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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.

    1992-07-01

    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.

  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.

    1992-01-01

    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.

  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. Induction of homochirality in achiral enantiomorphous monolayers.

    PubMed

    Parschau, Manfred; Romer, Sara; Ernst, Karl-Heinz

    2004-12-01

    We report the induction of homochirality in enantiomorphous layers of achiral succinic acid on a Cu(110) surface after doping with tartaric acid (TA) enantiomers. Succinic acid becomes chiral upon adsorption due to symmetry-breaking interactions with the Cu(110) surface. The doubly deprotonated bisuccinate forms mirror domains on the surface, which leads to a superposition of (11,-90) and (90,-11) patterns observed by low-energy electron diffraction (LEED). On average, however, the surface layer is racemic. An amount of 2 mol % of (R,R)- or (S,S)-tartaric acid in the monolayer, corresponding to an absolute coverage of 0.001 tartaric acid molecule per surface copper atom, is sufficient to make the LEED spots of one enantiomorphous lattice disappear. After thermally induced desorption of TA, the succinic acid lattice turns racemic again. In analogy to the "sergeants-and-soldiers" principle described for helical polymers, this effect is explained by a lateral cooperative interaction within the two-dimensional lattice.

  7. 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.

  8. The ChEMBL database in 2017

    PubMed Central

    Gaulton, Anna; Hersey, Anne; Nowotka, Michał; Bento, A. Patrícia; Chambers, Jon; Mendez, David; Mutowo, Prudence; Atkinson, Francis; Bellis, Louisa J.; Cibrián-Uhalte, Elena; Davies, Mark; Dedman, Nathan; Karlsson, Anneli; Magariños, María Paula; Overington, John P.; Papadatos, George; Smit, Ines; Leach, Andrew R.

    2017-01-01

    ChEMBL is an open large-scale bioactivity database (https://www.ebi.ac.uk/chembl), previously described in the 2012 and 2014 Nucleic Acids Research Database Issues. Since then, alongside the continued extraction of data from the medicinal chemistry literature, new sources of bioactivity data have also been added to the database. These include: deposited data sets from neglected disease screening; crop protection data; drug metabolism and disposition data and bioactivity data from patents. A number of improvements and new features have also been incorporated. These include the annotation of assays and targets using ontologies, the inclusion of targets and indications for clinical candidates, addition of metabolic pathways for drugs and calculation of structural alerts. The ChEMBL data can be accessed via a web-interface, RDF distribution, data downloads and RESTful web-services. PMID:27899562

  9. The ChEMBL database in 2017.

    PubMed

    Gaulton, Anna; Hersey, Anne; Nowotka, Michał; Bento, A Patrícia; Chambers, Jon; Mendez, David; Mutowo, Prudence; Atkinson, Francis; Bellis, Louisa J; Cibrián-Uhalte, Elena; Davies, Mark; Dedman, Nathan; Karlsson, Anneli; Magariños, María Paula; Overington, John P; Papadatos, George; Smit, Ines; Leach, Andrew R

    2017-01-04

    ChEMBL is an open large-scale bioactivity database (https://www.ebi.ac.uk/chembl), previously described in the 2012 and 2014 Nucleic Acids Research Database Issues. Since then, alongside the continued extraction of data from the medicinal chemistry literature, new sources of bioactivity data have also been added to the database. These include: deposited data sets from neglected disease screening; crop protection data; drug metabolism and disposition data and bioactivity data from patents. A number of improvements and new features have also been incorporated. These include the annotation of assays and targets using ontologies, the inclusion of targets and indications for clinical candidates, addition of metabolic pathways for drugs and calculation of structural alerts. The ChEMBL data can be accessed via a web-interface, RDF distribution, data downloads and RESTful web-services.

  10. The ChEMBL bioactivity database: an update

    PubMed Central

    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

  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.

  12. 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.

  13. Can enantiomorphic crystals like quartz play a role in the origin of homochirality on earth?

    PubMed

    Klabunovskii, E I

    2001-01-01

    This communication reviews the possible actions of enantiomorphic crystals on the surface of Earth as sources of homochirality of organic compounds. The discovery of asymmetric adsorption and asymmetric catalysis involving optically active quartz crystals has led some authors to conclude that this source of asymmetry played an important role as a source of homochirality in nature, a concept that later proved erroneous. Moreover, data regarding the preponderance in nature of l-quartz crystals have been used to confirm calculations of the parity violation energy difference (PVED) for l-quartz and, hence, to explain the prevalence of L-amino acids and D-sugars in living matter. As discussed here, quartz and other enantiomorphs such as sodium chlorate can produce chiral intermediates active in autocatalytical processes. Our most recent compilation of the literature, however, reveals that the distribution of d- and l-quartz crystals at the surface of the Earth when all possible locations are included is quite random. Although quartz can serve as an effective asymmetric inductor in autocatalytic processes, it cannot be the source of homochirality of living matter because of the random occurrence of the two types of enantiomorphs. The calculations of PVED values for quartz therefore lack a sound physical basis.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25883136

  15. 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.

  16. 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.

  17. 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

  18. Accessing and distributing EMBL data using CORBA (common object request broker architecture)

    PubMed Central

    Wang, Lichun; Rodriguez-Tomé, Patricia; Redaschi, Nicole; McNeil, Phil; Robinson, Alan; Lijnzaad, Philip

    2000-01-01

    Background: The EMBL Nucleotide Sequence Database is a comprehensive database of DNA and RNA sequences and related information traditionally made available in flat-file format. Queries through tools such as SRS (Sequence Retrieval System) also return data in flat-file format. Flat files have a number of shortcomings, however, and the resources therefore currently lack a flexible environment to meet individual researchers' needs. The Object Management Group's common object request broker architecture (CORBA) is an industry standard that provides platform-independent programming interfaces and models for portable distributed object-oriented computing applications. Its independence from programming languages, computing platforms and network protocols makes it attractive for developing new applications for querying and distributing biological data. Results: A CORBA infrastructure developed by EMBL-EBI provides an efficient means of accessing and distributing EMBL data. The EMBL object model is defined such that it provides a basis for specifying interfaces in interface definition language (IDL) and thus for developing the CORBA servers. The mapping from the object model to the relational schema in the underlying Oracle database uses the facilities provided by PersistenceTM, an object/relational tool. The techniques of developing loaders and 'live object caching' with persistent objects achieve a smart live object cache where objects are created on demand. The objects are managed by an evictor pattern mechanism. Conclusions: The CORBA interfaces to the EMBL database address some of the problems of traditional flat-file formats and provide an efficient means for accessing and distributing EMBL data. CORBA also provides a flexible environment for users to develop their applications by building clients to our CORBA servers, which can be integrated into existing systems. PMID:11178259

  19. 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.

  20. Kinetic resolution of racemic α-olefins with ansa-zirconocene polymerization catalysts: Enantiomorphic site vs. chain end control

    PubMed Central

    Byers, Jeffery A.; Bercaw, John E.

    2006-01-01

    Copolymerization of racemic α-olefins with ethylene and propylene was carried out in the presence of enantiopure C1-symmetric ansa metallocene, {1,2-(SiMe2)2(η5-C5H-3,5-(CHMe2)2)(η5-C5H3)}ZrCl2 to probe the effect of the polymer chain end on enantioselection for the R- or S-α-olefin during the kinetic resolution by polymerization catalysis. Copolymerizations with ethylene revealed that the polymer chain end is an important factor in the enantioselection of the reaction and that for homopolymerization, chain end control generally works cooperatively with enantiomorphic site control. Results from propylene copolymerizations suggested that chain end control arising from a methyl group at the β carbon along the main chain can drastically affect selectivity, but its importance as a stereo-directing element depends on the identity of the olefin. PMID:17032768

  1. 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

  2. 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.

  3. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2011-09-01

    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.

  5. Meeting report: 2012 Caenorhabditis elegans Neurobiology meeting, EMBL Advanced Training Centre, Germany.

    PubMed

    Kearn, James; Dallière, Nicolas; Dillon, James

    2013-06-01

    Some of the finest minds in the field of Caenorhabditis elegans neurobiology were brought together from 14 June to 17 June 2012 in the small, quaint and picturesque German city of Heidelberg for the biannual C. elegans neurobiology conference. Held at the EMBL Advanced Training Centre and wonderfully organised by Diah Yulianti, Jean-Louis Bessereau, Gert Jansen and William Schafer, the meeting contained 62 verbal presentations and hundreds of posters that were displayed around the double-helical walkways that looped throughout the conference centre. Presentations on recent advances in microfluidics, cell ablation and targeted gene expression exemplified the strengths of C. elegans as a model organism, with these advances allowing detailed high-throughput analysis and study. Interesting behaviours that were previously poorly characterised were widely discussed, as were the advantages of C. elegans as a model for neurodevelopment and neurodegeneration and the investigation of neuropeptide function. The examples discussed in this meeting report seek to illustrate the breadth and depth of presentations given on these recurring topics.

  6. Mining the ChEMBL database: an efficient chemoinformatics workflow for assembling an ion channel-focused screening library.

    PubMed

    Mok, N Yi; Brenk, Ruth

    2011-10-24

    The ChEMBL database was mined to efficiently assemble an ion channel-focused screening library. The compiled library consists of 3241 compounds representing 123 templates across nine ion channel categories. Compounds in the screening library are annotated with their respective ion channel category to facilitate back-tracing of prospective molecular targets from phenotypic screening results. The established workflow is adaptable to the construction of focused screening libraries for other therapeutic target classes with diverse recognition motifs.

  7. 1(st) EMBL/DFG Women in Science Network Conference Heidelberg 2016: From Genes, Cells and the Immune System towards Therapies - Meeting Report.

    PubMed

    Stripecke, Renata; Gouttefangeas, Cécile; Förster, Irmgard

    2016-11-01

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

  8. 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

  9. 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.

  10. Open Source Bayesian Models. 2. Mining a "Big Dataset" To Create and Validate Models with ChEMBL.

    PubMed

    Clark, Alex M; Ekins, Sean

    2015-06-22

    In an associated paper, we have described a reference implementation of Laplacian-corrected naïve Bayesian model building using extended connectivity (ECFP)- and molecular function class fingerprints of maximum diameter 6 (FCFP)-type fingerprints. As a follow-up, we have now undertaken a large-scale validation study in order to ensure that the technique generalizes to a broad variety of drug discovery datasets. To achieve this, we have used the ChEMBL (version 20) database and split it into more than 2000 separate datasets, each of which consists of compounds and measurements with the same target and activity measurement. In order to test these datasets with the two-state Bayesian classification, we developed an automated algorithm for detecting a suitable threshold for active/inactive designation, which we applied to all collections. With these datasets, we were able to establish that our Bayesian model implementation is effective for the large majority of cases, and we were able to quantify the impact of fingerprint folding on the receiver operator curve cross-validation metrics. We were also able to study the impact that the choice of training/testing set partitioning has on the resulting recall rates. The datasets have been made publicly available to be downloaded, along with the corresponding model data files, which can be used in conjunction with the CDK and several mobile apps. We have also explored some novel visualization methods which leverage the structural origins of the ECFP/FCFP fingerprints to attribute regions of a molecule responsible for positive and negative contributions to activity. The ability to score molecules across thousands of relevant datasets across organisms also may help to access desirable and undesirable off-target effects as well as suggest potential targets for compounds derived from phenotypic screens.

  11. Development and interrupting tests on 250KV 8KA HVDC circuit breaker

    SciTech Connect

    Tokuyama, S.; Arimatsu, K.; Hirata, K.; Kato, Y.; Yoshioka, Y.

    1985-09-01

    This paper describes the circuit and component selections, development and equivalent circuit test results on an HVDC circuit breaker for an HVDC transmission line. A puffer type SF/sub 6/ gas interrupter for AC circuit breakers is utilized for interrupting DC current with injection of high-frequency inverse current from a commutating capacitor precharged to HVDC line voltage. Also, the effectiveness of application of the HVDC breaker to an HVDC system with two parallel transmission lines is demonstrated through the EMTP simulation.

  12. 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

  13. Enantiomorphism of the Ca{sub 3}Ga{sub 2}Ge{sub 4}O{sub 14} compound and comparison of the Ca{sub 3}Ga{sub 2}Ge{sub 4}O{sub 14} and Sr{sub 3}Ga{sub 2}Ge{sub 4}O{sub 14} structures

    SciTech Connect

    Mill, B. V. Klimenkova, A. A.; Maximov, B. A.; Molchanov, V. N.; Pushcharovsky, D. Yu.

    2007-09-15

    The absolute crystal structures of two enantiomorphic forms of the Ca{sub 3}Ga{sub 2}Ge{sub 4}O{sub 14} crystals (a = 8.075(1) A, c = 4.9723(6) A, space group P321) with the positive and negative senses of the optical activity are determined using X-ray diffraction analysis. The final R factors are as follows: R = 1.75% and R{sub w} = 2.57% for the crystal with the positive sense of the optical activity and R = 1.86% and R{sub w} = 2.78% for the crystal with the negative sense of the optical activity. The replacement of the Ca{sup 2+} ions by larger Sr{sup 2+} ions (with the formation of the Sr{sub 3}Ga{sub 2}Ge{sub 4}O{sub 14} compound) leads to an anisotropic expansion of the crystal lattice (with a more considerable increase in the lattice parameter a as compared to the lattice parameter c), a change in the occupation of the 1a and 3f positions by the Ga{sup 3+} and Ge{sup 4+} ions, and symmetrization of the octahedra and tetrahedra forming the structural framework. The shape of the dodecahedron changes so that its size along the polar electric axis 2 increases significantly. This change is the main factor responsible for the increase in the piezoelectric activity of the Sr{sub 3}Ga{sub 2}Ge{sub 4}O{sub 14} compound as compared to the piezoelectric activity of the Ca{sub 3}Ga{sub 2}Ge{sub 4}O{sub 14} compound.

  14. 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.

  15. 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.

  16. 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.

  17. P13, the EMBL macromolecular crystallography beamline at the low-emittance PETRA III ring for high- and low-energy phasing with variable beam focusing

    PubMed Central

    Cianci, Michele; Bourenkov, Gleb; Pompidor, Guillaume; Karpics, Ivars; Kallio, Johanna; Bento, Isabel; Roessle, Manfred; Cipriani, Florent; Fiedler, Stefan; Schneider, Thomas R.

    2017-01-01

    The macromolecular crystallography P13 beamline is part of the European Molecular Biology Laboratory Integrated Facility for Structural Biology at PETRA III (DESY, Hamburg, Germany) and has been in user operation since mid-2013. P13 is tunable across the energy range from 4 to 17.5 keV to support crystallographic data acquisition exploiting a wide range of elemental absorption edges for experimental phase determination. An adaptive Kirk­patrick–Baez focusing system provides an X-ray beam with a high photon flux and tunable focus size to adapt to diverse experimental situations. Data collections at energies as low as 4 keV (λ = 3.1 Å) are possible due to a beamline design minimizing background and maximizing photon flux particularly at low energy (up to 1011 photons s−1 at 4 keV), a custom calibration of the PILATUS 6M-F detector for use at low energies, and the availability of a helium path. At high energies, the high photon flux (5.4 × 1011 photons s−1 at 17.5 keV) combined with a large area detector mounted on a 2θ arm allows data collection to sub-atomic resolution (0.55 Å). A peak flux of about 8.0 × 1012 photons s−1 is reached at 11 keV. Automated sample mounting is available by means of the robotic sample changer ‘MARVIN’ with a dewar capacity of 160 samples. In close proximity to the beamline, laboratories have been set up for sample preparation and characterization; a laboratory specifically equipped for on-site heavy atom derivatization with a library of more than 150 compounds is available to beamline users. PMID:28009574

  18. A day of systems and synthetic biology for non-experts: reflections on day 1 of the EMBL/EMBO joint conference on Science and Society.

