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Sample records for 250-kv embl enantiomorphic

  1. An enantiomorphic blumlein impulse generator

    SciTech Connect

    Rinehart, L.F.; Buttram, M.T.; Crowe, W.R.; Clark, R.S.; Lundstrom, J.M.; Patterson, P.E.

    1992-01-01

    Working designs exist for 1 GW, 1 kHz ultra-wideband (UWB) sources (e.g. SNIPER). As these generators are pressed to higher peak powers and repetition rates, insulation, energy loss due to stray capacitance, and system efficiency (including power supplies and modulators) become critical issues. The EnantioMorphic (mirror image) BLumlein (EMBL) is a new type of vector inversion transmission line pulser which is designed to alleviate some of these problems. The design goals for EMBL are : >500 kV, {approximately}1 kHz rep-rate and <100 ps risetime in a 50 ohm geometry. In addition to the pulse forming line (PFL), EMBL also requires a high rep-rate modulator, primary switch, and peaking switch which will be described. Empirical design equations for peaking switch performance are included.

  2. An enantiomorphic blumlein impulse generator

    SciTech Connect

    Rinehart, L.F.; Buttram, M.T.; Crowe, W.R.; Clark, R.S.; Lundstrom, J.M.; Patterson, P.E.

    1992-07-01

    Working designs exist for 1 GW, 1 kHz ultra-wideband (UWB) sources (e.g. SNIPER). As these generators are pressed to higher peak powers and repetition rates, insulation, energy loss due to stray capacitance, and system efficiency (including power supplies and modulators) become critical issues. The EnantioMorphic (mirror image) BLumlein (EMBL) is a new type of vector inversion transmission line pulser which is designed to alleviate some of these problems. The design goals for EMBL are : >500 kV, {approximately}1 kHz rep-rate and <100 ps risetime in a 50 ohm geometry. In addition to the pulse forming line (PFL), EMBL also requires a high rep-rate modulator, primary switch, and peaking switch which will be described. Empirical design equations for peaking switch performance are included.

  3. An EnantioMorphic BLumlein ultra-wideband source

    SciTech Connect

    Rinehart, L.F.; Buttram, M.T.; Crowe, W.R.; Clark, R.S.; Lundstrom, J.M.; Patterson, P.E.

    1992-01-01

    Working designs exist for 1 GW, 1 kHz ultra-wideband (UWB) sources (e. g. SNIPER). As these generators are pressed to higher peak powers and repetition rates, insulation, energy loss due to stray capacitance, and system efficiency (including power supplies and modulators) become critical issues. The EnantioMorphic (mirror image) BLumlein (EMBL) is a new type of vector inversion transmission line pulser which is designed to alleviate some of these problems. The design goals for EMBL are: 10 GW peak power, 700 kV,{approximately}1 kHz rep-rate and <100 ps risetime in a 50 ohm geometry. A gas spark gap peaking switch adds UWB frequency components to the EMBL output pulse.

  4. An EnantioMorphic BLumlein ultra-wideband source

    SciTech Connect

    Rinehart, L.F.; Buttram, M.T.; Crowe, W.R.; Clark, R.S.; Lundstrom, J.M.; Patterson, P.E.

    1992-09-01

    Working designs exist for 1 GW, 1 kHz ultra-wideband (UWB) sources (e. g. SNIPER). As these generators are pressed to higher peak powers and repetition rates, insulation, energy loss due to stray capacitance, and system efficiency (including power supplies and modulators) become critical issues. The EnantioMorphic (mirror image) BLumlein (EMBL) is a new type of vector inversion transmission line pulser which is designed to alleviate some of these problems. The design goals for EMBL are: 10 GW peak power, 700 kV,{approximately}1 kHz rep-rate and <100 ps risetime in a 50 ohm geometry. A gas spark gap peaking switch adds UWB frequency components to the EMBL output pulse.

  5. Showing Enantiomorphous Crystals of Tartaric Acid

    ERIC Educational Resources Information Center

    Andrade-Gamboa, Julio

    2007-01-01

    Most of the articles and textbooks that show drawings of enantiomorphous crystals use an inadequate view to appreciate the fact that they are non-superimposable mirror images of one another. If a graphical presentation of crystal chirality is not evident, the main attribute of crystal enantiomorphism can not be recognized by students. The classic…

  6. The EMBL-EBI channel.

    PubMed

    McEntyre, Jo; Birney, Ewan

    2016-01-01

    This editorial introduces the EMBL-EBI channel in F1000Research. The aims of the channel are to present EMBL-EBI outputs and collate research published on F1000Research contributed, in whole or in part, EMBL-EBI researchers. PMID:26913196

  7. The EMBL nucleotide sequence database.

    PubMed Central

    Stoesser, G; Moseley, M A; Sleep, J; McGowran, M; Garcia-Pastor, M; Sterk, P

    1998-01-01

    The EMBL Nucleotide Sequence Database (http://www.ebi.ac.uk/embl. html ) constitutes Europe's primary nucleotide sequence resource. DNA and RNA sequences are directly submitted from researchers and genome sequencing groups and collected from the scientific literature and patent applications (Fig. 1). In collaboration with DDBJ and GenBank the database is produced, maintained and distributed at the European Bioinformatics Institute. Database releases are produced quarterly and are distributed on CD-ROM. EBI's network services allow access to the most up-to-date data collection via Internet and World Wide Web interface, providing database searching and sequence similarity facilities plus access to a large number of additional databases. PMID:9399791

  8. Enantiomorph identification in organic crystals by electron diffraction

    NASA Astrophysics Data System (ADS)

    Tanaka, K.; Fujio, S.; Inui, H.; Ueji, R.; Sumida, N.

    2009-05-01

    The convergent-beam electron diffraction (CBED) method we proposed recently for enantiomorph identification has successfully been applied to some amino acid crystals such as glutamic acid and threonin. Enantiomorph identification (either left-handed or right-handed form) can readily be made within the framework of the proposed method by noting the asymmetric intensity distribution of Bijvoet pairs of reflections in the CBED pattern taken along an appropriate zone-axis orientation. Although the proposed method usually requires only a single CBED pattern, some effort to eliminate the ambiguity of 180°-rotation of the CBED pattern about the incident beam is needed for enantiomorph identification for these organic crystals because of the lack of HOLZ (higher-order Laue zone) reflection disks.

  9. Enantiomorphism of kaolinite: Manifestation at the levels of elementary layer and microcrystals

    SciTech Connect

    Samotoin, N. D.

    2011-03-15

    The right and left forms of the argillaceous mineral kaolinite (Al{sub 2} Si{sub 2}O{sub 5}(OH){sub 4}), which is wide-spread in nature, have been revealed for the first time by transmission electron microscopy and gold decoration in vacuum. The enantiomorphic forms of this mineral are established at the level of the elementary 7 Angstrom-Sign layer, which determines the kaolinite structure, and at the level of nano- and microcrystals typical of this mineral. Both kaolinite forms are widespread in ancient and young weathering crusts. Enantiomorphic kaolinite microcrystals are formed in two ways: through the periodic formation of 2D nuclei and via helical growth, which is dominant for both kaolinite forms. The right- and left-handed kaolinite forms are observed in the samples under study with equal probability.

  10. The ChEMBL database as linked open data

    PubMed Central

    2013-01-01

    Background Making data available as Linked Data using Resource Description Framework (RDF) promotes integration with other web resources. RDF documents can natively link to related data, and others can link back using Uniform Resource Identifiers (URIs). RDF makes the data machine-readable and uses extensible vocabularies for additional information, making it easier to scale up inference and data analysis. Results This paper describes recent developments in an ongoing project converting data from the ChEMBL database into RDF triples. Relative to earlier versions, this updated version of ChEMBL-RDF uses recently introduced ontologies, including CHEMINF and CiTO; exposes more information from the database; and is now available as dereferencable, linked data. To demonstrate these new features, we present novel use cases showing further integration with other web resources, including Bio2RDF, Chem2Bio2RDF, and ChemSpider, and showing the use of standard ontologies for querying. Conclusions We have illustrated the advantages of using open standards and ontologies to link the ChEMBL database to other databases. Using those links and the knowledge encoded in standards and ontologies, the ChEMBL-RDF resource creates a foundation for integrated semantic web cheminformatics applications, such as the presented decision support. PMID:23657106

  11. The ChEMBL bioactivity database: an update.

    PubMed

    Bento, A Patrícia; Gaulton, Anna; Hersey, Anne; Bellis, Louisa J; Chambers, Jon; Davies, Mark; Krüger, Felix A; Light, Yvonne; Mak, Lora; McGlinchey, Shaun; Nowotka, Michal; Papadatos, George; Santos, Rita; Overington, John P

    2014-01-01

    ChEMBL is an open large-scale bioactivity database (https://www.ebi.ac.uk/chembl), previously described in the 2012 Nucleic Acids Research Database Issue. Since then, a variety of new data sources and improvements in functionality have contributed to the growth and utility of the resource. In particular, more comprehensive tracking of compounds from research stages through clinical development to market is provided through the inclusion of data from United States Adopted Name applications; a new richer data model for representing drug targets has been developed; and a number of methods have been put in place to allow users to more easily identify reliable data. Finally, access to ChEMBL is now available via a new Resource Description Framework format, in addition to the web-based interface, data downloads and web services. PMID:24214965

  12. Parity Violating Energetic Difference and Enantiomorphous Crystalsp-Caveats; Reinvestigation of Tyrosine Crystallization

    NASA Astrophysics Data System (ADS)

    Lahav, Meir; Weissbuch, Isabelle; Shavit, Edna; Reiner, Clarissa; Nicholson, Graeme J.; Schurig, Volker

    2006-04-01

    The present article challenges reports claiming to have demonstrated the Parity Violating Energetic Difference (PVED) between enantiomorphous D- and L-crystals. Apart from PVED, the presence of minute quantities and differing profiles of impurities incorporated during their different history of preparation will affect the physical properties of D- and L-crystals. These impurities are anticipated to play a much greater role in affecting crystallization behavior than PVED. The effect of impurities on the growth and dissolution of enantiomorphous crystals is illustrated with some representative examples. Shinitzky et al. (2002) reported recently dramatic differences in the growth and dissolution properties of the D- and L-crystals of tyrosine. We have repeated these experiments using commercial samples from different sources and employing a validated enantioselective gas chromatographic technique. We attribute Shinitzky's findings either to the use of inappropriate analytical techniques for the determination of enantiomeric composition and/or to the presence of unidentified contaminants in the commercial tyrosine samples. Related caveats hold also for the recently published claims by Shinitzky (2006) and Scolnik et al. (2006) to have observed experimentally PVED between enantiomeric helices of poly-glutamic acid composed of 24 repeating units.

  13. Analysis Tool Web Services from the EMBL-EBI.

    PubMed

    McWilliam, Hamish; Li, Weizhong; Uludag, Mahmut; Squizzato, Silvano; Park, Young Mi; Buso, Nicola; Cowley, Andrew Peter; Lopez, Rodrigo

    2013-07-01

    Since 2004 the European Bioinformatics Institute (EMBL-EBI) has provided access to a wide range of databases and analysis tools via Web Services interfaces. This comprises services to search across the databases available from the EMBL-EBI and to explore the network of cross-references present in the data (e.g. EB-eye), services to retrieve entry data in various data formats and to access the data in specific fields (e.g. dbfetch), and analysis tool services, for example, sequence similarity search (e.g. FASTA and NCBI BLAST), multiple sequence alignment (e.g. Clustal Omega and MUSCLE), pairwise sequence alignment and protein functional analysis (e.g. InterProScan and Phobius). The REST/SOAP Web Services (http://www.ebi.ac.uk/Tools/webservices/) interfaces to these databases and tools allow their integration into other tools, applications, web sites, pipeline processes and analytical workflows. To get users started using the Web Services, sample clients are provided covering a range of programming languages and popular Web Service tool kits, and a brief guide to Web Services technologies, including a set of tutorials, is available for those wishing to learn more and develop their own clients. Users of the Web Services are informed of improvements and updates via a range of methods.

  14. Circular polarization of light by planet Mercury and enantiomorphism of its surface minerals.

    PubMed

    Meierhenrich, Uwe J; Thiemann, Wolfram H P; Barbier, Bernard; Brack, André; Alcaraz, Christian; Nahon, Laurent; Wolstencroft, Ray

    2002-04-01

    Different mechanisms for the generation of circular polarization by the surface of planets and satellites are described. The observed values for Venus, the Moon, Mars, and Jupiter obtained by photo-polarimetric measurements with Earth based telescopes, showed accordance with theory. However, for planet Mercury asymmetric parameters in the circular polarization were measured that do not fit with calculations. For BepiColombo, the ESA cornerstone mission 5 to Mercury, we propose to investigate this phenomenon using a concept which includes two instruments. The first instrument is a high-resolution optical polarimeter, capable to determine and map the circular polarization by remote scanning of Mercury's surface from the Mercury Planetary Orbiter MPO. The second instrument is an in situ sensor for the detection of the enantiomorphism of surface crystals and minerals, proposed to be included in the Mercury Lander MSE. PMID:12185675

  15. ChEMBL web services: streamlining access to drug discovery data and utilities.

    PubMed

    Davies, Mark; Nowotka, Michał; Papadatos, George; Dedman, Nathan; Gaulton, Anna; Atkinson, Francis; Bellis, Louisa; Overington, John P

    2015-07-01

    ChEMBL is now a well-established resource in the fields of drug discovery and medicinal chemistry research. The ChEMBL database curates and stores standardized bioactivity, molecule, target and drug data extracted from multiple sources, including the primary medicinal chemistry literature. Programmatic access to ChEMBL data has been improved by a recent update to the ChEMBL web services (version 2.0.x, https://www.ebi.ac.uk/chembl/api/data/docs), which exposes significantly more data from the underlying database and introduces new functionality. To complement the data-focused services, a utility service (version 1.0.x, https://www.ebi.ac.uk/chembl/api/utils/docs), which provides RESTful access to commonly used cheminformatics methods, has also been concurrently developed. The ChEMBL web services can be used together or independently to build applications and data processing workflows relevant to drug discovery and chemical biology.

  16. Growth surface topography of kaolinite-group minerals and their simulation based on the regular sequence of enantiomorphic layers

    NASA Astrophysics Data System (ADS)

    Samotoin, N. D.; Bortnikov, N. S.

    2014-07-01

    The regularities of manifestation of polytypism in a number of kaolinite-group minerals (kaolinite, dickite, halloysite, and nacrite) have been investigated by transmission electron microscopy and vacuum decoration. Growth patterns of elementary layers with a thickness of 7 Å, individual for each polytype, were observed on (001) faces of microcrystals. Specific features of the growth patterns of polytypes have been revealed by comparing them with simulated patterns constructed based on a packing of regularly alternating right- and left-handed (enantiomorphic) kaolinite layers. The new approach to the consideration of the polytypism of kaolinite minerals is substantiated by the absence of symmetry elements in the 7-Å-thick layer, which determines their structure; the formation of enantiomorphic forms of kaolinite; the presence of grazing-reflection planes in the growth patterns; and the structure of polytypes with a two-layer period. Packing of enantiomorphic layers may yield eight structures, two of which correspond to the right- and left-handed forms of kaolinite, one is for dickite, two are for halloysite, and three are for nacrite. It is shown that the simulated and real growth patterns of these minerals are in good correspondence.

  17. The EMBL-EBI bioinformatics web and programmatic tools framework.

    PubMed

    Li, Weizhong; Cowley, Andrew; Uludag, Mahmut; Gur, Tamer; McWilliam, Hamish; Squizzato, Silvano; Park, Young Mi; Buso, Nicola; Lopez, Rodrigo

    2015-07-01

    Since 2009 the EMBL-EBI Job Dispatcher framework has provided free access to a range of mainstream sequence analysis applications. These include sequence similarity search services (https://www.ebi.ac.uk/Tools/sss/) such as BLAST, FASTA and PSI-Search, multiple sequence alignment tools (https://www.ebi.ac.uk/Tools/msa/) such as Clustal Omega, MAFFT and T-Coffee, and other sequence analysis tools (https://www.ebi.ac.uk/Tools/pfa/) such as InterProScan. Through these services users can search mainstream sequence databases such as ENA, UniProt and Ensembl Genomes, utilising a uniform web interface or systematically through Web Services interfaces (https://www.ebi.ac.uk/Tools/webservices/) using common programming languages, and obtain enriched results with novel visualisations. Integration with EBI Search (https://www.ebi.ac.uk/ebisearch/) and the dbfetch retrieval service (https://www.ebi.ac.uk/Tools/dbfetch/) further expands the usefulness of the framework. New tools and updates such as NCBI BLAST+, InterProScan 5 and PfamScan, new categories such as RNA analysis tools (https://www.ebi.ac.uk/Tools/rna/), new databases such as ENA non-coding, WormBase ParaSite, Pfam and Rfam, and new workflow methods, together with the retirement of depreciated services, ensure that the framework remains relevant to today's biological community. PMID:25845596

  18. The EMBL-EBI bioinformatics web and programmatic tools framework.

    PubMed

    Li, Weizhong; Cowley, Andrew; Uludag, Mahmut; Gur, Tamer; McWilliam, Hamish; Squizzato, Silvano; Park, Young Mi; Buso, Nicola; Lopez, Rodrigo

    2015-07-01

    Since 2009 the EMBL-EBI Job Dispatcher framework has provided free access to a range of mainstream sequence analysis applications. These include sequence similarity search services (https://www.ebi.ac.uk/Tools/sss/) such as BLAST, FASTA and PSI-Search, multiple sequence alignment tools (https://www.ebi.ac.uk/Tools/msa/) such as Clustal Omega, MAFFT and T-Coffee, and other sequence analysis tools (https://www.ebi.ac.uk/Tools/pfa/) such as InterProScan. Through these services users can search mainstream sequence databases such as ENA, UniProt and Ensembl Genomes, utilising a uniform web interface or systematically through Web Services interfaces (https://www.ebi.ac.uk/Tools/webservices/) using common programming languages, and obtain enriched results with novel visualisations. Integration with EBI Search (https://www.ebi.ac.uk/ebisearch/) and the dbfetch retrieval service (https://www.ebi.ac.uk/Tools/dbfetch/) further expands the usefulness of the framework. New tools and updates such as NCBI BLAST+, InterProScan 5 and PfamScan, new categories such as RNA analysis tools (https://www.ebi.ac.uk/Tools/rna/), new databases such as ENA non-coding, WormBase ParaSite, Pfam and Rfam, and new workflow methods, together with the retirement of depreciated services, ensure that the framework remains relevant to today's biological community.

  19. The EMBL-EBI bioinformatics web and programmatic tools framework

    PubMed Central

    Li, Weizhong; Cowley, Andrew; Uludag, Mahmut; Gur, Tamer; McWilliam, Hamish; Squizzato, Silvano; Park, Young Mi; Buso, Nicola; Lopez, Rodrigo

    2015-01-01

    Since 2009 the EMBL-EBI Job Dispatcher framework has provided free access to a range of mainstream sequence analysis applications. These include sequence similarity search services (https://www.ebi.ac.uk/Tools/sss/) such as BLAST, FASTA and PSI-Search, multiple sequence alignment tools (https://www.ebi.ac.uk/Tools/msa/) such as Clustal Omega, MAFFT and T-Coffee, and other sequence analysis tools (https://www.ebi.ac.uk/Tools/pfa/) such as InterProScan. Through these services users can search mainstream sequence databases such as ENA, UniProt and Ensembl Genomes, utilising a uniform web interface or systematically through Web Services interfaces (https://www.ebi.ac.uk/Tools/webservices/) using common programming languages, and obtain enriched results with novel visualisations. Integration with EBI Search (https://www.ebi.ac.uk/ebisearch/) and the dbfetch retrieval service (https://www.ebi.ac.uk/Tools/dbfetch/) further expands the usefulness of the framework. New tools and updates such as NCBI BLAST+, InterProScan 5 and PfamScan, new categories such as RNA analysis tools (https://www.ebi.ac.uk/Tools/rna/), new databases such as ENA non-coding, WormBase ParaSite, Pfam and Rfam, and new workflow methods, together with the retirement of depreciated services, ensure that the framework remains relevant to today's biological community. PMID:25845596

  20. Enantiomorphs of a carbene-ruthenium(II)-porphyrin complex with four 'chiral pillars'.

    PubMed

    Hirasawa, Kai; Yuge, Hidetaka; Miyamoto, Takeshi Ken

    2008-02-01

    The chiral metalloporphyrin (dibenzoylmethylene-kappaC)(ethanol-kappaO){5,10,15,20-tetrakis[(1S,4R,5R,8S)-1,2,3,4,5,6,7,8-octahydro-1,4:5,8-dimethanoanthracen-9-yl]porphyrinato-kappa(4)N}ruthenium(II)-ethanol-dichloromethane (1/2/2), [Ru(C(84)H(76)N(4))(C(15)H(10)O(2))(C(2)H(6)O)].2C(2)H(6)O.2CH(2)Cl(2), and its enantiomorph were prepared from enantiomerically pure porphyrins. The enantiomers are potential versatile catalysts for asymmetric cyclopropanation, aziridination or epoxidation. In each compound, the rather large dibenzoylcarbene group is squeezed between four columnar 1,2,3,4,5,6,7,8-octahydro-1,4:5,8-dimethanoanthracen-9-yl groups at the meso positions resulting in a doming deformation of the porphyrin core. The dibenzoylcarbene group has an anti conformation. The benzoyl O atoms make short van der Waals contacts (< 2.6 A) with the methine groups of the chiral columnar substituents at the 10 and 20 positions of the porphyrin rings. A hydrogen-bonded supramolecular chain is formed parallel to the b axis by interactions between the benzoyl O atom and the hydroxy groups of the coordinated and uncoordinated ethanol molecules. PMID:18252997

  1. SureChEMBL: a large-scale, chemically annotated patent document database

    PubMed Central

    Papadatos, George; Davies, Mark; Dedman, Nathan; Chambers, Jon; Gaulton, Anna; Siddle, James; Koks, Richard; Irvine, Sean A.; Pettersson, Joe; Goncharoff, Nicko; Hersey, Anne; Overington, John P.

    2016-01-01

    SureChEMBL is a publicly available large-scale resource containing compounds extracted from the full text, images and attachments of patent documents. The data are extracted from the patent literature according to an automated text and image-mining pipeline on a daily basis. SureChEMBL provides access to a previously unavailable, open and timely set of annotated compound-patent associations, complemented with sophisticated combined structure and keyword-based search capabilities against the compound repository and patent document corpus; given the wealth of knowledge hidden in patent documents, analysis of SureChEMBL data has immediate applications in drug discovery, medicinal chemistry and other commercial areas of chemical science. Currently, the database contains 17 million compounds extracted from 14 million patent documents. Access is available through a dedicated web-based interface and data downloads at: https://www.surechembl.org/. PMID:26582922

  2. SureChEMBL: a large-scale, chemically annotated patent document database.

    PubMed

    Papadatos, George; Davies, Mark; Dedman, Nathan; Chambers, Jon; Gaulton, Anna; Siddle, James; Koks, Richard; Irvine, Sean A; Pettersson, Joe; Goncharoff, Nicko; Hersey, Anne; Overington, John P

    2016-01-01

    SureChEMBL is a publicly available large-scale resource containing compounds extracted from the full text, images and attachments of patent documents. The data are extracted from the patent literature according to an automated text and image-mining pipeline on a daily basis. SureChEMBL provides access to a previously unavailable, open and timely set of annotated compound-patent associations, complemented with sophisticated combined structure and keyword-based search capabilities against the compound repository and patent document corpus; given the wealth of knowledge hidden in patent documents, analysis of SureChEMBL data has immediate applications in drug discovery, medicinal chemistry and other commercial areas of chemical science. Currently, the database contains 17 million compounds extracted from 14 million patent documents. Access is available through a dedicated web-based interface and data downloads at: https://www.surechembl.org/.

  3. SureChEMBL: a large-scale, chemically annotated patent document database.

    PubMed

    Papadatos, George; Davies, Mark; Dedman, Nathan; Chambers, Jon; Gaulton, Anna; Siddle, James; Koks, Richard; Irvine, Sean A; Pettersson, Joe; Goncharoff, Nicko; Hersey, Anne; Overington, John P

    2016-01-01

    SureChEMBL is a publicly available large-scale resource containing compounds extracted from the full text, images and attachments of patent documents. The data are extracted from the patent literature according to an automated text and image-mining pipeline on a daily basis. SureChEMBL provides access to a previously unavailable, open and timely set of annotated compound-patent associations, complemented with sophisticated combined structure and keyword-based search capabilities against the compound repository and patent document corpus; given the wealth of knowledge hidden in patent documents, analysis of SureChEMBL data has immediate applications in drug discovery, medicinal chemistry and other commercial areas of chemical science. Currently, the database contains 17 million compounds extracted from 14 million patent documents. Access is available through a dedicated web-based interface and data downloads at: https://www.surechembl.org/. PMID:26582922

  4. The EBI Search engine: providing search and retrieval functionality for biological data from EMBL-EBI.

    PubMed

    Squizzato, Silvano; Park, Young Mi; Buso, Nicola; Gur, Tamer; Cowley, Andrew; Li, Weizhong; Uludag, Mahmut; Pundir, Sangya; Cham, Jennifer A; McWilliam, Hamish; Lopez, Rodrigo

    2015-07-01

    The European Bioinformatics Institute (EMBL-EBI-https://www.ebi.ac.uk) provides free and unrestricted access to data across all major areas of biology and biomedicine. Searching and extracting knowledge across these domains requires a fast and scalable solution that addresses the requirements of domain experts as well as casual users. We present the EBI Search engine, referred to here as 'EBI Search', an easy-to-use fast text search and indexing system with powerful data navigation and retrieval capabilities. API integration provides access to analytical tools, allowing users to further investigate the results of their search. The interconnectivity that exists between data resources at EMBL-EBI provides easy, quick and precise navigation and a better understanding of the relationship between different data types including sequences, genes, gene products, proteins, protein domains, protein families, enzymes and macromolecular structures, together with relevant life science literature.

  5. Chiral hide-and-seek: retention of enantiomorphism in laser-induced nucleation of molten sodium chlorate.

    PubMed

    Ward, Martin R; Copeland, Gary W; Alexander, Andrew J

    2011-09-21

    We report the observation of non-photochemical laser-induced nucleation (NPLIN) of sodium chlorate from its melt using nanosecond pulses of light at 1064 nm. The fraction of samples that nucleate is shown to depend linearly on the peak power density of the laser pulses. Remarkably, we observe that most samples are nucleated by the laser back into the enantiomorph (dextrorotatory or levorotatory) of the solid prior to melting. We do not observe a significant dependence on polarization of the light, and we put forward symmetry arguments that rule out an optical Kerr effect mechanism. Our observations of retention of chirality can be explained by decomposition of small amounts of the sodium chlorate to form sodium chloride, which provide cavities for retention of clusters of sodium chlorate even 18 °C above the melting point. These clusters remain sub-critical on cooling, but can be activated by NPLIN via an isotropic polarizability mechanism. We have developed a heterogeneous model of NPLIN in cavities, which reproduces the experimental data using simple physical data available for sodium chlorate.

  6. Etiologic theories of idiopathic scoliosis: enantiomorph disorder concept of bilateral symmetry, physeally-created growth conflicts and possible prevention.

    PubMed

    Burwell, R G; Freeman, B J C; Dangerfield, P H; Aujla, R K; Cole, A A; Kirby, A S; Pratt, R K; Webb, J K; Moulton, A

    2006-01-01

    The detection of anomalous extra-spinal left-right skeletal length asymmetries in the upper limbs, periapical ribs, ilia and lower limbs of subjects with adolescent idiopathic scoliosis (AIS) raises questions about skeletal bilateral symmetry of vertebrates in health and disorder, its origin and control. The vertebrate body plan externally has mirror-image bilateral symmetries that are highly conserved culminating in the adult form. The normal human body can be viewed as containing paired skeletal structures in the axial and appendicular skeleton as 1) separate left and right paired forms (eg long limb bones, ribs, ilia), and 2) united in paired forms (eg vertebrae, sternum, skull, mandible). Each of these separate and united pairs are mirror-image forms--enantiomorphs. Left-right asymmetries of growth plates (physes) may cause (1) in long bones length asymmetries, (2) within one or more vertebral physes putative growth conflict with distortion as deformity, and (3) between ribs and vertebrae putative growth conflict that triggers thoracic AIS suggesting preventive surgery on spine and ribs. There is evidence of a possible role for environmental factors in AIS development. Genes and the environment (nature/nurture) may interact pre- and/or post-natally to explain both the deformity of AIS and its association with widespread anomalous skeletal length asymmetries. If substantiated there may ultimately be a place for the prevention of AIS in some subjects.

  7. Using EMBL-EBI services via Web interface and programmatically via Web Services

    PubMed Central

    Lopez, Rodrigo; Cowley, Andrew; Li, Weizhong; McWilliam, Hamish

    2015-01-01

    The European Bioinformatics Institute (EMBL-EBI) provides access to a wide range of databases and analysis tools that are of key importance in bioinformatics. As well as providing Web interfaces to these resources, Web Services are available using SOAP and REST protocols that enable programmatic access to our resources and allow their integration into other applications and analytical workflows. This unit describes the various options available to a typical researcher or bioinformatician who wishes to use our resources via Web interface or programmatically via a range of programming languages. PMID:25501941

  8. Large-scale similarity search profiling of ChEMBL compound data sets.

    PubMed

    Heikamp, Kathrin; Bajorath, Jürgen

    2011-08-22

    A large-scale similarity search investigation has been carried out on 266 well-defined compound activity classes extracted from the ChEMBL database. The analysis was performed using two widely applied two-dimensional (2D) fingerprints that mark opposite ends of the current performance spectrum of these types of fingerprints, i.e., MACCS structural keys and the extended connectivity fingerprint with bond diameter four (ECFP4). For each fingerprint, three nearest neighbor search strategies were applied. On the basis of these search calculations, a similarity search profile of the ChEMBL database was generated. Overall, the fingerprint search campaign was surprisingly successful. In 203 of 266 test cases (∼76%), a compound recovery rate of at least 50% was observed with at least the better performing fingerprint and one search strategy. The similarity search profile also revealed several general trends. For example, fingerprint searching was often characterized by an early enrichment of active compounds in database selection sets. In addition, compound activity classes have been categorized according to different similarity search performance levels, which helps to put the results of benchmark calculations into perspective. Therefore, a compendium of activity classes falling into different search performance categories is provided. On the basis of our large-scale investigation, the performance range of state-of-the-art 2D fingerprinting has been delineated for compound data sets directed against a wide spectrum of pharmaceutical targets.

  9. Similarity Mapplet: Interactive Visualization of the Directory of Useful Decoys and ChEMBL in High Dimensional Chemical Spaces.

    PubMed

    Awale, Mahendra; Reymond, Jean-Louis

    2015-08-24

    An Internet portal accessible at www.gdb.unibe.ch has been set up to automatically generate color-coded similarity maps of the ChEMBL database in relation to up to two sets of active compounds taken from the enhanced Directory of Useful Decoys (eDUD), a random set of molecules, or up to two sets of user-defined reference molecules. These maps visualize the relationships between the selected compounds and ChEMBL in six different high dimensional chemical spaces, namely MQN (42-D molecular quantum numbers), SMIfp (34-D SMILES fingerprint), APfp (20-D shape fingerprint), Xfp (55-D pharmacophore fingerprint), Sfp (1024-bit substructure fingerprint), and ECfp4 (1024-bit extended connectivity fingerprint). The maps are supplied in form of Java based desktop applications called "similarity mapplets" allowing interactive content browsing and linked to a "Multifingerprint Browser for ChEMBL" (also accessible directly at www.gdb.unibe.ch ) to perform nearest neighbor searches. One can obtain six similarity mapplets of ChEMBL relative to random reference compounds, 606 similarity mapplets relative to single eDUD active sets, 30,300 similarity mapplets relative to pairs of eDUD active sets, and any number of similarity mapplets relative to user-defined reference sets to help visualize the structural diversity of compound series in drug optimization projects and their relationship to other known bioactive compounds. PMID:26207526

  10. Chemical Space Mapping and Structure-Activity Analysis of the ChEMBL Antiviral Compound Set.

    PubMed

    Klimenko, Kyrylo; Marcou, Gilles; Horvath, Dragos; Varnek, Alexandre

    2016-08-22

    Curation, standardization and data fusion of the antiviral information present in the ChEMBL public database led to the definition of a robust data set, providing an association of antiviral compounds to seven broadly defined antiviral activity classes. Generative topographic mapping (GTM) subjected to evolutionary tuning was then used to produce maps of the antiviral chemical space, providing an optimal separation of compound families associated with the different antiviral classes. The ability to pinpoint the specific spots occupied (responsibility patterns) on a map by various classes of antiviral compounds opened the way for a GTM-supported search for privileged structural motifs, typical for each antiviral class. The privileged locations of antiviral classes were analyzed in order to highlight underlying privileged common structural motifs. Unlike in classical medicinal chemistry, where privileged structures are, almost always, predefined scaffolds, privileged structural motif detection based on GTM responsibility patterns has the decisive advantage of being able to automatically capture the nature ("resolution detail"-scaffold, detailed substructure, pharmacophore pattern, etc.) of the relevant structural motifs. Responsibility patterns were found to represent underlying structural motifs of various natures-from very fuzzy (groups of various "interchangeable" similar scaffolds), to the classical scenario in medicinal chemistry (underlying motif actually being the scaffold), to very precisely defined motifs (specifically substituted scaffolds). PMID:27410486

  11. Submitting MIGS, MIMS, MIENS Information to EMBL and Standards and the Sequencing Pipelines of the Gordon and Betty Moore Foundation (GSC8 Meeting)

    SciTech Connect

    Vaughan, Bob; Kaye, Jon

    2009-09-09

    The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Bob Vaughan of EMBL on submitting MIGS/MIMS/MIENS information to EMBL-EBI's system, followed by a brief talk from Jon Kaye of the Gordon and Betty Moore Foundation on standards and the foundation's sequencing pipelines at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, Calif. on Sept. 9, 2009

  12. Submitting MIGS, MIMS, MIENS Information to EMBL and Standards and the Sequencing Pipelines of the Gordon and Betty Moore Foundation (GSC8 Meeting)

    ScienceCinema

    Vaughan, Bob [EMBL; Kaye, Jon [Gordon and Betty Moore Foundation

    2016-07-12

    The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Bob Vaughan of EMBL on submitting MIGS/MIMS/MIENS information to EMBL-EBI's system, followed by a brief talk from Jon Kaye of the Gordon and Betty Moore Foundation on standards and the foundation's sequencing pipelines at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, Calif. on Sept. 9, 2009

  13. Automated sample-changing robot for solution scattering experiments at the EMBL Hamburg SAXS station X33.

    PubMed

    Round, A R; Franke, D; Moritz, S; Huchler, R; Fritsche, M; Malthan, D; Klaering, R; Svergun, D I; Roessle, M

    2008-10-01

    There is a rapidly increasing interest in the use of synchrotron small-angle X-ray scattering (SAXS) for large-scale studies of biological macromolecules in solution, and this requires an adequate means of automating the experiment. A prototype has been developed of an automated sample changer for solution SAXS, where the solutions are kept in thermostatically controlled well plates allowing for operation with up to 192 samples. The measuring protocol involves controlled loading of protein solutions and matching buffers, followed by cleaning and drying of the cell between measurements. The system was installed and tested at the X33 beamline of the EMBL, at the storage ring DORIS-III (DESY, Hamburg), where it was used by over 50 external groups during 2007. At X33, a throughput of approximately 12 samples per hour, with a failure rate of sample loading of less than 0.5%, was observed. The feedback from users indicates that the ease of use and reliability of the user operation at the beamline were greatly improved compared with the manual filling mode. The changer is controlled by a client-server-based network protocol, locally and remotely. During the testing phase, the changer was operated in an attended mode to assess its reliability and convenience. Full integration with the beamline control software, allowing for automated data collection of all samples loaded into the machine with remote control from the user, is presently being implemented. The approach reported is not limited to synchrotron-based SAXS but can also be used on laboratory and neutron sources. PMID:25484841

  14. Growth of ligand-target interaction data in ChEMBL is associated with increasing and activity measurement-dependent compound promiscuity.

    PubMed

    Hu, Ye; Bajorath, Jürgen

    2012-10-22

    Compounds with high-confidence target annotations and activity measurements in the original and current release of the ChEMBL database have been compared to better understand how the growth of compound activity data might influence the spectrum of ligand-target interactions and the degree of target promiscuity among active compounds. Compared to the original ChEMBL release, a significant increase in the proportion of target promiscuous compounds was observed in the current version. The presence of these compounds led to large-magnitude changes in compound activity-based target and target family relationships and to a reorganization of major target communities. Surprisingly, however, this strong trend toward increasing target promiscuity was largely caused by growth of compounds with exclusive IC(50) measurements. By contrast, compounds with available equilibrium constants, which were also added in large amounts, did not substantially alter compound-based target relationships and notably contribute to increasing target promiscuity. These findings suggest that apparent compound promiscuity is much dependent on experimental conditions under which activities are determined and that care should be taken when evaluating promiscuity and polypharmacology on the basis of assay-dependent activity measurements.

  15. Enabling BioSharing - a report on the Annual Spring Workshop of the HUPO-PSI April 11-13, 2011, EMBL-Heidelberg, Germany.

    PubMed

    Orchard, Sandra; Albar, Juan Pablo; Deutsch, Eric W; Eisenacher, Martin; Vizcaíno, Juan A; Hermjakob, Henning

    2011-11-01

    The Annual Spring workshop of the HUPO-PSI was this year held at the EMBL International Centre for Advanced Training (EICAT) in Heidelberg, Germany. Delegates briefly reviewed the successes of the group to date. These include the wide spread implementation of the molecular interaction data exchange formats, PSI-MI XML2.5 and MITAB, and also of mzML, the standard output format for mass spectrometer output data. These successes have resulted in enhanced accessibility to published data, for example the development of the PSICQUIC common query interface for interaction data and the development of databases such as PRIDE to act as public repositories for proteomics data and increased biosharing, through the development of consortia, for example IMEx and ProteomeXchange which will both share the burden of curating the increasing amounts of data being published and work together to make this more accessible to the bench scientist. Work then started over the three days of the workshop, with a focus on advancing the draft format for handling quantitative mass spectrometry data (mzQuantML) and further developing TraML, a standardized format for the exchange and transmission of transition lists for SRM experiments.

  16. Discovery of potent positive allosteric modulators of the α3β2 nicotinic acetylcholine receptor by a chemical space walk in ChEMBL.

    PubMed

    Bürgi, Justus J; Awale, Mahendra; Boss, Silvan D; Schaer, Tifany; Marger, Fabrice; Viveros-Paredes, Juan M; Bertrand, Sonia; Gertsch, Jürg; Bertrand, Daniel; Reymond, Jean-Louis

    2014-05-21

    While a plethora of ligands are known for the well studied α7 and α4β2 nicotinic acetylcholine receptor (nAChR), only very few ligands address the related α3β2 nAChR expressed in the central nervous system and at the neuromuscular junction. Starting with the public database ChEMBL organized in the chemical space of Molecular Quantum Numbers (MQN, a series of 42 integer value descriptors of molecular structure), a visual survey of nearest neighbors of the α7 nAChR partial agonist N-(3R)-1-azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide (PNU-282,987) pointed to N-(2-halobenzyl)-3-aminoquinuclidines as possible nAChR modulators. This simple "chemical space walk" was performed using a web-browser available at www.gdb.unibe.ch . Electrophysiological recordings revealed that these ligands represent a new and to date most potent class of positive allosteric modulators (PAMs) of the α3β2 nAChR, which also exert significant effects in vivo. The present discovery highlights the value of surveying chemical space neighbors of known drugs within public databases to uncover new pharmacology. PMID:24593915

  17. Discovery of Potent Positive Allosteric Modulators of the α3β2 Nicotinic Acetylcholine Receptor by a Chemical Space Walk in ChEMBL

    PubMed Central

    2014-01-01

    While a plethora of ligands are known for the well studied α7 and α4β2 nicotinic acetylcholine receptor (nAChR), only very few ligands address the related α3β2 nAChR expressed in the central nervous system and at the neuromuscular junction. Starting with the public database ChEMBL organized in the chemical space of Molecular Quantum Numbers (MQN, a series of 42 integer value descriptors of molecular structure), a visual survey of nearest neighbors of the α7 nAChR partial agonist N-(3R)-1-azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide (PNU-282,987) pointed to N-(2-halobenzyl)-3-aminoquinuclidines as possible nAChR modulators. This simple “chemical space walk” was performed using a web-browser available at www.gdb.unibe.ch. Electrophysiological recordings revealed that these ligands represent a new and to date most potent class of positive allosteric modulators (PAMs) of the α3β2 nAChR, which also exert significant effects in vivo. The present discovery highlights the value of surveying chemical space neighbors of known drugs within public databases to uncover new pharmacology. PMID:24593915

  18. Template CoMFA Generates Single 3D-QSAR Models that, for Twelve of Twelve Biological Targets, Predict All ChEMBL-Tabulated Affinities

    PubMed Central

    Cramer, Richard D.

    2015-01-01

    The possible applicability of the new template CoMFA methodology to the prediction of unknown biological affinities was explored. For twelve selected targets, all ChEMBL binding affinities were used as training and/or prediction sets, making these 3D-QSAR models the most structurally diverse and among the largest ever. For six of the targets, X-ray crystallographic structures provided the aligned templates required as input (BACE, cdk1, chk2, carbonic anhydrase-II, factor Xa, PTP1B). For all targets including the other six (hERG, cyp3A4 binding, endocrine receptor, COX2, D2, and GABAa), six modeling protocols applied to only three familiar ligands provided six alternate sets of aligned templates. The statistical qualities of the six or seven models thus resulting for each individual target were remarkably similar. Also, perhaps unexpectedly, the standard deviations of the errors of cross-validation predictions accompanying model derivations were indistinguishable from the standard deviations of the errors of truly prospective predictions. These standard deviations of prediction ranged from 0.70 to 1.14 log units and averaged 0.89 (8x in concentration units) over the twelve targets, representing an average reduction of almost 50% in uncertainty, compared to the null hypothesis of “predicting” an unknown affinity to be the average of known affinities. These errors of prediction are similar to those from Tanimoto coefficients of fragment occurrence frequencies, the predominant approach to side effect prediction, which template CoMFA can augment by identifying additional active structural classes, by improving Tanimoto-only predictions, by yielding quantitative predictions of potency, and by providing interpretable guidance for avoiding or enhancing any specific target response. PMID:26065424

  19. Crystallization of an achiral cyclohexanone ethylene ketal in enantiomorphs and determination of the absolute structure.

    PubMed

    Graus, Sara; Tejedor, Rosa M; Uriel, Santiago; Serrano, José Luis; Alkorta, Ibon; Elguero, José

    2010-06-16

    The achiral 4-methoxy-4-(p-methoxyphenyl)-cyclohexanone ethylene ketal (1) resolves spontaneously. The crystal structure is solved in chiral spatial group P2(1). Because compound 1 is composed of only light atoms (C, H, O) it is not possible to determine its absolute structure configuration. An efficient procedure for the absolute structure configuration determination of flexible molecules containing only light atoms is proposed, based on the combination of X-ray diffraction, solid-state VCD, and DFT calculations.

  20. New Beamlines For Protein Crystallography At The EMBL-Outstation Hamburg

    NASA Astrophysics Data System (ADS)

    Hermes, C.; Gehrmann, T.; Jahn, D.; Ristau, U.; Robrahn, B.; Siambanis, T.

    2004-05-01

    Three new beamlines for Protein Crystallography were built up on a bending magnet fan of the DORIS III storage ring. A 10 mrad wide fan of white Synchrotron Radiation (SR) is evenly distributed among 3 individual stations: X12, a central, wavelength-tunable station intended for anomalous scattering experiments (MAD) and fixed wavelength, high intensity stations symmetrically on either side. The fixed wavelength beamlines X11 & X13 comprise triangular, asymmetrically cut Si (111) monochromators as horizontally focusing optical elements. The tunable station is based on a fixed-exit, horizontally focusing double crystal monochromator system. Vertical focusing is achieved on all three lines by trapezoidal shaped, continuous Rh-coated mirrors which can be dynamically bent. In all three lines the X-ray beam can be examined at various points on its way through the optical system by removable screens and PIN-diode based intensity monitors. Purpose built crystallographic end-stations complete the set-up. The design of individual components and their performance will be described.

  1. Sandia National Laboratories' high power electromagnetic impulse sources

    NASA Astrophysics Data System (ADS)

    Rinehart, L. F.; Buttram, M. T.; Denison, G. J.; Lundstrom, J. M.; Crowe, W. R.; Aurand, J. F.; Patterson, P. E.

    1994-05-01

    Three impulse sources have been developed to cover a wide range of peak power, bandwidth and center frequency requirements. Each of the sources can operate in single shot, rep-rate, or burst modes. These devices are of rugged construction and are suitable for field use. This paper will describe the specifications and principals of operation for each source. The sources to be described are: SNIPER (Sub-Nanosecond ImPulsE Radiator), a coaxial Blumlein pulser with an in-line (series) peaking switch; EMBL (EnantioMorphic BLurfflein), a bipolar parallel plate Blumlein with a crowbar type (parallel) peaking switch; and the LCO (L-C Oscillator) a spark-switched L-C oscillator with damped sinusoidal output. SNIPER and EMBL are ultra-wideband (UWB) sources which produce a very fast high voltage transition. When differentiated by the antenna, an impulse whose width corresponds to the transition time is radiated. The LCO operates with a center frequency up to 800 MHz and up to 100 MHz bandwidth. Because the LCO output is relatively narrow band, high gain antennas may be employed to produce very high radiated field strengths.

  2. Sandia National Laboratories` high power electromagnetic impulse sources

    SciTech Connect

    Rinehart, L.F.; Buttram, M.T.; Denison, G.J.; Lundstrom, J.M.; Crowe, W.R.; Aurand, J.F.; Patterson, P.E.

    1994-10-01

    Three impulse sources have been developed to cover a wide range of peak power, bandwidth and center frequency requirements. Each of the sources can operate in single shot, rep-rate, or burst modes. These devices are of rugged construction and are suitable for field use. This paper will describe the specifications and principals of operation for each source. The sources to be described are: SNIPER (Sub-Nanosecond ImPulsE Radiator), a coaxial Blumlein pulser with an in-line (series) peaking switch; EMBL (EnantioMorphic BLurfflein), a bipolar parallel plate Blumlein with a crowbar type (parallel) peaking switch; and the LCO (L-C Oscillator) a spark-switched L-C oscillator with damped sinusoidal output. SNIPER and EMBL are ultra-wideband (UWB) sources which produce a very fast high voltage transition. When differentiated by the antenna, an impulse whose width corresponds to the transition time is radiated. The LCO operates with a center frequency up to 800 MHz and up to 100 MHz bandwidth. Because the LCO output is relatively narrow band, high gain antennas may be employed to produce very high radiated field strengths.

  3. MQN-mapplet: visualization of chemical space with interactive maps of DrugBank, ChEMBL, PubChem, GDB-11, and GDB-13.

    PubMed

    Awale, Mahendra; van Deursen, Ruud; Reymond, Jean-Louis

    2013-02-25

    The MQN-mapplet is a Java application giving access to the structure of small molecules in large databases via color-coded maps of their chemical space. These maps are projections from a 42-dimensional property space defined by 42 integer value descriptors called molecular quantum numbers (MQN), which count different categories of atoms, bonds, polar groups, and topological features and categorize molecules by size, rigidity, and polarity. Despite its simplicity, MQN-space is relevant to biological activities. The MQN-mapplet allows localization of any molecule on the color-coded images, visualization of the molecules, and identification of analogs as neighbors on the MQN-map or in the original 42-dimensional MQN-space. No query molecule is necessary to start the exploration, which may be particularly attractive for nonchemists. To our knowledge, this type of interactive exploration tool is unprecedented for very large databases such as PubChem and GDB-13 (almost one billion molecules). The application is freely available for download at www.gdb.unibe.ch. PMID:23297797

  4. An overview of Sandia National Laboratories' plasma switched, gigawatt, ultra-wideband impulse transmitter program

    SciTech Connect

    Clark, R.S.; Rinehart, L.F.; Buttram, M.T.; Aurand, J.F.

    1992-01-01

    Sandia National Laboratories has developed several repetitive, ultra-wideband (UWB), impulse transmitters to address impulse source technology and to support experimental applications. The sources fall into two different classes, pulse peaking and pulse shorting depending on how the UWB frequency components are generated. ne frequency spectrum of the radiated pulse from these sources include the spectrum of 100-MHz to 3-GHz. Depending upon the source, repetitive operation from single shot to 5-kHz (1-kHz nominal) has been obtained with excellent reliability and repeatability. SNIPER (Sub-Nanosecond impulse Radiator) is a source which uses an oil peaking switch to obtain a fast risetime (250-pS) pulse of 2-nS duration. The output voltage ranges between few tens of kilovolts to 250-kV. EMBL (EnantioMorphic Blumlein) is a similar device (presently under development) which uses a gas switch to sharpen the trailing edge of a 2-nS pulse to approximately 100-pS. To date, an output voltage of approximately 600-kV has been obtained (700- kV is the design goal). Since the frequency spectra are identical between sources with sharpened leading or trailing edges, alternatively, one can use parallel switches to short the pulse at its peak voltage. The pulse is generated externally and then injected into the antenna. Due to the high powers involved and the need to radiate a broad spectrum of frequencies, Sandia has concentrated on TEM horn. antennas with special high voltage feed adapters. Several TEM horns have been built and used during this program. In those cases where higher gains are desired for the higher frequencies, TEM horn-fed, dish antennas have been employed. An overview of the UWB transmitters, including design and operation of the modulators, the PFN'S, the pulse sharpening switches and the antennas will be presented.

  5. Repetitive, plasma switched, gigawatt, ultra-wideband impulse transmitter development

    SciTech Connect

    Clark, R.S.; Rinehart, L.F.; Buttram, M.T.; Aurand, J.F.; Lundstrom, J.M.; Patterson, P.E.; Roose, L.D.; Crowe, W.

    1992-09-01

    Sandia National Laboratories has developed several repetitive, ultra-wideband (UWB), impulse transmitters to address impulse source, and to support experimental applications. The sources fall into two different classes, pulse peaking and pulse shorting. SNIPER (Sub-Nanosecond ImPulsE Radiator) is a source which uses an oil peaking switch to obtain a fast risetime (250-pS) pulse of 2-nS duration. The output voltage ranges between few tens of kilovolts to 250-kV. EMBL (EnantioMorphic Blumlein) is a similar device (presently under development) which uses a gas switch to short the falling portion of a 2-nS pulse to approximately 100-pS. To date, an output voltage of approximately 600-kV has been obtained (700-kV is the design goal). Depending upon the source, repetitive operation from single shot to 5-kHz (1-kHz nominal) has been obtained with excellent reliability and repeatability. Both sources are plasma switched impulse transmitters using a Hydrogen-thyratron based modulator, an oil-filled Blumlein (of two types), a peaking (or shorting) switch and a wideband TEM horn. Powers exceeding one-gigawatt are routinely generated. This technology appears to be extendable to at least 10-gigawatts. The frequency spectrum of the radiated pulse from these sources include the spectrum of 100-MHz to 3-GHz. The pulse is generated externally and then injected into the antenna. Due to the high powers involved and the need to radiate a broad spectrum of frequencies, Sandia has concentrated on TEM horn antennas. Several TEM horns have been built and used during this program. In those cases where higher gains are desired for the higher frequencies, TEM horn-fed dish antennas have been employed. A detailed overview of the UWB Transmitters along with measured radiated electric field strengths will be presented.

  6. Repetitive, plasma switched, gigawatt, ultra-wideband impulse transmitter development

    SciTech Connect

    Clark, R.S.; Rinehart, L.F.; Buttram, M.T.; Aurand, J.F.; Lundstrom, J.M.; Patterson, P.E.; Roose, L.D.; Crowe, W.

    1992-01-01

    Sandia National Laboratories has developed several repetitive, ultra-wideband (UWB), impulse transmitters to address impulse source, and to support experimental applications. The sources fall into two different classes, pulse peaking and pulse shorting. SNIPER (Sub-Nanosecond ImPulsE Radiator) is a source which uses an oil peaking switch to obtain a fast risetime (250-pS) pulse of 2-nS duration. The output voltage ranges between few tens of kilovolts to 250-kV. EMBL (EnantioMorphic Blumlein) is a similar device (presently under development) which uses a gas switch to short the falling portion of a 2-nS pulse to approximately 100-pS. To date, an output voltage of approximately 600-kV has been obtained (700-kV is the design goal). Depending upon the source, repetitive operation from single shot to 5-kHz (1-kHz nominal) has been obtained with excellent reliability and repeatability. Both sources are plasma switched impulse transmitters using a Hydrogen-thyratron based modulator, an oil-filled Blumlein (of two types), a peaking (or shorting) switch and a wideband TEM horn. Powers exceeding one-gigawatt are routinely generated. This technology appears to be extendable to at least 10-gigawatts. The frequency spectrum of the radiated pulse from these sources include the spectrum of 100-MHz to 3-GHz. The pulse is generated externally and then injected into the antenna. Due to the high powers involved and the need to radiate a broad spectrum of frequencies, Sandia has concentrated on TEM horn antennas. Several TEM horns have been built and used during this program. In those cases where higher gains are desired for the higher frequencies, TEM horn-fed dish antennas have been employed. A detailed overview of the UWB Transmitters along with measured radiated electric field strengths will be presented.

  7. An overview of Sandia National Laboratories' plasma switched, gigawatt, ultra-wideband impulse transmitter program

    NASA Astrophysics Data System (ADS)

    Clark, R. S.; Rinehart, L. F.; Buttram, M. T.; Aurand, J. F.

    Sandia National Laboratories has developed several repetitive, ultra-wideband (UWB), impulse transmitters to address impulse source technology and to support experimental applications. The sources fall into two different classes, pulse peaking and pulse shorting depending on how the UWB frequency components are generated. The frequency spectrum of the radiated pulse from these sources include the spectrum of 100-MHz to 3-GHz. Depending upon the source, repetitive operation from single shot to 5-kHz (1-kHz nominal) has been obtained with excellent reliability and repeatability. SNIPER (Sub-Nanosecond Impulse Radiator) is a source which uses an oil peaking switch to obtain a fast risetime (250-pS) pulse of 2-nS duration. The output voltage ranges between few tens of kilovolts to 250-kV. EMBL (EnantioMorphic Blumlein) is a similar device (presently under development) which uses a gas switch to sharpen the trailing edge of a 2-nS pulse to approximately 100-pS. To date, an output voltage of approximately 600-kV has been obtained (700-kV is the design goal). Since the frequency spectra are identical between sources with sharpened leading or trailing edges, alternatively, one can use parallel switches to short the pulse at its peak voltage. The pulse is generated externally and then injected into the antenna. Due to the high powers involved and the need to radiate a broad spectrum of frequencies, Sandia has concentrated on TEM horn antennas with special high voltage feed adapters. Several TEM horns have been built and used during this program. In those cases where higher gains are desired for the higher frequencies, TEM horn-fed, dish antennas have been employed. An overview of the UWB transmitters, including design and operation of the modulators, the PFN'S, the pulse sharpening switches and the antennas will be presented.

  8. An overview of Sandia National Laboratories` plasma switched, gigawatt, ultra-wideband impulse transmitter program

    SciTech Connect

    Clark, R.S.; Rinehart, L.F.; Buttram, M.T.; Aurand, J.F.

    1992-11-01

    Sandia National Laboratories has developed several repetitive, ultra-wideband (UWB), impulse transmitters to address impulse source technology and to support experimental applications. The sources fall into two different classes, pulse peaking and pulse shorting depending on how the UWB frequency components are generated. ne frequency spectrum of the radiated pulse from these sources include the spectrum of 100-MHz to 3-GHz. Depending upon the source, repetitive operation from single shot to 5-kHz (1-kHz nominal) has been obtained with excellent reliability and repeatability. SNIPER (Sub-Nanosecond impulse Radiator) is a source which uses an oil peaking switch to obtain a fast risetime (250-pS) pulse of 2-nS duration. The output voltage ranges between few tens of kilovolts to 250-kV. EMBL (EnantioMorphic Blumlein) is a similar device (presently under development) which uses a gas switch to sharpen the trailing edge of a 2-nS pulse to approximately 100-pS. To date, an output voltage of approximately 600-kV has been obtained (700- kV is the design goal). Since the frequency spectra are identical between sources with sharpened leading or trailing edges, alternatively, one can use parallel switches to short the pulse at its peak voltage. The pulse is generated externally and then injected into the antenna. Due to the high powers involved and the need to radiate a broad spectrum of frequencies, Sandia has concentrated on TEM horn. antennas with special high voltage feed adapters. Several TEM horns have been built and used during this program. In those cases where higher gains are desired for the higher frequencies, TEM horn-fed, dish antennas have been employed. An overview of the UWB transmitters, including design and operation of the modulators, the PFN`S, the pulse sharpening switches and the antennas will be presented.

  9. US Imperialism, Transmodernism and Education: A Marxist Critique

    ERIC Educational Resources Information Center

    Cole, Mike

    2004-01-01

    The author begins by discussing David Geoffrey Smith's analysis of the enantiomorphism inherent in the rhetoric of New American Imperialism. He goes on to examine critically Smith's defence of Enrique Dussel's advocacy of transmodernism as a way of understanding this enantiomorphism and of moving beyond what are seen as the constraints of both…

  10. Modelling Symmetry Classes 233 and 432.

    ERIC Educational Resources Information Center

    Dutch, Steven I.

    1986-01-01

    Offers instructions and geometrical data for constructing solids of the enantiomorphous symmetry classes 233 and 432. Provides background information for each class and highlights symmetrical relationships and construction patterns. (ML)

  11. Manifestation of optical activity in different materials

    NASA Astrophysics Data System (ADS)

    Konstantinova, A. F.; Golovina, T. G.; Konstantinov, K. K.

    2014-07-01

    Various manifestations of optical activity (OA) in crystals and organic materials are considered. Examples of optically active enantiomorphic and nonenantiomorphic crystals of 18 symmetry classes are presented. The OA of enantiomorphic organic materials as components of living nature (amino acids, sugars, and proteins) is analyzed. Questions related to the origin of life on earth are considered. Examples of differences in the enantiomers of drugs are shown. The consequences of replacing conventional left-handed amino acids with additionally right-handed amino acids for living organisms are indicated.

  12. Chiral habit selection on nanostructured epitaxial quartz films.

    PubMed

    Carretero-Genevrier, Adrián; Gich, Martí; Picas, Laura; Sanchez, Clément; Rodriguez-Carvajal, Juan

    2015-01-01

    Understanding the crystallization of enantiomorphically pure systems can be relevant to diverse fields such as the study of the origins of life or the purification of racemates. Here we report on polycrystalline epitaxial thin films of quartz on Si substrates displaying two distinct types of chiral habits that never coexist in the same film. We combine Atomic Force Microscopy (AFM) analysis and computer-assisted crystallographic calculations to make a detailed study of these habits of quartz. By estimating the surface energies of the observed crystallites we argue that the films are enantiomorphically pure and we briefly outline a possible mechanism to explain the habit and chiral selection in this system.

  13. Statistical models and NMR analysis of polymer microstructure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Statistical models can be used in conjunction with NMR spectroscopy to study polymer microstructure and polymerization mechanisms. Thus, Bernoullian, Markovian, and enantiomorphic-site models are well known. Many additional models have been formulated over the years for additional situations. Typica...

  14. Homochirality beyond grinding: deracemizing chiral crystals by temperature gradient under boiling.

    PubMed

    Viedma, Cristóbal; Cintas, Pedro

    2011-12-28

    A single-chirality solid phase can be obtained in boiling solutions containing a racemic mixture of left- and right-handed enantiomorphous crystals due to dissolution-crystallization cycles induced by a temperature gradient. This phenomenon provides further insights into asymmetric amplification mechanisms under presumably prebiotic conditions.

  15. Differential effects of opiates on the incorporation of [14C] thiamine in the central nervous system of the rat.

    PubMed

    Misra, A L; Vadlamani, N L; Pontani, R B

    1977-03-15

    Opiate agonist (morphine), pure antagonist (naloxone), mixed agonist-antagonist (nalorphine) and analgesically inactive enantiomorph (dextrorphan) produced differential stereoselective effects on the incorporation of [14C] thiamine in the central nervous system of the rats. The possible role of thiamine in opiate effects and its implications are discussed. PMID:858372

  16. True and false chirality, {ital CP} violation, and the breakdown of microscopic reversibility in chiral molecular and elementary particle processes

    SciTech Connect

    Barron, L.D.

    1996-07-01

    The concept of chirality is extended to cover systems that exhibit enantiomorphism on account of motion. This is achieved by applying time reversal in addition to space inversion and leads to a more precise definition of a chiral system. Although spatial enantiomorphism is sufficient to guarantee chirality in a stationary system such as a finite helix, enantiomorphous systems are not necessarily chiral when motion is involved, which leads to the concept of true and false chirality associated with time-invariant and time-noninvariant enantiomorphism, respectively. Only a truly chiral influence can induce an enantiomeric excess in a reaction that has reached true thermodynamic equilibrium (i.e., when all possible interconversion pathways have equilibrated); however, false chirality can suffice in a reaction under kinetic control due to a breakdown of microscopic reversibility analogous to that observed in particle-antiparticle processes involving the neutral K-meason as a result of {ital CP} violation, with the apparently contradictory kinetic and thermodynamic aspects being reconciled by an appeal to unitarity. This reveals that {ital CP} violation is analogous to chemical catalysis since it affects the rates of certain particle-antiparticle interconversion pathways without affecting the initial and final particle energies and hence the equilibrium thermodynamics. Consideration of falsely chiral influences, including the {open_quote}ratchet effect{close_quote} arising from the associated breakdown in microscopic reversibility, greatly enlarges the range of possible chiral advantage factors in prebiotic chemical processes if far from equilibrium. {copyright} {ital 1996 American Institute of Physics.}

  17. EMBO conference series: Chemical Biology 2014.

    PubMed

    Kennedy, Eileen J

    2014-12-15

    Around 300 people from 18 countries took part in the fourth biennial Chemical Biology conference at The European Molecular Biology Laboratory (EMBL) in Heidelberg, from August 20 to 23, 2014. Many advances in the field of chemical biology were presented in talks and poster sessions. Picture: Petra Riedinger (EMBL).

  18. TARA OCEANS: A Global Analysis of Oceanic Plankton Ecosystems (2013 DOE JGI Genomics of Energy and Environment 8th Annual User Meeting)

    SciTech Connect

    Karsenti, Eric

    2013-03-01

    Eric Karsenti of EMBL delivers the closing keynote on "TARA OCEANS: A Global Analysis of Oceanic Plankton Ecosystems" at the 8th Annual Genomics of Energy & Environment Meeting on March 28, 2013 in Walnut Creek, Calif.

  19. A Molecular Switch Based on Current-Driven Rotation of an Encapsulated Cluster within a Fullerene Cage

    SciTech Connect

    Huang, Tian; Zhao, Jin; Feng, Min; Popov, Alexey A.; Yang, Shangfeng; Dunsch, Lothar; Petek, Hrvoje

    2011-12-14

    By scanning tunneling microscopy imaging and electronic structure theory, we investigate a single-molecule switch based on tunneling electron-driven rotation of a triangular Sc3N cluster within an icosahedral C80 fullerene cage among three pairs of enantiomorphic configurations. Bias-dependent action spectra and modeling implicate the antisymmetric stretch vibration of Sc3N cluster as the gateway for energy transfer from the tunneling electrons into the cluster rotation. Hierarchical switching of conductivity among multiple stationary states while maintaining a constant molecular shape, offers an advantage for the integration of endohedral fullerene-based single-molecule switches into multiple logic state molecular devices.

  20. Optical activity and Alfred Werner's coordination chemistry.

    PubMed

    Ernst, Karl-Heinz; Berke, Heinz

    2011-03-01

    It is widely accepted, that Pasteur's seminal discovery of the opposite optical activity of ammonium sodium tartrate enantiomorphs in solution gave the spark to organic stereochemistry and led to the development of the tetrahedron model by van't Hoff and Le Bel. The proof that chirality is inherently connected to octahedral coordination chemistry fostered greatly Werner's spatial views of metal complexes and his coordination theory. The actual proof of principle was established via separation of diastereomeric camphor sulfonate salts of racemic metal complexes. PMID:20928897

  1. Spontaneous resolution to absolute chiral induction: pseudo-Kagomé type homochiral Zn(II)/Co(II) coordination polymers with achiral precursors.

    PubMed

    Bisht, Kamal Kumar; Suresh, Eringathodi

    2013-10-23

    It is observed that conglomerate crystallization of achiral precursors yielding racemate metal organic frameworks/coordination polymers (MOFs/CPs) can be driven to absolute homochiral crystallization of the desired enantiomorph by utilizing a suitable chiral induction agent. In a series of crystallization experiments isostructural Zn and Co homochiral CPs (1P, 1M and 2P, 2M) are prepared using the achiral precursors. In the presence of enantiopure camphoric acid, the crystallization process prefers absolute chiral induction over conglomerate formation which is established by single crystal X-ray diffraction and CD spectroscopy.

  2. Bioinformatics goes to school--new avenues for teaching contemporary biology.

    PubMed

    Wood, Louisa; Gebhardt, Philipp

    2013-01-01

    Since 2010, the European Molecular Biology Laboratory's (EMBL) Heidelberg laboratory and the European Bioinformatics Institute (EMBL-EBI) have jointly run bioinformatics training courses developed specifically for secondary school science teachers within Europe and EMBL member states. These courses focus on introducing bioinformatics, databases, and data-intensive biology, allowing participants to explore resources and providing classroom-ready materials to support them in sharing this new knowledge with their students. In this article, we chart our progress made in creating and running three bioinformatics training courses, including how the course resources are received by participants and how these, and bioinformatics in general, are subsequently used in the classroom. We assess the strengths and challenges of our approach, and share what we have learned through our interactions with European science teachers.

  3. The androgen receptor gene mutations database.

    PubMed

    Patterson, M N; Hughes, I A; Gottlieb, B; Pinsky, L

    1994-09-01

    The androgen receptor gene mutations database is a comprehensive listing of mutations published in journals and meetings proceedings. The majority of mutations are point mutations identified in patients with androgen insensitivity syndrome. Information is included regarding the phenotype, the nature and location of the mutations, as well as the effects of the mutations on the androgen binding activity of the receptor. The current version of the database contains 149 entries, of which 114 are unique mutations. The database is available from EMBL (NetServ@EMBL-Heidelberg.DE) or as a Macintosh Filemaker file (mc33001@musica.mcgill.ca).

  4. Ligand dependent topology and spontaneous resolution in high-spin cyano-bridged Ni3W2 clusters.

    PubMed

    Nowicka, Beata; Reczyński, Mateusz; Rams, Michał; Wasiutyński, Tadeusz; Nitek, Wojciech; Sieklucka, Barbara

    2016-08-01

    Two high-spin pentanuclear NiW clusters with diimine blocking ligands have been obtained: {[Ni(4,4'-MeObpy)2]3[W(CN)8]2}·12H2O (1) and {[Ni(phen)2(H2O)][Ni(phen)2]2[W(CN)8]2}·7H2O (2) (4,4'-MeObpy = 4,4'-dimethoxy-2,2'-bipyridine, phen = 1,10-phenanthroline). Despite the similarity of the building blocks and synthetic conditions the compounds show different topologies of the cluster core: 1 is a trigonal bipyramid while 2 is a decorated square. Both cluster structures are chiral with either ΔΔΔ or ΛΛΛ configuration around all three Ni centres. In 1 spontaneous resolution occurs and it crystallises in the P212121 space group forming a conglomerate containing both types of enantiomorphic crystals. 1Δ and 1Λ are the first pair of enantiomorphic structures of cyano-bridged clusters of trigonal bipyramidal topology obtained with achiral bidentate blocking ligands. 2 crystallises as a racemic compound in a centrosymmetric space group P1[combining macron] with both enantiomers present in the structure. 2 is an exceptional square-motif containing structure with an identical stereoconfiguration of all complex cations within one cluster. Ferromagnetic interactions are present in both clusters resulting in the ground spin state S = 4. PMID:27431481

  5. Ligand dependent topology and spontaneous resolution in high-spin cyano-bridged Ni3W2 clusters.

    PubMed

    Nowicka, Beata; Reczyński, Mateusz; Rams, Michał; Wasiutyński, Tadeusz; Nitek, Wojciech; Sieklucka, Barbara

    2016-08-01

    Two high-spin pentanuclear NiW clusters with diimine blocking ligands have been obtained: {[Ni(4,4'-MeObpy)2]3[W(CN)8]2}·12H2O (1) and {[Ni(phen)2(H2O)][Ni(phen)2]2[W(CN)8]2}·7H2O (2) (4,4'-MeObpy = 4,4'-dimethoxy-2,2'-bipyridine, phen = 1,10-phenanthroline). Despite the similarity of the building blocks and synthetic conditions the compounds show different topologies of the cluster core: 1 is a trigonal bipyramid while 2 is a decorated square. Both cluster structures are chiral with either ΔΔΔ or ΛΛΛ configuration around all three Ni centres. In 1 spontaneous resolution occurs and it crystallises in the P212121 space group forming a conglomerate containing both types of enantiomorphic crystals. 1Δ and 1Λ are the first pair of enantiomorphic structures of cyano-bridged clusters of trigonal bipyramidal topology obtained with achiral bidentate blocking ligands. 2 crystallises as a racemic compound in a centrosymmetric space group P1[combining macron] with both enantiomers present in the structure. 2 is an exceptional square-motif containing structure with an identical stereoconfiguration of all complex cations within one cluster. Ferromagnetic interactions are present in both clusters resulting in the ground spin state S = 4.

  6. Discovery of a solid solution of enantiomers in a racemate-forming system by seeding.

    PubMed

    Huang, Jun; Chen, Shuang; Guzei, Ilia A; Yu, Lian

    2006-09-13

    A racemic liquid of opposite enantiomers usually crystallizes as a racemic compound (racemate), rarely as a conglomerate, and even more rarely as a solid solution. We discovered a Type II solid solution (mixed crystal) of the enantiomers of the chiral drug tazofelone (TZF) by seeding its racemic liquid with enantiomerically pure crystals (enantiomorphs). Without seeding, the racemic liquid crystallized as a racemic compound. The crystal structure of this solid solution resembles that of the enantiomorph but has static disorder arising from the random substitution of enantiomers. This solid solution is a kinetic product of crystallization made possible by its faster growth rate compared to that of the competing racemate (by 4- to 40-fold between 80 and 146 degrees C). The free energy of the solid solution continuously varies with the enantiomeric composition between those of the conglomerate and the racemates. The existence of the TZF solid solution explains the absence of eutectic melting between crystals of different enantiomeric compositions. The ability of TZF to simultaneously form racemate and solid solution originates from its conformational flexibility. Similar solid solutions of enantiomers may exist in other systems and may be discovered in similar ways. The study demonstrates the use of cross-nucleation for discovering and engineering crystalline materials to optimize physical properties.

  7. Whole genome analysis of Klebsiella pneumoniae T2-1-1 from human oral cavity

    PubMed Central

    Chan, Kok-Gan; Yin, Wai-Fong; Chan, Xin-Yue

    2015-01-01

    Klebsiella pneumoniae T2-1-1 was isolated from the human tongue debris and subjected to whole genome sequencing on HiSeq platform and annotated on RAST. The nucleotide sequence of this genome was deposited into DDBJ/EMBL/GenBank under the accession JAQL00000000. PMID:26981378

  8. Whole genome analysis of Klebsiella pneumoniae T2-1-1 from human oral cavity.

    PubMed

    Chan, Kok-Gan; Yin, Wai-Fong; Chan, Xin-Yue

    2016-03-01

    Klebsiella pneumoniae T2-1-1 was isolated from the human tongue debris and subjected to whole genome sequencing on HiSeq platform and annotated on RAST. The nucleotide sequence of this genome was deposited into DDBJ/EMBL/GenBank under the accession JAQL00000000.

  9. Whole-genome sequence of Clostridium lituseburense L74, isolated from the larval gut of the rhinoceros beetle, Trypoxylus dichotomus.

    PubMed

    Lee, Yookyung; Lim, Sooyeon; Rhee, Moon-Soo; Chang, Dong-Ho; Kim, Byoung-Chan

    2016-03-01

    Clostridium lituseburense L74 was isolated from the larval gut of the rhinoceros beetle, Trypoxylus dichotomus collected in Yeong-dong, Chuncheongbuk-do, South Korea and subjected to whole genome sequencing on HiSeq platform and annotated on RAST. The nucleotide sequence of this genome was deposited into DDBJ/EMBL/GenBank under the accession NZ_LITJ00000000.

  10. [Benign myoclonic epilepsy in infancy: natural history and behavioral and cognitive outcome].

    PubMed

    Domínguez-Carral, Jana; García-Peñas, Juan José; Pérez-Jiménez, M Ángeles; Fournier-Del Castillo, M Concepción; Carreras-Sáez, Inmaculada; Jiménez-Echevarría, Saioa

    2014-02-01

    Introduccion. La epilepsia mioclonica benigna del lactante (EMBL) es un sindrome electroclinico de caracteristicas homogeneas y bien definidas, considerado clasicamente de buen pronostico. Sin embargo, en los ultimos años se han publicado estudios con resultados variables en cuanto a evolucion neuropsicologica. Objetivo. Analizar la evolucion natural y el pronostico neurocognitivo y conductual de los pacientes con EMBL. Pacientes y metodos. Estudio retrospectivo de 10 pacientes con EMBL, con un periodo de seguimiento de mas de cinco años, durante los cuales se realizo una evaluacion neurocognitiva y conductual. Resultados. En el 60% de los pacientes las crisis se controlaron con acido valproico en monoterapia, y el 80% no presento nuevas crisis durante su seguimiento. El cociente intelectual de la cohorte se situo entre 74 y 93; tres pacientes tuvieron un cociente intelectual en rango de inteligencia limite, y seis, en rango de inteligencia media-baja. Nueve pacientes cumplieron criterios de trastorno por deficit de atencion/hiperactividad y dos asociaban otro trastorno del aprendizaje, uno de ellos trastorno de aprendizaje no verbal, y el otro, trastorno especifico de la lectoescritura. Todos los pacientes presentaron datos de pobre coordinacion motriz y visuoespacial, y tres fueron diagnosticados de trastorno de conducta. Conclusiones. El termino 'benigno' en la EMBL debe utilizarse con precaucion en cuanto a su pronostico neurocognitivo y conductual. El inicio precoz y un peor control de las crisis podrian suponer factores de riesgo de evolucion neuropsicologica desfavorable.

  11. High genetic and epigenetic stability in Coffea arabica plants derived from embryogenic suspensions and secondary embryogenesis as revealed by AFLP, MSAP and the phenotypic variation rate.

    PubMed

    Bobadilla Landey, Roberto; Cenci, Alberto; Georget, Frédéric; Bertrand, Benoît; Camayo, Gloria; Dechamp, Eveline; Herrera, Juan Carlos; Santoni, Sylvain; Lashermes, Philippe; Simpson, June; Etienne, Hervé

    2013-01-01

    Embryogenic suspensions that involve extensive cell division are risky in respect to genome and epigenome instability. Elevated frequencies of somaclonal variation in embryogenic suspension-derived plants were reported in many species, including coffee. This problem could be overcome by using culture conditions that allow moderate cell proliferation. In view of true-to-type large-scale propagation of C. arabica hybrids, suspension protocols based on low 2,4-D concentrations and short proliferation periods were developed. As mechanisms leading to somaclonal variation are often complex, the phenotypic, genetic and epigenetic changes were jointly assessed so as to accurately evaluate the conformity of suspension-derived plants. The effects of embryogenic suspensions and secondary embryogenesis, used as proliferation systems, on the genetic conformity of somatic embryogenesis-derived plants (emblings) were assessed in two hybrids. When applied over a 6 month period, both systems ensured very low somaclonal variation rates, as observed through massive phenotypic observations in field plots (0.74% from 200,000 plant). Molecular AFLP and MSAP analyses performed on 145 three year-old emblings showed that polymorphism between mother plants and emblings was extremely low, i.e. ranges of 0-0.003% and 0.07-0.18% respectively, with no significant difference between the proliferation systems for the two hybrids. No embling was found to cumulate more than three methylation polymorphisms. No relation was established between the variant phenotype (27 variants studied) and a particular MSAP pattern. Chromosome counting showed that 7 of the 11 variant emblings analyzed were characterized by the loss of 1-3 chromosomes. This work showed that both embryogenic suspensions and secondary embryogenesis are reliable for true-to-type propagation of elite material. Molecular analyses revealed that genetic and epigenetic alterations are particularly limited during coffee somatic embryogenesis

  12. High Genetic and Epigenetic Stability in Coffea arabica Plants Derived from Embryogenic Suspensions and Secondary Embryogenesis as Revealed by AFLP, MSAP and the Phenotypic Variation Rate

    PubMed Central

    Bobadilla Landey, Roberto; Cenci, Alberto; Georget, Frédéric; Bertrand, Benoît; Camayo, Gloria; Dechamp, Eveline; Herrera, Juan Carlos; Santoni, Sylvain; Lashermes, Philippe; Simpson, June; Etienne, Hervé

    2013-01-01

    Embryogenic suspensions that involve extensive cell division are risky in respect to genome and epigenome instability. Elevated frequencies of somaclonal variation in embryogenic suspension-derived plants were reported in many species, including coffee. This problem could be overcome by using culture conditions that allow moderate cell proliferation. In view of true-to-type large-scale propagation of C. arabica hybrids, suspension protocols based on low 2,4-D concentrations and short proliferation periods were developed. As mechanisms leading to somaclonal variation are often complex, the phenotypic, genetic and epigenetic changes were jointly assessed so as to accurately evaluate the conformity of suspension-derived plants. The effects of embryogenic suspensions and secondary embryogenesis, used as proliferation systems, on the genetic conformity of somatic embryogenesis-derived plants (emblings) were assessed in two hybrids. When applied over a 6 month period, both systems ensured very low somaclonal variation rates, as observed through massive phenotypic observations in field plots (0.74% from 200 000 plant). Molecular AFLP and MSAP analyses performed on 145 three year-old emblings showed that polymorphism between mother plants and emblings was extremely low, i.e. ranges of 0–0.003% and 0.07–0.18% respectively, with no significant difference between the proliferation systems for the two hybrids. No embling was found to cumulate more than three methylation polymorphisms. No relation was established between the variant phenotype (27 variants studied) and a particular MSAP pattern. Chromosome counting showed that 7 of the 11 variant emblings analyzed were characterized by the loss of 1–3 chromosomes. This work showed that both embryogenic suspensions and secondary embryogenesis are reliable for true-to-type propagation of elite material. Molecular analyses revealed that genetic and epigenetic alterations are particularly limited during coffee somatic

  13. Stirring competes with chemical induction in chiral selection of soft matter aggregates.

    PubMed

    Petit-Garrido, Núria; Claret, Josep; Ignés-Mullol, Jordi; Sagués, Francesc

    2012-01-01

    Chirality, the absence of mirror symmetry, can be equally invoked in relation to physical forces and chemical induction processes, yet a competition between these two types of influence is rarely reported. Here we present a self-assembled soft matter system in which chiral selection is controlled by the combined independent action of a chiral dopant and vortical stirring, which are arbitrarily coupled, either constructively or destructively. In the latter case, perfect compensation, that is, absence of a net chiral effect, is realized. The induced enantiomorphic excess is measured in terms of the statistical imbalance of an ensemble of submillimetre domains, where achiral molecules self-assemble with a well-defined orientational chirality that is unambiguously resolved using optical microscopy. The possibility of combining top-down and bottom-up strategies to induce a chiral predominance in a supramolecular system of achiral components should be recognized as a new twist in the process of chiral recognition, selection and control. PMID:22893125

  14. Crystalline Isotactic Polar Polypropylene from the Palladium-Catalyzed Copolymerization of Propylene and Polar Monomers.

    PubMed

    Ota, Yusuke; Ito, Shingo; Kobayashi, Minoru; Kitade, Shinichi; Sakata, Kazuya; Tayano, Takao; Nozaki, Kyoko

    2016-06-20

    Moderately isospecific homopolymerization of propylene and the copolymerization of propylene and polar monomers have been achieved with palladium complexes bearing a phosphine-sulfonate ligand. Optimization of substituents on the phosphorus atom of the ligand revealed that the presence of bulky alkyl groups (e.g. menthyl) is crucial for the generation of high-molecular-weight polypropylenes (Mw ≈10(4) ), and the substituent at the ortho-position relative to the sulfonate group influences the molecular weight and isotactic regularity of the obtained polypropylenes. Statistical analysis suggested that the introduction of substituents at the ortho-position relative to the sulfonate group favors enantiomorphic site control over chain end control in the chain propagation step. The triad isotacticity could be increased to mm=0.55-0.59, with formation of crystalline polar polypropylenes, as supported by the presence of melting points and sharp peaks in the corresponding X-ray diffraction patterns. PMID:27161896

  15. Crystallization and preliminary X-ray analysis of a native human tRNA synthetase whose allelic variants are associated with Charcot-Marie-Tooth disease.

    PubMed

    Xie, Wei; Schimmel, Paul; Yang, Xiang-Lei

    2006-12-01

    Glycyl-tRNA synthetase (GlyRS) is one of a group of enzymes that catalyze the synthesis of aminoacyl-tRNAs for translation. Mutations of human and mouse GlyRSs are causally associated with Charcot-Marie-Tooth disease, the most common genetic disorder of the peripheral nervous system. As the first step towards a structure-function analysis of this disease, native human GlyRS was expressed, purified and crystallized. The crystal belonged to space group P4(3)2(1)2 or its enantiomorphic space group P4(1)2(1)2, with unit-cell parameters a = b = 91.74, c = 247.18 A, and diffracted X-rays to 3.0 A resolution. The asymmetric unit contained one GlyRS molecule and had a solvent content of 69%.

  16. 1',5'-Anhydro-L-ribo-hexitol Adenine Nucleic Acids (α-L-HNA-A): Synthesis and Chiral Selection Properties in the Mirror Image World.

