cl-cAMP on DOX cytotoxicity and mdr1 expression. Combinations of either SF or 8-Cl-cAMP with VER at clinically acceptable concentrations exhibited synergistic effects on cell growth inhibition in the resistant cell line. SF and 8-Cl-cAMP modulated MDR in NCI-H460/R cells, especially when applied before DOX administration. This feature, together with their ability to reverse MDR, renders the purine analogs (in combination with VER) as potential candidates for improving the clinical activity of existing lung cancer therapeutics.

  20. Mapping the Information Systems Curricula in UK Universities

    ERIC Educational Resources Information Center

    Stefanidis, Angelos; Fitzgerald, Guy

    2010-01-01

    Information Systems (IS) undergraduate student numbers in the UK have reduced by half in the last five years. An increasing number of researchers have been pondering the possible relationship between the modernity of IS curricula and its attractiveness to potential students. To support the debate about IS curricula in the UK and elsewhere, this…