    PubMed

    Moore, Andrew

    2009-01-01

    From understanding ageing to the creation of artificial membrane-bounded 'organisms', systems biology and synthetic biology are seen as the latest revolutions in the life sciences. They certainly represent a major change of gear, but paradigm shifts? This is open to debate, to say the least. For scientists they open up exciting ways of studying living systems, of formulating the 'laws of life', and the relationship between the origin of life, evolution and artificial biological systems. However, the ethical and societal considerations are probably indistinguishable from those of human genetics and genetically modified organisms. There are some tangible developments just around the corner for society, and as ever, our ability to understand the consequences of, and manage, our own progress lags far behind our technological abilities. Furthermore our educational systems are doing a bad job of preparing the next generation of scientists and non-scientists.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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…

  5. 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.

  6. 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.

  7. Enantiomer-specific oriented attachment: formation of macroscopic homochiral crystal aggregates from a racemic system.

    PubMed

    Viedma, Cristóbal; McBride, J Michael; Kahr, Bart; Cintas, Pedro

    2013-09-27

    Let's get together: Racemic samples of d- and l-enantiomorphous NaBrO3 (or NaClO3) crystals aggregate with nearly complete enantioselection. Centimeter-sized enantiopure megacrystals are often produced, and these can be sorted easily.

  8. Asymmetric Synthesis of an Amino Acid Derivative from Achiral Aroyl Acrylamide by Reversible Michael Addition and Preferential Crystallization.

    PubMed

    Kaji, Yuki; Uemura, Naohiro; Kasashima, Yoshio; Ishikawa, Hiroki; Yoshida, Yasushi; Mino, Takashi; Sakamoto, Masami

    2016-11-07

    Single-handed α-amino acid derivatives were generated from achiral precursors without an external chiral source. Conjugate addition of phenethylamine to an achiral aroyl acrylamide under homogeneous conditions gave the α-amino amides in quantitative yields, which crystallized as a conglomerate of a P21 crystal system. Dynamic preferential crystallization or attrition-enhanced deracemization resulted in the formation of enantiomorphic crystals of 99 % ee.

  9. Carl Friedrich Naumann and the introduction of enantio terminology: a review and analysis on the 150th anniversary.

    PubMed

    Gal, Joseph

    2007-02-01

    Enantiomorphism and enantiomorphous were the first enantio-based terms, introduced 150 years ago, by Carl Friedrich Naumann, a German crystallographer, to refer to non-superposable mirror-image crystals. The terminology was not adopted by Pasteur, the discoverer of molecular chirality, and was not embraced at first in the stereochemical context, until it was accepted in 1877 by Van't Hoff in the German edition of his proposal for the tetrahedral asymmetric carbon atom. In the 1890s the use of enantio terms began to spread in the research literature, and many new derivatives of Naumann's original two terms were subsequently introduced. Problems in the usage of some of the terms are often found in the literature, e.g., enantiomorphism is sometimes confused with chirality; enantiomeric is often misused; the meaning of some of the many derived terms, e.g., enantiosymmetric, enantioposition, etc., is unclear. All in all, Naumann should be remembered as the creator of essential terminology in the realm of chirality.

  10. 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.

  11. OCEAN: Optimized Cross rEActivity estimatioN.

    PubMed

    Czodrowski, Paul; Bolick, Wolf-Guido

    2016-10-24

    The prediction of molecular targets is highly beneficial during the drug discovery process, be it for off-target elucidation or deconvolution of phenotypic screens. Here, we present OCEAN, a target prediction tool exclusively utilizing publically available ChEMBL data. OCEAN uses a heuristics approach based on a validation set containing almost 1000 drug ← → target relationships. New ChEMBL data (ChEMBL20 as well as ChEMBL21) released after the validation was used for a prospective OCEAN performance check. The success rates of OCEAN to predict correctly the targets within the TOP10 ranks are 77% for recently marketed drugs and 62% for all new ChEMBL20 compounds and 51% for all new ChEMBL21 compounds. OCEAN is also capable of identifying polypharmacological compounds; the success rate for molecules simultaneously hitting at least two targets is 64% to be correctly predicted within the TOP10 ranks. The source code of OCEAN can be found at http://www.github.com/rdkit/OCEAN.

  12. The absolute configuration of (2S,4S)- and (2R,4R)-2-tert-butyl-4-methyl-3-(4-tolylsulfonyl)-1,3-oxazolidine-4-carbaldehyde.

    PubMed

    Flock, Susanne; Bruhn, Clemens; Fink, Heinrich; Frauenrath, Herbert

    2006-02-01

    The title enantiomorphic compounds, C16H23NO4S, have been obtained in an enantiomerically pure form by crystallization from a diastereomeric mixture either of (2S,4S)- and (2R,4S)- or of (2R,4R)- and (2S,4R)-2-tert-butyl-4-methyl-3-(4-tolylsulfonyl)-1,3-oxazolidine-4-carbaldehyde. These mixtures were prepared by an aziridination rearrangement process starting with (S)- or (R)-2-tert-butyl-5-methyl-4H-1,3-dioxine. The crystal structures indicate an envelope conformation of the oxazolidine moiety for both compounds.

  13. Crystallization and preliminary X-ray studies of the diphtheria Tox repressor from Corynebacterium diphtheriae.

    PubMed

    Schiering, N; Tao, X; Murphy, J R; Petsko, G A; Ringe, D

    1994-12-16

    Crystals of the diphtheria tox repressor (DtxR) from Corynebacterium diphtheriae suitable for structure determination have been obtained. DtxR activated with transition metal ions represses the expression of the structural gene for the diphtheria toxin, tox, which is encoded on the genome of a family of closely related corynebacteriophages. The space group of the obtained crystals is trigonal P3(1)21 or its enantiomorph P3(2)21 with a = b = 64.2 A, c = 220.5 A, alpha = beta = 90 degrees, gamma = 120 degrees. Two monomers comprise the asymmetric unit. The crystals diffract to a resolution of better than 3 A.

  14. A homochiral magnet based on D₃ symmetric [(NaO₃)Co₃] clusters: from spontaneous resolution to absolute chiral induction.

    PubMed

    Yao, Ru-Xin; Cui, Xin; Wang, Jun; Zhang, Xian-Ming

    2015-03-25

    A pair of novel enantiomeric 3D magnetic complexes [NaCo3(IA)6](NO3)·H2O (1Δ and 1Λ) have been synthesized using an achiral ligand HIA via spontaneous resolution, which crystallize in the hexagonal crystal system with a chiral P63 space group, and diamagnetic sodium cations are located at the center of D3 symmetric clusters. This kind of spontaneous resolution is uncontrollable and dependent on batches. By utilizing cheap enantiopure mandelic acid as a chiral inducing agent, they are driven to controllable homochiral crystallization of the desired enantiomorph, confirmed by circular dichroism spectra.

  15. Analysis of genetic stability at SSR loci during somatic embryogenesis in maritime pine (Pinus pinaster).

    PubMed

    Marum, Liliana; Rocheta, Margarida; Maroco, João; Oliveira, M Margarida; Miguel, Célia

    2009-04-01

    Somatic embryogenesis (SE) is a propagation tool of particular interest for accelerating the deployment of new high-performance planting stock in multivarietal forestry. However, genetic conformity in in vitro propagated plants should be assessed as early as possible, especially in long-living trees such as conifers. The main objective of this work was to study such conformity based on genetic stability at simple sequence repeat (SSR) loci during somatic embryogenesis in maritime pine (Pinus pinaster Ait.). Embryogenic cell lines (ECLs) subjected to tissue proliferation during 6, 14 or 22 months, as well as emblings regenerated from several ECLs, were analyzed. Genetic variation at seven SSR loci was detected in ECLs under proliferation conditions for all time points, and in 5 out of 52 emblings recovered from somatic embryos. Three of these five emblings showed an abnormal phenotype consisting mainly of plagiotropism and loss of apical dominance. Despite the variation found in somatic embryogenesis-derived plant material, no correlation was established between genetic stability at the analyzed loci and abnormal embling phenotype, present in 64% of the emblings. The use of microsatellites in this work was efficient for monitoring mutation events during the somatic embryogenesis in P. pinaster. These molecular markers should be useful in the implementation of new breeding and deployment strategies for improved trees using SE.

  16. 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).

  17. From cosmic chirality to protein structure: Lord Kelvin's legacy.

    PubMed

    Barron, Laurence D

    2012-11-01

    A selection of my work on chirality is sketched in two distinct parts of this lecture. Symmetry and Chirality explains how the discrete symmetries of parity P, time reversal T, and charge conjugation C may be used to characterize the properties of chiral systems. The concepts of true chirality (time-invariant enantiomorphism) and false chirality (time-noninvariant enantiomorphism) that emerge provide an extension of Lord Kelvin's original definition of chirality to situations where motion is an essential ingredient thereby clarifying, inter alia, the nature of physical influences able to induce absolute enantioselection. Consideration of symmetry violations reveals that strict enantiomers (exactly degenerate) are interconverted by the combined CP operation. Raman optical activity surveys work, from first observation to current applications, on a new chiroptical spectroscopy that measures vibrational optical activity via Raman scattering of circularly polarized light. Raman optical activity provides incisive information ranging from absolute configuration and complete solution structure of smaller chiral molecules and oligomers to protein and nucleic acid structure of intact viruses.

  18. Evolution of whole-body enantiomorphy in the tree snail genus Amphidromus

    PubMed Central

    SUTCHARIT, C; ASAMI, T; PANHA, S

    2007-01-01

    Diverse animals exhibit left–right asymmetry in development. However, no example of dimorphism for the left–right polarity of development (whole-body enantiomorphy) is known to persist within natural populations. In snails, whole-body enantiomorphs have repeatedly evolved as separate species. Within populations, however, snails are not expected to exhibit enantiomorphy, because of selection against the less common morph resulting from mating disadvantage. Here we present a unique example of evolutionarily stable whole-body enantiomorphy in snails. Our molecular phylogeny of South-east Asian tree snails in the genus Amphidromus indicates that enantiomorphy has likely persisted as the ancestral state over a million generations. Enantiomorphs have continuously coexisted in every population surveyed spanning a period of 10 years. Our results indicate that whole-body enantiomorphy is maintained within populations opposing the rule of directional asymmetry in animals. This study implicates the need for explicit approaches to disclosure of a maintenance mechanism and conservation of the genus. PMID:17305832

  19. The effect of stirring on sodium chlorate crystallization under symmetry breaking conditions

    NASA Astrophysics Data System (ADS)

    Veintemillas-Verdaguer, S.; Esteban, S. Osuna; Herrero, M. A.

    2007-05-01

    The effect of the stirring rate on the crystallization of sodium chlorate was studied in more than 200 experiments using a set-up that allows to perform sets of 20 simultaneous experiments. The crystallization conditions were those that according to previous results lead to only one of both L and D enantiomorphic forms under stirring. The probability of D crystallization was determined using a statistical analysis based on the central limit theorem. The stirring dependence of induction times and crystal size distribution is reported. The stirring effect was correlated with differences between surface and bulk crystallization. The probability of D crystallization was detected to be slightly higher than that of the L, in contradiction with some previous reports, and that might be attributed to the chiral contamination of the bio-organic world on the starting materials and on the system. Our analysis allows to detect that the D-enantiomorph induction by chiral contamination occurs mainly in the nucleation at the interface air/water, which can be related to the expected higher concentration of the contaminants (bioorganic chiral amphiphiles e.g. DNA or proteins) on the surface of the solution.

  20. JICST Factual Database JICST DNA Database

    NASA Astrophysics Data System (ADS)

    Shirokizawa, Yoshiko; Abe, Atsushi

    Japan Information Center of Science and Technology (JICST) has started the on-line service of DNA database in October 1988. This database is composed of EMBL Nucleotide Sequence Library and Genetic Sequence Data Bank. The authors outline the database system, data items and search commands. Examples of retrieval session are presented.

  1. JPRS Report, Science & Technology, Europe & Latin America

    DTIC Science & Technology

    1987-12-21

    Molecular Biology Institute (Charles Coutelle, et al.; SPECTRUM, No 3, 1987) ....... 108 GDR Interview With Soviet Biotechnology Specialist (furi...expand this area of research in the future. In Heidelberg, a European institution, the European Molecular Biology Laboratory (EMBL), is concerned...exclusively with molecular -biology, genetic engineering, protein-chemistry, and other basic research issues. In addition there is the Center for Molecular

  2. From metaphor to practices: The introduction of "information engineers" into the first DNA sequence database.

    PubMed

    García-Sancho, Miguel

    2011-01-01

    This paper explores the introduction of professional systems engineers and information management practices into the first centralized DNA sequence database, developed at the European Molecular Biology Laboratory (EMBL) during the 1980s. In so doing, it complements the literature on the emergence of an information discourse after World War II and its subsequent influence in biological research. By the careers of the database creators and the computer algorithms they designed, analyzing, from the mid-1960s onwards information in biology gradually shifted from a pervasive metaphor to be embodied in practices and professionals such as those incorporated at the EMBL. I then investigate the reception of these database professionals by the EMBL biological staff, which evolved from initial disregard to necessary collaboration as the relationship between DNA, genes, and proteins turned out to be more complex than expected. The trajectories of the database professionals at the EMBL suggest that the initial subject matter of the historiography of genomics should be the long-standing practices that emerged after World War II and to a large extent originated outside biomedicine and academia. Only after addressing these practices, historians may turn to their further disciplinary assemblage in fields such as bioinformatics or biotechnology.

  3. [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.

  4. 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

  5. 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.

  6. Crystallization and preliminary crystallographic data of purple acid phosphatase from red kidney bean.

    PubMed

    Sträter, N; Fröhlich, R; Schiemann, A; Krebs, B; Körner, M; Suerbaum, H; Witzel, H

    1992-03-20

    Purple acid phosphatase from red kidney bean has been crystallized from ammonium sulfate solutions in the pH range from 3.5 to 5.5. The crystal form is tetragonal bipyramidal and the largest crystals grew up to 2.0 mm long. Systematic absences indicate one of the enantiomorphic space groups P4(1)2(1)2 (92) or P4(3)2(1)2 (96) with cell dimensions a = b = 104.1(1) A and c = 308.7(2) A. The asymmetric unit contains one dimer with Mr of 110,700, determined by ultraviolet-laser desorption mass spectrometry. The crystals, with a salt-free density of 1.12 g/cm3 and a water content of 67%, diffract to 3.5 A.

  7. Origins of life: a route to nanotechnology.

    PubMed

    Sowerby, S J; Holm, N G; Petersen, G B

    2001-06-01

    The origins of life and nanotechnology are two seemingly disparate areas of scientific investigation. However, the fundamental questions of life's beginnings and the applied construction of a Drexlerian nanotechnology both share a similar problem; how did and how can self-reproducing molecular machines originate? Here we draw attention to the coincidence between nanotechnology and origins research with particular attention paid to the spontaneous adsorption and scanning tunneling microscopy investigation of purine and pyrimidine bases self-organized into monolayers, adsorbed to the surfaces of crystalline solids. These molecules which encode biological information in nucleic acids, can form supramolecular architectures exhibiting enantiomorphism with the complexity to store and encode putative protobiological information. We conclude that the application of nanotechnology to the investigation of life's origins, and vice versa, could provide a viable route to an evolution-driven synthetic life.

  8. 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.

  9. High-resolution spectroscopy, crystal-field calculations, and quadrupole helix chirality of DyFe3(BO3)4

    NASA Astrophysics Data System (ADS)

    Popova, M. N.; Malkin, B. Z.; Stanislavchuk, T. N.; Chukalina, E. P.; Boldyrev, K. N.; Gudim, I. A.

