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Sample records for discovered carbonic anhydrase

  1. Sulfonamide inhibition studies of the β-carbonic anhydrase from the newly discovered bacterium Enterobacter sp. B13.

    Science.gov (United States)

    Eminoğlu, Ayşenur; Vullo, Daniela; Aşık, Aycan; Çolak, Dilşat Nigar; Çanakçı, Sabriye; Beldüz, Ali Osman; Supuran, Claudiu T

    2016-04-01

    The genome of the newly identified bacterium Enterobacter sp. B13 encodes for a β-class carbonic anhydrases (CAs, EC 4.2.1.1), EspCA. This enzyme was recently cloned, and characterized kinetically by this group (J. Enzyme Inhib. Med. Chem. 2016, 31). Here we report an inhibition study with sulfonamides and sulfamates of this enzyme. The best EspCA inhibitors were some sulfanylated sulfonamides with elongated molecules, metanilamide, 4-aminoalkyl-benzenesulfonamides, acetazolamide, and deacetylated methazolamide (KIs in the range of 58.7-96.5nM). Clinically used agents such as methazolamide, ethoxzolamide, dorzolamide, brinzolamide, benzolamide, zonisamide, sulthiame, sulpiride, topiramate and valdecoxib were slightly less effective inhibitors (KIs in the range of 103-138nM). Saccharin, celecoxib, dichlorophenamide and many simple benzenesulfonamides were even less effective as EspCA inhibitors, with KIs in the range of 384-938nM. Identification of effective inhibitors of this bacterial enzyme may lead to pharmacological tools useful for understanding the physiological role(s) of the β-class CAs in bacterial pathogenicity/virulence. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Optimization of nutritional constituents for carbonic anhydrase ...

    African Journals Online (AJOL)

    Jane

    2011-08-08

    Aug 8, 2011 ... for the optimization of the culture media are to select the optimum .... Effect of different temperature on product of carbonic anhydrase. production, B. ... account that the enzyme is easy to inactivate under high temperature ...

  3. Thermostable Carbonic Anhydrases in Biotechnological Applications

    Directory of Open Access Journals (Sweden)

    Anna Di Fiore

    2015-07-01

    Full Text Available Carbonic anhydrases are ubiquitous metallo-enzymes which catalyze the reversible hydration of carbon dioxide in bicarbonate ions and protons. Recent years have seen an increasing interest in the utilization of these enzymes in CO2 capture and storage processes. However, since this use is greatly limited by the harsh conditions required in these processes, the employment of thermostable enzymes, both those isolated by thermophilic organisms and those obtained by protein engineering techniques, represents an interesting possibility. In this review we will provide an extensive description of the thermostable carbonic anhydrases so far reported and the main processes in which these enzymes have found an application.

  4. Regulation of Chloroplastic Carbonic Anhydrase 1

    Science.gov (United States)

    Porter, Michael A.; Grodzinski, Bernard

    1983-01-01

    It was previously reported that magnesium ion inhibited carbonic anhydrase (Bamberger and Avron 1975 Plant Physiol 56: 481-485). Studies with partially purified carbonic anhydrase from spinach (Spinacia oleracea L.) chloroplasts show that the effect was the result of the chloride counterion and not the magnesium ion. Enzyme activity was reduced 50% upon addition of 3 to 10 millimolar MgCl2 or KCl while all additions of MgSO4 between 0.3 and 10 millimolar were mildly stimulatory. PMID:16663052

  5. Coral Carbonic Anhydrases: Regulation by Ocean Acidification.

    Science.gov (United States)

    Zoccola, Didier; Innocenti, Alessio; Bertucci, Anthony; Tambutté, Eric; Supuran, Claudiu T; Tambutté, Sylvie

    2016-06-03

    Global change is a major threat to the oceans, as it implies temperature increase and acidification. Ocean acidification (OA) involving decreasing pH and changes in seawater carbonate chemistry challenges the capacity of corals to form their skeletons. Despite the large number of studies that have investigated how rates of calcification respond to ocean acidification scenarios, comparatively few studies tackle how ocean acidification impacts the physiological mechanisms that drive calcification itself. The aim of our paper was to determine how the carbonic anhydrases, which play a major role in calcification, are potentially regulated by ocean acidification. For this we measured the effect of pH on enzyme activity of two carbonic anhydrase isoforms that have been previously characterized in the scleractinian coral Stylophora pistillata. In addition we looked at gene expression of these enzymes in vivo. For both isoforms, our results show (1) a change in gene expression under OA (2) an effect of OA and temperature on carbonic anhydrase activity. We suggest that temperature increase could counterbalance the effect of OA on enzyme activity. Finally we point out that caution must, thus, be taken when interpreting transcriptomic data on carbonic anhydrases in ocean acidification and temperature stress experiments, as the effect of these stressors on the physiological function of CA will depend both on gene expression and enzyme activity.

  6. Coral Carbonic Anhydrases: Regulation by Ocean Acidification

    Directory of Open Access Journals (Sweden)

    Didier Zoccola

    2016-06-01

    Full Text Available Global change is a major threat to the oceans, as it implies temperature increase and acidification. Ocean acidification (OA involving decreasing pH and changes in seawater carbonate chemistry challenges the capacity of corals to form their skeletons. Despite the large number of studies that have investigated how rates of calcification respond to ocean acidification scenarios, comparatively few studies tackle how ocean acidification impacts the physiological mechanisms that drive calcification itself. The aim of our paper was to determine how the carbonic anhydrases, which play a major role in calcification, are potentially regulated by ocean acidification. For this we measured the effect of pH on enzyme activity of two carbonic anhydrase isoforms that have been previously characterized in the scleractinian coral Stylophora pistillata. In addition we looked at gene expression of these enzymes in vivo. For both isoforms, our results show (1 a change in gene expression under OA (2 an effect of OA and temperature on carbonic anhydrase activity. We suggest that temperature increase could counterbalance the effect of OA on enzyme activity. Finally we point out that caution must, thus, be taken when interpreting transcriptomic data on carbonic anhydrases in ocean acidification and temperature stress experiments, as the effect of these stressors on the physiological function of CA will depend both on gene expression and enzyme activity.

  7. Carborane-based inhibitors of carbonic anhydrases

    Czech Academy of Sciences Publication Activity Database

    Brynda, Jiří; Pachl, Petr; Šícha, Václav; Fábry, Milan; Grüner, Bohumír; Cígler, Petr; Řezáčová, Pavlína

    2015-01-01

    Roč. 22, č. 1 (2015), s. 3 ISSN 1211-5894. [Discussions in Structural Molecular Biology. Annual Meeting of the Czech Society for Structural Biology /13./. 19.03.2015-21.03.2015, Nové Hrady] R&D Projects: GA ČR GA15-05677S Institutional support: RVO:61388963 ; RVO:68378050 ; RVO:61388980 Keywords : carboranes * carbonic anhydrase Subject RIV: CE - Biochemistry

  8. Detecting Extracellular Carbonic Anhydrase Activity Using Membrane Inlet Mass Spectrometry

    Science.gov (United States)

    Delacruz, Joannalyn; Mikulski, Rose; Tu, Chingkuang; Li, Ying; Wang, Hai; Shiverick, Kathleen T.; Frost, Susan C.; Horenstein, Nicole A.; Silverman, David N.

    2010-01-01

    Current research into the function of carbonic anhydrases in cell physiology emphasizes the role of membrane-bound carbonic anhydrases, such as carbonic anhydrase IX that has been identified in malignant tumors and is associated with extracellular acidification as a response to hypoxia. We present here a mass spectrometric method to determine the extent to which total carbonic anhydrase activity is due to extracellular carbonic anhydrase in whole cell preparations. The method is based on the biphasic rate of depletion of 18O from CO2 measured by membrane inlet mass spectrometry. The slopes of the biphasic depletion are a sensitive measure of the presence of carbonic anhydrase outside and inside of the cells. This property is demonstrated here using suspensions of human red cells in which external carbonic anhydrase was added to the suspending solution. It is also applied to breast and prostate cancer cells which both express exofacial carbonic anhydrase IX. Inhibition of external carbonic anhydrase is achieved by use of a membrane impermeant inhibitor that was synthesized for this purpose, p-aminomethylbenzenesulfonamide attached to a polyethyleneglycol polymer. PMID:20417171

  9. Determination of activities of human carbonic anhydrase II inhibitors ...

    African Journals Online (AJOL)

    Purpose: To evaluate the activities of new curcumin analogs as carbonic anhydrase II (CA-II) inhibitor. Methods: Carbonic anhydrase II (CA-II) inhibition was determined by each ligand capability to inhibit the esterase activity of CA-II using 4-NPA as a substrate in 96-well plates. Dimethyl sulfoxide was used to dissolve each ...

  10. An Overview of the Bacterial Carbonic Anhydrases

    Directory of Open Access Journals (Sweden)

    Claudiu T. Supuran

    2017-11-01

    Full Text Available Bacteria encode carbonic anhydrases (CAs, EC 4.2.1.1 belonging to three different genetic families, the α-, β-, and γ-classes. By equilibrating CO2 and bicarbonate, these metalloenzymes interfere with pH regulation and other crucial physiological processes of these organisms. The detailed investigations of many such enzymes from pathogenic and non-pathogenic bacteria afford the opportunity to design both novel therapeutic agents, as well as biomimetic processes, for example, for CO2 capture. Investigation of bacterial CA inhibitors and activators may be relevant for finding antibiotics with a new mechanism of action.

  11. Intramolecular oxidative deselenization of acylselenoureas: a facile synthesis of benzoxazole amides and carbonic anhydrase inhibitors.

    Science.gov (United States)

    Angeli, A; Peat, T S; Bartolucci, G; Nocentini, A; Supuran, C T; Carta, F

    2016-12-28

    A mild, efficient and one pot procedure to access benzoxazoles using easily accessible acylselenoureas as starting materials has been discovered. Mechanistic studies revealed a pH dependent intramolecular oxidative deselenization, with ring closure due to an intramolecular nucleophilic attack of a phenoxide ion. All the benzoxazoles herein reported possessed a primary sulfonamide zinc binding group and showed effective inhibitory action on the enzymes, carbonic anhydrases.

  12. Carbonic anhydrase inhibitors: Design, synthesis and structural characterization of new heteroaryl-N-carbonylbenzenesulfonamides targeting druggable human carbonic anhydrase isoforms

    Czech Academy of Sciences Publication Activity Database

    Buemi, M. R.; De Luca, L.; Ferro, S.; Bruno, E.; Ceruso, M.; Supuran, C. T.; Pospíšilová, K.; Brynda, Jiří; Řezáčová, Pavlína; Gitto, R.

    2015-01-01

    Roč. 102, Sep 18 (2015), s. 223-232 ISSN 0223-5234 Institutional support: RVO:61388963 Keywords : human carbonic anhydrase * isoquinoline * quinoline * X-ray * molecular docking Subject RIV: CE - Biochemistry Impact factor: 3.902, year: 2015

  13. Kinetics of absorption of carbon dioxide in aqueous amine and carbonate solutions with carbonic anhydrase

    NARCIS (Netherlands)

    Penders-van Elk, Nathalie J. M. C.; Hamborg, Espen S.; Huttenhuis, Patrick J. G.; Fradette, Sylvie; Carley, Jonathan A.; Versteeg, Geert F.

    In the present work the absorption of carbon dioxide in aqueous N-methyldiethanolamine (MDEA) and aqueous sodium carbonate with and without carbonic anhydrase (CA) was studied in a stirred cell contactor in the temperature range 298-333 K. The CA was present as free enzyme and is compared to the

  14. Carbonic anhydrase inhibitors: Design, synthesis and structural characterization of new heteroaryl-N-carbonylbenzenesulfonamides targeting druggable human carbonic anhydrase isoforms

    Czech Academy of Sciences Publication Activity Database

    Buemi, M. R.; De Luca, L.; Ferro, S.; Bruno, E.; Ceruso, M.; Supuran, C. T.; Pospíšilová, K.; Brynda, Jiří; Řezáčová, Pavlína; Gitto, R.

    2015-01-01

    Roč. 102, SEP 18 (2015), s. 223-232 ISSN 0223-5234 R&D Projects: GA ČR GA15-05677S Grant - others:Fondo di Ateneo per la Ricerca (PRA)(IT) ORME09SPNC Institutional support: RVO:68378050 Keywords : Human carbonic anhydrase * Isoquinoline * Quinoline * X-ray * Molecular docking Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.902, year: 2015

  15. Carbonic anhydrase expression in kidney and renal cancer: implications for diagnosis and treatment

    NARCIS (Netherlands)

    Oosterwijk, E.

    2014-01-01

    Four different carbonic anhydrases are expressed in the human nephron, the functional unit of the kidney. These are specifically expressed in different nephron segments, emphasizing the critical role carbonic anhydrases play in maintaining the homeostasis of this crucial organ.Whereas the

  16. Radioimmunoassay of human muscle carbonic anhydrase III in dystrophic states

    Energy Technology Data Exchange (ETDEWEB)

    Heath, R.; Jeffery, S.; Carter, N. (Department of Child Health, St. George' s Hospital Medical School, London (UK))

    1982-03-12

    A radioimmunoassay for the human isozyme carbonic anhydrase III (CAIII) has been developed. The assay can detect levels as low as 4..mu..g/l of sample. Plasma CAIII levels in patients suffering from Duchenne muscular dystrophy were found to be up to 39 times greater than in a control group. Urine CAIII levels in patients suffering from Duchenne muscular dystrophy were not significantly different from the levels found in urine from normal adults. Measurement of plasma CAIII levels may be useful in prenatal diagnosis of Duchenne muscular dystrophy, and in investigation of adult skeletal muscle disease.

  17. Radioimmunoassay of human muscle carbonic anhydrase III in dystrophic states

    International Nuclear Information System (INIS)

    Heath, R.; Jeffery, S.; Carter, N.

    1982-01-01

    A radioimmunoassay for the human isozyme carbonic anhydrase III (CAIII) has been developed. The assay can detect levels as low as 4μg/l of sample. Plasma CAIII levels in patients suffering from Duchenne muscular dystrophy were found to be up to 39 times greater than in a control group. Urine CAIII levels in patients suffering from Duchenne muscular dystrophy were not significantly different from the levels found in urine from normal adults. Measurement of plasma CAIII levels may be useful in prenatal diagnosis of Duchenne muscular dystrophy, and in investigation of adult skeletal muscle disease. (Auth.)

  18. Genetics Home Reference: carbonic anhydrase VA deficiency

    Science.gov (United States)

    ... Salvarinova R, Yaplito-Lee J, Santra S, Shyr C, Horvath GA, Eydoux P, Lehman AM, Bernard V, Newlove T, Ukpeh H, Chakrapani A, Preece MA, Ball S, Pitt J, Vallance HD, Coulter-Mackie M, Nguyen H, Zhang LH, Bhavsar AP, Sinclair G, Waheed A, Wasserman WW, Stockler-Ipsiroglu S. Mitochondrial carbonic ...

  19. Carbonic Anhydrase: An Efficient Enzyme with Possible Global Implications

    Directory of Open Access Journals (Sweden)

    Christopher D. Boone

    2013-01-01

    Full Text Available As the global atmospheric emissions of carbon dioxide (CO2 and other greenhouse gases continue to grow to record-setting levels, so do the demands for an efficient and inexpensive carbon sequestration system. Concurrently, the first-world dependence on crude oil and natural gas provokes concerns for long-term availability and emphasizes the need for alternative fuel sources. At the forefront of both of these research areas are a family of enzymes known as the carbonic anhydrases (CAs, which reversibly catalyze the hydration of CO2 into bicarbonate. CAs are among the fastest enzymes known, which have a maximum catalytic efficiency approaching the diffusion limit of 108 M−1s−1. As such, CAs are being utilized in various industrial and research settings to help lower CO2 atmospheric emissions and promote biofuel production. This review will highlight some of the recent accomplishments in these areas along with a discussion on their current limitations.

  20. Carbonic anhydrase 5 regulates acid-base homeostasis in zebrafish.

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    Ruben Postel

    Full Text Available The regulation of the acid-base balance in cells is essential for proper cellular homeostasis. Disturbed acid-base balance directly affects cellular physiology, which often results in various pathological conditions. In every living organism, the protein family of carbonic anhydrases regulate a broad variety of homeostatic processes. Here we describe the identification, mapping and cloning of a zebrafish carbonic anhydrase 5 (ca5 mutation, collapse of fins (cof, which causes initially a collapse of the medial fins followed by necrosis and rapid degeneration of the embryo. These phenotypical characteristics can be mimicked in wild-type embryos by acetazolamide treatment, suggesting that CA5 activity in zebrafish is essential for a proper development. In addition we show that CA5 regulates acid-base balance during embryonic development, since lowering the pH can compensate for the loss of CA5 activity. Identification of selective modulators of CA5 activity could have a major impact on the development of new therapeutics involved in the treatment of a variety of disorders.

  1. Carbonic anhydrase from Apis mellifera: purification and inhibition by pesticides.

    Science.gov (United States)

    Soydan, Ercan; Güler, Ahmet; Bıyık, Selim; Şentürk, Murat; Supuran, Claudiu T; Ekinci, Deniz

    2017-12-01

    Carbonic anhydrase (CA) enzymes have been shown to play an important role in ion transport and in pH regulation in several organisms. Despite this information and the wealth of knowledge regarding the significance of CA enzymes, few studies have been reported about bee CA enzymes and the hazardous effects of chemicals. Using Apis mellifera as a model, this study aimed to determine the risk of pesticides on Apis mellifera Carbonic anhydrase enzyme (Am CA). CA was initially purified from Apis mellifera spermatheca for the first time in the literature. The enzyme was purified with an overall purification of ∼35-fold with a molecular weight of ∼32 kDa. The enzyme was then exposed to pesticides, including tebuconazole, propoxur, carbaryl, carbofuran, simazine and atrazine. The six pesticides dose-dependently inhibited in vitro AmCA activity at low micromolar concentrations. IC 50 values for the pesticides were 0.0030, 0.0321, 0.0031, 0.0087, 0.0273 and 0.0165 μM, respectively. The AmCA inhibition mechanism of these compounds is unknown at this moment.

  2. Optic nerve oxygen tension in pigs and the effect of carbonic anhydrase inhibitors

    DEFF Research Database (Denmark)

    Stefánsson, E; Jensen, P K; Eysteinsson, T

    1999-01-01

    To evaluate how the oxygen tension of the optic nerve (ONP(O)2) is affected by the administration of the carbonic anhydrase inhibitors dorzolamide and acetazolamide and by alterations in oxygen and carbon dioxide in the breathing mixture.......To evaluate how the oxygen tension of the optic nerve (ONP(O)2) is affected by the administration of the carbonic anhydrase inhibitors dorzolamide and acetazolamide and by alterations in oxygen and carbon dioxide in the breathing mixture....

  3. Carbonic Anhydrase Enhanced Carbon Capture: Kinetic Measurements and Pilot Plant Trials

    DEFF Research Database (Denmark)

    Gladis, Arne; Deslauriers, Maria Gundersen; Fosbøl, Philip Loldrup

    In this study the effect of carbonic anhydrase addition on the absorption of CO2 was investigated in a wetted wall column apparatus. Four different solvents: MEA (a primary amine), AMP (a sterically hindered primary amine), MDEA (a tertiary amine) and K2CO3 a carbonate salt solution were tested...

  4. Carbonic anhydrase III regulates peroxisome proliferator-activated receptor-{gamma}2

    Energy Technology Data Exchange (ETDEWEB)

    Mitterberger, Maria C. [Cell Metabolism and Differentiation Research Group, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, 6020 Innsbruck (Austria); Kim, Geumsoo [Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-8012 (United States); Rostek, Ursula [Cell Metabolism and Differentiation Research Group, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, 6020 Innsbruck (Austria); Levine, Rodney L. [Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-8012 (United States); Zwerschke, Werner, E-mail: werner.zwerschke@oeaw.ac.at [Cell Metabolism and Differentiation Research Group, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, 6020 Innsbruck (Austria)

    2012-05-01

    Carbonic anhydrase III (CAIII) is an isoenzyme of the CA family. Because of its low specific anhydrase activity, physiological functions in addition to hydrating CO{sub 2} have been proposed. CAIII expression is highly induced in adipogenesis and CAIII is the most abundant protein in adipose tissues. The function of CAIII in both preadipocytes and adipocytes is however unknown. In the present study we demonstrate that adipogenesis is greatly increased in mouse embryonic fibroblasts (MEFs) from CAIII knockout (KO) mice, as demonstrated by a greater than 10-fold increase in the induction of fatty acid-binding protein-4 (FABP4) and increased triglyceride formation in CAIII{sup -/-} MEFs compared with CAIII{sup +/+} cells. To address the underlying mechanism, we investigated the expression of the two adipogenic key regulators, peroxisome proliferator-activated receptor-{gamma}2 (PPAR{gamma}2) and CCAAT/enhancer binding protein-{alpha}. We found a considerable (approximately 1000-fold) increase in the PPAR{gamma}2 expression in the CAIII{sup -/-} MEFs. Furthermore, RNAi-mediated knockdown of endogenous CAIII in NIH 3T3-L1 preadipocytes resulted in a significant increase in the induction of PPAR{gamma}2 and FABP4. When both CAIII and PPAR{gamma}2 were knocked down, FABP4 was not induced. We conclude that down-regulation of CAIII in preadipocytes enhances adipogenesis and that CAIII is a regulator of adipogenic differentiation which acts at the level of PPAR{gamma}2 gene expression. -- Highlights: Black-Right-Pointing-Pointer We discover a novel function of Carbonic anhydrase III (CAIII). Black-Right-Pointing-Pointer We show that CAIII is a regulator of adipogenesis. Black-Right-Pointing-Pointer We demonstrate that CAIII acts at the level of PPAR{gamma}2 gene expression. Black-Right-Pointing-Pointer Our data contribute to a better understanding of the role of CAIII in fat tissue.

  5. Spectroscopic characterization of furosemide binding to human carbonic anhydrase II.

    Science.gov (United States)

    Ranjbar, Samira; Ghobadi, Sirous; Khodarahmi, Reza; Nemati, Houshang

    2012-05-01

    This study reports the interaction between furosemide and human carbonic anhydrase II (hCA II) using fluorescence, UV-vis and circular dichroism (CD) spectroscopy. Fluorescence data indicated that furosemide quenches the intrinsic fluorescence of the enzyme via a static mechanism and hydrogen bonding and van der Walls interactions play the major role in the drug binding. The binding average distance between furosemide and hCA II was estimated on the basis of the theory of Förster energy transfer. Decrease of protein surface hydrophobicity was also documented upon furosemide binding. Chemical modification of hCA II using N-bromosuccinimide indicated decrease of the number of accessible tryptophans in the presence of furosemide. CD results suggested the occurance of some alterations in α-helical content as well as tertiary structure of hCA II upon drug binding. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Fluorescence lifetime components reveal kinetic intermediate states upon equilibrium denaturation of carbonic anhydrase II.

    Science.gov (United States)

    Nemtseva, Elena V; Lashchuk, Olesya O; Gerasimova, Marina A; Melnik, Tatiana N; Nagibina, Galina S; Melnik, Bogdan S

    2017-12-21

    In most cases, intermediate states of multistage folding proteins are not 'visible' under equilibrium conditions but are revealed in kinetic experiments. Time-resolved fluorescence spectroscopy was used in equilibrium denaturation studies. The technique allows for detecting changes in the conformation and environment of tryptophan residues in different structural elements of carbonic anhydrase II which in its turn has made it possible to study the intermediate states of carbonic anhydrase II under equilibrium conditions. The results of equilibrium and kinetic experiments using wild-type bovine carbonic anhydrase II and its mutant form with the substitution of leucine for alanine at position 139 (L139A) were compared. The obtained lifetime components of intrinsic tryptophan fluorescence allowed for revealing that, the same as in kinetic experiments, under equilibrium conditions the unfolding of carbonic anhydrase II ensues through formation of intermediate states.

  7. Carbonic anhydrase inhibition increases retinal oxygen tension and dilates retinal vessels

    DEFF Research Database (Denmark)

    Pedersen, Daniella Bach; Koch Jensen, Peter; la Cour, Morten

    2005-01-01

    Carbonic anhydrase inhibitors (CAIs) increase blood flow in the brain and probably also in the optic nerve and retina. Additionally they elevate the oxygen tension in the optic nerve in the pig. We propose that they also raise the oxygen tension in the retina. We studied the oxygen tension in the...... in the pig retina and optic nerve before and after dorzolamide injection. Also the retinal vessel diameters during carbonic anhydrase inhibition were studied....

  8. Indomethacin lowers optic nerve oxygen tension and reduces the effect of carbonic anhydrase inhibition and carbon dioxide breathing

    DEFF Research Database (Denmark)

    Pedersen, D B; Eysteinsson, T; Stefánsson, E

    2004-01-01

    Prostaglandins are important in blood flow regulation. Carbon dioxide (CO(2)) breathing and carbonic anhydrase inhibition increase the oxygen tension in the retina and optic nerve. To study the mechanism of this effect and the role of cyclo-oxygenase in the regulation of optic nerve oxygen tension...... (ONPO(2)), the authors investigated how indomethacin affects ONPO(2) and the ONPO(2) increases caused by CO(2) breathing and carbonic anhydrase inhibition in the pig....

  9. Intrinsic thermodynamics of inhibitor binding to human carbonic anhydrase IX.

    Science.gov (United States)

    Linkuvienė, Vaida; Matulienė, Jurgita; Juozapaitienė, Vaida; Michailovienė, Vilma; Jachno, Jelena; Matulis, Daumantas

    2016-04-01

    Human carbonic anhydrase 9th isoform (CA IX) is an important marker of numerous cancers and is increasingly interesting as a potential anticancer drug target. Various synthetic aromatic sulfonamide-bearing compounds are being designed as potent inhibitors of CA IX. However, sulfonamide compound binding to CA IX is linked to several reactions, the deprotonation of the sulfonamide amino group and the protonation of the CA active site Zn(II)-bound hydroxide. These linked reactions significantly affect the affinities and other thermodynamic parameters such as enthalpies and entropies of binding. The observed and intrinsic affinities of compound binding to CA IX were determined by the fluorescent thermal shift assay. The enthalpies and entropies of binding were determined by the isothermal titration calorimetry. The pKa of CA IX was determined to be 6.8 and the enthalpy of CA IX-Zn(II)-bound hydroxide protonation was -24 kJ/mol. These values enabled the analysis of intrinsic thermodynamics of a library of compounds binding to CA IX. The most strongly binding compounds exhibited the intrinsic affinity of 0.01 nM and the observed affinity of 2 nM. The intrinsic thermodynamic parameters of compound binding to CA IX helped to draw the compound structure to thermodynamics relationship. It is important to distinguish the intrinsic from observed parameters of any disease target protein interaction with its inhibitors as drug candidates when drawing detailed compound structure to thermodynamics correlations. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Catecholamine-induced vasoconstriction is sensitive to carbonic anhydrase I activation

    Directory of Open Access Journals (Sweden)

    Puscas I.

    2001-01-01

    Full Text Available We studied the relationship between alpha- and beta-adrenergic agonists and the activity of carbonic anhydrase I and II in erythrocyte, clinical and vessel studies. Kinetic studies were performed. Adrenergic agonists increased erythrocyte carbonic anhydrase as follows: adrenaline by 75%, noradrenaline by 68%, isoprenaline by 55%, and orciprenaline by 62%. The kinetic data indicated a non-competitive mechanism of action. In clinical studies carbonic anhydrase I from erythrocytes increased by 87% after noradrenaline administration, by 71% after orciprenaline and by 82% after isoprenaline. The increase in carbonic anhydrase I paralleled the increase in blood pressure. Similar results were obtained in vessel studies on piglet vascular smooth muscle. We believe that adrenergic agonists may have a dual mechanism of action: the first one consists of a catecholamine action on its receptor with the formation of a stimulus-receptor complex. The second mechanism proposed completes the first one. By this second component of the mechanism, the same stimulus directly acts on the carbonic anhydrase I isozyme (that might be functionally coupled with adrenergic receptors, so that its activation ensures an adequate pH for stimulus-receptor coupling for signal transduction into the cell, resulting in vasoconstriction.

  11. Molecular and biochemical characterization of carbonic anhydrases of Paracoccidioides

    Directory of Open Access Journals (Sweden)

    Mariana Vieira Tomazett

    Full Text Available Abstract Carbonic anhydrases (CA belong to the family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate. In the present work, we characterized the cDNAs of four Paracoccidioides CAs (CA1, CA2, CA3, and CA4. In the presence of CO2, there was not a significant increase in fungal ca1, ca2 and ca4 gene expression. The ca1 transcript was induced during the mycelium-to-yeast transition, while ca2 and ca4 gene expression was much higher in yeast cells, when compared to mycelium and mycelium-to-yeast transition. The ca1 transcript was induced in yeast cells recovered directly from liver and spleen of infected mice, while transcripts for ca2 and ca4 were down-regulated. Recombinant CA1 (rCA1 and CA4 (rCA4, with 33 kDa and 32 kDa respectively, were obtained from bacteria. The enzymes rCA1 (β-class and rCA4 (α-class were characterized regarding pH, temperature, ions and amino acids addition influence. Both enzymes were stable at pHs 7.5-8.5 and temperatures of 30-35 °C. The enzymes were dramatically inhibited by Hg+2 and activated by Zn+2, while only rCA4 was stimulated by Fe2+. Among the amino acids tested (all in L configuration, arginine, lysine, tryptophan and histidine enhanced residual activity of rCA1 and rCA4.

  12. Molecular and biochemical characterization of carbonic anhydrases of Paracoccidioides.

    Science.gov (United States)

    Tomazett, Mariana Vieira; Zanoelo, Fabiana Fonseca; Bailão, Elisa Flávia Cardoso; Bailão, Alexandre Melo; Borges, Clayton Luiz; Soares, Célia Maria de Almeida

    2016-01-01

    Carbonic anhydrases (CA) belong to the family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate. In the present work, we characterized the cDNAs of four Paracoccidioides CAs (CA1, CA2, CA3, and CA4). In the presence of CO2, there was not a significant increase in fungal ca1, ca2 and ca4 gene expression. The ca1 transcript was induced during the mycelium-to-yeast transition, while ca2 and ca4 gene expression was much higher in yeast cells, when compared to mycelium and mycelium-to-yeast transition. The ca1 transcript was induced in yeast cells recovered directly from liver and spleen of infected mice, while transcripts for ca2 and ca4 were down-regulated. Recombinant CA1 (rCA1) and CA4 (rCA4), with 33 kDa and 32 kDa respectively, were obtained from bacteria. The enzymes rCA1 (β-class) and rCA4 (α-class) were characterized regarding pH, temperature, ions and amino acids addition influence. Both enzymes were stable at pHs 7.5-8.5 and temperatures of 30-35 °C. The enzymes were dramatically inhibited by Hg+2 and activated by Zn+2, while only rCA4 was stimulated by Fe2+. Among the amino acids tested (all in L configuration), arginine, lysine, tryptophan and histidine enhanced residual activity of rCA1 and rCA4.

  13. Legionella pneumophila Carbonic Anhydrases: Underexplored Antibacterial Drug Targets

    Directory of Open Access Journals (Sweden)

    Claudiu T. Supuran

    2016-06-01

    Full Text Available Carbonic anhydrases (CAs, EC 4.2.1.1 are metalloenzymes which catalyze the hydration of carbon dioxide to bicarbonate and protons. Many pathogenic bacteria encode such enzymes belonging to the α-, β-, and/or γ-CA families. In the last decade, enzymes from some of these pathogens, including Legionella pneumophila, have been cloned and characterized in detail. These enzymes were shown to be efficient catalysts for CO2 hydration, with kcat values in the range of (3.4–8.3 × 105 s−1 and kcat/KM values of (4.7–8.5 × 107 M−1·s−1. In vitro inhibition studies with various classes of inhibitors, such as anions, sulfonamides and sulfamates, were also reported for the two β-CAs from this pathogen, LpCA1 and LpCA2. Inorganic anions were millimolar inhibitors, whereas diethyldithiocarbamate, sulfamate, sulfamide, phenylboronic acid, and phenylarsonic acid were micromolar ones. The best LpCA1 inhibitors were aminobenzolamide and structurally similar sulfonylated aromatic sulfonamides, as well as acetazolamide and ethoxzolamide (KIs in the range of 40.3–90.5 nM. The best LpCA2 inhibitors belonged to the same class of sulfonylated sulfonamides, together with acetazolamide, methazolamide, and dichlorophenamide (KIs in the range of 25.2–88.5 nM. Considering such preliminary results, the two bacterial CAs from this pathogen represent promising yet underexplored targets for obtaining antibacterials devoid of the resistance problems common to most of the clinically used antibiotics, but further studies are needed to validate them in vivo as drug targets.

  14. Carbonic anhydrase levels and internal lacunar CO/sub 2/ concentrations in aquatic macrophytes

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, C.I.

    1979-01-01

    Carbonic anhydrase levels were examined in a variety of aquatic macrophytes from different habitats. In general, carbonic anhydrase levels increased across the habitat gradient such that activities were low in submersed aquatic macrophytes and high in emergent macrophytes with floating-leaved and free-floating plants exhibiting intermediate activities. Internal lacunar CO/sub 2/ concentrations were analyzed in relation to carbonic anhydrase activities. There was no correlation between these two parameters. Internal CO/sub 2/ concentrations ranged from low to high in submersed macrophytes, but were low in floating-leaved and emergent macrophytes. The observed internal CO/sub 2/ concentrations are discussed in relation to the individual morphologies of the plants and the environments in which they occurred.

  15. In vivo effects of radioactive properties of Tl-201 on human carbonic anhydrase activity

    Science.gov (United States)

    Sahin, Ali; Senturk, Murat

    2017-04-01

    Carbonic anhydrase (CA) is a family of metalloenzymes that requires Zn as a cofactor and catalyze the quick conversion of CO2 to HCO3- and H+. Inhibitors of the carbonic anhydrases (CAs) have medical usage of significant diseases such as glaucoma, epilepsy, gastroduodenal ulcers, acid-base disequilibria and neurological disorders. The most useful radioisotope, Tl-201, decays by electron capture, emitting Hg X-rays ( 70-80 keV), and photons of 135 and 167 keV in 10% total abundance. Therefore, it has good imaging characteristics without excessive patient radiation dose. It is the most popular isotope used for thallium 201 nuclear cardiac stress tests. In the present study, In vivo inhibitory effect of Tl-201 (Thallium-201) on human erythrocyte carbonic anhydrase (CA) activity were investigated.

  16. Ion mobility spectrometry focusing on speciation analysis of metals/metalloids bound to carbonic anhydrase.

    Science.gov (United States)

    Pessôa, Gustavo de Souza; Pilau, Eduardo Jorge; Gozzo, Fábio Cesar; Arruda, Marco Aurélio Zezzi

    2013-09-01

    In the present work, traveling wave ion mobility spectrometry-mass spectrometry (TWIMS-MS) was applied to speciation analysis of metalloproteins. The influence of pH on complexation conditions between some metals and bovine carbonic anhydrase was evaluated from pH 6 to 9, as well as the time involved in their complexation (0-24 h). Employing TWIMS-MS, two conformational states of bovine carbonic anhydrase were observed with charge states of +12 and +11; these configurations being evaluated in terms of the folded state of the apo form and this protein (at charge state +11) being linked to barium, lead, copper, and zinc in their divalent forms. Metalloprotein speciation analysis was carried out for copper (Cu(+) and Cu(2+)), lead (Pb(2+) and Pb(4+)), and selenium (Se(4+) and Se(6+)) species complexed with bovine carbonic anhydrase. Mobilities of all complexed species were compared, also considering the apo form of this protein.

  17. Effect of thyroid hormone on the levels of erythrocyte carbonic anhydrase isozymes and 2,3-diphosphoglycerate in rabbits.

    Science.gov (United States)

    Kondo, T; Taniguchi, N; Ishikawa, N; Ide, H; Takakuwa, E; Murao, M

    1978-05-01

    Levels of rabbit erythrocyte carbonic anhydrase B and C isozymes were determined in experimental hyperthyroidism using a quantitative immunologic technique. Levels of erythrocyte 2,3-diphosphoglycerate and protein binding iodine were simultaneously determined. Thyroxine and 3,5,3'-triiodothyronine were administered to rabbits orally for 30 days. A significant decrease in carbonic anhydrase B type was observed after 30 days, although no significant change was observed in carbonic anhydrase C type. These findings suggest that the steady state level of carbonic anhydrase B type in red cells is affected by thyroid hormone more readily than that of carbonic anhydrase C type. The level of red cell 2,3-diphosphoglycerate increased markedly after 10 days of treatment, corresponding to the increase of protein binding iodine. The clinical or pathologic significances were discussed in relation to the changes in the levels of these isozymes and 2,3-diphosphglycerate in red cells.

  18. Radioimmunoassay of rat carbonic anhydrases I and II. Application to central nervous system during ontogenesis

    International Nuclear Information System (INIS)

    Limozin, Nicole; Filippi, Danielle; Dalmasso, Christiane; Laurent, Georgette

    1979-01-01

    A specific radioimmunoassay method for rat erythrocyte carbonic anhydrases I and II was developed using a double antibody system. Its sensitivity was in the nanogram range for each of the two isozymes. The method has been applied to the assay of cerebral carbonic anhydrase. Only CAII has been found in brain extracts of perfused rats. Accordingly, the assay of CAI in cerebral tissue can be used to quantify erythrocyte contamination on condition that the ratio CAII/CAI in blood had been worked out. The developmental change in the soluble and the Triton X-100 solubilized brain CAII from birth to adult is reported [fr

  19. Carboxysomal carbonic anhydrases: Structure and role in microbial CO2 fixation

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, Gordon C.; Heinhorst, Sabine; Kerfeld, Cheryl A.

    2010-06-23

    Cyanobacteria and some chemoautotrophic bacteria are able to grow in environments with limiting CO2 concentrations by employing a CO2-concentrating mechanism (CCM) that allows them to accumulate inorganic carbon in their cytoplasm to concentrations several orders of magnitude higher than that on the outside. The final step of this process takes place in polyhedral protein microcompartments known as carboxysomes, which contain the majority of the CO2-fixing enzyme, RubisCO. The efficiency of CO2 fixation by the sequestered RubisCO is enhanced by co-localization with a specialized carbonic anhydrase that catalyzes dehydration of the cytoplasmic bicarbonate and ensures saturation of RubisCO with its substrate, CO2. There are two genetically distinct carboxysome types that differ in their protein composition and in the carbonic anhydrase(s) they employ. Here we review the existing information concerning the genomics, structure and enzymology of these uniquely adapted carbonic anhydrases, which are of fundamental importance in the global carbon cycle.

  20. Hydroxylamine-O-sulfonamide is a versatile lead compound for the development of carbonic anhydrase inhibitors.

    Science.gov (United States)

    Di Fiore, Anna; Vergara, Alessandro; Caterino, Marco; Alterio, Vincenzo; Monti, Simona M; Ombouma, Joanna; Dumy, Pascal; Vullo, Daniela; Supuran, Claudiu T; Winum, Jean-Yves; De Simone, Giuseppina

    2015-07-21

    Hydroxylamine-O-sulfonamide, a molecule incorporating two zinc-binding groups (ZBGs), has been investigated as a carbonic anhydrase inhibitor (CAI) by means of kinetic, crystallographic and Raman spectroscopy studies, highlighting interesting results on its mechanism of action. These data can be exploited to design new, effective and selective CAIs.

  1. Gastric hyperplasia in mice with targeted disruption of the carbonic anhydrase gene Car9

    Czech Academy of Sciences Publication Activity Database

    Ortova-Gut, M.; Parkkila, S.; Vernerová, Z.; Rohde, E.; Závada, Jan; Hocker, M.; Pastorek, J.; Karttunen, T.; Gibadulinová, A.; Závadová, Zuzana; Knobeloch, K.-P.; Wiedernmann, B.; Svoboda, Jan; Horak, I.; Pastoreková, S.

    2002-01-01

    Roč. 123, č. 6 (2002), s. 1889-1903 ISSN 0016-5085 R&D Projects: GA ČR GV312/96/K205 Institutional research plan: CEZ:AV0Z5052915 Keywords : mouse carbonic anhydrase Car9 * gastric hyperplasia Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 13.440, year: 2002

  2. Gastric Hyperplasia in Mice With Targeted Disruption of the Carbonic Anhydrase Gene Car9

    Czech Academy of Sciences Publication Activity Database

    Ortova Gut, M.; Parkkila, S.; Vernerová, Z.; Rohde, E.; Závada, Jan; Höcker, M.; Pastorek, J.; Karttunen, T.; Gibadulinová, G.; Závadová, Zuzana; Knobeloch, K. P.; Wiedenmann, B.; Svoboda, Jan; Horak, I.; Pastoreková, S.

    2002-01-01

    Roč. 123, č. 12 (2002), s. 1889-1903 ISSN 0016-5085 R&D Projects: GA ČR GV312/96/K205 Keywords : Carbonic Anhydrases * Knock-aou * Differantiation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 13.440, year: 2002

  3. Comparison of the Kinetic Promoters Piperazine and Carbonic Anhydrase for CO2 Absorption

    DEFF Research Database (Denmark)

    Gladis, Arne; Gundersen, Maria T.; Thomsen, Kaj

    2017-01-01

    Kinetic promoter that enhance the reaction kinetics with CO2 are enabling the use of the low heat of reaction of slow absorbing solvents like MDEA. Mass transfer experiments with 30 wt% MDEA promoted by either by 1.7 and 8.5g/L enzyme carbonic anhydrase (CA) or 5 wt% piperazine (PZ) where conduct...

  4. Carbonic anhydrase IX (CA IX) mediates tumor cell interactions with microenvironment

    Czech Academy of Sciences Publication Activity Database

    Závadová, Zuzana; Závada, Jan

    2005-01-01

    Roč. 13, č. 5 (2005), s. 977-982 ISSN 1021-335X R&D Projects: GA ČR(CZ) GA203/02/0405 Institutional research plan: CEZ:AV0Z50520514 Keywords : carbonic anhydrase IX * cell adhesion * microenvironment Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.572, year: 2005

  5. CO2 Mass transfer model for carbonic anhydrase-enhanced aqueous MDEA solutions

    DEFF Research Database (Denmark)

    Gladis, Arne Berthold; Deslauriers, Maria Gundersen; Neerup, Randi

    2018-01-01

    In this study a CO2 mass transfer model was developed for carbonic anhydrase-enhanced MDEA solutions based on a mechanistic kinetic enzyme model. Four different enzyme models were compared in their ability to predict the liquid side mass transfer coefficient at temperatures in the range of 298...

  6. The effect of L-carnitine on carbonic anhydrase level in rats exposed ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-07-06

    Jul 6, 2009 ... effects of dantrolene on carbonic anhydrase enzyme activities. Biol. Pharm. Bull. 27: 613-616. Gülçin I, Küfrevioğlu Öİ, Oktay M (2005). Purification and characterization of polyphenol oxidase from nettle (Urtica dioica L.) and inhibition effects of some chemicals on the enzyme activity. J. Enzym. Inhib. Med.

  7. Carbonic anhydrase inhibitor attenuates ischemia-reperfusion induced acute lung injury.

    Directory of Open Access Journals (Sweden)

    Chou-Chin Lan

    Full Text Available Ischemia-reperfusion (IR-induced acute lung injury (ALI is implicated in several clinical conditions including lung transplantation, cardiopulmonary bypass surgery, re-expansion of collapsed lung from pneumothorax or pleural effusion and etc. IR-induced ALI remains a challenge in the current treatment. Carbonic anhydrase has important physiological function and influences on transport of CO2. Some investigators suggest that CO2 influences lung injury. Therefore, carbonic anhydrase should have the role in ALI. This study was undertaken to define the effect of a carbonic anhydrase inhibitor, acetazolamide (AZA, in IR-induced ALI, that was conducted in a rat model of isolated-perfused lung with 30 minutes of ischemia and 90 minutes of reperfusion. The animals were divided into six groups (n = 6 per group: sham, sham + AZA 200 mg/kg body weight (BW, IR, IR + AZA 100 mg/kg BW, IR + AZA 200 mg/kg BW and IR+ AZA 400 mg/kg BW. IR caused significant pulmonary micro-vascular hyper-permeability, pulmonary edema, pulmonary hypertension, neutrophilic sequestration, and an increase in the expression of pro-inflammatory cytokines. Increases in carbonic anhydrase expression and perfusate pCO2 levels were noted, while decreased Na-K-ATPase expression was noted after IR. Administration of 200mg/kg BW and 400mg/kg BW AZA significantly suppressed the expression of pro-inflammatory cytokines (TNF-α, IL-1, IL-6 and IL-17 and attenuated IR-induced lung injury, represented by decreases in pulmonary hyper-permeability, pulmonary edema, pulmonary hypertension and neutrophilic sequestration. AZA attenuated IR-induced lung injury, associated with decreases in carbonic anhydrase expression and pCO2 levels, as well as restoration of Na-K-ATPase expression.

  8. Targeting carbonic anhydrase to treat diabetic retinopathy: Emerging evidences and encouraging results

    Energy Technology Data Exchange (ETDEWEB)

    Weiwei, Zhang [Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology, Shanghai Medical College, Fudan University, No. 12 Wulumuqi Road, Shanghai 200040 (China); Hu, Renming, E-mail: taylorzww@gmail.com [Department of Endocrinology and Metabolism, HuaShan Hospital, Institute of Endocrinology and Diabetology, Shanghai Medical College, Fudan University, No. 12 Wulumuqi Road, Shanghai 200040 (China)

    2009-12-18

    Diabetic retinopathy (DR) is the leading cause of vision loss among working-age populations in developed countries. Current treatment options are limited to tight glycemic, blood pressure control and destructive laser surgery. Carbonic anhydrases (CAs) are a group of enzymes involving in the rapid conversion of carbon dioxide to bicarbonate and protons. Emerging evidences reveal CA inhibitors hold the promise for the treatment of DR. This article summarizes encouraging results from clinical and animal studies, and reviews the possible mechanisms.

  9. Targeting carbonic anhydrase to treat diabetic retinopathy: Emerging evidences and encouraging results

    International Nuclear Information System (INIS)

    Weiwei, Zhang; Hu, Renming

    2009-01-01

    Diabetic retinopathy (DR) is the leading cause of vision loss among working-age populations in developed countries. Current treatment options are limited to tight glycemic, blood pressure control and destructive laser surgery. Carbonic anhydrases (CAs) are a group of enzymes involving in the rapid conversion of carbon dioxide to bicarbonate and protons. Emerging evidences reveal CA inhibitors hold the promise for the treatment of DR. This article summarizes encouraging results from clinical and animal studies, and reviews the possible mechanisms.

  10. Precipitation of hydrated Mg carbonate with the aid of carbonic anhydrase for CO2 sequestration

    Science.gov (United States)

    Power, I. M.; Harrison, A. L.; Dipple, G. M.

    2011-12-01

    Strategies for sequestering CO2 directly from the atmosphere are likely required to achieve the desired reduction in CO2 concentration and avoid the most damaging effects of climate change [1]. Numerous studies have demonstrated the accelerated precipitation of calcium carbonate minerals with the aid of carbonic anhydrase (CA) as a means of sequestering CO2 in solid carbonate form; however, no study has examined precipitation of magnesium carbonate minerals using CA. Precipitation of magnesite (MgCO3) is kinetically inhibited [2]; therefore, Mg2+ must be precipitated as hydrated carbonate minerals. In laboratory experiments, the uptake of atmospheric CO2 into brine solutions (0.1 M Mg) was rate-limiting for the precipitation of dypingite [Mg5(CO3)4(OH)2-5H2O] with initial precipitation requiring 15 days [3]. It was also found that dypingite precipitation outpaced the uptake of CO2 gas into solution. CO2 uptake is limited by the hydration of CO2 to form carbonate ions [4]. Carbonic anhydrase (CA) enzymes are among the fastest known in nature and are able to catalyze the hydration of CO2, i.e., converting CO2(aq) to CO32- and HCO3- [5]. CA plays an important role in the carbon concentrating mechanism of photoautotrophic, chemoautotrophic, and heterotrophic prokaryotes and is involved in pH homeostasis, facilitated diffusion of CO2, ion transport, and the interconversion of CO2 and HCO3- [6]. Introducing CA into buffered Mg-rich solutions should allow for more rapid precipitation of hydrated magnesium carbonate minerals. Batch experiments were conducted using 125 mL flasks containing 100 mL of Millipore deionized water with 0.2 M of MgCl2-6H2O. To buffer pH, 1.0 g of pulverized brucite [Mg(OH)2] or 1.0 g of NaOH was added to the systems, which were amended with Bovine carbonic anhydrase (BCA) (Sigma-Aldrich). Solutions were stirred continuously and kept at room temperature (~22°C) with laboratory air introduced by bubbling. Temperature and pH were measured routinely

  11. Crystallization, characterization and preliminary X-ray crystallographic analysis of GK2848, a putative carbonic anhydrase of Geobacillus kaustophilus

    International Nuclear Information System (INIS)

    Ragunathan, Preethi; Raghunath, Gokul; Kuramitsu, Seiki; Yokoyama, Shigeyuki; Kumarevel, Thirumananseri; Ponnuraj, Karthe

    2013-01-01

    The expression, purification, characterization and crystallization of GK2848, a carbonic anhydrase from G. kaustophilus, are described. The crystals diffracted to a resolution of 2.70 Å. GK2848, a hypothetical protein from the thermophilic organism Geobacillus kaustophilus, was cloned and overexpressed in Escherichia coli. The protein was purified to homogeneity using Ni–NTA affinity-column and gel-filtration chromatography. The purified protein was crystallized using the sitting-drop vapour-diffusion method. The crystals diffracted to a resolution of 2.70 Å and belonged to the orthorhombic space group P2 1 2 1 2. GK2848 bears sequence homology to carbonic anhydrases of various bacterial species, indicating that it belongs to the carbonic anhydrase family of proteins. A subsequent carbonic anhydrase activity assay of GK2848 using the Wilbur–Anderson method confirmed its function as a carbonic anhydrase. A preliminary structure solution was obtained by molecular replacement using MOLREP. Mutation and biochemical characterization of the protein are in progress. The structure and functional analysis of GK2848 might provide valuable information on a novel class of carbonic anhydrases, as none of its homologous structures have been characterized

  12. Inhibition of the α-carbonic anhydrase from Vibrio cholerae with amides and sulfonamides incorporating imidazole moieties.

    Science.gov (United States)

    De Vita, Daniela; Angeli, Andrea; Pandolfi, Fabiana; Bortolami, Martina; Costi, Roberta; Di Santo, Roberto; Suffredini, Elisabetta; Ceruso, Mariangela; Del Prete, Sonia; Capasso, Clemente; Scipione, Luigi; Supuran, Claudiu T

    2017-12-01

    We discovered novel and selective sulfonamides/amides acting as inhibitors of the α-carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic bacterium Vibrio cholerae (VchCA). This Gram-negative bacterium is the causative agent of cholera and colonises the upper small intestine where sodium bicarbonate is present at a high concentration. The secondary sulfonamides and amides investigated here were potent, low nanomolar VchCA inhibitors whereas their inhibition of the human cytosolic isoforms CA I and II was in the micromolar range or higher. The molecules represent an interesting lead for antibacterial agents with a possibly new mechanism of action, although their CA inhibition mechanism is unknown for the moment.

  13. Structural Basis for the Inhibition of Helicobacter pylori α-Carbonic Anhydrase by Sulfonamides.

    Directory of Open Access Journals (Sweden)

    Joyanta K Modak

    Full Text Available Periplasmic α-carbonic anhydrase of Helicobacter pylori (HpαCA, an oncogenic bacterium in the human stomach, is essential for its acclimation to low pH. It catalyses the conversion of carbon dioxide to bicarbonate using Zn(II as the cofactor. In H. pylori, Neisseria spp., Brucella suis and Streptococcus pneumoniae this enzyme is the target for sulfonamide antibacterial agents. We present structural analysis correlated with inhibition data, on the complexes of HpαCA with two pharmacological inhibitors of human carbonic anhydrases, acetazolamide and methazolamide. This analysis reveals that two sulfonamide oxygen atoms of the inhibitors are positioned proximal to the putative location of the oxygens of the CO2 substrate in the Michaelis complex, whilst the zinc-coordinating sulfonamide nitrogen occupies the position of the catalytic water molecule. The structures are consistent with acetazolamide acting as site-directed, nanomolar inhibitors of the enzyme by mimicking its reaction transition state. Additionally, inhibitor binding provides insights into the channel for substrate entry and product exit. This analysis has implications for the structure-based design of inhibitors of bacterial carbonic anhydrases.

  14. Construction of a system for heterologous production of carbonic anhydrase from Plasmodium falciparum in Pichia pastoris

    OpenAIRE

    Gullberg, Erik

    2008-01-01

    Malaria is one of the biggest current global health problems, and with the increasing occurance of drug resistant Plasmodium falciparum strains, there is an urgent need for new antimalarial drugs. Given the important role of carbonic anhydrase in Plasmodium falciparum (PfCA), it is a potential novel drug target. Heterologous expression of malaria proteins is problematic due to the unusual codon usage of the Plasmodium genome, so to overcome this problem a synthetic PfCA gene was designed, opt...

  15. Carbonic anhydrases are upstream regulators of CO2-controlled stomatal movements in guard cells

    KAUST Repository

    Hu, Honghong

    2009-12-13

    The continuing rise in atmospheric CO2 causes stomatal pores in leaves to close and thus globally affects CO2 influx into plants, water use efficiency and leaf heat stress. However, the CO2-binding proteins that control this response remain unknown. Moreover, which cell type responds to CO2, mesophyll or guard cells, and whether photosynthesis mediates this response are matters of debate. We demonstrate that Arabidopsis thaliana double-mutant plants in the beta-carbonic anhydrases betaCA1 and betaCA4 show impaired CO2-regulation of stomatal movements and increased stomatal density, but retain functional abscisic-acid and blue-light responses. betaCA-mediated CO2-triggered stomatal movements are not, in first-order, linked to whole leaf photosynthesis and can function in guard cells. Furthermore, guard cell betaca-overexpressing plants exhibit instantaneous enhanced water use efficiency. Guard cell expression of mammalian alphaCAII complements the reduced sensitivity of ca1 ca4 plants, showing that carbonic anhydrase-mediated catalysis is an important mechanism for betaCA-mediated CO2-induced stomatal closure and patch clamp analyses indicate that CO2/HCO3- transfers the signal to anion channel regulation. These findings, together with ht1-2 (ref. 9) epistasis analysis demonstrate that carbonic anhydrases function early in the CO2 signalling pathway, which controls gas-exchange between plants and the atmosphere.

  16. Strong topical steroid, NSAID, and carbonic anhydrase inhibitor cocktail for treatment of cystoid macular edema

    Directory of Open Access Journals (Sweden)

    Asahi MG

    2015-12-01

    Full Text Available Masumi G Asahi, Gabriela L Bobarnac Dogaru, Spencer M Onishi, Ron P GallemoreRetina Macula Institute, Torrance, CA, USA Purpose: To report the combination cocktail of strong steroid, non-steroidal anti-inflammatory drug (NSAID, and carbonic anhydrase inhibitor drops for treatment of cystoid macular edema. Methods: This is a retrospective case series of patients with cystoid macular edema managed with a topical combination of strong steroid (difluprednate, NSAID, and carbonic anhydrase inhibitor drops. The patients were followed with optical coherence tomography and fluorescein angiography. Results: In our six cases, resolution of the cystic edema with improvement in visual acuity was achieved with the use of a combination cocktail of drops. Leakage on fluorescein angiography and cystic edema on optical coherence tomography both responded to treatment with the topical cocktail of drops. Conclusion: A topical cocktail of strong steroid, NSAID, and carbonic anhydrase inhibitor drops are effective for managing cystoid macular edema. Further studies comparing this combination with more invasive treatments should be undertaken to determine the efficacy of this cocktail over other treatment options. Keywords: birdshot chorioretinopathy, diabetic macular edema, retinal vein occlusion

  17. Involvement of H(+)-ATPase and carbonic anhydrase in inorganic carbon uptake for endosymbiont photosynthesis.

    Science.gov (United States)

    Furla, P; Allemand, D; Orsenigo, M N

    2000-04-01

    Symbiotic cnidarians absorb inorganic carbon from seawater to supply intracellular dinoflagellates with CO(2) for their photosynthesis. To determine the mechanism of inorganic carbon transport by animal cells, we used plasma membrane vesicles prepared from ectodermal cells isolated from tentacles of the sea anemone, Anemonia viridis. H(14)CO(-)(3) uptake in the presence of an outward NaCl gradient or inward H(+) gradient, showed no evidence for a Cl(-)- or H(+)- driven HCO(-)(3) transport. H(14)CO(-)(3) and (36)Cl(-) uptakes were stimulated by a positive inside-membrane diffusion potential, suggesting the presence of HCO(-)(3) and Cl(-) conductances. A carbonic anhydrase (CA) activity was measured on plasma membrane (4%) and in the cytoplasm of the ectodermal cells (96%) and was sensitive to acetazolamide (IC(50) = 20 nM) and ethoxyzolamide (IC(50) = 2.5 nM). A strong DIDS-sensitive H(+)-ATPase activity was observed (IC(50) = 14 microM). This activity was also highly sensitive to vanadate and allyl isothiocyanate, two inhibitors of P-type H(+)-ATPases. Present data suggest that HCO(-)(3) absorption by ectodermal cells is carried out by H(+) secretion by H(+)-ATPase, resulting in the formation of carbonic acid in the surrounding seawater, which is quickly dehydrated into CO(2) by a membrane-bound CA. CO(2) then diffuses passively into the cell where it is hydrated in HCO(-)(3) by a cytosolic CA.

  18. Microbial Carbonic Anhydrases in Biomimetic Carbon Sequestration for Mitigating Global Warming: Prospects and Perspectives

    Directory of Open Access Journals (Sweden)

    Himadri Bose

    2017-08-01

    Full Text Available All the leading cities in the world are slowly becoming inhospitable for human life with global warming playing havoc with the living conditions. Biomineralization of carbon dioxide using carbonic anhydrase (CA is one of the most economical methods for mitigating global warming. The burning of fossil fuels results in the emission of large quantities of flue gas. The temperature of flue gas is quite high. Alkaline conditions are necessary for CaCO3 precipitation in the mineralization process. In order to use CAs for biomimetic carbon sequestration, thermo-alkali-stable CAs are, therefore, essential. CAs must be stable in the presence of various flue gas contaminants too. The extreme environments on earth harbor a variety of polyextremophilic microbes that are rich sources of thermo-alkali-stable CAs. CAs are the fastest among the known enzymes, which are of six basic types with no apparent sequence homology, thus represent an elegant example of convergent evolution. The current review focuses on the utility of thermo-alkali-stable CAs in biomineralization based strategies. A variety of roles that CAs play in various living organisms, the use of CA inhibitors as drug targets and strategies for overproduction of CAs to meet the demand are also briefly discussed.

  19. Microbial Carbonic Anhydrases in Biomimetic Carbon Sequestration for Mitigating Global Warming: Prospects and Perspectives.

    Science.gov (United States)

    Bose, Himadri; Satyanarayana, Tulasi

    2017-01-01

    All the leading cities in the world are slowly becoming inhospitable for human life with global warming playing havoc with the living conditions. Biomineralization of carbon dioxide using carbonic anhydrase (CA) is one of the most economical methods for mitigating global warming. The burning of fossil fuels results in the emission of large quantities of flue gas. The temperature of flue gas is quite high. Alkaline conditions are necessary for CaCO 3 precipitation in the mineralization process. In order to use CAs for biomimetic carbon sequestration, thermo-alkali-stable CAs are, therefore, essential. CAs must be stable in the presence of various flue gas contaminants too. The extreme environments on earth harbor a variety of polyextremophilic microbes that are rich sources of thermo-alkali-stable CAs. CAs are the fastest among the known enzymes, which are of six basic types with no apparent sequence homology, thus represent an elegant example of convergent evolution. The current review focuses on the utility of thermo-alkali-stable CAs in biomineralization based strategies. A variety of roles that CAs play in various living organisms, the use of CA inhibitors as drug targets and strategies for overproduction of CAs to meet the demand are also briefly discussed.

  20. Carbon- versus sulphur-based zinc binding groups for carbonic anhydrase inhibitors?

    Science.gov (United States)

    Supuran, Claudiu T

    2018-12-01

    A set of compounds incorporating carbon-based zinc-binding groups (ZBGs), of the type PhX (X = COOH, CONH 2 , CONHNH 2 , CONHOH, CONHOMe), and the corresponding derivatives with sulphur(VI)-based ZBGs (X = SO 3 H, SO 2 NH 2 , SO 2 NHNH 2 , SO 2 NHOH, SO 2 NHOMe) were tested as inhibitors of all mammalian isoforms of carbonic anhydrase (CA, EC 4.2.1.1), CA I-XV. Three factors connected with the ZBG influenced the efficacy as CA inhibitor (CAI) of the investigated compounds: (i) the pKa of the ZBG; (ii) its geometry (tetrahedral, i.e. sulphur-based, versus trigonal, i.e. carbon-based ZBGs), and (iii) orientation of the organic scaffold induced by the nature of the ZBG. Benzenesulphonamide was the best inhibitor of all isoforms, but other ZBGs led to interesting inhibition profiles, although with an efficacy generally reduced when compared to the sulphonamide. The nature of the ZBG also influenced the CA inhibition mechanism. Most of these derivatives were zinc binders, but some of them (sulfonates, carboxylates) may interact with the enzyme by anchoring to the zinc-coordinated water molecule or by other inhibition mechanisms (occlusion of the active site entrance, out of the active site binding, etc.). Exploring structurally diverse ZBGs may lead to interesting new developments in the field of CAIs.

  1. Identification and characterization of a novel zebrafish (Danio rerio pentraxin–carbonic anhydrase

    Directory of Open Access Journals (Sweden)

    Maarit S. Patrikainen

    2017-12-01

    Full Text Available Background Carbonic anhydrases (CAs are ubiquitous, essential enzymes which catalyze the conversion of carbon dioxide and water to bicarbonate and H+ ions. Vertebrate genomes generally contain gene loci for 15–21 different CA isoforms, three of which are enzymatically inactive. CA VI is the only secretory protein of the enzymatically active isoforms. We discovered that non-mammalian CA VI contains a C-terminal pentraxin (PTX domain, a novel combination for both CAs and PTXs. Methods We isolated and sequenced zebrafish (Danio rerio CA VI cDNA, complete with the sequence coding for the PTX domain, and produced the recombinant CA VI–PTX protein. Enzymatic activity and kinetic parameters were measured with a stopped-flow instrument. Mass spectrometry, analytical gel filtration and dynamic light scattering were used for biophysical characterization. Sequence analyses and Bayesian phylogenetics were used in generating hypotheses of protein structure and CA VI gene evolution. A CA VI–PTX antiserum was produced, and the expression of CA VI protein was studied by immunohistochemistry. A knock-down zebrafish model was constructed, and larvae were observed up to five days post-fertilization (dpf. The expression of ca6 mRNA was quantitated by qRT-PCR in different developmental times in morphant and wild-type larvae and in different adult fish tissues. Finally, the swimming behavior of the morphant fish was compared to that of wild-type fish. Results The recombinant enzyme has a very high carbonate dehydratase activity. Sequencing confirms a 530-residue protein identical to one of the predicted proteins in the Ensembl database (ensembl.org. The protein is pentameric in solution, as studied by gel filtration and light scattering, presumably joined by the PTX domains. Mass spectrometry confirms the predicted signal peptide cleavage and disulfides, and N-glycosylation in two of the four observed glycosylation motifs. Molecular modeling of the pentamer is

  2. Evidence that an internal carbonic anhydrase is present in 5% CO2-grown and air-grown Chlamydomonas

    International Nuclear Information System (INIS)

    Moroney, J.V.; Togasaki, R.K.; Husic, H.D.; Tolbert, N.E.

    1987-01-01

    Inorganic carbon (C/sub i/) uptake was measured in wild-type cells of Chlamydomonas reinhardtii, and in cia-3, a mutant strain of C. reinhardtii that cannot grow with air levels of CO 2 . Both air-grown cells, that have a CO 2 concentrating system, and 5% CO 2 -grown cells that do not have this system, were used. When the external pH was 5.1 or 7.3, air-grown, wild-type cells accumulated inorganic carbon (C/sub i/) and this accumulation was enhanced when the permeant carbonic anhydrase inhibitor, ethoxyzolamide, was added. When the external pH was 5.1, 5% CO 2 -grown cells also accumulated some C/sub i/, although not as much as air-grown cells and this accumulation was stimulated by the addition of ethoxyzolamide. At the same time, ethoxyzolamide inhibited CO 2 fixation by high CO 2 -grown, wild-type cells at both pH 5.1 and 7.3. These observations imply that 5% CO 2 -grown, wild-type cells, have a physiologically important internal carbonic anhydrase, although the major carbonic anhydrase located in the periplasmic space is only present in air-grown cells. Inorganic carbon uptake by cia-3 cells supported this conclusion. This mutant strain, which is thought to lack an internal carbonic anhydrase, was unaffected by ethoxyzolamide at pH 5.1. Other physiological characteristics of cia-3 resemble those of wild-type cells that have been treated with ethoxyzolamide. It is concluded that an internal carbonic anhydrase is under different regulatory control than the periplasmic carbonic anhydrase

  3. Cloning and expression of gamma carbonic anhydrase from Serratia sp. ISTD04 for sequestration of carbon dioxide and formation of calcite.

    Science.gov (United States)

    Srivastava, Shaili; Bharti, Randhir Kumar; Verma, Praveen Kumar; Thakur, Indu Shekhar

    2015-01-01

    Bacterial strains isolated from marble mines rock and enriched in the chemostat culture with different concentrations of sodium bicarbonate. The enriched consortium had six bacterial isolates. One of bacterium isolate showed carbonic anhydrase (CA) activity by catalyzing the reversible hydration reaction of carbon dioxide to bicarbonate. The bacterium was identified as Serratia sp. by 16S rRNA sequence analysis. The carbonic anhydrase gene from Serratia sp. was found to be homologous with gamma carbonic anhydrase. The carbonic anhydrase gene was cloned in PET21b(+) and expressed it in recombinant Escherichia coli BL21 (DE3) with His-tag at the C-terminus. The recombinant protein was purified efficiently by using one-step nickel affinity chromatography. Expected size of carbonic anhydrase was approximately 29 kDa in SDS-PAGE gel. Recombinant carbonic anhydrase enzyme was used for biomineralization-based conversion of atmospheric CO2 into valuable calcite minerals. The calcification was confirmed by using XRD, FTIR, EDX and SEM analysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Combined Effect of Temperature and pKa on the Kinetics of Absorption of Carbon Dioxide in Aqueous Alkanolamine and Carbonate Solutions with Carbonic Anhydrase

    NARCIS (Netherlands)

    Penders-Van Elk, Nathalie J M C; Oversteegen, S. Martijn; Versteeg, Geert F.

    2016-01-01

    In present work the absorption of carbon dioxide in aqueous N-methyldiethanolamine, N,N-dimethylethanolamine, and triisopropanolamine solutions with and without the enzyme carbonic anhydrase has been studied in a stirred cell reactor at temperatures varying between 278 and 313 K, at an alkanolamine

  5. Carbonic Anhydrase as Pollution Biomarker: An Ancient Enzyme with a New Use

    Directory of Open Access Journals (Sweden)

    Trifone Schettino

    2012-11-01

    Full Text Available The measurement of cellular and sub-cellular responses to chemical contaminants (referred to as biomarkers in living organisms represents a recent tool in environmental monitoring. The review focuses on carbonic anhydrase, a ubiquitous metalloenzyme which plays key roles in a wide variety of physiological processes involving CO2 and HCO3−. In the last decade a number of studies have demonstrated the sensitivity of this enzyme to pollutants such as heavy metals and organic chemicals in both humans and wildlife. The review analyses these studies and discusses the potentiality of this enzyme as novel biomarker in environmental monitoring and assessment.

  6. Carbonic anhydrase activity of integral-functional complexes of thylakoid membranes of spinach chloroplasts

    Directory of Open Access Journals (Sweden)

    A. V. Semenihin

    2015-06-01

    Full Text Available Isolated thylakoid membranes were disrupted by treatment with nonionic detergents digitonin or dodecyl maltoside. Solubilized polypeptide complexes were separated by native gel charge shift electrophoresis. The position of ATP-synthase complex and its isolated catalytic part (CF1 within gel was determined using the color reaction for ATPase activity. Due to the presence of cytochromes, the red band in unstained gels corresponded to the cytochrome b6f complex. Localization of the cytochrome b6f complex, ATP synthase and coupling CF1 in the native gel was confirmed by their subunit composition determined after SDS-electrophoretic analysis. Carbonic anhydrase (CA activity in polypeptide zones of PS II, cytochrome b6f complex, and ATP-synthase CF1 was identified in native gels using indicator bromothymol blue. CA activity of isolated CF1 in solution was determined by infrared gas analysis as the rate of bicarbonate dehydration. The water-soluble acetazolamide, an inhibitor of CA, unlike lipophilic ethoxyzolamide inhibited CA activity of CF1. Thus, it was shown for the first time that ATP-synthase has a component which is capable of catalyzing the interconversion of forms of carbonic acid associated with proton exchange. The data obtained suggest the presence of multiple forms of carbonic anhydrase in the thylakoid membranes of spinach chloroplasts and confirm their involvement in the proton transfer to the ATP synthase.

  7. Effects of sodium bicarbonate concentration on growth, photosynthesis, and carbonic anhydrase activity of macroalgae Gracilariopsis lemaneiformis, Gracilaria vermiculophylla, and Gracilaria chouae (Gracilariales, Rhodophyta).

    Science.gov (United States)

    Zhou, Wei; Sui, Zhenghong; Wang, Jinguo; Hu, Yiyi; Kang, Kyoung Ho; Hong, Hye Ran; Niaz, Zeeshan; Wei, Huihui; Du, Qingwei; Peng, Chong; Mi, Ping; Que, Zhou

    2016-06-01

    There is potential for bicarbonate to improve crop yields and economic efficiency of marine algae. However, few studies have focused on the effect of bicarbonate on the growth, photosynthesis, and enzyme activity associated with carbon utilization, especially in commercial macroalgae. Here, the addition of bicarbonate (up to 420 mg L(-1)) to macroalgal cultures has been evaluated for Gracilariopsis lemaneiformis, Gracilaria vermiculophylla, and Gracilaria chouae with respect to growth rate, photosynthetic activity, carbonic anhydrase activity, and biochemical composition. The results showed that the effects of NaHCO3 on growth, chlorophyll a, phycoerythrin, photosynthetic oxygen evolution, photochemical parameters of PSI and PSII, carbonic anhydrase activity, and nitrogen content were significant (P 336 mg L(-1) for Gp. lemaneiformis and >420 mg L(-1) for the other two species). Moreover, species-specific differences induced by supplementation with bicarbonate were discovered during culture. Optimal concentrations of NaHCO3 used in this study were 252 mg L(-1) for Gp. lemaneiformis and 336 mg L(-1) for G. vermiculophylla and G. chouae. These results suggest that an adequate supplementation of sodium bicarbonate is a viable strategy for promoting growth and photosynthetic activity in some macroalgae as well as for improving biochemical composition. The study will help to accelerate the growth rate of algae and improve the quality of thalli, and will also be useful for enhancing the understanding of carbon utilization in macroalgae.

  8. Electron Spin Resonance Studies of Carbonic Anhydrase: Transition Metal Ions and Spin-Labeled Sulfonamides*

    Science.gov (United States)

    Taylor, June S.; Mushak, Paul; Coleman, Joseph E.

    1970-01-01

    Electron spin resonance (esr) spectra of Cu(II) and Co(II) carbonic anhydrase, and a spin-labeled sulfonamide complex of the Zn(II) enzyme, are reported. The coordination geometry of Cu(II) bound in the enzyme appears to have approximately axial symmetry. Esr spectra of enzyme complexes with metal-binding anions also show axial symmetry and greater covalency, in the order ethoxzolamide cyanide complex suggests the presence of two, and probably three, equivalent nitrogen ligands from the protein. Esr spectra of the Co(II) enzyme and its complexes show two types of Co(II) environment, one typical of the native enzyme and the 1:1 CN- complex, and one typical of a 2:1 CN- complex. Co(II) in the 2:1 complex appears to be low-spin and probably has a coordination number of 5. Binding of a spin-labeled sulfonamide to the active center immobilizes the free radical. The similarity of the esr spectra of spin-labeled Zn(II) and Co(II) carbonic anhydrases suggests that the conformation at the active center is similar in the two metal derivatives. PMID:4320976

  9. Comparison of inhibition effects of some benzoic acid derivatives on sheep heart carbonic anhydrase

    Science.gov (United States)

    Kiliç, Deryanur; Yildiz, Melike; Şentürk, Murat; Erdoǧan, Orhan; Küfrevioǧlu, Ömer Irfan

    2016-04-01

    Carbonic anhydrase (CA) is a family of metalloenzymes that requires Zn as a cofactor and catalyze the quick conversion of CO2 to HCO3- and H+. Inhibitors of the carbonic anhydrases (CAs) have medical usage of significant diseases such as glaucoma, epilepsy, gastroduodenal ulcers, acid-base disequilibria and neurological disorders. In the present study, inhibition of CA with some benzoic derivatives (1-6) were investigated. Sheep heart CA (shCA) enzyme was isolated by means of designed affinity chromatography gel (cellulose-benzyl-sulfanylamide) 42.45-fold in a yield of 44 % with 564.65 EU/mg. Purified shCA enzyme was used in vitro studies. In the studies, IC50 values were calculated for 3-aminobenzoic acid (1), 4-aminobenzoic acid (2), 2-hydroxybenzoic acid (3), 2-benzoylbenzoic acid (4), 2,3-dimethoxybenzoic acid (5), and 3,4,5-trimethoxybenzoic acid (6), showing the inhibition effects on the purified enzyme. Such molecules can be used as pioneer for discovery of novel effective CA inhibitors for medicinal chemistry applications.

  10. Growth and Extracellular Carbonic Anhydrase Activity of Zooxanthellae Symbiodinium sp. in Response of Zinc Enrichment

    Directory of Open Access Journals (Sweden)

    WIDIASTUTI KARIM

    2011-12-01

    Full Text Available Coral reef communities contain a wide variety of mutualistic associations none more important than the relationship between corals and their symbiotic dinoflagellates of the genus Symbiodinium sp., commonly referred to as zooxanthellae. The function of Zinc (Zn as cofactor of several enzyme systems such as extracellular carbonic anhydrase (extracellular CA which catalyzes the interconversion of HCO3- and CO2. Concentrations of dissolved Zn in oligothropic waters are often very low therefore may limit the growth of zooxanthellae and their ability to fix CO2 from seawater via the carbonic anhydrase. The aim of this research is to investigate the effect of various concentrations of Zn on the growth and extracellular CA activity in zooxanthellae. Cell density was monitored daily by enumeration with hemocytometer-type chamber (0.1 mm. Extracellular CA was measured in homogenized intact whole cell by a pH drift assay. Results revealed that Zn status strongly influences the growth rate and extracelullar CA activity in zooxanthellae. The specific growth rate and cell density increased two-fold whilst extracelullar CA activity increased 10.5 times higher than that in control with increasing concentrations of Zn from 0 to 80 nM, but decreased when Zn was over 80 nM. Under a concentration of 80 nM was not Zn limited culture, consequently the growth rate of zooxanthellae not dependent on CO2 concentration yet offset by extracelullar CA activity.

  11. Growth and Extracellular Carbonic Anhydrase Activity of Zooxanthellae Symbiodinium sp. in Response of Zinc Enrichment

    Directory of Open Access Journals (Sweden)

    WIDIASTUTI KARIM

    2011-12-01

    Full Text Available Coral reef communities contain a wide variety of mutualistic associations none more important than the relationship between corals and their symbiotic dinoflagellates of the genus Symbiodinium sp., commonly referred to as zooxanthellae. The function of Zinc (Zn as cofactor of several enzyme systems such as extracellular carbonic anhydrase (extracellular CA which catalyzes the interconversion of HCO3− and CO2. Concentrations of dissolved Zn in oligothropic waters are often very low therefore may limit the growth of zooxanthellae and their ability to fix CO2 from seawater via the carbonic anhydrase. The aim of this research is to investigate the effect of various concentrations of Zn on the growth and extracellular CA activity in zooxanthellae. Cell density was monitored daily by enumeration with hemocytometer-type chamber (0.1 mm. Extracellular CA was measured in homogenized intact whole cell by a pH drift assay. Results revealed that Zn status strongly influences the growth rate and extracelullar CA activity in zooxanthellae. The specific growth rate and cell density increased two-fold whilst extracelullar CA activity increased 10.5 times higher than that in control with increasing concentrations of Zn from 0 to 80 nM, but decreased when Zn was over 80 nM. Under a concentration of 80 nM was not Zn limited culture, consequently the growth rate of zooxanthellae not dependent on CO2 concentration yet offset by extracelullar CA activity.