    PubMed

    D'Alonzo, Daniele; Froeyen, Mathy; Schepers, Guy; Di Fabio, Giovanni; Van Aerschot, Arthur; Herdewijn, Piet; Palumbo, Giovanni; Guaragna, Annalisa

    2015-05-15

    The synthesis and a preliminary investigation of the base pairing properties of (6' → 4')-linked 1',5'-anhydro-L-ribo-hexitol nucleic acids (α-L-HNA) have herein been reported through the study of a model oligoadenylate system in the mirror image world. Despite its considerable preorganization due to the rigidity of the "all equatorial" pyranyl sugar backbone, α-L-HNA represents a versatile informational biopolymer, in view of its capability to cross-communicate with natural and unnatural complements in both enantiomeric forms. This seems the result of an inherent flexibility of the oligonucleotide system, as witnessed by the singular formation of iso- and heterochiral associations composed of regular, enantiomorphic helical structures. The peculiar properties of α-L-HNA (and most generally of the α-HNA system) provide new elements in our understanding of the structural prerequisites ruling the stereoselectivity of the hybridization processes of nucleic acids.

  17. A Multi-State Single-Molecule Switch Actuated by Rotation of an Encapsulated Cluster within a Fullerene Cage

    SciTech Connect

    Huang, Tian; Zhao, Jin; Feng, Min; Popov, Alexey A.; Yang, Shangfeng; Dunsch, Lothar; Petek, Hrvoje

    2012-11-12

    We demonstrate a single-molecule switch based on tunneling electron-driven rotation of a triangular Sc₃N cluster within an icosahedral C 80 fullerene cage among three pairs of enantiomorphic configura-tions. Scanning tunneling microscopy imaging of switching within single molecules and electronic structure theory identify the conformational isomers and their isomerization pathways. Bias-dependent actionspectra and modeling identify the antisymmetric stretch vibration of Sc 3N cluster to be the gateway for energy transfer from the tunneling electrons to the cluster rotation. Hierarchical switching of conductivity through the internal cluster motion among multiple stationary states while maintaining a constant shape, is advantageous for the integration of endohedral fullerene-based single-molecule memory and logic devices into parallel molecular computing arc.

  18. A Diffraction System with an X-ray Beam of a Band of Wavelengths

    SciTech Connect

    Koganezawa, T.; Iwasaki, H.; Yoshimura, Y.; Nakamura, N.; Shoji, T.

    2004-05-12

    New diffraction system has been constructed at the Synchrotron Radiation Center at Ritsumeikan University, in which a parallel X-ray beam of a band of wavelengths is produced by reflection from a multilayer monochromator of depth-graded thicknesses. The band width is 0.013 nm and the useful wavelength range is from 0.16 nm to 0.20 nm. Diffraction patterns were taken from a single crystal of an enantiomorphous ferrocene-derivative compound employing an Imaging Plate as a detector. Bragg reflections are seen elongated with a characteristic intensity profile due to anomalous dispersion. Bijvoet pair of reflections show a clear difference in the profile on the short wavelength side of the absorption edge and distinction between the enantiomers can be made more easily than the classical method based on the comparison of integrated intensities.

  19. Scattering of an anisotropic sphere by an arbitrarily incident Hermite-Gaussian beam

    NASA Astrophysics Data System (ADS)

    Qu, Tan; Wu, Zhensen; Shang, Qingchao; Li, Zhengjun; Bai, Lu; Li, Haiying

    2016-02-01

    An analytic theory for the scattering of an off-axis Hermite-Gaussian (HG) beam obliquely incident on an anisotropic sphere is developed. Based on the complex-source-point method and coordinate rotation theory, a general expansion expression for an arbitrarily incident HG beam in terms of Spherical Vector Wave Functions (SVWFs) is derived, and its convergence is numerically discussed. By introducing the Fourier transformation, the internal field expressions of the anisotropic sphere are represented. With the continuous tangential boundary conditions applied, the unknown scattering coefficients are solved. The theory and code are verified from the comparisons between the degenerated cases using our theory and those in the references. Two eigenmodes inside the uniaxial anisotropic sphere are characterized. The influences of beam mode, oblique incident angles, permittivity and permeability tensors, and sphere radius on the scattered field are analyzed numerically. The scattering intensity distributions on uniaxial anisotropic sphere in xoz and yoz plane are enantiomorphous for on-axis oblique illumination.

  20. 2-tert-Butylamino-4-chloro-6-ethylamino-1,3,5-triazine: a structure with Z' = 4 containing two different molecular conformations and two independent chains of hydrogen-bonded R(2)2(8) rings.

    PubMed

    Quesada, Antonio; Fontecha, Maria A; López, Maria V; Low, John N; Glidewell, Christopher

    2008-08-01

    The title compound (trivial name terbutylazine), C(9)H(16)ClN(5), (I), crystallizes with Z' = 4 in the space group Pca2(1), and equal numbers of molecules adopt two different conformations for the ethylamine groups. The four independent molecules form two approximately enantiomorphic pairs. Eight independent N-H...N hydrogen bonds link the molecules into two independent chains of R(2)(2)(8) rings, in which the arrangement of the alkylamine substituents in the independent molecules precludes any further crystallographic symmetry. The significance of this study lies in its finding of two distinct molecular conformations within the structure and two distinct ways in which the molecules are organized into hydrogen-bonded chains, and in its comparison of the hydrogen-bonded structure of (I) with those of analogous 1,3,5-triazines and pyrimidines. PMID:18682660

  1. Electrical magnetochiral anisotropy in a bulk chiral molecular conductor.

    PubMed

    Pop, Flavia; Auban-Senzier, Pascale; Canadell, Enric; Rikken, Geert L J A; Avarvari, Narcis

    2014-01-01

    So far, no effect of chirality on the electrical properties of bulk chiral conductors has been observed. Introduction of chiral information in tetrathiafulvalene precursors represents a powerful strategy towards the preparation of crystalline materials in which the combination of chirality and conducting properties might allow the observation of the electrical magnetochiral anisotropy effect. Here we report the synthesis by electrocrystallization of both enantiomers of a bulk chiral organic conductor based on an enantiopure tetrathiafulvalene derivative. The enantiomeric salts crystallize in enantiomorphic hexagonal space groups. Single crystal resistivity measurements show metallic behaviour for the enantiopure salts down to 40 K, in agreement with band structure calculations. We describe here the first experimental evidence of electrical magnetochiral anisotropy in these crystals, confirming the chiral character of charge transport in our molecular materials. PMID:24796572

  2. Preliminary crystallographic analysis of l-2-keto-3-deoxyarabonate dehydratase, an enzyme involved in an alternative bacterial pathway of L-arabinose metabolism

    SciTech Connect

    Shimada, Naoko; Mikami, Bunzo; Watanabe, Seiya; Makino, Keisuke

    2007-05-01

    l-2-Keto-3-deoxyarabonate dehydratase was overexpressed, purified and crystallized at 291 K using the hanging-drop vapour-diffusion method. l-2-Keto-3-deoxyarabonate (l-KDA) dehydratase is a novel member of the dihydrodipicolinate synthase (DHDPS)/N-acetylneuraminate lyase (NAL) protein family and catalyzes the hydration of l-KDA to α-ketoglutaric semialdehyde. l-KDA dehydratase was overexpressed, purified and crystallized at 291 K using the hanging-drop vapour-diffusion method. The crystal diffracts to 2.0 Å resolution using synchrotron radiation and belongs to the trigonal space group P3{sub 1}21 or its enantiomorph P3{sub 2}21, with unit-cell parameters a = b = 78.91, c = 207.71 Å.

  3. Stereoselective Catalysis Achieved through in Situ Desymmetrization of an Achiral Iron Catalyst Precursor.

    PubMed

    Manna, Cesar M; Kaur, Aman; Yablon, Lauren M; Haeffner, Fredrik; Li, Bo; Byers, Jeffery A

    2015-11-18

    Stereoselective catalysis is described that proceeds with catalyst control but without the need to synthesize preformed chiral catalysts or ligands. Iron-based catalysts were discovered to effect the stereoselective polymerization of lactides starting from a single achiral precursor and the proper choice of an achiral silanol additive. Spectroscopic analysis of the polymer revealed that the stereoselectivity originates from an enantiomorphic site rather than a chain end stereocontrol mechanism. Iron intermediates that are stereogenic at iron are proposed to form in situ as a result of desymmetrization that occurs from a change in the metal coordination number. The proposed mechanism is supported by a combination of spectroscopic measurements, model complexes, kinetic measurements, and DFT calculations.

  4. Icosahedral quasiperiodic packing of fibres parallel to fivefold and threefold axes.

    PubMed

    Audier, M; Duneau, M

    2000-01-01

    Building rules are examined for an icosahedral quasiperiodic packing of fibres with axes parallel to the ten threefold axes, first employing an experimental construction and afterwards a mathematical demonstration using the cut-and-project method applied in hyperspace. As a result of this latter approach, very simple two-dimensional (2D) building rules are proposed. Similar simple 2D rules have also been proposed for the case of an icosahedral quasiperiodic packing with fibre axes parallel to the six fivefold axes [Duneau & Audier (1999). Acta Cryst. A55, 746-754]. Finally, the construction of another icosahedral quasiperiodic packing resulting from a combination of two groups of fibres respectively parallel to six fivefold and ten threefold axes is reported. A brief discussion is given on different particular mechanical behaviours which might a priori be expected from the various enantiomorphic properties of these packings.

  5. The race for megavoltage. X-rays versus telegamma.

    PubMed

    Robison, R F

    1995-01-01

    Roentgen's discovery was announced in January, 1896, and x-ray therapy trials followed in 1897. Becquerel rays and radioactive minerals were identified during 1896 through 1898. Radium was used for therapy by 1901, even though a pure standard was not achieved until 1910-1912. Quantities of radium finally became available after 1919, and for 20 years telegamma therapy machines underwent progressive development. Their megavoltage beam was much preferred over the standard 200-250 KV x-ray units of that time. Nuclear physicists during the Great Depression modified electron accelerators into giant 600-900 KV medical x-ray therapy machines and achieved one MV by 1937-1939. These were huge, complex, expensive, and unique to major academic and/or metropolitan centers. During World War II nuclear reactors superseded cyclotrons as efficient factories for few new radioisotopes, including "artificial radium". Few seemed interested in the latter for use in telegamma therapy until 1949-1951, when three competing teams from Canada and the USA designed telecobalt machines. From this competition, among then unknown innovators, emerged three future giants in radiation therapy: A.E.C.L., H. Johns, and G.H. Fletcher. The clinical application of telecobalt therapy was to revolutionize cancer care in community hospitals worldwide.

  6. Crystallization of a 2:2 complex of granulocyte-colony stimulating factor (GCSF) with the ligand-binding region of the GCSF receptor

    SciTech Connect

    Honjo, Eijiro; Tamada, Taro; Maeda, Yoshitake; Koshiba, Takumi; Matsukura, Yasuko; Okamoto, Tomoyuki; Ishibashi, Matsujiro; Tokunaga, Masao; Kuroki, Ryota

    2005-08-01

    A 2:2 complex of highly purified GCSF receptor (Ig-CRH) with GCSF was crystallized. The crystal diffracted to 2.8 Å resolution with sufficient quality for further structure determination. The granulocyte-colony stimulating factor (GCSF) receptor receives signals for regulating the maturation, proliferation and differentiation of the precursor cells of neutrophilic granulocytes. The signalling complex composed of two GCSFs (GCSF, 19 kDa) and two GCSF receptors (GCSFR, 34 kDa) consisting of an Ig-like domain and a cytokine-receptor homologous (CRH) domain was crystallized. A crystal of the complex was grown in 1.0 M sodium formate and 0.1 M sodium acetate pH 4.6 and belongs to space group P4{sub 1}2{sub 1}2 (or its enantiomorph P4{sub 3}2{sub 1}2), with unit-cell parameters a = b = 110.1, c = 331.8 Å. Unfortunately, this crystal form did not diffract beyond 5 Å resolution. Since the heterogeneity of GCSF receptor appeared to prevent the growth of good-quality crystals, the GCSF receptor was fractionated by anion-exchange chromatography. Crystals of the GCSF–fractionated GCSF receptor complex were grown as a new crystal form in 0.2 M ammonium phosphate. This new crystal form diffracted to beyond 3.0 Å resolution and belonged to space group P3{sub 1}21 (or its enantiomorph P3{sub 2}21), with unit-cell parameters a = b = 134.8, c = 105.7 Å.

  7. From hand to eye: the role of literacy, familiarity, graspability, and vision-for-action on enantiomorphy.

    PubMed

    Fernandes, Tânia; Kolinsky, Régine

    2013-01-01

    Literacy in a script with mirrored symbols boosts the ability to discriminate mirror images, i.e., enantiomorphy. In the present study we evaluated the impact of four factors on enantiomorphic abilities: (i) the degree of literacy of the participants; (ii) the familiarity of the material; (iii) the strength of the association between familiar objects and manipulation, i.e., graspability; and (iv) the involvement of vision-for-action in the task. Three groups of adults - unschooled illiterates, unschooled ex-illiterates, and schooled literates - participated in two experiments. In Experiment 1, participants performed a vision-for-perception task, i.e., an orientation-based same-different comparison task, on pictures of familiar objects and geometric shapes. Graspability of familiar objects and unfamiliarity of the stimuli facilitated orientation discrimination, but did not help illiterate participants to overcome their difficulties with enantiomorphy. Compared to a baseline, illiterate adults had the strongest performance drop for mirror images, whereas for plane rotations the performance drop was similar across groups. In Experiment 2, participants performed a vision-for-action task; they were asked to decide which hand they would use to grasp a familiar object according to its current position (e.g., indicating left-hand usage to grasp a cup with the handle on the left side, and right-hand usage for its mirror image). Illiterates were as skillful as literates to perform this task. The present study thus provided three important findings. First, once triggered by literacy, enantiomorphy generalizes to any visual object category, as part of vision-for-perception, i.e., in visual recognition and identification processes. Second, the impact of literacy is much stronger on enantiomorphy than on the processing of other orientation contrasts. Third, in vision-for-action tasks, illiterates are as sensitive as literates to enantiomorphic-related information.

  8. Crystallization and preliminary crystallographic analysis of a family 43 β-d-xylosidase from Geobacillus stearothermophilus T-6

    SciTech Connect

    Brüx, Christian; Niefind, Karsten; Ben-David, Alon; Leon, Maya; Shoham, Gil; Shoham, Yuval; Schomburg, Dietmar

    2005-12-01

    The crystallization and preliminary X-ray analysis of a β-d-xylosidase from G. stearothermophilus T-6, a family 43 glycoside hydrolase, is described. Native and catalytic inactive mutants of the enzymes were crystallized in two different space groups, orthorhombic P2{sub 1}2{sub 1}2 and tetragonal P4{sub 1}2{sub 1}2 (or the enantiomorphic space group P4{sub 3}2{sub 1}2), using a sensitive cryoprotocol. The latter crystal form diffracted X-rays to a resolution of 2.2 Å. β-d-Xylosidases (EC 3.2.1.37) are hemicellulases that cleave single xylose units from the nonreducing end of xylooligomers. In this study, the crystallization and preliminary X-ray analysis of a β-d-xylosidase from Geobacillus stearothermophilus T-6 (XynB3), a family 43 glycoside hydrolase, is described. XynB3 is a 535-amino-acid protein with a calculated molecular weight of 61 891 Da. Purified recombinant native and catalytic inactive mutant proteins were crystallized and cocrystallized with xylobiose in two different space groups, P2{sub 1}2{sub 1}2 (unit-cell parameters a = 98.32, b = 99.36, c = 258.64 Å) and P4{sub 1}2{sub 1}2 (or the enantiomorphic space group P4{sub 3}2{sub 1}2; unit-cell parameters a = b = 140.15, c = 233.11 Å), depending on the detergent. Transferring crystals to cryoconditions required a very careful protocol. Orthorhombic crystals diffract to 2.5 Å and tetragonal crystals to 2.2 Å.

  9. Compilation of DNA sequences of Escherichia coli (update 1990)

    PubMed Central

    Kröger, Manfred; Wahl, Ralf; Rice, Peter

    1990-01-01

    We have compiled the DNA sequence data for E.coli available from the GENBANK and EMBL data libraries and over a period of several years independently from the literature. This is the second listing replacing and increasing the former listing roughly by one third. After deletion of all detected overlaps a total of 1 248 696 individual bp is found to be determined till the beginning of 1990. This corresponds to a total of 26.46% of the entire E.coli chromosome consisting of about 4,720 kbp. This number may actually be higher by some extra 2% derived from the sequence of lysogenic bacteriophage lambda and various insertion sequences. This compilation is now available in machine readable form from the EMBL data library. PMID:2185457

  10. The European Bioinformatics Institute in 2016: Data growth and integration

    PubMed Central

    Cook, Charles E.; Bergman, Mary Todd; Finn, Robert D.; Cochrane, Guy; Birney, Ewan; Apweiler, Rolf

    2016-01-01

    New technologies are revolutionising biological research and its applications by making it easier and cheaper to generate ever-greater volumes and types of data. In response, the services and infrastructure of the European Bioinformatics Institute (EMBL-EBI, www.ebi.ac.uk) are continually expanding: total disk capacity increases significantly every year to keep pace with demand (75 petabytes as of December 2015), and interoperability between resources remains a strategic priority. Since 2014 we have launched two new resources: the European Variation Archive for genetic variation data and EMPIAR for two-dimensional electron microscopy data, as well as a Resource Description Framework platform. We also launched the Embassy Cloud service, which allows users to run large analyses in a virtual environment next to EMBL-EBI's vast public data resources. PMID:26673705

  11. The Androgen Receptor Gene Mutations Database.

    PubMed

    Gottlieb, B; Lehvaslaiho, H; Beitel, L K; Lumbroso, R; Pinsky, L; Trifiro, M

    1998-01-01

    The current version of the androgen receptor (AR) gene mutations database is described. The total number of reported mutations has risen from 272 to 309 in the past year. We have expanded the database: (i) by giving each entry an accession number; (ii) by adding information on the length of polymorphic polyglutamine (polyGln) and polyglycine (polyGly) tracts in exon 1; (iii) by adding information on large gene deletions; (iv) by providing a direct link with a completely searchable database (courtesy EMBL-European Bioinformatics Institute). The addition of the exon 1 polymorphisms is discussed in light of their possible relevance as markers for predisposition to prostate or breast cancer. The database is also available on the internet (http://www.mcgill. ca/androgendb/ ), from EMBL-European Bioinformatics Institute (ftp. ebi.ac.uk/pub/databases/androgen ), or as a Macintosh FilemakerPro or Word file (MC33@musica.mcgill.ca).

  12. Computational Method for the Systematic Identification of Analog Series and Key Compounds Representing Series and Their Biological Activity Profiles.

    PubMed

    Stumpfe, Dagmar; Dimova, Dilyana; Bajorath, Jürgen

    2016-08-25

    A computational methodology is introduced for detecting all unique series of analogs in large compound data sets, regardless of chemical relationships between analogs. No prior knowledge of core structures or R-groups is required, which are automatically determined. The approach is based upon the generation of retrosynthetic matched molecular pairs and analog networks from which distinct series are isolated. The methodology was applied to systematically extract more than 17 000 distinct series from the ChEMBL database. For comparison, analog series were also isolated from screening compounds and drugs. Known biological activities were mapped to series from ChEMBL, and in more than 13 000 of these series, key compounds were identified that represented substitution sites of all analogs within a series and its complete activity profile. The analog series, key compounds, and activity profiles are made freely available as a resource for medicinal chemistry applications.

  13. A large-scale crop protection bioassay data set.

    PubMed

    Gaulton, Anna; Kale, Namrata; van Westen, Gerard J P; Bellis, Louisa J; Bento, A Patrícia; Davies, Mark; Hersey, Anne; Papadatos, George; Forster, Mark; Wege, Philip; Overington, John P

    2015-01-01

    ChEMBL is a large-scale drug discovery database containing bioactivity information primarily extracted from scientific literature. Due to the medicinal chemistry focus of the journals from which data are extracted, the data are currently of most direct value in the field of human health research. However, many of the scientific use-cases for the current data set are equally applicable in other fields, such as crop protection research: for example, identification of chemical scaffolds active against a particular target or endpoint, the de-convolution of the potential targets of a phenotypic assay, or the potential targets/pathways for safety liabilities. In order to broaden the applicability of the ChEMBL database and allow more widespread use in crop protection research, an extensive data set of bioactivity data of insecticidal, fungicidal and herbicidal compounds and assays was collated and added to the database.

  14. The European Bioinformatics Institute's data resources.

    PubMed

    Brooksbank, Catherine; Camon, Evelyn; Harris, Midori A; Magrane, Michele; Martin, Maria Jesus; Mulder, Nicola; O'Donovan, Claire; Parkinson, Helen; Tuli, Mary Ann; Apweiler, Rolf; Birney, Ewan; Brazma, Alvis; Henrick, Kim; Lopez, Rodrigo; Stoesser, Guenter; Stoehr, Peter; Cameron, Graham

    2003-01-01

    As the amount of biological data grows, so does the need for biologists to store and access this information in central repositories in a free and unambiguous manner. The European Bioinformatics Institute (EBI) hosts six core databases, which store information on DNA sequences (EMBL-Bank), protein sequences (SWISS-PROT and TrEMBL), protein structure (MSD), whole genomes (Ensembl) and gene expression (ArrayExpress). But just as a cell would be useless if it couldn't transcribe DNA or translate RNA, our resources would be compromised if each existed in isolation. We have therefore developed a range of tools that not only facilitate the deposition and retrieval of biological information, but also allow users to carry out searches that reflect the interconnectedness of biological information. The EBI's databases and tools are all available on our website at www.ebi.ac.uk. PMID:12519944

  15. The European Bioinformatics Institute’s data resources 2014

    PubMed Central

    Brooksbank, Catherine; Bergman, Mary Todd; Apweiler, Rolf; Birney, Ewan; Thornton, Janet

    2014-01-01

    Molecular Biology has been at the heart of the ‘big data’ revolution from its very beginning, and the need for access to biological data is a common thread running from the 1965 publication of Dayhoff’s ‘Atlas of Protein Sequence and Structure’ through the Human Genome Project in the late 1990s and early 2000s to today’s population-scale sequencing initiatives. The European Bioinformatics Institute (EMBL-EBI; http://www.ebi.ac.uk) is one of three organizations worldwide that provides free access to comprehensive, integrated molecular data sets. Here, we summarize the principles underpinning the development of these public resources and provide an overview of EMBL-EBI’s database collection to complement the reviews of individual databases provided elsewhere in this issue. PMID:24271396

  16. A large-scale crop protection bioassay data set.

    PubMed

    Gaulton, Anna; Kale, Namrata; van Westen, Gerard J P; Bellis, Louisa J; Bento, A Patrícia; Davies, Mark; Hersey, Anne; Papadatos, George; Forster, Mark; Wege, Philip; Overington, John P

    2015-01-01

    ChEMBL is a large-scale drug discovery database containing bioactivity information primarily extracted from scientific literature. Due to the medicinal chemistry focus of the journals from which data are extracted, the data are currently of most direct value in the field of human health research. However, many of the scientific use-cases for the current data set are equally applicable in other fields, such as crop protection research: for example, identification of chemical scaffolds active against a particular target or endpoint, the de-convolution of the potential targets of a phenotypic assay, or the potential targets/pathways for safety liabilities. In order to broaden the applicability of the ChEMBL database and allow more widespread use in crop protection research, an extensive data set of bioactivity data of insecticidal, fungicidal and herbicidal compounds and assays was collated and added to the database. PMID:26175909

  17. Petabyte-scale innovations at the European Nucleotide Archive.

    PubMed

    Cochrane, Guy; Akhtar, Ruth; Bonfield, James; Bower, Lawrence; Demiralp, Fehmi; Faruque, Nadeem; Gibson, Richard; Hoad, Gemma; Hubbard, Tim; Hunter, Christopher; Jang, Mikyung; Juhos, Szilveszter; Leinonen, Rasko; Leonard, Steven; Lin, Quan; Lopez, Rodrigo; Lorenc, Dariusz; McWilliam, Hamish; Mukherjee, Gaurab; Plaister, Sheila; Radhakrishnan, Rajesh; Robinson, Stephen; Sobhany, Siamak; Hoopen, Petra Ten; Vaughan, Robert; Zalunin, Vadim; Birney, Ewan

    2009-01-01

    Dramatic increases in the throughput of nucleotide sequencing machines, and the promise of ever greater performance, have thrust bioinformatics into the era of petabyte-scale data sets. Sequence repositories, which provide the feed for these data sets into the worldwide computational infrastructure, are challenged by the impact of these data volumes. The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/embl), comprising the EMBL Nucleotide Sequence Database and the Ensembl Trace Archive, has identified challenges in the storage, movement, analysis, interpretation and visualization of petabyte-scale data sets. We present here our new repository for next generation sequence data, a brief summary of contents of the ENA and provide details of major developments to submission pipelines, high-throughput rule-based validation infrastructure and data integration approaches.

  18. MOCAT2: a metagenomic assembly, annotation and profiling framework

    PubMed Central

    Kultima, Jens Roat; Coelho, Luis Pedro; Forslund, Kristoffer; Huerta-Cepas, Jaime; Li, Simone S.; Driessen, Marja; Voigt, Anita Yvonne; Zeller, Georg; Sunagawa, Shinichi; Bork, Peer

    2016-01-01

    Summary: MOCAT2 is a software pipeline for metagenomic sequence assembly and gene prediction with novel features for taxonomic and functional abundance profiling. The automated generation and efficient annotation of non-redundant reference catalogs by propagating pre-computed assignments from 18 databases covering various functional categories allows for fast and comprehensive functional characterization of metagenomes. Availability and Implementation: MOCAT2 is implemented in Perl 5 and Python 2.7, designed for 64-bit UNIX systems and offers support for high-performance computer usage via LSF, PBS or SGE queuing systems; source code is freely available under the GPL3 license at http://mocat.embl.de. Contact: bork@embl.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153620

  19. The European Bioinformatics Institute in 2016: Data growth and integration.

    PubMed

    Cook, Charles E; Bergman, Mary Todd; Finn, Robert D; Cochrane, Guy; Birney, Ewan; Apweiler, Rolf

    2016-01-01

    New technologies are revolutionising biological research and its applications by making it easier and cheaper to generate ever-greater volumes and types of data. In response, the services and infrastructure of the European Bioinformatics Institute (EMBL-EBI, www.ebi.ac.uk) are continually expanding: total disk capacity increases significantly every year to keep pace with demand (75 petabytes as of December 2015), and interoperability between resources remains a strategic priority. Since 2014 we have launched two new resources: the European Variation Archive for genetic variation data and EMPIAR for two-dimensional electron microscopy data, as well as a Resource Description Framework platform. We also launched the Embassy Cloud service, which allows users to run large analyses in a virtual environment next to EMBL-EBI's vast public data resources. PMID:26673705

  20. The NRSub database: update 1997.

    PubMed

    Perrière, G; Moszer, I; Gojobori, T

    1997-01-01

    In the context of the international project aiming at sequencing the whole genome of Bacillus subtilis we have developed NRSub, a non-redundant database of sequences from this organism. Starting from the B.subtilis sequences available in the repository collections we have removed all encountered duplications, then we have added extra annotations to the sequences (e.g. accession numbers for the genes, locations on the genetic map, codon usage index). We have also added cross-references with EMBL/GenBank/DDBJ, MEDLINE, SWISS-PROT and ENZYME databases. NRSub is distributed through anonymous FTP as a text file in EMBL format and as an ACNUC database. It is also possible to access the database through two dedicated World Wide Web servers located in France (http://acnuc.univ-lyon1.fr/nrsub/nrsub.++ +html ) and in Japan (http://ddbjs4h.genes.nig.ac.jp/ ). PMID:9016504

  1. Polymorphix: a sequence polymorphism database.

    PubMed

    Bazin, Eric; Duret, Laurent; Penel, Simon; Galtier, Nicolas

    2005-01-01

    Within-species sequence variation data are of special interest since they contain information about recent population/species history, and the molecular evolutionary forces currently in action in natural populations. These data, however, are presently dispersed within generalist databases, and are difficult to access. To solve this problem, we have developed Polymorphix, a database dedicated to sequence polymorphism. It contains within-species homologous sequence families built using EMBL/GenBank under suitable similarity and bibliographic criteria. Polymorphix is an ACNUC structured database allowing both simple and complex queries for population genomic studies. Alignments within families as well as phylogenetic trees can be download. When available, outgroups are included in the alignment. Polymorphix contains sequences from the nuclear, mitochondrial and chloroplastic genomes of every eukaryote species represented in EMBL. It can be accessed by a web interface (http://pbil.univ-lyon1.fr/polymorphix/query.php).

  2. Draft genome sequence of extremely acidophilic bacterium Acidithiobacillus ferrooxidans DLC-5 isolated from acid mine drainage in Northeast China.

    PubMed

    Chen, Peng; Yan, Lei; Wu, Zhengrong; Xu, Ruixiang; Li, Suyue; Wang, Ningbo; Liang, Ning; Li, Hongyu

    2015-12-01

    Acidithiobacillus ferrooxidans type strain DLC-5, isolated from Wudalianchi in Heihe of Heilongjiang Province, China. Here, we present the draft genome of strain DLC-5 which contains 4,232,149 bp in 2745 contigs with 57.628% GC content and includes 32,719 protein-coding genes and 64 tRNA-encoding genes. The genome sequence can be accessed at DDBJ/EMBL/GenBank under the accession no. JNNH00000000.1.

  3. Effect of site-specific modification on restriction endonucleases and DNA modification methyltransferases.

    PubMed Central

    McClelland, M; Nelson, M; Raschke, E

    1994-01-01

    Restriction endonucleases have site-specific interactions with DNA that can often be inhibited by site-specific DNA methylation and other site-specific DNA modifications. However, such inhibition cannot generally be predicted. The empirically acquired data on these effects are tabulated for over 320 restriction endonucleases. In addition, a table of known site-specific DNA modification methyltransferases and their specificities is presented along with EMBL database accession numbers for cloned genes. PMID:7937074

  4. Draft genome of iron-oxidizing bacterium Leptospirillum sp. YQP-1 isolated from a volcanic lake in the Wudalianchi volcano, China.

    PubMed

    Yan, Lei; Zhang, Shuang; Yu, Gaobo; Ni, Yongqing; Wang, Weidong; Hu, Huixin; Chen, Peng

    2015-12-01

    Leptospirillum sp. YQP-1, a member of iron-oxidizing bacteria was isolated from volcanic lake in northeast China. Here, we report the draft genome sequence of the strain YQP-1 with a total genome size of 3,103,789 bp from 85 scaffolds (104 contigs) with 58.64% G + C content. The genome sequence can be accessed at DDBJ/EMBL/GenBank under the accession no. LIEB00000000. PMID:26697362

  5. Complete genome sequence of a giant Vibrio phage ValKK3 infecting Vibrio alginolyticus.

    PubMed

    Lal, Tamrin M; Sano, Motohiko; Hatai, Kishio; Ransangan, Julian

    2016-06-01

    This paper describes the complete sequence of a giant lytic marine myophage, Vibrio phage ValKK3 that is specific to Vibrio alginolyticus ATCC(®) 17749™. Vibrio phage ValKK3 was subjected to whole genome sequencing on MiSeq sequencing platform and annotated using Blast2Go. The complete sequence of ValKK3 genome was deposited in DBBJ/EMBL/GenBank under accession number KP671755. PMID:27114905

  6. Draft genome of iron-oxidizing bacterium Leptospirillum sp. YQP-1 isolated from a volcanic lake in the Wudalianchi volcano, China.

    PubMed

    Yan, Lei; Zhang, Shuang; Yu, Gaobo; Ni, Yongqing; Wang, Weidong; Hu, Huixin; Chen, Peng

    2015-12-01

    Leptospirillum sp. YQP-1, a member of iron-oxidizing bacteria was isolated from volcanic lake in northeast China. Here, we report the draft genome sequence of the strain YQP-1 with a total genome size of 3,103,789 bp from 85 scaffolds (104 contigs) with 58.64% G + C content. The genome sequence can be accessed at DDBJ/EMBL/GenBank under the accession no. LIEB00000000.

  7. SIRW: A web server for the Simple Indexing and Retrieval System that combines sequence motif searches with keyword searches.

    PubMed

    Ramu, Chenna

    2003-07-01

    SIRW (http://sirw.embl.de/) is a World Wide Web interface to the Simple Indexing and Retrieval System (SIR) that is capable of parsing and indexing various flat file databases. In addition it provides a framework for doing sequence analysis (e.g. motif pattern searches) for selected biological sequences through keyword search. SIRW is an ideal tool for the bioinformatics community for searching as well as analyzing biological sequences of interest.

  8. RNA-Seq analysis of urea nutrition responsive transcriptome of Oryza sativa elite indica cultivar RP Bio 226

    PubMed Central

    Reddy, Mettu Madhavi; Ulaganathan, Kandasamy

    2015-01-01

    Rice yield is greatly influenced by the nitrogen and rice varieties show variation in yield. For understanding the role of urea nutrition in the yield of elite indica rice cultivar RPBio-226, the urea responsive transcriptome was sequenced and analyzed. The raw reads and the Transcriptome Shotgun Assembly project has been deposited at DDBJ/EMBL/GenBank under the accession GDKM00000000. The version described in this paper is the first version, GDKM01000000. PMID:26697348

  9. Whole-genome sequence of Sunxiuqinia dokdonensis DH1(T), isolated from deep sub-seafloor sediment in Dokdo Island.

    PubMed

    Lim, Sooyeon; Chang, Dong-Ho; Kim, Byoung-Chan

    2016-09-01

    Sunxiuqinia dokdonensis DH1(T) was isolated from deep sub-seafloor sediment at a depth of 900 m below the seafloor off Seo-do (the west part of Dokdo Island) in the East Sea of the Republic of Korea and subjected to whole genome sequencing on HiSeq platform and annotated on RAST. The nucleotide sequence of this genome was deposited into DDBJ/EMBL/GenBank under the accession LGIA00000000.

  10. Whole genome sequence of Oscheius sp. TEL-2014 entomopathogenic nematodes isolated from South Africa

    PubMed Central

    Lephoto, Tiisetso E.; Mpangase, Phelelani T.; Aron, Shaun; Gray, Vincent M.

    2016-01-01

    We present the annotation of the draft genome sequence of Oscheius sp. TEL-2014 (Genbank accession number KM492926). This entomopathogenic nematode was isolated from grassland in Suikerbosrand Nature Reserve near Johannesburg in South Africa. Oscheius sp. Strain TEL has a genome size of 110,599,558 bp and a GC content of 42.24%. The genome sequence can be accessed at DDBJ/EMBL/GenBank under the accession number LNBV00000000. PMID:27054091

  11. Whole-genome sequence of Sunxiuqinia dokdonensis DH1(T), isolated from deep sub-seafloor sediment in Dokdo Island.

    PubMed

    Lim, Sooyeon; Chang, Dong-Ho; Kim, Byoung-Chan

    2016-09-01

    Sunxiuqinia dokdonensis DH1(T) was isolated from deep sub-seafloor sediment at a depth of 900 m below the seafloor off Seo-do (the west part of Dokdo Island) in the East Sea of the Republic of Korea and subjected to whole genome sequencing on HiSeq platform and annotated on RAST. The nucleotide sequence of this genome was deposited into DDBJ/EMBL/GenBank under the accession LGIA00000000. PMID:27437183

  12. Draft genome of iron-oxidizing bacterium Leptospirillum sp. YQP-1 isolated from a volcanic lake in the Wudalianchi volcano, China

    PubMed Central

    Yan, Lei; Zhang, Shuang; Yu, Gaobo; Ni, Yongqing; Wang, Weidong; Hu, Huixin; Chen, Peng

    2015-01-01

    Leptospirillum sp. YQP-1, a member of iron-oxidizing bacteria was isolated from volcanic lake in northeast China. Here, we report the draft genome sequence of the strain YQP-1 with a total genome size of 3,103,789 bp from 85 scaffolds (104 contigs) with 58.64% G + C content. The genome sequence can be accessed at DDBJ/EMBL/GenBank under the accession no. LIEB00000000. PMID:26697362

  13. Compilation of DNA sequences of Escherichia coli (update 1993).

    PubMed Central

    Kröger, M; Wahl, R; Rice, P

    1993-01-01

    We have compiled the DNA sequence data for E. coli available from the GENBANK and EMBL data libraries and over a period of several years independently from the literature. This is the fifth listing replacing and increasing the former listings substantially. However, in order to save space this printed version contains DNA sequence information only, if they are publically available in electronic form. The complete compilation including a full set of genetic map data and the E. coli protein index can be obtained in machine readable form from the EMBL data library (ECD release 15) as a part of the CD-ROM issue of the EMBL sequence database, released and updated every three months. After deletion of all detected overlaps a total of 2,353,635 individual bp is found to be determined till the end of April 1993. This corresponds to a total of 49.87% of the entire E. coli chromosome consisting of about 4,720 kbp. This number may actually be higher by 9161 bp derived from other strains of E. coli. PMID:8332520

  14. NRSub: a non-redundant database for Bacillus subtilis.

    PubMed

    Perrière, G; Moszer, I; Gojobori, T

    1996-01-01

    In the context of the international project aimed at sequencing the whole genome of Bacillus subtilis we have developed a non-redundant, fully annotated database of sequences from this organism. Starting from the B.subtilis sequences available in the EMBL, GenBank and DDBJ collections we have removed all encountered duplications and then added extra annotations to the sequences (e.g. accession numbers for the genes, locations on the genetic map, codon usage, etc.) We have also added cross-references to the EMBL, MEDLINE, SWISS-PROT and ENZYME data banks. The present system results from merging of the NRSub and SubtiList databases and the sequence contigs used in the two systems are identical. NRSub is distributed as a flatfile in EMBL format (which is supported by most sequence analysis software packages) and as an ACNUC database, while SubtiList is distributed as a relational database under 4th Dimension. It is possible to access the data through two dedicated World Wide Web servers located in France and Japan. PMID:8594597

  15. Commentary on "integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer." Weischenfeldt J, Simon R, Feuerbach L, Schlangen K, Weichenhan D, Minner S, Wuttig D, Warnatz HJ, Stehr H, Rausch T, Jäger N, Gu L, Bogatyrova O, Stütz AM, Claus R, Eils J, Eils R, Gerhäuser C, Huang PH, Hutter B, Kabbe R, Lawerenz C, Radomski S, Bartholomae CC, Fälth M, Gade S, Schmidt M, Amschler N, Haß T, Galal R, Gjoni J, Kuner R, Baer C, Masser S, von Kalle C, Zichner T, Benes V, Raeder B, Mader M, Amstislavskiy V, Avci M, Lehrach H, Parkhomchuk D, Sultan M, Burkhardt L, Graefen M, Huland H, Kluth M, Krohn A, Sirma H, Stumm L, Steurer S, Grupp K, Sültmann H, Sauter G, Plass C, Brors B, Yaspo ML, Korbel JO, Schlomm T, Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.: Cancer Cell 2013;23(2):159-70.

    PubMed

    Olumi, Aria F

    2014-02-01

    Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of>10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic "androgen-type" pathomechanism in EO-PCA.

  16. p53-Mediated apoptosis is the primary cause of radiation sensitivity in ataxia-telangiectasia

    SciTech Connect

    Meyn, M.S.; Strasfeld, L.; Allen, C.

    1994-09-01

    The autosomal recessive disease ataxia-telangiectasia (A-T) is characterized by ataxia, immune defects, genetic instability and cancer. A cardinal feature of A-T is a marked sensitivity to the killing effects of ionizing radiation. However, repair of DNA damage in A-T cells is grossly normal and the cause of the radiation sensitivity has remained puzzling despite numerous investigations. We now report that p53-mediated apoptosis is primarily responsible for the radiation sensitivity of A-T cells. We exposed representing three different complementation groups as well as two control cell lines to 0, 1.5 and 3 Gy of 250 kv X-radiation. Morphologic changes, the appearance of cells with sub-G{sub 1} DNA content and presence of nucleosome ladders in genomic DNA were considered evidence of apoptosis. By all three criteria, apoptosis was detectable in the A-T cells 24-48 hours after irradiation, peaking by 72 hours. In contrast, control cells underwent minimal apoptosis. Similar results were obtained with 24 hours` exposure to 0.25-0.5 ng/ml streptonigrin, a radiomimetic mutagen. Disruption of p53 function in an A-T fibroblast line by transfection of either the dominant-negative p53{sup 143ala} mutant or an HPV18 E6 gene was associated with acquisition of near-normal drug resistance and radiation-resistance, while transfection and expression of the p53{sup 143ala} mutant did not affect the streptonigrin sensitivity of a control fibroblast line. Our results support our hypothesis that an unusually low threshold for the activation of p53-mediated apoptosis by DNA damage may be the primary etiology for both in vivo and in vitro mutagen-sensitivity in A-T. These data also suggest an etiology for the neurological deterioration and immune defects seen in A-T patients: inappropriate activation of apoptosis by spontaneous DNA damage.

  17. 1D and 2D assembly structures by imidazole···chloride hydrogen bonds of iron(II) complexes [Fe(II)(HL(n-Pr))3]Cl·Y (HL(n-Pr) = 2-methylimidazol-4-yl-methylideneamino-n-propyl; Y = AsF6, BF4) and their spin states.

    PubMed

    Fujinami, Takeshi; Nishi, Koshiro; Matsumoto, Naohide; Iijima, Seiichiro; Halcrow, Malcolm A; Sunatsuki, Yukinari; Kojima, Masaaki

    2011-12-01

    Two Fe(II) complexes fac-[Fe(II)(HL(n-Pr))(3)]Cl·Y (Y = AsF(6) (1) and BF(4) (2)) were synthesized, where HL(n-Pr) is 2-methylimidazole-4-yl-methylideneamino-n-propyl. Each complex-cation has the same octahedral N(6) geometry coordinated by three bidentate ligands and assumes facial-isomerism, fac-[Fe(II)(HL(n-Pr))(3)](2+) with Δ- and Λ-enantiomorphs. Three imidazole groups per Δ- or Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) are hydrogen-bonded to three Cl(-) ions or, from the viewpoint of the Cl(-) ion, one Cl(-) ion is hydrogen-bonded to three neighbouring fac-[Fe(II)(HL(n-Pr))(3)](2+) cations. The 3 : 3 NH···Cl(-) hydrogen bonds between Δ- or Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) and Cl(-) generate two kinds of assembly structures. The directions of the 3 : 3 NH···Cl(-) hydrogen bonds and hence the resulting assembly structures are determined by the size of the anion Y, though Y is not involved into the network structure and just accommodated in the cavity. Compound 1 has a 1D ladder structure giving a larger cavity, in which the Δ- and Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) enantiomorphs are bridged by two NH···Cl(-) hydrogen bonds. Compound 2 has a 2D network structure with a net unit of a cyclic trimer of {fac-[Fe(II)(HL(n-Pr))(3)](2+)···Cl(-)}(3) giving a smaller cavity, in which Δ- or Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) species with the same chirality are linked by NH···Cl(-) hydrogen bonds to give a homochiral 2D network structure. Magnetic susceptibility and Mössbauer spectral measurements demonstrated that compound 1 showed an abrupt one-step spin crossover with 4.0 K thermal hysteresis of T(c↓) = 125.5 K and T(c↑) = 129.5 K and compound 2 showed no spin transition and stayed in the high-spin state over the 5-300 K temperature range.

  18. Draft genome sequence of Acidithiobacillus ferrooxidans YQH-1.

    PubMed

    Yan, Lei; Zhang, Shuang; Wang, Weidong; Hu, Huixin; Wang, Yanjie; Yu, Gaobo; Chen, Peng

    2015-12-01

    Acidithiobacillus ferrooxidans YQH-1 is a moderate acidophilic bacterium isolated from a river in a volcano of Northeast China. Here, we describe the draft genome of strain YQH-1, which was assembled into 123 contigs containing 3,111,222 bp with a G + C content of 58.63%. A large number of genes related to carbon dioxide fixation, dinitrogen fixation, pH tolerance, heavy metal detoxification, and oxidative stress defense were detected. The genome sequence can be accessed at DDBJ/EMBL/GenBank under the accession no. LJBT00000000. PMID:26697394

  19. Complete genome sequence of the gram-negative probiotic Escherichia coli strain Nissle 1917.

    PubMed

    Reister, Marten; Hoffmeier, Klaus; Krezdorn, Nicolas; Rotter, Bjoern; Liang, Chunguang; Rund, Stefan; Dandekar, Thomas; Sonnenborn, Ulrich; Oelschlaeger, Tobias A

    2014-10-10

    Escherichia coli strain Nissle 1917 (EcN) is the active principle of a probiotic preparation (trade name Mutaflor(®)) used for the treatment of patients with intestinal diseases such as ulcerative colitis and diarrhea. It has GRAS (generally recognized as save) status and has been shown to be a therapeutically effective drug (Sonnenborn and Schulze, 2009). The complete genomic DNA sequence will help in identifying genes and their products which are essential for the strains probiotic nature. Genbank/EMBL/DDBJ accession number: CP007799 (chromosome). PMID:25093936

  20. Draft genome sequence of the docosahexaenoic acid producing thraustochytrid Aurantiochytrium sp. T66.

    PubMed

    Liu, Bin; Ertesvåg, Helga; Aasen, Inga Marie; Vadstein, Olav; Brautaset, Trygve; Heggeset, Tonje Marita Bjerkan

    2016-06-01

    Thraustochytrids are unicellular, marine protists, and there is a growing industrial interest in these organisms, particularly because some species, including strains belonging to the genus Aurantiochytrium, accumulate high levels of docosahexaenoic acid (DHA). Here, we report the draft genome sequence of Aurantiochytrium sp. T66 (ATCC PRA-276), with a size of 43 Mbp, and 11,683 predicted protein-coding sequences. The data has been deposited at DDBJ/EMBL/Genbank under the accession LNGJ00000000. The genome sequence will contribute new insight into DHA biosynthesis and regulation, providing a basis for metabolic engineering of thraustochytrids. PMID:27222814

  1. Genome sequencing and annotation of Aeromonas sp. HZM

    PubMed Central

    Chua, Patric; Har, Zi Mei; Austin, Christopher M.; Yule, Catherine M.; Dykes, Gary A.; Lee, Sui Mae

    2015-01-01

    We report the draft genome sequence of Aeromonas sp. strain HZM, isolated from tropical peat swamp forest soil. The draft genome size is 4,451,364 bp with a G + C content of 61.7% and contains 10 rRNA sequences (eight copies of 5S rRNA genes, single copy of 16S and 23S rRNA each). The genome sequence can be accessed at DDBJ/EMBL/GenBank under the accession no. JEMQ00000000. PMID:26484220

  2. A CORBA server for the Radiation Hybrid DataBase.

    PubMed

    Rodriguez-Tomé, P; Helgesen, C; Lijnzaad, P; Jungfer, K

    1997-01-01

    Modern biology depends on a wide range of software interacting with a large number of data sources, varying both in size, complexity and structure. The range of important databases in molecular biology and genetics makes it crucial to overcome the problems which this multiplicity presents. At EMBL-EBI we have started to use CORBA technology to support interoperability between a variety of databases, as well as to facilitate the integration of tools that access these databases. Within the Radiation Hybrid DataBase project we are confronted daily with the interoperation and linking issues. In this paper we present a CORBA infrastructure implemented to access the Radiation Hybrid DataBase.

  3. Crystal growth and preliminary X-ray study of glutamic acid specific serine protease from Bacillus intermedius

    NASA Astrophysics Data System (ADS)

    Kuranova, I. P.; Blagova, E. V.; Levdikov, V. M.; Rudenskaya, G. N.; Balaban, N. P.; Shakirov, E. V.

    1999-01-01

    The glutamic acid specific protease (glutamyl-endopeptidase) from Bacillus intermedius, strain 3-19, was isolated and purified using ion exchange chromatography on CM-cellulose and Mono-S FPLC column. The conditions for crystallization of the enzyme have been discussed. The crystals of enzyme were grown using hanging-drop vapor-diffusion technique. Crystals belong to the space group C2 with unit cell parameters of a=61.62 Å, b=55.84 Å, c=60.40 Å, β=117.6° X-ray diffraction data to 1.68 Å resolution were collected using synchrotron radiation (EMBL, Hamburg) and an imaging plate scanner.

  4. Whole genome sequences and annotation of Micrococcus luteus SUBG006, a novel phytopathogen of mango.

    PubMed

    Rakhashiya, Purvi M; Patel, Pooja P; Thaker, Vrinda S

    2015-12-01

    Actinobaceria, Micrococcus luteus SUBG006 was isolated from infected leaves of Mangifera indica L. vr. Nylon in Rajkot, (22.30°N, 70.78°E), Gujarat, India. The genome size is 3.86 Mb with G + C content of 69.80% and contains 112 rRNA sequences (5S, 16S and 23S). The whole genome sequencing has been deposited in DDBJ/EMBL/GenBank under the accession number JOKP00000000. PMID:26697318

  5. Draft genome sequence of Acidithiobacillus ferrooxidans YQH-1

    PubMed Central

    Yan, Lei; Zhang, Shuang; Wang, Weidong; Hu, Huixin; Wang, Yanjie; Yu, Gaobo; Chen, Peng

    2015-01-01

    Acidithiobacillus ferrooxidans YQH-1 is a moderate acidophilic bacterium isolated from a river in a volcano of Northeast China. Here, we describe the draft genome of strain YQH-1, which was assembled into 123 contigs containing 3,111,222 bp with a G + C content of 58.63%. A large number of genes related to carbon dioxide fixation, dinitrogen fixation, pH tolerance, heavy metal detoxification, and oxidative stress defense were detected. The genome sequence can be accessed at DDBJ/EMBL/GenBank under the accession no. LJBT00000000. PMID:26697394

  6. Genome sequencing and annotation of multidrug resistant Mycobacterium tuberculosis (MDR-TB) PR10 strain.

    PubMed

    Halim, Mohd Zakihalani A; Jaafar, Mohammad Maaruf; Teh, Lay Kek; Ismail, Mohamad Izwan; Lee, Lian Shien; Ngeow, Yun Fong; Nor, Norazmi Mohd; Zainuddin, Zainul Fadziruddin; Tang, Thean Hock; Najimudin, Mohd Nazalan Mohd; Salleh, Mohd Zaki

    2016-03-01

    Here, we report the draft genome sequence and annotation of a multidrug resistant Mycobacterium tuberculosis strain PR10 (MDR-TB PR10) isolated from a patient diagnosed with tuberculosis. The size of the draft genome MDR-TB PR10 is 4.34 Mbp with 65.6% of G + C content and consists of 4637 predicted genes. The determinants were categorized by RAST into 400 subsystems with 4286 coding sequences and 50 RNAs. The whole genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession number CP010968.

  7. Draft genome sequence of a multidrug-resistant Chryseobacterium indologenes isolate from Malaysia

    PubMed Central

    Yu, Choo Yee; Ang, Geik Yong; Cheng, Huey Jia; Cheong, Yuet Meng; Yin, Wai-Fong; Chan, Kok-Gan

    2015-01-01

    Chryseobacterium indologenes is an emerging pathogen which poses a threat in clinical healthcare setting due to its multidrug-resistant phenotype and its common association with nosocomial infections. Here, we report the draft genome of a multidrug-resistant C. indologenes CI_885 isolated in 2014 from Malaysia. The 908,704-kb genome harbors a repertoire of putative antibiotic resistance determinants which may elucidate the molecular basis and underlying mechanisms of its resistant to various classes of antibiotics. The genome sequence has been deposited in DDBJ/EMBL/GenBank under the accession number LJOD00000000. PMID:26981402

  8. hERG me out.

    PubMed

    Czodrowski, Paul

    2013-09-23

    A detailed analysis of the hERG content inside the ChEMBL database is performed. The correlation between the outcome from binding assays and functional assays is probed. On the basis of descriptor distributions, design paradigms with respect to structural and physicochemical properties of hERG active and hERG inactive compounds are challenged. Finally, classification models with different data sets are trained. All source code is provided, which is based on the Python open source packages RDKit and scikit-learn to enable the community to rerun the experiments. The code is stored on github ( https://github.com/pzc/herg_chembl_jcim).

  9. Database on the structure of small ribosomal subunit RNA.

    PubMed Central

    Van de Peer, Y; Van den Broeck, I; De Rijk, P; De Wachter, R

    1994-01-01

    The database on small ribosomal subunit RNA structure contains (June 1994) 2824 nucleotide sequences. All these sequences are stored in the form of an alignment based on the adopted secondary structure model, which in turn is corroborated by the observation of compensating substitutions in the alignment. The complete database is made available to the scientific community through anonymous ftp on our server in Antwerp. A special effort was made to improve electronic retrieval and a program is supplied that allows to create different file formats. The database can also be obtained from the EMBL nucleotide sequence library. PMID:7524022

  10. hERG me out.

    PubMed

    Czodrowski, Paul

    2013-09-23

    A detailed analysis of the hERG content inside the ChEMBL database is performed. The correlation between the outcome from binding assays and functional assays is probed. On the basis of descriptor distributions, design paradigms with respect to structural and physicochemical properties of hERG active and hERG inactive compounds are challenged. Finally, classification models with different data sets are trained. All source code is provided, which is based on the Python open source packages RDKit and scikit-learn to enable the community to rerun the experiments. The code is stored on github ( https://github.com/pzc/herg_chembl_jcim). PMID:23944269

  11. Genome sequencing and annotation of multidrug resistant Mycobacterium tuberculosis (MDR-TB) PR10 strain

    PubMed Central

    Halim, Mohd Zakihalani A.; Jaafar, Mohammad Maaruf; Teh, Lay Kek; Ismail, Mohamad Izwan; Lee, Lian Shien; Ngeow, Yun Fong; Nor, Norazmi Mohd; Zainuddin, Zainul Fadziruddin; Tang, Thean Hock; Najimudin, Mohd Nazalan Mohd; Salleh, Mohd Zaki

    2016-01-01

    Here, we report the draft genome sequence and annotation of a multidrug resistant Mycobacterium tuberculosis strain PR10 (MDR-TB PR10) isolated from a patient diagnosed with tuberculosis. The size of the draft genome MDR-TB PR10 is 4.34 Mbp with 65.6% of G + C content and consists of 4637 predicted genes. The determinants were categorized by RAST into 400 subsystems with 4286 coding sequences and 50 RNAs. The whole genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession number CP010968. PMID:26981419

  12. Draft genome sequence of the docosahexaenoic acid producing thraustochytrid Aurantiochytrium sp. T66.

    PubMed

    Liu, Bin; Ertesvåg, Helga; Aasen, Inga Marie; Vadstein, Olav; Brautaset, Trygve; Heggeset, Tonje Marita Bjerkan

    2016-06-01

    Thraustochytrids are unicellular, marine protists, and there is a growing industrial interest in these organisms, particularly because some species, including strains belonging to the genus Aurantiochytrium, accumulate high levels of docosahexaenoic acid (DHA). Here, we report the draft genome sequence of Aurantiochytrium sp. T66 (ATCC PRA-276), with a size of 43 Mbp, and 11,683 predicted protein-coding sequences. The data has been deposited at DDBJ/EMBL/Genbank under the accession LNGJ00000000. The genome sequence will contribute new insight into DHA biosynthesis and regulation, providing a basis for metabolic engineering of thraustochytrids.

  13. Draft genome of Leisingera aquaemixtae CECT 8399T, a member of the Roseobacter clade isolated from a junction of fresh and ocean water in Jeju Island, South Korea

    PubMed Central

    Rodrigo-Torres, Lidia; Pujalte, María J.; Arahal, David R.

    2016-01-01

    We report the draft genome sequence and annotation of Leisingera aquaemixtae CECT 8399T (DDBJ/EMBL/GenBank accession number CYSR00000000) which comprises 4,614,060 bp, 4313 protein coding genes, 54 tRNA coding genes and 7 rRNA coding genes. General findings of the annotated genome, such as pigment indigoidine operon, phenylacetate oxidation genes or predictable number of replicons, are commented in comparison to other Leisingera species. Average Nucleotide Identity between available genomes of type strains of species of Leisingera and Phaeobacter genera has been calculated to evaluate its current classification. PMID:26981415

  14. Maize MeJA-responsive proteins identified by high-resolution 2-DE PAGE.

    PubMed

    Zhang, Yuliang; Pennerman, Kayla K; Yang, Fengshan; Yin, Guohua

    2015-12-01

    Exogenous methyl jasmonate (MeJA) is well-known to induce plant defense mechanisms effective against a wide variety of insect and microbial pests. High-resolution 2-DE gel electrophoresis was used to discover changes in the leaf proteome of maize exposed to MeJA. We sequenced 62 MeJA-responsive proteins by tandem mass spectroscopy, and deposited the mass spectra and identities in the EMBL-EBI PRIDE repository under reference number PXD001793. An analysis and discussion of the identified proteins in relation to maize defense against Asian corn borer is published by Zhang et al. (2015) [1]. PMID:26509185

  15. Compilation of 5S rRNA and 5S rRNA gene sequences

    PubMed Central

    Specht, Thomas; Wolters, Jörn; Erdmann, Volker A.

    1990-01-01

    The BERLIN RNA DATABANK as of Dezember 31, 1989, contains a total of 667 sequences of 5S rRNAs or their genes, which is an increase of 114 new sequence entries over the last compilation (1). It covers sequences from 44 archaebacteria, 267 eubacteria, 20 plastids, 6 mitochondria, 319 eukaryotes and 11 eukaryotic pseudogenes. The hardcopy shows only the list (Table 1) of those organisms whose sequences have been determined. The BERLIN RNA DATABANK uses the format of the EMBL Nucleotide Sequence Data Library complemented by a Sequence Alignment (SA) field including secondary structure information. PMID:1692116

  16. Genome sequencing and annotation of multidrug resistant Mycobacterium tuberculosis (MDR-TB) PR10 strain.

    PubMed

    Halim, Mohd Zakihalani A; Jaafar, Mohammad Maaruf; Teh, Lay Kek; Ismail, Mohamad Izwan; Lee, Lian Shien; Ngeow, Yun Fong; Nor, Norazmi Mohd; Zainuddin, Zainul Fadziruddin; Tang, Thean Hock; Najimudin, Mohd Nazalan Mohd; Salleh, Mohd Zaki

    2016-03-01

    Here, we report the draft genome sequence and annotation of a multidrug resistant Mycobacterium tuberculosis strain PR10 (MDR-TB PR10) isolated from a patient diagnosed with tuberculosis. The size of the draft genome MDR-TB PR10 is 4.34 Mbp with 65.6% of G + C content and consists of 4637 predicted genes. The determinants were categorized by RAST into 400 subsystems with 4286 coding sequences and 50 RNAs. The whole genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession number CP010968. PMID:26981419

  17. A common philosophy and FORTRAN 77 software package for implementing and searching sequence databases.

    PubMed

    Claverie, J M

    1984-01-11

    I present a common philosophy for implementing the EMBL and GENBANK (BBN-Los Alamos) nucleic acid sequence databases, as well as the National Biological Foundation (Dayhoff) protein sequence database. The associated FORTRAN 77 fully transportable software package includes: 1) modules for implementing each of these databases from the initial magnetic tape file, 2) modules performing a fast mnemonic access, 3) modules performing key-string access and allowing the definition of user-specific database subsets, 4) a common probe searching module allowing the stacking of multiple combined search requests over the databases. This software is particularly suitable for 32-bit mini/microcomputers but would eventually run on 16-bit computers.

  18. Identifying relevant data for a biological database: handcrafted rules versus machine learning.

    PubMed

    Sehgal, Aditya Kumar; Das, Sanmay; Noto, Keith; Saier, Milton H; Elkan, Charles

    2011-01-01

    With well over 1,000 specialized biological databases in use today, the task of automatically identifying novel, relevant data for such databases is increasingly important. In this paper, we describe practical machine learning approaches for identifying MEDLINE documents and Swiss-Prot/TrEMBL protein records, for incorporation into a specialized biological database of transport proteins named TCDB. We show that both learning approaches outperform rules created by hand by a human expert. As one of the first case studies involving two different approaches to updating a deployed database, both the methods compared and the results will be of interest to curators of many specialized databases.

  19. SHOT: a web server for the construction of genome phylogenies.

    PubMed

    Korbel, Jan O; Snel, Berend; Huynen, Martijn A; Bork, Peer

    2002-03-01

    With the increasing availability of genome sequences, new methods are being proposed that exploit information from complete genomes to classify species in a phylogeny. Here we present SHOT, a web server for the classification of genomes on the basis of shared gene content or the conservation of gene order that reflects the dominant, phylogenetic signal in these genomic properties. In general, the genome trees are consistent with classical gene-based phylogenies, although some interesting exceptions indicate massive horizontal gene transfer. SHOT is a useful tool for analysing the tree of life from a genomic point of view. It is available at http://www.Bork.EMBL-Heidelberg.de/SHOT.

  20. FatiGO: a web tool for finding significant associations of Gene Ontology terms with groups of genes.

    PubMed

    Al-Shahrour, Fátima; Díaz-Uriarte, Ramón; Dopazo, Joaquín

    2004-03-01

    We present a simple but powerful procedure to extract Gene Ontology (GO) terms that are significantly over- or under-represented in sets of genes within the context of a genome-scale experiment (DNA microarray, proteomics, etc.). Said procedure has been implemented as a web application, FatiGO, allowing for easy and interactive querying. FatiGO, which takes the multiple-testing nature of statistical contrast into account, currently includes GO associations for diverse organisms (human, mouse, fly, worm and yeast) and the TrEMBL/Swissprot GOAnnotations@EBI correspondences from the European Bioinformatics Institute.

  1. True perylene epitaxy on Ag(110) driven by site recognition effect

    NASA Astrophysics Data System (ADS)

    Bobrov, K.; Kalashnyk, N.; Guillemot, L.

    2015-03-01

    We present a STM study of room temperature perylene adsorption on the Ag(110) surface. We have found a 2D perylene crystalline phase coexisting with the perylene liquid phase under thermal equilibrium. The reversible precipitation of the liquid phase at sub-monolayer coverage reveals the well ordered chiral crystalline phase existing in two enantiomorphic configurations of the (- 2 5 3 2 ) and (2 5 3 -2 ) symmetry. This chiral phase is spatially separated into the 2D enantiopure islands of tens of nanometers size randomly distributed on the substrate and surrounded by the liquid medium. Analysis of surface registry of the crystalline phase combined with modeling of the intermolecular interactions indicates that its structure and symmetry is determined by a specific balance between the intermolecular attraction and intrinsic ability of the perylene aromatic board to recognize adsorption sites. The recognition effect was found to be strong enough to pin half of the perylene molecules into defined adsorption sites providing the structure skeleton. The attractive intermolecular interaction was found to be strong enough to bind another half of the molecules to the perylene skeleton shaping the true epitaxial structure.

  2. Corolla chirality does not contribute to directed pollen movement in Hypericum perforatum (Hypericaceae): mirror image pinwheel flowers function as radially symmetric flowers in pollination.

    PubMed

    Diller, Carolina; Fenster, Charles B

    2016-07-01

    Corolla chirality, the pinwheel arrangement of petals within a flower, is found throughout the core eudicots. In 15 families, different chiral type flowers (i.e., right or left rotated corolla) exist on the same plant, and this condition is referred to as unfixed/enantiomorphic corolla chirality. There are no investigations on the significance of unfixed floral chirality on directed pollen movement even though analogous mirror image floral designs, for example, enantiostyly, has evolved in response to selection to direct pollinator and pollen movement. Here, we examine the role of corolla chirality on directing pollen transfer, pollinator behavior, and its potential influence on disassortative mating. We quantified pollen transfer and pollinator behavior and movement for both right and left rotated flowers in two populations of Hypericum perforatum. In addition, we quantified the number of right and left rotated flowers at the individual level. Pollinators were indifferent to corolla chirality resulting in no difference in pollen deposition between right and left flowers. Corolla chirality had no effect on pollinator and pollen movement between and within chiral morphs. Unlike other mirror image floral designs, corolla chirality appears to play no role in promoting disassortative mating in this species. PMID:27547334

  3. Near-degenerate stereomorphs of the doubly-chiral hcp-{213̅1} surface

    NASA Astrophysics Data System (ADS)

    Jenkins, S. J.

    2010-09-01

    The surfaces of hcp crystals can show a variety of structural features and classes of symmetry that differ markedly from those of simpler fcc or bcc crystals. The hcp-{213̅1} surface, for example, can occur in four distinct stereomorphs, interconverted by a combination of mirror operations (linking degenerate enantiomorphically related surfaces) and/or the removal of the outermost atomic layer (linking non-degenerate diamorphically related surfaces). The strict pattern of degeneracy amongst these stereomorphs is analogous to that found for molecules with two chiral centres, and hence it is possible to view this system as doubly-chiral. Simple nearest-neighbour bond-counting arguments, however, suggest that for {213̅1} even the diamorphically related cases should be near-degenerate, despite the fact that they differ in having either a notably short or notably long interlayer spacing between the outermost layers (ideal spacing ratio 1:5). In the present work, this counterintuitive result is confirmed at the level of density functional theory, both for the ideal and relaxed {213̅1} surfaces of Co, Ru and Re.

  4. On the group-theoretical approach to the study of interpenetrating nets.

    PubMed

    Baburin, Igor A

    2016-05-01

    Using group-subgroup and group-supergroup relations, a general theoretical framework is developed to describe and derive interpenetrating 3-periodic nets. The generation of interpenetration patterns is readily accomplished by replicating a single net with a supergroup G of its space group H under the condition that site symmetries of vertices and edges are the same in both H and G. It is shown that interpenetrating nets cannot be mapped onto each other by mirror reflections because otherwise edge crossings would necessarily occur in the embedding. For the same reason any other rotation or roto-inversion axes from G \\ H are not allowed to intersect vertices or edges of the nets. This property significantly narrows the set of supergroups to be included in the derivation of interpenetrating nets. A procedure is described based on the automorphism group of a Hopf ring net [Alexandrov et al. (2012). Acta Cryst. A68, 484-493] to determine maximal symmetries compatible with interpenetration patterns. The proposed approach is illustrated by examples of twofold interpenetrated utp, dia and pcu nets, as well as multiple copies of enantiomorphic quartz (qtz) networks. Some applications to polycatenated 2-periodic layers are also discussed. PMID:27126113

  5. Bilateral symmetry in vision and influence of ocular surgical procedures on binocular vision: A topical review.

    PubMed

    Arba Mosquera, Samuel; Verma, Shwetabh

    2016-01-01

    We analyze the role of bilateral symmetry in enhancing binocular visual ability in human eyes, and further explore how efficiently bilateral symmetry is preserved in different ocular surgical procedures. The inclusion criterion for this review was strict relevance to the clinical questions under research. Enantiomorphism has been reported in lower order aberrations, higher order aberrations and cone directionality. When contrast differs in the two eyes, binocular acuity is better than monocular acuity of the eye that receives higher contrast. Anisometropia has an uncommon occurrence in large populations. Anisometropia seen in infancy and childhood is transitory and of little consequence for the visual acuity. Binocular summation of contrast signals declines with age, independent of inter-ocular differences. The symmetric associations between the right and left eye could be explained by the symmetry in pupil offset and visual axis which is always nasal in both eyes. Binocular summation mitigates poor visual performance under low luminance conditions and strong inter-ocular disparity detrimentally affects binocular summation. Considerable symmetry of response exists in fellow eyes of patients undergoing myopic PRK and LASIK, however the method to determine whether or not symmetry is maintained consist of comparing individual terms in a variety of ad hoc ways both before and after the refractive surgery, ignoring the fact that retinal image quality for any individual is based on the sum of all terms. The analysis of bilateral symmetry should be related to the patients' binocular vision status. The role of aberrations in monocular and binocular vision needs further investigation.

  6. Crystallization and preliminary X-ray analysis of a native human tRNA synthetase whose allelic variants are associated with Charcot–Marie–Tooth disease

    SciTech Connect

    Xie, Wei; Schimmel, Paul; Yang, Xiang-Lei

    2006-12-01

    Crystallization and preliminary X-ray analysis of a native human tRNA synthetase whose allelic variants are associated with Charcot–Marie–Tooth Disease. Glycyl-tRNA synthetase (GlyRS) is one of a group of enzymes that catalyze the synthesis of aminoacyl-tRNAs for translation. Mutations of human and mouse GlyRSs are causally associated with Charcot–Marie–Tooth disease, the most common genetic disorder of the peripheral nervous system. As the first step towards a structure–function analysis of this disease, native human GlyRS was expressed, purified and crystallized. The crystal belonged to space group P4{sub 3}2{sub 1}2 or its enantiomorphic space group P4{sub 1}2{sub 1}2, with unit-cell parameters a = b = 91.74, c = 247.18 Å, and diffracted X-rays to 3.0 Å resolution. The asymmetric unit contained one GlyRS molecule and had a solvent content of 69%.

  7. Theoretical estimates of the anapole magnetizabilities of C{sub 4}H{sub 4}X{sub 2} cyclic molecules for X=O, S, Se, and Te

    SciTech Connect

    Pagola, G. I.; Ferraro, M. B.; Provasi, P. F.; Pelloni, S.; Lazzeretti, P.

    2014-09-07

    Calculations have been carried out for C{sub 4}H{sub 4}X{sub 2} cyclic molecules, with X=O, S, Se, and Te, characterized by the presence of magnetic-field induced toroidal electron currents and associated orbital anapole moments. The orbital anapole induced by a static nonuniform magnetic field B, with uniform curl C=∇×B, is rationalized via a second-rank anapole magnetizability tensor a{sub αβ}, defined as minus the second derivative of the second-order interaction energy with respect to the components C{sub α} and B{sub β}. The average anapole magnetizability a{sup ¯} equals −χ{sup ¯}, the pseudoscalar obtained by spatial averaging of the dipole-quadrupole magnetizability χ{sub α,βγ}. It has different sign for D and L enantiomeric systems and can therefore be used for chiral discrimination. Therefore, in an isotropic chiral medium, a homogeneous magnetic field induces an electronic anapole A{sub α}, having the same magnitude, but opposite sign, for two enantiomorphs.

  8. Opiate modification of intracranial self-stimulation in the rat.

    PubMed

    Weibel, S L; Wolf, H H

    1979-01-01

    Studies were conducted to confirm the involvement of central opiate receptors in the expression of opiate modulation of intracranial self-stimulation (ICSS). Biphasic, dose-related changes in ICSS responding are described following IP administration of morphine sulfate (1-25 mg/kg) and levorphanol tartrate (LEV, 0.5-5 mg/kg). Similar patterns of response modification are reported following intraventricular (IVt) administration of LEV (0.01-0.2 muMoles) LEV's enantiomorph, dextrorphan, was not found to elicit comparable effects after either IP or IVt administration. Both the facilitatory and the depressant phases of LEV's action were antagonized by naltrexone (10 microgram, IVt), which had no apparent effect on ICSS by itself. Complete tolerance developed to the suppression of responding by 2.5 mg/kg LEV (IP) but not to the facilitatory effect of 0.5 mg/kg (IP), during a 5-day course of administration. The implications of these results for opiate reinforcement theory are discussed and possible mechanisms are advanced.

  9. Purification, Crystallization and Preliminary X-ray Crystallographic Studies of RAIDD Death-Domain (DD)

    SciTech Connect

    Jang, T.; Park, H

    2009-01-01

    Caspase-2 activation by formation of PIDDosome is critical for genotoxic stress induced apoptosis. PIDDosome is composed of three proteins, RAIDD, PIDD, and Caspase-2. RAIDD is an adaptor protein containing an N-terminal Caspase-Recruiting-Domain (CARD) and a C-terminal Death-Domain (DD). Its interactions with Caspase-2 and PIDD through CARD and DD respectively and formation of PIDDosome are important for the activation of Caspase-2. RAIDD DD cloned into pET26b vector was expressed in E. coli cells and purified by nickel affinity chromatography and gel filtration. Although it has been known that the most DDs are not soluble in physiological condition, RAIDD DD was soluble and interacts tightly with PIDD DD in physiological condition. The purified RAIDD DD alone has been crystallized. Crystals are trigonal and belong to space group P3121 (or its enantiomorph P3221) with unit-cell parameters a = 56.3, b = 56.3, c = 64.9 and ? = 120 degrees. The crystals were obtained at room temperature and diffracted to 2.0 A resolution.

  10. HIV-1 Nef protein: purification, crystallizations, and preliminary X-ray diffraction studies.

    PubMed

    Franken, P; Arold, S; Padilla, A; Bodeus, M; Hoh, F; Strub, M P; Boyer, M; Jullien, M; Benarous, R; Dumas, C

    1997-12-01

    Human immunodeficiency virus Nef protein accelerates virulent progression of AIDS by its interaction with specific cellular proteins involved in cellular activation and signal transduction. Here we report the purification and crystallization of the conserved core of HIV-1LAI Nef protein in the unliganded form and in complex with the wild-type SH3 domain of the P59fyn protein-tyrosine kinase. One-dimensional NMR experiments show that full-length protein and truncated fragment corresponding to the product of HIV-1 protease cleavage have a well-folded compact tertiary structure. The ligand-free HIV-1 Nefcore protein forms cubic crystals belonging to space group P23 with unit cell dimensions of a = b = c = 86.4 A. The Nef-Fyn SH3 cocrystals belong to the space group P6(1)22 or its enantiomorph, P6(5)22, with unit cell dimensions of a = b = 108.2 A and c = 223.7 A. Both crystal forms diffract to a resolution limit of 3.0 A resolution using synchrotron radiation, and are thus suitable for X-ray structure determination.

  11. Inversion twinning in a second polymorph of the hydrochloride salt of the recreational drug ethylone.

    PubMed

    Cameron, T Stanley; Grossert, J Stuart; Maheux, Chad R; Alarcon, Idralyn Q; Copeland, Catherine R; Linden, Anthony

    2015-04-01

    A second polymorph of the hydrochloride salt of the recreational drug ethylone, C12H16NO3(+)·Cl(-), is reported [systematic name: (±)-2-ethylammonio-1-(3,4-methylenedioxyphenyl)propane-1-one chloride]. This polymorph, denoted form (A), appears in crystallizations performed above 308 K. The originally reported form (B) [Wood et al. (2015). Acta Cryst. C71, 32-38] crystallizes preferentially at room temperature. The conformations of the cations in the two forms differ by a 180° rotation about the C-C bond linking the side chain to the aromatic ring. Hydrogen bonding links the cations and anions in both forms into similar extended chains in which any one chain contains only a single enantiomer of the chiral cation, but the packing of the ions is different. In form (A), the aromatic rings of adjacent chains interleave, but pack equally well if neighbouring chains contain the same or opposite enantiomorph of the cation. The consequence of this is then near perfect inversion twinning in the structure. In form (B), neighbouring chains are always inverted, leading to a centrosymmetric space group. The question as to why the polymorphs crystallize at slightly different temperatures has been examined by density functional theory (DFT) and lattice energy calculations and a consideration of packing compactness. The free energy (ΔG) of the crystal lattice for polymorph (A) lies some 52 kJ mol(-1) above that of polymorph (B). PMID:25836283

  12. A lifelong Odyssey: from structural and morphological engineering of functional solids to bio-chirogenisis and pathological crystallization

    NASA Astrophysics Data System (ADS)

    Lahav, Meir; Leiserowitz, Leslie

    2015-11-01

    This cooperative endeavour first describes early studies in chemical crystallography, encompassing molecular packing modes, characterization of weak hydrogen bonds, the engineering of functional crystals and monitoring of reaction pathways in molecular crystals by x-ray and neutron diffraction. With the design of ‘tailor-made’ auxiliary molecules, it became possible to correlate molecular enantiomerism and crystal enantiomorphism, to control the early stages of crystal nucleation, to resolve enantiomers by crystallization, induce the precipitation of metastable polymorphs, and shed light on the role played by solvent on crystal growth. With such auxiliaries, the structure of mixed crystals was revised and the ability to perform ‘absolute’ asymmetric synthesis in host centrosymmetric crystals demonstrated. With the introduction of grazing incidence synchrotron x-ray diffraction from liquid surfaces it also became possible to design and characterize crystalline thin film architectures at the air-water interface providing a general insight on the mechanism of crystal nucleation at the molecular level, in particular that of ice and cholesterol. Finally the collective knowhow from these studies were crucial for obtaining homochiral peptides prepared from the polymerization of racemates of amphiphilic amino acids dissolved in aqueous solution, and for experiments towards elucidating the pathological crystallization of cholesterol and the malaria pigment in Plasmodium-infected red blood cells.

  13. Cloning, purification and preliminary crystallographic analysis of a putative DNA-binding membrane protein, YmfM, from Staphylococcus aureus

    SciTech Connect

    Xu, Ling; Sedelnikova, Svetlana E.; Baker, Patrick J.; Rice, David W.

    2008-07-01

    Truncation by the removal of the C-terminal hydrophobic transmembrane anchor has enabled the overexpression of a soluble domain of S. aureus YmfM in Escherichia coli, which has then been purified and subsequently crystallized. The Staphylococcus aureus protein YmfM contains a helix–turn–helix motif and is thought to be a putative DNA-binding protein which is associated with the membrane through a C-terminal hydrophobic transmembrane anchor. Truncation of the protein by the removal of this C-terminal hydrophobic segment has enabled the overexpression of a soluble domain of S. aureus YmfM (ΔYmfM) in Escherichia coli, which has been purified and subsequently crystallized. Crystals of ΔYmfM diffract to beyond 1.0 Å resolution and belong to one of the pair of enantiomorphic tetragonal space groups P4{sub 1}2{sub 1}2 or P4{sub 3}2{sub 1}2, with unit-cell parameters a = b = 45.5, c = 72.9 Å and one molecule in the asymmetric unit. The crystals of ΔYmfM have an unusually low V{sub M} of 1.6 Å{sup 3} Da{sup −1}, which is one of the lowest values observed for any protein to date. A full structure determination is under way in order to provide insights into the function of this protein.

  14. Robust Cross-Linked Stereocomplexes and C60 Inclusion Complexes of Vinyl-Functionalized Stereoregular Polymers Derived from Chemo/Stereoselective Coordination Polymerization.

    PubMed

    Vidal, Fernando; Falivene, Laura; Caporaso, Lucia; Cavallo, Luigi; Chen, Eugene Y-X

    2016-08-01

    The successful synthesis of highly syndiotactic polar vinyl polymers bearing the reactive pendant vinyl group on each repeat unit, which is enabled by perfectly chemoselective and highly syndiospecific coordination polymerization of divinyl polar monomers developed through this work, has allowed the construction of robust cross-linked supramolecular stereocomplexes and C60 inclusion complexes. The metal-mediated coordination polymerization of three representative polar divinyl monomers, including vinyl methacrylate (VMA), allyl methacrylate (AMA), and N,N-diallyl acrylamide (DAA) by Cs-ligated zirconocenium ester enolate catalysts under ambient conditions exhibits complete chemoselectivity and high stereoselectivity, thus producing the corresponding vinyl-functionalized polymers with high (92% rr) to quantitative (>99% rr) syndiotacticity. A combined experimental (synthetic, kinetic, and mechanistic) and theoretical (DFT) investigation has yielded a unimetallic, enantiomorphic-site-controlled propagation mechanism. Postfunctionalization of the obtained syndiotactic vinyl-functionalized polymers via the thiol-ene click and photocuring reactions readily produced the corresponding thiolated polymers and flexible cross-linked thin-film materials, respectively. Complexation of such syndiotactic vinyl-functionalized polymers with isotactic poly(methyl methacrylate) and fullerene C60 generates supramolecular crystalline helical stereocomplexes and inclusion complexes, respectively. Cross-linking of such complexes affords robust cross-linked stereocomplexes that are solvent-resistant and also exhibit considerably enhanced thermal and mechanical properties compared with the un-cross-linked stereocomplexes. PMID:27388024

  15. Thyroxine revisited.

    PubMed

    Katrusiak, Andrzej; Katrusiak, Anna

    2004-12-01

    The crystal structure of the common therapeutic agent, the pentahydrated sodium salt of L-thyroxine hormone (3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]-L-alanine), has been determined and discussed in relation to the drug's stability. The stoichiometry and absolute configuration (-)-C(8)S-[C15H10I4NO4]-.Na+.5H2O have been confirmed. The crystals are built of a three-dimensional supramolecular network with two symmetry-independent L-thyroxine anions, in two distinct conformations not previously reported, linked by strong NH-O hydrogen bonds into dimers. Two independent sodium cations are fivefold and sixfold coordinated. The cations and two independent water molecules not involved in coordinating the Na cations form sheets along the crystallographic (001) planes. The presence of differently coordinated cations and non-coordinating water molecules may be responsible for water transport and loss, for decay of the crystals, and subsequent low stability of the drug. Only a conglomerate could be obtained when racemic sodium thyroxine was crystallized from ethanol and methanol solutions by evaporation, which explains the equal penta-hydration of the sodium salts of enantiomorphic and racemic thyroxine, and the fact that there are no apparent differences in their stability.

  16. Nucleation-controlled crystallization of a new, spontaneously resolved solvate of [Ru(bpy)3](PF6)2 and its desolvation reaction.

    PubMed

    Breu, Josef; Seidl, Wolfgang; Huttner, Dominikus; Kraus, Florian

    2002-10-01

    Simply by increasing the supersaturation level, racemic [Ru(bpy)(3)](PF(6))(2) no longer crystallises as the well-known true racemate (beta-modification; P$\\bar 3$c1, a=10.6453(5), c=16.2987(9) A, Z=2). Rather, it spontaneously resolves and forms a conglomerate of pure Lambda- and pure Delta-crystals with a so far unknown structure type. This new modification actually is a solvate ([Ru(bpy)(3)](PF(6))(2).1.5 CH(3)COCH(3); delta-type; P32, a=13.8133(7) A, c=11.6523(7) A, Z=2). By a solution-mediated equilibration the new modification is shown to be the metastable (Ostwald) product, which is formed based on nucleation kinetics. Upon desolvation the solvate transforms into a second enantiomorphic crystal structure (gamma-type; P3(1), a=10.3809(4), c=26.2576(13) A, Z=3). The latter could previously only be obtained by chemical resolution prior to crystallisation, but could not be accessed directly from racemic solutions. However, the new delta-modification can now be utilised for optical resolution by the so-called method of "resolution by entrainment". This example emphasises the potential that both kinetically controlled crystallisation and desolvation of solvates bear with respect to crystal engineering.