    2016-12-01

    High-resolution polarized transmission spectra of DyFe3(BO3)4 single crystals were investigated in broad spectral (10-23000 cm-1) and temperature (3.5-300 K) ranges. Energies of the dysprosium levels in the paramagnetic and antiferromagnetic phases were determined. On the basis of these data and preliminary calculations in the frameworks of the exchange-charge model, we determined the crystal-field and Dy-Fe exchange interaction parameters of the Dy3+ ions at sites with the point C2 symmetry corresponding to the enantiomorphic P3121 and P3221 space groups. The values of electronic quadrupole moments of the Dy3+ ions were calculated, which enabled us to interpret results of the work [Usui et al., Nature Mater. 13, 611 (2014)] on the observation of domains of different quadrupole chirality in DyFe3(BO3)4.

  10. [From symmetries to the laws of evolution. I. Chirality as a means of active media stratification].

    PubMed

    Tverdislov, V A; Sidorova, A É; Iakovenko, L V

    2012-01-01

    Features of the hypothetical evolution of a hierarchy of chiral objects formed by active media are discussed. On the basis of experimental facts a new synergetic generalization is made: an evolving system can repeatedly broaden the spectrum of its symmetry types within one level of organization which increases its complexity and change the sign of chirality during transition to a higher level. Switching the chirality sign of macroscopic objects provides irreversibility of stratification. The known chirality of biological structures at different levels suggests that the chiral L/D-stratification should be universal and the hierarchical paths are stable and determined. A high level enantiomorph with reciprocal chirality demonstrates a wider spectrum of functionality. A fractal description of natural hierarchical systems is pointed out to be inadequate because it implicates invariance of the chirality sign of the objects at different scales.

  11. Crystallization and preliminary X-ray investigation of holotryptophanases from Escherichia coli and Proteus vulgaris.

    PubMed

    Dementieva, I S; Zakomirdina, L N; Sinitzina, N I; Antson, A A; Wilson, K S; Isupov, M N; Lebedev, A A; Harutyunyan, E H

    1994-01-14

    Crystals of Proteus vulgaris holotryptophanase have been grown by the hanging-drop technique using polyethylene glycol 4000 as precipitant in the presence of monovalent cations K+ or Cs+. Orthorhombic crystals (P2(1)2(1)2(1)) grown with Cs+ have unit cell parameters a = 115.0 A, b = 118.2 A and c = 153.7 A and diffract to 1.8 A. There are four subunits of the tetrameric molecule in the asymmetric unit. Native data have been collected to 2.5 A resolution. The 3.4 A data were collected from tetragonal crystals of Escherichia coli holotryptophanase grown under conditions described by Kawata et al. (1991). The molecular replacement solution for this crystal form has been found using tyrosine phenol-lyase coordinates. The correct enantiomorph is P4(3)2(1)2. There are two subunits in the asymmetric unit.

  12. Identification of beta-aminoisobutyric acid in uremic serum.

    PubMed

    Gejyo, F; Kinoshita, Y; Ikenaka, T

    1976-08-02

    An unidentified ninhydrin-positive substance found in uremic sera but not found in normal sera was isolated by gel-filtration through Sephadex G-75 followed by high voltage paper electrophoresis (pH 3.5), and identified as beta-aminoisobutyric acid using paper chromatography and automated amino acid analyzer. The quantitative determination of beta-aminoisobutyric acid in serum revealed that the level of beta-aminoisobutyric acid in uremic sera was much higher than that of normal sera. Gas chromatographic determination of the enantiomorphs of beta-aminoisobutyric acid showed that uremic sera contain R- and S-isomers of the amino acid, but with the R-isomer as the dominating form.

  13. 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.

  14. 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.

  15. DARA: a web server for rapid search of structural neighbours using solution small angle X-ray scattering data

    PubMed Central

    Kikhney, Alexey G.; Panjkovich, Alejandro; Sokolova, Anna V.; Svergun, Dmitri I.

    2016-01-01

    Motivation: Small angle X-ray scattering (SAXS) is an established method for studying biological macromolecules in solution, whereby the experimental scattering patterns relate to the quaternary and tertiary structure of the macromolecule. Here we present DARA, a web-server, that queries over 150 000 scattering profiles pre-computed from the high resolution models of macromolecules and biological assemblies in the Protein Data Bank, to rapidly find nearest neighbours of a given experimental or theoretical SAXS pattern. Identification of the best scattering equivalents provides a straightforward and automated way of structural assessment of macromolecules based on a SAXS profile. DARA results are useful e.g. for fold recognition and finding of biologically active oligomers. Availability and implementation: http://dara.embl-hamburg.de/ Contact: svergun@embl-hamburg.de PMID:26504146

  16. 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).

  17. 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

  18. 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

  19. A large-scale crop protection bioassay data set

    NASA Astrophysics Data System (ADS)

    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.

    2015-07-01

    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.

  20. A large-scale crop protection bioassay data set

    PubMed Central

    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

  1. 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.

  2. Variation among matsutake ectomycorrhizae in four clones of Pinus sylvestris.

    PubMed

    Vaario, Lu-Min; Lu, Jinrong; Koistinen, Arto; Tervahauta, Arja; Aronen, Tuija

    2015-04-01

    Tricholoma matsutake is an ectomycorrhizal fungus that forms commercially important mushrooms in coniferous forests. In this study, we explored the ability of T. matsutake to form mycorrhizae with Pinus sylvestris by inoculating emblings produced through somatic embryogenesis (SE) in an aseptic culture system. Two months after inoculation, clones with less phenolic compounds in the tissue culture phase formed mycorrhizae with T. matsutake, while clones containing more phenols did not. Effects of inoculation on embling growth varied among clones; two of the four tested showed a significant increase in biomass and two had a significant increase in root density. In addition, results suggest that clones forming well-developed mycorrhizae absorbed more Al, Fe, Na, P, and Zn after 8 weeks of inoculation. This study illustrates the value of SE materials in experimental work concerning T. matsutake as well as the role played by phenolic compounds in host plant response to infection by mycorrhizal fungi.

  3. 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.

  4. The National Shipbuilding Research Program 1985 Ship Production Symposium Volume 1

    DTIC Science & Technology

    1985-09-01

    34, and Zones. E. For Electrical - Cableway installation for each module/zone including part lists. Cable lengths and numbers per section for each...Fittings Task S-43, Cableway Standards: o Standard for Cableway Components and Ass,emblies Task S-44, Deck Covering Guide: o Standard Guide for Deck...MIL-C-4556) Deck Covering in Electrical/Electronic Gear Fibrous Double–Braided Polyester Rope Acceptable Methods for Fitting Chocks Water Trap for

  5. The National Shipbuilding Research Program 1985 Ship Production Symposium. Volume 1, Paper Number 17: Overview of Panel SP-6 - Marine Industry Standards

    DTIC Science & Technology

    1985-09-01

    Task S-43, Cableway Standards: o Standard for Cableway Components and Ass,emblies Task S-44, Deck Covering Guide: o Standard Guide for Deck Covering...4556) Deck Covering in Electrical/Electronic Gear Fibrous Double–Braided Polyester Rope Acceptable Methods for Fitting Chocks Water Trap for Diesel...Engines Terminals, Air, Diffusing, Circular Rope , Nylon Paint, Aluminum, Heat Resisting Corrosion-Prevention Compound, Solvent Cutback, Cold Application

  6. 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

  7. Update of KEYnet: a gene and protein names database for biosequences functional organisation.

    PubMed

    Catalano, D; Licciulli, F; D'Elia, D; Attimonelli, M

    2000-01-01

    KEYnet is a database where gene and protein names are hierarchically structured. Particular care has been devoted to the search and organisation of synonyms. The structuring is based on biological criteria in order to assist the user in data search and to minimise the risk of information loss. Links to the EMBL data library by the entry name and the accession number are implemented. KEYnet is available through the WWW at the following site: http://www.ba.cnr.it/keynet.html

  8. 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.

  9. Computational Tools and Resources for Metabolism-Related Property Predictions. 1. Overview of Publicly Available (Free and Commercial) Databases and Software

    DTIC Science & Technology

    2012-01-01

    Metabolizing enzymes, reaction data, metabolic stability [260] BioPrint Cerep Commercial Drugs Measured bioactivities [89,257] ChEMBL European...the most well- known program for regioselectivity predictions [214]. It is based on the alignment of 3D inter- action points calculated for a substrate...cating over an SSH connection with the remote server in Switzerland. This graphical interface allows the preparation of 3D structures for the input

  10. Draft genome sequence of Corynebacterium diphtheriae biovar intermedius NCTC 5011.

    PubMed

    Sangal, Vartul; Tucker, Nicholas P; Burkovski, Andreas; Hoskisson, Paul A

    2012-09-01

    We report an annotated draft genome of the human pathogen Corynebacterium diphtheriae bv. intermedius NCTC 5011. This strain is the first C. diphtheriae bv. intermedius strain to be sequenced, and our results provide a useful comparison to the other primary disease-causing biovars, C. diphtheriae bv. gravis and C. diphtheriae bv. mitis. The sequence has been deposited at DDBJ/EMBL/GenBank with the accession number AJVH01000000.

  11. Cloning of a hemolysin gene from Leptospira interrogans serovar hardjo.

    PubMed Central

    del Real, G; Segers, R P; van der Zeijst, B A; Gaastra, W

    1989-01-01

    A DNA fragment encoding both hemolysin and sphingomyelinase C activity was cloned from the pathogenic bacterium Leptospira interrogans serovar hardjo. Initial clones were obtained by screening a genomic library in EMBL3 for hemolytic activity. Both hemolytic and sphingomyelinase C activities were coded for by a 3.9-kilobase BamHI fragment. The hemolysin was expressed from its own promoter in Escherichia coli K-12. Similar DNA sequences were also present in the serovars tarassovi and ballum. Images PMID:2744864

  12. Collation and data-mining of literature bioactivity data for drug discovery.

    PubMed

    Bellis, Louisa J; Akhtar, Ruth; Al-Lazikani, Bissan; Atkinson, Francis; Bento, A Patricia; Chambers, Jon; Davies, Mark; Gaulton, Anna; Hersey, Anne; Ikeda, Kazuyoshi; Krüger, Felix A; Light, Yvonne; McGlinchey, Shaun; Santos, Rita; Stauch, Benjamin; Overington, John P

    2011-10-01

    The challenge of translating the huge amount of genomic and biochemical data into new drugs is a costly and challenging task. Historically, there has been comparatively little focus on linking the biochemical and chemical worlds. To address this need, we have developed ChEMBL, an online resource of small-molecule SAR (structure-activity relationship) data, which can be used to support chemical biology, lead discovery and target selection in drug discovery. The database contains the abstracted structures, properties and biological activities for over 700000 distinct compounds and in excess of more than 3 million bioactivity records abstracted from over 40000 publications. Additional public domain resources can be readily integrated into the same data model (e.g. PubChem BioAssay data). The compounds in ChEMBL are largely extracted from the primary medicinal chemistry literature, and are therefore usually 'drug-like' or 'lead-like' small molecules with full experimental context. The data cover a significant fraction of the discovery of modern drugs, and are useful in a wide range of drug design and discovery tasks. In addition to the compound data, ChEMBL also contains information for over 8000 protein, cell line and whole-organism 'targets', with over 4000 of those being proteins linked to their underlying genes. The database is searchable both chemically, using an interactive compound sketch tool, protein sequences, family hierarchies, SMILES strings, compound research codes and key words, and biologically, using a variety of gene identifiers, protein sequence similarity and protein families. The information retrieved can then be readily filtered and downloaded into various formats. ChEMBL can be accessed online at https://www.ebi.ac.uk/chembldb.

  13. A germline-centric view of cell fate commitment, reprogramming and immortality.

    PubMed

    Torres-Padilla, Maria-Elena; Ciosk, Rafal

    2013-02-01

    To ensure species continuity, the tantalising developmental plasticity of early embryonic cells, also called totipotency, must be transmitted to the offspring. This responsibility rests within the reproductive cell lineage: the germ line. At the recent EMBO/EMBL symposium 'Germline - Immortality through Totipotency', researchers discussed the mechanisms that establish and control totipotency, with an eye towards the mechanisms that may endow germ cells with the ability to propagate totipotency across generations.

  14. Recent changes in the GenBank On-line Service.

    PubMed Central

    Benton, D

    1990-01-01

    The GenBank On-line Service provides access to the GenBank and EMBL nucleic acid sequence databases and to the Swiss-Prot and GenPept protein sequence databases. Users can query the databases by sequence similarity and annotation keywords and retrieve entries of interest. This access is available through e-mail servers, anonymous FTP, anonymous interactive login, and login to established, password-protected, individual accounts. PMID:2326192

  15. 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

  16. Identification of the integration host factor genes of Erwinia chrysanthemi 3937.

    PubMed

    Douillié, A; Toussaint, A; Faelen, M

    1994-01-01

    Two Erwinia chrysanthemi homologues of the himA and himD genes of Escherichia coli which encode the integration host factor (IHF) were cloned, sequenced and compared to their homolog in other enterobacteria (EMBL accession nos X74749 and X74750). Both genes were inactivated by the insertion of an antibiotic resistance cassette, allowing for the isolation of IHF- mutants of E chrysanthemi.

  17. JINN, an integrated software package for molecular geneticists.

    PubMed Central

    Johnsen, M

    1984-01-01

    I describe JINN, a microcomputer-based system designed to maintain and search a strain collection, to enter, modify and analyze sequences, and to use the EMBL Sequence Data Base. The major objective during development of this program has been integration of individual program modules to ensure a consistent and helpful user interface. The system is running under the CP/M operating system and requires little in the way of particular hardware configuration. PMID:6320101

  18. 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

  19. Designing a Quantitative Structure-Activity Relationship for the ...

    EPA Pesticide Factsheets

    Toxicokinetic models serve a vital role in risk assessment by bridging the gap between chemical exposure and potentially toxic endpoints. While intrinsic metabolic clearance rates have a strong impact on toxicokinetics, limited data is available for environmentally relevant chemicals including nearly 8000 chemicals tested for in vitro bioactivity in the Tox21 program. To address this gap, a quantitative structure-activity relationship (QSAR) for intrinsic metabolic clearance rate was developed to offer reliable in silico predictions for a diverse array of chemicals. Models were constructed with curated in vitro assay data for both pharmaceutical-like chemicals (ChEMBL database) and environmentally relevant chemicals (ToxCast screening) from human liver microsomes (2176 from ChEMBL) and human hepatocytes (757 from ChEMBL and 332 from ToxCast). Due to variability in the experimental data, a binned approach was utilized to classify metabolic rates. Machine learning algorithms, such as random forest and k-nearest neighbor, were coupled with open source molecular descriptors and fingerprints to provide reasonable estimates of intrinsic metabolic clearance rates. Applicability domains defined the optimal chemical space for predictions, which covered environmental chemicals well. A reduced set of informative descriptors (including relative charge and lipophilicity) and a mixed training set of pharmaceuticals and environmentally relevant chemicals provided the best intr

  20. Vibrio neptunius sp. nov., Vibrio brasiliensis sp. nov. and Vibrio xuii sp. nov., isolated from the marine aquaculture environment (bivalves, fish, rotifers and shrimps).

    PubMed

    Thompson, F L; Li, Y; Gomez-Gil, B; Thompson, C C; Hoste, B; Vandemeulebroecke, K; Rupp, G S; Pereira, A; De Bem, M M; Sorgeloos, P; Swings, J

    2003-01-01

    The fluorescent amplified fragment length polymorphism (FAFLP) groups A5 (21 isolates), A8 (6 isolates) and A23 (3 isolates) distinguished in an earlier paper (Thompson et al., Syst Appl Microbiol 24, 520-538, 2001) were examined in more depth. These three groups were phylogenetically related to Vibrio tubiashii, but DNA-DNA hybridization experiments proved that the three AFLP groups are in fact novel species. Chemotaxonomic and phenotypic analyses further revealed several differences among the 30 isolates and known Vibrio species. It is proposed to accommodate these isolates in three novel species, namely Vibrio neptunius (type strain LMG 20536T; EMBL accession no. AJ316171; G +C content of the type strain 46.0 mol%), Vibrio brasiliensis (type strain LMG 20546T; EMBL accession no. AJ316172; G + C content of the type strain 45.9 mol%) and Vibrio xuii (type strain LMG 21346T; EMBL accession no. AJ316181; G +C content of the type strain 46.6 mol%). These species can be differentiated on the basis of phenotypic features, including fatty acid composition (particularly 14:0 iso, 14:0 iso 3-OH, 16:0 iso, 16:0, 17:0 and 17:1 omega8c), enzyme activities and utilization and fermentation of various carbon sources.