  12. β-carbonic anhydrases play a role in salicylic acid perception in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Laura Medina-Puche

    Full Text Available The plant hormone salicylic acid (SA is required for defense responses. NON EXPRESSER OF PATHOGENESIS RELATED 1 (NPR1 and NON RECOGNITION OF BTH-4 (NRB4 are required for the response to SA in Arabidopsis (Arabidopsis thaliana. Here, we isolated several interactors of NRB4 using yeast two-hybrid assays. Two of these interactors, βCA1 and βCA2, are β-carbonic anhydrase family proteins. Since double mutant βca1 βca2 plants did not show any obvious phenotype, we investigated other βCAs and found that NRB4 also interacts with βCA3 and βCA4. Moreover, several βCAs interacted with NPR1 in yeast, including one that interacted in a SA-dependent manner. This interaction was abolished in loss-of-function alleles of NPR1. Interactions between βCAs and both NRB4 and NPR1 were also detected in planta, with evidence for a triple interaction, NRB4-βCA1-NPR1. The quintuple mutant βca1 βca2 βca3 βca4 βca6 showed partial insensitivity to SA. These findings suggest that one of the functions of carbonic anhydrases is to modulate the perception of SA in plants.

  13. Influence of temperature and solvent concentration on the kinetics of the enzyme carbonic anhydrase in carbon capture technology

    DEFF Research Database (Denmark)

    Gladis, Arne; Deslauriers, Maria Gundersen; Fosbøl, Philip Loldrup

    2017-01-01

    In this study the effect of carbonic anhydrase addition on the absorption of CO2 was investigated in a wetted wall column apparatus. Four different solvents: the primary amine monoethanolamine (MEA), the sterically hindered primary amine 2-amino-2-methyl-1-propanol (AMP), the tertiary amine N......-methyl-diethanolamine (MDEA) and the carbonate salt solution K2CO3 were compared in concentrations from 5 to 50 wt% in a temperature range of 298–328 K with and without enzyme. Necessary mass transfer parameters such as liquid side mass transfer coefficient and solvent and enzyme reaction rates were determined...

  14. In folio study of carbonic anhydrase and Rubisco activities in higher C3 plants using 18O and mass spectrometry

    International Nuclear Information System (INIS)

    Peltier, G.; Despax, V.; Dimon, B.; Rumeau, D.; Tourneux, C.

    1994-01-01

    This document studies the effects of a mild water stress and carbonic anhydrase activity by ethoxyzolamide (EZA) on the diffusion of CO 2 in leaves, by 18 O labelling of O 2 and of CO 2 associated to mass spectrometry. (A.B.). 5 refs., 2 figs

  15. Soluble form of carbonic anhydrase IX (CA IX) in the serum and urine of renal carcinoma patients

    Czech Academy of Sciences Publication Activity Database

    Závada, Jan; Závadová, Zuzana; Zaťovičová, M.; Hyršl, L.; Kawaciuk, I.

    2003-01-01

    Roč. 89, - (2003), s. 1067-1071 ISSN 0007-0920 R&D Projects: GA ČR GA301/99/0356 Institutional research plan: CEZ:AV0Z5052915 Keywords : carbonic anhydrase IX * tumor antigens * cancer diagnostics Subject RIV: EC - Immunology Impact factor: 3.894, year: 2003

  16. Recognition and Binding of a Helix-Loop-Helix Peptide to Carbonic Anhydrase Occurs via Partly Folded Intermediate Structures

    Science.gov (United States)

    Lignell, Martin; Becker, Hans-Christian

    2010-01-01

    Abstract We have studied the association of a helix-loop-helix peptide scaffold carrying a benzenesulfonamide ligand to carbonic anhydrase using steady-state and time-resolved fluorescence spectroscopy. The helix-loop-helix peptide, developed for biosensing applications, is labeled with the fluorescent probe dansyl, which serves as a polarity-sensitive reporter of the binding event. Using maximum entropy analysis of the fluorescence lifetime of dansyl at 1:1 stoichiometry reveals three characteristic fluorescence lifetime groups, interpreted as differently interacting peptide/protein structures. We characterize these peptide/protein complexes as mostly bound but unfolded, bound and partly folded, and strongly bound and folded. Furthermore, analysis of the fluorescence anisotropy decay resulted in three different dansyl rotational correlation times, namely 0.18, 1.2, and 23 ns. Using the amplitudes of these times, we can correlate the lifetime groups with the corresponding fluorescence anisotropy component. The 23-ns rotational correlation time, which appears with the same amplitude as a 17-ns fluorescence lifetime, shows that the dansyl fluorophore follows the rotational diffusion of carbonic anhydrase when it is a part of the folded peptide/protein complex. A partly folded and partly hydrated interfacial structure is manifested in an 8-ns dansyl fluorescence lifetime and a 1.2-ns rotational correlation time. This structure, we believe, is similar to a molten-globule-like interfacial structure, which allows segmental movement and has a higher degree of solvent exposure of dansyl. Indirect excitation of dansyl on the helix-loop-helix peptide through Förster energy transfer from one or several tryptophans in the carbonic anhydrase shows that the helix-loop-helix scaffold binds to a tryptophan-rich domain of the carbonic anhydrase. We conclude that binding of the peptide to carbonic anhydrase involves a transition from a disordered to an ordered structure of the

  17. Production and X-ray crystallographic analysis of fully deuterated human carbonic anhydrase II

    Energy Technology Data Exchange (ETDEWEB)

    Budayova-Spano, Monika [European Molecular Biology Laboratory Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble (France); Institut Laue-Langevin, 6 Rue Jules Horowitz, BP 156, 38042 Grenoble (France); Fisher, S. Zoë [Department of Biochemistry and Molecular Biology, PO Box 100245, University of Florida, Gainesville, FL 32610 (United States); Dauvergne, Marie-Thérèse [European Molecular Biology Laboratory Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble (France); Agbandje-McKenna, Mavis [Department of Biochemistry and Molecular Biology, PO Box 100245, University of Florida, Gainesville, FL 32610 (United States); Silverman, David N. [Department of Pharmacology and Therapeutics, PO Box 100267, University of Florida, Gainesville, FL 32610 (United States); Myles, Dean A. A. [European Molecular Biology Laboratory Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble (France); Oak Ridge National Laboratory, PO Box 2008, Oak Ridge, TN 37831 (United States); McKenna, Robert, E-mail: rmckenna@ufl.edu [Department of Biochemistry and Molecular Biology, PO Box 100245, University of Florida, Gainesville, FL 32610 (United States); European Molecular Biology Laboratory Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble (France)

    2006-01-01

    This article reports the production, crystallization and X-ray structure determination of perdeuterated human carbonic anhydrase (HCA II). The refined structure is shown to be highly isomorphous with hydrogenated HCA II, especially with regard to the active site architecture and solvent network. Human carbonic anhydrase II (HCA II) is a zinc metalloenzyme that catalyzes the reversible hydration and dehydration of carbon dioxide and bicarbonate, respectively. The rate-limiting step in catalysis is the intramolecular transfer of a proton between the zinc-bound solvent (H{sub 2}O/OH{sup −}) and the proton-shuttling residue His64. This distance (∼7.5 Å) is spanned by a well defined active-site solvent network stabilized by amino-acid side chains (Tyr7, Asn62, Asn67, Thr199 and Thr200). Despite the availability of high-resolution (∼1.0 Å) X-ray crystal structures of HCA II, there is currently no definitive information available on the positions and orientations of the H atoms of the solvent network or active-site amino acids and their ionization states. In preparation for neutron diffraction studies to elucidate this hydrogen-bonding network, perdeuterated HCA II has been expressed, purified, crystallized and its X-ray structure determined to 1.5 Å resolution. The refined structure is highly isomorphous with hydrogenated HCA II, especially with regard to the active-site architecture and solvent network. This work demonstrates the suitability of these crystals for neutron macromolecular crystallography.

  18. Conformational effects on the circular dichroism of Human Carbonic Anhydrase II: a multilevel computational study.

    Directory of Open Access Journals (Sweden)

    Tatyana G Karabencheva-Christova

    Full Text Available Circular Dichroism (CD spectroscopy is a powerful method for investigating conformational changes in proteins and therefore has numerous applications in structural and molecular biology. Here a computational investigation of the CD spectrum of the Human Carbonic Anhydrase II (HCAII, with main focus on the near-UV CD spectra of the wild-type enzyme and it seven tryptophan mutant forms, is presented and compared to experimental studies. Multilevel computational methods (Molecular Dynamics, Semiempirical Quantum Mechanics, Time-Dependent Density Functional Theory were applied in order to gain insight into the mechanisms of interaction between the aromatic chromophores within the protein environment and understand how the conformational flexibility of the protein influences these mechanisms. The analysis suggests that combining CD semi empirical calculations, crystal structures and molecular dynamics (MD could help in achieving a better agreement between the computed and experimental protein spectra and provide some unique insight into the dynamic nature of the mechanisms of chromophore interactions.

  19. Lansoprazole and carbonic anhydrase IX inhibitors sinergize against human melanoma cells.

    Science.gov (United States)

    Federici, Cristina; Lugini, Luana; Marino, Maria Lucia; Carta, Fabrizio; Iessi, Elisabetta; Azzarito, Tommaso; Supuran, Claudiu T; Fais, Stefano

    2016-01-01

    Proton Pump Inhibitors (PPIs) reduce tumor acidity and therefore resistance of tumors to drugs. Carbonic Anhydrase IX (CA IX) inhibitors have proven to be effective against tumors, while tumor acidity might impair their full effectiveness. To analyze the effect of PPI/CA IX inhibitors combined treatment against human melanoma cells. The combination of Lansoprazole (LAN) and CA IX inhibitors (FC9-399A and S4) has been investigated in terms of cell proliferation inhibition and cell death in human melanoma cells. The combination of these inhibitors was more effective than the single treatments in both inhibiting cell proliferation and in inducing cell death in human melanoma cells. These results represent the first successful attempt in combining two different proton exchanger inhibitors. This is the first evidence on the effectiveness of a new approach against tumors based on the combination of PPI and CA IX inhibitors, thus providing an alternative strategy against tumors.

  20. Virtual screening of combinatorial library of novel benzenesulfonamides on mycobacterial carbonic anhydrase II

    Directory of Open Access Journals (Sweden)

    Dikant F.

    2016-12-01

    Full Text Available Combinatorial library of novel benzenesulfonamides was docked (Schrodinger Glide into mycobacterial carbonic anhydrase (mtCA II and human (hCA II isoforms with an aim to find drug candidates with selective activity on mtCA II. The predicted selectivity was calculated based on optimized MM-GBSA free energies for ligand enzyme interactions. Selectivity, LogP (o/w and interaction energy were used to calculate the selection index which determined the subset of best scoring molecules selected for further evaluation. Structure-activity relationship was found for fragment subsets, showing us the possible way regarding how to influence lipophilicity without affecting ligand-enzyme binding properties.

  1. Acidic sweep gas with carbonic anhydrase coated hollow fiber membranes synergistically accelerates CO2 removal from blood

    OpenAIRE

    Arazawa, D. T.; Kimmel, J. D.; Finn, M.C.; Federspiel, W. J.

    2015-01-01

    The use of extracorporeal carbon dioxide removal (ECCO2R) is well established as a therapy for patients suffering from acute respiratory failure. Development of next generation low blood flow (< 500 mL/min) ECCO2R devices necessitates more efficient gas exchange devices. Since over 90% of blood CO2 is transported as bicarbonate (HCO3−), we previously reported development of a carbonic anhydrase (CA) immobilized bioactive hollow fiber membrane (HFM) which significantly accelerates CO2 removal ...

  2. Malaria parasite carbonic anhydrase: inhibition of aromatic/heterocyclic sulfonamides and its therapeutic potential

    Science.gov (United States)

    Krungkrai, Sudaratana R; Krungkrai, Jerapan

    2011-01-01

    Plasmodium falciparum (P. falciparum) is responsible for the majority of life-threatening cases of human malaria, causing 1.5-2.7 million annual deaths. The global emergence of drug-resistant malaria parasites necessitates identification and characterization of novel drug targets and their potential inhibitors. We identified the carbonic anhydrase (CA) genes in P. falciparum. The pfCA gene encodes anα-carbonic anhydrase, a Zn2+-metalloenzme, possessing catalytic properties distinct from that of the human host CA enzyme. The amino acid sequence of the pfCA enzyme is different from the analogous protozoan and human enzymes. A library of aromatic/heterocyclic sulfonamides possessing a large diversity of scaffolds were found to be very good inhibitors for the malarial enzyme at moderate-low micromolar and submicromolar inhibitions. The structure of the groups substituting the aromatic-ureido- or aromatic-azomethine fragment of the molecule and the length of the parent sulfonamide were critical parameters for the inhibitory properties of the sulfonamides. One derivative, that is, 4- (3, 4-dichlorophenylureido)thioureido-benzenesulfonamide (compound 10) was the most effective in vitro Plasmodium falciparum CA inhibitor, and was also the most effective antimalarial compound on the in vitro P. falciparum growth inhibition. The compound 10 was also effective in vivo antimalarial agent in mice infected with Plasmodium berghei, an animal model of drug testing for human malaria infection. It is therefore concluded that the sulphonamide inhibitors targeting the parasite CA may have potential for the development of novel therapies against human malaria. PMID:23569766

  3. Molecular Cloning and Characterization of Carbonic Anhydrase XII from Pufferfish (Takifugu rubripes

    Directory of Open Access Journals (Sweden)

    Kanij Rukshana Sumi

    2018-03-01

    Full Text Available In this study, an 1888-bp carbonic anhydrase XII (CA XII sequence was cloned from the brain of the pufferfish, Takifugu rubripes. The cloned sequence contained a coding region of 1470-bp, which was predicted to translate into a protein of 490 amino acid residues. The predicted protein showed between 68–56% identity with the large yellow croaker (Larimichthys crocea, tilapia (Oreochromis niloticus, and Asian arowana (Scleropages formosus CA XII proteins. It also exhibited 36% and 53% identity with human CA II and CA XII, respectively. The cloned sequence contained a 22 amino acid NH2-terminal signal sequence and three Asn-Xaa-Ser/Thr sequons, among which one was potentially glycosylated. Four cysteine residues were also identified (Cys-21, Cys-201, Cys-355, and Cys-358, two of which (Cys-21 and Cys-201 could potentially form a disulfide bond. A 22-amino acid COOH-terminal cytoplasmic tail containing a potential site for phosphorylation by protein kinase A was also found. The cloned sequence might be a transmembrane protein, as predicted from in silico and phylogenetic analyses. The active site analysis of the predicted protein showed that its active site residues were highly conserved with tilapia CA XII protein. Homology modeling of the pufferfish CA XII was done using the crystal structure of the extracellular domain of human carbonic anhydrase XII at 1.55 Å resolution as a template. Semi-quantitative reverse transcription (RT-PCR, quantitative PCR (q-PCR, and in situ hybridization confirmed that pufferfish CA XII is highly expressed in the brain.

  4. Mitochondrial carbonic anhydrase in the nervous system: expression in neuronal and glial cells.

    Science.gov (United States)

    Ghandour, M S; Parkkila, A K; Parkkila, S; Waheed, A; Sly, W S

    2000-11-01

    Carbonic anhydrase (CA) V is a mitochondrial enzyme that has been reported in several tissues of the gastrointestinal tract. In liver, it participates in ureagenesis and gluconeogenesis by providing bicarbonate ions for two other mitochondrial enzymes: carbamyl phosphate synthetase I and pyruvate carboxylase. This study presents evidence of immunohistochemical localization of CA V in the rodent nervous tissue. Polyclonal rabbit antisera against a polypeptide of 17 C-terminal amino acids of rat CA V and against purified recombinant mouse isozyme were used in western blotting and immunoperoxidase stainings. Immunohistochemistry showed that CA V is expressed in astrocytes and neurons but not in oligodendrocytes, which are rich in CA II, or capillary endothelial cells, which express CA IV on their plasma face. The specificity of the immunohistochemical results was confirmed by western blotting, which identified a major 30-kDa polypeptide band of CA V in mouse cerebral cortex, hippocampus, cerebellum, spinal cord, and sciatic nerve. The expression of CA V in astrocytes and neurons suggests that this isozyme has a cell-specific, physiological role in the nervous system. In astrocytes, CA V may play an important role in gluconeogenesis by providing bicarbonate ions for the pyruvate carboxylase. The neuronal CA V could be involved in the regulation of the intramitochondrial calcium level, thus contributing to the stability of the intracellular calcium concentration. CA V may also participate in bicarbonate ion-induced GABA responses by regulating the bicarbonate homeostasis in neurons, and its inhibition could be the basis of some neurotropic effects of carbonic anhydrase inhibitors.

  5. Effect of pKa on the kinetics of carbon dioxide absorption in aqueous alkanolamine solutions containing carbonic anhydrase at 298K

    NARCIS (Netherlands)

    Penders-van Elk, Nathalie J M C; Fradette, Sylvie; Versteeg, Geert F.

    2015-01-01

    The absorption of carbon dioxide in various aqueous alkanolamine solutions have been studied with and without carbonic anhydrase respectively in a stirred cell reactor at 298K. The examined alkanolamines were: N,N-diethylethanolamine (DEMEA), N,N-dimethylethanolamine (DMMEA), monoethanolamine (MEA),

  6. The filamentous ascomycete Sordaria macrospora can survive in ambient air without carbonic anhydrases.

    Science.gov (United States)

    Lehneck, Ronny; Elleuche, Skander; Pöggeler, Stefanie

    2014-06-01

    The rapid interconversion of carbon dioxide and bicarbonate (hydrogen carbonate) is catalysed by metalloenzymes termed carbonic anhydrases (CAs). CAs have been identified in all three domains of life and can be divided into five evolutionarily unrelated classes (α, β, γ, δ and ζ) that do not share significant sequence similarities. The function of the mammalian, prokaryotic and plant α-CAs has been intensively studied but the function of CAs in filamentous ascomycetes is mostly unknown. The filamentous ascomycete Sordaria macrospora codes for four CAs, three of the β-class and one of the α-class. Here, we present a functional analysis of CAS4, the S. macrospora α-class CA. The CAS4 protein was post-translationally glycosylated and secreted. The knockout strain Δcas4 had a significantly reduced rate of ascospore germination. To determine the cas genes required for S. macrospora growth under ambient air conditions, we constructed double and triple mutations of the four cas genes in all possible combinations and a quadruple mutant. Vegetative growth rate of the quadruple mutant lacking all cas genes was drastically reduced compared to the wild type and invaded the agar under normal air conditions. Likewise the fruiting bodies were embedded in the agar and completely devoid of mature ascospores. © 2014 John Wiley & Sons Ltd.

  7. Mimic Carbonic Anhydrase Using Metal-Organic Frameworks for CO2 Capture and Conversion.

    Science.gov (United States)

    Jin, Chaonan; Zhang, Sainan; Zhang, Zhenjie; Chen, Yao

    2018-02-19

    Carbonic anhydrase (CA) is a zinc-containing metalloprotein, in which the Zn active center plays the key role to transform CO 2 into carbonate. Inspired by nature, herein we used metal-organic frameworks (MOFs) to mimic CA for CO 2 conversion, on the basis of the structural similarity between the Zn coordination in MOFs and CA active center. The biomimetic activity of MOFs was investigated by detecting the hydrolysis of para-nitrophenyl acetate, which is a model reaction used to evaluate CA activity. The biomimetic materials (e.g., CFA-1) showed good catalytic activity, and excellent reusability, and solvent and thermal stability, which is very important for practical applications. In addition, ZIF-100 and CFA-1 were used to mimic CA to convert CO 2 gas, and exhibited good efficiency on CO 2 conversion compared with those of other porous materials (e.g., MCM-41, active carbon). This biomimetic study revealed a novel CO 2 treatment method. Instead of simply using MOFs to absorb CO 2 , ZIF-100 and CFA-1 were used to mimic CA for in situ CO 2 conversion, which provides a new prospect in the biological and industrial applications of MOFs.

  8. The role of carbonic anhydrase in C4 photosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Studer, Anthony [Life Sciences Research Foundation, Baltimore, MD (United States)

    2015-10-01

    Current pressures on the global food supply have accelerated the urgency for a second green revolution using novel and sustainable approaches to increase crop yield and efficiency. This proposal outlines experiments to address fundamental questions regarding the biology of C4 photosynthesis, the method of carbon fixation utilized by the most productive food, feed and bioenergy crops. Carbonic anhydrase (CA) has been implicated in multiple cellular functions including nitrogen metabolism, water use efficiency, and photosynthesis. CA catalyzes the first dedicated step in C4 photosynthesis, the hydration of CO2 into bicarbonate, and is potentially rate limiting in C4 grasses. Using insertional mutagenesis, we have generated CA mutants in maize, and propose the characterization of these mutants using phenotypic, physiological, and transcriptomic profiling to assay the plant’s response to altered CA activity. In addition, florescent protein tagging experiments will be employed to study the subcellular localization of CA paralogs, providing critical data for modeling carbon fixation in C4 plants. Finally, I propose parallel experiments in Setaria viridis to explore its relevance as model C4 grass. Using a multifaceted approach, this proposal addresses important questions in basic biology, as well as the need for translation research in response to looming global food challenges.

  9. Carbonic anhydrase I in a cartilaginous fish, the shortspine spurdog ( Squalus mitsukurii)

    Science.gov (United States)

    Kim, Soo Cheol; Sumi, Kanij Rukshana; Kim, Jung Woo; Choi, Myeong Rak; Min, Byung Hwa; Kho, Kang Hee

    2016-09-01

    Carbonic anhydrase (CA), a ubiquitous enzyme found in many species, including fishes, is involved in physiological functions such as pH homeostasis, calcification, photosynthesis, and ionic regulation. CA I, a member of the α-CA family, is a cytoplasmic isozyme involved in carbon dioxide transport, ion exchange, and acid-base balance. Approximately half of the extant shark species occur only in deep waters; however, few published studies on sharks include these taxa. As fisheries worldwide enter deeper waters, the provision of biological data for these little-known taxa is critical to their management and conservation. To address this limitation, we aimed to detect CA I in various tissues of the shortspine spurdog ( Squalus mitsukurii) and characterize its physicochemical properties by using sodium dodecyl-sulfate polyacrylamide gel electrophoresis and isoelectric focusing, together with immunohistochemistry. CA I was detected on SDS-PAGE and western blot analysis as a specific band at 29 kDa in various tissues of the shortspine spurdog, and as a specific band at pI 6.5 in various tissues of the shortspine spurdog by IEF and western blot analysis. CA I immunoreactivity in various tissues of the shortspine spurdog was detected in intracellular locations. To our knowledge, this is the first report of the localization of CA isozymes in various tissues of S. mitsukurii.

  10. Cancer Drug Development of Carbonic Anhydrase Inhibitors beyond the Active Site

    Directory of Open Access Journals (Sweden)

    Srishti Singh

    2018-04-01

    Full Text Available Carbonic anhydrases (CAs catalyze the reversible hydration of carbon dioxide to produce bicarbonate and a proton. Multiple CA isoforms are implicated in a range of diseases, including cancer. In solid tumors, continuously dividing cells create hypoxic conditions that eventually lead to an acidic microenvironment. Hypoxic tumor cells have different mechanisms in place to regulate and adjust the surrounding microenvironment for survival. These mechanisms include expression of CA isoform IX (CA IX and XII (CA XII. These enzymes help maintain a physiological intracellular pH while simultaneously contributing to an acidic extracellular pH, leading to tumor cell survival. Expression of CA IX and CA XII has also been shown to promote tumor cell invasion and metastasis. This review discusses the characteristics of CA IX and CA XII, their mechanism of action, and validates their prospective use as anticancer targets. We discuss the current status of small inhibitors that target these isoforms, both classical and non-classical, and their future design in order to obtain isoform-specificity for CA IX and CA XII. Biologics, such as monoclonal antibodies, monoclonal-radionuclide conjugated chimeric antibodies, and antibody-small molecule conjugates are also discussed.

  11. Characterization and function of carbonic anhydrases in the zooxanthellae-giant clam symbiosis.

    Science.gov (United States)

    Baillie, B K; Yellowlees, D

    1998-03-22

    Carbonic anhydrase (CA) has been purified from the host tissue of Tridacna gigas, a clam that lives in symbiosis with the dinoflagellate alga, Symbiodinium. At least two isoforms of CA were identified in both gill and mantle tissue. The larger (70 kDa) isoform is a glycoprotein with both N- and O-glycans attached and has highest homology to CAII. It is associated with the membrane fraction while the smaller (32 kDa) is present in the aqueous phase in both tissues. The 32 kDa CA has high homology with mammalian CAI at the N-terminus. Both isoforms cross-reacted with antibodies to CAII from chicken. Immunohistology demonstrated that the 70 kDa CA is present within the ciliated branchial filaments and cells lining the tertiary water channels in the gills of T. gigas. This is consistent with a role in the transport of inorganic carbon (Ci) to the haemolymph and therefore supply of Ci to the zooxanthellae. CA was also detected in mantle epithelial cells where it may also contribute to Ci supply to the zooxanthellae. The hyaline body and nerve tissue in the mantle express the 70 kDa CA where it may be involved in light sensing and nervous transmission.

  12. An experimental study on the effect of carbonic anhydrase on the oxygen isotope exchange kinetics and equilibrium in the carbonic acid system

    Science.gov (United States)

    Uchikawa, J.; Zeebe, R. E.

    2011-12-01

    Stable oxygen isotopes of marine biogenic carbonates are often depleted in 18O relative to the values expected for thermodynamic equilibrium with ambient seawater. One possibility is that 18O-depletion in carbonates is kinetically controlled. The kinetic isotope effect associated with the hydration of CO2 results in 18O-depleted HCO3-. If the HCO3- is utilized before re-establishing equilibrium with ambient water under rapid calcification, the 18O-depletion will be recorded in carbonates. But one caveat in this kinetic model is the fact that many marine calcifiers posses carbonic anhydrase, a zinc-bearing enzyme that catalyzes the CO2 hydration reaction. It is expected that this enzyme accelerates 18O-equilibration in the carbonic acid system by facilitating direct oxygen isotope exchange between HCO3- and H2O via CO2 hydration. Clearly this argues against the conceptual framework of the kinetic model. Yet the critical variable here is the effectiveness of the carbonic anhydrase, which is likely to depend on its concentration and the carbonate chemistry of the aqueous medium. It is also hitherto unknown whether the presence of carbonic anhydrase alters the equilibrium oxygen isotope fractionations between dissolved carbonate species and water. We performed a series of quantitative inorganic carbonate precipitation experiments to examine the changes in the oxygen isotope equilibration time as a function of carbonic anhydrase concentrations. We conducted experiments at pH 8.3 and 8.9. These pH values are similar to the average surface ocean pH and the elevated pH levels observed within calcification microenvironments of certain corals and planktonic foraminifera. A summary of our new experimental results will be presented.

  13. Effect of carbonic anhydrase on silicate weathering and carbonate formation at present day CO₂ concentrations compared to primordial values.

    Science.gov (United States)

    Xiao, Leilei; Lian, Bin; Hao, Jianchao; Liu, Congqiang; Wang, Shijie

    2015-01-13

    It is widely recognized that carbonic anhydrase (CA) participates in silicate weathering and carbonate formation. Nevertheless, it is still not known if the magnitude of the effect produced by CA on surface rock evolution changes or not. In this work, CA gene expression from Bacillus mucilaginosus and the effects of recombination protein on wollastonite dissolution and carbonate formation under different conditions are explored. Real-time fluorescent quantitative PCR was used to explore the correlation between CA gene expression and sufficiency or deficiency in calcium and CO₂ concentration. The results show that the expression of CA genes is negatively correlated with both CO₂ concentration and ease of obtaining soluble calcium. A pure form of the protein of interest (CA) is obtained by cloning, heterologous expression, and purification. The results from tests of the recombination protein on wollastonite dissolution and carbonate formation at different levels of CO₂ concentration show that the magnitudes of the effects of CA and CO₂ concentration are negatively correlated. These results suggest that the effects of microbial CA in relation to silicate weathering and carbonate formation may have increased importance at the modern atmospheric CO₂ concentration compared to 3 billion years ago.

  14. Effect of carbonic anhydrase on silicate weathering and carbonate formation at present day CO2 concentrations compared to primordial values

    Science.gov (United States)

    Xiao, Leilei; Lian, Bin; Hao, Jianchao; Liu, Congqiang; Wang, Shijie

    2015-01-01

    It is widely recognized that carbonic anhydrase (CA) participates in silicate weathering and carbonate formation. Nevertheless, it is still not known if the magnitude of the effect produced by CA on surface rock evolution changes or not. In this work, CA gene expression from Bacillus mucilaginosus and the effects of recombination protein on wollastonite dissolution and carbonate formation under different conditions are explored. Real-time fluorescent quantitative PCR was used to explore the correlation between CA gene expression and sufficiency or deficiency in calcium and CO2 concentration. The results show that the expression of CA genes is negatively correlated with both CO2 concentration and ease of obtaining soluble calcium. A pure form of the protein of interest (CA) is obtained by cloning, heterologous expression, and purification. The results from tests of the recombination protein on wollastonite dissolution and carbonate formation at different levels of CO2 concentration show that the magnitudes of the effects of CA and CO2 concentration are negatively correlated. These results suggest that the effects of microbial CA in relation to silicate weathering and carbonate formation may have increased importance at the modern atmospheric CO2 concentration compared to 3 billion years ago. PMID:25583135

  15. Urinary carbonic anhydrase VI as a biomarker for kidney disease in pigs.

    Science.gov (United States)

    Nishita, Toshiho; Yatsu, Juro; Watanabe, Kazuo; Ochiai, Hideharu; Ichihara, Nobutsune; Orito, Kensuke; Arishima, Kazuyoshi

    2014-11-01

    This study investigated whether carbonic anhydrase (CA)-VI has utility as a biomarker in swine kidney disease. Serum chemistry, histopathology, immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA) analyses were performed. In the kidney of normal healthy pigs, CA-VI was localized in the epithelial cells of the renal distal straight tubules. CA-VI levels were 16 ± 35 ng/g wet tissue and 50 ± 66 ng/mL in normal pig kidney and urine, respectively, and 136 ± 173 ng/mL in the urine of pigs with kidney disease. CA-VI urinary concentration was not correlated with urinary urea nitrogen (UUN), urinary creatinine (Cre), or urinary albumin levels in pigs with kidney disease. However, UUN and Cre levels were positively correlated in the urine of pigs with kidney disease. These data suggest that urinary CA-VI may represent a biomarker for kidney disease in pigs, particularly for disorders affecting distal straight tubules. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Autoantibodies Against Carbonic Anhydrase I and II in Patients with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Ahmet Menteşe

    2017-12-01

    Full Text Available Objective: Cancer, one of the principal causes of death, is a global social health problem. Autoantibodies developed against the organism’s self-antigens are detected in the sera of subjects with cancer. In recent years carbonic anhydrase (CA I and II autoantibodies have been shown in some autoimmune diseases and carcinomas, but the mechanisms underlying this immune response have not yet been explained. The aim of this study was to evaluate CA I and II autoantibodies in patients with acute myeloid leukemia (AML and to provide a novel perspective regarding the autoimmune basis of the disease. Materials and Methods: Anti-CA I and II antibody levels were investigated using ELISA in serum samples from 30 patients with AML and 30 healthy peers. Results: Anti-CA I and II antibody titers in the AML group were significantly higher compared with the control group (p=0.0001 and 0.018, respectively. A strong positive correlation was also determined between titers of anti-CA I and II antibodies (r=0.613, p=0.0001. Conclusion: Our results suggest that these autoantibodies may be involved in the pathogenesis of AML. More extensive studies are now needed to reveal the entire mechanism.

  17. Phosphorylation of carbonic anhydrase IX controls its ability to mediate extracellular acidification in hypoxic tumors.

    Science.gov (United States)

    Ditte, Peter; Dequiedt, Franck; Svastova, Eliska; Hulikova, Alzbeta; Ohradanova-Repic, Anna; Zatovicova, Miriam; Csaderova, Lucia; Kopacek, Juraj; Supuran, Claudiu T; Pastorekova, Silvia; Pastorek, Jaromir

    2011-12-15

    In the hypoxic regions of a tumor, carbonic anhydrase IX (CA IX) is an important transmembrane component of the pH regulatory machinery that participates in bicarbonate transport. Because tumor pH has implications for growth, invasion, and therapy, determining the basis for the contributions of CA IX to the hypoxic tumor microenvironment could lead to new fundamental and practical insights. Here, we report that Thr443 phosphorylation at the intracellular domain of CA IX by protein kinase A (PKA) is critical for its activation in hypoxic cells, with the fullest activity of CA IX also requiring dephosphorylation of Ser448. PKA is activated by cAMP, which is elevated by hypoxia, and we found that attenuating PKA in cells disrupted CA IX-mediated extracellular acidification. Moreover, following hypoxia induction, CA IX colocalized with the sodium-bicarbonate cotransporter and other PKA substrates in the leading edge membranes of migrating tumor cells, in support of the concept that bicarbonate metabolism is spatially regulated at cell surface sites with high local ion transport and pH control. Using chimeric CA IX proteins containing heterologous catalytic domains derived from related CA enzymes, we showed that CA IX activity was modulated chiefly by the intracellular domain where Thr443 is located. Our findings indicate that CA IX is a pivotal mediator of the hypoxia-cAMP-PKA axis, which regulates pH in the hypoxic tumor microenvironment.

  18. The Structure of Carbonic Anhydrase IX Is Adapted for Low-pH Catalysis.

    Science.gov (United States)

    Mahon, Brian P; Bhatt, Avni; Socorro, Lilien; Driscoll, Jenna M; Okoh, Cynthia; Lomelino, Carrie L; Mboge, Mam Y; Kurian, Justin J; Tu, Chingkuang; Agbandje-McKenna, Mavis; Frost, Susan C; McKenna, Robert

    2016-08-23

    Human carbonic anhydrase IX (hCA IX) expression in many cancers is associated with hypoxic tumors and poor patient outcome. Inhibitors of hCA IX have been used as anticancer agents with some entering Phase I clinical trials. hCA IX is transmembrane protein whose catalytic domain faces the extracellular tumor milieu, which is typically associated with an acidic microenvironment. Here, we show that the catalytic domain of hCA IX (hCA IX-c) exhibits the necessary biochemical and biophysical properties that allow for low pH stability and activity. Furthermore, the unfolding process of hCA IX-c appears to be reversible, and its catalytic efficiency is thought to be correlated directly with its stability between pH 3.0 and 8.0 but not above pH 8.0. To rationalize this, we determined the X-ray crystal structure of hCA IX-c to 1.6 Å resolution. Insights from this study suggest an understanding of hCA IX-c stability and activity in low-pH tumor microenvironments and may be applicable to determining pH-related effects on enzymes.

  19. The Evolutionary History of Daphniid α-Carbonic Anhydrase within Animalia

    Science.gov (United States)

    Culver, Billy W.; Morton, Philip K.

    2015-01-01

    Understanding the mechanisms that drive acid-base regulation in organisms is important, especially for organisms in aquatic habitats that experience rapidly fluctuating pH conditions. Previous studies have shown that carbonic anhydrases (CAs), a family of zinc metalloenzymes, are responsible for acid-base regulation in many organisms. Through the use of phylogenetic tools, this present study attempts to elucidate the evolutionary history of the α-CA superfamily, with particular interest in the emerging model aquatic organism Daphnia pulex. We provide one of the most extensive phylogenies of the evolution of α-CAs, with the inclusion of 261 amino acid sequences across taxa ranging from Cnidarians to Homo sapiens. While the phylogeny supports most of our previous understanding on the relationship of how α-CAs have evolved, we find that, contrary to expectations, amino acid conservation with bacterial α-CAs supports the supposition that extracellular α-CAs are the ancestral state of animal α-CAs. Furthermore, we show that two cytosolic and one GPI-anchored α-CA in Daphnia genus have homologs in sister taxa that are possible candidate genes to study for acid-base regulation. In addition, we provide further support for previous findings of a high rate of gene duplication within Daphnia genus, as compared with other organisms. PMID:25893130

  20. Tobacco Nectarin III is a bifunctional enzyme with monodehydroascorbate reductase and carbonic anhydrase activities.

    Science.gov (United States)

    Carter, Clay J; Thornburg, Robert W

    2004-02-01

    Tobacco plants secrete a limited array of proteins (nectarins) into their floral nectar. N-terminal sequencing of the Nectarin II ( NEC2; 35kD) and the Nectarin III ( NEC3; 40kD) proteins revealed that they both share identity with dioscorin, the major soluble protein of yam tubers. These sequences also revealed that NEC2 is a breakdown product of NEC3. Using these N-terminal peptide sequences, degenerate oligonucleotides were designed that permitted the isolation of a partial NEC3 cDNA. This cDNA was then used to probe a nectary specific cDNA library and a full-length NEC3 cDNA clone was isolated. Complete sequence analysis confirmed the identity of NEC3 as a dioscorin-like protein. MALDI-TOF mass spectrometric fingerprinting of tryptic peptides derived from the purified NEC3 confirmed that this protein was encoded by the isolated cDNA. NEC3 was shown to possess both carbonic anhydrase and monodehydroascorbate reductase activities. RT-PCR based expression analyses demonstrated that NEC3 transcript is expressed throughout nectary development as well as in other floral organs. A proposed function in the maintenance of pH and oxidative balance in nectar is discussed.

  1. Functional interaction between bicarbonate transporters and carbonic anhydrase modulates lactate uptake into mouse cardiomyocytes.

    Science.gov (United States)

    Peetz, Jan; Barros, L Felipe; San Martín, Alejandro; Becker, Holger M

    2015-07-01

    Blood-derived lactate is a precious energy substrate for the heart muscle. Lactate is transported into cardiomyocytes via monocarboxylate transporters (MCTs) together with H(+), which couples lactate uptake to cellular pH regulation. In this study, we have investigated how the interplay between different acid/base transporters and carbonic anhydrases (CA), which catalyze the reversible hydration of CO2, modulates the uptake of lactate into isolated mouse cardiomyocytes. Lactate transport was estimated both as lactate-induced acidification and as changes in intracellular lactate levels measured with a newly developed Förster resonance energy transfer (FRET) nanosensor. Recordings of intracellular pH showed an increase in the rate of lactate-induced acidification when CA was inhibited by 6-ethoxy-2-benzothiazolesulfonamide (EZA), while direct measurements of lactate flux demonstrated a decrease in MCT transport activity, when CA was inhibited. The data indicate that catalytic activity of extracellular CA increases lactate uptake and counteracts intracellular lactate-induced acidification. We propose a hypothetical model, in which HCO3 (-), formed from cell-derived CO2 at the outer surface of the cardiomyocyte plasma membrane by membrane-anchored, extracellular CA, is transported into the cell via Na(+)/HCO3 (-) cotransport to counteract intracellular acidification, while the remaining H(+) stabilizes extracellular pH at the surface of the plasma membrane during MCT activity to enhance lactate influx into cardiomyocytes.

  2. Extracellular carbonic anhydrase in the dogfish, Squalus acanthias: a role in CO2 excretion.

    Science.gov (United States)

    Gilmour, K M; Perry, S F; Bernier, N J; Henry, R P; Wood, C M

    2001-01-01

    In Pacific spiny dogfish (Squalus acanthias), plasma CO(2) reactions have access to plasma carbonic anhydrase (CA) and gill membrane-associated CA. The objectives of this study were to characterise the gill membrane-bound CA and investigate whether extracellular CA contributes significantly to CO(2) excretion in dogfish. A subcellular fraction containing membrane-associated CA activity was isolated from dogfish gills and incubated with phosphatidylinositol-specific phospholipase C. This treatment caused significant release of CA activity from its membrane association, a result consistent with identification of the dogfish gill membrane-bound CA as a type IV isozyme. Inhibition constants (K(i)) against acetazolamide and benzolamide were 4.2 and 3.5 nmol L(-1), respectively. Use of a low dose (1.3 mg kg(-1) or 13 micromol L(-1)) of benzolamide to selectively inhibit extracellular CA in vivo caused a significant 30%-60% reduction in the arterial-venous total CO(2) concentration difference, a significant increase in Pco(2) and an acidosis, without affecting blood flow or ventilation. No effect of benzolamide on any measure of CO(2) excretion was detected in rainbow trout (Oncorhynchus mykiss). These results indicate that extracellular CA contributes substantially to CO(2) excretion in the dogfish, an elasmobranch, and confirm that CA is not available to plasma CO(2) reactions in rainbow trout, a teleost.

  3. Carbonic anhydrases and their functional differences in human and mouse sperm physiology.

    Science.gov (United States)

    José, O; Torres-Rodríguez, P; Forero-Quintero, L S; Chávez, J C; De la Vega-Beltrán, J L; Carta, F; Supuran, C T; Deitmer, J W; Treviño, C L

    2015-12-25

    Fertilization is a key reproductive event in which sperm and egg fuse to generate a new individual. Proper regulation of certain parameters (such as intracellular pH) is crucial for this process. Carbonic anhydrases (CAs) are among the molecular entities that control intracellular pH dynamics in most cells. Unfortunately, little is known about the function of CAs in mammalian sperm physiology. For this reason, we re-explored the expression of CAI, II, IV and XIII in human and mouse sperm. We also measured the level of CA activity, determined by mass spectrometry, and found that it is similar in non-capacitated and capacitated mouse sperm. Importantly, we found that CAII activity accounts for half of the total CA activity in capacitated mouse sperm. Using the general CA inhibitor ethoxyzolamide, we studied how CAs participate in fundamental sperm physiological processes such as motility and acrosome reaction in both species. We found that capacitated human sperm depend strongly on CA activity to support normal motility, while capacitated mouse sperm do not. Finally, we found that CA inhibition increases the acrosome reaction in capacitated human sperm, but not in capacitated mouse sperm. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. A systematic quantification of carbonic anhydrase transcripts in the mouse digestive system

    Directory of Open Access Journals (Sweden)

    Parkkila Seppo

    2007-03-01

    Full Text Available Abstract Background Carbonic anhydrases (CAs are physiologically important enzymes which participate in many gastrointestinal processes such as acid and bicarbonate secretion and metabolic pathways including gluconeogenesis and ureagenesis. The genomic data suggests that there are thirteen enzymatically active members of the mammalian CA isozyme family. In the present study, we systematically examined the mRNA expression levels of all known CA isozymes by quantitative real-time PCR in eight tissues of the digestive system of male and female mice. Results The CAs expressed in all tissues were Car5b, Car7, and Car15, among which Car5b showed moderate and Car7 and Car15 extremely low expression levels. Car3, Car12, Car13, and Car14 were detected in seven out of eight tissues and Car2 and Car4 were expressed in six tissues. Importantly, Car1, Car3, and Car13 showed very high expression levels in certain tissues as compared to the other CAs, suggesting that these low activity isozymes may also participate in physiological processes other than CA catalysis and high expression levels are required to fulfil their functions in the body. Conclusion A comprehensive mRNA expression profile of the 13 enzymatically active CAs in the murine gastrointestinal tract was produced in the present study. It contributes to a deeper understanding of the distribution of CA isozymes and their potential roles in the mouse digestive system.

  5. Diuretics: from classical carbonic anhydrase inhibitors to novel applications of the sulfonamides.

    Science.gov (United States)

    Supuran, Claudiu T

    2008-01-01

    The widely clinically used benzothiadiazines and high ceiling diuretics, such as hydrochlorothiazide, hydroflumethiazide, quinethazone, metolazone, chlorthalidone, indapamide, furosemide and bumetanide, contain SO(2)NH(2) moieties acting as an effective zinc-binding function in carbonic anhydrases (CAs, EC 4.2.1.1) inhibitors. These drugs were launched in a period when only isoform CA II was known and considered physiologically/pharmacologically relevant. Although acting as moderate-weak inhibitors of CA II, all these drugs considerably inhibit other CA isozymes known nowadays to be involved in critical physiologic processes, among the 16 CAs present in vertebrates. Some low nanomolar (or even subnanomolar) inhibitors against such isoforms were recently detected, such as metholazone against CA VII, XII and XIII, chlorthalidone against CA VB, VII, IX, XII and XIII, indapamide against CA VII, IX, XII and XIII, furosemide against CA I, II and XIV, and bumethanide against CA IX and XII. The X-ray crystal structure of the CA II-indapamide adduct was also reported recently, revealing interesting aspects useful for the drug design of CA inhibitors. It has also been proposed that the recently observed beneficial effect of indapamide for the treatment of patients with hypertension and type 2 diabetes might be due to its potent inhibition of CA isoforms present in kidneys and blood vessels, which would thus explain both the blood pressure lowering effects as well as organ-protective activity of the drug. Thus, these old drugs may be useful as leads for new applications.

  6. SYNTHESIS AND EVALUATION OF NEW PHTHALAZINE SUBSTITUTED β-LACTAM DERIVATIVES AS CARBONIC ANHYDRASE INHIBITORS.

    Science.gov (United States)

    Berber, Nurcan; Arslan, Mustafa; Bilen, Çiğdem; Sackes, Zübeyde; Gençer, Nahit; Arslan, Oktay

    2015-01-01

    A new series of phthalazine substituted β-lactam derivatives were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase (hCA I and II) were evaluated. 2H-Indazolo[2,1-b]phthala- zine-trione derivative was prepared with 4-nitrobenzaldehyde, dimedone, and phthalhydrazide in the presence of TFA in DMF, and the nitro group was reduced to 13-(4-aminophenyl)-3,3-dimethyl-3,4-dihydro- 2H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione with SnCl2 · 2H2O. The reduced compound was re- acted with different aromatic aldehydes, and phthalazine substituted imines were synthesized. The imine compounds undergo (2+2) cycloaddition reactions with ketenes to produce 2H-indazolo[2,1-b]phthala-zine-trione substituted β-lactam derivatives. The β-lactam compounds were tested as inhibitors of the CA isoenzyme activity. The results showed that all the synthesized compounds inhibited the CA isoenzyme activity. 1-(4-(3,3-dimethyl- 1,6,1 1-trioxo-2,3,4,6,11,13-hexahydro-1H-indazolo[1,2-b]phthalazin-13- yl)phenyl)-2-oxo-4-p-tolylazetidin-3-yl acetate (IC50 = 6.97 µM for hCA I and 8.48 µM for hCA II) had the most inhibitory effect.

  7. Spectroscopic and MD simulation studies on unfolding processes of mitochondrial carbonic anhydrase VA induced by urea.

    Science.gov (United States)

    Idrees, Danish; Prakash, Amresh; Haque, Md Anzarul; Islam, Asimul; Ahmad, Faizan; Hassan, Md Imtaiyaz

    2016-09-01

    Carbonic anhydrase VA (CAVA) is primarily expressed in the mitochondria and involved in numerous physiological processes including lipogenesis, insulin secretion from pancreatic cells, ureagenesis, gluconeogenesis and neuronal transmission. To understand the biophysical properties of CAVA, we carried out a reversible urea-induced isothermal denaturation at pH 7.0 and 25°C. Spectroscopic probes, [θ]222 (mean residue ellipticity at 222 nm), F344 (Trp-fluorescence emission intensity at 344 nm) and Δε280 (difference absorption at 280 nm) were used to monitor the effect of urea on the structure and stability of CAVA. The urea-induced reversible denaturation curves were used to estimate [Formula: see text], Gibbs free energy in the absence of urea; Cm, the mid-point of the denaturation curve, i.e. molar urea concentration ([urea]) at which ΔGD = 0; and m, the slope (=∂ΔGD/∂[urea]). Coincidence of normalized transition curves of all optical properties suggests that unfolding/refolding of CAVA is a two-state process. We further performed 40 ns molecular dynamics simulation of CAVA to see the dynamics at different urea concentrations. An excellent agreement was observed between in silico and in vitro studies.

  8. Stereoselective hydrogenation of olefins using rhodium-substituted carbonic anhydrase--a new reductase.

    Science.gov (United States)

    Jing, Qing; Okrasa, Krzysztof; Kazlauskas, Romas J

    2009-01-01

    One useful synthetic reaction missing from nature's toolbox is the direct hydrogenation of substrates using hydrogen. Instead nature uses cofactors like NADH to reduce organic substrates, which adds complexity and cost to these reductions. To create an enzyme that can directly reduce organic substrates with hydrogen, researchers have combined metal hydrogenation catalysts with proteins. One approach is an indirect link where a ligand is linked to a protein and the metal binds to the ligand. Another approach is direct linking of the metal to protein, but nonspecific binding of the metal limits this approach. Herein, we report a direct hydrogenation of olefins catalyzed by rhodium(I) bound to carbonic anhydrase (CA-[Rh]). We minimized nonspecific binding of rhodium by replacing histidine residues on the protein surface using site-directed mutagenesis or by chemically modifying the histidine residues. Hydrogenation catalyzed by CA-[Rh] is slightly slower than for uncomplexed rhodium(I), but the protein environment induces stereoselectivity favoring cis- over trans-stilbene by about 20:1. This enzyme is the first cofactor-independent reductase that reduces organic molecules using hydrogen. This catalyst is a good starting point to create variants with tailored reactivity and selectivity. This strategy to insert transition metals in the active site of metalloenzymes opens opportunities to a wider range of enzyme-catalyzed reactions.

  9. Suppression of CHRN endocytosis by carbonic anhydrase CAR3 in the pathogenesis of myasthenia gravis.

    Science.gov (United States)

    Du, Ailian; Huang, Shiqian; Zhao, Xiaonan; Feng, Kuan; Zhang, Shuangyan; Huang, Jiefang; Miao, Xiang; Baggi, Fulvio; Ostrom, Rennolds S; Zhang, Yanyun; Chen, Xiangjun; Xu, Congfeng

    2017-01-01

    Myasthenia gravis is an autoimmune disorder of the neuromuscular junction manifested as fatigable muscle weakness, which is typically caused by pathogenic autoantibodies against postsynaptic CHRN/AChR (cholinergic receptor nicotinic) in the endplate of skeletal muscle. Our previous studies have identified CA3 (carbonic anhydrase 3) as a specific protein insufficient in skeletal muscle from myasthenia gravis patients. In this study, we investigated the underlying mechanism of how CA3 insufficiency might contribute to myasthenia gravis. Using an experimental autoimmune myasthenia gravis animal model and the skeletal muscle cell C2C12, we find that inhibition of CAR3 (the mouse homolog of CA3) promotes CHRN internalization via a lipid raft-mediated pathway, leading to accelerated degradation of postsynaptic CHRN. Activation of CAR3 reduces CHRN degradation by suppressing receptor endocytosis. CAR3 exerts this effect by suppressing chaperone-assisted selective autophagy via interaction with BAG3 (BCL2-associated athanogene 3) and by dampening endoplasmic reticulum stress. Collectively, our study illustrates that skeletal muscle cell CAR3 is critical for CHRN homeostasis in the neuromuscular junction, and its deficiency leads to accelerated degradation of CHRN and development of myasthenia gravis, potentially revealing a novel therapeutic approach for this disorder.

  10. An update on anticancer drug development and delivery targeting carbonic anhydrase IX

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    Justina Kazokaitė

    2017-11-01

    Full Text Available The expression of carbonic anhydrase (CA IX is up-regulated in many types of solid tumors in humans under hypoxic and acidic microenvironment. Inhibition of CA IX enzymatic activity with selective inhibitors, antibodies or labeled probes has been shown to reverse the acidic environment of solid tumors and reduce the tumor growth establishing the significant role of CA IX in tumorigenesis. Thus, the development of potent antitumor drugs targeting CA IX with minimal toxic effects is important for the target-specific tumor therapy. Recently, several promising antitumor agents against CA IX have been developed to treat certain types of cancers in combination with radiation and chemotherapy. Here we review the inhibition of CA IX by small molecule compounds and monoclonal antibodies. The methods of enzymatic assays, biophysical methods, animal models including zebrafish and Xenopus oocytes, and techniques of diagnostic imaging to detect hypoxic tumors using CA IX-targeted conjugates are discussed with the aim to overview the recent progress related to novel therapeutic agents that target CA IX in hypoxic tumors.

  11. Transmembrane carbonic anhydrase isozymes IX and XII in the female mouse reproductive organs

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    Tomas Eija

    2004-10-01

    Full Text Available Abstract Background Carbonic anhydrase (CA classically catalyses the reversible hydration of dissolved CO2 to form bicarbonate ions and protons. The twelve active CA isozymes are thought to regulate a variety of cellular functions including several processes in the reproductive systems. Methods The present study was designed to investigate the expression of transmembrane CAs, CA IX and XII, in the mouse uterus, ovary and placenta. The expression of CA IX and XII was examined by immunoperoxidase staining method and western blotting. CA II and XIII served as positive controls since they are known to be present in the mouse reproductive tract. Results The data of our study indicated that CA XII is expressed in the mouse endometrium. Only very faint signal was observed in the corpus luteum of the ovary and the placenta remained mainly negative. CA IX showed weak reaction in the endometrial epithelium, while it was completely absent in the ovary and placenta. Conclusion The conservation of CA XII expression in both mouse and human endometrium suggests a role for this isozyme in reproductive physiology.

  12. Carbonic anhydrase XII expression is associated with histologic grade of cervical cancer and superior radiotherapy outcome

    International Nuclear Information System (INIS)

    Yoo, Chong Woo; Nam, Byung-Ho; Kim, Joo-Young; Shin, Hye-Jin; Lim, Hyunsun; Lee, Sun; Lee, Su-Kyoung; Lim, Myong-Cheol; Song, Yong-Jung

    2010-01-01

    To investigate whether expression of carbonic anhydrase XII (CA12) is associated with histologic grade of the tumors and radiotherapy outcomes of the patients with invasive cervical cancer. CA12 expression was examined by immunohistochemical stains in cervical cancer tissues from 183 radiotherapy patients. Histological grading was classified as well (WD), moderately (MD) or poorly differentiated (PD). Oligonucleotide microarray experiment was performed using seven cervical cancer samples to examine differentially expressed genes between WD and PD cervical cancers. The association between CA12 and histological grade was analyzed by chi-square test. CA12 and histological grades were analyzed individually and as combined CA12 and histologic grade categories for effects on survival outcome. Immunohistochemical expression of CA12 was highly associated with the histologic grade of cervical cancer. Lack of CA12 expression was associated with PD histology, with an odds ratio of 3.9 (P = 0.01). Microarray analysis showed a fourfold reduction in CA12 gene expression in PD tumors. CA12 expression was marginally associated with superior disease-free survival. Application of the new combined categories resulted in further discrimination of the prognosis of patients with moderate and poorly differentiated tumor grade. Our study indicates that CA12 may be used as a novel prognostic marker in combination with histologic grade of the tumors

  13. Synthesis and Evaluation of New Phthalazine Urea and Thiourea Derivatives as Carbonic Anhydrase Inhibitors

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    Nurcan Berber

    2013-01-01

    Full Text Available A new series of phthalazine substituted urea and thiourea derivatives were synthesized, and their inhibitory effects on the activity of purified human carbonic anhydrases (hCAs I and II were evaluated. 2H-Indazolo[2,1-b]phthalazine-trione derivative (1 was prepared with 4-nitrobenzaldehyde, dimedone, and phthalhydrazide in the presence of TFA in DMF, and nitro group was reduced to amine derivative (2 with SnCl2·2H2O. The compound was reacted with isocyanates and isothiocyanates to get the final products (3a–p. The results showed that all the synthesized compounds inhibited the CA isoenzymes activity. 3a (IC50 = 6.40 µM for hCA I and 6.13 µM for hCA II has the most inhibitory effect. The synthesized compounds are very bulky to be able to bind near the zinc ion, and they much more probably bind as the coumarin derivatives.

  14. GdnHCl-induced unfolding intermediate in the mitochondrial carbonic anhydrase VA.

    Science.gov (United States)

    Idrees, Danish; Prakash, Amresh; Haque, Md Anzarul; Islam, Asimul; Hassan, Md Imtaiyaz; Ahmad, Faizan

    2016-10-01

    Carbonic anhydrase VA (CAVA) is a mitochondrial enzyme belonging to the α-family of CAs, which is involved in several physiological processes including ureagenesis, lipogenesis, gluconeogenesis and neuronal transmission. Here, we have tried to understand the folding mechanism of CAVA using guanidine hydrochloride (GdnHCl)-induced denaturation at pH 8.0 and 25°C. The conformational stability was measured from the GdnHCl-induced denaturation study of CAVA monitored by circular dichroism (CD) and fluorescence measurements. On increasing the concentration of GdnHCl up to 5.0, a stable intermediate was observed between the concentrations 3.25M to 3.40M of the denaturant. However, CAVA gets completely denatured at 4.0M GdnHCl. The existence of a stable intermediate state was validated by 1-anilinonaphthalene-8-sulfonic acid (ANS binding) fluorescence and near-UV CD measurements. In silico studies were also performed to analyse the effect of GdnHCl on the structure and stability of CAVA under explicit conditions. Molecular dynamics simulations for 40ns were carried out and a well-defined correlation was established for both in vitro and in silico studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Crystal structures of two tetrameric β-carbonic anhydrases from the filamentous ascomycete Sordaria macrospora.

    Science.gov (United States)

    Lehneck, Ronny; Neumann, Piotr; Vullo, Daniela; Elleuche, Skander; Supuran, Claudiu T; Ficner, Ralf; Pöggeler, Stefanie

    2014-04-01

    Carbonic anhydrases (CAs) are metalloenzymes catalyzing the reversible hydration of carbon dioxide to bicarbonate (hydrogen carbonate) and protons. CAs have been identified in archaea, bacteria and eukaryotes and can be classified into five groups (α, β, γ, δ, ζ) that are unrelated in sequence and structure. The fungal β-class has only recently attracted attention. In the present study, we investigated the structure and function of the plant-like β-CA proteins CAS1 and CAS2 from the filamentous ascomycete Sordaria macrospora. We demonstrated that both proteins can substitute for the Saccharomyces cerevisiae β-CA Nce103 and exhibit an in vitro CO2 hydration activity (kcat /Km of CAS1: 1.30 × 10(6) m(-1) ·s(-1) ; CAS2: 1.21 × 10(6 ) m(-1) ·s(-1) ). To further investigate the structural properties of CAS1 and CAS2, we determined their crystal structures to a resolution of 2.7 Å and 1.8 Å, respectively. The oligomeric state of both proteins is tetrameric. With the exception of the active site composition, no further major differences have been found. In both enzymes, the Zn(2) (+) -ion is tetrahedrally coordinated; in CAS1 by Cys45, His101 and Cys104 and a water molecule and in CAS2 by the side chains of four residues (Cys56, His112, Cys115 and Asp58). Both CAs are only weakly inhibited by anions, making them good candidates for industrial applications. CAS1 and CAS2 bind by x-ray crystallography (View interaction) Structural data have been deposited in the Protein Data Bank database under accession numbers 4O1J for CAS1 and 4O1K for CAS2. © 2014 FEBS.

  16. Carbonic anhydrase (acetazolamide-sensitive esterase) activity in the blood, gill and kidney of the thermally acclimated rainbow trout, Salmo gairdneri

    Energy Technology Data Exchange (ETDEWEB)

    Houston, A.H.; McCarty, L.S.

    1978-04-01

    Gill, kidney and blood levels of acetazolamide-sensitive esterase (carbonic anhydrase) activity were estimated at acclimation temperature and at a common temperature (25/sup 0/C) in rainbow trout acclimated to 2, 10, and 18/sup 0/C. Plasma levels of sodium, potassium and chloride were also examined for possible acclimatory variations. Plasma sodium and chloride levels, and the sodium:chloride ratio were unaffected by thermal acclimation; potassium concentrations were significantly elevated at 18/sup 0/C. Significant, but modest changes in renal and branchial carbonic anhydrase activity were observed under physiologically realistic incubation temperature conditions. Blood carbonic anhydrase activity was sharply elevated at higher acclimation temperatures. The data are discussed in relation to the hypothesis that carbonic anhydrase in this relatively stenothermal freshwater salmonid, through its intimate association with the coupled HCO/sub 3//sup -//Cl/sup -/ and H/sup +/ + NH/sub 4//sup +//Na/sup +/ exchange systems may provide for relatively thermostable basal rates of sodium and chloride uptake from the medium and recovery from urine. The renal, and more notably the branchial (Na/sup +//K/sup +/)-simulated ATPase systems, and erythrocytic carbonic anhydrase may then serve primarily as high-temperature amplifiers of sodium and chloride recruitment respectively.

  17. Evaluation of enhanced thermostability and operational stability of carbonic anhydrase from Micrococcus species.

    Science.gov (United States)

    Bhattacharya, Abhishek; Shrivastava, Ankita; Sharma, Anjana

    2013-06-01

    Carbonic anhydrase (CA) was purified from Micrococcus lylae and Micrococcus luteus with 49.90 and 53.8 % yield, respectively, isolated from calcium carbonate kilns. CA from M. lylae retained 80 % stability in the pH and temperature range of 6.0-8.0 and 35-45 °C, respectively. However, CA from M. luteus was stable in the pH and temperature range of 7.5-10.0 and 35-55 °C, respectively. Cross-linked enzyme aggregates (CLEAs) raised the transition temperature of M. lylae and M. luteus CA up to 67.5 and 74.0 °C, while the operational stability (T(1/20) of CA at 55 °C was calculated to be 7.7 and 12.0 h, respectively. CA from both the strains was found to be monomeric in nature with subunit molecular weight and molecular mass of 29 kDa. Ethoxozolamide was identified as the most potent inhibitor based on both IC(50) values and inhibitory constant measurement (K(i)). The K(m) and V(max) for M. lylae CA (2.31 mM; 769.23 μmol/mg/min) and M. luteus CA (2.0 mM; 1,000 μmol/mg/min) were calculated from Lineweaver-Burk plots in terms of esterase activity. Enhanced thermostability of CLEAs alleviates its role in operational stability for application at an on-site scrubber. The characteristic profile of purified CA from Micrococcus spp. advocates its effective application in biomimetic CO(2) sequestration.

  18. Characterization and expression of the maize β-carbonic anhydrase gene repeat regions.

    Science.gov (United States)

    Tems, Ursula; Burnell, James N

    2010-12-01

    In maize, carbonic anhydrase (CA; EC 4.2.1.1) catalyzes the first reaction of the C(4) photosynthetic pathway; it catalyzes the hydration of CO(2) to bicarbonate and provides an inorganic carbon source for the primary carboxylation reaction catalyzed by phosphoenolpyruvate (PEP) carboxylase. The β-CA isozymes from maize, as well as other agronomically important NADP-malic enzyme (NADP-ME) type C(4) crops, have remained relatively uncharacterized but differ significantly from the β-CAs of other C(4) monocot species primarily due to transcript length and the presence of repeat sequences. This research confirmed earlier findings of repeat sequences in maize CA transcripts, and demonstrated that the gene encoding these transcripts is also composed of repeat sequences. One of the maize CA genes was sequenced and found to encode two domains, with distinct groups of exons corresponding to the repeat regions of the transcript. We have also shown that expression of a single repeat region of the CA transcript produced active enzyme that associated as a dimer and was composed primarily of α-helices, consistent with that observed for other plant CAs. As the presence of repeat regions in the CA gene is unique to NADP-ME type C(4) monocot species, the implications of these findings in the context of the evolution of the location and function of this C(4) pathway enzyme are strongly suggestive of CA gene duplication resulting in an evolutionary advantage and a higher photosynthetic efficiency. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  19. Effect of pH on structure, function, and stability of mitochondrial carbonic anhydrase VA.

    Science.gov (United States)

    Idrees, Danish; Shahbaaz, Mohd; Bisetty, Krishna; Islam, Asimul; Ahmad, Faizan; Hassan, Md Imtaiyaz

    2017-02-01

    Mitochondrial carbonic anhydrase VA (CAVA) catalyzes the hydration of carbon dioxide to produce proton and bicarbonate which is primarily expressed in the mitochondrial matrix of liver, and involved in numerous physiological processes including lipogenesis, insulin secretion from pancreatic cells, ureagenesis, gluconeogenesis, and neuronal transmission. To understand the effect of pH on the structure, function, and stability of CAVA, we employed spectroscopic techniques such as circular dichroism, fluorescence, and absorbance measurements in wide range of pH (from pH 2.0 to pH 11.5). CAVA showed an aggregation at acidic pH range from pH 2.0 to pH 5.0. However, it remains stable and maintains its secondary structure in the pH range, pH 7.0-pH 11.5. Furthermore, this enzyme has an appreciable activity at more than pH 7.0 (7.0 < pH ≤ 11.5) with maximum activity at pH 9.0. The maximal values of k cat and k cat /K m at pH 9.0 are 3.7 × 10 6  s -1 and 5.5 × 10 7  M -1  s -1 , respectively. However, this enzyme loses its activity in the acidic pH range. We further performed 20-ns molecular dynamics simulation of CAVA to see the dynamics at different pH values. An excellent agreement was observed between in silico and in vitro studies. This study provides an insight into the activity of CAVA in the pH range of subcellular environment.

  20. Suitability of the alkalistable carbonic anhydrase from a polyextremophilic bacterium Aeribacillus pallidus TSHB1 in biomimetic carbon sequestration.

    Science.gov (United States)

    Bose, Himadri; Satyanarayana, T

    2016-10-01

    Carbonic anhydrase (CA) was produced from the polyextremophilic (halotolerant, moderately thermophilic and alkaliphilic) bacterium Aeribacillus pallidus TSHB1 isolated from water and sediment samples of Choti Anhoni hot spring of Pipariya, Madhya Pradesh (India), is being reported to be suitable for carbon sequestration. Growth and CA production were inhibited at higher CO2 concentration (5-10 %). Under optimized culture variables (tryptone 0.8 %, yeast extract 0.08 %, glucose 1 %, micronutrient solution 1 %, inoculums size 1.10 %, agitation 200 at pH 8, and temperature 55 °C), 3.7-fold higher CA production was attained than that under unoptimized conditions. The zymogram analysis of the partially purified CA revealed an activity band corresponding to 32 kDa. The enzyme is stable in the pH range between 8.0 and 11.0 with T 1/2 of 40, 15, and 8 min at 60, 70, and 80 °C, respectively. The CA of A. pallidus displayed a marked enhancement in the rate of CaCO3 precipitation from aqueous CO2. The CA-aided formation of CaCO3 was 42.5 mg mg(-1) protein. Scanning electron microscopy revealed the formation of rhomboid calcite crystals. This is the first report on the production and applicability of CA from the polyextremophilic A. pallidus in carbon sequestration.

  1. Beta-carbonic anhydrases play a role in fruiting body development and ascospore germination in the filamentous fungus Sordaria macrospora.

    Directory of Open Access Journals (Sweden)

    Skander Elleuche

    Full Text Available Carbon dioxide (CO(2 is among the most important gases for all organisms. Its reversible interconversion to bicarbonate (HCO(3 (- reaches equilibrium spontaneously, but slowly, and can be accelerated by a ubiquitous group of enzymes called carbonic anhydrases (CAs. These enzymes are grouped by their distinct structural features into alpha-, beta-, gamma-, delta- and zeta-classes. While physiological functions of mammalian, prokaryotic, plant and algal CAs have been extensively studied over the past years, the role of beta-CAs in yeasts and the human pathogen Cryptococcus neoformans has been elucidated only recently, and the function of CAs in multicellular filamentous ascomycetes is mostly unknown. To assess the role of CAs in the development of filamentous ascomycetes, the function of three genes, cas1, cas2 and cas3 (carbonic anhydrase of Sordaria encoding beta-class carbonic anhydrases was characterized in the filamentous ascomycetous fungus Sordaria macrospora. Fluorescence microscopy was used to determine the localization of GFP- and DsRED-tagged CAs. While CAS1 and CAS3 are cytoplasmic enzymes, CAS2 is localized to the mitochondria. To assess the function of the three isoenzymes, we generated knock-out strains for all three cas genes (Deltacas1, Deltacas2, and Deltacas3 as well as all combinations of double mutants. No effect on vegetative growth, fruiting-body and ascospore development was seen in the single mutant strains lacking cas1 or cas3, while single mutant Deltacas2 was affected in vegetative growth, fruiting-body development and ascospore germination, and the double mutant strain Deltacas1/2 was completely sterile. Defects caused by the lack of cas2 could be partially complemented by elevated CO(2 levels or overexpression of cas1, cas3, or a non-mitochondrial cas2 variant. The results suggest that CAs are required for sexual reproduction in filamentous ascomycetes and that the multiplicity of isoforms results in redundancy of

  2. Beta-carbonic anhydrases play a role in fruiting body development and ascospore germination in the filamentous fungus Sordaria macrospora.

    Science.gov (United States)

    Elleuche, Skander; Pöggeler, Stefanie

    2009-01-01

    Carbon dioxide (CO(2)) is among the most important gases for all organisms. Its reversible interconversion to bicarbonate (HCO(3) (-)) reaches equilibrium spontaneously, but slowly, and can be accelerated by a ubiquitous group of enzymes called carbonic anhydrases (CAs). These enzymes are grouped by their distinct structural features into alpha-, beta-, gamma-, delta- and zeta-classes. While physiological functions of mammalian, prokaryotic, plant and algal CAs have been extensively studied over the past years, the role of beta-CAs in yeasts and the human pathogen Cryptococcus neoformans has been elucidated only recently, and the function of CAs in multicellular filamentous ascomycetes is mostly unknown. To assess the role of CAs in the development of filamentous ascomycetes, the function of three genes, cas1, cas2 and cas3 (carbonic anhydrase of Sordaria) encoding beta-class carbonic anhydrases was characterized in the filamentous ascomycetous fungus Sordaria macrospora. Fluorescence microscopy was used to determine the localization of GFP- and DsRED-tagged CAs. While CAS1 and CAS3 are cytoplasmic enzymes, CAS2 is localized to the mitochondria. To assess the function of the three isoenzymes, we generated knock-out strains for all three cas genes (Deltacas1, Deltacas2, and Deltacas3) as well as all combinations of double mutants. No effect on vegetative growth, fruiting-body and ascospore development was seen in the single mutant strains lacking cas1 or cas3, while single mutant Deltacas2 was affected in vegetative growth, fruiting-body development and ascospore germination, and the double mutant strain Deltacas1/2 was completely sterile. Defects caused by the lack of cas2 could be partially complemented by elevated CO(2) levels or overexpression of cas1, cas3, or a non-mitochondrial cas2 variant. The results suggest that CAs are required for sexual reproduction in filamentous ascomycetes and that the multiplicity of isoforms results in redundancy of specific and

  3. Ultrastructural changes in the membrane system of isolated chloroplasts of spinach under the influence of carbonic anhydrase inhibitors AA and EA

    Directory of Open Access Journals (Sweden)

    Marina V. Vodka

    2013-04-01

    Full Text Available The effects of carbonic anhydrase inhibitors (АА and EA on the membrane system of isolated chloroplasts of spinach were investigated. Under the influence of AA the considerable alterations in granal structure occurred, the thickness of the granal thylakoids increased by 36% and the interspace between thylakoids by 10% comparable with the control. As a result of EA treatment, the thickness of granal thylakoids enhanced by 31% and the interspace between thylakoids increased by 8% in comparison to the control. It was shown that structure of the granal system of the chloroplast was more sensitive to AA than EA. The data obtained can indicate a decrease in the activity of the thylakoid carbonic anhydrase, inhibition of electron transport and photosynthetic process as a whole in the presence of carbonic anhydrase inhibitors (AA and EA.

  4. Carbonic anhydrase IX inhibition affects viability of cancer cells adapted to extracellular acidosis.

    Science.gov (United States)

    Andreucci, Elena; Peppicelli, Silvia; Carta, Fabrizio; Brisotto, Giulia; Biscontin, Eva; Ruzzolini, Jessica; Bianchini, Francesca; Biagioni, Alessio; Supuran, Claudiu T; Calorini, Lido

    2017-12-01

    Among the players of the adaptive response of cancer cells able to promote a resistant and aggressive phenotype, carbonic anhydrase IX (CAIX) recently has emerged as one of the most relevant drug targets. Indeed, CAIX targeting has received a lot of interest, and selective inhibitors are currently under clinical trials. Hypoxia has been identified as the master inductor of CAIX, but, to date, very few is known about the influence that another important characteristic of tumor microenvironment, i.e., extracellular acidosis, exerts on CAIX expression and activity. In the last decades, acidic microenvironment has been associated with aggressive tumor phenotype endowed with epithelial-to-mesenchymal transition (EMT) profile, high invasive and migratory ability, apoptosis, and drug resistance. We demonstrated that melanoma, breast, and colorectal cancer cells transiently and chronically exposed to acidified medium (pH 6.7 ± 0.1) showed a significantly increased CAIX expression compared to those grown in standard conditions (pH 7.4 ± 0.1). Moreover, we observed that the CAIX inhibitor FC16-670A (also named SLC-0111, which just successfully ended phase I clinical trials) not only prevents such increased expression under acidosis but also promotes apoptotic and necrotic programs only in acidified cancer cells. Thus, CAIX could represent a selective target of acidic cancer cells and FC16-670A inhibitor as a useful tool to affect this aggressive subpopulation characterized by conventional therapy escape. Cancer cells overexpress CAIX under transient and chronic extracellular acidosis. Acidosis-induced CAIX overexpression is NF-κB mediated and HIF-1α independent. FC16-670A prevents CAIX overexpression and induces acidified cancer cell death.

  5. Studies on bicarbonate transporters and carbonic anhydrase in porcine non-pigmented ciliary epithelium

    Science.gov (United States)

    Shahidullah, Mohammad; C-H, To; Pelis, Ryan M.; Delamere, Nicholas A

    2009-01-01

    Purpose Bicarbonate transport plays a role in aqueous humor (AH) secretion. Here, we examined bicarbonate transport mechanisms and carbonic anhydrase (CA) in porcine non-pigmented ciliary epithelium (NPE). Methods Cytoplasmic pH (pHi) was measured in cultured porcine NPE loaded with BCECF. Anion exchanger (AE), sodium bicarbonate cotransporter (NBC) and CA were examined by RT-PCR and immunolocalization. AH secretion was measured in the intact porcine eye using a fluorescein dilution technique. Results Anion exchanger AE2, CAII and CAIV were abundant in the NPE layer. In cultured NPE superfused with a CO2/HCO3− free HEPES buffer, exposure to a CO2/HCO3−-containing buffer caused a rapid acidification followed by a gradual pHi increase. Subsequent removal of CO2/HCO3− with HEPES buffer caused rapid alkalinization followed by gradual pHi decrease. The rate of gradual alkalinization after addition of HCO3−/CO2 was inhibited by sodium-free conditions, DIDS, CA inhibitors acetazolamide and methazolamide but not by Na-H exchange inhibitor dimethylamiloride or low chloride buffer. The phase of gradual acidification after removal of HCO3−/CO2 was inhibited by DIDS, acetazolamide, methazolamide and by low chloride buffer. DIDS reduced baseline pHi. In the intact eye, DIDS and acetazolamide reduced AH secretion by 25% and 44% respectively. Conclusion The results suggest the NPE uses a Na+-HCO3− cotransporter to import bicarbonate and a Cl−/HCO3− exchanger to export bicarbonate. CA influences the rate of bicarbonate transport. AE2, CAII and CAIV are enriched in the NPE layer of the ciliary body and their coordinated function may contribute to AH secretion by effecting bicarbonate transport into the eye. PMID:19011010

  6. Type IV carbonic anhydrase is present in the gills of spiny dogfish (Squalus acanthias).

    Science.gov (United States)

    Gilmour, K M; Bayaa, M; Kenney, L; McNeill, B; Perry, S F

    2007-01-01

    Physiological and biochemical studies have provided indirect evidence for a membrane-associated carbonic anhydrase (CA) isoform, similar to mammalian type IV CA, in the gills of dogfish (Squalus acanthias). This CA isoform is linked to the plasma membrane of gill epithelial cells by a glycosylphosphatidylinositol anchor and oriented toward the plasma, such that it can catalyze the dehydration of plasma HCO(3)(-) ions. The present study directly tested the hypothesis that CA IV is present in dogfish gills in a location amenable to catalyzing plasma HCO(3)(-) dehydration. Homology cloning techniques were used to assemble a 1,127 base pair cDNA that coded for a deduced protein of 306 amino acids. Phylogenetic analysis suggested that this protein was a type IV CA. For purposes of comparison, a second cDNA (1,107 base pairs) was cloned from dogfish blood; it encoded a deduced protein of 260 amino acids that was identified as a cytosolic CA through phylogenetic analysis. Using real-time PCR and in situ hybridization, mRNA expression for the dogfish type IV CA was detected in gill tissue and specifically localized to pillar cells and branchial epithelial cells that flanked the pillar cells. Immunohistochemistry using a polyclonal antibody raised against rainbow trout type IV CA revealed a similar pattern of CA IV immunoreactivity and demonstrated a limited degree of colocalization with Na(+)-K(+)-ATPase immunoreactivity. The presence and localization of a type IV CA isoform in the gills of dogfish is consistent with the hypothesis that branchial membrane-bound CA with an extracellular orientation contributes to CO(2) excretion in dogfish by catalyzing the dehydration of plasma HCO(3)(-) ions.