  17. Chiral symmetry breaking and polymorphism in 1,1'-binaphthyl melt crystallization.

    PubMed

    Sainz-Díaz, C Ignacio; Martín-Islan, Africa P; Cartwright, Julyan H E

    2005-10-13

    We have studied chiral symmetry breaking in the melt crystallization of 1,1'-binaphthyl. We confirm that chiral symmetry breaking can be induced by stirring the melt as it crystallizes. We find an additional process of vapor crystallization to occur alongside the melt crystallization. This complicates the analysis of the enantiomorphism by introducing a further phenomenon: that of polymorphism. Crystallographic studies by X-ray diffraction reveal two polymorphs of 1,1'-binaphthyl that are made up of two different conformers of each of the two enantiomeric forms of the molecule. Crystals from the melt are generally chiral tetragonal crystals (P42(1)2(1)) composed of (R)- or (S)-1,1'-binaphthyl in a transoid conformer, while those from the vapor are racemic monoclinic crystals (C2/c) made up of the cisoid conformer of both (R)- and (S)-1,1'-binaphthyl enantiomers. The main intermolecular interactions in all these crystals are weak aromatic CH/pi hydrogen bonds, which are responsible for the enantiomeric discrimination in the molecular recognition during crystallization. A tendency for whisker crystal formation is notable in 1,1'-binaphthyl. In stirred crystallization, fluid and mechanical forces can break off these whiskers, which provide secondary nuclei for further crystallization. This autocatalytic mechanism induces chiral symmetry breaking during the crystallization.

  18. Crystal chemistry of layered structures formed by linear rigid silyl-capped molecules

    PubMed Central

    Lumpi, Daniel; Kautny, Paul; Stöger, Berthold; Fröhlich, Johannes

    2015-01-01

    The crystallization behavior of methylthio- or methylsulfonyl-containing spacer extended Z,Z-bis-ene–yne molecules capped with trimethylsilyl groups obtained by (tandem) thiophene ring fragmentation and of two non-spacer extended analogs were investigated. The rigid and linear molecules generally crystallized in layers whereby the flexibility of the layer interfaces formed by the silyl groups leads to a remarkably rich crystal chemistry. The molecules with benzene and thiophene spacers both crystallized with C2/c symmetry and can be considered as merotypes. Increasing the steric bulk of the core by introduction of ethylenedioxythiophene (EDOT) gave a structure incommensurately modulated in the [010] direction. Further increase of steric demand in the case of a dimethoxythiophene restored periodicity along [010] but resulted in a doubling of the c vector. Two different polytypes were observed, which feature geometrically different layer interfaces (non-OD, order–disorder, polytypes), one with a high stacking fault probability. Oxidation of the methylthio groups of the benzene-based molecule to methylsulfonyl groups led to three polymorphs (two temperature-dependent), which were analyzed by Hirshfeld surface d e/d i fingerprint plots. The analogously oxidized EDOT-based molecule crystallized as systematic twins owing to its OD polytypism. Shortening of the backbone by removal of the aryl core resulted in an enantiomorphic structure and a further shortening by removal of a methylthio-ene fragment again in a systematically twinned OD polytype. PMID:26306200

  19. Crystallization and preliminary X-ray diffraction studies of the epsilonzeta addiction system encoded by Streptococcus pyogenes plasmid pSM19035.

    PubMed

    Meinhart, A; Alings, C; Sträter, N; Camacho, A G; Alonso, J C; Saenger, W

    2001-05-01

    The proteins encoded by the Streptococcus pyogenes broad-host range and low copy-number plasmid pSM19035 form a toxin-antitoxin module that secures stable maintenance by causing the death of plasmid-free segregants. The epsilonzeta protein complex was crystallized in four different forms at pH 5.0 and pH 7.0 using the vapour-diffusion method with PEG 3350 and ethylene glycol as precipitants. Three of the crystal forms were obtained in the same droplet under identical conditions at pH 5.0. One form belongs to the enantiomorphic space groups P4(3)2(1)2 or P4(1)2(1)2. For the other two, the X-ray reflection conditions match those of space group P2(1)2(1)2(1), one representing a superlattice of the other. A crystal form growing at pH 7.0 also belongs to space group P2(1)2(1)2(1), but there is no indication of a structural relationship to the other orthorhombic forms. Initially, the crystals diffracted to 2.9 A resolution and diffracted to 1.95 A after soaking at pH 7.0. A preparation of selenomethionyl epsilonzeta protein complex yielded single crystals suitable for X-ray diffraction experiments using synchrotron sources.

  20. Crystallization and preliminary crystallographic analysis of a family 43 β-d-xylosidase from Geobacillus stearothermophilus T-6

    PubMed Central

    Brüx, Christian; Niefind, Karsten; Ben-David, Alon; Leon, Maya; Shoham, Gil; Shoham, Yuval; Schomburg, Dietmar

    2005-01-01

    β-d-Xylosidases (EC 3.2.1.37) are hemicellulases that cleave single xylose units from the nonreducing end of xylooligomers. In this study, the crystallization and preliminary X-ray analysis of a β-d-xylosidase from Geobacillus stearothermophilus T-6 (XynB3), a family 43 glycoside hydrolase, is described. XynB3 is a 535-amino-acid protein with a calculated molecular weight of 61 891 Da. Purified recombinant native and catalytic inactive mutant proteins were crystallized and cocrystallized with xylobiose in two different space groups, P21212 (unit-cell parameters a = 98.32, b = 99.36, c = 258.64 Å) and P41212 (or the enantiomorphic space group P43212; unit-cell parameters a = b = 140.15, c = 233.11 Å), depending on the detergent. Transferring crystals to cryoconditions required a very careful protocol. Orthorhombic crystals diffract to 2.5 Å and tetragonal crystals to 2.2 Å. PMID:16511233

  1. The Time 'Onewayness' Shared by Quantum Mechanics and Relativity

    SciTech Connect

    Guzzetta, Giuseppe

    2006-11-03

    The measure of the mutation, or change, any material elementary particle unceasingly undergoes, is defined as that of the displacement of a point moving in a three-dimensional Euclidean space, at the velocity of light, on a trajectory decomposable in a rotation and a translation. The rotation accounts for the spin angular momentum of the particle, the translation for its change of location. Then, an elementary mutation is proportional to an elementary interval of universal time. The connection between space and time is such that the operation of universal time conjugation, that is, the change of sign of t, involves space inversion, so coinciding with the operation currently defined as TCP. It implies that to a given physical process, another equally possible one corresponds in which the sequence of events (that still follow the same time course) is reversed, and actors are the enantiomorphic counterparts (anti-particles instead of particles, and vice versa) of those playing in the first physical process. Since no alternative is left to any elementary particle, that exists in that it undergoes an everlasting mutation, the unidirectionality of time must not be understood as a choice between two alternative directions. Many formalisms of Special Relativity can be derived from the above definition of the mutation of a material elementary particle. Anyhow, some discordances seems to crop out whose discussion is beyond the purpose of the present paper.

  2. Molecular structure and absolute configuration of the diterpene lactone, praelolide.

    PubMed

    Dai, J B; Wan, Z L; Rao, Z H; Liang, D C; Fang, Z; Luo, Y K; Long, K H

    1985-11-01

    Praelolide is a new compound which was isolated out from the gorgonian, Menella praelonga (Ridley), collected from the South Sea of China at Zhanjiang, Guangdong. The molecular formula is C28H35O12Cl. The research result by X-ray diffraction method on the crystal structure is presented. The compound is orthorhombic with space group P2(1)2(1)2, cell dimensions a = 16.936, b = 16.709, c = 10.333 A, and Z = 4. The structure has been solved by direct method and refined to R = 0.055 for 2257 unique observable reflexions by least-squares. The molecule is composed of the major conformational isomer in which the three main rings (a six-membered ring, an eight-membered ring, a six-membered ring) take separately the form of chair-chairboat-chair, a five-membered actone ring, a C1 substitution, 4 acetate groups, and a three-membered epoxide ring. The absolute configuration of the molecule has also been determined by statistics (R factor ratio R = 1.012) and Bijvoet pairs observation. For 30 pairs of the greatest anomalous contributions the residuals are R'(+) = 0.057 for the first enantiomorph and R'(-) = 0.005 for the second one, so the latter should unambiguously correspond to the absolute configuration of the molecule.

  3. Web services at the European Bioinformatics Institute-2009

    PubMed Central

    Mcwilliam, Hamish; Valentin, Franck; Goujon, Mickael; Li, Weizhong; Narayanasamy, Menaka; Martin, Jenny; Miyar, Teresa; Lopez, Rodrigo

    2009-01-01

    The European Bioinformatics Institute (EMBL-EBI) has been providing access to mainstream databases and tools in bioinformatics since 1997. In addition to the traditional web form based interfaces, APIs exist for core data resources such as EMBL-Bank, Ensembl, UniProt, InterPro, PDB and ArrayExpress. These APIs are based on Web Services (SOAP/REST) interfaces that allow users to systematically access databases and analytical tools. From the user's point of view, these Web Services provide the same functionality as the browser-based forms. However, using the APIs frees the user from web page constraints and are ideal for the analysis of large batches of data, performing text-mining tasks and the casual or systematic evaluation of mathematical models in regulatory networks. Furthermore, these services are widespread and easy to use; require no prior knowledge of the technology and no more than basic experience in programming. In the following we wish to inform of new and updated services as well as briefly describe planned developments to be made available during the course of 2009–2010. PMID:19435877

  4. ArrayExpress update--simplifying data submissions.

    PubMed

    Kolesnikov, Nikolay; Hastings, Emma; Keays, Maria; Melnichuk, Olga; Tang, Y Amy; Williams, Eleanor; Dylag, Miroslaw; Kurbatova, Natalja; Brandizi, Marco; Burdett, Tony; Megy, Karyn; Pilicheva, Ekaterina; Rustici, Gabriella; Tikhonov, Andrew; Parkinson, Helen; Petryszak, Robert; Sarkans, Ugis; Brazma, Alvis

    2015-01-01

    The ArrayExpress Archive of Functional Genomics Data (http://www.ebi.ac.uk/arrayexpress) is an international functional genomics database at the European Bioinformatics Institute (EMBL-EBI) recommended by most journals as a repository for data supporting peer-reviewed publications. It contains data from over 7000 public sequencing and 42,000 array-based studies comprising over 1.5 million assays in total. The proportion of sequencing-based submissions has grown significantly over the last few years and has doubled in the last 18 months, whilst the rate of microarray submissions is growing slightly. All data in ArrayExpress are available in the MAGE-TAB format, which allows robust linking to data analysis and visualization tools and standardized analysis. The main development over the last two years has been the release of a new data submission tool Annotare, which has reduced the average submission time almost 3-fold. In the near future, Annotare will become the only submission route into ArrayExpress, alongside MAGE-TAB format-based pipelines. ArrayExpress is a stable and highly accessed resource. Our future tasks include automation of data flows and further integration with other EMBL-EBI resources for the representation of multi-omics data.

  5. CART—a chemical annotation retrieval toolkit

    PubMed Central

    Deghou, Samy; Zeller, Georg; Iskar, Murat; Driessen, Marja; Castillo, Mercedes; van Noort, Vera; Bork, Peer

    2016-01-01

    Motivation: Data on bioactivities of drug-like chemicals are rapidly accumulating in public repositories, creating new opportunities for research in computational systems pharmacology. However, integrative analysis of these data sets is difficult due to prevailing ambiguity between chemical names and identifiers and a lack of cross-references between databases. Results: To address this challenge, we have developed CART, a Chemical Annotation Retrieval Toolkit. As a key functionality, it matches an input list of chemical names into a comprehensive reference space to assign unambiguous chemical identifiers. In this unified space, bioactivity annotations can be easily retrieved from databases covering a wide variety of chemical effects on biological systems. Subsequently, CART can determine annotations enriched in the input set of chemicals and display these in tabular format and interactive network visualizations, thereby facilitating integrative analysis of chemical bioactivity data. Availability and Implementation: CART is available as a Galaxy web service (cart.embl.de). Source code and an easy-to-install command line tool can also be obtained from the web site. Contact: bork@embl.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27256313

  6. ArrayExpress update—simplifying data submissions

    PubMed Central

    Kolesnikov, Nikolay; Hastings, Emma; Keays, Maria; Melnichuk, Olga; Tang, Y. Amy; Williams, Eleanor; Dylag, Miroslaw; Kurbatova, Natalja; Brandizi, Marco; Burdett, Tony; Megy, Karyn; Pilicheva, Ekaterina; Rustici, Gabriella; Tikhonov, Andrew; Parkinson, Helen; Petryszak, Robert; Sarkans, Ugis; Brazma, Alvis

    2015-01-01

    The ArrayExpress Archive of Functional Genomics Data (http://www.ebi.ac.uk/arrayexpress) is an international functional genomics database at the European Bioinformatics Institute (EMBL-EBI) recommended by most journals as a repository for data supporting peer-reviewed publications. It contains data from over 7000 public sequencing and 42 000 array-based studies comprising over 1.5 million assays in total. The proportion of sequencing-based submissions has grown significantly over the last few years and has doubled in the last 18 months, whilst the rate of microarray submissions is growing slightly. All data in ArrayExpress are available in the MAGE-TAB format, which allows robust linking to data analysis and visualization tools and standardized analysis. The main development over the last two years has been the release of a new data submission tool Annotare, which has reduced the average submission time almost 3-fold. In the near future, Annotare will become the only submission route into ArrayExpress, alongside MAGE-TAB format-based pipelines. ArrayExpress is a stable and highly accessed resource. Our future tasks include automation of data flows and further integration with other EMBL-EBI resources for the representation of multi-omics data. PMID:25361974

  7. The experimental uncertainty of heterogeneous public K(i) data.

    PubMed

    Kramer, Christian; Kalliokoski, Tuomo; Gedeck, Peter; Vulpetti, Anna

    2012-06-14

    The maximum achievable accuracy of in silico models depends on the quality of the experimental data. Consequently, experimental uncertainty defines a natural upper limit to the predictive performance possible. Models that yield errors smaller than the experimental uncertainty are necessarily overtrained. A reliable estimate of the experimental uncertainty is therefore of high importance to all originators and users of in silico models. The data deposited in ChEMBL was analyzed for reproducibility, i.e., the experimental uncertainty of independent measurements. Careful filtering of the data was required because ChEMBL contains unit-transcription errors, undifferentiated stereoisomers, and repeated citations of single measurements (90% of all pairs). The experimental uncertainty is estimated to yield a mean error of 0.44 pK(i) units, a standard deviation of 0.54 pK(i) units, and a median error of 0.34 pK(i) units. The maximum possible squared Pearson correlation coefficient (R(2)) on large data sets is estimated to be 0.81.

  8. Open PHACTS computational protocols for in silico target validation of cellular phenotypic screens: knowing the knowns† †The authors declare no competing interests. ‡ ‡Electronic supplementary information (ESI) available: Pipeline Pilot protocols, xls file with the output of the Pipeline Pilot protocols, KNIME workflows, and supplementary figures showing the Pipeline Pilot protocols. See DOI: 10.1039/c6md00065g Click here for additional data file.

    PubMed Central

    Zdrazil, B.; Neefs, J.-M.; Van Vlijmen, H.; Herhaus, C.; Caracoti, A.; Brea, J.; Roibás, B.; Loza, M. I.; Queralt-Rosinach, N.; Furlong, L. I.; Gaulton, A.; Bartek, L.; Senger, S.; Chichester, C.; Engkvist, O.; Evelo, C. T.; Franklin, N. I.; Marren, D.; Ecker, G. F.

    2016-01-01

    Phenotypic screening is in a renaissance phase and is expected by many academic and industry leaders to accelerate the discovery of new drugs for new biology. Given that phenotypic screening is per definition target agnostic, the emphasis of in silico and in vitro follow-up work is on the exploration of possible molecular mechanisms and efficacy targets underlying the biological processes interrogated by the phenotypic screening experiments. Herein, we present six exemplar computational protocols for the interpretation of cellular phenotypic screens based on the integration of compound, target, pathway, and disease data established by the IMI Open PHACTS project. The protocols annotate phenotypic hit lists and allow follow-up experiments and mechanistic conclusions. The annotations included are from ChEMBL, ChEBI, GO, WikiPathways and DisGeNET. Also provided are protocols which select from the IUPHAR/BPS Guide to PHARMACOLOGY interaction file selective compounds to probe potential targets and a correlation robot which systematically aims to identify an overlap of active compounds in both the phenotypic as well as any kinase assay. The protocols are applied to a phenotypic pre-lamin A/C splicing assay selected from the ChEMBL database to illustrate the process. The computational protocols make use of the Open PHACTS API and data and are built within the Pipeline Pilot and KNIME workflow tools. PMID:27774140

  9. SeqinR 1.0-2: A Contributed Package to the R Project for Statistical Computing Devoted to Biological Sequences Retrieval and Analysis

    NASA Astrophysics Data System (ADS)

    Charif, Delphine; Lobry, Jean R.

    The seqinR package for the R environment is a library of utilities to retrieve and analyze biological sequences. It provides an interface between: (i) the R language and environment for statistical computing and graphics, and (ii) the ACNUC sequence retrieval system for nucleotide and protein sequence databases such as GenBank, EMBL, SWISS-PROT. ACNUC is very efficient in providing direct access to subsequences of biological interest (e.g., protein coding regions, tRNA, or rRNA coding regions) present in GenBank and in EMBL. Thanks to a simple query language, it is then easy under R to select sequences of interest and then use all the power of the R environment to analyze them. The ACNUC databases can be locally installed but they are more conveniently accessed through a web server to take advantage of centralized daily updates. The aim of this chapter is to provide a handout on basic sequence analyses under seqinR with a special focus on multivariate methods.

  10. Non-redundant patent sequence databases with value-added annotations at two levels.

    PubMed

    Li, Weizhong; McWilliam, Hamish; de la Torre, Ana Richart; Grodowski, Adam; Benediktovich, Irina; Goujon, Mickael; Nauche, Stephane; Lopez, Rodrigo

    2010-01-01

    The European Bioinformatics Institute (EMBL-EBI) provides public access to patent data, including abstracts, chemical compounds and sequences. Sequences can appear multiple times due to the filing of the same invention with multiple patent offices, or the use of the same sequence by different inventors in different contexts. Information relating to the source invention may be incomplete, and biological information available in patent documents elsewhere may not be reflected in the annotation of the sequence. Search and analysis of these data have become increasingly challenging for both the scientific and intellectual-property communities. Here, we report a collection of non-redundant patent sequence databases, which cover the EMBL-Bank nucleotides patent class and the patent protein databases and contain value-added annotations from patent documents. The databases were created at two levels by the use of sequence MD5 checksums. Sequences within a level-1 cluster are 100% identical over their whole length. Level-2 clusters were defined by sub-grouping level-1 clusters based on patent family information. Value-added annotations, such as publication number corrections, earliest publication dates and feature collations, significantly enhance the quality of the data, allowing for better tracking and cross-referencing. The databases are available format: http://www.ebi.ac.uk/patentdata/nr/.

  11. Compilation of DNA sequences of Escherichia coli (update 1992)

    PubMed Central

    Kröger, Manfred; Wahl, Ralf; Schachtel, Gabriel; Rice, Peter

    1992-01-01

    We have compiled the DNA sequence data for E.coli available from the GENBANK and EMBL data libraries and over a period of several years independently from the literature. This is the fourth listing replacing and increasing the former listings substantially. However, in order to save space this printed version contains DNA sequence information only, if they are publically available in electronic form. The complete compilation including a full set of genetic map data and the E.coli protein index can be obtained in machine readable form from the EMBL data library (ECD release 10) or from the CD-ROM version of this supplement issue directly. After deletion of all detected overlaps a total of 1 820 237 individual bp is found to be determined till the beginning of 1992. This corresponds to a total of 38.56% of the entire E.coli chromosome consisting of about 4,720 kbp. This number may actually be higher by some extra 2,5% derived from lysogenic bacteriophage lambda and various DNA sequences already received for other strains of E.coli. PMID:1598239

  12. Disentangling true shape differences and experimenter bias: are dextral and sinistral snail shells exact mirror images?

    PubMed

    Schilthuizen, M; Haase, M

    2010-11-01

    IN THEORY, SNAILS CAN COME IN TWO ENANTIOMORPHS: either dextral (coiling clockwise) or sinistral (coiling counter-clockwise). In snail species where both forms are actually present, coiling direction is determined by a single gene with delayed maternal inheritance; there is no predictable relationship between a snail's own coiling genotype and its actual coiling direction. Because of this genetic decoupling, it might be expected that dextral and sinistral individuals would be exact mirror images of one another. However, indications exist that there is a subtle but detectable shape difference between dextral and sinistral individuals that derive from the same gene pool. In this paper, we attempt to detect such differences in 50 dextral and 50 sinistral individuals of Amphidromus inversus, a species of land snail that is consistently chirally dimorphic. Four out of 18 volunteers who measured the shells with Vernier calipers found that sinistrals are stouter to a significant degree. A similar result was found by one out of five volunteers who measured the shells from photographs. These results do not allow distinguishing between real shape differences and a handling bias of sinistral as compared with dextral shells. However, when the same set of shells was subjected to a geometric morphometric analysis, we were able to show that sinistrals indeed exhibit a slight but significant widening and twisting of the shell near the palatal and parietal apertural areas. This result is surprising because species of the subgenus Amphidromus s. str. share a long history of chiral dimorphism, and the species would be expected to have been purged from disadvantageous interactions between direction of coil and general shell shape. We conclude that selection on the shape differences is either very weak or constrained by the fact that the pleiotropic effects of the chirality gene are of importance very early in development only.

  13. Cloning, purification and preliminary crystallographic analysis of a putative pyridoxal kinase from Bacillus subtilis

    SciTech Connect

    Newman, Joseph A.; Das, Sanjan K.; Sedelnikova, Svetlana E.; Rice, David W.

    2006-10-01

    A putative pyridoxal kinase from B. subtilis has been cloned, overexpressed, purified and crystallized and data have been collected to 2.8 Å resolution. Pyridoxal kinases (PdxK) are able to catalyse the phosphorylation of three vitamin B{sub 6} precursors, pyridoxal, pyridoxine and pyridoxamine, to their 5′-phosphates and play an important role in the vitamin B{sub 6} salvage pathway. Recently, the thiD gene of Bacillus subtilis was found to encode an enzyme which has the activity expected of a pyridoxal kinase despite its previous assignment as an HMPP kinase owing to higher sequence similarity. As such, this enzyme would appear to represent a new class of ‘HMPP kinase-like’ pyridoxal kinases. B. subtilis thiD has been cloned and the protein has been overexpressed in Escherichia coli, purified and subsequently crystallized in a binary complex with ADP and Mg{sup 2+}. X-ray diffraction data have been collected from crystals to 2.8 Å resolution at 100 K. The crystals belong to a primitive tetragonal system, point group 422, and analysis of the systematic absences suggest that they belong to one of the enantiomorphic pair of space groups P4{sub 1}2{sub 1}2 or P4{sub 3}2{sub 1}2. Consideration of the space-group symmetry and unit-cell parameters (a = b = 102.9, c = 252.6 Å, α = β = γ = 90°) suggest that the crystals contain between three and six molecules in the asymmetric unit. A full structure determination is under way to provide insights into aspects of the enzyme mechanism and substrate specificity.

  14. Crystallization and preliminary x-ray diffraction analysis of P450terp and the hemoprotein domain of P450BM-3, enzymes belonging to two distinct classes of the cytochrome P450 superfamily.

    PubMed Central

    Boddupalli, S S; Hasemann, C A; Ravichandran, K G; Lu, J Y; Goldsmith, E J; Deisenhofer, J; Peterson, J A

    1992-01-01

    Cytochromes P450 are members of a superfamily of hemoproteins that are involved in the metabolism of various physiologic and xenobiotic organic compounds. This superfamily of proteins can be divided into two classes based on the electron donor proximal to the P450: an iron-sulfur protein for class I P450s or a flavoprotein for class II. The only known tertiary structure of any of the cytochromes P450 is that of P450cam, a class I soluble enzyme isolated from Pseudomonas putida (product of the CYP101 gene). To understand the details of the structure-function relationships within and between the two classes, structural studies on additional cytochromes P450 are crucial. We report here characterization of the crystal forms of two soluble, bacterial enzymes: cytochrome P450terp [class I enzyme from a Pseudomonas species (product of CYP108 gene)] and the hemoprotein domain of cytochrome P450BM-3 [class II enzyme from Bacillus megaterium (product of the CYP102 gene)]. The crystals of cytochrome P450terp are hexagonal and belong to the space group P6(1)22 (or its enantiomorph, P6(5)22) with unit cell dimensions a = b = 68.9 A and c = 458.7 A. The crystals of the hemoprotein domain of cytochrome P450BM-3 are monoclinic and belong to the space group P2(1) with unit cell dimensions a = 59.4 A, b = 154.0 A, c = 62.2 A, and beta = 94.7 degrees. Diffraction data for the crystals of these two proteins were obtained to a resolution better than 2.2 A. Assuming the presence of two molecules in the asymmetric unit for the hemoprotein domain of P450BM-3 and one molecule for P450terp, the calculated values of Vm are 2.6 and 3.3 A3/Da, respectively. Images PMID:1608967

  15. Design of highly active binary catalyst systems for CO2/epoxide copolymerization: polymer selectivity, enantioselectivity, and stereochemistry control.

    PubMed

    Lu, Xiao-Bing; Shi, Lei; Wang, Yi-Ming; Zhang, Rong; Zhang, Ying-Ju; Peng, Xiao-Jun; Zhang, Zhi-Chao; Li, Bo

    2006-02-01

    Asymmetric, regio- and stereoselective alternating copolymerization of CO(2) and racemic aliphatic epoxides proceeds effectively under mild temperature and pressure by using a binary catalyst system of a chiral tetradentate Schiff base cobalt complex [SalenCo(III)X] as the electrophile in conjunction with an ionic organic ammonium salt or a sterically hindered strong organic base as the nucleophile. The substituent groups on the aromatic rings, chiral diamine backbone, and axial X group of the electrophile, as well as the nucleophilicity, leaving ability, and coordination ability of the nucleophile, all significantly affect the catalyst activity, polymer selectivity, enantioselectivity, and stereochemistry. A bulky chiral cyclohexenediimine backbone complex [SalcyCo(III)X] with an axial X group of poor leaving ability as the electrophile, combined with a bulky nuclephile with poor leaving ability and low coordination ability, is an ideal binary catalyst system for the copolymerization of CO(2) and a racemic aliphatic epoxide to selectively produce polycarbonates with relatively high enantioselectivity, >95% head-to-tail connectivity, and >99% carbonate linkages. A fast copolymerization of CO(2) and epoxides was observed when the concentration of the electrophile or/and the nucleophile was increased, and the number of polycarbonate chains was proportional to the concentration of the nucleophile. Electrospray ionization mass spectrometry, in combination with a kinetic study, showed that the copolymerization involved the coordination activation of the monomer by the electrophile and polymer chain growth predominately occurring in the nucleophile. Both the enantiomorphic site effect resulting from the chiral electrophile and the polymer chain end effect mainly from the bulky nucleophile cooperatively control the stereochemistry of the CO(2)/epoxide copolymerization.

  16. Supramolecular structures of 1-phenylethylammonium tartrates.

    PubMed

    Turkington, David E; MacLean, Elizabeth J; Lough, Alan J; Ferguson, George; Glidewell, Christopher

    2005-02-01

    The structures of six 1-phenylethylammonium tartrates have been determined and in each of them a distinctive hydrogen-bonded anion substructure can be identified. (S)-1-Phenylethylammonium (R,R)-hydrogen tartrate [(I), P21, Z'=1] contains anion sheets built from a single type of R4(4)(22) ring with cations pendent, via three N-H...O hydrogen bonds, from just one face of the sheet. (S)-1-Phenylethylammonium rac-hydrogen tartrate [(II), P21, Z'=2] and its enantiomorph (R)-1-phenylethylammonium rac-hydrogen tartrate [(III), P21, Z'=2] contain anion sheets built from four types of ring, R2(2)(10), R2(2)(12), R2(4)(14) and R4(4)(20), and there are cations pendent from both faces of the sheet. The anion substructure in bis[(S)-1-phenylethylammonium] (R,R)-tartrate [(IV), P2(1), Z'=1] consists of simple C(5) chains, which are linked into sheets by the cations, while in bis(rac-1-phenylethylammonium) (R,R)-tartrate [(V), P2(1), Z'=2] there are anion sheets containing two distinct types of R4(4)(22) ring, with equal numbers of (R) and (S) cations pendent from each face of the anion sheet. Bis[(R)-1-phenylethylammonium] rac-tartrate methanol hemisolvate [(VI), P1, Z'=4, with 14 independent components in the asymmetric unit] contains anion sheets built from two types of R2(2)(12) ring and two types of R6(6)(32) ring; half of the cations and half of the methanol molecules are pendent from each face of the sheet.

  17. Louis Pasteur, language, and molecular chirality. I. Background and dissymmetry.

    PubMed

    Gal, Joseph

    2011-01-01

    Louis Pasteur resolved sodium ammonium (±)-tartrate in 1848, thereby discovering molecular chirality. Although hindered by the primitive state of organic chemistry, he introduced new terminology and nomenclature for his new science of molecular and crystal chirality. He was well prepared for this task by his rigorous education and innate abilities, and his linguistic achievements eventually earned him membership in the supreme institution for the French language, the Académie française. Dissymmetry had been in use in French from the early 1820s for disruption or absence of symmetry or for dissimilarity or difference in appearance between two objects, and Pasteur initially used it in the latter connotation, without any reference to handedness or enantiomorphism. Soon, however, he adopted it in the meaning of chirality. Asymmetry had been in use in French since 1691 but Pasteur ignored it in favor of dissymmetry. The two terms are not synonymous but it is not clear whether Pasteur recognized this difference in choosing the former over the latter. However, much of the literature mistranslates his dissymmetry as asymmetry. Twenty years before Pasteur the British polymath John Herschel proposed that optical rotation in the noncrystalline state is due to the "unsymmetrical" [his term] nature of the molecules and later used dissymmetrical for handed. Chirality, coined by Lord Kelvin in 1894 and introduced into chemistry by Mislow in 1962, has nearly completely replaced dissymmetry in the meaning of handedness, but the use of dissymmetry continues today in other contexts for lack of symmetry, reduction of symmetry, or dissimilarity.

  18. The complete mitochondrial genome of the Antarctic stalked jellyfish, Haliclystus antarcticus Pfeffer, 1889 (Staurozoa: Stauromedusae).

    PubMed

    Li, Hsing-Hui; Sung, Ping-Jyun; Ho, Hsuan-Ching

    2016-06-01

    In present study, the complete mitogenome sequence of the Antarctic stalked jellyfish, Haliclystus antarcticus Pfeffer (Staurozoa: Stauromedusae) has been sequenced by next-generation sequencing method. The assembled mitogenome comprises of 15,766 bp including 13 protein coding genes, 7 transfer RNAs, and 2 ribosomal RNA genes. The overall base of Antarctic stalked jellyfish constitutes of 26.5% for A, 19.6% for C, 19.8% for G, 34.1% for T and show 90% identity to Sessile Jelly, Haliclystus sanjuanensis, in the northeastern Pacific Ocean. The complete mitogenome of the Antarctic stalked jellyfish, contributes fundamental and significant DNA molecular data for further phylogeography and evolutionary analysis for seahorse phylogeny. The complete sequence was deposited in DBBJ/EMBL/GenBank under accession number KU947038. PMID:27222813

  19. High-quality draft genome sequence of Enterobacter sp. Bisph2, a glyphosate-degrading bacterium isolated from a sandy soil of Biskra, Algeria.

    PubMed

    Benslama, Ouided; Boulahrouf, Abderrahmane

    2016-06-01

    Enterobacter sp. strain Bisph2 was isolated from a sandy soil from Biskra, Algeria and exhibits glyphosate-degrading activity. Multilocus sequence analysis of the 16S rRNA, rpoB, hsp60, gyrB and dnaJ genes demonstrated that Bisph2 might be a member of a new species of the genus Enterobacter. Genomic sequencing of Bisph2 was used to better clarify the relationships among Enterobacter species. Annotation and analysis of the genome sequence showed that the 5.535.656 bp genome of Enterobacter sp. Bisph2 consists in one chromosome and no detectable plasmid, has a 53.19% GC content and 78% of genes were assigned a putative function. The genome contains four prophages of which 3 regions are intact and no CRISPER was detected. The nucleotide sequence of this genome was deposited into DDBJ/EMBL/GenBank under the accession JXAF00000000. PMID:27222800

  20. Whole genome sequence of the emerging oomycete pathogen Pythium insidiosum strain CDC-B5653 isolated from an infected human in the USA

    PubMed Central

    Ascunce, Marina S.; Huguet-Tapia, Jose C.; Braun, Edward L.; Ortiz-Urquiza, Almudena; Keyhani, Nemat O.; Goss, Erica M.

    2015-01-01

    Pythium insidiosum ATCC 200269 strain CDC-B5653, an isolate from necrotizing lesions on the mouth and eye of a 2-year-old boy in Memphis, Tennessee, USA, was sequenced using a combination of Illumina MiSeq (300 bp paired-end, 14 millions reads) and PacBio (10  Kb fragment library, 356,001 reads). The sequencing data were assembled using SPAdes version 3.1.0, yielding a total genome size of 45.6 Mb contained in 8992 contigs, N50 of 13 Kb, 57% G + C content, and 17,867 putative protein-coding genes. This Whole Genome Shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession JRHR00000000. PMID:26981361

  1. Whole genome sequence of the emerging oomycete pathogen Pythium insidiosum strain CDC-B5653 isolated from an infected human in the USA.

    PubMed

    Ascunce, Marina S; Huguet-Tapia, Jose C; Braun, Edward L; Ortiz-Urquiza, Almudena; Keyhani, Nemat O; Goss, Erica M

    2016-03-01

    Pythium insidiosum ATCC 200269 strain CDC-B5653, an isolate from necrotizing lesions on the mouth and eye of a 2-year-old boy in Memphis, Tennessee, USA, was sequenced using a combination of Illumina MiSeq (300 bp paired-end, 14 millions reads) and PacBio (10  Kb fragment library, 356,001 reads). The sequencing data were assembled using SPAdes version 3.1.0, yielding a total genome size of 45.6 Mb contained in 8992 contigs, N50 of 13 Kb, 57% G + C content, and 17,867 putative protein-coding genes. This Whole Genome Shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession JRHR00000000. PMID:26981361

  2. Overview of selected molecular biological databases

    SciTech Connect

    Rayl, K.D.; Gaasterland, T.

    1994-11-01

    This paper presents an overview of the purpose, content, and design of a subset of the currently available biological databases, with an emphasis on protein databases. Databases included in this summary are 3D-ALI, Berlin RNA databank, Blocks, DSSP, EMBL Nucleotide Database, EMP, ENZYME, FSSP, GDB, GenBank, HSSP, LiMB, PDB, PIR, PKCDD, ProSite, and SWISS-PROT. The goal is to provide a starting point for researchers who wish to take advantage of the myriad available databases. Rather than providing a complete explanation of each database, we present its content and form by explaining the details of typical entries. Pointers to more complete ``user guides`` are included, along with general information on where to search for a new database.

  3. Sentra, a database of signal transduction proteins.

    SciTech Connect

    Maltsev, N.; Marland, E.; Yu, G. X.; Bhatnagar, S.; Lusk, R.; Mathematics and Computer Science

    2002-01-01

    Sentra (http://www-wit.mcs.anl.gov/sentra) is a database of signal transduction proteins with the emphasis on microbial signal transduction. The database was updated to include classes of signal transduction systems modulated by either phosphorylation or methylation reactions such as PAS proteins and serine/threonine kinases, as well as the classical two-component histidine kinases and methyl-accepting chemotaxis proteins. Currently, Sentra contains signal transduction proteins from 43 completely sequenced prokaryotic genomes as well as sequences from SWISS-PROT and TrEMBL. Signal transduction proteins are annotated with information describing conserved domains, paralogous and orthologous sequences, and conserved chromosomal gene clusters. The newly developed user interface supports flexible search capabilities and extensive visualization of the data.

  4. SENTRA, a database of signal transduction proteins.

    SciTech Connect

    D'Souza, M.; Romine, M. F.; Maltsev, N.; Mathematics and Computer Science; PNNL

    2000-01-01

    SENTRA, available via URL http://wit.mcs.anl.gov/WIT2/Sentra/, is a database of proteins associated with microbial signal transduction. The database currently includes the classical two-component signal transduction pathway proteins and methyl-accepting chemotaxis proteins, but will be expanded to also include other classes of signal transduction systems that are modulated by phosphorylation or methylation reactions. Although the majority of database entries are from prokaryotic systems, eukaroytic proteins with bacterial-like signal transduction domains are also included. Currently SENTRA contains signal transduction proteins in 34 complete and almost completely sequenced prokaryotic genomes, as well as sequences from 243 organisms available in public databases (SWISS-PROT and EMBL). The analysis was carried out within the framework of the WIT2 system, which is designed and implemented to support genetic sequence analysis and comparative analysis of sequenced genomes.

  5. Development of internal components for M38999 type connectors, for use in advanced photonic applications and with specialty optical fibers

    NASA Astrophysics Data System (ADS)

    Whitebook, Alan; Caloz, Francois

    2014-09-01

    This presentation outlines development work performed to produce internal components (connector insert assemblies & optical terminus assemblies) to be fit into MIL-DTL-38999, or commercial off the shelf (COTS) equivalent, connector housings. Connectors modified with these internal components are then suitable for optical termination and transmission through specialty fibers such as polarization maintaining, small core single-mode, and others, with the ability to achieve high levels of performance in the areas of insertion loss, return loss, polarization extinction ratio (as applicable) and power handling capability (as applicable.) Technical details are presented to illustrate features within the optical terminus, and its insert cavity, which serves to allow for fiber/ferrule polar orientation, concentricity of mated termini ferrules and fibers terminated within, and other attributes designed to support optical performance goals. Finally, optical performance data is given and discussed to illustrate results achieved by production of evaluation cable assemblies. emblies.

  6. KEMP: A program script for automated biological x-ray absorption spectroscopy data reduction

    SciTech Connect

    Korbas, Malgorzata; Fulla Marsa, Daniel; Meyer-Klaucke, Wolfram

    2006-06-15

    Automation of x-ray absorption spectroscopic (XAS) data reduction is essential to cope with high-throughput data collection becoming available at an increasing number of synchrotron radiation centers. A flexible script called KEMP has been developed and implemented at the XAS beamline at EMBL Hamburg. It automatically processes fluorescence XAS data. The pipeline includes dead time correction, energy calibration, selection of fluorescence detector channels, as well as the extraction of x-ray absorption near-edge structure and extended x-ray-absorption fine structure. The output is quickly available and thus can be included in the design of further experiments, which results in a more efficient use of the beam time.

  7. Designing Multi-target Compound Libraries with Gaussian Process Models.

    PubMed

    Bieler, Michael; Reutlinger, Michael; Rodrigues, Tiago; Schneider, Petra; Kriegl, Jan M; Schneider, Gisbert

    2016-05-01

    We present the application of machine learning models to selecting G protein-coupled receptor (GPCR)-focused compound libraries. The library design process was realized by ant colony optimization. A proprietary Boehringer-Ingelheim reference set consisting of 3519 compounds tested in dose-response assays at 11 GPCR targets served as training data for machine learning and activity prediction. We compared the usability of the proprietary data with a public data set from ChEMBL. Gaussian process models were trained to prioritize compounds from a virtual combinatorial library. We obtained meaningful models for three of the targets (5-HT2c , MCH, A1), which were experimentally confirmed for 12 of 15 selected and synthesized or purchased compounds. Overall, the models trained on the public data predicted the observed assay results more accurately. The results of this study motivate the use of Gaussian process regression on public data for virtual screening and target-focused compound library design.

  8. PDEStrIAn: A Phosphodiesterase Structure and Ligand Interaction Annotated Database As a Tool for Structure-Based Drug Design.

    PubMed

    Jansen, Chimed; Kooistra, Albert J; Kanev, Georgi K; Leurs, Rob; de Esch, Iwan J P; de Graaf, Chris

    2016-08-11

    A systematic analysis is presented of the 220 phosphodiesterase (PDE) catalytic domain crystal structures present in the Protein Data Bank (PDB) with a focus on PDE-ligand interactions. The consistent structural alignment of 57 PDE ligand binding site residues enables the systematic analysis of PDE-ligand interaction fingerprints (IFPs), the identification of subtype-specific PDE-ligand interaction features, and the classification of ligands according to their binding modes. We illustrate how systematic mining of this phosphodiesterase structure and ligand interaction annotated (PDEStrIAn) database provides new insights into how conserved and selective PDE interaction hot spots can accommodate the large diversity of chemical scaffolds in PDE ligands. A substructure analysis of the cocrystallized PDE ligands in combination with those in the ChEMBL database provides a toolbox for scaffold hopping and ligand design. These analyses lead to an improved understanding of the structural requirements of PDE binding that will be useful in future drug discovery studies.

  9. Candida middelhoveniana sp. nov., a new yeast species found on the rhizoplane of organically cultivated sugarcane.

    PubMed

    Ribeiro, José R de A; Carvalho, Patrícia M B de; Cabral, Anderson de S; Macrae, Andrew; Mendonça-Hagler, Leda C S; Berbara, Ricardo L L; Hagler, Allen N

    2011-10-01

    A novel yeast species within the Metschnikowiaceae is described based on a strain from the sugarcane (Saccharum sp.) rhizoplane of an organically managed farm in Rio de Janeiro, Brazil. The D1/D2 domain of the large subunit ribosomal RNA gene sequence analysis showed that the closest related species were Candida tsuchiyae with 86.2% and Candida thailandica with 86.7% of sequence identity. All three are anamorphs in the Clavispora opuntiae clade. The name Candida middelhoveniana sp. nov. is proposed to accommodate this highly divergent organism with the type strain Instituto de Microbiologia, Universidade Federal do Rio de Janeiro (IMUFRJ) 51965(T) (=Centraalbureau voor Schimmelcultures (CBS) 12306(T), Universidade Federal de Minas Gerais (UFMG)-70(T), DBVPG 8031(T)) and the GenBank/EMBL/DDBJ accession number for the D1/D2 domain LSU rDNA sequence is FN428871. The Mycobank deposit number is MB 519801.

  10. Identity crisis? The need for systematic gene IDs.

    PubMed

    Parsons, Marilyn; Myler, Peter J; Berriman, Matthew; Roos, David S; Stuart, Kenneth D

    2011-05-01

    Recent years have seen an explosion in the availability of protozoan pathogen genome sequences. Although data regarding the underlying genome sequence remain relatively stable after the initial draft, understanding of specific gene function is increasing rapidly. This dichotomy is reflected in the relative stability of systematic gene identifiers (SysIDs(*)) in genome sequence databases, as compared to evolving and/or conflicting gene and gene product names. GenBank/EMBL/DDBJ accession numbers are important, but most protozoan parasite researchers use organism-based databases such as EuPathDB or GeneDB as their immediate resource for gene-based information because they not only provide sequence information but also functional information and links to references. Reference to SysIDs therefore provides a valuable bridge to this repository of information.

  11. Isolation and complete genome sequencing of Mimivirus bombay, a Giant Virus in sewage of Mumbai, India.

    PubMed

    Chatterjee, Anirvan; Ali, Farhan; Bange, Disha; Kondabagil, Kiran

    2016-09-01

    We report the isolation and complete genome sequencing of a new Mimiviridae family member, infecting Acanthamoeba castellanii, from sewage in Mumbai, India. The isolated virus has a particle size of about 435 nm and a 1,182,200-bp genome. A phylogeny based on the DNA polymerase sequence placed the isolate as a new member of the Mimiviridae family lineage A and was named as Mimivirus bombay. Extensive presence of Mimiviridae family members in different environmental niches, with remarkably similar genome size and genetic makeup, point towards an evolutionary advantage that needs to be further investigated. The complete genome sequence of Mimivirus bombay was deposited at GenBank/EMBL/DDBJ under the accession number KU761889. PMID:27330993

  12. Prediction of the anti-inflammatory mechanisms of curcumin by module-based protein interaction network analysis.

    PubMed

    Gan, Yanxiong; Zheng, Shichao; Baak, Jan P A; Zhao, Silei; Zheng, Yongfeng; Luo, Nini; Liao, Wan; Fu, Chaomei

    2015-11-01

    Curcumin, the medically active component from Curcuma longa (Turmeric), is widely used to treat inflammatory diseases. Protein interaction network (PIN) analysis was used to predict its mechanisms of molecular action. Targets of curcumin were obtained based on ChEMBL and STITCH databases. Protein-protein interactions (PPIs) were extracted from the String database. The PIN of curcumin was constructed by Cytoscape and the function modules identified by gene ontology (GO) enrichment analysis based on molecular complex detection (MCODE). A PIN of curcumin with 482 nodes and 1688 interactions was constructed, which has scale-free, small world and modular properties. Based on analysis of these function modules, the mechanism of curcumin is proposed. Two modules were found to be intimately associated with inflammation. With function modules analysis, the anti-inflammatory effects of curcumin were related to SMAD, ERG and mediation by the TLR family. TLR9 may be a potential target of curcumin to treat inflammation. PMID:26713275

  13. Development and implementation of (Q)SAR modeling within the CHARMMing web-user interface.

    PubMed

    Weidlich, Iwona E; Pevzner, Yuri; Miller, Benjamin T; Filippov, Igor V; Woodcock, H Lee; Brooks, Bernard R

    2015-01-01

    Recent availability of large publicly accessible databases of chemical compounds and their biological activities (PubChem, ChEMBL) has inspired us to develop a web-based tool for structure activity relationship and quantitative structure activity relationship modeling to add to the services provided by CHARMMing (www.charmming.org). This new module implements some of the most recent advances in modern machine learning algorithms-Random Forest, Support Vector Machine, Stochastic Gradient Descent, Gradient Tree Boosting, so forth. A user can import training data from Pubchem Bioassay data collections directly from our interface or upload his or her own SD files which contain structures and activity information to create new models (either categorical or numerical). A user can then track the model generation process and run models on new data to predict activity.

  14. Genome Information Broker for Viruses (GIB-V): database for comparative analysis of virus genomes

    PubMed Central

    Hirahata, Masaki; Abe, Takashi; Tanaka, Naoto; Kuwana, Yoshikazu; Shigemoto, Yasumasa; Miyazaki, Satoru; Suzuki, Yoshiyuki; Sugawara, Hideaki

    2007-01-01

    Genome Information Broker for Viruses (GIB-V) is a comprehensive virus genome/segment database. We extracted 18 418 complete virus genomes/segments from the International Nucleotide Sequence Database Collaboration (INSDC, ) by DNA Data Bank of Japan (DDBJ), EMBL and GenBank and stored them in our system. The list of registered viruses is arranged hierarchically according to taxonomy. Keyword searches can be performed for genome/segment data or biological features of any virus stored in GIB-V. GIB-V is equipped with a BLAST search function, and search results are displayed graphically or in list form. Moreover, the BLAST results can be used online with the ClustalW feature of the DDBJ. All available virus genome/segment data can be collected by the GIB-V download function. GIB-V can be accessed at no charge at . PMID:17158166

  15. Cloning of fragments of novel homeobox genes expressed during regeneration in planarians

    SciTech Connect

    Lukyanov, K.A.; Tarabykin, V.S.; Potapov, V.K.

    1994-11-01

    The polymerase chain reaction with degenerate primers corresponding to the most conservative amino acids 16-21 (ELEKEF) and 49-54 (WPQNRR) of the Antennapedia class homeodomains was used for the amplification of cDNA from regenerating planarians (asexual race of Dugesia tigrina). A total of six new Antennapedia-like homeobox sequences, designated Dutarh-1-Dutarh-6 (Dugesia tigrina asexual race homeobox gene), have been identified. Their comparison with other homeobox genes using a Genebee software (the EMBL Data Library) showed that all sequences except Dutarh-6 belong to the Antennapedia class. Dutarh-6 is closely related to a recently described novel homeobox gene subfamily which includes mouse mesodermal homeobox genes Max-1 and Max-2 and rat homeobox gene Gax. 17 refs., 2 figs.

  16. Species determination: the role and use of the cytochrome b gene.

    PubMed

    Linacre, Adrian; Lee, James Chun-I

    2005-01-01

    Many large mammalian species are on the verge of extinction in part because of the trade in their skin, bone, horn, or body parts for supposed medicinal purposes. Identification of the species is required to determine that a crime has been committed. This chapter details a robust DNA technique using part of the cytochrome b gene on the mitochondrial genome that will work on poor-quality samples such as powdered horn. An appropriate deoxyribonucleic acid (DNA) extraction technique is required to obtain at least 10 ng of DNA. Amplification of part of the cytochrome b gene using universal primers produces a fragment of approx 486 bp in size. Direct sequencing of the PCR products allows comparison of the DNA sequence at this locus to those already described on the EMBL DNA database.

  17. High-quality draft genome sequence of Enterobacter sp. Bisph2, a glyphosate-degrading bacterium isolated from a sandy soil of Biskra, Algeria.

    PubMed

    Benslama, Ouided; Boulahrouf, Abderrahmane

    2016-06-01

    Enterobacter sp. strain Bisph2 was isolated from a sandy soil from Biskra, Algeria and exhibits glyphosate-degrading activity. Multilocus sequence analysis of the 16S rRNA, rpoB, hsp60, gyrB and dnaJ genes demonstrated that Bisph2 might be a member of a new species of the genus Enterobacter. Genomic sequencing of Bisph2 was used to better clarify the relationships among Enterobacter species. Annotation and analysis of the genome sequence showed that the 5.535.656 bp genome of Enterobacter sp. Bisph2 consists in one chromosome and no detectable plasmid, has a 53.19% GC content and 78% of genes were assigned a putative function. The genome contains four prophages of which 3 regions are intact and no CRISPER was detected. The nucleotide sequence of this genome was deposited into DDBJ/EMBL/GenBank under the accession JXAF00000000.

  18. Draft genome sequence of Bacillus okhensis Kh10-101T, a halo-alkali tolerant bacterium from Indian saltpan.

    PubMed

    Krishna, Pilla Sankara; Sreenivas, Ara; Singh, Deepak Kumar; Shivaji, Sisinthy; Prakash, Jogadhenu S S

    2015-12-01

    We report the 4.86-Mb draft genome sequence of Bacillus okhensis strain Kh10-101T, a halo-alkali tolerant rod shaped bacterium isolated from a salt pan near port of Okha, India. This bacterium is a potential model to study the molecular response of bacteria to salt as well as alkaline stress, as it thrives under both high salt and high pH conditions. The draft genome consist of 4,865,284 bp with 38.2% G + C, 4952 predicted CDS, 157 tRNAs and 8 rRNAs. Sequence was deposited at DDBJ/EMBL/GenBank under the project accession JRJU00000000. PMID:26697400

  19. High-quality complete genome sequence of Microbacterium sp. SUBG005, a plant pathogen.

    PubMed

    Rakhashiya, Purvi M; Patel, Pooja P; Thaker, Vrinda S

    2015-09-01

    Microbacterium sp. SUBG005 is a Gram positive bacterium, isolated from infected leaf of Mangifera indica L. in Rajkot (22.30°N, 70.78°E), Gujarat, India. The genome sequencing of Microbacterium sp. SUBG005 is having type I secretion system genes of pathogenicity as well as heavy metal resistance unique genes. The genome size is 7.01 Mb with G + C content of 64.80% and contains rRNA sequences. Genome sequencing analysis provides information about the microbe role in host-pathogen interaction. The whole genome sequencing has been deposited in DDBJ/EMBL/GenBank under the accession number JNNT00000000. PMID:26484276

  20. The androgen receptor gene mutations database.

    PubMed

    Gottlieb, B; Trifiro, M; Lumbroso, R; Pinsky, L

    1997-01-01

    The current version of the androgen receptor (AR) gene mutations database is described. The total number of reported mutations has risen from 212 to 272. We have expanded the database: (i) by adding a large amount of new data on somatic mutations in prostatic cancer tissue; (ii) by defining a new constitutional phenotype, mild androgen insensitivity (MAI); (iii) by placing additional relevant information on an internet site (http://www.mcgill.ca/androgendb/ ). The database has allowed us to examine the contribution of CpG sites to the multiplicity of reports of the same mutation in different families. The database is also available from EMBL (ftp.ebi.ac.uk/pub/databases/androgen) or as a Macintosh Filemaker Pro or Word file (MC33@musica,mcgill.ca)

  1. Update of the androgen receptor gene mutations database.

    PubMed

    Gottlieb, B; Beitel, L K; Lumbroso, R; Pinsky, L; Trifiro, M

    1999-01-01

    The current version of the androgen receptor (AR) gene mutations database is described. The total number of reported mutations has risen from 309 to 374 during the past year. We have expanded the database by adding information on AR-interacting proteins; and we have improved the database by identifying those mutation entries that have been updated. Mutations of unknown significance have now been reported in both the 5' and 3' untranslated regions of the AR gene, and in individuals who are somatic mosaics constitutionally. In addition, single nucleotide polymorphisms, including silent mutations, have been discovered in normal individuals and in individuals with male infertility. A mutation hotspot associated with prostatic cancer has been identified in exon 5. The database is available on the internet (http://www.mcgill.ca/androgendb/), from EMBL-European Bioinformatics Institute (ftp.ebi.ac.uk/pub/databases/androgen), or as a Macintosh FilemakerPro or Word file (MC33@musica.mcgill.ca).

  2. Transporter taxonomy - a comparison of different transport protein classification schemes.

    PubMed

    Viereck, Michael; Gaulton, Anna; Digles, Daniela; Ecker, Gerhard F

    2014-06-01

    Currently, there are more than 800 well characterized human membrane transport proteins (including channels and transporters) and there are estimates that about 10% (approx. 2000) of all human genes are related to transport. Membrane transport proteins are of interest as potential drug targets, for drug delivery, and as a cause of side effects and drug–drug interactions. In light of the development of Open PHACTS, which provides an open pharmacological space, we analyzed selected membrane transport protein classification schemes (Transporter Classification Database, ChEMBL, IUPHAR/BPS Guide to Pharmacology, and Gene Ontology) for their ability to serve as a basis for pharmacology driven protein classification. A comparison of these membrane transport protein classification schemes by using a set of clinically relevant transporters as use-case reveals the strengths and weaknesses of the different taxonomy approaches.

  3. Draft genome sequence of strain MC1A, a UV-resistant bacterium isolated from dry soil in Puerto Rico

    PubMed Central

    Cuebas-Irizarry, Mara F.; Pietri-Toro, Jariselle M.; Montalvo-Rodríguez, Rafael

    2016-01-01

    We report here the draft genome sequence of a novel UV-resistant bacterium isolated from dry soil on the south coast of Puerto Rico. Based on polyphasic taxonomy, strain MC1A represents a new species and the name Solirubrum puertoriconensis is proposed. Assembly was performed using NGEN Assembler into eight contigs (N50 = 1,292,788), the largest of which included 1,549,887 bp. The draft genome consists of 4,810,875 bp and has a GC content of 58.7%. Several genes related to DNA repair and UV resistance were found. The Whole Genome Shotgun project is available at DDBJ/EMBL/GenBank under the accession LNAL00000000. PMID:26981418

  4. Draft genome sequence of the Algerian bee Apis mellifera intermissa

    PubMed Central

    Haddad, Nizar Jamal; Loucif-Ayad, Wahida; Adjlane, Noureddine; Saini, Deepti; Manchiganti, Rushiraj; Krishnamurthy, Venkatesh; AlShagoor, Banan; Batainh, Ahmed Mahmud; Mugasimangalam, Raja

    2015-01-01

    Apis mellifera intermissa is the native honeybee subspecies of Algeria. A. m. intermissa occurs in Tunisia, Algeria and Morocco, between the Atlas and the Mediterranean and Atlantic coasts. This bee is very important due to its high ability to adapt to great variations in climatic conditions and due to its preferable cleaning behavior. Here we report the draft genome sequence of this honey bee, its Whole Genome Shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession JSUV00000000. The 240-Mb genome is being annotated and analyzed. Comparison with the genome of other Apis mellifera sub-species promises to yield insights into the evolution of adaptations to high temperature and resistance to Varroa parasite infestation. PMID:26484171

  5. Organization and nucleotide sequence of a gene cluster comprising the translation elongation factor 1 alpha, ribosomal protein S10 and tRNA(Ala) from Halobacterium halobium.

    PubMed

    Fujita, T; Itoh, T

    1995-09-01

    Lambda EMBL clone containing a gene cluster coding for the translation elongation factor 1alpha, ribosomal protein S10 and tRNA(ala) was identified in a genomic library for the halophilic archaebacterium Halobacterium halobium using a PCR probe amplified by two oligonucleotide primers for conserved amino acid sequences of the elongation factor 1 alpha family. The gene coding for elongation factor EF-2 was also found 4.3kb upstream from the 5'end of the elongation factor 1 alpha by hybridization analysis using a DNA fragment specific for EF-2 from Halobacterium halobium [1]. Halobacterial and eukaryotic elongation factor 1 alpha homologues are very similar in sequence and in length and appear to be more closely related to each other than to the eubacterial protein. PMID:8653072

  6. Arrêt cardiocirculatoire par accidents d’électrisations: intérêt du défibrillateur semi-automatique

    PubMed Central

    Siah, S.; Fouadi, F.E.; Ababou, K.; Ihrai, I.; Drissi, N.K.

    2011-01-01

    Summary Les brûlures par accidents électriques sont graves car elles peuvent entraîner le décès par arrêt cardiocirculatoire. Les arrêts cardiocirculatoires induits par le courant de basse tension sont en règle générale dûs à une fibrillation ventriculaire, plutôt de bon pronostic si la chaîne des secours est efficace. Il faut donner la priorité à la défibrillation systématique d’emblée en utilisant un défibrillateur semi-automatique. La défibrillation électrique est susceptible de procurer immédiatement une restauration de l’activité circulatoire spontanée. PMID:21991238

  7. High quality, small molecule-activity datasets for kinase research.

    PubMed

    Sharma, Rajan; Schürer, Stephan C; Muskal, Steven M

    2016-01-01

    Kinases regulate cell growth, movement, and death. Deregulated kinase activity is a frequent cause of disease. The therapeutic potential of kinase inhibitors has led to large amounts of published structure activity relationship (SAR) data. Bioactivity databases such as the Kinase Knowledgebase (KKB), WOMBAT, GOSTAR, and ChEMBL provide researchers with quantitative data characterizing the activity of compounds across many biological assays. The KKB, for example, contains over 1.8M kinase structure-activity data points reported in peer-reviewed journals and patents. In the spirit of fostering methods development and validation worldwide, we have extracted and have made available from the KKB 258K structure activity data points and 76K associated unique chemical structures across eight kinase targets. These data are freely available for download within this data note. PMID:27429748

  8. Genome sequence and description of Corynebacterium ihumii sp. nov.

    PubMed Central

    Padmanabhan, Roshan; Dubourg, Grégory; Lagier, Jean-Christophe; Couderc, Carine; Michelle, Caroline; Raoult, Didier; Fournier, Pierre-Edouard

    2014-01-01

    Corynebacterium ihumii strain GD7T sp. nov. is proposed as the type strain of a new species, which belongs to the family Corynebacteriaceae of the class Actinobacteria. This strain was isolated from the fecal flora of a 62 year-old male patient, as a part of the culturomics study. Corynebacterium ihumii is a Gram positive, facultativly anaerobic, nonsporulating bacillus. Here, we describe the features of this organism, together with the high quality draft genome sequence, annotation and the comparison with other member of the genus Corynebacteria. C. ihumii genome is 2,232,265 bp long (one chromosome but no plasmid) containing 2,125 protein-coding and 53 RNA genes, including 4 rRNA genes. The whole-genome shotgun sequence of Corynebacterium ihumii strain GD7T sp. nov has been deposited in EMBL under accession number GCA_000403725. PMID:25197488

  9. Ligand-Based Virtual Screening in a Search for Novel Anti-HIV-1 Chemotypes.

    PubMed

    Kurczyk, Agata; Warszycki, Dawid; Musiol, Robert; Kafel, Rafał; Bojarski, Andrzej J; Polanski, Jaroslaw

    2015-10-26

    In a search for new anti-HIV-1 chemotypes, we developed a multistep ligand-based virtual screening (VS) protocol combining machine learning (ML) methods with the privileged structures (PS) concept. In its learning step, the VS protocol was based on HIV integrase (IN) inhibitors fetched from the ChEMBL database. The performances of various ML methods and PS weighting scheme were evaluated and applied as VS filtering criteria. Finally, a database of 1.5 million commercially available compounds was virtually screened using a multistep ligand-based cascade, and 13 selected unique structures were tested by measuring the inhibition of HIV replication in infected cells. This approach resulted in the discovery of two novel chemotypes with moderate antiretroviral activity, that, together with their topological diversity, make them good candidates as lead structures for future optimization.

  10. Genenames.org: the HGNC resources in 2015

    PubMed Central

    Gray, Kristian A.; Yates, Bethan; Seal, Ruth L.; Wright, Mathew W.; Bruford, Elspeth A.

    2015-01-01

    The HUGO Gene Nomenclature Committee (HGNC) based at the European Bioinformatics Institute (EMBL-EBI) assigns unique symbols and names to human genes. To date the HGNC have assigned over 39 000 gene names and, representing an increase of over 5000 entries in the past two years. As well as increasing the size of our database, we have continued redesigning our website http://www.genenames.org and have modified, updated and improved many aspects of the site including a faster and more powerful search, a vastly improved HCOP tool and a REST service to increase the number of ways users can retrieve our data. This article provides an overview of our current online data and resources, and highlights the changes we have made in recent years. PMID:25361968

  11. Development and implementation of (Q)SAR modeling within the CHARMMing web-user interface.

    PubMed

    Weidlich, Iwona E; Pevzner, Yuri; Miller, Benjamin T; Filippov, Igor V; Woodcock, H Lee; Brooks, Bernard R

    2015-01-01

    Recent availability of large publicly accessible databases of chemical compounds and their biological activities (PubChem, ChEMBL) has inspired us to develop a web-based tool for structure activity relationship and quantitative structure activity relationship modeling to add to the services provided by CHARMMing (www.charmming.org). This new module implements some of the most recent advances in modern machine learning algorithms-Random Forest, Support Vector Machine, Stochastic Gradient Descent, Gradient Tree Boosting, so forth. A user can import training data from Pubchem Bioassay data collections directly from our interface or upload his or her own SD files which contain structures and activity information to create new models (either categorical or numerical). A user can then track the model generation process and run models on new data to predict activity. PMID:25362883

  12. Predicting protein disorder by analyzing amino acid sequence

    PubMed Central

    Yang, Jack Y; Yang, Mary Qu

    2008-01-01

    Background Many protein regions and some entire proteins have no definite tertiary structure, presenting instead as dynamic, disorder ensembles under different physiochemical circumstances. These proteins and regions are known as Intrinsically Unstructured Proteins (IUP). IUP have been associated with a wide range of protein functions, along with roles in diseases characterized by protein misfolding and aggregation. Results Identifying IUP is important task in structural and functional genomics. We exact useful features from sequences and develop machine learning algorithms for the above task. We compare our IUP predictor with PONDRs (mainly neural-network-based predictors), disEMBL (also based on neural networks) and Globplot (based on disorder propensity). Conclusion We find that augmenting features derived from physiochemical properties of amino acids (such as hydrophobicity, complexity etc.) and using ensemble method proved beneficial. The IUP predictor is a viable alternative software tool for identifying IUP protein regions and proteins. PMID:18831799

  13. The complete mitochondrial genome of the Antarctic stalked jellyfish, Haliclystus antarcticus Pfeffer, 1889 (Staurozoa: Stauromedusae).

    PubMed

    Li, Hsing-Hui; Sung, Ping-Jyun; Ho, Hsuan-Ching

    2016-06-01

    In present study, the complete mitogenome sequence of the Antarctic stalked jellyfish, Haliclystus antarcticus Pfeffer (Staurozoa: Stauromedusae) has been sequenced by next-generation sequencing method. The assembled mitogenome comprises of 15,766 bp including 13 protein coding genes, 7 transfer RNAs, and 2 ribosomal RNA genes. The overall base of Antarctic stalked jellyfish constitutes of 26.5% for A, 19.6% for C, 19.8% for G, 34.1% for T and show 90% identity to Sessile Jelly, Haliclystus sanjuanensis, in the northeastern Pacific Ocean. The complete mitogenome of the Antarctic stalked jellyfish, contributes fundamental and significant DNA molecular data for further phylogeography and evolutionary analysis for seahorse phylogeny. The complete sequence was deposited in DBBJ/EMBL/GenBank under accession number KU947038.

  14. Designing Multi-target Compound Libraries with Gaussian Process Models.

    PubMed

    Bieler, Michael; Reutlinger, Michael; Rodrigues, Tiago; Schneider, Petra; Kriegl, Jan M; Schneider, Gisbert

    2016-05-01

    We present the application of machine learning models to selecting G protein-coupled receptor (GPCR)-focused compound libraries. The library design process was realized by ant colony optimization. A proprietary Boehringer-Ingelheim reference set consisting of 3519 compounds tested in dose-response assays at 11 GPCR targets served as training data for machine learning and activity prediction. We compared the usability of the proprietary data with a public data set from ChEMBL. Gaussian process models were trained to prioritize compounds from a virtual combinatorial library. We obtained meaningful models for three of the targets (5-HT2c , MCH, A1), which were experimentally confirmed for 12 of 15 selected and synthesized or purchased compounds. Overall, the models trained on the public data predicted the observed assay results more accurately. The results of this study motivate the use of Gaussian process regression on public data for virtual screening and target-focused compound library design. PMID:27492085

  15. Analysis of expressed sequence tags from a naked foraminiferan Reticulomyxa filosa.

    PubMed

    Burki, Fabien; Nikolaev, Sergey I; Bolivar, Ignacio; Guiard, Jackie; Pawlowski, Jan

    2006-08-01

    Foraminifers are a major component of modern marine ecosystems and one of the most important oceanic producers of calcium carbonate. They are a key phylogenetic group among amoeboid protists, but our knowledge of their genome is still mostly limited to a few conserved genes. Here, we report the first study of expressed genes by means of expressed sequence tag (EST) from the freshwater naked foraminiferan Reticulomyxa filosa. Cluster analysis of 1630 valid ESTs enabled the identification of 178 groups of related sequences and 871 singlets. Approximately 50% of the putative unique 1059 ESTs could be annotated using Blast searches against the protein database SwissProt + TrEMBL. The EST database described here is the first step towards gene discovery in Foraminifera and should provide the basis for new insights into the genomic and transcriptomic characteristics of these interesting but poorly understood protists.

  16. Prediction of the anti-inflammatory mechanisms of curcumin by module-based protein interaction network analysis

    PubMed Central

    Gan, Yanxiong; Zheng, Shichao; Baak, Jan P.A.; Zhao, Silei; Zheng, Yongfeng; Luo, Nini; Liao, Wan; Fu, Chaomei

    2015-01-01

    Curcumin, the medically active component from Curcuma longa (Turmeric), is widely used to treat inflammatory diseases. Protein interaction network (PIN) analysis was used to predict its mechanisms of molecular action. Targets of curcumin were obtained based on ChEMBL and STITCH databases. Protein–protein interactions (PPIs) were extracted from the String database. The PIN of curcumin was constructed by Cytoscape and the function modules identified by gene ontology (GO) enrichment analysis based on molecular complex detection (MCODE). A PIN of curcumin with 482 nodes and 1688 interactions was constructed, which has scale-free, small world and modular properties. Based on analysis of these function modules, the mechanism of curcumin is proposed. Two modules were found to be intimately associated with inflammation. With function modules analysis, the anti-inflammatory effects of curcumin were related to SMAD, ERG and mediation by the TLR family. TLR9 may be a potential target of curcumin to treat inflammation. PMID:26713275

  17. Construction of a chromosome specific library of human MARs and mapping of matrix attachment regions on human chromosome 19.

    PubMed

    Nikolaev, L G; Tsevegiyn, T; Akopov, S B; Ashworth, L K; Sverdlov, E D

    1996-04-01

    Using a novel procedure a representative human chromosome 19-specific library was constructed of short sequences, which bind preferentially to the nuclear matrix (matrix attachment regions, or MARs). Judging by 20 clones sequenced so far, the library contains > 50% of human inserts, about 90% of which are matrix-binding by the in vitro test. Computer analysis of sequences of eight human MARs did not reveal any significant homologies with the EMBL Nucleotide Data Base entries as well as between MARs themselves. Eight MARs were assigned to individual positions on the chromosome 19 physical map. The library constructed can serve as a good source of MAR sequences for comparative analysis and classification and for further chromosome mapping of MARs as well.

  18. Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees.

    PubMed

    Letunic, Ivica; Bork, Peer

    2016-07-01

    Interactive Tree Of Life (http://itol.embl.de) is a web-based tool for the display, manipulation and annotation of phylogenetic trees. It is freely available and open to everyone. The current version was completely redesigned and rewritten, utilizing current web technologies for speedy and streamlined processing. Numerous new features were introduced and several new data types are now supported. Trees with up to 100,000 leaves can now be efficiently displayed. Full interactive control over precise positioning of various annotation features and an unlimited number of datasets allow the easy creation of complex tree visualizations. iTOL 3 is the first tool which supports direct visualization of the recently proposed phylogenetic placements format. Finally, iTOL's account system has been redesigned to simplify the management of trees in user-defined workspaces and projects, as it is heavily used and currently handles already more than 500,000 trees from more than 10,000 individual users.

  19. Whole genome sequence of the emerging oomycete pathogen Pythium insidiosum strain CDC-B5653 isolated from an infected human in the USA.

    PubMed

    Ascunce, Marina S; Huguet-Tapia, Jose C; Braun, Edward L; Ortiz-Urquiza, Almudena; Keyhani, Nemat O; Goss, Erica M

    2016-03-01

    Pythium insidiosum ATCC 200269 strain CDC-B5653, an isolate from necrotizing lesions on the mouth and eye of a 2-year-old boy in Memphis, Tennessee, USA, was sequenced using a combination of Illumina MiSeq (300 bp paired-end, 14 millions reads) and PacBio (10  Kb fragment library, 356,001 reads). The sequencing data were assembled using SPAdes version 3.1.0, yielding a total genome size of 45.6 Mb contained in 8992 contigs, N50 of 13 Kb, 57% G + C content, and 17,867 putative protein-coding genes. This Whole Genome Shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession JRHR00000000.

  20. Draft genome sequence of Staphylococcus aureus KT/312045, an ST1-MSSA PVL positive isolated from pus sample in East Coast Malaysia.

    PubMed

    Suhaili, Zarizal; Lean, Soo-Sum; Mohamad, Noor Muzamil; Rachman, Abdul R Abdul; Desa, Mohd Nasir Mohd; Yeo, Chew Chieng

    2016-09-01

    Most of the efforts in elucidating the molecular relatedness and epidemiology of Staphylococcus aureus in Malaysia have been largely focused on methicillin-resistant S. aureus (MRSA). Therefore, here we report the draft genome sequence of the methicillin-susceptible Staphylococcus aureus (MSSA) with sequence type 1 (ST1), spa type t127 with Panton-Valentine Leukocidin (pvl) pathogenic determinant isolated from pus sample designated as KT/314250 strain. The size of the draft genome is 2.86 Mbp with 32.7% of G + C content consisting 2673 coding sequences. The draft genome sequence has been deposited in DDBJ/EMBL/GenBank under the accession number AOCP00000000. PMID:27508119

  1. Construction of a chromosome specific library of human MARs and mapping of matrix attachment regions on human chromosome 19.

    PubMed Central

    Nikolaev, L G; Tsevegiyn, T; Akopov, S B; Ashworth, L K; Sverdlov, E D

    1996-01-01

    Using a novel procedure a representative human chromosome 19-specific library was constructed of short sequences, which bind preferentially to the nuclear matrix (matrix attachment regions, or MARs). Judging by 20 clones sequenced so far, the library contains > 50% of human inserts, about 90% of which are matrix-binding by the in vitro test. Computer analysis of sequences of eight human MARs did not reveal any significant homologies with the EMBL Nucleotide Data Base entries as well as between MARs themselves. Eight MARs were assigned to individual positions on the chromosome 19 physical map. The library constructed can serve as a good source of MAR sequences for comparative analysis and classification and for further chromosome mapping of MARs as well. PMID:8614638

  2. IS406 and IS407, two gene-activating insertion sequences for Pseudomonas cepacia.

    PubMed

    Wood, M S; Byrne, A; Lessie, T G

    1991-08-30

    We have determined the nucleotide sequences of IS406 (1368 bp) and IS407 (1236 bp), two insertion sequence (IS) elements isolated from Pseudomonas cepacia 249 on the basis of their abilities to activate the expression of the lac genes of Tn951. IS406 and IS407 when inserted into the lac promoter/operator region of Tn951 generated, respectively, duplications of 8 and 4 bp of target DNA. IS406 had 41-bp terminal inverted repeat (IR) sequences with eleven mismatches. IR-L (left) contained a 12-bp motif present at the ends of Tn2501. In other respects, IS406 was distinct from previously described bacterial IS elements listed in the GenBank and EMBL databases. IS407 had 49-bp terminal IRs with 18 mismatches. IR-R (right) contained an outwardly directed sigma 70-like promoter. IS407 was closely related to IS476 and ISR1 from Xanthomonas and Rhizobium sp., respectively. PMID:1718819

  3. High quality, small molecule-activity datasets for kinase research

    PubMed Central

    Sharma, Rajan; Schürer, Stephan C.; Muskal, Steven M.

    2016-01-01

    Kinases regulate cell growth, movement, and death. Deregulated kinase activity is a frequent cause of disease. The therapeutic potential of kinase inhibitors has led to large amounts of published structure activity relationship (SAR) data. Bioactivity databases such as the Kinase Knowledgebase (KKB), WOMBAT, GOSTAR, and ChEMBL provide researchers with quantitative data characterizing the activity of compounds across many biological assays. The KKB, for example, contains over 1.8M kinase structure-activity data points reported in peer-reviewed journals and patents. In the spirit of fostering methods development and validation worldwide, we have extracted and have made available from the KKB 258K structure activity data points and 76K associated unique chemical structures across eight kinase targets. These data are freely available for download within this data note. PMID:27429748

  4. Development and implementation of (Q)SAR modeling within the CHARMMing Web-user interface

    PubMed Central

    Weidlich, Iwona E.; Pevzner, Yuri; Miller, Benjamin T.; Filippov, Igor V.; Woodcock, H. Lee; Brooks, Bernard R.

    2014-01-01

    Recent availability of large publicly accessible databases of chemical compounds and their biological activities (PubChem, ChEMBL) has inspired us to develop a Web-based tool for SAR and QSAR modeling to add to the services provided by CHARMMing (www.charmming.org). This new module implements some of the most recent advances in modern machine learning algorithms – Random Forest, Support Vector Machine (SVM), Stochastic Gradient Descent, Gradient Tree Boosting etc. A user can import training data from Pubchem Bioassay data collections directly from our interface or upload his or her own SD files which contain structures and activity information to create new models (either categorical or numerical). A user can then track the model generation process and run models on new data to predict activity. PMID:25362883

  5. OGEE: an online gene essentiality database.

    PubMed

    Chen, Wei-Hua; Minguez, Pablo; Lercher, Martin J; Bork, Peer

    2012-01-01

    OGEE is an Online GEne Essentiality database. Its main purpose is to enhance our understanding of the essentiality of genes. This is achieved by collecting not only experimentally tested essential and non-essential genes, but also associated gene features such as expression profiles, duplication status, conservation across species, evolutionary origins and involvement in embryonic development. We focus on large-scale experiments and complement our data with text-mining results. Genes are organized into data sets according to their sources. Genes with variable essentiality status across data sets are tagged as conditionally essential, highlighting the complex interplay between gene functions and environments. Linked tools allow the user to compare gene essentiality among different gene groups, or compare features of essential genes to non-essential genes, and visualize the results. OGEE is freely available at http://ogeedb.embl.de.

  6. [Bacteriophage lambda:lux: design and expression of bioluminescence in E. coli cells].

    PubMed

    Duzhiĭ, D E; Zavil'gel'skiĭ, G B

    1994-01-01

    The bacteriophages lambda:lux and lambda:luxAB have been constructed by ligation of phage arms generated by BamHI or SalGI restriction endonucleases digestion of EMBL4 to BamHI digested plasmid pF1 lux+ or to SalGI digested plasmid pF2 lambda:luxA+B+. Cells of Escherichia coli prototrophic strain Cs were infected with lambda:lux or lambda:luxAB and intensity of bioluminiscence of the samples registered at different time intervals determined. The signal of bioluminiscence was first detected 15 min after infection and its level increased exponentially thereafter demonstrating replication of the lambda:lux bacteriophages. We have used the recombinant lambda:luxAB bacteriophage to detect the enteric indicator bacteria without enrichment in 15 min, provided that they are present at levels higher than 10(4).

  7. Meeting report: How to get wrong things right--a discussion over current and future pandemic infectious diseases.

    PubMed

    Frischknecht, Friedrich; Lepper, Simone; Cyrklaff, Marek

    2008-08-01

    Infectious diseases have played a substantial part in shaping the history of humanity. In a discussion at a recent EMBL-EMBO science and society symposium entitled 'The future of our species', several experts discussed how infectious diseases are still influencing our world today. Here we present examples from recent and current infectious disease epidemics followed by a discussion of the local, national and international response to these. Special emphasis is laid on how the change of our environment can augment the world-wide spread of infectious diseases and the role of education in limiting this spread. An urgent need for improved coordinative efforts in globally combating infectious diseases is called for and examples are highlighted.

  8. Compilation of small ribosomal subunit RNA structures.

    PubMed Central

    Neefs, J M; Van de Peer, Y; De Rijk, P; Chapelle, S; De Wachter, R

    1993-01-01

    The database on small ribosomal subunit RNA structure contained 1804 nucleotide sequences on April 23, 1993. This number comprises 365 eukaryotic, 65 archaeal, 1260 bacterial, 30 plastidial, and 84 mitochondrial sequences. These are stored in the form of an alignment in order to facilitate the use of the database as input for comparative studies on higher-order structure and for reconstruction of phylogenetic trees. The elements of the postulated secondary structure for each molecule are indicated by special symbols. The database is available on-line directly from the authors by ftp and can also be obtained from the EMBL nucleotide sequence library by electronic mail, ftp, and on CD ROM disk. PMID:8332525

  9. Draft genome sequence of Mameliella alba strain UMTAT08 isolated from clonal culture of toxic dinoflagellate Alexandrium tamiyavanichii.

    PubMed

    Danish-Daniel, Muhd; Han Ming, Gan; Noor, Mohd Ezhar Mohd; Yeong, Yik Sung; Usup, Gires

    2016-12-01

    Mameliella alba strain UMTAT08 was isolated from clonal culture of paralytic shellfish toxin producing dinoflagellate, Alexandrium tamiyavanichii. Genome of the strain UMTAT08 was sequenced in order to gain insights into the dinoflagellate-bacteria interactions. The draft genome sequence of strain UMTAT08 contains 5.84Mbp with an estimated G + C content of 65%, 5717 open reading frames, 5 rRNAs and 49 tRNAs. It contains genes related to nutrients uptake, quorum sensing and environmental tolerance related genes. Gene clusters for the biosynthesis of type 1 polyketide synthase, bacteriocin, microcin, terpene and ectoine were also identified. This is suggesting that the bacterium possesses diverse adaptation strategy to survive within the dinoflagellate phycosphere. The draft genome sequence and annotation have been deposited at DDBJ/EMBL/GenBank under the accession number JSUQ00000000. PMID:27625991

  10. Reassessing Domain Architecture Evolution of Metazoan Proteins: Major Impact of Gene Prediction Errors

    PubMed Central

    Nagy, Alinda; Szláma, György; Szarka, Eszter; Trexler, Mária; Bányai, László; Patthy, László

    2011-01-01

    In view of the fact that appearance of novel protein domain architectures (DA) is closely associated with biological innovations, there is a growing interest in the genome-scale reconstruction of the evolutionary history of the domain architectures of multidomain proteins. In such analyses, however, it is usually ignored that a significant proportion of Metazoan sequences analyzed is mispredicted and that this may seriously affect the validity of the conclusions. To estimate the contribution of errors in gene prediction to differences in DA of predicted proteins, we have used the high quality manually curated UniProtKB/Swiss-Prot database as a reference. For genome-scale analysis of domain architectures of predicted proteins we focused on RefSeq, EnsEMBL and NCBI's GNOMON predicted sequences of Metazoan species with completely sequenced genomes. Comparison of the DA of UniProtKB/Swiss-Prot sequences of worm, fly, zebrafish, frog, chick, mouse, rat and orangutan with those of human Swiss-Prot entries have identified relatively few cases where orthologs had different DA, although the percentage with different DA increased with evolutionary distance. In contrast with this, comparison of the DA of human, orangutan, rat, mouse, chicken, frog, zebrafish, worm and fly RefSeq, EnsEMBL and NCBI's GNOMON predicted protein sequences with those of the corresponding/orthologous human Swiss-Prot entries identified a significantly higher proportion of domain architecture differences than in the case of the comparison of Swiss-Prot entries. Analysis of RefSeq, EnsEMBL and NCBI's GNOMON predicted protein sequences with DAs different from those of their Swiss-Prot orthologs confirmed that the higher rate of domain architecture differences is due to errors in gene prediction, the majority of which could be corrected with our FixPred protocol. We have also demonstrated that contamination of databases with incomplete, abnormal or mispredicted sequences introduces a bias in DA

  11. The non-redundant Bacillus subtilis (NRSub) database: update 1998.

    PubMed

    Perrière, G; Gouy, M; Gojobori, T

    1998-01-01

    The non-redundant Bacillus subtilis database (NRSub) has been developed in the context of the sequencing project devoted to this bacterium. As this project has reached completion, the whole genome is now available as a single contig. Thanks to the ACNUC database management system and its associated retrieval system Query_win, each functional region of the genome can be accessed individually. Extra annotations have been added such as accession numbers for the genes, locations on the genetic map, codon adaptation index values, as well as cross-references with other collections. NRSub is distributed through anonymous FTP as a text file in EMBL format and as an ACNUC database. It is also possible to access NRSub through two dedicated World Wide Web servers located in France (http://acnuc. univ-lyon1.fr/nrsub/nrsub.html ) and in Japan (http://ddbjs4h.genes. nig.ac.jp/ ). PMID:9399801

  12. Interactive Tree Of Life v2: online annotation and display of phylogenetic trees made easy.

    PubMed

    Letunic, Ivica; Bork, Peer

    2011-07-01

    Interactive Tree Of Life (http://itol.embl.de) is a web-based tool for the display, manipulation and annotation of phylogenetic trees. It is freely available and open to everyone. In addition to classical tree viewer functions, iTOL offers many novel ways of annotating trees with various additional data. Current version introduces numerous new features and greatly expands the number of supported data set types. Trees can be interactively manipulated and edited. A free personal account system is available, providing management and sharing of trees in user defined workspaces and projects. Export to various bitmap and vector graphics formats is supported. Batch access interface is available for programmatic access or inclusion of interactive trees into other web services.