  1. Identifying duplicate crystal structures: XTALCOMP, an open-source solution

    NASA Astrophysics Data System (ADS)

    Lonie, David C.; Zurek, Eva

    2012-03-01

    applications may consider enantiomorphic structures to be identical. Solution method: The XtalComp algorithm overcomes these issues to detect duplicate structures regardless of differences in representation. It begins by performing a Niggli reduction on the inputs, standardizing the translation vectors and orientations. A transform search is performed to identify candidate sets of rotations, reflections, and translations that potentially map the description of one crystal onto the other, solving the problems of enantiomorphs and rotationally degenerate lattices. The atomic positions resulting from each candidate transform are then compared, using a cell-expansion technique to remove periodic boundary issues. Computational noise is treated by comparing non-integer quantities using a specified tolerance. Running time: The test run provided takes less than a second to complete.

  2. 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

    2011-12-07

    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.

  3. Bioinformatic Identification of Rare Codon Clusters (RCCs) in HBV Genome and Evaluation of RCCs in Proteins Structure of Hepatitis B Virus

    PubMed Central

    Mortazavi, Mojtaba; Zarenezhad, Mohammad; Gholamzadeh, Saeid; Alavian, Seyed Moayed; Ghorbani, Mohammad; Dehghani, Reza; Malekpour, Abdorrasoul; Meshkibaf, Mohammadhasan; Fakhrzad, Ali

    2016-01-01

    Background Hepatitis B virus (HBV) as an infectious disease that has nine genotypes (A - I) and a ‘putative’ genotype J. Objectives The aim of this study was to identify the rare codon clusters (RCC) in the HBV genome and to evaluate these RCCs in the HBV proteins structure. Methods For detection of protein family accession numbers (Pfam) in HBV proteins, the UniProt database and Pfam search tool were used. Protein family accession numbers is a comprehensive and accurate collection of protein domains and families. It contains annotation of each family in the form of textual descriptions, links to other resources and literature references. Genome projects have used Pfam extensively for large-scale functional annotation of genomic data; Pfam database is a large collection of protein families, each represented by multiple sequence alignments and hidden Markov models (HMMs). The Pfam search tools are databases that identify Pfam of proteins. These Pfam IDs were analyzed in Sherlocc program and the location of RCCs in HBV genome and proteins were detected and reported as translated EMBL nucleotide sequence data library (TrEMBL) entries. The TrEMBL is a computer-annotated supplement of SWISS-PROT that contains all the translations of European molecular biology laboratory (EMBL) nucleotide sequence entries not yet integrated in SWISS-PROT. Furthermore, the structures of TrEMBL entries proteins were studied in the PDB database and 3D structures of the HBV proteins and locations of RCCs were visualized and studied using Swiss PDB Viewer software®. Results The Pfam search tool found nine protein families in three frames. Results of Pfams studies in the Sherlocc program showed that this program has not identified RCCs in the external core antigen (PF08290) and truncated HBeAg gene (PF08290) of HBV. By contrast, the RCCs were identified in gene of hepatitis core antigen (PF00906 and the residues 224 - 234 and 251 - 255), large envelope protein S (PF00695 and the residues

  4. An Improved Canine Genome and a Comprehensive Catalogue of Coding Genes and Non-Coding Transcripts

    PubMed Central

    Hoeppner, Marc P.; Lundquist, Andrew; Pirun, Mono; Meadows, Jennifer R. S.; Zamani, Neda; Johnson, Jeremy; Sundström, Görel; Cook, April; FitzGerald, Michael G.; Swofford, Ross; Mauceli, Evan; Moghadam, Behrooz Torabi; Greka, Anna; Alföldi, Jessica; Abouelleil, Amr; Aftuck, Lynne; Bessette, Daniel; Berlin, Aaron; Brown, Adam; Gearin, Gary; Lui, Annie; Macdonald, J. Pendexter; Priest, Margaret; Shea, Terrance; Turner-Maier, Jason; Zimmer, Andrew; Lander, Eric S.; di Palma, Federica

    2014-01-01

    The domestic dog, Canis familiaris, is a well-established model system for mapping trait and disease loci. While the original draft sequence was of good quality, gaps were abundant particularly in promoter regions of the genome, negatively impacting the annotation and study of candidate genes. Here, we present an improved genome build, canFam3.1, which includes 85 MB of novel sequence and now covers 99.8% of the euchromatic portion of the genome. We also present multiple RNA-Sequencing data sets from 10 different canine tissues to catalog ∼175,000 expressed loci. While about 90% of the coding genes previously annotated by EnsEMBL have measurable expression in at least one sample, the number of transcript isoforms detected by our data expands the EnsEMBL annotations by a factor of four. Syntenic comparison with the human genome revealed an additional ∼3,000 loci that are characterized as protein coding in human and were also expressed in the dog, suggesting that those were previously not annotated in the EnsEMBL canine gene set. In addition to ∼20,700 high-confidence protein coding loci, we found ∼4,600 antisense transcripts overlapping exons of protein coding genes, ∼7,200 intergenic multi-exon transcripts without coding potential, likely candidates for long intergenic non-coding RNAs (lincRNAs) and ∼11,000 transcripts were reported by two different library construction methods but did not fit any of the above categories. Of the lincRNAs, about 6,000 have no annotated orthologs in human or mouse. Functional analysis of two novel transcripts with shRNA in a mouse kidney cell line altered cell morphology and motility. All in all, we provide a much-improved annotation of the canine genome and suggest regulatory functions for several of the novel non-coding transcripts. PMID:24625832

  5. An improved canine genome and a comprehensive catalogue of coding genes and non-coding transcripts.

    PubMed

    Hoeppner, Marc P; Lundquist, Andrew; Pirun, Mono; Meadows, Jennifer R S; Zamani, Neda; Johnson, Jeremy; Sundström, Görel; Cook, April; FitzGerald, Michael G; Swofford, Ross; Mauceli, Evan; Moghadam, Behrooz Torabi; Greka, Anna; Alföldi, Jessica; Abouelleil, Amr; Aftuck, Lynne; Bessette, Daniel; Berlin, Aaron; Brown, Adam; Gearin, Gary; Lui, Annie; Macdonald, J Pendexter; Priest, Margaret; Shea, Terrance; Turner-Maier, Jason; Zimmer, Andrew; Lander, Eric S; di Palma, Federica; Lindblad-Toh, Kerstin; Grabherr, Manfred G

    2014-01-01

    The domestic dog, Canis familiaris, is a well-established model system for mapping trait and disease loci. While the original draft sequence was of good quality, gaps were abundant particularly in promoter regions of the genome, negatively impacting the annotation and study of candidate genes. Here, we present an improved genome build, canFam3.1, which includes 85 MB of novel sequence and now covers 99.8% of the euchromatic portion of the genome. We also present multiple RNA-Sequencing data sets from 10 different canine tissues to catalog ∼175,000 expressed loci. While about 90% of the coding genes previously annotated by EnsEMBL have measurable expression in at least one sample, the number of transcript isoforms detected by our data expands the EnsEMBL annotations by a factor of four. Syntenic comparison with the human genome revealed an additional ∼3,000 loci that are characterized as protein coding in human and were also expressed in the dog, suggesting that those were previously not annotated in the EnsEMBL canine gene set. In addition to ∼20,700 high-confidence protein coding loci, we found ∼4,600 antisense transcripts overlapping exons of protein coding genes, ∼7,200 intergenic multi-exon transcripts without coding potential, likely candidates for long intergenic non-coding RNAs (lincRNAs) and ∼11,000 transcripts were reported by two different library construction methods but did not fit any of the above categories. Of the lincRNAs, about 6,000 have no annotated orthologs in human or mouse. Functional analysis of two novel transcripts with shRNA in a mouse kidney cell line altered cell morphology and motility. All in all, we provide a much-improved annotation of the canine genome and suggest regulatory functions for several of the novel non-coding transcripts.

  6. 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.

  7. Cloning of the Rhodobacter capsulatus hemA gene.

    PubMed Central

    Biel, S W; Wright, M S; Biel, A J

    1988-01-01

    Portions of the Rhodobacter capsulatus hemA gene have been cloned from a hemA::Tn5 insertion strain into the lambda bacteriophage derivative EMBL3. A cosmid containing the wild-type R. capsulatus hemA gene was isolated by complementation of the hemA::Tn5 mutant. The cosmid contains a 1.4-kilobase EcoRI fragment that spans the hemA::Tn5 insertion site. The entire hemA gene is contained in this fragment and the adjacent 0.6-kilobase EcoRI fragment. Images PMID:2842318

  8. Data mining parasite genomes: haystack searching with a computer.

    PubMed

    Lawson, D

    1999-01-01

    A number of genomes of parasitic organisms are presently being sequenced in the public domain, including Plasmodium falciparum, Leishmania major and Trypanosoma brucei with the likelihood of at least expressed sequence tag (EST) projects for several filarial and apicomplexan species. The early and timely release of sequence data to the community via the World Wide Web (www), and the public databases, (EMBL and GENBANK), forms an invaluable resource. Data mining, or 'haystack searching' this resource is becoming more fruitful to all members of the scientific community as the volume of data, diversity of genomes sampled, and accessibility increase.

  9. 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.

  10. 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

  11. 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

  12. Virulence genome analysis of Pseudomonas aeruginosa VRFPA10 recovered from patient with scleritis.

    PubMed

    Murugan, Nandagopal; Malathi, Jambulingam; Umashankar, Vetrivel; Madhavan, Hajib Narahari Rao

    2017-06-01

    Infectious keratitis is a major cause of blindness, next to cataract and majority of cases are mainly caused by gram negative bacterium Pseudomonas aeruginosa (P. aeruginosa). In this study, we investigated a P. aeruginosa VRFPA10 genome which exhibited susceptibility to commonly used drugs in vitro but the patient had poor prognosis due to its hyper virulent nature. Genomic analysis of VRFPA10 deciphered multiple virulence factors and P.aeruginosa Genomic Islands (PAGIs) VRFPA10 genome which correlated with hyper virulence nature of the organism. The genome sequence has been deposited in DDBJ/EMBL/GenBank under the accession numbers LFMZ01000001-LFMZ01000044.

  13. 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).

  14. Draft genome sequence of Thermoactinomyces sp. Gus2-1 isolated from the hot-spring Gusikha in Bargusin Valley (Baikal Rift Zone, Russia).

    PubMed

    Rozanov, Aleksey S; Bryanskaya, Alla V; Kotenko, Anastasia V; Peltek, Sergey E

    2017-03-01

    The Thermoactinomyces sp. strain Gus2-1 was isolated from hot-spring sediments sample from the hot-spring Gusikha in Bargusin Valley (Baikal Rift Zone, Russia). The sequenced and annotated genome is 2,623,309 bp and encodes 2513 genes. The draft genome sequence of the Thermoactinomyces sp. strain Gus2-1 has been deposited at DDBJ/EMBL/GenBank under the accession JPZM01000000 and the sequences could be found at the site https://www.ncbi.nlm.nih.gov/nuccore/JPZM01000000.

  15. Opacités nodulaires diffuses et calcifiées

    PubMed Central

    Jabri, Hasna; Bopaka, Régis Gothard; Lakhdar, Nawal; Moubachir, Houda; Khattabi, Wiam El; Afif, Hicham

    2016-01-01

    L’adénocarcinome pulmonaire est difficile à évoquer d’emblée devant les données anamnestiques et même radiologiques. Nous rapportons une observation d’une femme présentant une dyspnée avec la radiographie une opacité micronodulaire disséminée, confluente dans les deux champs pulmonaires avec des calcifications par endroit. L’histologie à travers les biopsies transbronchiques a permis de poser le diagnostic. Le pronostic était sombre par le décès de la patiente. PMID:27795800

  16. Construction of a gene library from Azospirillum brasilense and characterization of a recombinant containing the nif structural genes.

    PubMed

    Schrank, I S; Zaha, A; de Araújo, E F; Santos, D S

    1987-01-01

    1. We have constructed a gene library, from Azospirillum brasilense using the vector EMBL4. 2. A recombinant containing the nif structural genes from A. brasilense was isolated and characterized. This recombinant contains a DNA insert of about 15 kilobases (kb) which gives rise to five fragments after cleavage with EcoRI. Only one of the DNA fragments (6.5 kb) hybridized to the nifHDK genes of Klebsiella pneumoniae. 3. The organization of the nif genes in this DNA fragment was determined using different DNA segments containing the nifH, nifK or nifD genes of K. pneumoniae as probes.

  17. Yeast Genetics for Delineating Bax/Bcl Pathway of Cell Death Regulation.

    DTIC Science & Technology

    1998-07-01

    J.C., van Ommen, G.B., J.C., Ord, T., and Bredesen, D.E. (1993). Bcl-2 inhibition of neural and Kluin, P.M. (1994). Subcellular localization of the bcl...J.C., van Ommen, G.B., Kluck, R.M., Bossy-Wetzel, E., Green, D.R., and Newmeyer, D.D. and Kluin, P.M. (1994). Subcellular localization of the bcl-2...constructed by trans- quences. The putative Arabidopsis homolog (EMBL forming the Bax-expression plasmid YEp5i-Bax, en- #Z97343) is 261 residues in length

  18. Genomic organization of the human lysosomal acid lipase gene (LIPA)

    SciTech Connect

    Aslandis, C.; Klima, H.; Lackner, K.J.; Schmitz, G. )

    1994-03-15

    Defects in the human lysosomal acid lipase gene are responsible for cholesteryl ester storage disease (CESD) and Wolman disease. Exon skipping as the cause for CESD has been demonstrated. The authors present here a summary of the exon structure of the entire human lysosomal acid lipase gene consisting of 10 exons, together with the sizes of genomic EcoRI and SacI fragments hybridizing to each exon. In addition, the DNA sequence of the putative promoter region is presented. The EMBL accession numbers for adjacent intron sequences are given. 7 refs., 2 figs., 1 tab.

  19. 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

  20. Nitric oxide is necessary for visual learning in Octopus vulgaris.

    PubMed

    Robertson, J D; Bonaventura, J; Kohm, A; Hiscat, M

    1996-12-22

    We recently reported that inhibition of nitric oxide synthase (NOS) in Octopus vulgaris by intramuscular injections of an analog of L-arginine, N-omega-nitro-L-arginine methyl ester (L-NAME), blocked touch learning in Octopus vulgaris. The inactive enantiomorph (D-NAME), which had no effect on learning, was used for control. We now report that essentially the same procedures block visual learning in this animal. We used a visual paradigm in which the octopus was trained to respond positively to a smooth black plastic ball 2.5 cm diameter and negatively to a similar white ball, or vice versa. One set of eight animals was trained to the black ball positive, and another set of six to the white ball positive. Each set was trained at different times by two different trainers. We found that a 1 h pretreatment with the nitric oxide synthase inhibitor L-NAME blocks visual learning in Octopus vulgaris in both sets of animals.

  1. 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.