  7. Heterologous gene expression driven by carbonic anhydrase gene promoter in Dunaliella salina

    Science.gov (United States)

    Yurong, Chai; Yumin, Lu; Tianyun, Wang; Weihong, Hou; Lexun, Xue

    2006-12-01

    Dunaliella salina, a halotolerant unicellular green alga without a rigid cell wall, can live in salinities ranging from 0.05 to 5 mol/L NaCl. These features of D. salina make it an ideal host for the production of antibodies, oral vaccine, and commercially valuable polypeptides. To produce high level of heterologous proteins from D. salina, highly efficient promoters are required to drive expression of target genes under controlled condition. In the present study, we cloned a 5' franking region of 1.4 kb from the carbonic anhydrase ( CAH) gene of D. salina by genomic walking and PCR. The fragment was ligated to the pMD18-T vector and characterized. Sequence analysis indicated that this region contained conserved motifs, including a TATA- like box and CAAT-box. Tandem (GT)n repeats that had a potential role of transcriptional control, were also found in this region. The transcription start site (TSS) of the CAH gene was determined by 5' RACE and nested PCR method. Transformation assays showed that the 1.4 kb fragment was able to drive expression of the selectable bar (bialaphos resistance) gene when the fusion was transformed into D. salina by biolistics. Northern blotting hybridizations showed that the bar transcript was most abundant in cells grown in 2 mol/L NaCl, and less abundant in 0.5 mol/L NaCl, indicating that expression of the bar gene was induced at high salinity. These results suggest the potential use of the CAH gene promoter to induce the expression of heterologous genes in D. salina under varied salt condition.

  8. Diuretics with carbonic anhydrase inhibitory action: a patent and literature review (2005 - 2013).

    Science.gov (United States)

    Carta, Fabrizio; Supuran, Claudiu T

    2013-01-01

    The benzothiadiazines and high ceiling diuretics (hydrochlorothiazide, hydroflumethiazide, quinethazone, metolazone, chlorthalidone, indapamide, furosemide and bumetanide) contain primary sulfamoyl moieties acting as zinc-binding groups in the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). These drugs are widely used clinically and were recently shown to weakly inhibit isoforms CA I and II, but to possess stronger activity against isoforms involved in other important pathologies, for example, obesity, cancer, epilepsy and hypertension. The class of clinically used diuretics, with CA inhibitory properties, is the main topic of the review. A patent literature review covering the period from 2005 to 2013 is presented. This section presents an overview of the patent literature in the sulfonamide diuretic field. Most of the patents deal with the combination of diuretic sulfonamide CA inhibitors with other agents useful in the management of cardiovascular diseases and obesity. Such combinations exert a better therapeutic activity compared to similar diuretics that do not inhibit CAs, raising the question of the polypharmacological and drug repositioning effects of these old drugs. These effects seem to be due to the potent inhibition of such drugs against CA isoforms present in kidneys and blood vessels, which explain both the blood pressure lowering effects as well as organ-protective activity of the drugs. An explanation of these data is provided by the fact that inhibition of the renal CAs leads to a large increase of the nitrite excretion in urine, suggesting that renal CAs are involved in nitrite reabsorption in humans. Important lessons for the drug design of sulfonamide CA inhibitors (CAIs) can be drawn from these data.

  9. Reaction Coordinate, Free Energy, and Rate of Intramolecular Proton Transfer in Human Carbonic Anhydrase II.

    Science.gov (United States)

    Paul, Sanjib; Paul, Tanmoy Kumar; Taraphder, Srabani

    2018-03-22

    The role of structure and dynamics of an enzyme has been investigated at three different stages of its function including the chemical event it catalyzes. A one-pot computational method has been designed for each of these stages on the basis of classical and/or quantum mechanical-molecular mechanical molecular dynamics and transition path sampling simulations. For a pair of initial and final states A and B separated by a high free-energy barrier, using a two-stage selection process, several collective variables (CVs) are identified that can delineate A and B. However, these CVs are found to exhibit strong cross-coupling over the transition paths. A set of mutually orthogonal order parameters is then derived from these CVs and an optimal reaction coordinate, r, determined applying half-trajectory likelihood maximization along with a Bayesian information criterion. The transition paths are also used to project the multidimensional free energy surface and barrier crossing dynamics along r. The proposed scheme has been applied to the rate-determining intramolecular proton transfer reaction of the well-known enzyme human carbonic anhydrase II. The potential of mean force, F( r), in the absence of the chemical step is found to reproduce earlier results on the equilibrium population of two side-chain orientations of key residue His-64. Estimation of rate constants, k, from mean first passage times for the three different stages of catalysis shows that the rate-determining step of intramolecular proton transfer occurs with k ≃ 1.0 × 10 6 s -1 , in close agreement with known experimental results.

  10. Chemical Rescue of Enzymes: Proton Transfer in Mutants of Human Carbonic Anhydrase II

    Science.gov (United States)

    Maupin, C. Mark; Castillo, Norberto; Taraphder, Srabani; Tu, Chingkuang; McKenna, Robert; Silverman, David N.; Voth, Gregory A.

    2011-01-01

    In human carbonic anhydrase II (HCA II) the mutation of position 64 from histidine to alanine (H64A) disrupts the rate limiting proton transfer (PT) event, resulting in a reduction of the catalytic activity of the enzyme as compared to the wild-type. Potential of mean force (PMF) calculations utilizing the multistate empirical valence bond (MS-EVB) methodology for H64A HCA II give a PT free energy barrier significantly higher than that found in the wild-type enzyme. This high barrier, determined in the absence of exogenous buffer and assuming no additional ionizable residues in the PT pathway, indicates the likelihood of alternate enzyme pathways that utilize either ionizable enzyme residues (self-rescue) and/or exogenous buffers (chemical rescue). It has been shown experimentally that the catalytic activity of H64A HCA II can be chemically rescued to near wild type levels by the addition of the exogenous buffer 4-methylimidazole (4MI). Crystallographic studies have identified two 4MI binding sites, yet site specific mutations intended to disrupt 4MI binding have demonstrated these sites to be non-productive. In the present work MS-EVB simulations show that binding of 4MI near Thr199 in the H64A HCA II mutant, a binding site determined by NMR spectroscopy, results in a viable chemical rescue pathway. Additional viable rescue pathways are also identified where 4MI acts as a proton transport intermediary from the active site to ionizable residues on the rim of the active site, revealing a probable mode of action for the chemical rescue pathway PMID:21452838

  11. Structural insight into activity enhancement and inhibition of H64A carbonic anhydrase II by imidazoles

    Directory of Open Access Journals (Sweden)

    Mayank Aggarwal

    2014-03-01

    Full Text Available Human carbonic anhydrases (CAs are zinc metalloenzymes that catalyze the hydration and dehydration of CO2 and HCO3−, respectively. The reaction follows a ping-pong mechanism, in which the rate-limiting step is the transfer of a proton from the zinc-bound solvent (OH−/H2O in/out of the active site via His64, which is widely believed to be the proton-shuttling residue. The decreased catalytic activity (∼20-fold lower with respect to the wild type of a variant of CA II in which His64 is replaced with Ala (H64A CA II can be enhanced by exogenous proton donors/acceptors, usually derivatives of imidazoles and pyridines, to almost the wild-type level. X-ray crystal structures of H64A CA II in complex with four imidazole derivatives (imidazole, 1-methylimidazole, 2-methylimidazole and 4-methylimidazole have been determined and reveal multiple binding sites. Two of these imidazole binding sites have been identified that mimic the positions of the `in' and `out' rotamers of His64 in wild-type CA II, while another directly inhibits catalysis by displacing the zinc-bound solvent. The data presented here not only corroborate the importance of the imidazole side chain of His64 in proton transfer during CA catalysis, but also provide a complete structural understanding of the mechanism by which imidazoles enhance (and inhibit when used at higher concentrations the activity of H64A CA II.

  12. Deficiency of Carbonic Anhydrase II Results in a Urinary Concentrating Defect

    Directory of Open Access Journals (Sweden)

    Devishree Krishnan

    2018-01-01

    Full Text Available Carbonic anhydrase II (CAII is expressed along the nephron where it interacts with a number of transport proteins augmenting their activity. Aquaporin-1 (AQP1 interacts with CAII to increase water flux through the water channel. Both CAII and aquaporin-1 are expressed in the thin descending limb (TDL; however, the physiological role of a CAII-AQP1 interaction in this nephron segment is not known. To determine if CAII was required for urinary concentration, we studied water handling in CAII-deficient mice. CAII-deficient mice demonstrate polyuria and polydipsia as well as an alkaline urine and bicarbonaturia, consistent with a type III renal tubular acidosis. Natriuresis and hypercalciuria cause polyuria, however, CAII-deficient mice did not have increased urinary sodium nor calcium excretion. Further examination revealed dilute urine in the CAII-deficient mice. Urinary concentration remained reduced in CAII-deficient mice relative to wild-type animals even after water deprivation. The renal expression and localization by light microscopy of NKCC2 and aquaporin-2 was not altered. However, CAII-deficient mice had increased renal AQP1 expression. CAII associates with and increases water flux through aquaporin-1. Water flux through aquaporin-1 in the TDL of the loop of Henle is essential to the concentration of urine, as this is required to generate a concentrated medullary interstitium. We therefore measured cortical and medullary interstitial concentration in wild-type and CAII-deficient mice. Mice lacking CAII had equivalent cortical interstitial osmolarity to wild-type mice: however, they had reduced medullary interstitial osmolarity. We propose therefore that reduced water flux through aquaporin-1 in the TDL in the absence of CAII prevents the generation of a maximally concentrated medullary interstitium. This, in turn, limits urinary concentration in CAII deficient mice.

  13. Characterization of carbonic anhydrase XIII in the erythrocytes of the Burmese python, Python molurus bivittatus.

    Science.gov (United States)

    Esbaugh, A J; Secor, S M; Grosell, M

    2015-09-01

    Carbonic anhydrase (CA) is one of the most abundant proteins found in vertebrate erythrocytes with the majority of species expressing a low activity CA I and high activity CA II. However, several phylogenetic gaps remain in our understanding of the expansion of cytoplasmic CA in vertebrate erythrocytes. In particular, very little is known about isoforms from reptiles. The current study sought to characterize the erythrocyte isoforms from two squamate species, Python molurus and Nerodia rhombifer, which was combined with information from recent genome projects to address this important phylogenetic gap. Obtained sequences grouped closely with CA XIII in phylogenetic analyses. CA II mRNA transcripts were also found in erythrocytes, but found at less than half the levels of CA XIII. Structural analysis suggested similar biochemical activity as the respective mammalian isoforms, with CA XIII being a low activity isoform. Biochemical characterization verified that the majority of CA activity in the erythrocytes was due to a high activity CA II-like isoform; however, titration with copper supported the presence of two CA pools. The CA II-like pool accounted for 90 % of the total activity. To assess potential disparate roles of these isoforms a feeding stress was used to up-regulate CO2 excretion pathways. Significant up-regulation of CA II and the anion exchanger was observed; CA XIII was strongly down-regulated. While these results do not provide insight into the role of CA XIII in the erythrocytes, they do suggest that the presence of two isoforms is not simply a case of physiological redundancy. Copyright © 2015. Published by Elsevier Inc.

  14. Crucial role of carbonic anhydrase IX in tumorigenicity of xenotransplanted adult T-cell leukemia-derived cells.

    Science.gov (United States)

    Nasu, Kentaro; Yamaguchi, Kazunori; Takanashi, Tomoka; Tamai, Keiichi; Sato, Ikuro; Ine, Shoji; Sasaki, Osamu; Satoh, Kennichi; Tanaka, Nobuyuki; Tanaka, Yuetsu; Fukushima, Takuya; Harigae, Hideo; Sugamura, Kazuo

    2017-03-01

    Carbonic anhydrase IX (CA9) is a membrane-associated carbonic anhydrase that regulates cellular pH, is upregulated in various solid tumors, and is considered to be a therapeutic target. Here, we describe the essential role of CA9 in the tumorigenicity of cells derived from human adult T-cell leukemia/lymphoma (ATL). We previously established the highly tumorigenic ST1-N6 subline from the ATL-derived ST1 cell line by serial xenotransplantation in NOG mice. In the present study, we first show that CA9 expression is strongly enhanced in ST1-N6 cells. We then sorted ST1 cells by high or low CA9 expression and established ST1-CA9 high and ST1-CA9 low sublines. ST1-CA9 high cells, like ST1-N6 cells, were more strongly tumorigenic than ST1-CA9 low or parental ST1 cells when injected into NOG mice. Knockdown of CA9 with shRNAs suppressed the ability of ST1-CA9 high cells to initiate tumors, and the tumorigenicity of ST1 cells was significantly enhanced by introducing wild-type CA9 or a CA9 mutant with deletion of an intracytoplasmic domain. However, a CA9 with point mutations in the catalytic site did not increase the tumorigenicity of ST1 cells. Furthermore, we detected a small population of CA9 + CD25 + cells in lymph nodes of ATL patients. These findings suggest that CA9, and particularly its carbonic anhydrase activity, promotes the tumorigenicity of ATL-derived cells and may be involved in malignant development of lymphoma-type ATL. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  15. Generation of nitric oxide from nitrite by carbonic anhydrase: a possible link between metabolic activity and vasodilation

    DEFF Research Database (Denmark)

    Aamand, Rasmus; Dalsgaard, Thomas; Jensen, Frank Bo

    2009-01-01

    In catalyzing the reversible hydration of CO2 to bicarbonate and protons, the ubiquitous enzyme carbonic anhydrase (CA) plays a crucial role in CO2 transport, in acid-base balance, and in linking local acidosis to O2 unloading from hemoglobin. Considering the structural similarity between...... bicarbonate and nitrite, we hypothesized that CA uses nitrite as a substrate to produce the potent vasodilator nitric oxide (NO) to increase local blood flow to metabolically active tissues. Here we show that CA readily reacts with nitrite to generate NO, particularly at low pH, and that the NO produced...

  16. The role of soil pH on soil carbonic anhydrase activity

    Science.gov (United States)

    Sauze, Joana; Jones, Sam P.; Wingate, Lisa; Wohl, Steven; Ogée, Jérôme

    2018-01-01

    Carbonic anhydrases (CAs) are metalloenzymes present in plants and microorganisms that catalyse the interconversion of CO2 and water to bicarbonate and protons. Because oxygen isotopes are also exchanged during this reaction, the presence of CA also modifies the contribution of soil and plant CO18O fluxes to the global budget of atmospheric CO18O. The oxygen isotope signatures (δ18O) of these fluxes differ as leaf water pools are usually more enriched than soil water pools, and this difference is used to partition the net CO2 flux over land into soil respiration and plant photosynthesis. Nonetheless, the use of atmospheric CO18O as a tracer of land surface CO2 fluxes requires a good knowledge of soil CA activity. Previous studies have shown that significant differences in soil CA activity are found in different biomes and seasons, but our understanding of the environmental and ecological drivers responsible for the spatial and temporal patterns observed in soil CA activity is still limited. One factor that has been overlooked so far is pH. Soil pH is known to strongly influence microbial community composition, richness and diversity in addition to governing the speciation of CO2 between the different carbonate forms. In this study we investigated the CO2-H2O isotopic exchange rate (kiso) in six soils with pH varying from 4.5 to 8.5. We also artificially increased the soil CA concentration to test how pH and other soil properties (texture and phosphate content) affected the relationship between kiso and CA concentration. We found that soil pH was the primary driver of kiso after CA addition and that the chemical composition (i.e. phosphate content) played only a secondary role. We also found an offset between the δ18O of the water pool with which CO2 equilibrates and total soil water (i.e. water extracted by vacuum distillation) that varied with soil texture. The reasons for this offset are still unknown.

  17. The role of soil pH on soil carbonic anhydrase activity

    Directory of Open Access Journals (Sweden)

    J. Sauze

    2018-01-01

    Full Text Available Carbonic anhydrases (CAs are metalloenzymes present in plants and microorganisms that catalyse the interconversion of CO2 and water to bicarbonate and protons. Because oxygen isotopes are also exchanged during this reaction, the presence of CA also modifies the contribution of soil and plant CO18O fluxes to the global budget of atmospheric CO18O. The oxygen isotope signatures (δ18O of these fluxes differ as leaf water pools are usually more enriched than soil water pools, and this difference is used to partition the net CO2 flux over land into soil respiration and plant photosynthesis. Nonetheless, the use of atmospheric CO18O as a tracer of land surface CO2 fluxes requires a good knowledge of soil CA activity. Previous studies have shown that significant differences in soil CA activity are found in different biomes and seasons, but our understanding of the environmental and ecological drivers responsible for the spatial and temporal patterns observed in soil CA activity is still limited. One factor that has been overlooked so far is pH. Soil pH is known to strongly influence microbial community composition, richness and diversity in addition to governing the speciation of CO2 between the different carbonate forms. In this study we investigated the CO2–H2O isotopic exchange rate (kiso in six soils with pH varying from 4.5 to 8.5. We also artificially increased the soil CA concentration to test how pH and other soil properties (texture and phosphate content affected the relationship between kiso and CA concentration. We found that soil pH was the primary driver of kiso after CA addition and that the chemical composition (i.e. phosphate content played only a secondary role. We also found an offset between the δ18O of the water pool with which CO2 equilibrates and total soil water (i.e. water extracted by vacuum distillation that varied with soil texture. The reasons for this offset are still unknown.

  18. Structural elucidation of the hormonal inhibition mechanism of the bile acid cholate on human carbonic anhydrase II

    Energy Technology Data Exchange (ETDEWEB)

    Boone, Christopher D. [University of Florida, PO Box 100267, Gainesville, FL 32610 (United States); Tu, Chingkuang [University of Florida, PO Box 100245, Gainesville, FL 32610 (United States); McKenna, Robert, E-mail: rmckenna@ufl.edu [University of Florida, PO Box 100267, Gainesville, FL 32610 (United States)

    2014-06-01

    The structure of human carbonic anhydrase II in complex with cholate has been determined to 1.54 Å resolution. Elucidation of the novel inhibition mechanism of cholate will aid in the development of a nonsulfur-containing, isoform-specific therapeutic agent. The carbonic anhydrases (CAs) are a family of mostly zinc metalloenzymes that catalyze the reversible hydration/dehydration of CO{sub 2} into bicarbonate and a proton. Human isoform CA II (HCA II) is abundant in the surface epithelial cells of the gastric mucosa, where it serves an important role in cytoprotection through bicarbonate secretion. Physiological inhibition of HCA II via the bile acids contributes to mucosal injury in ulcerogenic conditions. This study details the weak biophysical interactions associated with the binding of a primary bile acid, cholate, to HCA II. The X-ray crystallographic structure determined to 1.54 Å resolution revealed that cholate does not make any direct hydrogen-bond interactions with HCA II, but instead reconfigures the well ordered water network within the active site to promote indirect binding to the enzyme. Structural knowledge of the binding interactions of this nonsulfur-containing inhibitor with HCA II could provide the template design for high-affinity, isoform-specific therapeutic agents for a variety of diseases/pathological states, including cancer, glaucoma, epilepsy and osteoporosis.

  19. Effects of cryoprotectants on the structure and thermostability of the human carbonic anhydrase II–acetazolamide complex

    International Nuclear Information System (INIS)

    Aggarwal, Mayank; Boone, Christopher D.; Kondeti, Bhargav; Tu, Chingkuang; Silverman, David N.; McKenna, Robert

    2013-01-01

    Here, a case study of the effects of cryoprotectants on the kinetics of carbonic anhydrase II (CA II) and its inhibition by the clinically used inhibitor acetazolamide (AZM) is presented. Protein X-ray crystallography has seen a progressive shift from data collection at cool/room temperature (277–298 K) to data collection at cryotemperature (100 K) because of its ease of crystal preparation and the lessening of the detrimental effects of radiation-induced crystal damage, with 20–25%(v/v) glycerol (GOL) being the preferred choice of cryoprotectant. Here, a case study of the effects of cryoprotectants on the kinetics of carbonic anhydrase II (CA II) and its inhibition by the clinically used inhibitor acetazolamide (AZM) is presented. Comparative studies of crystal structure, kinetics, inhibition and thermostability were performed on CA II and its complex with AZM in the presence of either GOL or sucrose. These results suggest that even though the cryoprotectant GOL was previously shown to be directly bound in the active site and to interact with AZM, it affects neither the thermostability of CA II nor the binding of AZM in the crystal structure or in solution. However, addition of GOL does affect the kinetics of CA II, presumably as it displaces the water proton-transfer network in the active site

  20. Effects of cryoprotectants on the structure and thermostability of the human carbonic anhydrase II–acetazolamide complex

    Energy Technology Data Exchange (ETDEWEB)

    Aggarwal, Mayank; Boone, Christopher D.; Kondeti, Bhargav; Tu, Chingkuang; Silverman, David N.; McKenna, Robert, E-mail: rmckenna@ufl.edu [University of Florida, 1600 SW Archer Road, PO Box 100245, Gainesville, FL 32610 (United States)

    2013-05-01

    Here, a case study of the effects of cryoprotectants on the kinetics of carbonic anhydrase II (CA II) and its inhibition by the clinically used inhibitor acetazolamide (AZM) is presented. Protein X-ray crystallography has seen a progressive shift from data collection at cool/room temperature (277–298 K) to data collection at cryotemperature (100 K) because of its ease of crystal preparation and the lessening of the detrimental effects of radiation-induced crystal damage, with 20–25%(v/v) glycerol (GOL) being the preferred choice of cryoprotectant. Here, a case study of the effects of cryoprotectants on the kinetics of carbonic anhydrase II (CA II) and its inhibition by the clinically used inhibitor acetazolamide (AZM) is presented. Comparative studies of crystal structure, kinetics, inhibition and thermostability were performed on CA II and its complex with AZM in the presence of either GOL or sucrose. These results suggest that even though the cryoprotectant GOL was previously shown to be directly bound in the active site and to interact with AZM, it affects neither the thermostability of CA II nor the binding of AZM in the crystal structure or in solution. However, addition of GOL does affect the kinetics of CA II, presumably as it displaces the water proton-transfer network in the active site.

  1. Expression of transmembrane carbonic anhydrases, CAIX and CAXII, in human development

    Directory of Open Access Journals (Sweden)

    Lerman Michael I

    2009-03-01

    Full Text Available Abstract Background Transmembrane CAIX and CAXII are members of the alpha carbonic anhydrase (CA family. They play a crucial role in differentiation, proliferation, and pH regulation. Expression of CAIX and CAXII proteins in tumor tissues is primarily induced by hypoxia and this is particularly true for CAIX, which is regulated by the transcription factor, hypoxia inducible factor-1 (HIF-1. Their distributions in normal adult human tissues are restricted to highly specialized cells that are not always hypoxic. The human fetus exists in a relatively hypoxic environment. We examined expression of CAIX, CAXII and HIF-1α in the developing human fetus and postnatal tissues to determine whether expression of CAIX and CAXII is exclusively regulated by HIF-1. Results The co-localization of CAIX and HIF-1α was limited to certain cell types in embryonic and early fetal tissues. Those cells comprised the primitive mesenchyma or involved chondrogenesis and skin development. Transient CAIX expression was limited to immature tissues of mesodermal origin and the skin and ependymal cells. The only tissues that persistently expressed CAIX protein were coelomic epithelium (mesothelium and its remnants, the epithelium of the stomach and biliary tree, glands and crypt cells of duodenum and small intestine, and the cells located at those sites previously identified as harboring adult stem cells in, for example, the skin and large intestine. In many instances co-localization of CAIX and HIF-1α was not evident. CAXII expression is restricted to cells involved in secretion and water absorption such as parietal cells of the stomach, acinar cells of the salivary glands and pancreas, epithelium of the large intestine, and renal tubules. Co-localization of CAXII with CAIX or HIF-1α was not observed. Conclusion The study has showed that: 1 HIF-1α and CAIX expression co- localized in many, but not all, of the embryonic and early fetal tissues; 2 There is no evidence of

  2. Topical carbonic anhydrase inhibitors and visual function in glaucoma and ocular hypertension.

    Science.gov (United States)

    Gugleta, Konstantin

    2010-06-01

    Dorzolamide and brinzolamide are topical carbonic anhydrase inhibitors (CAI) indicated for patients with glaucoma and ocular hypertension. An evidence-based review of clinical trials of dorzolamide and brinzolamide was undertaken to determine an effect of these medications on visual function (primarily visual field) in open-angle glaucoma and ocular hypertension. Using the keywords 'dorzolamide' and 'brinzolamide', all articles describing trials of these medications reporting on visual acuity, contrast sensitivity and visual field from September 1966 to July 2009 were found in MEDLINE and EMBASE databases. No information from other sources was included in this review. A relatively modest number of trials was identified, where impact of therapy on one or more of the visual function modes was reported. In the studies of less than 1 year duration (3 days to 1 year, 23 studies) in all but three studies treatment with topical CAIs did not influence visual function, in two studies with dorzolamide some improvement in the contrast sensitivity was observed and in one open-label retrospective no-control-group study with dorzolamide visual field indices improved significantly. A different picture was seen in long-term studies, which were designed and powered to detect changes in visual field. One large study (European Glaucoma Prevention Study) with dorzolamide versus placebo failed to detect significant protective effect of the drug on glaucoma occurrence in ocular hypertensives. Several interesting aspects of this study are discussed in detail. The other two long-term studies reported on the superiority of adding dorzolamide over timolol therapy alone, and the superiority of the combination of dorzolamide and timolol over brinzolamide and timolol in terms of improving ocular blood flow (retrobulbar Color Doppler Imaging--CDI parameters) as well as in terms of visual field preservation in glaucoma patients over 4 to 5 years. For the first time one study could demonstrate

  3. H,K-ATPase and carbonic anhydrase response to chronic systemic rat gastric hypoxia

    Directory of Open Access Journals (Sweden)

    Ulfah Lutfiah

    2015-11-01

    Full Text Available Background: Hypoxia may induce gastric ulcer associated with excessive hidrogen chloride (HCl secretion. Synthesis of HCl involves 2 enzymes, H,K-ATPase and carbonic anhydrase (CA. This study aimed to clarify the underlying cause of gastric ulcer in chronic hypoxic condition, by investigating the H,K-ATPase and CA9 response in rats.Methods: This study was an in vivo experiment, to know the relationship between hypoxia to expression of H,K-ATPase and CA9 mRNA, and H,K-ATPase and total CA specific activity of chronic systemic rat gastric hypoxia. The result was compared to control. Data was analyzed by SPSS. If the data distribution was normal and homogeneous, ANOVA and LSD post-hoc test were used. However, if the distribution was not normal and not homogeneous, and still as such after transformation, data was treated in non-parametric using Kruskal-Wallis and Mann Whitney test. Twenty five male Sprague-Dawley rats were divided into 5 groups: rats undergoing hypoxia for 1, 3, 5, and 7 days placed in hypoxia chamber (10% O2, 90% N2, and one control group. Following this treatment, stomach of the rats was extracted and homogenized. Expression of H,K-ATPase and CA9 mRNA was measured using real time RT-PCR. Specific activity of H,K-ATPase was measured using phosphate standard solution, and specific activity of total CA was measured using p-nitrophenol solution.Results: The expression of H,K-ATPase mRNA was higher in the first day (2.159, and drastically lowered from the third to seventh day (0.289; 0.108; 0.062. Specific activities of H,K-ATPase was slightly higher in the first day (0.765, then was lowered in the third (0.685 and fifth day (0.655, and was higher in the seventh day (0.884. The expression of CA9 mRNA was lowered progressively from the first to seventh day (0.84; 0.766; 0.736; 0.343. Specific activities of total CA was low in the first day (0.083, and was higher from the third to seventh day (0.111; 0.136; 0.144.Conclusion: In hypoxia

  4. Analyzing the 3D Structure of Human Carbonic Anhydrase II and Its Mutants Using Deep View and the Protein Data Bank

    Science.gov (United States)

    Ship, Noam J.; Zamble, Deborah B.

    2005-01-01

    The self directed study of a 3D image of a biomolecule stresses the complex nature of the intra- and intermolecular interactions that come together to define its structure. This is made up of a series of in vitro experiments with a wild-type and mutants forms of human carbonic anhydrase II (hCAII) that examine the structure function relationship…

  5. In folio study of carbonic anhydrase and Rubisco activities in higher C{sub 3} plants using {sup 18}O and mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Peltier, G.; Despax, V.; Dimon, B.; Rumeau, D.; Tourneux, C.

    1994-12-31

    This document studies the effects of a mild water stress and carbonic anhydrase activity by ethoxyzolamide (EZA) on the diffusion of CO{sub 2} in leaves, by {sup 18}O labelling of O{sub 2} and of CO{sub 2} associated to mass spectrometry. (A.B.). 5 refs., 2 figs.

  6. β-Carbonic Anhydrases Play a Role in Fruiting Body Development and Ascospore Germination in the Filamentous Fungus Sordaria macrospora

    Science.gov (United States)

    Elleuche, Skander; Pöggeler, Stefanie

    2009-01-01

    Carbon dioxide (CO2) is among the most important gases for all organisms. Its reversible interconversion to bicarbonate (HCO3 −) reaches equilibrium spontaneously, but slowly, and can be accelerated by a ubiquitous group of enzymes called carbonic anhydrases (CAs). These enzymes are grouped by their distinct structural features into α-, β-, γ-, δ- and ζ-classes. While physiological functions of mammalian, prokaryotic, plant and algal CAs have been extensively studied over the past years, the role of β-CAs in yeasts and the human pathogen Cryptococcus neoformans has been elucidated only recently, and the function of CAs in multicellular filamentous ascomycetes is mostly unknown. To assess the role of CAs in the development of filamentous ascomycetes, the function of three genes, cas1, cas2 and cas3 (carbonic anhydrase of Sordaria) encoding β-class carbonic anhydrases was characterized in the filamentous ascomycetous fungus Sordaria macrospora. Fluorescence microscopy was used to determine the localization of GFP- and DsRED-tagged CAs. While CAS1 and CAS3 are cytoplasmic enzymes, CAS2 is localized to the mitochondria. To assess the function of the three isoenzymes, we generated knock-out strains for all three cas genes (Δcas1, Δcas2, and Δcas3) as well as all combinations of double mutants. No effect on vegetative growth, fruiting-body and ascospore development was seen in the single mutant strains lacking cas1 or cas3, while single mutant Δcas2 was affected in vegetative growth, fruiting-body development and ascospore germination, and the double mutant strain Δcas1/2 was completely sterile. Defects caused by the lack of cas2 could be partially complemented by elevated CO2 levels or overexpression of cas1, cas3, or a non-mitochondrial cas2 variant. The results suggest that CAs are required for sexual reproduction in filamentous ascomycetes and that the multiplicity of isoforms results in redundancy of specific and non-specific functions. PMID:19365544

  7. Non-destructive estimates of soil carbonic anhydrase activity and associated soil water oxygen isotope composition

    Science.gov (United States)

    Jones, Sam P.; Ogée, Jérôme; Sauze, Joana; Wohl, Steven; Saavedra, Noelia; Fernández-Prado, Noelia; Maire, Juliette; Launois, Thomas; Bosc, Alexandre; Wingate, Lisa

    2017-12-01

    The contribution of photosynthesis and soil respiration to net land-atmosphere carbon dioxide (CO2) exchange can be estimated based on the differential influence of leaves and soils on budgets of the oxygen isotope composition (δ18O) of atmospheric CO2. To do so, the activity of carbonic anhydrases (CAs), a group of enzymes that catalyse the hydration of CO2 in soils and plants, needs to be understood. Measurements of soil CA activity typically involve the inversion of models describing the δ18O of CO2 fluxes to solve for the apparent, potentially catalysed, rate of CO2 hydration. This requires information about the δ18O of CO2 in isotopic equilibrium with soil water, typically obtained from destructive, depth-resolved sampling and extraction of soil water. In doing so, an assumption is made about the soil water pool that CO2 interacts with, which may bias estimates of CA activity if incorrect. Furthermore, this can represent a significant challenge in data collection given the potential for spatial and temporal variability in the δ18O of soil water and limited a priori information with respect to the appropriate sampling resolution and depth. We investigated whether we could circumvent this requirement by inferring the rate of CO2 hydration and the δ18O of soil water from the relationship between the δ18O of CO2 fluxes and the δ18O of CO2 at the soil surface measured at different ambient CO2 conditions. This approach was tested through laboratory incubations of air-dried soils that were re-wetted with three waters of different δ18O. Gas exchange measurements were made on these soils to estimate the rate of hydration and the δ18O of soil water, followed by soil water extraction to allow for comparison. Estimated rates of CO2 hydration were 6.8-14.6 times greater than the theoretical uncatalysed rate of hydration, indicating that CA were active in these soils. Importantly, these estimates were not significantly different among water treatments, suggesting

  8. Extraction of superoxide dismutase, catalase, and carbonic anhydrase from stroma-free red blood cell hemolysate for the preparation of the nanobiotechnological complex of polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase.

    Science.gov (United States)

    Guo, C; Gynn, M; Chang, T M S

    2015-06-01

    We report a novel method to simultaneously extract superoxide dismutase (SOD), catalase (CAT), and carbonic anhydrase (CA) from the same sample of red blood cells (RBCs). This avoids the need to use expensive commercial enzymes, thus enabling a cost-effective process for large-scale production of a nanobiotechnological polyHb-SOD-CAT-CA complex, with enhancement of all three red blood cell functions. An optimal concentration of phosphate buffer for ethanol-chloroform treatment results in good recovery of CAT, SOD, and CA after extraction. Different concentrations of the enzymes can be used to enhance the activity of polyHb-SOD-CAT-CA to 2, 4, or 6 times that of RBC.

  9. Synthesis and biological evaluation of phloroglucinol derivatives possessing α-glycosidase, acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase inhibitory activity.

    Science.gov (United States)

    Burmaoglu, Serdar; Yilmaz, Ali O; Taslimi, Parham; Algul, Oztekin; Kilic, Deryanur; Gulcin, Ilhami

    2018-02-01

    A series of novel phloroglucinol derivatives were designed, synthesized, characterized spectroscopically and tested for their inhibitory activity against selected metabolic enzymes, including α-glycosidase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase I and II (hCA I and II). These compounds displayed nanomolar inhibition levels and showed K i values of 1.14-3.92 nM against AChE, 0.24-1.64 nM against BChE, 6.73-51.10 nM against α-glycosidase, 1.80-5.10 nM against hCA I, and 1.14-5.45 nM against hCA II. © 2018 Deutsche Pharmazeutische Gesellschaft.

  10. Designing of phenol-based β-carbonic anhydrase1 inhibitors through QSAR, molecular docking, and MD simulation approach.

    Science.gov (United States)

    Ahamad, Shahzaib; Hassan, Md Imtaiyaz; Dwivedi, Neeraja

    2018-05-01

    Tuberculosis (Tb) is an airborne infectious disease caused by Mycobacterium tuberculosis. Beta-carbonic anhydrase 1 ( β-CA1 ) has emerged as one of the potential targets for new antitubercular drug development. In this work, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular docking, and molecular dynamics (MD) simulation approaches were performed on a series of natural and synthetic phenol-based β-CA1 inhibitors. The developed 3D-QSAR model ( r 2  = 0.94, q 2  = 0.86, and pred_r 2  = 0.74) indicated that the steric and electrostatic factors are important parameters to modulate the bioactivity of phenolic compounds. Based on this indication, we designed 72 new phenolic inhibitors, out of which two compounds (D25 and D50) effectively stabilized β-CA1 receptor and, thus, are potential candidates for new generation antitubercular drug discovery program.

  11. Carbon anhydrase IX specific immune responses in patients with metastatic renal cell carcinoma potentially cured by interleukin-2 based immunotherapy

    DEFF Research Database (Denmark)

    Rasmussen, Susanne; Donskov, Frede; Pedersen, Johannes W

    2013-01-01

    Abstract The majority of clear-cell renal cell carcinomas (ccRCC) show high and homogeneous expression levels of the tumor associated antigen (TAA) carbonic anhydrase IX (CAIX), and treatment with interleukin-2 (IL-2) based immunotherapy can lead to cure in patients with metastatic renal cell...... of disease (NED) following treatment with IL-2 based immunotherapy, and thus potentially cured. Immune reactivity in these patients was compared with samples from patients with dramatic tumor response obtained immediately at the cessation of therapy, samples from patients that experienced progressive disease...... interest in future cancer vaccines, but more studies are needed to elucidate the immunological mechanisms of action in potentially cured patients treated with an immunotherapeutic agent....

  12. Carbonic anhydrase inhibition boosts the antitumor effects of Imatinib mesylate via potentiating the antiangiogenic and antimetastatic machineries

    Energy Technology Data Exchange (ETDEWEB)

    Abd-El Fattah, Amal A. [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Darwish, Hebatallah A. [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University, Cairo (Egypt); Fathy, Nevine, E-mail: nevine.abdallah@pharma.cu.edu.eg [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Shouman, Samia A. [Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11796 (Egypt)

    2017-02-01

    Carbonic anhydrase inhibitors have emerged in the past few years as an interesting candidate for the development of novel unconventional strategies. Despite their effect in tumor regression via inhibition of tumor acidification, their potential role is not yet fully elucidated. Herein, we investigated whether acetazolamide (AZ) could modulate imatinib (IM) anticancer activity, both in breast cancer cells (T47D) and in isolated tumor specimens of Ehrlich ascites carcinoma (EAC). The impact of this combination on angiogenesis was evidenced by decreasing PDGF-A expression and enhancing that of TSP-1. In the meantime, AZ significantly suppressed IM-induced attenuation of VEGF secretion in T47D cells, most probably due to NO inhibition. The combination also dramatically decreased the metastatic activity of T47D cells by mitigating the protein levels of MMP-2 and -9 and phosphorylation of p38 MAPK, while increasing the expression of TIMP-1 and -2. In addition, a strong proapoptotic effect was observed in T47D cells after combining AZ and IM in terms of increased caspase-9 and -3 activities. Interestingly, these results were confirmed by the reduction in the isolated tumor volume, MVD, Ki-67 and VEGF expression. Eventually, the study provides a new therapeutic strategy for treating cancer. - Highlights: • A novel combination of imatinib and a carbonic anhydrase was studied. • The impact was evaluated in T47D cells and EAC-bearing mice. • The interaction suppressed PDGF-A and VEGF while enhanced TSP-1. • MMPs and p38 MAPK phosphorylation were suppressed while TIMPs were enhanced. • The interaction triggered caspase-9 and -3 activation.

  13. Hepatoprotective effects of Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] on alcohol-damaged primary rat hepatocyte culture in vitro.

    Science.gov (United States)

    Jiang, Wenhua; Bian, Yuzhu; Wang, Zhenghui; Chang, Thomas Ming Swi

    2017-02-01

    We have prepared a novel nanobiotherapeutic, Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase], which not only transports both oxygen and carbon dioxide but also a therapeutic antioxidant. Our previous study in a severe sustained 90 min hemorrhagic shock rat model shows that it has a hepatoprotective effect. We investigate its hepatoprotective effect further in this present report using an alcohol-damaged primary hepatocyte culture model. Results show that it significantly reduced ethanol-induced AST release, lipid peroxidation, and ROS production in rat primary hepatocytes culture. It also significantly enhanced the viability of ethanol-treated hepatocytes. Thus, the result shows that Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] also has some hepatoprotective effects against alcohol-induced injury in in vitro rat primary hepatocytes cell culture. This collaborate our previous observation of its hepatoprotective effect in a severe sustained 90-min hemorrhagic shock rat model.

  14. Gymnocypris przewalskii decreases cytosolic carbonic anhydrase expression to compensate for respiratory alkalosis and osmoregulation in the saline-alkaline lake Qinghai.

    Science.gov (United States)

    Yao, Zongli; Guo, Wenfei; Lai, Qifang; Shi, Jianquan; Zhou, Kai; Qi, Hongfang; Lin, Tingting; Li, Ziniu; Wang, Hui

    2016-01-01

    Naked carp (Gymnocypris przewalskii), endemic to the saline-alkaline Lake Qinghai, have the capacity to tolerate combined high salinity and alkalinity, but migrate to spawn in freshwater rivers each year. In this study, the full-length cDNA of the cytosolic carbonic anhydrase c isoform of G. przewalskii (GpCAc) was amplified and sequenced; mRNA levels and enzyme activity of GpCAc and blood chemistry were evaluated to understand the compensatory responses as the naked carp returned to the saline-alkaline lake after spawning. We found that GpCAc had a total length of 1400 bp and encodes a peptide of 260 amino acids. Comparison of the deduced amino acid sequences and phylogenetic analysis showed that GpCAc was a member of the cytosolic carbonic anhydrase II-like c family. Cytosolic-carbonic-anhydrase-c-specific primers were used to analyze the tissue distribution of GpCAc mRNA expression. Expression of GpCAc mRNA was found in brain, gill, liver, kidney, gut, and muscle tissues, but primarily in the gill and posterior kidney; however, none was evident in red blood cells. Transferring fish from river water to lake water resulted in a respiratory alkalosis, osmolality, and ion rise in the blood, as well as significant decreases in the expression and enzyme activity of GpCAc in both the gill and kidney within 96 h. These results indicate that GpCAc may play an important role in the acclimation to both high salinity and carbonate alkalinity. Specifically, G. przewalskii decreases cytosolic carbonic anhydrase c expression to compensate for a respiratory alkalosis and to aid in osmoregulation during the transition from river to saline-alkaline lake.

  15. Mapping of carbonic anhydrase and estrone sulphatase in rat brain using 16-α-[18F]fluoroestradiol-3,17-β-disulphamate ([18F]FESDS)

    International Nuclear Information System (INIS)

    Rodig, H.; Brust, P.; Bergmann, R.; Roemer, J.; Fuechtner, F.; Steinbach, J.; Kasch, H.

    2002-01-01

    16α-[ 18 F]Fluoroestradiol-3,17β-disulphamate ([ 18 F]FESDS) was recently found to display affinities to carbonic anhydrase (CA) and estrone sulphatase (ES), enzymes which are expressed in the CNS and probably play a regulatory role in various brain diseases. In this study the radioligand was used to provide quantitative data on the regional distribution of these enzymes in the rat brain. (orig.)

  16. Hydrogen/deuterium fractionation factors of the aqueous ligand of cobalt in Co(H2O)62+ and Co(II)-substituted carbonic anhydrase

    International Nuclear Information System (INIS)

    Kassebaum, J.W.

    1988-01-01

    The author has measured the hydrogen/deuterium fractionation factor for the rapidly exchanging aqueous ligands of cobalt in Co(H 2 O) 6 2+ and in three Co(II)-substituted isozymes of carbonic anhydrase. The fractionation factor was determined from NMR relaxation rates at 300 MHz of the protons of water in mixed solutions of H 2 O and D 2 O containing these complexes. In each case, the paramagnetic contribution to 1/T 2 was greater than to 1/T 1 , consistent with a chemical shift mechanism affecting 1/T 2 . The fractionation factors obtained from T 2 were 0.73 ± 0.02 for Co(H 2 O) 6 2+ , 0.72 ± 0.02 for Co(II)-substituted carbonic anhydrase I, 0.77 ± 0.01 for Co(II)-substituted carbonic anhydrase II, and 1.00 ± 0.07 for Co(Il)-substituted carbonic anhydrase III. He concluded that fractionation factors in these cases determined from T 1 and T 2 measured isotope preferences for different populations of ligand sites. Since T 2 has a large contribution from a chemical shift mechanism, the fractionation factor determined from T 2 has a large contribution of the fractionation of inner shell ligands. The fractionation factor of Co(H 2 O) 6 2+ was used to interpret the solvent hydrogen isotope effects on the formation of complexes of cobalt with the bidentate ligands glycine, N,N-dimethylglycine, and acetylacetone. The contribution of the fractionation factor of the inner water shell in Co(H 2 O) 6 2+ did not account completely for the measured isotope effect, and that the hydrogen/deuterium fractionation of outer shell water makes a large contribution to the isotope effect on the formation of these complexes

  17. Acidic sweep gas with carbonic anhydrase coated hollow fiber membranes synergistically accelerates CO2 removal from blood.

    Science.gov (United States)

    Arazawa, D T; Kimmel, J D; Finn, M C; Federspiel, W J

    2015-10-01

    The use of extracorporeal carbon dioxide removal (ECCO2R) is well established as a therapy for patients suffering from acute respiratory failure. Development of next generation low blood flow (carbonic anhydrase (CA) immobilized bioactive hollow fiber membrane (HFM) which significantly accelerates CO2 removal from blood in model gas exchange devices by converting bicarbonate to CO2 directly at the HFM surface. This present study tested the hypothesis that dilute sulfur dioxide (SO2) in oxygen sweep gas could further increase CO2 removal by creating an acidic microenvironment within the diffusional boundary layer adjacent to the HFM surface, facilitating dehydration of bicarbonate to CO2. CA was covalently immobilized onto poly (methyl pentene) (PMP) HFMs through glutaraldehyde activated chitosan spacers, potted in model gas exchange devices (0.0151 m(2)) and tested for CO2 removal rate with oxygen (O2) sweep gas and a 2.2% SO2 in oxygen sweep gas mixture. Using pure O2 sweep gas, CA-PMP increased CO2 removal by 31% (258 mL/min/m(2)) compared to PMP (197 mL/min/m(2)) (Premoval by 17% (230 mL/min/m(2)) compared to pure oxygen sweep gas control (Premoval increased by 109% (411 mL/min/m(2)) (Premoval, and when used in combination with bioactive CA-HFMs has a synergistic effect to more than double CO2 removal while maintaining physiologic pH. Through these technologies the next generation of intravascular and paracorporeal respiratory assist devices can remove more CO2 with smaller blood contacting surface areas. A clinical need exists for more efficient respiratory assist devices which utilize low blood flow rates (removal efficiency by shifting equilibrium from bicarbonate to gaseous CO2, through either a bioactive carbonic anhydrase enzyme coating or bulk blood acidification with lactic acid. In this study we demonstrate a novel approach to local blood acidification using an acidified sweep gas in combination with a bioactive coating to more than double CO2 removal

  18. Synthesis and discovery of potent carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase, and α-glycosidase enzymes inhibitors: The novel N,N'-bis-cyanomethylamine and alkoxymethylamine derivatives.

    Science.gov (United States)

    Taslimi, Parham; Caglayan, Cuneyt; Farzaliyev, Vagif; Nabiyev, Oruj; Sujayev, Afsun; Turkan, Fikret; Kaya, Ruya; Gulçin, İlhami

    2018-04-01

    During this investigation, N,N'-bis-azidomethylamines, N,N'-bis-cyanomethylamine, new alkoxymethylamine and chiral derivatives, which are considered to be a new generation of multifunctional compounds, were synthesized, functional properties were investigated, and anticholinergic and antidiabetic properties of those compounds were studied through the laboratory tests, and it was approved that they contain physiologically active compounds rather than analogues. Novel N-bis-cyanomethylamine and alkoxymethylamine derivatives were effective inhibitors of the α-glycosidase, cytosolic carbonic anhydrase I and II isoforms, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) with K i values in the range of 0.15-13.31 nM for α-glycosidase, 2.77-15.30 nM for human carbonic anhydrase isoenzymes I (hCA I), 3.12-21.90 nM for human carbonic anhydrase isoenzymes II (hCA II), 23.33-73.23 nM for AChE, and 3.84-48.41 nM for BChE, respectively. Indeed, the inhibition of these metabolic enzymes has been considered as a promising factor for pharmacologic intervention in a diversity of disturbances. © 2018 Wiley Periodicals, Inc.

  19. Bioinformatics Approach Based Research of Profile Protein Carbonic Anhydrase II Analysis as a Potential Candidate Cause Autism for The Variation of Learning Subjects Biotechnology

    Directory of Open Access Journals (Sweden)

    Dian Eka A. F. Ningrum

    2017-03-01

    Full Text Available This study aims to determine the needs of learning variations on Biotechnology courses using bioinformatics approaches. One example of applied use of bioinformatics in biotechnology course is the analysis of protein profiles carbonic anhydrase II as a potential cause of autism candidate. This research is a qualitative descriptive study consisted of two phases. The first phase of the data obtained from observations of learning, student questionnaires, and questionnaires lecturer. Results from the first phase, namely the need for variations learning in Biotechnology course using bioinformatics. Collecting data on the second stage uses three webserver to predict the target protein and scientific articles. Visualization of proteins using PyMOL software. 3 based webserver which is used, the candidate of target proteins associated with autism is carbonic anhydrase II. The survey results revealed that the protein carbonic anhydrase II as a potential candidate for the cause of autism classified metaloenzim are able to bind with heavy metals. The content of heavy metals in autistic patients high that affect metabolism. This prediction of protein candidate cause autism is applied use to solve the problem in society, so that can achieve the learning outcome in biotechnology course.

  20. Cloning, expression and biochemical characterization of a β-carbonic anhydrase from the soil bacterium Enterobacter sp. B13.

    Science.gov (United States)

    Eminoğlu, Ayşenur; Vullo, Daniela; Aşık, Aycan; Çolak, Dilşat Nigar; Supuran, Claudiu T; Çanakçı, Sabriye; Osman Beldüz, Ali

    2016-12-01

    A recombinant carbonic anhydrase (CA, EC 4.2.1.1) from the soil-dwelling bacterium Enterobacter sp. B13 was cloned and purified by Co(2+) affinity chromatography. Bioinformatic analysis showed that the new enzyme (denominated here B13-CA) belongs to the β-class CAs and to possess 95% homology with the ortholog enzyme from Escherichia coli encoded by the can gene, whereas its sequence homology with the other such enzyme from E. coli (encoded by the cynT gene) was of 33%. B13-CA was characterized kinetically as a catalyst for carbon dioxide hydration to bicarbonate and protons. The enzyme shows a significant catalytic activity, with the following kinetic parameters at 20 °C and pH of 8.3: kcat of 4.8 × 10(5) s(-1) and kcat/Km of 5.6 × 10(7) M(-1) × s(-1). This activity was potently inhibited by acetazolamide which showed a KI of 78.9 nM. Although only this compound was investigated for the moment as B13-CA inhibitor, further studies may reveal new classes of inhibitors/activators of this enzyme which may show biomedical or environmental applications, considering the posssible role of this enzyme in CaCO3 biomineralization processes.

  1. Cloning, characterization and anion inhibition study of a β-class carbonic anhydrase from the caries producing pathogen Streptococcus mutans.

    Science.gov (United States)

    Dedeoglu, Nurcan; De Luca, Viviana; Isik, Semra; Yildirim, Hatice; Kockar, Feray; Capasso, Clemente; Supuran, Claudiu T

    2015-07-01

    The oral pathogenic bacterium involved in human dental caries formation Streptococcus mutans, encodes for two carbonic anhydrase (CA, EC 4.2.1.1) one belonging to the α- and the other one to the β-class. This last enzyme (SmuCA) has been cloned, characterized and investigated for its inhibition profile with a major class of CA inhibitors, the inorganic anions. Here we show that SmuCA has a good catalytic activity for the CO2 hydration reaction, with kcat 4.2×10(5)s(-1) and kcat/Km of 5.8×10(7)M(-1)×s(-1), being inhibited by cyanate, carbonate, stannate, divannadate and diethyldithiocarbamate in the submillimolar range (KIs of 0.30-0.64mM) and more efficiently by sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid (KIs of 15-46μM). The anion inhibition profile of the S. mutans enzyme is very different from other α- and β-CAs investigated earlier. Identification of effective inhibitors of this new enzyme may lead to pharmacological tools useful for understanding the role of S. mutans CAs in dental caries formation, and eventually the development of pharmacological agents with a new mechanism of antibacterial action. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Synthesis of a new series of dithiocarbamates with effective human carbonic anhydrase inhibitory activity and antiglaucoma action.

    Science.gov (United States)

    Bozdag, Murat; Carta, Fabrizio; Vullo, Daniela; Akdemir, Atilla; Isik, Semra; Lanzi, Cecilia; Scozzafava, Andrea; Masini, Emanuela; Supuran, Claudiu T

    2015-05-15

    A new series of dithiocarbamates (DTCs) was prepared from primary/secondary amines incorporating amino/hydroxyl-alkyl, mono- and bicyclic aliphatic ring systems based on the quinuclidine, piperidine, hydroxy-/carboxy-/amino-substituted piperidine, morpholine and piperazine scaffolds, and carbon disulfide. The compounds were investigated for the inhibition of four mammalian α-carbonic anhydrases (CAs, EC 4.2.1.1) of pharmacologic relevance, that is, the human (h) hCA I, II, IX and XII, drug targets for antiglaucoma (hCA II and XII) or antitumor (hCA IX/XII) agents. The compounds were moderate or inefficient hCA I inhibitors (off-target isoform for both applications), efficiently inhibited hCA II, whereas some of them were low nanomolar/subnanomolar hCA IX/XII inhibitors. One DTC showed excellent intraocular pressure (IOP) lowering properties in an animal model of glaucoma, with a two times better efficiency compared to the clinically used sulfonamide dorzolamide. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Fluoroalkyl and Alkyl Chains Have Similar Hydrophobicities in Binding to the “Hydrophobic Wall” of Carbonic Anhydrase

    Energy Technology Data Exchange (ETDEWEB)

    J Mecinovic; P Snyder; K Mirica; S Bai; E Mack; R Kwant; D Moustakas; A Heroux; G Whitesides

    2011-12-31

    The hydrophobic effect, the free-energetically favorable association of nonpolar solutes in water, makes a dominant contribution to binding of many systems of ligands and proteins. The objective of this study was to examine the hydrophobic effect in biomolecular recognition using two chemically different but structurally similar hydrophobic groups, aliphatic hydrocarbons and aliphatic fluorocarbons, and to determine whether the hydrophobicity of the two groups could be distinguished by thermodynamic and biostructural analysis. This paper uses isothermal titration calorimetry (ITC) to examine the thermodynamics of binding of benzenesulfonamides substituted in the para position with alkyl and fluoroalkyl chains (H{sub 2}NSO{sub 2}C{sub 6}H{sub 4}-CONHCH{sub 2}(CX{sub 2}){sub n}CX{sub 3}, n = 0-4, X = H, F) to human carbonic anhydrase II (HCA II). Both alkyl and fluoroalkyl substituents contribute favorably to the enthalpy and the entropy of binding; these contributions increase as the length of chain of the hydrophobic substituent increases. Crystallography of the protein-ligand complexes indicates that the benzenesulfonamide groups of all ligands examined bind with similar geometry, that the tail groups associate with the hydrophobic wall of HCA II (which is made up of the side chains of residues Phe131, Val135, Pro202, and Leu204), and that the structure of the protein is indistinguishable for all but one of the complexes (the longest member of the fluoroalkyl series). Analysis of the thermodynamics of binding as a function of structure is compatible with the hypothesis that hydrophobic binding of both alkyl and fluoroalkyl chains to hydrophobic surface of carbonic anhydrase is due primarily to the release of nonoptimally hydrogen-bonded water molecules that hydrate the binding cavity (including the hydrophobic wall) of HCA II and to the release of water molecules that surround the hydrophobic chain of the ligands. This study defines the balance of enthalpic and

  4. Involvement of β-carbonic anhydrase (β-CA) genes in bacterial genomic islands and horizontal transfer to protists.

    Science.gov (United States)

    Zolfaghari Emameh, Reza; Barker, Harlan R; Hytönen, Vesa P; Parkkila, Seppo

    2018-05-25

    Genomic islands (GIs) are a type of mobile genetic element (MGE) that are present in bacterial chromosomes. They consist of a cluster of genes which produce proteins that contribute to a variety of functions, including, but not limited to, regulation of cell metabolism, anti-microbial resistance, pathogenicity, virulence, and resistance to heavy metals. The genes carried in MGEs can be used as a trait reservoir in times of adversity. Transfer of genes using MGEs, occurring outside of reproduction, is called horizontal gene transfer (HGT). Previous literature has shown that numerous HGT events have occurred through endosymbiosis between prokaryotes and eukaryotes.Beta carbonic anhydrase (β-CA) enzymes play a critical role in the biochemical pathways of many prokaryotes and eukaryotes. We have previously suggested horizontal transfer of β-CA genes from plasmids of some prokaryotic endosymbionts to their protozoan hosts. In this study, we set out to identify β-CA genes that might have transferred between prokaryotic and protist species through HGT in GIs. Therefore, we investigated prokaryotic chromosomes containing β-CA-encoding GIs and utilized multiple bioinformatics tools to reveal the distinct movements of β-CA genes among a wide variety of organisms. Our results identify the presence of β-CA genes in GIs of several medically and industrially relevant bacterial species, and phylogenetic analyses reveal multiple cases of likely horizontal transfer of β-CA genes from GIs of ancestral prokaryotes to protists. IMPORTANCE The evolutionary process is mediated by mobile genetic elements (MGEs), such as genomic islands (GIs). A gene or set of genes in the GIs are exchanged between and within various species through horizontal gene transfer (HGT). Based on the crucial role that GIs can play in bacterial survival and proliferation, they were introduced as the environmental- and pathogen-associated factors. Carbonic anhydrases (CAs) are involved in many critical

  5. The ability of anti-carbonic anhydrase II antibody to distinguish autoimmune cholangitis from primary biliary cirrhosis in Japanese patients.

    Science.gov (United States)

    Akisawa, N; Nishimori, I; Miyaji, E; Iwasaki, S; Maeda, T; Shimizu, H; Sato, N; Onishi, S

    1999-06-01

    Serum antibody against carbonic anhydrase (CA) II has been described as a serological marker for distinguishing autoimmune cholangitis (AIC) from primary biliary cirrhosis (PBC). To validate this finding in a Japanese population, we evaluated sera from patients with PBC and AIC for antibody to human CA II. An enzyme-linked immunosorbent assay was employed to quantify serum antibody against CA II in patients with PBC (n = 40), AIC (n = 23), autoimmune hepatitis (n = 10), and extrahepatic obstructive jaundice (n = 10). Compared with the finding of a 4% prevalence of anti-CAII antibody in healthy subjects (n = 24), a significantly higher prevalence of anti-CA II antibody was detected in patients with PBC (35%) and AIC (30%) (P jaundice. No significant difference was observed between PBC and AIC patients. These results showed that AIC and PBC would be indistinguishable by anti-CA II antibody testing in Japanese patients. However, the finding of serum anti-CA II antibody in patients with PBC and AIC supports the disease concept of autoimmune exocrinopathy.

  6. Novel genetic markers of the carbonic anhydrase II gene associated with egg production and reproduction traits in Tsaiya ducks.

    Science.gov (United States)

    Chang, M-T; Cheng, Y-S; Huang, M-C

    2013-02-01

    In our previous cDNA microarray study, we found that the carbonic anhydrase II (CA2) gene is one of the differentially expressed transcripts in the duck isthmus epithelium during egg formation period. The aim of this study was to identify the single-nucleotide polymorphisms (SNPs) in the CA2 gene of Tsaiya ducks. The relationship of SNP genotype with egg production and reproduction traits was also investigated. A total of 317 ducks from two lines, a control line with no selection and a selected line, were employed for testing. Three SNPs (C37T, A62G and A65G) in the 3'-untranslated region of the CA2 gene were found. SNP-trait association analysis showed that SNP C37T and A62G were associated with duck egg weight besides fertility. The ducks with the CT and AG genotypes had a 1.46 and 1.62 g/egg lower egg weight as compared with ducks with the CC and AA genotypes, respectively (p ducks with CT and AG genotypes had 5.20% and 4.22% higher fertility than those with CC and AA genotypes, respectively (p duck fertility, and the diplotype H1H4 was dominant for duck fertility. These findings might provide the basis for balanced selection and may be used in marker-assisted selection to improve egg weight and fertility simultaneously in the Tsaiya ducks. © 2012 Blackwell Verlag GmbH.

  7. Sulfonamide inhibition studies of two β-carbonic anhydrases from the ascomycete fungus Sordaria macrospora, CAS1 and CAS2.

    Science.gov (United States)

    Vullo, Daniela; Lehneck, Ronny; Pöggeler, Stefanie; Supuran, Claudiu T

    2018-12-01

    The two β-carbonic anhydrases (CAs, EC 4.2.1.1) recently cloned and purified from the ascomycete fungus Sordaria macrospora, CAS1 and CAS2, were investigated for their inhibition with a panel of 39 aromatic, heterocyclic, and aliphatic sulfonamides and one sulfamate, many of which are clinically used agents. CAS1 was efficiently inhibited by tosylamide, 3-fluorosulfanilamide, and 3-chlorosulfanilamide (K I s in the range of 43.2-79.6 nM), whereas acetazolamide, methazolamide, topiramate, ethoxzolamide, dorzolamide, and brinzolamide were medium potency inhibitors (K I s in the range of 360-445 nM). CAS2 was less sensitive to sulfonamide inhibitors. The best CAS2 inhibitors were 5-amino-1,3,4-thiadiazole-2-sulfonamide (the deacetylated acetazolamide precursor) and 4-hydroxymethyl-benzenesulfonamide, with K I s in the range of 48.1-92.5 nM. Acetazolamide, dorzolamide, ethoxzolamide, topiramate, sulpiride, indisulam, celecoxib, and sulthiame were medium potency CAS2 inhibitors (K I s of 143-857 nM). Many other sulfonamides showed affinities in the high micromolar range or were ineffective as CAS1/2 inhibitors. Small changes in the structure of the inhibitor led to important differences of the activity. As these enzymes may show applications for the removal of anthropically generated polluting gases, finding modulators of their activity may be crucial for designing environmental-friendly CO 2 capture processes.

  8. Early increase in circulating carbonic anhydrase IX during neoadjuvant treatment predicts favourable outcome in locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Hektoen, Helga Helseth; Flatmark, Kjersti; Andersson, Yvonne; Dueland, Svein; Redalen, Kathrine Røe; Ree, Anne Hansen

    2015-01-01

    Locally advanced rectal cancer (LARC) comprises heterogeneous tumours with predominant hypoxic components. The hypoxia-inducible metabolic shift causes microenvironmental acidification generated by carbonic anhydrase IX (CAIX) and facilitates metastatic progression, the dominant cause of failure in LARC. Using a commercially available immunoassay, circulating CAIX was assessed in prospectively archived serial serum samples collected during combined-modality neoadjuvant treatment of LARC patients and correlated to histologic tumour response and progression-free survival (PFS). Patients who from their individual baseline level displayed serum CAIX increase above a threshold of 224 pg/ml (with 96 % specificity and 39 % sensitivity) after completion of short-course neoadjuvant chemotherapy (NACT) prior to long-course chemoradiotherapy and definitive surgery had significantly better 5-year PFS (94 %) than patients with below-threshold post-NACT versus baseline alteration (PFS rate of 56 %; p < 0.01). This particular CAIX parameter, ΔNACT, was significantly correlated with histologic ypT0–2 and ypN0 outcome (p < 0.01) and remained an independent PFS predictor in multivariate analysis wherein it was entered as continuous variable (p = 0.04). Our results indicate that low ΔNACT, i.e., a weak increase in serum CAIX level following initial neoadjuvant treatment (in this case two cycles of the Nordic FLOX regimen), might be used as risk-adapted stratification to postoperative therapy or other modes of intensification of the combined-modality protocol in LARC. ClinicalTrials.gov: NCT00278694

  9. Dioscorin, the major tuber storage protein of yam (Dioscorea batatas decne) with carbonic anhydrase and trypsin inhibitor activities.

    Science.gov (United States)

    Hou, W C; Liu, J S; Chen, H J; Chen, T E; Chang, C F; Lin, Y H

    1999-05-01

    Dioscorin, the tuber storage protein of yam (Dioscorea batatas Decne), was purified successively by ammonium sulfate fractionation, DE-52 ion exchange chromatography, and Sephadex G-75 column. Two protein bands (82 and 28 kDa) were found under nonreducing conditions after SDS-PAGE; but only one band (32 kDa) was detected under reducing conditions. The first 21 amino acids in the N-terminal region of the 28 kDa form were VEDEFSYIEGNPNGPENWGNL, which was highly homologous to deductive sequence of dioscorin from cDNA of another yam species (Dioscoreacayenensis Lam) reported by Conlan et al. (Plant Mol. Biol. 1995, 28, 369-380). Hewett-Emmett and Tashian (Mol. Phylogenet. Evol. 1996, 5, 50 -77) mentioned that, according to DNA alignments, dioscorin from yam (D. cayenensis) was alpha-carbonic anhydrase (alpha-CA) related. In this report, we found that the purified dioscorin showed both CA dehydration activity using sodium bicarbonate as a substrate and CA activity staining after SDS-PAGE. A polyclonal antibody, which was raised against trypsin inhibitor (TI), a storage protein of sweet potato (Ipomoea batatas [L.] Lam var. Tainong 57), cross-reacted with dioscorin, which also showed TI activity determined by both activity staining after SDS-PAGE and trypsin inhibition determination.

  10. Evaluation of in vitro effects of some analgesic drugs on erythrocyte and recombinant carbonic anhydrase I and II.

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    Gökçe, Başak; Gençer, Nahit; Arslan, Oktay; Turkoğlu, Sumeyye Aydogan; Alper, Meltem; Köçkar, Feray

    2012-02-01

    The in vitro effects of the injectable form of analgesic drugs, dexketoprofen trometamol, dexamethasone sodium phosphate, metamizole sodium, diclofenac sodium, thiocolchicoside, on the activity of purified human carbonic anhydrase I and II were evaluated. The effect of these drugs on erythrocyte hCA I and hCA II was compared to recombinant hCA I and hCA II expressed in Ecoli. IC(50) values of the drugs that caused inhibition were determined by means of activity percentage diagrams. The IC(50) concentrations of dexketoprofen trometamol and dexamethasone sodium phosphate on hCA I were 683 μM and 4250 μM and for hCA II 950 μM and 6200 μM respectively. Conversely, the enzyme activity was increased by diflofenac sodium. In addition, thiocolchicoside has not any affect on hCA I and hCA II. The effect of these drugs on erythrocyte hCA I and hCA II were consistent with the inhibition of recombinant enzymes.

  11. Novel 6- and 7-Substituted Coumarins with Inhibitory Action against Lipoxygenase and Tumor-Associated Carbonic Anhydrase IX

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    Aikaterini Peperidou

    2018-01-01

    Full Text Available A series of carboxamide derivatives of 6- and 7-substituted coumarins have been prepared by an original procedure starting from the corresponding 6- or 7-hydroxycoumarins which were alkylated with ethyl iodoacetate, and the obtained ester was converted to the corresponding carboxylic acids which were thereafter reacted with a series of aromatic/aliphatic/heterocyclic amines leading to the desired amides. The new derivatives were investigated as inhibitors of two enzymes, human carbonic anhydrases (hCAs and soy bean lipoxygenase (LOX. Compounds 4a and 4b were potent LOX inhibitors, whereas many effective hCA IX inhibitors (KIs in the range of 30.2–30.5 nM were detected in this study. Two compounds, 4b and 5b, showed the phenomenon of dual inhibition. Furthermore, these coumarins did not significantly inhibit the widespread cytosolic isoforms hCA I and II, whereas they were weak hCA IV inhibitors, making them hCA IX-selective inhibitors. As hCA IX and LOX are validated antitumor targets, these results are promising for the investigation of novel drug targets involved in tumorigenesis.

  12. Transport activity of the sodium bicarbonate cotransporter NBCe1 is enhanced by different isoforms of carbonic anhydrase.

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    Christina Schueler

    Full Text Available Transport metabolons have been discussed between carbonic anhydrase II (CAII and several membrane transporters. We have now studied different CA isoforms, expressed in Xenopus oocytes alone and together with the electrogenic sodium bicarbonate cotransporter 1 (NBCe1, to determine their catalytic activity and their ability to enhance NBCe1 transport activity. pH measurements in intact oocytes indicated similar activity of CAI, CAII and CAIII, while in vitro CAIII had no measurable activity and CAI only 30% of the activity of CAII. All three CA isoforms increased transport activity of NBCe1, as measured by the transport current and the rate of intracellular sodium rise in oocytes. Two CAII mutants, altered in their intramolecular proton pathway, CAII-H64A and CAII-Y7F, showed significant catalytic activity and also enhanced NBCe1 transport activity. The effect of CAI, CAII, and CAII mutants on NBCe1 activity could be reversed by blocking CA activity with ethoxyzolamide (EZA, 10 µM, while the effect of the less EZA-sensitive CAIII was not reversed. Our results indicate that different CA isoforms and mutants, even if they show little enzymatic activity in vitro, may display significant catalytic activity in intact cells, and that the ability of CA to enhance NBCe1 transport appears to depend primarily on its catalytic activity.

  13. Intrinsic Thermodynamics and Structures of 2,4- and 3,4-Substituted Fluorinated Benzenesulfonamides Binding to Carbonic Anhydrases.

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    Zubrienė, Asta; Smirnov, Alexey; Dudutienė, Virginija; Timm, David D; Matulienė, Jurgita; Michailovienė, Vilma; Zakšauskas, Audrius; Manakova, Elena; Gražulis, Saulius; Matulis, Daumantas

    2017-01-20

    The goal of rational drug design is to understand structure-thermodynamics correlations in order to predict the chemical structure of a drug that would exhibit excellent affinity and selectivity for a target protein. In this study we explored the contribution of added functionalities of benzenesulfonamide inhibitors to the intrinsic binding affinity, enthalpy, and entropy for recombinant human carbonic anhydrases (CA) CA I, CA II, CA VII, CA IX, CA XII, and CA XIII. The binding enthalpies of compounds possessing similar chemical structures and affinities were found to be very different, spanning a range from -90 to +10 kJ mol -1 , and are compensated by a similar opposing entropy contribution. The intrinsic parameters of binding were determined by subtracting the linked protonation reactions. The sulfonamide group pK a values of the compounds were measured spectrophotometrically, and the protonation enthalpies were measured by isothermal titration calorimetry (ITC). Herein we describe the development of meta- or ortho-substituted fluorinated benzenesulfonamides toward the highly potent compound 10 h, which exhibits an observed dissociation constant value of 43 pm and an intrinsic dissociation constant value of 1.1 pm toward CA IX, an anticancer target that is highly overexpressed in various tumors. Fluorescence thermal shift assays, ITC, and X-ray crystallography were all applied in this work. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Purification and inhibition studies with anions and sulfonamides of an α-carbonic anhydrase from the Antarctic seal Leptonychotes weddellii.

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    Cincinelli, Alessandra; Martellini, Tania; Innocenti, Alessio; Scozzafava, Andrea; Supuran, Claudiu T

    2011-03-15

    A high activity α-carbonic anhydrase (CA, EC 4.2.1.1) has been purified from various tissues of the Antarctic seal Leptonychotes weddellii. The new enzyme, denominated lwCA, has a catalytic activity for the physiologic CO(2) hydration to bicarbonate reaction, similar to that of the high activity human isoform hCA II, with a k(cat) of 1.1×10(6) s(-1), and a k(cat)/K(m) of 1.4×10(8) M(-1) s(-1). The enzyme was highly inhibited by cyanate, thiocyanate, cyanide, bicarbonate, carbonate, as well as sulfamide, sulfamate, phenylboronic/phenylarsonic acids (K(I)s in the range of 46-100 μM). Many clinically used sulfonamides, such as acetazolamide, methazolamide, dorzolamide, brinzolamide and benzolamide were low nanomolar inhibitors, with K(I)s in the range of 5.7-67 nM. Dichlorophenamide, zonisamide, saccharin and hydrochlorothiazide were weaker inhibitors, with K(I)s in the range of 513-5390 nM. The inhibition profile with anions and sulfonamides of the seal enzyme was rather different from those of the human isoforms hCA I and II. The high sensitivity to bicarbonate inhibition of lwCA, unlike that of the human enzymes, may reflect an evolutionary adaptation to the deep water, high CO(2) partial pressure and hypoxic conditions in which Weddell seals spend much of their life. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Carbonic Anhydrase and Zinc in Plant Physiology Anhidrasa Carbónica y Zinc en Fisiología Vegetal

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    Dalila Jacqueline Escudero-Almanza

    2012-03-01

    Full Text Available Carbonic anhydrase (CA (EC: 2.4.1.1 catalyzes the rapid conversion of carbon dioxide plus water into a proton and the bicarbonate ion (HCO3- that can be found in prokaryotes and higher organisms; it is represented by four different families. Carbonic anhydrase is a metalloenzyme that requires Zn as a cofactor and is involved in diverse biological processes including pH regulation, CO2 transfer, ionic exchange, respiration, CO2 photosynthetic fixation, and stomatal closure. Therefore, the review includes relevant aspects about CA morphology, oligomerization, and structural differences in the active site. On the other hand, we consider the general characteristics of Zn, its geometry, reactions, and physiology. We then consider the CA catalysis mechanism that is carried out by the metal ion and where Zn acts as a cofactor. Zinc deficiency can inhibit growth and protein synthesis, and there is evidence that it reduces the CA content in some plants, which is a relationship addressed in this review. In leaves, CA represents 20.1% of total soluble protein, while it is the second most abundant in the chloroplast after ribulose 1,5-disphosphate carboxylase/oxygenase (RuBisCO. This facilitates the supply of CO2 to the phosphoenolpyruvate carboxylase in C4 and CAM plants and RuBisCO in C3 plants.La anhidrasa carbónica (CA (EC: 4.2.1.1 cataliza la conversión rápida de dióxido de carbono más agua en un protón y el ion bicarbonato (HCO3-; la cual puede encontrarse en procariotas y en organismos superiores y está representada por cuatro familias distintas. La CA es una metaloenzima que requiere Zn como cofactor y está implicada en diversos procesos biológicos, incluyendo la regulación del pH, la transferencia de CO2, intercambio iónico, la respiración, la fijación fotosintética de CO2, y el cierre estomático. Por lo cual, la revisión incluye aspectos relevantes sobre la morfología de laAC, su oligomerización y diferencias estructurales en el

  16. Carbonic anhydrase 2-like and Na⁺-K⁺-ATPase α gene expression in medaka (Oryzias latipes) under carbonate alkalinity stress.

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    Yao, Zongli; Lai, Qifang; Hao, Zhuoran; Chen, Ling; Lin, Tingting; Zhou, Kai; Wang, Hui

    2015-12-01

    High carbonate alkalinity is one of the major stress factors for living organisms in saline-alkaline water areas. Acute and chronic effects of carbonate alkalinity on expression of two genes, carbonic anhydrase 2-like (CA2-like) and Na(+)-K(+)-ATPase α subunit (NKA-α) mRNA in medaka (Oryzias latipes) were evaluated to better understand the responses important for coping with a carbonate alkalinity stress. In the acute exposure experiment, the expression of CA2-like and NKA-α mRNA in the gill and kidney of medaka were examined from 0 h to 7 days exposed to 30.4 mM carbonate alkalinity water. Exposure to high carbonate alkalinity resulted in a transitory alkalosis, followed by a transient increase in gill and kidney CA2-like and NKA-α mRNA expression. In the chronic exposure experiment, the expression of these two genes was examined in the gill and kidney at 50 days post-exposure to six different carbonate alkalinity concentrations ranging from 1.5 to 30.4 mM. Gill and kidney CA2-like mRNA levels in 30.4 mM were approximately 10 and 30 times higher than that of the control (1.5 mM), respectively. Less differences were found in NKA-α expression in the 50-days exposure. The results indicate that when transferred to high carbonate alkalinity water, a transitory alkalosis may occur in medaka, followed by compensatory acid-base and ion regulatory responses. Thus, CA2-like and NKA-α are at least two of the important factors that contribute to the regulation of alkalinity stress.

  17. Relationship among salivary carbonic anhydrase VI activity and flow rate, biofilm pH and caries in primary dentition.