  13. The Pfam protein families database.

    PubMed

    Bateman, Alex; Birney, Ewan; Cerruti, Lorenzo; Durbin, Richard; Etwiller, Laurence; Eddy, Sean R; Griffiths-Jones, Sam; Howe, Kevin L; Marshall, Mhairi; Sonnhammer, Erik L L

    2002-01-01

    Pfam is a large collection of protein multiple sequence alignments and profile hidden Markov models. Pfam is available on the World Wide Web in the UK at http://www.sanger.ac.uk/Software/Pfam/, in Sweden at http://www.cgb.ki.se/Pfam/, in France at http://pfam.jouy.inra.fr/ and in the US at http://pfam.wustl.edu/. The latest version (6.6) of Pfam contains 3071 families, which match 69% of proteins in SWISS-PROT 39 and TrEMBL 14. Structural data, where available, have been utilised to ensure that Pfam families correspond with structural domains, and to improve domain-based annotation. Predictions of non-domain regions are now also included. In addition to secondary structure, Pfam multiple sequence alignments now contain active site residue mark-up. New search tools, including taxonomy search and domain query, greatly add to the functionality and usability of the Pfam resource.

  14. ProDom: automated clustering of homologous domains.

    PubMed

    Servant, Florence; Bru, Catherine; Carrère, Sébastien; Courcelle, Emmanuel; Gouzy, Jérĵme; Peyruc, David; Kahn, Daniel

    2002-09-01

    The ProDom database is a comprehensive set of protein domain families automatically generated from the SWISS-PROT and TrEMBL sequence databases. An associated database, ProDom-CG, has been derived as a restriction of ProDom to completely sequenced genomes. The ProDom construction method is based on iterative PSI-BLAST searches and multiple alignments are generated for each domain family. The ProDom web server provides the user with a set of tools to visualise multiple alignments, phylogenetic trees and domain architectures of proteins, as well as a BLAST-based server to analyse new sequences for homologous domains. The comprehensive nature of ProDom makes it particularly useful to help sustain the growth of InterPro.

  15. The NCBI Taxonomy database.

    PubMed

    Federhen, Scott

    2012-01-01

    The NCBI Taxonomy database (http://www.ncbi.nlm.nih.gov/taxonomy) is the standard nomenclature and classification repository for the International Nucleotide Sequence Database Collaboration (INSDC), comprising the GenBank, ENA (EMBL) and DDBJ databases. It includes organism names and taxonomic lineages for each of the sequences represented in the INSDC's nucleotide and protein sequence databases. The taxonomy database is manually curated by a small group of scientists at the NCBI who use the current taxonomic literature to maintain a phylogenetic taxonomy for the source organisms represented in the sequence databases. The taxonomy database is a central organizing hub for many of the resources at the NCBI, and provides a means for clustering elements within other domains of NCBI web site, for internal linking between domains of the Entrez system and for linking out to taxon-specific external resources on the web. Our primary purpose is to index the domain of sequences as conveniently as possible for our user community.

  16. WWW-query: an on-line retrieval system for biological sequence banks.

    PubMed

    Perrière, G; Gouy, M

    1996-01-01

    We have developed a World Wide Web (WWW) version of the sequence retrieval system Query: WWW-Query. This server allows to query nucleotide sequence banks in the EMBL/GenBank/DDBJ formats and protein sequence banks in the NBRF/PIR format. WWW-Query includes all the features of the on-line sequences browsers already available: possibility to build complex queries, integration of cross-references with different data banks, and access to the functional zones of biological interest. It also provides original services not available elsewhere: introduction of the notion of re-usable sequence lists, integration of dedicated helper applications for visualizing alignments and phylogenetic trees and links with multivariate methods for studying codon usage or for complementing phylogenies.

  17. Next Generation Models for Storage and Representation of Microbial Biological Annotation

    SciTech Connect

    Quest, Daniel J; Land, Miriam L; Brettin, Thomas S; Cottingham, Robert W

    2010-01-01

    Background Traditional genome annotation systems were developed in a very different computing era, one where the World Wide Web was just emerging. Consequently, these systems are built as centralized black boxes focused on generating high quality annotation submissions to GenBank/EMBL supported by expert manual curation. The exponential growth of sequence data drives a growing need for increasingly higher quality and automatically generated annotation. Typical annotation pipelines utilize traditional database technologies, clustered computing resources, Perl, C, and UNIX file systems to process raw sequence data, identify genes, and predict and categorize gene function. These technologies tightly couple the annotation software system to hardware and third party software (e.g. relational database systems and schemas). This makes annotation systems hard to reproduce, inflexible to modification over time, difficult to assess, difficult to partition across multiple geographic sites, and difficult to understand for those who are not domain experts. These systems are not readily open to scrutiny and therefore not scientifically tractable. The advent of Semantic Web standards such as Resource Description Framework (RDF) and OWL Web Ontology Language (OWL) enables us to construct systems that address these challenges in a new comprehensive way. Results Here, we develop a framework for linking traditional data to OWL-based ontologies in genome annotation. We show how data standards can decouple hardware and third party software tools from annotation pipelines, thereby making annotation pipelines easier to reproduce and assess. An illustrative example shows how TURTLE (Terse RDF Triple Language) can be used as a human readable, but also semantically-aware, equivalent to GenBank/EMBL files. Conclusions The power of this approach lies in its ability to assemble annotation data from multiple databases across multiple locations into a representation that is understandable to

  18. Helix Nebula and CERN: A Symbiotic approach to exploiting commercial clouds

    NASA Astrophysics Data System (ADS)

    Barreiro Megino, Fernando H.; Jones, Robert; Kucharczyk, Katarzyna; Medrano Llamas, Ramón; van der Ster, Daniel

    2014-06-01

    The recent paradigm shift toward cloud computing in IT, and general interest in "Big Data" in particular, have demonstrated that the computing requirements of HEP are no longer globally unique. Indeed, the CERN IT department and LHC experiments have already made significant R&D investments in delivering and exploiting cloud computing resources. While a number of technical evaluations of interesting commercial offerings from global IT enterprises have been performed by various physics labs, further technical, security, sociological, and legal issues need to be address before their large-scale adoption by the research community can be envisaged. Helix Nebula - the Science Cloud is an initiative that explores these questions by joining the forces of three European research institutes (CERN, ESA and EMBL) with leading European commercial IT enterprises. The goals of Helix Nebula are to establish a cloud platform federating multiple commercial cloud providers, along with new business models, which can sustain the cloud marketplace for years to come. This contribution will summarize the participation of CERN in Helix Nebula. We will explain CERN's flagship use-case and the model used to integrate several cloud providers with an LHC experiment's workload management system. During the first proof of concept, this project contributed over 40.000 CPU-days of Monte Carlo production throughput to the ATLAS experiment with marginal manpower required. CERN's experience, together with that of ESA and EMBL, is providing a great insight into the cloud computing industry and highlighted several challenges that are being tackled in order to ease the export of the scientific workloads to the cloud environments.

  19. Chemical, Target, and Bioactive Properties of Allosteric Modulation

    PubMed Central

    van Westen, Gerard J. P.; Gaulton, Anna; Overington, John P.

    2014-01-01

    Allosteric modulators are ligands for proteins that exert their effects via a different binding site than the natural (orthosteric) ligand site and hence form a conceptually distinct class of ligands for a target of interest. Here, the physicochemical and structural features of a large set of allosteric and non-allosteric ligands from the ChEMBL database of bioactive molecules are analyzed. In general allosteric modulators are relatively smaller, more lipophilic and more rigid compounds, though large differences exist between different targets and target classes. Furthermore, there are differences in the distribution of targets that bind these allosteric modulators. Allosteric modulators are over-represented in membrane receptors, ligand-gated ion channels and nuclear receptor targets, but are underrepresented in enzymes (primarily proteases and kinases). Moreover, allosteric modulators tend to bind to their targets with a slightly lower potency (5.96 log units versus 6.66 log units, p<0.01). However, this lower absolute affinity is compensated by their lower molecular weight and more lipophilic nature, leading to similar binding efficiency and surface efficiency indices. Subsequently a series of classifier models are trained, initially target class independent models followed by finer-grained target (architecture/functional class) based models using the target hierarchy of the ChEMBL database. Applications of these insights include the selection of likely allosteric modulators from existing compound collections, the design of novel chemical libraries biased towards allosteric regulators and the selection of targets potentially likely to yield allosteric modulators on screening. All data sets used in the paper are available for download. PMID:24699297

  20. Structures of two Arabidopsis thaliana major latex proteins represent novel helix-grip folds

    SciTech Connect

    Lytle, Betsy L.; Song, Jikui; de la Cruz, Norberto B.; Peterson, Francis C.; Johnson, Kenneth A.; Bingman, Craig A.; Phillips, Jr., George N.; Volkman, Brian F.

    2009-06-02

    Here we report the first structures of two major latex proteins (MLPs) which display unique structural differences from the canonical Bet v 1 fold described earlier. MLP28 (SwissProt/TrEMBL ID Q9SSK9), the product of gene At1g70830.1, and the At1g24000.1 gene product (Swiss- Prot/TrEMBL ID P0C0B0), proteins which share 32% sequence identity, were independently selected as foldspace targets by the Center for Eukaryotic Structural Genomics. The structure of a single domain (residues 17-173) of MLP28 was solved by NMR spectroscopy, while the full-length At1g24000.1 structure was determined by X-ray crystallography. MLP28 displays greater than 30% sequence identity to at least eight MLPs from other species. For example, the MLP28 sequence shares 64% identity to peach Pp-MLP119 and 55% identity to cucumber Csf2.20 In contrast, the At1g24000.1 sequence is highly divergent (see Fig. 1), containing a gap of 33 amino acids when compared with all other known MLPs. Even when the gap is excluded, the sequence identity with MLPs from other species is less than 30%. Unlike some of the MLPs from other species, none of the A. thaliana MLPs have been characterized biochemically. We show by NMR chemical shift mapping that At1g24000.1 binds progesterone, demonstrating that despite its sequence dissimilarity, the hydrophobic binding pocket is conserved and, therefore, may play a role in its biological function and that of the MLP family in general.

  1. In silico target predictions: defining a benchmarking data set and comparison of performance of the multiclass Naïve Bayes and Parzen-Rosenblatt window.

    PubMed

    Koutsoukas, Alexios; Lowe, Robert; Kalantarmotamedi, Yasaman; Mussa, Hamse Y; Klaffke, Werner; Mitchell, John B O; Glen, Robert C; Bender, Andreas

    2013-08-26

    In this study, two probabilistic machine-learning algorithms were compared for in silico target prediction of bioactive molecules, namely the well-established Laplacian-modified Naïve Bayes classifier (NB) and the more recently introduced (to Cheminformatics) Parzen-Rosenblatt Window. Both classifiers were trained in conjunction with circular fingerprints on a large data set of bioactive compounds extracted from ChEMBL, covering 894 human protein targets with more than 155,000 ligand-protein pairs. This data set is also provided as a benchmark data set for future target prediction methods due to its size as well as the number of bioactivity classes it contains. In addition to evaluating the methods, different performance measures were explored. This is not as straightforward as in binary classification settings, due to the number of classes, the possibility of multiple class memberships, and the need to translate model scores into "yes/no" predictions for assessing model performance. Both algorithms achieved a recall of correct targets that exceeds 80% in the top 1% of predictions. Performance depends significantly on the underlying diversity and size of a given class of bioactive compounds, with small classes and low structural similarity affecting both algorithms to different degrees. When tested on an external test set extracted from WOMBAT covering more than 500 targets by excluding all compounds with Tanimoto similarity above 0.8 to compounds from the ChEMBL data set, the current methodologies achieved a recall of 63.3% and 66.6% among the top 1% for Naïve Bayes and Parzen-Rosenblatt Window, respectively. While those numbers seem to indicate lower performance, they are also more realistic for settings where protein targets need to be established for novel chemical substances.

  2. The Characterization, Expression and in Silico Studies on the SLC39A13 Gene; It's Involvement in Breast Cancer

    NASA Astrophysics Data System (ADS)

    Zahari, Normawati Mohamad; Chong, Teoh Teow

    The zinc transporters superfamily is divided into four subfamilies, and SLC39A is one of the subfamilies. The SLC39A subfamily has 9 members. Based on our computer searchers, all 9 sequences each contain 8 transmembranes domains. Since it is related to the zinc transporters superfamily, the SLC39A subfamily may have the same function that is to transport zinc ion. This paper focus on SLC39A13 studies and using the recombinant technology with CHO cells, it is shown that the recombinant protein, pcDNA5/FRT/V5-His-TOPO®-SLC39A13, has 43kD molecular weight. A second study using immunofluorescence technique with MCF-7 cells, it is shown that the recombinant protein expresses intracellularly. Both studies demonstrate that SLC39A13 expresses in breast cancer cells line, therefore the gene has involvement in the development of breast cancer disease. In our computational studies which is divided into two; the homologous study and sequence analysis, both results are supporting our laboratory results. The homologous study using EMBL-EBI and UniProt tools concluded that SLC39A13 is a member to SLC39A subfamily and it is closely related to SLC39A7 member. Although the sequence analysis shows that the molecular weight of SLC39A13 is 38.35kD it is still comparable to our laboratory result. Separately, using Swiss-EMBnet tools, TMpred, has shown that SLC39A13 has 8 transmembranes domains similar to other family members of SLC39A subfamily. Another analysis using EMBL-EBI tools, PPsearch, shows that SLC39A13 has various protein motif such as the protein kinase C phospho, casein kinase II phospho, leucine zipper and ASN-glycosylation sites. These are the useful information that we need when we study its tertiary structure and simulation in the future.

  3. Stereochemical Recognition of Helicenes on Metal Surfaces.

    PubMed

    Ernst, Karl-Heinz

    2016-06-21

    molecular handedness from single molecules into extended two-dimensional supramolecular structures are identified. For the problem of racemate versus conglomerate crystallization, the impact of surface and molecular structure and their interplay are analyzed. This leads to detailed conclusions about the importance of the match of molecular and surface binding sites for long-range self-assembly. The absence of polar groups puts emphasis on van der Waals interaction and their maximization by steric overlap of molecular parts in enantiomeric and diastereomeric interactions. With STM as a manipulation tool, dimers are manually separated in order to analyze their chiral composition. And finally, new nonlinear cooperative effects induced by small enantiospecific bias are discovered that lead to single enantiomorphism in two-dimensional racemate crystals as well as in racemic multilayered films. By means of these model studies many details that govern chiral recognition at surfaces are rationalized. PMID:27251099

  4. Stepwise enforcement of the notochord and its intersection with the myoseptum: an evolutionary path leading to development of the vertebra?

    PubMed

    Grotmol, Sindre; Kryvi, Harald; Keynes, Roger; Krossøy, Christel; Nordvik, Kari; Totland, Geir K

    2006-09-01

    The notochord constitutes the main axial support during the embryonic and larval stages, and the arrangement of collagen fibrils within the notochord sheath is assumed to play a decisive role in determining its functional properties as a fibre-wound hydrostatic skeleton. We have found that during early ontogeny in Atlantic salmon stepwise changes occur in the configuration of the collagen fibre-winding of the notochord sheath. The sheath consists of a basal lamina, a layer of type II collagen, and an elastica externa that delimits the notochord; and these constituents are secreted in a specific order. Initially, the collagen fibrils are circumferentially arranged perpendicular to the longitudinal axis, and this specific spatial fibril configuration is maintained until hatching when the collagen becomes reorganized into distinct layers or lamellae. Within each lamella, fibrils are parallel to each other, forming helices around the longitudinal axis of the notochord, with a tangent angle of 75-80 degrees to the cranio-caudal axis. The helical geometry shifts between adjacent lamellae, forming enantiomorphous left- and right-handed coils, respectively, thus enforcing the sheath. The observed changes in the fibre-winding configuration may reflect adaptation of the notochord to functional demands related to stage in ontogeny. When the vertebral bodies initially form as chordacentra, the collagen lamellae of the sheath in the vertebral region are fixed by the deposition of minerals; in the intervertebral region, however, they represent a pre-adaptation providing torsional stability to the intervertebral joint. Hence, these modifications of the sheath transform the notochord per se into a functional vertebral column. The elastica externa, encasing the notochord, has serrated surfaces, connected inward to the type II collagen of the sheath, and outward to type I collagen of the mesenchymal connective tissue surrounding the notochord. In a similar manner, the collagen

  5. Amino ketone formation and aminopropanol-dehydrogenase activity in rat-liver preparations

    PubMed Central

    Turner, J. M.; Willetts, A. J.

    1967-01-01

    1. Rat tissue homogenates convert dl-1-aminopropan-2-ol into aminoacetone. Liver homogenates have relatively high aminopropanol-dehydrogenase activity compared with kidney, heart, spleen and muscle preparations. 2. Maximum activity of liver homogenates is exhibited at pH9·8. The Km for aminopropanol is approx. 15mm, calculated for a single enantiomorph, and the maximum activity is approx. 9mμmoles of aminoacetone formed/mg. wet wt. of liver/hr.at 37°. Aminoacetone is also formed from l-threonine, but less rapidly. An unidentified amino ketone is formed from dl-4-amino-3-hydroxybutyrate, the Km for which is approx. 200mm at pH9·8. 3. Aminopropanol-dehydrogenase activity in homogenates is inhibited non-competitively by dl-3-hydroxybutyrate, the Ki being approx. 200mm. EDTA and other chelating agents are weakly inhibitory, and whereas potassium chloride activates slightly at low concentrations, inhibition occurs at 50–100mm. 4. It is concluded that aminopropanol-dehydrogenase is located in mitochondria, and in contrast with l-threonine dehydrogenase can be readily solubilized from mitochondrial preparations by ultrasonic treatment. 5. Soluble extracts of disintegrated mitochondria exhibit maximum aminopropanol-dehydrogenase activity at pH9·1 At this pH, Km values for the amino alcohol and NAD+ are approx. 200 and 1·3mm respectively. Under optimum conditions the maximum velocity is approx. 70mμmoles of aminoacetone formed/mg. of protein/hr. at 37°. Chelating agents and thiol reagents appear to have little effect on enzyme activity, but potassium chloride inhibits at all concentrations tested up to 80mm. dl-3-Hydroxybutyrate is only slightly inhibitory. 6. Dehydrogenase activities for l-threonine and dl-4-amino-3-hydroxybutyrate appear to be distinct from that for aminopropanol. 7. Intraperitoneal injection of aminopropanol into rats leads to excretion of aminoacetone in the urine. Aminoacetone excretion proportional to the amount of the amino alcohol

  6. Helical tubuland diols: a synthetic and crystal engineering quest.

    PubMed

    Bishop, Roger

    2009-01-20

    Despite many advances in recent years, crystal engineering remains a risky venture. A successful outcome requires manipulation of the noncovalent bonding and properties such as size, shape, repulsion, attraction, polarity, and chirality. In this Account, we describe the interplay of crystal engineering and synthetic organic chemistry required to develop the family of helical tubuland diol hosts, the members of which exhibit a wide range of tube dimensions and inclusion properties. Certain alicyclic dialcohols crystallize with a hydrogen-bonded network structure, termed the helical tubuland lattice, in space group P3(1)21 (or its enantiomorph P3(2)21). Double helices of diol molecules surround parallel tubes that contain guest molecules, which are included on the basis of size and shape rather than functional group. The crystal structure of (diol)(3).(chloroacetic acid)(1.2) is illustrative. These chiral helical tubulate lattice inclusion compounds are formed when the racemic host diol is allowed to crystallize from solution. Complete enantiomer separation occurs during this process, producing a 1:1 mixture of pure (+)- and pure (-)-crystals (a conglomerate). The challenge of creating this family of compounds required the development of much synthetic chemistry, in particular new pathways to alicyclic ring systems with specific substitution patterns. It was also necessary to understand and control the supramolecular properties of the diol molecules. What makes the original compound tick, and why did it behave in this remarkable manner, when most of its structural neighbors crystallize totally differently? The synthesis of new helical tubuland diols requires not just preparation of a new molecular structure but also a transplant of the original unchanged hydrogen-bonding supramolecular synthon. Synthesis of the specific crystal space group is necessary. This was achieved by defining structural characteristics, termed molecular determinants, which are essential for

  7. Stereochemical Recognition of Helicenes on Metal Surfaces.

    PubMed

    Ernst, Karl-Heinz

    2016-06-21

    molecular handedness from single molecules into extended two-dimensional supramolecular structures are identified. For the problem of racemate versus conglomerate crystallization, the impact of surface and molecular structure and their interplay are analyzed. This leads to detailed conclusions about the importance of the match of molecular and surface binding sites for long-range self-assembly. The absence of polar groups puts emphasis on van der Waals interaction and their maximization by steric overlap of molecular parts in enantiomeric and diastereomeric interactions. With STM as a manipulation tool, dimers are manually separated in order to analyze their chiral composition. And finally, new nonlinear cooperative effects induced by small enantiospecific bias are discovered that lead to single enantiomorphism in two-dimensional racemate crystals as well as in racemic multilayered films. By means of these model studies many details that govern chiral recognition at surfaces are rationalized.

  8. Two highly connected POM-based hybrids varying from 2D to 3D: The use of the isomeric ligands

    SciTech Connect

    Zhang Chunjing; Pang Haijun; Hu Mixia; Li Jia; Chen Yaguang

    2009-07-15

    Through employing two isomeric ligands, isonicotinic acid (HINA) and nicotinic acid (HNA), with different electron delocalization nature, two high-dimensional hybrids based on highly connected alpha-metatungstate clusters, [Na{sub 2}(H{sub 2}O){sub 8}Ag{sub 2}(HINA){sub 3}(INA)][Na(H{sub 2}O){sub 2}Ag{sub 2}(HINA){sub 4}(H{sub 2}W{sub 12}O{sub 40})].2H{sub 2}O (1) and [Na{sub 2}(H{sub 2}O){sub 4}Ag{sub 6}(HNA){sub 2}(NA){sub 2}(H{sub 2}W{sub 12}O{sub 40})].8H{sub 2}O (2), have been conventionally synthesized and structurally characterized. 1 exhibits an unusual 1D-in-2D pseudo-polyrotaxane entangled structure, namely, the 2D sheets [Na(H{sub 2}O){sub 2}Ag{sub 2}(HINA){sub 4}(H{sub 2}W{sub 12}O{sub 40})]{sub n}{sup 3n-} are penetrated by enantiomorphous meso-helical chains [Na{sub 2}(H{sub 2}O){sub 8}Ag{sub 2}(HINA){sub 3}(INA)]{sub n}{sup 3n+}. In the 2D sheets, each [H{sub 2}W{sub 12}O{sub 40}]{sup 6-} cluster is surrounded by six Ag and two Na atoms. 2 exhibits a 3D (4, 6)-net structure with (3{sup 2}6{sup 2}7{sup 2})(3{sup 2}4{sup 4}5{sup 4}6{sup 4}7)(3{sup 2}4{sup 4}6{sup 8}7) topology, in which each [H{sub 2}W{sub 12}O{sub 40}]{sup 6-} cluster is connected with ten Ag atoms. These facts indicate that the isomeric ligands play a key role in the formation of final structures. From 1 to 2, the connection number of the [H{sub 2}W{sub 12}O{sub 40}]{sup 6-} cluster changes from 8 to 10 and the dimensionality increases from 2 to 3. Moreover, 1 and 2 display photoluminescent properties in the blue range at room temperature. - Graphical abstract: Two high-dimensional and highly connected alpha-metatungstate-compounds modified by Ag{sup I}-HINA/HNA TMCs were successful obtained and the effect of isomeric organic ligands on the structures was systematically elucidated.

  9. Drug-likeness and increased hydrophobicity of commercially available compound libraries for drug screening.

    PubMed

    Zuegg, Johannes; Cooper, Matthew A

    2012-01-01

    Most drug discovery programs today originate by selection of 'hit' molecules resulting from assays against large compound screening libraries. The chemical space in which these hits reside has implications for its biological activity in vivo and likelihood of progression to a drug candidate. We have created a database of commercially available screening compounds and natural products in order to analyse the drug- and lead-likeness of commercial screening compounds and compare them with i) orally administered drugs, ii) non-orally administered drugs, and iii) compounds with significant biological activity but unspecified or not yet determined route of administration from the public databases DrugBank and ChEMBL. The data set contained 15.5 million entries from 102 vendors, which resulted in just over 8 million unique chemical structures. We review these data for current drug/lead-likeness, then utilise substructure-based filters for promiscuity and unwanted groups, and finally compare chemical properties for structures within the different sub-sets. While the majority of the commercial compounds satisfy various drug-likeness rules, they show a larger molecular weight and higher hydrophobicity compared to orally available drugs, with generally higher aromaticity and lower solubility. This 'right shift' of chemical properties has also been found in the majority of the compounds with significant biological activity in ChEMBL, reflecting a common trend in current drug discovery, towards larger, more hydrophobic compounds and fewer drug-like compounds. In particular, successful drugs were found to possess much lower median logD values than those found for compound collections. In addition, commercial compounds show a quite narrow distribution in molecular weight, with a median absolute deviation of only 78 Da around a median of 387 Da. For high-throughput screening a highly stringent combination of several lead-likeness and substructure filters against unwanted groups

  10. Mapping chemical structure-activity information of HAART-drug cocktails over complex networks of AIDS epidemiology and socioeconomic data of U.S. counties.

    PubMed

    Herrera-Ibatá, Diana María; Pazos, Alejandro; Orbegozo-Medina, Ricardo Alfredo; Romero-Durán, Francisco Javier; González-Díaz, Humberto

    2015-06-01

    Using computational algorithms to design tailored drug cocktails for highly active antiretroviral therapy (HAART) on specific populations is a goal of major importance for both pharmaceutical industry and public health policy institutions. New combinations of compounds need to be predicted in order to design HAART cocktails. On the one hand, there are the biomolecular factors related to the drugs in the cocktail (experimental measure, chemical structure, drug target, assay organisms, etc.); on the other hand, there are the socioeconomic factors of the specific population (income inequalities, employment levels, fiscal pressure, education, migration, population structure, etc.) to study the relationship between the socioeconomic status and the disease. In this context, machine learning algorithms, able to seek models for problems with multi-source data, have to be used. In this work, the first artificial neural network (ANN) model is proposed for the prediction of HAART cocktails, to halt AIDS on epidemic networks of U.S. counties using information indices that codify both biomolecular and several socioeconomic factors. The data was obtained from at least three major sources. The first dataset included assays of anti-HIV chemical compounds released to ChEMBL. The second dataset is the AIDSVu database of Emory University. AIDSVu compiled AIDS prevalence for >2300 U.S. counties. The third data set included socioeconomic data from the U.S. Census Bureau. Three scales or levels were employed to group the counties according to the location or population structure codes: state, rural urban continuum code (RUCC) and urban influence code (UIC). An analysis of >130,000 pairs (network links) was performed, corresponding to AIDS prevalence in 2310 counties in U.S. vs. drug cocktails made up of combinations of ChEMBL results for 21,582 unique drugs, 9 viral or human protein targets, 4856 protocols, and 10 possible experimental measures. The best model found with the original

  11. Drug-likeness and increased hydrophobicity of commercially available compound libraries for drug screening.

    PubMed

    Zuegg, Johannes; Cooper, Matthew A

    2012-01-01

    Most drug discovery programs today originate by selection of 'hit' molecules resulting from assays against large compound screening libraries. The chemical space in which these hits reside has implications for its biological activity in vivo and likelihood of progression to a drug candidate. We have created a database of commercially available screening compounds and natural products in order to analyse the drug- and lead-likeness of commercial screening compounds and compare them with i) orally administered drugs, ii) non-orally administered drugs, and iii) compounds with significant biological activity but unspecified or not yet determined route of administration from the public databases DrugBank and ChEMBL. The data set contained 15.5 million entries from 102 vendors, which resulted in just over 8 million unique chemical structures. We review these data for current drug/lead-likeness, then utilise substructure-based filters for promiscuity and unwanted groups, and finally compare chemical properties for structures within the different sub-sets. While the majority of the commercial compounds satisfy various drug-likeness rules, they show a larger molecular weight and higher hydrophobicity compared to orally available drugs, with generally higher aromaticity and lower solubility. This 'right shift' of chemical properties has also been found in the majority of the compounds with significant biological activity in ChEMBL, reflecting a common trend in current drug discovery, towards larger, more hydrophobic compounds and fewer drug-like compounds. In particular, successful drugs were found to possess much lower median logD values than those found for compound collections. In addition, commercial compounds show a quite narrow distribution in molecular weight, with a median absolute deviation of only 78 Da around a median of 387 Da. For high-throughput screening a highly stringent combination of several lead-likeness and substructure filters against unwanted groups

  12. Mapping chemical structure-activity information of HAART-drug cocktails over complex networks of AIDS epidemiology and socioeconomic data of U.S. counties.

    PubMed

    Herrera-Ibatá, Diana María; Pazos, Alejandro; Orbegozo-Medina, Ricardo Alfredo; Romero-Durán, Francisco Javier; González-Díaz, Humberto

    2015-06-01

    Using computational algorithms to design tailored drug cocktails for highly active antiretroviral therapy (HAART) on specific populations is a goal of major importance for both pharmaceutical industry and public health policy institutions. New combinations of compounds need to be predicted in order to design HAART cocktails. On the one hand, there are the biomolecular factors related to the drugs in the cocktail (experimental measure, chemical structure, drug target, assay organisms, etc.); on the other hand, there are the socioeconomic factors of the specific population (income inequalities, employment levels, fiscal pressure, education, migration, population structure, etc.) to study the relationship between the socioeconomic status and the disease. In this context, machine learning algorithms, able to seek models for problems with multi-source data, have to be used. In this work, the first artificial neural network (ANN) model is proposed for the prediction of HAART cocktails, to halt AIDS on epidemic networks of U.S. counties using information indices that codify both biomolecular and several socioeconomic factors. The data was obtained from at least three major sources. The first dataset included assays of anti-HIV chemical compounds released to ChEMBL. The second dataset is the AIDSVu database of Emory University. AIDSVu compiled AIDS prevalence for >2300 U.S. counties. The third data set included socioeconomic data from the U.S. Census Bureau. Three scales or levels were employed to group the counties according to the location or population structure codes: state, rural urban continuum code (RUCC) and urban influence code (UIC). An analysis of >130,000 pairs (network links) was performed, corresponding to AIDS prevalence in 2310 counties in U.S. vs. drug cocktails made up of combinations of ChEMBL results for 21,582 unique drugs, 9 viral or human protein targets, 4856 protocols, and 10 possible experimental measures. The best model found with the original

  13. Leading European Intergovernmental Research Organisations at FP6 Launch Conference

    NASA Astrophysics Data System (ADS)

    2002-11-01

    EIROforum at "European Research 2002" (Brussels, November 11-13, 2002) Go to the EIROforum website Last year, seven of Europe's leading intergovernmental research organisations set up a high-level co-ordination and collaboration group, known as EIROforum , cf. ESO PR 12/01. They include CERN (particle physics), EMBL (molecular biology), ESA (space activities), ESO (astronomy and astrophysics), ESRF (synchrotron radiation), ILL (neutron source) and EFDA (fusion). All of them have powerful research infrastructures and laboratories which are used by an extensive network of scientists. Together, they represent European spearheads in some of the most crucial basic and applied research fields. The EIROforum organisations will be highly visible at the upcoming EU-conference on "European Research 2002 - The European Research Area and the Framework Programme" , to be held on November 11-13, 2002, at the "Palais du Heysel" in Brussels (Belgium). This meeting will be attended by more than 8000 scientists and decision-makers from all over Europe and serves to launch the 6th EC Framework Programme (2002 - 2006), which will have an important impact on Europe's R&D landscape during the coming years. A joint 400 sq.m. exhibition , featuring the individual EIROforum organisations, their current programmes and many front-line achievements in their respective areas of activity, will be set up at Stand L in Hall 11 . It includes a central area, with a small cinema, displaying information about their current interactions via EIROforum. The stands will be manned throughout the conference by high-level representatives from the seven organisations. On Tuesday, November 12, 2002, 14:00 hrs, a Press Conference will take place at this exhibition stand, in the presence of the European Commissioner for Research, M. Phillippe Busquin, and most of the Directors General (or equivalent) of the EIROforum organisations. The main themes will be the increasingly intense interaction and co

  14. A Multi-Platform Draft de novo Genome Assembly and Comparative Analysis for the Scarlet Macaw (Ara macao)

    PubMed Central

    Seabury, Christopher M.; Dowd, Scot E.; Seabury, Paul M.; Raudsepp, Terje; Brightsmith, Donald J.; Liboriussen, Poul; Halley, Yvette; Fisher, Colleen A.; Owens, Elaine; Viswanathan, Ganesh; Tizard, Ian R.

    2013-01-01

    Data deposition to NCBI Genomes This Whole Genome Shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession AMXX00000000 (SMACv1.0, unscaffolded genome assembly). The version described in this paper is the first version (AMXX01000000). The scaffolded assembly (SMACv1.1) has been deposited at DDBJ/EMBL/GenBank under the accession AOUJ00000000, and is also the first version (AOUJ01000000). Strong biological interest in traits such as the acquisition and utilization of speech, cognitive abilities, and longevity catalyzed the utilization of two next-generation sequencing platforms to provide the first-draft de novo genome assembly for the large, new world parrot Ara macao (Scarlet Macaw). Despite the challenges associated with genome assembly for an outbred avian species, including 951,507 high-quality putative single nucleotide polymorphisms, the final genome assembly (>1.035 Gb) includes more than 997 Mb of unambiguous sequence data (excluding N’s). Cytogenetic analyses including ZooFISH revealed complex rearrangements associated with two scarlet macaw macrochromosomes (AMA6, AMA7), which supports the hypothesis that translocations, fusions, and intragenomic rearrangements are key factors associated with karyotype evolution among parrots. In silico annotation of the scarlet macaw genome provided robust evidence for 14,405 nuclear gene annotation models, their predicted transcripts and proteins, and a complete mitochondrial genome. Comparative analyses involving the scarlet macaw, chicken, and zebra finch genomes revealed high levels of nucleotide-based conservation as well as evidence for overall genome stability among the three highly divergent species. Application of a new whole-genome analysis of divergence involving all three species yielded prioritized candidate genes and noncoding regions for parrot traits of interest (i.e., speech, intelligence, longevity) which were independently supported by the results of previous human GWAS studies. We

  15. Detection and identification of genotypes of Prototheca zopfii in clinical samples by quantitative PCR analysis.

    PubMed

    Onozaki, Masanobu; Makimura, Koichi; Satoh, Kazuo; Hasegawa, Atsuhiko

    2013-01-01

    In this study, a specific quantitative PCR system for the detection and identification of Prototheca zopfii genotypes was developed using a TaqMan(®) MGB probe and ResoLight dye. The P. zopfii-specific primers 18PZF1 and 18PZR1 were generated on the basis of the alignment of the small subunit ribosomal DNA domain base sequences of the genera Chlorella and Prototheca obtained from DDBJ/EMBL/GenBank, and the TaqMan(®) MGB probe PZP1 was designed corresponding to this amplification region. Analysis of the melting curves of the amplicons using ResoLight dye was able to differentiate between P. zopfii genotypes 1 and 2. The specificity of this detection system was examined using strains from a culture collection (28 strains) and clinical isolates (140 strains). The TaqMan(®) MGB probe amplicon was detected only in reference strains of P. zopfii (n = 12) and clinical isolates (n = 135). Ninety-two clinical specimens from cows with mastitis (36 samples) and healthy controls (56 samples) were also tested. All isolates from milk samples (n = 92) and clinical isolates (n = 135) were identified as P. zopfii genotype 2. PMID:24047735

  16. Structure of the coding region and mRNA variants of the apyrase gene from pea (Pisum sativum)

    NASA Technical Reports Server (NTRS)

    Shibata, K.; Abe, S.; Davies, E.

    2001-01-01

    Partial amino acid sequences of a 49 kDa apyrase (ATP diphosphohydrolase, EC 3.6.1.5) from the cytoskeletal fraction of etiolated pea stems were used to derive oligonucleotide DNA primers to generate a cDNA fragment of pea apyrase mRNA by RT-PCR and these primers were used to screen a pea stem cDNA library. Two almost identical cDNAs differing in just 6 nucleotides within the coding regions were found, and these cDNA sequences were used to clone genomic fragments by PCR. Two nearly identical gene fragments containing 8 exons and 7 introns were obtained. One of them (H-type) encoded the mRNA sequence described by Hsieh et al. (1996) (DDBJ/EMBL/GenBank Z32743), while the other (S-type) differed by the same 6 nucleotides as the mRNAs, suggesting that these genes may be alleles. The six nucleotide differences between these two alleles were found solely in the first exon, and these mutation sites had two types of consensus sequences. These mRNAs were found with varying lengths of 3' untranslated regions (3'-UTR). There are some similarities between the 3'-UTR of these mRNAs and those of actin and actin binding proteins in plants. The putative roles of the 3'-UTR and alternative polyadenylation sites are discussed in relation to their possible role in targeting the mRNAs to different subcellular compartments.

  17. A phylogeny-based benchmarking test for orthology inference reveals the limitations of function-based validation.

    PubMed

    Trachana, Kalliopi; Forslund, Kristoffer; Larsson, Tomas; Powell, Sean; Doerks, Tobias; von Mering, Christian; Bork, Peer

    2014-01-01

    Accurate orthology prediction is crucial for many applications in the post-genomic era. The lack of broadly accepted benchmark tests precludes a comprehensive analysis of orthology inference. So far, functional annotation between orthologs serves as a performance proxy. However, this violates the fundamental principle of orthology as an evolutionary definition, while it is often not applicable due to limited experimental evidence for most species. Therefore, we constructed high quality "gold standard" orthologous groups that can serve as a benchmark set for orthology inference in bacterial species. Herein, we used this dataset to demonstrate 1) why a manually curated, phylogeny-based dataset is more appropriate for benchmarking orthology than other popular practices and 2) how it guides database design and parameterization through careful error quantification. More specifically, we illustrate how function-based tests often fail to identify false assignments, misjudging the true performance of orthology inference methods. We also examined how our dataset can instruct the selection of a "core" species repertoire to improve detection accuracy. We conclude that including more genomes at the proper evolutionary distances can influence the overall quality of orthology detection. The curated gene families, called Reference Orthologous Groups, are publicly available at http://eggnog.embl.de/orthobench2. PMID:25369365

  18. 'Candidatus Phytoplasma omanense', associated with witches'-broom of Cassia italica (Mill.) Spreng. in Oman.

    PubMed

    Al-Saady, Nadiya Abubakar; Khan, Akhtar Jamal; Calari, Alberto; Al-Subhi, Ali Masoud; Bertaccini, Assunta

    2008-02-01

    Samples from plants of Cassia italica exhibiting typical witches'-broom symptoms (Cassia witches'-broom; CWB) were examined for the presence of plant pathogenic phytoplasmas by PCR amplification using universal phytoplasma primers. All affected plants yielded positive results. RFLP analyses of rRNA gene products indicated that the phytoplasmas detected were different from those described previously. Phylogenetic analysis of 16S rRNA gene sequences confirmed that CWB represents a distinct lineage and shares a common ancestor with 'Candidatus Phytoplasma phoenicium'. Molecular comparison revealed that the 16S rRNA gene sequences of the four CWB strains (IM-1, IM-2, IM-3 and IM-4) identified in symptomatic C. italica samples were nearly identical (99.6-100 % similarity). The closest relatives were members of the pigeon pea witches'-broom phytoplasma ribosomal group (16SrIX; 95-97 % sequence similarity). On the basis of unique 16S rRNA gene sequences and biological properties, the phytoplasma associated with witches'-broom of C. italica in Oman represents a coherent but discrete novel phytoplasma, 'Candidatus Phytoplasma omanense', with GenBank/DDBJ/EMBL accession number EF666051 representing the reference strain.

  19. From ontology selection and semantic web to an integrated information system for food-borne diseases and food safety.

    PubMed

    Yan, Xianghe; Peng, Yun; Meng, Jianghong; Ruzante, Juliana; Fratamico, Pina M; Huang, Lihan; Juneja, Vijay; Needleman, David S

    2011-01-01

    Several factors have hindered effective use of information and resources related to food safety due to inconsistency among semantically heterogeneous data resources, lack of knowledge on profiling of food-borne pathogens, and knowledge gaps among research communities, government risk assessors/managers, and end-users of the information. This paper discusses technical aspects in the establishment of a comprehensive food safety information system consisting of the following steps: (a) computational collection and compiling publicly available information, including published pathogen genomic, proteomic, and metabolomic data; (b) development of ontology libraries on food-borne pathogens and design automatic algorithms with formal inference and fuzzy and probabilistic reasoning to address the consistency and accuracy of distributed information resources (e.g., PulseNet, FoodNet, OutbreakNet, PubMed, NCBI, EMBL, and other online genetic databases and information); (c) integration of collected pathogen profiling data, Foodrisk.org ( http://www.foodrisk.org ), PMP, Combase, and other relevant information into a user-friendly, searchable, "homogeneous" information system available to scientists in academia, the food industry, and government agencies; and (d) development of a computational model in semantic web for greater adaptability and robustness.

  20. The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledgebase of drug targets and their ligands.

    PubMed

    Pawson, Adam J; Sharman, Joanna L; Benson, Helen E; Faccenda, Elena; Alexander, Stephen P H; Buneman, O Peter; Davenport, Anthony P; McGrath, John C; Peters, John A; Southan, Christopher; Spedding, Michael; Yu, Wenyuan; Harmar, Anthony J

    2014-01-01

    The International Union of Basic and Clinical Pharmacology/British Pharmacological Society (IUPHAR/BPS) Guide to PHARMACOLOGY (http://www.guidetopharmacology.org) is a new open access resource providing pharmacological, chemical, genetic, functional and pathophysiological data on the targets of approved and experimental drugs. Created under the auspices of the IUPHAR and the BPS, the portal provides concise, peer-reviewed overviews of the key properties of a wide range of established and potential drug targets, with in-depth information for a subset of important targets. The resource is the result of curation and integration of data from the IUPHAR Database (IUPHAR-DB) and the published BPS 'Guide to Receptors and Channels' (GRAC) compendium. The data are derived from a global network of expert contributors, and the information is extensively linked to relevant databases, including ChEMBL, DrugBank, Ensembl, PubChem, UniProt and PubMed. Each of the ∼6000 small molecule and peptide ligands is annotated with manually curated 2D chemical structures or amino acid sequences, nomenclature and database links. Future expansion of the resource will complete the coverage of all the targets of currently approved drugs and future candidate targets, alongside educational resources to guide scientists and students in pharmacological principles and techniques.

  1. [InterPro as a new tool for whole genome analysis. A comparative analysis of Mycobacterium tuberculosis, Bacillus subtilis and Escherichia coli as a case study].

    PubMed

    Mulder, N; Fleischmann, W; Kanapin, A; Arwailer, R

    2006-01-01

    InterPro was developed as a new integrated documentation resource for protein families, domains and functional sites to rationalize the complementary efforts of the PROSITE, PRINTS, Pfam and ProDom database projects and has applications in computational functional classification of newly determined sequences lacking biochemical characterization and in comparative genome analysis. InterPro contains over 3500 entries, with more than 1000000 hits in SWISS-PROT and TrEMBL. The database is accessible for text- and sequence-based searches at http://www.ebi.ac.uk/interpro/. InterPro was used for whole proteome analysis of the pathogenic microorganism, Mycobacterium tuberculosis, and comparison with the predicted protein coding sequences of the complete genomes of Bacillus subtilis and Escherichia coli. 64.8% of the M. tuberculosis proteins in the proteome matched InterPro entries, and these could be classified according to function. The comparison with B. subtilis and E. coli provided information on the most common protein families and domains, and the most highly represented families in each organism. InterPro thus provides a useful tool for global views of whole proteomes and their compositions.

  2. Molecular characterization of selected dermatophytes and their identification by electrophoretic mutation scanning.

    PubMed

    Cafarchia, Claudia; Otranto, Domenico; Weigl, Stefania; Campbell, Bronwyn E; Parisi, Antonio; Cantacessi, Cinzia; Mancianti, Francesca; Danesi, Patrizia; Gasser, Robin B

    2009-10-01

    Dermatophytes are fungi that can be contagious and cause infections in the keratinized skin of mammals, including humans. The etiological diagnosis of dermatophytosis relies on a combination of in vitro-culture and microscopic methods. Effective molecular tools could overcome the limitations of conventional methods of identification. In the present study, following phenetic identification as M. canis, M. fulvum, M. gypseum, T. mentagrophytes and T. terrestre, we genetically characterized key dermatophytes, employing the sequences of the first and second internal transcribed spacers of nuclear ribosomal DNA as well as part of the chitin synthase-1 gene, and assessed the utility of these DNA regions (based on levels of nucleotide variation within and among species/taxa) as markers for the classification of species and genotypes. Employing partial chitin synthase-1 gene as the marker, we also established a PCR-coupled SSCP approach as a diagnostic/analytical mutation-scanning tool. This tool should facilitate fundamental investigations of the ecology, epidemiology and population genetics of dermatophytes and, importantly, should assist in allowing a more rapid diagnosis of dermatophytoses in humans and other animals, thus overcoming the significant delays in targeted chemotherapy following diagnosis using conventional methods. (Nucleotide sequence data reported in this paper are available in the EMBL, GenBank and DDJB datadases under accession numbers FJ897707-FJ897713 (ITS-1), FJ897714-FJ897720 (ITS-2) and FJ897700-FJ897706 (pchs-1)). PMID:19862737

  3. The draft genome sequence of Mangrovibacter sp. strain MP23, an endophyte isolated from the roots of Phragmites karka.

    PubMed

    Behera, Pratiksha; Vaishampayan, Parag; Singh, Nitin K; Mishra, Samir R; Raina, Vishakha; Suar, Mrutyunjay; Pattnaik, Ajit K; Rastogi, Gurdeep

    2016-09-01

    Till date, only one draft genome has been reported within the genus Mangrovibacter. Here, we report the second draft genome shotgun sequence of a Mangrovibacter sp. strain MP23 that was isolated from the roots of Phargmites karka (P. karka), an invasive weed growing in the Chilika Lagoon, Odisha, India. Strain MP23 is a facultative anaerobic, nitrogen-fixing endophytic bacteria that grows optimally at 37 °C, 7.0 pH, and 1% NaCl concentration. The draft genome sequence of strain MP23 contains 4,947,475 bp with an estimated G + C content of 49.9% and total 4392 protein coding genes. The genome sequence has provided information on putative genes that code for proteins involved in oxidative stress, uptake of nutrients, and nitrogen fixation that might offer niche specific ecological fitness and explain the invasive success of P. karka in Chilika Lagoon. The draft genome sequence and annotation have been deposited at DDBJ/EMBL/GenBank under the accession number LYRP00000000. PMID:27508122

  4. The relationship between target-class and the physicochemical properties of antibacterial drugs

    PubMed Central

    Mugumbate, Grace; Overington, John P.

    2015-01-01

    The discovery of novel mechanism of action (MOA) antibacterials has been associated with the concept that antibacterial drugs occupy a differentiated region of physicochemical space compared to human-targeted drugs. With, in broad terms, antibacterials having higher molecular weight, lower log P and higher polar surface area (PSA). By analysing the physicochemical properties of about 1700 approved drugs listed in the ChEMBL database, we show, that antibacterials for whose targets are riboproteins (i.e., composed of a complex of RNA and protein) fall outside the conventional human ‘drug-like’ chemical space; whereas antibacterials that modulate bacterial protein targets, generally comply with the ‘rule-of-five’ guidelines for classical oral human drugs. Our analysis suggests a strong target-class association for antibacterials—either protein-targeted or riboprotein-targeted. There is much discussion in the literature on the failure of screening approaches to deliver novel antibacterial lead series, and linkage of this poor success rate for antibacterials with the chemical space properties of screening collections. Our analysis suggests that consideration of target-class may be an underappreciated factor in antibacterial lead discovery, and that in fact bacterial protein-targets may well have similar binding site characteristics to human protein targets, and questions the assumption that larger, more polar compounds are a key part of successful future antibacterial discovery. PMID:25975639

  5. PoSSuM v.2.0: data update and a new function for investigating ligand analogs and target proteins of small-molecule drugs.

    PubMed

    Ito, Jun-ichi; Ikeda, Kazuyoshi; Yamada, Kazunori; Mizuguchi, Kenji; Tomii, Kentaro

    2015-01-01

    PoSSuM (http://possum.cbrc.jp/PoSSuM/) is a database for detecting similar small-molecule binding sites on proteins. Since its initial release in 2011, PoSSuM has grown to provide information related to 49 million pairs of similar binding sites discovered among 5.5 million known and putative binding sites. This enlargement of the database is expected to enhance opportunities for biological and pharmaceutical applications, such as predictions of new functions and drug discovery. In this release, we have provided a new service named PoSSuM drug search (PoSSuMds) at http://possum.cbrc.jp/PoSSuM/drug_search/, in which we selected 194 approved drug compounds retrieved from ChEMBL, and detected their known binding pockets and pockets that are similar to them. Users can access and download all of the search results via a new web interface, which is useful for finding ligand analogs as well as potential target proteins. Furthermore, PoSSuMds enables users to explore the binding pocket universe within PoSSuM. Additionally, we have improved the web interface with new functions, including sortable tables and a viewer for visualizing and downloading superimposed pockets.

  6. Deciphering the microbiota of Tuwa hot spring, India using shotgun metagenomic sequencing approach.

    PubMed

    Mangrola, Amitsinh; Dudhagara, Pravin; Koringa, Prakash; Joshi, C G; Parmar, Mansi; Patel, Rajesh

    2015-06-01

    Here, we report metagenome from the Tuwa hot spring, India using shotgun sequencing approach. Metagenome consisted of 541,379 sequences with 98.7 Mbps size with 46% G + C content. Metagenomic sequence reads were deposited into the EMBL database under accession number ERP009321. Community analysis presented 99.1% sequences belong to bacteria, 0.3% of eukaryotic origin, 0.2% virus derived and 0.05% from archea. Unclassified and unidentified sequences were 0.4% and 0.07% respectively. A total of 22 bacterial phyla include 90 families and 201 species were observed in the hot spring metagenome. Firmicutes (97.0%), Proteobacteria (1.3%) and Actinobacteria (0.4%) were reported as dominant bacterial phyla. In functional analysis using Cluster of Orthologous Group (COG), 21.5% drops in the poorly characterized group. Using subsystem based annotation, 4.0% genes were assigned for stress responses and 3% genes were fit into the metabolism of aromatic compounds. The hot spring metagenome is very rich with novel sequences affiliated to unclassified and unidentified lineages, suggesting the potential source for novel microbial species and their products. PMID:26484204

  7. In Silico Mining for Antimalarial Structure-Activity Knowledge and Discovery of Novel Antimalarial Curcuminoids.

    PubMed

    Viira, Birgit; Gendron, Thibault; Lanfranchi, Don Antoine; Cojean, Sandrine; Horvath, Dragos; Marcou, Gilles; Varnek, Alexandre; Maes, Louis; Maran, Uko; Loiseau, Philippe M; Davioud-Charvet, Elisabeth

    2016-01-01

    Malaria is a parasitic tropical disease that kills around 600,000 patients every year. The emergence of resistant Plasmodium falciparum parasites to artemisinin-based combination therapies (ACTs) represents a significant public health threat, indicating the urgent need for new effective compounds to reverse ACT resistance and cure the disease. For this, extensive curation and homogenization of experimental anti-Plasmodium screening data from both in-house and ChEMBL sources were conducted. As a result, a coherent strategy was established that allowed compiling coherent training sets that associate compound structures to the respective antimalarial activity measurements. Seventeen of these training sets led to the successful generation of classification models discriminating whether a compound has a significant probability to be active under the specific conditions of the antimalarial test associated with each set. These models were used in consensus prediction of the most likely active from a series of curcuminoids available in-house. Positive predictions together with a few predicted as inactive were then submitted to experimental in vitro antimalarial testing. A large majority from predicted compounds showed antimalarial activity, but not those predicted as inactive, thus experimentally validating the in silico screening approach. The herein proposed consensus machine learning approach showed its potential to reduce the cost and duration of antimalarial drug discovery. PMID:27367660

  8. Mapping of the gene encoding the melanocortin-1 ([alpha]-melanocyte stimulating hormone) receptor (MC1R) to human chromosome 16q24. 3 by fluorescence in situ hybridization

    SciTech Connect

    Gantz, I.; Yamada, Tadataka; Tashiro, Takao; Konda, Yoshitaka; Shimoto, Yoshimasa; Miwa, Hiroto; Trent, J.M. )

    1994-01-15

    [alpha]-Melanocyte stimulating hormone ([alpha]-MSH), a hormone originally named for its ability to regulate pigmentation of melanocytes, is a 13-amino-acid post-translational product of the pro-opiomelanocortin (POMC) gene. [alpha]-MSH and the other products of POMC processing, which share the core heptapeptide amino acid sequence Met-Glu (Gly)-His-Phe-Arg-Trp-Gly (Asp), the adrenocorticotropic hormone (ACTH), [beta]-MSH, and [gamma]-MSH, are collectively referred to as melanocortins. While best known for their effects on the melanocyte (pigmentation) and adrenal cortical cells (steroidogenesis), melanocortins have been postulated to function in diverse activities, including enhancement of learning and memory, control of the cardiovascular system, analgesia, thermoregulation, immunomodulation, parturition, and neurotrophism. To identify the chromosomal band encoding the human melanocortin-1 receptor gene, 1 [mu]g of an EMBL clone coding region of the human MC1R and approximately 15 kb of surrounding DNA was labeled with biotin and hybridized to human metaphase chromosomes as previously described. The results indicate that the human MC1R gene is localized to 16q24.3. 15 refs., 1 fig.

  9. Rat Gene Mapping Using Pcr-Analyzed Microsatellites

    PubMed Central

    Serikawa, T.; Kuramoto, T.; Hilbert, P.; Mori, M.; Yamada, J.; Dubay, C. J.; Lindpainter, K.; Ganten, D.; Guenet, J. L.; Lathrop, G. M.; Beckmann, J. S.

    1992-01-01

    One hundred and seventy-four rat loci which contain short tandem repeat sequences were extracted from the GenBank or EMBL data bases and used to define primers for amplification by the polymerase chain reaction (PCR) of the microsatellite regions, creating PCR-formatted sequence-tagged microsatellite sites (STMSs). One hundred and thirty-four STMSs for 118 loci, including 6 randomly cloned STMSs, were characterized: (i) PCR-analyzed loci were assigned to specific chromosomes using a panel of rat X mouse somatic cell hybrid clones. (ii) Length variation of the STMSs among 8 inbred rat strains could be visualized at 85 of 107 loci examined (79.4%). (iii) A genetic map, integrating biochemical, coat color, mutant and restriction fragment length polymorphism loci, was constructed based on the segregation of 125 polymorphic markers in seven rat backcrosses and in two F(2) crosses. Twenty four linkage groups were identified, all of which were assigned to a defined chromosome. As a reflection of the bias for coding sequences in the public data bases, the STMSs described herein are often associated with genes. Hence, the genetic map we report coincides with a gene map. The corresponding map locations of the homologous mouse and human genes are also listed for comparative mapping purposes. PMID:1628813

  10. Assessment of the Food Habits of the Moroccan Dorcas Gazelle in M’Sabih Talaa, West Central Morocco, Using the trnL Approach

    PubMed Central

    Ait Baamrane, Moulay Abdeljalil; Shehzad, Wasim; Ouhammou, Ahmed; Abbad, Abdelaziz; Naimi, Mohamed; Coissac, Eric; Taberlet, Pierre; Znari, Mohammed

    2012-01-01

    Food habits of the Moroccan dorcas gazelle, Gazella dorcas massaesyla, previously investigated in the 1980s using microhistological fecal analysis, in the M’Sabih Talaa Reserve, west central Morocco, were re-evaluated over three seasons (spring, summer and autumn 2009) using the trnL approach to determine the diet composition and its seasonal variation from fecal samples. Taxonomic identification was carried out using the identification originating from the database built from EMBL and the list of plant species within the reserve. The total taxonomic richness in the reserve was 130 instead of 171 species in the 1980s. The diet composition revealed to be much more diversified (71 plant taxa belonging to 57 genus and 29 families) than it was 22 years ago (29 identified taxa). Thirty-four taxa were newly identified in the diet while 13 reported in 1986–87 were not found. Moroccan dorcas gazelle showed a high preference to Acacia gummifera, Anagallis arvensis, Glebionis coronaria, Cladanthus arabicus, Diplotaxis tenuisiliqua, Erodium salzmannii, Limonium thouini, Lotus arenarius and Zizyphus lotus. Seasonal variations occurred in both number (40–41 taxa in spring-summer and 49 taxa in autumn vs. respectively 23–22 and 26 in 1986–1987) and taxonomic type of eaten plant taxa. This dietary diversification could be attributed either to the difference in methods of analysis, trnL approach having a higher taxonomic resolution, or a potential change in nutritional quality of plants over time. PMID:22558187

  11. iPath2.0: interactive pathway explorer.

    PubMed

    Yamada, Takuji; Letunic, Ivica; Okuda, Shujiro; Kanehisa, Minoru; Bork, Peer

    2011-07-01

    iPath2.0 is a web-based tool (http://pathways.embl.de) for the visualization and analysis of cellular pathways. Its primary map summarizes the metabolism in biological systems as annotated to date. Nodes in the map correspond to various chemical compounds and edges represent series of enzymatic reactions. In two other maps, iPath2.0 provides an overview of secondary metabolite biosynthesis and a hand-picked selection of important regulatory pathways and other functional modules, allowing a more general overview of protein functions in a genome or metagenome. iPath2.0's main interface is an interactive Flash-based viewer, which allows users to easily navigate and explore the complex pathway maps. In addition to the default pre-computed overview maps, iPath offers several data mapping tools. Users can upload various types of data and completely customize all nodes and edges of iPath2.0's maps. These customized maps give users an intuitive overview of their own data, guiding the analysis of various genomics and metagenomics projects.

  12. A Rational Approach for the Identification of Non-Hydroxamate HDAC6-Selective Inhibitors

    NASA Astrophysics Data System (ADS)

    Goracci, Laura; Deschamps, Nathalie; Randazzo, Giuseppe Marco; Petit, Charlotte; Dos Santos Passos, Carolina; Carrupt, Pierre-Alain; Simões-Pires, Claudia; Nurisso, Alessandra

    2016-07-01

    The human histone deacetylase isoform 6 (HDAC6) has been demonstrated to play a major role in cell motility and aggresome formation, being interesting for the treatment of multiple tumour types and neurodegenerative conditions. Currently, most HDAC inhibitors in preclinical or clinical evaluations are non-selective inhibitors, characterised by a hydroxamate zinc-binding group (ZBG) showing off-target effects and mutagenicity. The identification of selective HDAC6 inhibitors with novel chemical properties has not been successful yet, also because of the absence of crystallographic information that makes the rational design of HDAC6 selective inhibitors difficult. Using HDAC inhibitory data retrieved from the ChEMBL database and ligand-based computational strategies, we identified 8 original new non-hydroxamate HDAC6 inhibitors from the SPECS database, with activity in the low μM range. The most potent and selective compound, bearing a hydrazide ZBG, was shown to increase tubulin acetylation in human cells. No effects on histone H4 acetylation were observed. To the best of our knowledge, this is the first report of an HDAC6 selective inhibitor bearing a hydrazide ZBG. Its capability to passively cross the blood-brain barrier (BBB), as observed through PAMPA assays, and its low cytotoxicity in vitro, suggested its potential for drug development.

  13. Microscopic, chemical, and molecular-biological investigation of the decayed medieval stained window glasses of two Catalonian churches

    PubMed Central

    Piñar, Guadalupe; Garcia-Valles, Maite; Gimeno-Torrente, Domingo; Fernandez-Turiel, Jose Luis; Ettenauer, Jörg; Sterflinger, Katja

    2013-01-01

    We investigated the decayed historical church window glasses of two Catalonian churches, both under Mediterranean climate. Glass surfaces were studied by scanning electron microscopy (SEM), energy dispersive spectrometry (EDS), and X-ray diffraction (XRD). Their chemical composition was determined by wavelength-dispersive spectrometry (WDS) microprobe analysis. The biodiversity was investigated by molecular methods: DNA extraction from glass, amplification by PCR targeting the16S rRNA and ITS regions, and fingerprint analyses by denaturing gradient gel electrophoresis (DGGE). Clone libraries containing either PCR fragments of the bacterial 16S rDNA or the fungal ITS regions were screened by DGGE. Clone inserts were sequenced and compared with the EMBL database. Similarity values ranged from 89 to 100% to known bacteria and fungi. Biological activity in both sites was evidenced in the form of orange patinas, bio-pitting, and mineral precipitation. Analyses revealed complex bacterial communities consisting of members of the phyla Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria. Fungi showed less diversity than bacteria, and species of the genera Cladosporium and Phoma were dominant. The detected Actinobacteria and fungi may be responsible for the observed bio-pitting phenomenon. Moreover, some of the detected bacteria are known for their mineral precipitation capabilities. Sequence results also showed similarities with bacteria commonly found on deteriorated stone monuments, supporting the idea that medieval stained glass biodeterioration in the Mediterranean area shows a pattern comparable to that on stone. PMID:24092957

  14. SuperTarget and Matador: resources for exploring drug-target relationships

    PubMed Central

    Günther, Stefan; Kuhn, Michael; Dunkel, Mathias; Campillos, Monica; Senger, Christian; Petsalaki, Evangelia; Ahmed, Jessica; Urdiales, Eduardo Garcia; Gewiess, Andreas; Jensen, Lars Juhl; Schneider, Reinhard; Skoblo, Roman; Russell, Robert B.; Bourne, Philip E.; Bork, Peer; Preissner, Robert

    2008-01-01

    The molecular basis of drug action is often not well understood. This is partly because the very abundant and diverse information generated in the past decades on drugs is hidden in millions of medical articles or textbooks. Therefore, we developed a one-stop data warehouse, SuperTarget that integrates drug-related information about medical indication areas, adverse drug effects, drug metabolization, pathways and Gene Ontology terms of the target proteins. An easy-to-use query interface enables the user to pose complex queries, for example to find drugs that target a certain pathway, interacting drugs that are metabolized by the same cytochrome P450 or drugs that target the same protein but are metabolized by different enzymes. Furthermore, we provide tools for 2D drug screening and sequence comparison of the targets. The database contains more than 2500 target proteins, which are annotated with about 7300 relations to 1500 drugs; the vast majority of entries have pointers to the respective literature source. A subset of these drugs has been annotated with additional binding information and indirect interactions and is available as a separate resource called Matador. SuperTarget and Matador are available at http://insilico.charite.de/supertarget and http://matador.embl.de PMID:17942422

  15. The Mechanism Research of Qishen Yiqi Formula by Module-Network Analysis

    PubMed Central

    Zheng, Shichao; Zhang, Yanling; Qiao, Yanjiang

    2015-01-01

    Qishen Yiqi formula (QSYQ) has the effect of tonifying Qi and promoting blood circulation, which is widely used to treat the cardiovascular diseases with Qi deficiency and blood stasis syndrome. However, the mechanism of QSYQ to tonify Qi and promote blood circulation is rarely reported at molecular or systems level. This study aimed to elucidate the mechanism of QSYQ based on the protein interaction network (PIN) analysis. The targets' information of the active components was obtained from ChEMBL and STITCH databases and was further used to search against protein-protein interactions by String database. Next, the PINs of QSYQ were constructed by Cytoscape and were analyzed by gene ontology enrichment analysis based on Markov Cluster algorithm. Finally, based on the topological parameters, the properties of scale-free, small world, and modularity of the QSYQ's PINs were analyzed. And based on function modules, the mechanism of QSYQ was elucidated. The results indicated that Qi-tonifying efficacy of QSYQ may be partly attributed to the regulation of amino acid metabolism, carbohydrate metabolism, lipid metabolism, and cAMP metabolism, while QSYQ improves the blood stasis through the regulation of blood coagulation and cardiac muscle contraction. Meanwhile, the “synergy” of formula compatibility was also illuminated. PMID:26379745

  16. Recent improvements to the SMART domain-based sequence annotation resource.

    PubMed

    Letunic, Ivica; Goodstadt, Leo; Dickens, Nicholas J; Doerks, Tobias; Schultz, Joerg; Mott, Richard; Ciccarelli, Francesca; Copley, Richard R; Ponting, Chris P; Bork, Peer

    2002-01-01

    SMART (Simple Modular Architecture Research Tool, http://smart.embl-heidelberg.de) is a web-based resource used for the annotation of protein domains and the analysis of domain architectures, with particular emphasis on mobile eukaryotic domains. Extensive annotation for each domain family is available, providing information relating to function, subcellular localization, phyletic distribution and tertiary structure. The January 2002 release has added more than 200 hand-curated domain models. This brings the total to over 600 domain families that are widely represented among nuclear, signalling and extracellular proteins. Annotation now includes links to the Online Mendelian Inheritance in Man (OMIM) database in cases where a human disease is associated with one or more mutations in a particular domain. We have implemented new analysis methods and updated others. New advanced queries provide direct access to the SMART relational database using SQL. This database now contains information on intrinsic sequence features such as transmembrane regions, coiled-coils, signal peptides and internal repeats. SMART output can now be easily included in users' documents. A SMART mirror has been created at http://smart.ox.ac.uk. PMID:11752305

  17. Remote access to ACNUC nucleotide and protein sequence databases at PBIL.

    PubMed

    Gouy, Manolo; Delmotte, Stéphane

    2008-04-01

    The ACNUC biological sequence database system provides powerful and fast query and extraction capabilities to a variety of nucleotide and protein sequence databases. The collection of ACNUC databases served by the Pôle Bio-Informatique Lyonnais includes the EMBL, GenBank, RefSeq and UniProt nucleotide and protein sequence databases and a series of other sequence databases that support comparative genomics analyses: HOVERGEN and HOGENOM containing families of homologous protein-coding genes from vertebrate and prokaryotic genomes, respectively; Ensembl and Genome Reviews for analyses of prokaryotic and of selected eukaryotic genomes. This report describes the main features of the ACNUC system and the access to ACNUC databases from any internet-connected computer. Such access was made possible by the definition of a remote ACNUC access protocol and the implementation of Application Programming Interfaces between the C, Python and R languages and this communication protocol. Two retrieval programs for ACNUC databases, Query_win, with a graphical user interface and raa_query, with a command line interface, are also described. Altogether, these bioinformatics tools provide users with either ready-to-use means of querying remote sequence databases through a variety of selection criteria, or a simple way to endow application programs with an extensive access to these databases. Remote access to ACNUC databases is open to all and fully documented (http://pbil.univ-lyon1.fr/databases/acnuc/acnuc.html).

  18. Directory of Useful Decoys, Enhanced (DUD-E): Better Ligands and Decoys for Better Benchmarking

    PubMed Central

    2012-01-01

    A key metric to assess molecular docking remains ligand enrichment against challenging decoys. Whereas the directory of useful decoys (DUD) has been widely used, clear areas for optimization have emerged. Here we describe an improved benchmarking set that includes more diverse targets such as GPCRs and ion channels, totaling 102 proteins with 22886 clustered ligands drawn from ChEMBL, each with 50 property-matched decoys drawn from ZINC. To ensure chemotype diversity, we cluster each target’s ligands by their Bemis–Murcko atomic frameworks. We add net charge to the matched physicochemical properties and include only the most dissimilar decoys, by topology, from the ligands. An online automated tool (http://decoys.docking.org) generates these improved matched decoys for user-supplied ligands. We test this data set by docking all 102 targets, using the results to improve the balance between ligand desolvation and electrostatics in DOCK 3.6. The complete DUD-E benchmarking set is freely available at http://dude.docking.org. PMID:22716043

  19. PoSSuM v.2.0: data update and a new function for investigating ligand analogs and target proteins of small-molecule drugs

    PubMed Central

    Ito, Jun-ichi; Ikeda, Kazuyoshi; Yamada, Kazunori; Mizuguchi, Kenji; Tomii, Kentaro

    2015-01-01

    PoSSuM (http://possum.cbrc.jp/PoSSuM/) is a database for detecting similar small-molecule binding sites on proteins. Since its initial release in 2011, PoSSuM has grown to provide information related to 49 million pairs of similar binding sites discovered among 5.5 million known and putative binding sites. This enlargement of the database is expected to enhance opportunities for biological and pharmaceutical applications, such as predictions of new functions and drug discovery. In this release, we have provided a new service named PoSSuM drug search (PoSSuMds) at http://possum.cbrc.jp/PoSSuM/drug_search/, in which we selected 194 approved drug compounds retrieved from ChEMBL, and detected their known binding pockets and pockets that are similar to them. Users can access and download all of the search results via a new web interface, which is useful for finding ligand analogs as well as potential target proteins. Furthermore, PoSSuMds enables users to explore the binding pocket universe within PoSSuM. Additionally, we have improved the web interface with new functions, including sortable tables and a viewer for visualizing and downloading superimposed pockets. PMID:25404129

  20. MetaboLights: An Open-Access Database Repository for Metabolomics Data.

    PubMed

    Kale, Namrata S; Haug, Kenneth; Conesa, Pablo; Jayseelan, Kalaivani; Moreno, Pablo; Rocca-Serra, Philippe; Nainala, Venkata Chandrasekhar; Spicer, Rachel A; Williams, Mark; Li, Xuefei; Salek, Reza M; Griffin, Julian L; Steinbeck, Christoph

    2016-01-01

    MetaboLights is the first general purpose, open-access database repository for cross-platform and cross-species metabolomics research at the European Bioinformatics Institute (EMBL-EBI). Based upon the open-source ISA framework, MetaboLights provides Metabolomics Standard Initiative (MSI) compliant metadata and raw experimental data associated with metabolomics experiments. Users can upload their study datasets into the MetaboLights Repository. These studies are then automatically assigned a stable and unique identifier (e.g., MTBLS1) that can be used for publication reference. The MetaboLights Reference Layer associates metabolites with metabolomics studies in the archive and is extensively annotated with data fields such as structural and chemical information, NMR and MS spectra, target species, metabolic pathways, and reactions. The database is manually curated with no specific release schedules. MetaboLights is also recommended by journals for metabolomics data deposition. This unit provides a guide to using MetaboLights, downloading experimental data, and depositing metabolomics datasets using user-friendly submission tools.

  1. In Silico Mining for Antimalarial Structure-Activity Knowledge and Discovery of Novel Antimalarial Curcuminoids.

    PubMed

    Viira, Birgit; Gendron, Thibault; Lanfranchi, Don Antoine; Cojean, Sandrine; Horvath, Dragos; Marcou, Gilles; Varnek, Alexandre; Maes, Louis; Maran, Uko; Loiseau, Philippe M; Davioud-Charvet, Elisabeth

    2016-06-29

    Malaria is a parasitic tropical disease that kills around 600,000 patients every year. The emergence of resistant Plasmodium falciparum parasites to artemisinin-based combination therapies (ACTs) represents a significant public health threat, indicating the urgent need for new effective compounds to reverse ACT resistance and cure the disease. For this, extensive curation and homogenization of experimental anti-Plasmodium screening data from both in-house and ChEMBL sources were conducted. As a result, a coherent strategy was established that allowed compiling coherent training sets that associate compound structures to the respective antimalarial activity measurements. Seventeen of these training sets led to the successful generation of classification models discriminating whether a compound has a significant probability to be active under the specific conditions of the antimalarial test associated with each set. These models were used in consensus prediction of the most likely active from a series of curcuminoids available in-house. Positive predictions together with a few predicted as inactive were then submitted to experimental in vitro antimalarial testing. A large majority from predicted compounds showed antimalarial activity, but not those predicted as inactive, thus experimentally validating the in silico screening approach. The herein proposed consensus machine learning approach showed its potential to reduce the cost and duration of antimalarial drug discovery.

  2. Using Molecular Initiating Events to Develop a Structural Alert Based Screening Workflow for Nuclear Receptor Ligands Associated with Hepatic Steatosis.

    PubMed

    Mellor, Claire L; Steinmetz, Fabian P; Cronin, Mark T D

    2016-02-15

    In silico models are essential for the development of integrated alternative methods to identify organ level toxicity and lead toward the replacement of animal testing. These models include (quantitative) structure-activity relationships ((Q)SARs) and, importantly, the identification of structural alerts associated with defined toxicological end points. Structural alerts are able both to predict toxicity directly and assist in the formation of categories to facilitate read-across. They are particularly important to decipher the myriad mechanisms of action that result in organ level toxicity. The aim of this study was to develop novel structural alerts for nuclear receptor (NR) ligands that are associated with inducing hepatic steatosis and to show the vast number of existing data that are available. Current knowledge on NR agonists was extended with data from the ChEMBL database (12,713 chemicals in total) of bioactive molecules and from studying NR ligand-binding interactions within the protein database (PDB, 624 human NR structure files). A computational structural alert based workflow was developed using KNIME from these data using molecular fragments and other relevant chemical features. In total, 214 structural features were recorded computationally as SMARTS strings, and therefore, they can be used for grouping and screening during drug development and hazard assessment and provide knowledge to anchor adverse outcome pathways (AOPs) via their molecular initiating events (MIEs). PMID:26787004

  3. Gramene 2016: comparative plant genomics and pathway resources.

    PubMed

    Tello-Ruiz, Marcela K; Stein, Joshua; Wei, Sharon; Preece, Justin; Olson, Andrew; Naithani, Sushma; Amarasinghe, Vindhya; Dharmawardhana, Palitha; Jiao, Yinping; Mulvaney, Joseph; Kumari, Sunita; Chougule, Kapeel; Elser, Justin; Wang, Bo; Thomason, James; Bolser, Daniel M; Kerhornou, Arnaud; Walts, Brandon; Fonseca, Nuno A; Huerta, Laura; Keays, Maria; Tang, Y Amy; Parkinson, Helen; Fabregat, Antonio; McKay, Sheldon; Weiser, Joel; D'Eustachio, Peter; Stein, Lincoln; Petryszak, Robert; Kersey, Paul J; Jaiswal, Pankaj; Ware, Doreen

    2016-01-01

    Gramene (http://www.gramene.org) is an online resource for comparative functional genomics in crops and model plant species. Its two main frameworks are genomes (collaboration with Ensembl Plants) and pathways (The Plant Reactome and archival BioCyc databases). Since our last NAR update, the database website adopted a new Drupal management platform. The genomes section features 39 fully assembled reference genomes that are integrated using ontology-based annotation and comparative analyses, and accessed through both visual and programmatic interfaces. Additional community data, such as genetic variation, expression and methylation, are also mapped for a subset of genomes. The Plant Reactome pathway portal (http://plantreactome.gramene.org) provides a reference resource for analyzing plant metabolic and regulatory pathways. In addition to ∼ 200 curated rice reference pathways, the portal hosts gene homology-based pathway projections for 33 plant species. Both the genome and pathway browsers interface with the EMBL-EBI's Expression Atlas to enable the projection of baseline and differential expression data from curated expression studies in plants. Gramene's archive website (http://archive.gramene.org) continues to provide previously reported resources on comparative maps, markers and QTL. To further aid our users, we have also introduced a live monthly educational webinar series and a Gramene YouTube channel carrying video tutorials.

  4. Molecular cloning of the gene encoding the mouse parathyroid hormone/parathyroid hormone-related peptide receptor.

    PubMed Central

    McCuaig, K A; Clarke, J C; White, J H

    1994-01-01

    The parathyroid hormone/parathyroid hormone-related peptide receptor (PTHR) is a G-protein-coupled receptor containing seven predicted transmembrane domains. We have isolated and characterized recombinant bacteriophage lambda EMBL3 genomic clones containing the mouse PTHR gene, including 10 kilobases of the promoter region. The gene spans > 32 kilobases and is divided into 15 exons, 8 of which contain the transmembrane domains. The PTHR exons containing the predicted membrane-spanning domains are heterogeneous in length and three of the exon-intron boundaries fall within putative transmembrane sequences, suggesting that the exons did not arise from duplication events. This arrangement is closely related to that of the growth hormone releasing factor receptor gene, particularly in the transmembrane region, providing strong evidence that the two genes evolved from a common precursor. Transcription is initiated principally at a series of sites over a 15-base-pair region. The proximal promoter region is highly (G+C)-rich and lacks an apparent TATA box or initiator element homologies but does contain CCGCCC motifs. The presumptive amino acid sequence of the encoded receptor is 99%, 91%, and 76% identical to those of the rat, human, and opossum receptors, respectively. There is no consensus polyadenylation signal in the 3' untranslated region. The poly(A) tail of the PTHR transcript begins 32 bases downstream of a 35-base-long A-rich sequence, suggesting that this region directs polyadenylylation. Images PMID:8197183

  5. Organization, structure and alternate splicing of the murine RFC-1 gene encoding a folate transporter.

    PubMed

    Tolner, B; Roy, K; Sirotnak, F M

    1997-04-11

    The structural organization of the murine RFC-1 gene encoding a folate transporter has been determined. The entire nucleotide sequence of the L1210 cell RFC-1 cDNA, the 3'- and 5'-untranslated regions and the coding sequence were found to be distributed in eight exons, including six primary exons and alternates to exon 1 and exon 5, spanning 10.4 kb. Splice variants were identified in an L1210 cell cDNA library. The most common incorporates exons 1 through 6, encoding a 58-kDa polypeptide. The two least common incorporate exons 1 and 2, a truncated version of exon 3 and exons 4 through 6; or exons 1 through 4, an alternate to exon 5, and exon 6, encoding polypeptides of 53.6 and 43.4 kDa, respectively. A fourth variant reported earlier (GenBank/EMBL accession No. L36539) by others incorporates what we have found to be an alternate of exon 1 and exons 2 through 6. A relatively GC-rich region of the genome just 5' of exon 1 as well as exon 1a appears to be distinctly promoter-like and encodes a number of putative cis-acting elements. The findings pertaining to alternates of exon 1 suggest that the transcription of RFC-1 variants results from two different promoters.

  6. The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA.

    PubMed Central

    von Lindern, M; Fornerod, M; van Baal, S; Jaegle, M; de Wit, T; Buijs, A; Grosveld, G

    1992-01-01

    The translocation (6;9) is associated with a specific subtype of acute myeloid leukemia (AML). Previously, it was found that breakpoints on chromosome 9 are clustered in one of the introns of a large gene named Cain (can). cDNA probes derived from the 3' part of can detect an aberrant, leukemia-specific 5.5-kb transcript in bone marrow cells from t(6;9) AML patients. cDNA cloning of this mRNA revealed that it is a fusion of sequences encoded on chromosome 6 and 3' can. A novel gene on chromosome 6 which was named dek was isolated. In dek the t(6;9) breakpoints also occur in one intron. As a result the dek-can fusion gene, present in t(6;9) AML, encodes an invariable dek-can transcript. Sequence analysis of the dek-can cDNA showed that dek and can are merged without disruption of the original open reading frames and therefore the fusion mRNA encodes a chimeric DEK-CAN protein of 165 kDa. The predicted DEK and CAN proteins have molecular masses of 43 and 220 kDa, respectively. Sequence comparison with the EMBL data base failed to show consistent homology with any known protein sequences. Images PMID:1549122

  7. Domain fusion analysis by applying relational algebra to protein sequence and domain databases

    PubMed Central

    Truong, Kevin; Ikura, Mitsuhiko

    2003-01-01

    Background Domain fusion analysis is a useful method to predict functionally linked proteins that may be involved in direct protein-protein interactions or in the same metabolic or signaling pathway. As separate domain databases like BLOCKS, PROSITE, Pfam, SMART, PRINTS-S, ProDom, TIGRFAMs, and amalgamated domain databases like InterPro continue to grow in size and quality, a computational method to perform domain fusion analysis that leverages on these efforts will become increasingly powerful. Results This paper proposes a computational method employing relational algebra to find domain fusions in protein sequence databases. The feasibility of this method was illustrated on the SWISS-PROT+TrEMBL sequence database using domain predictions from the Pfam HMM (hidden Markov model) database. We identified 235 and 189 putative functionally linked protein partners in H. sapiens and S. cerevisiae, respectively. From scientific literature, we were able to confirm many of these functional linkages, while the remainder offer testable experimental hypothesis. Results can be viewed at . Conclusion As the analysis can be computed quickly on any relational database that supports standard SQL (structured query language), it can be dynamically updated along with the sequence and domain databases, thereby improving the quality of predictions over time. PMID:12734020

  8. Pseudomonas aeruginosa outer membrane lipoprotein I gene: molecular cloning, sequence, and expression in Escherichia coli.