  2. Crystal structure of (E)-N'-(4-chloro-benzyl-idene)-4-methyl-benzene-sulfono-hydrazide: a hexa-gonal polymorph.

    PubMed

    Balaji, J; John Francis Xavier, J; Prabu, S; Srinivasan, P

    2014-12-01

    The title compound, C14H13ClN2O2S, crystallized in the enanti-omorphic defining hexa-gonal space group P61 [Flack parameter = -0.02 (7)]. The partially hydrated form of the same compound, crystallizing in the triclinic space group P-1, has been reported previously [Kia et al. (2009b). Acta Cryst. E65, o1119], as has the crystal structure of the bromo derivative, also crystallizing in the space group P-1 [Kia et al. (2009a). Acta Cryst. E65, o821]. The title mol-ecule is non-planar with the planes of the benzene rings being inclined to one another by 76.62 (13)°, and has an E conformation about the C=N bond. In the crystal, mol-ecules are linked via N-H⋯O hydrogen bonds forming 61 helical chains running along [001]. The chains are linked via C-H⋯O hydrogen bonds, C-H⋯π inter-actions and short Cl⋯O [3.015 (3) Å] inter-actions, forming a three-dimensional structure.

  3. 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.

  4. 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

  5. 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.

  6. Monitoring structural transformations in crystals. 11. Yang photocyclizations--one type of reaction, but diversity of structural changes.

    PubMed

    Turowska-Tyrk, Ilona; Bakowicz, Julia; Scheffer, John R

    2007-12-01

    Structural changes proceeding in a crystal during the Yang photocyclization of the salt 6,6-diethyl-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate with (1S)-1-(4-methylphenyl)ethylamine were monitored by means of X-ray structure analysis. The course of the photoreaction was evaluated on the basis of the geometrical parameters for the pure reactant crystal. Variations in the cell constants, the product content, the geometry of the reaction centre, the orientation of molecular fragments and the geometry of hydrogen bonds were described and analyzed. It was found that the cell volume increased until 56% product content and decreased thereafter. The distance between the directly reacting C atoms was constant, approximately 3.0 A, until approximately 75% reaction progress. Analysis of the distance between atoms that would participate in the formation of the second (unobserved) enantiomorph excluded the formation of such an isomer. Molecular fragments varied their orientation during the photoreaction, and the largest change was observed for the carboxylate group despite its participation in strong hydrogen bonds. The geometry of the hydrogen bonds changed during the photoreaction. The largest change was 0.17 A for the D...A distance and 13 degrees for the D-H...A angle. A comparison of the intra- and intermolecular parameters for the studied salt with data for other compounds undergoing the Yang photocyclization in crystals revealed a diversity of structural changes brought about by this type of photochemical reaction.

  7. Incomplete factorial search for conditions leading to high quality crystals of Escherichia coli cytidine deaminase complexed to a transition state analog inhibitor.

    PubMed

    Betts, L; Frick, L; Wolfenden, R; Carter, C W

    1989-04-25

    We have used an incomplete factorial design (Carter, C. W., and Carter, C. W., Jr. (1979) J. Biol. Chem. 254, 12219-12223) to find conditions for growing high quality crystals of Escherichia coli cytidine deaminase (EC 3.5.4.5). Crystals grow at pH 6.0 in hanging or sitting drops with either 1.6 M ammonium sulfate or 2.4-2.5 M sodium phosphate as precipitant. Both conditions produce crystals with identical morphologies and unit cell constants. The space group is P3(1)21 (or its enantiomorph P3(2)21), and the unit cell constants are a = b = 120.3 A, c = 78.4 A. The asymmetric unit is most reasonably one dimer of 66,000 Mr. The crystal size is very dependent on the supersaturation ratio, S = [initial protein concentration]/[equilibrium protein concentration], exhibiting a maximum at S = 7.7. The largest crystals diffract to at least 2.5 A and have a lifetime of 4 to 5 days in the x-ray beam at room temperature. The enzyme in these crystals is complexed with the transition state analog inhibitor 1-(beta-D-ribofuranosyl)-5-fluoropyrimidin-2-one (5-fluoropyrimidin-2-one riboside). We have collected data from parent crystals and from a heavy atom derivative in which the transition state analog is replaced by the active site directed inhibitor 5-(chloromercuri)cytidine.

  8. 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%.

  9. The Product of the reaction of [Co(en) 2( N, S Bound-( R)cystein)] 2+ with CH 2l 2 in DMSO solution: [Co(en) 2( N, S-bound- S-iodomethyl-( R)cystein)]Cl 3·2H 2O( 1)

    NASA Astrophysics Data System (ADS)

    Cai, Jiwen; Bernal, Ivan; Gregory Jackson, W.

    1998-10-01

    ( 1), ICOCl 3SO 4N 5C 8H 25- N, S, was prepared by the reaction of diiodomethane with the [Co(en) 2( R)cysteinato- N, S] 2+ cation in DMSO solution. It crystallizes in space group P2 1 (no. 4) with lattice constants of a=11.914(3), b=12.714(4), c=14.573(4) Å, β=107.79(2)°; V=2101.83 A 3 and d(calc; MW=577.55, z=4)=1.825 g cm -3. A total of 2178 data were collected over the range of 4°≤2θ≤50° of these, 1778 [independent and with I≥3σ( I)] were used in the structural analysis. Data were corrected for absorption(μ=40.3 cm -1) and the transmission coefficients ranged from 0.5862 to 0.8357. The correct enantiomorph was determined by the method of Flack. For ( 1), the two cations in the asymmetric unit were found to be Co1=Λ(λδλ) and Co2=Λ(λλλ), where the last symbol in parenthesis defines the helical chirality at the cystein ring; the -COOH substituent is equatorially disposed in both cations. The configurations of the alkylated sulfur centers and the asymmetric carbons of the cystein ligands for both metal cations are, respectively, S and R; the latter is the natural configuration for cystein.

  10. 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.

  11. 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.

  12. 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.

  13. Crystallization and preliminary X-ray crystallographic analysis of the heterodimeric crotoxin complex and the isolated subunits crotapotin and phospholipase A{sub 2}

    SciTech Connect

    Santos, K. F.; Murakami, M. T.; Toyama, M. H.; Marangoni, S.; Forrer, V. P.; Brandão Neto, J. R.; Polikarpov, I.; Arni, R. K.

    2007-04-01

    Crotoxin, a potent neurotoxin from the venom of the South American rattlesnake Crotalus durissus terrificus, exists as a heterodimer formed between a phospholipase A{sub 2} and a catalytically inactive acidic phospholipase A{sub 2} analogue (crotapotin). Large single crystals of the crotoxin complex and of the isolated subunits have been obtained. Crotoxin, a potent neurotoxin from the venom of the South American rattlesnake Crotalus durissus terrificus, exists as a heterodimer formed between a phospholipase A{sub 2} and a catalytically inactive acidic phospholipase A{sub 2} analogue (crotapotin). Large single crystals of the crotoxin complex and of the isolated subunits have been obtained. The crotoxin complex crystal belongs to the orthorhombic space group P2{sub 1}2{sub 1}2, with unit-cell parameters a = 38.2, b = 68.7, c = 84.2 Å, and diffracted to 1.75 Å resolution. The crystal of the phospholipase A{sub 2} domain belongs to the hexagonal space group P6{sub 1}22 (or its enantiomorph P6{sub 5}22), with unit-cell parameters a = b = 38.7, c = 286.7 Å, and diffracted to 2.6 Å resolution. The crotapotin crystal diffracted to 2.3 Å resolution; however, the highly diffuse diffraction pattern did not permit unambiguous assignment of the unit-cell parameters.

  14. Formulation of predictive models for use in first principles design of non-centrosymmetric perovskite oxides

    NASA Astrophysics Data System (ADS)

    Young, Joshua; Rondinelli, James

    2014-03-01

    Because many useful electronic properties such as ferroelectricity arise solely due to the lack of inversion in a material's crystal structure, predictive microscopic models describing how to deterministically remove this symmetry operation can allow for the rapid identification and design of new polar compounds. By understanding how structural distortions influence the connectivity between oxygen polyhedra in solid state oxides, we elucidate a series of geometric design rules necessary to develop polar materials. We then apply these criteria to the family of ABO3 perovskite oxides by systematically investigating how distortions of the corner-connected BO6 polyhedral network influence the A-site environments, resulting in a detailed description of the octahedral rotation patterns and A- and B-site cation ordering arrangements capable of producing centrosymmetric, polar, and enantiomorphic structures. Using this as a guide, we then show how such a method allows for the targeted design of new non-centrosymmetric oxides. We conclude by using these rules in combination with density functional theory calculations to predict a series of rhombohedral (A,A')B2O6 perovskites displaying electric polarizations in their ground state.

  15. On Flagellar Structure in Certain Flagellates

    PubMed Central

    Gibbons, I. R.; Grimstone, A. V.

    1960-01-01

    This paper describes the structure of the flagella, basal bodies, and some of the associated fibre systems in three genera of complex flagellates, Trichonympha, Pseudotrichonympha, and Holomastigotoides. Three groups of longitudinal fibres occur in a flagellum: two central and nine outer fibres such as have been repeatedly described in other material, and an additional set of nine smaller secondary fibres not previously identified as such. Each central fibre shows a helical substructure; the pair of them are enveloped in a common sheath. Each outer fibre is a doublet with one subfibre bearing projections—called arms—that extend toward the adjacent outer fibre. The basal body is formed by a cylinder of nine triplet outer fibres. Two subfibres of each triplet continue into the flagellum and constitute the doublets. The third subfibre terminates at the transition of basal body to flagellum, possibly giving rise to the nine radial transitional fibres that seem to attach the end of the basal body to the surface of the organism. The central and secondary flagellar fibres are not present in the lumen of the basal body, but other complex structures occur there. The form of these intraluminal structures differs from genus to genus. The flagellar unit is highly asymmetrical. All the flagella examined have possessed the same one of the two possible enantiomorphic forms. At least two systems of fibres are associated with the basal bodies of all three genera. PMID:13827900

  16. Two new species of Elopicola (Digenea: Aporocotylidae) from Hawaiian ladyfish, Elops hawaiensis (Eastern Sea) and Atlantic tarpon, Megalops atlanticus (Gulf of Mexico) with a comment on monophyly of elopomorph blood flukes.

    PubMed

    Orélis-Ribeiro, Raphael; Halanych, Kenneth M; Dang, Binh T; Bakenhaster, Micah D; Arias, Cova R; Bullard, Stephen A

    2017-06-01

    Elopicola bristowi sp. n. infects the blood vascular system of Hawaiian ladyfish, Elops hawaiensis, in the Eastern Sea. It differs from the only nominal congener Elopicola nolancribbi by the combination of having rows of ventrolateral tegumental spines, a proportionally long oesophagus, anterior caeca, vasa efferentia coalescing ventral to the posterodextral margin of the testis, a post-testicular metraterm, a dextral common genital pore lateral to the oötype, and genitalia that are enantiomorphic relative to those of E. nolancribbi. Elopicola franksi sp. n. infects the heart and blood vascular system of Atlantic tarpon, Megalops atlanticus, in the Gulf of Mexico. It differs from its congeners by the combination of lacking ventrolateral tegumental spines and having an elongate body (6× longer than wide), a proportionally long oesophagus, a compact testis at level of the distal ends of the posterior caeca, and a post-testicular common genital pore at level of the oötype. Phylogenetic analyses based on the small subunit ribosomal DNA (18S), large subunit ribosomal DNA (28S), and internal transcribed spacer 2 (ITS2) genes revealed considerable genetic differences between these taxa. The 18S+28S tree showed a monophyletic Elopicola sister to all aporocotylids infecting fishes of Euteleosteomorpha. The ITS2 tree showed Paracardicoloides yamagutii as the sister taxon to Elopicola spp.

  17. Expression, purification, crystallization and preliminary X-ray diffraction analysis of the novel modular DNA-binding protein BurrH in its apo form and in complex with its target DNA.

    PubMed

    Stella, Stefano; Molina, Rafael; Bertonatti, Claudia; Juillerrat, Alexandre; Montoya, Guillermo

    2014-01-01

    Different genome-editing strategies have fuelled the development of new DNA-targeting molecular tools allowing precise gene modifications. Here, the expression, purification, crystallization and preliminary X-ray diffraction of BurrH, a novel DNA-binding protein from Burkholderia rhizoxinica, are reported. Crystallization experiments of BurrH in its apo form and in complex with its target DNA yielded crystals suitable for X-ray diffraction analysis. The crystals of the apo form belonged to the primitive hexagonal space group P3(1) or its enantiomorph P3(2), with unit-cell parameters a = b = 73.28, c = 268.02 Å, α = β = 90, γ = 120°. The BurrH-DNA complex crystallized in the monoclinic space group P2(1), with unit-cell parameters a = 70.15, b = 95.83, c = 76.41 Å, α = γ = 90, β = 109.51°. The self-rotation function and the Matthews coefficient suggested the presence of two protein molecules per asymmetric unit in the apo crystals and one protein-DNA complex in the monoclinic crystals. The crystals diffracted to resolution limits of 2.21 and 2.65 Å, respectively, using synchrotron radiation.

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

    PubMed

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

    2015-09-01

    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.

  19. Hydrodynamic interactions between two forced objects of arbitrary shape. II. Relative translation

    NASA Astrophysics Data System (ADS)

    Goldfriend, Tomer; Diamant, Haim; Witten, Thomas A.

    2016-04-01

    We study the relative translation of two arbitrarily shaped objects, caused by their hydrodynamic interaction as they are forced through a viscous fluid in the limit of zero Reynolds number. It is well known that in the case of two rigid spheres in an unbounded fluid, the hydrodynamic interaction does not produce relative translation. More generally, such an effective pair-interaction vanishes in configurations with spatial inversion symmetry; for example, an enantiomorphic pair in mirror image positions has no relative translation. We show that the breaking of inversion symmetry by boundaries of the system accounts for the interactions between two spheres in confined geometries, as observed in experiments. The same general principle also provides new predictions for interactions in other object configurations near obstacles. We examine the time-dependent relative translation of two self-aligning objects, extending the numerical analysis of our preceding publication [Goldfriend, Diamant, and Witten, Phys. Fluids 27, 123303 (2015)], 10.1063/1.4936894. The interplay between the orientational interaction and the translational one, in most cases, leads over time to repulsion between the two objects. The repulsion is qualitatively different for self-aligning objects compared to the more symmetric case of uniform prolate spheroids. The separation between the two objects increases with time t as t1 /3 in the former case, and more strongly, as t , in the latter.

  20. Superenantioselective chiral surface explosions.

    PubMed

    Gellman, Andrew J; Huang, Ye; Feng, Xu; Pushkarev, Vladimir V; Holsclaw, Brian; Mhatre, Bharat S

    2013-12-26

    Chiral inorganic materials predated life on Earth, and their enantiospecific surface chemistry may have played a role in the origins of biomolecular homochirality. However, enantiospecific differences in the interaction energies of chiral molecules with chiral surfaces are small and typically lead to modest enantioselectivities in adsorption, catalysis, and chemistry on chiral surfaces. To yield high enantioselectivities, small energy differences must be amplified by reaction mechanisms such as autocatalytic surface explosions which have nonlinear kinetics. Herein, we report the first observations of superenantiospecificity resulting from an autocatalytic surface explosion reaction of a chiral molecule on a naturally chiral surface. R,R- and S,S-tartaric acid decompose via a vacancy-mediated surface explosion mechanism on Cu single crystal surfaces. When coupled with surface chirality, this leads to decomposition rates that exhibit extraordinarily high enantiospecificity. On the enantiomorphs of naturally chiral Cu(643)(R&S), Cu(17,5,1)(R&S), Cu(531)(R&S) and Cu(651)(R&S) single crystal surfaces, R,R- and S,S-tartaric acid exhibit enantiospecific decomposition rates that differ by as much as 2 orders of magnitude, despite the fact that the effective rates constants for decomposition differ by less than a factor of 2.