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    Frasseto, F; Parisotto, T M; Peres, R C R; Marques, M R; Line, S R P; Nobre Dos Santos, M

    2012-01-01

    This study aimed to determine the activity of carbonic anhydrase isoenzyme VI (CAVI) in the saliva of preschool children with caries and to investigate the relationship between caries and salivary CAVI activity, salivary flow rate and biofilm pH before and after a 20% sucrose rinse. Thirty preschool children aged 45.3-80.3 months were divided into two groups: a caries-free group and a caries group. Clinical examinations were conducted by one examiner (κ = 0.95) according to WHO criteria (dmfs) and early caries lesions. From each subject, CAVI activity, salivary flow rate and plaque pH were determined before and after a sucrose rinse. The results were submitted to Wilcoxon, Mann-Whitney and Spearman correlation tests (α = 0.05). The results showed that prerinse CAVI activity and its variation were higher in the saliva from caries children than from caries-free children. No difference was found between the two groups in postrinse salivary CAVI activity. After rinsing, biofilm pH differences were lower in both groups (p = 0.0012 and p = 0.0037 for the caries and caries-free groups, respectively). Also, after the sucrose rinse, salivary flow rate significantly increased in caries and caries-free groups (p = 0.0003, p = 0.0037). The variation of salivary CAVI activity was negatively correlated with caries (r = -0.501, p = 0.005). Child's age showed a positive correlation with caries (r = 0.456, p = 0.011). These results suggest that variation of salivary CAVI activity and child's age are associated with dental caries in preschool children. Copyright © 2012 S. Karger AG, Basel.

  18. Carbonic Anhydrase and Urease Inhibitory Potential of Various Plant Phenolics Using in vitro and in silico Methods.

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    Rauf, Abdur; Raza, Muslim; Saleem, Muhammad; Ozgen, Ufuk; Karaoglan, Esen Sezen; Renda, Gulin; Palaska, Erhan; Orhan, Ilkay Erdogan

    2017-06-01

    Plant phenolics are known to display many pharmacological activities. In the current study, eight phenolic compounds, e.g., luteolin 5-O-β-glucoside (1), methyl rosmarinate (2), apigenin (3), vicenin 2 (4), lithospermic acid (5), soyasaponin II (6), rubiadin 3-O-β-primeveroside (7), and 4-(β-d-glucopyranosyloxy)benzyl 3,4-dihydroxybenzoate (8), isolated from various plant species were tested at 0.2 mm against carbonic anhydrase-II (CA-II) and urease using microtiter assays. Urease inhibition rate for compounds 1 - 8 ranged between 5.0 - 41.7%, while only compounds 1, 2, and 4 showed a considerable inhibition over 50% against CA-II with the IC 50 values of 73.5 ± 1.05, 39.5 ± 1.14, and 104.5 ± 2.50 μm, respectively, where IC 50 of the reference (acetazolamide) was 21.0 ± 0.12 μm. In silico experiments were also performed through two docking softwares (Autodock Vina and i-GEMDOCK) in order to find out interactions between the compounds and CA-II. Actually, compounds 6 (30.0%) and 7 (42.0%) possessed a better binding capability toward the active site of CA-II. According to our results obtained in this study, among the phenolic compounds screened, particularly 1, 2, and 4 appear to be the promising inhibitors of CA-II and may be further investigated as possible leads for diuretic, anti-glaucoma, and antiepileptic agents. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  19. High Stromal Carbonic Anhydrase IX Expression Is Associated With Decreased Survival in p16-Negative Head-and-Neck Tumors

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    Brockton, Nigel; Dort, Joseph; Lau, Harold; Hao, Desiree; Brar, Sony; Klimowicz, Alexander; Petrillo, Stephanie; Diaz, Roman; Doll, Corinne; Magliocco, Anthony

    2011-01-01

    Purpose: Head-and-neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide. Alcohol use and tobacco use are the most established risk factors; however, human papilloma virus (HPV) infection is a major risk factor for a subset of HNSCCs. Although HPV-positive tumors typically present at a more advanced stage at diagnosis, they are associated with a better prognosis. Tumor hypoxia confers poor prognosis and treatment failure, but direct tumor oxygen measurement is challenging. Endogenous markers of hypoxia (EMHs) have been proposed but have not replicated the prognostic utility of direct oxygen measurement. The expression of endogenous markers of hypoxia may be influenced by oxygen-independent factors, such as the HPV status of the tumor. Methods and Materials: Consecutive cases of locally advanced HNSCC, treated with a uniform regimen of combined radiotherapy and chemotherapy, were identified. Tissue microarrays were assembled from triplicate 0.6-mm cores of archived tumor tissue. HPV status was inferred from semiquantitative p16 immunostaining and directly measured by use of HPV-specific chromogenic in situ hybridization and polymerase chain reaction. Automated quantitative fluorescent immunohistochemistry was conducted to measure epithelial and stromal expression of carbonic anhydrase IX (CAIX) and glucose transporter 1 (GLUT1). Results: High stromal CAIX expression was associated with significantly reduced overall survival (p = 0.03) in patients with p16-negative tumors. Conclusions: This is the first study to use quantitative immunohistochemistry to examine endogenous markers of hypoxia stratified by tumor p16/HPV status. Assessment of CAIX expression in p16-negative HNSCC could identify patients with the least favorable prognosis and inform therapeutic strategies.

  20. Tumor microenvironmental changes induced by the sulfamate carbonic anhydrase IX inhibitor S4 in a laryngeal tumor model.

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    Tineke W H Meijer

    Full Text Available BACKGROUND AND PURPOSE: Carbonic anhydrase IX (CAIX plays a pivotal role in pH homeostasis, which is essential for tumor cell survival. We examined the effect of the CAIX inhibitor 4-(3'(3",5"-dimethylphenyl-ureidophenyl sulfamate (S4 on the tumor microenvironment in a laryngeal tumor model by analyzing proliferation, apoptosis, necrosis, hypoxia, metabolism and CAIX ectodomain shedding. METHODS: SCCNij202 tumor bearing-mice were treated with S4 for 1, 3 or 5 days. CAIX ectodomain shedding was measured in the serum after therapy. Effects on tumor cell proliferation, apoptosis, necrosis, hypoxia (pimonidazole and CAIX were investigated with quantitative immunohistochemistry. Metabolic transporters and enzymes were quantified with qPCR. RESULTS: CAIX ectodomain shedding decreased after treatment with S4 (p<0.01. S4 therapy did neither influence tumor cell proliferation nor the amount of apoptosis and necrosis. Hypoxia (pimonidazole and CAIX expression were also not affected by S4. CHOP and MMP9 mRNA as a reference of intracellular pH did not change upon treatment with S4. Compensatory mechanisms of pH homeostasis at the mRNA level were not observed. CONCLUSION: As the clinical and biological meaning of the decrease in CAIX ectodomain shedding after S4 therapy is not clear, studies are required to elucidate whether the CAIX ectodomain has a paracrine or autocrine signaling function in cancer biology. S4 did not influence the amount of proliferation, apoptosis, necrosis and hypoxia. Therefore, it is unlikely that S4 can be used as single agent to influence tumor cell kill and proliferation, and to target primary tumor growth.

  1. Gene expression and enzyme activities of carbonic anhydrase and glutaminase in rat kidneys induced by chronic systemic hypoxia

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    Andi N.K. Syarifin

    2015-11-01

    Full Text Available Background: Hypoxia can cause acidosis. Kidney plays an essential role in maintaining acid-base balance, which involves the activities of carbonic anhydrase (CA and glutaminase (GLS. This study is aimed to determine the expression and activities of the CA9 and GLS1 enzymes in relation to hypoxia inducible factor-1α (HIF-1α, a transcription factor protein which is a marker of hypoxia.Methods: This study was an in vivo experimental study with coupled paralel design. used 25 male Sprague-Dawley rats weighing 150-200 g. Rats were divided into 5 groups: the control group (normoxic condition and 4 treatment groups. The latter were kept in a hypoxic chamber (10% O2: 90% N2 for 1, 3, 5 and 7 days. All rats were euthanized after treatment, kidneys excised, tissues homogenized and investigated for gene expression of CA9, GLS1 and HIF-1α. On protein level, total enzymatic activities of CA and GLS and protein of HIF-1α were also investigated. Data were analyzed statistically using ANOVA for significance, and as its alternative, used Mann-Whitney and Kruskal-Wallis test.Results: Results showed that HIF-1α mRNA increased during hypoxia, but not HIF-1α protein. It seemed that acidosis occurs in kidney tissue, indicated by increased CA9 and GLS1 mRNA expression and specific activity of total CA and GLS1. Expression of CA9 and GLS1 mRNA both showed strong positive correlation with HIF-1α mRNA, but not with HIF-1α protein.Conclusion: It is suggested that during chronic systemic hypoxia, gene expression of CA9 and GLS1 and their enzyme activities were increased as a response to acidosis and related with the expression of HIF-1α mRNA.

  2. Importance of post-translational modifications for functionality of a chloroplast-localized carbonic anhydrase (CAH1 in Arabidopsis thaliana.

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    Stefan Burén

    Full Text Available BACKGROUND: The Arabidopsis CAH1 alpha-type carbonic anhydrase is one of the few plant proteins known to be targeted to the chloroplast through the secretory pathway. CAH1 is post-translationally modified at several residues by the attachment of N-glycans, resulting in a mature protein harbouring complex-type glycans. The reason of why trafficking through this non-canonical pathway is beneficial for certain chloroplast resident proteins is not yet known. Therefore, to elucidate the significance of glycosylation in trafficking and the effect of glycosylation on the stability and function of the protein, epitope-labelled wild type and mutated versions of CAH1 were expressed in plant cells. METHODOLOGY/PRINCIPAL FINDINGS: Transient expression of mutant CAH1 with disrupted glycosylation sites showed that the protein harbours four, or in certain cases five, N-glycans. While the wild type protein trafficked through the secretory pathway to the chloroplast, the non-glycosylated protein formed aggregates and associated with the ER chaperone BiP, indicating that glycosylation of CAH1 facilitates folding and ER-export. Using cysteine mutants we also assessed the role of disulphide bridge formation in the folding and stability of CAH1. We found that a disulphide bridge between cysteines at positions 27 and 191 in the mature protein was required for correct folding of the protein. Using a mass spectrometric approach we were able to measure the enzymatic activity of CAH1 protein. Under circumstances where protein N-glycosylation is blocked in vivo, the activity of CAH1 is completely inhibited. CONCLUSIONS/SIGNIFICANCE: We show for the first time the importance of post-translational modifications such as N-glycosylation and intramolecular disulphide bridge formation in folding and trafficking of a protein from the secretory pathway to the chloroplast in higher plants. Requirements for these post-translational modifications for a fully functional native

  3. Knock-down of hypoxia-induced carbonic anhydrases IX and XII radiosensitizes tumor cells by increasing intracellular acidosis

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    Doyen, Jérome [Institute for Research on Cancer and Aging of Nice, CNRS UMR 7284, University of Nice Sophia-Antipolis,, Nice (France); Department of Radiation Oncology, Centre Antoine-Lacassagne, Nice (France); Parks, Scott K. [Institute for Research on Cancer and Aging of Nice, CNRS UMR 7284, University of Nice Sophia-Antipolis,, Nice (France); Marcié, Serge [Department of Radiation Oncology, Centre Antoine-Lacassagne, Nice (France); Pouysségur, Jacques [Institute for Research on Cancer and Aging of Nice, CNRS UMR 7284, University of Nice Sophia-Antipolis,, Nice (France); Centre Scientifique de Monaco (Monaco); Chiche, Johanna, E-mail: chiche@unice.fr [Institute for Research on Cancer and Aging of Nice, CNRS UMR 7284, University of Nice Sophia-Antipolis,, Nice (France)

    2013-01-07

    The relationship between acidosis within the tumor microenvironment and radioresistance of hypoxic tumor cells remains unclear. Previously we reported that hypoxia-induced carbonic anhydrases (CA) IX and CAXII constitute a robust intracellular pH (pH{sub i})-regulating system that confers a survival advantage on hypoxic human colon carcinoma LS174Tr cells in acidic microenvironments. Here we investigate the role of acidosis, CAIX and CAXII knock-down in combination with ionizing radiation. Fibroblasts cells (-/+ CAIX) and LS174Tr cells (inducible knock-down for ca9/ca12) were analyzed for cell cycle phase distribution and survival after irradiation in extracellular pH{sub o} manipulations and hypoxia (1% O{sub 2}) exposure. Radiotherapy was used to target ca9/ca12-silenced LS174Tr tumors grown in nude mice. We found that diminishing the pH{sub i}-regulating capacity of fibroblasts through inhibition of Na{sup +}/H{sup +} exchanger 1 sensitize cells to radiation-induced cell death. Secondly, the pH{sub i}-regulating function of CAIX plays a key protective role in irradiated fibroblasts in an acidic environment as accompanied by a reduced number of cells in the radiosensitive phases of the cell cycle. Thirdly, we demonstrate that irradiation of LS174Tr spheroids, silenced for either ca9 or both ca9/ca12, showed a respective 50 and 75% increase in cell death as a result of a decrease in cell number in the radioresistant S phase and a disruption of CA-mediated pH{sub i} regulation. Finally, LS174Tr tumor progression was strongly decreased when ca9/ca12 silencing was combined with irradiation in vivo. These findings highlight the combinatory use of radiotherapy with targeting of the pH{sub i}-regulating CAs as an anti-cancer strategy.

  4. The in vitro effects of some pesticides on carbonic anhydrase activity of Oncorhynchus mykiss and Cyprinus carpio carpio fish.

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    Doğan, Serap

    2006-05-20

    Systemic carbonic anhydrase (CA) inhibitors are among the most powerful agents to lower intraocular pressure. Unfortunately, their use is frequently accompanied by undesired side effects. Some are due to the relatively large amounts of drug that have to be systematically administered to inhibit the CA in the ciliary processes. The aim of the present work was to study in vitro effects of some pesticides on CA enzyme obtained from blood of fish, which play a key role in salt- and osmoregulation and acid-base balance in the fish, Oncorhynchus mykiss and Cyprinus carpio carpio living in freshwaters, and compared with CA inhibitors. CA activities were significantly inhibited by pesticides and inhibitors. I(50) values of O. mykiss CA enzyme inhibited by lambda-cyhalothrin, deltametrin, diozinon, dorzolamide and brinzolamide were 6.05 x 10(-4), 1.48 x 10(-5), 6.84 x 10(-3), 3.82 x 10(-5) and 1.80 x 10(-6) mol/l, and that for C. c. carpio 6.86 x 10(-4), 4.70 x 10(-4), 3.92 x 10(-3), 8.34 x 10(-6) and 1.42 x 10(-6) mol/l, respectively. The pesticides used in this study inhibited the CA activity from different fish species to various degrees. It was found that the most effective inhibitor of CA enzyme within pesticides used was detrametrin. These findings observed in vitro could be useful in the understanding of the toxic effects that pesticides elicit on aquatic organisms in vivo.

  5. Gene encoding gamma-carbonic anhydrase is cotranscribed with argC and induced in response to stationary phase and high CO2 in Azospirillum brasilense Sp7.

    Science.gov (United States)

    Kaur, Simarjot; Mishra, Mukti N; Tripathi, Anil K

    2010-07-04

    Carbonic anhydrase (CA) is a ubiquitous enzyme catalyzing the reversible hydration of CO2 to bicarbonate, a reaction underlying diverse biochemical and physiological processes. Gamma class carbonic anhydrases (gamma-CAs) are widespread in prokaryotes but their physiological roles remain elusive. At present, only gamma-CA of Methanosarcina thermophila (Cam) has been shown to have CA activity. Genome analysis of a rhizobacterium Azospirillum brasilense, revealed occurrence of ORFs encoding one beta-CA and two gamma-CAs. One of the putative gamma-CA encoding genes of A. brasilense was cloned and overexpressed in E. coli. Electrometric assays for CA activity of the whole cell extracts overexpressing recombinant GCA1 did not show CO2 hydration activity. Reverse transcription-PCR analysis indicated that gca1 in A. brasilense is co-transcribed with its upstream gene annotated as argC, which encodes a putative N-acetyl-gamma-glutamate-phosphate reductase. 5'-RACE also demonstrated that there was no transcription start site between argC and gca1, and the transcription start site located upstream of argC transcribed both the genes (argC-gca1). Using transcriptional fusions of argC-gca1 upstream region with promoterless lacZ, we further demonstrated that gca1 upstream region did not have any promoter and its transcription occurred from a promoter located in the argC upstream region. The transcription of argC-gca1 operon was upregulated in stationary phase and at elevated CO2 atmosphere. This study shows lack of CO2 hydration activity in a recombinant protein expressed from a gene predicted to encode a gamma-carbonic anhydrase in A. brasilense although it cross reacts with anti-Cam antibody raised against a well characterized gamma-CA. The organization and regulation of this gene along with the putative argC gene suggests its involvement in arginine biosynthetic pathway instead of the predicted CO2 hydration.

  6. Extending the scope of amantadine drug by incorporation of phenolic azo Schiff bases as potent selective inhibitors of carbonic anhydrase II, drug likeness and binding analysis.

    Science.gov (United States)

    Channar, Pervaiz Ali; Saeed, Aamer; Shahzad, Danish; Larik, Fayaz Ali; Hassan, Mubashir; Raza, Hussain; Abbas, Qamar; Seo, Sung-Yum

    2018-05-16

    A series of Amantadine based azo Schiff base dyes 6a-6e have been synthesized and characterized by 1 H NMR and 13 C NMR and evaluated for their in vitro carbonic anhydrase II inhibition activity and antioxidant activity. All of the synthesized showed excellent carbonic inhibition. Compound 6b was found to be the most potent derivative in the series, the IC 50 of 6b was found to be 0.0849 ± 0.00245μM (standard Acetazolamide IC 50 =0.9975±0.049μM). The binding interactions of the most active analogs were confirmed through molecular docking studies. Docking studies showed 6b is interacting by making two hydrogen bonds w at His93 and Ser1 residues respectively. All compounds showed a good drug score and followed Lipinski's rule. In summary, our studies have shown that these amantadine derived phenolic azo Schiff base derivatives are a new class of carbonic anhydrase II inhibitors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. A High-Resolution Crystal Structure of a Psychrohalophilic α-Carbonic Anhydrase from Photobacterium profundum Reveals a Unique Dimer Interface.

    Directory of Open Access Journals (Sweden)

    Vijayakumar Somalinga

    Full Text Available Bacterial α-carbonic anhydrases (α-CA are zinc containing metalloenzymes that catalyze the rapid interconversion of CO2 to bicarbonate and a proton. We report the first crystal structure of a pyschrohalophilic α-CA from a deep-sea bacterium, Photobacterium profundum. Size exclusion chromatography of the purified P. profundum α-CA (PprCA reveals that the protein is a heterogeneous mix of monomers and dimers. Furthermore, an "in-gel" carbonic anhydrase activity assay, also known as protonography, revealed two distinct bands corresponding to monomeric and dimeric forms of PprCA that are catalytically active. The crystal structure of PprCA was determined in its native form and reveals a highly conserved "knot-topology" that is characteristic of α-CA's. Similar to other bacterial α-CA's, PprCA also crystallized as a dimer. Furthermore, dimer interface analysis revealed the presence of a chloride ion (Cl- in the interface which is unique to PprCA and has not been observed in any other α-CA's characterized so far. Molecular dynamics simulation and chloride ion occupancy analysis shows 100% occupancy for the Cl- ion in the dimer interface. Zinc coordinating triple histidine residues, substrate binding hydrophobic patch residues, and the hydrophilic proton wire residues are highly conserved in PprCA and are identical to other well-studied α-CA's.

  8. Regulation of expression and biochemical characterization of a beta-class carbonic anhydrase from the plant growth-promoting rhizobacterium, Azospirillum brasilense Sp7.

    Science.gov (United States)

    Kaur, Simarjot; Mishra, Mukti Nath; Tripathi, Anil K

    2009-10-01

    Carbonic anhydrase (CA; [EC 4.2.1.1]) is a ubiquitous enzyme catalysing the reversible hydration of CO(2) to bicarbonate, a reaction that supports various biochemical and physiological functions. Genome analysis of Azospirillum brasilense, a nonphotosynthetic, nitrogen-fixing, rhizobacterium, revealed an ORF with homology to beta-class carbonic anhydrases (CAs). Biochemical characteristics of the beta-class CA of A. brasilense, analysed after cloning the gene (designated as bca), overexpressing in Escherichia coli and purifying the protein by affinity purification, revealed that the native recombinant enzyme is a homotetramer, inhibited by the known CA inhibitors. CA activity in A. brasilense cell extracts, reverse transcriptase (RT)-PCR and Western blot analyses showed that bca was constitutively expressed under aerobic conditions. Lower beta-galactosidase activity in A. brasilense cells harbouring bca promoter: lacZ fusion during the stationary phase or during growth on 3% CO(2) enriched air or at acidic pH indicated that the transcription of bca was downregulated by the stationary phase, elevated CO(2) levels and acidic pH conditions. These observations were also supported by RT-PCR analysis. Thus, beta-CA in A. brasilense seems to be required for scavenging CO(2) from the ambient air and the requirement of CO(2) hydration seems to be higher for the cultures growing exponentially at neutral to alkaline pH.

  9. Purification of chicken carbonic anhydrase isozyme-III (CA-III and its measurement in White Leghorn chickens

    Directory of Open Access Journals (Sweden)

    Nishita Toshiho

    2011-11-01

    Full Text Available Abstract Background The developmental profile of chicken carbonic anhydrase-III (CA-III blood levels has not been previously determined or reported. We isolated CA-III from chicken muscle and investigated age-related changes in the levels of CA-III in blood. Methods CA-III was purified from chicken muscle. The levels of CA-III in plasma and erythrocytes from 278 female chickens (aged 1-93 weeks and 68 male chickens (aged 3-59 weeks were determined by ELISA. Results The mean level of CA-III in female chicken erythrocytes (1 week old was 4.6 μg/g of Hb, and the CA-III level did not change until 16 weeks of age. The level then increased until 63 weeks of age (11.8 μg/g of Hb, decreased to 4.7 μg/g of Hb at 73 weeks of age, and increased again until 93 weeks of age (8.6 μg/g of Hb. The mean level of CA-III in erythrocytes from male chickens (3 weeks old was 2.4 μg/g of Hb, and this level remained steady until 59 weeks of age. The mean plasma level of CA-III in 1-week-old female chickens was 60 ng/mL, and this level was increased at 3 weeks of age (141 ng/mL and then remained steady until 80 weeks of age (122 ng/mL. The mean plasma level of CA-III in 3-week-old male chickens was 58 ng/mL, and this level remained steady until 59 weeks of age. Conclusion We observed both developmental changes and sex differences in CA-III concentrations in White Leghorn (WL chicken erythrocytes and plasma. Simple linear regression analysis showed a significant association between the erythrocyte CA-III level and egg-laying rate in WL-chickens 16-63 weeks of age (p

  10. Carnosine inhibits carbonic anhydrase IX-mediated extracellular acidosis and suppresses growth of HeLa tumor xenografts

    International Nuclear Information System (INIS)

    Ditte, Zuzana; Ditte, Peter; Labudova, Martina; Simko, Veronika; Iuliano, Filippo; Zatovicova, Miriam; Csaderova, Lucia; Pastorekova, Silvia; Pastorek, Jaromir

    2014-01-01

    Carbonic anhydrase IX (CA IX) is a transmembrane enzyme that is present in many types of solid tumors. Expression of CA IX is driven predominantly by the hypoxia-inducible factor (HIF) pathway and helps to maintain intracellular pH homeostasis under hypoxic conditions, resulting in acidification of the tumor microenvironment. Carnosine (β-alanyl-L-histidine) is an anti-tumorigenic agent that inhibits the proliferation of cancer cells. In this study, we investigated the role of CA IX in carnosine-mediated antitumor activity and whether the underlying mechanism involves transcriptional and translational modulation of HIF-1α and CA IX and/or altered CA IX function. The effect of carnosine was studied using two-dimensional cell monolayers of several cell lines with endogenous CA IX expression as well as Madin Darby canine kidney transfectants, three-dimensional HeLa spheroids, and an in vivo model of HeLa xenografts in nude mice. mRNA and protein expression and protein localization were analyzed by real-time PCR, western blot analysis, and immunofluorescence staining, respectively. Cell viability was measured by a flow cytometric assay. Expression of HIF-1α and CA IX in tumors was assessed by immunohistochemical staining. Real-time measurement of pH was performed using a sensor dish reader. Binding of CA IX to specific antibodies and metabolon partners was investigated by competitive ELISA and proximity ligation assays, respectively. Carnosine increased the expression levels of HIF-1α and HIF targets and increased the extracellular pH, suggesting an inhibitory effect on CA IX-mediated acidosis. Moreover, carnosine significantly inhibited the growth of three-dimensional spheroids and tumor xenografts compared with untreated controls. Competitive ELISA showed that carnosine disrupted binding between CA IX and antibodies specific for its catalytic domain. This finding was supported by reduced formation of the functional metabolon of CA IX and anion exchanger 2 in the

  11. Identification and characterization of a carboxysomal γ-carbonic anhydrase from the cyanobacterium Nostoc sp. PCC 7120.

    Science.gov (United States)

    de Araujo, Charlotte; Arefeen, Dewan; Tadesse, Yohannes; Long, Benedict M; Price, G Dean; Rowlett, Roger S; Kimber, Matthew S; Espie, George S

    2014-09-01

    Carboxysomes are proteinaceous microcompartments that encapsulate carbonic anhydrase (CA) and ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco); carboxysomes, therefore, catalyze reversible HCO3 (-) dehydration and the subsequent fixation of CO2. The N- and C-terminal domains of the β-carboxysome scaffold protein CcmM participate in a network of protein-protein interactions that are essential for carboxysome biogenesis, organization, and function. The N-terminal domain of CcmM in the thermophile Thermosynechococcus elongatus BP-1 is also a catalytically active, redox regulated γ-CA. To experimentally determine if CcmM from a mesophilic cyanobacterium is active, we cloned, expressed and purified recombinant, full-length CcmM from Nostoc sp. PCC 7120 as well as the N-terminal 209 amino acid γ-CA-like domain. Both recombinant proteins displayed ethoxyzolamide-sensitive CA activity in mass spectrometric assays, as did the carboxysome-enriched TP fraction. NstCcmM209 was characterized as a moderately active and efficient γ-CA with a k cat of 2.0 × 10(4) s(-1) and k cat/K m of 4.1 × 10(6) M(-1) s(-1) at 25 °C and pH 8, a pH optimum between 8 and 9.5 and a temperature optimum spanning 25-35 °C. NstCcmM209 also catalyzed the hydrolysis of the CO2 analog carbonyl sulfide. Circular dichroism and intrinsic tryptophan fluorescence analysis demonstrated that NstCcmM209 was progressively and irreversibly denatured above 50 °C. NstCcmM209 activity was inhibited by the reducing agent tris(hydroxymethyl)phosphine, an effect that was fully reversed by a molar excess of diamide, a thiol oxidizing agent, consistent with oxidative activation being a universal regulatory mechanism of CcmM orthologs. Immunogold electron microscopy and Western blot analysis of TP pellets indicated that Rubisco and CcmM co-localize and are concentrated in Nostoc sp. PCC 7120 carboxysomes.

  12. Purification of chicken carbonic anhydrase isozyme-III (CA-III) and its measurement in White Leghorn chickens.

    Science.gov (United States)

    Nishita, Toshiho; Tomita, Yuichiro; Yorifuji, Daisuke; Orito, Kensuke; Ochiai, Hideharu; Arishima, Kazuyosi

    2011-11-26

    The developmental profile of chicken carbonic anhydrase-III (CA-III) blood levels has not been previously determined or reported. We isolated CA-III from chicken muscle and investigated age-related changes in the levels of CA-III in blood. CA-III was purified from chicken muscle. The levels of CA-III in plasma and erythrocytes from 278 female chickens (aged 1-93 weeks) and 68 male chickens (aged 3-59 weeks) were determined by ELISA. The mean level of CA-III in female chicken erythrocytes (1 week old) was 4.6 μg/g of Hb, and the CA-III level did not change until 16 weeks of age. The level then increased until 63 weeks of age (11.8 μg/g of Hb), decreased to 4.7 μg/g of Hb at 73 weeks of age, and increased again until 93 weeks of age (8.6 μg/g of Hb). The mean level of CA-III in erythrocytes from male chickens (3 weeks old) was 2.4 μg/g of Hb, and this level remained steady until 59 weeks of age. The mean plasma level of CA-III in 1-week-old female chickens was 60 ng/mL, and this level was increased at 3 weeks of age (141 ng/mL) and then remained steady until 80 weeks of age (122 ng/mL). The mean plasma level of CA-III in 3-week-old male chickens was 58 ng/mL, and this level remained steady until 59 weeks of age. We observed both developmental changes and sex differences in CA-III concentrations in White Leghorn (WL) chicken erythrocytes and plasma. Simple linear regression analysis showed a significant association between the erythrocyte CA-III level and egg-laying rate in WL-chickens 16-63 weeks of age (p < 0.01).

  13. Roles of the conserved aspartate and arginine in the catalytic mechanism of an archaeal beta-class carbonic anhydrase.

    Science.gov (United States)

    Smith, Kerry S; Ingram-Smith, Cheryl; Ferry, James G

    2002-08-01

    The roles of an aspartate and an arginine, which are completely conserved in the active sites of beta-class carbonic anhydrases, were investigated by steady-state kinetic analyses of replacement variants of the beta-class enzyme (Cab) from the archaeon Methanobacterium thermoautotrophicum. Previous kinetic analyses of wild-type Cab indicated a two-step zinc-hydroxide mechanism of catalysis in which the k(cat)/K(m) value depends only on the rate constants for the CO(2) hydration step, whereas k(cat) also depends on rate constants from the proton transfer step (K. S. Smith, N. J. Cosper, C. Stalhandske, R. A. Scott, and J. G. Ferry, J. Bacteriol. 182:6605-6613, 2000). The recently solved crystal structure of Cab shows the presence of a buffer molecule within hydrogen bonding distance of Asp-34, implying a role for this residue in the proton transport step (P. Strop, K. S. Smith, T. M. Iverson, J. G. Ferry, and D. C. Rees, J. Biol. Chem. 276:10299-10305, 2001). The k(cat)/K(m) values of Asp-34 variants were decreased relative to those of the wild type, although not to an extent which supports an essential role for this residue in the CO(2) hydration step. Parallel decreases in k(cat) and k(cat)/K(m) values for the variants precluded any conclusions regarding a role for Asp-34 in the proton transfer step; however, the k(cat) of the D34A variant was chemically rescued by replacement of 2-(N-morpholino)propanesulfonic acid buffer with imidazole at pH 7.2, supporting a role for the conserved aspartate in the proton transfer step. The crystal structure of Cab also shows Arg-36 with two hydrogen bonds to Asp-34. Arg-36 variants had both k(cat) and k(cat)/K(m) values that were decreased at least 250-fold relative to those of the wild type, establishing an essential function for this residue. Imidazole was unable to rescue the k(cat) of the R36A variant; however, partial rescue of the kinetic parameter was obtained with guanidine-HCl indicating that the guanido group of this

  14. MODELLING THE INHIBITORY ACTIVITY ON CARBONIC ANHYDRASE IV OF SUBSTITUTED THIADIAZOLE - AND THIADIAZOLINE - DISULFONAMIDES: INTEGRATION OF STRUCTURE INFORMATION

    Directory of Open Access Journals (Sweden)

    Sorana Daniela Bolboaca

    2006-07-01

    Full Text Available ABSTRACT:Purpose: To analyze the relationships between inhibitory activities on carbonic anhydrase IV and structures of substituted 1,3,4-thiadiazole and 1,3,4-thiadiazoline disulfonamide through integration of compounds complex structure information by the use of Molecular Descriptors Family.Method: A number of forty compounds were used to generate and compute the molecular descriptors family and to build structure-activity relationships models. The obtained multi-varied models (the models with two, respectively with four descriptors were validated by computing the cross-validation leave-one-out score (r2cv-loo, and analyzed through assessment of the squared correlation coefficients (r2, and the models stability (r2 - r2cv-loo. The estimation abilities of the multi-varied MDF-SAR model with four descriptors were analyzed in training and test sets.Results: Analysis of the obtained models shows that the best results was obtained by the multi-varied model with four molecular descriptors (r2 = 0.920. The prediction abilities of this model is sustained by the cross validation leave-one-out score (r2cv-loo = 0.903, the model stability (r2 - r2cv-loo = 0.017, and the results on training versus test analysis (no significant differences between correlation coefficients in training and test sets, p > 0.05. The multi-varied model which used four descriptors proved to render higher value of correlation coefficient comparing with previous reported models (p 0.05. El modelo multivariante que utilizó cuatro descriptores mostró un valor más alto del coeficiente de correlación en comparación con los modelos divulgados anteriormente (p < 0.01.Conclusión: El modelo multivariante con cuatro descriptores es sólido y fiable e indica que la actividad de la inhibición en la carboanhidrasa IV producida por las sufonamidas sustituidas del 1,3,4-tiadiazol- y de la 1,3,4-tiadiazolina- dependen de la naturaleza de la geometría y de la topología del compuesto

  15. Carbon dioxide is a powerful inducer of monokaryotic hyphae and spore development in Cryptococcus gattii and carbonic anhydrase activity is dispensable in this dimorphic transition.

    Science.gov (United States)

    Ren, Ping; Chaturvedi, Vishnu; Chaturvedi, Sudha

    2014-01-01

    Cryptococcus gattii is unique among human pathogenic fungi with specialized ecological niche on trees. Since leaves concentrate CO2, we investigated the role of this gaseous molecule in C. gattii biology and virulence. We focused on the genetic analyses of β-carbonic anhydrase (β-CA) encoded by C. gattii CAN1 and CAN2 as later is critical for CO2 sensing in a closely related pathogen C. neoformans. High CO2 conditions induced robust development of monokaryotic hyphae and spores in C. gattii. Conversely, high CO2 completely repressed hyphae development in sexual mating. Both CAN1 and CAN2 were dispensable for CO2 induced morphogenetic transitions. However, C. gattii CAN2 was essential for growth in ambient air similar to its reported role in C. neoformans. Both can1 and can2 mutants retained full pathogenic potential in vitro and in vivo. These results provide insight into C. gattii adaptation for arboreal growth and production of infectious propagules by β-CA independent mechanism(s).

  16. Overlap of epitopes recognized by anti-carbonic anhydrase I IgG in patients with malignancy-related aplastic anemia-like syndrome and in patients with aplastic anemia

    Czech Academy of Sciences Publication Activity Database

    Jankovičová, B.; Škultéty, L'udovít; Dubrovčáková, M.; Stern, M.; Bílková, Z.; Lakota, J.

    2013-01-01

    Roč. 153, 1-2 (2013), s. 47-49 ISSN 0165-2478 Institutional support: RVO:61388971 Keywords : Carbonic anhydrase I * Epitope extraction * Anti-CA I autoantibodies Subject RIV: EC - Immunology Impact factor: 2.367, year: 2013

  17. Gene encoding γ-carbonic anhydrase is cotranscribed with argC and induced in response to stationary phase and high CO2 in Azospirillum brasilense Sp7

    Science.gov (United States)

    2010-01-01

    Background Carbonic anhydrase (CA) is a ubiquitous enzyme catalyzing the reversible hydration of CO2 to bicarbonate, a reaction underlying diverse biochemical and physiological processes. Gamma class carbonic anhydrases (γ-CAs) are widespread in prokaryotes but their physiological roles remain elusive. At present, only γ-CA of Methanosarcina thermophila (Cam) has been shown to have CA activity. Genome analysis of a rhizobacterium Azospirillum brasilense, revealed occurrence of ORFs encoding one β-CA and two γ-CAs. Results One of the putative γ-CA encoding genes of A. brasilense was cloned and overexpressed in E. coli. Electrometric assays for CA activity of the whole cell extracts overexpressing recombinant GCA1 did not show CO2 hydration activity. Reverse transcription-PCR analysis indicated that gca1 in A. brasilense is co-transcribed with its upstream gene annotated as argC, which encodes a putative N-acetyl-γ-glutamate-phosphate reductase. 5'-RACE also demonstrated that there was no transcription start site between argC and gca1, and the transcription start site located upstream of argC transcribed both the genes (argC-gca1). Using transcriptional fusions of argC-gca1 upstream region with promoterless lacZ, we further demonstrated that gca1 upstream region did not have any promoter and its transcription occurred from a promoter located in the argC upstream region. The transcription of argC-gca1 operon was upregulated in stationary phase and at elevated CO2 atmosphere. Conclusions This study shows lack of CO2 hydration activity in a recombinant protein expressed from a gene predicted to encode a γ-carbonic anhydrase in A. brasilense although it cross reacts with anti-Cam antibody raised against a well characterized γ-CA. The organization and regulation of this gene along with the putative argC gene suggests its involvement in arginine biosynthetic pathway instead of the predicted CO2 hydration. PMID:20598158

  18. Gene encoding γ-carbonic anhydrase is cotranscribed with argC and induced in response to stationary phase and high CO2 in Azospirillum brasilense Sp7

    Directory of Open Access Journals (Sweden)

    Mishra Mukti N

    2010-07-01

    Full Text Available Abstract Background Carbonic anhydrase (CA is a ubiquitous enzyme catalyzing the reversible hydration of CO2 to bicarbonate, a reaction underlying diverse biochemical and physiological processes. Gamma class carbonic anhydrases (γ-CAs are widespread in prokaryotes but their physiological roles remain elusive. At present, only γ-CA of Methanosarcina thermophila (Cam has been shown to have CA activity. Genome analysis of a rhizobacterium Azospirillum brasilense, revealed occurrence of ORFs encoding one β-CA and two γ-CAs. Results One of the putative γ-CA encoding genes of A. brasilense was cloned and overexpressed in E. coli. Electrometric assays for CA activity of the whole cell extracts overexpressing recombinant GCA1 did not show CO2 hydration activity. Reverse transcription-PCR analysis indicated that gca1 in A. brasilense is co-transcribed with its upstream gene annotated as argC, which encodes a putative N-acetyl-γ-glutamate-phosphate reductase. 5'-RACE also demonstrated that there was no transcription start site between argC and gca1, and the transcription start site located upstream of argC transcribed both the genes (argC-gca1. Using transcriptional fusions of argC-gca1 upstream region with promoterless lacZ, we further demonstrated that gca1 upstream region did not have any promoter and its transcription occurred from a promoter located in the argC upstream region. The transcription of argC-gca1 operon was upregulated in stationary phase and at elevated CO2 atmosphere. Conclusions This study shows lack of CO2 hydration activity in a recombinant protein expressed from a gene predicted to encode a γ-carbonic anhydrase in A. brasilense although it cross reacts with anti-Cam antibody raised against a well characterized γ-CA. The organization and regulation of this gene along with the putative argC gene suggests its involvement in arginine biosynthetic pathway instead of the predicted CO2 hydration.

  19. A physically interpretable quantum-theoretic QSAR for some carbonic anhydrase inhibitors with diverse aromatic rings, obtained by a new QSAR procedure.

    Science.gov (United States)

    Clare, Brian W; Supuran, Claudiu T

    2005-03-15

    A QSAR based almost entirely on quantum theoretically calculated descriptors has been developed for a large and heterogeneous group of aromatic and heteroaromatic carbonic anhydrase inhibitors, using orbital energies, nodal angles, atomic charges, and some other intuitively appealing descriptors. Most calculations have been done at the B3LYP/6-31G* level of theory. For the first time we have treated five-membered rings by the same means that we have used for benzene rings in the past. Our flip regression technique has been expanded to encompass automatic variable selection. The statistical quality of the results, while not equal to those we have had with benzene derivatives, is very good considering the noncongeneric nature of the compounds. The most significant correlation was with charge on the atoms of the sulfonamide group, followed by the nodal orientation and the solvation energy calculated by COSMO and the charge polarization of the molecule calculated as the mean absolute Mulliken charge over all atoms.

  20. N-ethyl-N-nitrosourea-induced null mutation at the mouse Car-2 locus: An animal model for human carbonic anhydrase II deficiency syndrome

    International Nuclear Information System (INIS)

    Lewis, S.E.; Barnett, L.B.; Erickson, R.P.; Venta, P.J.; Tashian, R.E.

    1988-01-01

    Electrophoretic screening of (C57BL/6J x DBA/2J)F 1 progeny of male mice treated with N-ethyl-N-nitrosourea revealed a mouse that lacked the paternal carbonic anhydrase II (Ca II). Breeding tests showed that this trait was heritable and due to a null mutation at the Car-2 locus on chromosome 3. Like humans with the same inherited enzyme defect, animals homozygous for the new null allele are runted and have renal tubular acidosis. However, the prominent osteopetrosis found in humans with CA II deficiency could be detected even in very old homozygous null mice. A molecular analysis of the deficient mice shows that the mutant gene is not deleted and is transcribed. The CA II protein, which is normally expressed in most tissues, could not be detected by immunodiffusion analysis in any tissues of the CA II-deficient mice, suggesting a nonsense or a missense mutation at the Car-2 locus

  1. Apoptosis-inducing signal sequence mutation in carbonic anhydrase IV identified in patients with the RP17 form of retinitis pigmentosa

    Science.gov (United States)

    Rebello, George; Ramesar, Rajkumar; Vorster, Alvera; Roberts, Lisa; Ehrenreich, Liezle; Oppon, Ekow; Gama, Dumisani; Bardien, Soraya; Greenberg, Jacquie; Bonapace, Giuseppe; Waheed, Abdul; Shah, Gul N.; Sly, William S.

    2004-01-01

    Genetic and physical mapping of the RP17 locus on 17q identified a 3.6-megabase candidate region that includes the gene encoding carbonic anhydrase IV (CA4), a glycosylphosphatidylinositol-anchored protein that is highly expressed in the choriocapillaris of the human eye. By sequencing candidate genes in this region, we identified a mutation that causes replacement of an arginine with a tryptophan (R14W) in the signal sequence of the CA4 gene at position -5 relative to the signal sequence cleavage site. This mutation was found to cosegregate with the disease phenotype in two large families and was not found in 36 unaffected family members or 100 controls. Expression of the mutant cDNA in COS-7 cells produced several findings, suggesting a mechanism by which the mutation can explain the autosomal dominant disease. In transfected COS-7 cells, the R14W mutation (i) reduced the steady-state level of carbonic anhydrase IV activity expressed by 28% due to a combination of decreased synthesis and accelerated turnover; (ii) led to up-regulation of immunoglobulin-binding protein, double-stranded RNA-regulated protein kinase-like ER kinase, and CCAAT/enhancer-binding protein homologous protein, markers of the unfolded protein response and endoplasmic reticulum stress; and (iii) induced apoptosis, as evidenced by annexin V binding and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining, in most cells expressing the mutant, but not the WT, protein. We suggest that a high level of expression of the mutant allele in the endothelial cells of the choriocapillaris leads to apoptosis, leading in turn to ischemia in the overlying retina and producing autosomal dominant retinitis pigmentosa. PMID:15090652

  2. Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

    Directory of Open Access Journals (Sweden)

    Marcelo Zerati

    2013-07-01

    Full Text Available Introduction The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC is evolving, and Carbonic Anhydrase type IX (CA-IX has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1 overall survival, and 2 with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion. Materials and Methods This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS, TNM stage, tumor size (TS, Fuhrman nuclear grade (FNG, microvascular invasion (MVI, peri-renal fat invasion (PFI. We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: Th e mean follow-up time was 7.9 years (range 1.9 to 19.5 years. The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790; T stage (p = 0.179; tumor size (p = 0.143; grouped Fuhrman nuclear grade (p = 0.598; microvascular invasion (p = 0.685, and peri-renal fat invasion (p = 0.104. Conclusion Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma.

  3. Comparative study of carbonic anhydrase activity in waters among different geological eco-environments of Yangtze River basin and its ecological significance.

    Science.gov (United States)

    Nzung'a, Sila Onesmus; Pan, Weizhi; Shen, Taiming; Li, Wei; Qin, Xiaoqun; Wang, Chenwei; Zhang, Liankai; Yu, Longjiang

    2018-04-01

    This study provides the presence of carbonic anhydrase (CA) activity in waters of the Yangtze River basin, China, as well as the correlation of CA activity with HCO 3 - concentration and CO 2 sink flux. Different degrees of CA activity could be detected in almost all of the water samples from different geological eco-environments in all four seasons. The CA activity of water samples from karst areas was significantly higher than from non-karst areas (PP3 - concentration (r=0.672, P2 sink flux (r=0.602, P=0.076) in karst areas. This suggests that CA in waters might have a promoting effect on carbon sinks for atmospheric CO 2 in karst river basins. In conditions of similar geological type, higher CA activity was generally detected in water samples taken from areas that exhibited better eco-environments, implying that the CA activity index of waters could be used as an indicator for monitoring ecological environments and protection of river basins. These findings suggest that the role of CA in waters in the karst carbon sink potential of river basins is worthy of further in-depth studies. Copyright © 2017. Published by Elsevier B.V.

  4. Investigating the adduct formation of organic mercury species with carbonic anhydrase and hemoglobin from human red blood cell hemolysate by means of LC/ESI-TOF-MS and LC/ICP-MS.

    Science.gov (United States)

    Hogeback, Jens; Schwarzer, Miriam; Wehe, Christoph A; Sperling, Michael; Karst, Uwe

    2016-01-01

    The interaction of mercury species with human erythrocytes is studied to investigate possible high molecular binding partners for mercury species. Human blood hemolysate was spiked with methylmercury and investigated by means of liquid chromatography (LC) coupled to electrospray ionization time of flight mass spectrometry (ESI-ToF-MS) and inductively coupled plasma mass spectrometry (ICP-MS). Beside adduct formation of mercury species with hemoglobin, the main compound of the erythrocytes, mercury binding to the enzyme carbonic anhydrase was revealed. Due to an enzymatic digest of the protein-mercury adduct, the binding site at the free thiol group of the protein was identified. These results indicate that carbonic anhydrase might play a role in mercury toxicity.

  5. Nacre calcification in the freshwater mussel Unio pictorum: carbonic anhydrase activity and purification of a 95 kDa calcium-binding glycoprotein.

    Science.gov (United States)

    Marie, Benjamin; Luquet, Gilles; Bédouet, Laurent; Milet, Christian; Guichard, Nathalie; Medakovic, Davorin; Marin, Frédéric

    2008-10-13

    The formation of the molluscan shell is finely tuned by macromolecules of the shell organic matrix. Previous results have shown that the acid-soluble fraction of the nacre matrix of the freshwater paleoheterodont bivalve Unio pictorum shell displays a number of remarkable properties, such as calcium-binding activity, the presence of extensive glycosylations and the capacity to interfere at low concentration with in vitro calcium carbonate precipitation. Here we have found that the nacre-soluble matrix exhibits a carbonic anhydrase activity, an important function in calcification processes. This matrix is composed of three main proteinaceous discrete fractions. The one with the highest apparent molecular weight is a 95 kDa glycoprotein that is specific to the nacreous layer. P95, as it is provisionally named, is enriched in Gly, Glx and Asx and exhibits an apparent pI value of approximately 4, or approximately 7 when chemically deglycosylated. Furthermore, its glycosyl moiety, consisting of sulfated polysaccharides, is involved in calcium binding. Purified fractions of the three main proteins were digested with trypsin, and the resulting peptides were analysed by mass spectrometry. Our results suggest that identical peptides are constitutive domains of the different proteins. Partial primary structures were obtained by de novo sequencing and compared with known sequences from other mollusc shell proteins. Our results are discussed from an evolutionary viewpoint.

  6. Radionuclide and Fluorescence Imaging of Clear Cell Renal Cell Carcinoma Using Dual Labeled Anti-Carbonic Anhydrase IX Antibody G250.

    Science.gov (United States)

    Muselaers, Constantijn H J; Rijpkema, Mark; Bos, Desirée L; Langenhuijsen, Johan F; Oyen, Wim J G; Mulders, Peter F A; Oosterwijk, Egbert; Boerman, Otto C

    2015-08-01

    Tumor targeted optical imaging using antibodies labeled with near infrared fluorophores is a sensitive imaging modality that might be used during surgery to assure complete removal of malignant tissue. We evaluated the feasibility of dual modality imaging and image guided surgery with the dual labeled anti-carbonic anhydrase IX antibody preparation (111)In-DTPA-G250-IRDye800CW in mice with intraperitoneal clear cell renal cell carcinoma. BALB/c nu/nu mice with intraperitoneal SK-RC-52 lesions received 10 μg DTPA-G250-IRDye800CW labeled with 15 MBq (111)In or 10 μg of the dual labeled irrelevant control antibody NUH-82 (20 mice each). To evaluate when tumors could be detected, 4 mice per group were imaged weekly during 5 weeks with single photon emission computerized tomography/computerized tomography and the fluorescence imaging followed by ex vivo biodistribution studies. As early as 1 week after tumor cell inoculation single photon emission computerized tomography and fluorescence images showed clear delineation of intraperitoneal clear cell renal cell carcinoma with good concordance between single photon emission computerized tomography/computerized tomography and fluorescence images. The high and specific accumulation of the dual labeled antibody conjugate in tumors was confirmed in the biodistribution studies. Maximum tumor uptake was observed 1 week after inoculation (mean ± SD 58.5% ± 18.7% vs 5.6% ± 2.3% injected dose per gm for DTPA-G250-IRDye800CW vs NUH-82, respectively). High tumor uptake was also observed at other time points. This study demonstrates the feasibility of dual modality imaging with dual labeled antibody (111)In-DTPA-G250-IRDye800CW in a clear cell renal cell carcinoma model. Results indicate that preoperative and intraoperative detection of carbonic anhydrase IX expressing tumors, positive resection margins and metastasis might be feasible with this approach. Copyright © 2015 American Urological Association Education and Research

  7. The Relationship of Oxidation Sensitivity of Red Blood Cells and Carbonic Anhydrase Activity in Stored Human Blood: Effect of Certain Phenolic Compounds

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    Zübeyir Huyut

    2016-01-01

    Full Text Available It has been reported that many modifications occur with the increase of oxidative stress during storage in erythrocytes. In order to delay these negative changes, we evaluated whether the addition of substances likely to protect antioxidant capacity in stored blood would be useful. Therefore, we investigated the effects of resveratrol, tannic acid, and caffeic acid in lipid peroxidation and antioxidant capacity of erythrocytes in stored blood. Donated blood was taken into four CPD containing blood bags. One bag was used as the control, and the others were supplemented with caffeic acid (30 μg/mL, resveratrol (30 μg/mL, and tannic acid (15 μg/mL, respectively. Erythrocyte lipid peroxidation, sensitivity to oxidation, glutathione levels and carbonic anhydrase, glutathione peroxidase, and catalase activities were measured on days 0, 7, 14, 21, and 28. In the control group, erythrocyte malondialdehyde levels and sensitivity to oxidation were increased whereas glutathione, glutathione peroxidase, and catalase levels were decreased (p<0.05. Resveratrol and caffeic acid prevented malondialdehyde accumulation and preserved glutathione, glutathione peroxidase, and catalase activities in erythrocytes. We demonstrated that resveratrol, caffeic acid, and tannic acid in stored blood could decrease the sensitivity to oxidation of erythrocytes in vitro but did not exhibit such effects on CA activity.

  8. Regulation of photosynthesis and stomatal and mesophyll conductance under water stress and recovery in olive trees: correlation with gene expression of carbonic anhydrase and aquaporins.

    Science.gov (United States)

    Perez-Martin, Alfonso; Michelazzo, Chiara; Torres-Ruiz, Jose M; Flexas, Jaume; Fernández, José E; Sebastiani, Luca; Diaz-Espejo, Antonio

    2014-07-01

    The hypothesis that aquaporins and carbonic anhydrase (CA) are involved in the regulation of stomatal (g s) and mesophyll (g m) conductance to CO2 was tested in a short-term water-stress and recovery experiment in 5-year-old olive plants (Olea europaea) growing outdoors. The evolution of leaf gas exchange, chlorophyll fluorescence, and plant water status, and a quantitative analysis of photosynthesis limitations, were followed during water stress and recovery. These variables were correlated with gene expression of the aquaporins OePIP1.1 and OePIP2.1, and stromal CA. At mild stress and at the beginning of the recovery period, stomatal limitations prevailed, while the decline in g m accounted for up to 60% of photosynthesis limitations under severe water stress. However, g m was restored to control values shortly after rewatering, facilitating the recovery of the photosynthetic rate. CA was downregulated during water stress and upregulated after recovery. The use of structural equation modelling allowed us to conclude that both OePIP1.1 and OePIP2.1 expression could explain most of the variations observed for g s and g m. CA expression also had a small but significant effect on g m in olive under water-stress conditions. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  9. Mice deficient in carbonic anhydrase type 8 exhibit motor dysfunctions and abnormal calcium dynamics in the somatic region of cerebellar granule cells.

    Science.gov (United States)

    Lamont, Matthew G; Weber, John T

    2015-06-01

    The waddles (wdl) mouse is characterized by a namesake "side-to-side" waddling gait due to a homozygous mutation of the Car8 gene. This mutation results in non-functional copies of the protein carbonic anhydrase type 8. Rota-rod testing was conducted to characterize the wdl mutations' effect on motor output. Results indicated that younger homozygotes outperformed their older cohorts, an effect not seen in previous studies. Heterozygotes, which were thought to be free of motor impairment, displayed motor learning deficiencies when compared with wild type performance. Acute cerebellar slices were then utilized for fluorescent calcium imaging experiments, which revealed significant alterations in cerebellar granule cell somatic calcium signaling when exposed to glutamate. The contribution of GABAergic signaling to these alterations was also verified using bath application of bicuculline. Changes in somatic calcium signals were found to be applicable to an in vivo scenario by comparing group responses to electrical stimulation of afferent mossy fiber projections. Finally, intracellular calcium store function was also found to be altered by the wdl mutation when slices were treated with thapsigargin. These findings, taken together with previous work on the wdl mouse, indicate a widespread disruption in cerebellar circuitry hampering proper neuronal communication. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Expression and characterization of a recombinant psychrophilic γ-carbonic anhydrase (NcoCA) identified in the genome of the Antarctic cyanobacteria belonging to the genus Nostoc.

    Science.gov (United States)

    De Luca, Viviana; Del Prete, Sonia; Vullo, Daniela; Carginale, Vincenzo; Di Fonzo, Pietro; Osman, Sameh M; AlOthman, Zeid; Supuran, Claudiu T; Capasso, Clemente

    2016-10-01

    Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the CO2 hydration/dehydration reversible reaction: CO2 + H2O ⇄ [Formula: see text] + H(+). Living organisms encode for at least six distinct genetic families of such catalyst, the α-, β-, γ-, δ-, ζ- and η-CAs. The main function of the CAs is to quickly process the CO2 derived by metabolic processes in order to regulate acid-base homeostasis, connected to the production of protons (H(+)) and bicarbonate. Few data are available in the literature on Antarctic CAs and most of the scientific information regards CAs isolated from mammals or prokaryotes (as well as other mesophilic sources). It is of great interest to study the biochemical behavior of such catalysts identified in organism living in the Antarctic sea where temperatures average -1.9 °C all year round. The enzymes isolated from Antarctic organisms represent a useful tool to study the relations among structure, stability and function of proteins in organisms adapted to living at constantly low temperatures. In the present paper, we report in detail the cloning, purification, and physico-chemical properties of NcoCA, a γ-CA isolated from the Antarctic cyanobacterium Nostoc commune. This enzyme showed a higher catalytic efficiency at lower temperatures compared to mesophilic counterparts belonging to α-, β-, γ-classes, as well as a limited stability at moderate temperatures.

  11. The investigation of genetic polymorphisms in the carbonic anhydrase VI gene exon 2 and salivary parameters in type 2 diabetic patients and healthy adults.

    Science.gov (United States)

    Koç Öztürk, Leyla; Ulucan, Korkut; Akyüz, Serap; Furuncuoğlu, Halit; Bayer, Hikmet; Yarat, Ayşen

    2012-05-01

    The aim of this study was to investigate carbonic anhydrase (CA) VI Exon 2 single nucleotide polymorphism (SNP) and its possible association with salivary parameters in type 2 diabetic patients compared to healthy adults. Caries status was measured by using the DMFT (number of decayed, missing, and filled teeth) index. Unstimulated whole saliva and blood samples were taken. SNPs of CA gene exon 2 were determined by PCR and DNA sequencing. Salivary CA activity and buffering capacity were determined by the method of Verpoorte and Ericson, respectively. Furthermore, salivary pH was measured with pH paper and salivary flow rate was calculated. Salivary buffering capacity and pH were significantly lower in diabetic patients than those of healthy subjects (P Salivary flow rate, CA activity and DMFT levels did not differ between groups (P > 0.05). Four SNPs were detected; their pubmed database number are rs2274327 (C/T), rs2274328 (A/C), rs2274329 (G/C) and rs2274330. While first three of those were responsible for amino acid changes, the last one was not. The frequencies of SNPs were not significant between groups (P > 0.05). Positive significant correlation was found between CA activity and the frequency of SNPs. There was no correlation between the SNPs frequencies and pH or buffering capacity. SNPs found in this study may be related to salivary CA activity in diabetics.

  12. Peroxisome Proliferator Activated Receptor-α/Hypoxia Inducible Factor-1α Interplay Sustains Carbonic Anhydrase IX and Apoliprotein E Expression in Breast Cancer Stem Cells

    Science.gov (United States)

    Papi, Alessio; Storci, Gianluca; Guarnieri, Tiziana; De Carolis, Sabrina; Bertoni, Sara; Avenia, Nicola; Sanguinetti, Alessandro; Sidoni, Angelo; Santini, Donatella; Ceccarelli, Claudio; Taffurelli, Mario; Orlandi, Marina; Bonafé, Massimiliano

    2013-01-01

    Aims Cancer stem cell biology is tightly connected to the regulation of the pro-inflammatory cytokine network. The concept of cancer stem cells “inflammatory addiction” leads to envisage the potential role of anti-inflammatory molecules as new anti-cancer targets. Here we report on the relationship between nuclear receptors activity and the modulation of the pro-inflammatory phenotype in breast cancer stem cells. Methods Breast cancer stem cells were expanded as mammospheres from normal and tumor human breast tissues and from tumorigenic (MCF7) and non tumorigenic (MCF10) human breast cell lines. Mammospheres were exposed to the supernatant of breast tumor and normal mammary gland tissue fibroblasts. Results In mammospheres exposed to the breast tumor fibroblasts supernatant, autocrine tumor necrosis factor-α signalling engenders the functional interplay between peroxisome proliferator activated receptor-α and hypoxia inducible factor-1α (PPARα/HIF1α). The two proteins promote mammospheres formation and enhance each other expression via miRNA130b/miRNA17-5p-dependent mechanism which is antagonized by PPARγ. Further, the PPARα/HIF1α interplay regulates the expression of the pro-inflammatory cytokine interleukin-6, the hypoxia survival factor carbonic anhydrase IX and the plasma lipid carrier apolipoprotein E. Conclusion Our data demonstrate the importance of exploring the role of nuclear receptors (PPARα/PPARγ) in the regulation of pro-inflammatory pathways, with the aim to thwart breast cancer stem cells functioning. PMID:23372804

  13. The Role of Hypoxia-Inducible Factor-1α, Glucose Transporter-1, (GLUT-1 and Carbon Anhydrase IX in Endometrial Cancer Patients

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    Pawel Sadlecki

    2014-01-01

    Full Text Available Hypoxia-inducible factor-1α (HIF-1α, glucose transporter-1 (GLUT-1, and carbon anhydrase IX (CAIX are important molecules that allow adaptation to hypoxic environments. The aim of our study was to investigate the correlation between HIF-1α, GLUT-1, and CAIX protein level with the clinicopathological features of endometrial cancer patients. Materials and Methods. 92 endometrial cancer patients, aged 37–84, were enrolled to our study. In all patients clinical stage, histologic grade, myometrial invasion, lymph node, and distant metastases were determined. Moreover, the survival time was assessed. Immunohistochemical analyses were performed on archive formalin fixed paraffin embedded tissue sections. Results. High significant differences (P=0.0115 were reported between HIF-1α expression and the histologic subtype of cancer. Higher HIF-1α expression was associated with the higher risk of recurrence (P=0.0434. The results of GLUT-1 and CAIX expression did not reveal any significant differences between the proteins expression in the primary tumor and the clinicopathological features. Conclusion. The important role of HIF-1α in the group of patients with the high risk of recurrence and the negative histologic subtype of the tumor suggest that the expression of this factor might be useful in the panel of accessory pathomorphological tests and could be helpful in establishing more accurate prognosis in endometrial cancer patients.

  14. Kinetics of CO2 diffusion in human carbonic anhydrase: a study using molecular dynamics simulations and the Markov-state model.

    Science.gov (United States)

    Chen, Gong; Kong, Xian; Lu, Diannan; Wu, Jianzhong; Liu, Zheng

    2017-05-10

    Molecular dynamics (MD) simulations, in combination with the Markov-state model (MSM), were applied to probe CO 2 diffusion from an aqueous solution into the active site of human carbonic anhydrase II (hCA-II), an enzyme useful for enhanced CO 2 capture and utilization. The diffusion process in the hydrophobic pocket of hCA-II was illustrated in terms of a two-dimensional free-energy landscape. We found that CO 2 diffusion in hCA-II is a rate-limiting step in the CO 2 diffusion-binding-reaction process. The equilibrium distribution of CO 2 shows its preferential accumulation within a hydrophobic domain in the protein core region. An analysis of the committors and reactive fluxes indicates that the main pathway for CO 2 diffusion into the active site of hCA-II is through a binding pocket where residue Gln 136 contributes to the maximal flux. The simulation results offer a new perspective on the CO 2 hydration kinetics and useful insights toward the development of novel biochemical processes for more efficient CO 2 sequestration and utilization.

  15. Salivary carbonic anhydrase VI and its relation to salivary flow rate and buffer capacity in pregnant and non-pregnant women.

    Science.gov (United States)

    Kivelä, Jyrki; Laine, Merja; Parkkila, Seppo; Rajaniemi, Hannu

    2003-08-01

    Previous studies have shown that pregnancy may have unfavourable effects on oral health. The pH and buffer capacity (BC) of paraffin-stimulated saliva, for example, have been found to decrease towards late pregnancy. Salivary carbonic anhydrase VI (CA VI) probably protects the teeth by accelerating the neutralization of hydrogen ions in the enamel pellicle on dental surfaces. Since estrogens and androgens are known to regulate CA expression in some tissues, we studied here whether salivary CA VI concentration shows pregnancy-related changes. Paraffin-stimulated salivary samples were collected from nine pregnant women 1 month before delivery and about 2 months afterwards and assayed for salivary CA VI concentration, BC and flow rate. The enzyme concentration was determined using a specific time-resolved immunofluorometric assay. The control group consisted of 17 healthy non-pregnant women. The results indicated that salivary CA VI levels varied markedly among individuals, but no significant differences in mean concentrations were seen between the samples collected during late pregnancy and postpartum. BC values were lower during pregnancy, however. Our findings suggest that CA VI secretion is not significantly affected by the hormonal alterations associated with pregnancy, and confirm the earlier reports that CA VI is not involved in the regulation of actual salivary BC.

  16. The role of hypoxia response element in TGFβ-induced carbonic anhydrase IX expression in Hep3B human hepatoma cells

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    Yildirim Hatice

    2017-01-01

    Full Text Available Carbonic anhydrase IX (CAIX is a hypoxia-regulated gene. It is over expressed in a variety of cancers, including hepatocellular cancer. Transforming growth factor β (TGFβ is considered to have an impact on cancer biology due to its important roles in cell proliferation and differentiation. The effect of the TGFβ on CAIX expression under hypoxia and the mechanism underlying the role of the hypoxia response element (HRE on this expression are unknown. In this study, we demonstrate that TGFβ upregulates CAIX expression under hypoxic conditions in the Hep3B hepatoma cell line, indicating that the mitogen-activated protein kinase (MAPK- and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K-signaling pathways might be responsible for this response. Site-directed mutagenesis of the HRE region in CAIX promoter reduced the TGFβ-induced CAIX promoter activity, pointing to the significance of HRE for this response. Up regulation of TGFβ-stimulated CAIX expression was consistent with the up regulation of promoter activity of five different truncated constructs of the CAIX promoter under hypoxia. Our findings show that the HRE region is critical for TGFβ-induced CAIX expression, which is mainly controlled by MAPK and PI3K pathways.

  17. Intrinsic Thermodynamics and Structure Correlation of Benzenesulfonamides with a Pyrimidine Moiety Binding to Carbonic Anhydrases I, II, VII, XII, and XIII.

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    Miglė Kišonaitė

    Full Text Available The early stage of drug discovery is often based on selecting the highest affinity lead compound. To this end the structural and energetic characterization of the binding reaction is important. The binding energetics can be resolved into enthalpic and entropic contributions to the binding Gibbs free energy. Most compound binding reactions are coupled to the absorption or release of protons by the protein or the compound. A distinction between the observed and intrinsic parameters of the binding energetics requires the dissection of the protonation/deprotonation processes. Since only the intrinsic parameters can be correlated with molecular structural perturbations associated with complex formation, it is these parameters that are required for rational drug design. Carbonic anhydrase (CA isoforms are important therapeutic targets to treat a range of disorders including glaucoma, obesity, epilepsy, and cancer. For effective treatment isoform-specific inhibitors are needed. In this work we investigated the binding and protonation energetics of sixteen [(2-pyrimidinylthioacetyl]benzenesulfonamide CA inhibitors using isothermal titration calorimetry and fluorescent thermal shift assay. The compounds were built by combining four sulfonamide headgroups with four tailgroups yielding 16 compounds. Their intrinsic binding thermodynamics showed the limitations of the functional group energetic additivity approach used in fragment-based drug design, especially at the level of enthalpies and entropies of binding. Combined with high resolution crystal structural data correlations were drawn between the chemical functional groups on selected inhibitors and intrinsic thermodynamic parameters of CA-inhibitor complex formation.

  18. Proteochemometric Modeling of the Interaction Space of Carbonic Anhydrase and its Inhibitors: An Assessment of Structure-based and Sequence-based Descriptors.

    Science.gov (United States)

    Rasti, Behnam; Namazi, Mohsen; Karimi-Jafari, M H; Ghasemi, Jahan B

    2017-04-01

    Due to its physiological and clinical roles, carbonic anhydrase (CA) is one of the most interesting case studies. There are different classes of CAinhibitors including sulfonamides, polyamines, coumarins and dithiocarbamates (DTCs). However, many of them hardly act as a selective inhibitor against a specific isoform. Therefore, finding highly selective inhibitors for different isoforms of CA is still an ongoing project. Proteochemometrics modeling (PCM) is able to model the bioactivity of multiple compounds against different isoforms of a protein. Therefore, it would be extremely applicable when investigating the selectivity of different ligands towards different receptors. Given the facts, we applied PCM to investigate the interaction space and structural properties that lead to the selective inhibition of CA isoforms by some dithiocarbamates. Our models have provided interesting structural information that can be considered to design compounds capable of inhibiting different isoforms of CA in an improved selective manner. Validity and predictivity of the models were confirmed by both internal and external validation methods; while Y-scrambling approach was applied to assess the robustness of the models. To prove the reliability and the applicability of our findings, we showed how ligands-receptors selectivity can be affected by removing any of these critical findings from the modeling process. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Intermediate conformation between native β-sheet and non-native α-helix is a precursor of trifluoroethanol-induced aggregation of Human Carbonic Anhydrase-II

    International Nuclear Information System (INIS)

    Gupta, Preeti; Deep, Shashank

    2014-01-01

    Highlights: • HCAII forms amyloid-like aggregates at moderate concentration of trifluoroethanol. • Protein adopts a state between β-sheet and α-helix at moderate % of TFE. • Hydrophobic surface(s) of partially structured conformation forms amyloid. • High % of TFE induces stable α-helical state preventing aggregation. - Abstract: In the present work, we examined the correlation between 2,2,2-trifluoroethanol (TFE)-induced conformational transitions of human carbonic anhydrase II (HCAII) and its aggregation propensity. Circular dichroism data indicates that protein undergoes a transition from β-sheet to α-helix on addition of TFE. The protein was found to aggregate maximally at moderate concentration of TFE at which it exists somewhere between β-sheet and α-helix, probably in extended non-native β-sheet conformation. Thioflavin-T (ThT) and Congo-Red (CR) assays along with fluorescence microscopy and transmission electron microscopy (TEM) data suggest that the protein aggregates induced by TFE possess amyloid-like features. Anilino-8-naphthalene sulfonate (ANS) binding studies reveal that the exposure of hydrophobic surface(s) was maximum in intermediate conformation. Our study suggests that the exposed hydrophobic surface and/or the disruption of the structural features protecting a β-sheet protein might be the major reason(s) for the high aggregation propensity of non-native intermediate conformation of HCAII

  20. In Vivo Loss of Function Screening Reveals Carbonic Anhydrase IX as a Key Modulator of Tumor Initiating Potential in Primary Pancreatic Tumors

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    Nabendu Pore

    2015-06-01

    Full Text Available Reprogramming of energy metabolism is one of the emerging hallmarks of cancer. Up-regulation of energy metabolism pathways fuels cell growth and division, a key characteristic of neoplastic disease, and can lead to dependency on specific metabolic pathways. Thus, targeting energy metabolism pathways might offer the opportunity for novel therapeutics. Here, we describe the application of a novel in vivo screening approach for the identification of genes involved in cancer metabolism using a patient-derived pancreatic xenograft model. Lentiviruses expressing short hairpin RNAs (shRNAs targeting 12 different cell surface protein transporters were separately transduced into the primary pancreatic tumor cells. Transduced cells were pooled and implanted into mice. Tumors were harvested at different times, and the frequency of each shRNA was determined as a measure of which ones prevented tumor growth. Several targets including carbonic anhydrase IX (CAIX, monocarboxylate transporter 4, and anionic amino acid transporter light chain, xc- system (xCT were identified in these studies and shown to be required for tumor initiation and growth. Interestingly, CAIX was overexpressed in the tumor initiating cell population. CAIX expression alone correlated with a highly tumorigenic subpopulation of cells. Furthermore, CAIX expression was essential for tumor initiation because shRNA knockdown eliminated the ability of cells to grow in vivo. To the best of our knowledge, this is the first parallel in vivo assessment of multiple novel oncology target genes using a patient-derived pancreatic tumor model.

  1. Inhibition of Carbonic Anhydrase IX by Ureidosulfonamide Inhibitor U104 Reduces Prostate Cancer Cell Growth, But Does Not Modulate Daunorubicin or Cisplatin Cytotoxicity.

    Science.gov (United States)

    Riemann, Anne; Güttler, Antje; Haupt, Verena; Wichmann, Henri; Reime, Sarah; Bache, Matthias; Vordermark, Dirk; Thews, Oliver

    2018-03-05

    Carbonic anhydrase (CA) IX has emerged as a promising target for cancer therapy. It is highly upregulated in hypoxic regions and mediates pH regulation critical for tumor cell survival as well as extracellular acidification of the tumor microenvironment, which promotes tumor aggressiveness via various mechanisms, such as augmenting metastatic potential. Therefore, the aim of this study was to analyze the complex interdependency between CA IX and the tumor microenvironment in prostate tumor cells with regard to potential therapeutic implications. CA IX was upregulated by hypoxia as well as acidosis in prostate cancer cells. This induction did not modulate intracellular pH but led to extracellular acidification. Pharmacological inhibition of CA IX activity by U104 (SLC-0111) resulted in a reduction in tumor cell growth and an increase in apoptotic cell death. Intracellular pH was reduced under normoxic and even more so under hypoxic conditions when CA IX level was high. However, although intracellular pH regulation was disturbed, targeting CA IX in combination with daunorubicin or cisplatin did not intensify apoptotic tumor cell death. Hence, targeting CA IX in prostate cancer cells can lead to intracellular pH dysregulation and, consequently, can reduce cellular growth and elevate apoptotic cell death. Attenuation of extracellular acidification by blocking CA IX might additionally impede tumor progression and metastasis. However, no beneficial effect was seen when targeting CA IX in combination with chemotherapeutic drugs.

  2. Targeting carbonic anhydrase IX by nitroimidazole based sulfamides enhances the therapeutic effect of tumor irradiation: A new concept of dual targeting drugs

    International Nuclear Information System (INIS)

    Dubois, Ludwig; Peeters, Sarah G.J.A.; Kuijk, Simon J.A. van; Yaromina, Ala; Lieuwes, Natasja G.; Saraya, Ruchi; Biemans, Rianne; Rami, Marouan; Parvathaneni, Nanda Kumar; Vullo, Daniela; Vooijs, Marc; Supuran, Claudiu T.; Winum, Jean-Yves

    2013-01-01

    Background and purpose: Carbonic anhydrase IX (CAIX) plays an important role in pH regulation processes critical for tumor cell growth and metastasis. We hypothesize that a dual targeting bioreductive nitroimidazole based anti-CAIX sulfamide drug (DH348) will reduce tumor growth and sensitize tumors to irradiation in a CAIX dependent manner. Material and methods: The effect of the dual targeting anti-CAIX (DH348) and its single targeting control drugs on extracellular acidification and radiosensitivity was examined in HT-29 colorectal carcinoma cells. Tumor growth and time to reach 4× start volume (T4×SV) was monitored for animals receiving DH348 (10 mg/kg) combined with tumor single dose irradiation (10 Gy). Results: In vitro, DH348 reduced hypoxia-induced extracellular acidosis, but did not change hypoxic radiosensitivity. In vivo, DH348 monotherapy decreased tumor growth rate and sensitized tumors to radiation (enhancement ratio 1.50) without systemic toxicity only for CAIX expressing tumors. Conclusions: A newly designed nitroimidazole and sulfamide dual targeting drug reduces hypoxic extracellular acidification, slows down tumor growth at nontoxic doses and sensitizes tumors to irradiation all in a CAIX dependent manner, suggesting no “off-target” effects. Our data therefore indicate the potential utility of a dual drug approach as a new strategy for tumor-specific targeting

  3. Synthesis and In Vitro Inhibition Effect of New Pyrido[2,3-d]pyrimidine Derivatives on Erythrocyte Carbonic Anhydrase I and II

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    Hilal Kuday

    2014-01-01

    Full Text Available In vitro inhibition effects of indolylchalcones and new pyrido[2,3-d]pyrimidine derivatives on purified human carbonic anhydrase I and II (hCA I and II were investigated by using CO2 as a substrate. The results showed that all compounds inhibited the hCA I and hCA II enzyme activities. Among all the synthesized compounds, 7e (IC50=6.79 µM was found to be the most active compound for hCA I inhibitory activity and 5g (IC50=7.22 µM showed the highest hCA II inhibitory activity. Structure-activity relationships study showed that indolylchalcone derivatives have higher inhibitory activities than pyrido[2,3-d]pyrimidine derivatives on hCA I and hCA II. Additionally, methyl group bonded to uracil ring increases inhibitory activities on both hCA I and hCA II.