    PubMed Central

    Duchêne, M; Barron, C; Schweizer, A; von Specht, B U; Domdey, H

    1989-01-01

    Lipoprotein I (OprI) is one of the major proteins of the outer membrane of Pseudomonas aeruginosa. Like porin protein F (OprF), it is a vaccine candidate because it antigenically cross-reacts with all serotype strains of the International Antigenic Typing Scheme. Since lipoprotein I was expressed in Escherichia coli under the control of its own promoter, we were able to isolate the gene by screening a lambda EMBL3 phage library with a mouse monoclonal antibody directed against lipoprotein I. The monocistronic OprI mRNA encodes a precursor protein of 83 amino acid residues including a signal peptide of 19 residues. The mature protein has a molecular weight of 6,950, not including bound glycerol and lipid. Although the amino acid sequences of protein I of P. aeruginosa and Braun's lipoprotein of E. coli differ considerably (only 30.1% identical amino acid residues), peptidoglycan in E. coli, are identical. Using lipoprotein I expressed in E. coli, it can now be tested whether this protein alone, without P. aeruginosa lipopolysaccharide contaminations, has a protective effect against P. aeruginosa infections. Images PMID:2502533

  9. Radiation and phylogeography in the Japanese macaque, Macaca fuscata.

    PubMed

    Marmi, Josep; Bertranpetit, Jaume; Terradas, Jaume; Takenaka, Osamu; Domingo-Roura, Xavier

    2004-03-01

    The Japanese macaque (Macaca fuscata) presumably differentiated from eastern rhesus macaque (Macaca mulatta) populations during the Pleistocene and the two species are closely related. In order to analyse speciation and subspeciation events in the Japanese macaque and to describe historical and current relationships among their populations, we sequenced and analysed a fragment of 392bp of mitochondrial DNA (mtDNA) control region in 50 individuals belonging to six populations of Japanese macaque and compared these sequences with 89 eastern rhesus macaque control region sequences from GenBank/EMBL database. There were high genetic similarities between both species and only two positions were fixed within each species, which supports the inclusion of the Japanese macaque in a single species with eastern populations of rhesus macaques. Japanese macaque ancestors colonised Japan after the separation of the two species, estimated at between 0.31 and 0.88 million years ago (Mya). The star-like phylogeny, multimodal mismatch distribution, and lack of correlation between geographic and genetic distances are in accordance with a rapid dispersion of macaques throughout the archipelago after the arrival into Japan. The species shows low genetic variation within populations and high levels of genetic differentiation among populations with no mtDNA haplotype shared across populations. Genetic distances between Yakushima macaques (Macaca fuscata yakui) and any other population of Macaca fuscata fuscata subspecies are comparable to the distances between populations of Honshu, Awajishima, and Kyushu, not supporting the classification of Yakushima macaques as a different subspecies.

  10. BioSAXS Sample Changer: a robotic sample changer for rapid and reliable high-throughput X-ray solution scattering experiments

    PubMed Central

    Round, Adam; Felisaz, Franck; Fodinger, Lukas; Gobbo, Alexandre; Huet, Julien; Villard, Cyril; Blanchet, Clement E.; Pernot, Petra; McSweeney, Sean; Roessle, Manfred; Svergun, Dmitri I.; Cipriani, Florent

    2015-01-01

    Small-angle X-ray scattering (SAXS) of macromolecules in solution is in increasing demand by an ever more diverse research community, both academic and industrial. To better serve user needs, and to allow automated and high-throughput operation, a sample changer (BioSAXS Sample Changer) that is able to perform unattended measurements of up to several hundred samples per day has been developed. The Sample Changer is able to handle and expose sample volumes of down to 5 µl with a measurement/cleaning cycle of under 1 min. The samples are stored in standard 96-well plates and the data are collected in a vacuum-mounted capillary with automated positioning of the solution in the X-ray beam. Fast and efficient capillary cleaning avoids cross-contamination and ensures reproducibility of the measurements. Independent temperature control for the well storage and for the measurement capillary allows the samples to be kept cool while still collecting data at physiological temperatures. The Sample Changer has been installed at three major third-generation synchrotrons: on the BM29 beamline at the European Synchrotron Radiation Facility (ESRF), the P12 beamline at the PETRA-III synchrotron (EMBL@PETRA-III) and the I22/B21 beamlines at Diamond Light Source, with the latter being the first commercial unit supplied by Bruker ASC. PMID:25615861

  11. MobiDB 2.0: an improved database of intrinsically disordered and mobile proteins

    PubMed Central

    Potenza, Emilio; Domenico, Tomás Di; Walsh, Ian; Tosatto, Silvio C.E.

    2015-01-01

    MobiDB (http://mobidb.bio.unipd.it/) is a database of intrinsically disordered and mobile proteins. Intrinsically disordered regions are key for the function of numerous proteins. Here we provide a new version of MobiDB, a centralized source aimed at providing the most complete picture on different flavors of disorder in protein structures covering all UniProt sequences (currently over 80 million). The database features three levels of annotation: manually curated, indirect and predicted. Manually curated data is extracted from the DisProt database. Indirect data is inferred from PDB structures that are considered an indication of intrinsic disorder. The 10 predictors currently included (three ESpritz flavors, two IUPred flavors, two DisEMBL flavors, GlobPlot, VSL2b and JRONN) enable MobiDB to provide disorder annotations for every protein in absence of more reliable data. The new version also features a consensus annotation and classification for long disordered regions. In order to complement the disorder annotations, MobiDB features additional annotations from external sources. Annotations from the UniProt database include post-translational modifications and linear motifs. Pfam annotations are displayed in graphical form and are link-enabled, allowing the user to visit the corresponding Pfam page for further information. Experimental protein–protein interactions from STRING are also classified for disorder content. PMID:25361972

  12. Fermentation and genomic analysis of acetone-uncoupled butanol production by Clostridium tetanomorphum.

    PubMed

    Gong, Fuyu; Bao, Guanhui; Zhao, Chunhua; Zhang, Yanping; Li, Yin; Dong, Hongjun

    2016-02-01

    In typical acetone-butanol-ethanol (ABE) fermentation, acetone is the main by-product (50 % of butanol mass) of butanol production, resulting in a low yield of butanol. It is known that some Clostridium tetanomorphum strains are able to produce butanol without acetone in nature. Here, we described that C. tetanomorphum strain DSM665 can produce 4.16 g/L butanol and 4.98 g/L ethanol at pH 6.0, and 9.81 g/L butanol and 1.01 g/L ethanol when adding 1 mM methyl viologen. Butyrate and acetate could be reassimilated and no acetone was produced. Further analysis indicated that the activity of the acetate/butyrate:acetoacetyl-CoA transferase responsible for acetone production is lost in C. tetanomorphum DSM665. The genome of C. tetanomorphum DSM665 was sequenced and deposited in DDBJ, EMBL, and GenBank under the accession no. APJS00000000. Sequence analysis indicated that there are no typical genes (ctfA/B and adc) that are typically parts of an acetone synthesis pathway in C. tetanomorphum DSM665. This work provides new insights in the mechanism of clostridial butanol production and should prove useful for the design of a high-butanol-producing strain.

  13. Linking the Resource Description Framework to cheminformatics and proteochemometrics

    PubMed Central

    2011-01-01

    Background Semantic web technologies are finding their way into the life sciences. Ontologies and semantic markup have already been used for more than a decade in molecular sciences, but have not found widespread use yet. The semantic web technology Resource Description Framework (RDF) and related methods show to be sufficiently versatile to change that situation. Results The work presented here focuses on linking RDF approaches to existing molecular chemometrics fields, including cheminformatics, QSAR modeling and proteochemometrics. Applications are presented that link RDF technologies to methods from statistics and cheminformatics, including data aggregation, visualization, chemical identification, and property prediction. They demonstrate how this can be done using various existing RDF standards and cheminformatics libraries. For example, we show how IC50 and Ki values are modeled for a number of biological targets using data from the ChEMBL database. Conclusions We have shown that existing RDF standards can suitably be integrated into existing molecular chemometrics methods. Platforms that unite these technologies, like Bioclipse, makes this even simpler and more transparent. Being able to create and share workflows that integrate data aggregation and analysis (visual and statistical) is beneficial to interoperability and reproducibility. The current work shows that RDF approaches are sufficiently powerful to support molecular chemometrics workflows. PMID:21388575

  14. Using Molecular Initiating Events to Develop a Structural Alert Based Screening Workflow for Nuclear Receptor Ligands Associated with Hepatic Steatosis.

    PubMed

    Mellor, Claire L; Steinmetz, Fabian P; Cronin, Mark T D

    2016-02-15

    In silico models are essential for the development of integrated alternative methods to identify organ level toxicity and lead toward the replacement of animal testing. These models include (quantitative) structure-activity relationships ((Q)SARs) and, importantly, the identification of structural alerts associated with defined toxicological end points. Structural alerts are able both to predict toxicity directly and assist in the formation of categories to facilitate read-across. They are particularly important to decipher the myriad mechanisms of action that result in organ level toxicity. The aim of this study was to develop novel structural alerts for nuclear receptor (NR) ligands that are associated with inducing hepatic steatosis and to show the vast number of existing data that are available. Current knowledge on NR agonists was extended with data from the ChEMBL database (12,713 chemicals in total) of bioactive molecules and from studying NR ligand-binding interactions within the protein database (PDB, 624 human NR structure files). A computational structural alert based workflow was developed using KNIME from these data using molecular fragments and other relevant chemical features. In total, 214 structural features were recorded computationally as SMARTS strings, and therefore, they can be used for grouping and screening during drug development and hazard assessment and provide knowledge to anchor adverse outcome pathways (AOPs) via their molecular initiating events (MIEs).

  15. NRLiSt BDB, the manually curated nuclear receptors ligands and structures benchmarking database.

    PubMed

    Lagarde, Nathalie; Ben Nasr, Nesrine; Jérémie, Aurore; Guillemain, Hélène; Laville, Vincent; Labib, Taoufik; Zagury, Jean-François; Montes, Matthieu

    2014-04-10

    Nuclear receptors (NRs) constitute an important class of drug targets. We created the most exhaustive NR-focused benchmarking database to date, the NRLiSt BDB (NRs ligands and structures benchmarking database). The 9905 compounds and 339 structures of the NRLiSt BDB are ready for structure-based and ligand-based virtual screening. In the present study, we detail the protocol used to generate the NRLiSt BDB and its features. We also give some examples of the errors that we found in ChEMBL that convinced us to manually review all original papers. Since extensive and manually curated experimental data about NR ligands and structures are provided in the NRLiSt BDB, it should become a powerful tool to assess the performance of virtual screening methods on NRs, to assist the understanding of NR's function and modulation, and to support the discovery of new drugs targeting NRs. NRLiSt BDB is freely available online at http://nrlist.drugdesign.fr .

  16. Isolation and characterization of a gene from Aspergillus parasiticus associated with the conversion of versicolorin A to sterigmatocystin in aflatoxin biosynthesis.

    PubMed Central

    Skory, C D; Chang, P K; Cary, J; Linz, J E

    1992-01-01

    DNA isolated from the wild-type aflatoxin-producing (Afl+) fungus Aspergillus parasiticus NRRL 5862 was used to construct a cosmid genomic DNA library employing the homologous gene (pyrG) encoding orotidine monophosphate decarboxylase for selection of fungal transformants. The cosmid library was transformed into an Afl- mutant, A. parasiticus CS10 (ver-1 wh-1 pyrG), deficient in the conversion of the aflatoxin biosynthetic intermediate versicolorin A to sterigmatocystin. One pyrG+ Afl+ transformant was identified. DNA fragments from this transformant, recovered by marker rescue, contained part of the cosmid vector including the pyrG gene, the ampr gene, and a piece of the original genomic insert DNA. Transformation of these rescued DNA fragments into A. parasiticus CS10 resulted in production of wild-type levels of aflatoxin and abundant formation of sclerotia. The gene responsible for this complementation (ver-1) was identified by Northern RNA analysis and transformation with subcloned DNA fragments. The approximate locations of transcription initiation and polyadenylation sites of ver-1 were determined by an RNase protection assay and cDNA sequence analysis. The predicted amino acid sequence, deduced from the ver-1 genomic and cDNA nucleotide sequences, was compared with the EMBL and GenBank data bases. The search revealed striking similarity with Streptomyces ketoreductases involved in polyketide biosynthesis. Images PMID:1339261

  17. Quantitative Structure-Antioxidant Activity Models of Isoflavonoids: A Theoretical Study.

    PubMed

    Castellano, Gloria; Torrens, Francisco

    2015-01-01

    Seventeen isoflavonoids from isoflavone, isoflavanone and isoflavan classes are selected from Dalbergia parviflora. The ChEMBL database is representative from these molecules, most of which result highly drug-like. Binary rules appear risky for the selection of compounds with high antioxidant capacity in complementary xanthine/xanthine oxidase, ORAC, and DPPH model assays. Isoflavonoid structure-activity analysis shows the most important properties (log P, log D, pKa, QED, PSA, NH + OH ≈ HBD, N + O ≈ HBA). Some descriptors (PSA, HBD) are detected as more important than others (size measure Mw, HBA). Linear and nonlinear models of antioxidant potency are obtained. Weak nonlinear relationships appear between log P, etc. and antioxidant activity. The different capacity trends for the three complementary assays are explained. Isoflavonoids potency depends on the chemical form that determines their solubility. Results from isoflavonoids analysis will be useful for activity prediction of new sets of flavones and to design drugs with antioxidant capacity, which will prove beneficial for health with implications for antiageing therapy. PMID:26062128

  18. iPPI-DB: an online database of modulators of protein-protein interactions.

    PubMed

    Labbé, Céline M; Kuenemann, Mélaine A; Zarzycka, Barbara; Vriend, Gert; Nicolaes, Gerry A F; Lagorce, David; Miteva, Maria A; Villoutreix, Bruno O; Sperandio, Olivier

    2016-01-01

    In order to boost the identification of low-molecular-weight drugs on protein-protein interactions (PPI), it is essential to properly collect and annotate experimental data about successful examples. This provides the scientific community with the necessary information to derive trends about privileged physicochemical properties and chemotypes that maximize the likelihood of promoting a given chemical probe to the most advanced stages of development. To this end we have developed iPPI-DB (freely accessible at http://www.ippidb.cdithem.fr), a database that contains the structure, some physicochemical characteristics, the pharmacological data and the profile of the PPI targets of several hundreds modulators of protein-protein interactions. iPPI-DB is accessible through a web application and can be queried according to two general approaches: using physicochemical/pharmacological criteria; or by chemical similarity to a user-defined structure input. In both cases the results are displayed as a sortable and exportable datasheet with links to external databases such as Uniprot, PubMed. Furthermore each compound in the table has a link to an individual ID card that contains its physicochemical and pharmacological profile derived from iPPI-DB data. This includes information about its binding data, ligand and lipophilic efficiencies, location in the PPI chemical space, and importantly similarity with known drugs, and links to external databases like PubChem, and ChEMBL.

  19. IDChase: Mitigating Identifier Migration Trap in Biological Databases

    NASA Astrophysics Data System (ADS)

    Bhattacharjee, Anupam; Islam, Aminul; Jamil, Hasan; Wildman, Derek

    A convenient mechanism to refer to large biological objects such as sequences, structures and networks is the use of identifiers or handles, commonly called IDs. IDs function as a unique place holder in an application for objects too large to be of immediate use in a table which is retrieved from a secondary archive when needed. Usually, applications use IDs of objects managed by remote databases that the applications do not have any control over such as GenBank, EMBL and UCSC. Unfortunately, IDs are generally not unique and frequently change as the objects they refer to change. Consequently, applications built using such IDs need to adapt by monitoring possible ID migration occurring in databases they do not control, or risk producing inconsistent, or out of date results, or even face loss of functionality. In this paper, we develop a wrapper based approach to recognizing ID migration in secondary databases, mapping obsolete IDs to valid new IDs, and updating databases to restore their intended functionality. We present our technique in detail using an example involving NCBI RefSeq as primary, and OCPAT as secondary databases. Based on the proposed technique, we introduce a new wrapper like tool, called IDChase, to address the ID migration problem in biological databases and as a general platform.

  20. Nomenclature for factors of the SLA class-I system, 2004.

    PubMed

    Smith, D M; Lunney, J K; Martens, G W; Ando, A; Lee, J-H; Ho, C-S; Schook, L; Renard, C; Chardon, P

    2005-02-01

    A systematic nomenclature for the genes and alleles of the swine major histocompatibility complex (MHC) is essential to the development and communication of research in swine immunology. The Swine Leucocyte Antigen (SLA) Nomenclature Committee of the International Society for Animal Genetics has reviewed all of the DNA sequence information for MHC class-I genes, available in GenBank/EMBL/DDBJ databases, and the associated published reports in order to develop such a systematic nomenclature. This report summarizes the proposed nomenclature, which parallels the World Health Organization's nomenclature for factors of the human MHC. The classical class-I SLA genes are designated as SLA-1, SLA-2 and SLA-3; the non-classical as SLA-6, SLA-7 and SLA-8. Nomenclature assignments for all SLA class-I GenBank sequences are now noted. The Committee will add new SLA class-I allele designations, as they are discovered, and will maintain a publicly available list of all recognized genes and alleles by using the International ImMunoGeneTics Project and its Immuno Polymorphism Database/MHC (IPD/MHC) sequence database for MHC sequences in veterinary species.

  1. Prediction of Metabolic Pathway Involvement in Prokaryotic UniProtKB Data by Association Rule Mining

    PubMed Central

    Hoehndorf, Robert; Martin, Maria J.; Solovyev, Victor

    2016-01-01

    The widening gap between known proteins and their functions has encouraged the development of methods to automatically infer annotations. Automatic functional annotation of proteins is expected to meet the conflicting requirements of maximizing annotation coverage, while minimizing erroneous functional assignments. This trade-off imposes a great challenge in designing intelligent systems to tackle the problem of automatic protein annotation. In this work, we present a system that utilizes rule mining techniques to predict metabolic pathways in prokaryotes. The resulting knowledge represents predictive models that assign pathway involvement to UniProtKB entries. We carried out an evaluation study of our system performance using cross-validation technique. We found that it achieved very promising results in pathway identification with an F1-measure of 0.982 and an AUC of 0.987. Our prediction models were then successfully applied to 6.2 million UniProtKB/TrEMBL reference proteome entries of prokaryotes. As a result, 663,724 entries were covered, where 436,510 of them lacked any previous pathway annotations. PMID:27390860

  2. The Universal Protein Resource (UniProt): an expanding universe of protein information.

    PubMed

    Wu, Cathy H; Apweiler, Rolf; Bairoch, Amos; Natale, Darren A; Barker, Winona C; Boeckmann, Brigitte; Ferro, Serenella; Gasteiger, Elisabeth; Huang, Hongzhan; Lopez, Rodrigo; Magrane, Michele; Martin, Maria J; Mazumder, Raja; O'Donovan, Claire; Redaschi, Nicole; Suzek, Baris

    2006-01-01

    The Universal Protein Resource (UniProt) provides a central resource on protein sequences and functional annotation with three database components, each addressing a key need in protein bioinformatics. The UniProt Knowledgebase (UniProtKB), comprising the manually annotated UniProtKB/Swiss-Prot section and the automatically annotated UniProtKB/TrEMBL section, is the preeminent storehouse of protein annotation. The extensive cross-references, functional and feature annotations and literature-based evidence attribution enable scientists to analyse proteins and query across databases. The UniProt Reference Clusters (UniRef) speed similarity searches via sequence space compression by merging sequences that are 100% (UniRef100), 90% (UniRef90) or 50% (UniRef50) identical. Finally, the UniProt Archive (UniParc) stores all publicly available protein sequences, containing the history of sequence data with links to the source databases. UniProt databases continue to grow in size and in availability of information. Recent and upcoming changes to database contents, formats, controlled vocabularies and services are described. New download availability includes all major releases of UniProtKB, sequence collections by taxonomic division and complete proteomes. A bibliography mapping service has been added, and an ID mapping service will be available soon. UniProt databases can be accessed online at http://www.uniprot.org or downloaded at ftp://ftp.uniprot.org/pub/databases/.

  3. Gramene 2016: comparative plant genomics and pathway resources

    PubMed Central

    Tello-Ruiz, Marcela K.; Stein, Joshua; Wei, Sharon; Preece, Justin; Olson, Andrew; Naithani, Sushma; Amarasinghe, Vindhya; Dharmawardhana, Palitha; Jiao, Yinping; Mulvaney, Joseph; Kumari, Sunita; Chougule, Kapeel; Elser, Justin; Wang, Bo; Thomason, James; Bolser, Daniel M.; Kerhornou, Arnaud; Walts, Brandon; Fonseca, Nuno A.; Huerta, Laura; Keays, Maria; Tang, Y. Amy; Parkinson, Helen; Fabregat, Antonio; McKay, Sheldon; Weiser, Joel; D'Eustachio, Peter; Stein, Lincoln; Petryszak, Robert; Kersey, Paul J.; Jaiswal, Pankaj; Ware, Doreen

    2016-01-01

    Gramene (http://www.gramene.org) is an online resource for comparative functional genomics in crops and model plant species. Its two main frameworks are genomes (collaboration with Ensembl Plants) and pathways (The Plant Reactome and archival BioCyc databases). Since our last NAR update, the database website adopted a new Drupal management platform. The genomes section features 39 fully assembled reference genomes that are integrated using ontology-based annotation and comparative analyses, and accessed through both visual and programmatic interfaces. Additional community data, such as genetic variation, expression and methylation, are also mapped for a subset of genomes. The Plant Reactome pathway portal (http://plantreactome.gramene.org) provides a reference resource for analyzing plant metabolic and regulatory pathways. In addition to ∼200 curated rice reference pathways, the portal hosts gene homology-based pathway projections for 33 plant species. Both the genome and pathway browsers interface with the EMBL-EBI's Expression Atlas to enable the projection of baseline and differential expression data from curated expression studies in plants. Gramene's archive website (http://archive.gramene.org) continues to provide previously reported resources on comparative maps, markers and QTL. To further aid our users, we have also introduced a live monthly educational webinar series and a Gramene YouTube channel carrying video tutorials. PMID:26553803

  4. Determination of internal transcribed spacer regions (ITS) in Trichomonas vaginalis isolates and differentiation among Trichomonas species.

    PubMed

    Ibáñez-Escribano, Alexandra; Nogal-Ruiz, Juan José; Arán, Vicente J; Escario, José Antonio; Gómez-Barrio, Alicia; Alderete, J F

    2014-04-01

    The nucleotide sequence of the 5.8S rRNA gene and the flanked internal transcribed spacer (ITS) regions of six Trichomonas vaginalis isolates with different metronidazole sensitivity and geographic origin were genotyped. A multiple sequence alignment was performed with different sequences of other isolates available at the GenBank/EMBL/DDBJ databases, which revealed 5 different sequence patterns. Although a stable mutation in position 66 of the ITS1 (C66T) was observed in 26% (9/34) of the T. vaginalis sequences analyzed, there was 99.7% ITS nucleotide sequence identity among isolates for this sequence. The nucleotide sequence variation among other species of the genus Trichomonas ranged from 3.4% to 9.1%. Surprisingly, the % identity between T. vaginalis and Pentatrichomonas hominis was ~83%. There was >40% divergence in the ITS sequence between T. vaginalis and Tritrichomonas spp., including Tritrichomonas augusta, Tritrichomonas muris, and Tritrichomonas nonconforma and with Tetratrichomonas prowazeki. Dendrograms grouped the trichomonadid sequences in robust clades according to their genera. The absence of nucleotide divergence in the hypervariable ITS regions between T. vaginalis isolates suggests the early divergence of the parasite. Importantly, these data show this ITS1-5.8S rRNA-ITS2 region suitable for inter-species differentiation.

  5. Draft genome sequence of pathogenic bacteria Vibrio parahaemolyticus strain Ba94C2, associated with acute hepatopancreatic necrosis disease isolate from South America.

    PubMed

    Restrepo, Leda; Bayot, Bonny; Betancourt, Irma; Pinzón, Andres

    2016-09-01

    Vibrio parahaemolyticus is a pathogenic bacteria which has been associated to the early mortality syndrome (EMS) also known as hepatopancreatic necrosis disease (AHPND) causing high mortality in shrimp farms. Pathogenic strains contain two homologous genes related to insecticidal toxin genes, PirA and PirB, these toxin genes are located on a plasmid contained within the bacteria. Genomic sequences have allowed the finding of two strains with a divergent structure related to the geographic region from where they were found. The isolates from the geographic collection of Southeast Asia and Mexico show variable regions on the plasmid genome, indicating that even though they are not alike they still conserve the toxin genes. In this paper, we report for the first time, a pathogenic V. parahaemolyticus strain in shrimp from South America that showed symptoms of AHPND. The genomic analysis revealed that this strain of V. parahaemolyticus found in South America appears to be more related to the Southeast Asia as compared to the Mexican strains. This finding is of major importance for the shrimp industry, especially in regards to the urgent need for disease control strategies to avoid large EMS outbreaks and economic loss, and to determine its dispersion in South America. The whole-genome shotgun project of V. parahaemolyticus strain Ba94C2 have been deposited at DDBJ/EMBL/GenBank under the accession PRJNA335761. PMID:27570736

  6. Homologs of Escherichia coli recJ, gltX and of a putative 'early' gene of avian Chlamydia psittaci are located upstream of the 'late' omp2 locus of Chlamydia psittaci strain guinea pig inclusion conjunctivitis.

    PubMed

    Hsia, R C; Bavoil, P M

    1996-10-17

    The nucleotide sequence of nearly 6 kb of genomic DNA located immediately upstream of the omp3-omp2 operon of Chlamydia psittaci strain GPIC was obtained, revealing four significant open reading frames (ORFs), named ORF1, ORF2, ORF4 and ORF5. Searches for homologous sequences in the GenBank/EMBL databases have revealed that: (a) the open-ended ORF1 putatively encodes an homolog of RecJ of Escherichia coli, thought to be required for RecBCD-independent and conjugational recombination, and for UV repair; (b) the predicted translation product of ORF4 is highly homologous to the putative product of EUO, a previously described ORF of avian C. psittaci strain 6BC which is preferentially transcribed early during the life cycle; and (c) ORF5 putatively encodes an homolog of bacterial glutamyl-tRNA synthetases. This analysis establishes the genetic linkage of late (omp3-omp2) and of a proposed early (EUO) genes in Chlamydia.

  7. Yams (Dioscorea spp.) from the South Pacific Islands contain many novel badnaviruses: implications for international movement of yam germplasm.

    PubMed

    Kenyon, Lawrence; Lebas, B S M; Seal, S E

    2008-01-01

    Yam (Dioscorea spp.) samples (n = 690) from seven South Pacific Islands were screened for badnavirus infection by ELISA using two antisera to African badnaviruses. Positive readings were obtained for 26.4-34.6% of samples representing both known (D. bulbifera, D. nummularia and D. pentaphylla) and unreported host species (D. alata, D. esculenta, D. rotundata and D. trifida) in this region. Total DNAs were extracted from 25 ELISA-positive plants and 4 ELISA-negative controls and subjected to PCR amplification with badnavirus-specific primers targeting the reverse transcriptase (RT)-RNaseH genes. All 29 samples yielded the expected size PCR-product for badnaviruses, which were cloned and sequenced. Phylogenetic analyses of the resulting 45 partial (500-527 bp) RT-RNaseH sequences revealed 11 new sequence groups with <79% nucleotide identity to each other or any EMBL sequence. Three sequences (two groups) were highly divergent to the other nine new South Pacific yam badnavirus groups (47.9-57.2% identity) and probably represent either new Caulimoviridae genera or endogenous pararetrovirus sequences. Some sequence groups appeared specific to particular Dioscorea host species. Four 99.9% identical RT-RNaseH sequences possessing nine amino acid deletions from D. esculenta from three islands represent a putative integrated sequence group. The distribution of sequence groups across the islands indicates that badnaviruses have spread extensively between islands and continents through infected germplasm.

  8. BioSAXS Sample Changer: a robotic sample changer for rapid and reliable high-throughput X-ray solution scattering experiments.

    PubMed

    Round, Adam; Felisaz, Franck; Fodinger, Lukas; Gobbo, Alexandre; Huet, Julien; Villard, Cyril; Blanchet, Clement E; Pernot, Petra; McSweeney, Sean; Roessle, Manfred; Svergun, Dmitri I; Cipriani, Florent

    2015-01-01

    Small-angle X-ray scattering (SAXS) of macromolecules in solution is in increasing demand by an ever more diverse research community, both academic and industrial. To better serve user needs, and to allow automated and high-throughput operation, a sample changer (BioSAXS Sample Changer) that is able to perform unattended measurements of up to several hundred samples per day has been developed. The Sample Changer is able to handle and expose sample volumes of down to 5 µl with a measurement/cleaning cycle of under 1 min. The samples are stored in standard 96-well plates and the data are collected in a vacuum-mounted capillary with automated positioning of the solution in the X-ray beam. Fast and efficient capillary cleaning avoids cross-contamination and ensures reproducibility of the measurements. Independent temperature control for the well storage and for the measurement capillary allows the samples to be kept cool while still collecting data at physiological temperatures. The Sample Changer has been installed at three major third-generation synchrotrons: on the BM29 beamline at the European Synchrotron Radiation Facility (ESRF), the P12 beamline at the PETRA-III synchrotron (EMBL@PETRA-III) and the I22/B21 beamlines at Diamond Light Source, with the latter being the first commercial unit supplied by Bruker ASC. PMID:25615861

  9. Influences of aging and cloning methods on the capacity for somatic embryogenesis of a mature Hevea brasiliensis genotype.

    PubMed

    Lardet, Ludovic; Dessailly, Florence; Carron, Marc-Philippe; Montoro, Pascal; Monteuuis, Olivier

    2009-02-01

    We compared embryogenic capacities of integument explants excised from three sources of the Hevea brasiliensis (Müll. Arg.) mature genotype PB 260. The three sources were 17-year-old (BT 86) and 7-year-old (BT 96) budded trees and 7-year-old emblings (EM 96). The highest proportions of embryogenic calluses obtained from the total number of integument explants initially used were from trees of EM 96 origin, followed by BT 96 trees, with explants from BT 86 trees producing the lowest number of embryogenic calluses. Further initiation of embryogenic callus lines from the primary somatic embryos derived from the three sources was successful only for EM 96. Somatic embryo cultures from BT 86 and BT 96 sources produced only friable calluses that could not be further amplified. Overall, somatic embryo explants derived from EM 96 responded over a wider range of 3,4-dichlorophenoxyacetic acid and kinetin concentrations than the somatic embryo explants from BT 86 and BT 96 origins. The effects of chronologic, ontogenetic and physiologic aging on explant capacity for somatic embryogenesis and on the overall efficiency of the process in H. brasiliensis are discussed. PMID:19203954

  10. Characterization and genome functional analysis of a novel metamitron-degrading strain Rhodococcus sp. MET via both triazinone and phenyl rings cleavage

    NASA Astrophysics Data System (ADS)

    Fang, Hua; Xu, Tianheng; Cao, Duantao; Cheng, Longyin; Yu, Yunlong

    2016-08-01

    A novel bacterium capable of utilizing metamitron as the sole source of carbon and energy was isolated from contaminated soil and identified as Rhodococcus sp. MET based on its morphological characteristics, BIOLOG GP2 microplate profile, and 16S rDNA phylogeny. Genome sequencing and functional annotation of the isolate MET showed a 6,340,880 bp genome with a 62.47% GC content and 5,987 protein-coding genes. In total, 5,907 genes were annotated with the COG, GO, KEGG, Pfam, Swiss-Prot, TrEMBL, and nr databases. The degradation rate of metamitron by the isolate MET obviously increased with increasing substrate concentrations from 1 to 10 mg/l and subsequently decreased at 100 mg/l. The optimal pH and temperature for metamitron biodegradation were 7.0 and 20–30 °C, respectively. Based on genome annotation of the metamitron degradation genes and the metabolites detected by HPLC-MS/MS, the following metamitron biodegradation pathways were proposed: 1) Metamitron was transformed into 2-(3-hydrazinyl-2-ethyl)-hydrazono-2-phenylacetic acid by triazinone ring cleavage and further mineralization; 2) Metamitron was converted into 3-methyl-4-amino-6(2-hydroxy-muconic acid)-1,2,4-triazine-5(4H)-one by phenyl ring cleavage and further mineralization. The coexistence of diverse mineralization pathways indicates that our isolate may effectively bioremediate triazinone herbicide-contaminated soils.

  11. Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees

    PubMed Central

    Letunic, Ivica; Bork, Peer

    2016-01-01

    Interactive Tree Of Life (http://itol.embl.de) is a web-based tool for the display, manipulation and annotation of phylogenetic trees. It is freely available and open to everyone. The current version was completely redesigned and rewritten, utilizing current web technologies for speedy and streamlined processing. Numerous new features were introduced and several new data types are now supported. Trees with up to 100,000 leaves can now be efficiently displayed. Full interactive control over precise positioning of various annotation features and an unlimited number of datasets allow the easy creation of complex tree visualizations. iTOL 3 is the first tool which supports direct visualization of the recently proposed phylogenetic placements format. Finally, iTOL's account system has been redesigned to simplify the management of trees in user-defined workspaces and projects, as it is heavily used and currently handles already more than 500,000 trees from more than 10,000 individual users. PMID:27095192

  12. SPdb – a signal peptide database

    PubMed Central

    Choo, Khar Heng; Tan, Tin Wee; Ranganathan, Shoba

    2005-01-01

    Background The signal peptide plays an important role in protein targeting and protein translocation in both prokaryotic and eukaryotic cells. This transient, short peptide sequence functions like a postal address on an envelope by targeting proteins for secretion or for transfer to specific organelles for further processing. Understanding how signal peptides function is crucial in predicting where proteins are translocated. To support this understanding, we present SPdb signal peptide database , a repository of experimentally determined and computationally predicted signal peptides. Results SPdb integrates information from two sources (a) Swiss-Prot protein sequence database which is now part of UniProt and (b) EMBL nucleotide sequence database. The database update is semi-automated with human checking and verification of the data to ensure the correctness of the data stored. The latest release SPdb release 3.2 contains 18,146 entries of which 2,584 entries are experimentally verified signal sequences; the remaining 15,562 entries are either signal sequences that fail to meet our filtering criteria or entries that contain unverified signal sequences. Conclusion SPdb is a manually curated database constructed to support the understanding and analysis of signal peptides. SPdb tracks the major updates of the two underlying primary databases thereby ensuring that its information remains up-to-date. PMID:16221310

  13. Robots, pipelines, polyproteins: enabling multiprotein expression in prokaryotic and eukaryotic cells.

    PubMed

    Vijayachandran, Lakshmi Sumitra; Viola, Cristina; Garzoni, Frederic; Trowitzsch, Simon; Bieniossek, Christoph; Chaillet, Maxime; Schaffitzel, Christiane; Busso, Didier; Romier, Christophe; Poterszman, Arnaud; Richmond, Timothy J; Berger, Imre

    2011-08-01

    Multiprotein complexes catalyze vital biological functions in the cell. A paramount objective of the SPINE2 project was to address the structural molecular biology of these multiprotein complexes, by enlisting and developing enabling technologies for their study. An emerging key prerequisite for studying complex biological specimens is their recombinant overproduction. Novel reagents and streamlined protocols for rapidly assembling co-expression constructs for this purpose have been designed and validated. The high-throughput pipeline implemented at IGBMC Strasbourg and the ACEMBL platform at the EMBL Grenoble utilize recombinant overexpression systems for heterologous expression of proteins and their complexes. Extension of the ACEMBL platform technology to include eukaryotic hosts such as insect and mammalian cells has been achieved. Efficient production of large multicomponent protein complexes for structural studies using the baculovirus/insect cell system can be hampered by a stoichiometric imbalance of the subunits produced. A polyprotein strategy has been developed to overcome this bottleneck and has been successfully implemented in our MultiBac baculovirus expression system for producing multiprotein complexes.

  14. iPPI-DB: an online database of modulators of protein-protein interactions.

    PubMed

    Labbé, Céline M; Kuenemann, Mélaine A; Zarzycka, Barbara; Vriend, Gert; Nicolaes, Gerry A F; Lagorce, David; Miteva, Maria A; Villoutreix, Bruno O; Sperandio, Olivier

    2016-01-01

    In order to boost the identification of low-molecular-weight drugs on protein-protein interactions (PPI), it is essential to properly collect and annotate experimental data about successful examples. This provides the scientific community with the necessary information to derive trends about privileged physicochemical properties and chemotypes that maximize the likelihood of promoting a given chemical probe to the most advanced stages of development. To this end we have developed iPPI-DB (freely accessible at http://www.ippidb.cdithem.fr), a database that contains the structure, some physicochemical characteristics, the pharmacological data and the profile of the PPI targets of several hundreds modulators of protein-protein interactions. iPPI-DB is accessible through a web application and can be queried according to two general approaches: using physicochemical/pharmacological criteria; or by chemical similarity to a user-defined structure input. In both cases the results are displayed as a sortable and exportable datasheet with links to external databases such as Uniprot, PubMed. Furthermore each compound in the table has a link to an individual ID card that contains its physicochemical and pharmacological profile derived from iPPI-DB data. This includes information about its binding data, ligand and lipophilic efficiencies, location in the PPI chemical space, and importantly similarity with known drugs, and links to external databases like PubChem, and ChEMBL. PMID:26432833

  15. The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledgebase of drug targets and their ligands.

    PubMed

    Pawson, Adam J; Sharman, Joanna L; Benson, Helen E; Faccenda, Elena; Alexander, Stephen P H; Buneman, O Peter; Davenport, Anthony P; McGrath, John C; Peters, John A; Southan, Christopher; Spedding, Michael; Yu, Wenyuan; Harmar, Anthony J

    2014-01-01

    The International Union of Basic and Clinical Pharmacology/British Pharmacological Society (IUPHAR/BPS) Guide to PHARMACOLOGY (http://www.guidetopharmacology.org) is a new open access resource providing pharmacological, chemical, genetic, functional and pathophysiological data on the targets of approved and experimental drugs. Created under the auspices of the IUPHAR and the BPS, the portal provides concise, peer-reviewed overviews of the key properties of a wide range of established and potential drug targets, with in-depth information for a subset of important targets. The resource is the result of curation and integration of data from the IUPHAR Database (IUPHAR-DB) and the published BPS 'Guide to Receptors and Channels' (GRAC) compendium. The data are derived from a global network of expert contributors, and the information is extensively linked to relevant databases, including ChEMBL, DrugBank, Ensembl, PubChem, UniProt and PubMed. Each of the ∼6000 small molecule and peptide ligands is annotated with manually curated 2D chemical structures or amino acid sequences, nomenclature and database links. Future expansion of the resource will complete the coverage of all the targets of currently approved drugs and future candidate targets, alongside educational resources to guide scientists and students in pharmacological principles and techniques. PMID:24234439

  16. Biological X-ray absorption spectroscopy and metalloproteomics.

    PubMed

    Ascone, Isabella; Strange, Richard

    2009-05-01

    In the past seven years the size of the known protein sequence universe has been rapidly expanding. At present, more then five million entries are included in the UniProtKB/TrEMBL protein database. In this context, a retrospective evaluation of recent X-ray absorption studies is undertaken to assess its potential role in metalloproteomics. Metalloproteomics is the structural and functional characterization of metal-binding proteins. This is a new area of active research which has particular relevance to biology and for which X-ray absorption spectroscopy is ideally suited. In the last three years, biological X-ray absorption spectroscopy (BioXAS) has been included among the techniques used in post-genomics initiatives for metalloprotein characterization. The emphasis of this review is on the progress in BioXAS that has emerged from recent meetings in 2007-2008. Developments required to enable BioXAS studies to better contribute to metalloproteomics throughput are also discussed. Overall, this paper suggests that X-ray absorption spectroscopy could have a higher impact on metalloproteomics, contributing significantly to the understanding of metal site structures and of reaction mechanisms for metalloproteins. PMID:19395808

  17. [Typing of cattle leukemia virus circulating in the Ukraine].

    PubMed

    Limanskiĭ, A P; Geue, L; Limanskaia, O Iu; Beier, D

    2004-01-01

    Bovine leucosis virus (BLV), circulating in the Ukrainian territory, was characterized through the definition of its subspecies affiliation. The pro-viral BLV DNA was isolated from peripheral-blood lymphocytes of naturally-HIV-infected black-variegate animals taken from leucosis-affected farms in the Kharkov Region. The env-gene fragment of pro-viral DNA was amplified, sequenced and analyzed after the amplicon had been treated by three restriction enzymes, i.e. BamH I, Bcl I and Pvu II. According to the analysis of restriction-fragments' length polymorphism, the Ukrainian BLV isolate can be classified as belonging to the Australian subspecies, i.e. to one of the 3 known subspecies. Multiple alignment and phylogenetic analysis of the env-gene fragment of BLV isolates from the EMBL database showed that evolutionally the Ukrainian isolate is distantly located from the isolates' clusters of the Belgian, Japanese and Australian subspecie and has the biggest quantity (4) of non-coinciding nucleotides for the analyzed highly conservative locus of the BLV env-gene with a length of 444 pair of nucleotides. PMID:15017853

  18. Exploring new scaffolds for angiotensin II receptor antagonism.

    PubMed

    Kritsi, Eftichia; Matsoukas, Minos-Timotheos; Potamitis, Constantinos; Karageorgos, Vlasios; Detsi, Anastasia; Magafa, Vasilliki; Liapakis, George; Mavromoustakos, Thomas; Zoumpoulakis, Panagiotis

    2016-09-15

    Nowadays, AT1 receptor (AT1R) antagonists (ARBs) constitute the one of the most prevalent classes of antihypertensive drugs that modulate the renin-angiotensin system (RAS). Their main uses include also treatment of diabetic nephropathy (kidney damage due to diabetes) and congestive heart failure. Towards this direction, our study has been focused on the discovery of novel agents bearing different scaffolds which may evolve as a new class of AT1 receptor antagonists. To fulfill this aim, a combination of computational approaches and biological assays were implemented. Particularly, a pharmacophore model was established and served as a 3D search query to screen the ChEMBL15 database. The reliability and accuracy of virtual screening results were improved by using molecular docking studies. In total, 4 compounds with completely diverse chemical scaffolds from potential ARBs, were picked and tested for their binding affinity to AT1 receptor. Results revealed high nanomolar to micromolar affinity (IC50) for all the compounds. Especially, compound 4 exhibited a binding affinity of 199nM. Molecular dynamics simulations were utilized in an effort to provide a molecular basis of their binding to AT1R in accordance to their biological activities. PMID:27480029

  19. Cloning of the cDNA for the human ATP synthase OSCP subunit (ATP5O) by exon trapping and mapping to chromosome 21q22.1-q22.2

    SciTech Connect

    Chen, Haiming; Morris, M.A.; Rossier, C.

    1995-08-10

    Exon trapping was used to clone portions of potential genes from human chromosome 21. One trapped sequence showed striking homology with the bovine and rat ATP synthase OSCP (oligomycin sensitivity conferring protein) subunit. We subsequently cloned the full-length human ATP synthase OSCP cDNA (GDB/HGMW approved name ATP50) from infant brain and muscle libraries and determined its nucleotide and deduced amino acid sequence (EMBL/GenBank Accession No. X83218). The encoded polypeptide contains 213 amino acids, with more than 80% identity to bovine and murine ATPase OSCP subunits and over 35% identity to Saccharomyces cerevisiae and sweet potato sequences. The human ATP5O gene is located at 21q22.1-q22.2, just proximal to D21S17, in YACs 860G11 and 838C7 of the Chumakov et al. YAC contig. The gene is expressed in all human tissues examined, most strongly in muscle and heart. This ATP5O subunit is a key structural component of the stalk of the mitochondrial respiratory chain F{sub 1}F{sub 0}-ATP synthase and as such may contribute in a gene dosage-dependent manner to the phenotype of Down syndrome (trisomy 21). 39 refs., 5 figs.

  20. Analyzing compound activity records and promiscuity degrees in light of publication statistics

    PubMed Central

    Hu, Ye; Bajorath, Jürgen

    2016-01-01

    For the generation of contemporary databases of bioactive compounds, activity information is usually extracted from the scientific literature. However, when activity data are analyzed, source publications are typically no longer taken into consideration. Therefore, compound activity data selected from ChEMBL were traced back to thousands of original publications, activity records including compound, assay, and target information were systematically generated, and their distributions across the literature were determined. In addition, publications were categorized on the basis of activity records. Furthermore, compound promiscuity, defined as the ability of small molecules to specifically interact with multiple target proteins, was analyzed in light of publication statistics, thus adding another layer of information to promiscuity assessment. It was shown that the degree of compound promiscuity was not influenced by increasing numbers of source publications. Rather, most non-promiscuous as well as promiscuous compounds, regardless of their degree of promiscuity, originated from single publications, which emerged as a characteristic feature of the medicinal chemistry literature. PMID:27347396

  1. The use of a mini-κ goniometer head in macromolecular crystallography diffraction experiments

    SciTech Connect

    Brockhauser, Sandor; Ravelli, Raimond B. G.; McCarthy, Andrew A.

    2013-07-01

    Hardware and software solutions for MX data-collection strategies using the EMBL/ESRF miniaturized multi-axis goniometer head are presented. Most macromolecular crystallography (MX) diffraction experiments at synchrotrons use a single-axis goniometer. This markedly contrasts with small-molecule crystallography, in which the majority of the diffraction data are collected using multi-axis goniometers. A novel miniaturized κ-goniometer head, the MK3, has been developed to allow macromolecular crystals to be aligned. It is available on the majority of the structural biology beamlines at the ESRF, as well as elsewhere. In addition, the Strategy for the Alignment of Crystals (STAC) software package has been developed to facilitate the use of the MK3 and other similar devices. Use of the MK3 and STAC is streamlined by their incorporation into online analysis tools such as EDNA. The current use of STAC and MK3 on the MX beamlines at the ESRF is discussed. It is shown that the alignment of macromolecular crystals can result in improved diffraction data quality compared with data obtained from randomly aligned crystals.

  2. Characterization of recombinant bacteriophages containing mosquito ribosomal RNA genes

    SciTech Connect

    Park, Y.J.

    1988-01-01

    A family of nine recombinant bacteriophages containing rRNA genes from cultured cells of the mosquito, Aedes albopictus, has been isolated by screening two different genomic DNA libraries - Charon 30 and EMBL 3 using {sup 32}P-labeled 18S and 28S rRNA as probes. These nine recombinant bacteriophages were characterized by restriction mapping, Southern blotting, and S1 nuclease analysis. The 18S rRNA coding region contains an evolutionarily conserved EcoRI site near the 3{prime}-end, and measures 1800 bp. The 28S rRNA genes were divided into {alpha} and {beta} coding regions measuring 1750 bp and 2000 bp, respectively. The gap between these two regions measures about 340 bp. No insertion sequences were found in the rRNA coding regions. The entire rDNA repeat unit had a minimum length of 15.6 kb, including a nontranscribed spacer region. The non-transcribed spacer region of cloned A. albopictus rDNA contained a common series of seven PvuI sites within a 1250 bp region upstream of the 18S rRNA coding region, and a proportion of this region also showed heterogeneity both in the length and in the restriction sites.

  3. A Rational Approach for the Identification of Non-Hydroxamate HDAC6-Selective Inhibitors

    PubMed Central

    Goracci, Laura; Deschamps, Nathalie; Randazzo, Giuseppe Marco; Petit, Charlotte; Dos Santos Passos, Carolina; Carrupt, Pierre-Alain; Simões-Pires, Claudia; Nurisso, Alessandra

    2016-01-01

    The human histone deacetylase isoform 6 (HDAC6) has been demonstrated to play a major role in cell motility and aggresome formation, being interesting for the treatment of multiple tumour types and neurodegenerative conditions. Currently, most HDAC inhibitors in preclinical or clinical evaluations are non-selective inhibitors, characterised by a hydroxamate zinc-binding group (ZBG) showing off-target effects and mutagenicity. The identification of selective HDAC6 inhibitors with novel chemical properties has not been successful yet, also because of the absence of crystallographic information that makes the rational design of HDAC6 selective inhibitors difficult. Using HDAC inhibitory data retrieved from the ChEMBL database and ligand-based computational strategies, we identified 8 original new non-hydroxamate HDAC6 inhibitors from the SPECS database, with activity in the low μM range. The most potent and selective compound, bearing a hydrazide ZBG, was shown to increase tubulin acetylation in human cells. No effects on histone H4 acetylation were observed. To the best of our knowledge, this is the first report of an HDAC6 selective inhibitor bearing a hydrazide ZBG. Its capability to passively cross the blood-brain barrier (BBB), as observed through PAMPA assays, and its low cytotoxicity in vitro, suggested its potential for drug development. PMID:27404291

  4. BioSAXS Sample Changer: a robotic sample changer for rapid and reliable high-throughput X-ray solution scattering experiments.

    PubMed

    Round, Adam; Felisaz, Franck; Fodinger, Lukas; Gobbo, Alexandre; Huet, Julien; Villard, Cyril; Blanchet, Clement E; Pernot, Petra; McSweeney, Sean; Roessle, Manfred; Svergun, Dmitri I; Cipriani, Florent

    2015-01-01

    Small-angle X-ray scattering (SAXS) of macromolecules in solution is in increasing demand by an ever more diverse research community, both academic and industrial. To better serve user needs, and to allow automated and high-throughput operation, a sample changer (BioSAXS Sample Changer) that is able to perform unattended measurements of up to several hundred samples per day has been developed. The Sample Changer is able to handle and expose sample volumes of down to 5 µl with a measurement/cleaning cycle of under 1 min. The samples are stored in standard 96-well plates and the data are collected in a vacuum-mounted capillary with automated positioning of the solution in the X-ray beam. Fast and efficient capillary cleaning avoids cross-contamination and ensures reproducibility of the measurements. Independent temperature control for the well storage and for the measurement capillary allows the samples to be kept cool while still collecting data at physiological temperatures. The Sample Changer has been installed at three major third-generation synchrotrons: on the BM29 beamline at the European Synchrotron Radiation Facility (ESRF), the P12 beamline at the PETRA-III synchrotron (EMBL@PETRA-III) and the I22/B21 beamlines at Diamond Light Source, with the latter being the first commercial unit supplied by Bruker ASC.

  5. Sequence and molecular characterization of a DNA region encoding the dibenzothiophene desulfurization operon of Rhodococcus sp. strain IGTS8.

    PubMed

    Piddington, C S; Kovacevich, B R; Rambosek, J

    1995-02-01

    Dibenzothiophene (DBT), a model compound for sulfur-containing organic molecules found in fossil fuels, can be desulfurized to 2-hydroxybiphenyl (2-HBP) by Rhodococcus sp. strain IGTS8. Complementation of a desulfurization (dsz) mutant provided the genes from Rhodococcus sp. strain IGTS8 responsible for desulfurization. A 6.7-kb TaqI fragment cloned in Escherichia coli-Rhodococcus shuttle vector pRR-6 was found to both complement this mutation and confer desulfurization to Rhodococcus fascians, which normally is not able to desulfurize DBT. Expression of this fragment in E. coli also conferred the ability to desulfurize DBT. A molecular analysis of the cloned fragment revealed a single operon containing three open reading frames involved in the conversion of DBT to 2-HBP. The three genes were designated dszA, dszB, and dszC. Neither the nucleotide sequences nor the deduced amino acid sequences of the enzymes exhibited significant similarity to sequences obtained from the GenBank, EMBL, and Swiss-Prot databases, indicating that these enzymes are novel enzymes. Subclone analyses revealed that the gene product of dszC converts DBT directly to DBT-sulfone and that the gene products of dszA and dszB act in concert to convert DBT-sulfone to 2-HBP.

  6. Toward a general predictive QSAR model for gamma-secretase inhibitors.

    PubMed

    Ajmani, Subhash; Janardhan, Sridhara; Viswanadhan, Vellarkad N

    2013-08-01

    Gamma secretase (GS) is an appealing drug target for Alzheimer disease and cancer because of its central role in the processing of amyloid precursor protein and the notch family of proteins. In the absence of three-dimensional structure of GS, there is an urgent need for new methods for the prediction and screening of GS inhibitors, for facilitating discovery of novel GS inhibitors. The present study reports QSAR studies on diverse chemical classes comprising 233 compounds collected from the ChEMBL database. Herein, continuous [PLS regression and neural-network (NN)] and categorical QSAR models (NN and linear discriminant analysis) were developed to obtain pertinent descriptors responsible for variation of GS inhibitor potency. Also, SAR within various chemical classes of compounds is analyzed with respect to important QSAR descriptors, which revealed the significance of electronegative substitutions on aryl rings (PEOE3) in determining variation of GS inhibitor potency. Furthermore, substitution of acyclic amines with N-substituted cyclic amines appears to be favorable for enhancing GS inhibitor potency by increasing the values of sssN_Cnt and number of aliphatic rings. The models developed are statistically significant and improve our understanding of compounds contributing toward GS inhibitor potency and aid in the rational design of novel potent GS inhibitors. PMID:23612850

  7. Automated acquisition and analysis of small angle X-ray scattering data

    NASA Astrophysics Data System (ADS)

    Franke, Daniel; Kikhney, Alexey G.; Svergun, Dmitri I.

    2012-10-01

    Small Angle X-ray Scattering (SAXS) is a powerful tool in the study of biological macromolecules providing information about the shape, conformation, assembly and folding states in solution. Recent advances in robotic fluid handling make it possible to perform automated high throughput experiments including fast screening of solution conditions, measurement of structural responses to ligand binding, changes in temperature or chemical modifications. Here, an approach to full automation of SAXS data acquisition and data analysis is presented, which advances automated experiments to the level of a routine tool suitable for large scale structural studies. The approach links automated sample loading, primary data reduction and further processing, facilitating queuing of multiple samples for subsequent measurement and analysis and providing means of remote experiment control. The system was implemented and comprehensively tested in user operation at the BioSAXS beamlines X33 and P12 of EMBL at the DORIS and PETRA storage rings of DESY, Hamburg, respectively, but is also easily applicable to other SAXS stations due to its modular design.

  8. Organising multi-dimensional biological image information: the BioImage Database.

    PubMed

    Carazo, J M; Stelzer, E H; Engel, A; Fita, I; Henn, C; Machtynger, J; McNeil, P; Shotton, D M; Chagoyen, M; de Alarcón, P A; Fritsch, R; Heymann, J B; Kalko, S; Pittet, J J; Rodriguez-Tomé, P; Boudier, T

    1999-01-01

    Nowadays it is possible to unravel complex information at all levels of cellular organization by obtaining multi-dimensional image information. At the macromolecular level, three-dimensional (3D) electron microscopy, together with other techniques, is able to reach resolutions at the nanometer or subnanometer level. The information is delivered in the form of 3D volumes containing samples of a given function, for example, the electron density distribution within a given macromolecule. The same situation happens at the cellular level with the new forms of light microscopy, particularly confocal microscopy, all of which produce biological 3D volume information. Furthermore, it is possible to record sequences of images over time (videos), as well as sequences of volumes, bringing key information on the dynamics of living biological systems. It is in this context that work on BioImage started two years ago, and that its first version is now presented here. In essence, BioImage is a database specifically designed to contain multi-dimensional images, perform queries and interactively work with the resulting multi-dimensional information on the World Wide Web, as well as accomplish the required cross-database links. Two sister home pages of BioImage can be accessed at http://www. bioimage.org and http://www-embl.bioimage.org

  9. Draft genome sequence of pathogenic bacteria Vibrio parahaemolyticus strain Ba94C2, associated with acute hepatopancreatic necrosis disease isolate from South America.

    PubMed

    Restrepo, Leda; Bayot, Bonny; Betancourt, Irma; Pinzón, Andres

    2016-09-01

    Vibrio parahaemolyticus is a pathogenic bacteria which has been associated to the early mortality syndrome (EMS) also known as hepatopancreatic necrosis disease (AHPND) causing high mortality in shrimp farms. Pathogenic strains contain two homologous genes related to insecticidal toxin genes, PirA and PirB, these toxin genes are located on a plasmid contained within the bacteria. Genomic sequences have allowed the finding of two strains with a divergent structure related to the geographic region from where they were found. The isolates from the geographic collection of Southeast Asia and Mexico show variable regions on the plasmid genome, indicating that even though they are not alike they still conserve the toxin genes. In this paper, we report for the first time, a pathogenic V. parahaemolyticus strain in shrimp from South America that showed symptoms of AHPND. The genomic analysis revealed that this strain of V. parahaemolyticus found in South America appears to be more related to the Southeast Asia as compared to the Mexican strains. This finding is of major importance for the shrimp industry, especially in regards to the urgent need for disease control strategies to avoid large EMS outbreaks and economic loss, and to determine its dispersion in South America. The whole-genome shotgun project of V. parahaemolyticus strain Ba94C2 have been deposited at DDBJ/EMBL/GenBank under the accession PRJNA335761.

  10. InterPro, progress and status in 2005.

    PubMed

    Mulder, Nicola J; Apweiler, Rolf; Attwood, Teresa K; Bairoch, Amos; Bateman, Alex; Binns, David; Bradley, Paul; Bork, Peer; Bucher, Phillip; Cerutti, Lorenzo; Copley, Richard; Courcelle, Emmanuel; Das, Ujjwal; Durbin, Richard; Fleischmann, Wolfgang; Gough, Julian; Haft, Daniel; Harte, Nicola; Hulo, Nicolas; Kahn, Daniel; Kanapin, Alexander; Krestyaninova, Maria; Lonsdale, David; Lopez, Rodrigo; Letunic, Ivica; Madera, Martin; Maslen, John; McDowall, Jennifer; Mitchell, Alex; Nikolskaya, Anastasia N; Orchard, Sandra; Pagni, Marco; Ponting, Chris P; Quevillon, Emmanuel; Selengut, Jeremy; Sigrist, Christian J A; Silventoinen, Ville; Studholme, David J; Vaughan, Robert; Wu, Cathy H

    2005-01-01

    InterPro, an integrated documentation resource of protein families, domains and functional sites, was created to integrate the major protein signature databases. Currently, it includes PROSITE, Pfam, PRINTS, ProDom, SMART, TIGRFAMs, PIRSF and SUPERFAMILY. Signatures are manually integrated into InterPro entries that are curated to provide biological and functional information. Annotation is provided in an abstract, Gene Ontology mapping and links to specialized databases. New features of InterPro include extended protein match views, taxonomic range information and protein 3D structure data. One of the new match views is the InterPro Domain Architecture view, which shows the domain composition of protein matches. Two new entry types were introduced to better describe InterPro entries: these are active site and binding site. PIRSF and the structure-based SUPERFAMILY are the latest member databases to join InterPro, and CATH and PANTHER are soon to be integrated. InterPro release 8.0 contains 11 007 entries, representing 2573 domains, 8166 families, 201 repeats, 26 active sites, 21 binding sites and 20 post-translational modification sites. InterPro covers over 78% of all proteins in the Swiss-Prot and TrEMBL components of UniProt. The database is available for text- and sequence-based searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro).

  11. Pneumothorax spontané secondaire post opératoire compliquant une paralysie récurrentielle

    PubMed Central

    Joulali, Toufik; Derkaou, Ali; Shimi, Abdelkarim; Khatouf, Mohammed

    2014-01-01

    Le Pneumothorax spontané est défini par un épanchement gazeux de la grande cavité pleurale en dehors de tout traumatisme ou manipulation instrumentale. Son incidence est estimée à 28/100000 pour les hommes et 6/100000 pour les femmes. Les étiologies sont dominées par la broncho-pneumopathies chroniques et obstructives. Le tableau clinique est souvent grave d'emblé nécessitant une exsufflation à l'aiguille et/ou un drainage thoracique. Les récidives sont assez fréquentes et la mortalité reste assez élevée en comparaison avec les pneumothorax post traumatique ou les pneumothorax primaires. Nous rapportons le cas d'une patiente présentant en post opératoire un pneumothorax spontané sur un poumon métastatique et compliquant une paralysie récurrentielle. PMID:25419334

  12. Cloning and characterization of a cDNA encoding an A-kinase anchoring protein located in the centrosome, AKAP450.

    PubMed Central

    Witczak, O; Skålhegg, B S; Keryer, G; Bornens, M; Taskén, K; Jahnsen, T; Orstavik, S

    1999-01-01

    A combination of protein kinase A type II (RII) overlay screening, database searches and PCR was used to identify a centrosomal A-kinase anchoring protein. A cDNA with an 11.7 kb open reading frame was characterized and found to correspond to 50 exons of genomic sequence on human chromosome 7q21-22. This cDNA clone encoded a 3908 amino acid protein of 453 kDa, that was designated AKAP450 (DDBJ/EMBL/GenBank accession No. AJ131693). Sequence comparison demonstrated that the open reading frame contained a previously characterized cDNA encoding Yotiao, as well as the human homologue of AKAP120. Numerous coiled-coil structures were predicted from AKAP450, and weak homology to pericentrin, giantin and other structural proteins was observed. A putative RII-binding site was identified involving amino acid 2556 of AKAP450 by mutation analysis combined with RII overlay and an amphipatic helix was predicted in this region. Immunoprecipitation of RII from RIPA-buffer extracts of HeLa cells demonstrated co-precipitation of AKAP450. By immunofluorecent labeling with specific antibodies it was demonstrated that AKAP450 localized to centrosomes. Furthermore, AKAP450 was shown to co-purify in centrosomal preparations. The observation of two mRNAs and several splice products suggests additional functions for the AKAP450 gene. PMID:10202149

  13. Xlink Analyzer: software for analysis and visualization of cross-linking data in the context of three-dimensional structures.

    PubMed

    Kosinski, Jan; von Appen, Alexander; Ori, Alessandro; Karius, Kai; Müller, Christoph W; Beck, Martin

    2015-03-01

    Structural characterization of large multi-subunit protein complexes often requires integrating various experimental techniques. Cross-linking mass spectrometry (XL-MS) identifies proximal protein residues and thus is increasingly used to map protein interactions and determine the relative orientation of subunits within the structure of protein complexes. To fully adapt XL-MS as a structure characterization technique, we developed Xlink Analyzer, a software tool for visualization and analysis of XL-MS data in the context of the three-dimensional structures. Xlink Analyzer enables automatic visualization of cross-links, identifies cross-links violating spatial restraints, calculates violation statistics, maps chemically modified surfaces, and allows interactive manipulations that facilitate analysis of XL-MS data and aid designing new experiments. We demonstrate these features by mapping interaction sites within RNA polymerase I and the Rvb1/2 complex. Xlink Analyzer is implemented as a plugin to UCSF Chimera, a standard structural biology software tool, and thus enables seamless integration of XL-MS data with, e.g. fitting of X-ray structures to EM maps. Xlink Analyzer is available for download at http://www.beck.embl.de/XlinkAnalyzer.html.

  14. Kernel Target Alignment Parameter: A New Modelability Measure for Regression Tasks.

    PubMed

    Marcou, Gilles; Horvath, Dragos; Varnek, Alexandre

    2016-01-25

    In this paper, we demonstrate that the kernel target alignment (KTA) parameter can efficiently be used to estimate the relevance of molecular descriptors for QSAR modeling on a given data set, i.e., as a modelability measure. The efficiency of KTA to assess modelability was demonstrated in two series of QSAR modeling studies, either varying different descriptor spaces for one same data set, or comparing various data sets within one same descriptor space. Considered data sets included 25 series of various GPCR binders with ChEMBL-reported pKi values, and a toxicity data set. Employed descriptor spaces covered more than 100 different ISIDA fragment descriptor types, and ChemAxon BCUT terms. Model performances (RMSE) were seen to anticorrelate consistently with the KTA parameter. Two other modelability measures were employed for benchmarking purposes: the Jaccard distance average over the data set (Div), and a measure related to the normalized mean absolute error (MAE) obtained in 1-nearest neighbors calculations on the training set (Sim = 1 - MAE). It has been demonstrated that both Div and Sim perform similarly to KTA. However, a consensus index combining KTA, Div and Sim provides a more robust correlation with RMSE than any of the individual modelability measures.

  15. Toucan: deciphering the cis-regulatory logic of coregulated genes

    PubMed Central

    Aerts, Stein; Thijs, Gert; Coessens, Bert; Staes, Mik; Moreau, Yves; De Moor, Bart

    2003-01-01

    TOUCAN is a Java application for the rapid discovery of significant cis-regulatory elements from sets of coexpressed or coregulated genes. Biologists can automatically (i) retrieve genes and intergenic regions, (ii) identify putative regulatory regions, (iii) score sequences for known transcription factor binding sites, (iv) identify candidate motifs for unknown binding sites, and (v) detect those statistically over-represented sites that are characteristic for a gene set. Genes or intergenic regions are retrieved from Ensembl or EMBL, together with orthologs and supporting information. Orthologs are aligned and syntenic regions are selected as candidate regulatory regions. Putative sites for known transcription factors are detected using our MotifScanner, which scores position weight matrices using a probabilistic model. New motifs are detected using our MotifSampler based on Gibbs sampling. Binding sites characteristic for a gene set—and thus statistically over-represented with respect to a reference sequence set—are found using a binomial test. We have validated Toucan by analyzing muscle-specific genes, liver-specific genes and E2F target genes; we have easily detected many known binding sites within intergenic DNA and identified new biologically plausible sites for known and unknown transcription factors. Software available at http://www.esat.kuleuven.ac.be/∼dna/BioI/Software.html. PMID:12626717

  16. Candida famata (Debaryomyces hansenii) DNA sequences containing genes involved in riboflavin synthesis.

    PubMed

    Voronovsky, Andriy Y; Abbas, Charles A; Dmytruk, Kostyantyn V; Ishchuk, Olena P; Kshanovska, Barbara V; Sybirna, Kateryna A; Gaillardin, Claude; Sibirny, Andriy A

    2004-11-01

    Previously cloned Candida famata (Debaryomyces hansenii) strain VKM Y-9 genomic DNA fragments containing genes RIB1 (codes for GTP cyclohydrolase II), RIB2 (encodes specific reductase), RIB5 (codes for dimethylribityllumazine synthase), RIB6 (encodes dihydroxybutanone phosphate synthase) and RIB7 (codes for riboflavin synthase) were sequenced. The derived amino acid sequences of C. famata RIB genes showed extensive homology to the corresponding sequences of riboflavin synthesis enzymes of other yeast species. The highest identity was observed to homologues of D. hansenii CBS767, as C. famata is the anamorph of this hemiascomycetous yeast. The D. hansenii CBS767 RIB3 gene encoding specific deaminase was cloned. This gene successfully complemented riboflavin auxotrophy of the rib3 mutant of flavinogenic yeast, Pichia guilliermondii. Putative iron-responsive elements (potential sites for binding of the transcription factors Fep1p or Aft1p and Aft2p) were found in the upstream regions of some C. famata and D. hansenii RIB genes. The sequences of C. famata RIB genes have been submitted to the EMBL data library under Accession Nos AJ810169-AJ810173. PMID:15543522

  17. Quantitative Structure-Antioxidant Activity Models of Isoflavonoids: A Theoretical Study.

    PubMed

    Castellano, Gloria; Torrens, Francisco

    2015-06-08

    Seventeen isoflavonoids from isoflavone, isoflavanone and isoflavan classes are selected from Dalbergia parviflora. The ChEMBL database is representative from these molecules, most of which result highly drug-like. Binary rules appear risky for the selection of compounds with high antioxidant capacity in complementary xanthine/xanthine oxidase, ORAC, and DPPH model assays. Isoflavonoid structure-activity analysis shows the most important properties (log P, log D, pKa, QED, PSA, NH + OH ≈ HBD, N + O ≈ HBA). Some descriptors (PSA, HBD) are detected as more important than others (size measure Mw, HBA). Linear and nonlinear models of antioxidant potency are obtained. Weak nonlinear relationships appear between log P, etc. and antioxidant activity. The different capacity trends for the three complementary assays are explained. Isoflavonoids potency depends on the chemical form that determines their solubility. Results from isoflavonoids analysis will be useful for activity prediction of new sets of flavones and to design drugs with antioxidant capacity, which will prove beneficial for health with implications for antiageing therapy.

  18. Pseudothionin-St1, a potato peptide active against potato pathogens.

    PubMed

    Moreno, M; Segura, A; García-Olmedo, F

    1994-07-01

    A 5-kDa polypeptide, pseudothionin Solanum tuberosum 1 (Pth-St1), which was active against Clavibacter michiganensis subspecies sepedonicus, a bacterial pathogen of potatoes, has been purified from the buffer-insoluble fraction of potato tubers by salt extraction and HPCL. Pth-St1 was also active against other potato pathogens tested (Pseudomonas solanacearum and Fusarium solani). The N-terminal amino acid sequence of this peptide was identical (except for a N/H substitution at position 2) to that deduced from a previously reported cDNA sequence (EMBL accession number X-13180), which had been misclassified as a Browman-Birk protease inhibitor. Pth-St1 did not inhibit either trypsin or insect alpha-amylase activities, and, in contrast with true thionins, did not affect cell-free protein synthesis or beta-glucuronidase activity. Northern-blot and tissue-print analyses showed that steady-state mRNA levels were highest in flowers (especially in petals), followed by tubers (especially in the epidermal cell layers and in leaf primordia), stems and leaves. Infection of leaves with a bacterial pathogen suspended in 10 mM MgCl2 switched off the gene, whereas mock inoculation with 10 mM MgCl2 alone induced higher mRNA levels.

  19. The Bioperl toolkit: Perl modules for the life sciences.

    PubMed

    Stajich, Jason E; Block, David; Boulez, Kris; Brenner, Steven E; Chervitz, Stephen A; Dagdigian, Chris; Fuellen, Georg; Gilbert, James G R; Korf, Ian; Lapp, Hilmar; Lehväslaiho, Heikki; Matsalla, Chad; Mungall, Chris J; Osborne, Brian I; Pocock, Matthew R; Schattner, Peter; Senger, Martin; Stein, Lincoln D; Stupka, Elia; Wilkinson, Mark D; Birney, Ewan

    2002-10-01

    The Bioperl project is an international open-source collaboration of biologists, bioinformaticians, and computer scientists that has evolved over the past 7 yr into the most comprehensive library of Perl modules available for managing and manipulating life-science information. Bioperl provides an easy-to-use, stable, and consistent programming interface for bioinformatics application programmers. The Bioperl modules have been successfully and repeatedly used to reduce otherwise complex tasks to only a few lines of code. The Bioperl object model has been proven to be flexible enough to support enterprise-level applications such as EnsEMBL, while maintaining an easy learning curve for novice Perl programmers. Bioperl is capable of executing analyses and processing results from programs such as BLAST, ClustalW, or the EMBOSS suite. Interoperation with modules written in Python and Java is supported through the evolving BioCORBA bridge. Bioperl provides access to data stores such as GenBank and SwissProt via a flexible series of sequence input/output modules, and to the emerging common sequence data storage format of the Open Bioinformatics Database Access project. This study describes the overall architecture of the toolkit, the problem domains that it addresses, and gives specific examples of how the toolkit can be used to solve common life-sciences problems. We conclude with a discussion of how the open-source nature of the project has contributed to the development effort. PMID:12368254

  20. Candida famata (Debaryomyces hansenii) DNA sequences containing genes involved in riboflavin synthesis.

    PubMed

    Voronovsky, Andriy Y; Abbas, Charles A; Dmytruk, Kostyantyn V; Ishchuk, Olena P; Kshanovska, Barbara V; Sybirna, Kateryna A; Gaillardin, Claude; Sibirny, Andriy A

    2004-11-01

    Previously cloned Candida famata (Debaryomyces hansenii) strain VKM Y-9 genomic DNA fragments containing genes RIB1 (codes for GTP cyclohydrolase II), RIB2 (encodes specific reductase), RIB5 (codes for dimethylribityllumazine synthase), RIB6 (encodes dihydroxybutanone phosphate synthase) and RIB7 (codes for riboflavin synthase) were sequenced. The derived amino acid sequences of C. famata RIB genes showed extensive homology to the corresponding sequences of riboflavin synthesis enzymes of other yeast species. The highest identity was observed to homologues of D. hansenii CBS767, as C. famata is the anamorph of this hemiascomycetous yeast. The D. hansenii CBS767 RIB3 gene encoding specific deaminase was cloned. This gene successfully complemented riboflavin auxotrophy of the rib3 mutant of flavinogenic yeast, Pichia guilliermondii. Putative iron-responsive elements (potential sites for binding of the transcription factors Fep1p or Aft1p and Aft2p) were found in the upstream regions of some C. famata and D. hansenii RIB genes. The sequences of C. famata RIB genes have been submitted to the EMBL data library under Accession Nos AJ810169-AJ810173.

  1. Dynamics based pharmacophore models for screening potential inhibitors of mycobacterial cyclopropane synthase.

    PubMed

    Choudhury, Chinmayee; Priyakumar, U Deva; Sastry, G Narahari

    2015-04-27

    The therapeutic challenges in the treatment of tuberculosis demand multidisciplinary approaches for the identification of potential drug targets as well as fast and accurate techniques to screen huge chemical libraries. Mycobacterial cyclopropane synthase (CmaA1) has been shown to be essential for the survival of the bacteria due to its critical role in the synthesis of mycolic acids. The present study proposes pharmacophore models based on the structure of CmaA1 taking into account its various states in the cyclopropanation process, and their dynamic nature as assessed using molecular dynamics (MD) simulations. The qualities of these pharmacophore models were validated by mapping 23 molecules that have been previously reported to exhibit inhibitory activities on CmaA1. Additionally, 1398 compounds that have been shown to be inactive for tuberculosis were collected from the ChEMBL database and were screened against the models for validation. The models were further validated by comparing the results from pharmacophore mapping with the results obtained from docking these molecules with the respective protein structures. The best models are suggested by validating all the models based on their screening abilities and by comparing with docking results. The models generated from the MD trajectories were found to perform better than the one generated based on the crystal structure demonstrating the importance of incorporating receptor flexibility in drug design.

  2. MetaboLights: An Open-Access Database Repository for Metabolomics Data.

    PubMed

    Kale, Namrata S; Haug, Kenneth; Conesa, Pablo; Jayseelan, Kalaivani; Moreno, Pablo; Rocca-Serra, Philippe; Nainala, Venkata Chandrasekhar; Spicer, Rachel A; Williams, Mark; Li, Xuefei; Salek, Reza M; Griffin, Julian L; Steinbeck, Christoph

    2016-01-01

    MetaboLights is the first general purpose, open-access database repository for cross-platform and cross-species metabolomics research at the European Bioinformatics Institute (EMBL-EBI). Based upon the open-source ISA framework, MetaboLights provides Metabolomics Standard Initiative (MSI) compliant metadata and raw experimental data associated with metabolomics experiments. Users can upload their study datasets into the MetaboLights Repository. These studies are then automatically assigned a stable and unique identifier (e.g., MTBLS1) that can be used for publication reference. The MetaboLights Reference Layer associates metabolites with metabolomics studies in the archive and is extensively annotated with data fields such as structural and chemical information, NMR and MS spectra, target species, metabolic pathways, and reactions. The database is manually curated with no specific release schedules. MetaboLights is also recommended by journals for metabolomics data deposition. This unit provides a guide to using MetaboLights, downloading experimental data, and depositing metabolomics datasets using user-friendly submission tools. PMID:27010336

  3. One of the fumarate reductase isoenzymes from Saccharomyces cerevisiae is encoded by the OSM1 gene.

    PubMed

    Muratsubaki, H; Enomoto, K

    1998-04-15

    Soluble fumarate reductase from yeast irreversibly catalyzes the reduction of fumarate to succinate and has noncovalently bound flavin adenine dinucleotide. In yeast, there are two isoenzymes of fumarate reductase, which can be distinguished on the basis of their absorption or nonabsorption to DE-52 columns. Previously, we have purified FRDS1 and isolated its gene (FRDS) from Saccharomyces cerevisiae. In the present study, FRDS2 was purified to homogeneity by four chromatography steps. The N-terminal and C-terminal amino acid sequences of FRDS2 were identical to the deduced amino acid sequence of the OSM1 gene (EMBL Database Accession No. L-26347), whose isolation and biochemical properties have not been studied up until now. From these results, we conclude that FRDS2 is encoded by the OSM1 gene. The deduced amino acid sequence of the OSM1 gene revealed that FRDS2 is synthesized as a precursor protein containing a presequence composed of 32 amino acid residues. The mature enzyme consists of a protein of 469 amino acid residues with a molecular weight of 51,370. The N-terminal extension had the characteristics of a typical signal sequence required for targeting and sorting to a noncytosolic destination. In fact, FRDS2 was found to be located in promitochondria.

  4. Protein folds and families: sequence and structure alignments.

    PubMed

    Holm, L; Sander, C

    1999-01-01

    Dali and HSSP are derived databases organizing protein space in the structurally known regions. We use an automatic structure alignment program (Dali) for the classification of all known 3D structures based on all-against-all comparison of 3D structures in the Protein Data Bank. The HSSP database associates 1D sequences with known 3D structures using a position-weighted dynamic programming method for sequence profile alignment (MaxHom). As a result, the HSSP database not only provides aligned sequence families, but also implies secondary and tertiary structures covering 36% of all sequences in Swiss-Prot. The structure classification by Dali and the sequence families in HSSP can be browsed jointly from a web interface providing a rich network of links between neighbours in fold space, between domains and proteins, and between structures and sequences. In particular, this results in a database of explicit multiple alignments of protein families in the twilight zone of sequence similarity. The organization of protein structures and families provides a map of the currently known regions of the protein universe that is useful for the analysis of folding principles, for the evolutionary unification of protein families and for maximizing the information return from experimental structure determination. The databases are available from http://www.embl-ebi.ac.uk/dali/

  5. Application of an efficient strategy with a phage lambda vector for constructing a physical map of the amyloplast genome of sycamore (Acer pseudoplatanus).

    PubMed

    Ngernprasirtsiri, J; Kobayashi, H

    1990-01-01

    Amyloplasts were isolated from a heterotrophic culture cell line of a woody plant, sycamore (Acer pseudoplatanus), and their DNA was purified. Conventional procedures for making a physical map were not easily applicable to the amyloplast DNA, since the yield of DNA was too low and the presence of repeated sequences interfered with the analysis. Therefore, the pieces of amyloplast DNA starting with a few micrograms of DNA were cloned in the lambda Fix vector, which is a derivative of lambda EMBL vectors improved for efficient cloning and gene walking. Cloned DNA fragments were randomly picked, mapped for restriction endonuclease sites by a refined procedure, and combined by overlapping their physical maps. The DNA library was also subjected to screening by gene walking using promoters recognized by T3 and T7 RNA polymerases in the vector to fill the gaps between sequences determined by overlapping the physical maps. In this way, we constructed the entire DNA library and the complete physical map of the amyloplast DNA. The sycamore amyloplast genome was composed of 141.7-kbp nucleotides with the same gene arrangement as that of tobacco chloroplasts.

  6. Isolation of nine gene sequences induced by silica in murine macrophages

    SciTech Connect

    Segade, F.; Claudio, E.; Wrobel, K.; Ramos, S.; Lazo, P.S.

    1995-03-01

    Macrophage activation by silica is the initial step in the development of silicosis. To identify genes that might be involved in silica-mediated activation, RAW 264.7 mouse macrophages were treated with silica for 48 h, and a subtracted cDNA library enriched for silica-induced genes (SIG) was constructed and differently screened. Nine cDNA clones (designated SIG-12, -14, -20, -41, -61, -81, -91, and -111) were partially sequenced and compared with sequences in GenBank/EMBL databases. SIG-12, -14, and -20 corresponded to the genes for ribosomal proteins L13A, L32, and L26, respectively. SIG-61 is the mouse homologue of p21 RhoC. SIG-91 is identical to the 67-kDa high-affinity laminin receptor. Four genes were not identified and are novel. All of the mRNAs corresponding to the nine cloned cDNAs were inducible by silica. Steady-state levels of mRNAs in RAW 264.7 cells treated with various macrophage activators and inducers of signal transduction pathways were determined. A complex pattern of induction and repression was found, indicating that upon phagocytosis of silica particles, many regulatory mechanisms of genes expression are simultaneously triggered. 55 refs., 4 figs., 1 tab.

  7. Determination of internal transcribed spacer regions (ITS) in Trichomonas vaginalis isolates and differentiation among Trichomonas species.

    PubMed

    Ibáñez-Escribano, Alexandra; Nogal-Ruiz, Juan José; Arán, Vicente J; Escario, José Antonio; Gómez-Barrio, Alicia; Alderete, J F

    2014-04-01

    The nucleotide sequence of the 5.8S rRNA gene and the flanked internal transcribed spacer (ITS) regions of six Trichomonas vaginalis isolates with different metronidazole sensitivity and geographic origin were genotyped. A multiple sequence alignment was performed with different sequences of other isolates available at the GenBank/EMBL/DDBJ databases, which revealed 5 different sequence patterns. Although a stable mutation in position 66 of the ITS1 (C66T) was observed in 26% (9/34) of the T. vaginalis sequences analyzed, there was 99.7% ITS nucleotide sequence identity among isolates for this sequence. The nucleotide sequence variation among other species of the genus Trichomonas ranged from 3.4% to 9.1%. Surprisingly, the % identity between T. vaginalis and Pentatrichomonas hominis was ~83%. There was >40% divergence in the ITS sequence between T. vaginalis and Tritrichomonas spp., including Tritrichomonas augusta, Tritrichomonas muris, and Tritrichomonas nonconforma and with Tetratrichomonas prowazeki. Dendrograms grouped the trichomonadid sequences in robust clades according to their genera. The absence of nucleotide divergence in the hypervariable ITS regions between T. vaginalis isolates suggests the early divergence of the parasite. Importantly, these data show this ITS1-5.8S rRNA-ITS2 region suitable for inter-species differentiation. PMID:24412628

  8. Functional expression of pig renal organic anion transporter 3 (pOAT3).

    PubMed

    Hagos, Yohannes; Braun, Isabella M; Krick, Wolfgang; Burckhardt, Gerhard; Bahn, Andrew

    2005-05-01

    With the cloning of pig renal organic anion transporter 1 (pOAT1) (Biochimie 84 (2002) 1219) we set up a model system for comparative studies of cloned and natively isolated membrane located transport proteins. Meanwhile, another transport protein involved in p-aminohippurate (PAH) uptake on the basolateral side of the proximal tubule cells was identified, designated organic anion transporter 3 (OAT3). To explore the contribution of pOAT1 to the PAH clearance in comparison to OAT3, it was the aim of this study to extend our model by cloning of the pig ortholog of OAT3. Sequence comparisons of human organic anion transporter 3 (hOAT3) with the expressed sequence tag (EST) database revealed a clone and partial sequence of the pig renal organic anion transporter 3 (pOAT3) ortholog. Sequencing of the entire open reading frame resulted in a protein of 543 amino acid residues encoded by 1632 base pairs (EMBL Acc. No. AJ587003). It showed high homologies of 81%, 80%, 76%, and 77% to the human, rabbit, rat, and mouse OAT3, respectively. A functional characterization of pOAT3 in Xenopus laevis oocytes yielded an apparent Km (Kt) for [3H]estrone sulfate of 7.8 +/- 1.3 microM. Moreover, pOAT3 mediated [3H]estrone sulfate uptake was almost abolished by 0.5 mM of glutarate, dehydroepiandosterone sulfate, or probenecid consistent with the hallmarks of OAT3 function.