  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. FourCSeq: analysis of 4C sequencing data

    PubMed Central

    Klein, Felix A.; Pakozdi, Tibor; Anders, Simon; Ghavi-Helm, Yad; Furlong, Eileen E. M.; Huber, Wolfgang

    2015-01-01

    Motivation: Circularized Chromosome Conformation Capture (4C) is a powerful technique for studying the spatial interactions of a specific genomic region called the ‘viewpoint’ with the rest of the genome, both in a single condition or comparing different experimental conditions or cell types. Observed ligation frequencies typically show a strong, regular dependence on genomic distance from the viewpoint, on top of which specific interaction peaks are superimposed. Here, we address the computational task to find these specific peaks and to detect changes between different biological conditions. Results: We model the overall trend of decreasing interaction frequency with genomic distance by fitting a smooth monotonically decreasing function to suitably transformed count data. Based on the fit, z-scores are calculated from the residuals, and high z-scores are interpreted as peaks providing evidence for specific interactions. To compare different conditions, we normalize fragment counts between samples, and call for differential contact frequencies using the statistical method DESeq2 adapted from RNA-Seq analysis. Availability and implementation: A full end-to-end analysis pipeline is implemented in the R package FourCSeq available at www.bioconductor.org. Contact: felix.klein@embl.de or whuber@embl.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26034064

  3. Molecular pathogenesis of Bernard-Soulier syndrome.

    PubMed

    Hayashi, T; Suzuki, K

    2000-01-01

    Bernard-Soulier syndrome (BSS), a hereditary qualitative platelet disorder, is now proved to be caused by a qualitative or quantitative abnormality of the platelet glycoprotein (GP) Ib/IX/V complex. We investigated the genetic background of two Japanese females with BSS and identified the molecular defects underlying this disease. The first case was a single base pair deletion within seven adenine repeats at position 4464-4470 (EMBL, no. M22403) of the GPIbalpha gene resulting in a frameshift and a premature stop codon. The second case was a single T-->C substitution at nucleotide 1856 (EMBL, no. M80478) of the GPIX gene resulting in Phe55(TTT)-->Ser(TCT) substitution. The latter case is of interest in considering the pathogenesis of BSS, because all four GPs consisting of the GPIb/IX/V complex have the same structural unit called leucine-rich repeat (LRR). Because this mutation is located within the LRR of the GPIX polypeptide, Phe55-->Ser substitution may result in an alteration of the LRR that leads to impaired surface expression of the GPIb/IX/V complex. To clarify the effect of this mutation on surface expression of the GPIb/IX complex, we performed transfection studies with a plasmid having this mutation. Mutant GPIX could not increase surface expression of the GPIb/IX complex, thus demonstrating an important role of the LRR of the GPIX polypeptide during biosynthesis.

  4. 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

  5. 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

  6. Plant Protein Annotation in the UniProt Knowledgebase1

    PubMed Central

    Schneider, Michel; Bairoch, Amos; Wu, Cathy H.; Apweiler, Rolf

    2005-01-01

    The Swiss-Prot, TrEMBL, Protein Information Resource (PIR), and DNA Data Bank of Japan (DDBJ) protein database activities have united to form the Universal Protein Resource (UniProt) Consortium. UniProt presents three database layers: the UniProt Archive, the UniProt Knowledgebase (UniProtKB), and the UniProt Reference Clusters. The UniProtKB consists of two sections: UniProtKB/Swiss-Prot (fully manually curated entries) and UniProtKB/TrEMBL (automated annotation, classification and extensive cross-references). New releases are published fortnightly. A specific Plant Proteome Annotation Program (http://www.expasy.org/sprot/ppap/) was initiated to cope with the increasing amount of data produced by the complete sequencing of plant genomes. Through UniProt, our aim is to provide the scientific community with a single, centralized, authoritative resource for protein sequences and functional information that will allow the plant community to fully explore and utilize the wealth of information available for both plant and nonplant model organisms. PMID:15888679

  7. Towards a Universal SMILES representation - A standard method to generate canonical SMILES based on the InChI

    PubMed Central

    2012-01-01

    Background There are two line notations of chemical structures that have established themselves in the field: the SMILES string and the InChI string. The InChI aims to provide a unique, or canonical, identifier for chemical structures, while SMILES strings are widely used for storage and interchange of chemical structures, but no standard exists to generate a canonical SMILES string. Results I describe how to use the InChI canonicalisation to derive a canonical SMILES string in a straightforward way, either incorporating the InChI normalisations (Inchified SMILES) or not (Universal SMILES). This is the first description of a method to generate canonical SMILES that takes stereochemistry into account. When tested on the 1.1 m compounds in the ChEMBL database, and a 1 m compound subset of the PubChem Substance database, no canonicalisation failures were found with Inchified SMILES. Using Universal SMILES, 99.79% of the ChEMBL database was canonicalised successfully and 99.77% of the PubChem subset. Conclusions The InChI canonicalisation algorithm can successfully be used as the basis for a common standard for canonical SMILES. While challenges remain – such as the development of a standard aromatic model for SMILES – the ability to create the same SMILES using different toolkits will mean that for the first time it will be possible to easily compare the chemical models used by different toolkits. PMID:22989151

  8. Human expressed tagged sites on the X chromosome: A mapping resource for heritable sex-linked chorioretinal disorders

    SciTech Connect

    MacDonald, I.M.; Nesslinger, N.; Wong, P.

    1994-09-01

    We have isolated a bank of human X-specific genomic clones which harbor chorioretinal expressed sequences using library to library cross-screening. The steps included (1) the creation of a {lambda}gt-10 library of human chorioretinal cDNA, (2) the creation of a human X-specific EMBL-3 genomic library from a somatic cell hybrid (82082a) containing the X chromosome as its only human component and lacking the hamster X, and (3) a PCR-based cross-screen to identify 78 clones expressed in choroid and retina. The characterization of one human X-specific EMBL-3 clone (XEH.8; DXS542) has provided a clear illustration of the feasibility of this approach. FISH mapping confirms the regional localization of XEH.8 to Xp11. Localization of additional clones, XEH.1, XEH.34, XEH.41, and XEH.52 will be presented along with partial sequencing and characterization. Our approach has focused on the search for expressed sequences which can serve as expressed tagged sites (ESTs) in mapping or candidate genes for heritable eye disorders.

  9. 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

  10. Mirror-imaged doublets of Tetmemena pustulata: implications for the development of left-right asymmetry.

    PubMed

    Bell, Aaron J; Satir, Peter; Grimes, Gary W

    2008-02-01

    Ciliated protozoa possess cellular axes reflected in the arrangement of their ciliature. Upon transverse fission, daughter cells develop an identical ciliary pattern, ensuring perpetuation of the cellular phenotype. Experimentally manipulated cells can be induced to form atypical phenotypes, capable of intraclonal propagation and regeneration after encystment. One such phenotype in the ciliate Tetmemena pustulata (formerly Stylonychia pustulata) is the mirror-imaged doublet. These cells possess two distinct sets of ciliature, juxtaposed on the surfaces in mirror image symmetry, with a common anterior-posterior axis. We have examined whether individual ciliary components of Tetmemena mirror-image doublets are mirror imaged. Ultrastructural analysis indicates that despite global mirror imaging of the ciliature, detailed organization of the membranelles is reversed in the mirror-image oral apparatus (OA), such that the ciliary effective stroke propels food away from the OA. Assembly of compound ciliary structures of both OAs starts out identically, but as the structures associated with the mirror-image OA continue to form, the new set of membranelles undergoes a 180 degrees planar rotation on the ventral surface relative to the same structures in the typical OA. The overall symmetry of the OA thus appears to be separable from the more localized assembly of individual basal bodies. True mirror imagery of the membranelles would require new enantiomorphic forms of the individual ciliary components, particularly the basal bodies, which is never observed. These observations suggest a mechanistic hypothesis with implications for the development of left-right asymmetry not only in ciliates, but perhaps also in development of left-right asymmetry in general.

  11. Expression, purification, crystallization and preliminary X-ray analysis of the DNA-binding domain of a Chlamydia trachomatis OmpR/PhoB-subfamily response regulator homolog, ChxR.

    PubMed

    Hickey, John M; Hefty, P Scott; Lamb, Audrey L

    2009-08-01

    Two-component signal transduction systems in bacteria are a primary mechanism for responding to environmental stimuli and adjusting gene expression accordingly. Generally in these systems a sensor kinase phosphorylates a response regulator that regulates transcription. Response regulators contain two domains: a receiver domain and an effector domain. The receiver domain is typically phosphorylated and as a result facilitates the DNA-binding and transcriptional activity of the effector domain. The OmpR/PhoB subfamily is the largest of the response-regulator subfamilies and is primarily defined by the winged helix-turn-helix DNA-binding motif within the effector domain. The overall structure of effector domains is highly conserved and contains three defined elements that are critical for transcriptional regulation: a DNA major-groove binding helix, a DNA minor-groove binding wing and a transcriptional activation loop. These functional elements are often diverse in sequence and conformation and reflect the functional differences observed between individual subfamily members. ChxR from Chlamydia trachomatis is an atypical OmpR/PhoB response regulator homolog that has transcriptional activity in the absence of phosphorylation. To facilitate the precise identification of the functional elements of the ChxR effector domain, this protein was cloned, expressed, purified and crystallized. Crystals were obtained from two separate mother liquors, producing two morphologically distinct crystals. The space group of both crystals was P4(3)2(1)2 (or its enantiomorph P4(1)2(1)2) with isomorphous unit-cell parameters; the crystals diffracted to 2.2-2.5 A resolution.

  12. 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.

  13. An inter-basinal comparison of the sedimentology of Late Holocene to recent sediments in the Rift Valley, Lake Turkana, Kenya

    NASA Astrophysics Data System (ADS)

    Olago, D. O.; Odada, E. O.

    2000-08-01

    Grain size variations, sediment chemistry and general mineralogical assemblages of sediments in Lake Turkana reflect provenance. Allogenic sediments in Lake Turkana are mainly supplied by the Omo and Kerio-Turkwel Rivers. Minor inputs are from seasonal streams and strong southeasterly winds. The depth profiles of the grain size distributions in lake sediment cores exhibit enantiomorphism, which is interpreted as being diagnostic both of shifts in the equilibrium energy regime of the transporting media and of the dominant provenance of particular size grades within the specific basins of the lake. The North Sub-basin is dominated by fine-grained sediments, which reflect the texture of the volcanic rocks of the Omo River drainage basin. The Central Sub-basin sediments reflect, as sources, the coarser metamorphic terrane of the Kerio-Turkwel Rivers drainage basin. Kaolinite and fine-grained iron oxides are brought into the lake mainly by the two large fluvial input systems: the Omo River in the North Sub-basin and the Kerio-Turkwel Rivers in the Central Sub-basin. Some fine-grained overflow of this material makes its way into the South Sub-basin. Illite in the North and Central Sub-basins is strongly related to transport of material from near-shore sediments and, in the Central Sub-basin and northern reaches of the South Sub-basin, from the Kerio and Turkwel Rivers input. Smectite and calcite are mainly authigenic. In the South Sub-basin, however, the relatively coarser detrital particles are derived from silt and sand-sized in situ biogenic (calcitic and siliceous) debris and ˦olian-transported particles from regions southeast of the lake. The ˦olian fraction accounts largely for the ubiquitous and distinct very fine sand size grade, and consists of quartz, feldspar and blue-green amphiboles.

  14. Hands-on Symmetry, Building and Using 3-D Crystal Models in Mineralogy

    NASA Astrophysics Data System (ADS)

    Cole, K.

    2002-12-01

    Symmetry has historically been the most difficult subject in mineralogy and because so much of the science of mineralogy and crystallography builds on the fundamentals of form and symmetry, it is essential students understand it well. I concluded in recent years that better manipulatives might hold the key to better student comprehension. Mineralogy lab exercises related to symmetry typically involve the use of line drawings of 3-D crystal shapes sometimes augmented with a selection of small wooden models. Many students find the line drawings difficult to envision as 3-D solids. This makes the leap to identifying symmetry elements almost impossible for them and very time consuming for the instructor. The few line drawings for which models were available to my students were readily understood. Following the purchase of a new chop saw, I discovered that it is easy to cut most crystal models from scrap lumber and spent two weeks calculating, cutting, and finishing wooden models. For each of the line drawings used in my symmetry labs two models were cut, 200 models total. Models were also cut to show form development, distorted growth, enantiomorphism, and twinning. The models were cut to a final size of 5 to 15 cm and can be written on with chalk. The large model size and chalkability allowed students to more easily identify, mark, and erase mirrors, axes, forms, etc. Use of these models resulted in 50% less lab time needed in teaching the concepts of symmetry and form and 75% less time for students to complete the exercises. Scores on the symmetry labs averaged 55% to 65% in 1999-2001. The Fall 2002 averages were 85% and the errors made were much more trivial in nature, a dramatic improvement indeed.

  15. Inhibition by Levorphanol and Related Drugs of Amino Acid Transport by Isolated Membrane Vesicles from Escherichia coli

    PubMed Central

    Holland, Mary J. C.; Simon, Eric J.

    1975-01-01

    Levorphanol inhibits the transport of the amino acids proline and lysine by cytoplasmic membrane vesicles derived from Escherichia coli. The degree of inhibition increases with increasing levorphanol concentration and ranges from 26% at 10−6 M levorphanol to 92% at 10−3 M levorphanol. The effect is independent of the energy source, since levorphanol inhibits proline uptake to the same extent in the presence of 20 mM d-lactate or 20 mM succinate and in the absence of an exogenous energy source. Levorphanol does not irreversibly alter the ability of membrane vesicles to transport proline, since incubation of membrane vesicles for 15 min in the presence of 0.25 mM levorphanol, a concentration which inhibits proline transport by more than 75%, has no effect on the rate of proline transport by these vesicles once the drug is removed. Both the maximum velocity and the Km of proline transport are modified by levorphanol, hence, the type of inhibition produced by levorphanol is mixed. The inhibitor constant (Ki) for levorphanol inhibition of proline transport is approximately 3 × 10−4 M. Membrane vesicles incubated in the presence of levorphanol accumulate much less proline at the steady state than do control vesicles. Furthermore, the addition of levorphanol to membrane vesicles preloaded to the steady state with proline produces a marked net efflux of proline. Levorphanol does not block either temperature-induced efflux or exchange of external proline with [14C]proline present in the intravesicular pool. Dextrorphan, the enantiomorph of levorphanol, and levallorphan, the N-allyl analogue of levorphanol, inhibit proline and lysine transport in a similar manner. Possible mechanisms of the effects of these drugs on cell membranes are discussed. PMID:1096802

  16. 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.

  17. 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

  18. Isolation and characterization of tyramine-producing Enterococcus faecium strains from red wine.

    PubMed

    Capozzi, Vittorio; Ladero, Victor; Beneduce, Luciano; Fernández, María; Alvarez, Miguel A; Benoit, Bach; Laurent, Barnavon; Grieco, Francesco; Spano, Giuseppe

    2011-05-01

    Enterococcus faecium strains were isolated from red wines undergoing malolactic fermentation and identified by comparison of their 16S rDNA gene sequences with those included in the GenEMBL Databases. The tyrosine decarboxylase gene was identified in all the strains analysed by PCR using gene-specific primers and the ability to produce tyramine in a synthetic media was analysed by RP-HPLC. Survival of an E. faecium strain was also evaluated in microvinification assays using two different musts with different ethanol concentrations (10% and 12% (v/v)). Tyramine production was monitored during the vinification trials. Our results suggest that E. faecium strains isolated from wine are able to produce tyramine and tolerate wine conditions following a pre-acidic stress.

  19. 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.

  20. 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.

  1. 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.

  2. ExCAPE-DB: an integrated large scale dataset facilitating Big Data analysis in chemogenomics.

    PubMed

    Sun, Jiangming; Jeliazkova, Nina; Chupakin, Vladimir; Golib-Dzib, Jose-Felipe; Engkvist, Ola; Carlsson, Lars; Wegner, Jörg; Ceulemans, Hugo; Georgiev, Ivan; Jeliazkov, Vedrin; Kochev, Nikolay; Ashby, Thomas J; Chen, Hongming

    2017-01-01

    Chemogenomics data generally refers to the activity data of chemical compounds on an array of protein targets and represents an important source of information for building in silico target prediction models. The increasing volume of chemogenomics data offers exciting opportunities to build models based on Big Data. Preparing a high quality data set is a vital step in realizing this goal and this work aims to compile such a comprehensive chemogenomics dataset. This dataset comprises over 70 million SAR data points from publicly available databases (PubChem and ChEMBL) including structure, target information and activity annotations. Our aspiration is to create a useful chemogenomics resource reflecting industry-scale data not only for building predictive models of in silico polypharmacology and off-target effects but also for the validation of cheminformatics approaches in general.