  4. Intrinsic Thermodynamics and Structure Correlation of Benzenesulfonamides with a Pyrimidine Moiety Binding to Carbonic Anhydrases I, II, VII, XII, and XIII

    Science.gov (United States)

    Kišonaitė, Miglė; Zubrienė, Asta; Čapkauskaitė, Edita; Smirnov, Alexey; Smirnovienė, Joana; Kairys, Visvaldas; Michailovienė, Vilma; Manakova, Elena; Gražulis, Saulius; Matulis, Daumantas

    2014-01-01

    The early stage of drug discovery is often based on selecting the highest affinity lead compound. To this end the structural and energetic characterization of the binding reaction is important. The binding energetics can be resolved into enthalpic and entropic contributions to the binding Gibbs free energy. Most compound binding reactions are coupled to the absorption or release of protons by the protein or the compound. A distinction between the observed and intrinsic parameters of the binding energetics requires the dissection of the protonation/deprotonation processes. Since only the intrinsic parameters can be correlated with molecular structural perturbations associated with complex formation, it is these parameters that are required for rational drug design. Carbonic anhydrase (CA) isoforms are important therapeutic targets to treat a range of disorders including glaucoma, obesity, epilepsy, and cancer. For effective treatment isoform-specific inhibitors are needed. In this work we investigated the binding and protonation energetics of sixteen [(2-pyrimidinylthio)acetyl]benzenesulfonamide CA inhibitors using isothermal titration calorimetry and fluorescent thermal shift assay. The compounds were built by combining four sulfonamide headgroups with four tailgroups yielding 16 compounds. Their intrinsic binding thermodynamics showed the limitations of the functional group energetic additivity approach used in fragment-based drug design, especially at the level of enthalpies and entropies of binding. Combined with high resolution crystal structural data correlations were drawn between the chemical functional groups on selected inhibitors and intrinsic thermodynamic parameters of CA-inhibitor complex formation. PMID:25493428

  5. The Cytoplasmic Carbonic Anhydrases βCA2 and βCA4 Are Required for Optimal Plant Growth at Low CO2.

    Science.gov (United States)

    DiMario, Robert J; Quebedeaux, Jennifer C; Longstreth, David J; Dassanayake, Maheshi; Hartman, Monica M; Moroney, James V

    2016-05-01

    Carbonic anhydrases (CAs) are zinc metalloenzymes that interconvert CO2 and HCO3 (-) In plants, both α- and β-type CAs are present. We hypothesize that cytoplasmic βCAs are required to modulate inorganic carbon forms needed in leaf cells for carbon-requiring reactions such as photosynthesis and amino acid biosynthesis. In this report, we present evidence that βCA2 and βCA4 are the two most abundant cytoplasmic CAs in Arabidopsis (Arabidopsis thaliana) leaves. Previously, βCA4 was reported to be localized to the plasma membrane, but here, we show that two forms of βCA4 are expressed in a tissue-specific manner and that the two proteins encoded by βCA4 localize to two different regions of the cell. Comparing transfer DNA knockout lines with wild-type plants, there was no reduction in the growth rates of the single mutants, βca2 and βca4 However, the growth rate of the double mutant, βca2βca4, was reduced significantly when grown at 200 μL L(-1) CO2 The reduction in growth of the double mutant was not linked to a reduction in photosynthetic rate. The amino acid content of leaves from the double mutant showed marked reduction in aspartate when compared with the wild type and the single mutants. This suggests the cytoplasmic CAs play an important but not previously appreciated role in amino acid biosynthesis. © 2016 American Society of Plant Biologists. All Rights Reserved.

  6. Recombinant thermoactive phosphoenolpyruvate carboxylase (PEPC) from Thermosynechococcus elongatus and its coupling with mesophilic/thermophilic bacterial carbonic anhydrases (CAs) for the conversion of CO2 to oxaloacetate.

    Science.gov (United States)

    Del Prete, Sonia; De Luca, Viviana; Capasso, Clemente; Supuran, Claudiu T; Carginale, Vincenzo

    2016-01-15

    With the continuous increase of atmospheric CO2 in the last decades, efficient methods for carbon capture, sequestration, and utilization are urgently required. The possibility of converting CO2 into useful chemicals could be a good strategy to both decreasing the CO2 concentration and for achieving an efficient exploitation of this cheap carbon source. Recently, several single- and multi-enzyme systems for the catalytic conversion of CO2 mainly to bicarbonate have been implemented. In order to design and construct a catalytic system for the conversion of CO2 to organic molecules, we implemented an in vitro multienzyme system using mesophilic and thermophilic enzymes. The system, in fact, was constituted by a recombinant phosphoenolpyruvate carboxylase (PEPC) from the thermophilic cyanobacterium Thermosynechococcus elongatus, in combination with mesophilic/thermophilic bacterial carbonic anhydrases (CAs), for converting CO2 into oxaloacetate, a compound of potential utility in industrial processes. The catalytic procedure is in two steps: the conversion of CO2 into bicarbonate by CA, followed by the carboxylation of phosphoenolpyruvate with bicarbonate, catalyzed by PEPC, with formation of oxaloacetate (OAA). All tested CAs, belonging to α-, β-, and γ-CA classes, were able to increase OAA production compared to procedures when only PEPC was used. Interestingly, the efficiency of the CAs tested in OAA production was in good agreement with the kinetic parameters for the CO2 hydration reaction of these enzymes. This PEPC also revealed to be thermoactive and thermostable, and when coupled with the extremely thermostable CA from Sulphurhydrogenibium azorense (SazCA) the production of OAA was achieved even if the two enzymes were exposed to temperatures up to 60 °C, suggesting a possible role of the two coupled enzymes in biotechnological processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Carbonic anhydrase 2-like in the giant clam, Tridacna squamosa: characterization, localization, response to light, and possible role in the transport of inorganic carbon from the host to its symbionts.

    Science.gov (United States)

    Ip, Yuen K; Koh, Clarissa Z Y; Hiong, Kum C; Choo, Celine Y L; Boo, Mel V; Wong, Wai P; Neo, Mei L; Chew, Shit F

    2017-12-01

    The fluted giant clam, Tridacna squamosa , lives in symbiosis with zooxanthellae which reside extracellularly inside a tubular system. Zooxanthellae fix inorganic carbon (C i ) during insolation and donate photosynthate to the host. Carbonic anhydrases catalyze the interconversion of CO 2 and HCO3-, of which carbonic anhydrase 2 (CA2) is the most ubiquitous and involved in many biological processes. This study aimed to clone a CA2 homolog ( CA2-like ) from the fleshy and colorful outer mantle as well as the thin and whitish inner mantle of T. squamosa , to determine its cellular and subcellular localization, and to examine the effects of light exposure on its gene and protein expression levels. The cDNA coding sequence of CA2-like from T. squamosa comprised 789 bp, encoding 263 amino acids with an estimated molecular mass of 29.6 kDa. A phenogramic analysis of the deduced CA2-like sequence denoted an animal origin. CA2-like was not detectable in the shell-facing epithelium of the inner mantle adjacent to the extrapallial fluid. Hence, CA2-like is unlikely to participate directly in light-enhanced calcification. By contrast, the outer mantle, which contains the highest density of tertiary tubules and zooxanthellae, displayed high level of CA2-like expression, and CA2-like was localized to the tubule epithelial cells. More importantly, exposure to light induced significant increases in the protein abundance of CA2-like in the outer mantle. Hence, CA2-like could probably take part in the increased supply of inorganic carbon (C i ) from the host clam to the symbiotic zooxanthellae when the latter conduct photosynthesis to fix C i during light exposure. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  8. A shell-formation related carbonic anhydrase in Crassostrea gigas modulates intracellular calcium against CO2 exposure: Implication for impacts of ocean acidification on mollusk calcification.

    Science.gov (United States)

    Wang, Xiudan; Wang, Mengqiang; Jia, Zhihao; Song, Xiaorui; Wang, Lingling; Song, Linsheng

    2017-08-01

    Ocean acidification (OA) could decrease the shells and skeletons formation of mollusk by reducing the availability of carbonate ions at calcification sites. Carbonic anhydrases (CAs) convert CO 2 to HCO 3 - and play important roles in biomineralization process from invertebrate to vertebrate. In the present study, a CA (designated as CgCA) was identified and characterized in Pacific oyster C. gigas. The cDNA of CgCA was of 927bp encoding a predicted polypeptide of 308 amino acids with a signal peptide and a CA catalytic function domain. The mRNA transcripts of CgCA were constitutively expressed in all tested tissues with the highest levels in mantle and hemocytes. During the early development period, the mRNA transcripts of CgCA could be detected in all the stages with the highest level in D-veliger larvae. Elevated CO 2 increased the mRNA transcripts of CgCA in muscle, mantle, hepatopancreas, gill and hemocytes significantly (p<0.05) and induced the translocation of CgCA in hemocytes and mantle. Moreover, elevated CO 2 also caused the decrease of intracellular Ca 2+ in hemocytes (p<0.05). The inhibition of CA by acetazolamide and suppression of CgCA gene via RNA interference could increase the intracellular Ca 2+ in hemocytes (p<0.05). Besides, the decrease of intracellular Ca 2+ content caused by Ca 2+ reagent ionomycin could affect localization of CgCA in mantle tissue. The results indicated CgCA played essential roles in calcification and elevated CO 2 accelerated the mutual modulation between calcium and CgCA, implying reduced calcification rate and dissolved shells under OA. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Structural and catalytic characterization of a thermally stable and acid-stable variant of human carbonic anhydrase II containing an engineered disulfide bond

    Energy Technology Data Exchange (ETDEWEB)

    Boone, Christopher D.; Habibzadegan, Andrew [University of Florida, PO Box 100245, Gainesville, FL 32610 (United States); Tu, Chingkuang; Silverman, David N. [University of Florida, PO Box 100267, Gainesville, FL 32610 (United States); McKenna, Robert, E-mail: rmckenna@ufl.edu [University of Florida, PO Box 100245, Gainesville, FL 32610 (United States)

    2013-08-01

    The X-ray crystallographic structure of the disulfide-containing HCAII (dsHCAII) has been solved to 1.77 Å resolution and revealed that successful oxidation of the cysteine bond was achieved while also retaining desirable active-site geometry. The carbonic anhydrases (CAs) are a family of mostly zinc metalloenzymes that catalyze the reversible hydration of CO{sub 2} to bicarbonate and a proton. Recently, there has been industrial interest in utilizing CAs as biocatalysts for carbon sequestration and biofuel production. The conditions used in these processes, however, result in high temperatures and acidic pH. This unfavorable environment results in rapid destabilization and loss of catalytic activity in CAs, ultimately resulting in cost-inefficient high-maintenance operation of the system. In order to negate these detrimental industrial conditions, cysteines at residues 23 (Ala23Cys) and 203 (Leu203Cys) were engineered into a wild-type variant of human CA II (HCAII) containing the mutation Cys206Ser. The X-ray crystallographic structure of the disulfide-containing HCAII (dsHCAII) was solved to 1.77 Å resolution and revealed that successful oxidation of the cysteine bond was achieved while also retaining desirable active-site geometry. Kinetic studies utilizing the measurement of {sup 18}O-labeled CO{sub 2} by mass spectrometry revealed that dsHCAII retained high catalytic efficiency, and differential scanning calorimetry showed acid stability and thermal stability that was enhanced by up to 14 K compared with native HCAII. Together, these studies have shown that dsHCAII has properties that could be used in an industrial setting to help to lower costs and improve the overall reaction efficiency.

  10. Preliminary results with a torsion microbalance indicate that carbon dioxide and exposed carbonic anhydrase in the organic matrix are the basis of calcification on the skeleton surface of living corals

    Directory of Open Access Journals (Sweden)

    Ian M Sandeman

    2012-03-01

    Full Text Available Ocean acidification is altering the calcification of corals, but the mechanism is still unclear. To explore what controls calcification, small pieces from the edges of thin plates of Agaricia agaricites were suspended from a torsion microbalance into gently stirred, temperaturecontrolled, seawater. Net calcification rates were monitored while light, temperature and pH were manipulated singly. The living coral pieces were sensitive to changes in conditions, especially light, and calcification was often suspended for one or two hours or overnight. The mean calcification rate increased from 0.06 in the dark to 0.10 mg.h-1.cm-2 (T test, n=8, p<0.01 in low light (15 μmol.s-1.m-2 and showed a positive linear relationship with temperature. With a reduction of mean pH from 8.2 to 7.6 the mean calcification rate in the light (65 μmol.s-1.m-2 increased from 0.19 to 0.28 mg.h-1.cm-2 (T test, n=8, p<0.05 indicating a dependency on carbon dioxide. After waterpiking and exposure of the skeletal surface/organic matrix to seawater, calcification showed an astonishing initial increase of more than an order of magnitude then decreased following a non-linear generalised Michaelis-Menten growth curve and reached a steady rate. Calcification rate of the freshly waterpiked coral was not influenced by light and was positively correlated with temperature. For a mean pH reduction from 8.1 to 7.6 the mean calcification rate increased from 0.18 to 0.32 mg.h-1.cm-2 (T test, n=11, p<0.02 again indicating a dependency on carbon dioxide. Calcification ceased in the presence of the carbonic anhydrase inhibitor azolamide. Staining confirmed the presence of carbonic anhydrase, particularly on the ridges of septae. After immersion of waterpiked corals in seawater for 48 hours weight gain and loss became linear and positively correlated to temperature. When the mean pH was reduced from 8.2 to 7.5 the mean rate of weight gain decreased from 0.25 to 0.13 mg.h-1.cm-2 (T test, n=6

  11. Evaluation of 177Lu[Lu]-CHX-A″-DTPA-6A10 Fab as a radioimmunotherapy agent targeting carbonic anhydrase XII.

    Science.gov (United States)

    Fiedler, L; Kellner, M; Gosewisch, A; Oos, R; Böning, G; Lindner, S; Albert, N; Bartenstein, P; Reulen, H-J; Zeidler, R; Gildehaus, F J

    2018-05-01

    Due to their infiltrative growth behavior, gliomas have, even after surgical resection, a high recurrence tendency. The approach of intracavitary radioimmunotherapy (RIT) is aimed at inhibiting tumor re-growth by directly administering drugs into the resection cavity (RC). Direct application of the radioconjugate into the RC has the advantage of bypassing the blood-brain barrier, which allows the administration of higher radiation doses than systemic application. Carbonic anhydrase XII (CA XII) is highly expressed on glioma cells while being absent from normal brain and thus an attractive target molecule for RIT. We evaluated a CA XII-specific 6A10 Fab (fragment antigen binding) labelled with 177 Lu as an agent for RIT. 6A10 Fab fragment was modified and radiolabelled with 177 Lu and characterized by MALDI-TOF, flow cytometry and radio-TLC. In vitro stability was determined under physiological conditions. Biodistribution studies, autoradiography tumor examinations and planar scintigraphy imaging were performed on SCID-mice bearing human glioma xenografts. The in vitro CA XII binding capacity of the modified Fab was confirmed. Radiochemical purity was determined to be >90% after 72 h of incubation under physiological conditions. Autoradiography experiments proved the specific binding of the Fab to CA XII on tumor cells. Biodistribution studies revealed a tumor uptake of 3.0%ID/g after 6 h and no detectable brain uptake. The tumor-to-contralateral ratio of 10/1 was confirmed by quantitative planar scintigraphy. The radiochemical stability in combination with a successful in vivo tumor uptake shows the potential suitability for future RIT applications with the 6A10 Fab. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Modelling the impact of soil Carbonic Anhydrase on the net ecosystem exchange of OCS at Harvard forest using the MuSICA model

    Science.gov (United States)

    Launois, Thomas; Ogée, Jérôme; Commane, Roisin; Wehr, Rchard; Meredith, Laura; Munger, Bill; Nelson, David; Saleska, Scott; Wofsy, Steve; Zahniser, Mark; Wingate, Lisa

    2016-04-01

    The exchange of CO2 between the terrestrial biosphere and the atmosphere is driven by photosynthetic uptake and respiratory loss, two fluxes currently estimated with considerable uncertainty at large scales. Model predictions indicate that these biosphere fluxes will be modified in the future as CO2 concentrations and temperatures increase; however, it still unclear to what extent. To address this challenge there is a need for better constraints on land surface model parameterisations. Additional atmospheric tracers of large-scale CO2 fluxes have been identified as potential candidates for this task. In particular carbonyl sulphide (OCS) has been proposed as a complementary tracer of gross photosynthesis over land, since OCS uptake by plants is dominated by carbonic anhydrase (CA) activity, an enzyme abundant in leaves that catalyses CO2 hydration during photosynthesis. However, although the mass budget at the ecosystem is dominated by the flux of OCS into leaves, some OCS is also exchanged between the atmosphere and the soil and this component of the budget requires constraining. In this study, we adapted the process-based isotope-enabled model MuSICA (Multi-layer Simulator of the Interactions between a vegetation Canopy and the Atmosphere) to include the transport, reaction, diffusion and production of OCS within a forested ecosystem. This model was combined with 3 years (2011-2013) of in situ measurements of OCS atmospheric concentration profiles and fluxes at the Harvard Forest (Massachussets, USA) to test hypotheses on the mechanisms responsible for CA-driven uptake by leaves and soils as well as possible OCS emissions during litter decomposition. Model simulations over the three years captured well the impact of diurnally and seasonally varying environmental conditions on the net ecosystem OCS flux. A sensitivity analysis on soil CA activity and soil OCS emission rates was also performed to quantify their impact on the vertical profiles of OCS inside the

  13. Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference.

    Science.gov (United States)

    Temperini, Claudia; Cecchi, Alessandro; Scozzafava, Andrea; Supuran, Claudiu T

    2009-02-01

    Thiazide and high ceiling diuretics were recently shown to inhibit all mammalian isoforms of carbonic anhydrase (CA, EC 4.2.1.1) with a very different profile as compared to classical inhibitors, such as acetazolamide, methazolamide, and ethoxzolamide. Some of these structurally related compounds have a very different behavior against the widespread isozyme CA II, with chlorthalidone, trichloromethiazide, and furosemide being efficient inhibitors against CA II (K(I)s of 65-138 nM), whereas indapamide is a much weaker one (K(I) of 2520 nM). Furthermore, some of these diuretics are quite efficient (low nanomolar) inhibitors of other isoforms, for example, chlorthalidone against hCA VB, VII, IX, and XIII; indapamide against CA VII, IX, XII, and XIII, trichloromethiazide against CA VII and IX, and furosemide against CA I and XIV. Examining the four X-ray crystal structures of their CA II adducts, we observed several (2-3) active site water molecules interacting with the chlorthalidone, trichloromethiazide, and furosemide scaffolds which may be responsible for this important difference of activity. Indeed, indapamide bound to CA II has no interactions with active site water molecules. Chlorthalidone bound within the CA II active site is in an enolic (lactimic) tautomeric form, with the enolic OH also participating in two strong hydrogen bonds with Asn67 and a water molecule. The newly evidenced binding modes of these diuretics may be exploited for designing better CA II inhibitors as well as compounds with selectivity/affinity for various isoforms with medicinal chemistry applications.

  14. Reconstitution of CO2 Regulation of SLAC1 Anion Channel and Function of CO2-Permeable PIP2;1 Aquaporin as CARBONIC ANHYDRASE4 Interactor

    Science.gov (United States)

    Zeise, Brian; Xu, Danyun; Rappel, Wouter-Jan; Boron, Walter F.; Schroeder, Julian I.

    2016-01-01

    Dark respiration causes an increase in leaf CO2 concentration (Ci), and the continuing increases in atmospheric [CO2] further increases Ci. Elevated leaf CO2 concentration causes stomatal pores to close. Here, we demonstrate that high intracellular CO2/HCO3− enhances currents mediated by the Arabidopsis thaliana guard cell S-type anion channel SLAC1 upon coexpression of any one of the Arabidopsis protein kinases OST1, CPK6, or CPK23 in Xenopus laevis oocytes. Split-ubiquitin screening identified the PIP2;1 aquaporin as an interactor of the βCA4 carbonic anhydrase, which was confirmed in split luciferase, bimolecular fluorescence complementation, and coimmunoprecipitation experiments. PIP2;1 exhibited CO2 permeability. Mutation of PIP2;1 in planta alone was insufficient to impair CO2- and abscisic acid-induced stomatal closing, likely due to redundancy. Interestingly, coexpression of βCA4 and PIP2;1 with OST1-SLAC1 or CPK6/23-SLAC1 in oocytes enabled extracellular CO2 enhancement of SLAC1 anion channel activity. An inactive PIP2;1 point mutation was identified that abrogated water and CO2 permeability and extracellular CO2 regulation of SLAC1 activity. These findings identify the CO2-permeable PIP2;1 as key interactor of βCA4 and demonstrate functional reconstitution of extracellular CO2 signaling to ion channel regulation upon coexpression of PIP2;1, βCA4, SLAC1, and protein kinases. These data further implicate SLAC1 as a bicarbonate-responsive protein contributing to CO2 regulation of S-type anion channels. PMID:26764375

  15. Ancillary contributions of heterologous biotin protein ligase and carbonic anhydrase for CO2 incorporation into 3-hydroxypropionate by metabolically engineered Pyrococcus furiosus.

    Science.gov (United States)

    Lian, Hong; Zeldes, Benjamin M; Lipscomb, Gina L; Hawkins, Aaron B; Han, Yejun; Loder, Andrew J; Nishiyama, Declan; Adams, Michael W W; Kelly, Robert M

    2016-12-01

    Acetyl-Coenzyme A carboxylase (ACC), malonyl-CoA reductase (MCR), and malonic semialdehyde reductase (MRS) convert HCO 3 - and acetyl-CoA into 3-hydroxypropionate (3HP) in the 3-hydroxypropionate/4-hydroxybutyrate carbon fixation cycle resident in the extremely thermoacidophilic archaeon Metallosphaera sedula. These three enzymes, when introduced into the hyperthermophilic archaeon Pyrococcus furiosus, enable production of 3HP from maltose and CO 2 . Sub-optimal function of ACC was hypothesized to be limiting for production of 3HP, so accessory enzymes carbonic anhydrase (CA) and biotin protein ligase (BPL) from M. sedula were produced recombinantly in Escherichia coli to assess their function. P. furiosus lacks a native, functional CA, while the M. sedula CA (Msed_0390) has a specific activity comparable to other microbial versions of this enzyme. M. sedula BPL (Msed_2010) was shown to biotinylate the β-subunit (biotin carboxyl carrier protein) of the ACC in vitro. Since the native BPLs in E. coli and P. furiosus may not adequately biotinylate the M. sedula ACC, the carboxylase was produced in P. furiosus by co-expression with the M. sedula BPL. The baseline production strain, containing only the ACC, MCR, and MSR, grown in a CO 2 -sparged bioreactor reached titers of approximately 40 mg/L 3HP. Strains in which either the CA or BPL accessory enzyme from M. sedula was added to the pathway resulted in improved titers, 120 or 370 mg/L, respectively. The addition of both M. sedula CA and BPL, however, yielded intermediate titers of 3HP (240 mg/L), indicating that the effects of CA and BPL on the engineered 3HP pathway were not additive, possible reasons for which are discussed. While further efforts to improve 3HP production by regulating gene dosage, improving carbon flux and optimizing bioreactor operation are needed, these results illustrate the ancillary benefits of accessory enzymes for incorporating CO 2 into 3HP production in metabolically engineered P

  16. Intracellular pH homeostasis and serotonin-induced pH changes in Calliphora salivary glands: the contribution of V-ATPase and carbonic anhydrase.

    Science.gov (United States)

    Schewe, Bettina; Schmälzlin, Elmar; Walz, Bernd

    2008-03-01

    Blowfly salivary gland cells have a vacuolar-type H(+)-ATPase (V-ATPase) in their apical membrane that energizes secretion of a KCl-rich saliva upon stimulation with serotonin (5-hydroxytryptamine, 5-HT). We have used BCECF to study microfluometrically whether V-ATPase and carbonic anhydrase (CA) are involved in intracellular pH (pH(i)) regulation, and we have localized CA activity by histochemistry. We show: (1) mean pH(i) in salivary gland cells is 7.5+/-0.3 pH units (N=96), higher than that expected from passive H(+) distribution; (2) low 5-HT concentrations (0.3-3 nmol l(-1)) induce a dose-dependent acidification of up to 0.2 pH units, with 5-HT concentrations >10 nmol l(-1), causing monophasic or multiphasic pH changes; (3) the acidifying effect of 5-HT is mimicked by bath application of cAMP, forskolin or IBMX; (4) salivary gland cells exhibit CA activity; (5) CA inhibition with acetazolamide and V-ATPase inhibition with concanamycin A lead to a slow acidification of steady-state pH(i); (6) 5-HT stimuli in the presence of acetazolamide induce an alkalinization that can be decreased by simultaneous application of the V-ATPase inhibitor concanamycin A; (7) concanamycin A removes alkali-going components from multiphasic 5-HT-induced pH changes; (8) NHE activity and a Cl(-)-dependent process are involved in generating 5-HT-induced pH changes; (9) the salivary glands probably contain a Na(+)-driven amino acid transporter. We conclude that V-ATPase and CA contribute to steady-state pH(i) regulation and 5-HT-induced outward H(+) pumping does not cause an alkalinization of pH(i) because of cytosolic H(+) accumulation attributable to stimulated cellular respiration and AE activity, masking the alkalizing effect of V-ATPase-mediated acid extrusion.

  17. A critical analysis of carbonic anhydrase function, respiratory gas exchange, and the acid-base control of secretion in the rectal gland of Squalus acanthias.

    Science.gov (United States)

    Shuttleworth, Trevor J; Thompson, Jill; Munger, R Stephen; Wood, Chris M

    2006-12-01

    We compared in vivo responses of rectal gland secretion to carbonic anhydrase (CA) inhibition (10(-4) mol l(-1) acetazolamide) in volume-loaded dogfish with in vitro responses in an isolated-perfused gland stimulated with 5 x 10(-6) mol l(-1) forskolin and removed from systemic influences. We also measured respiratory gas exchange in the perfused gland, described the acid-base status of the secreted fluid, and determined the relative importance of various extracellular and intracellular acid-base parameters in controlling rectal gland secretion in vitro. In vivo, acetazolamide inhibited Cl(-) secretion and decreased pHi in the rectal gland, but interpretation was confounded by an accompanying systemic respiratory acidosis, which would also have contributed to the inhibition. In the perfused gland, M(CO(2)) and M(O(2)) increased in linear relation to increases in Cl(-) secretion rate. CA inhibition (10(-4) mol l(-1) acetazolamide) had no effect on Cl(-) secretion rate or pHi in the perfused gland, in contrast to in vivo, but caused a transitory 30% inhibition of M(CO(2)) (relative to stable M(O(2))) and elevation in secretion P(CO(2)) effects, which peaked at 2 h and attenuated by 3.5-4 h. Secretion was inhibited by acidosis and stimulated by alkalosis; the relationship between relative Cl(-) secretion rate and pHe was almost identical to that seen in vivo. Experimental manipulations of perfusate pH, P(CO(2)) and HCO(3)(-) concentration, together with measurements of pHi, demonstrated that these responses were most strongly correlated with changes in pHe, and were not related to changes in P(CO(2)), extracellular HCO(3)(-), or intracellular HCO(3)(-) levels, though changes in pHi may also have played a role. The acid-base status of the secreted fluid varied with that of the perfusate, secretion pH remaining about 0.3-0.5 units lower, and changing in concert with pHe rather than pHi; secretion HCO(3)(-) concentrations remained low, even in the face of greatly

  18. Molecular Characterization of a Dual Domain Carbonic Anhydrase From the Ctenidium of the Giant Clam, Tridacna squamosa, and Its Expression Levels After Light Exposure, Cellular Localization, and Possible Role in the Uptake of Exogenous Inorganic Carbon

    Directory of Open Access Journals (Sweden)

    Clarissa Z. Y. Koh

    2018-03-01

    Full Text Available A Dual-Domain Carbonic Anhydrase (DDCA had been sequenced and characterized from the ctenidia (gills of the giant clam, Tridacna squamosa, which lives in symbiosis with zooxanthellae. DDCA was expressed predominantly in the ctenidium. The complete cDNA coding sequence of DDCA from T. squamosa comprised 1,803 bp, encoding a protein of 601 amino acids and 66.7 kDa. The deduced DDCA sequence contained two distinct α-CA domains, each with a specific catalytic site. It had a high sequence similarity with tgCA from Tridacna gigas. In T. squamosa, the DDCA was localized apically in certain epithelial cells near the base of the ctenidial filament and the epithelial cells surrounding the tertiary water channels. Due to the presence of two transmembrane regions in the DDCA, one of the Zn2+-containing active sites could be located externally and the other one inside the cell. These results denote that the ctenidial DDCA was positioned to dehydrate HCO3- to CO2 in seawater, and to hydrate the CO2 that had permeated the apical membrane back to HCO3- in the cytoplasm. During insolation, the host clam needs to increase the uptake of inorganic carbon from the ambient seawater to benefit the symbiotic zooxanthellae; only then, can the symbionts conduct photosynthesis and share the photosynthates with the host. Indeed, the transcript and protein levels of DDCA/DDCA in the ctenidium of T. squamosa increased significantly after 6 and 12 h of exposure to light, respectively, denoting that DDCA could participate in the light-enhanced uptake and assimilation of exogenous inorganic carbon.

  19. 1,3-Oxazole-based selective picomolar inhibitors of cytosolic human carbonic anhydrase II alleviate ocular hypertension in rabbits: Potency is supported by X-ray crystallography of two leads.

    Science.gov (United States)

    Ferraroni, Marta; Lucarini, Laura; Masini, Emanuela; Korsakov, Mikhail; Scozzafava, Andrea; Supuran, Claudiu T; Krasavin, Mikhail

    2017-09-01

    Two lead 1,3-oxazole-based carbonic anhydrase inhibitors (CAIs) earlier identified as selective, picomolar inhibitors of hCA II (a cytosolic target for treatment of glaucoma) have been investigated further. Firstly, they were found to be conveniently synthesized on multigram scale, which enables further development. These compounds were found to be comparable in efficacy to dorzolamide eye drops when applied in the eye drop form as well. Finally, the reasons for unusually high potency of these compounds became understood from their high-resolution X-ray crystallography structures. These data significantly expand our understanding of heterocycle-based primary sulfonamides, many of which have recently emerged from our labs - particularly, from the corneal permeability standpoint. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Fluoride Alters Serum Elemental (Calcium, Magnesium, Copper, and Zinc) Homeostasis Along with Erythrocyte Carbonic Anhydrase Activity in Fluorosis Endemic Villages and Restores on Supply of Safe Drinking Water in School-Going Children of Nalgonda District, India.

    Science.gov (United States)

    Khandare, Arjun L; Validandi, Vakdevi; Boiroju, Naveen

    2018-02-17

    The present study aimed to determine the serum trace elements (copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg)) along with erythrocyte carbonic anhydrase (CA) activity and effect of intervention with safe drinking water for 5 years in the school children of fluorosis endemic area. For this purpose, three categories of villages were selected based on drinking water fluoride (F): Category I (control, F = 1.68 mg/L), category II (affected F = 3.77 mg/L), and category III (intervention village) where initial drinking water F was 4.51 mg/L, and since the last 5 years, they were drinking water containing water for 5 years in school-going children.

  1. The effect of carbonic anhydrase on the kinetics and equilibrium of the oxygen isotope exchange in the CO2-H2O system: Implications for δ18O vital effects in biogenic carbonates

    Science.gov (United States)

    Uchikawa, Joji; Zeebe, Richard E.

    2012-10-01

    Interpretations of the primary paleoceanographic information recorded in stable oxygen isotope values (δ18O) of biogenic CaCO3 can be obscured by disequilibrium effects. CaCO3 is often depleted in 18O relative to the δ18O values expected for precipitation in thermodynamic equilibrium with ambient seawater as a result of vital effects. Vital effects in δ18O have been explained in terms of the influence of fluid pH on the overall δ18O of the sum of dissolved inorganic carbon (DIC) species (often referred to as "pH model") and in terms of 18O depletion as a result of the kinetic effects associated with CO2 hydration (CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+) and CO2 hydroxylation (CO2 + OH- ↔ HCO3-) in the calcification sites (so-called "kinetic model"). This study addresses the potential role of an enzyme, carbonic anhydrase (CA), that catalyzes inter-conversion of CO2 and HCO3- in relation to the underlying mechanism of vital effects. We performed quantitative inorganic carbonate precipitation experiments in order to examine the changes in 18O equilibration rate as a function of CA concentration. Experiments were performed at pH 8.3 and 8.9. These pH values are comparable to the average surface ocean pH and elevated pH levels observed in the calcification sites of some coral and foraminiferal species, respectively. The rate of uncatalyzed 18O exchange in the CO2-H2O system is governed by the pH-dependent DIC speciation and the kinetic rate constant for CO2 hydration and hydroxylation, which can be summarized by a simple mathematical expression. The results from control experiments (no CA addition) are in agreement with this expression. The results from control experiments also suggest that the most recently published kinetic rate constant for CO2 hydroxylation has been overestimated. When CA is present, the 18O equilibration process is greatly enhanced at both pH levels due to the catalysis of CO2 hydration by the enzyme. For example, the time required for 18O

  2. Carbonic anhydrase inhibitors. A general approach for the preparation of water-soluble sulfonamides incorporating polyamino-polycarboxylate tails and of their metal complexes possessing long-lasting, topical intraocular pressure-lowering properties.

    Science.gov (United States)

    Scozzafava, Andrea; Menabuoni, Luca; Mincione, Francesco; Supuran, Claudiu T

    2002-03-28

    Reaction of polyamino-polycarboxylic acids or their dianhydrides with aromatic/heterocyclic sulfonamides possessing a free amino/imino/hydrazino/hydroxy group afforded mono- and bis-sulfonamides containing polyamino-polycarboxylic acid moieties in their molecule. The acids/anhydrides used in synthesis included IDA, NTA, EDDA, EDTA and EDTA dianhydride, DTPA and DTPA dianhydride, EGTA and EGTA dianhydride, and EDDHA, among others. All the newly prepared derivatives showed strong affinity toward isozymes I, II, and IV of carbonic anhydrase (CA). Metal complexes of the new compounds have also been prepared. Metal ions used in such preparations included di- and trivalent main-group and transition cations, such as Zn(II), Cu(II), Al(III), etc. Some of the new sulfonamides/disulfonamides obtained in this way, as well as their metal complexes, behaved as nanomolar CA inhibitors against isozymes II and IV, being slightly less effective in inhibiting isozyme I. Some of these sulfonamides as well as their metal complexes strongly lowered intraocular pressure (IOP) when applied topically, directly into the normotensive/glaucomatous rabbit eye, as 1-2% water solutions/suspensions. The good water solubility of these sulfonamide CA inhibitors, correlated with the neutral pH of their water solutions used in the ophthalmologic applications and the long duration of action of the IOP-lowering effect, makes them interesting candidates for developing novel types of antiglaucoma drugs devoid of serious topical side effects.

  3. A Carbonic Anhydrase Serves as an Important Acid-Base Regulator in Pacific Oyster Crassostrea gigas Exposed to Elevated CO2: Implication for Physiological Responses of Mollusk to Ocean Acidification.

    Science.gov (United States)

    Wang, Xiudan; Wang, Mengqiang; Jia, Zhihao; Qiu, Limei; Wang, Lingling; Zhang, Anguo; Song, Linsheng

    2017-02-01

    Carbonic anhydrases (CAs) have been demonstrated to play an important role in acid-base regulation in vertebrates. However, the classification and modulatory function of CAs in marine invertebrates, especially their responses to ocean acidification remain largely unknown. Here, a cytosolic α-CA (designated as CgCAII-1) was characterized from Pacific oyster Crassostrea gigas and its molecular activities against CO 2 exposure were investigated. CgCAII-1 possessed a conserved CA catalytic domain, with high similarity to invertebrate cytoplasmic or mitochondrial α-CAs. Recombinant CgCAII-1 could convert CO 2 to HCO 3 - with calculated activity as 0.54 × 10 3  U/mg, which could be inhibited by acetazolamide (AZ). The mRNA transcripts of CgCAII-1 in muscle, mantle, hepatopancreas, gill, and hemocytes increased significantly after exposure to elevated CO 2 . CgCAII-1 could interact with the hemocyte membrane proteins and the distribution of CgCAII-1 protein became more concentrated and dense in gill and mantle under CO 2 exposure. The intracellular pH (pHi) of hemocytes under CO 2 exposure increased significantly (p ocean acidification and participate in acid-base regulation. Such cytoplasmic CA-based physiological regulation mechanism might explain other physiological responses of marine organisms to OA.

  4. Insights into methane dynamics from analysis of authigenic carbonates and chemosynthetic mussels at newly-discovered Atlantic Margin seeps

    Science.gov (United States)

    Prouty, Nancy G.; Sahy, Diana; Ruppel, Carolyn D.; Roark, E. Brendan; Condon, Dan; Brooke, Sandra; Ross, Steve W.; Demopoulos, Amanda W.J.

    2016-01-01

    The recent discovery of active methane venting along the US northern and mid-Atlantic margin represents a new source of global methane not previously accounted for in carbon budgets from this region. However, uncertainty remains as to the origin and history of methane seepage along this tectonically inactive passive margin. Here we present the first isotopic analyses of authigenic carbonates and methanotrophic deep-sea mussels, Bathymodiolus   sp., and the first direct constraints on the timing of past methane emission, based on samples collected at the upper slope Baltimore Canyon (∼385 m water depth) and deepwater Norfolk (∼1600 m) seep fields within the area of newly-discovered venting. The authigenic carbonates at both sites were dominated by aragonite, with an average  signature of −47‰, a value consistent with microbially driven anaerobic oxidation of methane-rich fluids occurring at or near the sediment–water interface. Authigenic carbonate U and Sr isotope data further support the inference of carbonate precipitation from seawater-derived fluids rather than from formation fluids from deep aquifers. Carbonate stable and radiocarbon ( and ) isotope values from living Bathymodiolus   sp. specimens are lighter than those of seawater dissolved inorganic carbon, highlighting the influence of fossil carbon from methane on carbonate precipitation. U–Th dates on authigenic carbonates suggest seepage at Baltimore Canyon between 14.7±0.6 ka to 15.7±1.6 ka, and at the Norfolk seep field between 1.0±0.7 ka to 3.3±1.3 ka, providing constraint on the longevity of methane efflux at these sites. The age of the brecciated authigenic carbonates and the occurrence of pockmarks at the Baltimore Canyon upper slope could suggest a link between sediment delivery during Pleistocene sea-level lowstand, accumulation of pore fluid overpressure from sediment compaction, and release of overpressure through subsequent venting. Calculations show that

  5. A Direct Comparison of the MM-GB/SA Scoring Procedure and Free-Energy Perturbation Calculations Using Carbonic Anhydrase as a Test Case: Strengths and Pitfalls of Each Approach.

    Science.gov (United States)

    Guimarães, Cristiano R W

    2011-07-12

    MM-GB/SA scoring and free energy perturbation (FEP) calculations have emerged as reliable methodologies to understand structural and energetic relationships to binding. In spite of successful applications to elucidate the structure-activity relationships for few pairs of ligands, the reality is that the performance of FEP calculations has rarely been tested for more than a handful of compounds. In this work, a series of 13 benzene sulfonamide inhibitors of carbonic anhydrase with binding free energies determined by isothermal titration calorimetry was selected as a test case. R(2) values of 0.70, 0.71, and 0.49 with the experiment were obtained with MM-GB/SA and FEP simulations run with MCPRO+ and Desmond, respectively. All methods work well, but the results obtained with Desmond are inferior to MM-GB/SA and MCPRO+. The main contrast between the methods is the level of sampling, ranging from full to restricted flexibility to single conformation for the complexes in Desmond, MCPRO+, and MM-GB/SA, respectively. The current and historical results obtained with MM-GB/SA qualify this approach as a more attractive alternative for rank-ordering; it can achieve equivalent or superior predictive accuracy and handle more structurally dissimilar ligands at a fraction of the computational cost of the rigorous free-energy methods. As for the large theoretical dynamic range for the binding energies, that seems to be a direct result of the degree of sampling in the simulations since MCPRO+ as well as MM-GB/SA are plagued by this. Van't Hoff analysis for selected pairs of ligands suggests that the wider scoring spread is not only affected by missing entropic contributions due to restricted sampling but also exaggerated enthalpic separation between the weak and potent compounds caused by diminished shielding of electrostatic interactions, thermal effects, and protein relaxation/strain.

  6. Genetic disruption of the pHi-regulating proteins Na+/H+ exchanger 1 (SLC9A1) and carbonic anhydrase 9 severely reduces growth of colon cancer cells.

    Science.gov (United States)

    Parks, Scott K; Cormerais, Yann; Durivault, Jerome; Pouyssegur, Jacques

    2017-02-07

    Hypoxia and extracellular acidosis are pathophysiological hallmarks of aggressive solid tumors. Regulation of intracellular pH (pHi) is essential for the maintenance of tumor cell metabolism and proliferation in this microenvironment and key proteins involved in pHi regulation are of interest for therapeutic development. Carbonic anhydrase 9 (CA9) is one of the most robustly regulated proteins by the hypoxia inducible factor (HIF) and contributes to pHi regulation. Here, we have investigated for the first time, the role of CA9 via complete genomic knockout (ko) and compared its impact on tumor cell physiology with the essential pHi regulator Na+/H+ exchanger 1 (NHE1). Initially, we established NHE1-ko LS174 cells with inducible CA9 knockdown. While increased sensitivity to acidosis for cell survival in 2-dimensions was not observed, clonogenic proliferation and 3-dimensional spheroid growth in particular were greatly reduced. To avoid potential confounding variables with use of tetracycline-inducible CA9 knockdown, we established CA9-ko and NHE1/CA9-dko cells. NHE1-ko abolished recovery from NH4Cl pre-pulse cellular acid loading while both NHE1 and CA9 knockout reduced resting pHi. NHE1-ko significantly reduced tumor cell proliferation both in normoxia and hypoxia while CA9-ko dramatically reduced growth in hypoxic conditions. Tumor xenografts revealed substantial reductions in tumor growth for both NHE1-ko and CA9-ko. A notable induction of CA12 occurred in NHE1/CA9-dko tumors indicating a potential means to compensate for loss of pH regulating proteins to maintain growth. Overall, these genomic knockout results strengthen the pursuit of targeting tumor cell pH regulation as an effective anti-cancer strategy.

  7. Close Association of Carbonic Anhydrase (CA2a and CA15a), Na+/H+ Exchanger (Nhe3b), and Ammonia Transporter Rhcg1 in Zebrafish Ionocytes Responsible for Na+ Uptake

    Science.gov (United States)

    Ito, Yusuke; Kobayashi, Sayako; Nakamura, Nobuhiro; Miyagi, Hisako; Esaki, Masahiro; Hoshijima, Kazuyuki; Hirose, Shigehisa

    2013-01-01

    Freshwater (FW) fishes actively absorb salt from their environment to tolerate low salinities. We previously reported that vacuolar-type H+-ATPase/mitochondrion-rich cells (H-MRCs) on the skin epithelium of zebrafish larvae (Danio rerio) are primary sites for Na+ uptake. In this study, in an attempt to clarify the mechanism for the Na+ uptake, we performed a systematic analysis of gene expression patterns of zebrafish carbonic anhydrase (CA) isoforms and found that, of 12 CA isoforms, CA2a and CA15a are highly expressed in H-MRCs at larval stages. The ca2a and ca15a mRNA expression were salinity-dependent; they were upregulated in 0.03 mM Na+ water whereas ca15a but not ca2a was down-regulated in 70 mM Na+ water. Immunohistochemistry demonstrated cytoplasmic distribution of CA2a and apical membrane localization of CA15a. Furthermore, cell surface immunofluorescence staining revealed external surface localization of CA15a. Depletion of either CA2a or CA15a expression by Morpholino antisense oligonucleotides resulted in a significant decrease in Na+ accumulation in H-MRCs. An in situ proximity ligation assay demonstrated a very close association of CA2a, CA15a, Na+/H+ exchanger 3b (Nhe3b), and Rhcg1 ammonia transporter in H-MRC. Our findings suggest that CA2a, CA15a, and Rhcg1 play a key role in Na+uptake under FW conditions by forming a transport metabolon with Nhe3b. PMID:23565095

  8. Extra and intracelular activities of carbonic anhydrase of the marine microalga Tetraselmis gracilis (Chlorophyta Atividade extra e intracelular da Anidrase Carbônica na microalga marinha Tetraselmis gracilis (Chlorophyta

    Directory of Open Access Journals (Sweden)

    Marilda Rigobello-Masini

    2003-07-01

    Full Text Available The activities of extra and intracellular carbonic anhydrases (CA were studied in the microalgae Tetraselmis gracilis (Kylin Butcher (Chlorophyta, Prasinophyceae growing in laboratory cultivation. During ten days of batch cultivation, daily determinations of pH, cell number, enzymatic activity, and total dissolved inorganic carbon (DIC, as well as its main species, CO2 and HCO3-, were performed. Enzymatic activity increased as the growing cell population depleted inorganic carbon from the medium. Carbon dioxide concentration decreased quickly, especially in the third day of cultivation, when a significant increase of the intracellular enzymatic activity was observed. Bicarbonate concentration had its largest decrease in the cultivation medium in the fourth day, when the activity of the extracellular enzyme had its largest increase, suggesting its use by the alga through CA activity. After the fourth cultivation day, half of the cultures were aerated with CO2-free atmospheric air, which caused an increase in the total and external activity of the enzyme, although, in this condition, the stationary growth phase began earlier than in cultures aerated with atmospheric air. The pH of the media was measured daily, increasing from the first to the fourth day, and remaining almost constant until the end of the cultivation. Algal material transferred to the dark lost all enzymatic activity.As atividades da Anidrase Carbônica (AC extra e intracelular foram estudadas na microalga marinha Tetraselmis gracilis (Kylin Butcher (Chlorophyta, Prasinophyceae crescendo em cultivos laboratoriais. Durante dez dias de cultivo, determinações diárias do pH, número de células, atividades enzimáticas, carbono inorgânico total dissolvido (CID e suas principais espécies CO2 e HCO3- foram feitas. A atividade enzimática aumentou na medida em que a população celular em crescimento retirava carbono inorgânico do meio de cultivo. A concentração de dióxido de

  9. Discovering Wavelets

    CERN Document Server

    Aboufadel, Edward

    1999-01-01

    An accessible and practical introduction to wavelets. With applications in image processing, audio restoration, seismology, and elsewhere, wavelets have been the subject of growing excitement and interest over the past several years. Unfortunately, most books on wavelets are accessible primarily to research mathematicians. Discovering Wavelets presents basic and advanced concepts of wavelets in a way that is accessible to anyone with only a fundamental knowledge of linear algebra. The basic concepts of wavelet theory are introduced in the context of an explanation of how the FBI uses wavelets

  10. Discovering Technicolor

    DEFF Research Database (Denmark)

    R. Andersen, J.; Antipin, O.; Azuelos, G.

    2011-01-01

    We provide a pedagogical introduction to extensions of the Standard Model in which the Higgs is composite. These extensions are known as models of dynamical electroweak symmetry breaking or, in brief, Technicolor. Material covered includes: motivations for Technicolor, the construction of underly...... the relevant experimental benchmarks for Vanilla, Running, Walking, and Custodial Technicolor, and a natural fourth family of leptons, by laying out the framework to discover these models at the Large Hadron Collider....... of underlying gauge theories leading to minimal models of Technicolor, the comparison with electroweak precision data, the low energy effective theory, the spectrum of the states common to most of the Technicolor models, the decays of the composite particles and the experimental signals at the Large Hadron...... Collider. The level of the presentation is aimed at readers familiar with the Standard Model but who have little or no prior exposure to Technicolor. Several extensions of the Standard Model featuring a composite Higgs can be reduced to the effective Lagrangian introduced in the text. We establish...

  11. Authigenic carbonates from newly discovered active cold seeps on the northwestern slope of the South China Sea: Constraints on fluid sources, formation environments, and seepage dynamics

    Science.gov (United States)

    Liang, Qianyong; Hu, Yu; Feng, Dong; Peckmann, Jörn; Chen, Linying; Yang, Shengxiong; Liang, Jinqiang; Tao, Jun; Chen, Duofu

    2017-06-01

    Authigenic carbonates recovered from two newly discovered active cold seeps on the northwestern slope of the South China Sea have been studied using petrography, mineralogy, stable carbon and oxygen isotopic, as well as trace element compositions, together with AMS 14C ages of shells of seep-dwelling bivalves to unravel fluid sources, formation conditions, and seepage dynamics. The two seeps (ROV1 and ROV2), referred to as 'Haima seeps' herein, are approximately 7 kilometers apart, and are typified by abundant carbonate rocks represented bycrusts and nodules. Aragonite and high-Mg calcite are the main carbonate minerals. Based on low δ13Ccarbonate values ranging from -43.0‰ to -27.5‰ (V-PDB) methane is apparently the predominant carbon source of seep carbonates. The corresponding δ18O values, varying from 2.5‰ to 5.8‰ (V-PDB), mostly are higher than calculated values representing precipitation in equilibrium with seawater (2.5‰ to 3.8‰), which probably reflects past destabilization of locally abundant gas hydrates. In addition, we found that carbonates with bivalve shells are generally aragonite-dominated, and bear no barium enrichment but uranium enrichments, reflecting shallow formation depths close to the seafloor. In contrast, carbonate crusts without bivalve shells and nodules contain more calcite, and are characterized by major molybdenum enrichment and different degrees of barium enrichment, agreeing with precipitation at greater depth under strictly anoxic conditions. AMS 14C ages suggest that a major episode of carbonate precipitation occurred between 6.1 ka and 5.1 ka BP at the Haima seeps, followed by a possibly subordinate episode from approximately 3.9 ka to 2.9 ka BP. The common occurrence of dead bivalves at both sites indicates that chemosynthesis-based communities flourished to a greater extent in the past, probably reflecting a decline of seepage activity in recent times. Overall, these results confirm that authigenic carbonates from

  12. Temperature stability of Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] in the form of a solution or in the lyophilized form during storage at -80 °C, 4 °C, 25 °C and 37 °C or pasteurization at 70 °C.

    Science.gov (United States)

    Bian, Y Z; Guo, C; Chang, T M S

    2016-01-01

    Polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase (Poly-[Hb-SOD-CAT-CA]) contains all three major functions of red blood cells (RBCs) at an enhanced level. It transports oxygen, removes oxygen radicals and transports carbon dioxide. Our previous studies in a 90-min 30 mm Hg Mean Arterial Pressure (MAP) sustained hemorrhagic shock rat model shows that it is more effective than blood in the lowering of elevated intracellular pCO2, recovery of ST-elevation and histology of the heart and intestine. This paper is to analyze the storage and temperature stability. Allowable storage time for RBC is about 1 d at room temperature and 42 d at 4 °C. Also, RBC cannot be pasteurized to remove infective agents like HIV and Ebola. PolyHb can be heat sterilized and can be stored for 1 year even at room temperature. However, Poly-[Hb-SOD-CAT-CA] contains both Hb and enzymes and enzymes are particularly sensitive to storage and heat. We thus carried out studies to analyze its storage stability at different temperatures and heat pasteurization stability. Results of storage stability show that lyophilization extends the storage time to 1 year at 4 °C and 40 d at room temperature (compared to respectively, 42 d and 1 d for RBC). After the freeze-dry process, the enzyme activities of Poly-[SFHb-SOD-CAT-CA] was 100 ± 2% for CA, 100 ± 2% for SOD and 93 ± 3.5% for CAT. After heat pasteurization at 70 °C for 2 h, lyophilized Poly-[Hb-SOD-CAT-CA] retained good enzyme activities of CA 97 ± 4%, SOD 100 ± 2.5% and CAT 63.8 ± 4%. More CAT can be added during the crosslinking process to maintain the same enzyme ratio after heat pasteurization. Heat pasteurization is possible only for the lyophilized form of Poly-[Hb-SOD-CAT-CA] and not for the solution. It can be easily reconstituted by dissolving in suitable solutions that continues to have good storage stability though less than that for the lyophilized form. According to the P50 value, Poly-[SFHb-SOD-CAT-CA] retains its

  13. Pairwise comparison of 89Zr- and 124I-labeled cG250 based on positron emission tomography imaging and nonlinear immunokinetic modeling: in vivo carbonic anhydrase IX receptor binding and internalization in mouse xenografts of clear-cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Cheal, Sarah M.; Punzalan, Blesida; Doran, Michael G.; Osborne, Joseph R.; Evans, Michael J.; Lewis, Jason S.; Zanzonico, Pat; Larson, Steven M.

    2014-01-01

    The PET tracer, 124 I-cG250, directed against carbonic anhydrase IX (CAIX) shows promise for presurgical diagnosis of clear-cell renal cell carcinoma (ccRCC) (Divgi et al. in Lancet Oncol 8:304-310, 2007; Divgi et al. in J Clin Oncol 31:187-194, 2013). The radiometal 89 Zr, however, may offer advantages as a surrogate PET nuclide over 124 I in terms of greater tumor uptake and retention (Rice et al. in Semin Nucl Med 41:265-282, 2011). We have developed a nonlinear immunokinetic model to facilitate a quantitative comparison of absolute uptake and antibody turnover between 124 I-cG250 and 89 Zr-cG250 using a human ccRCC xenograft tumor model in mice. We believe that this unique model better relates quantitative imaging data to the salient biological features of tumor antibody-antigen binding and turnover. We conducted experiments with 89 Zr-cG250 and 124 I-cG250 using a human ccRCC cell line (SK-RC-38) to characterize the binding affinity and internalization kinetics of the two tracers in vitro. Serial PET imaging was performed in mice bearing subcutaneous ccRCC tumors to simultaneously detect and quantify time-dependent tumor uptake in vivo. Using the known specific activities of the two tracers, the equilibrium rates of antibody internalization and turnover in the tumors were derived from the PET images using nonlinear compartmental modeling. The two tracers demonstrated virtually identical tumor cell binding and internalization but showed markedly different retentions in vitro. Superior PET images were obtained using 89 Zr-cG250, owing to the more prolonged trapping of the radiolabel in the tumor and simultaneous washout from normal tissues. Estimates of cG250/CAIX complex turnover were 1.35 - 5.51 x 10 12 molecules per hour per gram of tumor (20 % of receptors internalized per hour), and the ratio of 124 I/ 89 Zr atoms released per unit time by tumor was 17.5. Pairwise evaluation of 89 Zr-cG250 and 124 I-cG250 provided the basis for a nonlinear immunokinetic

  14. Pairwise comparison of {sup 89}Zr- and {sup 124}I-labeled cG250 based on positron emission tomography imaging and nonlinear immunokinetic modeling: in vivo carbonic anhydrase IX receptor binding and internalization in mouse xenografts of clear-cell renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Cheal, Sarah M.; Punzalan, Blesida; Doran, Michael G.; Osborne, Joseph R. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Evans, Michael J. [Memorial Sloan-Kettering Cancer Center, Human Oncology and Pathogenesis Program, New York, NY (United States); Lewis, Jason S. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Radiochemistry and Imaging Sciences Service, New York, NY (United States); Zanzonico, Pat [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Molecular Pharmacology and Therapy Service, New York, NY (United States); Memorial-Sloan Kettering Cancer Center, New York, NY (United States); Larson, Steven M. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Molecular Pharmacology and Therapy Service, New York, NY (United States)

    2014-05-15

    The PET tracer, {sup 124}I-cG250, directed against carbonic anhydrase IX (CAIX) shows promise for presurgical diagnosis of clear-cell renal cell carcinoma (ccRCC) (Divgi et al. in Lancet Oncol 8:304-310, 2007; Divgi et al. in J Clin Oncol 31:187-194, 2013). The radiometal {sup 89}Zr, however, may offer advantages as a surrogate PET nuclide over {sup 124}I in terms of greater tumor uptake and retention (Rice et al. in Semin Nucl Med 41:265-282, 2011). We have developed a nonlinear immunokinetic model to facilitate a quantitative comparison of absolute uptake and antibody turnover between {sup 124}I-cG250 and {sup 89}Zr-cG250 using a human ccRCC xenograft tumor model in mice. We believe that this unique model better relates quantitative imaging data to the salient biological features of tumor antibody-antigen binding and turnover. We conducted experiments with {sup 89}Zr-cG250 and {sup 124}I-cG250 using a human ccRCC cell line (SK-RC-38) to characterize the binding affinity and internalization kinetics of the two tracers in vitro. Serial PET imaging was performed in mice bearing subcutaneous ccRCC tumors to simultaneously detect and quantify time-dependent tumor uptake in vivo. Using the known specific activities of the two tracers, the equilibrium rates of antibody internalization and turnover in the tumors were derived from the PET images using nonlinear compartmental modeling. The two tracers demonstrated virtually identical tumor cell binding and internalization but showed markedly different retentions in vitro. Superior PET images were obtained using {sup 89}Zr-cG250, owing to the more prolonged trapping of the radiolabel in the tumor and simultaneous washout from normal tissues. Estimates of cG250/CAIX complex turnover were 1.35 - 5.51 x 10{sup 12} molecules per hour per gram of tumor (20 % of receptors internalized per hour), and the ratio of {sup 124}I/{sup 89}Zr atoms released per unit time by tumor was 17.5. Pairwise evaluation of {sup 89}Zr-cG250 and {sup

  15. Pilot absorption experiments with carbonic anhydrase enhanced MDEA

    DEFF Research Database (Denmark)

    Gladis, Arne; F. Lomholdt, Niels; Fosbøl, Philip Loldrup

    2017-01-01

    was determined by both a density method and the BaCl2 method. After the solvent was loaded to equilibrium it was heated up and reintroduced into the column, where CO2 was stripped off using air as stripping gas. The addition of CA increased the mass transfer significantly in all experiments. Lower absorption......Mass transfer experiments were carried out on DTU’s pilot absorber unit, a 10 m high column packed with 250 Y Mellapak structured packing. The influence of temperature, solvent loading, column height and liquid flow rates on absorption performance were determined for a 30 wt% N-methyl...

  16. Determination of activities of human carbonic anhydrase II inhibitors ...

    African Journals Online (AJOL)

    the esterase activity of CA-II using 4-NPA as a substrate in 96-well plates. Dimethyl sulfoxide was used ... intensive search for novel drugs is ongoing, through synthesis of new ..... License (http://creativecommons.org/licenses/by/. 4.0) and the ...

  17. Effects of solar UV radiation on photosynthesis and enzyme activities (carbonic anhydrase and nitrate reductase in marine macroalgae from southern Spain Efectos de la radiación solar UV sobre la fotosíntesis y actividades enzimáticas (anhidrasa carbónica y nitrato reductasa en macralgas marinas del sur de España

    Directory of Open Access Journals (Sweden)

    FÉLIX L. FIGUEROA

    2001-06-01

    Full Text Available The effects of solar ultraviolet (UV radiation during daily cycles on photosynthesis and two key enzymes involved in carbon incorporation, the carbonic anhydrase, and in inorganic nitrogen reduction, the nitrate reductase, of macroalgae from southern Spain are presented. During daily cycles, photoinhibition in several intertidal macroalgae, expressed as decrease in the effective quantum yield from the morning to noon time, was linearly dependent on the daily integrated irradiance. However, recovery, expressed as the increase in the effective quantum yield from noon to the afternoon, presented a different pattern; full recovery was found below daily integrated irradiance of 1.0 x10(4 kJ m-2. However, recovery reached only 50 % at higher irradiances. The existence of daily photoinhibition and full recovery in intertidal algae suggests that photoinhibition is a photoprotective mechanism against high solar radiation as in higher plants, and that patterns of photoinhibition and recovery are affected by accumulative doses. Activities of carbonic anhidrase and nitrate reductase were determined in three marine macroalgae (Plocamium cartilagineum, Ulva rigida and Fucus spiralis under full (PAR + UV-A + UV-B and excluded UV solar radiation (PAR. Under PAR + UV-A + UV-B, peaks of enzyme activity were found in P. cartilagineum during the evening, and accordingly to data previously published for other red macroalgae. This situation was modified by the absence of UV radiation since the increase in the activities was delayed several hours. In the three macroalgae and under full solar radiation, a significant and negative correlation was found only when data from nitrate reductase activity was shifted in time during at least four hours. This correlation is lost in Ulva rigida when UV radiation is excluded. The existence of these daily variations with a negative correlation of both enzyme activities could reflect a complex regulatory link between carbon and

  18. Discovering the Solar System

    Science.gov (United States)

    Jones, Barrie W.

    1999-04-01

    Discovering the Solar System Barrie W. Jones The Open University, Milton Keynes, UK Discovering the Solar System is a comprehensive, up-to-date account of the Solar System and of the ways in which the various bodies have been investigated and modelled. The approach is thematic, with sequences of chapters on the interiors of planetary bodies, on their surfaces, and on their atmospheres. Within each sequence there is a chapter on general principles and processes followed by one or two chapters on specific bodies. There is also an introductory chapter, a chapter on the origin of the Solar System, and a chapter on asteroids, comets and meteorites. Liberally illustrated with diagrams, black and white photographs and colour plates, Discovering the Solar System also features: * tables of essential data * question and answers within the text * end of section review questions with answers and comments Discovering the Solar System is essential reading for all undergraduate students for whom astronomy or planetary science are components of their degrees, and for those at a more advanced level approaching the subject for the first time. It will also be of great interest to non-specialists with a keen interest in astronomy. A small amount of scientific knowledge is assumed plus familiarity with basic algebra and graphs. There is no calculus. Praise for this book includes: ".certainly qualifies as an authoritative text. The author clearly has an encyclopedic knowledge of the subject." Meteorics and Planetary Science ".liberally doused with relevant graphs, tables, and black and white figures of good quality." EOS, Transactions of the American Geophysical Union ".one of the best books on the Solar System I have seen. The general accuracy and quality of the content is excellent." Journal of the British Astronomical Association

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

    Science.gov (United States)

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

    2014-07-01

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

  20. Discovering Phonemes of Bidayuh

    Directory of Open Access Journals (Sweden)

    Jecky Misieng

    2012-07-01

    Full Text Available There are generally three views of the notion of a phoneme. The structuralist view of the phoneme focuses on this language phenomenon as a phonetic reality. In discovering phonemes of a language, phonologists who hold this view will look for minimal contrasting pairs as a way to determine contrasting sounds of that language. They will also look for allophones or two sounds of the same phoneme which may appear in complementary distribution. This paper will discuss the possible application of the structuralist approach to analyzing the phonemes of a dialect of Bidayuh, one of the Malayo-Polynesian languages spoken in the northern region of Borneo.

  1. New bioactive silver(I) complexes: Synthesis, characterization, anticancer, antibacterial and anticarbonic anhydrase II activities

    Science.gov (United States)

    Ozdemir, Ummuhan O.; Ozbek, Neslihan; Genc, Zuhal Karagoz; İlbiz, Firdevs; Gündüzalp, Ayla Balaban

    2017-06-01

    Silver(I) complexes of alkyl sulfonic acide hydrazides were newly synthesized as homologous series. Methanesulfonic acide hydrazide (L1), ethanesulfonic acide hydrazide (L2), propanesulfonic acide hydrazide (L3) and butanesulfonic acide hydrazide (L4) were used for complexation with Ag(I) ions. The silver complexes obtained in the mol ratio of 1:2 have the structural formula as Ag(L1)2NO3 (I), Ag(L2)2NO3 (II), Ag(L3)2NO3(III), (Ag(L4)2NO3 (IV). The Ag(I) complexes exhibit distorted linear two-fold coordination in [AgL2]+ cations with uncoordinated nitrates. Ligands are chelated with silver(I) ions through unsubstituted primary nitrogen in hydrazide group. Ag(I) complexes were characterized by using elemental analysis, spectroscopic methods (FT-IR, LC-MS), magnetic susceptibility and conductivity measurements. Silver(I) complexes were optimized using PBEPBE/LanL2DZ/DEF2SV basic set performed by DFT method with the Gaussian 09 program package. The geometrical parameters, frontier molecular orbitals (HOMOs and LUMOs) and molecular electrostatic potential (MEP) mapped surfaces of the optimized geometries were also determined by this quantum set. The anticancer activities of silver(I) complexes on MCF-7 human breast cancer cell line were investigated by comparing IC50 values. The antibacterial activities of complexes were studied against Gram positive bacteria; S. aureus ATCC 6538, B. subtilis ATCC 6633, B. cereus NRRL-B-3711, E. faecalis ATCC 29212 and Gram negative bacteria; E. coli ATCC 11230, P. aeruginosa ATCC 15442, K. pneumonia ATCC 70063 by using disc diffusion method. The inhibition activities of Ag(I) complexes on carbonic anhydrase II enzyme (hCA II) were also investigated by comparing IC50 and Ki values. The biological activity screening shows that Ag(I) complex of butanesulfonicacidehydrazide (IV) has the highest activity against tested breast cancer cell lines MCF-7, Gram positive/Gram negative bacteria and carbonic anhydrase II (hCA II) isoenzyme.

  2. Top quark discovered

    International Nuclear Information System (INIS)

    Anon.

    1995-01-01

    Nine months after a careful announcement of tentative evidence for the long-awaited sixth 'top' quark, physicists from the CDF and DO experiments at Fermilab's Tevatron proton-antiproton collider declared on 2 March that they had finally discovered the top quark. Last year (June 1994, page 1), the CDF experiment at the Tevatron reported a dozen candidate top events. These, said CDF, had all the characteristics expected of top, but the difficulties of extracting the tiny signal from a trillion proton-antiproton collisions made them shy of claiming a discovery. For its part, the companion DO Tevatron experiment reported a few similar events but were even more guarded about their interpretation as top quarks. Just after these hesitant announcements, performance at the Tevatron improved dramatically last summer. After the commissioning of a new linear accelerator and a magnet realignment, the machine reached a new world record proton-antiproton collision luminosity of 1.28 x 10 31 per sq cm per s, ten times that originally planned. Data began to pour in at an unprecedented rate and the data sample grew to six trillion collisions. Luminosity has subsequently climbed to 1.7 x 10 31 . The top quark is the final letter in the alphabet of Standard Model particles. According to this picture, all matter is composed of six stronglyinteracting subnuclear particles, the quarks, and six weakly interacting particles, the leptons. Both sextets are neatly arranged as three pairs in order of increasing mass. The fifth quark, the 'beauty' or 'b' quark, was also discovered at Fermilab, back in 1977. Since then physicists have been eagerly waiting for the top to turn up, but have been frustrated by its heaviness - the top is some 40 times the mass of its 'beautiful' partner. Not only is the top quark the heaviest by far, but it is the only quark which has been actively hunted. After the quarry was glimpsed last year, the net has now been

  3. Discovering genes underlying QTL

    Energy Technology Data Exchange (ETDEWEB)

    Vanavichit, Apichart [Kasetsart University, Kamphaengsaen, Nakorn Pathom (Thailand)

    2002-02-01

    A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

  4. Chandra Discovers Cosmic Cannonball

    Science.gov (United States)

    2007-11-01

    One of the fastest moving stars ever seen has been discovered with NASA's Chandra X-ray Observatory. This cosmic cannonball is challenging theories to explain its blistering speed. Astronomers used Chandra to observe a neutron star, known as RX J0822-4300, over a period of about five years. During that span, three Chandra observations clearly show the neutron star moving away from the center of the Puppis A supernova remnant. This remnant is the stellar debris field created during the same explosion in which the neutron star was created about 3700 years ago. Chandra X-ray Image of RX J0822-4300 in Puppis A Chandra X-ray Image of RX J0822-4300 in Puppis A By combining how far it has moved across the sky with its distance from Earth, astronomers determined the neutron star is moving at over 3 million miles per hour. At this rate, RX J0822-4300 is destined to escape from the Milky Way after millions of years, even though it has only traveled about 20 light years so far. "This star is moving at 3 million miles an hour, but it's so far away that the apparent motion we see in five years is less than the height of the numerals in the date on a penny, seen from the length of a football field," said Frank Winkler of Middlebury College in Vermont. "It's remarkable, and a real testament to the power of Chandra, that such a tiny motion can be measured." Labeled Image of RX J0822-4300 in Puppis A Labeled Image of RX J0822-4300 in Puppis A "Just after it was born, this neutron star got a one-way ticket out of the Galaxy," said co-author Robert Petre of NASA's Goddard Space Flight Center in Greenbelt, Md. "Astronomers have seen other stars being flung out of the Milky Way, but few as fast as this." So-called hypervelocity stars have been previously discovered shooting out of the Milky Way with speeds around one million miles per hour. One key difference between RX J0822-4300 and these other reported galactic escapees is the source of their speed. The hypervelocity stars are

  5. Discovering Hands - México

    OpenAIRE

    Salamanca Cárdenas, Daniela; Castelblanco Domínguez, Junio Andrés; Aguilar Ardila, Laura Andrea

    2016-01-01

    El modelo de Discovering Hands ha sido reconocido internacionalmente como un proyecto innovador que se ha expandido por diferentes países del mundo, como Austria, y se ha empezado a estudiar la propuesta en países como República Checa, India y Colombia. (Discovering Hands, 2016). Esto se debe a que no solo mejora el tratamiento de cáncer de mama, sino que también reduce los costos totales de tratamiento de la enfermedad y aumenta la fuerza laborar de los países donde esté presente. Al represe...

  6. Scientists Discover Sugar in Space

    Science.gov (United States)

    2000-06-01

    The prospects for life in the Universe just got sweeter, with the first discovery of a simple sugar molecule in space. The discovery of the sugar molecule glycolaldehyde in a giant cloud of gas and dust near the center of our own Milky Way Galaxy was made by scientists using the National Science Foundation's 12 Meter Telescope, a radio telescope on Kitt Peak, Arizona. "The discovery of this sugar molecule in a cloud from which new stars are forming means it is increasingly likely that the chemical precursors to life are formed in such clouds long before planets develop around the stars," said Jan M. Hollis of the NASA Goddard Space Flight Center in Greenbelt, MD. Hollis worked with Frank J. Lovas of the University of Illinois and Philip R. Jewell of the National Radio Astronomy Observatory (NRAO) in Green Bank, WV, on the observations, made in May. The scientists have submitted their results to the Astrophysical Journal Letters. "This discovery may be an important key to understanding the formation of life on the early Earth," said Jewell. Conditions in interstellar clouds may, in some cases, mimic the conditions on the early Earth, so studying the chemistry of interstellar clouds may help scientists understand how bio-molecules formed early in our planet's history. In addition, some scientists have suggested that Earth could have been "seeded" with complex molecules by passing comets, made of material from the interstellar cloud that condensed to form the Solar System. Glycolaldehyde, an 8-atom molecule composed of carbon, oxygen and hydrogen, can combine with other molecules to form the more-complex sugars Ribose and Glucose. Ribose is a building block of nucleic acids such as RNA and DNA, which carry the genetic code of living organisms. Glucose is the sugar found in fruits. Glycolaldehyde contains exactly the same atoms, though in a different molecular structure, as methyl formate and acetic acid, both of which were detected previously in interstellar clouds

  7. Glowing Hot Transiting Exoplanet Discovered

    Science.gov (United States)

    2003-04-01

    VLT Spectra Indicate Shortest-Known-Period Planet Orbiting OGLE-TR-3 Summary More than 100 exoplanets in orbit around stars other than the Sun have been found so far. But while their orbital periods and distances from their central stars are well known, their true masses cannot be determined with certainty, only lower limits. This fundamental limitation is inherent in the common observational method to discover exoplanets - the measurements of small and regular changes in the central star's velocity, caused by the planet's gravitational pull as it orbits the star. However, in two cases so far, it has been found that the exoplanet's orbit happens to be positioned in such a way that the planet moves in front of the stellar disk, as seen from the Earth. This "transit" event causes a small and temporary dip in the star's brightness, as the planet covers a small part of its surface, which can be observed. The additional knowledge of the spatial orientation of the planetary orbit then permits a direct determination of the planet's true mass. Now, a group of German astronomers [1] have found a third star in which a planet, somewhat larger than Jupiter, but only half as massive, moves in front of the central star every 28.5 hours . The crucial observation of this solar-type star, designated OGLE-TR-3 [2] was made with the high-dispersion UVES spectrograph on the Very Large Telescope (VLT) at the ESO Paranal Observatory (Chile). It is the exoplanet with the shortest period found so far and it is very close to the star, only 3.5 million km away. The hemisphere that faces the star must be extremely hot, about 2000 °C and the planet is obviously losing its atmosphere at high rate . PR Photo 10a/03 : The star OGLE-TR-3 . PR Photo 10b/03 : VLT UVES spectrum of OGLE-TR-3. PR Photo 10c/03 : Relation between stellar brightness and velocity (diagram). PR Photo 10d/03 : Observed velocity variation of OGLE-TR-3. PR Photo 10e/03 : Observed brightness variation of OGLE-TR-3. The search

  8. Carbonic anhydrases are upstream regulators of CO2-controlled stomatal movements in guard cells

    KAUST Repository

    Hu, Honghong; Boisson-Dernier, Auré lien; Israelsson-Nordströ m, Maria; Bö hmer, Maik; Xue, Shaowu; Ries, Amber; Godoski, Jan; Kuhn, Josef M.; Schroeder, Julian I.

    2009-01-01

    photosynthesis and can function in guard cells. Furthermore, guard cell betaca-overexpressing plants exhibit instantaneous enhanced water use efficiency. Guard cell expression of mammalian alphaCAII complements the reduced sensitivity of ca1 ca4 plants, showing

  9. Gastric hyperplasia in mice with targeted disruption of the carbonic anhydrase gene Car9

    Czech Academy of Sciences Publication Activity Database

    Ortová-Gut, M.; Parkkila, S.; Vernerová, Z.; Rohde, E.; Závada, Jan; Hoecker, M.; Pastorek, J.; Karttunen, T.; Gibadulinová, A.; Závadová, Zuzana; Knobeloch, K. P.; Wiedenmann, B.; Svoboda, Jan; Horák, I.; Pastoreková, S.

    2002-01-01

    Roč. 2002, č. 123 (2002), s. 1889-1903 ISSN 0016-5085 Institutional research plan: CEZ:AV0Z5052915 Keywords : Transcription factor FKH6 * parietal-cells * mn/ca-IX Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 13.440, year: 2002

  10. Synthesis of 4-(2-substituted hydrazinyl)benzenesulfonamides and their carbonic anhydrase inhibitory effects.

    Science.gov (United States)

    Gul, Halise Inci; Kucukoglu, Kaan; Yamali, Cem; Bilginer, Sinan; Yuca, Hafize; Ozturk, Iknur; Taslimi, Parham; Gulcin, Ilhami; Supuran, Claudiu T

    2016-08-01

    In this study, 4-(2-substituted hydrazinyl)benzenesulfonamides were synthesized by microwave irradiation and their chemical structures were confirmed by (1)H NMR, (13)CNMR, and HRMS. Ketones used were: Acetophenone (S1), 4-methylacetophenone (S2), 4-chloroacetophenone (S3), 4-fluoroacetophenone (S4), 4-bromoacetophenone (S5), 4-methoxyacetophenone (S6), 4-nitroacetophenone (S7), 2-acetylthiophene (S8), 2-acetylfuran (S9), 1-indanone (S10), 2-indanone (S11). The compounds S9, S10 and S11 were reported for the first time, while S1-S8 was synthesized by different method than literature reported using microwave irradiation method instead of conventional heating in this study. The inhibitory effects of 4-(2-substituted hydrazinyl)benzenesulfonamide derivatives (S1-S11) against hCA I and II were studied. Cytosolic hCA I and II isoenzymes were potently inhibited by new synthesized sulphonamide derivatives with Kis in the range of 1.79 ± 0.22-2.73 ± 0.08 nM against hCA I and in the range of 1.72 ± 0.58-11.64 ± 5.21 nM against hCA II, respectively.

  11. Deficiency of Carbonic Anhydrase II Results in a Urinary Concentrating Defect

    DEFF Research Database (Denmark)

    Krishnan, Devishree; Pan, Wanling; Beggs, Megan R

    2018-01-01

    (TDL); however, the physiological role of a CAII-AQP1 interaction in this nephron segment is not known. To determine if CAII was required for urinary concentration, we studied water handling in CAII-deficient mice. CAII-deficient mice demonstrate polyuria and polydipsia as well as an alkaline urine...... and bicarbonaturia, consistent with a type III renal tubular acidosis. Natriuresis and hypercalciuria cause polyuria, however, CAII-deficient mice did not have increased urinary sodium nor calcium excretion. Further examination revealed dilute urine in the CAII-deficient mice. Urinary concentration remained reduced...

  12. The effect of L-carnitine on carbonic anhydrase level in rats exposed ...

    African Journals Online (AJOL)

    It plays an important regulatory role in the mitochondria and is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids or fats for the generation of metabolic energy. The functions of L-carnitine in skeletal muscle are critical to sustaining normal bioenergetics during exercise ...

  13. Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration.

    NARCIS (Netherlands)

    Yang, Z.; Alvarez, B.V.; Chakarova, C.; Jiang, L.; Karan, G.; Frederick, J.M.; Zhao, Y.; Sauve, Y.; Li, X.; Zrenner, E.; Wissinger, B.; Hollander, A.I. den; Katz, B.; Baehr, W.; Cremers, F.P.M.; Casey, J.R.; Bhattacharya, S.S.; Zhang, K.

    2005-01-01

    Retina and retinal pigment epithelium (RPE) belong to the metabolically most active tissues in the human body. Efficient removal of acid load from retina and RPE is a critical function mediated by the choriocapillaris. However, the mechanism by which pH homeostasis is maintained is largely unknown.

  14. Discovering workflow nets using integer linear programming

    NARCIS (Netherlands)

    van Zelst, S.J.; van Dongen, B.F.; van der Aalst, W.M.P.; Verbeek, H.M.W.

    Process mining is concerned with the analysis, understanding and improvement of business processes. Process discovery, i.e. discovering a process model based on an event log, is considered the most challenging process mining task. State-of-the-art process discovery algorithms only discover local

  15. Discovering the essence of soil

    Science.gov (United States)

    Frink, D.