  9. Quantitative Structure-Antioxidant Activity Models of Isoflavonoids: A Theoretical Study

    PubMed Central

    Castellano, Gloria; Torrens, Francisco

    2015-01-01

    Seventeen isoflavonoids from isoflavone, isoflavanone and isoflavan classes are selected from Dalbergia parviflora. The ChEMBL database is representative from these molecules, most of which result highly drug-like. Binary rules appear risky for the selection of compounds with high antioxidant capacity in complementary xanthine/xanthine oxidase, ORAC, and DPPH model assays. Isoflavonoid structure-activity analysis shows the most important properties (log P, log D, pKa, QED, PSA, NH + OH ≈ HBD, N + O ≈ HBA). Some descriptors (PSA, HBD) are detected as more important than others (size measure Mw, HBA). Linear and nonlinear models of antioxidant potency are obtained. Weak nonlinear relationships appear between log P, etc. and antioxidant activity. The different capacity trends for the three complementary assays are explained. Isoflavonoids potency depends on the chemical form that determines their solubility. Results from isoflavonoids analysis will be useful for activity prediction of new sets of flavones and to design drugs with antioxidant capacity, which will prove beneficial for health with implications for antiageing therapy. PMID:26062128

  10. STITCH 3: zooming in on protein–chemical interactions

    PubMed Central

    Kuhn, Michael; Szklarczyk, Damian; Franceschini, Andrea; von Mering, Christian; Jensen, Lars Juhl; Bork, Peer

    2012-01-01

    To facilitate the study of interactions between proteins and chemicals, we have created STITCH, an aggregated database of interactions connecting over 300 000 chemicals and 2.6 million proteins from 1133 organisms. Compared to the previous version, the number of chemicals with interactions and the number of high-confidence interactions both increase 4-fold. The database can be accessed interactively through a web interface, displaying interactions in an integrated network view. It is also available for computational studies through downloadable files and an API. As an extension in the current version, we offer the option to switch between two levels of detail, namely whether stereoisomers of a given compound are shown as a merged entity or as separate entities. Separate display of stereoisomers is necessary, for example, for carbohydrates and chiral drugs. Combining the isomers increases the coverage, as interaction databases and publications found through text mining will often refer to compounds without specifying the stereoisomer. The database is accessible at http://stitch.embl.de/. PMID:22075997

  11. Gramene 2016: comparative plant genomics and pathway resources.

    PubMed

    Tello-Ruiz, Marcela K; Stein, Joshua; Wei, Sharon; Preece, Justin; Olson, Andrew; Naithani, Sushma; Amarasinghe, Vindhya; Dharmawardhana, Palitha; Jiao, Yinping; Mulvaney, Joseph; Kumari, Sunita; Chougule, Kapeel; Elser, Justin; Wang, Bo; Thomason, James; Bolser, Daniel M; Kerhornou, Arnaud; Walts, Brandon; Fonseca, Nuno A; Huerta, Laura; Keays, Maria; Tang, Y Amy; Parkinson, Helen; Fabregat, Antonio; McKay, Sheldon; Weiser, Joel; D'Eustachio, Peter; Stein, Lincoln; Petryszak, Robert; Kersey, Paul J; Jaiswal, Pankaj; Ware, Doreen

    2016-01-01

    Gramene (http://www.gramene.org) is an online resource for comparative functional genomics in crops and model plant species. Its two main frameworks are genomes (collaboration with Ensembl Plants) and pathways (The Plant Reactome and archival BioCyc databases). Since our last NAR update, the database website adopted a new Drupal management platform. The genomes section features 39 fully assembled reference genomes that are integrated using ontology-based annotation and comparative analyses, and accessed through both visual and programmatic interfaces. Additional community data, such as genetic variation, expression and methylation, are also mapped for a subset of genomes. The Plant Reactome pathway portal (http://plantreactome.gramene.org) provides a reference resource for analyzing plant metabolic and regulatory pathways. In addition to ∼ 200 curated rice reference pathways, the portal hosts gene homology-based pathway projections for 33 plant species. Both the genome and pathway browsers interface with the EMBL-EBI's Expression Atlas to enable the projection of baseline and differential expression data from curated expression studies in plants. Gramene's archive website (http://archive.gramene.org) continues to provide previously reported resources on comparative maps, markers and QTL. To further aid our users, we have also introduced a live monthly educational webinar series and a Gramene YouTube channel carrying video tutorials. PMID:26553803

  12. Molecular phylogeny of the fungi of the Iceman's grass clothing.

    PubMed

    Rollo, F; Sassaroli, S; Ubaldi, M

    1995-08-01

    To investigate the origin of the fungal hyphae that cover the grass clothing (cloak, boots) found near the neolithic mummy known as the Tyrolean Iceman, two radiocarbon-dated samples of grass were submitted to DNA extraction. The DNA was then PCR amplified using, respectively, primers specific for the region containing the internal transcribed spacers and the 5.8s rDNA (ITS), and primers specific for an approximately 600-bp long fragment of the nuclear small-subunit ribosomal DNA (SSU rDNA) repeat units of eukaryotes. The amplification products were cloned and sequenced. Sequence analysis of 20 individual ITS clones and of ten SSU rDNA clones indicated that three types of fungal DNA can be extracted from the grass. Phylogenetic analyses, using 5.8s and SSU rDNA fungal reference sequences from EMBL and GenBank databases, suggest that the DNAs come, respectively, from a psychrophilic basidiomycetous yeast, phylogenetically close to Leucosporidium scottii, and from two ascomycetes, one of which is possibly related to the Eurotiales.

  13. Expanding the fragrance chemical space for virtual screening.

    PubMed

    Ruddigkeit, Lars; Awale, Mahendra; Reymond, Jean-Louis

    2014-01-01

    The properties of fragrance molecules in the public databases SuperScent and Flavornet were analyzed to define a "fragrance-like" (FL) property range (Heavy Atom Count ≤ 21, only C, H, O, S, (O + S) ≤ 3, Hydrogen Bond Donor ≤ 1) and the corresponding chemical space including FL molecules from PubChem (NIH repository of molecules), ChEMBL (bioactive molecules), ZINC (drug-like molecules), and GDB-13 (all possible organic molecules up to 13 atoms of C, N, O, S, Cl). The FL subsets of these databases were classified by MQN (Molecular Quantum Numbers, a set of 42 integer value descriptors of molecular structure) and formatted for fast MQN-similarity searching and interactive exploration of color-coded principal component maps in form of the FL-mapplet and FL-browser applications freely available at http://www.gdb.unibe.ch. MQN-similarity is shown to efficiently recover 15 different fragrance molecule families from the different FL subsets, demonstrating the relevance of the MQN-based tool to explore the fragrance chemical space. PMID:24876890

  14. The new NCPSS BL19U2 beamline at the SSRF for small-angle X-ray scattering from biological macromolecules in solution1

    PubMed Central

    Li, Na; Li, Xiuhong; Wang, Yuzhu; Liu, Guangfeng; Zhou, Ping; Wu, Hongjin; Hong, Chunxia; Bian, Fenggang; Zhang, Rongguang

    2016-01-01

    The beamline BL19U2 is located in the Shanghai Synchrotron Radiation Facility (SSRF) and is its first beamline dedicated to biological material small-angle X-ray scattering (BioSAXS). The electrons come from an undulator which can provide high brilliance for the BL19U2 end stations. A double flat silicon crystal (111) monochromator is used in BL19U2, with a tunable monochromatic photon energy ranging from 7 to 15 keV. To meet the rapidly growing demands of crystallographers, biochemists and structural biologists, the BioSAXS beamline allows manual and automatic sample loading/unloading. A Pilatus 1M detector (Dectris) is employed for data collection, characterized by a high dynamic range and a short readout time. The highly automated data processing pipeline SASFLOW was integrated into BL19U2, with help from the BioSAXS group of the European Molecular Biology Laboratory (EMBL, Hamburg), which provides a user-friendly interface for data processing. The BL19U2 beamline was officially opened to users in March 2015. To date, feedback from users has been positive and the number of experimental proposals at BL19U2 is increasing. A description of the new BioSAXS beamline and the setup characteristics is given, together with examples of data obtained. PMID:27738413

  15. Prioritization of active antimalarials using structural interaction profile of Plasmodium falciparum enoyl-acyl carrier protein reductase (PfENR)-triclosan derivatives.

    PubMed

    Kumar, S P; George, L B; Jasrai, Y T; Pandya, H A

    2015-01-01

    An empirical relationship between the experimental inhibitory activities of triclosan derivatives and its computationally predicted Plasmodium falciparum enoyl-acyl carrier protein (ACP) reductase (PfENR) dock poses was developed to model activities of known antimalarials. A statistical model was developed using 57 triclosan derivatives with significant measures (r = 0.849, q(2) = 0.619, s = 0.481) and applied on structurally related and structurally diverse external datasets. A substructure-based search on ChEMBL malaria dataset (280 compounds) yielded only two molecules with significant docking energy, whereas eight active antimalarials (EC(50) < 100 nM, tested on 3D7 strain) with better predicted activities (pIC(50) ~ 7) from Open Access Malaria Box (400 compounds) were prioritized. Further, calculations on the structurally diverse rhodanine molecules (known PfENR inhibitors) distinguished actives (experimental IC(50) = 0.035 μM; predicted pIC(50) = 6.568) and inactives (experimental IC(50) = 50 μM; predicted pIC50 = -4.078), which showed that antimalarials possessing dock poses similar to experimental interaction profiles can be used as leads to test experimentally on enzyme assays.

  16. Molecular analysis of functional and nonfunctional genes for human ferrochelatase: Isolation and characterization of a FECH pseudogene and its sublocation on chromosome 3

    SciTech Connect

    Whitcombe, D.M.; Albertson, D.G. ); Cox, T.M. )

    1994-04-01

    A pseudogene related to the functional gene (FECH) for the heme biosynthetic enzyme ferrochelatase (ferroheme-protolyase; EC 4.99.1.1.) was isolated from a human genomic library using a ferrochelatase cDNA hybridization probe. The pseudogene shows >80% overall nucleotide sequence identity to the functional gene (including the 3[prime] untranslated region and polyadenylation signals) but contains no intronic sequences in the region corresponding to the open reading frame of expressed ferrochelatase. Furthermore, the pseudogene sequence contains small deletions and insertions creating frameshifts and numerous termination codons, indicating that it does not encode a functional polypeptide. Northern blot analysis using pseudogene-specific probes failed to demonstrate transcripts in samples of human erythroid cell RNA in which ferrochelatase mRNA was readily detected. Southern blot experiments using restriction endonuclease-digested human genomic DNA probed either with ferrochelatase-specific cDNA fragments or pseudogene-specific genomic sequences confirmed the presence of distinct loci for the expressed and nonfunctional genes, respectively. Localization of the human ferrochelatase pseudogene to 3p22-p23 was determined by fluorescent metaphase chromosomal hybridization in situ using three genomic clones in [lambda]EMBL3 spanning a contiguous region of [approximately] 30 kb. This newly identified locus, distinct from the expressed FECH gene, on 18q22, is characteristic of a processed human pseudogene. The existence of the ferrochelatase pseudogene has practical implications for the molecular analysis of mutations responsible for erythropoietic protoporphyria in man. 24 refs., 3 figs.

  17. Identification of Damaging nsSNVs in HumanERCC2 Gene.

    PubMed

    Fang, Shuo; Zhang, Yuntong; Xu, Miao; Xue, Chunyu; He, Lin; Cai, Lei; Xing, Xin

    2016-09-01

    The hERCC2 gene is an important DNA repair molecule for initiating Cutaneous melanoma (CM). Therefore, it is advisable to study the possible functional SNVs in hERCC2. To achieve this goal, we collected total 2, 253 SNVs in hERCC2from the EMBL website, of which 303 are non-synonymous single nucleotide variants (nsSNVs). Then, SIFT and PolyPhen were used to predict the damaging nsSNVs, and four nsSNVs (rs368866996, rs377739017, rs370819591, and rs121913022) were suggested to be damaging mutations. Since I-Mutant2.0 showed a decrease in stability for the mutants containing each of the four nsSNVs, a 3D protein structure was modeled. Based on the comparison of the energy after minimization, RMSD and stabilizing residues between the native and mutant proteins' structure, rs121913022 was proposed to be the most damaging variant among the nsSNVs in hERCC2 gene by decreasing the stability of protein. The mutant G713R of hERCC2 protein caused by rs121913022 was found to have less expression level than native hERCC2 protein in melanoma cells. These results suggest that rs121913022 may have potentially important clinical and drug target implications.

  18. Identification of a mannoprotein present in the inner layer of the cell wall of Saccharomyces cerevisiae.

    PubMed Central

    Moukadiri, I; Armero, J; Abad, A; Sentandreu, R; Zueco, J

    1997-01-01

    Cell wall extracts from the double-mutant mnn1 mnn9 strain were used as the immunogen to obtain a monoclonal antibody (MAb), SAC A6, that recognizes a specific mannoprotein--which we have named Icwp--in the walls of cells of Saccharomyces cerevisiae. Icwp runs as a polydisperse band of over 180 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of Zymolyase extracts of cell walls, although an analysis of the secretory pattern of the mannoprotein shows that at the level of secretory vesicles, it behaves like a discrete band of 140 kDa. Immunofluorescence analysis with the MAb showed that Icwp lies at the inner layer of the cell wall, being accessible to the antibody only after the outer layer of mannoproteins is disturbed by treatment with tunicamycin. The screening of a lambda gt11 expression library enabled us to identify the open reading frame (ORF) coding for Icwp. ICWP (EMBL accession number YLR391w, frame +3) codes for 238 amino acids, of which over 40% are serine or threonine, and contains a putative N-glycosylation site and a putative glycosylphosphatidylinositol attachment signal. Both disruption and overexpression of the ORF caused increased sensitivities to calcofluor white and Congo red, while the disruption caused an increased sensitivity to Zymolyase digestion, suggesting for Icwp a structural role in association with glucan. PMID:9079899

  19. RSAT: regulatory sequence analysis tools.

    PubMed

    Thomas-Chollier, Morgane; Sand, Olivier; Turatsinze, Jean-Valéry; Janky, Rekin's; Defrance, Matthieu; Vervisch, Eric; Brohée, Sylvain; van Helden, Jacques

    2008-07-01

    The regulatory sequence analysis tools (RSAT, http://rsat.ulb.ac.be/rsat/) is a software suite that integrates a wide collection of modular tools for the detection of cis-regulatory elements in genome sequences. The suite includes programs for sequence retrieval, pattern discovery, phylogenetic footprint detection, pattern matching, genome scanning and feature map drawing. Random controls can be performed with random gene selections or by generating random sequences according to a variety of background models (Bernoulli, Markov). Beyond the original word-based pattern-discovery tools (oligo-analysis and dyad-analysis), we recently added a battery of tools for matrix-based detection of cis-acting elements, with some original features (adaptive background models, Markov-chain estimation of P-values) that do not exist in other matrix-based scanning tools. The web server offers an intuitive interface, where each program can be accessed either separately or connected to the other tools. In addition, the tools are now available as web services, enabling their integration in programmatic workflows. Genomes are regularly updated from various genome repositories (NCBI and EnsEMBL) and 682 organisms are currently supported. Since 1998, the tools have been used by several hundreds of researchers from all over the world. Several predictions made with RSAT were validated experimentally and published.

  20. Enriching screening libraries with bioactive fragment space.

    PubMed

    Zhang, Na; Zhao, Hongtao

    2016-08-01

    By deconvoluting 238,073 bioactive molecules in the ChEMBL library into extended Murcko ring systems, we identified a set of 2245 ring systems present in at least 10 molecules. These ring systems belong to 2221 clusters by ECFP4 fingerprints with a minimum intracluster similarity of 0.8. Their overlap with ring systems in commercial libraries was further quantified. Our findings suggest that success of a small fragment library is driven by the convergence of effective coverage of bioactive ring systems (e.g., 10% coverage by 1000 fragments vs. 40% by 2million HTS compounds), high enrichment of bioactive ring systems, and low molecular complexity enhancing the probability of a match with the protein targets. Reconciling with the previous studies, bioactive ring systems are underrepresented in screening libraries. As such, we propose a library of virtual fragments with key functionalities via fragmentation of bioactive molecules. Its utility is exemplified by a prospective application on protein kinase CK2, resulting in the discovery of a series of novel inhibitors with the most potent compound having an IC50 of 0.5μM and a ligand efficiency of 0.41kcal/mol per heavy atom.

  1. Deciphering the microbiota of Tuwa hot spring, India using shotgun metagenomic sequencing approach

    PubMed Central

    Mangrola, Amitsinh; Dudhagara, Pravin; Koringa, Prakash; Joshi, C.G.; Parmar, Mansi; Patel, Rajesh

    2015-01-01

    Here, we report metagenome from the Tuwa hot spring, India using shotgun sequencing approach. Metagenome consisted of 541,379 sequences with 98.7 Mbps size with 46% G + C content. Metagenomic sequence reads were deposited into the EMBL database under accession number ERP009321. Community analysis presented 99.1% sequences belong to bacteria, 0.3% of eukaryotic origin, 0.2% virus derived and 0.05% from archea. Unclassified and unidentified sequences were 0.4% and 0.07% respectively. A total of 22 bacterial phyla include 90 families and 201 species were observed in the hot spring metagenome. Firmicutes (97.0%), Proteobacteria (1.3%) and Actinobacteria (0.4%) were reported as dominant bacterial phyla. In functional analysis using Cluster of Orthologous Group (COG), 21.5% drops in the poorly characterized group. Using subsystem based annotation, 4.0% genes were assigned for stress responses and 3% genes were fit into the metabolism of aromatic compounds. The hot spring metagenome is very rich with novel sequences affiliated to unclassified and unidentified lineages, suggesting the potential source for novel microbial species and their products. PMID:26484204

  2. The SIDER database of drugs and side effects.

    PubMed

    Kuhn, Michael; Letunic, Ivica; Jensen, Lars Juhl; Bork, Peer

    2016-01-01

    Unwanted side effects of drugs are a burden on patients and a severe impediment in the development of new drugs. At the same time, adverse drug reactions (ADRs) recorded during clinical trials are an important source of human phenotypic data. It is therefore essential to combine data on drugs, targets and side effects into a more complete picture of the therapeutic mechanism of actions of drugs and the ways in which they cause adverse reactions. To this end, we have created the SIDER ('Side Effect Resource', http://sideeffects.embl.de) database of drugs and ADRs. The current release, SIDER 4, contains data on 1430 drugs, 5880 ADRs and 140 064 drug-ADR pairs, which is an increase of 40% compared to the previous version. For more fine-grained analyses, we extracted the frequency with which side effects occur from the package inserts. This information is available for 39% of drug-ADR pairs, 19% of which can be compared to the frequency under placebo treatment. SIDER furthermore contains a data set of drug indications, extracted from the package inserts using Natural Language Processing. These drug indications are used to reduce the rate of false positives by identifying medical terms that do not correspond to ADRs.

  3. Complete VAX/VMS DNA/protein sequence analysis system

    SciTech Connect

    Smith, D.W.

    1987-05-01

    A complete yet flexible system of programs and database libraries for analysis of DNA, RNA and protein sequences is implemented for VAX/VMS computers. Types of analysis include 1) construction and analysis of chimeric sequences (cloning in the VAX), 2) multiple analysis of one or more single sequences, 3) search and comparison studies using sequence libraries, and 4) direct input and analysis of experimental data. Published groups of programs, including the Staden, Los Alamos, Zuker, Pearson, and PHYLIP programs, are used. GenBank and EMBL DNA libraries and PIR and Doolittle NEWAT protein libraries are available, with associated programs. The system is tutorial, with online documentation for relevent VAX software, the programs, and the databases. The complete documentation is flexibly maintained on reserve via computer printout placed in 3-ring binders. Command files are used extensively; porting of the entire system to another VAX/VMS system requires modification of a single command. Users of the system are members of a VAX group, with automatic implementation of the system upon login. The present system occupies about 140,000 blocks, and is easily expanded, or contracted, as desired. The UCSD system is used extensively for both teaching and research purposes. Use of microcomputers emulating Tektronix 4014 graphics terminals permits saving of graphics output to disk for subsequent modification to generate high quality publishable figures.

  4. [A new unique HIV-1 recombinant form detected in Belarus].

    PubMed

    Eremin, V F; Gasich, E L; Sosinovich, S V

    2012-01-01

    Republican Research-and-Practical Center for Epidemiology and Microbiology, Ministry of Health of Belarus, Minsk The paper presents data on the molecular genetic characteristics of a new HIV-1 recombinant form. The study has shown that the virus is referred to as HIV-1 subtype B in terms of the gag gene and HIV-1 subtype A in terms of the pol and env genes. At the same time the new isolate is closer, in terms of the gag gene, to the HIV-1 DQ207943 strain isolated in Georgia, in terms of the pol gene, to the HIV-1 AF413987.1 strain isolated in Ukraine and, in terms of the env gene to the HIV-1 AY500393 strain isolated in Russia. Thus, the described new HIV-1 recombinant form has the following structure: BgagApolAenv. The gag, pol, and env gene sequences from the new unique HIV-1 recombinant form have been registered in the international database EMBL/Genbank/DDBJ under accession numbers FR775442.1, FN995656.1, and FR775443.1.

  5. eggNOG 4.5: a hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences.

    PubMed

    Huerta-Cepas, Jaime; Szklarczyk, Damian; Forslund, Kristoffer; Cook, Helen; Heller, Davide; Walter, Mathias C; Rattei, Thomas; Mende, Daniel R; Sunagawa, Shinichi; Kuhn, Michael; Jensen, Lars Juhl; von Mering, Christian; Bork, Peer

    2016-01-01

    eggNOG is a public resource that provides Orthologous Groups (OGs) of proteins at different taxonomic levels, each with integrated and summarized functional annotations. Developments since the latest public release include changes to the algorithm for creating OGs across taxonomic levels, making nested groups hierarchically consistent. This allows for a better propagation of functional terms across nested OGs and led to the novel annotation of 95 890 previously uncharacterized OGs, increasing overall annotation coverage from 67% to 72%. The functional annotations of OGs have been expanded to also provide Gene Ontology terms, KEGG pathways and SMART/Pfam domains for each group. Moreover, eggNOG now provides pairwise orthology relationships within OGs based on analysis of phylogenetic trees. We have also incorporated a framework for quickly mapping novel sequences to OGs based on precomputed HMM profiles. Finally, eggNOG version 4.5 incorporates a novel data set spanning 2605 viral OGs, covering 5228 proteins from 352 viral proteomes. All data are accessible for bulk downloading, as a web-service, and through a completely redesigned web interface. The new access points provide faster searches and a number of new browsing and visualization capabilities, facilitating the needs of both experts and less experienced users. eggNOG v4.5 is available at http://eggnog.embl.de. PMID:26582926

  6. Expanding the fragrance chemical space for virtual screening

    PubMed Central

    2014-01-01

    The properties of fragrance molecules in the public databases SuperScent and Flavornet were analyzed to define a “fragrance-like” (FL) property range (Heavy Atom Count ≤ 21, only C, H, O, S, (O + S) ≤ 3, Hydrogen Bond Donor ≤ 1) and the corresponding chemical space including FL molecules from PubChem (NIH repository of molecules), ChEMBL (bioactive molecules), ZINC (drug-like molecules), and GDB-13 (all possible organic molecules up to 13 atoms of C, N, O, S, Cl). The FL subsets of these databases were classified by MQN (Molecular Quantum Numbers, a set of 42 integer value descriptors of molecular structure) and formatted for fast MQN-similarity searching and interactive exploration of color-coded principal component maps in form of the FL-mapplet and FL-browser applications freely available at http://www.gdb.unibe.ch. MQN-similarity is shown to efficiently recover 15 different fragrance molecule families from the different FL subsets, demonstrating the relevance of the MQN-based tool to explore the fragrance chemical space. PMID:24876890

  7. SMIfp (SMILES fingerprint) chemical space for virtual screening and visualization of large databases of organic molecules.

    PubMed

    Schwartz, Julian; Awale, Mahendra; Reymond, Jean-Louis

    2013-08-26

    SMIfp (SMILES fingerprint) is defined here as a scalar fingerprint describing organic molecules by counting the occurrences of 34 different symbols in their SMILES strings, which creates a 34-dimensional chemical space. Ligand-based virtual screening using the city-block distance CBD(SMIfp) as similarity measure provides good AUC values and enrichment factors for recovering series of actives from the directory of useful decoys (DUD-E) and from ZINC. DrugBank, ChEMBL, ZINC, PubChem, GDB-11, GDB-13, and GDB-17 can be searched by CBD(SMIfp) using an online SMIfp-browser at www.gdb.unibe.ch. Visualization of the SMIfp chemical space was performed by principal component analysis and color-coded maps of the (PC1, PC2)-planes, with interactive access to the molecules enabled by the Java application SMIfp-MAPPLET available from www.gdb.unibe.ch. These maps spread molecules according to their fraction of aromatic atoms, size and polarity. SMIfp provides a new and relevant entry to explore the small molecule chemical space.

  8. Enriching screening libraries with bioactive fragment space.

    PubMed

    Zhang, Na; Zhao, Hongtao

    2016-08-01

    By deconvoluting 238,073 bioactive molecules in the ChEMBL library into extended Murcko ring systems, we identified a set of 2245 ring systems present in at least 10 molecules. These ring systems belong to 2221 clusters by ECFP4 fingerprints with a minimum intracluster similarity of 0.8. Their overlap with ring systems in commercial libraries was further quantified. Our findings suggest that success of a small fragment library is driven by the convergence of effective coverage of bioactive ring systems (e.g., 10% coverage by 1000 fragments vs. 40% by 2million HTS compounds), high enrichment of bioactive ring systems, and low molecular complexity enhancing the probability of a match with the protein targets. Reconciling with the previous studies, bioactive ring systems are underrepresented in screening libraries. As such, we propose a library of virtual fragments with key functionalities via fragmentation of bioactive molecules. Its utility is exemplified by a prospective application on protein kinase CK2, resulting in the discovery of a series of novel inhibitors with the most potent compound having an IC50 of 0.5μM and a ligand efficiency of 0.41kcal/mol per heavy atom. PMID:27311891

  9. Identification and molecular analysis of a multigene family encoding calliphorin, the major larval serum protein of Calliphora vicina

    PubMed Central

    Schenkel, Heide; Kejzlarová-Lepesant, Jana; Berreur, Paul; Moreau, Jacques; Scheller, Klaus; Brègègére, François; Lepesant, Jean-Antoine

    1985-01-01

    A library of Calliphora vicina genomic DNA was constructed in the λEMBL3 vector and screened for recombinant phages containing chromosomal segments encoding calliphorin, the major larval serum protein (LSP) of Calliphora. A large series of recombinants hybridizing with in vitro labelled poly(A)+ RNA from Calliphora larval fat bodies and with specific probes derived from the LSP-1 genes of Drosophila melanogaster was isolated. Five of these phages, chosen at random, were shown by hybrid selection to retain calliphorin mRNA specifically. Eleven calliphorin mRNA-homologous regions were located on restriction maps of these phages by hybridization with 5' end-labelled poly(A)+ RNA from Calliphora larval fat bodies. Each phage contains at least two calliphorin genes arranged in direct repeat orientation and seperated by 3.5–5 kb intergenic regions. The genes display similar but not identical restriction patterns. Filter hybridization and heteroduplex analysis indicate that they share a detectable homology with the LSP-1β gene of D. melanogaster. Whole genome Southern analysis showed that these genes belong to a large family of closely related calliphorin genes which were found by in situ hybridization to polytene chromosomes of trichogen cells to be clustered in region 4a of chromosome 2 of Calliphora vicina. ImagesFig. 1.Fig. 3.Fig. 4.Fig. 5.Fig. 6.Fig. 7.Fig. 8. PMID:16453643

  10. A small and robust active beamstop for scattering experiments on high-brilliance undulator beamlines.

    PubMed

    Blanchet, Clement E; Hermes, Christoph; Svergun, Dmitri I; Fiedler, Stefan

    2015-03-01

    A small active in-vacuum beamstop has been developed to monitor the flux of intense third-generation synchrotron X-ray beams protecting the downstream detector from the direct beam. Standard active beamstops, where a built-in diode directly absorbs the beam, have limitations in size and lifetime. In the present design, a silicon PIN diode detects the photons back-scattered from a cavity in the beamstop. This approach drastically reduces the radiation dose on the diode and thus increases its lifetime. The beamstop with a diameter of 2 mm has been fabricated to meet the requirements for the P12 bioSAXS beamline of EMBL Hamburg at PETRA III (DESY). The beamstop is in regular user operation at the beamline and displays a good response over the range of energies tested (6-20 keV). Further miniaturization of the diode is easily possible as its size is not limited by the PIN diode used. PMID:25723949

  11. A small and robust active beamstop for scattering experiments on high-brilliance undulator beamlines

    PubMed Central

    Blanchet, Clement E.; Hermes, Christoph; Svergun, Dmitri I.; Fiedler, Stefan

    2015-01-01

    A small active in-vacuum beamstop has been developed to monitor the flux of intense third-generation synchrotron X-ray beams protecting the downstream detector from the direct beam. Standard active beamstops, where a built-in diode directly absorbs the beam, have limitations in size and lifetime. In the present design, a silicon PIN diode detects the photons back-scattered from a cavity in the beamstop. This approach drastically reduces the radiation dose on the diode and thus increases its lifetime. The beamstop with a diameter of 2 mm has been fabricated to meet the requirements for the P12 bioSAXS beamline of EMBL Hamburg at PETRA III (DESY). The beamstop is in regular user operation at the beamline and displays a good response over the range of energies tested (6–20 keV). Further miniaturization of the diode is easily possible as its size is not limited by the PIN diode used. PMID:25723949

  12. eggNOG 4.5: a hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences

    PubMed Central

    Huerta-Cepas, Jaime; Szklarczyk, Damian; Forslund, Kristoffer; Cook, Helen; Heller, Davide; Walter, Mathias C.; Rattei, Thomas; Mende, Daniel R.; Sunagawa, Shinichi; Kuhn, Michael; Jensen, Lars Juhl; von Mering, Christian; Bork, Peer

    2016-01-01

    eggNOG is a public resource that provides Orthologous Groups (OGs) of proteins at different taxonomic levels, each with integrated and summarized functional annotations. Developments since the latest public release include changes to the algorithm for creating OGs across taxonomic levels, making nested groups hierarchically consistent. This allows for a better propagation of functional terms across nested OGs and led to the novel annotation of 95 890 previously uncharacterized OGs, increasing overall annotation coverage from 67% to 72%. The functional annotations of OGs have been expanded to also provide Gene Ontology terms, KEGG pathways and SMART/Pfam domains for each group. Moreover, eggNOG now provides pairwise orthology relationships within OGs based on analysis of phylogenetic trees. We have also incorporated a framework for quickly mapping novel sequences to OGs based on precomputed HMM profiles. Finally, eggNOG version 4.5 incorporates a novel data set spanning 2605 viral OGs, covering 5228 proteins from 352 viral proteomes. All data are accessible for bulk downloading, as a web-service, and through a completely redesigned web interface. The new access points provide faster searches and a number of new browsing and visualization capabilities, facilitating the needs of both experts and less experienced users. eggNOG v4.5 is available at http://eggnog.embl.de. PMID:26582926

  13. PhyloPat: an updated version of the phylogenetic pattern database contains gene neighborhood.

    PubMed

    Hulsen, Tim; Groenen, Peter M A; de Vlieg, Jacob; Alkema, Wynand

    2009-01-01

    Phylogenetic patterns show the presence or absence of certain genes in a set of full genomes derived from different species. They can also be used to determine sets of genes that occur only in certain evolutionary branches. Previously, we presented a database named PhyloPat which allows the complete Ensembl gene database to be queried using phylogenetic patterns. Here, we describe an updated version of PhyloPat which can be queried by an improved web server. We used a single linkage clustering algorithm to create 241,697 phylogenetic lineages, using all the orthologies provided by Ensembl v49. PhyloPat offers the possibility of querying with binary phylogenetic patterns or regular expressions, or through a phylogenetic tree of the 39 included species. Users can also input a list of Ensembl, EMBL, EntrezGene or HGNC IDs to check which phylogenetic lineage any gene belongs to. A link to the FatiGO web interface has been incorporated in the HTML output. For each gene, the surrounding genes on the chromosome, color coded according to their phylogenetic lineage can be viewed, as well as FASTA files of the peptide sequences of each lineage. Furthermore, lists of omnipresent, polypresent, oligopresent and anticorrelating genes have been included. PhyloPat is freely available at http://www.cmbi.ru.nl/phylopat.

  14. eggNOG v4.0: nested orthology inference across 3686 organisms.

    PubMed

    Powell, Sean; Forslund, Kristoffer; Szklarczyk, Damian; Trachana, Kalliopi; Roth, Alexander; Huerta-Cepas, Jaime; Gabaldón, Toni; Rattei, Thomas; Creevey, Chris; Kuhn, Michael; Jensen, Lars J; von Mering, Christian; Bork, Peer

    2014-01-01

    With the increasing availability of various 'omics data, high-quality orthology assignment is crucial for evolutionary and functional genomics studies. We here present the fourth version of the eggNOG database (available at http://eggnog.embl.de) that derives nonsupervised orthologous groups (NOGs) from complete genomes, and then applies a comprehensive characterization and analysis pipeline to the resulting gene families. Compared with the previous version, we have more than tripled the underlying species set to cover 3686 organisms, keeping track with genome project completions while prioritizing the inclusion of high-quality genomes to minimize error propagation from incomplete proteome sets. Major technological advances include (i) a robust and scalable procedure for the identification and inclusion of high-quality genomes, (ii) provision of orthologous groups for 107 different taxonomic levels compared with 41 in eggNOGv3, (iii) identification and annotation of particularly closely related orthologous groups, facilitating analysis of related gene families, (iv) improvements of the clustering and functional annotation approach, (v) adoption of a revised tree building procedure based on the multiple alignments generated during the process and (vi) implementation of quality control procedures throughout the entire pipeline. As in previous versions, eggNOGv4 provides multiple sequence alignments and maximum-likelihood trees, as well as broad functional annotation. Users can access the complete database of orthologous groups via a web interface, as well as through bulk download.

  15. eggNOG 4.5: a hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences.

    PubMed

    Huerta-Cepas, Jaime; Szklarczyk, Damian; Forslund, Kristoffer; Cook, Helen; Heller, Davide; Walter, Mathias C; Rattei, Thomas; Mende, Daniel R; Sunagawa, Shinichi; Kuhn, Michael; Jensen, Lars Juhl; von Mering, Christian; Bork, Peer

    2016-01-01

    eggNOG is a public resource that provides Orthologous Groups (OGs) of proteins at different taxonomic levels, each with integrated and summarized functional annotations. Developments since the latest public release include changes to the algorithm for creating OGs across taxonomic levels, making nested groups hierarchically consistent. This allows for a better propagation of functional terms across nested OGs and led to the novel annotation of 95 890 previously uncharacterized OGs, increasing overall annotation coverage from 67% to 72%. The functional annotations of OGs have been expanded to also provide Gene Ontology terms, KEGG pathways and SMART/Pfam domains for each group. Moreover, eggNOG now provides pairwise orthology relationships within OGs based on analysis of phylogenetic trees. We have also incorporated a framework for quickly mapping novel sequences to OGs based on precomputed HMM profiles. Finally, eggNOG version 4.5 incorporates a novel data set spanning 2605 viral OGs, covering 5228 proteins from 352 viral proteomes. All data are accessible for bulk downloading, as a web-service, and through a completely redesigned web interface. The new access points provide faster searches and a number of new browsing and visualization capabilities, facilitating the needs of both experts and less experienced users. eggNOG v4.5 is available at http://eggnog.embl.de.

  16. The SYSTERS Protein Family Database in 2005.

    PubMed

    Meinel, Thomas; Krause, Antje; Luz, Hannes; Vingron, Martin; Staub, Eike

    2005-01-01

    The SYSTERS project aims to provide a meaningful partitioning of the whole protein sequence space by a fully automatic procedure. A refined two-step algorithm assigns each protein to a family and a superfamily. The sequence data underlying SYSTERS release 4 now comprise several protein sequence databases derived from completely sequenced genomes (ENSEMBL, TAIR, SGD and GeneDB), in addition to the comprehensive Swiss-Prot/TrEMBL databases. The SYSTERS web server (http://systers.molgen.mpg.de) provides access to 158 153 SYSTERS protein families. To augment the automatically derived results, information from external databases like Pfam and Gene Ontology are added to the web server. Furthermore, users can retrieve pre-processed analyses of families like multiple alignments and phylogenetic trees. New query options comprise a batch retrieval tool for functional inference about families based on automatic keyword extraction from sequence annotations. A new access point, PhyloMatrix, allows the retrieval of phylogenetic profiles of SYSTERS families across organisms with completely sequenced genomes.

  17. PTMcode: a database of known and predicted functional associations between post-translational modifications in proteins.

    PubMed

    Minguez, Pablo; Letunic, Ivica; Parca, Luca; Bork, Peer

    2013-01-01

    Post-translational modifications (PTMs) are involved in the regulation and structural stabilization of eukaryotic proteins. The combination of individual PTM states is a key to modulate cellular functions as became evident in a few well-studied proteins. This combinatorial setting, dubbed the PTM code, has been proposed to be extended to whole proteomes in eukaryotes. Although we are still far from deciphering such a complex language, thousands of protein PTM sites are being mapped by high-throughput technologies, thus providing sufficient data for comparative analysis. PTMcode (http://ptmcode.embl.de) aims to compile known and predicted PTM associations to provide a framework that would enable hypothesis-driven experimental or computational analysis of various scales. In its first release, PTMcode provides PTM functional associations of 13 different PTM types within proteins in 8 eukaryotes. They are based on five evidence channels: a literature survey, residue co-evolution, structural proximity, PTMs at the same residue and location within PTM highly enriched protein regions (hotspots). PTMcode is presented as a protein-based searchable database with an interactive web interface providing the context of the co-regulation of nearly 75 000 residues in >10 000 proteins.

  18. eggNOG v3.0: orthologous groups covering 1133 organisms at 41 different taxonomic ranges.

    PubMed

    Powell, Sean; Szklarczyk, Damian; Trachana, Kalliopi; Roth, Alexander; Kuhn, Michael; Muller, Jean; Arnold, Roland; Rattei, Thomas; Letunic, Ivica; Doerks, Tobias; Jensen, Lars J; von Mering, Christian; Bork, Peer

    2012-01-01

    Orthologous relationships form the basis of most comparative genomic and metagenomic studies and are essential for proper phylogenetic and functional analyses. The third version of the eggNOG database (http://eggnog.embl.de) contains non-supervised orthologous groups constructed from 1133 organisms, doubling the number of genes with orthology assignment compared to eggNOG v2. The new release is the result of a number of improvements and expansions: (i) the underlying homology searches are now based on the SIMAP database; (ii) the orthologous groups have been extended to 41 levels of selected taxonomic ranges enabling much more fine-grained orthology assignments; and (iii) the newly designed web page is considerably faster with more functionality. In total, eggNOG v3 contains 721,801 orthologous groups, encompassing a total of 4,396,591 genes. Additionally, we updated 4873 and 4850 original COGs and KOGs, respectively, to include all 1133 organisms. At the universal level, covering all three domains of life, 101,208 orthologous groups are available, while the others are applicable at 40 more limited taxonomic ranges. Each group is amended by multiple sequence alignments and maximum-likelihood trees and broad functional descriptions are provided for 450,904 orthologous groups (62.5%).

  19. eggNOG: automated construction and annotation of orthologous groups of genes.

    PubMed

    Jensen, Lars Juhl; Julien, Philippe; Kuhn, Michael; von Mering, Christian; Muller, Jean; Doerks, Tobias; Bork, Peer

    2008-01-01

    The identification of orthologous genes forms the basis for most comparative genomics studies. Existing approaches either lack functional annotation of the identified orthologous groups, hampering the interpretation of subsequent results, or are manually annotated and thus lag behind the rapid sequencing of new genomes. Here we present the eggNOG database ('evolutionary genealogy of genes: Non-supervised Orthologous Groups'), which contains orthologous groups constructed from Smith-Waterman alignments through identification of reciprocal best matches and triangular linkage clustering. Applying this procedure to 312 bacterial, 26 archaeal and 35 eukaryotic genomes yielded 43 582 course-grained orthologous groups of which 9724 are extended versions of those from the original COG/KOG database. We also constructed more fine-grained groups for selected subsets of organisms, such as the 19 914 mammalian orthologous groups. We automatically annotated our non-supervised orthologous groups with functional descriptions, which were derived by identifying common denominators for the genes based on their individual textual descriptions, annotated functional categories, and predicted protein domains. The orthologous groups in eggNOG contain 1 241 751 genes and provide at least a broad functional description for 77% of them. Users can query the resource for individual genes via a web interface or download the complete set of orthologous groups at http://eggnog.embl.de.

  20. PeroxiBase: a class III plant peroxidase database.

    PubMed

    Bakalovic, Nenad; Passardi, Filippo; Ioannidis, Vassilios; Cosio, Claudia; Penel, Claude; Falquet, Laurent; Dunand, Christophe

    2006-03-01

    Class III plant peroxidases (EC 1.11.1.7), which are encoded by multigenic families in land plants, are involved in several important physiological and developmental processes. Their varied functions are not yet clearly determined, but their characterization will certainly lead to a better understanding of plant growth, differentiation and interaction with the environment, and hence to many exciting applications. Since there is currently no central database for plant peroxidase sequences and many plant sequences are not deposited in the EMBL/GenBank/DDBJ repository or the UniProt KnowledgeBase, this prevents researchers from easily accessing all peroxidase sequences. Furthermore, gene expression data are poorly covered and annotations are inconsistent. In this rapidly moving field, there is a need for continual updating and correction of the peroxidase superfamily in plants. Moreover, consolidating information about peroxidases will allow for comparison of peroxidases between species and thus significantly help making correlations of function, structure or phylogeny. We report a new database (PeroxiBase) accessible through a web server with specific tools dedicated to facilitate query, classification and submission of peroxidase sequences. Recent developments in the field of plant peroxidase are also mentioned.

  1. ATDB: a uni-database platform for animal toxins.

    PubMed

    He, Quan-Yuan; He, Quan-Ze; Deng, Xing-Can; Yao, Lei; Meng, Er; Liu, Zhong-Hua; Liang, Song-Ping

    2008-01-01

    Venomous animals possess an arsenal of toxins for predation and defense. These toxins have great diversity in function and structure as well as evolution and therefore are of value in both basic and applied research. Recently, toxinomics researches using cDNA library sequencing and proteomics profiling have revealed a large number of new toxins. Although several previous groups have attempted to manage these data, most of them are restricted to certain taxonomic groups and/or lack effective systems for data query and access. In addition, the description of the function and the classification of toxins is rather inconsistent resulting in a barrier against exchanging and comparing the data. Here, we report the ATDB database and website which contains more than 3235 animal toxins from UniProtKB/Swiss-Prot and TrEMBL and related toxin databases as well as published literature. A new ontology (Toxin Ontology) was constructed to standardize the toxin annotations, which includes 745 distinct terms within four term spaces. Furthermore, more than 8423 TO terms have been manually assigned to 2132 toxins by trained biologists. Queries to the database can be conducted via a user-friendly web interface at http://protchem.hunnu.edu.cn/toxin.

  2. iProClass: an integrated database of protein family, function and structure information.

    PubMed

    Huang, Hongzhan; Barker, Winona C; Chen, Yongxing; Wu, Cathy H

    2003-01-01

    The iProClass database provides comprehensive, value-added descriptions of proteins and serves as a framework for data integration in a distributed networking environment. The protein information in iProClass includes family relationships as well as structural and functional classifications and features. The current version consists of about 830 000 non-redundant PIR-PSD, SWISS-PROT, and TrEMBL proteins organized with more than 36 000 PIR superfamilies, 145 000 families, 4000 domains, 1300 motifs and 550 000 FASTA similarity clusters. It provides rich links to over 50 database of protein sequences, families, functions and pathways, protein-protein interactions, post-translational modifications, protein expressions, structures and structural classifications, genes and genomes, ontologies, literature and taxonomy. Protein and superfamily summary reports present extensive annotation information and include membership statistics and graphical display of domains and motifs. iProClass employs an open and modular architecture for interoperability and scalability. It is implemented in the Oracle object-relational database system and is updated biweekly. The database is freely accessible from the web site at http://pir.georgetown.edu/iproclass/ and searchable by sequence or text string. The data integration in iProClass supports exploration of protein relationships. Such knowledge is fundamental to the understanding of protein evolution, structure and function and crucial to functional genomic and proteomic research.

  3. Structure and chemical reactivity of the polar three-fold surfaces of GaPd: a density-functional study.

    PubMed

    Krajčí, M; Hafner, J

    2013-03-28

    The polar threefold surfaces of the GaPd compound crystallizing in the B20 (FeSi-type) structure (space group P2(1)3) have been investigated using density-functional methods. Because of the lack of inversion symmetry the B20 structure exists in two enantiomorphic forms denoted as A and B. The threefold {111} surfaces have polar character. In both nonequivalent (111) and (111) directions several surface terminations differing in structure and chemical composition are possible. The formation of the threefold surfaces has been studied by simulated cleavage experiments and by calculations of the surface energies. Because of the polar character of the threefold surfaces calculations for stoichiometric slabs permit only the determination of the average energy of the surfaces exposed on both sides of the slab. Calculations for nonstoichiometric slabs performed in the grand canonical ensemble yield differences of the surface energies for the possible terminations as a function of the chemical potential in the reactive atmosphere above the surface and predict a transition between Ga- and Pd-terminated surfaces as a function of the chemical potential. The {100} surfaces are stoichiometric and uniquely defined. The calculated surface energies are identical to the average energies of the {100} surfaces of the pure metals. The {210} surfaces are also stoichiometric, with an energy very close to that of the {100} surfaces. Assuming that for the {111} surfaces the energies of different possible terminations are in a proportion equal to that of the concentration-weighted energies of the {111} surfaces of the pure metals, surface energies for all possible {111} terminations may be calculated. The preferable termination perpendicular to the A<111> direction consists of a bilayer with three Ga atoms in the upper and three Pd atoms in the lower part. The surface energy of this termination further decreases if the Pd triplet is covered by additional Ga atom. Perpendicular to the A<111

  4. RNA-Seq provides new insights in the transcriptome responses induced by the carcinogen benzo[a]pyrene.

    PubMed

    van Delft, Joost; Gaj, Stan; Lienhard, Matthias; Albrecht, Marcus W; Kirpiy, Alexander; Brauers, Karen; Claessen, Sandra; Lizarraga, Daneida; Lehrach, Hans; Herwig, Ralf; Kleinjans, Jos

    2012-12-01

    Whole-genome transcriptome measurements are pivotal for characterizing molecular mechanisms of chemicals and predicting toxic classes, such as genotoxicity and carcinogenicity, from in vitro and in vivo assays. In recent years, deep sequencing technologies have been developed that hold the promise of measuring the transcriptome in a more complete and unbiased manner than DNA microarrays. Here, we applied this RNA-seq technology for the characterization of the transcriptomic responses in HepG2 cells upon exposure to benzo[a]pyrene (BaP), a well-known DNA damaging human carcinogen. Based on EnsEMBL genes, we demonstrate that RNA-seq detects ca 20% more genes than microarray-based technology but almost threefold more significantly differentially expressed genes. Functional enrichment analyses show that RNA-seq yields more insight into the biology and mechanisms related to the toxic effects caused by BaP, i.e., two- to fivefold more affected pathways and biological processes. Additionally, we demonstrate that RNA-seq allows detecting alternative isoform expression in many genes, including regulators of cell death and DNA repair such as TP53, BCL2 and XPA, which are relevant for genotoxic responses. Moreover, potentially novel isoforms were found, such as fragments of known transcripts, transcripts with additional exons, intron retention or exon-skipping events. The biological function(s) of these isoforms remain for the time being unknown. Finally, we demonstrate that RNA-seq enables the investigation of allele-specific gene expression, although no changes could be observed. Our results provide evidence that RNA-seq is a powerful tool for toxicology, which, compared with microarrays, is capable of generating novel and valuable information at the transcriptome level for characterizing deleterious effects caused by chemicals.

  5. BioSAXS Sample Changer: a robotic sample changer for rapid and reliable high-throughput X-ray solution scattering experiments

    SciTech Connect

    Round, Adam Felisaz, Franck; Fodinger, Lukas; Gobbo, Alexandre; Huet, Julien; Villard, Cyril; Blanchet, Clement E.; Roessle, Manfred; Svergun, Dmitri I.

    2015-01-01

    A robotic sample changer for solution X-ray scattering experiments optimized for speed and to use the minimum amount of material has been developed. This system is now in routine use at three high-brilliance European synchrotron sites, each capable of several hundred measurements per day. Small-angle X-ray scattering (SAXS) of macromolecules in solution is in increasing demand by an ever more diverse research community, both academic and industrial. To better serve user needs, and to allow automated and high-throughput operation, a sample changer (BioSAXS Sample Changer) that is able to perform unattended measurements of up to several hundred samples per day has been developed. The Sample Changer is able to handle and expose sample volumes of down to 5 µl with a measurement/cleaning cycle of under 1 min. The samples are stored in standard 96-well plates and the data are collected in a vacuum-mounted capillary with automated positioning of the solution in the X-ray beam. Fast and efficient capillary cleaning avoids cross-contamination and ensures reproducibility of the measurements. Independent temperature control for the well storage and for the measurement capillary allows the samples to be kept cool while still collecting data at physiological temperatures. The Sample Changer has been installed at three major third-generation synchrotrons: on the BM29 beamline at the European Synchrotron Radiation Facility (ESRF), the P12 beamline at the PETRA-III synchrotron (EMBL@PETRA-III) and the I22/B21 beamlines at Diamond Light Source, with the latter being the first commercial unit supplied by Bruker ASC.

  6. Characterization and genome functional analysis of a novel metamitron-degrading strain Rhodococcus sp. MET via both triazinone and phenyl rings cleavage

    PubMed Central

    Fang, Hua; Xu, Tianheng; Cao, Duantao; Cheng, Longyin; Yu, Yunlong

    2016-01-01

    A novel bacterium capable of utilizing metamitron as the sole source of carbon and energy was isolated from contaminated soil and identified as Rhodococcus sp. MET based on its morphological characteristics, BIOLOG GP2 microplate profile, and 16S rDNA phylogeny. Genome sequencing and functional annotation of the isolate MET showed a 6,340,880 bp genome with a 62.47% GC content and 5,987 protein-coding genes. In total, 5,907 genes were annotated with the COG, GO, KEGG, Pfam, Swiss-Prot, TrEMBL, and nr databases. The degradation rate of metamitron by the isolate MET obviously increased with increasing substrate concentrations from 1 to 10 mg/l and subsequently decreased at 100 mg/l. The optimal pH and temperature for metamitron biodegradation were 7.0 and 20–30 °C, respectively. Based on genome annotation of the metamitron degradation genes and the metabolites detected by HPLC-MS/MS, the following metamitron biodegradation pathways were proposed: 1) Metamitron was transformed into 2-(3-hydrazinyl-2-ethyl)-hydrazono-2-phenylacetic acid by triazinone ring cleavage and further mineralization; 2) Metamitron was converted into 3-methyl-4-amino-6(2-hydroxy-muconic acid)-1,2,4-triazine-5(4H)-one by phenyl ring cleavage and further mineralization. The coexistence of diverse mineralization pathways indicates that our isolate may effectively bioremediate triazinone herbicide-contaminated soils. PMID:27578531

  7. Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs

    PubMed Central

    Wiemann, Stefan; Weil, Bernd; Wellenreuther, Ruth; Gassenhuber, Johannes; Glassl, Sabine; Ansorge, Wilhelm; Böcher, Michael; Blöcker, Helmut; Bauersachs, Stefan; Blum, Helmut; Lauber, Jürgen; Düsterhöft, Andreas; Beyer, Andreas; Köhrer, Karl; Strack, Normann; Mewes, Hans-Werner; Ottenwälder, Birgit; Obermaier, Brigitte; Tampe, Jens; Heubner, Dagmar; Wambutt, Rolf; Korn, Bernhard; Klein, Michaela; Poustka, Annemarie

    2001-01-01

    With the complete human genomic sequence being unraveled, the focus will shift to gene identification and to the functional analysis of gene products. The generation of a set of cDNAs, both sequences and physical clones, which contains the complete and noninterrupted protein coding regions of all human genes will provide the indispensable tools for the systematic and comprehensive analysis of protein function to eventually understand the molecular basis of man. Here we report the sequencing and analysis of 500 novel human cDNAs containing the complete protein coding frame. Assignment to functional categories was possible for 52% (259) of the encoded proteins, the remaining fraction having no similarities with known proteins. By aligning the cDNA sequences with the sequences of the finished chromosomes 21 and 22 we identified a number of genes that either had been completely missed in the analysis of the genomic sequences or had been wrongly predicted. Three of these genes appear to be present in several copies. We conclude that full-length cDNA sequencing continues to be crucial also for the accurate identification of genes. The set of 500 novel cDNAs, and another 1000 full-coding cDNAs of known transcripts we have identified, adds up to cDNA representations covering 2%–5 % of all human genes. We thus substantially contribute to the generation of a gene catalog, consisting of both full-coding cDNA sequences and clones, which should be made freely available and will become an invaluable tool for detailed functional studies. [The sequence data described in this paper have been submitted to the EMBL database under the accession nos. given in Table 2.] PMID:11230166

  8. Modelling ligand selectivity of serine proteases using integrative proteochemometric approaches improves model performance and allows the multi-target dependent interpretation of features.

    PubMed

    Ain, Qurrat U; Méndez-Lucio, Oscar; Ciriano, Isidro Cortés; Malliavin, Thérèse; van Westen, Gerard J P; Bender, Andreas

    2014-11-01

    Serine proteases, implicated in important physiological functions, have a high intra-family similarity, which leads to unwanted off-target effects of inhibitors with insufficient selectivity. However, the availability of sequence and structure data has now made it possible to develop approaches to design pharmacological agents that can discriminate successfully between their related binding sites. In this study, we have quantified the relationship between 12,625 distinct protease inhibitors and their bioactivity against 67 targets of the serine protease family (20,213 data points) in an integrative manner, using proteochemometric modelling (PCM). The benchmarking of 21 different target descriptors motivated the usage of specific binding pocket amino acid descriptors, which helped in the identification of active site residues and selective compound chemotypes affecting compound affinity and selectivity. PCM models performed better than alternative approaches (models trained using exclusively compound descriptors on all available data, QSAR) employed for comparison with R(2)/RMSE values of 0.64 ± 0.23/0.66 ± 0.20 vs. 0.35 ± 0.27/1.05 ± 0.27 log units, respectively. Moreover, the interpretation of the PCM model singled out various chemical substructures responsible for bioactivity and selectivity towards particular proteases (thrombin, trypsin and coagulation factor 10) in agreement with the literature. For instance, absence of a tertiary sulphonamide was identified to be responsible for decreased selective activity (by on average 0.27 ± 0.65 pChEMBL units) on FA10. Among the binding pocket residues, the amino acids (arginine, leucine and tyrosine) at positions 35, 39, 60, 93, 140 and 207 were observed as key contributing residues for selective affinity on these three targets.

  9. Plastid genome characterisation in Brassica and Brassicaceae using a new set of nine SSRs.

    PubMed

    Flannery, M L; Mitchell, F J G; Coyne, S; Kavanagh, T A; Burke, J I; Salamin, N; Dowding, P; Hodkinson, T R

    2006-11-01

    We report a new set of nine primer pairs specifically developed for amplification of Brassica plastid SSR markers. The wide utility of these markers is demonstrated for haplotype identification and detection of polymorphism in B. napus, B. nigra, B. oleracea, B. rapa and in related genera Arabidopsis, Camelina, Raphanus and Sinapis. Eleven gene regions (ndhB-rps7 spacer, rbcL-accD spacer, rpl16 intron, rps16 intron, atpB-rbcL spacer, trnE-trnT spacer, trnL intron, trnL-trnF spacer, trnM-atpE spacer, trnR-rpoC2 spacer, ycf3-psaA spacer) were sequenced from a range of Brassica and related genera for SSR detection and primer design. Other sequences were obtained from GenBank/EMBL. Eight out of nine selected SSR loci showed polymorphism when amplified using the new primers and a combined analysis detected variation within and between Brassica species, with the number of alleles detected per locus ranging from 5 (loci MF-6, MF-1) to 11 (locus MF-7). The combined SSR data were used in a neighbour-joining analysis (SMM, D (DM) distances) to group the samples based on the presence and absence of alleles. The analysis was generally able to separate plastid types into taxon-specific groups. Multi-allelic haplotypes were plotted onto the neighbour joining tree. A total number of 28 haplotypes were detected and these differentiated 22 of the 41 accessions screened from all other accessions. None of these haplotypes was shared by more than one species and some were not characteristic of their predicted type. We interpret our results with respect to taxon differentiation, hybridisation and introgression patterns relating to the 'Triangle of U'.

  10. Rational genomics I: antisense open reading frames and codon bias in short-chain oxido reductase enzymes and the evolution of the genetic code.

    PubMed

    Duax, William L; Huether, Robert; Pletnev, Vladimir Z; Langs, David; Addlagatta, Anthony; Connare, Sonjay; Habegger, Lukas; Gill, Jay

    2005-12-01

    The short-chain oxidoreductase (SCOR) family of enzymes includes over 6000 members, extending from bacteria and archaea to humans. Nucleic acid sequence analysis reveals that significant numbers of these genes are remarkably free of stopcodons in reading frames other than the coding frame, including those on the antisense strand. The genes from this subset also use almost entirely the GC-rich half of the 64 codons. Analysis of a million hypothetical genes having random nucleotide composition shows that the percentage of SCOR genes having multiple open reading frames exceeds random by a factor of as much as 1 x 10(6). Nevertheless, screening the content of the SWISS-PROT TrEMBL database reveals that 15% of all genes contain multiple open reading frames. The SCOR genes having multiple open reading frames and a GC-rich coding bias exhibit a similar GC bias in the nucleotide triple composition of their DNA. This bias is not correlated with the GC content of the species in which the SCOR genes are found. One possible explanation for the conservation of multiple open reading frames and extreme bias in nucleic acid composition in the family of Rossman folds is that the primordial member of this family was encoded early using only very stable GC-rich DNA and that evolution proceeded with extremely limited introduction of any codons having two or more adenine or thymine nucleotides. These and other data suggest that the SCOR family of enzymes may even have diverged from a common ancestor before most of the AT-rich half of the genetic code was fully defined.

  11. Selective amplification of an mRNA and related pseudogene for a human ADP-ribosylation factor, a guanine nucleotide-dependent protein activator of cholera toxin

    SciTech Connect

    Monaco, L.; Murtagh, J.J.; Newman, K.B.; Tsai, Su-Chen; Moss, J.; Vaughan, M. )

    1990-03-01

    ADP-ribosylation factors (ARFs) are {approx}20-kDa proteins that act as GTP-dependent allosteric activators of cholera toxin. With deoxyinosine-containing degenerate oligonucleotide primers corresponding to conserved GTP-binding domains in ARFs, the polymerase chain reaction (PCR) was used to amplify simultaneously from human DNA portions of three ARF genes that include codons for 102 amino acids, with intervening sequences. Amplification products that differed in size because of differences in intron sizes were separated by agarose gel electrophoresis. One amplified DNA contained no introns and had a sequence different from those of known AFRs. Based on this sequence, selective oligonucleotide probes were prepared and used to isolate clone {Psi}ARF 4, a putative ARF pseudogene, from a human genomic library in {lambda} phage EMBL3. Reverse transcription-PCR was then used to clone from human poly(A){sup +} RNA the cDNA corresponding to the expressed homolog of {Psi}ARF 4, referred to as human ARF 4. It appears that {Psi}ARF 4 arose during human evolution by integration of processed ARF 4 mRNA into the genome. Human ARF 4 differs from previously identified mammalian ARFs 1, 2, and 3. Hybridization of ARF 4-specific oligonucleotide probes with human, bovine, and rat RNA revealed a single 1.8-kilobase mRNA, which was clearly distinguished from the 1.9-kilobase mRNA for ARF 1 in these tissues. The PCR provides a powerful tool for investigating diversity in this and other multigene families, especially with primers targeted at domains believed to have functional significance.

  12. Privacy-preserving search for chemical compound databases

    PubMed Central

    2015-01-01

    Background Searching for similar compounds in a database is the most important process for in-silico drug screening. Since a query compound is an important starting point for the new drug, a query holder, who is afraid of the query being monitored by the database server, usually downloads all the records in the database and uses them in a closed network. However, a serious dilemma arises when the database holder also wants to output no information except for the search results, and such a dilemma prevents the use of many important data resources. Results In order to overcome this dilemma, we developed a novel cryptographic protocol that enables database searching while keeping both the query holder's privacy and database holder's privacy. Generally, the application of cryptographic techniques to practical problems is difficult because versatile techniques are computationally expensive while computationally inexpensive techniques can perform only trivial computation tasks. In this study, our protocol is successfully built only from an additive-homomorphic cryptosystem, which allows only addition performed on encrypted values but is computationally efficient compared with versatile techniques such as general purpose multi-party computation. In an experiment searching ChEMBL, which consists of more than 1,200,000 compounds, the proposed method was 36,900 times faster in CPU time and 12,000 times as efficient in communication size compared with general purpose multi-party computation. Conclusion We proposed a novel privacy-preserving protocol for searching chemical compound databases. The proposed method, easily scaling for large-scale databases, may help to accelerate drug discovery research by making full use of unused but valuable data that includes sensitive information. PMID:26678650

  13. Nucleotide sequence of the tobacco (Nicotiana tabacum) anionic peroxidase gene

    SciTech Connect

    Diaz-De-Leon, F.; Klotz, K.L.; Lagrimini, L.M. )

    1993-03-01

    Peroxidases have been implicated in numerous physiological processes including lignification (Grisebach, 1981), wound-healing (Espelie et al., 1986), phenol oxidation (Lagrimini, 1991), pathogen defense (Ye et al., 1990), and the regulation of cell elongation through the formation of interchain covalent bonds between various cell wall polymers (Fry, 1986; Goldberg et al., 1986; Bradley et al., 1992). However, a complete description of peroxidase action in vivo is not available because of the vast number of potential substrates and the existence of multiple isoenzymes. The tobacco anionic peroxidase is one of the better-characterized isoenzymes. This enzyme has been shown to oxidize a number of significant plant secondary compounds in vitro including cinnamyl alcohols, phenolic acids, and indole-3-acetic acid (Maeder, 1980; Lagrimini, 1991). A cDNA encoding the enzyme has been obtained, and this enzyme was shown to be expressed at the highest levels in lignifying tissues (xylem and tracheary elements) and also in epidermal tissue (Lagrimini et al., 1987). It was shown at this time that there were four distinct copies of the anionic peroxidase gene in tobacco (Nicotiana tabacum). A tobacco genomic DNA library was constructed in the [lambda]-phase EMBL3, from which two unique peroxidase genes were sequenced. One of these clones, [lambda]POD1, was designated as a pseudogene when the exonic sequences were found to differ from the cDNA sequences by 1%, and several frame shifts in the coding sequences indicated a dysfunctional gene (the authors' unpublished results). The other clone, [lambda]POD3, described in this manuscript, was designated as the functional tobacco anionic peroxidase gene because of 100% homology with the cDNA. Significant structural elements include an AS-2 box indicated in shoot-specific expression (Lam and Chua, 1989), a TATA box, and two intervening sequences. 10 refs., 1 tab.

  14. The obligate respiratory supercomplex from Actinobacteria.

    PubMed

    Kao, Wei-Chun; Kleinschroth, Thomas; Nitschke, Wolfgang; Baymann, Frauke; Neehaul, Yashvin; Hellwig, Petra; Richers, Sebastian; Vonck, Janet; Bott, Michael; Hunte, Carola

    2016-10-01

    Actinobacteria are closely linked to human life as industrial producers of bioactive molecules and as human pathogens. Respiratory cytochrome bcc complex and cytochrome aa3 oxidase are key components of their aerobic energy metabolism. They form a supercomplex in the actinobacterial species Corynebacterium glutamicum. With comprehensive bioinformatics and phylogenetic analysis we show that genes for cyt bcc-aa3 supercomplex are characteristic for Actinobacteria (Actinobacteria and Acidimicrobiia, except the anaerobic orders Actinomycetales and Bifidobacteriales). An obligatory supercomplex is likely, due to the lack of genes encoding alternative electron transfer partners such as mono-heme cyt c. Instead, subunit QcrC of bcc complex, here classified as short di-heme cyt c, will provide the exclusive electron transfer link between the complexes as in C. glutamicum. Purified to high homogeneity, the C. glutamicum bcc-aa3 supercomplex contained all subunits and cofactors as analyzed by SDS-PAGE, BN-PAGE, absorption and EPR spectroscopy. Highly uniform supercomplex particles in electron microscopy analysis support a distinct structural composition. The supercomplex possesses a dimeric stoichiometry with a ratio of a-type, b-type and c-type hemes close to 1:1:1. Redox titrations revealed a low potential bcc complex (Em(ISP)=+160mV, Em(bL)=-291mV, Em(bH)=-163mV, Em(cc)=+100mV) fined-tuned for oxidation of menaquinol and a mixed potential aa3 oxidase (Em(CuA)=+150mV, Em(a/a3)=+143/+317mV) mediating between low and high redox potential to accomplish dioxygen reduction. The generated molecular model supports a stable assembled supercomplex with defined architecture which permits energetically efficient coupling of menaquinol oxidation and dioxygen reduction in one supramolecular entity. PMID:27472998

  15. Characterization of the bovine C alpha gene.

    PubMed Central

    Brown, W R; Rabbani, H; Butler, J E; Hammarström, L

    1997-01-01

    The complete genomic sequence of a bovine C alpha gene is reported here. The genomic sequence was obtained from a C alpha phage clone that had been cloned from a genomic EMBL4 phage vector library. The C alpha sequence had previously been expressed as a chimeric antibody and identified as IgA using IgA-specific antibodies. Intron/exon boundaries were determined by comparison of the genomic sequence with an expressed bovine C alpha sequence obtained from spleen by reverse transcription-polymerase chain reaction (RT-PCR). Analysis of 50 Swedish bovine genomic DNA samples using genomic blots and five different restriction enzymes failed to detect evidence of polymorphism. However, PstI digests of Brown Swiss DNA showed a restriction fragment length polymorphism (RFLP), suggesting that at least two allelic variants of bovine IgA exist. Comparison of the deduced amino acid sequence of bovine IgA with sequences available for other species indicated that the highest homology was with that of swine, another artiodactyl. This was the highest homology observed for all mammalian IgA compared except for that between IgA1 and IgA2 in humans. Bovine IgA shares with rabbit IgA3 and IgA4, an additional N-linked glycosylation site at position 282. However, the collective data indicate that cattle are like swine and rodents and unlike rabbits in having a single locus of the gene encoding IgA of this species. Images Figure 4 PMID:9203958

  16. Differentiation of Bacillus pumilus and Bacillus safensis Using MALDI-TOF-MS

    PubMed Central

    Branquinho, Raquel; Sousa, Clara; Lopes, João; Pintado, Manuela E.; Peixe, Luísa V.; Osório, Hugo

    2014-01-01

    Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) despite being increasingly used as a method for microbial identification, still present limitations in which concerns the differentiation of closely related species. Bacillus pumillus and Bacillus safensis, are species of biotechnological and pharmaceutical significance, difficult to differentiate by conventional methodologies. In this study, using a well-characterized collection of B. pumillus and B. safensis isolates, we demonstrated the suitability of MALDI-TOF-MS combined with chemometrics to accurately and rapidly identify them. Moreover, characteristic species-specific ion masses were tentatively assigned, using UniProtKB/Swiss-Prot and UniProtKB/TrEMBL databases and primary literature. Delineation of B. pumilus (ions at m/z 5271 and 6122) and B. safensis (ions at m/z 5288, 5568 and 6413) species were supported by a congruent characteristic protein pattern. Moreover, using a chemometric approach, the score plot created by partial least square discriminant analysis (PLSDA) of mass spectra demonstrated the presence of two individualized clusters, each one enclosing isolates belonging to a species-specific spectral group. The generated pool of species-specific proteins comprised mostly ribosomal and SASPs proteins. Therefore, in B. pumilus the specific ion at m/z 5271 was associated with a small acid-soluble spore protein (SASP O) or with 50S protein L35, whereas in B. safensis specific ions at m/z 5288 and 5568 were associated with SASP J and P, respectively, and an ion at m/z 6413 with 50S protein L32. Thus, the resulting unique protein profile combined with chemometric analysis, proved to be valuable tools for B. pumilus and B. safensis discrimination, allowing their reliable, reproducible and rapid identification. PMID:25314655

  17. Indexing molecules for their hERG liability.

    PubMed

    Rayan, Anwar; Falah, Mizied; Raiyn, Jamal; Da'adoosh, Beny; Kadan, Sleman; Zaid, Hilal; Goldblum, Amiram

    2013-07-01

    The human Ether-a-go-go-Related-Gene (hERG) potassium (K(+)) channel is liable to drug-inducing blockage that prolongs the QT interval of the cardiac action potential, triggers arrhythmia and possibly causes sudden cardiac death. Early prediction of drug liability to hERG K(+) channel is therefore highly important and preferably obligatory at earlier stages of any drug discovery process. In vitro assessment of drug binding affinity to hERG K(+) channel involves substantial expenses, time, and labor; and therefore computational models for predicting liabilities of drug candidates for hERG toxicity is of much importance. In the present study, we apply the Iterative Stochastic Elimination (ISE) algorithm to construct a large number of rule-based models (filters) and exploit their combination for developing the concept of hERG Toxicity Index (ETI). ETI estimates the molecular risk to be a blocker of hERG potassium channel. The area under the curve (AUC) of the attained model is 0.94. The averaged ETI of hERG binders, drugs from CMC, clinical-MDDR, endogenous molecules, ACD and ZINC, were found to be 9.17, 2.53, 3.3, -1.98, -2.49 and -3.86 respectively. Applying the proposed hERG Toxicity Index Model on external test set composed of more than 1300 hERG blockers picked from chEMBL shows excellent performance (Matthews Correlation Coefficient of 0.89). The proposed strategy could be implemented for the evaluation of chemicals in the hit/lead optimization stages of the drug discovery process, improve the selection of drug candidates as well as the development of safe pharmaceutical products. PMID:23727540

  18. Antagonistic activity of Bacillus sp. obtained from an Algerian oilfield and chemical biocide THPS against sulfate-reducing bacteria consortium inducing corrosion in the oil industry.

    PubMed

    Gana, Mohamed Lamine; Kebbouche-Gana, Salima; Touzi, Abdelkader; Zorgani, Mohamed Amine; Pauss, André; Lounici, Hakim; Mameri, Nabil

    2011-03-01

    The present study enlightens the role of the antagonistic potential of nonpathogenic strain B21 against sulfate-reducing bacteria (SRB) consortium. The inhibitor effects of strain B21 were compared with those of the chemical biocide tetrakishydroxymethylphosphonium sulfate (THPS), generally used in the petroleum industry. The biological inhibitor exhibited much better and effective performance. Growth of SRB in coculture with bacteria strain B21 antagonist exhibited decline in SRB growth, reduction in production of sulfides, with consumption of sulfate. The observed effect seems more important in comparison with the effect caused by the tested biocide (THPS). Strain B21, a dominant facultative aerobic species, has salt growth requirement always above 5% (w/v) salts with optimal concentration of 10-15%. Phylogenetic analysis based on partial 16S rRNA gene sequences showed that strain B21 is a member of the genus Bacillus, being most closely related to Bacillus qingdaonensis DQ115802 (94.0% sequence similarity), Bacillus aidingensis DQ504377 (94.0%), and Bacillus salarius AY667494 (92.2%). Comparative analysis of partial 16S rRNA gene sequence data plus physiological, biochemical, and phenotypic features of the novel isolate and related species of Bacillus indicated that strain B21 may represent a novel species within the genus Bacillus, named Bacillus sp. (EMBL, FR671419). The results of this study indicate the application potential of Bacillus strain B21 as a biocontrol agent to fight corrosion in the oil industry.

  19. Tuning hERG out: Antitarget QSAR Models for Drug Development

    PubMed Central

    Braga, Rodolpho C.; Alves, Vinícius M.; Silva, Meryck F. B.; Muratov, Eugene; Fourches, Denis; Tropsha, Alexander; Andrade, Carolina H.

    2015-01-01

    Several non-cardiovascular drugs have been withdrawn from the market due to their inhibition of hERG K+ channels that can potentially lead to severe heart arrhythmia and death. As hERG safety testing is a mandatory FDA-required procedure, there is a considerable interest for developing predictive computational tools to identify and filter out potential hERG blockers early in the drug discovery process. In this study, we aimed to generate predictive and well-characterized quantitative structure–activity relationship (QSAR) models for hERG blockage using the largest publicly available dataset of 11,958 compounds from the ChEMBL database. The models have been developed and validated according to OECD guidelines using four types of descriptors and four different machine-learning techniques. The classification accuracies discriminating blockers from non-blockers were as high as 0.83–0.93 on external set. Model interpretation revealed several SAR rules, which can guide structural optimization of some hERG blockers into non-blockers. We have also applied the generated models for screening the World Drug Index (WDI) database and identify putative hERG blockers and non-blockers among currently marketed drugs. The developed models can reliably identify blockers and non-blockers, which could be useful for the scientific community. A freely accessible web server has been developed allowing users to identify putative hERG blockers and non-blockers in chemical libraries of their interest (http://labmol.farmacia.ufg.br/predherg). PMID:24805060

  20. Data collection with a tailored X-ray beam size at 2.69 Å wavelength (4.6 keV): sulfur SAD phasing of Cdc23Nterm

    PubMed Central

    Cianci, Michele; Groves, Matthew R.; Barford, David; Schneider, Thomas R.

    2016-01-01

    The capability to reach wavelengths of up to 3.1 Å at the newly established EMBL P13 beamline at PETRA III, the new third-generation synchrotron at DESY in Hamburg, provides the opportunity to explore very long wavelengths to harness the sulfur anomalous signal for phase determination. Data collection at λ = 2.69 Å (4.6 keV) allowed the crystal structure determination by sulfur SAD phasing of Cdc23Nterm, a subunit of the multimeric anaphase-promoting complex (APC/C). At this energy, Cdc23Nterm has an expected Bijvoet ratio 〈|F anom|〉/〈F〉 of 2.2%, with 282 residues, including six cysteines and five methionine residues, and two molecules in the asymmetric unit (65.4 kDa; 12 Cys and ten Met residues). Selectively illuminating two separate portions of the same crystal with an X-ray beam of 50 µm in diameter allowed crystal twinning to be overcome. The crystals diffracted to 3.1 Å resolution, with unit-cell parameters a = b = 61.2, c = 151.5 Å, and belonged to space group P43. The refined structure to 3.1 Å resolution has an R factor of 18.7% and an R free of 25.9%. This paper reports the structure solution, related methods and a discussion of the instrumentation. PMID:26960127

  1. pgaA and pgaB encode two constitutively expressed endopolygalacturonases of Aspergillus niger.

    PubMed Central

    Parenicová, L; Benen, J A; Kester, H C; Visser, J

    2000-01-01

    The nucleotide sequence data for pgaA and pgaB have been deposited with the EMBL, GenBank and DDBJ Databases under accession numbers Y18804 and Y18805 respectively. pgaA and pgaB, two genes encoding endopolygalacturonases (PGs, EC 3.2.1.15) A and B, were isolated from a phage genomic library of Aspergillus niger N400. The 1167 bp protein coding region of the pgaA gene is interrupted by one intron, whereas the 1234 bp coding region of the pgaB gene contains two introns. The corresponding proteins, PGA and PGB, consist of 370 and 362 amino acid residues respectively. Northern-blot analysis revealed that pgaA- and pgaB-specific mRNA accumulate in mycelia grown on sucrose. mRNAs are also present upon transfer to media containing D-galacturonic acid and pectin. Recombinant PGA and PGB were characterized with respect to pH optimum, activity on polygalacturonic acid, and mode of action and kinetics on oligogalacturonates of different chain length (n=3-7). At their pH optimum the specific activities in a standard assay for PGA (pH 4.2) and PGB (pH 5.0) were 16.5 mu+kat.mg(-1) and 8.3 mu+kat.mg(-1) respectively. Product progression analysis, using polygalacturonate as a substrate, revealed a random cleavage pattern for both enzymes and indicated processive behaviour for PGA. This result was confirmed by analysis of the mode of action using oligogalacturonates. Processivity was observed when the degree of polymerization of the substrate exceeded 6. Using pectins of various degrees of methyl esterification, it was shown that PGA and PGB both preferred partially methylated substrates. PMID:10642523

  2. Amyotrophic Lateral Sclerosis Type 20 - In Silico Analysis and Molecular Dynamics Simulation of hnRNPA1.

    PubMed

    Krebs, Bruna Baumgarten; De Mesquita, Joelma Freire

    2016-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that affects the upper and lower motor neurons. 5-10% of cases are genetically inherited, including ALS type 20, which is caused by mutations in the hnRNPA1 gene. The goals of this work are to analyze the effects of non-synonymous single nucleotide polymorphisms (nsSNPs) on hnRNPA1 protein function, to model the complete tridimensional structure of the protein using computational methods and to assess structural and functional differences between the wild type and its variants through Molecular Dynamics simulations. nsSNP, PhD-SNP, Polyphen2, SIFT, SNAP, SNPs&GO, SNPeffect and PROVEAN were used to predict the functional effects of nsSNPs. Ab initio modeling of hnRNPA1 was made using Rosetta and refined using KoBaMIN. The structure was validated by PROCHECK, Rampage, ERRAT, Verify3D, ProSA and Qmean. TM-align was used for the structural alignment. FoldIndex, DICHOT, ELM, D2P2, Disopred and DisEMBL were used to predict disordered regions within the protein. Amino acid conservation analysis was assessed by Consurf, and the molecular dynamics simulations were performed using GROMACS. Mutations D314V and D314N were predicted to increase amyloid propensity, and predicted as deleterious by at least three algorithms, while mutation N73S was predicted as neutral by all the algorithms. D314N and D314V occur in a highly conserved amino acid. The Molecular Dynamics results indicate that all mutations increase protein stability when compared to the wild type. Mutants D314N and N319S showed higher overall dimensions and accessible surface when compared to the wild type. The flexibility level of the C-terminal residues of hnRNPA1 is affected by all mutations, which may affect protein function, especially regarding the protein ability to interact with other proteins. PMID:27414033

  3. The 2016 database issue of Nucleic Acids Research and an updated molecular biology database collection.

    PubMed

    Rigden, Daniel J; Fernández-Suárez, Xosé M; Galperin, Michael Y

    2016-01-01

    The 2016 Database Issue of Nucleic Acids Research starts with overviews of the resources provided by three major bioinformatics centers, the U.S. National Center for Biotechnology Information (NCBI), the European Bioinformatics Institute (EMBL-EBI) and Swiss Institute for Bioinformatics (SIB). Also included are descriptions of 62 new databases and updates on 95 databases that have been previously featured in NAR plus 17 previously described elsewhere. A number of papers in this issue deal with resources on nucleic acids, including various kinds of non-coding RNAs and their interactions, molecular dynamics simulations of nucleic acid structure, and two databases of super-enhancers. The protein database section features important updates on the EBI's Pfam, PDBe and PRIDE databases, as well as a variety of resources on pathways, metabolomics and metabolic modeling. This issue also includes updates on popular metagenomics resources, such as MG-RAST, EBI Metagenomics, and probeBASE, as well as a newly compiled Human Pan-Microbe Communities database. A significant fraction of the new and updated databases are dedicated to the genetic basis of disease, primarily cancer, and various aspects of drug research, including resources for patented drugs, their side effects, withdrawn drugs, and potential drug targets. A further six papers present updated databases of various antimicrobial and anticancer peptides. The entire Database Issue is freely available online on the Nucleic Acids Research website (http://nar.oxfordjournals.org/). The NAR online Molecular Biology Database Collection, http://www.oxfordjournals.org/nar/database/c/, has been updated with the addition of 88 new resources and removal of 23 obsolete websites, which brought the current listing to 1685 databases. PMID:26740669

  4. Next-generation sequencing: a challenge to meet the increasing demand for training workshops in Australia

    PubMed Central

    Watson-Haigh, Nathan S.; Shang, Catherine A.; Haimel, Matthias; Kostadima, Myrto; Loos, Remco; Deshpande, Nandan; Duesing, Konsta; Li, Xi; McGrath, Annette; McWilliam, Sean; Michnowicz, Simon; Moolhuijzen, Paula; Quenette, Steve; Revote, Jerico Nico De Leon; Tyagi, Sonika; Schneider, Maria V.