  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. 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.

  5. 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

  6. 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.

  7. The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog)

    PubMed Central

    MacArthur, Jacqueline; Bowler, Emily; Cerezo, Maria; Gil, Laurent; Hall, Peggy; Hastings, Emma; Junkins, Heather; McMahon, Aoife; Milano, Annalisa; Morales, Joannella; Pendlington, Zoe May; Welter, Danielle; Burdett, Tony; Hindorff, Lucia; Flicek, Paul; Cunningham, Fiona; Parkinson, Helen

    2017-01-01

    The NHGRI-EBI GWAS Catalog has provided data from published genome-wide association studies since 2008. In 2015, the database was redesigned and relocated to EMBL-EBI. The new infrastructure includes a new graphical user interface (www.ebi.ac.uk/gwas/), ontology supported search functionality and an improved curation interface. These developments have improved the data release frequency by increasing automation of curation and providing scaling improvements. The range of available Catalog data has also been extended with structured ancestry and recruitment information added for all studies. The infrastructure improvements also support scaling for larger arrays, exome and sequencing studies, allowing the Catalog to adapt to the needs of evolving study design, genotyping technologies and user needs in the future. PMID:27899670

  8. 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

  9. 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

  10. 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.

  11. Genetic and chemical characterization of a mutant that disrupts synthesis of the lipopolysaccharide core tetrasaccharide in Rhizobium leguminosarum.

    PubMed Central

    Allaway, D; Jeyaretnam, B; Carlson, R W; Poole, P S

    1996-01-01

    A 2-kb region that complements the Tn5-derived lipopolysaccharide (LPS) rough mutant Rhizobium leguminosarum RU301 was sequenced. Two open reading frames (ORFs) were identified. The first ORF (lpcA) is homologous to a family of bacterial sugar transferases involved in LPS core tetrasaccharide biosynthesis. ORF2 (lpcB), in which Tn5 transposed, has no significant homology to any DNA in the GenBank-EMBL databases. Chemical characterization of LPS produced by strain RU301 demonstrated that the 3-deoxy-D-manno-2-octulosonic acid (Kdo) residue which normally attaches the core tetrasaccharide to the O chain was missing, suggesting that IpcB may encode a CMP-Kdo:LPS Kdo transferase. PMID:8892852

  12. Sequence of the luxD gene encoding acyltransferase of the lux operon from Photobacterium leiognathi.

    PubMed

    Chao, Y F; Weng, S F; Lin, J W

    1993-04-15

    The nucleotide sequence of luxD (EMBL accession No. X65611), encoding acyltransferase (ACT), of the lux operon from Photobacterium leiognathi PL741 was determined, and the amino acid (aa) sequence was deduced. ACT is a component of the fatty acid reductase complex, which is responsible for converting fatty acid to aldehyde that serves as the substrate in the luciferase-catalyzed bioluminescent reactions. The protein has a calculated M(r) of 34,384 and comprises 305 aa residues. Alignment and comparison of the ACT of P. leiognathi with that of Vibrio fischeri ATCC7744, V. harveyi B392 and Xenorhabdus luminescens Hm shows that there is 66%, 59% and 61% aa identity, respectively.

  13. Nucleotide sequence of the luxC gene encoding fatty acid reductase of the lux operon from Photobacterium leiognathi.

    PubMed

    Lin, J W; Chao, Y F; Weng, S F

    1993-02-26

    The nucleotide sequence of the luxC gene (EMBL Accession No. 65156) encoding fatty acid reductase (FAR) of the lux operon from Photobacterium leiognathi PL741 was determined and the encoded amino acid sequence deduced. The fatty acid reductase is a component of the fatty acid reductase complex. The complex is responsible for converting fatty acid to aldehyde which serves as the substrate in the luciferase-catalyzed bioluminescent reaction. The protein comprises 478 amino acid residues and has a calculated M(r) of 53,858. Alignment and comparison of the fatty acid reductase of P. leiognathi with that of Vibrio harveyi B392 and Vibrio fischeri ATCC 7744 shows that there is 70% and 59% amino acid residues identity, respectively.

  14. 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.

  15. A desirability function-based scoring scheme for selecting fragment-like class A aminergic GPCR ligands

    NASA Astrophysics Data System (ADS)

    Kelemen, Ádám A.; Ferenczy, György G.; Keserű, György M.

    2015-01-01

    A physicochemical property-based desirability scoring scheme for fragment-based drug discovery was developed for class A aminergic GPCR targeted fragment libraries. Physicochemical property distributions of known aminergic GPCR-active fragments from the ChEMBL database were examined and used for a desirability function-based score. Property-distributions such as log D (at pH 7.4), PSA, pKa (strongest basic center), number of nitrogen atoms, number of oxygen atoms, and the number of rotatable bonds were combined into a desirability score (FrAGS). The validation of the scoring scheme was carried out using both public and proprietary experimental screening data. The scoring scheme is suitable for the design of aminergic GPCR targeted fragment libraries and might be useful for preprocessing fragments before structure based virtual or wet screening.

  16. 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.

  17. QSAR modeling and chemical space analysis of antimalarial compounds.

    PubMed

    Sidorov, Pavel; Viira, Birgit; Davioud-Charvet, Elisabeth; Maran, Uko; Marcou, Gilles; Horvath, Dragos; Varnek, Alexandre

    2017-04-03

    Generative topographic mapping (GTM) has been used to visualize and analyze the chemical space of antimalarial compounds as well as to build predictive models linking structure of molecules with their antimalarial activity. For this, a database, including ~3000 molecules tested in one or several of 17 anti-Plasmodium activity assessment protocols, has been compiled by assembling experimental data from in-house and ChEMBL databases. GTM classification models built on subsets corresponding to individual bioassays perform similarly to the earlier reported SVM models. Zones preferentially populated by active and inactive molecules, respectively, clearly emerge in the class landscapes supported by the GTM model. Their analysis resulted in identification of privileged structural motifs of potential antimalarial compounds. Projection of marketed antimalarial drugs on this map allowed us to delineate several areas in the chemical space corresponding to different mechanisms of antimalarial activity. This helped us to make a suggestion about the mode of action of the molecules populating these zones.

  18. 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)

  19. 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).

  20. 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.

  1. 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.

  2. STITCH: interaction networks of chemicals and proteins

    PubMed Central

    Kuhn, Michael; von Mering, Christian; Campillos, Monica; Jensen, Lars Juhl; Bork, Peer

    2008-01-01

    The knowledge about interactions between proteins and small molecules is essential for the understanding of molecular and cellular functions. However, information on such interactions is widely dispersed across numerous databases and the literature. To facilitate access to this data, STITCH (‘search tool for interactions of chemicals’) integrates information about interactions from metabolic pathways, crystal structures, binding experiments and drug–target relationships. Inferred information from phenotypic effects, text mining and chemical structure similarity is used to predict relations between chemicals. STITCH further allows exploring the network of chemical relations, also in the context of associated binding proteins. Each proposed interaction can be traced back to the original data sources. Our database contains interaction information for over 68 000 different chemicals, including 2200 drugs, and connects them to 1.5 million genes across 373 genomes and their interactions contained in the STRING database. STITCH is available at http://stitch.embl.de/ PMID:18084021

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

    PubMed

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

    2015-06-01

    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.

  4. Exploiting open data: a new era in pharmacoinformatics.

    PubMed

    Goldmann, Daria; Montanari, Floriane; Richter, Lars; Zdrazil, Barbara; Ecker, Gerhard F

    2014-04-01

    Within the last decade open data concepts has been gaining increasing interest in the area of drug discovery. With the launch of ChEMBL and PubChem, an enormous amount of bioactivity data was made easily accessible to the public domain. In addition, platforms that semantically integrate those data, such as the Open PHACTS Discovery Platform, permit querying across different domains of open life science data beyond the concept of ligand-target-pharmacology. However, most public databases are compiled from literature sources and are thus heterogeneous in their coverage. In addition, assay descriptions are not uniform and most often lack relevant information in the primary literature and, consequently, in databases. This raises the question how useful large public data sources are for deriving computational models. In this perspective, we highlight selected open-source initiatives and outline the possibilities and also the limitations when exploiting this huge amount of bioactivity data.

  5. Status of the crystallography beamlines at PETRA III

    NASA Astrophysics Data System (ADS)

    Burkhardt, Anja; Pakendorf, Tim; Reime, Bernd; Meyer, Jan; Fischer, Pontus; Stübe, Nicolas; Panneerselvam, Saravanan; Lorbeer, Olga; Stachnik, Karolina; Warmer, Martin; Rödig, Philip; Göries, Dennis; Meents, Alke

    2016-03-01

    Since 2013, three beamlines for macromolecular crystallography are available to users at the third-generation synchrotron PETRA III in Hamburg: P11, P13 and P14, the latter two operated by EMBL. Beamline P11 is operated by DESY and is equipped with a Pilatus 6M detector. Together with the photon flux of 2× 10^{13} ph/s provided by the very brilliant X-ray source of PETRA III, a full data set can be typically collected in less than 2min. P11 provides state-of-the-art microfocusing capabilities with beam sizes down to 1× 1 μ m2, which makes the beamline ideally suited for investigation of microcrystals and serial crystallography experiments. An automatic sample changer allows fast sample exchange in less than 20s, which enables high-throughput crystallography and fast crystal screening. For sample preparation, an S2 biosafety laboratory is available in close proximity to the beamline.

  6. A side effect resource to capture phenotypic effects of drugs

    PubMed Central

    Kuhn, Michael; Campillos, Monica; Letunic, Ivica; Jensen, Lars Juhl; Bork, Peer

    2010-01-01

    The molecular understanding of phenotypes caused by drugs in humans is essential for elucidating mechanisms of action and for developing personalized medicines. Side effects of drugs (also known as adverse drug reactions) are an important source of human phenotypic information, but so far research on this topic has been hampered by insufficient accessibility of data. Consequently, we have developed a public, computer-readable side effect resource (SIDER) that connects 888 drugs to 1450 side effect terms. It contains information on frequency in patients for one-third of the drug–side effect pairs. For 199 drugs, the side effect frequency of placebo administration could also be extracted. We illustrate the potential of SIDER with a number of analyses. The resource is freely available for academic research at http://sideeffects.embl.de. PMID:20087340

  7. Primer design for identifying economically important Liriomyza species (Diptera: Agromyzidae) by multiplex PCR.

    PubMed

    Nakamura, Shigeo; Masuda, Toshio; Mochizuki, Atsushi; Konishi, Kazuhiko; Tokumaru, Susumu; Ueno, Keiichiro; Yamaguchi, Takuhiro

    2013-01-01

    Leafminer flies, especially, Liriomyza huidobrensis, Liriomyza sativae and Liriomyza trifolii, are quarantine species in many countries. Their morphological similarity makes identification difficult. To develop a rapid, reliable, sensitive and simple molecular identification method using multiplex PCR, we newly sequenced the mitochondrial cytochrome oxidase I (COI) genes of Liriomyza bryoniae, Liriomyza chinensis, L. huidobrensis, L. sativae, L. trifolii, Chromatomyia horticola and four parasitoid species. We aligned them with all the COI sequences of the leafminer flies found in the international DNA nucleotide sequence databases (DDBJ/EMBL/GenBank). We then designed species-specific primers to allow us to differentiate between L. bryoniae, L. chinensis, L. huidobrensis, L. sativae, and L. trifolii.

  8. 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

  9. Computing fuzzy associations for the analysis of biological literature.

    PubMed

    Perez-Iratxeta, Carolina; Keer, Harindar S; Bork, Peer; Andrade, Miguel A

    2002-06-01

    The increase of information in biology makes it difficult for researchers in any field to keep current with the literature. The MEDLINE database of scientific abstracts can be quickly scanned using electronic mechanisms. Potentially interesting abstracts can be selected by matching words joined by Boolean operators. However this means of selecting documents is not optimal. Nonspecific queries have to be effected, resulting in large numbers of irrelevant abstracts that have to be manually scanned To facilitate this analysis, we have developed a system that compiles a summary of subjects and related documents on the results of a MEDLINE query. For this, we have applied a fuzzy binary relation formalism that deduces relations between words present in a set of abstracts preprocessed with a standard grammatical tagger. Those relations are used to derive ensembles of related words and their associated subsets of abstracts. The algorithm can be used publicly at http:// www.bork.embl-heidelberg.de/xplormed/.

  10. 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

  11. Sequence analysis of two cosmids from Schizosaccharomyces pombe chromosome III.

    PubMed

    Lucas, M; Gwillam, R; Lepingle, A; Lyne, M; Rajandream, M A; Rochet, M; Wood, V; Gaillardin, C

    2000-12-01

    We report the complete sequence of two cosmids, SPCC895 (38457 bp insert, EMBL Accession No. AL035247) and SPCC1322 (42068 bp insert, EMBL Accession No. AL035259), localized on chromosome III of the Schizosaccharomyces pombe genome. Fourteen Coding DNA sequences (CDSs) were identified in SPCC895 and 17 in SPCC1322. Two known genes were found in each cosmid: map2 and gms1 on SPCC895, encoding the mating type P-factor precursor and an UDP-galactose transporter, respectively, and bub1 and ade6 in SPCC1322, encoding a protein kinase and a phosphoribosylaminoimidazole carboxylase, respectively. The fission yeast K RNA gene has been localized to SPCC895. Three ribosomal proteins have been predicted among these two cosmids. Nine CDSs similar to known proteins were found on SPCC895, and seven on SPCC1322. They include putative genes for an uridylate kinase, a proteasome catalytic component, an ion transporter, a checkpoint protein, a translation initiation protein, a SNARE complex protein, a protein involved in cytoskeletal organization, a spindle pole body-associating protein, pre-mRNA splicing factor RNA helicase, a 3'-5' exonuclease for RNA 3' ss-tail, an UTP-glucose-1-phosphate uridylyltransferase, a leukotriene A(4) hydrolase, a member of the RanBP7-importin beta-Cse1p superfamily, a Ca(++)-calmodulin-dependent serine/threonine protein kinase and a prohibitin antiproliferative protein. One CDS is predicted to be an integral membrane protein. One CDS from SPCC895 is similar to a CDS of unknown function from Saccharomyces cerevisiae and three from SPCC1322 are similar to CDSs of unknown function from Candida albicans, S. cerevisiae and Sz. pombe, respectively. Finally, one CDS of SPCC895 and three of SPCC1322 correspond to orphan genes.

  12. Annotation error in public databases: misannotation of molecular function in enzyme superfamilies.

    PubMed

    Schnoes, Alexandra M; Brown, Shoshana D; Dodevski, Igor; Babbitt, Patricia C

    2009-12-01

    Due to the rapid release of new data from genome sequencing projects, the majority of protein sequences in public databases have not been experimentally characterized; rather, sequences are annotated using computational analysis. The level of misannotation and the types of misannotation in large public databases are currently unknown and have not been analyzed in depth. We have investigated the misannotation levels for molecular function in four public protein sequence databases (UniProtKB/Swiss-Prot, GenBank NR, UniProtKB/TrEMBL, and KEGG) for a model set of 37 enzyme families for which extensive experimental information is available. The manually curated database Swiss-Prot shows the lowest annotation error levels (close to 0% for most families); the two other protein sequence databases (GenBank NR and TrEMBL) and the protein sequences in the KEGG pathways database exhibit similar and surprisingly high levels of misannotation that average 5%-63% across the six superfamilies studied. For 10 of the 37 families examined, the level of misannotation in one or more of these databases is >80%. Examination of the NR database over time shows that misannotation has increased from 1993 to 2005. The types of misannotation that were found fall into several categories, most associated with "overprediction" of molecular function. These results suggest that misannotation in enzyme superfamilies containing multiple families that catalyze different reactions is a larger problem than has been recognized. Strategies are suggested for addressing some of the systematic problems contributing to these high levels of misannotation.