    2012-04-01

    ancient prebiotic soils. Furthermore, the physiological approach sheds light on the emergence of new soil components (e.g. spodic horizons) as ancient prebiotic soils adapt to a plethora of biotic carbon compounds. Other emergent soil properties and behaviors can be linked to the kinds, frequencies, order and intensities of various ubiquitous pedo-perturbations.

  16. Carbon isotopes in mollusk shell carbonates

    Science.gov (United States)

    McConnaughey, Ted A.; Gillikin, David Paul

    2008-10-01

    Mollusk shells contain many isotopic clues about calcification physiology and environmental conditions at the time of shell formation. In this review, we use both published and unpublished data to discuss carbon isotopes in both bivalve and gastropod shell carbonates. Land snails construct their shells mainly from respired CO2, and shell δ13C reflects the local mix of C3 and C4 plants consumed. Shell δ13C is typically >10‰ heavier than diet, probably because respiratory gas exchange discards CO2, and retains the isotopically heavier HCO3 -. Respired CO2 contributes less to the shells of aquatic mollusks, because CO2/O2 ratios are usually higher in water than in air, leading to more replacement of respired CO2 by environmental CO2. Fluid exchange with the environment also brings additional dissolved inorganic carbon (DIC) into the calcification site. Shell δ13C is typically a few ‰ lower than ambient DIC, and often decreases with age. Shell δ13C retains clues about processes such as ecosystem metabolism and estuarine mixing. Ca2+ ATPase-based models of calcification physiology developed for corals and algae likely apply to mollusks, too, but lower pH and carbonic anhydrase at the calcification site probably suppress kinetic isotope effects. Carbon isotopes in biogenic carbonates are clearly complex, but cautious interpretation can provide a wealth of information, especially after vital effects are better understood.

  17. Decision Mining Revisited – Discovering Overlapping Rules

    NARCIS (Netherlands)

    Mannhardt, F.; de Leoni, M.; Reijers, H.A.; van der Aalst, W.M.P.

    2016-01-01

    Decision mining enriches process models with rules underlying decisions in processes using historical process execution data. Choices between multiple activities are specified through rules defined over process data. Existing decision mining methods focus on discovering mutually-exclusive rules,

  18. Decision Mining Revisited - Discovering Overlapping Rules

    NARCIS (Netherlands)

    Mannhardt, F.; De Leoni, M.; Reijers, H.A.; van der Aalst, W.M.P.; Nurcan, S.; Soffer, P.; Bajec, M.; Eder, J.

    2016-01-01

    Decision mining enriches process models with rules underlying decisions in processes using historical process execution data. Choices between multiple activities are specified through rules defined over process data. Existing decision mining methods focus on discovering mutually-exclusive rules,

  19. Decision mining revisited - Discovering overlapping rules

    NARCIS (Netherlands)

    Mannhardt, Felix; De Leoni, Massimiliano; Reijers, Hajo A.; Van Der Aalst, Wil M P

    2016-01-01

    Decision mining enriches process models with rules underlying decisions in processes using historical process execution data. Choices between multiple activities are specified through rules defined over process data. Existing decision mining methods focus on discovering mutually-exclusive rules,

  20. Did the ancient egyptians discover Algol?

    Science.gov (United States)

    Jetsu, L.; Porceddu, S.; Porceddu, S.; Lyytinen, J.; Kajatkari, P.; Markkanen, T.; Toivari-Viitala, J.

    2013-02-01

    Fabritius discovered the first variable star, Mira, in 1596. Holwarda determined the 11 months period of Mira in 1638. Montanari discovered the next variable star, Algol, in 1669. Its period, 2.867 days, was determined by Goodricke (178). Algol was associated with demon-like creatures, "Gorgon" in ancient Greek and "ghoul" in ancient Arab mythology. This indicates that its variability was discovered much before 1669 (Wilk 1996), but this mythological evidence is ambiguous (Davis 1975). For thousands of years, the Ancient Egyptian Scribes (AES) observed stars for timekeeping in a region, where there are nearly 300 clear nights a year. We discovered a significant periodicity of 2.850 days in their calendar for lucky and unlucky days dated to 1224 BC, "the Cairo Calendar". Several astrophysical and astronomical tests supported our conclusion that this was the period of Algol three millennia ago. The "ghoulish habits" of Algol could explain this 0.017 days period increase (Battersby 2012).

  1. Discovering Diabetes Complications: an Ontology Based Model.

    Science.gov (United States)

    Daghistani, Tahani; Shammari, Riyad Al; Razzak, Muhammad Imran

    2015-12-01

    Diabetes is a serious disease that spread in the world dramatically. The diabetes patient has an average of risk to experience complications. Take advantage of recorded information to build ontology as information technology solution will help to predict patients who have average of risk level with certain complication. It is helpful to search and present patient's history regarding different risk factors. Discovering diabetes complications could be useful to prevent or delay the complications. We designed ontology based model, using adult diabetes patients' data, to discover the rules of diabetes with its complications in disease to disease relationship. Various rules between different risk factors of diabetes Patients and certain complications generated. Furthermore, new complications (diseases) might be discovered as new finding of this study, discovering diabetes complications could be useful to prevent or delay the complications. The system can identify the patients who are suffering from certain risk factors such as high body mass index (obesity) and starting controlling and maintaining plan.

  2. Unique biological properties of catalytic domain directed human anti-CAIX antibodies discovered through phage-display technology.

    Directory of Open Access Journals (Sweden)

    Chen Xu

    2010-03-01

    Full Text Available Carbonic anhydrase IX (CAIX, gene G250/MN-encoded transmembrane protein is highly expressed in various human epithelial tumors such as renal clear cell carcinoma (RCC, but absent from the corresponding normal tissues. Besides the CA signal transduction activity, CAIX may serve as a biomarker in early stages of oncogenesis and also as a reliable marker of hypoxia, which is associated with tumor resistance to chemotherapy and radiotherapy. Although results from preclinical and clinical studies have shown CAIX as a promising target for detection and therapy for RCC, only a limited number of murine monoclonal antibodies (mAbs and one humanized mAb are available for clinical testing and development. In this study, paramagnetic proteoliposomes of CAIX (CAIX-PMPLs were constructed and used for anti-CAIX antibody selection from our 27 billion human single-chain antibody (scFv phage display libraries. A panel of thirteen human scFvs that specifically recognize CAIX expressed on cell surface was identified, epitope mapped primarily to the CA domain, and affinity-binding constants (KD determined. These human anti-CAIX mAbs are diverse in their functions including induction of surface CAIX internalization into endosomes and inhibition of the carbonic anhydrase activity, the latter being a unique feature that has not been previously reported for anti-CAIX antibodies. These human anti-CAIX antibodies are important reagents for development of new immunotherapies and diagnostic tools for RCC treatment as well as extending our knowledge on the basic structure-function relationships of the CAIX molecule.

  3. Carbonization

    Energy Technology Data Exchange (ETDEWEB)

    Hennebutte, H G; Goutal, E

    1921-07-04

    Materials such as coal, peat, or schist are subjected to a rising temperature in successive stages in apparatus in which the distillation products are withdrawn at each stage. For example in a three-stage process, the acid products of the first or low-temperature stage are fixed in a suitable reagent, the basic products from a second or higher-temperature stage are absorbed in an acid reagent, hydrocarbons being retained by solvents, while the third are subjected to a pyrogenation process carried out in a closed vessel. Wherein the material is subjected in stages to a rising temperature, the gasified products being withdrawn at each stage, and are prevented as far as possible from mixing with the carbonized products.

  4. New Perspectives on Acetate and One-Carbon Metabolism in the Methanoarchaea

    Energy Technology Data Exchange (ETDEWEB)

    Ferry, James [Pennsylvania State Univ., University Park, PA (United States)

    2017-03-20

    Carbonic anhydrases catalyze the reversible hydration of carbon dioxide to bicarbonate. Although widespread in prokaryotes of the domains Bacteria and Archaea, few have been investigated and the physiological functions are largely unknown. Carbonic anhydrases are of biotechnological interest for carbon dioxide capture and sequestration at point sources. Prokaryotes encode three independently evolved classes. The alpha-class is restricted to a few pathogens and the other two are uniformly distributed in phylogenetically and physiologically diverse species. Although wide-spread in prokaryotes, only three gamma-class enzymes have been biochemically characterized and the physiological functions have not been investigated. The gamma-class is prominent in anaerobic acetate-utilizing methane-producing species of the genus Methanosarcina that encode three subclasses. Enzymes from two of the subclasses, Cam and CamH from Methanosarcina thermophila, have been characterized and found to utilize iron in the active site which is the first example of an iron-containing carbonic anhydrase. No representative of the third subclass has been isolated, although this subclass constitutes the great majority of the β-class. This grant application proposed to characterize gamma-class carbonic anhydrases from diverse anaerobic prokaryotes from the domains Bacteria and Archaea to broaden the understanding of this enzyme. In particular, the three subclasses present the genetically tractable acetate-utilizing methanogen Methanosarcina acetivorans will be investigated to extend studies of acetate and one-carbon metabolism in this species. A genetic approach will be taken to ascertain the physiological functions. It is also proposed to delve deeper into the mechanism of Cam from M. thermophila, the archetype of the gamma-class, via a high resolution neutron structure and kinetic analysis of site-specific amino acid replacement variants. In the course of the investigation, goals were added to

  5. Proteomic analysis of carbon concentrating chemolithotrophic bacteria Serratia sp. for sequestration of carbon dioxide.

    Science.gov (United States)

    Bharti, Randhir K; Srivastava, Shaili; Thakur, Indu Shekhar

    2014-01-01

    A chemolithotrophic bacterium enriched in the chemostat in presence of sodium bicarbonate as sole carbon source was identified as Serratia sp. by 16S rRNA sequencing. Carbon dioxide sequestering capacity of bacterium was detected by carbonic anhydrase enzyme and ribulose-1, 5- bisphosphate carboxylase/oxygenase (RuBisCO). The purified carbonic anhydrase showed molecular weight of 29 kDa. Molecular weight of RuBisCO was 550 kDa as determined by fast protein liquid chromatography (FPLC), however, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) showed presence of two subunits whose molecular weights were 56 and 14 kDa. The Western blot analysis of the crude protein and purified sample cross reacted with RuBisCO large-subunit polypeptides antibodies showed strong band pattern at molecular weight around 56 kDa regions. Whole cell soluble proteins of Serratia sp. grown under autotrophic and heterotrophic conditions were resolved by two-dimensional gel electrophoresis and MALDI-TOF/MS for differential expression of proteins. In proteomic analysis of 63 protein spots, 48 spots were significantly up-regulated in the autotrophically grown cells; seven enzymes showed its utilization in autotrophic carbon fixation pathways and other metabolic activities of bacterium including lipid metabolisms indicated sequestration potency of carbon dioxide and production of biomaterials.

  6. Proteomic analysis of carbon concentrating chemolithotrophic bacteria Serratia sp. for sequestration of carbon dioxide.

    Directory of Open Access Journals (Sweden)

    Randhir K Bharti

    Full Text Available A chemolithotrophic bacterium enriched in the chemostat in presence of sodium bicarbonate as sole carbon source was identified as Serratia sp. by 16S rRNA sequencing. Carbon dioxide sequestering capacity of bacterium was detected by carbonic anhydrase enzyme and ribulose-1, 5- bisphosphate carboxylase/oxygenase (RuBisCO. The purified carbonic anhydrase showed molecular weight of 29 kDa. Molecular weight of RuBisCO was 550 kDa as determined by fast protein liquid chromatography (FPLC, however, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE showed presence of two subunits whose molecular weights were 56 and 14 kDa. The Western blot analysis of the crude protein and purified sample cross reacted with RuBisCO large-subunit polypeptides antibodies showed strong band pattern at molecular weight around 56 kDa regions. Whole cell soluble proteins of Serratia sp. grown under autotrophic and heterotrophic conditions were resolved by two-dimensional gel electrophoresis and MALDI-TOF/MS for differential expression of proteins. In proteomic analysis of 63 protein spots, 48 spots were significantly up-regulated in the autotrophically grown cells; seven enzymes showed its utilization in autotrophic carbon fixation pathways and other metabolic activities of bacterium including lipid metabolisms indicated sequestration potency of carbon dioxide and production of biomaterials.

  7. Discovering English with the Sketch Engine

    Science.gov (United States)

    Thomas, James

    2014-01-01

    "Discovering English with the Sketch Engine" is the title of a new book (Thomas, 2014) which introduces the use of corpora in language study, teaching, writing and translating. It focuses on using the Sketch Engine to identify patterns of normal usage in many aspects of English ranging from morphology to discourse and pragmatics. This…

  8. Discovering Science through Art-Based Activities

    Science.gov (United States)

    Alberts, Rebecca

    2010-01-01

    Art and science are intrinsically linked; the essence of art and science is discovery. Both artists and scientists work in a systematic but creative way--knowledge and understanding are built up through pieces of art or a series of labs. In the classroom, integrating science and visual art can provide students with the latitude to think, discover,…

  9. Two Newly Discovered Plants in Taiwan

    OpenAIRE

    Tian-Chuan Hsu; Jia-Jung Lin; Shih-Wen Chung

    2009-01-01

    Two herbs are newly discovered in Taiwan. Limnophila fragrans (G. Forst.) Seem. (Scrophulariaceae), native in SE Asia, is recognized from southern lowlands. Anagallis minima (L.) E. H. L. Krause (Primulaceae), native in N America and Europe, was found from northern mountainous region at low altitudes. In this study, descriptions, line drawings, color photos and a distribution map of the two species are provided.

  10. Did Viking discover life on Mars?

    Science.gov (United States)

    Klein, H. P.

    1999-01-01

    A major argument in the claim that life had been discovered during the Viking mission to Mars is that the results obtained in the Labeled Release (LR) experiment are analogous to those observed with terrestrial microorganisms. This assertion is critically examined and found to be implausible.

  11. Discovering Alaska's Salmon: A Children's Activity Book.

    Science.gov (United States)

    Devaney, Laurel

    This children's activity book helps students discover Alaska's salmon. Information is provided about salmon and where they live. The salmon life cycle and food chains are also discussed. Different kinds of salmon such as Chum Salmon, Chinook Salmon, Coho Salmon, Sockeye Salmon, and Pink Salmon are introduced, and various activities on salmon are…

  12. Challenges in service mining : record, check, discover

    NARCIS (Netherlands)

    Aalst, van der W.M.P.; Daniel, F.; Dolog, P.; Li, Q.

    2013-01-01

    Process mining aims to discover, monitor and improve real processes by extracting knowledge from event logs abundantly available in today’s information systems. Although process mining has been applied in hundreds of organizations and process mining techniques have been embedded in a variety of

  13. The discovered preference hypothesis - an empirical test

    DEFF Research Database (Denmark)

    Lundhede, Thomas; Ladenburg, Jacob; Olsen, Søren Bøye

    Using stated preference methods for valuation of non-market goods is known to be vulnerable to a range of biases. Some authors claim that these so-called anomalies in effect render the methods useless for the purpose. However, the Discovered Preference Hypothesis, as put forth by Plott [31], offers...... an nterpretation and explanation of biases which entails that the stated preference methods need not to be completely written off. In this paper we conduct a test for the validity and relevance of the DPH interpretation of biases. In a choice experiment concerning preferences for protection of Danish nature areas...... as respondents evaluate more and more choice sets. This finding supports the Discovered Preference Hypothesis interpretation and explanation of starting point bias....

  14. Discovering the secrets of the Olifants sediments

    CSIR Research Space (South Africa)

    Petersen, C

    2012-07-01

    Full Text Available is an important component of an aquatic ecosystem in that it provides habitat, feed- ing and spawning areas for aquatic fauna such as fish and benthic Discovering the secrets of THE OLIFANTS SEDIMENTS The polluted Upper Olifants River, in Mpumalanga, has... the distribution of bed material sizes. This allows for the determination ? Top right: The Koffie- spruit, a tributary of the Upper Olifants River. Middle right: Bank erosion was evident throughout the Koffiespruit study reach. This section of river...

  15. Two Newly Discovered Plants in Taiwan

    Directory of Open Access Journals (Sweden)

    Tian-Chuan Hsu

    2009-11-01

    Full Text Available Two herbs are newly discovered in Taiwan. Limnophila fragrans (G. Forst. Seem. (Scrophulariaceae, native in SE Asia, is recognized from southern lowlands. Anagallis minima (L. E. H. L. Krause (Primulaceae, native in N America and Europe, was found from northern mountainous region at low altitudes. In this study, descriptions, line drawings, color photos and a distribution map of the two species are provided.

  16. Discovering More Accurate Frequent Web Usage Patterns

    OpenAIRE

    Bayir, Murat Ali; Toroslu, Ismail Hakki; Cosar, Ahmet; Fidan, Guven

    2008-01-01

    Web usage mining is a type of web mining, which exploits data mining techniques to discover valuable information from navigation behavior of World Wide Web users. As in classical data mining, data preparation and pattern discovery are the main issues in web usage mining. The first phase of web usage mining is the data processing phase, which includes the session reconstruction operation from server logs. Session reconstruction success directly affects the quality of the frequent patterns disc...

  17. What if Fleming had not discovered penicillin?

    Science.gov (United States)

    Alharbi, Sulaiman Ali; Wainwright, Milton; Alahmadi, Tahani Awad; Salleeh, Hashim Bin; Faden, Asmaa A; Chinnathambi, Arunachalam

    2014-09-01

    What would have happened had Alexander Fleming not discovered penicillin in 1928? Perhaps the obvious answer is that, someone else would have discovered penicillin during 1930s and the Oxford group, would still have purified it sometime in the early 1940s. Here, however, in this counterfactual account of the penicillin story, it is argued that without Fleming, penicillin might still be undiscovered and the antibiotic age would never have dawned. As a result, many of the recent developments in medicine, such as organ transplantation, might have been delayed or, at best, made more hazardous. Penicillin might have come onto the scene a few years later but, had Fleming overlooked the discovery, it seems certain that penicillin would not have saved countless Allied lives, during and after D-Day. Instead of having enjoyed fifty and more years of the antibiotic age, it is argued here, that we would have had to rely upon highly developed sulphonamides, so-called "supasulfas", and other chemically-derived antibacterial drugs. Indeed, it might be the case that, even well into this new millennium, the antibiotic age has yet to dawn, and medicine is still waiting for someone to chance upon penicillin. Here we discuss what might have happened had Fleming not discovered penicillin and come to the conclusion that the medical armoury available today would have been far different and might have relied solely upon highly developed varieties of sulphonamides or similar, synthetic, non-antibiotic antibacterial agents.

  18. Inorganic Carbon Utilization of the Freshwater Red Alga Compsopogon coeruleus (Balbis Montagne (Compsopogonaceae, Rhodophyta Evaluated by in situ Measurement of Chlorophyll Fluorescence

    Directory of Open Access Journals (Sweden)

    Shao-Lun Liu

    2004-09-01

    Full Text Available To explore the inorganic carbon utilization of the freshwater red alga Compsopogon coeruleus, photosynthetic rates in response to increasing of bicarbonate concentration, the addition of alkaline HEPES buffer (pH 8.8, acid HEPES buffer (pH 4.0 and the extracellular carbonic anhydrase inhibitor (acetazolamide, AZ, respectively, were examined in situ by using a submersible pulse amplitude modulated (PAM fluorometer. Among the treatments, adding acid HEPES buffer significantly reduced photosynthetic rates of the alga, while others showed no effect. Accordingly, we concluded that C. coeruleus had less or no inorganic carbon (Ci limitation in its natural habitat. The alga might have higher affinity for bicarbonate and directly uptake bicarbonate as main Ci source without the aid of extracellular carbonic anhydrase.

  19. Hemoglobin as a nitrite anhydrase: modeling methemoglobin-mediated N2O3 formation.

    Science.gov (United States)

    Hopmann, Kathrin H; Cardey, Bruno; Gladwin, Mark T; Kim-Shapiro, Daniel B; Ghosh, Abhik

    2011-05-27

    Nitrite has recently been recognized as a storage form of NO in blood and as playing a key role in hypoxic vasodilation. The nitrite ion is readily reduced to NO by hemoglobin in red blood cells, which, as it happens, also presents a conundrum. Given NO's enormous affinity for ferrous heme, a key question concerns how it escapes capture by hemoglobin as it diffuses out of the red cells and to the endothelium, where vasodilation takes place. Dinitrogen trioxide (N(2)O(3)) has been proposed as a vehicle that transports NO to the endothelium, where it dissociates to NO and NO(2). Although N(2)O(3) formation might be readily explained by the reaction Hb-Fe(3+)+NO(2)(-)+NO⇌Hb-Fe(2+)+N(2)O(3), the exact manner in which methemoglobin (Hb-Fe(3+)), nitrite and NO interact with one another is unclear. Both an "Hb-Fe(3+)-NO(2)(-)+NO" pathway and an "Hb-Fe(3+)-NO+NO(2)(-) " pathway have been proposed. Neither pathway has been established experimentally. Nor has there been any attempt until now to theoretically model N(2)O(3) formation, the so-called nitrite anhydrase reaction. Both pathways have been examined here in a detailed density functional theory (DFT, B3LYP/TZP) study and both have been found to be feasible based on energetics criteria. Modeling the "Hb-Fe(3+)-NO(2)(-)+NO" pathway proved complex. Not only are multiple linkage-isomeric (N- and O-coordinated) structures conceivable for methemoglobin-nitrite, multiple isomeric forms are also possible for N(2)O(3) (the lowest-energy state has an N-N-bonded nitronitrosyl structure, O(2)N-NO). We considered multiple spin states of methemoglobin-nitrite as well as ferromagnetic and antiferromagnetic coupling of the Fe(3+) and NO spins. Together, the isomerism and spin variables result in a diabolically complex combinatorial space of reaction pathways. Fortunately, transition states could be successfully calculated for the vast majority of these reaction channels, both M(S)=0 and M(S)=1. For a six-coordinate Fe(3+)-O

  20. Youngest Stellar Explosion in Our Galaxy Discovered

    Science.gov (United States)

    2008-05-01

    Astronomers have found the remains of the youngest supernova, or exploded star, in our Galaxy. The supernova remnant, hidden behind a thick veil of gas and dust, was revealed by the National Science Foundation's Very Large Array (VLA) and NASA's Chandra X-Ray Observatory, which could see through the murk. The object is the first example of a "missing population" of young supernova remnants. 1985 and 2008 VLA Images Move cursor over image to blink. VLA Images of G1.9+0.3 in 1985 and 2008: Circle for size comparison. CREDIT: Green, et al., NRAO/AUI/NSF From observing supernovae in other galaxies, astronomers have estimated that about three such stellar explosions should occur in our Milky Way every century. However, the most recent one known until now occurred around 1680, creating the remnant called Cassiopeia A. The newly-discovered object is the remnant of an explosion only about 140 years ago. "If the supernova rate estimates are correct, there should be the remnants of about 10 supernova explosions in the Milky Way that are younger than Cassiopeia A," said David Green of the University of Cambridge in the UK, who led the VLA study. "It's great to finally track one of them down." Supernova explosions, which mark the violent death of a star, release tremendous amounts of energy and spew heavy elements such as calcium and iron into interstellar space. They thus seed the clouds of gas and dust from which new stars and planets are formed and, through their blast shocks, can even trigger such formation. The lack of evidence for young supernova remnants in the Milky Way had caused astronomers to wonder if our Galaxy, which appears otherwise normal, differed in some unknown way from others. Alternatively, scientists thought that the "missing" Milky Way supernovae perhaps indicated that their understanding of the relationship between supernovae and other galactic processes was in error. The astronomers made their discovery by measuring the expansion of the debris from

  1. The Universe for all to discover

    Science.gov (United States)

    Ortiz-Gil, A.; Ballesteros, F.; Espinós, H.; Fernández-Soto, A.; Lanzara, M.; Moya, M. J.; Navarro, J.

    2015-05-01

    In the title of this paper, we have changed the slogan of the International Year of Astronomy, ``The Universe yours to discover" to ``The Universe for all to discover" in order to emphasize the need to think about broader audiences when we plan astronomical activities at school or during outreach events. The strategy we propose follows what is known as the Universal Design for Learning (UDL). UDL allows to reach to the general public as well as to audiences which might be regarded as ``special" because they have some disability. It has been shown that everybody has a preferred style of learning (some remember better what they see, others what they hear or what they touch) and therefore, everybody is more or less able under the different styles of learning. Through this talk I am going to outline some of the principles of the UDL that can be applied in the teaching and communication of Astronomy, along with an example of its implementation in the project ``A Touch of the Universe".

  2. Discovering context-aware conditional functional dependencies

    Institute of Scientific and Technical Information of China (English)

    Yuefeng DU; Derong SHEN; Tiezheng NIE; Yue KOU; Ge YU

    2017-01-01

    Conditional functional dependencies(CFDs) are important techniques for data consistency.However,CFDs are limited to 1) provide the reasonable values for consistency repairing and 2) detect potential errors.This paper presents context-aware conditional functional dependencies(CCFDs) which contribute to provide reasonable values and detect potential errors.Especially,we focus on automatically discovering minimal CCFDs.In this paper,we present context relativity to measure the relationship of CFDs.The overlap of the related CFDs can provide reasonable values which result in more accuracy consistency repairing,and some related CFDs are combined into CCFDs.Moreover,we prove that discovering minimal CCFDs is NP-complete and we design the precise method and the heuristic method.We also present the dominating value to facilitate the process in both the precise method and the heuristic method.Additionally,the context relativity of the CFDs affects the cleaning results.We will give an approximate threshold of context relativity according to data distribution for suggestion.The repairing results are approved more accuracy,even evidenced by our empirical evaluation.

  3. Discovering, Indexing and Interlinking Information Resources.

    Science.gov (United States)

    Celli, Fabrizio; Keizer, Johannes; Jaques, Yves; Konstantopoulos, Stasinos; Vudragović, Dušan

    2015-01-01

    The social media revolution is having a dramatic effect on the world of scientific publication. Scientists now publish their research interests, theories and outcomes across numerous channels, including personal blogs and other thematic web spaces where ideas, activities and partial results are discussed. Accordingly, information systems that facilitate access to scientific literature must learn to cope with this valuable and varied data, evolving to make this research easily discoverable and available to end users. In this paper we describe the incremental process of discovering web resources in the domain of agricultural science and technology. Making use of Linked Open Data methodologies, we interlink a wide array of custom-crawled resources with the AGRIS bibliographic database in order to enrich the user experience of the AGRIS website. We also discuss the SemaGrow Stack, a query federation and data integration infrastructure used to estimate the semantic distance between crawled web resources and AGRIS.

  4. Discovering Multidimensional Structure in Relational Data

    DEFF Research Database (Denmark)

    Jensen, Mikael Rune; Holmgren, Thomas; Pedersen, Torben Bach

    2004-01-01

    On-Line Analytical Processing (OLAP) systems based on multidimensional databases are essential elements of decision support. However, most existing data is stored in “ordinary” relational OLTP databases, i.e., data has to be (re-) modeled as multidimensional cubes before the advantages of OLAP to...... algorithms for discovering multidimensional schemas from relational databases. The algorithms take a wide range of available metadata into account in the discovery process, including functional and inclusion dependencies, and key and cardinality information....... tools are available. In this paper we present an approach for the automatic construction of multidimensional OLAP database schemas from existing relational OLTP databases, enabling easy OLAP design and analysis for most existing data sources. This is achieved through a set of practical and effective...

  5. Discovering new information in bibliographic databases

    Directory of Open Access Journals (Sweden)

    Emil Hudomalj

    2005-01-01

    Full Text Available Databases contain information that can usually not be revealed by standard query systems. For that purpose, the methods for knowledge discovery from databases can be applied, which enable the user to browse aggregated data, discover trends, produce online reports, explore possible new associations within the data etc. Such methods are successfully employed in various fields, such as banking, insurance and telecommunications, while they are seldom used in libraries. The article reviews the development of query systems for bibliographic databases, including some early attempts to apply modern knowledge discovery methods. Analytical databases are described in more detail, since they usually serve as the basis for knowledge discovery. Data mining approaches are presented, since they are a central step in the knowledge discovery process. The key role of librarians who can play a key part in developing systems for finding new information in existing bibliographic databases is stressed.

  6. Michael Maier--nine newly discovered letters.

    Science.gov (United States)

    Lenke, Nils; Roudet, Nicolas; Tilton, Hereward

    2014-02-01

    The authors provide a transcription, translation, and evaluation of nine newly discovered letters from the alchemist Michael Maier (1568-1622) to Gebhardt Johann von Alvensleben (1576-1631), a noble landholder in the vicinity of Magdeburg. Stemming from the final year of his life, this correspondence casts new light on Maier's biography, detailing his efforts to secure patronage amid the financial crisis of the early Thirty Years' War. While his ill-fated quest to perfect potable gold continued to form the central focus of his patronage suits, Maier also offered his services in several arts that he had condemned in his printed works, namely astrology and "supernatural" magic. Remarks concerning his previously unknown acquaintance with Heinrich Khunrath call for a re-evaluation of Maier's negotiation of the discursive boundaries between Lutheran orthodoxy and Paracelsianism. The letters also reveal Maier's substantial contribution to a work previously ascribed solely to the English alchemist Francis Anthony.

  7. Nuclear fission discovered fifty years ago

    International Nuclear Information System (INIS)

    Weis, M.

    1988-01-01

    Fifty years ago, Otto Hahn, Lise Meitner and Fritz Strassmann discovered the process of nuclear fission which, more than other scientific discoveries to date, profoundly has changed the world and continues to influence our life significantly: This discovery made the up to then incontestable physicists' view of the atom as an inseparable whole suddenly shatter to pieces. It has brought about the invaluable advantages of a peaceful utilization of nuclear energy, and at the same time put scientists in the position to build the most terrible weapon ever, threatening mankind and earth with complete destruction. All this certainly is reason enough to recall the scientists, their work and the spirit of the time. (orig.) [de

  8. Discovering network behind infectious disease outbreak

    Science.gov (United States)

    Maeno, Yoshiharu

    2010-11-01

    Stochasticity and spatial heterogeneity are of great interest recently in studying the spread of an infectious disease. The presented method solves an inverse problem to discover the effectively decisive topology of a heterogeneous network and reveal the transmission parameters which govern the stochastic spreads over the network from a dataset on an infectious disease outbreak in the early growth phase. Populations in a combination of epidemiological compartment models and a meta-population network model are described by stochastic differential equations. Probability density functions are derived from the equations and used for the maximal likelihood estimation of the topology and parameters. The method is tested with computationally synthesized datasets and the WHO dataset on the SARS outbreak.

  9. Discovering the Library with Google Earth

    Directory of Open Access Journals (Sweden)

    Michaela Brenner

    2008-06-01

    Full Text Available Libraries need to provide attractive and exciting discovery tools to draw patrons to the valuable resources in their catalogs. The authors conducted a pilot project to explore the free version of Google Earth as such a discover tool for Portland State Library’s digital collection of urban planning documents. They created eye-catching placemarks with links to parts of this collection, as well as to other pertinent materials like books, images, and historical background information. The detailed how-to-do part of this article is preceded by a discussion about discovery of library materials and followed by possible applications of this Google Earth project.

  10. Pancreatic sarcoidosis discovered during Whipple procedure.

    Science.gov (United States)

    Cook, Jonathan; Spees, Tanner; Telefus, Phillip; Ranaudo, Jeffrey M; Carryl, Stephen; Xiao, Philip

    2013-04-04

    Pancreatic sarcoidosis is a rare variant of systemic sarcoidosis, with cases described in literature as recently as January 2010. We present here a case of pancreatic involvement with non-caseating granulomas discovered on laparotomy in a patient with a preoperative diagnosis of pancreatic carcinoma. Computer tomography scan without contrast revealed a well-marginated smooth-shaped tumor in the head of the pancreas morphologically consistent with malignancy. During Whipple procedure, the mass was found to be a large lymph node that contained numerous non-caseating granulomas. Radiologically and clinically, non-caseating granulomas of the pancreas are often misdiagnosed as malignant tumor. Special attention given to this differential diagnosis by surgeons, pathologists and clinicians can avoid misdiagnosis and unnecessary treatment. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2013.

  11. Discovering Sentinel Rules for Business Intelligence

    Science.gov (United States)

    Middelfart, Morten; Pedersen, Torben Bach

    This paper proposes the concept of sentinel rules for multi-dimensional data that warns users when measure data concerning the external environment changes. For instance, a surge in negative blogging about a company could trigger a sentinel rule warning that revenue will decrease within two months, so a new course of action can be taken. Hereby, we expand the window of opportunity for organizations and facilitate successful navigation even though the world behaves chaotically. Since sentinel rules are at the schema level as opposed to the data level, and operate on data changes as opposed to absolute data values, we are able to discover strong and useful sentinel rules that would otherwise be hidden when using sequential pattern mining or correlation techniques. We present a method for sentinel rule discovery and an implementation of this method that scales linearly on large data volumes.

  12. CORNELL: CLEO discovers B meson penguins

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    The CLEO collaboration at Cornell's CESR electron-positron storage ring has discovered a rare type of B meson decay in which only a high energy photon and a K* meson are produced. These decays provide the first unambiguous evidence for an alternative route for heavy quark decay that has been given the whimsical name ''penguin diagram''. In the mid-1970s penguin diagrams were proposed to explain the puzzling strangeness quantum number selection rules in the decay of K mesons. At the same time it was realized that penguin diagrams could also be important in the CP violation seen in neutral K meson decay. CP violation, an asymmetry between matter and antimatter, is an essential ingredient in understanding why there is much more matter than antimatter in the universe. CP violation introduces a definite direction to the arrow of time, which could otherwise point equally forwards or backwards. In addition, penguin decays are very sensitive to some extensions of the Standard Model of weak decay. Although penguin diagrams were first proposed to explain an effect in K meson decay, the K system gives no unique signature for them, and verification of penguin processes meant looking elsewhere. In the Standard Model, quarks decay under the influence of the weak force, emitting a W boson. Since the W is charged, the charge of the initial quark differs from that of the final quark, so the charge of the quark changes as well as its flavour

  13. Discovering Alzheimer Genetic Biomarkers Using Bayesian Networks

    Directory of Open Access Journals (Sweden)

    Fayroz F. Sherif

    2015-01-01

    Full Text Available Single nucleotide polymorphisms (SNPs contribute most of the genetic variation to the human genome. SNPs associate with many complex and common diseases like Alzheimer’s disease (AD. Discovering SNP biomarkers at different loci can improve early diagnosis and treatment of these diseases. Bayesian network provides a comprehensible and modular framework for representing interactions between genes or single SNPs. Here, different Bayesian network structure learning algorithms have been applied in whole genome sequencing (WGS data for detecting the causal AD SNPs and gene-SNP interactions. We focused on polymorphisms in the top ten genes associated with AD and identified by genome-wide association (GWA studies. New SNP biomarkers were observed to be significantly associated with Alzheimer’s disease. These SNPs are rs7530069, rs113464261, rs114506298, rs73504429, rs7929589, rs76306710, and rs668134. The obtained results demonstrated the effectiveness of using BN for identifying AD causal SNPs with acceptable accuracy. The results guarantee that the SNP set detected by Markov blanket based methods has a strong association with AD disease and achieves better performance than both naïve Bayes and tree augmented naïve Bayes. Minimal augmented Markov blanket reaches accuracy of 66.13% and sensitivity of 88.87% versus 61.58% and 59.43% in naïve Bayes, respectively.

  14. CORNELL: CLEO discovers B meson penguins

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1993-06-15

    The CLEO collaboration at Cornell's CESR electron-positron storage ring has discovered a rare type of B meson decay in which only a high energy photon and a K* meson are produced. These decays provide the first unambiguous evidence for an alternative route for heavy quark decay that has been given the whimsical name ''penguin diagram''. In the mid-1970s penguin diagrams were proposed to explain the puzzling strangeness quantum number selection rules in the decay of K mesons. At the same time it was realized that penguin diagrams could also be important in the CP violation seen in neutral K meson decay. CP violation, an asymmetry between matter and antimatter, is an essential ingredient in understanding why there is much more matter than antimatter in the universe. CP violation introduces a definite direction to the arrow of time, which could otherwise point equally forwards or backwards. In addition, penguin decays are very sensitive to some extensions of the Standard Model of weak decay. Although penguin diagrams were first proposed to explain an effect in K meson decay, the K system gives no unique signature for them, and verification of penguin processes meant looking elsewhere. In the Standard Model, quarks decay under the influence of the weak force, emitting a W boson. Since the W is charged, the charge of the initial quark differs from that of the final quark, so the charge of the quark changes as well as its flavour.

  15. Astronomers Discover Fastest-Spinning Pulsar

    Science.gov (United States)

    2006-01-01

    Astronomers using the National Science Foundation's Robert C. Byrd Green Bank Telescope have discovered the fastest-spinning neutron star ever found, a 20-mile-diameter superdense pulsar whirling faster than the blades of a kitchen blender. Their work yields important new information about the nature of one of the most exotic forms of matter known in the Universe. Pulsar Graphic Pulsars Are Spinning Neutron Stars CREDIT: Bill Saxton, NRAO/AUI/NSF (Click on image for larger version) "We believe that the matter in neutron stars is denser than an atomic nucleus, but it is unclear by how much. Our observations of such a rapidly rotating star set a hard upper limit on its size, and hence on how dense the star can be.," said Jason Hessels, a graduate student at McGill University in Montreal. Hessels and his colleagues presented their findings to the American Astronomical Society's meeting in Washington, DC. Pulsars are spinning neutron stars that sling "lighthouse beams" of radio waves or light around as they spin. A neutron star is what is left after a massive star explodes at the end of its "normal" life. With no nuclear fuel left to produce energy to offset the stellar remnant's weight, its material is compressed to extreme densities. The pressure squeezes together most of its protons and electrons to form neutrons; hence, the name "neutron star." "Neutron stars are incredible laboratories for learning about the physics of the fundamental particles of nature, and this pulsar has given us an important new limit," explained Scott Ransom, an astronomer at the National Radio Astronomy Observatory and one of Hessels' collaborators on this work. The scientists discovered the pulsar, named PSR J1748-2446ad, in a globular cluster of stars called Terzan 5, located some 28,000 light-years from Earth in the constellation Sagittarius. The newly-discovered pulsar is spinning 716 times per second, or at 716 Hertz (Hz), readily beating the previous record of 642 Hz from a pulsar

  16. Inorganic carbon acquisition in potentially toxic and non-toxic diatoms: the effect of pH-induced changes in the seawater carbonate chemistry

    DEFF Research Database (Denmark)

    Trimborn, S; Lundholm, Nina; Thoms, S

    2008-01-01

    . In terms of carbon source, all species took up both CO2 and HCO3-. K-1/2 values for inorganic carbon uptake decreased with increasing pH in two species, while in N. navis-varingica apparent affinities did not change. While the contribution of HCO3- to net fixation was more than 85% in S. stellaris......The effects of pH-induced changes in seawater carbonate chemistry on inorganic carbon (C-i) acquisition and domoic acid (DA) production were studied in two potentially toxic diatom species, Pseudo-nitzschia multiseries and Nitzschia navis-varingica, and the non-toxic Stellarima stellaris. In vivo...... activities of carbonic anhydrase (CA), photosynthetic O-2 evolution and CO2 and HCO3- uptake rates were measured by membrane inlet MS in cells acclimated to low (7.9) and high pH (8.4 or 8.9). Species-specific differences in the mode of carbon acquisition were found. While extracellular carbonic anhydrase (e...

  17. Discovering biological progression underlying microarray samples.

    Directory of Open Access Journals (Sweden)

    Peng Qiu

    2011-04-01

    Full Text Available In biological systems that undergo processes such as differentiation, a clear concept of progression exists. We present a novel computational approach, called Sample Progression Discovery (SPD, to discover patterns of biological progression underlying microarray gene expression data. SPD assumes that individual samples of a microarray dataset are related by an unknown biological process (i.e., differentiation, development, cell cycle, disease progression, and that each sample represents one unknown point along the progression of that process. SPD aims to organize the samples in a manner that reveals the underlying progression and to simultaneously identify subsets of genes that are responsible for that progression. We demonstrate the performance of SPD on a variety of microarray datasets that were generated by sampling a biological process at different points along its progression, without providing SPD any information of the underlying process. When applied to a cell cycle time series microarray dataset, SPD was not provided any prior knowledge of samples' time order or of which genes are cell-cycle regulated, yet SPD recovered the correct time order and identified many genes that have been associated with the cell cycle. When applied to B-cell differentiation data, SPD recovered the correct order of stages of normal B-cell differentiation and the linkage between preB-ALL tumor cells with their cell origin preB. When applied to mouse embryonic stem cell differentiation data, SPD uncovered a landscape of ESC differentiation into various lineages and genes that represent both generic and lineage specific processes. When applied to a prostate cancer microarray dataset, SPD identified gene modules that reflect a progression consistent with disease stages. SPD may be best viewed as a novel tool for synthesizing biological hypotheses because it provides a likely biological progression underlying a microarray dataset and, perhaps more importantly, the

  18. THE MOST LUMINOUS GALAXIES DISCOVERED BY WISE

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Chao-Wei; Eisenhardt, Peter R. M.; Stern, Daniel; Moustakas, Leonidas A. [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Dr., Pasadena, CA 91109 (United States); Wu, Jingwen; Wright, Edward L. [Department of Physics and Astronomy, UCLA, Los Angeles, CA 90095-1547 (United States); Assef, Roberto J. [Núcleo de Astronomía de la Facultad deIngeniería, Universidad Diego Portales, Av. Ejército Libertador 441, Santiago (Chile); Blain, Andrew W. [Department of Physics and Astronomy, University of Leicester, 1 University Road, Leicester, LE1 7RH (United Kingdom); Bridge, Carrie R.; Sayers, Jack [Division of Physics, Math, and Astronomy, California Institute of Technology, Pasadena, CA 91125 (United States); Benford, Dominic J.; Leisawitz, David T. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Cutri, Roc M.; Masci, Frank J.; Yan, Lin [Infrared Processing and Analysis Center, California Institute of Technology, Pasadena, CA 91125 (United States); Griffith, Roger L. [Department of Astronomy and Astrophysics, The Pennsylvania State University, 525 Davey Lab, University Park, PA 16802 (United States); Jarrett, Thomas H. [Astronomy Department, University of Cape Town, Private Bag X3, Rondebosch 7701 (South Africa); Lonsdale, Carol J. [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22903 (United States); Petty, Sara M. [Department of Physics, Virginia Tech, Blacksburg, VA 24061 (United States); Stanford, S. Adam, E-mail: Chao-Wei.Tsai@jpl.nasa.gov [Department of Physics, University of California Davis, One Shields Avenue, Davis, CA 95616 (United States); and others

    2015-06-01

    We present 20 Wide-field Infrared Survey Explorer (WISE)-selected galaxies with bolometric luminosities L{sub bol} > 10{sup 14} L{sub ☉}, including five with infrared luminosities L{sub IR} ≡ L{sub (rest} {sub 8–1000} {sub μm)} > 10{sup 14} L{sub ☉}. These “extremely luminous infrared galaxies,” or ELIRGs, were discovered using the “W1W2-dropout” selection criteria which requires marginal or non-detections at 3.4 and 4.6 μm (W1 and W2, respectively) but strong detections at 12 and 22 μm in the WISE survey. Their spectral energy distributions are dominated by emission at rest-frame 4–10 μm, suggesting that hot dust with T{sub d} ∼ 450 K is responsible for the high luminosities. These galaxies are likely powered by highly obscured active galactic nuclei (AGNs), and there is no evidence suggesting these systems are beamed or lensed. We compare this WISE-selected sample with 116 optically selected quasars that reach the same L{sub bol} level, corresponding to the most luminous unobscured quasars in the literature. We find that the rest-frame 5.8 and 7.8 μm luminosities of the WISE-selected ELIRGs can be 30%–80% higher than that of the unobscured quasars. The existence of AGNs with L{sub bol} > 10{sup 14} L{sub ☉} at z > 3 suggests that these supermassive black holes are born with large mass, or have very rapid mass assembly. For black hole seed masses ∼10{sup 3} M{sub ☉}, either sustained super-Eddington accretion is needed, or the radiative efficiency must be <15%, implying a black hole with slow spin, possibly due to chaotic accretion.

  19. ROSAT Discovers Unique, Distant Cluster of Galaxies

    Science.gov (United States)

    1995-06-01

    Brightest X-ray Cluster Acts as Strong Gravitational Lens Based on exciting new data obtained with the ROSAT X-ray satellite and a ground-based telescope at the ESO La Silla Observatory, a team of European astronomers [2] has just discovered a very distant cluster of galaxies with unique properties. It emits the strongest X-ray emission of any cluster ever observed by ROSAT and is accompanied by two extraordinarily luminous arcs that represent the gravitationally deflected images of even more distant objects. The combination of these unusual characteristics makes this cluster, now known as RXJ1347.5-1145, a most interesting object for further cosmological studies. DISCOVERY AND FOLLOW-UP OBSERVATIONS This strange cluster of galaxies was discovered during the All Sky Survey with the ROSAT X-ray satellite as a moderately intense X-ray source in the constellation of Virgo. It could not be identified with any already known object and additional ground-based observations were therefore soon after performed with the Max-Planck-Society/ESO 2.2-metre telescope at the La Silla observatory in Chile. These observations took place within a large--scale redshift survey of X-ray clusters of galaxies detected by the ROSAT All Sky Survey, a so-called ``ESO Key Programme'' led by astronomers from the Max-Planck-Institut fur Extraterrestrische Physik and the Osservatorio Astronomico di Brera. The main aim of this programme is to identify cluster X-ray sources, to determine the distance to the X-ray emitting clusters and to investigate their overall properties. These observations permitted to measure the redshift of the RXJ1347.5-1145 cluster as z = 0.45, i.e. it moves away from us with a velocity (about 106,000 km/sec) equal to about one-third of the velocity of light. This is an effect of the general expansion of the universe and it allows to determine the distance as about 5,000 million light-years (assuming a Hubble constant of 75 km/sec/Mpc). In other words, we see these

  20. Rate-based modelling and validation of a pilot absorber using MDEA enhanced with carbonic anhydrase (CA)

    DEFF Research Database (Denmark)

    Gaspar, Jozsef; Gladis, Arne; Woodley, John

    2017-01-01

    solvent-regeneration energy demand.The focus of this work is to develop a rate-based model for CO2 absorption using MDEA enhanced with CA and to validate it against pilot-scale absorption experiments. In this work, we compare model predictions to measured temperature and CO2 concentration profiles...

  1. Design and simulation of rate-based CO2 capture processes using carbonic anhydrase (CA) applied to biogas

    DEFF Research Database (Denmark)

    Fosbøl, Philip Loldrup; Gaspar, Jozsef; Jacobsen, Bjartur

    2017-01-01

    Today the mix of the energy sector is changing from reduction of CO2 emission from fossil fueled power industry into a general focus on renewable industry which is emitting less greenhouse gases. Renewable fuels like biomass for electricity production or biogas for bio-methane production have a p...

  2. Evolution of the mammary capillary network and carbonic anhydrase activity throughout lactation and during somatotropin treatment in goats

    DEFF Research Database (Denmark)

    Nielsen, Mette Benedicte Olaf; Cvek, Katarina; Dahlborn, Kristina

    2010-01-01

    involved in the coordination of mammary blood flow (MBF) and metabolic activity. Milk vein blood velocity was determined as a measure of MBF, and fine needle mammary biopsies were obtained at different time points during lactation and by the end of a 14-d bovine somatotropin (BST) treatment initiated 3...... almost tripled in size, whereas number of capillaries surrounding each alveolus decreased by 1/3, and CA activity more than halved. BST treatment did not affect capillary traits but increased number of alveoli in mammary sections, and BST thus appeared to be targeted mostly towards the mammary epithelial...

  3. Combination of carbonic anhydrase inhibitor, acetazolamide, and sulforaphane, reduces the viability and growth of bronchial carcinoid cell lines

    International Nuclear Information System (INIS)

    Mokhtari, Reza Bayat; Kumar, Sushil; Islam, Syed S; Yazdanpanah, Mehrdad; Adeli, Khosrow; Cutz, Ernest; Yeger, Herman

    2013-01-01

    Bronchial carcinoids are pulmonary neuroendocrine cell-derived tumors comprising typical (TC) and atypical (AC) malignant phenotypes. The 5-year survival rate in metastatic carcinoid, despite multiple current therapies, is 14-25%. Hence, we are testing novel therapies that can affect the proliferation and survival of bronchial carcinoids. In vitro studies were used for the dose–response (AlamarBlue) effects of acetazolamide (AZ) and sulforaphane (SFN) on clonogenicity, serotonin-induced growth effect and serotonin content (LC-MS) on H-727 (TC) and H-720 (AC) bronchial carcinoid cell lines and their derived NOD/SCID mice subcutaneous xenografts. Tumor ultra structure was studied by electron microscopy. Invasive fraction of the tumors was determined by matrigel invasion assay. Immunohistochemistry was conducted to study the effect of treatment(s) on proliferation (Ki67, phospho histone-H3) and neuroendocrine phenotype (chromogranin-A, tryptophan hydroxylase). Both compounds significantly reduced cell viability and colony formation in a dose-dependent manner (0–80 μM, 48 hours and 7 days) in H-727 and H-720 cell lines. Treatment of H-727 and H-720 subcutaneous xenografts in NOD/SCID mice with the combination of AZ + SFN for two weeks demonstrated highly significant growth inhibition and reduction of 5-HT content and reduced the invasive capacity of H-727 tumor cells. In terms of the tumor ultra structure, a marked reduction in secretory vesicles correlated with the decrease in 5-HT content. The combination of AZ and SFN was more effective than either single agent. Since the effective doses are well within clinical range and bioavailability, our results suggest a potential new therapeutic strategy for the treatment of bronchial carcinoids

  4. VLA Discovers Giant Rings Around Galaxy Cluster

    Science.gov (United States)

    2006-11-01

    Astronomers using the National Science Foundation's Very Large Array (VLA) radio telescope have discovered giant, ring-like structures around a cluster of galaxies. The discovery provides tantalizing new information about how such galaxy clusters are assembled, about magnetic fields in the vast spaces between galaxy clusters, and possibly about the origin of cosmic rays. Radio-Optical Image of Cluster Galaxy Cluster Abell 3376 (Radio/Optical) CREDIT: Joydeep Bagchi, IUCAA, NRAO/AUI/NSF Above, a combined radio/optical image shows the galaxy cluster Abell 3376 in visible light (blue) and radio (red) images. The giant radio arcs surrounding the cluster were discovered using the Very Large Array. The visible-light image is from the Digitized Sky survey. Below, an X-ray image of Abell 3376 made using the European Space Agency's XMM-Newton telescope shows a spectacular, bullet-shaped region of X-rays coming from gas heated to 60 million degrees Kelvin. The bullet shape results from the supersonic collision of a smaller smaller galaxy subcluster with the main body of the larger cluster. Click on images for larger version. X-Ray Image of Cluster Galaxy Cluster Abell 3376 (X-Ray) CREDIT: Joydeep Bagchi, IUCAA, ESA "These giant, radio-emitting rings probably are the result of shock waves caused by violent collisions of smaller groups of galaxies within the cluster," said Joydeep Bagchi, of the Inter-University Centre for Astronomy and Astrophysics in Pune, India, who led an international research team. The scientists reported their findings in the November 3 edition of the journal Science. The newly-discovered ring segments, some 6 million light-years across, surround a galaxy cluster called Abell 3376, more than 600 million light-years from Earth. They were revealed because fast-moving electrons emitted radio waves as they spiraled around magnetic field lines in intergalactic space. "Even from this large distance, the feeble radio waves were easily picked up by the VLA

  5. The Impact of Discovering Life beyond Earth

    Science.gov (United States)

    Dick, Steven J.

    2016-01-01

    Introduction: astrobiology and society Steven J. Dick; Part I. Motivations and Approaches. How Do We Frame the Problems of Discovery and Impact?: Introduction; 1. Current approaches to finding life beyond earth, and what happens if we do Seth Shostak; 2. The philosophy of astrobiology: the Copernican and Darwinian presuppositions Iris Fry; 3. History, discovery, analogy: three approaches to the impact of discovering life beyond earth Steven J. Dick; 4. Silent impact: why the discovery of extraterrestrial life should be silent Clément Vidal; Part II. Transcending Anthropocentrism. How Do We Move beyond our Own Preconceptions of Life, Intelligence and Culture?: Introduction; 5. The landscape of life Dirk Schulze-Makuch; 6. The landscape of intelligence Lori Marino; 7. Universal biology: assessing universality from a single example Carlos Mariscal; 8. Equating culture, civilization, and moral development in imagining extraterrestrial intelligence: anthropocentric assumptions? John Traphagan; 9. Communicating with the other: infinity, geometry, and universal math and science Douglas Vakoch; Part III. Philosophical, Theological, and Moral Impact. How Do We Comprehend the Cultural Challenges Raised by Discovery?: Introduction; 10. Life, intelligence and the pursuit of value in cosmic evolution Mark Lupisella; 11. 'Klaatu barada nikto' - or, do they really think like us? Michael Ruse; 12. Alien minds Susan Schneider; 13. The moral subject of astrobiology: guideposts for exploring our ethical and political responsibilities towards extraterrestrial life Elspeth Wilson and Carol Cleland; 14. Astrobiology and theology Robin Lovin; 15. Would you baptize an extraterrestrial? Guy Consolmagno, SJ; Part IV. Practical Considerations: How Should Society Prepare for Discovery - and Non-Discovery?: Introduction; 16. Is there anything new about astrobiology and society? Jane Maienschein; 17. Evaluating preparedness for the discovery of extraterrestrial life: considering potential

  6. Scientix in our school- discovering STEM

    Science.gov (United States)

    Melcu, Cornelia

    2017-04-01

    My name is Cornelia Melcu and I am a primary school teacher in Brasov. Additionally, I am a teacher trainer of Preparatory Class Curriculum, Google Application in Education Course and European Projects Course and a mentor to new teachers and students in university. I am an eTwinning, Scientix and ESERO ambassador too. During the last three school years my school was involved in several STEM projects, part of Scientix community. The main goal of those projects was to develop basic STEM skills of our students based on project work integrated into the curriculum. Open the Gates to the Universe (http://gatestotheuniverse.blogspot.ro; https://twinspace.etwinning.net/12520/home) is an eTwinning project for primary school students started on September 2015 and finished on September 2016. Some of our partners were from the Mediterranean area. The students discovered different aspects of space science and astronomy working on international groups. They explored some aspects of Science included in their curriculum using resources from ESERO, ROEDUSEIS and Space Awareness (e.g. Calculate with Rosetta, Writing the travel diary, Build Rosetta, How to become an astronaut, etc.) The project was a great opportunity to apply integrated learning methods for developing competencies which are a part of the primary school curriculum in Romania. In Language and Communication classes the students talked about their partners living places and their traditions and habits. They learnt some basic words in their partners language related to the weather. They created stories- both in Romanian and English; they described life in space and astronomical phenomena. They talked to the other partners during the several online meetings we organized and wrote short stories in English. In Mathematics and Science they found out about the Milky Way, the Solar System, the weather, famous astronauts and astronomers. They calculated, solved problems, made experiments and explained specific natural phenomena

  7. Astronomers Discover Six-Image Gravitational Lens

    Science.gov (United States)

    2001-08-01

    An international team of astronomers has used the National Science Foundation's Very Long Baseline Array (VLBA) radio telescope and NASA's Hubble Space Telescope (HST) to discover the first gravitational lens in which the single image of a very distant galaxy has been split into six different images. The unique configuration is produced by the gravitational effect of three galaxies along the line of sight between the more-distant galaxy and Earth. Optical and Radio Images of Gravitational Lens "This is the first gravitational lens with more than four images of the background object that is produced by a small group of galaxies rather than a large cluster of galaxies," said David Rusin, who just received his Ph.D. from the University of Pennsylvania. "Such systems are expected to be extremely rare, so this discovery is an important stepping stone. Because this is an intermediate case between gravitational lenses produced by single galaxies and lenses produced by large clusters of galaxies, it will give us insights we can't get from other types of lenses," Rusin added. The gravitational lens, called CLASS B1359+154, consists of a galaxy more than 11 billion light-years away in the constellation Bootes, with a trio of galaxies more than 7 billion light-years away along the same line of sight. The more-distant galaxy shows signs that it contains a massive black hole at its core and also has regions in which new stars are forming. The gravitational effect of the intervening galaxies has caused the light and radio waves from the single, more-distant galaxy to be "bent" to form six images as seen from Earth. Four of these images appear outside the triangle formed by the three intermediate galaxies and two appear inside that triangle. "This lens system is a very interesting case to study because it is more complicated than lenses produced by single galaxies, and yet simpler than lenses produced by clusters of numerous galaxies," said Chris Kochanek of the Harvard

  8. Discover the benefits of residential wood heating

    International Nuclear Information System (INIS)

    2003-01-01

    This publication described how residential wood-heating systems are being used to reduce energy costs and increase home comfort. Biomass energy refers to all forms are renewable energy that is derived from plant materials. The source of fuel may include sawmills, woodworking shops, forest operations and farms. The combustion of biomass is also considered to be carbon dioxide neutral, and is not considered to be a major producer of greenhouse gases (GHG) linked to global climate change. Wood burning does, however, release air pollutants, particularly if they are incompletely burned. Incomplete combustion of wood results in dense smoke consisting of toxic gases. Natural Resources Canada helped create new safety standards and the development of the Wood Energy Technical Training Program to ensure that all types of wood-burning appliances are installed correctly and safely to reduce the risk of fire and for effective wood heating. In Canada, more than 3 million families heat with wood as a primary or secondary heating source in homes and cottages. Wood heating offers security from energy price fluctuations and electrical power failures. This paper described the benefits of fireplace inserts that can transform old fireplaces into modern heating systems. It also demonstrated how an add-on wood furnace can be installed next to oil furnaces to convert an oil-only heating system to a wood-oil combination system, thereby saving thousands of dollars in heating costs. Wood pellet stoves are another wood burning option. The fuel for the stoves is produced from dried, finely ground wood waste that is compressed into hard pellets that are loaded into a hopper. The stove can run automatically for up to 24 hours. New high-efficiency advanced fireplaces also offer an alternative heating system that can reduce heating costs while preserving Canada's limited supply of fossil fuels such as oil and gas. 13 figs

  9. Most Powerful Eruption in the Universe Discovered

    Science.gov (United States)

    2005-01-01

    emission within the cavities shows that jets from the black hole erupted to create the cavities. Gas is being pushed away from the black hole at supersonic speeds over a distance of about a million light years. The mass of the displaced gas equals about a trillion Suns, more than the mass of all the stars in the Milky Way. LA Radio & Chandra X-ray Composite of MS 0735.6+7421 VLA Radio & Chandra X-ray Composite of MS 0735.6+7421 The rapid growth of supermassive black holes is usually detected by observing very bright radiation from the centers of galaxies in the optical and X-ray wavebands, or luminous radio jets. In MS 0735 no bright central radiation is found and the radio jets are faint. Therefore, the true nature of MS 0735 is only revealed through X-ray observations of the hot cluster gas. "Until now we had no idea that this black hole was gorging itself", said co-author Michael Wise of the Massachusetts Institute of Technology. "The discovery of this eruption shows that X-ray telescopes are necessary to understand some of the most violent events in the Universe." The astronomers estimated how much energy was needed to create the cavities by calculating the density, temperature and pressure of the hot gas. By making a standard assumption, that 10% of the gravitational energy goes into launching the jets, they estimated how much material the black hole swallowed. Size Comparison of MS 0735.6+7421 & Perseus Cluster Size Comparison of MS 0735.6+7421 & Perseus Cluster Besides generating the cavities, some of the energy from this eruption should keep the hot gas around the black hole from cooling, and some of it may also generate large-scale magnetic fields in the galaxy cluster. Chandra observers have discovered other cavities in galaxy clusters, but this one is easily the largest and the most powerful. For example, the energy content here exceeds that of the Perseus cavities by 250 times, and dwarfs the cavities in M87 by a factor of 10,000. NASA's Marshall Space Flight

  10. 14C fixation by leaves and leaf cell protoplasts of the submerged aquatic angiosperm Potamogeton lucens: Carbon dioxide or bicarbonate?

    International Nuclear Information System (INIS)

    Staal, M.; Elzenga, J.T.M.; Prins, H.B.A.

    1989-01-01

    Protoplasts were isolated from leaves of the aquatic angiosperm Potamogeton lucens L. The leaves utilize bicarbonate as a carbon source for photosynthesis, and show polarity; that is acidification of the periplasmic space of the lower, and alkalinization of the space near the upper leaf side. At present there are two models under consideration for this photosynthetic bicarbonate utilization process: conversion of bicarbonate into free carbon dioxide as a result of acidification and, second, a bicarbonate-proton symport across the plasma membrane. Carbon fixation of protoplasts was studied at different pH values and compared with that in leaf strips. Using the isotopic disequilibrium technique, it was established that carbon dioxide and not bicarbonate was the form in which DIC actually crossed the plasma membrane. It is concluded that there is probably no true bicarbonate transport system at the plasma membrane of these cells and that bicarbonate utilization in this species apparently rests on the conversion of bicarbonate into carbon dioxide. Experiments with acetazolamide, an inhibitor of periplasmic carbonic anhydrase, and direct measurements of carbonic anhydrase activity in intact leaves indicate that in this species the role of this enzyme for periplasmic conversion of bicarbonate into carbon dioxide is insignificant

  11. The potential of the ILC for discovering new particles

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Keisuke [High Energy Accelerator Research Organization (KEK), Ibaraki (Japan); Grojean, Christophe [DESY, Hamburg (Germany); Humboldt-Univ., Berlin (Germany). Inst. fuer Physik; ICREA, Barcelona (Spain); Peskin, Michael E. [Stanford Univ., Menlo Park, CA (United States). SLAC; Collaboration: LCC Physics Working Group; and others

    2017-02-15

    This paper addresses the question of whether the International Linear Collider has the capability of discovering new particles that have not already been discovered at the CERN Large Hadron Collider. We summarize the various paths to discovery offered by the ILC, and discuss them in the context of three different scenarios: 1. LHC does not discover any new particles, 2. LHC discovers some new low mass states and 3. LHC discovers new heavy particles. We will show that in each case, ILC plays a critical role in discovery of new phenomena and in pushing forward the frontiers of high-energy physics as well as our understanding of the universe in a manner which is highly complementary to that of LHC. For the busy reader, a two-page executive summary is provided at the beginning of the document.

  12. The potential of the ILC for discovering new particles

    International Nuclear Information System (INIS)

    Fujii, Keisuke; Grojean, Christophe; Peskin, Michael E.

    2017-02-01

    This paper addresses the question of whether the International Linear Collider has the capability of discovering new particles that have not already been discovered at the CERN Large Hadron Collider. We summarize the various paths to discovery offered by the ILC, and discuss them in the context of three different scenarios: 1. LHC does not discover any new particles, 2. LHC discovers some new low mass states and 3. LHC discovers new heavy particles. We will show that in each case, ILC plays a critical role in discovery of new phenomena and in pushing forward the frontiers of high-energy physics as well as our understanding of the universe in a manner which is highly complementary to that of LHC. For the busy reader, a two-page executive summary is provided at the beginning of the document.

  13. A new screening method for discovering antibacterial agents from ...

    African Journals Online (AJOL)

    A new screening method for discovering antibacterial agents from filamentous fungi. ... African Journal of Biotechnology ... Keywords: Drug-resistant bacterial pathogens, novel antibiotics; screening method, filamentous fungi products ...

  14. On a New Technique for Discovering Variable Stars

    Directory of Open Access Journals (Sweden)

    Mironov A. V.

    2003-12-01

    Full Text Available A technique for discovering variable stars based on the calculation of the correlation coefficients is proposed. Applications of the technique are shown on the results of numerical experiments and on the Hipparcos photometric data.

  15. Scientists discover how deadly fungal microbes enter host cells

    OpenAIRE

    Whyte, Barry James

    2010-01-01

    A research team led by scientists at the Virginia Bioinformatics Institute at Virginia Tech has discovered a fundamental entry mechanism that allows dangerous fungal microbes to infect plants and cause disease.

  16. Strontium-90 Error Discovered in Subcontract Laboratory Spreadsheet. Topical Report

    International Nuclear Information System (INIS)

    Brown, D.D.; Nagel, A.S.

    1999-07-01

    West Valley Demonstration Project health physicists and environment scientists discovered a series of errors in a subcontractor's spreadsheet being used to reduce data as part of their strontium-90 analytical process

  17. MICRO-STRUCTURAL INVESTIGATION OF SOME ARTIFACTS DISCOVERED AT POROLISSUM

    Directory of Open Access Journals (Sweden)

    MUNTEANU Mihai

    2014-09-01

    Full Text Available the paper presents the investigation of two fragments of roman bronze artefacts, discovered during archaeological works performed at Porolissum, an important military and economical point on the northern limes of Dacia Province. One of the analyzed fragments (Mi1 was taken from a consistent fragment of a Roman bronze statue, while the second (Mi2 was among a lot of small metal pieces, discovered in the same investigated area. Using highly sophisticated micro-structural analysing techniques – X-Ray diffraction, the paper investigates the possibility that the Mi2 fragment may have belonged to the same statue from which the sample Mi1 was taken

  18. The Magic of Mathematics Discovering the Spell of Mathematics

    CERN Document Server

    Pappas, Theoni

    2011-01-01

    Delves into the world of ideas, explores the spell mathematics casts on our lives, and helps you discover mathematics where you least expect it. Be spellbound by the mathematical designs found in nature. Learn how knots may untie the mysteries of life. Be mesmerized by the computer revolution. Discover how the hidden forces of mathematics hold architectural structures together connect your telephone calls help airplanes get off the ground solve the mysteries of the living cell. See how some artists use a mathematical palette in their works and how many writers draw upon the wealth of its ideas

  19. Preclinical evaluation of carbon-11 and fluorine-18 sulfonamide derivatives for in vivo radiolabeling of erythrocytes

    OpenAIRE

    Gheysens, Olivier; Akurathi, Vamsidhar; Chekol, Rufael; Dresselaers, Tom; Celen, Sofie; Koole, Michel; Dauwe, Dieter; Cleynhens, Bernard J; Claus, Piet; Janssens, Stefan; Verbruggen, Alfons M; Nuyts, Johan; Himmelreich, Uwe; Bormans, Guy M

    2013-01-01

    Background To date, few PET tracers for in vivo labeling of red blood cells (RBCs) are available. In this study, we report the radiosynthesis and in vitro and in vivo evaluation of 11C and 18F sulfonamide derivatives targeting carbonic anhydrase II (CA II), a metallo-enzyme expressed in RBCs, as potential blood pool tracers. A proof-of-concept in vivo imaging study was performed to demonstrate the feasibility to assess cardiac function and volumes using electrocardiogram (ECG)-gated positron ...

  20. Carbon used in electrotechnology

    International Nuclear Information System (INIS)

    Coulon, M.; Reynvaan, C.; Maire, J.

    1994-01-01

    The carbon is the essential or single component of several materials. After having recalled the general properties of carbon and graphite some traditional processes of fabrication are described and some new products are studied then we tackle the applications with electric current: -electrodes in the electric piles where we use the carbon chemical inertia -coals of electric arc where we use the refractory properties and the low resistivity of graphite -Joule effect where we work on an enough wide field of material resistivity -electric fixed or sliding contacts where in addition to the refractory properties it is its unweldability which makes it indispensable particularly in the brooms for electric motors. The future is good for carbon and its compounds particularly for the new discovered fullerenes, spheric molecules of carbon, the properties of which are bad known (supraconductivity, lubrication, energy storage). 21 refs., 26 figs., 14 tab

  1. Carbon dioxide capture using resin-wafer electrodeionization

    Science.gov (United States)

    Lin, YuPo J.; Snyder, Seth W.; Trachtenberg, Michael S.; Cowan, Robert M.; Datta, Saurav

    2015-09-08

    The present invention provides a resin-wafer electrodeionization (RW-EDI) apparatus including cathode and anode electrodes separated by a plurality of porous solid ion exchange resin wafers, which when in use are filled with an aqueous fluid. The apparatus includes one or more wafers comprising a basic ion exchange medium, and preferably includes one or more wafers comprising an acidic ion exchange medium. The wafers are separated from one another by ion exchange membranes. The fluid within the acidic and/or basic ion exchange wafers preferably includes, or is in contact with, a carbonic anhydrase (CA) enzyme to facilitate conversion of bicarbonate ion to carbon dioxide within the acidic medium. A pH suitable for exchange of CO.sub.2 is electrochemically maintained within the basic and acidic ion exchange wafers by applying an electric potential across the cathode and anode.

  2. Discover 4-H Clubs: The Essential Resource for 4-H

    Science.gov (United States)

    MacArthur, Stacey; Nelson, Cindy; Brower, Naomi; Memmott, Margie; Peterson, Gaelynn

    2016-01-01

    Obstacles facing new 4-H volunteers include time constraints and difficulty finding project-specific information, resources, and opportunities available for club members. As a solution to these obstacles and an aid for assisting volunteers in becoming confident in delivering information to youth, content experts produced Discover 4-H Clubs, a…

  3. US NSF: scientists discover planetary system similar to our own

    CERN Multimedia

    2003-01-01

    An international team of scientists has discovered a planet and star that may share the same relationship as Jupiter and our Sun, the closest comparison that researchers have found since they began their search for extra-solar planets nearly a decade ago (1 page).

  4. Scientists discover planetary system similar to our own

    CERN Multimedia

    2003-01-01

    'An international team of scientists has discovered a planet and star that may share the same relationship as Jupiter and our Sun, the closest comparison that researchers have found since they began their search for extra-solar planets nearly a decade ago' (1 page).

  5. Re-discovering indigenous knowledge – Ulwazi Lwemveli for ...

    African Journals Online (AJOL)

    Therefore, the imperative to re-discover and re-store IK cannot be underestimated since building on this knowledge is particularly effective in helping to reach those living in rural communities. This knowledge is often the main asset they control, and certainly one with which they are more familiar. The case studies discussed ...

  6. REVIEW: Discovering Statistics Using SPSS for Windows ANDY FIELD (2000)

    OpenAIRE

    SHARMA, Reviewed By Ashok

    2015-01-01

    The book "Discovering Statistics Using SPSS for Windows" is exactly that! Since it calculates amazingly fast, in the recent years, the computer has become the most useful and helpful tool for the researchers in almost every field of knowledge - be it open and distance education, psychology, sociology, management or else.

  7. The Spy VI child : A newly discovered Neandertal infant

    NARCIS (Netherlands)

    Crevecoeur, Isabelle; Bayle, Priscilla; Rougier, Helene; Maureille, Bruno; Higham, Thomas; van der Plicht, Johannes; De Clerck, Nora; Semal, Patrick

    2010-01-01

    Spy cave (Jemeppe-sur-Sambre Belgium) is reputed for the two adult Neandertal individuals discovered in situ in 1886 Recent reassessment of the Spy collections has allowed direct radiocarbon dating of these individuals The sorting of all of the faunal collections has also led to the discovery of the

  8. How to Discover the Rogers–Ramanujan Identities

    Indian Academy of Sciences (India)

    IAS Admin

    The purpose of this article is to introduce you to the. Rogers–Ramanujan identities, by discussing an approach to discover them. When you see that they appear from a very simple generalization of the simplest possible in- finite continued fraction, that in turn is related to the celebrated Fibonacci sequence, perhaps you may ...

  9. Metagenomic approach for discovering new pathogens in infection disease outbreaks

    Directory of Open Access Journals (Sweden)

    Emanuela Giombini

    2011-09-01

    Full Text Available Viruses represent the most abundant biological components on earth.They can be found in every environment, from deep layers of oceans to animal bodies.Although several viruses have been isolated and sequenced, in each environment there are millions of different types of viruses that have not been identified yet.The advent of nextgeneration sequencing technologies with their high throughput capabilities make possible to study in a single experiment all the community of microorganisms present in a particular sample “microbioma”.They made more feasible the application of the metagenomic approach, by which it is also possible to discover and identify new pathogens, that may pose a threat to public health.This paper summarizes the most recent applications of nextgeneration sequencing to discover new viral pathogens during the occurrence of infection disease outbreaks.

  10. Possible origin of Saturn's newly discovered outer ring

    International Nuclear Information System (INIS)

    Moehlmann, D.

    1986-01-01

    Within a planetogonic model the self-gravitationally caused formation of pre-planetary and pre-satellite rings from an earlier thin disk is reported. The theoretically derived orbital radii of these rings are compared with the orbital levels in the planetary system and the satellite systems of Jupiter, Saturn and Uranus. From this comparison it is concluded that at the radial position of Saturn's newly discovered outer ring an early pre-satellite ring of more or less evolved satellites could have existed. These satellites should have been disturbed in their evolution by the gravitation of the neighbouring massive satellite Titan. The comparison also may indicate similarities between the asteroidal belt and the newly discovered outer ring of Saturn

  11. Decision Tree Approach to Discovering Fraud in Leasing Agreements

    OpenAIRE

    Horvat Ivan; Pejić Bach Mirjana; Merkač Skok Marjana

    2014-01-01

    Background: Fraud attempts create large losses for financing subjects in modern economies. At the same time, leasing agreements have become more and more popular as a means of financing objects such as machinery and vehicles, but are more vulnerable to fraud attempts. Objectives: The goal of the paper is to estimate the usability of the data mining approach in discovering fraud in leasing agreements. Methods/Approach: Real-world data from one Croatian leasing firm was used for creating tow mo...

  12. Discovering and Promoting Commodity Health Attributes: Programs and Issues

    OpenAIRE

    Carman, Hoy F.

    2007-01-01

    There is a growing consumer segment demanding healthy foods and diets, health and nutrition messages can expand food demand, and governments in the U.S. and EU, faced with increasing obesity and associated health outcomes, want consumers to have reliable information to choose healthy diets. California commodity organizations, charged with expanding the demand for almonds, avocados, strawberries and walnuts, are funding health and nutrition research as a means to discover a unique selling prop...

  13. Discovering the quantum universe the role of particle colliders

    CERN Document Server

    2006-01-01

    What does "Quantum Universe" mean? To discover what the universe is made of and how it works is the challenge of particle physics. "Quantum Universe" defines the quest to explain the universe in terms of quantum physics, which governs the behavior of the microscopic, subatomic world. It describes a revolution in particle physics and a quantum leap in our understanding of the mystery and beauty of the universe.

  14. Discovering Social Circles in Ego Networks (Author’s Manuscript)

    Science.gov (United States)

    2013-01-10

    refer to as social cir- cles. Practically all major social networks provide such functionality, for example, ‘circles’ on Google+, and ‘lists’ on Facebook ...Discovering Social Circles in Ego Networks Julian McAuley and Jure Leskovec Stanford jmcauley@cs.stanford.edu, jure@cs.stanford.edu January 11, 2013...Abstract People’s personal social networks are big and cluttered, and currently there is no good way to automatically organize them. Social networking

  15. A systematic framework to discover pattern for web spam classification

    OpenAIRE

    Jelodar, Hamed; Wang, Yongli; Yuan, Chi; Jiang, Xiaohui

    2017-01-01

    Web spam is a big problem for search engine users in World Wide Web. They use deceptive techniques to achieve high rankings. Although many researchers have presented the different approach for classification and web spam detection still it is an open issue in computer science. Analyzing and evaluating these websites can be an effective step for discovering and categorizing the features of these websites. There are several methods and algorithms for detecting those websites, such as decision t...

  16. Discovering Authentication Credentials in Volatile Memory of Android Mobile Devices

    OpenAIRE

    Apostolopoulos , Dimitris; Marinakis , Giannis; Ntantogian , Christoforos; Xenakis , Christos

    2013-01-01

    Part 5: Adoption Issues in e/m-Services; International audience; This paper investigates whether authentication credentials in the volatile memory of Android mobile devices can be discovered using freely available tools. The experiments that we carried out for each application included two different sets: In the first set, our goal was to check if we could recover our own submitted credentials from the memory dump of the mobile device. In the second set of experiments, the goal was to find pa...