    2013-01-01

    The widespread adoption of high-throughput next-generation sequencing (NGS) technology among the Australian life science research community is highlighting an urgent need to up-skill biologists in tools required for handling and analysing their NGS data. There is currently a shortage of cutting-edge bioinformatics training courses in Australia as a consequence of a scarcity of skilled trainers with time and funding to develop and deliver training courses. To address this, a consortium of Australian research organizations, including Bioplatforms Australia, the Commonwealth Scientific and Industrial Research Organisation and the Australian Bioinformatics Network, have been collaborating with EMBL-EBI training team. A group of Australian bioinformaticians attended the train-the-trainer workshop to improve training skills in developing and delivering bioinformatics workshop curriculum. A 2-day NGS workshop was jointly developed to provide hands-on knowledge and understanding of typical NGS data analysis workflows. The road show–style workshop was successfully delivered at five geographically distant venues in Australia using the newly established Australian NeCTAR Research Cloud. We highlight the challenges we had to overcome at different stages from design to delivery, including the establishment of an Australian bioinformatics training network and the computing infrastructure and resource development. A virtual machine image, workshop materials and scripts for configuring a machine with workshop contents have all been made available under a Creative Commons Attribution 3.0 Unported License. This means participants continue to have convenient access to an environment they had become familiar and bioinformatics trainers are able to access and reuse these resources. PMID:23543352

  5. Analysis of beta-carotene hydroxylase gene cDNA isolated from the American oil-palm (Elaeis oleifera) mesocarp tissue cDNA library

    PubMed Central

    Bhore, Subhash J; Kassim, Amelia; Loh, Chye Ying; Shah, Farida H

    2010-01-01

    It is well known that the nutritional quality of the American oil-palm (Elaeis oleifera) mesocarp oil is superior to that of African oil-palm (Elaeis guineensis Jacq. Tenera) mesocarp oil. Therefore, it is of important to identify the genetic features for its superior value. This could be achieved through the genome sequencing of the oil-palm. However, the genome sequence is not available in the public domain due to commercial secrecy. Hence, we constructed a cDNA library and generated expressed sequence tags (3,205) from the mesocarp tissue of the American oil-palm. We continued to annotate each of these cDNAs after submitting to GenBank/DDBJ/EMBL. A rough analysis turned our attention to the beta-carotene hydroxylase (Chyb) enzyme encoding cDNA. Then, we completed the full sequencing of cDNA clone for its both strands using M13 forward and reverse primers. The full nucleotide and protein sequence was further analyzed and annotated using various Bioinformatics tools. The analysis results showed the presence of fatty acid hydroxylase superfamily domain in the protein sequence. The multiple sequence alignment of selected Chyb amino acid sequences from other plant species and algal members with E. oleifera Chyb using ClustalW and its phylogenetic analysis suggest that Chyb from monocotyledonous plant species, Lilium hubrid, Crocus sativus and Zea mays are the most evolutionary related with E. oleifera Chyb. This study reports the annotation of E. oleifera Chyb. Abbreviations ESTs - expressed sequence tags, EoChyb - Elaeis oleifera beta-carotene hydroxylase, MC - main cluster PMID:21364789

  6. GOLD: The Genomes Online Database

    DOE Data Explorer

    Kyrpides, Nikos; Liolios, Dinos; Chen, Amy; Tavernarakis, Nektarios; Hugenholtz, Philip; Markowitz, Victor; Bernal, Alex

    Since its inception in 1997, GOLD has continuously monitored genome sequencing projects worldwide and has provided the community with a unique centralized resource that integrates diverse information related to Archaea, Bacteria, Eukaryotic and more recently Metagenomic sequencing projects. As of September 2007, GOLD recorded 639 completed genome projects. These projects have their complete sequence deposited into the public archival sequence databases such as GenBank EMBL,and DDBJ. From the total of 639 complete and published genome projects as of 9/2007, 527 were bacterial, 47 were archaeal and 65 were eukaryotic. In addition to the complete projects, there were 2158 ongoing sequencing projects. 1328 of those were bacterial, 59 archaeal and 771 eukaryotic projects. Two types of metadata are provided by GOLD: (i) project metadata and (ii) organism/environment metadata. GOLD CARD pages for every project are available from the link of every GOLD_STAMP ID. The information in every one of these pages is organized into three tables: (a) Organism information, (b) Genome project information and (c) External links. [The Genomes On Line Database (GOLD) in 2007: Status of genomic and metagenomic projects and their associated metadata, Konstantinos Liolios, Konstantinos Mavromatis, Nektarios Tavernarakis and Nikos C. Kyrpides, Nucleic Acids Research Advance Access published online on November 2, 2007, Nucleic Acids Research, doi:10.1093/nar/gkm884]

    The basic tables in the GOLD database that can be browsed or searched include the following information:

    • Gold Stamp ID
    • Organism name
    • Domain
    • Links to information sources
    • Size and link to a map, when available
    • Chromosome number, Plas number, and GC content
    • A link for downloading the actual genome data
    • Institution that did the sequencing
    • Funding source
    • Database where information resides
    • Publication status and information

    • Oncorhyncin III: a potent antimicrobial peptide derived from the non-histone chromosomal protein H6 of rainbow trout, Oncorhynchus mykiss.

      PubMed Central

      Fernandes, Jorge M O; Saint, Nathalie; Kemp, Graham D; Smith, Valerie J

      2003-01-01

      The partial N-terminal amino acid sequence of the antimicrobial peptide reported in the present paper has been submitted to the TrEMBL database under the accession number P83338. A 6.7 kDa antimicrobial peptide was isolated from trout skin secretions using acid extraction followed by cation-exchange chromatography, (t)C(18) solid-phase extraction, and C(18) reversed-phase HPLC. The molecular mass of this peptide, which is tentatively named oncorhyncin III, is 6671 Da, as determined by matrix-assisted laser-desorption ionization MS. N-terminal amino acid sequencing revealed that the first 13 residues of oncorhyncin III are identical with those of the non-histone chromosomal protein H6 from rainbow trout. Hence these data combined with the MS results indicate that oncorhyncin III is likely to be a cleavage product of the non-histone chromosomal protein H6 (residues 1-66) and that it probably contains two methylated residues or one double methylation. The purified peptide exhibits potent antibacterial activity against both Gram-positive and Gram-negative bacteria, with minimal inhibitory concentrations in the submicromolar range. The peptide is sensitive to NaCl, and displays no haemolytic activity towards trout erythrocytes at concentrations below 1 microM. Scanning electron microscopy revealed that oncorhyncin III does not cause direct disruption of bacterial cells. Reconstitution of the peptide in planar lipid bilayers strongly disturbs the membranes, but does not induce the formation of stable ion channels. Taken together, these results support the hypothesis that oncorhyncin III plays a role in mucosal innate host defence. PMID:12713443

    • "helix Nebula - the Science Cloud", a European Science Driven Cross-Domain Initiative Implemented in via AN Active Ppp Set-Up

      NASA Astrophysics Data System (ADS)

      Lengert, W.; Mondon, E.; Bégin, M. E.; Ferrer, M.; Vallois, F.; DelaMar, J.

      2015-12-01

      Helix Nebula, a European science cross-domain initiative building on an active PPP, is aiming to implement the concept of an open science commons[1] while using a cloud hybrid model[2] as the proposed implementation solution. This approach allows leveraging and merging of complementary data intensive Earth Science disciplines (e.g. instrumentation[3] and modeling), without introducing significant changes in the contributors' operational set-up. Considering the seamless integration with life-science (e.g. EMBL), scientific exploitation of meteorological, climate, and Earth Observation data and models open an enormous potential for new big data science. The work of Helix Nebula has shown that is it feasible to interoperate publicly funded infrastructures, such as EGI [5] and GEANT [6], with commercial cloud services. Such hybrid systems are in the interest of the existing users of publicly funded infrastructures and funding agencies because they will provide "freedom and choice" over the type of computing resources to be consumed and the manner in which they can be obtained. But to offer such freedom and choice across a spectrum of suppliers, various issues such as intellectual property, legal responsibility, service quality agreements and related issues need to be addressed. Finding solutions to these issues is one of the goals of the Helix Nebula initiative. [1] http://www.egi.eu/news-and-media/publications/OpenScienceCommons_v3.pdf [2] http://www.helix-nebula.eu/events/towards-the-european-open-science-cloud [3] e.g. https://sentinel.esa.int/web/sentinel/sentinel-data-access [5] http://www.egi.eu/ [6] http://www.geant.net/

    • MMpI: A WideRange of Available Compounds of Matrix Metalloproteinase Inhibitors.

      PubMed

      Muvva, Charuvaka; Patra, Sanjukta; Venkatesan, Subramanian

      2016-01-01

      Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in the regulation of the extracellular signaling and structural matrix environment of cells and tissues. MMPs are considered as promising targets for the treatment of many diseases. Therefore, creation of database on the inhibitors of MMP would definitely accelerate the research activities in this area due to its implication in above-mentioned diseases and associated limitations in the first and second generation inhibitors. In this communication, we report the development of a new MMpI database which provides resourceful information for all researchers working in this field. It is a web-accessible, unique resource that contains detailed information on the inhibitors of MMP including small molecules, peptides and MMP Drug Leads. The database contains entries of ~3000 inhibitors including ~72 MMP Drug Leads and ~73 peptide based inhibitors. This database provides the detailed molecular and structural details which are necessary for the drug discovery and development. The MMpI database contains physical properties, 2D and 3D structures (mol2 and pdb format files) of inhibitors of MMP. Other data fields are hyperlinked to PubChem, ChEMBL, BindingDB, DrugBank, PDB, MEROPS and PubMed. The database has extensive searching facility with MMpI ID, IUPAC name, chemical structure and with the title of research article. The MMP inhibitors provided in MMpI database are optimized using Python-based Hierarchical Environment for Integrated Xtallography (Phenix) software. MMpI Database is unique and it is the only public database that contains and provides the complete information on the inhibitors of MMP. Database URL: http://clri.res.in/subramanian/databases/mmpi/index.php.

    • Revised sequence of the Porphyromonas gingivalis prtT cysteine protease/hemagglutinin gene: homology with streptococcal pyrogenic exotoxin B/streptococcal proteinase.

      PubMed Central

      Madden, T E; Clark, V L; Kuramitsu, H K

      1995-01-01

      The prtT gene from Porphyromonas gingivalis ATCC 53977 was previously isolated from an Escherichia coli clone possessing trypsinlike protease activity upstream of a region encoding hemagglutinin activity (J. Otogoto and H. Kuramitsu, Infect. Immun. 61;117-123, 1993). Subsequent molecular analysis of this gene has revealed that the PrtT protein is larger than originally reported, encompassing the hemagglutination region. Results of primer extension experiments indicate that the translation start site was originally misidentified. An alternate open reading frame of nearly 2.7 kb, which encodes a protein in the size range of 96 to 99 kDa, was identified. In vitro transcription-translation experiments confirm this size, and Northern (RNA) blot experiments indicate that the protease is translated from a 3.3-kb mRNA. Searching the EMBL protein database revealed that the amino acid sequence of the revised PrtT is similar to sequences of two related proteins from Streptococcus pyogenes. PrtT is 31% identical and 73% similar over 401 amino acids to streptococcal pyrogenic exotoxin B. In addition, it is 36% identical and 74% similar over 244 amino acids with streptococcal proteinase, which is closely related to streptococcal pyrogenic exotoxin B. The similarity is particularly high at the putative active site of streptococcal proteinase, which is similar to the active sites of the family of cysteine proteases. Thus, we conclude that PrtT is a 96- to 99-kDa cysteine protease and hemagglutinin with significant similarity to streptococcal enzymes. PMID:7806362

    • Identification and expression analysis of the cyclophilin gene in Kandelia candel under stress of salt.

      PubMed

      Huang, Wei; Lin, Qi Feng; Li, Guan Yi; Zhao, Wen Ming

      2003-06-01

      Two cDNA fragments, named for SRGKC2 and SRGKC3, encoding cyclophilin in Kandelia candel were isolated by Representational Difference Analysis of cDNA. The two cDNA fragments were 282 bp and 160 bp, respectively. Sequence analysis shows that both of the SRGKC2 and SRGKC3 come from the same gene region, and SRGKC3 is a part of SRGKC2. In addition the SRGKC2 displayed 90% sequence identity over a region of 84 amino acids to the cyclophilin from Euphorbia esula and the SRGKC3 displayed 93% sequence identity over a region of 47 amino acids to the fava bean. The Northern blotting showed that the expression of SRGKC2 was suppressed under stress of salt. Based on the sequence of SRGKC2, a full-length cDNA (KCCYP1) was isolated by RACE reaction (This sequence data has been submitted to the EMBL databases under accession No. AY150052). The full-length cDNA was about 0.9 kb, which contained an open reading frame (ORF) of 516 bp and coded for 172 amino acid residues with isoelectric point of 8.57 and molecular weight of 18.2 kD. The motif A of the ATP/GTP-binding site in KCCYP1 appears at amino acid residues of 41-49, and seven-amino-acids-residue was inserted at 48-54 amino acid residues. The expression patterns of SRGKC2 in various species were also investigated. PMID:12966731

    • Making Transporter Models for Drug-Drug Interaction Prediction Mobile.

      PubMed

      Ekins, Sean; Clark, Alex M; Wright, Stephen H

      2015-10-01

      The past decade has seen increased numbers of studies publishing ligand-based computational models for drug transporters. Although they generally use small experimental data sets, these models can provide insights into structure-activity relationships for the transporter. In addition, such models have helped to identify new compounds as substrates or inhibitors of transporters of interest. We recently proposed that many transporters are promiscuous and may require profiling of new chemical entities against multiple substrates for a specific transporter. Furthermore, it should be noted that virtually all of the published ligand-based transporter models are only accessible to those involved in creating them and, consequently, are rarely shared effectively. One way to surmount this is to make models shareable or more accessible. The development of mobile apps that can access such models is highlighted here. These apps can be used to predict ligand interactions with transporters using Bayesian algorithms. We used recently published transporter data sets (MATE1, MATE2K, OCT2, OCTN2, ASBT, and NTCP) to build preliminary models in a commercial tool and in open software that can deliver the model in a mobile app. In addition, several transporter data sets extracted from the ChEMBL database were used to illustrate how such public data and models can be shared. Predicting drug-drug interactions for various transporters using computational models is potentially within reach of anyone with an iPhone or iPad. Such tools could help prioritize which substrates should be used for in vivo drug-drug interaction testing and enable open sharing of models. PMID:26199424

    • Meeting Report from the Genomic Standards Consortium (GSC) Workshops 6 and 7.

      PubMed

      Field, Dawn; Sterk, Peter; Kyrpides, Nikos; Kottmann, Renzo; Glöckner, Frank Oliver; Hirschman, Lynette; Garrity, George M; Wooley, John; Gilna, Paul

      2009-01-01

      This report summarizes the proceedings of the 6th and 7th workshops of the Genomic Standards Consortium (GSC), held back-to-back in 2008. GSC 6 focused on furthering the activities of GSC working groups, GSC 7 focused on outreach to the wider community. GSC 6 was held October 10-14, 2008 at the European Bioinformatics Institute, Cambridge, United Kingdom and included a two-day workshop focused on the refinement of the Genomic Contextual Data Markup Language (GCDML). GSC 7 was held as the opening day of the International Congress on Metagenomics 2008 in San Diego California. Major achievements of these combined meetings included an agreement from the International Nucleotide Sequence Database Consortium (INSDC) to create a "MIGS" keyword for capturing "Minimum Information about a Genome Sequence" compliant information within INSDC (DDBJ/EMBL /Genbank) records, launch of GCDML 1.0, MIGS compliance of the first set of "Genomic Encyclopedia of Bacteria and Archaea" project genomes, approval of a proposal to extend MIGS to 16S rRNA sequences within a "Minimum Information about an Environmental Sequence", finalization of plans for the GSC eJournal, "Standards in Genomic Sciences" (SIGS), and the formation of a GSC Board. Subsequently, the GSC has been awarded a Research Co-ordination Network (RCN4GSC) grant from the National Science Foundation, held the first SIGS workshop and launched the journal. The GSC will also be hosting outreach workshops at both ISMB 2009 and PSB 2010 focused on "Metagenomics, Metadata and MetaAnalysis" (M(3)). Further information about the GSC and its range of activities can be found at http://gensc.org, including videos of all the presentations at GSC 7.

    • Inferring multi-target QSAR models with taxonomy-based multi-task learning

      PubMed Central

      2013-01-01

      Background A plethora of studies indicate that the development of multi-target drugs is beneficial for complex diseases like cancer. Accurate QSAR models for each of the desired targets assist the optimization of a lead candidate by the prediction of affinity profiles. Often, the targets of a multi-target drug are sufficiently similar such that, in principle, knowledge can be transferred between the QSAR models to improve the model accuracy. In this study, we present two different multi-task algorithms from the field of transfer learning that can exploit the similarity between several targets to transfer knowledge between the target specific QSAR models. Results We evaluated the two methods on simulated data and a data set of 112 human kinases assembled from the public database ChEMBL. The relatedness between the kinase targets was derived from the taxonomy of the humane kinome. The experiments show that multi-task learning increases the performance compared to training separate models on both types of data given a sufficient similarity between the tasks. On the kinase data, the best multi-task approach improved the mean squared error of the QSAR models of 58 kinase targets. Conclusions Multi-task learning is a valuable approach for inferring multi-target QSAR models for lead optimization. The application of multi-task learning is most beneficial if knowledge can be transferred from a similar task with a lot of in-domain knowledge to a task with little in-domain knowledge. Furthermore, the benefit increases with a decreasing overlap between the chemical space spanned by the tasks. PMID:23842210

    • Benchmarking the Predictive Power of Ligand Efficiency Indices in QSAR.

      PubMed

      Cortes-Ciriano, Isidro

      2016-08-22

      Compound physicochemical properties favoring in vitro potency are not always correlated to desirable pharmacokinetic profiles. Therefore, using potency (i.e., IC50) as the main criterion to prioritize candidate drugs at early stage drug discovery campaigns has been questioned. Yet, the vast majority of the virtual screening models reported in the medicinal chemistry literature predict the biological activity of compounds by regressing in vitro potency on topological or physicochemical descriptors. Two studies published in this journal showed that higher predictive power on external molecules can be achieved by using ligand efficiency indices as the dependent variable instead of a metric of potency (IC50) or binding affinity (Ki). The present study aims at filling the shortage of a thorough assessment of the predictive power of ligand efficiency indices in QSAR. To this aim, the predictive power of 11 ligand efficiency indices has been benchmarked across four algorithms (Gradient Boosting Machines, Partial Least Squares, Random Forest, and Support Vector Machines), two descriptor types (Morgan fingerprints, and physicochemical descriptors), and 29 data sets collected from the literature and ChEMBL database. Ligand efficiency metrics led to the highest predictive power on external molecules irrespective of the descriptor type or algorithm used, with an R(2)test difference of ∼0.3 units and a this difference ∼0.4 units when modeling small data sets and a normalized RMSE decrease of >0.1 units in some cases. Polarity indices, such as SEI and NSEI, led to higher predictive power than metrics based on molecular size, i.e., BEI, NBEI, and LE. LELP, which comprises a polarity factor (cLogP) and a size parameter (LE) constantly led to the most predictive models, suggesting that these two properties convey a complementary predictive signal. Overall, this study suggests that using ligand efficiency indices as the dependent variable might be an efficient strategy to model

    • Get Your Atoms in Order--An Open-Source Implementation of a Novel and Robust Molecular Canonicalization Algorithm.

      PubMed

      Schneider, Nadine; Sayle, Roger A; Landrum, Gregory A

      2015-10-26

      Finding a canonical ordering of the atoms in a molecule is a prerequisite for generating a unique representation of the molecule. The canonicalization of a molecule is usually accomplished by applying some sort of graph relaxation algorithm, the most common of which is the Morgan algorithm. There are known issues with that algorithm that lead to noncanonical atom orderings as well as problems when it is applied to large molecules like proteins. Furthermore, each cheminformatics toolkit or software provides its own version of a canonical ordering, most based on unpublished algorithms, which also complicates the generation of a universal unique identifier for molecules. We present an alternative canonicalization approach that uses a standard stable-sorting algorithm instead of a Morgan-like index. Two new invariants that allow canonical ordering of molecules with dependent chirality as well as those with highly symmetrical cyclic graphs have been developed. The new approach proved to be robust and fast when tested on the 1.45 million compounds of the ChEMBL 20 data set in different scenarios like random renumbering of input atoms or SMILES round tripping. Our new algorithm is able to generate a canonical order of the atoms of protein molecules within a few milliseconds. The novel algorithm is implemented in the open-source cheminformatics toolkit RDKit. With this paper, we provide a reference Python implementation of the algorithm that could easily be integrated in any cheminformatics toolkit. This provides a first step toward a common standard for canonical atom ordering to generate a universal unique identifier for molecules other than InChI.

    • Whole-genome sequence of Chryseobacterium oranimense, a colistin-resistant bacterium isolated from a cystic fibrosis patient in France.

      PubMed

      Sharma, Poonam; Gupta, Sushim Kumar; Diene, Seydina M; Rolain, Jean-Marc

      2015-03-01

      For the first time, we report the whole-genome sequence analysis of Chryseobacterium oranimense G311, a multidrug-resistant bacterium, from a cystic fibrosis patient in France, including resistance to colistin. Whole-genome sequencing of C. oranimense G311 was performed using Ion Torrent PGM, and RAST, the EMBL-EBI server, and the Antibiotic Resistance Gene-ANNOTation (ARG-ANNOT) database were used for annotation of all genes, including antibiotic resistance (AR) genes. General features of the C. oranimense G311 draft genome were compared to the other available genomes of Chryseobacterium gleum and Chryseobacterium sp. strain CF314. C. oranimense G311 was found to be resistant to all β-lactams, including imipenem, and to colistin. The genome size of C. oranimense G311 is 4,457,049 bp in length, with 37.70% GC content. We found 27 AR genes in the genome, including β-lactamase genes which showed little similarity to the known β-lactamase genes and could likely be novel. We found the type I polyketide synthase operon followed by a zeaxanthin glycosyltransferase gene in the genome, which could impart the yellow pigmentation of the isolate. We located the O-antigen biosynthesis cluster, and we also discovered a novel capsular polysaccharide biosynthesis cluster. We also found known mutations in the orthologs of the pmrA (E8D), pmrB (L208F and P360Q), and lpxA (G68D) genes. We speculate that the presence of the capsular cluster and mutations in these genes could explain the resistance of this bacterium to colistin. We demonstrate that whole-genome sequencing was successfully applied to decipher the resistome of a multidrug resistance bacterium associated with cystic fibrosis patients.

    • The 2016 database issue of Nucleic Acids Research and an updated molecular biology database collection

      PubMed Central

      Rigden, Daniel J.; Fernández-Suárez, Xosé M.; Galperin, Michael Y.

      2016-01-01

      The 2016 Database Issue of Nucleic Acids Research starts with overviews of the resources provided by three major bioinformatics centers, the U.S. National Center for Biotechnology Information (NCBI), the European Bioinformatics Institute (EMBL-EBI) and Swiss Institute for Bioinformatics (SIB). Also included are descriptions of 62 new databases and updates on 95 databases that have been previously featured in NAR plus 17 previously described elsewhere. A number of papers in this issue deal with resources on nucleic acids, including various kinds of non-coding RNAs and their interactions, molecular dynamics simulations of nucleic acid structure, and two databases of super-enhancers. The protein database section features important updates on the EBI's Pfam, PDBe and PRIDE databases, as well as a variety of resources on pathways, metabolomics and metabolic modeling. This issue also includes updates on popular metagenomics resources, such as MG-RAST, EBI Metagenomics, and probeBASE, as well as a newly compiled Human Pan-Microbe Communities database. A significant fraction of the new and updated databases are dedicated to the genetic basis of disease, primarily cancer, and various aspects of drug research, including resources for patented drugs, their side effects, withdrawn drugs, and potential drug targets. A further six papers present updated databases of various antimicrobial and anticancer peptides. The entire Database Issue is freely available online on the Nucleic Acids Research website (http://nar.oxfordjournals.org/). The NAR online Molecular Biology Database Collection, http://www.oxfordjournals.org/nar/database/c/, has been updated with the addition of 88 new resources and removal of 23 obsolete websites, which brought the current listing to 1685 databases. PMID:26740669

    • Identification of a novel yolk protein in the hermatypic coral Galaxea fascicularis.

      PubMed

      Hayakawa, Hideki; Andoh, Tadashi; Watanabe, Toshiki

      2007-03-01

      The reef-building (or hermatypic) coral Galaxea fascicularis (Anthozoa, Hexacorallia, Scleractinia) has an annual reproductive cycle. Females of G. fascicularis release packages (or ;bundles') of eggs for external fertilization, whereas male individuals form bundles consisting of sperm and infertile ;pseudo-eggs' that are thought to confer buoyancy to the male bundle. In the egg of G. fascicularis, four proteins (GfEP-1 to 4) were found to be stored in high abundance, and three of them (GfEP-1, 2 and 3) are generated by processing of a vitellogenin (Vg)-like precursor. In the present study, a cDNA encoding GfEP-4 was cloned and its sequence determined (GenBank/EMBL/DDBJ accession no. AB259859). The amino acid sequence of this protein does not exhibit similarity to known proteins, including Vgs or other yolk proteins found in some invertebrates. The expression of GfEP-4 mRNA was observed in females, and also in the majority of males examined, although expression levels were lower than in females. The GfEP-4 protein was detected in pseudo-eggs, where its concentration was 20-100 times lower than in eggs. In contrast, GfEP-1, 2 and 3 were not detected in pseudo-eggs. A protein (28 kDa) which cross-reacted with anti-GfEP-4 antibodies was detected in eggs of the coral Montipora digitata, suggesting the possibility that homologs of this protein are present in the eggs of other scleractinian corals. PMID:17551245

    • Heterogeneous classifier fusion for ligand-based virtual screening: or, how decision making by committee can be a good thing.

      PubMed

      Riniker, Sereina; Fechner, Nikolas; Landrum, Gregory A

      2013-11-25

      The concept of data fusion - the combination of information from different sources describing the same object with the expectation to generate a more accurate representation - has found application in a very broad range of disciplines. In the context of ligand-based virtual screening (VS), data fusion has been applied to combine knowledge from either different active molecules or different fingerprints to improve similarity search performance. Machine-learning (ML) methods based on fusion of multiple homogeneous classifiers, in particular random forests, have also been widely applied in the ML literature. The heterogeneous version of classifier fusion - fusing the predictions from different model types - has been less explored. Here, we investigate heterogeneous classifier fusion for ligand-based VS using three different ML methods, RF, naïve Bayes (NB), and logistic regression (LR), with four 2D fingerprints, atom pairs, topological torsions, RDKit fingerprint, and circular fingerprint. The methods are compared using a previously developed benchmarking platform for 2D fingerprints which is extended to ML methods in this article. The original data sets are filtered for difficulty, and a new set of challenging data sets from ChEMBL is added. Data sets were also generated for a second use case: starting from a small set of related actives instead of diverse actives. The final fused model consistently outperforms the other approaches across the broad variety of targets studied, indicating that heterogeneous classifier fusion is a very promising approach for ligand-based VS. The new data sets together with the adapted source code for ML methods are provided in the Supporting Information .

  1. DNA sequence of the serum opacity factor of group A streptococci: identification of a fibronectin-binding repeat domain.

    PubMed Central

    Rakonjac, J V; Robbins, J C; Fischetti, V A

    1995-01-01

    The serum opacity factor (SOF) is a group A streptococcal protein that induces opacity of mammalian serum. The serum opacity factor 22 gene (sof22) from an M type 22 strain was cloned from an EMBL4 library by screening for plaques exhibiting serum opacity activity. DNA sequencing yielded an open reading frame of 3,075 bp. Its deduced amino acid sequence predicts a protein of 1,025 residues with a molecular weight of 112,735, a size that approximates that of the SOF22 protein isolated from both the original streptococcal strain and Escherichia coli harboring the cloned sof22 gene. The molecule is composed of three domains: an N-terminal domain responsible for the opacity reaction (opacity domain), a repeat domain with fibronectin-binding (Fn-binding) activity, and a C-terminal cell attachment domain. The C-terminal end of SOF22 is characterized by a hexameric LPXTGX motif, an adjacent hydrophobic region, and a charged C terminus, which are the hallmarks of cell-bound surface proteins found on nearly all gram-positive bacteria. Immediately upstream of this cell anchor region, SOF22 contains four tandem repeat sequence blocks, flanked by prolinerich segments. The repeats share up to 50% identity with a repeated motif found in other group A streptococcal Fn-binding proteins and exhibit Fn-binding activity, as shown by subcloning experiments. According to deletion analysis, the opacity domain is confined to the region N terminal to the repeat segment. Thus, SOF22 is unique among the known Fn-binding proteins from gram-positive bacteria in containing an independent module with a defined function in its N-terminal portion. Southern blot analysis with a probe from this N-terminal region indicates that the opacity domain of SOF varies extensively among different SOF-producing M types. PMID:7822031

  2. Sequence of a cloned pR72H fragment and its use for detection of Vibrio parahaemolyticus in shellfish with the PCR.

    PubMed Central

    Lee, C Y; Pan, S F; Chen, C H

    1995-01-01

    The nucleotide sequence of pR72H cloned from Vibrio parahaemolyticus 93 was determined. We examined all V. parahaemolyticus gene sequences published in the GenBank-EMBL databases for homology and found that no other DNA sequence of V. parahaemolyticus was highly homologous to the sequence reported in this study. A pair of primers, VP33-VP32, derived from a pR72H fragment were selected to detect V. parahaemolyticus. The sensitivity of PCR detection for a pure culture of V. parahaemolyticus was 10 cells from crude bacterial lysates. Furthermore, a detection level of 2.6 fg, equivalent to 1 cell, was obtained by using purified chromosomal DNA as the template. The expected PCR products were obtained from all V. parahaemolyticus strains tested (n = 124), while no PCR amplicons were found in other vibrios or related genera (n = 50). High levels (10(6) to 10(10) CFU/ml) of Escherichia coli cells did not affect the PCR assay sensitivity. The presence of 10(8) V. parahaemolyticus cells or 10(9) E. coli cells in the PCR mixtures completely inhibited the PCR. When oyster samples were inoculated with V. parahaemolyticus 93 and cultured in tryptic soy broth containing 3% NaCl for 3 h at 35 degrees C, an initial sample inoculum level of 9.3 CFU/g was detected in a PCR assay with crude bacterial lysates. The PCR assay with enrichment culturing in salt polymyxin broth was compared with the conventional method for naturally contaminated shellfish and fish samples. We conclude that this PCR assay with enrichment culturing is a good alternative method for the detection of V. parahaemolyticus. PMID:7747952

  3. Laminin alpha 5, a major transcript of normal and malignant rat liver epithelial cells, is differentially expressed in developing and adult liver.

    PubMed

    Seebacher, T; Medina, J L; Bade, E G

    1997-11-25

    The laminin family of extracellular matrix glycoproteins plays a major role in cell migration and differentiation and in tumor cell invasion. As previously shown, the laminin deposited by normal and malignant rat liver epithelial cells in their extracellular matrix (ECM) and into their ECM migration tracks does not contain a typical (EHS-like) alpha 1 heavy chain. By RT-PCR screening we have now identified two alpha chains among a total of five additional laminin chains produced by these cells. Three of the newly identified chains were not previously known for the rat. Their sequences have been deposited in the EMBL nucleotide sequence data bank. The alpha 5 chain now identified is expressed at comparably high levels by both the normal and the malignant liver epithelial cells. The chain is also expressed in fetal liver together with the alpha 2 and beta 2 chains, but it is only vestigially expressed in the mature organ as shown by RT-PCR. These results suggest for alpha 5 a role in development and production of the chain by only a small subset of cells in adult liver. At the level of detection used, no changes were observed in regenerating liver after partial hepatectomy. In addition to the alpha 5 chain, the cultured cells express the beta 1 and beta 2 light chains, indicating the expression of more than one laminin isoform by the same cell line. The expression of the alpha 5 chain and of the other new non-EHS isoform chains was also analyzed in various tissues. The malignant liver epithelial cells, but not their nontumorigenic parental cells, also express, in addition to the alpha 5 chain the alpha 2 chain, which is expressed at high level by the NBT II bladder carcinoma cell line, suggesting a relationship with malignancy. PMID:9417868

  4. Analysis of Litopenaeus vannamei Transcriptome Using the Next-Generation DNA Sequencing Technique

    PubMed Central

    Li, Chaozheng; Weng, Shaoping; Chen, Yonggui; Yu, Xiaoqiang; Lü, Ling; Zhang, Haiqing; He, Jianguo; Xu, Xiaopeng

    2012-01-01

    Background Pacific white shrimp (Litopenaeus vannamei), the major species of farmed shrimps in the world, has been attracting extensive studies, which require more and more genome background knowledge. The now available transcriptome data of L. vannamei are insufficient for research requirements, and have not been adequately assembled and annotated. Methodology/Principal Findings This is the first study that used a next-generation high-throughput DNA sequencing technique, the Solexa/Illumina GA II method, to analyze the transcriptome from whole bodies of L. vannamei larvae. More than 2.4 Gb of raw data were generated, and 109,169 unigenes with a mean length of 396 bp were assembled using the SOAP denovo software. 73,505 unigenes (>200 bp) with good quality sequences were selected and subjected to annotation analysis, among which 37.80% can be matched in NCBI Nr database, 37.3% matched in Swissprot, and 44.1% matched in TrEMBL. Using BLAST and BLAST2Go softwares, 11,153 unigenes were classified into 25 Clusters of Orthologous Groups of proteins (COG) categories, 8171 unigenes were assigned into 51 Gene ontology (GO) functional groups, and 18,154 unigenes were divided into 220 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. To primarily verify part of the results of assembly and annotations, 12 assembled unigenes that are homologous to many embryo development-related genes were chosen and subjected to RT-PCR for electrophoresis and Sanger sequencing analyses, and to real-time PCR for expression profile analyses during embryo development. Conclusions/Significance The L. vannamei transcriptome analyzed using the next-generation sequencing technique enriches the information of L. vannamei genes, which will facilitate our understanding of the genome background of crustaceans, and promote the studies on L. vannamei. PMID:23071809

  5. Characterization and genome functional analysis of a novel metamitron-degrading strain Rhodococcus sp. MET via both triazinone and phenyl rings cleavage.

    PubMed

    Fang, Hua; Xu, Tianheng; Cao, Duantao; Cheng, Longyin; Yu, Yunlong

    2016-01-01

    A novel bacterium capable of utilizing metamitron as the sole source of carbon and energy was isolated from contaminated soil and identified as Rhodococcus sp. MET based on its morphological characteristics, BIOLOG GP2 microplate profile, and 16S rDNA phylogeny. Genome sequencing and functional annotation of the isolate MET showed a 6,340,880 bp genome with a 62.47% GC content and 5,987 protein-coding genes. In total, 5,907 genes were annotated with the COG, GO, KEGG, Pfam, Swiss-Prot, TrEMBL, and nr databases. The degradation rate of metamitron by the isolate MET obviously increased with increasing substrate concentrations from 1 to 10 mg/l and subsequently decreased at 100 mg/l. The optimal pH and temperature for metamitron biodegradation were 7.0 and 20-30 °C, respectively. Based on genome annotation of the metamitron degradation genes and the metabolites detected by HPLC-MS/MS, the following metamitron biodegradation pathways were proposed: 1) Metamitron was transformed into 2-(3-hydrazinyl-2-ethyl)-hydrazono-2-phenylacetic acid by triazinone ring cleavage and further mineralization; 2) Metamitron was converted into 3-methyl-4-amino-6(2-hydroxy-muconic acid)-1,2,4-triazine-5(4H)-one by phenyl ring cleavage and further mineralization. The coexistence of diverse mineralization pathways indicates that our isolate may effectively bioremediate triazinone herbicide-contaminated soils. PMID:27578531

  6. Isolation and characterisation of crocodile and python ovotransferrins.

    PubMed

    Ciuraszkiewicz, Justyna; Olczak, Mariusz; Watorek, Wiesław

    2007-01-01

    Transferrins play a major role in iron homeostasis and metabolism. In vertebrates, these proteins are synthesised in the liver and dispersed within the organism by the bloodstream. In oviparous vertebrates additional expression is observed in the oviduct and the synthesised protein is deposited in egg white as ovotransferrin. Most research on ovotransferrin has been performed on the chicken protein. There is a limited amount of information on other bird transferrins, and until our previous paper on red-eared turtle protein there was no data on the isolation, sequencing and biochemical properties of reptilian ovotransferrins. Recently our laboratory deposited ten new sequences of reptilian transferrins in the EMBL database. A comparative analysis of these sequences indicates a possibility of different mechanisms of iron release among crocodile and snake transferrin. In the present paper we follow with the purification and analysis of the basic biochemical properties of two crocodile (Crocodilus niloticus, C. rhombifer) and one snake (Python molurus bivittatus) ovotransferrins. The proteins were purified by anion exchange and hydrophobic chromatography, and their N-terminal amino-acid sequences, molecular mass and isoelectric points were determined. All three proteins are glycosylated and their N-glycan chromatographic profiles show the largest contribution of neutral oligosaccharides in crocodile and disialylated glycans in python ovotransferrin. The absorption spectra of iron-saturated transferrins were analysed. Iron release from these proteins is pH-dependent, showing a biphasic character in crocodile ovotransferrins and a monophasic type in the python protein. The reason for the different types of iron release is discussed.

  7. Phylogenetic analysis of torque teno virus genome from Pakistani isolate and incidence of co-infection among HBV/HCV infected patients

    PubMed Central

    2012-01-01

    Background Torque Teno Virus (TTV) was the first single stranded circular DNA virus to be discovered that infects humans. Although there have been numerous reports regarding the prevalence of TTV from other countries of South Asia, there is severe lack of information regarding its prevalence in Pakistan. Thus the present study compiles the first indigenous report to comprehensively illustrate the incidence of the virus in uninfected and hepatitis infected population from Pakistan. Another aim of the study was to present the sequence of full length TTV genome from a local isolate and compare it with the already reported genome sequences from other parts of the world. Methods TTV DNA was screened in the serum of 116, 100 and 40 HBV infected, HCV infected and uninfected individuals respectively. Nearly full length genome of TTV was cloned from a HBV patient. The genome sequence was subjected to in-silico analysis using CLC Workbench, ClustalW, ClustalX and TreeView. Statistical analysis was carried out in SPSS v17.0. Results Our results report that 89.7%, 90.0% and 92.5% of HBV, HCV patients and healthy control population were positive for TTV infection. TTV genome of 3603 bp was also cloned from a local isolate and given the identity of TPK01. The TTV genome sequence mentioned in this paper is submitted in the GenBank/EMBL/DDBJ under the accession number JN980171. Phylogenetic analysis of TPK01 revealed that the Pakistani isolate has sequence similarities with genotype 23 and 22 (Genogroup 2). Conclusion The results of the current study indicate that the high frequency of TTV viremia in Pakistan conforms to the reports from other areas of the world, wherever screening of TTV DNA was performed against 5′-UTR of the genome. The high sequence diversity among TTV genome sequences and the high frequency of prevalence makes it harder to study this virus in cellular systems. PMID:23270330

  8. Amyotrophic Lateral Sclerosis Type 20 - In Silico Analysis and Molecular Dynamics Simulation of hnRNPA1

    PubMed Central

    Krebs, Bruna Baumgarten

    2016-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that affects the upper and lower motor neurons. 5–10% of cases are genetically inherited, including ALS type 20, which is caused by mutations in the hnRNPA1 gene. The goals of this work are to analyze the effects of non-synonymous single nucleotide polymorphisms (nsSNPs) on hnRNPA1 protein function, to model the complete tridimensional structure of the protein using computational methods and to assess structural and functional differences between the wild type and its variants through Molecular Dynamics simulations. nsSNP, PhD-SNP, Polyphen2, SIFT, SNAP, SNPs&GO, SNPeffect and PROVEAN were used to predict the functional effects of nsSNPs. Ab initio modeling of hnRNPA1 was made using Rosetta and refined using KoBaMIN. The structure was validated by PROCHECK, Rampage, ERRAT, Verify3D, ProSA and Qmean. TM-align was used for the structural alignment. FoldIndex, DICHOT, ELM, D2P2, Disopred and DisEMBL were used to predict disordered regions within the protein. Amino acid conservation analysis was assessed by Consurf, and the molecular dynamics simulations were performed using GROMACS. Mutations D314V and D314N were predicted to increase amyloid propensity, and predicted as deleterious by at least three algorithms, while mutation N73S was predicted as neutral by all the algorithms. D314N and D314V occur in a highly conserved amino acid. The Molecular Dynamics results indicate that all mutations increase protein stability when compared to the wild type. Mutants D314N and N319S showed higher overall dimensions and accessible surface when compared to the wild type. The flexibility level of the C-terminal residues of hnRNPA1 is affected by all mutations, which may affect protein function, especially regarding the protein ability to interact with other proteins. PMID:27414033

  9. Automatic Discovery and Inferencing of Complex Bioinformatics Web Interfaces

    SciTech Connect

    Ngu, A; Rocco, D; Critchlow, T; Buttler, D

    2003-12-22

    The World Wide Web provides a vast resource to genomics researchers in the form of web-based access to distributed data sources--e.g. BLAST sequence homology search interfaces. However, the process for seeking the desired scientific information is still very tedious and frustrating. While there are several known servers on genomic data (e.g., GeneBank, EMBL, NCBI), that are shared and accessed frequently, new data sources are created each day in laboratories all over the world. The sharing of these newly discovered genomics results are hindered by the lack of a common interface or data exchange mechanism. Moreover, the number of autonomous genomics sources and their rate of change out-pace the speed at which they can be manually identified, meaning that the available data is not being utilized to its full potential. An automated system that can find, classify, describe and wrap new sources without tedious and low-level coding of source specific wrappers is needed to assist scientists to access to hundreds of dynamically changing bioinformatics web data sources through a single interface. A correct classification of any kind of Web data source must address both the capability of the source and the conversation/interaction semantics which is inherent in the design of the Web data source. In this paper, we propose an automatic approach to classify Web data sources that takes into account both the capability and the conversational semantics of the source. The ability to discover the interaction pattern of a Web source leads to increased accuracy in the classification process. At the same time, it facilitates the extraction of process semantics, which is necessary for the automatic generation of wrappers that can interact correctly with the sources.

  10. The Protein Information Resource: an integrated public resource of functional annotation of proteins

    PubMed Central

    Wu, Cathy H.; Huang, Hongzhan; Arminski, Leslie; Castro-Alvear, Jorge; Chen, Yongxing; Hu, Zhang-Zhi; Ledley, Robert S.; Lewis, Kali C.; Mewes, Hans-Werner; Orcutt, Bruce C.; Suzek, Baris E.; Tsugita, Akira; Vinayaka, C. R.; Yeh, Lai-Su L.; Zhang, Jian; Barker, Winona C.

    2002-01-01

    The Protein Information Resource (PIR) serves as an integrated public resource of functional annotation of protein data to support genomic/proteomic research and scientific discovery. The PIR, in collaboration with the Munich Information Center for Protein Sequences (MIPS) and the Japan International Protein Information Database (JIPID), produces the PIR-International Protein Sequence Database (PSD), the major annotated protein sequence database in the public domain, containing about 250 000 proteins. To improve protein annotation and the coverage of experimentally validated data, a bibliography submission system is developed for scientists to submit, categorize and retrieve literature information. Comprehensive protein information is available from iProClass, which includes family classification at the superfamily, domain and motif levels, structural and functional features of proteins, as well as cross-references to over 40 biological databases. To provide timely and comprehensive protein data with source attribution, we have introduced a non-redundant reference protein database, PIR-NREF. The database consists of about 800 000 proteins collected from PIR-PSD, SWISS-PROT, TrEMBL, GenPept, RefSeq and PDB, with composite protein names and literature data. To promote database interoperability, we provide XML data distribution and open database schema, and adopt common ontologies. The PIR web site (http://pir.georgetown.edu/) features data mining and sequence analysis tools for information retrieval and functional identification of proteins based on both sequence and annotation information. The PIR databases and other files are also available by FTP (ftp://nbrfa.georgetown.edu/pir_databases). PMID:11752247

  11. Characterization of genes for an alternative nitrogenase in the cyanobacterium Anabaena variabilis.

    PubMed Central

    Thiel, T

    1993-01-01

    Anabaena variabilis ATCC 29413 is a heterotrophic, nitrogen-fixing cyanobacterium that has been reported to fix nitrogen and reduce acetylene to ethane in the absence of molybdenum. DNA from this strain hybridized well at low stringency to the nitrogenase 2 (vnfDGK) genes of Azotobacter vinelandii. The hybridizing region was cloned from a lambda EMBL3 genomic library of A. variabilis, mapped, and sequenced. The deduced amino acid sequences of the vnfD and vnfK genes of A. variabilis showed only about 56% similarity to the nifDK genes of Anabaena sp. strain PCC 7120 but were 76 to 86% similar to the anfDK or vnfDK genes of A. vinelandii. The organization of the vnf gene cluster in A. variabilis was similar to that of A. vinelandii. However, in A. variabilis, the vnfG gene was fused to vnfD; hence, this gene is designated vnfDG. A vnfH gene was not contiguous with the vnfDG gene and has not yet been identified. A mutant strain, in which a neomycin resistance cassette was inserted into the vnf cluster, grew well in a medium lacking a source of fixed nitrogen in the presence of molybdenum but grew poorly when vanadium replaced molybdenum. In contrast, the parent strain grew equally well in media containing either molybdenum or vanadium. The vnf genes were transcribed in the absence of molybdenum, with or without vanadium. The vnf gene cluster did not hybridize to chromosomal DNA from Anabaena sp. strain PCC 7120 or from the heterotrophic strains, Nostoc sp. strain Mac and Nostoc sp. strain ATCC 29150. A hybridizing ClaI fragment very similar in size to the A. variabilis ClaI fragment was present in DNA isolated from several independent, cultured isolates of Anabaena sp. from the Azolla symbiosis. Images PMID:8407800

  12. Benchmarking the next generation of homology inference tools

    PubMed Central

    Saripella, Ganapathi Varma; Sonnhammer, Erik L. L.; Forslund, Kristoffer

    2016-01-01

    Motivation: Over the last decades, vast numbers of sequences were deposited in public databases. Bioinformatics tools allow homology and consequently functional inference for these sequences. New profile-based homology search tools have been introduced, allowing reliable detection of remote homologs, but have not been systematically benchmarked. To provide such a comparison, which can guide bioinformatics workflows, we extend and apply our previously developed benchmark approach to evaluate the ‘next generation’ of profile-based approaches, including CS-BLAST, HHSEARCH and PHMMER, in comparison with the non-profile based search tools NCBI-BLAST, USEARCH, UBLAST and FASTA. Method: We generated challenging benchmark datasets based on protein domain architectures within either the PFAM + Clan, SCOP/Superfamily or CATH/Gene3D domain definition schemes. From each dataset, homologous and non-homologous protein pairs were aligned using each tool, and standard performance metrics calculated. We further measured congruence of domain architecture assignments in the three domain databases. Results: CSBLAST and PHMMER had overall highest accuracy. FASTA, UBLAST and USEARCH showed large trade-offs of accuracy for speed optimization. Conclusion: Profile methods are superior at inferring remote homologs but the difference in accuracy between methods is relatively small. PHMMER and CSBLAST stand out with the highest accuracy, yet still at a reasonable computational cost. Additionally, we show that less than 0.1% of Swiss-Prot protein pairs considered homologous by one database are considered non-homologous by another, implying that these classifications represent equivalent underlying biological phenomena, differing mostly in coverage and granularity. Availability and Implementation: Benchmark datasets and all scripts are placed at (http://sonnhammer.org/download/Homology_benchmark). Contact: forslund@embl.de Supplementary information: Supplementary data are available at

  13. Open Source Bayesian Models. 3. Composite Models for Prediction of Binned Responses

    PubMed Central

    2016-01-01

    Bayesian models constructed from structure-derived fingerprints have been a popular and useful method for drug discovery research when applied to bioactivity measurements that can be effectively classified as active or inactive. The results can be used to rank candidate structures according to their probability of activity, and this ranking benefits from the high degree of interpretability when structure-based fingerprints are used, making the results chemically intuitive. Besides selecting an activity threshold, building a Bayesian model is fast and requires few or no parameters or user intervention. The method also does not suffer from such acute overtraining problems as quantitative structure–activity relationships or quantitative structure–property relationships (QSAR/QSPR). This makes it an approach highly suitable for automated workflows that are independent of user expertise or prior knowledge of the training data. We now describe a new method for creating a composite group of Bayesian models to extend the method to work with multiple states, rather than just binary. Incoming activities are divided into bins, each covering a mutually exclusive range of activities. For each of these bins, a Bayesian model is created to model whether or not the compound belongs in the bin. Analyzing putative molecules using the composite model involves making a prediction for each bin and examining the relative likelihood for each assignment, for example, highest value wins. The method has been evaluated on a collection of hundreds of data sets extracted from ChEMBL v20 and validated data sets for ADME/Tox and bioactivity. PMID:26750305

  14. Flavobacterium panaciterrae sp. nov., a β-glucosidase producing bacterium with ginsenoside-converting activity isolated from the soil of a ginseng field.

    PubMed

    Jin, Yan; Kim, Yeon-Ju; Hoang, Van-An; Young Jung, Sun; Nguyen, Ngoc-Lan; Woo Min, Jin; Wang, Chao; Yang, Deok-Chun

    2014-01-01

    The GenBank/EMBL/DDBJ accession number for the 16S rRNA gene sequence of strain DCY69(T) is JX233806. A Gram-reaction-negative, oxidase- and catalase-positive, non-gliding motile strain, designated strain DCY69(T), was isolated from the soil of a ginseng field in the Republic of Korea. Colonies of strain DCY69(T) were circular, 0.5-1.5 mm diameter, yellow, and convex on an R2A agar plate after 2 days. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain DCY69(T) belonged to the genus Flavobacterium with 90.5-98.3% gene sequence similarity. The major predominant quinone was MK-6. The major cellular fatty acids were iso-C15:0, iso-C17:0 3-OH, iso-C15:0 3-OH and summed feature 3 (containing C16:1ω7c and/or C16:1ω6c). The major polar lipids were phosphatidylethanolamine, one unidentified aminolipid and unidentified polar lipids (L1, L2). The genomic DNA G+C content of strain DCY69(T) was 35.0mol%. The strain DCY69(T) transformed ginsenoside Rb1 into Rd and F2. Based on the polyphasic taxonomic data, strain DCY69(T) is considered to represent a novel species of the genus Flavobacterium, for which the name Flavobacterium panaciterrae sp. nov. is proposed. The type strain is DCY69(T)(= KCTC 32392(T) = JCM 19161(T)), isolated from the soil of a ginseng field in the Republic of Korea.

  15. [Dynamics of Purple Sulfur Bacteria in a Meromictic Saline Lake Shunet (Khakassia, Siberia) in 2007-2013].

    PubMed

    Rogozin, D Yu; Zykova, V V; Tarnovskii, M O

    2016-01-01

    According to the results of seasonal monitoring, in 2007-2013 purple sulfur bacteria morphologically similar to Thiocapsa sp. Shira_1 (AJ633676 in EMBL/GenBank) predominated in the anoxygenic phototrophic community of the water column of the meromictic Lake Shira (Khakassia, Siberia). No pronounced seasonal periodicity in the total cell number in the water column was revealed during the period of observation. In some years cell number during the period when the lake was covered with ice was reliably higher than in summer. The absence ofseasonal periodicity was probably due to the low amplitude of seasonal variations in temperature and illumination in the redox zone, resulting from its relatively deep location (12-16 m). The year-to-year dynamics was characterized by a reliable decrease of the total cell number in 2009-2010 and maxima in 2007 and 2011-2012. Canonical correlation analysis revealed that water temperature in the redox zone was the best predictor of the PSB abundance in Lake Shira. Water temperature, in turn, depended on the depth of mixing of the water column. Intense mixing in 2009-2011 was probably responsible for decreased PSB abundance in the lake. On the other hand, the absence of deep winter mixing, resulting in stable conditions in the chemocline, favored the preservation of relatively high PSB biomass. Prediction of circulation depth, which.depends mainly on the weather conditions and dynamics of the water level, is required for prediction of PSB abundance in Lake Shira. These results may be useful for paleolimnological reconstructions of the history of the lake based on the remnants of purple sulfur bacteria in bottom sediments. PMID:27301131

  16. Detailed Transcriptome Description of the Neglected Cestode Taenia multiceps

    PubMed Central

    Wu, Xuhang; Fu, Yan; Yang, Deying; Zhang, Runhui; Zheng, Wanpeng; Nie, Huaming; Xie, Yue; Yan, Ning; Hao, Guiying; Gu, Xiaobin; Wang, Shuxian; Peng, Xuerong; Yang, Guangyou

    2012-01-01

    Background The larval stage of Taenia multiceps, a global cestode, encysts in the central nervous system (CNS) of sheep and other livestock. This frequently leads to their death and huge socioeconomic losses, especially in developing countries. This parasite can also cause zoonotic infections in humans, but has been largely neglected due to a lack of diagnostic techniques and studies. Recent developments in next-generation sequencing provide an opportunity to explore the transcriptome of T. multiceps. Methodology/Principal Findings We obtained a total of 31,282 unigenes (mean length 920 bp) using Illumina paired-end sequencing technology and a new Trinity de novo assembler without a referenced genome. Individual transcription molecules were determined by sequence-based annotations and/or domain-based annotations against public databases (Nr, UniprotKB/Swiss-Prot, COG, KEGG, UniProtKB/TrEMBL, InterPro and Pfam). We identified 26,110 (83.47%) unigenes and inferred 20,896 (66.8%) coding sequences (CDS). Further comparative transcripts analysis with other cestodes (Taenia pisiformis, Taenia solium, Echincoccus granulosus and Echincoccus multilocularis) and intestinal parasites (Trichinella spiralis, Ancylostoma caninum and Ascaris suum) showed that 5,100 common genes were shared among three Taenia tapeworms, 261 conserved genes were detected among five Taeniidae cestodes, and 109 common genes were found in four zoonotic intestinal parasites. Some of the common genes were genes required for parasite survival, involved in parasite-host interactions. In addition, we amplified two full-length CDS of unigenes from the common genes using RT-PCR. Conclusions/Significance This study provides an extensive transcriptome of the adult stage of T. multiceps, and demonstrates that comparative transcriptomic investigations deserve to be further studied. This transcriptome dataset forms a substantial public information platform to achieve a fundamental understanding of the biology of

  17. Whole genome analysis of Vietnamese G2P[4] rotavirus strains possessing the NSP2 gene sharing an ancestral sequence with Chinese sheep and goat rotavirus strains.

    PubMed

    Do, Loan Phuong; Doan, Yen Hai; Nakagomi, Toyoko; Gauchan, Punita; Kaneko, Miho; Agbemabiese, Chantal; Dang, Anh Duc; Nakagomi, Osamu

    2015-10-01

    Because imminent introduction into Vietnam of a vaccine against Rotavirus A is anticipated, baseline information on the whole genome of representative strains is needed to understand changes in circulating strains that may occur after vaccine introduction. In this study, the whole genomes of two G2P[4] strains detected in Nha Trang, Vietnam in 2008 were sequenced, this being the last period during which virtually no rotavirus vaccine was used in this country. The two strains were found to be >99.9% identical in sequence and had a typical DS-1 like G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genotype constellation. Analysis of the Vietnamese strains with >184 G2P[4] strains retrieved from GenBank/EMBL/DDBJ DNA databases placed the Vietnamese strains in one of the lineages commonly found among contemporary strains, with the exception of the NSP2 and NSP4 genes. The NSP2 genes were found to belong to a previously undescribed lineage that diverged from Chinese sheep and goat rotavirus strains, including a Chinese rotavirus vaccine strain LLR with 95% nucleotide identity; the time of their most recent common ancestor was 1975. The NSP4 genes were found to belong, together with Thai and USA strains, to an emergent lineage (VIII), adding further diversity to ever diversifying NSP4 lineages. Thus, there is a need to enhance surveillance of locally-circulating strains from both children and animals at the whole genome level to address the effect of rotavirus vaccines on changing strain distribution.

  18. MMpI: A WideRange of Available Compounds of Matrix Metalloproteinase Inhibitors.

    PubMed

    Muvva, Charuvaka; Patra, Sanjukta; Venkatesan, Subramanian

    2016-01-01

    Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in the regulation of the extracellular signaling and structural matrix environment of cells and tissues. MMPs are considered as promising targets for the treatment of many diseases. Therefore, creation of database on the inhibitors of MMP would definitely accelerate the research activities in this area due to its implication in above-mentioned diseases and associated limitations in the first and second generation inhibitors. In this communication, we report the development of a new MMpI database which provides resourceful information for all researchers working in this field. It is a web-accessible, unique resource that contains detailed information on the inhibitors of MMP including small molecules, peptides and MMP Drug Leads. The database contains entries of ~3000 inhibitors including ~72 MMP Drug Leads and ~73 peptide based inhibitors. This database provides the detailed molecular and structural details which are necessary for the drug discovery and development. The MMpI database contains physical properties, 2D and 3D structures (mol2 and pdb format files) of inhibitors of MMP. Other data fields are hyperlinked to PubChem, ChEMBL, BindingDB, DrugBank, PDB, MEROPS and PubMed. The database has extensive searching facility with MMpI ID, IUPAC name, chemical structure and with the title of research article. The MMP inhibitors provided in MMpI database are optimized using Python-based Hierarchical Environment for Integrated Xtallography (Phenix) software. MMpI Database is unique and it is the only public database that contains and provides the complete information on the inhibitors of MMP. Database URL: http://clri.res.in/subramanian/databases/mmpi/index.php. PMID:27509041

  19. Syndrome de Peutz-Jeghers, à propos de 3 cas dans la fratrie

    PubMed Central

    Zinelabidine, Kaoutar; Meziane, Meriame; Mernissi, Fatima Zahra

    2012-01-01

    Le SPJ est une maladie rare de transmission autosomique dominante, défini par l’association d’une atteinte cutanée à type de lentiginose péri-orificielle d’une atteinte digestive, pulmonaire et des organes reproducteurs. Le gène de PJS a été localisé sur le chromosome 19p13.13. Les signes cutanés sont affichants et constituent un signe révélateur de la maladie, ils sont à type de lentigines, Ils siègent le plus souvent sur les lèvres, la muqueuse buccale. Les polypes digestifs constituent le deuxième signe cardinal de ce syndrome et ils peuvent révéler la maladie lorsqu’ils se manifestent d’emblée par leur complication telles les hémorragies digestives et les obstructions. Les personnes atteintes de SPJ courent un risque accru de cancers, le risque cumulatif de cancer est estimé à 93%, Les organes les plus fréquemment touchés sont le tractus gastro-intestinal (oesophage, estomac, intestin grêle, côlon, rectum et pancréas), le poumon, la prostate, le sein et les organes reproducteurs. La prise en charge des SPJ est basée principalement sur la surveillance et le traitement des polypes hamartomateux. Il n′existe aucun traitement standarisé pour la pigmentation cutanéo-muqueuse. Le traitement fait appel à la cryochirurgie, la dermabrasion et au laser Q-switched. PMID:22593795

  20. Selective binding of specific mouse genomic DNA fragments by mouse vimentin filaments in vitro.

    PubMed

    Wang, X; Tolstonog, G; Shoeman, R L; Traub, P

    1996-03-01

    Mouse vimentin intermediate filaments (IFs) reconstituted in vitro were analyzed for their capacity to select certain DNA sequences from a mixture of about 500-bp-long fragments of total mouse genomic DNA. The fragments preferentially bound by the IFs and enriched by several cycles of affinity binding and polymerase chain reaction (PCR) amplification were cloned and sequenced. In general, they were G-rich and highly repetitive in that they often contained Gn, (GT)n, and (GA)n repeat elements. Other, more complex repeat sequences were identified as well. Apart from the capacity to adopt a Z-DNA and triple helix configuration under superhelical tension, many fragments were potentially able to form cruciform structures and contained consensus binding sites for various transcription factors. All of these sequence elements are known to occur in introns and 5'/3'-flanking regions of genes and to play roles in DNA transcription, recombination and replication. A FASTA search of the EMBL data bank indeed revealed that sequences homologous to the mouse repetitive DNA fragments are commonly associated with gene-regulatory elements. Unexpectedly, vimentin IFs also bound a large number of apparently overlapping, AT-rich DNA fragments that could be aligned into a composite sequence highly homologous to the 234-bp consensus centromere repeat sequence of gamma-satellite DNA. Previous experiments have shown a high affinity of vimentin for G-rich, repetitive telomere DNA sequences, superhelical DNA, and core histones. Taken together, these data support the hypothesis that, after penetration of the double nuclear membrane via an as yet unidentified mechanism, vimentin IFs cooperatively fix repetitive DNA sequence elements in a differentiation-specific manner in the nuclear periphery subjacent to the nuclear lamina and thus participate in the organization of chromatin and in the control of transcription, replication, and recombination processes. This includes aspects of global

  1. Amyotrophic Lateral Sclerosis Type 20 - In Silico Analysis and Molecular Dynamics Simulation of hnRNPA1.

    PubMed

    Krebs, Bruna Baumgarten; De Mesquita, Joelma Freire

    2016-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that affects the upper and lower motor neurons. 5-10% of cases are genetically inherited, including ALS type 20, which is caused by mutations in the hnRNPA1 gene. The goals of this work are to analyze the effects of non-synonymous single nucleotide polymorphisms (nsSNPs) on hnRNPA1 protein function, to model the complete tridimensional structure of the protein using computational methods and to assess structural and functional differences between the wild type and its variants through Molecular Dynamics simulations. nsSNP, PhD-SNP, Polyphen2, SIFT, SNAP, SNPs&GO, SNPeffect and PROVEAN were used to predict the functional effects of nsSNPs. Ab initio modeling of hnRNPA1 was made using Rosetta and refined using KoBaMIN. The structure was validated by PROCHECK, Rampage, ERRAT, Verify3D, ProSA and Qmean. TM-align was used for the structural alignment. FoldIndex, DICHOT, ELM, D2P2, Disopred and DisEMBL were used to predict disordered regions within the protein. Amino acid conservation analysis was assessed by Consurf, and the molecular dynamics simulations were performed using GROMACS. Mutations D314V and D314N were predicted to increase amyloid propensity, and predicted as deleterious by at least three algorithms, while mutation N73S was predicted as neutral by all the algorithms. D314N and D314V occur in a highly conserved amino acid. The Molecular Dynamics results indicate that all mutations increase protein stability when compared to the wild type. Mutants D314N and N319S showed higher overall dimensions and accessible surface when compared to the wild type. The flexibility level of the C-terminal residues of hnRNPA1 is affected by all mutations, which may affect protein function, especially regarding the protein ability to interact with other proteins.

  2. Benzo- and thienobenzo- diazepines: multi-target drugs for CNS disorders.

    PubMed

    Mendonça Júnior, F J B; Scotti, L; Ishiki, H; Botelho, S P S; Da Silva, M S; Scotti, M T

    2015-01-01

    Benzodiazepines (BZ or BZD) are a class of gabaminergic psychoactive chemicals used in hypnotics, sedation, in the treatment of anxiety, and in other CNS disorders. These drugs include alprazolam (Xanax), diazepam (Valium), clonazepam (Klonopin), and others. There are two distinct types of pharmacological binding sites for benzodiazepines in the brain (BZ1 and BZ2), these sites are on GABA-A receptors, and are classified as short, intermediate, or long-acting. From the thienobenzodiazepine class (TBZ), Olanzapine (2-methyl-4-(4-methyl-l-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine) (Zyprexa) was used as an example to demonstrate the antagonism of this class of compounds for multiples receptors including: dopamine D1-D5, α-adrenoreceptor, histamine H1, muscarinic M1-M5 and 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3 and 5-HT6 receptors. Olanzapine is an atypical antipsychotic agent, structurally related to clozapine, and extensively used for the treatment of schizophrenia, bipolar disorder-associated mania, and the behavioral symptoms of Alzheimer's disease. The functional blockade of these multiple receptors contributes to the wide range of its pharmacologic and therapeutic activities, having relatively few side effects when compared to other antipsychotics agents. Thienobenzodiazepines (such as Olanzapine) are characterized as multi- receptor- targeted- acting- agents. This mini-review discusses these 2 drug classes that act on the central nervous system, the main active compounds used, and the various receptors with which they interact. In addition, we propose 12 olanzapine analogues, and generated Random Forest models, from a data set obtained from the ChEMBL database, to classify the structures as active or inactive against 5 dopamine receptors (D1, D2, D3, D4, D5 and D6), and dopamine transporter. PMID:25694077

  3. Predicting targets of compounds against neurological diseases using cheminformatic methodology.

    PubMed

    Nikolic, Katarina; Mavridis, Lazaros; Bautista-Aguilera, Oscar M; Marco-Contelles, José; Stark, Holger; do Carmo Carreiras, Maria; Rossi, Ilaria; Massarelli, Paola; Agbaba, Danica; Ramsay, Rona R; Mitchell, John B O

    2015-02-01

    Recently developed multi-targeted ligands are novel drug candidates able to interact with monoamine oxidase A and B; acetylcholinesterase and butyrylcholinesterase; or with histamine N-methyltransferase and histamine H3-receptor (H3R). These proteins are drug targets in the treatment of depression, Alzheimer's disease, obsessive disorders, and Parkinson's disease. A probabilistic method, the Parzen-Rosenblatt window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Molecular structures were represented based on the circular fingerprint methodology. The same approach was used to build a "predictor" model from the DrugBank dataset to determine the main pharmacological groups of the compound. The study of off-target interactions is now recognised as crucial to the understanding of both drug action and toxicology. Primary pharmaceutical targets and off-targets for the novel multi-target ligands were examined by use of the developed cheminformatic method. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. The cheminformatic targets identifications were in agreement with four 3D-QSAR (H3R/D1R/D2R/5-HT2aR) models and by in vitro assays for serotonin 5-HT1a and 5-HT2a receptor binding of the most promising ligand (71/MBA-VEG8).

  4. Whole-Genome Sequence of Chryseobacterium oranimense, a Colistin-Resistant Bacterium Isolated from a Cystic Fibrosis Patient in France

    PubMed Central

    Sharma, Poonam; Gupta, Sushim Kumar; Diene, Seydina M.

    2015-01-01

    For the first time, we report the whole-genome sequence analysis of Chryseobacterium oranimense G311, a multidrug-resistant bacterium, from a cystic fibrosis patient in France, including resistance to colistin. Whole-genome sequencing of C. oranimense G311 was performed using Ion Torrent PGM, and RAST, the EMBL-EBI server, and the Antibiotic Resistance Gene-ANNOTation (ARG-ANNOT) database were used for annotation of all genes, including antibiotic resistance (AR) genes. General features of the C. oranimense G311 draft genome were compared to the other available genomes of Chryseobacterium gleum and Chryseobacterium sp. strain CF314. C. oranimense G311 was found to be resistant to all β-lactams, including imipenem, and to colistin. The genome size of C. oranimense G311 is 4,457,049 bp in length, with 37.70% GC content. We found 27 AR genes in the genome, including β-lactamase genes which showed little similarity to the known β-lactamase genes and could likely be novel. We found the type I polyketide synthase operon followed by a zeaxanthin glycosyltransferase gene in the genome, which could impart the yellow pigmentation of the isolate. We located the O-antigen biosynthesis cluster, and we also discovered a novel capsular polysaccharide biosynthesis cluster. We also found known mutations in the orthologs of the pmrA (E8D), pmrB (L208F and P360Q), and lpxA (G68D) genes. We speculate that the presence of the capsular cluster and mutations in these genes could explain the resistance of this bacterium to colistin. We demonstrate that whole-genome sequencing was successfully applied to decipher the resistome of a multidrug resistance bacterium associated with cystic fibrosis patients. PMID:25583710

  5. Tuning HERG out: antitarget QSAR models for drug development.

    PubMed

    Braga, Rodolpho C; Alves, Vinicius M; Silva, Meryck F B; Muratov, Eugene; Fourches, Denis; Tropsha, Alexander; Andrade, Carolina H

    2014-01-01

    Several non-cardiovascular drugs have been withdrawn from the market due to their inhibition of hERG K+ channels that can potentially lead to severe heart arrhythmia and death. As hERG safety testing is a mandatory FDArequired procedure, there is a considerable interest for developing predictive computational tools to identify and filter out potential hERG blockers early in the drug discovery process. In this study, we aimed to generate predictive and well-characterized quantitative structure-activity relationship (QSAR) models for hERG blockage using the largest publicly available dataset of 11,958 compounds from the ChEMBL database. The models have been developed and validated according to OECD guidelines using four types of descriptors and four different machine-learning techniques. The classification accuracies discriminating blockers from non-blockers were as high as 0.83-0.93 on external set. Model interpretation revealed several SAR rules, which can guide structural optimization of some hERG blockers into non-blockers. We have also applied the generated models for screening the World Drug Index (WDI) database and identify putative hERG blockers and non-blockers among currently marketed drugs. The developed models can reliably identify blockers and non-blockers, which could be useful for the scientific community. A freely accessible web server has been developed allowing users to identify putative hERG blockers and non-blockers in chemical libraries of their interest (http://labmol.farmacia.ufg.br/predherg).

  6. Substrate-Driven Mapping of the Degradome by Comparison of Sequence Logos

    PubMed Central

    Fuchs, Julian E.; von Grafenstein, Susanne; Huber, Roland G.; Kramer, Christian; Liedl, Klaus R.

    2013-01-01

    Sequence logos are frequently used to illustrate substrate preferences and specificity of proteases. Here, we employed the compiled substrates of the MEROPS database to introduce a novel metric for comparison of protease substrate preferences. The constructed similarity matrix of 62 proteases can be used to intuitively visualize similarities in protease substrate readout via principal component analysis and construction of protease specificity trees. Since our new metric is solely based on substrate data, we can engraft the protease tree including proteolytic enzymes of different evolutionary origin. Thereby, our analyses confirm pronounced overlaps in substrate recognition not only between proteases closely related on sequence basis but also between proteolytic enzymes of different evolutionary origin and catalytic type. To illustrate the applicability of our approach we analyze the distribution of targets of small molecules from the ChEMBL database in our substrate-based protease specificity trees. We observe a striking clustering of annotated targets in tree branches even though these grouped targets do not necessarily share similarity on protein sequence level. This highlights the value and applicability of knowledge acquired from peptide substrates in drug design of small molecules, e.g., for the prediction of off-target effects or drug repurposing. Consequently, our similarity metric allows to map the degradome and its associated drug target network via comparison of known substrate peptides. The substrate-driven view of protein-protein interfaces is not limited to the field of proteases but can be applied to any target class where a sufficient amount of known substrate data is available. PMID:24244149

  7. MALDI-ToF mass spectrometry coupled with multivariate pattern recognition analysis for the rapid biomarker profiling of Escherichia coli in different growth phases.

    PubMed

    Momo, Remi A; Povey, Jane F; Smales, C Mark; O'Malley, Christopher J; Montague, Gary A; Martin, Elaine B

    2013-10-01

    Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-ToF MS) has been exploited extensively in the field of microbiology for the characterisation of bacterial species, the detection of biomarkers for early disease diagnosis and bacterial identification. Here, the multivariate data analysis technique of partial least squares-discriminant analysis (PLS-DA) was applied to 'intact cell' MALDI-ToF MS data obtained from Escherichia coli cell samples to determine if such an approach could be used to distinguish between, and characterise, different growth phases. PLS-DA is a technique that has the potential to extract systematic variation from large and noisy data sets by identifying a lower-dimensional subspace that contains latent information. The application of PLS-DA to the MALDI-ToF data obtained from cells at different stages of growth resulted in the successful classification of the samples according to the growth phase of the bacteria cultures. A further outcome of the analysis was that it was possible to identify the mass-to-charge (m/z) ratio peaks or ion signals that contributed to the classification of the samples. The Swiss-Prot/TrEMBL database and primary literature were then used to provisionally assign a small number of these m/z ion signals to proteins, and these tentative assignments revealed that the major contributors from the exponential phase were ribosomal proteins. Additional assignments were possible for the stationary phase and the decline phase cultures where the proteins identified were consistent with previously observed biological interpretation. In summary, the results show that MALDI-ToF MS, PLS-DA and a protein database search can be used in combination to discriminate between 'intact cell' E. coli cell samples in different growth phases and thus could potentially be used as a tool in process development in the bioprocessing industry to enhance cell growth and cell engineering strategies.

  8. Analysis of Edg-Like LPA Receptor-Ligand Interactions.

    PubMed

    Balogh, Balazs; Pazmany, Tamas; Matyus, Peter

    2015-01-01

    The phospholipid derivative lysophosphatidic acid (LPA) serves as a signalling molecule through the activation of LPA receptors, which belong to the G-protein-coupled receptors. From a pharmacological point of view, the ('EDG-like') LPA1-3 receptors have attracted much attention, therefore we have also been focusing in our study on these subtypes. The LPA1receptors are widely expressed in the human body; interestingly, LPA1 might have a role in the pathomechanism of obesity. In order to recognize key structural features of the molecular interactions of human LPA1with its agonists, we built up the 3D structure of the LPA1 through homology modeling. Next, LPA1 agonists and antagonists were docked into the model. The mode of binding and the interactions between ligands and key amino acids (R3.28 and Q3.29) were consistent with mutagenesis assays and previously published models, indicating that this model is able to discriminate high-affinity compounds and may be useful for the development of novel agonists of LPA1. Homology models were also constructed for LPA2 and LPA3. All available agonists with published EC50 values, antagonists with IC50 values and compounds with Ki values for either of LPA1, LPA2 or LPA3 were collected from the ChEMBL database and were docked into the corresponding model.Ourmodels for the LPA1-3 receptors can discriminate high-affinity compounds identified in silico HTS studies and may be useful for the development of novel agonistsof LPA receptors. With a better understanding of the differences between LPA1-3 receptors new, selective agonists and antagonist could be designed, which could be used in the therapy of various diseases with a better side-effect profile. PMID:25686617

  9. Prediction of drug-target interaction by label propagation with mutual interaction information derived from heterogeneous network.

    PubMed

    Yan, Xiao-Ying; Zhang, Shao-Wu; Zhang, Song-Yao

    2016-02-01

    The identification of potential drug-target interaction pairs is very important, which is useful not only for providing greater understanding of protein function, but also for enhancing drug research, especially for drug function repositioning. Recently, numerous machine learning-based algorithms (e.g. kernel-based, matrix factorization-based and network-based inference methods) have been developed for predicting drug-target interactions. All these methods implicitly utilize the assumption that similar drugs tend to target similar proteins and yield better results for predicting interactions between drugs and target proteins. To further improve the accuracy of prediction, a new method of network-based label propagation with mutual interaction information derived from heterogeneous networks, namely LPMIHN, is proposed to infer the potential drug-target interactions. LPMIHN separately performs label propagation on drug and target similarity networks, but the initial label information of the target (or drug) network comes from the drug (or target) label network and the known drug-target interaction bipartite network. The independent label propagation on each similarity network explores the cluster structure in its network, and the label information from the other network is used to capture mutual interactions (bicluster structures) between the nodes in each pair of the similarity networks. As compared to other recent state-of-the-art methods on the four popular benchmark datasets of binary drug-target interactions and two quantitative kinase bioactivity datasets, LPMIHN achieves the best results in terms of AUC and AUPR. In addition, many of the promising drug-target pairs predicted from LPMIHN are also confirmed on the latest publicly available drug-target databases such as ChEMBL, KEGG, SuperTarget and Drugbank. These results demonstrate the effectiveness of our LPMIHN method, indicating that LPMIHN has a great potential for predicting drug-target interactions. PMID

  10. Use of 18S rRNA Gene-Based PCR Assay for Diagnosis of Acanthamoeba Keratitis in Non-Contact Lens Wearers in India

    PubMed Central

    Pasricha, Gunisha; Sharma, Savitri; Garg, Prashant; Aggarwal, Ramesh K.

    2003-01-01

    Identification of Acanthamoeba cysts and trophozoites in ocular tissues requires considerable expertise and is often time-consuming. An 18S rRNA gene-based PCR test, highly specific for the genus Acanthamoeba, has recently been reported in the molecular diagnosis of Acanthamoeba keratitis. This PCR assay was compared with conventional microbiological tests for the diagnosis of Acanthamoeba keratitis. In a pilot study, the PCR conditions with modifications were first tested on corneal scrapings from patients with culture-proven non-contact lens-related Acanthamoeba, bacterial, and fungal keratitis. This was followed by testing of corneal scrapings from 53 consecutive cases of microbial keratitis to determine sensitivity, specificity, and predictive values of the assay. All corneal scrapings from patients with proven Acanthamoeba keratitis showed a 463-bp amplicon, while no amplicon was obtained from patients with bacterial or fungal keratitis. Some of these amplified products were sequenced and compared with EMBL database reference sequences to validate these to be of Acanthamoeba origin. Out of 53 consecutive cases of microbial keratitis included for evaluating the PCR, 10 (18.9%) cases were diagnosed as Acanthamoeba keratitis on the basis of combined results of culture, smear, and PCR of corneal scrapings. Based on culture results as the “gold standard,” the sensitivity of PCR was the same as that of the smear (87.5%); however, the specificity and the positive and negative predictive values of PCR were marginally higher than the smear examination (97.8 versus 95.6%, 87.5 versus 77.8%, and 97.8 versus 97.7%) although the difference was not significant. This study confirms the efficacy of the PCR assay and is the first study to evaluate a PCR-based assay against conventional methods of diagnosis in a clinical setting. PMID:12843065

  11. Historeceptomic Fingerprints for Drug-Like Compounds

    PubMed Central

    Shmelkov, Evgeny; Grigoryan, Arsen; Swetnam, James; Xin, Junyang; Tivon, Doreen; Shmelkov, Sergey V.; Cardozo, Timothy

    2015-01-01

    Most drugs exert their beneficial and adverse effects through their combined action on several different molecular targets (polypharmacology). The true molecular fingerprint of the direct action of a drug has two components: the ensemble of all the receptors upon which a drug acts and their level of expression in organs/tissues. Conversely, the fingerprint of the adverse effects of a drug may derive from its action in bystander tissues. The ensemble of targets is almost always only partially known. Here we describe an approach improving upon and integrating both components: in silico identification of a more comprehensive ensemble of targets for any drug weighted by the expression of those receptors in relevant tissues. Our system combines more than 300,000 experimentally determined bioactivity values from the ChEMBL database and 4.2 billion molecular docking scores. We integrated these scores with gene expression data for human receptors across a panel of human tissues to produce drug-specific tissue-receptor (historeceptomics) scores. A statistical model was designed to identify significant scores, which define an improved fingerprint representing the unique activity of any drug. These multi-dimensional historeceptomic fingerprints describe, in a novel, intuitive, and easy to interpret style, the holistic, in vivo picture of the mechanism of any drug's action. Valuable applications in drug discovery and personalized medicine, including the identification of molecular signatures for drugs with polypharmacologic modes of action, detection of tissue-specific adverse effects of drugs, matching molecular signatures of a disease to drugs, target identification for bioactive compounds with unknown receptors, and hypothesis generation for drug/compound phenotypes may be enabled by this approach. The system has been deployed at drugable.org for access through a user-friendly web site. PMID:26733872

  12. A Subtracted cDNA Library from the Zebrafish (Danio rerio) Embryonic Inner Ear

    PubMed Central

    Coimbra, Roney S.; Weil, Dominique; Brottier, Phillipe; Blanchard, Stéphane; Levi, Michael; Hardelin, Jean-Pierre; Weissenbach, Jean; Petit, Christine

    2002-01-01

    A database was built that consists of 4694 sequence contigs of ∼18,000 reads of cDNAs isolated from the microdissected otocysts of zebrafish embryos at 20–30 hour postfertilization, following subtraction with a pool of liver cDNAs from adult fish. These sequences were compared with those of public databanks. Significant similarity were recorded and organized in a relational database at http://www.genoscope.cns.fr/zie. A first group of 2067 sequences correspond to 1428 known zebrafish genes or ESTs present in the Danio rerio section of UniGene. A second group of 302 sequences encode putative proteins that showed significant similarity (50%–100%) with 302 nonzebrafish proteins in the nr databank, a public databank containing an exhaustive nonredundant collection of protein sequences from different species (ftp://ftp.ncbi.nlm.nih.gov/blast/db/nr). The remaining 2325 (49.5%) sequence contigs or singletons showed no significant similarity with sequences available in public databanks. Several genes known to be expressed in the developing inner ear were represented in the present database, in particular genes involved in hair cell differentiation or innervation The occurrence of these genes validates the outcome of this study as the first collection of ESTs preferentially expressed in the zebrafish inner ear during the period of hair cell differentiation and neuroblast delamination from the otic vesicle epithelium. Novel zebrafish genes also involved in these processes are thus likely to be represented among the sequences obtained herein, for which no homology was found in the D. rerio section of UniGene. [The sequence data from this study have been submitted to EMBL under accession nos. AL714032–AL731531]. PMID:12045154

  13. Evaluating the Impact of Different Sequence Databases on Metaproteome Analysis: Insights from a Lab-Assembled Microbial Mixture

    PubMed Central

    Tanca, Alessandro; Palomba, Antonio; Deligios, Massimo; Cubeddu, Tiziana; Fraumene, Cristina; Biosa, Grazia; Pagnozzi, Daniela; Addis, Maria Filippa; Uzzau, Sergio

    2013-01-01

    Metaproteomics enables the investigation of the protein repertoire expressed by complex microbial communities. However, to unleash its full potential, refinements in bioinformatic approaches for data analysis are still needed. In this context, sequence databases selection represents a major challenge. This work assessed the impact of different databases in metaproteomic investigations by using a mock microbial mixture including nine diverse bacterial and eukaryotic species, which was subjected to shotgun metaproteomic analysis. Then, both the microbial mixture and the single microorganisms were subjected to next generation sequencing to obtain experimental metagenomic- and genomic-derived databases, which were used along with public databases (namely, NCBI, UniProtKB/SwissProt and UniProtKB/TrEMBL, parsed at different taxonomic levels) to analyze the metaproteomic dataset. First, a quantitative comparison in terms of number and overlap of peptide identifications was carried out among all databases. As a result, only 35% of peptides were common to all database classes; moreover, genus/species-specific databases provided up to 17% more identifications compared to databases with generic taxonomy, while the metagenomic database enabled a slight increment in respect to public databases. Then, database behavior in terms of false discovery rate and peptide degeneracy was critically evaluated. Public databases with generic taxonomy exhibited a markedly different trend compared to the counterparts. Finally, the reliability of taxonomic attribution according to the lowest common ancestor approach (using MEGAN and Unipept software) was assessed. The level of misassignments varied among the different databases, and specific thresholds based on the number of taxon-specific peptides were established to minimize false positives. This study confirms that database selection has a significant impact in metaproteomics, and provides critical indications for improving depth and

  14. MMpI: A WideRange of Available Compounds of Matrix Metalloproteinase Inhibitors

    PubMed Central

    Muvva, Charuvaka; Patra, Sanjukta; Venkatesan, Subramanian

    2016-01-01

    Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in the regulation of the extracellular signaling and structural matrix environment of cells and tissues. MMPs are considered as promising targets for the treatment of many diseases. Therefore, creation of database on the inhibitors of MMP would definitely accelerate the research activities in this area due to its implication in above-mentioned diseases and associated limitations in the first and second generation inhibitors. In this communication, we report the development of a new MMpI database which provides resourceful information for all researchers working in this field. It is a web-accessible, unique resource that contains detailed information on the inhibitors of MMP including small molecules, peptides and MMP Drug Leads. The database contains entries of ~3000 inhibitors including ~72 MMP Drug Leads and ~73 peptide based inhibitors. This database provides the detailed molecular and structural details which are necessary for the drug discovery and development. The MMpI database contains physical properties, 2D and 3D structures (mol2 and pdb format files) of inhibitors of MMP. Other data fields are hyperlinked to PubChem, ChEMBL, BindingDB, DrugBank, PDB, MEROPS and PubMed. The database has extensive searching facility with MMpI ID, IUPAC name, chemical structure and with the title of research article. The MMP inhibitors provided in MMpI database are optimized using Python-based Hierarchical Environment for Integrated Xtallography (Phenix) software. MMpI Database is unique and it is the only public database that contains and provides the complete information on the inhibitors of MMP. Database URL: http://clri.res.in/subramanian/databases/mmpi/index.php. PMID:27509041

  15. Sequence and transcriptional start site of the Pseudomonas aeruginosa outer membrane porin protein F gene.

    PubMed Central

    Duchêne, M; Schweizer, A; Lottspeich, F; Krauss, G; Marget, M; Vogel, K; von Specht, B U; Domdey, H

    1988-01-01

    Porin F is one of the major proteins of the outer membrane of Pseudomonas aeruginosa. It forms water-filled pores of variable size. Porin F is a candidate for a vaccine against P. aeruginosa because it antigenically cross-reacts in all serotype strains of the International Antigenic Typing Scheme. We have isolated the gene for porin F from a lambda EMBL3 bacteriophage library by using oligodeoxynucleotide hybridization probes and have determined its nucleotide sequence. Different peptide sequences obtained from isolated porin F confirmed the deduced protein sequence. The mature protein consists of 326 amino acid residues and has a molecular weight of 35,250. The precursor contains an N-terminal signal peptide of 24 amino acid residues. S1 protection and primer extension experiments, together with Northern (RNA) blots, indicate that the mRNA coding for porin F is monocistronic with short untranslated regions of about 58 bases at the 5' end and about 47 bases at the 3' end. The sequences in the -10 and -35 regions upstream of the transcriptional start site are closely related to the Escherichia coli promoter consensus sequences, which explains why the porin F gene is expressed in E. coli under the control of its own promoter. The amino acid sequence of porin F is not homologous to the different E. coli porins OmpF, OmpC, LamB, and PhoE. On the other hand, a highly homologous region of 30 amino acids between the OmpA proteins of different enteric bacteria and porin F of P. aeruginosa was detected. The core region of the homology to E. coli OmpA had 11 of 12 amino acid residues in common. Images PMID:2447060

  16. Expression of the fibronectin-binding components of Streptococcus pyogenes in Escherichia coli demonstrates that they are proteins.