  17. Does Aerobic Respiration Produce Carbon Dioxide or Hydrogen Ion and Bicarbonate?

    Science.gov (United States)

    Swenson, Erik R

    2018-05-01

    Maintenance of intracellular pH is critical for clinical homeostasis. The metabolism of glucose, fatty acids, and amino acids yielding the generation of adenosine triphosphate in the mitochondria is accompanied by the production of acid in the Krebs cycle. Both the nature of this acidosis and the mechanism of its disposal have been argued by two investigators with a long-abiding interest in acid-base physiology. They offer different interpretations and views of the molecular mechanism of this intracellular pH regulation during normal metabolism. Dr. John Severinghaus has posited that hydrogen ion and bicarbonate are the direct end products in the Krebs cycle. In the late 1960s, he showed in brain and brain homogenate experiments that acetazolamide, a carbonic anhydrase inhibitor, reduces intracellular pH. This led him to conclude that hydrogen ion and bicarbonate are the end products, and the role of intracellular carbonic anhydrase is to rapidly generate diffusible carbon dioxide to minimize acidosis. Dr. Erik Swenson posits that carbon dioxide is a direct end product in the Krebs cycle, a more widely accepted view, and that acetazolamide prevents rapid intracellular bicarbonate formation, which can then codiffuse with carbon dioxide to the cell surface and there be reconverted for exit from the cell. Loss of this "facilitated diffusion of carbon dioxide" leads to intracellular acidosis as the still appreciable uncatalyzed rate of carbon dioxide hydration generates more protons. This review summarizes the available evidence and determines that resolution of this question will require more sophisticated measurements of intracellular pH with faster temporal resolution.

  18. Interaction of multiwalled carbon nanotube produces structural ...

    African Journals Online (AJOL)

    Abstract. Multiwalled carbon nanotube (MWCNT) has been found to produce structural changes in Calf Thymus-DNA (CT-DNA). The interaction or binding of the multi-walled carbon nanotubes (MWCNT) was investigated in order to discover if it brings about any significant changes of the DNA double helix using CD spectra ...

  19. Sorbents based on carbonized rice peel

    International Nuclear Information System (INIS)

    Mansurova, R. M.; Taipova, R. A.; Zhylybaeva, N. K.; Mansurov, Z. A.; Bijsenbaev, M. A.

    2004-01-01

    The process receiving of sorbents based on carbonized rice peel (RP) was received and their sorption properties were investigated. Processing carbonization of samples leading on station, this was developed in laboratory of hybrid technology. Carbonization of samples was realized in nitric atmosphere on 400-8000 deg. C. On raising temperature of carbonization content of carbon in samples is rice, hydrogen and oxygen is reduce as a result isolation of volatility products is discover. The samples carbonized on 650 deg. C (910 m 2 /g) owners with maximum removed surface is discover. On carbonization temperature 600-800 deh. C the sorption of ions, which carbonized by sorbents based on rice peel is run to 95-100 %. Electron-microscopic investigation of samples leaded on EM-125 mechanism by accelerating pressure 100 kV. From electron-microscopic print of original samples of RP it is evident, that sample consists of carbonic fractions of different species: carbonic fiber of rounded fractions, fractions of ellipsoid form and of more thickly carbonic structure. Increasing sizes of pores and modification structure of synthesized sorbent is occur during carbonization process. The RP-samples, which carbonized by 650 deg. C has the higher specific surface. Samples consist of thin carbonic scum and reducing specific surface, by higher temperature

  20. Biological conversion of carbon dioxide and hydrogen into liquid fuels and industrial chemicals.

    Science.gov (United States)

    Hawkins, Aaron S; McTernan, Patrick M; Lian, Hong; Kelly, Robert M; Adams, Michael W W

    2013-06-01

    Non-photosynthetic routes for biological fixation of carbon dioxide into valuable industrial chemical precursors and fuels are moving from concept to reality. The development of 'electrofuel'-producing microorganisms leverages techniques in synthetic biology, genetic and metabolic engineering, as well as systems-level multi-omic analysis, directed evolution, and in silico modeling. Electrofuel processes are being developed for a range of microorganisms and energy sources (e.g. hydrogen, formate, electricity) to produce a variety of target molecules (e.g. alcohols, terpenes, alkenes). This review examines the current landscape of electrofuel projects with a focus on hydrogen-utilizing organisms covering the biochemistry of hydrogenases and carbonic anhydrases, kinetic and energetic analyses of the known carbon fixation pathways, and the state of genetic systems for current and prospective electrofuel-producing microorganisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. High pH microbial ecosystems in a newly discovered, ephemeral, serpentinizing fluid seep at Yanartaş (Chimera), Turkey.

    Science.gov (United States)

    Meyer-Dombard, D'Arcy R; Woycheese, Kristin M; Yargıçoğlu, Erin N; Cardace, Dawn; Shock, Everett L; Güleçal-Pektas, Yasemin; Temel, Mustafa

    2014-01-01

    Gas seeps emanating from Yanartaş (Chimera), Turkey, have been documented for thousands of years. Active serpentinization produces hydrogen and a range of carbon gases that may provide fuel for life. Here we report a newly discovered, ephemeral fluid seep emanating from a small gas vent at Yanartaş. Fluids and biofilms were sampled at the source and points downstream. We describe site conditions, and provide microbiological data in the form of enrichment cultures, Scanning electron microscopy (SEM), carbon and nitrogen isotopic composition of solids, and PCR screens of nitrogen cycle genes. Source fluids are pH 11.95, with a Ca:Mg of ~200, and sediments under the ignited gas seep measure 60°C. Collectively, these data suggest the fluid is the product of active serpentinization at depth. Source sediments are primarily calcite and alteration products (chlorite and montmorillonite). Downstream, biofilms are mixed with montmorillonite. SEM shows biofilms distributed homogeneously with carbonates. Organic carbon accounts for 60% of the total carbon at the source, decreasing downstream to <15% as inorganic carbon precipitates. δ(13)C ratios of the organic carbon fraction of solids are depleted (-25 to -28‰) relative to the carbonates (-11 to -20‰). We conclude that heterotrophic processes are dominant throughout the surface ecosystem, and carbon fixation may be key down channel. δ(15)N ratios ~3‰, and absence of nifH in extracted DNA suggest that nitrogen fixation is not occurring in sediments. However, the presence of narG and nirS at most locations and in enrichments indicates genomic potential for nitrate and nitrite reduction. This small seep with shallow run-off is likely ephemeral, but abundant preserved microterracettes in the outflow and the surrounding area suggest it has been present for some time. This site and others like it present an opportunity for investigations of preserved deep biosphere signatures, and subsurface-surface interactions.

  2. High pH microbial ecosystems in a newly discovered, ephemeral, serpentinizing fluid seep at Yanartaş (Chimaera, Turkey

    Directory of Open Access Journals (Sweden)

    D'Arcy Renee Meyer-Dombard

    2015-01-01

    Full Text Available Gas seeps emanating from ophiolites at Yanartaş (Chimaera, Turkey, have been documented for thousands of years. Active serpentinization produces hydrogen and a range of carbon gases that may provide fuel for life. Here we report a newly discovered, ephemeral fluid seep emanating from a small gas vent at Yanartaş. Fluids and biofilms were sampled at the source and points downstream. We describe site conditions, and provide microbiological data in the form of enrichment cultures, scanning electron microscopy (SEM, carbon and nitrogen isotopic composition of solids, and PCR screens of nitrogen cycle genes. Source fluids are pH 11.95, with a Ca:Mg of ~200, and sediments under the ignited gas seep measure 60°C. Collectively, these data suggest the fluid is the product of active serpentinization at depth. Source sediments are primarily calcite and alteration products (chlorite and montmorillonite. Downstream, biofilms are mixed with montmorillonite. SEM shows biofilms distributed homogeneously with carbonates. Organic carbon accounts for 60% of the total carbon at the source, decreasing downstream to <15% as inorganic carbon precipitates. δ13C ratios of the organic carbon fraction of solids are depleted (−25 to −28 ‰ relative to the carbonates (−11 to −20‰. We conclude that heterotrophic processes are dominant throughout the surface ecosystem, and carbon fixation may be key down channel. δ15N ratios ~ 3‰, and absence of nifH in extracted DNA suggest that nitrogen fixation is not occurring in sediments. However, the presence of narG and nirS at most locations and in enrichments indicates genomic potential for nitrate and nitrite reduction. This small seep with shallow run-off is likely ephemeral, but abundant preserved microterracettes in the outflow and the surrounding area suggest it has been present for some time. This site and others like it present an opportunity for investigations of preserved deep biosphere signatures, and

  3. Tools and strategies for discovering novel enzymes and metabolic pathways

    Directory of Open Access Journals (Sweden)

    John A. Gerlt

    2016-12-01

    Full Text Available The number of entries in the sequence databases continues to increase exponentially – the UniProt database is increasing with a doubling time of ∼4 years (2% increase/month. Approximately 50% of the entries have uncertain, unknown, or incorrect function annotations because these are made by automated methods based on sequence homology. If the potential in complete genome sequences is to be realized, strategies and tools must be developed to facilitate experimental assignment of functions to uncharacterized proteins discovered in genome projects. The Enzyme Function Initiative (EFI; previously supported by U54GM093342 from the National Institutes of Health, now supported by P01GM118303 developed web tools for visualizing and analyzing (1 sequence and function space in protein families (EFI-EST and (2 genome neighbourhoods in microbial and fungal genomes (EFI-GNT to assist the design of experimental strategies for discovering the in vitro activities and in vivo metabolic functions of uncharacterized enzymes. The EFI developed an experimental platform for large-scale production of the solute binding proteins (SBPs for ABC, TRAP, and TCT transport systems and their screening with a physical ligand library to identify the identities of the ligands for these transport systems. Because the genes that encode transport systems are often co-located with the genes that encode the catabolic pathways for the transported solutes, the identity of the SBP ligand together with the EFI-EST and EFI-GNT web tools can be used to discover new enzyme functions and new metabolic pathways. This approach is demonstrated with the characterization of a novel pathway for ethanolamine catabolism.

  4. NLRC5: a newly discovered MHC class I transactivator (CITA)

    OpenAIRE

    Meissner, Torsten B.; Li, Amy; Kobayashi, Koichi S.

    2011-01-01

    Major histocompatibility complex (MHC) class I and class II are crucial for the function of the human adaptive immune system. An NLR protein, CIITA (MHC class II transactivator), is a master regulator of MHC class II gene expression as well as of some of the genes involved in MHC class II antigen presentation. It has recently been discovered that another member of the NLR protein family, NLRC5, transcriptionally activates MHC class I genes, and thus acts as “CITA” (MHC class I transactivator)...

  5. Knots and surfaces a guide to discovering mathematics

    CERN Document Server

    Farmer, David W

    1995-01-01

    In most mathematics textbooks, the most exciting part of mathematics-the process of invention and discovery-is completely hidden from the reader. The aim of Knots and Surfaces is to change all that. By means of a series of carefully selected tasks, this book leads readers to discover some real mathematics. There are no formulas to memorize; no procedures to follow. The book is a guide: its job is to start you in the right direction and to bring you back if you stray too far. Discovery is left to you. Suitable for a one-semester course at the beginning undergraduate level, there are no prerequi

  6. Growing Self-Estemm and Discovering Intelligences through Oral Production

    Directory of Open Access Journals (Sweden)

    Ochoa Dora Liliana

    2002-08-01

    Full Text Available After having applied a needs analysis in an eleventh grade course of English, I could notice that there was a big lack of security and self-confidence in the students. They expressed in different data-gathering instruments their fear when speaking in front of the class. Also, they talked about their insecurity when pronouncing English and the need for more opportunities for developing speaking. Therefore, the implementation of an innovation in class was carried out in order to respond to the students¿ needs and make them discover their talents. The implementation was successful and students improved some areas of their communicative competence.

  7. An approach for discovering keywords from Spanish tweets using Wikipedia

    Directory of Open Access Journals (Sweden)

    Daniel AYALA

    2016-05-01

    Full Text Available Most approaches to keywords discovery when analyzing microblogging messages (among them those from Twitter are based on statistical and lexical information about the words that compose the text. The lack of context in the short messages can be problematic due to the low co-occurrence of words. In this paper, we present a new approach for keywords discovering from Spanish tweets based on the addition of context information using Wikipedia as a knowledge base. We present four different ways to use Wikipedia and two ways to rank the new keywords. We have tested these strategies using more than 60000 Spanish tweets, measuring performance and analyzing particularities of each strategy.

  8. Discovering Communicable Scientific Knowledge from Spatio-Temporal Data

    Science.gov (United States)

    Schwabacher, Mark; Langley, Pat; Norvig, Peter (Technical Monitor)

    2001-01-01

    This paper describes how we used regression rules to improve upon a result previously published in the Earth science literature. In such a scientific application of machine learning, it is crucially important for the learned models to be understandable and communicable. We recount how we selected a learning algorithm to maximize communicability, and then describe two visualization techniques that we developed to aid in understanding the model by exploiting the spatial nature of the data. We also report how evaluating the learned models across time let us discover an error in the data.

  9. Very Bright CV discovered by MASTER-ICATE (Argentina)

    Science.gov (United States)

    Saffe, C.; Levato, H.; Mallamaci, C.; Lopez, C.; Lipunov, F. Podest V.; Denisenko, D.; Gorbovskoy, E.; Tiurina, N.; Balanutsa, P.; Kornilov, V.; Belinski, A.; Shatskiy, N.; Chazov, V.; Kuznetsov, A.; Yecheistov, V.; Yurkov, V.; Sergienko, Y.; Varda, D.; Sinyakov, E.; Gabovich, A.; Ivanov, K.; Yazev, S.; Budnev, N.; Konstantinov, E.; Chuvalaev, O.; Poleshchuk, V.; Gress, O.; Frolova, A.; Krushinsky, V.; Zalozhnih, I.; Popov, A.; Bourdanov, A.; Parkhomenko, A.; Tlatov, A.; Dormidontov, D.; Senik, V.; Podvorotny, P.; Shumkov, V.; Shurpakov, S.

    2013-06-01

    MASTER-ICATE very wide-field camera (d=72mm f/1.2 lens + 11 Mpix CCD) located near San Juan, Argentina has discovered OT source at (RA, Dec) = 14h 20m 23.5s -48d 55m 40s on the combined image (exposure 275 sec) taken on 2013-06-08.048 UT. The OT unfiltered magnitude is 12.1m (limit 13.1m). There is no minor planet at this place. The OT is seen in more than 10 images starting from 2013-06-02.967 UT (275 sec exposure) when it was first detected at 12.4m.

  10. Micromotor-Based Biomimetic Carbon Dioxide Sequestration: Towards Mobile Microscrubbers.

    Science.gov (United States)

    Uygun, Murat; Singh, Virendra V; Kaufmann, Kevin; Uygun, Deniz A; de Oliveira, Severina D S; Wang, Joseph

    2015-10-26

    We describe a mobile CO2 scrubbing platform that offers a greatly accelerated biomimetic sequestration based on a self-propelled carbonic anhydrase (CA) functionalized micromotor. The CO2 hydration capability of CA is coupled with the rapid movement of catalytic micromotors, and along with the corresponding fluid dynamics, results in a highly efficient mobile CO2 scrubbing microsystem. The continuous movement of CA and enhanced mass transport of the CO2 substrate lead to significant improvements in the sequestration efficiency and speed over stationary immobilized or free CA platforms. This system is a promising approach to rapid and enhanced CO2 sequestration platforms for addressing growing concerns over the buildup of greenhouse gas. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Discovering the cosmos with small spacecraft the American explorer program

    CERN Document Server

    Harvey, Brian

    2018-01-01

    Explorer was the original American space program and Explorer 1 its first satellite, launched in 1958. Sixty years later, it is the longest continuously running space program in the world, demonstrating to the world how we can explore the cosmos with small spacecraft. Almost a hundred Explorers have already been launched.  Explorers have made some of the fundamental discoveries of the Space Age.Explorer 1 discovered Earth’s radiation belts. Later Explorers surveyed the Sun, the X-ray and ultraviolet universes, black holes, magnetars and gamma ray bursts. An Explorer found the remnant of the Big Bang. One Explorer chased and was the first to intercept a comet. The program went through a period of few launches during the crisis of funding for space science in the 1980s. However, with the era of ‘faster, cheaper, better,’ the program was reinvented, and new exiting missions began to take shape, like Swift and the asteroid hunter WISE.  Discovering the Cosmos with Small Spacecraft gives an account of ...

  12. Discovering objects in a blood recipient information system.

    Science.gov (United States)

    Qiu, D; Junghans, G; Marquardt, K; Kroll, H; Mueller-Eckhardt, C; Dudeck, J

    1995-01-01

    Application of object-oriented (OO) methodologies has been generally considered as a solution to the problem of improving the software development process and managing the so-called software crisis. Among them, object-oriented analysis (OOA) is the most essential and is a vital prerequisite for the successful use of other OO methodologies. Though there are already a good deal of OOA methods published, the most important aspect common to all these methods: discovering objects classes truly relevant to the given problem domain, has remained a subject to be intensively researched. In this paper, using the successful development of a blood recipient information system as an example, we present our approach which is based on the conceptual framework of responsibility-driven OOA. In the discussion, we also suggest that it may be inadequate to simply attribute the software crisis to the waterfall model of the software development life-cycle. We are convinced that the real causes for the failure of some software and information systems should be sought in the methodologies used in some crucial phases of the software development process. Furthermore, a software system can also fail if object classes essential to the problem domain are not discovered, implemented and visualized, so that the real-world situation cannot be faithfully traced by it.

  13. Learning Faster by Discovering and Exploiting Object Similarities

    Directory of Open Access Journals (Sweden)

    Tadej Janež

    2013-03-01

    Full Text Available In this paper we explore the question: “Is it possible to speed up the learning process of an autonomous agent by performing experiments in a more complex environment (i.e., an environment with a greater number of different objects?” To this end, we use a simple robotic domain, where the robot has to learn a qualitative model predicting the change in the robot's distance to an object. To quantify the environment's complexity, we defined cardinal complexity as the number of objects in the robot's world, and behavioural complexity as the number of objects' distinct behaviours. We propose Error reduction merging (ERM, a new learning method that automatically discovers similarities in the structure of the agent's environment. ERM identifies different types of objects solely from the data measured and merges the observations of objects that behave in the same or similar way in order to speed up the agent's learning. We performed a series of experiments in worlds of increasing complexity. The results in our simple domain indicate that ERM was capable of discovering structural similarities in the data which indeed made the learning faster, clearly superior to conventional learning. This observed trend occurred with various machine learning algorithms used inside the ERM method.

  14. Screening individual hybridomas by microengraving to discover monoclonal antibodies

    Science.gov (United States)

    Ogunniyi, Adebola O; Story, Craig M; Papa, Eliseo; Guillen, Eduardo; Love, J Christopher

    2014-01-01

    The demand for monoclonal antibodies (mAbs) in biomedical research is significant, but the current methodologies used to discover them are both lengthy and costly. Consequently, the diversity of antibodies available for any particular antigen remains limited. Microengraving is a soft lithographic technique that provides a rapid and efficient alternative for discovering new mAbs. This protocol describes how to use microengraving to screen mouse hybridomas to establish new cell lines producing unique mAbs. Single cells from a polyclonal population are isolated into an array of microscale wells (~105 cells per screen). The array is then used to print a protein microarray, where each element contains the antibodies captured from individual wells. The antibodies on the microarray are screened with antigens of interest, and mapped to the corresponding cells, which are then recovered from their microwells by micromanipulation. Screening and retrieval require approximately 1–3 d (9–12 d including the steps for preparing arrays of microwells). PMID:19528952

  15. Thymolipoma combined with hyperthyroidism discovered by neurological symptoms.

    Science.gov (United States)

    Takahashi, Hidenobu; Harada, Masahiko; Kimura, Masakazu; Kato, Harubumi

    2007-04-01

    Thymolipomas are rare slow-growing mediastinal thymic neoplasms. Most cases are asymptomatic and are sometimes discovered as a huge mass on chest x-ray films. A few cases have been discovered during examinations for other diseases. We report the second case of thymolipoma combined with hyperthyroidism in the English language literature. Neurological symptoms suddenly appeared in a 45-year-old woman. Central nervous system disorder was suggested but no significant abnormalities were found on brain MR nor were there any neurological signs. Several months later, neurological and systemic examinations on admission revealed hyperthyroidism and an anterior mediastinal tumor, 9.0x5.0x3.0 cm in size on chest CT films. Despite treatment of hyperthyroidism by medication, her neurological symptoms remained. Neurologists recommended resection of the mediastinal tumor. Malignancy could not be ruled out because of the irregularity of the tumor appearance on contrast-enhanced chest CT. Furthermore, the tumor appeared to be attached to the ascending aorta, so cytological and/or pathological diagnosis by CT-guided needle biopsy before operation were contraindicated. Extended thymectomy was performed in May 2005. The pathological diagnosis was benign thymolipoma consisting of mature fatty tissue and thymic tissue structures with Hassall's corpuscles. Her neurological symptoms seemed slightly but not markedly improved. The relationship between thymolipoma and hyperthyroidism is still unknown.

  16. Generating Electricity from Water through Carbon Nanomaterials.

    Science.gov (United States)

    Xu, Yifan; Chen, Peining; Peng, Huisheng

    2018-01-09

    Over the past ten years, electricity generation from water in carbon-based materials has aroused increasing interest. Water-induced mechanical-to-electrical conversion has been discovered in carbon nanomaterials, including carbon nanotubes and graphene, through the interaction with flowing water as well as moisture. In this Concept article, we focus on the basic principles of electric energy harvesting from flowing water through carbon nanomaterials, and summarize the material modification and structural design of these nanogenerators. The current challenges and potential applications of power conversion with carbon nanomaterials are finally highlighted. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Discovery of carbon nanotubes. Sara ni carbon nanotube e

    Energy Technology Data Exchange (ETDEWEB)

    Iijima, S

    1994-01-20

    This paper describes the following matters on carbon nanotubes (CNt): CNt is discovered in carbon deposits generated in the tip of a negative electrode during DC arc discharge between carbon electrodes. CNt has a construction in which cylinders made of normally several layers are superposed, based on cylindrical crystals in a single layer with six-member rings of carbon atoms laid out. Spiral arrangement of carbon six-member rings has been discovered in the single-layered crystals. Five-member rings exist in a location where the CNt tip is closed, and seven-member rings in a location where the CNt presents a saddle-like curve, without exceptions. It is introduced theoretically that the electronic structure of the single-layered CNt depends on the cylinder diameter and spiral pitch. Replacing part of the carbon negative electrode with iron, and vaporizing iron and carbon simultaneously through arc discharge can result in a single-layered CNt with a diameter of 1 nm. Heating the CNt deposited with metallic lead in an oxygen atmosphere can form CNt containing lead compounds. 19 refs., 9 figs.

  18. Simultaneously Discovering and Localizing Common Objects in Wild Images.

    Science.gov (United States)

    Wang, Zhenzhen; Yuan, Junsong

    2018-09-01

    Motivated by the recent success of supervised and weakly supervised common object discovery, in this paper, we move forward one step further to tackle common object discovery in a fully unsupervised way. Generally, object co-localization aims at simultaneously localizing objects of the same class across a group of images. Traditional object localization/detection usually trains specific object detectors which require bounding box annotations of object instances, or at least image-level labels to indicate the presence/absence of objects in an image. Given a collection of images without any annotations, our proposed fully unsupervised method is to simultaneously discover images that contain common objects and also localize common objects in corresponding images. Without requiring to know the total number of common objects, we formulate this unsupervised object discovery as a sub-graph mining problem from a weighted graph of object proposals, where nodes correspond to object proposals, and edges represent the similarities between neighbouring proposals. The positive images and common objects are jointly discovered by finding sub-graphs of strongly connected nodes, with each sub-graph capturing one object pattern. The optimization problem can be efficiently solved by our proposed maximal-flow-based algorithm. Instead of assuming that each image contains only one common object, our proposed solution can better address wild images where each image may contain multiple common objects or even no common object. Moreover, our proposed method can be easily tailored to the task of image retrieval in which the nodes correspond to the similarity between query and reference images. Extensive experiments on PASCAL VOC 2007 and Object Discovery data sets demonstrate that even without any supervision, our approach can discover/localize common objects of various classes in the presence of scale, view point, appearance variation, and partial occlusions. We also conduct broad

  19. A new hard X-ray transient discovered by INTEGRAL

    DEFF Research Database (Denmark)

    Gibaud, L.; Bazzano, A.; Bozzo, E.

    2011-01-01

    INTEGRAL discovered a new hard X-ray transient, IGR J17498-2921, during the observations performed from 2011-08-11 22:45 to 2011-08-12 05:54 UTC. The source is detected in the IBIS/ISGRI mosaic at a preliminary significance level of 11 and 9 sigma in the 20-40 keV and 40-80 keV energy bands......, respectively. The corresponding fluxes are 19+/-2 and 23+/-3 mCrab (68% c.l., only statistical). The best determined source position is at RA=17:49:49; DEC=-29:21:14 (J2000) with a 90% confinement radius of 2.3 arcmin. The IBIS/ISGRI spectrum (exposure time 15.9 ks) can be well described by a a power...

  20. Discovering Mira Ceti: Celestial Change and Cosmic Continuity

    Science.gov (United States)

    Hatch, Robert Alan

    In the short narrative that follows I introduce two new heroes. Although we begin with Fabricius's first sighting in 1596, the new pivot point in the drama is the collaboration between Hevelius and Boulliau that began around 1660. As it happens, Learned Europe paid little attention to Mira in the generation after the first scattered sightings of 1596, indeed, nearly 70 years passed before the New Star was given a working identity. Like Columbus discovering America, Fabricius and Holwarda saw different things - for convenience, I call them Fabricius's Star and Holwarda's Star. Hevelius's Historiola (Danzig, 1662) and Boulliau's Ad astronomos (Paris, 1667) presented a different vision. It made Mira famous. As I shall argue, if Hevelius gave Mira a history, Boulliau gave Mira a future.5 In the end, the New Star not only challenged the ancient cosmos, it became an enduring icon for the New Science, a returning reminder of celestial continuity and cosmic order.

  1. SOLAR SYSTEM ANALOGS AROUND IRAS-DISCOVERED DEBRIS DISKS

    International Nuclear Information System (INIS)

    Chen, Christine H.; Sheehan, Patrick; Watson, Dan M.; Manoj, P.; Najita, Joan R.

    2009-01-01

    We have rereduced Spitzer IRS spectra and reanalyzed the spectral energy distributions (SEDs) of three nearby debris disks: λ Boo, HD 139664, and HR 8799. We find that the thermal emission from these objects is well modeled using two single temperature black body components. For HR 8799 - with no silicate emission features despite a relatively hot inner dust component (T gr = 150 K) - we infer the presence of an asteroid belt interior to and a Kuiper Belt exterior to the recently discovered orbiting planets. For HD 139664, which has been imaged in scattered light, we infer the presence of strongly forward scattering grains, consistent with porous grains, if the cold, outer disk component generates both the observed scattered light and thermal emission. Finally, careful analysis of the λ Boo SED suggests that this system possesses a central clearing, indicating that selective accretion of solids onto the central star does not occur from a dusty disk.

  2. Discovering Related Clinical Concepts Using Large Amounts of Clinical Notes.

    Science.gov (United States)

    Ganesan, Kavita; Lloyd, Shane; Sarkar, Vikren

    2016-01-01

    The ability to find highly related clinical concepts is essential for many applications such as for hypothesis generation, query expansion for medical literature search, search results filtering, ICD-10 code filtering and many other applications. While manually constructed medical terminologies such as SNOMED CT can surface certain related concepts, these terminologies are inadequate as they depend on expertise of several subject matter experts making the terminology curation process open to geographic and language bias. In addition, these terminologies also provide no quantifiable evidence on how related the concepts are. In this work, we explore an unsupervised graphical approach to mine related concepts by leveraging the volume within large amounts of clinical notes. Our evaluation shows that we are able to use a data driven approach to discovering highly related concepts for various search terms including medications, symptoms and diseases.

  3. Discovering Related Clinical Concepts Using Large Amounts of Clinical Notes

    Directory of Open Access Journals (Sweden)

    Kavita Ganesan

    2016-01-01

    Full Text Available The ability to find highly related clinical concepts is essential for many applications such as for hypothesis generation, query expansion for medical literature search, search results filtering, ICD-10 code filtering and many other applications. While manually constructed medical terminologies such as SNOMED CT can surface certain related concepts, these terminologies are inadequate as they depend on expertise of several subject matter experts making the terminology curation process open to geographic and language bias. In addition, these terminologies also provide no quantifiable evidence on how related the concepts are. In this work, we explore an unsupervised graphical approach to mine related concepts by leveraging the volume within large amounts of clinical notes. Our evaluation shows that we are able to use a data driven approach to discovering highly related concepts for various search terms including medications, symptoms and diseases.

  4. Occult carcinoma discovered after simple hysterectomy treated with postoperative radiotherapy

    International Nuclear Information System (INIS)

    Crane, Christopher H.; Schneider, Bernard F.

    1999-01-01

    Purpose: Treatment of patients with occult carcinoma of the cervix discovered after simple hysterectomy is controversial. The purpose of this review is to examine our results with postoperative radiotherapy and to compare them to similar reports and to reports of treatment with radical parametrectomy. Methods and Materials: Between November 1979 and April:, 18 patients were treated with radiotherapy at the University of Virginia for invasive carcinoma of the cervix discovered after simple hysterectomy. Simple hysterectomy was performed in all 18 patients for a variety of indications. After surgery gross residual carcinoma remained in four patients; and microscopic disease was present at the surgical margins in two patients. The remaining patients had no evidence of residual disease. All 18 patients had postoperative radiotherapy with or without brachytherapy. The endpoints for this study were local control, survival, and treatment-related toxicity. Actuarial rates were calculated using the Life method. Results: Median follow-up for all 18 patients was 42 months (range 2-202 months). Both the 5 and the 10-year actuarial local control rates were 88%. Five and 10-year actuarial overall survival rates were both 93%. Two patients had both local and distant cancer recurrences. There were no recurrences among the six patients treated with external beam alone. The remaining patients are all alive without evidence of disease, including two patients who had gross residual disease after surgery, and one patient with both microscopic positive margin and a positive lymph node (the only patient to undergo lymph node sampling). There was no severe acute morbidity and only one patient had severe late morbidity. Conclusions: Invasive carcinoma found after simple hysterectomy may be treated safely and effectively with postoperative radiotherapy. Patients with known residual disease following surgery do poorly with either radiotherapy or reoperation, but treatment with radiotherapy

  5. Risk of appendicitis in patients with incidentally discovered appendicoliths.

    Science.gov (United States)

    Khan, Muhammad Sohaib; Chaudhry, Mustafa Belal Hafeez; Shahzad, Noman; Tariq, Marvi; Memon, Wasim Ahmed; Alvi, Abdul Rehman

    2018-01-01

    An appendicolith-related appendiceal obstruction leading to appendicitis is a commonly encountered surgical emergency that has clear evidence-based management plans. However, there is no consensus on management of asymptomatic patients when appendicoliths are found incidentally. The objective of this study was to determine the risk of appendicitis in patients with an incidental finding of the appendicolith. A retrospective matched cohort study of patients with appendicolith discovered incidentally on computed tomographic scan from January 2008 to December 2014 at our institution was completed. The size and position of the appendicolith were ascertained. The study group was matched by age and gender to a control group. Both groups were contacted and interviewed regarding development of appendicitis. In total, 111 patients with appendicolith were successfully contacted and included in the study. Mean age was found to be 38 ± 15 y with 36 (32%) of the study population being females. Mean length of appendix was 66 ± 16 mm, and mean width was 5.8 ± 0.9 mm. Mean size of the appendicolith was 3.6 ± 1.1 mm (1.4-7.8 mm). Fifty-eight percent of appendicoliths was located at the proximal end or whole of appendix, 31% at mid area, and 11% at the distal end of appendix. All patients of the study and control groups were contacted, and at a mean follow-up of 4.0 ± 1.7 y, there was no occurrence of acute appendicitis in either group. Patients with incidentally discovered appendicolith on radiological imaging did not develop appendicitis. Hence, the risk of developing acute appendicitis for these patients does not seem higher than the general population. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Carborane-based carbonic anhydrase inhibitors: insight into CAII/CAIX specificity from a high-resolution crystal structure, modeling, and quantum chemical calculations

    Czech Academy of Sciences Publication Activity Database

    Mader, Pavel; Pecina, Adam; Cígler, Petr; Lepšík, Martin; Šícha, Václav; Hobza, Pavel; Grüner, Bohumír; Fanfrlík, Jindřich; Brynda, Jiří; Řezáčová, Pavlína

    2014-01-01

    Roč. 2014, Sept 18 (2014), 389869/1-389869/9 ISSN 2314-6133 R&D Projects: GA TA ČR(CZ) TE01020028; GA ČR GBP208/12/G016 Institutional support: RVO:61388980 ; RVO:68378050 ; RVO:61388963 Keywords : Drug design * Identification * Accuracy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.579, year: 2014

  7. Stabilization of antibody structure upon association to a human carbonic anhydrase IX epitope studied by X-ray crystallography, microcalorimetry, and molecular dynamics simulations

    Czech Academy of Sciences Publication Activity Database

    Král, Vlastimil; Mader, Pavel; Collard, Renata; Fábry, Milan; Hořejší, Magdalena; Řezáčová, Pavlína; Kožíšek, Milan; Závada, Jan; Sedláček, Juraj; Rulíšek, Lubomír; Brynda, Jiří

    2008-01-01

    Roč. 71, č. 3 (2008), s. 1275-1287 ISSN 0887-3585 R&D Projects: GA MŠk OE 210; GA MPO 2A-2TP1/076; GA MŠk 1M0508; GA MŠk 1M0505; GA MŠk LC512; GA ČR GA203/02/0405 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z40550506 Keywords : antigen-antibody recognition * CDR loop rearrangement * Fab crystal structure Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.419, year: 2008

  8. In vitro effects of estrogen and progesterone containing drugs on human erythrocyte carbonic anhydrase I and II isozymes in women smokers and nonsmokers

    Directory of Open Access Journals (Sweden)

    Mine Islimye Taskin

    2015-09-01

    Conclusion: The results of the current study provide important information to clinicians about how to consider the possible adverse effects of these drugs which are produced as a result of inhibition of CA I and CA II enzyme. Clinicians should take into consideration the side effects caused by CA I and CA II enzyme inhibition when prescribing these drugs in the treatment of different clinical conditions, especially in women who smoke.

  9. In vitro evaluation of the monoclonal antibody Cu-64-IgG M75 against human carbonic anhydrase IX and its in vivo imaging

    Czech Academy of Sciences Publication Activity Database

    Čepa, Adam; Ráliš, Jan; Král, Vlastimil; Paurová, M.; Kučka, Jan; Humajová, J.; Lázníček, M.; Lebeda, Ondřej

    2018-01-01

    Roč. 133, č. March (2018), s. 9-13 ISSN 0969-8043 Institutional support: RVO:61389005 ; RVO:68378050 ; RVO:61389013 Keywords : IgG M75 * immunoaffinity * imaging * monoclonal atibody * Cu-64 Subject RIV: FP - Other Medical Disciplines; CD - Macromolecular Chemistry (UMCH-V); EB - Genetics ; Molecular Biology (UMG-J) OBOR OECD: Radiology, nuclear medicine and medical imaging; Polymer science (UMCH-V); Biochemical research methods (UMG-J) Impact factor: 1.128, year: 2016

  10. QM/MM Calculations Reveal the Different Nature of the Interaction of Two Carborane-Based Sulfamide Inhibitors of Human Carbonic Anhydrase II

    Czech Academy of Sciences Publication Activity Database

    Pecina, Adam; Lepšík, Martin; Řezáč, Jan; Brynda, Jiří; Mader, Pavel; Řezáčová, Pavlína; Hobza, Pavel; Fanfrlík, Jindřich

    2013-01-01

    Roč. 117, č. 50 (2013), s. 16096-16104 ISSN 1520-6106 R&D Projects: GA ČR GBP208/12/G016 Grant - others:Operational Program Research and Development for Innovations(XE) CZ 1.05/2.1.00/03/0058 Institutional support: RVO:61388963 ; RVO:68378050 Keywords : neutron-capture therapy * dodecaborate cluster lipids * boron clusters Subject RIV: CF - Physical ; Theoretical Chemistry ; EB - Genetics ; Molecular Biology (UMG-J) Impact factor: 3.377, year: 2013

  11. Carbonic anhydrase IX and response to postmastectomy radiotherapy in high-risk breast cancer: a subgroup analysis of the DBCG82 b and c trials

    DEFF Research Database (Denmark)

    Kyndi, M.; Sorensen, F.B.; Alsner, J.

    2008-01-01

    -points were loco-regional recurrence, distant metastases, disease-specific survival and overall survival. Statistical analyses included kappa statistics, chi(2) or exact tests, Kaplan-Meier probability plots, Log-rank test and Cox regression analyses. Results CA IX was assessable in 945 cores. The percentage...

  12. Radiolabeling of antibody for epitope of human carbonic anhydrase IX (IgG M75) by 61Cu and 64Cu and its biological testing

    Czech Academy of Sciences Publication Activity Database

    Čepa, Adam; Ráliš, Jan; Pavelka, A.; Marešová, L.; Kleinová, M.; Seifert, Daniel; Sieglová, Irena; Král, Vlastimil; Polášek, Miroslav; Lebeda, Ondřej; Paúrová, M.; Lázníček, M.

    2015-01-01

    Roč. 42, S (2015), s. 465-466 ISSN 1619-7070. [28th Annual congress of the European-Association-of-Nuclear-Medicine (EANM). 10.10.2015-14.10.2015, Hamburg] R&D Projects: GA TA ČR TA02010797; GA MŠk(CZ) LM2011019 Institutional support: RVO:61389005 ; RVO:68378050 Keywords : antibodies * Cu-61 * Cu-64 Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders; EB - Genetics ; Molecular Biology (UMG-J)

  13. Data Recommender: An Alternative Way to Discover Open Scientific Datasets

    Science.gov (United States)

    Klump, J. F.; Devaraju, A.; Williams, G.; Hogan, D.; Davy, R.; Page, J.; Singh, D.; Peterson, N.

    2017-12-01

    Over the past few years, institutions and government agencies have adopted policies to openly release their data, which has resulted in huge amounts of open data becoming available on the web. When trying to discover the data, users face two challenges: an overload of choice and the limitations of the existing data search tools. On the one hand, there are too many datasets to choose from, and therefore, users need to spend considerable effort to find the datasets most relevant to their research. On the other hand, data portals commonly offer keyword and faceted search, which depend fully on the user queries to search and rank relevant datasets. Consequently, keyword and faceted search may return loosely related or irrelevant results, although the results may contain the same query. They may also return highly specific results that depend more on how well metadata was authored. They do not account well for variance in metadata due to variance in author styles and preferences. The top-ranked results may also come from the same data collection, and users are unlikely to discover new and interesting datasets. These search modes mainly suits users who can express their information needs in terms of the structure and terminology of the data portals, but may pose a challenge otherwise. The above challenges reflect that we need a solution that delivers the most relevant (i.e., similar and serendipitous) datasets to users, beyond the existing search functionalities on the portals. A recommender system is an information filtering system that presents users with relevant and interesting contents based on users' context and preferences. Delivering data recommendations to users can make data discovery easier, and as a result may enhance user engagement with the portal. We developed a hybrid data recommendation approach for the CSIRO Data Access Portal. The approach leverages existing recommendation techniques (e.g., content-based filtering and item co-occurrence) to produce

  14. The Carbonation of Wollastonite: A Model Reaction to Test Natural and Biomimetic Catalysts for Enhanced CO2 Sequestration

    Directory of Open Access Journals (Sweden)

    Fulvio Di Lorenzo

    2018-05-01

    Full Text Available One of the most promising strategies for the safe and permanent disposal of anthropogenic CO2 is its conversion into carbonate minerals via the carbonation of calcium and magnesium silicates. However, the mechanism of such a reaction is not well constrained, and its slow kinetics is a handicap for the implementation of silicate mineral carbonation as an effective method for CO2 capture and storage (CCS. Here, we studied the different steps of wollastonite (CaSiO3 carbonation (silicate dissolution → carbonate precipitation as a model CCS system for the screening of natural and biomimetic catalysts for this reaction. Tested catalysts included carbonic anhydrase (CA, a natural enzyme that catalyzes the reversible hydration of CO2(aq, and biomimetic metal-organic frameworks (MOFs. Our results show that dissolution is the rate-limiting step for wollastonite carbonation. The overall reaction progresses anisotropically along different [hkl] directions via a pseudomorphic interface-coupled dissolution–precipitation mechanism, leading to partial passivation via secondary surface precipitation of amorphous silica and calcite, which in both cases is anisotropic (i.e., (hkl-specific. CA accelerates the final carbonate precipitation step but hinders the overall carbonation of wollastonite. Remarkably, one of the tested Zr-based MOFs accelerates the dissolution of the silicate. The use of MOFs for enhanced silicate dissolution alone or in combination with other natural or biomimetic catalysts for accelerated carbonation could represent a potentially effective strategy for enhanced mineral CCS.

  15. Discovering geothermal supercritical fluids: a new frontier for seismic exploration.

    Science.gov (United States)

    Piana Agostinetti, Nicola; Licciardi, Andrea; Piccinini, Davide; Mazzarini, Francesco; Musumeci, Giovanni; Saccorotti, Gilberto; Chiarabba, Claudio

    2017-11-06

    Exploiting supercritical geothermal resources represents a frontier for the next generation of geothermal electrical power plant, as the heat capacity of supercritical fluids (SCF),which directly impacts on energy production, is much higher than that of fluids at subcritical conditions. Reconnaissance and location of intensively permeable and productive horizons at depth is the present limit for the development of SCF geothermal plants. We use, for the first time, teleseismic converted waves (i.e. receiver function) for discovering those horizons in the crust. Thanks to the capability of receiver function to map buried anisotropic materials, the SCF-bearing horizon is seen as the 4km-depth abrupt termination of a shallow, thick, ultra-high (>30%) anisotropic rock volume, in the center of the Larderello geothermal field. The SCF-bearing horizon develops within the granites of the geothermal field, bounding at depth the vapor-filled heavily-fractured rock matrix that hosts the shallow steam-dominated geothermal reservoirs. The sharp termination at depth of the anisotropic behavior of granites, coinciding with a 2 km-thick stripe of seismicity and diffuse fracturing, points out the sudden change in compressibility of the fluid filling the fractures and is a key-evidence of deep fluids that locally traversed the supercritical conditions. The presence of SCF and fracture permeability in nominally ductile granitic rocks open new scenarios for the understanding of magmatic systems and for geothermal exploitation.

  16. Metabolome analysis for discovering biomarkers of gastroenterological cancer.

    Science.gov (United States)

    Suzuki, Makoto; Nishiumi, Shin; Matsubara, Atsuki; Azuma, Takeshi; Yoshida, Masaru

    2014-09-01

    Improvements in analytical technologies have made it possible to rapidly determine the concentrations of thousands of metabolites in any biological sample, which has resulted in metabolome analysis being applied to various types of research, such as clinical, cell biology, and plant/food science studies. The metabolome represents all of the end products and by-products of the numerous complex metabolic pathways operating in a biological system. Thus, metabolome analysis allows one to survey the global changes in an organism's metabolic profile and gain a holistic understanding of the changes that occur in organisms during various biological processes, e.g., during disease development. In clinical metabolomic studies, there is a strong possibility that differences in the metabolic profiles of human specimens reflect disease-specific states. Recently, metabolome analysis of biofluids, e.g., blood, urine, or saliva, has been increasingly used for biomarker discovery and disease diagnosis. Mass spectrometry-based techniques have been extensively used for metabolome analysis because they exhibit high selectivity and sensitivity during the identification and quantification of metabolites. Here, we describe metabolome analysis using liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and capillary electrophoresis-mass spectrometry. Furthermore, the findings of studies that attempted to discover biomarkers of gastroenterological cancer are also outlined. Finally, we discuss metabolome analysis-based disease diagnosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. AN EFFICIENT WEB PERSONALIZATION APPROACH TO DISCOVER USER INTERESTED DIRECTORIES

    Directory of Open Access Journals (Sweden)

    M. Robinson Joel

    2014-04-01

    Full Text Available Web Usage Mining is the application of data mining technique used to retrieve the web usage from web proxy log file. Web Usage Mining consists of three major stages: preprocessing, clustering and pattern analysis. This paper explains each of these stages in detail. In this proposed approach, the web directories are discovered based on the user’s interestingness. The web proxy log file undergoes a preprocessing phase to improve the quality of data. Fuzzy Clustering Algorithm is used to cluster the user and session into disjoint clusters. In this paper, an effective approach is presented for Web personalization based on an Advanced Apriori algorithm. It is used to select the user interested web directories. The proposed method is compared with the existing web personalization methods like Objective Probabilistic Directory Miner (OPDM, Objective Community Directory Miner (OCDM and Objective Clustering and Probabilistic Directory Miner (OCPDM. The result shows that the proposed approach provides better results than the aforementioned existing approaches. At last, an application is developed with the user interested directories and web usage details.

  18. The 3D model of debriefing: defusing, discovering, and deepening.

    Science.gov (United States)

    Zigmont, Jason J; Kappus, Liana J; Sudikoff, Stephanie N

    2011-04-01

    The experiential learning process involves participation in key experiences and analysis of those experiences. In health care, these experiences can occur through high-fidelity simulation or in the actual clinical setting. The most important component of this process is the postexperience analysis or debriefing. During the debriefing, individuals must reflect upon the experience, identify the mental models that led to behaviors or cognitive processes, and then build or enhance new mental models to be used in future experiences. On the basis of adult learning theory, the Kolb Experiential Learning Cycle, and the Learning Outcomes Model, we structured a framework for facilitators of debriefings entitled "the 3D Model of Debriefing: Defusing, Discovering, and Deepening." It incorporates common phases prevalent in the debriefing literature, including description of and reactions to the experience, analysis of behaviors, and application or synthesis of new knowledge into clinical practice. It can be used to enhance learning after real or simulated events. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Can doubly strange dibaryon resonances be discovered at RHIC?

    International Nuclear Information System (INIS)

    Paganis, S. D.; Hoffmann, G. W.; Ray, R. L.; Tang, J.-L.; Udagawa, T.; Longacre, R. S.

    2000-01-01

    The baryon-baryon continuum invariant mass spectrum generated from relativistic nucleus + nucleus collision data may reveal the existence of doubly strange dibaryons not stable against strong decay if they lie within a few MeV of threshold. Furthermore, since the dominant component of these states is a superposition of two color-octet clusters which can be produced intermediately in a color-deconfined quark-gluon plasma (QGP), an enhanced production of dibaryon resonances could be a signal of QGP formation. A total of eight, doubly strange dibaryon states are considered for experimental search using the STAR detector (solenoidal tracker at RHIC) at the new Relativistic Heavy Ion Collider (RHIC). These states may decay to ΛΛ and/or pΞ - , depending on the resonance energy. STAR's large acceptance, precision tracking and vertex reconstruction capabilities, and large data volume capacity, make it an ideal instrument to use for such a search. Detector performance and analysis sensitivity are studied as a function of resonance production rate and width for one particular dibaryon which can directly strong decay to pΞ - , but not ΛΛ. Results indicate that such resonances may be discovered using STAR if the resonance production rates are comparable to coalescence model predictions for dibaryon bound states. (c) 2000 The American Physical Society

  20. Inner solar system material discovered in the Oort cloud.

    Science.gov (United States)

    Meech, Karen J; Yang, Bin; Kleyna, Jan; Hainaut, Olivier R; Berdyugina, Svetlana; Keane, Jacqueline V; Micheli, Marco; Morbidelli, Alessandro; Wainscoat, Richard J

    2016-04-01

    We have observed C/2014 S3 (PANSTARRS), a recently discovered object on a cometary orbit coming from the Oort cloud that is physically similar to an inner main belt rocky S-type asteroid. Recent dynamical models successfully reproduce the key characteristics of our current solar system; some of these models require significant migration of the giant planets, whereas others do not. These models provide different predictions on the presence of rocky material expelled from the inner solar system in the Oort cloud. C/2014 S3 could be the key to verifying these predictions of the migration-based dynamical models. Furthermore, this object displays a very faint, weak level of comet-like activity, five to six orders of magnitude less than that of typical ice-rich comets on similar Orbits coming from the Oort cloud. For the nearly tailless appearance, we are calling C/2014 S3 a Manx object. Various arguments convince us that this activity is produced by sublimation of volatile ice, that is, normal cometary activity. The activity implies that C/2014 S3 has retained a tiny fraction of the water that is expected to be present at its formation distance in the inner solar system. We may be looking at fresh inner solar system Earth-forming material that was ejected from the inner solar system and preserved for billions of years in the Oort cloud.

  1. More Far-Side Deep Moonquake Nests Discovered

    Science.gov (United States)

    Nakamura, Y.; Jackson, John A.; Jackson, Katherine G.

    2004-01-01

    As reported last year, we started to reanalyze the seismic data acquired from 1969 to 1977 with a network of stations established on the Moon during the Apollo mission. The reason for the reanalysis was because recent advances in computer technology make it possible to employ much more sophisticated analysis techniques than was possible previously. The primary objective of the reanalysis was to search for deep moonquakes on the far side of the Moon and, if found, to use them to infer the structure of the Moon's deep interior, including a possible central core. The first step was to identify any new deep moonquakes that escaped our earlier search by applying a combination of waveform cross-correlation and single-link cluster analysis, and then to see if any of them are from previously unknown nests of deep moonquakes. We positively identified 7245 deep moonquakes, more than a five-fold increase from the previous 1360. We also found at least 88 previously unknown deep-moonquake nests. The question was whether any of these newly discovered nets were on the far side of the Moon, and we now report that our analysis of the data indicates that some of them are indeed on the far side.

  2. Discovering Patterns in Brain Signals Using Decision Trees

    Directory of Open Access Journals (Sweden)

    Narusci S. Bastos

    2016-01-01

    Full Text Available Even with emerging technologies, such as Brain-Computer Interfaces (BCI systems, understanding how our brains work is a very difficult challenge. So we propose to use a data mining technique to help us in this task. As a case of study, we analyzed the brain’s behaviour of blind people and sighted people in a spatial activity. There is a common belief that blind people compensate their lack of vision using the other senses. If an object is given to sighted people and we asked them to identify this object, probably the sense of vision will be the most determinant one. If the same experiment was repeated with blind people, they will have to use other senses to identify the object. In this work, we propose a methodology that uses decision trees (DT to investigate the difference of how the brains of blind people and people with vision react against a spatial problem. We choose the DT algorithm because it can discover patterns in the brain signal, and its presentation is human interpretable. Our results show that using DT to analyze brain signals can help us to understand the brain’s behaviour.

  3. Prediction of Human Activity by Discovering Temporal Sequence Patterns.

    Science.gov (United States)

    Li, Kang; Fu, Yun

    2014-08-01

    Early prediction of ongoing human activity has become more valuable in a large variety of time-critical applications. To build an effective representation for prediction, human activities can be characterized by a complex temporal composition of constituent simple actions and interacting objects. Different from early detection on short-duration simple actions, we propose a novel framework for long -duration complex activity prediction by discovering three key aspects of activity: Causality, Context-cue, and Predictability. The major contributions of our work include: (1) a general framework is proposed to systematically address the problem of complex activity prediction by mining temporal sequence patterns; (2) probabilistic suffix tree (PST) is introduced to model causal relationships between constituent actions, where both large and small order Markov dependencies between action units are captured; (3) the context-cue, especially interactive objects information, is modeled through sequential pattern mining (SPM), where a series of action and object co-occurrence are encoded as a complex symbolic sequence; (4) we also present a predictive accumulative function (PAF) to depict the predictability of each kind of activity. The effectiveness of our approach is evaluated on two experimental scenarios with two data sets for each: action-only prediction and context-aware prediction. Our method achieves superior performance for predicting global activity classes and local action units.

  4. Commentary: discovering a different model of medical student education.

    Science.gov (United States)

    Watson, Robert T

    2012-12-01

    Traditional medical schools in modern academic health centers make discoveries, create new knowledge and technology, provide innovative care to the sickest patients, and educate future academic and practicing physicians. Unfortunately, the growth of the research and clinical care missions has sometimes resulted in a loss of emphasis on the general professional education of medical students. The author concludes that it may not be practical for many established medical schools to functionally return to the reason they were created: for the education of medical students.He had the opportunity to discover a different model of medical student education at the first new MD-granting medical school created in the United States in 25 years (in 2000), the Florida State University College of Medicine. He was initially skeptical about how its distributed regional campuses model, using practicing primary care physicians to help medical students learn in mainly ambulatory settings, could be effective. But his experience as a faculty member at the school convinced him that the model works very well.He proposes a better alignment of form and function for many established medical schools and an extension of the regional community-based model to the formation of community-based primary care graduate medical education programs determined by physician workforce needs and available resources.

  5. Unified Photo Enhancement by Discovering Aesthetic Communities From Flickr.

    Science.gov (United States)

    Hong, Richang; Zhang, Luming; Tao, Dacheng

    2016-03-01

    Photo enhancement refers to the process of increasing the aesthetic appeal of a photo, such as changing the photo aspect ratio and spatial recomposition. It is a widely used technique in the printing industry, graphic design, and cinematography. In this paper, we propose a unified and socially aware photo enhancement framework which can leverage the experience of photographers with various aesthetic topics (e.g., portrait and landscape). We focus on photos from the image hosting site Flickr, which has 87 million users and to which more than 3.5 million photos are uploaded daily. First, a tagwise regularized topic model is proposed to describe the aesthetic topic of each Flickr user, and coherent and interpretable topics are discovered by leveraging both the visual features and tags of photos. Next, a graph is constructed to describe the similarities in aesthetic topics between the users. Noticeably, densely connected users have similar aesthetic topics, which are categorized into different communities by a dense subgraph mining algorithm. Finally, a probabilistic model is exploited to enhance the aesthetic attractiveness of a test photo by leveraging the photographic experiences of Flickr users from the corresponding communities of that photo. Paired-comparison-based user studies show that our method performs competitively on photo retargeting and recomposition. Moreover, our approach accurately detects aesthetic communities in a photo set crawled from nearly 100000 Flickr users.

  6. Systematic Serendipity: A Method to Discover the Anomalous

    Science.gov (United States)

    Giles, Daniel; Walkowicz, Lucianne

    2018-01-01

    One of the challenges in the era of big data astronomical surveys is identifying anomalous data, data that exhibits as-of-yet unobserved behavior. These data may result from systematic errors, extreme (or rare) forms of known phenomena, or, most interestingly, truly novel phenomena that has historically required a trained eye and often fortuitous circumstance to identify. We describe a method that uses machine clustering techniques to discover anomalous data in Kepler lightcurves, as a step towards systematizing the detection of novel phenomena in the era of LSST. As a proof of concept, we apply our anomaly detection method to Kepler data including Boyajian's Star (KIC 8462852). We examine quarters 4, 8, 11, and 16 of the Kepler data which contain Boyajian’s Star acting normally (quarters 4 and 11) and anomalously (quarters 8 and 16). We demonstrate that our method is capable of identifying Boyajian’s Star’s anomalous behavior in quarters of interest, and we further identify other anomalous light curves that exhibit a range of interesting variability.

  7. Decision Tree Approach to Discovering Fraud in Leasing Agreements

    Directory of Open Access Journals (Sweden)

    Horvat Ivan

    2014-09-01

    Full Text Available Background: Fraud attempts create large losses for financing subjects in modern economies. At the same time, leasing agreements have become more and more popular as a means of financing objects such as machinery and vehicles, but are more vulnerable to fraud attempts. Objectives: The goal of the paper is to estimate the usability of the data mining approach in discovering fraud in leasing agreements. Methods/Approach: Real-world data from one Croatian leasing firm was used for creating tow models for fraud detection in leasing. The decision tree method was used for creating a classification model, and the CHAID algorithm was deployed. Results: The decision tree model has indicated that the object of the leasing agreement had the strongest impact on the probability of fraud. Conclusions: In order to enhance the probability of the developed model, it would be necessary to develop software that would enable automated, quick and transparent retrieval of data from the system, processing according to the rules and displaying the results in multiple categories.

  8. Discovering EEG resting state alterations of semantic dementia.

    Science.gov (United States)

    Grieder, Matthias; Koenig, Thomas; Kinoshita, Toshihiko; Utsunomiya, Keita; Wahlund, Lars-Olof; Dierks, Thomas; Nishida, Keiichiro

    2016-05-01

    Diagnosis of semantic dementia relies on cost-intensive MRI or PET, although resting EEG markers of other dementias have been reported. Yet the view still holds that resting EEG in patients with semantic dementia is normal. However, studies using increasingly sophisticated EEG analysis methods have demonstrated that slightest alterations of functional brain states can be detected. We analyzed the common four resting EEG microstates (A, B, C, and D) of 8 patients with semantic dementia in comparison with 8 healthy controls and 8 patients with Alzheimer's disease. Topographical differences between the groups were found in microstate classes B and C, while microstate classes A and D were comparable. The data showed that the semantic dementia group had a peculiar microstate E, but the commonly found microstate C was lacking. Furthermore, the presence of microstate E was significantly correlated with lower MMSE and language scores. Alterations in resting EEG can be found in semantic dementia. Topographical shifts in microstate C might be related to semantic memory deficits. This is the first study that discovered resting state EEG abnormality in semantic dementia. The notion that resting EEG in this dementia subtype is normal has to be revised. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  9. Carbon Micronymphaea: Graphene on Vertically Aligned Carbon Nanotubes

    Directory of Open Access Journals (Sweden)

    Jong Won Choi

    2013-01-01

    Full Text Available This paper describes the morphology of carbon nanomaterials such as carbon nanotube (CNT, graphene, and their hybrid structure under various operating conditions during a one-step synthesis via plasma-enhanced chemical vapor deposition (PECVD. We focus on the synthetic aspects of carbon hybrid material composed of heteroepitaxially grown graphene on top of a vertical array of carbon nanotubes, called carbon micronymphaea. We characterize the structural features of this unique nanocomposite by uses of electron microscopy and micro-Raman spectroscopy. We observe carbon nanofibers, poorly aligned and well-aligned vertical arrays of CNT sequentially as the growth temperature increases, while we always discover the carbon hybrids, called carbon micronymphaea, at specific cooling rate of 15°C/s, which is optimal for the carbon precipitation from the Ni nanoparticles in this study. We expect one-pot synthesized graphene-on-nanotube hybrid structure poses great potential for applications that demand ultrahigh surface-to-volume ratios with intact graphitic nature and directional electronic and thermal transports.

  10. Three new organisms of the 'third kind' discovered

    Energy Technology Data Exchange (ETDEWEB)

    1981-11-01

    Until a few years ago, only two groups of organisms were distinguished: Prokaryotes, which do not have a cell nucleus, and eukaryotes, whose cell nucleus is enclosed by a membrane. Today, relationships founded in development or history are derived from the structure of proteins and nucleic acids; using 16 S-rRNA as molecule of reference, the existence of two strains of prokaryotes has been proven which have been named eubacteria and archaebacteria. Among other characteristics, the membranes of these can resist high temperatures, high acidity and high ion concentrations; also, they are resistant to antibiotics. Scientists of the Max-Planck Institute of Biochemistry have recently found three specimens of a new, hitherto unknown order of archaebacteria in the vulcanic fields of Iceland. The new specimens have been named thermoproteals. They are extremely anaerobic and at the same time extremely thermoacidophilic. Thermoproteus tenax has a unique metabolism in that it produces hydrogen sulphide from hydrogen and sulphur. Experiments have shown that it can live on carbon monoxide alone as its only carbon source. Apart from their purely scientific aspects, these thermoproteals with their highly resistant cell membranes may lead to the development of organic materials with quite new properties.

  11. PALFA Discovers Neutron Stars on a Collision Course

    Science.gov (United States)

    Kohler, Susanna

    2018-03-01

    Got any plans in 46 million years? If not, you should keep an eye out for PSR J1946+2052 around that time this upcoming merger of two neutron stars promises to be an exciting show!Survey SuccessAverage profile for PSR J1946+2052 at 1.43 GHz from a 2 hr observation from the Arecibo Observatory. [Stovall et al. 2018]It seems like we just wrote about the dearth of known double-neutron-star systems, and about how new surveys are doing their best to find more of these compact binaries. Observing these systems improves our knowledge of how pairs of evolved stars behave before they eventually spiral in, merge, and emit gravitational waves that detectors like the Laser Interferometer Gravitational-wave Observatory might observe.Todays study, led by Kevin Stovall (National Radio Astronomy Observatory), goes to show that these surveys are doing a great job so far! Yet another double-neutron-star binary, PSR J1946+2052, has now been discovered as part of the Arecibo L-Band Feed Array pulsar (PALFA) survey. This one is especially unique due to the incredible speed with which these neutron stars orbit each other and their correspondingly (relatively!) short timescale for merger.An Extreme ExampleThe PALFA survey, conducted with the enormous 305-meter radio dish at Arecibo, has thus far resulted in the discovery of 180 pulsars including two double-neutron-star systems. The most recent discovery by Stovall and collaborators brings that number up to three, for a grand total of 16 binary-neutron-star systems (confirmed and unconfirmed) known to date.The 305-m Arecibo Radio Telescope, built into the landscape at Arecibo, Puerto Rico. [NOAO/AURA/NSF/H. Schweiker/WIYN]The newest binary in this collection, PSR J1946+2052, exhibits a pulsar with a 17-millisecond spin period thatwhips around its compact companion at a terrifying rate: the binary period is just 1.88 hours. Follow-up observations with the Jansky Very Large Array and other telescopes allowed the team to identify the binarys

  12. Discovering significant evolution patterns from satellite image time series.

    Science.gov (United States)

    Petitjean, François; Masseglia, Florent; Gançarski, Pierre; Forestier, Germain

    2011-12-01

    Satellite Image Time Series (SITS) provide us with precious information on land cover evolution. By studying these series of images we can both understand the changes of specific areas and discover global phenomena that spread over larger areas. Changes that can occur throughout the sensing time can spread over very long periods and may have different start time and end time depending on the location, which complicates the mining and the analysis of series of images. This work focuses on frequent sequential pattern mining (FSPM) methods, since this family of methods fits the above-mentioned issues. This family of methods consists of finding the most frequent evolution behaviors, and is actually able to extract long-term changes as well as short term ones, whenever the change may start and end. However, applying FSPM methods to SITS implies confronting two main challenges, related to the characteristics of SITS and the domain's constraints. First, satellite images associate multiple measures with a single pixel (the radiometric levels of different wavelengths corresponding to infra-red, red, etc.), which makes the search space multi-dimensional and thus requires specific mining algorithms. Furthermore, the non evolving regions, which are the vast majority and overwhelm the evolving ones, challenge the discovery of these patterns. We propose a SITS mining framework that enables discovery of these patterns despite these constraints and characteristics. Our proposal is inspired from FSPM and provides a relevant visualization principle. Experiments carried out on 35 images sensed over 20 years show the proposed approach makes it possible to extract relevant evolution behaviors.

  13. A DISK MIRROR RECENTLY DISCOVERED SOUTH THE LOWER MUREȘ

    Directory of Open Access Journals (Sweden)

    Vitalie Bârcă

    2016-11-01

    Full Text Available The object of this study is the analysis of the disk mirror discovered in 2010 during the rescue archaeological excavations carried out in occasion of the construction of the Arad-Timişoara motorway, respectively the Arad-Seceani sector. The mirror was found at  ca. 1 m north grave 1 in site B0_6, where beside other two cremation graves, poorly preserved, other 129 archaeological features were also investigated.Though not exhaustively, we attempt herein to present the origin, distribution of this mirror type in the Sarmatian world and the chronological interval of their use within said environment.The author notes that these disk mirror types from the funerary Sarmatian features of the Great Hungarian Plain count amongst the most numerous, being found within funerary contexts on the entire duration of the Sarmatian inhabitancy of this geographical area. Further, the author notes that mirrors of the type are widely spread on broad geographical areas, hence the establishment of any production centres is highly difficult, but also that very likely, they were produced in various cultural environments over several centuries. Their high numbers in the Sarmatian world proves it is possible they made them, although there is no certain substantiating evidence. The author does not exclude either the possibility of the presence of travelling artisans in the Sarmatian environment making certain item categories upon order, mirrors of the type included.In terms of the dating of G 1 at Arad (site B_06, where the mirror most definitely originates, the author concludes that together with the other two graves (G 2 and G 3 are contemporary and date sometime to the end of the 2nd century – early decades of the 3rd century AD.

  14. Discovering Higgs Bosons of the MSSM using Jet Substructure

    International Nuclear Information System (INIS)

    Kribs, Graham D.; Martin, Adam; Roy, Tuhin S.; Spannowsky, Michael

    2010-01-01

    We present a qualitatively new approach to discover Higgs bosons of the MSSM at the LHC using jet substructure techniques applied to boosted Higgs decays. These techniques are ideally suited to the MSSM, since the lightest Higgs boson overwhelmingly decays to b(bar b) throughout the entire parameter space, while the heavier neutral Higgs bosons, if light enough to be produced in a cascade, also predominantly decay to b(bar b). The Higgs production we consider arises from superpartner production where superpartners cascade decay into Higgs bosons. We study this mode of Higgs production for several superpartner hierarchies: m # tilde q#,m # tilde g# > m # tilde W#, # tilde B# > m h + μ; m(tilde q);m # tilde q#,m # tilde g# > m # tilde W#, # tilde B# > m h,H,A + μ; and m # tilde q#,m # tilde g# > m # tilde W# > m h + μ with m # tilde B# ∼ μ. In these cascades, the Higgs bosons are boosted, with pT > 200 GeV a large fraction of the time. Since Higgs bosons appear in cascades originating from squarks and/or gluinos, the cross section for events with at least one Higgs boson can be the same order as squark/gluino production. Given 10 fb -1 of 14 TeV LHC data, with m # tilde q# ∼< 1 TeV, and one of the above superpartner mass hierarchies, our estimate of S√ B of the Higgs signal is sufficiently high that the b(bar b) mode can become the discovery mode of the lightest Higgs boson of the MSSM.

  15. Discovering Higgs bosons of the MSSM using jet substructure

    International Nuclear Information System (INIS)

    Kribs, Graham D.; Roy, Tuhin S.; Spannowsky, Michael; Martin, Adam

    2010-01-01

    We present a qualitatively new approach to discover Higgs bosons of the minimal supersymmetric standard model (MSSM) at the LHC using jet substructure techniques applied to boosted Higgs decays. These techniques are ideally suited to the MSSM, since the lightest Higgs boson overwhelmingly decays to bb throughout the entire parameter space, while the heavier neutral Higgs bosons, if light enough to be produced in a cascade, also predominantly decay to bb. The Higgs production we consider arises from superpartner production where superpartners cascade decay into Higgs bosons. We study this mode of Higgs production for several superpartner hierarchies: m q -tilde, m g -tilde>m W -tilde ,B -tilde>m h +μ; m q -tilde, m g -tilde>m W -tilde ,B -tilde>m h,H,A +μ; and m q -tilde, m g -tilde>m W -tilde>m h +μ with m B -tilde≅μ. In these cascades, the Higgs bosons are boosted, with p T >200 GeV a large fraction of the time. Since Higgses appear in cascades originating from squarks and/or gluinos, the cross section for events with at least one Higgs can be the same order as squark/gluino production. Given 10 fb -1 of 14 TeV LHC data, with m q -tilde < or approx. 1 TeV, and one of the above superpartner mass hierarchies, our estimate of S/√(B) of the Higgs signal is sufficiently high that the bb mode can become the discovery mode of the lightest Higgs boson of the MSSM.

  16. Feature-based morphometry: discovering group-related anatomical patterns.

    Science.gov (United States)

    Toews, Matthew; Wells, William; Collins, D Louis; Arbel, Tal

    2010-02-01

    This paper presents feature-based morphometry (FBM), a new fully data-driven technique for discovering patterns of group-related anatomical structure in volumetric imagery. In contrast to most morphometry methods which assume one-to-one correspondence between subjects, FBM explicitly aims to identify distinctive anatomical patterns that may only be present in subsets of subjects, due to disease or anatomical variability. The image is modeled as a collage of generic, localized image features that need not be present in all subjects. Scale-space theory is applied to analyze image features at the characteristic scale of underlying anatomical structures, instead of at arbitrary scales such as global or voxel-level. A probabilistic model describes features in terms of their appearance, geometry, and relationship to subject groups, and is automatically learned from a set of subject images and group labels. Features resulting from learning correspond to group-related anatomical structures that can potentially be used as image biomarkers of disease or as a basis for computer-aided diagnosis. The relationship between features and groups is quantified by the likelihood of feature occurrence within a specific group vs. the rest of the population, and feature significance is quantified in terms of the false discovery rate. Experiments validate FBM clinically in the analysis of normal (NC) and Alzheimer's (AD) brain images using the freely available OASIS database. FBM automatically identifies known structural differences between NC and AD subjects in a fully data-driven fashion, and an equal error classification rate of 0.80 is achieved for subjects aged 60-80 years exhibiting mild AD (CDR=1). Copyright (c) 2009 Elsevier Inc. All rights reserved.

  17. Circumstellar grain extinction properties of recently discovered post AGB stars

    International Nuclear Information System (INIS)

    Buss, R.H. Jr.; Lamers, H.J.G.L.M.; Snow, T.P. Jr.

    1989-01-01

    The circumstellar grains of two hot evolved post asymptotic giant branch (post AGB) stars, HD 89353 and HD 213985 were examined. From ultraviolet spectra, energy balance of the flux, and Kurucz models, the extinction around 2175 A was derived. With visual spectra, an attempt was made to detect 6614 A diffuse band absorption arising from the circumstellar grains so that we could examine the relationship of these features to the infrared features. For both stars, we did not detect any diffuse band absorption at 6614 A, implying the carrier of this diffuse band is not the carrier of the unidentified infrared features not of the 2175 A bump. The linear ultraviolet extinction of the carbon-rich star HD 89353 was determined to continue across the 2175 A region with no sign of the bump; for HD 213985 it was found to be the reverse: a strong, wide bump in the mid-ultraviolet. The 213985 bump was found to be positioned at 2340 A, longward of its usual position in the interstellar medium. Since HD 213985 was determined to have excess carbon, the bump probably arises from a carbonaceous grain. Thus, in view of the ultraviolet and infrared properties of the two post AGB stars, ubiquitous interstellar infrared emission features do not seem to be associated with the 2175 A bump. Instead, the infrared features seem related to the linear ultraviolet extinction component: hydrocarbon grains of radius less than 300 A are present with the linear HD 89353 extinction; amorphous anhydrous carbonaceous grains of radius less than 50 A might cause the shifted ultraviolet extinction bump of HD 213985

  18. Brain carbonic acid acidosis after acetazolamide

    DEFF Research Database (Denmark)

    Heuser, D; Astrup, J; Lassen, N A

    1975-01-01

    acidosis by I.V. injection of HCO3-minus. Acetazolamide (25 mg/kg) i.v. was followed by a marked brain acidosis which after 10 min had progressed to a drop in pH of 0.203 plus or minus 0.046 (x bar plus or minus S.D., n equals 8). The slowness ofthe development of acidosis points to a direct effect......In cats in barbiturate anesthesia extracellular pH and potassium were continously recorded from brian cortex by implanted microelectrodes. Implantation of the electrodes preserved the low permeability of the blood-brain-barrier to HCO3-minus and H+ions as indicated by the development of brain...... of the carbonic anhydrase inhibition on the brain tissue. As a further support for this conclusion was considered the finding of a prolonged response time of brain pH to HCO3-minus i.v. to CO2-minus inhalation, and to hyperventilation after the acetazolamide inhibtion. No changes in brain extracelllular potassium...

  19. Carbon-concentrating mechanisms in seagrasses.

    Science.gov (United States)

    Larkum, Anthony William D; Davey, Peter A; Kuo, John; Ralph, Peter J; Raven, John A

    2017-06-01

    Seagrasses are unique angiosperms that carry out growth and reproduction submerged in seawater. They occur in at least three families of the Alismatales. All have chloroplasts mainly in the cells of the epidermis. Living in seawater, the supply of inorganic carbon (Ci) to the chloroplasts is diffusion limited, especially under unstirred conditions. Therefore, the supply of CO2 and bicarbonate across the diffusive boundary layer on the outer side of the epidermis is often a limiting factor. Here we discuss the evidence for mechanisms that enhance the uptake of Ci into the epidermal cells. Since bicarbonate is plentiful in seawater, a bicarbonate pump might be expected; however, the evidence for such a pump is not strongly supported. There is evidence for a carbonic anhydrase outside the outer plasmalemma. This, together with evidence for an outward proton pump, suggests the possibility that local acidification leads to enhanced concentrations of CO2 adjacent to the outer tangential epidermal walls, which enhances the uptake of CO2, and this could be followed by a carbon-concentrating mechanism (CCM) in the cytoplasm and/or chloroplasts. The lines of evidence for such an epidermal CCM are discussed, including evidence for special 'transfer cells' in some but not all seagrass leaves in the tangential inner walls of the epidermal cells. It is concluded that seagrasses have a CCM but that the case for concentration of CO2 at the site of Rubisco carboxylation is not proven. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. Carbon nanotubes for high-performance logic

    NARCIS (Netherlands)

    Chen, Zhihong; Philip Wong, H.-S.; Mitra, S.; Bol, A.A.; Peng, Lianmao; Hills, Gage; Thissen, N.F.W.

    2014-01-01

    Single-wall carbon nanotubes (CNTs) were discovered in 1993 and have been an area of intense research since then. They offer the right dimensions to explore material science and physical chemistry at the nanoscale and are the perfect system to study low-dimensional physics and transport. In the past

  1. Promising carbons for supercapacitors derived from fungi

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Hui; Wang, Xiaolei; Yang, Fan; Yang, Xiurong [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022 (China)

    2011-06-24

    Activated carbons with promising performance in capacitors are produced from fungi via a hydrothermal assistant pyrolysis approach. This study introduces a facile strategy to discover carbonaceous materials and triggers interest in exploring fungi for material science applications. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  2. Planetary dreams : the quest to discover life beyond earth

    Science.gov (United States)

    Shapiro, Robert

    1999-03-01

    The Quest To Discover Life Beyond Earth. "The 'dreams' that I write of are not the usual ones, the images that come up in our minds involuntarily during certain stages of sleep, but rather the hopes and expectations that we have lavished upon other worlds around us."-from the Preface. The surprisingly long history of debate over extraterrestrial life is full of marvelous visions of what life "out there" might be like, as well as remarkable stories of alleged sightings and heated disputes about the probability that life might actually have arisen more than once. In Planetary Dreams, acclaimed author Robert Shapiro explores this rich history of dreams and debates in search of the best current answers to the most elusive and compelling of all questions: Are we alone? In his pursuit, he presents three contrasting views regarding how life might have started: through Divine Creation, by a highly unlikely stroke of luck, or by the inevitable process of a natural law that he terms the Life Principle. We are treated to a lively fictional dinner debate among the leading proponents of these schools of thought-with the last named group arguing that life has almost surely formed in many places throughout the universe, and the others that life may well be entirely unique to our own blue planet. To set the stage for a deep exploration of the question, the author then leads us on a fantastic journey through the museum of the cosmos, an imagined building that holds models of the universe at different degrees of magnification. We then journey deep into inner space to view the astonishingly intricate life of a single cell, and learn why the origin of such a complex object from simple chemical mixtures poses one of the most profound enigmas known to science. Writing in a wonderfully entertaining style, Shapiro then reviews the competing theories about the start of life on Earth, and suggests the debate may best be settled by finding signs of life on the other worlds of our solar

  3. Hydrothermal vent fields discovered in the southern Gulf of California clarify role of habitat in augmenting regional diversity.

    Science.gov (United States)

    Goffredi, Shana K; Johnson, Shannon; Tunnicliffe, Verena; Caress, David; Clague, David; Escobar, Elva; Lundsten, Lonny; Paduan, Jennifer B; Rouse, Greg; Salcedo, Diana L; Soto, Luis A; Spelz-Madero, Ronald; Zierenberg, Robert; Vrijenhoek, Robert

    2017-07-26

    Hydrothermal vent communities are distributed along mid-ocean spreading ridges as isolated patches. While distance is a key factor influencing connectivity among sites, habitat characteristics are also critical. The Pescadero Basin (PB) and Alarcón Rise (AR) vent fields, recently discovered in the southern Gulf of California, are bounded by previously known vent localities (e.g. Guaymas Basin and 21° N East Pacific Rise); yet, the newly discovered vents differ markedly in substrata and vent fluid attributes. Out of 116 macrofaunal species observed or collected, only three species are shared among all four vent fields, while 73 occur at only one locality. Foundation species at basalt-hosted sulfide chimneys on the AR differ from the functional equivalents inhabiting sediment-hosted carbonate chimneys in the PB, only 75 km away. The dominant species of symbiont-hosting tubeworms and clams, and peripheral suspension-feeding taxa, differ between the sites. Notably, the PB vents host a limited and specialized fauna in which 17 of 26 species are unknown at other regional vents and many are new species. Rare sightings and captured larvae of the 'missing' species revealed that dispersal limitation is not responsible for differences in community composition at the neighbouring vent localities. Instead, larval recruitment-limiting habitat suitability probably favours species differentially. As scenarios develop to design conservation strategies around mining of seafloor sulfide deposits, these results illustrate that models encompassing habitat characteristics are needed to predict metacommunity structure. © 2017 The Authors.