    PubMed

    Talay, S R; Ehrenfeld, E; Chhatwal, G S; Timmis, K N

    1991-07-01

    The fibronectin-binding components (fbcs) of two clinical isolates and a culture collection strain of Streptococcus pyogenes have been analysed. Western immunoblotting of bacterial lysates which had been fractionated on polyacrylamide gels revealed trypsin-sensitive fibronectin-binding species. The genes specifying the fbcs were cloned from all three strains and expressed in Escherichia coli using a lambda EMBL3 vector. An fbc gene from the culture collection strain was subcloned and expressed in the E. coli expression vector pJLA601, and subjected to deletion analysis. The fibronectin-binding domain was thereby localized within a 40 kDa truncated peptide encoded by the 1000 bp C-terminal region of the gene. Southern hybridization experiments demonstrated that the analysed gene was present in the parental S. pyogenes chromosome, but not in the DNA of fbc expressing lambda clones obtained from the two clinical isolates. Further evidence for the existence of at least two different types of fbcs in group A streptococci was provided by Western blot analysis of recombinant phage lysates which revealed a complex series of fibronectin-binding species ranging from 120 to 200 kDa in size and showing strain-dependent variation in their patterns. As was the case with parental streptococcal strains all of the recombinant fbcs were protease-sensitive, and treatment with trypsin or pronase resulted in a total loss of fibronectin-binding activity. Competitive inhibition experiments indicated that lipoteichoic acid was not a significant fbc in the tested streptococcal strains.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Calf spleen purine nucleoside phosphorylase: structure of its ternary complex with an N(7)-acycloguanosine inhibitor and a phosphate anion.

    PubMed

    Luić, M; Koellner, G; Shugar, D; Saenger, W; Bzowska, A

    2001-01-01

    The calf spleen purine nucleoside phosphorylase (PNP) ternary complex with an N(7)-acycloguanosine inhibitor and a phosphate ion has been crystallized in the cubic space group P2(1)3, with unit-cell parameter a = 94.11 A and one monomer per asymmetric unit. X-ray diffraction data were collected using synchrotron radiation (Station X31, EMBL Outstation, DESY, Hamburg). The crystal structure was refined to a resolution of 2.2 A and R and R(free) values of 17.5 and 24.5%, respectively. The acyclonucleoside inhibitor is bound in the active site in an inverted ('upside-down') orientation of the purine base compared with natural substrates. The side chain of Asp243 forms two hydrogen bonds with the base ring: N(delta) donates a hydrogen to N(3) and O(delta) accepts a hydrogen from the guanine N(2)-amino group. N(1)--H of the base is hydrogen bonded to O(epsilon) of Glu201, while N(9) accepts a hydrogen bond from Thr242 O(gamma). In addition, a water molecule (W417) bridges the N(2)-amino group of the base and O(epsilon) of Glu201. In the phosphate-binding site, a phosphate ion is bound to Ser33, His64, Arg84, His86, Ala116 and Ser220. The acyclic chain of the N(7)-acycloguanosine inhibitor is in a folded conformation and together with a water molecule (W388) occupies the pentose-binding site, with possible hydrogen bonds to Tyr88 O(eta) and His257 N(delta 1). This new binding mode fully accounts for the previously observed substrate properties of 7-beta-D-ribofuranosides of hypoxanthine and guanine. It also provides a new starting point for the design of inhibitors of PNP for therapeutic and other applications.

  18. The 2016 database issue of Nucleic Acids Research and an updated molecular biology database collection.

    PubMed

    Rigden, Daniel J; Fernández-Suárez, Xosé M; Galperin, Michael Y

    2016-01-01

    The 2016 Database Issue of Nucleic Acids Research starts with overviews of the resources provided by three major bioinformatics centers, the U.S. National Center for Biotechnology Information (NCBI), the European Bioinformatics Institute (EMBL-EBI) and Swiss Institute for Bioinformatics (SIB). Also included are descriptions of 62 new databases and updates on 95 databases that have been previously featured in NAR plus 17 previously described elsewhere. A number of papers in this issue deal with resources on nucleic acids, including various kinds of non-coding RNAs and their interactions, molecular dynamics simulations of nucleic acid structure, and two databases of super-enhancers. The protein database section features important updates on the EBI's Pfam, PDBe and PRIDE databases, as well as a variety of resources on pathways, metabolomics and metabolic modeling. This issue also includes updates on popular metagenomics resources, such as MG-RAST, EBI Metagenomics, and probeBASE, as well as a newly compiled Human Pan-Microbe Communities database. A significant fraction of the new and updated databases are dedicated to the genetic basis of disease, primarily cancer, and various aspects of drug research, including resources for patented drugs, their side effects, withdrawn drugs, and potential drug targets. A further six papers present updated databases of various antimicrobial and anticancer peptides. The entire Database Issue is freely available online on the Nucleic Acids Research website (http://nar.oxfordjournals.org/). The NAR online Molecular Biology Database Collection, http://www.oxfordjournals.org/nar/database/c/, has been updated with the addition of 88 new resources and removal of 23 obsolete websites, which brought the current listing to 1685 databases.

  19. Insights into corn genes derived from large-scale cDNA sequencing.

    PubMed

    Alexandrov, Nickolai N; Brover, Vyacheslav V; Freidin, Stanislav; Troukhan, Maxim E; Tatarinova, Tatiana V; Zhang, Hongyu; Swaller, Timothy J; Lu, Yu-Ping; Bouck, John; Flavell, Richard B; Feldmann, Kenneth A

    2009-01-01

    We present a large portion of the transcriptome of Zea mays, including ESTs representing 484,032 cDNA clones from 53 libraries and 36,565 fully sequenced cDNA clones, out of which 31,552 clones are non-redundant. These and other previously sequenced transcripts have been aligned with available genome sequences and have provided new insights into the characteristics of gene structures and promoters within this major crop species. We found that although the average number of introns per gene is about the same in corn and Arabidopsis, corn genes have more alternatively spliced isoforms. Examination of the nucleotide composition of coding regions reveals that corn genes, as well as genes of other Poaceae (Grass family), can be divided into two classes according to the GC content at the third position in the amino acid encoding codons. Many of the transcripts that have lower GC content at the third position have dicot homologs but the high GC content transcripts tend to be more specific to the grasses. The high GC content class is also enriched with intronless genes. Together this suggests that an identifiable class of genes in plants is associated with the Poaceae divergence. Furthermore, because many of these genes appear to be derived from ancestral genes that do not contain introns, this evolutionary divergence may be the result of horizontal gene transfer from species not only with different codon usage but possibly that did not have introns, perhaps outside of the plant kingdom. By comparing the cDNAs described herein with the non-redundant set of corn mRNAs in GenBank, we estimate that there are about 50,000 different protein coding genes in Zea. All of the sequence data from this study have been submitted to DDBJ/GenBank/EMBL under accession numbers EU940701-EU977132 (FLI cDNA) and FK944382-FL482108 (EST). PMID:18937034

  20. Whole genome analysis of Vietnamese G2P[4] rotavirus strains possessing the NSP2 gene sharing an ancestral sequence with Chinese sheep and goat rotavirus strains.

    PubMed

    Do, Loan Phuong; Doan, Yen Hai; Nakagomi, Toyoko; Gauchan, Punita; Kaneko, Miho; Agbemabiese, Chantal; Dang, Anh Duc; Nakagomi, Osamu

    2015-10-01

    Because imminent introduction into Vietnam of a vaccine against Rotavirus A is anticipated, baseline information on the whole genome of representative strains is needed to understand changes in circulating strains that may occur after vaccine introduction. In this study, the whole genomes of two G2P[4] strains detected in Nha Trang, Vietnam in 2008 were sequenced, this being the last period during which virtually no rotavirus vaccine was used in this country. The two strains were found to be >99.9% identical in sequence and had a typical DS-1 like G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genotype constellation. Analysis of the Vietnamese strains with >184 G2P[4] strains retrieved from GenBank/EMBL/DDBJ DNA databases placed the Vietnamese strains in one of the lineages commonly found among contemporary strains, with the exception of the NSP2 and NSP4 genes. The NSP2 genes were found to belong to a previously undescribed lineage that diverged from Chinese sheep and goat rotavirus strains, including a Chinese rotavirus vaccine strain LLR with 95% nucleotide identity; the time of their most recent common ancestor was 1975. The NSP4 genes were found to belong, together with Thai and USA strains, to an emergent lineage (VIII), adding further diversity to ever diversifying NSP4 lineages. Thus, there is a need to enhance surveillance of locally-circulating strains from both children and animals at the whole genome level to address the effect of rotavirus vaccines on changing strain distribution. PMID:26382233

  1. Versatile sample environments and automation for biological solution X-ray scattering experiments at the P12 beamline (PETRA III, DESY)

    PubMed Central

    Blanchet, Clement E.; Spilotros, Alessandro; Schwemmer, Frank; Graewert, Melissa A.; Kikhney, Alexey; Jeffries, Cy M.; Franke, Daniel; Mark, Daniel; Zengerle, Roland; Cipriani, Florent; Fiedler, Stefan; Roessle, Manfred; Svergun, Dmitri I.

    2015-01-01

    A high-brilliance synchrotron P12 beamline of the EMBL located at the PETRA III storage ring (DESY, Hamburg) is dedicated to biological small-angle X-ray scattering (SAXS) and has been designed and optimized for scattering experiments on macromolecular solutions. Scatterless slits reduce the parasitic scattering, a custom-designed miniature active beamstop ensures accurate data normalization and the photon-counting PILATUS 2M detector enables the background-free detection of weak scattering signals. The high flux and small beam size allow for rapid experiments with exposure time down to 30–50 ms covering the resolution range from about 300 to 0.5 nm. P12 possesses a versatile and flexible sample environment system that caters for the diverse experimental needs required to study macromolecular solutions. These include an in-vacuum capillary mode for standard batch sample analyses with robotic sample delivery and for continuous-flow in-line sample purification and characterization, as well as an in-air capillary time-resolved stopped-flow setup. A novel microfluidic centrifugal mixing device (SAXS disc) is developed for a high-throughput screening mode using sub-microlitre sample volumes. Automation is a key feature of P12; it is controlled by a beamline meta server, which coordinates and schedules experiments from either standard or nonstandard operational setups. The integrated SASFLOW pipeline automatically checks for consistency, and processes and analyses the data, providing near real-time assessments of overall parameters and the generation of low-resolution models within minutes of data collection. These advances, combined with a remote access option, allow for rapid high-throughput analysis, as well as time-resolved and screening experiments for novice and expert biological SAXS users. PMID:25844078

  2. Degradation of 4-amylphenol and 4-hexylphenol by a new activated sludge isolate of Pseudomonas veronii and proposal for a new subspecies status.

    PubMed

    Ajithkumar, Bindu; Ajithkumar, Vasudevan P; Iriye, Ryozo

    2003-01-01

    Novel Pseudomonas strains INA04, INA05, and INA06, were isolated from activated sludge. Strain INA06 was found to degrade long chain alkylphenols such as 4-n-amylphenol and 4-n-hexylphenol as the sole source of carbon, apart from co-metabolic degradation of 4-n-nonylphenol in the presence of phenol, while INA04 and INA05 could grow on phenol, but could not grow well on alkylphenols. Induction studies on strain INA06 revealed a broad substrate-specific phenol hydroxylase, for the metabolism of phenol and alkylphenols, inducible with phenol or para-substituted alkylphenol. They bore close resemblance to members of Pseudomonas sensu stricto. 16S rDNA sequence homology of INA06 was closest to P. veronii (99.7%). DNA-DNA hybridization pointed out higher linkage (64% similarity) to the type strain of P. veronii than to other species of Pseudomonas sensu stricto (>60%). The BOX-PCR profile of all INA strains was similar, but different from that of P. veronii. Since biochemical characteristics were similar to those of P. veronii, and genetic relatedness was at the margin of species differentiation level (70%), we propose these strains to be treated as a new subspecies of P. veronii. The type strain of this new subspecies, named P. veronii subsp. inensis subsp. nov., is strain INA06. The accession number of strain INA05 is CIP 107595=JCM11829, and that of INA06 is CIP107594(T)=JCM11828(T). The 16S rDNA sequence accession number (DDBJ/EMBL/GenBank) of strain INA06 is AB056120. PMID:12576154

  3. The obligate respiratory supercomplex from Actinobacteria.

    PubMed

    Kao, Wei-Chun; Kleinschroth, Thomas; Nitschke, Wolfgang; Baymann, Frauke; Neehaul, Yashvin; Hellwig, Petra; Richers, Sebastian; Vonck, Janet; Bott, Michael; Hunte, Carola

    2016-10-01

    Actinobacteria are closely linked to human life as industrial producers of bioactive molecules and as human pathogens. Respiratory cytochrome bcc complex and cytochrome aa3 oxidase are key components of their aerobic energy metabolism. They form a supercomplex in the actinobacterial species Corynebacterium glutamicum. With comprehensive bioinformatics and phylogenetic analysis we show that genes for cyt bcc-aa3 supercomplex are characteristic for Actinobacteria (Actinobacteria and Acidimicrobiia, except the anaerobic orders Actinomycetales and Bifidobacteriales). An obligatory supercomplex is likely, due to the lack of genes encoding alternative electron transfer partners such as mono-heme cyt c. Instead, subunit QcrC of bcc complex, here classified as short di-heme cyt c, will provide the exclusive electron transfer link between the complexes as in C. glutamicum. Purified to high homogeneity, the C. glutamicum bcc-aa3 supercomplex contained all subunits and cofactors as analyzed by SDS-PAGE, BN-PAGE, absorption and EPR spectroscopy. Highly uniform supercomplex particles in electron microscopy analysis support a distinct structural composition. The supercomplex possesses a dimeric stoichiometry with a ratio of a-type, b-type and c-type hemes close to 1:1:1. Redox titrations revealed a low potential bcc complex (Em(ISP)=+160mV, Em(bL)=-291mV, Em(bH)=-163mV, Em(cc)=+100mV) fined-tuned for oxidation of menaquinol and a mixed potential aa3 oxidase (Em(CuA)=+150mV, Em(a/a3)=+143/+317mV) mediating between low and high redox potential to accomplish dioxygen reduction. The generated molecular model supports a stable assembled supercomplex with defined architecture which permits energetically efficient coupling of menaquinol oxidation and dioxygen reduction in one supramolecular entity.

  4. Genomic clones of Aspergillus nidulans containing alcA, the structural gene for alcohol dehydrogenase and alcR, a regulatory gene for ethanol metabolism.

    PubMed

    Doy, C H; Pateman, J A; Olsen, J E; Kane, H J; Creaser, E H

    1985-04-01

    Our aim was to obtain from Aspergillus nidulans a genomic bank and then clone a region we expected from earlier genetic mapping to contain two closely linked genes, alcA, the structural gene for alcohol dehydrogenase (ADH) and alcR, a positive trans-acting regulatory gene for ethanol metabolism. The expression of alcA is repressed by carbon catabolites. A genomic restriction fragment characteristic of the alcA-alcR region was identified, cloned in pBR322, and used to select from a genomic bank in lambda EMBL3A three overlapping clones covering 24 kb of DNA. Southern genomic analysis of wild-type, alcA and alcR mutants showed that the mutants contained extra DNA at sites near the center of the cloned DNA and are close together, as expected for alcA and alcR. Transcription from the cloned DNA and hybridization with a clone carrying the Saccharomyces cerevisiae gene for ADHI (ADC1) are both confined to the alcA-alcR region. At least one of several species of mature mRNA is about 1 kb, the size required to code for ADH. For all species, carbon catabolite repression overrides control by induction. The overall characteristics of transcription, hybridization to ADC1 and earlier work suggest that alcA consists of a number of exons and/or that the alcA-alcR region represents a cluster of alcA-related genes or sequences.

  5. Implications of structural genomics target selection strategies: Pfam5000, whole genome, and random approaches

    SciTech Connect

    Chandonia, John-Marc; Brenner, Steven E.

    2004-07-14

    The structural genomics project is an international effort to determine the three-dimensional shapes of all important biological macromolecules, with a primary focus on proteins. Target proteins should be selected according to a strategy which is medically and biologically relevant, of good value, and tractable. As an option to consider, we present the Pfam5000 strategy, which involves selecting the 5000 most important families from the Pfam database as sources for targets. We compare the Pfam5000 strategy to several other proposed strategies that would require similar numbers of targets. These include including complete solution of several small to moderately sized bacterial proteomes, partial coverage of the human proteome, and random selection of approximately 5000 targets from sequenced genomes. We measure the impact that successful implementation of these strategies would have upon structural interpretation of the proteins in Swiss-Prot, TrEMBL, and 131 complete proteomes (including 10 of eukaryotes) from the Proteome Analysis database at EBI. Solving the structures of proteins from the 5000 largest Pfam families would allow accurate fold assignment for approximately 68 percent of all prokaryotic proteins (covering 59 percent of residues) and 61 percent of eukaryotic proteins (40 percent of residues). More fine-grained coverage which would allow accurate modeling of these proteins would require an order of magnitude more targets. The Pfam5000 strategy may be modified in several ways, for example to focus on larger families, bacterial sequences, or eukaryotic sequences; as long as secondary consideration is given to large families within Pfam, coverage results vary only slightly. In contrast, focusing structural genomics on a single tractable genome would have only a limited impact in structural knowledge of other proteomes: a significant fraction (about 30-40 percent of the proteins, and 40-60 percent of the residues) of each proteome is classified in small

  6. The genetic diversity of Citrus dwarfing viroid populations is mainly dependent on the infected host species.

    PubMed

    Tessitori, Matilde; Rizza, Serena; Reina, Antonella; Causarano, Giovanni; Di Serio, Francesco

    2013-03-01

    As with viruses, viroids infect their hosts as polymorphic populations of variants. Identifying possible sources of genetic variability is significant in the case of the species Citrus dwarfing viroid (CDVd) which has been proposed as a dwarfing agent for high-density citrus plantings. Here, a natural CDVd isolate (CMC) was used as an inoculum source for long-term (25 years) and short-term (1 year) bioassays in different citrus host species. Characterization of progenies indicated that the genetic stability of CDVd populations was high in certain hosts (trifoliate orange, Troyer citrange, Etrog citron, Navelina sweet orange), which preserve viroid populations similar to the original CMC isolate even after 25 years. By contrast, CDVd variant populations in Interdonato lemon and Volkamer lemon were completely different to those in the inoculated sources, highlighting how influential the host is on the genetic variability of CDVd populations. Implications for risk assessment of CDVd as a dwarfing agent are discussed. The GenBank/EMBL/DDBJ accession numbers for the complete sequences of the Citrus dwarfing viroid variants are JF970266.1 forH2-2, JF970267.1 for H2-7, EU938647.1 for H6-2, EU938651.1 forH6-10, JF970268.1 for H10-7, EU938652.1 for H14-13, EU938653.1for H14-14, JF970269.1 for H14-16, EU938648.1 for H15-9,EU938649.1 for H16-2, JF970265.1 for H16-9, EU938654.1 forH16-13, EU938650.1 for H20-3, JF970270.1 for H20-7, EU938641.1for PR-1, EU938642.1 for PR-3, EU938643.1 for PR-7, EU938644.1for CR-1, EU938639.1 for VR-4, JF12070.1 for VR-15, JF812069.1LS-4, EU938640.1 for LS-10 and JF970264.1 for LS-11.

  7. Bioinformatic and phylogenetic analysis of the CLAVATA3/EMBRYO-SURROUNDING REGION (CLE) and the CLE-LIKE signal peptide genes in the Pinophyta

    PubMed Central

    2014-01-01

    Background There is a rapidly growing awareness that plant peptide signalling molecules are numerous and varied and they are known to play fundamental roles in angiosperm plant growth and development. Two closely related peptide signalling molecule families are the CLAVATA3-EMBRYO-SURROUNDING REGION (CLE) and CLE-LIKE (CLEL) genes, which encode precursors of secreted peptide ligands that have roles in meristem maintenance and root gravitropism. Progress in peptide signalling molecule research in gymnosperms has lagged behind that of angiosperms. We therefore sought to identify CLE and CLEL genes in gymnosperms and conduct a comparative analysis of these gene families with angiosperms. Results We undertook a meta-analysis of the GenBank/EMBL/DDBJ gymnosperm EST database and the Picea abies and P. glauca genomes and identified 93 putative CLE genes and 11 CLEL genes among eight Pinophyta species, in the genera Cryptomeria, Pinus and Picea. The predicted conifer CLE and CLEL protein sequences had close phylogenetic relationships with their homologues in Arabidopsis. Notably, perfect conservation of the active CLE dodecapeptide in presumed orthologues of the Arabidopsis CLE41/44-TRACHEARY ELEMENT DIFFERENTIATION (TDIF) protein, an inhibitor of tracheary element (xylem) differentiation, was seen in all eight conifer species. We cloned the Pinus radiata CLE41/44-TDIF orthologues. These genes were preferentially expressed in phloem in planta as expected, but unexpectedly, also in differentiating tracheary element (TE) cultures. Surprisingly, transcript abundances of these TE differentiation-inhibitors sharply increased during early TE differentiation, suggesting that some cells differentiate into phloem cells in addition to TEs in these cultures. Applied CLE13 and CLE41/44 peptides inhibited root elongation in Pinus radiata seedlings. We show evidence that two CLEL genes are alternatively spliced via 3′-terminal acceptor exons encoding separate CLEL peptides

  8. Probing the origins of human acetylcholinesterase inhibition via QSAR modeling and molecular docking.

    PubMed

    Simeon, Saw; Anuwongcharoen, Nuttapat; Shoombuatong, Watshara; Malik, Aijaz Ahmad; Prachayasittikul, Virapong; Wikberg, Jarl E S; Nantasenamat, Chanin

    2016-01-01

    Alzheimer's disease (AD) is a chronic neurodegenerative disease which leads to the gradual loss of neuronal cells. Several hypotheses for AD exists (e.g., cholinergic, amyloid, tau hypotheses, etc.). As per the cholinergic hypothesis, the deficiency of choline is responsible for AD; therefore, the inhibition of AChE is a lucrative therapeutic strategy for the treatment of AD. Acetylcholinesterase (AChE) is an enzyme that catalyzes the breakdown of the neurotransmitter acetylcholine that is essential for cognition and memory. A large non-redundant data set of 2,570 compounds with reported IC50 values against AChE was obtained from ChEMBL and employed in quantitative structure-activity relationship (QSAR) study so as to gain insights on their origin of bioactivity. AChE inhibitors were described by a set of 12 fingerprint descriptors and predictive models were constructed from 100 different data splits using random forest. Generated models afforded R (2), [Formula: see text] and [Formula: see text] values in ranges of 0.66-0.93, 0.55-0.79 and 0.56-0.81 for the training set, 10-fold cross-validated set and external set, respectively. The best model built using the substructure count was selected according to the OECD guidelines and it afforded R (2), [Formula: see text] and [Formula: see text] values of 0.92 ± 0.01, 0.78 ± 0.06 and 0.78 ± 0.05, respectively. Furthermore, Y-scrambling was applied to evaluate the possibility of chance correlation of the predictive model. Subsequently, a thorough analysis of the substructure fingerprint count was conducted to provide informative insights on the inhibitory activity of AChE inhibitors. Moreover, Kennard-Stone sampling of the actives were applied to select 30 diverse compounds for further molecular docking studies in order to gain structural insights on the origin of AChE inhibition. Site-moiety mapping of compounds from the diversity set revealed three binding anchors encompassing both hydrogen bonding and van der Waals

  9. Improved Chemical Structure-Activity Modeling Through Data Augmentation.

    PubMed

    Cortes-Ciriano, Isidro; Bender, Andreas

    2015-12-28

    Extending the original training data with simulated unobserved data points has proven powerful to increase both the generalization ability of predictive models and their robustness against changes in the structure of data (e.g., systematic drifts in the response variable) in diverse areas such as the analysis of spectroscopic data or the detection of conserved domains in protein sequences. In this contribution, we explore the effect of data augmentation in the predictive power of QSAR models, quantified by the RMSE values on the test set. We collected 8 diverse data sets from the literature and ChEMBL version 19 reporting compound activity as pIC50 values. The original training data were replicated (i.e., augmented) N times (N ∈ 0, 1, 2, 4, 6, 8, 10), and these replications were perturbed with Gaussian noise (μ = 0, σ = σnoise) on either (i) the pIC50 values, (ii) the compound descriptors, (iii) both the compound descriptors and the pIC50 values, or (iv) none of them. The effect of data augmentation was evaluated across three different algorithms (RF, GBM, and SVM radial) and two descriptor types (Morgan fingerprints and physicochemical-property-based descriptors). The influence of all factor levels was analyzed with a balanced fixed-effect full-factorial experiment. Overall, data augmentation constantly led to increased predictive power on the test set by 10-15%. Injecting noise on (i) compound descriptors or on (ii) both compound descriptors and pIC50 values led to the highest drop of RMSEtest values (from 0.67-0.72 to 0.60-0.63 pIC50 units). The maximum increase in predictive power provided by data augmentation is reached when the training data is replicated one time. Therefore, extending the original training data with one perturbed repetition thereof represents a reasonable trade-off between the increased performance of the models and the computational cost of data augmentation, namely increase of (i) model complexity due to the need for optimizing

  10. De Novo Characterization of the Mung Bean Transcriptome and Transcriptomic Analysis of Adventitious Rooting in Seedlings Using RNA-Seq

    PubMed Central

    Li, Shi-Weng; Shi, Rui-Fang; Leng, Yan

    2015-01-01

    Adventitious rooting is the most important mechanism underlying vegetative propagation and an important strategy for plant propagation under environmental stress. The present study was conducted to obtain transcriptomic data and examine gene expression using RNA-Seq and bioinformatics analysis, thereby providing a foundation for understanding the molecular mechanisms controlling adventitious rooting. Three cDNA libraries constructed from mRNA samples from mung bean hypocotyls during adventitious rooting were sequenced. These three samples generated a total of 73 million, 60 million, and 59 million 100-bp reads, respectively. These reads were assembled into 78,697 unigenes with an average length of 832 bp, totaling 65 Mb. The unigenes were aligned against six public protein databases, and 29,029 unigenes (36.77%) were annotated using BLASTx. Among them, 28,225 (35.75%) and 28,119 (35.62%) unigenes had homologs in the TrEMBL and NCBI non-redundant (Nr) databases, respectively. Of these unigenes, 21,140 were assigned to gene ontology classes, and a total of 11,990 unigenes were classified into 25 KOG functional categories. A total of 7,357 unigenes were annotated to 4,524 KOs, and 4,651 unigenes were mapped onto 342 KEGG pathways using BLAST comparison against the KEGG database. A total of 11,717 unigenes were differentially expressed (fold change>2) during the root induction stage, with 8,772 unigenes down-regulated and 2,945 unigenes up-regulated. A total of 12,737 unigenes were differentially expressed during the root initiation stage, with 9,303 unigenes down-regulated and 3,434 unigenes up-regulated. A total of 5,334 unigenes were differentially expressed between the root induction and initiation stage, with 2,167 unigenes down-regulated and 3,167 unigenes up-regulated. qRT-PCR validation of the 39 genes with known functions indicated a strong correlation (92.3%) with the RNA-Seq data. The GO enrichment, pathway mapping, and gene expression profiles reveal

  11. Le mélanome malin: une tumeur rare des fosses nasales - à propos d'une série de 10 cas

    PubMed Central

    Errachdi, Amal; Epala, Brice Nkoua; Asabbane, Amal; Kabbali, Naoual; Hemmich, Mariem; Kebdani, Tayeb; Benjaafar, Noureddine

    2014-01-01

    Le mélanome malin des fosses nasales est une tumeur rare mais très agressive, de traitement complexe et de pronostic défavorable. Son traitement relève en principe d'une prise en charge essentiellement chirurgicale complétée par une radiothérapie. L'objectif de ce travail est de rapporter les caractéristiques cliniques, thérapeutiques et évolutives des mélanomes des fosses nasales. Nous avons analysé rétrospectivement 10 cas de mélanomes des fosses nasales suivis à l'institut national d'oncologie de Rabat. La rhinoscopie avec biopsie a permis la confirmation histologique du diagnostic de mélanome. Le bilan d'extension comprenait une tomodensitométrie ou imagerie par résonnance magnétique du massif facial, une radiographie thoracique et une échographie abdominale. Dans notre série, l’âge médian était de 67.5 ans, avec une prédominance féminine (7femmes et 3hommes). Le délai médian de découverte était de 6 mois. Deux patients étaient métastatiques d'emblée, et toutes les tumeurs étaient localement avancées au moment du diagnostic. Sept patients ont été opérés avec des limites chirurgicales envahies dans 2 cas et 3 patients étaient inopérables. 2 patients ont été irradiés après la chirurgie et 2 patients ont reçu une chimiothérapie arrêtée au moment de la progression. Deux patients ont récidivé après traitement, et un patient était en mauvais état général et a bénéficié uniquement de soins palliatifs. Tous les patients sont décédés avec un délai médian de survie de 12 mois. Le mélanome malin muqueux des fosses nasales, bien que rare, demeure une pathologie de pronostic défavorable et pose des problèmes de prise en charge. PMID:25404963

  12. A SINE species from hippopotamus and its distribution among animal species.

    PubMed

    Nomura, O; Lin, Z H; Muladno; Wada, Y; Yasue, H

    1998-07-01

    Thirty sequences of a short interspersed repetitive element (SINE) were isolated from genomic DNA of Hippopotamus amphibius (hippopotamus). RNA polymerase III split promoter sequence was observed in all of the 30 sequences; and poly(A)-like structure at 3'-end, as well as direct repeat flanking to the repetitive sequence in many of the 30 sequences. A comparison of the consensus sequence of the 30 sequences with sequences in a DNA database (DDBJ/GENBANK/EMBL) revealed 93% homology to the consensus sequence of a whale SINE, CHR-2, and 73% homology to mouse glutamic acid tRNA. Phylogenetic analysis of tRNA-related regions of the sequences with all of the mouse tRNAs revealed that glutamic acid tRNA was genetically closest to the hippopotamus SINE. In addition, the tRNA-related region of the consensus sequence was folded into a cloverleaf structure as with mouse glutamic acid tRNA. These findings led us to conclude that the SINE of hippopotamus was genetically related to a whale SINE, CHR-2 [the hippopotamus SINE was named CHR-2(hippo)] and was a retroposon derived from glutamic acid tRNA. Hipo53 and hipo95, which were the genetically most separated CHR-2(hippo) sequences in the present study, were used as a probe for dot-blot hybridization to examine the distribution of their homologous sequences among animal species. Although the distribution spectra of hipo53 and hipo95 homologous sequences in animal species differed to some extent, large amounts of both sequences were found in Hippopotamus amphibius and Globicephala macrorhynchus (whale); and small amounts in most of the animal species in Artiodactyla examined. These findings indicated that the hippopotamus and whale had more recently branched off from the clade that includes chevrotain and pecorans than the other animal species in the clade. The 30 CHR-2(hippo) sequences were aligned, and the substitution rates among the sequences were calculated with a different substitution rate model for transition and for

  13. Metatranscriptomics Reveals the Diversity of Genes Expressed by Eukaryotes in Forest Soils

    PubMed Central

    Damon, Coralie; Lehembre, Frédéric; Oger-Desfeux, Christine; Luis, Patricia; Ranger, Jacques; Fraissinet-Tachet, Laurence; Marmeisse, Roland

    2012-01-01

    Eukaryotic organisms play essential roles in the biology and fertility of soils. For example the micro and mesofauna contribute to the fragmentation and homogenization of plant organic matter, while its hydrolysis is primarily performed by the fungi. To get a global picture of the activities carried out by soil eukaryotes we sequenced 2×10,000 cDNAs synthesized from polyadenylated mRNA directly extracted from soils sampled in beech (Fagus sylvatica) and spruce (Picea abies) forests. Taxonomic affiliation of both cDNAs and 18S rRNA sequences showed a dominance of sequences from fungi (up to 60%) and metazoans while protists represented less than 12% of the 18S rRNA sequences. Sixty percent of cDNA sequences from beech forest soil and 52% from spruce forest soil had no homologs in the GenBank/EMBL/DDJB protein database. A Gene Ontology term was attributed to 39% and 31.5% of the spruce and beech soil sequences respectively. Altogether 2076 sequences were putative homologs to different enzyme classes participating to 129 KEGG pathways among which several were implicated in the utilisation of soil nutrients such as nitrogen (ammonium, amino acids, oligopeptides), sugars, phosphates and sulfate. Specific annotation of plant cell wall degrading enzymes identified enzymes active on major polymers (cellulose, hemicelluloses, pectin, lignin) and glycoside hydrolases represented 0.5% (beech soil)–0.8% (spruce soil) of the cDNAs. Other sequences coding enzymes active on organic matter (extracellular proteases, lipases, a phytase, P450 monooxygenases) were identified, thus underlining the biotechnological potential of eukaryotic metatranscriptomes. The phylogenetic affiliation of 12 full-length carbohydrate active enzymes showed that most of them were distantly related to sequences from known fungi. For example, a putative GH45 endocellulase was closely associated to molluscan sequences, while a GH7 cellobiohydrolase was closest to crustacean sequences, thus suggesting a

  14. Etiologies des hypertensions artérielles endocrines: à propos d'une série de cas

    PubMed Central

    Bouznad, Naima; El Mghari, Ghizlane; El Ansari, Nawal

    2016-01-01

    Les hypertensions artérielles (HTA) d'origine endocrine restent une cause rare d'HTA, sa prévalence globale n'excède pas 4% des hypertendus. L'intérêt de la recherche des HTA endocrines réside dans la gravité de certaines formes parfois mortelles et le caractère potentiellement curable et réversible de ces HTA. Le but du travail est de déterminer le profil clinique, para clinique, étiologique et thérapeutique des HTA secondaires d'origine endocrine chez les patients suivis au service d'endocrinologie au CHU Mohamed IV à Marrakech. Il s'agit d'une étude descriptive prospective s’étalant sur une période de 4 ans incluant 45 patients ayant une HTA endocrinienne. La moyenne d’âge est de 44,89 ans, avec une nette prédominance du sexe féminine (sexe ratio de 0,49). Les étiologies des HTA endocrines étaient dominées par le phéochromocytome (17 cas), l'hypercorticisme (11 cas) et l'acromégalie (8 cas). L'HTA était paroxystique dans 24,4%. Elle était d'emblée sevère classée grade 3 dans 40% des cas. L'HTA a été compliquée de cardiopathie dans 24% des cas et de néphropathie dans 20% des cas. Le traitement curatif a permis une guérison de l'HTA chez 60% (27 cas). Le diagnostic des HTA secondaires endocrines est parfois difficile du fait de l'absence de spécificité clinique. Il n'est pas exceptionnel que l'HTA soit l'unique manifestation de la maladie. Dans notre travail nous notons le caractère paroxystique et sévère de l'HTA. Le caractère éventuellement curable des HTA endocrines, dans plus des deux tiers des cas, fait qu'il est important de la dépister devant toute HTA sévère, résistante au traitement, ou en présence de signes cliniques, biologiques ou radiologiques évocateurs. PMID:27303586

  15. Do not hesitate to use Tversky-and other hints for successful active analogue searches with feature count descriptors.

    PubMed

    Horvath, Dragos; Marcou, Gilles; Varnek, Alexandre

    2013-07-22

    This study is an exhaustive analysis of the neighborhood behavior over a large coherent data set (ChEMBL target/ligand pairs of known Ki, for 165 targets with >50 associated ligands each). It focuses on similarity-based virtual screening (SVS) success defined by the ascertained optimality index. This is a weighted compromise between purity and retrieval rate of active hits in the neighborhood of an active query. One key issue addressed here is the impact of Tversky asymmetric weighing of query vs candidate features (represented as integer-value ISIDA colored fragment/pharmacophore triplet count descriptor vectors). The nearly a 3/4 million independent SVS runs showed that Tversky scores with a strong bias in favor of query-specific features are, by far, the most successful and the least failure-prone out of a set of nine other dissimilarity scores. These include classical Tanimoto, which failed to defend its privileged status in practical SVS applications. Tversky performance is not significantly conditioned by tuning of its bias parameter α. Both initial "guesses" of α = 0.9 and 0.7 were more successful than Tanimoto (at its turn, better than Euclid). Tversky was eventually tested in exhaustive similarity searching within the library of 1.6 M commercial + bioactive molecules at http://infochim.u-strasbg.fr/webserv/VSEngine.html , comparing favorably to Tanimoto in terms of "scaffold hopping" propensity. Therefore, it should be used at least as often as, perhaps in parallel to Tanimoto in SVS. Analysis with respect to query subclasses highlighted relationships of query complexity (simply expressed in terms of pharmacophore pattern counts) and/or target nature vs SVS success likelihood. SVS using more complex queries are more robust with respect to the choice of their operational premises (descriptors, metric). Yet, they are best handled by "pro-query" Tversky scores at α > 0.5. Among simpler queries, one may distinguish between "growable" (allowing for active

  16. Drug Design for CNS Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3D-QSAR and Virtual Screening Methodologies.

    PubMed

    Nikolic, Katarina; Mavridis, Lazaros; Djikic, Teodora; Vucicevic, Jelica; Agbaba, Danica; Yelekci, Kemal; Mitchell, John B O

    2016-01-01

    HIGHLIGHTS Many CNS targets are being explored for multi-target drug designNew databases and cheminformatic methods enable prediction of primary pharmaceutical target and off-targets of compoundsQSAR, virtual screening and docking methods increase the potential of rational drug design The diverse cerebral mechanisms implicated in Central Nervous System (CNS) diseases together with the heterogeneous and overlapping nature of phenotypes indicated that multitarget strategies may be appropriate for the improved treatment of complex brain diseases. Understanding how the neurotransmitter systems interact is also important in optimizing therapeutic strategies. Pharmacological intervention on one target will often influence another one, such as the well-established serotonin-dopamine interaction or the dopamine-glutamate interaction. It is now accepted that drug action can involve plural targets and that polypharmacological interaction with multiple targets, to address disease in more subtle and effective ways, is a key concept for development of novel drug candidates against complex CNS diseases. A multi-target therapeutic strategy for Alzheimer's disease resulted in the development of very effective Multi-Target Designed Ligands (MTDL) that act on both the cholinergic and monoaminergic systems, and also retard the progression of neurodegeneration by inhibiting amyloid aggregation. Many compounds already in databases have been investigated as ligands for multiple targets in drug-discovery programs. A probabilistic method, the Parzen-Rosenblatt Window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. Based on all these findings, it is concluded that multipotent ligands

  17. Probing the origins of human acetylcholinesterase inhibition via QSAR modeling and molecular docking.

    PubMed

    Simeon, Saw; Anuwongcharoen, Nuttapat; Shoombuatong, Watshara; Malik, Aijaz Ahmad; Prachayasittikul, Virapong; Wikberg, Jarl E S; Nantasenamat, Chanin

    2016-01-01

    Alzheimer's disease (AD) is a chronic neurodegenerative disease which leads to the gradual loss of neuronal cells. Several hypotheses for AD exists (e.g., cholinergic, amyloid, tau hypotheses, etc.). As per the cholinergic hypothesis, the deficiency of choline is responsible for AD; therefore, the inhibition of AChE is a lucrative therapeutic strategy for the treatment of AD. Acetylcholinesterase (AChE) is an enzyme that catalyzes the breakdown of the neurotransmitter acetylcholine that is essential for cognition and memory. A large non-redundant data set of 2,570 compounds with reported IC50 values against AChE was obtained from ChEMBL and employed in quantitative structure-activity relationship (QSAR) study so as to gain insights on their origin of bioactivity. AChE inhibitors were described by a set of 12 fingerprint descriptors and predictive models were constructed from 100 different data splits using random forest. Generated models afforded R (2), [Formula: see text] and [Formula: see text] values in ranges of 0.66-0.93, 0.55-0.79 and 0.56-0.81 for the training set, 10-fold cross-validated set and external set, respectively. The best model built using the substructure count was selected according to the OECD guidelines and it afforded R (2), [Formula: see text] and [Formula: see text] values of 0.92 ± 0.01, 0.78 ± 0.06 and 0.78 ± 0.05, respectively. Furthermore, Y-scrambling was applied to evaluate the possibility of chance correlation of the predictive model. Subsequently, a thorough analysis of the substructure fingerprint count was conducted to provide informative insights on the inhibitory activity of AChE inhibitors. Moreover, Kennard-Stone sampling of the actives were applied to select 30 diverse compounds for further molecular docking studies in order to gain structural insights on the origin of AChE inhibition. Site-moiety mapping of compounds from the diversity set revealed three binding anchors encompassing both hydrogen bonding and van der Waals

  18. De Novo Characterization of the Mung Bean Transcriptome and Transcriptomic Analysis of Adventitious Rooting in Seedlings Using RNA-Seq.

    PubMed

    Li, Shi-Weng; Shi, Rui-Fang; Leng, Yan

    2015-01-01

    Adventitious rooting is the most important mechanism underlying vegetative propagation and an important strategy for plant propagation under environmental stress. The present study was conducted to obtain transcriptomic data and examine gene expression using RNA-Seq and bioinformatics analysis, thereby providing a foundation for understanding the molecular mechanisms controlling adventitious rooting. Three cDNA libraries constructed from mRNA samples from mung bean hypocotyls during adventitious rooting were sequenced. These three samples generated a total of 73 million, 60 million, and 59 million 100-bp reads, respectively. These reads were assembled into 78,697 unigenes with an average length of 832 bp, totaling 65 Mb. The unigenes were aligned against six public protein databases, and 29,029 unigenes (36.77%) were annotated using BLASTx. Among them, 28,225 (35.75%) and 28,119 (35.62%) unigenes had homologs in the TrEMBL and NCBI non-redundant (Nr) databases, respectively. Of these unigenes, 21,140 were assigned to gene ontology classes, and a total of 11,990 unigenes were classified into 25 KOG functional categories. A total of 7,357 unigenes were annotated to 4,524 KOs, and 4,651 unigenes were mapped onto 342 KEGG pathways using BLAST comparison against the KEGG database. A total of 11,717 unigenes were differentially expressed (fold change>2) during the root induction stage, with 8,772 unigenes down-regulated and 2,945 unigenes up-regulated. A total of 12,737 unigenes were differentially expressed during the root initiation stage, with 9,303 unigenes down-regulated and 3,434 unigenes up-regulated. A total of 5,334 unigenes were differentially expressed between the root induction and initiation stage, with 2,167 unigenes down-regulated and 3,167 unigenes up-regulated. qRT-PCR validation of the 39 genes with known functions indicated a strong correlation (92.3%) with the RNA-Seq data. The GO enrichment, pathway mapping, and gene expression profiles reveal

  19. Transcriptome sequencing and differential gene expression analysis of delayed gland morphogenesis in Gossypium australe during seed germination.

    PubMed

    Tao, Tao; Zhao, Liang; Lv, Yuanda; Chen, Jiedan; Hu, Yan; Zhang, Tianzhen; Zhou, Baoliang

    2013-01-01

    The genus Gossypium is a globally important crop that is used to produce textiles, oil and protein. However, gossypol, which is found in cultivated cottonseed, is toxic to humans and non-ruminant animals. Efforts have been made to breed improved cultivated cotton with lower gossypol content. The delayed gland morphogenesis trait possessed by some Australian wild cotton species may enable the widespread, direct usage of cottonseed. However, the mechanisms about the delayed gland morphogenesis are still unknown. Here, we sequenced the first Australian wild cotton species (Gossypiumaustrale) and a diploid cotton species (Gossypiumarboreum) using the Illumina Hiseq 2000 RNA-seq platform to help elucidate the mechanisms underlying gossypol synthesis and gland development. Paired-end Illumina short reads were de novo assembled into 226,184, 213,257 and 275,434 transcripts, clustering into 61,048, 47,908 and 72,985 individual clusters with N50 lengths of 1,710 bp, 1544 BP and 1,743 bp, respectively. The clustered Unigenes were searched against three public protein databases (TrEMBL, SwissProt and RefSeq) and the nucleotide and protein sequences of Gossypiumraimondii using BLASTx and BLASTn. A total of 21,987, 17,209 and 25,325 Unigenes were annotated. Of these, 18,766 (85.4%), 14,552 (84.6%) and 21,374 (84.4%) Unigenes could be assigned to GO-term classifications. We identified and analyzed 13,884 differentially expressed Unigenes by clustering and functional enrichment. Terpenoid-related biosynthesis pathways showed differentially regulated expression patterns between the two cotton species. Phylogenetic analysis of the terpene synthases family was also carried out to clarify the classifications of TPSs. RNA-seq data from two distinct cotton species provide comprehensive transcriptome annotation resources and global gene expression profiles during seed germination and gland and gossypol formation. These data may be used to further elucidate various mechanisms and help

  20. Magna Carta for Researchers

    NASA Astrophysics Data System (ADS)

    2006-12-01

    Today, Janez Potočnik, European Commissioner for Science and Research received a statement of support for the European Charter for Researchers and the Code of Conduct for the Recruitment of Researchers from EIROforum. "The EIROforum partners warmly welcome this valuable initiative by the European Commission", said Prof. William G. Stirling, Director General of ESRF and present Chairman of EIROforum."This is an important step towards the implementation of the European Research Area." ESO PR Photo 47/06 ESO PR Photo 47a/06 Janez Potočnik, European Commissioner for Science and Research receives the statement of support from Bill Stirling, Director General of ESRF and present Chairman of EIROforum. The European Charter for Researchers addresses the roles, responsibilities and entitlements of researchers and their employers or funding organisations. It aims at ensuring that the relationship between these parties contributes to successful performance in the generation, transfer and sharing of knowledge, and to the career development of researchers. The Code of Conduct for the Recruitment of Researchers aims to improve recruitment, to make selection procedures fairer and more transparent and proposes different means of judging merit. Merit should not just be measured on the number of publications but on a wider range of evaluation criteria, such as teaching, supervision, teamwork, knowledge transfer, management and public awareness activities. ESO PR Photo 47/06 ESO PR Photo 47b/06 The signature of the statement of support last November. From left to right: Richard Wagner, Director of the ILL, David Southwood, Scientific Director of ESA, Robert Aymar, Director General of CERN, Bill Stirling, Director General of ESRF, Catherine Cesarsky, Director General of ESO, Francesco Romanelli, EFDA-JET leader and Silke Schumacher, Coordinator International Relations and Communication of the EMBL. In their statement, signed at the EIROforum Assembly on 15 November 2006, the seven

  1. Phylogenomic Study of Burkholderia glathei-like Organisms, Proposal of 13 Novel Burkholderia Species and Emended Descriptions of Burkholderia sordidicola, Burkholderia zhejiangensis, and Burkholderia grimmiae

    PubMed Central

    Peeters, Charlotte; Meier-Kolthoff, Jan P.; Verheyde, Bart; De Brandt, Evie; Cooper, Vaughn S.; Vandamme, Peter

    2016-01-01

    68415T). Furthermore, we present emended descriptions of the species Burkholderia sordidicola, Burkholderia zhejiangensis and Burkholderia grimmiae. The GenBank/EMBL/DDBJ accession numbers for the 16S rRNA and gyrB gene sequences determined in this study are LT158612-LT158624 and LT158625-LT158641, respectively. PMID:27375597

  2. A Type II Protein Secretory Pathway Required for Levansucrase Secretion by Gluconacetobacter diazotrophicus

    PubMed Central

    Arrieta, Juan G.; Sotolongo, Mailin; Menéndez, Carmen; Alfonso, Dubiel; Trujillo, Luis E.; Soto, Melvis; Ramírez, Ricardo; Hernández, Lázaro

    2004-01-01

    The endophytic diazotroph Gluconacetobacter diazotrophicus secretes a constitutively expressed levansucrase (LsdA, EC 2.4.1.10) to utilize plant sucrose. LsdA, unlike other extracellular levansucrases from gram-negative bacteria, is transported to the periplasm by a signal-peptide-dependent pathway. We identified an unusually organized gene cluster encoding at least the components LsdG, -O, -E, -F, -H, -I, -J, -L, -M, -N, and -D of a type II secretory system required for LsdA translocation across the outer membrane. Another open reading frame, designated lsdX, is located between the operon promoter and lsdG, but it was not identified in BLASTX searches of the DDBJ/EMBL/GenBank databases. The lsdX, -G, and -O genes were isolated from a cosmid library of strain SRT4 by complementation of an ethyl methanesulfonate mutant unable to transport LsdA across the outer membrane. The downstream genes lsdE, -F, -H, -I, -J, -L, -M, -N, and -D were isolated through chromosomal walking. The high G+C content (64 to 74%) and the codon usage of the genes identified are consistent with the G+C content and codon usage of the standard G. diazotrophicus structural gene. Sequence analysis of the gene cluster indicated that a polycistronic transcript is synthesized. Targeted disruption of lsdG, lsdO, or lsdF blocked LsdA secretion, and the bacterium failed to grow on sucrose. Replacement of Cys162 by Gly at the C terminus of the pseudopilin LsdG abolished the protein functionality, suggesting that there is a relationship with type IV pilins. Restriction fragment length polymorphism analysis revealed conservation of the type II secretion operon downstream of the levansucrase-levanase (lsdA-lsdB) locus in 14 G. diazotrophicus strains representing 11 genotypes recovered from four different host plants in diverse geographical regions. To our knowledge, this is the first report of a type II pathway for protein secretion in the Acetobacteraceae. PMID:15262940

  3. Comparative genomics of citric-acid producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88

    SciTech Connect

    Grigoriev, Igor V.; Baker, Scott E.; Andersen, Mikael R.; Salazar, Margarita P.; Schaap, Peter J.; Vondervoot, Peter J.I. van de; Culley, David; Thykaer, Jette; Frisvad, Jens C.; Nielsen, Kristen F.; Albang, Richard; Albermann, Kaj; Berka, Randy M.; Braus, Gerhard H.; Braus-Stromeyer, Susanna A.; Corrochano, Luis M.; Dai, Ziyu; Dijck, Piet W.M. van; Hofmann, Gerald; Lasure, Linda L.; Magnusson, Jon K.; Meijer, Susan L.; Nielsen, Jakob B.; Nielsen, Michael L.; Ooyen, Albert J.J. van; Panther, Kathyrn S.; Pel, Herman J.; Poulsen, Lars; Samson, Rob A.; Stam, Hen; Tsang, Adrian; Brink, Johannes M. van den; Atkins, Alex; Aerts, Andrea; Shapiro, Harris; Pangilinan, Jasmyn; Salamov, Asaf; Lou, Yigong; Lindquist, Erika; Lucas, Susan; Grimwood, Jane; Kubicek, Christian P.; Martinez, Diego; Peij, Noel N.M.E. van; Roubos, Johannes A.; Nielsen, Jens

    2011-04-28

    . The whole genome sequence for A. niger ATCC 1015 is available from NBCI under acc. no ACJE00000000. The up-dated sequence for A. niger CBS 513.88 is available from EMBL under acc. no AM269948-AM270415. The sequence data from the phylogeny study has been submitted to NCBI (GU296686-296739). Microarray data from this study is submitted to GEO as series GSE10983. Accession for reviewers is possible through: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi token GSE10983] The dsmM_ANIGERa_coll511030F library and platform information is deposited at GEO under number GPL6758

  4. Drug Design for CNS Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3D-QSAR and Virtual Screening Methodologies

    PubMed Central

    Nikolic, Katarina; Mavridis, Lazaros; Djikic, Teodora; Vucicevic, Jelica; Agbaba, Danica; Yelekci, Kemal; Mitchell, John B. O.

    2016-01-01

    HIGHLIGHTS Many CNS targets are being explored for multi-target drug designNew databases and cheminformatic methods enable prediction of primary pharmaceutical target and off-targets of compoundsQSAR, virtual screening and docking methods increase the potential of rational drug design The diverse cerebral mechanisms implicated in Central Nervous System (CNS) diseases together with the heterogeneous and overlapping nature of phenotypes indicated that multitarget strategies may be appropriate for the improved treatment of complex brain diseases. Understanding how the neurotransmitter systems interact is also important in optimizing therapeutic strategies. Pharmacological intervention on one target will often influence another one, such as the well-established serotonin-dopamine interaction or the dopamine-glutamate interaction. It is now accepted that drug action can involve plural targets and that polypharmacological interaction with multiple targets, to address disease in more subtle and effective ways, is a key concept for development of novel drug candidates against complex CNS diseases. A multi-target therapeutic strategy for Alzheimer‘s disease resulted in the development of very effective Multi-Target Designed Ligands (MTDL) that act on both the cholinergic and monoaminergic systems, and also retard the progression of neurodegeneration by inhibiting amyloid aggregation. Many compounds already in databases have been investigated as ligands for multiple targets in drug-discovery programs. A probabilistic method, the Parzen-Rosenblatt Window approach, was used to build a “predictor” model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. Based on all these findings, it is concluded that multipotent

  5. Regulation of the cnr Cobalt and Nickel Resistance Determinant of Ralstonia eutropha (Alcaligenes eutrophus) CH34

    PubMed Central

    Tibazarwa, C.; Wuertz, S.; Mergeay, M.; Wyns, L.; van der Lelie, D.

    2000-01-01

    The linked resistance to nickel and cobalt of Ralstonia eutropha-like strain CH34 (Alcaligenes eutrophus CH34) is encoded by the cnr operon, which is localized on the megaplasmid pMOL28. The regulatory genes cnrYXH have been cloned, overexpressed, and purified in Escherichia coli. CnrY fractionated as a 10.7-kDa protein in in vitro translation assays. CnrX, a periplasmic protein of 16.5 kDa, was overproduced and purified as a histidine-tagged fusion protein in E. coli. His-CnrX was found to posses a secondary structure content rich in alpha-helical and beta-sheet structures. CnrH, a sigma factor of the extracytoplasmic function family, was purified as an N-terminally histidine-tagged fusion. In gel shift mobility assays, His-CnrH, in the presence of E. coli core RNA polymerase enzyme, could retard at least two different promoter DNA targets, cnrYp and cnrHp, localized within the cnrYXH locus. These promoters and their transcription start sites were confirmed by primer extension. Purified His-CnrX did not inhibit the DNA-binding activity of His-CnrH and is therefore unlikely to be an anti-sigma factor, as previously hypothesized (EMBL M91650 description entry). To study the transcriptional response of the regulatory locus to metals and to probe promoter regions, transcriptional fusions were constructed between fragments of cnrYXH and the luxCDABE, luciferase reporter genes. Nickel and cobalt specifically induced the cnrYXH-luxCDABE fusion at optimal concentrations of 0.3 mM Ni2+ and 2.0 mM Co2+ in a noncomplexing medium for metals. The two promoter regions PY (upstream cnrY) and PH (upstream cnrH) were probed and characterized using this vector and were found to control the nickel-inducible regulatory response of the cnr operon. The cnrHp promoter was responsible for full transcription of the cnrCBA structural resistance genes, while the cnrYp promoter was necessary to obtain metal-inducible transcription from the cnrHp promoter. The zinc resistance phenotype (Zin

  6. Cloning of two members of the SIRP alpha family of protein tyrosine phosphatase binding proteins in cattle that are expressed on monocytes and a subpopulation of dendritic cells and which mediate binding to CD4 T cells.

    PubMed

    Brooke, G P; Parsons, K R; Howard, C J

    1998-01-01

    Recent experimental studies have greatly clarified the function of cell surface molecules in the induction and modulation of T cell responses by antigen-presenting cells (APC). However, the differences in ability to stimulate T cells evident for different types and subpopulations of the same APC, such as dendritic cell subsets, is less well understood. This report details an investigation of an antigen expressed on monocytes that is also expressed on a subset of cattle afferent lymph veiled cells (ALVC). A cDNA library derived from cattle monocytes was screened with monoclonal antibodies (mAb) for expression in COS-7 cells. Using separate mAb for screening, two cDNA were cloned, the sequences of which showed a single long open reading frame encoding a predicted type I glycoprotein of 506 amino acids that contained three immunoglobulin superfamily domains and a long 112-amino acid cytoplasmic tail. We have termed this antigen MyD-1, reflecting its myeloid and dendritic cell distribution. Analysis of the EMBL database revealed that the molecule is a member of the recently described family of signal regulatory proteins (SIRP). The outeremost Ig domain was of the adhesion/receptor I-type, suggesting that MyD-1 might bind to a ligand on another cell. Evidence for this was subsequently obtained by demonstrating that COS-7 cells transfected with MyD-1 cDNA bound CD4 T cells and this binding was blocked by specific mAb. The potential importance of this interaction was supported by the finding that the proliferation of resting memory CD4 T cells to ovalbumin-pulsed monocytes was significantly reduced in the presence of mAb to MyD-1. A role for the molecule in the modulation of the monocyte/dendritic APC response is also predicted from the existence of multiple potential tyrosine phosphorylation sites in the cytoplasmic domain, including the presence of an immunoreceptor tyrosine-based inhibitory motif (ITIM) and the observation that the SIRP alpha family members have been

  7. Structure and Sequence of the Human Fast Skeletal Troponin T (TNNT3) Gene: Insight Into the Evolution of the Gene and the Origin of the Developmentally Regulated Isoforms

    PubMed Central

    Stefancsik, Raymund; Randall, Jeffrey D.; Mao, Chengjian

    2003-01-01

    We describe the cloning, sequencing and structure of the human fast skeletal troponin T (TNNT3) gene located on chromosome 11p15.5. The single-copy gene encodes 19 exons and 18 introns. Eleven of these exons, 1–3, 9–15 and 18, are constitutively spliced, whereas exons 4–8 are alternatively spliced. The gene contains an additional subset of developmentally regulated and alternatively spliced exons, including a foetal exon located between exon 8 and 9 and exon 16 or α (adult) and 17 or β (foetal and neonatal). Exon phasing suggests that the majority of the alternatively spliced exons located at the 5′ end of the gene may have evolved as a result of exon shuffling, because they are of the same phase class. In contrast, the 3′ exons encoding an evolutionarily conserved heptad repeat domain, shared by both TnT and troponin I (TnI), may be remnants of an ancient ancestral gene. The sequence of the 5′ flanking region shows that the putative promoter contains motifs including binding sites for MyoD, MEF-2 and several transcription factors which may play a role in transcriptional regulation and tissue-specific expression of TnT. The coding region of TNNT3 exhibits strong similarity to the corresponding rat sequence. However, unlike the rat TnT gene, TNNT3 possesses two repeat regions of CCA and TC. The exclusive presence of these repetitive elements in the human gene indicates divergence in the evolutionary dynamics of mammalian TnT genes. Homologous muscle-specific splicing enhancer motifs are present in the introns upstream and downstream of the foetal exon, and may play a role in the developmental pattern of alternative splicing of the gene. The genomic correlates of TNNT3 are relevant to our understanding of the evolution and regulation of expression of the gene, as well as the structure and function of the protein isoforms. The nucleotide sequence of TNNT3 has been submitted to EMBL/GenBank under Accession No. AF026276. PMID:18629027

  8. Mappability of drug-like space: towards a polypharmacologically competent map of drug-relevant compounds.

    PubMed

    Sidorov, Pavel; Gaspar, Helena; Marcou, Gilles; Varnek, Alexandre; Horvath, Dragos

    2015-12-01

    Intuitive, visual rendering--mapping--of high-dimensional chemical spaces (CS), is an important topic in chemoinformatics. Such maps were so far dedicated to specific compound collections--either limited series of known activities, or large, even exhaustive enumerations of molecules, but without associated property data. Typically, they were challenged to answer some classification problem with respect to those same molecules, admired for their aesthetical virtues and then forgotten--because they were set-specific constructs. This work wishes to address the question whether a general, compound set-independent map can be generated, and the claim of "universality" quantitatively justified, with respect to all the structure-activity information available so far--or, more realistically, an exploitable but significant fraction thereof. The "universal" CS map is expected to project molecules from the initial CS into a lower-dimensional space that is neighborhood behavior-compliant with respect to a large panel of ligand properties. Such map should be able to discriminate actives from inactives, or even support quantitative neighborhood-based, parameter-free property prediction (regression) models, for a wide panel of targets and target families. It should be polypharmacologically competent, without requiring any target-specific parameter fitting. This work describes an evolutionary growth procedure of such maps, based on generative topographic mapping, followed by the validation of their polypharmacological competence. Validation was achieved with respect to a maximum of exploitable structure-activity information, covering all of Homo sapiens proteins of the ChEMBL database, antiparasitic and antiviral data, etc. Five evolved maps satisfactorily solved hundreds of activity-based ligand classification challenges for targets, and even in vivo properties independent from training data. They also stood chemogenomics-related challenges, as cumulated responsibility vectors

  9. Using collective expert judgements to evaluate quality measures of mass spectrometry images

    PubMed Central

    Palmer, Andrew; Ovchinnikova, Ekaterina; Thuné, Mikael; Lavigne, Régis; Guével, Blandine; Dyatlov, Andrey; Vitek, Olga; Pineau, Charles; Borén, Mats; Alexandrov, Theodore

    2015-01-01

    and the Matlab source code for data processing can be found at: https://github.com/alexandrovteam/IMS_quality. Contact: theodore.alexandrov@embl.de PMID:26072506

  10. Helix Nebula: Enabling federation of existing data infrastructures and data services to an overarching cross-domain e-infrastructure

    NASA Astrophysics Data System (ADS)

    Lengert, Wolfgang; Farres, Jordi; Lanari, Riccardo; Casu, Francesco; Manunta, Michele; Lassalle-Balier, Gerard

    2014-05-01

    Helix Nebula has established a growing public private partnership of more than 30 commercial cloud providers, SMEs, and publicly funded research organisations and e-infrastructures. The Helix Nebula strategy is to establish a federated cloud service across Europe. Three high-profile flagships, sponsored by CERN (high energy physics), EMBL (life sciences) and ESA/DLR/CNES/CNR (earth science), have been deployed and extensively tested within this federated environment. The commitments behind these initial flagships have created a critical mass that attracts suppliers and users to the initiative, to work together towards an "Information as a Service" market place. Significant progress in implementing the following 4 programmatic goals (as outlined in the strategic Plan Ref.1) has been achieved: × Goal #1 Establish a Cloud Computing Infrastructure for the European Research Area (ERA) serving as a platform for innovation and evolution of the overall infrastructure. × Goal #2 Identify and adopt suitable policies for trust, security and privacy on a European-level can be provided by the European Cloud Computing framework and infrastructure. × Goal #3 Create a light-weight governance structure for the future European Cloud Computing Infrastructure that involves all the stakeholders and can evolve over time as the infrastructure, services and user-base grows. × Goal #4 Define a funding scheme involving the three stake-holder groups (service suppliers, users, EC and national funding agencies) into a Public-Private-Partnership model to implement a Cloud Computing Infrastructure that delivers a sustainable business environment adhering to European level policies. Now in 2014 a first version of this generic cross-domain e-infrastructure is ready to go into operations building on federation of European industry and contributors (data, tools, knowledge, ...). This presentation describes how Helix Nebula is being used in the domain of earth science focusing on geohazards. The

  11. Anoplastie périnéale simple pour le traitement des malformations anorectales basses chez l'adulte, à propos de deux cas

    PubMed Central

    Echchaoui, Abdelmoughit; Benyachou, Malika; Hafidi, Jawad; Fathi, Nahed; Mohammadine, Elhamid; ELmazouz, Samir; Gharib, Nour-eddine; Abbassi, Abdellah

    2014-01-01

    Les malformations anorectales chez l'adulte sont des anomalies congénitales rares du tube digestif qui prédominent chez le sexe féminin. Notre étude porte sur deux observations de malformation anorectale basses vues et traitées au stade adulte par les 2 équipes (plasticiens et viscéralistes) à l'Hôpital Avicenne à Rabat. Il s'agit d'un homme de 24 ans avec une dyschésie anale l'autre cas est une femme de 18 ans avec une malformation anovulvaire Les caractéristiques cliniques combinées avec les imageries radiologiques (lavement baryté, et la manométrie anorectale) ont confirmé qu'il s'agit d'une malfomation anorectale basse. Les deux cas sont corrigés par une reconstruction sphinctérienne, réimplantation anale avec anoplastie périnéale. Les suites opératoires étaient simples, pas de souffrance cutanée ou nécrose, avec changement de pansement gras chaque jour. Le résultat fonctionnel (la continence) était favorable pour les 2 patients. La présentation des MAR à l’âge adulte est rare, d’étiologie mal connu, elles apparaissent selon le mode sporadique. Les caractéristiques cliniques, couplées à l'imagerie (lavement baryté, IRM pelvienne), l'endoscopie et la manométrie anorectale, permettent de confirmer le diagnostic et classer ces anomalies en 3 types: basses, intermédiaires, et hautes. Les formes basses sont traités d'emblée par une réimplantation anale et anoplastie périnéale simple tels nos deux cas, elles peuvent être traités dans certains cas par un abaissement anorectale associé à une plastie V-Y permettant ainsi un emplacement anatomique correct de l'anus; alors que les formes hautes ou intermédiaires relèvent d'une chirurgie complexe avec souvent une dérivation digestive transitoire. Contrairement aux autres formes, Les formes basses ont un pronostic fonctionnel favorable. PMID:25667689

  12. Synthesis of the vitamin E amino acid esters with an enhanced anticancer activity and in silico screening for new antineoplastic drugs.

    PubMed

    Gagic, Zarko; Ivkovic, Branka; Srdic-Rajic, Tatjana; Vucicevic, Jelica; Nikolic, Katarina; Agbaba, Danica

    2016-06-10

    virtual screening of the ChEMBL database identified new compounds with a potential antiproliferative activity on MCF-7 and on multi-drug resistant MDA-MB 231 breast cancer cells. PMID:27063330

  13. Cancer pulmonaire: parcours de soins au service de radiothérapie à l'institut national d'oncologie de Rabat

    PubMed Central

    Lachgar, Amine; Sahli, Nadir; Toulba, Ahmedou; Kebdani, Tayeb; Benjaafar, Noureddine

    2015-01-01

    L'objectif de cette étude est d'expliquer la discordance entre le nombre important de patients présentant un cancer du poumon localement avancé demandeurs de consultations en service de radiothérapie et le faible nombre de patients effectivement traité. Il s'agit d'une étude décrivant le circuit de soins des patients admis au service de radiothérapie de l'Institut national d'oncologie de Rabat entre le premier mars 2011 et le 29 février 2012 pour la prise en charge d'un cancer du poumon inopérable et/ou non résécable. On a utilisé pour la collecte des données les dossiers cliniques, le registre des nouveaux patients du bureau des admissions de l'institut ainsi que les registres des rendez-vous de consultation et de traitement du service de radiothérapie. 117 patients ont été collectés. Le stade de la maladie n'a pu être déterminé que chez 102 patients, on a ainsi trouvé 53 cancers non métastatiques et 49 cancers métastatiques. Chez les patients avec un cancer non métastatique une radiothérapie palliative a été réalisée chez 9 patients, chez 2 patients la radiothérapie a été contre indiquée, une chimiothérapie néo-adjuvante a été réalisée chez 7 patients et la radio-chimiothérapie concomitante d'emblée fut proposée à 35 patients, mais 34 patients seulement ont pu avoir leur première séance de radiothérapie à visée curative. Cette étude nous a permis de décrire le circuit de soins de nos patients en repérant les points critiques, auxquels on propose des mesures correctives. PMID:26523190

  14. Isolation of S-locus F-box alleles in Prunus avium and their application in a novel method to determine self-incompatibility genotype.

    PubMed

    Vaughan, S P; Russell, K; Sargent, D J; Tobutt, K R

    2006-03-01

    This study characterises a series of 12 S-locus haplotype-specific F-box protein genes (SFB) in cherry (Prunus avium) that are likely candidates for the pollen component of gametophytic self-incompatibility in this species. Primers were designed to amplify 12 SFB alleles,including the introns present in the 50 untranslated region;sequences representing the S-alleles S1, S2, S3, S4, S40, S5,S6, S7, S10, S12, S13 and S16 were cloned and characterized. [The nucleotide sequences reported in this paper have been submitted to the EMBL/GenBank database under the following accession numbers: PaSFB1(AY805048), PaSFB2 (AY805049), PaSFB3 (AY805057),PaSFB4 (AY649872), PaSFB40 (AY649873), PaSFB5(AY805050), PaSFB6 (AY805051), PaSFB7 (AY805052),PaSFB10 (AY805053), PaSFB12 (AY805054), PaSFB13(AY805055), PaSFB16 (AY805056).] Though the coding regions of six of these alleles have been reported previously,the intron sequence has previously been reported only for S6. Analysis of the introns revealed sequence and length polymorphisms. A novel, PCR-based method to genotype cultivars and wild accessions was developed which combines fluorescently labelled primers amplifying the intron of SFB with similar primers for the first intron of S-RNase alleles. Intron length polymorphisms were then ascertained using a semi-automated sequencer. The convenience and reliability of this method for the determination of the self-incompatibility (SI) genotype was demonstrated both in sweet cherry cultivars representing alleles S1 to S16 and in individuals from a wild population encompassing S-alleles S17 to S22. This method will greatly expedite SI characterisation in sweet cherry and also facilitate large-scale studies of self-incompatibility in wild cherry and other Prunus populations.

  15. Metatranscriptomics reveals the diversity of genes expressed by eukaryotes in forest soils.

    PubMed

    Damon, Coralie; Lehembre, Frédéric; Oger-Desfeux, Christine; Luis, Patricia; Ranger, Jacques; Fraissinet-Tachet, Laurence; Marmeisse, Roland

    2012-01-01

    Eukaryotic organisms play essential roles in the biology and fertility of soils. For example the micro and mesofauna contribute to the fragmentation and homogenization of plant organic matter, while its hydrolysis is primarily performed by the fungi. To get a global picture of the activities carried out by soil eukaryotes we sequenced 2×10,000 cDNAs synthesized from polyadenylated mRNA directly extracted from soils sampled in beech (Fagus sylvatica) and spruce (Picea abies) forests. Taxonomic affiliation of both cDNAs and 18S rRNA sequences showed a dominance of sequences from fungi (up to 60%) and metazoans while protists represented less than 12% of the 18S rRNA sequences. Sixty percent of cDNA sequences from beech forest soil and 52% from spruce forest soil had no homologs in the GenBank/EMBL/DDJB protein database. A Gene Ontology term was attributed to 39% and 31.5% of the spruce and beech soil sequences respectively. Altogether 2076 sequences were putative homologs to different enzyme classes participating to 129 KEGG pathways among which several were implicated in the utilisation of soil nutrients such as nitrogen (ammonium, amino acids, oligopeptides), sugars, phosphates and sulfate. Specific annotation of plant cell wall degrading enzymes identified enzymes active on major polymers (cellulose, hemicelluloses, pectin, lignin) and glycoside hydrolases represented 0.5% (beech soil)-0.8% (spruce soil) of the cDNAs. Other sequences coding enzymes active on organic matter (extracellular proteases, lipases, a phytase, P450 monooxygenases) were identified, thus underlining the biotechnological potential of eukaryotic metatranscriptomes. The phylogenetic affiliation of 12 full-length carbohydrate active enzymes showed that most of them were distantly related to sequences from known fungi. For example, a putative GH45 endocellulase was closely associated to molluscan sequences, while a GH7 cellobiohydrolase was closest to crustacean sequences, thus suggesting a

  16. Molecular cloning, gene organization and expression of the human UDP-GalNAc:Neu5Acalpha2-3Galbeta-R beta1,4-N-acetylgalactosaminyltransferase responsible for the biosynthesis of the blood group Sda/Cad antigen: evidence for an unusual extended cytoplasmic domain.

    PubMed Central

    Montiel, Maria-Dolores; Krzewinski-Recchi, Marie-Ange; Delannoy, Philippe; Harduin-Lepers, Anne

    2003-01-01

    The nucleotide sequence of the short and long transcripts of beta1,4- N -acetylgalactosaminyltransferase have been submitted to the DDBJ, EMBL, GenBank(R) and GSDB Nucleotide Sequence Databases under accession nos AJ517770 and AJ517771 respectively. The human Sd(a) antigen is formed through the addition of an N -acetylgalactosamine residue via a beta1,4-linkage to a sub-terminal galactose residue substituted with an alpha2,3-linked sialic acid residue. We have taken advantage of the previously cloned mouse cDNA sequence of the UDP-GalNAc:Neu5Acalpha2-3Galbeta-R beta1,4- N -acetylgalactosaminyltransferase (Sd(a) beta1,4GalNAc transferase) to screen the human EST and genomic databases and to identify the corresponding human gene. The sequence spans over 35 kb of genomic DNA on chromosome 17 and comprises at least 12 exons. As judged by reverse transcription PCR, the human gene is expressed widely since it is detected in various amounts in almost all cell types studied. Northern blot analysis indicated that five Sd(a) beta1,4GalNAc transferase transcripts of 8.8, 6.1, 4.7, 3.8 and 1.65 kb were highly expressed in colon and to a lesser extent in kidney, stomach, ileum and rectum. The complete coding nucleotide sequence was amplified from Caco-2 cells. Interestingly, the alternative use of two first exons, named E1(S) and E1(L), leads to the production of two transcripts. These nucleotide sequences give rise potentially to two proteins of 506 and 566 amino acid residues, identical in their sequence with the exception of their cytoplasmic tail. The short form is highly similar (74% identity) to the mouse enzyme whereas the long form shows an unusual long cytoplasmic tail of 66 amino acid residues that is as yet not described for any other mammalian glycosyltransferase. Upon transient transfection in Cos-7 cells of the common catalytic domain, a soluble form of the protein was obtained, which catalysed the transfer of GalNAc residues to alpha2,3-sialylated acceptor

  17. Molecular cloning and characterization of a HSP70 gene from Schistosoma japonicum.

    PubMed

    Yang, Jie; Yang, Linlin; Lv, Zhiyue; Wang, Juan; Zhang, Qixian; Zheng, Huanqin; Wu, Zhongdao

    2012-05-01

    Schistosoma japonicum is the pathogen responsible for schistosomiasis japonica, one of the major infectious diseases targeted for prevention nationally in China. Expression of heat shock proteins (HSPs) following stress plays a very important biological role in many organisms including S. japonicum. Among the HSP family, the 70-kDa HSPs are most responsible for intracellular chaperone and extracellular immunoregulatory functions. Based on the published sequences in GenBank/EMBL (AF044412.1), open reading frame belonging to HSP70 protein corresponds to a full-length cDNA containing an open reading frame of 1,947 bp encoded of 648 amino acids was identified as HSP70 from schistosome. In this study, the coding region that we named rSj648/hsp70 was amplified from S. japonicum adult worm cDNA library, and the recombinant protein was expressed in vector pET32a(+) and purified using a Ni-NTA purification system. The target protein rSj648/hsp70 was determined by matrix-assisted laser desorption/ionization mass spectrometer after thrombin digestion and dialysis. Reverse transcriptase polymerase chain reaction and Western blotting analysis confirmed that Sj648/hsp70 could be expressed in the eggs, normal cercariae, ultraviolet-attenuated cercariae (UVAC), and adult worms of S. japonicum. Real-time quantitative PCR analysis indicated that Sj648/hsp70 was expressed significantly higher in eggs than that in cercariae and adult worms, and the expression in UVAC was higher than that in normal cercariae. A thermotolerance assay showed that rSj648/hsp70 could protect Escherichia coli cells from heat damage. The detection of specific antibody levels by indirect enzyme-linked immunosorbent assay demonstrated that mice immunized with rSj648/hsp70 induced higher level of specific anti-rSj648/hsp70 IgG1 compared with those vaccinated with adjuvant alone, indicating that rSj648/hsp70 was able to elicit Th2-type bias immune response. Our results suggest that Sj648/hsp70 might be an

  18. Characterization of Two Microbial Isolates from Andean Lakes in Bolivia

    NASA Technical Reports Server (NTRS)

    Demergasso, C.; Blamey, J.; Escudero, L.; Chong, G.; Casamayor, E. O.; Cabrol, N. A.; Grin, E. A.; Hock, A.; Kiss, A.; Borics, G.

    2004-01-01

    miniprep protocol. The 16S rRNA genes were amplified by PCR using both Bacteria- and Archaeauniversal primer sets: 27f and 1492r, 21f and 1492r respectively. Sequences of 16S rRNA gene were determined and initially compared with reference sequences contained in the EMBL nucleotide sequence database by using the BLAST program and were subsequently aligned with 16S rRNA reference sequences in the ARB package (http://www.mikro.biologie.tu-muenchen.de). Aligned sequences were inserted within a stable phylogenetic tree by using the ARB parsimony tool. In this work we report the morphology and phylogenetic characterization of two isolates belonged to Laguna Blanca sediments.

  19. Isolation and characterization of two overlapping cosmid clones from the 4q35 region, near the facioscapulohumeral muscular dystrophy locus

    SciTech Connect

    Deidda, G.; Grisanti, P.; Vigneti, E.

    1994-09-01

    The gene for facioscapulohumeral muscular dystrophy (FSHD) has been localized by linkage analysis to the 4q35 region. The most telomeric p13E-11 prove has been shown to detect 4q35 DNA rearrangements in both sporadic and familial cases of the disease. With the aim of constructing a detailed physical map of the 4q35 region and searching for the mutant gene, we used p13E-11 probe to isolate cosmid clones from a human genomic library in a pCos-EMBL 2 vector. Two positive clones were isolated, clones 3 and 5, which partially overlap and carry human genomic inserts of 42 and 45 kb, respectively. The cosmids share a common region containing the p13E-11 region and a stretch of KpnI units consisting of 3.2 kb tandemly repeated sequences (about 10). The restriction maps were constructed using the following enzymes: Bam HI, BgIII, Eco RI, EcoRV, KpnI and Sfi I. Clone 3 extends 4 kb upstream of C5 and stops within the Kpn repeats. Clone 5 extends 4 kb downstream from the Kpn repeats and it presents an additional EcoRI site. Clone 5 contains a stretch of Kpn sequences of nearly 32 kb, corresponding to 10 Kpn repeats; clone 3 contains a stretch of 29 kb corresponding to 9 Kpn repeats, as determined by PFGE analysis of partial digestion of the clones. Clone 5 seems to contain the entire Eco RI region prone to rearrangements in FSHD patients. From clone 5 several subclones were obtained, from the Kpn region and from the region spanning from the last Kpn repeat to the cloning site. No single copy sequences were detected. Subclones from the 3{prime} end region contain beta-satellite or Sau3A-like sequences. In situ hybridization with the whole C5 cosmid shows hybridization signals at the tip of chromosome 4 (4q35) and chromosome 10 (10q26), in the pericentromeric region of chromosome 1 (1q12) and in the p12 region of the acrocentric chromosomes (chr. 21, 22, 13, 14, 15).

  20. Leading European Research Organisations Join Forces in EIROFORUM

    NASA Astrophysics Data System (ADS)

    2001-05-01

    Since the early 1950s, a number of powerful research infrastructures and laboratories which are used by an extensive network of scientists have been developed and deployed within Europe by European Intergovernmental Research Organisations (EIRO). Together, they represent European spearheads in some of the most crucial basic and applied research fields. Seven of these organisations have set up a co-ordination and collaboration group ( EIROFORUM ) with their top executives (Directors General or equivalent) as members. They include CERN (particle physics), EMBL (molecular biology), ESA (space activities), ESO (astronomy and astrophysics), ESRF (synchrotron radiation), ILL (neutron source) and EFDA (fusion). A primary goal of EIROFORUM is to play an active and constructive role in promoting the quality and impact of European Research. In particular, the group will be a basis for effective, high-level inter-organisational interaction and co-ordination. It will mobilise its substantial combined expertise in basic research and in the management of large international projects for the benefit of European research and development. This will be possible by exploiting the existing intimate links between the member organisations and their respective European research communities. According to the EIROFORUM Charter , the main aims of the collaboration are to: 1. Encourage and facilitate discussions among its members on issues of common interest, which are relevant to research and development. 2. Maximise the scientific return and optimise the use of resources by sharing relevant developments and results, whenever feasible. 3. Co-ordinate the education and outreach activities of the organisations, including technology transfer and public understanding. 4. Take an active part, in collaboration with other European scientific organisations, in taking a forward-look at promising and/or developing research directions and priorities, in particular in relation to new large