  4. Biogeochemistry of Recently Discovered Oxygen-Depleted Mesoscale Eddies in the Open Eastern Tropical North Atlantic

    Science.gov (United States)

    Fiedler, B.; Grundle, D.; Löscher, C. R.; Schütte, F.; Hauss, H.; Karstensen, J.; Silva, P.; Koertzinger, A.

    2016-02-01

    Severely oxygen-depleted mesoscale features in the open eastern tropical North Atlantic, which are formed in the Mauritanian upwelling region, were discovered only recently. So far, few remote surveys conducted with autonomous platforms such as moorings, underwater gliders and profiling floats have provided a very first insight into these mesoscale eddies. Due to their hydrographic properties such water bodies are well isolated from ambient waters and therefore can develop severe near-surface oxygen deficits. In this presentation we show results from the first-ever biogeochemical survey of one of these anticyclonic mode-water eddies conducted in spring 2014 at the Cape Verde Ocean Observatory (CVOO) off West Africa. Very low oxygen concentrations of 4.5 µmol kg-1 associated with a CO2 partial pressure of 1164 µatm were found close to the core of the eddy (at 100 m depth). Measurements for nitrate and phosphate also show exceptional high values. Findings point to rapid oxygen consumption through remineralization of organic matter along with depressed lateral mixing of this water body. Indeed, rates for oxygen utilization (OUR) were found to be enhanced when compared to known values in the Atlantic. A closer look into the carbonate system inside the eddýs core revealed disadvantageous conditions for calcifying organisms with the pH dropping down to 7.6 and the Aragonite saturation level reaching 1 at the lower boundary of the euphotic zone. Finally, strong indications for a shift in nitrogen cycling in the core of the eddy from nitrification towards denitrification were found based on gene abundance and N2O-isotope analyses. To our knowledge such severe hypoxic and even suboxic near-surface conditions along with active denitrification have never been reported before in the open Atlantic Ocean.

  5. A knowledge-based integrated approach for discovering and repairing declare maps

    NARCIS (Netherlands)

    Maggi, F.M.; Jagadeesh Chandra Bose, R.P.; Aalst, van der W.M.P.; Salinesi, C.; Norrie, M.C.; Pastor, O.

    2013-01-01

    Process mining techniques can be used to discover process models from event data. Often the resulting models are complex due to the variability of the underlying process. Therefore, we aim at discovering declarative process models that can deal with such variability. However, for real-life event

  6. 32 CFR 644.533 - Contamination discovered after return of land to owner, or sale.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Contamination discovered after return of land to owner, or sale. 644.533 Section 644.533 National Defense Department of Defense (Continued) DEPARTMENT OF... Other Contamination from Proposed Excess Land and Improvements § 644.533 Contamination discovered after...

  7. The Use of a Performance Assessment for Identifying Gifted Lebanese Students: Is DISCOVER Effective?

    Science.gov (United States)

    Sarouphim, Ketty M.

    2009-01-01

    The purpose of this study was to investigate the effectiveness of DISCOVER, a performance- based assessment in identifying gifted Lebanese students. The sample consisted of 248 students (121 boys, 127 girls) from Grades 3-5 at two private schools in Beirut, Lebanon. Students were administered DISCOVER and the Raven Standard Progressive Matrices…

  8. Distant World in Peril Discovered from La Silla

    Science.gov (United States)

    2003-01-01

    Giant Exoplanet Orbits Giant Star Summary When, in a distant future, the Sun begins to expand and evolves into a "giant" star, the surface temperature on the Earth will rise dramatically and our home planet will eventually be incinerated by that central body. Fortunately for us, this dramatic event is several billion years away. However, that sad fate will befall another planet, just discovered in orbit about the giant star HD 47536, already within a few tens of millions of years. At a distance of nearly 400 light-years from us, it is the second-remotest planetary system discovered to date [1]. This is an interesting side-result of a major research project, now carried out by a European-Brazilian team of astronomers [2]. In the course of a three-year spectroscopic survey, they have observed about 80 giant stars in the southern sky with the advanced FEROS spectrograph on the 1.52-m telescope installed at the ESO La Silla Observatory (Chile). It is one of these stars that has just been found to host a giant planet. This is only the fourth such case known and with a diameter of about 33 million km (or 23.5 times that of our Sun), HD 47536 is by far the largest of those giant stars [1]. The distance of the planet from the star is still of the order of 300 million km (or twice the distance of the Earth from the Sun), a safe margin now, but this will not always be so. The orbital period is 712 days, i.e., somewhat less than two Earth years, and the planet's mass is 5 - 10 times that of Jupiter. The presence of exoplanets in orbit around giant stars, some of which will eventually perish into their central star (be "cannibalized"), provides a possible explanation of the anomalous abundance of certain chemical elements that is observed in the atmospheres of some stars, cf. ESO PR 10/01. This interesting discovery bodes well for coming observations of exoplanetary systems with new, more powerful instruments, like HARPS to be installed next year at the ESO 3.6-m telescope on

  9. LIGO Discovers the Merger of Two Black Holes

    Science.gov (United States)

    Kohler, Susanna

    2016-02-01

    is: how do binary black holes form? Two primary mechanisms have been proposed:A binary star system contains two stars that are each massive enough to individually collapse into a black hole. If the binary isnt disrupted during the two collapse events, this forms an isolated black-hole binary.Single black holes form in dense cluster environments and then because they are the most massive objects sink to the center of the cluster. There they form pairs through dynamical interactions.Now that were able to observe black-hole binaries through gravitational-wave detections, one way we could distinguish between the two formation mechanisms is from spin measurements. If we discover a clear preference for the misalignment of the two black holes spins, this would favor formation in clusters, where theres no reason for the original spins to be aligned.The current, single detection is not enough to provide constraints, but if we can compile a large enough sample of events, we can start to present a statistical case favoring one channel over the other.What does GW150914 mean for the future of gravitational-wave detection?The fact that Advanced LIGO detected an event even before the start of its first official observing run is certainly promising! The LIGO team estimates that the volume the detectors can probe will still increase by at least a factor of ~10 as the observing runs become more sensitive and of longer duration.Aerial view of the Virgo interferometer near Pisa, Italy. [Virgo Collaboration]In addition, LIGO is not alone in the gravitational-wave game. LIGOs counterpart in Europe, Virgo, is also undergoing design upgrades to increase its sensitivity. Within this year, Virgo should be able to take data simultaneously with LIGO, allowing for better localization of sources. And the launch of (e)LISA, ESAs planned space-based interferometer, will grant us access to a new frequency range, opening a further window to the gravitational-wave sky.The detection of GW150914 marks

  10. SwissProt search result: AK060777 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK060777 001-033-C01 (P17067) Carbonic anhydrase, chloroplast precursor (EC 4.2.1.1) (Carbon...ate dehydratase) [Contains: Carbonic anhydrase, 27 kDa isoform; Carbonic anhydrase, 25 kDa isoform] CAHC_PEA 2e-44 ...

  11. Bacillus megaterium mediated mineralization of calcium carbonate as biogenic surface treatment of green building materials.

    Science.gov (United States)

    Dhami, Navdeep Kaur; Reddy, M Sudhakara; Mukherjee, Abhijit

    2013-12-01

    Microbially induced calcium carbonate precipitation is a biomineralization process that has various applications in remediation and restoration of range of building materials. In the present study, calcifying bacteria, Bacillus megaterium SS3 isolated from calcareous soil was applied as biosealant to enhance the durability of low energy, green building materials (soil-cement blocks). This bacterial isolate produced high amounts of urease, carbonic anhydrase, extra polymeric substances and biofilm. The calcium carbonate polymorphs produced by B. megaterium SS3 were analyzed by scanning electron microscopy, confocal laser scanning microscopy, X-ray diffraction and Fourier transmission infra red spectroscopy. These results suggested that calcite is the most predominant carbonate formed by this bacteria followed by vaterite. Application of B. megaterium SS3 as biogenic surface treatment led to 40 % decrease in water absorption, 31 % decrease in porosity and 18 % increase in compressive strength of low energy building materials. From the present investigation, it is clear that surface treatment of building materials by B. megaterium SS3 is very effective and eco friendly way of biodeposition of coherent carbonates that enhances the durability of building materials.

  12. Characterization of carbon dioxide concentrating chemolithotrophic bacterium Serratia sp. ISTD04 for production of biodiesel.

    Science.gov (United States)

    Kumar, Manish; Morya, Raj; Gnansounou, Edgard; Larroche, Christian; Thakur, Indu Shekhar

    2017-11-01

    Proteomics and metabolomics analysis has become a powerful tool for characterization of microbial ability for fixation of Carbon dioxide. Bacterial community of palaeoproterozoic metasediments was enriched in the shake flask culture in the presence of NaHCO 3 . One of the isolate showed resistance to NaHCO 3 (100mM) and was identified as Serratia sp. ISTD04 by 16S rRNA sequence analysis. Carbon dioxide fixing ability of the bacterium was established by carbonic anhydrase enzyme assay along with proteomic analysis by LC-MS/MS. In proteomic analysis 96 proteins were identified out of these 6 protein involved in carbon dioxide fixation, 11 in fatty acid metabolism, indicating the carbon dioxide fixing potency of bacterium along with production of biofuel. GC-MS analysis revealed that hydrocarbons and FAMEs produced by bacteria within the range of C 13 -C 24 and C 11 -C 19 respectively. Presence of 59% saturated and 41% unsaturated organic compounds, make it a better fuel composition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Carbon-enhanced VRLA batteries.

    Energy Technology Data Exchange (ETDEWEB)

    Enos, David George; Hund, Thomas D.; Shane, Rod (East Penn Manufacturing, Lyon Station, PA)

    2010-10-01

    The addition of certain forms of carbon to the negative plate in valve regulated lead acid (VRLA) batteries has been demonstrated to increase the cycle life of such batteries by an order of magnitude or more under high-rate, partial-state-of-charge operation. Such performance will provide a significant impact, and in some cases it will be an enabling feature for applications including hybrid electric vehicles, utility ancillary regulation services, wind farm energy smoothing, and solar photovoltaic energy smoothing. There is a critical need to understnd how the carbon interacts with the negative plate and achieves the aforementioned benefits at a fundamental level. Such an understanding will not only enable the performance of such batteries to be optimzied, but also to explore the feasibility of applying this technology to other battery chemistries. In partnership with the East Penn Manufacturing, Sandia will investigate the electrochemical function of the carbon and possibly identify improvements to its anti-sulfation properties. Shiomi, et al. (1997) discovered that the addition of carbon to the negative active material (NAM) substantially reduced PbSO{sub 4} accumulation in high rate, partial state of charge (HRPSoC) cycling applications. This improved performance with a minimal cost. Cycling applications that were uneconomical for traditional VRLA batteries are viable for the carbon enhanced VRLA. The overall goal of this work is to quantitatively define the role that carbon plays in the electrochemistry of a VRLA battery.

  14. Carbon nanotube: the inside story.

    Science.gov (United States)

    Ando, Yoshinori

    2010-06-01

    Carbon nanotubes (CNTs) were serendipitously discovered as a byproduct of fullerenes by direct current (DC) arc discharge; and today this is the most-wanted material in the nanotechnology research. In this brief review, I begin with the history of the discovery of CNTs and focus on CNTs produced by arc discharge in hydrogen atmosphere, which is little explored outside my laboratory. DC arc discharge evaporation of pure graphite rod in pure hydrogen gas results in multi-walled carbon nanotubes (MWCNTs) of high crystallinity in the cathode deposit. As-grown MWCNTs have very narrow inner diameter. Raman spectra of these MWCNTs show high-intensity G-band, unusual high-frequency radial breathing mode at 570 cm(-1), and a new characteristic peak near 1850 cm(-1). Exciting carbon nanowires (CNWs), consisting of a linear carbon chain in the center of MWCNTs are also produced. Arc evaporation of graphite rod containing metal catalysts results in single-wall carbon nanotubes (SWCNTs) in the whole chamber like macroscopic webs. Two kinds of arc method have been developed to produce SWCNTs: Arc plasma jet (APJ) and Ferrum-Hydrogen (FH) arc methods. Some new purification methods for as-produced SWCNTs are reviewed. Finally, double-walled carbon nanotubes (DWCNTs) are also described.

  15. Carbon/carbon composite materials

    International Nuclear Information System (INIS)

    Thebault, J.; Orly, P.

    2006-01-01

    Carbon/carbon composites are singular materials from their components, their manufacturing process as well as their characteristics. This paper gives a global overview of these particularities and applications which make them now daily used composites. (authors)

  16. Interactive Gaussian Graphical Models for Discovering Depth Trends in ChemCam Data

    Science.gov (United States)

    Oyen, D. A.; Komurlu, C.; Lanza, N. L.

    2018-04-01

    Interactive Gaussian graphical models discover surface compositional features on rocks in ChemCam targets. Our approach visualizes shot-to-shot relationships among LIBS observations, and identifies the wavelengths involved in the trend.

  17. ISLSCP II IGBP DISCover and SiB Land Cover, 1992-1993

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set describes the geographic distributions of 17 classes of land cover based on the International Geosphere-Biosphere DISCover land cover legend (Loveland...

  18. Strategic Sustainability Performance Plan. Discovering Sustainable Solutions to Power and Secure America’s Future

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2010-09-01

    Sustainability is fundamental to the Department of Energy’s research mission and operations as reflected in the Department’s Strategic Plan. Our overarching mission is to discover the solutions to power and secure America’s future.

  19. Carbon Nanotube based Nanotechnolgy

    Science.gov (United States)

    Meyyappan, M.

    2000-10-01

    Carbon nanotube(CNT) was discovered in the early 1990s and is an off-spring of C60(the fullerene or buckyball). CNT, depending on chirality and diameter, can be metallic or semiconductor and thus allows formation of metal-semiconductor and semiconductor-semiconductor junctions. CNT exhibits extraordinary electrical and mechanical properties and offers remarkable potential for revolutionary applications in electronics devices, computing and data storage technology, sensors, composites, storage of hydrogen or lithium for battery development, nanoelectromechanical systems(NEMS), and as tip in scanning probe microscopy(SPM) for imaging and nanolithography. Thus the CNT synthesis, characterization and applications touch upon all disciplines of science and engineering. A common growth method now is based on CVD though surface catalysis is key to synthesis, in contrast to many CVD applications common in microelectronics. A plasma based variation is gaining some attention. This talk will provide an overview of CNT properties, growth methods, applications, and research challenges and opportunities ahead.

  20. Discovering functions of unannotated genes from a transcriptome survey of wild fungal isolates.

    Science.gov (United States)

    Ellison, Christopher E; Kowbel, David; Glass, N Louise; Taylor, John W; Brem, Rachel B

    2014-04-01

    Most fungal genomes are poorly annotated, and many fungal traits of industrial and biomedical relevance are not well suited to classical genetic screens. Assigning genes to phenotypes on a genomic scale thus remains an urgent need in the field. We developed an approach to infer gene function from expression profiles of wild fungal isolates, and we applied our strategy to the filamentous fungus Neurospora crassa. Using transcriptome measurements in 70 strains from two well-defined clades of this microbe, we first identified 2,247 cases in which the expression of an unannotated gene rose and fell across N. crassa strains in parallel with the expression of well-characterized genes. We then used image analysis of hyphal morphologies, quantitative growth assays, and expression profiling to test the functions of four genes predicted from our population analyses. The results revealed two factors that influenced regulation of metabolism of nonpreferred carbon and nitrogen sources, a gene that governed hyphal architecture, and a gene that mediated amino acid starvation resistance. These findings validate the power of our population-transcriptomic approach for inference of novel gene function, and we suggest that this strategy will be of broad utility for genome-scale annotation in many fungal systems. IMPORTANCE Some fungal species cause deadly infections in humans or crop plants, and other fungi are workhorses of industrial chemistry, including the production of biofuels. Advances in medical and industrial mycology require an understanding of the genes that control fungal traits. We developed a method to infer functions of uncharacterized genes by observing correlated expression of their mRNAs with those of known genes across wild fungal isolates. We applied this strategy to a filamentous fungus and predicted functions for thousands of unknown genes. In four cases, we experimentally validated the predictions from our method, discovering novel genes involved in the

  1. Discovering the energy, economic and environmental potentials of urban wastes: An input–output model for a metropolis case

    International Nuclear Information System (INIS)

    Song, Junnian; Yang, Wei; Li, Zhaoling; Higano, Yoshiro; Wang, Xian’en

    2016-01-01

    Highlights: • A waste-to-energy system is constructed incorporating various urban wastes and technologies. • Waste-to-energy industries are formed and introduced into current socioeconomic system. • A novel input–output simulation model is developed and applied to a metropolis. • Complete energy, economic and environmental potentials of urban wastes are discovered. - Abstract: Tremendous amounts of wastes are generated in urban areas due to accelerating industrialization and urbanization. The current unreasonable waste disposal patterns and potential energy value of urban wastes necessitates the promotion of waste-to-energy implementation. This study is intent on discovering the complete energy, economic and environmental potentials of urban wastes taking municipal solid wastes, waste oil, organic wastewater and livestock manure into consideration. A waste-to-energy system is constructed incorporating these wastes and five waste-to-energy technologies. A novel input–output simulation model is developed and applied to a metropolis to introduce the waste-to-energy system into the current socioeconomic system and form five waste-to-energy industries. The trends in waste generation and energy recovery potential, economic benefits and greenhouse gas mitigation contribution for the study area are estimated and explored from 2011 to 2025. By 2025, biodiesel production and power generation could amount to 72.11 thousand t and 1.59 billion kW h respectively. Due to the highest energy recovery and the most subsidies, the organic wastewater biogas industry has the highest output and net profit, followed by the waste incineration power generation industry. In total 17.97 million t (carbon dioxide-equivalent) accumulative greenhouse gas emission could be mitigated. The organic wastewater biogas industry and waste incineration power generation industry are more advantageous for the study area in terms of better energy, economic and environmental performances. The

  2. Discovering Greatness

    Science.gov (United States)

    Ali, Muhammad

    2012-01-01

    People are confronting the most pressing challenge facing every family, school, and community--raising respectful children in a toxic world. In simpler societies, raising children was a shared task of the whole community, as adults and youth worked in harmony and mutual respect. Today, humans are the only species in creation living out of balance.…

  3. Discovering Mozart.

    Science.gov (United States)

    Rusk, Nicole

    2010-06-01

    High-throughput imaging of genome-wide RNA interference screens and systematic analysis of protein complexes involved in mitosis yield valuable resources and reveal new subunits of well-characterized complexes.

  4. Carbonate aquifers

    Science.gov (United States)

    Cunningham, Kevin J.; Sukop, Michael; Curran, H. Allen

    2012-01-01

    Only limited hydrogeological research has been conducted using ichnology in carbonate aquifer characterization. Regardless, important applications of ichnology to carbonate aquifer characterization include its use to distinguish and delineate depositional cycles, correlate mappable biogenically altered surfaces, identify zones of preferential groundwater flow and paleogroundwater flow, and better understand the origin of ichnofabric-related karst features. Three case studies, which include Pleistocene carbonate rocks of the Biscayne aquifer in southern Florida and Cretaceous carbonate strata of the Edwards–Trinity aquifer system in central Texas, demonstrate that (1) there can be a strong relation between ichnofabrics and groundwater flow in carbonate aquifers and (2) ichnology can offer a useful methodology for carbonate aquifer characterization. In these examples, zones of extremely permeable, ichnofabric-related macroporosity are mappable stratiform geobodies and as such can be represented in groundwater flow and transport simulations.

  5. Nanophase Carbonates on Mars: Implications for Carbonate Formation and Habitability

    Science.gov (United States)

    Archer, P. Douglas, Jr.; Lauer, H. Vern; Ming, Douglas W.; Niles, Paul B.; Morris, Richard V.; Rampe, Elizabeth B.; Sutter, Brad

    2014-01-01

    Despite having an atmosphere composed primarily of CO2 and evidence for abundant water in the past, carbonate minerals have only been discovered in small amounts in martian dust [1], in outcrops of very limited extent [2, 3], in soils in the Northern Plains (the landing site of the 2007 Phoenix Mars Scout Mission) [4] and may have recently been detected in aeolian material and drilled and powdered sedimentary rock in Gale Crater (the Mars Science Laboratory [MSL] landing site) [5]. Thermal analysis of martian soils by instruments on Phoenix and MSL has demonstrated a release of CO2 at temperatures as low as 250-300 degC, much lower than the traditional decomposition temperatures of calcium or magnesium carbonates. Thermal decomposition temperature can depend on a number of factors such as instrument pressure and ramp rate, and sample particle size [6]. However, if the CO2 released at low temperatures is from carbonates, small particle size is the only effect that could have such a large impact on decomposition temperature, implying the presence of extremely fine-grained (i.e., "nanophase" or clay-sized) carbonates. We hypothesize that this lower temperature release is the signature of small particle-sized (clay-sized) carbonates formed by the weathering of primary minerals in dust or soils through interactions with atmospheric water and carbon dioxide and that this process may persist under current martian conditions. Preliminary work has shown that clay-sized carbonate grains can decompose at much lower temperatures than previously thought. The first work took carbonate, decomposed it to CaO, then flowed CO2 over these samples held at temperatures >100 degC to reform carbonates. Thermal analysis confirmed that carbonates were indeed formed and transmission electron microsopy was used to determine crystal sized were on the order of 10 nm. The next step used minerals such as diopside and wollastonite that were sealed in a glass tube with a CO2 and H2O source. After

  6. Degassing of reduced carbon from planetary basalts.

    Science.gov (United States)

    Wetzel, Diane T; Rutherford, Malcolm J; Jacobsen, Steven D; Hauri, Erik H; Saal, Alberto E

    2013-05-14

    Degassing of planetary interiors through surface volcanism plays an important role in the evolution of planetary bodies and atmospheres. On Earth, carbon dioxide and water are the primary volatile species in magmas. However, little is known about the speciation and degassing of carbon in magmas formed on other planets (i.e., Moon, Mars, Mercury), where the mantle oxidation state [oxygen fugacity (fO2)] is different from that of the Earth. Using experiments on a lunar basalt composition, we confirm that carbon dissolves as carbonate at an fO2 higher than -0.55 relative to the iron wustite oxygen buffer (IW-0.55), whereas at a lower fO2, we discover that carbon is present mainly as iron pentacarbonyl and in smaller amounts as methane in the melt. The transition of carbon speciation in mantle-derived melts at fO2 less than IW-0.55 is associated with a decrease in carbon solubility by a factor of 2. Thus, the fO2 controls carbon speciation and solubility in mantle-derived melts even more than previous data indicate, and the degassing of reduced carbon from Fe-rich basalts on planetary bodies would produce methane-bearing, CO-rich early atmospheres with a strong greenhouse potential.

  7. Fast Ss-Ilm a Computationally Efficient Algorithm to Discover Socially Important Locations

    Science.gov (United States)

    Dokuz, A. S.; Celik, M.

    2017-11-01

    Socially important locations are places which are frequently visited by social media users in their social media lifetime. Discovering socially important locations provide several valuable information about user behaviours on social media networking sites. However, discovering socially important locations are challenging due to data volume and dimensions, spatial and temporal calculations, location sparseness in social media datasets, and inefficiency of current algorithms. In the literature, several studies are conducted to discover important locations, however, the proposed approaches do not work in computationally efficient manner. In this study, we propose Fast SS-ILM algorithm by modifying the algorithm of SS-ILM to mine socially important locations efficiently. Experimental results show that proposed Fast SS-ILM algorithm decreases execution time of socially important locations discovery process up to 20 %.

  8. Einstein@Home discovers a radio-quiet gamma-ray millisecond pulsar

    Science.gov (United States)

    Clark, Colin J.; Pletsch, Holger J.; Wu, Jason; Guillemot, Lucas; Kerr, Matthew; Johnson, Tyrel J.; Camilo, Fernando; Salvetti, David; Allen, Bruce; Anderson, David; Aulbert, Carsten; Beer, Christian; Bock, Oliver; Cuéllar, Andres; Eggenstein, Heinz-Bernd; Fehrmann, Henning; Kramer, Michael; Kwang, Shawn A.; Machenschalk, Bernd; Nieder, Lars; Ackermann, Markus; Ajello, Marco; Baldini, Luca; Ballet, Jean; Barbiellini, Guido; Bastieri, Denis; Bellazzini, Ronaldo; Bissaldi, Elisabetta; Blandford, Roger D.; Bloom, Elliott D.; Bonino, Raffaella; Bottacini, Eugenio; Brandt, Terri J.; Bregeon, Johan; Bruel, Philippe; Buehler, Rolf; Burnett, Toby H.; Buson, Sara; Cameron, Rob A.; Caputo, Regina; Caraveo, Patrizia A.; Cavazzuti, Elisabetta; Cecchi, Claudia; Charles, Eric; Chekhtman, Alexandre; Ciprini, Stefano; Cominsky, Lynn R.; Costantin, Denise; Cutini, Sara; D’Ammando, Filippo; De Luca, Andrea; Desiante, Rachele; Di Venere, Leonardo; Di Mauro, Mattia; Di Lalla, Niccolò; Digel, Seth W.; Favuzzi, Cecilia; Ferrara, Elizabeth C.; Franckowiak, Anna; Fukazawa, Yasushi; Funk, Stefan; Fusco, Piergiorgio; Gargano, Fabio; Gasparrini, Dario; Giglietto, Nico; Giordano, Francesco; Giroletti, Marcello; Gomez-Vargas, Germán A.; Green, David; Grenier, Isabelle A.; Guiriec, Sylvain; Harding, Alice K.; Hewitt, John W.; Horan, Deirdre; Jóhannesson, Guðlaugur; Kensei, Shiki; Kuss, Michael; La Mura, Giovanni; Larsson, Stefan; Latronico, Luca; Li, Jian; Longo, Francesco; Loparco, Francesco; Lovellette, Michael N.; Lubrano, Pasquale; Magill, Jeffrey D.; Maldera, Simone; Manfreda, Alberto; Mazziotta, Mario N.; McEnery, Julie E.; Michelson, Peter F.; Mirabal, Nestor; Mitthumsiri, Warit; Mizuno, Tsunefumi; Monzani, Maria Elena; Morselli, Aldo; Moskalenko, Igor V.; Nuss, Eric; Ohsugi, Takashi; Omodei, Nicola; Orienti, Monica; Orlando, Elena; Palatiello, Michele; Paliya, Vaidehi S.; de Palma, Francesco; Paneque, David; Perkins, Jeremy S.; Persic, Massimo; Pesce-Rollins, Melissa; Porter, Troy A.; Principe, Giacomo; Rainò, Silvia; Rando, Riccardo; Ray, Paul S.; Razzano, Massimiliano; Reimer, Anita; Reimer, Olaf; Romani, Roger W.; Saz Parkinson, Pablo M.; Sgrò, Carmelo; Siskind, Eric J.; Smith, David A.; Spada, Francesca; Spandre, Gloria; Spinelli, Paolo; Thayer, Jana B.; Thompson, David J.; Torres, Diego F.; Troja, Eleonora; Vianello, Giacomo; Wood, Kent; Wood, Matthew

    2018-01-01

    Millisecond pulsars (MSPs) are old neutron stars that spin hundreds of times per second and appear to pulsate as their emission beams cross our line of sight. To date, radio pulsations have been detected from all rotation-powered MSPs. In an attempt to discover radio-quiet gamma-ray MSPs, we used the aggregated power from the computers of tens of thousands of volunteers participating in the Einstein@Home distributed computing project to search for pulsations from unidentified gamma-ray sources in Fermi Large Area Telescope data. This survey discovered two isolated MSPs, one of which is the only known rotation-powered MSP to remain undetected in radio observations. These gamma-ray MSPs were discovered in completely blind searches without prior constraints from other observations, raising hopes for detecting MSPs from a predicted Galactic bulge population. PMID:29503868

  9. A strategy to discover new organizers identifies a putative heart organizer.

    Science.gov (United States)

    Anderson, Claire; Khan, Mohsin A F; Wong, Frances; Solovieva, Tatiana; Oliveira, Nidia M M; Baldock, Richard A; Tickle, Cheryll; Burt, Dave W; Stern, Claudio D

    2016-08-25

    Organizers are regions of the embryo that can both induce new fates and impart pattern on other regions. So far, surprisingly few organizers have been discovered, considering the number of patterned tissue types generated during development. This may be because their discovery has relied on transplantation and ablation experiments. Here we describe a new approach, using chick embryos, to discover organizers based on a common gene expression signature, and use it to uncover the anterior intestinal portal (AIP) endoderm as a putative heart organizer. We show that the AIP can induce cardiac identity from non-cardiac mesoderm and that it can pattern this by specifying ventricular and suppressing atrial regional identity. We also uncover some of the signals responsible. The method holds promise as a tool to discover other novel organizers acting during development.

  10. Orbits of the Asteroids Discovered at the Molėtai Observatory in 2000–2004

    Directory of Open Access Journals (Sweden)

    Černis K.

    2014-12-01

    Full Text Available The paper presents statistics of the asteroids observed and discovered at the Molėtai Observatory, Lithuania in 2000–2004 within the project for astrometric observations of the near-Earth objects (NEOs, the main belt asteroids and comets. CCD observations of asteroids were obtained with the 35/51 cm Maksutov-type meniscus telescope and the 1.65 m Ritchey-Chretien reflector. In the Minor Planet Circulars and the Minor Planet Electronic Circulars (2000–2004 we published 6629 astrometric positions of 1114 asteroids. Among them 78 were newly discovered asteroids at Molėtai, a few NEOs were found by our team independently. For the 67 asteroids discovered at Molėtai the precise orbits were calculated. Because of small number of observations, a few asteroids have low-precision orbits and some asteroids have been lost. For seven objects we present their ephemerides for 2015.

  11. FAST SS-ILM: A COMPUTATIONALLY EFFICIENT ALGORITHM TO DISCOVER SOCIALLY IMPORTANT LOCATIONS

    Directory of Open Access Journals (Sweden)

    A. S. Dokuz

    2017-11-01

    Full Text Available Socially important locations are places which are frequently visited by social media users in their social media lifetime. Discovering socially important locations provide several valuable information about user behaviours on social media networking sites. However, discovering socially important locations are challenging due to data volume and dimensions, spatial and temporal calculations, location sparseness in social media datasets, and inefficiency of current algorithms. In the literature, several studies are conducted to discover important locations, however, the proposed approaches do not work in computationally efficient manner. In this study, we propose Fast SS-ILM algorithm by modifying the algorithm of SS-ILM to mine socially important locations efficiently. Experimental results show that proposed Fast SS-ILM algorithm decreases execution time of socially important locations discovery process up to 20 %.

  12. Einstein@Home discovers a radio-quiet gamma-ray millisecond pulsar.

    Science.gov (United States)

    Clark, Colin J; Pletsch, Holger J; Wu, Jason; Guillemot, Lucas; Kerr, Matthew; Johnson, Tyrel J; Camilo, Fernando; Salvetti, David; Allen, Bruce; Anderson, David; Aulbert, Carsten; Beer, Christian; Bock, Oliver; Cuéllar, Andres; Eggenstein, Heinz-Bernd; Fehrmann, Henning; Kramer, Michael; Kwang, Shawn A; Machenschalk, Bernd; Nieder, Lars; Ackermann, Markus; Ajello, Marco; Baldini, Luca; Ballet, Jean; Barbiellini, Guido; Bastieri, Denis; Bellazzini, Ronaldo; Bissaldi, Elisabetta; Blandford, Roger D; Bloom, Elliott D; Bonino, Raffaella; Bottacini, Eugenio; Brandt, Terri J; Bregeon, Johan; Bruel, Philippe; Buehler, Rolf; Burnett, Toby H; Buson, Sara; Cameron, Rob A; Caputo, Regina; Caraveo, Patrizia A; Cavazzuti, Elisabetta; Cecchi, Claudia; Charles, Eric; Chekhtman, Alexandre; Ciprini, Stefano; Cominsky, Lynn R; Costantin, Denise; Cutini, Sara; D'Ammando, Filippo; De Luca, Andrea; Desiante, Rachele; Di Venere, Leonardo; Di Mauro, Mattia; Di Lalla, Niccolò; Digel, Seth W; Favuzzi, Cecilia; Ferrara, Elizabeth C; Franckowiak, Anna; Fukazawa, Yasushi; Funk, Stefan; Fusco, Piergiorgio; Gargano, Fabio; Gasparrini, Dario; Giglietto, Nico; Giordano, Francesco; Giroletti, Marcello; Gomez-Vargas, Germán A; Green, David; Grenier, Isabelle A; Guiriec, Sylvain; Harding, Alice K; Hewitt, John W; Horan, Deirdre; Jóhannesson, Guðlaugur; Kensei, Shiki; Kuss, Michael; La Mura, Giovanni; Larsson, Stefan; Latronico, Luca; Li, Jian; Longo, Francesco; Loparco, Francesco; Lovellette, Michael N; Lubrano, Pasquale; Magill, Jeffrey D; Maldera, Simone; Manfreda, Alberto; Mazziotta, Mario N; McEnery, Julie E; Michelson, Peter F; Mirabal, Nestor; Mitthumsiri, Warit; Mizuno, Tsunefumi; Monzani, Maria Elena; Morselli, Aldo; Moskalenko, Igor V; Nuss, Eric; Ohsugi, Takashi; Omodei, Nicola; Orienti, Monica; Orlando, Elena; Palatiello, Michele; Paliya, Vaidehi S; de Palma, Francesco; Paneque, David; Perkins, Jeremy S; Persic, Massimo; Pesce-Rollins, Melissa; Porter, Troy A; Principe, Giacomo; Rainò, Silvia; Rando, Riccardo; Ray, Paul S; Razzano, Massimiliano; Reimer, Anita; Reimer, Olaf; Romani, Roger W; Saz Parkinson, Pablo M; Sgrò, Carmelo; Siskind, Eric J; Smith, David A; Spada, Francesca; Spandre, Gloria; Spinelli, Paolo; Thayer, Jana B; Thompson, David J; Torres, Diego F; Troja, Eleonora; Vianello, Giacomo; Wood, Kent; Wood, Matthew

    2018-02-01

    Millisecond pulsars (MSPs) are old neutron stars that spin hundreds of times per second and appear to pulsate as their emission beams cross our line of sight. To date, radio pulsations have been detected from all rotation-powered MSPs. In an attempt to discover radio-quiet gamma-ray MSPs, we used the aggregated power from the computers of tens of thousands of volunteers participating in the Einstein@Home distributed computing project to search for pulsations from unidentified gamma-ray sources in Fermi Large Area Telescope data. This survey discovered two isolated MSPs, one of which is the only known rotation-powered MSP to remain undetected in radio observations. These gamma-ray MSPs were discovered in completely blind searches without prior constraints from other observations, raising hopes for detecting MSPs from a predicted Galactic bulge population.

  13. Carbon-On-Carbon Manufacturing

    Science.gov (United States)

    Mungas, Gregory S. (Inventor); Buchanan, Larry (Inventor); Banzon, Jr., Jose T. (Inventor)

    2017-01-01

    The presently disclosed technology relates to carbon-on-carbon (C/C) manufacturing techniques and the resulting C/C products. One aspect of the manufacturing techniques disclosed herein utilizes two distinct curing operations that occur at different times and/or using different temperatures. The resulting C/C products are substantially non-porous, even though the curing operation(s) substantially gasify a liquid carbon-entrained filler material that saturates a carbon fabric that makes up the C/C products.

  14. Porous carbons

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    Abstract. Carbon in dense as well as porous solid form is used in a variety of applications. Activated porous carbons are made through pyrolysis and activation of carbonaceous natural as well as synthetic precursors. Pyrolysed woods replicate the structure of original wood but as such possess very low surface areas and ...

  15. Carbon photonics

    Energy Technology Data Exchange (ETDEWEB)

    Konov, V I [A M Prokhorov General Physics Institute, Russian Academy of Sciences, Moscow (Russian Federation)

    2015-11-30

    The properties of new carbon materials (single-crystal and polycrystalline CVD diamond films and wafers, single-wall carbon nanotubes and graphene) and the prospects of their use as optical elements and devices are discussed. (optical elements of laser devices)

  16. Synthesis of high luminescent carbon nanoparticles

    Science.gov (United States)

    Gvozdyuk, Alina A.; Petrova, Polina S.; Goryacheva, Irina Y.; Sukhorukov, Gleb B.

    2017-03-01

    In this article we report an effective and simple method for synthesis of high luminescent carbon nanodots (CDs). In our work as a carbon source sodium dextran sulfate (DS) was used because it is harmless, its analogs are used in medicine as antithrombotic compounds and blood substitutes after hemorrhage. was used as a substrate We investigated the influence of temperature parameters of hydrothermal synthesis on the photoluminescence (PL) intensity and position of emission maxima. We discovered that the PL intensity can be tuned by changing of synthesis temperature and CD concentration.

  17. Starlight detectives how astronomers, inventors, and eccentrics discovered the modern universe

    CERN Document Server

    Hirshfeld, Alan

    2014-01-01

    NBC News “Top Science and Tech Books of the Year" selectionScientific American/FSG “Favorite Science Books of the Year" selectionNature.com “Top Reads of the Year" selectionKirkus Reviews “Best Books of the Year" selectionDiscover magazine “Top 5 Summer Read"“A masterful balance of science, history and rich narrative." —Discover magazine“Hirshfeld tells this climactic discovery of the expanding universe with great verve and sweep, as befits a story whose scope, characters and import leave

  18. Bifunctional cis-Abienol Synthase from Abies balsamea Discovered by Transcriptome Sequencing and Its Implications for Diterpenoid Fragrance Production*

    Science.gov (United States)

    Zerbe, Philipp; Chiang, Angela; Yuen, Macaire; Hamberger, Björn; Hamberger, Britta; Draper, Jason A.; Britton, Robert; Bohlmann, Jörg

    2012-01-01

    The labdanoid diterpene alcohol cis-abienol is a major component of the aromatic oleoresin of balsam fir (Abies balsamea) and serves as a valuable bioproduct material for the fragrance industry. Using high-throughput 454 transcriptome sequencing and metabolite profiling of balsam fir bark tissue, we identified candidate diterpene synthase sequences for full-length cDNA cloning and functional characterization. We discovered a bifunctional class I/II cis-abienol synthase (AbCAS), along with the paralogous levopimaradiene/abietadiene synthase and isopimaradiene synthase, all of which are members of the gymnosperm-specific TPS-d subfamily. The AbCAS-catalyzed formation of cis-abienol proceeds via cyclization and hydroxylation at carbon C-8 of a postulated carbocation intermediate in the class II active site, followed by cleavage of the diphosphate group and termination of the reaction sequence without further cyclization in the class I active site. This reaction mechanism is distinct from that of synthases of the isopimaradiene- or levopimaradiene/abietadiene synthase type, which employ deprotonation reactions in the class II active site and secondary cyclizations in the class I active site, leading to tricyclic diterpenes. Comparative homology modeling suggested the active site residues Asp-348, Leu-617, Phe-696, and Gly-723 as potentially important for the specificity of AbCAS. As a class I/II bifunctional enzyme, AbCAS is a promising target for metabolic engineering of cis-abienol production. PMID:22337889

  19. Production and characterization of biodiesel from carbon dioxide concentrating chemolithotrophic bacteria, Serratia sp. ISTD04.

    Science.gov (United States)

    Bharti, Randhir K; Srivastava, Shaili; Thakur, Indu Shekhar

    2014-02-01

    A chemolithotrophic bacterium, Serratia sp. ISTD04, enriched in the chemostat in presence of sodium bicarbonate as sole carbon source was evaluated for potential of carbon dioxide (CO2) sequestration and biofuel production. CO2 sequestration efficiency of the bacterium was determined by enzymatic activity of carbonic anhydrase and ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO). Further, Western blot analysis confirmed presence of RuBisCO. The bacterium produced 0.487 and 0.647mgmg(-1) per unit cell dry weight of hydrocarbons and lipids respectively. The hydrocarbons were within the range of C13-C24 making it equivalent to light oil. GC-MS analysis of lipids produced by the bacterium indicated presence of C15-C20 organic compounds that made it potential source of biodiesel after transesterification. GC-MS, FTIR and NMR spectroscopic characterization of the fatty acid methyl esters revealed the presence of 55% and 45% of unsaturated and saturated organic compounds respectively, thus making it a balanced biodiesel composition. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Functional materials based on carbon nanotubes: Carbon nanotube actuators and noncovalent carbon nanotube modification

    Science.gov (United States)

    Fifield, Leonard S.

    Carbon nanotubes have attractive inherent properties that encourage the development of new functional materials and devices based on them. The use of single wall carbon nanotubes as electromechanical actuators takes advantage of the high mechanical strength, surface area and electrical conductivity intrinsic to these molecules. The work presented here investigates the mechanisms that have been discovered for actuation of carbon nanotube paper: electrostatic, quantum chemical charge injection, pneumatic and viscoelastic. A home-built apparatus for the measurement of actuation strain is developed and utilized in the investigation. An optical fiber switch, the first demonstrated macro-scale device based on the actuation of carbon nanotubes, is described and its performance evaluated. Also presented here is a new general process designed to modify the surface of carbon nanotubes in a non-covalent, non-destructive way. This method can be used to impart new functionalities to carbon nanotube samples for a variety of applications including sensing, solar energy conversion and chemical separation. The process described involves the achievement of large degrees of graphitic surface coverage with polycyclic aromatic hydrocarbons through the use of supercritical fluids. These molecules are bifunctional agents that anchor a desired chemical group to the aromatic surface of the carbon nanotubes without adversely disrupting the conjugated backbone that gives rise the attractive electronic and physical properties of the nanotubes. Both the nanotube functionalization work and the actuator work presented here emphasize how an understanding and control of nanoscale structure and phenomena can be of vital importance in achieving desired performance for active materials. Opportunities for new devices with improved function over current state-of-the-art can be envisioned and anticipated based on this understanding and control.

  1. Carbon monoxide

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-31

    The document identifies the main sources of carbon monoxide (CO) in the general outdoor atmosphere, describes methods of measuring and monitoring its concentration levels in the United Kingdom, and discusses the effects of carbon monoxide on human health. Following its review, the Panel has put forward a recommendation for an air quality standard for carbon monoxide in the United Kingdom of 10 ppm, measured as a running 8-hour average. The document includes tables and graphs of emissions of CO, in total and by emission source, and on the increase in blood levels of carboxyhaemoglobin with continuing exposure to CO. 11 refs., 4 figs., 4 tabs.

  2. Discovering and explaining work-family strategies of parents in Luxembourg

    NARCIS (Netherlands)

    Zhelyazkova, Nevena

    2014-01-01

    The presented analysis discovers and explains typical patterns of work-family reconciliation for parents who had a child in the same period (2003) and in the same country (Luxembourg), thus facing the same macroeconomic and institutional conditions. Work-family trajectories are reconstructed as

  3. The navel orangeworm, Amyelois transtilla (Walker) (Lepidoptera: Pyralidae) discovered in northeastern Mexico feeding on Sapindaceae

    Science.gov (United States)

    Amyelois transitella (Walker) (Lepidoptera: Pyralidae), the navel orangeworm, is an important pest of a wide variety fruits and their seeds. We discovered and report for the first time A. transitella feeding on Sapindaceae in wild populations of U. speciosa (Endl.) in northeastern Mexico. We provid...

  4. Discovering Inexpensive, Effective Catalysts for Solar Energy Conversion: An Authentic Research Laboratory Experience

    Science.gov (United States)

    Shaner, Sarah E.; Hooker, Paul D.; Nickel, Anne-Marie; Leichtfuss, Amanda R.; Adams, Carissa S.; de la Cerda, Dionisia; She, Yuqi; Gerken, James B.; Pokhrel, Ravi; Ambrose, Nicholas J.; Khaliqi, David; Stahl, Shannon S.; Schuttlefield Christus, Jennifer D.

    2016-01-01

    Electrochemical water oxidation is a major focus of solar energy conversion efforts. A new laboratory experiment has been developed that utilizes real-time, hands-on research to discover catalysts for solar energy conversion. The HARPOON, or Heterogeneous Anodes Rapidly Perused for Oxygen Overpotential Neutralization, experiment allows an array of…

  5. Incidence of and sequels to medical problems discovered in medical students during study-related activities

    NARCIS (Netherlands)

    Pols, J; Boendermaker, PM; Muntinghe, H

    2003-01-01

    Purpose Students often act as subjects during practical and clinical skills training sessions. This routine seems to be quite acceptable for them but may present side-effects. Disorders, sometimes of a serious nature, have been discovered in medical students during clinical skills training. Because

  6. Examining Pre-K Professional Development Programs: Discovering the Road to Exceptional Instructional Practices

    Science.gov (United States)

    Williams, Sheila D.

    2016-01-01

    The purpose of this qualitative research study was to discover and interpret the experiences of pre-k teachers in an urban school district located in a Northeastern region of the United States. Using a basic qualitative research design, fifteen participants were recruited by a purposeful sampling method to be interviewed after the implementation…

  7. Discovering frequently recurring movement sequences in team-sport athlete spatiotemporal data.

    Science.gov (United States)

    Sweeting, Alice J; Aughey, Robert J; Cormack, Stuart J; Morgan, Stuart

    2017-12-01

    Athlete external load is typically analysed from predetermined movement thresholds. The combination of movement sequences and differences in these movements between playing positions is also currently unknown. This study developed a method to discover the frequently recurring movement sequences across playing position during matches. The external load of 12 international female netball athletes was collected by a local positioning system during four national-level matches. Velocity, acceleration and angular velocity were calculated from positional (X, Y) data, clustered via one-dimensional k-means and assigned a unique alphabetic label. Combinations of velocity, acceleration and angular velocity movement were compared using the Levenshtein distance and similarities computed by the longest common substring problem. The contribution of each movement sequence, according to playing position and relative to the wider data set, was then calculated via the Minkowski distance. A total of 10 frequently recurring combinations of movement were discovered, regardless of playing position. Only the wing attack, goal attack and goal defence playing positions are closely related. We developed a technique to discover the movement sequences, according to playing position, performed by elite netballers. This methodology can be extended to discover the frequently recurring movements within other team sports and across levels of competition.

  8. Newly Discovered Items of the Zoomorphic Style from the Left Bank of the Lower Dniester

    Directory of Open Access Journals (Sweden)

    Sinika Vitalij S.

    2017-09-01

    Full Text Available The article presents an overview of items corresponding to the Scythian zoomorphic style discovered at barbaric and ancient sites of the Northwestern Black Sea Region, and a publication of two new findings. They were discovered on the left bank of the Lower Dniester. The first item discovered at Parkany-II settlement is a fragment of a bronze horse plaque (its lower part crafted in the shape of a "rooster"-hippocampus. The other artifact discovered near Tokmazeya village also represents a horse plaque with an image of a cat predator's head. Presently, there are no counterparts of the images on these findings in the Northwestern Black Sea Region, which is the westmost periphery of the Scythian steppe culture. These fragments of horse apparel broaden our knowledge of the Scythian "bestiary" in the region. Besides, apart from the other items of material culture, the published findings confirm the presence of Scythian population at settlement sites, which contradicts the generally accepted opinion on the exclusively nomadic cattle breeding lifestyle of the Scythians in 5th –4th centuries B.C.

  9. Tuppiap Qeqertaa (Tobias Island): a newly discovered island off northeast Greenland

    DEFF Research Database (Denmark)

    Bennike, O.; Mikkelsen, N.; Forsberg, René

    2006-01-01

    The small island of Tuppiap Qeqertaa, formerly known as Tobias circle divide or Tobias Island, is situated 80 km off the northeast Greenland coast. The island was discovered in 1993 and is approximately 2 km long and 1.5 km wide. Most of the island is covered by an ice cap that rises to 35 in abo...

  10. Discovering Trigonometric Relationships Implied by the Law of Sines and the Law of Cosines

    Science.gov (United States)

    Skurnick, Ronald; Javadi, Mohammad

    2006-01-01

    The Law of Sines and The Law of Cosines are of paramount importance in the field of trigonometry because these two theorems establish relationships satisfied by the three sides and the three angles of any triangle. In this article, the authors use these two laws to discover a host of other trigonometric relationships that exist within any…

  11. A Phenomenological Study to Discover Low-Income Adults' Perceptions and Expectations Regarding Financial Literacy

    Science.gov (United States)

    Schaffer, Brigid Ann

    2013-01-01

    This phenomenological study explored the perceptions and expectations of low income adults regarding financial literacy to discover ways to increase attendance in financial literacy programs designs for this cohort. The study utilized interviews with closed-ended questions to establish the participants' backgrounds, then opened-ended questions to…

  12. Communication between the right and circumflex coronary arteries discovered incidentally by multidetector computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Se Hwan; Kim, Eui Jong; Woo, Jong Shin; Kim, Soo Joong; Youn, Hyo Chul; Oh, Joo Hyeong [College of Medicine, Kyung Hee University, Seoul (Korea, Republic of)

    2016-09-15

    Intercoronary communication is a rare congenital coronary anomaly. We present a case of a 48-year-old man with an incidentally discovered communication between the right and circumflex coronary arteries, who was admitted with chest tightness and exertional dyspnea. The initial diagnosis was made using electrocardiogram-gated multidetector computed tomography.

  13. Discovering the Art of Mathematics: Using String Art to Investigate Calculus

    Science.gov (United States)

    von Renesse, Christine; Ecke, Volker

    2016-01-01

    One goal of our Discovering the Art of Mathematics project is to empower students in the liberal arts to become confident creators of art and imaginative creators of mathematics. In this paper, we describe our experience with using string art to guide liberal arts students in exploring ideas of calculus. We provide excerpts from our inquiry-based…

  14. "Discovering the Cell": An Educational Game about Cell and Molecular Biology

    Science.gov (United States)

    Spiegel, Carolina N.; Alves, Gutemberg G.; Cardona, Tania da S.; Melim, Leandra M. C.; Luz, Mauricio R. M. P.; Araujo-Jorge, Tania C.; Henriques-Pons, Andrea

    2008-01-01

    The role of games within education becomes clearer as students become more active and are able to take decisions, solve problems and react to the results of those decisions. The educational board game "Discovering the Cell" ("Celula Adentro"), is based on problem-solving learning. This investigative game attempts to stimulate…

  15. A highly abundant bacteriophage discovered in the unknown sequences of human faecal metagenomes

    NARCIS (Netherlands)

    Dutilh, Bas E; Cassman, Noriko; McNair, Katelyn; Sanchez, Savannah E; Silva, Genivaldo G Z; Boling, Lance; Barr, Jeremy J; Speth, Daan R; Seguritan, Victor; Aziz, Ramy K; Felts, Ben; Dinsdale, Elizabeth A; Mokili, John L; Edwards, Robert A

    2014-01-01

    Metagenomics, or sequencing of the genetic material from a complete microbial community, is a promising tool to discover novel microbes and viruses. Viral metagenomes typically contain many unknown sequences. Here we describe the discovery of a previously unidentified bacteriophage present in the

  16. CWI cryptanalyst discovers new cryptographic attack variant in Flame spy malware

    NARCIS (Netherlands)

    M.M.J. Stevens (Marc); R.J.F. Cramer (Ronald)

    2012-01-01

    htmlabstractCryptanalyst Marc Stevens from the Centrum Wiskunde & Informatica (CWI) in Amsterdam, known for breaking the https security in 2008 using a cryptanalytic attack on MD5, analyzed the recent Flame virus this week. He discovered that for this spy malware an as yet unknown cryptographic

  17. Discovering and Exploring State-based Models for Multi-perspective Processes

    NARCIS (Netherlands)

    van Eck, M.L.; Sidorova, N.; van der Aalst, W.M.P.; La Rosa, M.; Loos, P.; Pastor, O.

    2016-01-01

    Process mining provides fact-based insights into process behaviour captured in event data. In this work we aim to discover models for processes where different facets, or perspectives, of the process can be identified. Instead of focussing on the events or activities that are executed in the context

  18. A non-parametric hierarchical model to discover behavior dynamics from tracks

    NARCIS (Netherlands)

    Kooij, J.F.P.; Englebienne, G.; Gavrila, D.M.

    2012-01-01

    We present a novel non-parametric Bayesian model to jointly discover the dynamics of low-level actions and high-level behaviors of tracked people in open environments. Our model represents behaviors as Markov chains of actions which capture high-level temporal dynamics. Actions may be shared by

  19. Two Herbig-Haro objects discovered by narrow-band CCD imagery

    International Nuclear Information System (INIS)

    Ogura, Katsuo

    1990-01-01

    Two new Herbig-Haro objects, HH 132 and HH 133, have been discovered by CCD imagery behind interference filters on and just off the forbidden S II lines in the red. They are located in Puppis R2 and in Vela R2. Possible locations of their exciting sources are discussed. 12 refs

  20. Using Appreciative Inquiry to Discover and Deliver Change for Surgical Technology Students

    Science.gov (United States)

    Cabai, Katherine A.

    2012-01-01

    The purpose of this study was to examine efficacious teaching-learning strategies that community college stakeholders employ that enhance surgical technology student outcomes. Knowles's adult learning theory, constructivist theory, and appreciative inquiry served as the theoretical foundation for this study. Discovering effective aspects and…

  1. Bioprecipitation of Calcium Carbonate Crystals by Bacteria Isolated from Saline Environments Grown in Culture Media Amended with Seawater and Real Brine

    Directory of Open Access Journals (Sweden)

    G. A. Silva-Castro

    2015-01-01

    Full Text Available The precipitation of calcium carbonate and calcium sulphate by isolated bacteria from seawater and real brine obtained in a desalination plant growth in culture media containing seawater and brine as mineral sources has been studied. However, only bioprecipitation was detected when the bacteria were grown in media with added organic matter. Biomineralization process started rapidly, crystal formation taking place in the beginning a few days after inoculation of media; roughly 90% of total cultivated bacteria showed. Six major colonies with carbonate precipitation capacity dominated bacterial community structure cultivated in heterotrophic platable bacteria medium. Taxonomic identification of these six strains through partial 16S rRNA gene sequences showed their affiliation with Gram-positive Bacillus and Virgibacillus genera. These strains were able to form calcium carbonate minerals, which precipitated as calcite and aragonite crystals and showed bacterial fingerprints or bacteria calcification. Also, carbonic anhydrase activity was observed in three of these isolated bacteria. The results of this research suggest that microbiota isolated from sea water and brine is capable of precipitation of carbonate biominerals, which can occur in situ with mediation of organic matter concentrations. Moreover, calcium carbonate precipitation ability of this microbiota could be of importance in bioremediation of CO2 and calcium in certain environments.

  2. Calcium Carbonate

    Science.gov (United States)

    ... Calcium is needed by the body for healthy bones, muscles, nervous system, and heart. Calcium carbonate also ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

  3. Low oxygen affects photophysiology and the level of expression of two-carbon metabolism genes in the seagrass Zostera muelleri.

    Science.gov (United States)

    Kim, Mikael; Brodersen, Kasper Elgetti; Szabó, Milán; Larkum, Anthony W D; Raven, John A; Ralph, Peter J; Pernice, Mathieu

    2018-05-01

    Seagrasses are a diverse group of angiosperms that evolved to live in shallow coastal waters, an environment regularly subjected to changes in oxygen, carbon dioxide and irradiance. Zostera muelleri is the dominant species in south-eastern Australia, and is critical for healthy coastal ecosystems. Despite its ecological importance, little is known about the pathways of carbon fixation in Z. muelleri and their regulation in response to environmental changes. In this study, the response of Z. muelleri exposed to control and very low oxygen conditions was investigated by using (i) oxygen microsensors combined with a custom-made flow chamber to measure changes in photosynthesis and respiration, and (ii) reverse transcription quantitative real-time PCR to measure changes in expression levels of key genes involved in C 4 metabolism. We found that very low levels of oxygen (i) altered the photophysiology of Z. muelleri, a characteristic of C 3 mechanism of carbon assimilation, and (ii) decreased the expression levels of phosphoenolpyruvate carboxylase and carbonic anhydrase. These molecular-physiological results suggest that regulation of the photophysiology of Z. muelleri might involve a close integration between the C 3 and C 4 , or other CO 2 concentrating mechanisms metabolic pathways. Overall, this study highlights that the photophysiological response of Z. muelleri to changing oxygen in water is capable of rapid acclimation and the dynamic modulation of pathways should be considered when assessing seagrass primary production.

  4. Microalgal bacterial flocs treating paper mill effluent: A sunlight-based approach for removing carbon, nitrogen, phosphorus, and calcium.

    Science.gov (United States)

    Van Den Hende, Sofie; Rodrigues, André; Hamaekers, Helen; Sonnenholzner, Stanislaus; Vervaeren, Han; Boon, Nico

    2017-10-25

    Treatment of upflow anaerobic sludge blanket (UASB) effluent from a paper mill in aerated activated sludge reactors involves high aeration costs. Moreover, this calcium-rich effluent leads to problematic scale formation. Therefore, a novel strategy for the aerobic treatment of paper mill UASB effluent in microalgal bacterial floc sequencing batch reactors (MaB-floc SBRs) is proposed, in which oxygen is provided via photosynthesis, and calcium is removed via bio-mineralization. Based on the results of batch experiments in the course of this study, a MaB-floc SBR was operated at an initial neutral pH. This SBR removed 58±21% organic carbon, 27±8% inorganic carbon, 77±5% nitrogen, 73±2% phosphorus, and 27±11% calcium. MaB-flocs contained 10±3% calcium, including biologically-influenced calcite crystals. The removal of calcium and inorganic carbon by MaB-flocs significantly decreased when inhibiting extracellular carbonic anhydrase (CA), an enzyme that catalyses the hydration and dehydration of CO 2 . This study demonstrates the potential of MaB-floc SBRs for the alternative treatment of calcium-rich paper mill effluent, and highlights the importance of extracellular CA in this treatment process. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Infiltrated carbon foam composites

    Science.gov (United States)

    Lucas, Rick D. (Inventor); Danford, Harry E. (Inventor); Plucinski, Janusz W. (Inventor); Merriman, Douglas J. (Inventor); Blacker, Jesse M. (Inventor)

    2012-01-01

    An infiltrated carbon foam composite and method for making the composite is described. The infiltrated carbon foam composite may include a carbonized carbon aerogel in cells of a carbon foam body and a resin is infiltrated into the carbon foam body filling the cells of the carbon foam body and spaces around the carbonized carbon aerogel. The infiltrated carbon foam composites may be useful for mid-density ablative thermal protection systems.

  6. Discovering Land Cover Web Map Services from the Deep Web with JavaScript Invocation Rules

    Directory of Open Access Journals (Sweden)

    Dongyang Hou

    2016-06-01

    Full Text Available Automatic discovery of isolated land cover web map services (LCWMSs can potentially help in sharing land cover data. Currently, various search engine-based and crawler-based approaches have been developed for finding services dispersed throughout the surface web. In fact, with the prevalence of geospatial web applications, a considerable number of LCWMSs are hidden in JavaScript code, which belongs to the deep web. However, discovering LCWMSs from JavaScript code remains an open challenge. This paper aims to solve this challenge by proposing a focused deep web crawler for finding more LCWMSs from deep web JavaScript code and the surface web. First, the names of a group of JavaScript links are abstracted as initial judgements. Through name matching, these judgements are utilized to judge whether or not the fetched webpages contain predefined JavaScript links that may prompt JavaScript code to invoke WMSs. Secondly, some JavaScript invocation functions and URL formats for WMS are summarized as JavaScript invocation rules from prior knowledge of how WMSs are employed and coded in JavaScript. These invocation rules are used to identify the JavaScript code for extracting candidate WMSs through rule matching. The above two operations are incorporated into a traditional focused crawling strategy situated between the tasks of fetching webpages and parsing webpages. Thirdly, LCWMSs are selected by matching services with a set of land cover keywords. Moreover, a search engine for LCWMSs is implemented that uses the focused deep web crawler to retrieve and integrate the LCWMSs it discovers. In the first experiment, eight online geospatial web applications serve as seed URLs (Uniform Resource Locators and crawling scopes; the proposed crawler addresses only the JavaScript code in these eight applications. All 32 available WMSs hidden in JavaScript code were found using the proposed crawler, while not one WMS was discovered through the focused crawler

  7. Discovering Pediatric Asthma Phenotypes on the Basis of Response to Controller Medication Using Machine Learning.

    Science.gov (United States)

    Ross, Mindy K; Yoon, Jinsung; van der Schaar, Auke; van der Schaar, Mihaela

    2018-01-01

    Pediatric asthma has variable underlying inflammation and symptom control. Approaches to addressing this heterogeneity, such as clustering methods to find phenotypes and predict outcomes, have been investigated. However, clustering based on the relationship between treatment and clinical outcome has not been performed, and machine learning approaches for long-term outcome prediction in pediatric asthma have not been studied in depth. Our objectives were to use our novel machine learning algorithm, predictor pursuit (PP), to discover pediatric asthma phenotypes on the basis of asthma control in response to controller medications, to predict longitudinal asthma control among children with asthma, and to identify features associated with asthma control within each discovered pediatric phenotype. We applied PP to the Childhood Asthma Management Program study data (n = 1,019) to discover phenotypes on the basis of asthma control between assigned controller therapy groups (budesonide vs. nedocromil). We confirmed PP's ability to discover phenotypes using the Asthma Clinical Research Network/Childhood Asthma Research and Education network data. We next predicted children's asthma control over time and compared PP's performance with that of traditional prediction methods. Last, we identified clinical features most correlated with asthma control in the discovered phenotypes. Four phenotypes were discovered in both datasets: allergic not obese (A + /O - ), obese not allergic (A - /O + ), allergic and obese (A + /O + ), and not allergic not obese (A - /O - ). Of the children with well-controlled asthma in the Childhood Asthma Management Program dataset, we found more nonobese children treated with budesonide than with nedocromil (P = 0.015) and more obese children treated with nedocromil than with budesonide (P = 0.008). Within the obese group, more A + /O + children's asthma was well controlled with nedocromil than with budesonide (P = 0.022) or with placebo

  8. Carbon sequestration.

    Science.gov (United States)

    Lal, Rattan

    2008-02-27

    Developing technologies to reduce the rate of increase of atmospheric concentration of carbon dioxide (CO2) from annual emissions of 8.6PgCyr-1 from energy, process industry, land-use conversion and soil cultivation is an important issue of the twenty-first century. Of the three options of reducing the global energy use, developing low or no-carbon fuel and sequestering emissions, this manuscript describes processes for carbon (CO2) sequestration and discusses abiotic and biotic technologies. Carbon sequestration implies transfer of atmospheric CO2 into other long-lived global pools including oceanic, pedologic, biotic and geological strata to reduce the net rate of increase in atmospheric CO2. Engineering techniques of CO2 injection in deep ocean, geological strata, old coal mines and oil wells, and saline aquifers along with mineral carbonation of CO2 constitute abiotic techniques. These techniques have a large potential of thousands of Pg, are expensive, have leakage risks and may be available for routine use by 2025 and beyond. In comparison, biotic techniques are natural and cost-effective processes, have numerous ancillary benefits, are immediately applicable but have finite sink capacity. Biotic and abiotic C sequestration options have specific nitches, are complementary, and have potential to mitigate the climate change risks.

  9. Chemical Abundance Measurements of Ultra-Faint Dwarf Galaxies Discovered by the Dark Energy Survey

    Science.gov (United States)

    Nagasawa, Daniel; Marshall, Jennifer L.; Simon, Joshua D.; Hansen, Terese; Li, Ting; Bernstein, Rebecca; Balbinot, Eduardo; Drlica-Wagner, Alex; Pace, Andrew; Strigari, Louis; Pellegrino, Craig; DePoy, Darren L.; Suntzeff, Nicholas; Bechtol, Keith; Dark Energy Suvey

    2018-01-01

    We present chemical abundance analysis results derived from high-resolution spectroscopy of ultra-faint dwarfs discovered by the Dark Energy Survey. Ultra-faint dwarf galaxies preserve a fossil record of the chemical abundance patterns imprinted by the first stars in the Universe. High-resolution spectroscopic observations of member stars in several recently discovered Milky Way satellites reveal a range of abundance patterns among ultra-faint dwarfs suggesting that star formation processes in the early Universe were quite diverse. The chemical content provides a glimpse not only of the varied nucleosynthetic processes and chemical history of the dwarfs themselves, but also the environment in which they were formed. We present the chemical abundance analysis of these objects and discuss possible explanations for the observed abundance patterns.

  10. Incidentally found and unexpected tumors discovered by MRI examination for temporomandibular joint arthrosis

    Energy Technology Data Exchange (ETDEWEB)

    Yanagi, Yoshinobu; Asaumi, Jun-ichi E-mail: asaumi@md.okayama-u.ac.jp; Maki, Yuu; Murakami, Jun; Hisatomi, Miki; Matsuzaki, Hidenobu; Konouchi, Hironobu; Honda, Yosutoshi; Kishi, Kanji

    2003-07-01

    We examined the frequency of incidentally found or unexpected tumors discovered at the time of magnetic resonance imaging (MRI) examinations in the temporomandibular joint (TMJ) region for patients with suspicion of TMJ arthrosis. Five MR images (T1-weighted transverse scout image and proton density and T2-weighted oblique sagittal images at the open and closed mouth) were acquired. In 2776 MRI examinations of TMJ arthrosis, two tumors were discovered. They consisted of an adenoid cystic carcinoma in the deep portion of the parotid gland, and a malignant tumor extending from the infratemporal fossa to the parapharyngeal space. The rate of incidentally founded or unexpected tumors in TMJ examinations was low (0.072%), but the two tumors found were malignant tumors, and therefore, scout image should be carefully examined, not only used for positing the slice.

  11. Description of a newly discovered Triatoma infestans (Hemiptera: Reduviidae Foci in Ibipeba, State of Bahia, Brazil

    Directory of Open Access Journals (Sweden)

    Renato Freitas Araújo

    2014-07-01

    Full Text Available Introduction Chagas disease transmitted by the Triatoma infestans was eradicated from Brazil in 2006. However, reports of triatomine foci threaten the control of Chagas disease. The goal of this study was to determine T. infestans foci in the City of Ibipeba, State of Bahia. Methods Triatominae specimens were collected in Ibipeba and entomologic indicators were calculated using indices of domiciliary infestation, density, and colonization. Results T. infestans foci was discovery in Ibipeba, State of Bahia. Approximately 95% of the specimens were discovered inside dwellings, of which 34% were T. infestans. This species was also discovered forming a colony in tree bark in the peridomicile. Conclusions Triatoma infestans foci in peridomestic ecotopes in Ibipeba, BA, indicate increased the risk of transmission Chagas disease.

  12. Discovering disease-associated genes in weighted protein-protein interaction networks

    Science.gov (United States)

    Cui, Ying; Cai, Meng; Stanley, H. Eugene

    2018-04-01

    Although there have been many network-based attempts to discover disease-associated genes, most of them have not taken edge weight - which quantifies their relative strength - into consideration. We use connection weights in a protein-protein interaction (PPI) network to locate disease-related genes. We analyze the topological properties of both weighted and unweighted PPI networks and design an improved random forest classifier to distinguish disease genes from non-disease genes. We use a cross-validation test to confirm that weighted networks are better able to discover disease-associated genes than unweighted networks, which indicates that including link weight in the analysis of network properties provides a better model of complex genotype-phenotype associations.

  13. Incidentally found and unexpected tumors discovered by MRI examination for temporomandibular joint arthrosis

    International Nuclear Information System (INIS)

    Yanagi, Yoshinobu; Asaumi, Jun-ichi; Maki, Yuu; Murakami, Jun; Hisatomi, Miki; Matsuzaki, Hidenobu; Konouchi, Hironobu; Honda, Yosutoshi; Kishi, Kanji

    2003-01-01

    We examined the frequency of incidentally found or unexpected tumors discovered at the time of magnetic resonance imaging (MRI) examinations in the temporomandibular joint (TMJ) region for patients with suspicion of TMJ arthrosis. Five MR images (T1-weighted transverse scout image and proton density and T2-weighted oblique sagittal images at the open and closed mouth) were acquired. In 2776 MRI examinations of TMJ arthrosis, two tumors were discovered. They consisted of an adenoid cystic carcinoma in the deep portion of the parotid gland, and a malignant tumor extending from the infratemporal fossa to the parapharyngeal space. The rate of incidentally founded or unexpected tumors in TMJ examinations was low (0.072%), but the two tumors found were malignant tumors, and therefore, scout image should be carefully examined, not only used for positing the slice

  14. New background quasars in the vicinity of the Andromeda Galaxy discovered with the Guoshoujing Telescope (LAMOST)

    International Nuclear Information System (INIS)

    Huo Zhiying; Liu Xiaowei; Yuan Haibo; Zhang Huihua; Zhang Huawei; Zhao Yongheng; Chen Jianjun; Bai Zhongrui; Zhang Haotong; Yan Hongliang; Ren Juanjuan; Sun Shiwei; GarcIa-Benito, Ruben; Xiang Maosheng; Zhang Yong; Li Yeping; Lu Qishuai; Wang You; Ni Jijun; Wang Hai

    2010-01-01

    We present preliminary analyses of spectra of quasar candidates in two Guoshoujing Telescope (GSJT, formerly named the Large Sky Area Multi-Object Fiber Spectroscopic Telescope - LAMOST) test fields near M 31 where one is close to the optical center of the disk and the other is towards the northeastern outskirts of the halo, obtained during the early stage of the GSJT commissioning in the last season of 2009. Both fields contain background low-redshift quasar candidates selected from the SDSS photometry. In total, 14 new quasars with redshifts up to 2 and i magnitudes between 16.7 and 19.2, are discovered, including 7 within the 2.5 0 central region of M 31. We briefly discuss the potential applications of these newly discovered bright quasars. (editor's recommendation)

  15. Caught in the act: discovering secreted proteins from fungi and oomycetes in action

    DEFF Research Database (Denmark)

    Roth, Doris; Grell, Morten Nedergaard; Jensen, Annette Bruun

    Host-microbe relationships largely rely on secreted proteins like enzymes, virulence factors and antimicrobial peptides. To discover proteins secreted by microbe and host during the interaction with each other, we produced dual-organism cDNA libraries from three different fungus- or oomycete-infe......, by applying a similar strategy with a fungus-only library. As a result, we will show that our approach is widely applicable and allows us to deepen the understanding a variety of different host-microbe systems.......Host-microbe relationships largely rely on secreted proteins like enzymes, virulence factors and antimicrobial peptides. To discover proteins secreted by microbe and host during the interaction with each other, we produced dual-organism cDNA libraries from three different fungus- or oomycete...

  16. GraphTeams: a method for discovering spatial gene clusters in Hi-C sequencing data.

    Science.gov (United States)

    Schulz, Tizian; Stoye, Jens; Doerr, Daniel

    2018-05-08

    Hi-C sequencing offers novel, cost-effective means to study the spatial conformation of chromosomes. We use data obtained from Hi-C experiments to provide new evidence for the existence of spatial gene clusters. These are sets of genes with associated functionality that exhibit close proximity to each other in the spatial conformation of chromosomes across several related species. We present the first gene cluster model capable of handling spatial data. Our model generalizes a popular computational model for gene cluster prediction, called δ-teams, from sequences to graphs. Following previous lines of research, we subsequently extend our model to allow for several vertices being associated with the same label. The model, called δ-teams with families, is particular suitable for our application as it enables handling of gene duplicates. We develop algorithmic solutions for both models. We implemented the algorithm for discovering δ-teams with families and integrated it into a fully automated workflow for discovering gene clusters in Hi-C data, called GraphTeams. We applied it to human and mouse data to find intra- and interchromosomal gene cluster candidates. The results include intrachromosomal clusters that seem to exhibit a closer proximity in space than on their chromosomal DNA sequence. We further discovered interchromosomal gene clusters that contain genes from different chromosomes within the human genome, but are located on a single chromosome in mouse. By identifying δ-teams with families, we provide a flexible model to discover gene cluster candidates in Hi-C data. Our analysis of Hi-C data from human and mouse reveals several known gene clusters (thus validating our approach), but also few sparsely studied or possibly unknown gene cluster candidates that could be the source of further experimental investigations.

  17. Yes, Aboriginal Australians can and did discover the variability of Betelgeuse

    Science.gov (United States)

    Schaefer, Bradley E.

    2018-04-01

    Recently, a widely publicized claim has been made that the Aboriginal Australians discovered the variability of the red star Betelgeuse in the modern Orion, plus the variability of two other prominent red stars: Aldebaran and Antares. This result has excited the usual healthy skepticism, with questions about whether any untrained peoples can discover the variability and whether such a discovery is likely to be placed into lore and transmitted for long periods of time. Here, I am offering an independent evaluation, based on broad experience with naked-eye sky viewing and astro-history. I find that it is easy for inexperienced observers to detect the variability of Betelgeuse over its range in brightness from V = 0.0 to V = 1.3, for example in noticing from season-to-season that the star varies from significantly brighter than Procyon to being greatly fainter than Procyon. Further, indigenous peoples in the Southern Hemisphere inevitably kept watch on the prominent red star, so it is inevitable that the variability of Betelgeuse was discovered many times over during the last 65 millennia. The processes of placing this discovery into a cultural context (in this case, put into morality stories) and the faithful transmission for many millennia is confidently known for the Aboriginal Australians in particular. So this shows that the whole claim for a changing Betelgeuse in the Aboriginal Australian lore is both plausible and likely. Given that the discovery and transmission is easily possible, the real proof is that the Aboriginal lore gives an unambiguous statement that these stars do indeed vary in brightness, as collected by many ethnographers over a century ago from many Aboriginal groups. So I strongly conclude that the Aboriginal Australians could and did discover the variability of Betelgeuse, Aldebaran, and Antares.

  18. National Security Cutter: Enhanced Oversight Needed to Ensure Problems Discovered during Testing and Operations Are Addressed

    Science.gov (United States)

    2016-01-01

    May Lead to NSCs and Future DHS Assets Deploying without Having Demonstrated Full Capabilities 22 Performance Issues Discovered Outside of IOT &E...Examples of National Security Cutter Critical Operational Issues and Key Performance Parameters 10 Table 3: National Security Cutter Major...Cutter IOT &E Initial Operational Test and Evaluation KPP Key Performance Parameter LRI-II Long-Range Interceptor II NSC National Security Cutter

  19. Discover Earth: an earth system science program for libraries and their communities

    Science.gov (United States)

    Dusenbery, P.

    2011-12-01

    The view from space has deepened our understanding of Earth as a global, dynamic system. Instruments on satellites and spacecraft, coupled with advances in ground-based research, have provided us with astonishing new perspectives of our planet. Now more than ever, enhancing the public's understanding of Earth's physical and biological systems is vital to helping citizens make informed policy decisions especially when they are faced with the consequences of global climate change. While the focus for education reform is on school improvement, there is considerable research that supports the role that out-of-school experiences can play in student achievement. Libraries provide an untapped resource for engaging underserved youth and their families in fostering an appreciation and deeper understanding of science and technology topics. The Space Science Institute's National Center for Interactive Learning (NCIL) in partnership with the American Library Association (ALA), the Lunar and Planetary Institute (LPI), and the National Girls Collaborative Project (NGCP) have received funding from NSF to develop a national project called the STAR Library Education Network: a hands-on learning program for libraries and their communities (or STAR-Net for short). STAR stands for Science-Technology, Activities and Resources. STAR-Net includes two exhibitions: Discover Earth and Discover Tech. The Discover Earth exhibition will focus on local earth science topics-such as weather, water cycle, and ecosystem changes-as well as a global view of our changing planet. The main take-away message (or Big Idea) for this exhibition is that the global environment changes - and is changed by - the host community's local environment. The project team is testing whether this approach will be a good strategy for engaging the public, especially in rural America. This presentation will provide an overview of the Discover Earth project and how it is integrating climate change ideas into the exhibit

  20. Discovering and explaining work-family strategies of parents in Luxembourg

    OpenAIRE

    Zhelyazkova, Nevena

    2014-01-01

    The presented analysis discovers and explains typical patterns of work-family reconciliation for parents who had a child in the same period (2003) and in the same country (Luxembourg), thus facing the same macroeconomic and institutional conditions. Work-family trajectories are reconstructed as sequences of states using administrative records, so that working hours and use of leave provisions or other social security benefits are taken into account. Next, a clustering algorithm is applied to ...