  13. 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.

  14. 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

  15. Cryptococcus lacticolor sp. nov. and Rhodotorula oligophaga sp. nov., novel yeasts isolated from the nasal smear microbiota of Queensland koalas kept in Japanese zoological parks.

    PubMed

    Satoh, Kazuo; Maeda, Mari; Umeda, Yoshiko; Sugamata, Miho; Makimura, Koichi

    2013-07-01

    A total of 515 yeast strains were isolated from the nasal smears of Queensland koalas and their breeding environments in Japanese zoological parks between 2005 and 2012. The most frequent species in the basidiomycetous yeast biota isolated from koala nasal passages was Cryptococcus neoformans, followed by Rhodotorula minuta. R. minuta was the most frequent species in the breeding environments, while C. neoformans was rare. Seven strains representing two novel yeast species were identified. Analyses of the 26S rDNA (LSU) D1/D2 domain and nuclear ribosomal DNA internal transcribed spacer region sequences indicated that these strains represent new species with close phylogenetic relationships to Cryptococcus and Rhodotorula. A sexual state was not found for either of these two novel yeasts. Key phenotypic characters confirmed that these strains could be placed in Cryptococcus and Rhodotorula. The names Cryptococcus lacticolor sp. nov. (type strain TIMM 10013(T) = JCM 15449(T) = CBS 10915(T) = DSM 21093(T), DDBJ/EMBL/Genbank Accession No.; AB375774 (ITS) and AB375775 (26S rDNA D1/D2 region), MycoBank ID; MB 802688, Fungal Barcoding Database ID; 3174), and Rhodotorula oligophaga sp. nov. (type strain TIMM 10017(T) = JCM 18398(T) = CBS 12623(T) = DSM 25814(T), DDBJ/EMBL/Genbank Accession No.; AB702967 (ITS) and AB702967 (26S rDNA D1/D2 region), MycoBank ID; MB 802689, Fungal Barcoding Database ID; 3175) are proposed for these new species.

  16. 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.

  17. QSAR Modeling Using Large-Scale Databases: Case Study for HIV-1 Reverse Transcriptase Inhibitors.

    PubMed

    Tarasova, Olga A; Urusova, Aleksandra F; Filimonov, Dmitry A; Nicklaus, Marc C; Zakharov, Alexey V; Poroikov, Vladimir V

    2015-07-27

    Large-scale databases are important sources of training sets for various QSAR modeling approaches. Generally, these databases contain information extracted from different sources. This variety of sources can produce inconsistency in the data, defined as sometimes widely diverging activity results for the same compound against the same target. Because such inconsistency can reduce the accuracy of predictive models built from these data, we are addressing the question of how best to use data from publicly and commercially accessible databases to create accurate and predictive QSAR models. We investigate the suitability of commercially and publicly available databases to QSAR modeling of antiviral activity (HIV-1 reverse transcriptase (RT) inhibition). We present several methods for the creation of modeling (i.e., training and test) sets from two, either commercially or freely available, databases: Thomson Reuters Integrity and ChEMBL. We found that the typical predictivities of QSAR models obtained using these different modeling set compilation methods differ significantly from each other. The best results were obtained using training sets compiled for compounds tested using only one method and material (i.e., a specific type of biological assay). Compound sets aggregated by target only typically yielded poorly predictive models. We discuss the possibility of "mix-and-matching" assay data across aggregating databases such as ChEMBL and Integrity and their current severe limitations for this purpose. One of them is the general lack of complete and semantic/computer-parsable descriptions of assay methodology carried by these databases that would allow one to determine mix-and-matchability of result sets at the assay level.

  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. Secondary neoplasms after radiotherapy for a childhood solid tumor.

    PubMed

    Paulino, Arnold C; Fowler, B Zach

    2005-03-01

    This study was conducted to determine the outcome of patients who develop a second neoplasm after radiotherapy (RT) for a childhood solid tumor. From 1956 to 1998, 429 children with a malignant solid tumor were treated at a single radiation oncology facility. The medical records and radiotherapy charts were reviewed to determine if the patient developed a secondary neoplasm after treatment for malignancy. Twenty-three (5.4%) patients developed a secondary neoplasm. There were 12 males and 11 females with a median age at RT of 6.6 years (range, 2 months to 20 years). There were 14 malignant neoplasms in 13 (3.0%) and 14 benign neoplasms in 11 patients (2.6%). The types of initial solid tumors treated with RT were Ewing sarcoma in 6, Wilms tumor in 6, medulloblastoma in 5, neuroblastoma in 3, and other in 3. Median RT dose was 45 Gy (range, 12.3 to 60 Gy) using 4 MV in 9, 1.25 MV in 8, 250 KV in 4, and 6 MV photons in 1 patient. One child was treated using 15-MeV electrons. Fourteen had chemotherapy. Median follow-up was 23.2 years (range, 5.3 to 44.4 years). For the 14 malignant neoplasms, the median time interval from initial tumor to second malignancy was 10.1 years. The 14 second malignant neoplasms (SMN) were osteosarcoma in 3, breast carcinoma in 2, melanoma in 2, malignant fibrous histiocytoma in 1, dermatofibrosarcoma in 1, leiomyosarcoma in 1, mucoepidermoid carcinoma in 1, colon cancer in 1, chronic myelogenous leukemia in 1, and basal cell carcinoma in 1. Ten of the 14 SMN (71%) were at the edge or inside the RT field. The 5- and 10-year overall survival rate after diagnosis of an SMN was 69.2%; it was 70% for children with a SMN at the edge or inside the RT field and 66.7% for those outside of the RT field. The 14 benign neoplasms appeared at a median time of 16.9 years and included cervical intraepithelial neoplasia in 3, osteochondroma in 3, thyroid adenoma in 1, duodenal adenoma in 1, lipoma in 1, cherry angioma in 1, uterine leiomyoma in 1, ovarian

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

    PubMed Central

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

    2006-01-01

    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° 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 matrix of

  1. Cleavage of the peptide bond of beta-alanyl-L-histidine (carnosine) induced by a Co(III)-amine complexes: reaction, structure and mechanism.

    PubMed

    Saha, Manas K; Mukhopadhyay, Uday; Bernal, Ivan

    2004-05-07

    Cleavage of the peptide bond occurs when beta]-alanyl-L-histidine (carnosine) reacts with [Co(tren)Cl2]+ (tren = tris(2-aminoethyl)amine) to give [Co(tren)(histidine)](2+) 1 and [Co(tren)(beta-alanine)](2+) 2. [Co(tren)(histidine)](2+) 1 crystallizes in the enantiomorphic space group P2(1)2(1)2(1) and 2 crystallizes in the P2(1)/c space group. The mechanism of the cleavage reactions were studied in detail for the precursor [Co(tren)Cl2]+ and [Co(trien)Cl2]+, which convert into [Co(tren)(OH)2]+/[Co(tren)(OH)(OH2)]2+ and [Co(trien)(OH)2]+/[Co(trien)(OH)(OH2)]2+ in water at basic pH (trien = 1,4,7,10-tetraazadecane). At a slightly basic pH, the initial coordination of the substrate (beta-alanyl-L-histidine) is by the carboxylate group for the reaction with [Co(tren)Cl2]+. This is followed by a rate-limiting nucleophilic attack of the hydroxide group at the beta-alanyl-L-histidine carbonyl group. In a strongly basic reaction medium substrate, binding of the metal was through carboxylate and amine terminals. On the other hand, for the reaction between [cis-beta-Co(trien)Cl2]+ and beta-alanyl-L-histidine, the initial coordination of the substrate takes place via an imidazole ring nitrogen, independently, and followed by a nucleophilic attack of the hydroxide group at the beta-alanyl-L-histidine carbonyl group. The circular dichroism spectrum for 1 suggests that a very small extent of racemization of the amino acid (L-histidine) takes place during the cleavage reaction between [Co(tren)Cl2]+ and beta-alanyl-L-histidine. Reaction between [cis-beta-Co(trien)Cl2]+ and beta-alanyl-L-histidine also causes cleavage of the peptide bond, producing a free beta-alanyl molecule and a cationic fragment [cis-alpha-Co(trien)(histidine)](2+) 3 that crystallizes in the optically active space group P2(1)2(1)2(1). Unlike the previous case an appreciable degree of racemization of the L-histidine takes place during the reaction between [cis-beta-Co(trien)Cl2]+ and beta

  2. Molecular mechanism of uncompetitive inhibition of human placental and germ-cell alkaline phosphatase.

    PubMed Central

    Hoylaerts, M F; Manes, T; Millán, J L

    1992-01-01

    Placental (PLAP) and germ-cell (GCAP) alkaline phosphatases are inhibited uncompetitively by L-Leu and L-Phe. Whereas L-Phe inhibits PLAP and GCAP to the same extent, L-Leu inhibits GCAP 17-fold more strongly than it does PLAP. This difference has been attributed [Hummer & Millán (1991) Biochem. J 274, 91-95] to a Glu----Gly substitution at position 429 in GCAP. The D-Phe and D-Leu enantiomorphs are also inhibitory through an uncompetitive mechanism but with greatly decreased efficiencies. Replacement of the active-site residue Arg-166 by Ala-166 changes the inhibition mechanism of the resulting PLAP mutant to a more complex mixed-type inhibition, with decreased affinities for L-Leu and L-Phe. The uncompetitive mechanism is restored on the simultaneous introduction of Gly-429 in the Ala-166 mutant, but the inhibitions of [Ala166,Gly429]PLAP and even [Lys166,Gly429]PLAP by L-Leu and L-Phe are considerably decreased compared with that of [Gly429]PLAP. These findings point to the importance of Arg-166 during inhibition. Active-site binding of L-Leu requires the presence of covalently bound phosphate in the active-site pocket, and the inhibition of PLAP by L-Leu is pH-sensitive, gradually disappearing when the pH is decreased from 10.5 to 7.5. Our data are compatible with the following molecular model for the uncompetitive inhibition of PLAP and GCAP by L-Phe and L-Leu: after binding of a phosphorylated substrate to the active site, the guanidinium group of Arg-166 (normally involved in positioning phosphate) is redirected to the carboxy group of L-Leu (or L-Phe), thus stabilizing the inhibitor in the active site. Therefore leucinamide and leucinol are weaker inhibitors of [Gly429]PLAP than is L-Leu. During this Arg-166-regulated event, the amino acid side group is positioned in the loop containing Glu-429 or Gly-429, leading to further stabilization. Replacement of Glu-429 by Gly-429 eliminates steric constraints experienced by the bulky L-Leu side group during its

  3. 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.

  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. Nuclear receptors, nuclear-receptor factors, and nuclear-receptor-like orphans form a large paralog cluster in Homo sapiens.

    PubMed

    Garcia-Vallvé, S; Palau, J

    1998-06-01

    We studied a human protein paralog cluster formed by 38 nonredundant sequences taken from the Swiss-Prot database and its supplement, TrEMBL. These sequences include nuclear receptors, nuclear-receptor factors and nuclear-receptor-like orphans. Working separately with both the central cysteine-rich DNA-binding domain and the carboxy-terminal ligand-binding domain, we performed multialignment analyses that included drawings of paralog trees. Our results show that the cluster is highly multibranched, with considerable differences in the amino acid sequence in the ligand-binding domain (LBD), and 17 proximal subbranches which are identifiable and fully coincident when independent trees from both domains are compared. We identified the six recently proposed subfamilies as groups of neighboring clusters in the LBD paralog tree. We found similarities of 80%-100% for the N-terminal transactivation domain among mammalian ortholog receptors, as well as some paralog resemblances within diverse subbranches. Our studies suggest that during the evolutionary process, the three domains were assembled in a modular fashion with a nonshuffled modular fusion of the LBD. We used the EMBL server PredictProtein to make secondary-structure predictions for all 38 LBD subsequences. Amino acid residues in the multialigned homologous domains--taking the beginning of helix H3 of the human retinoic acid receptor-gamma as the initial point of reference--were substituted with H or E, which identify residues predicted to be helical or extended, respectively. The result was a secondary structure multialignment with the surprising feature that the prediction follows a canonical pattern of alignable alpha-helices with some short extended elements in between, despite the fact that a number of subsequences resemble each other by less than 25% in terms of the similarity index. We also identified the presence of a binary patterning in all of the predicted helices that were conserved throughout the 38

  6. 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

  7. Training based on ligand efficiency improves prediction of bioactivities of ligands and drug target proteins in a machine learning approach.

    PubMed

    Sugaya, Nobuyoshi

    2013-10-28

    Machine learning methods based on ligand-protein interaction data in bioactivity databases are one of the current strategies for efficiently finding novel lead compounds as the first step in the drug discovery process. Although previous machine learning studies have succeeded in predicting novel ligand-protein interactions with high performance, all of the previous studies to date have been heavily dependent on the simple use of raw bioactivity data of ligand potencies measured by IC50, EC50, K(i), and K(d) deposited in databases. ChEMBL provides us with a unique opportunity to investigate whether a machine-learning-based classifier created by reflecting ligand efficiency other than the IC50, EC50, K(i), and Kd values can also offer high predictive performance. Here we report that classifiers created from training data based on ligand efficiency show higher performance than those from data based on IC50 or K(i) values. Utilizing GPCRSARfari and KinaseSARfari databases in ChEMBL, we created IC50- or K(i)-based training data and binding efficiency index (BEI) based training data then constructed classifiers using support vector machines (SVMs). The SVM classifiers from the BEI-based training data showed slightly higher area under curve (AUC), accuracy, sensitivity, and specificity in the cross-validation tests. Application of the classifiers to the validation data demonstrated that the AUCs and specificities of the BEI-based classifiers dramatically increased in comparison with the IC50- or K(i)-based classifiers. The improvement of the predictive power by the BEI-based classifiers can be attributed to (i) the more separated distributions of positives and negatives, (ii) the higher diversity of negatives in the BEI-based training data in a feature space of SVMs, and (iii) a more balanced number of positives and negatives in the BEI-based training data. These results strongly suggest that training data based on ligand efficiency as well as data based on classical IC50

  8. 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

  9. 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

  10. Identifying native-like protein structures using physics-based potentials.

    PubMed

    Dominy, Brian N; Brooks, Charles L

    2002-01-15

    As the field of structural genomics matures, new methods will be required that can accurately and rapidly distinguish reliable structure predictions from those that are more dubious. We present a method based on the CHARMM gas phase implicit hydrogen force field in conjunction with a generalized Born implicit solvation term that allows one to make such discrimination. We begin by analyzing pairs of threaded structures from the EMBL database, and find that it is possible to identify the misfolded structures with over 90% accuracy. Further, we find that misfolded states are generally favored by the solvation term due to the mispairing of favorable intramolecular ionic contacts. We also examine 29 sets of 29 misfolded globin sequences from Levitt's "Decoys 'R' Us" database generated using a sequence homology-based method. Again, we find that discrimination is possible with approximately 90% accuracy. Also, even in these less distorted structures, mispairing of ionic contacts results in a more favorable solvation energy for misfolded states. This is also found to be the case for collapsed, partially folded conformations of CspA and protein G taken from folding free energy calculations. We also find that the inclusion of the generalized Born solvation term, in postprocess energy evaluation, improves the correlation between structural similarity and energy in the globin database. This significantly improves the reliability of the hypothesis that more energetically favorable structures are also more similar to the native conformation. Additionally, we examine seven extensive collections of misfolded structures created by Park and Levitt using a four-state reduced model also contained in the "Decoys 'R' Us" database. Results from these large databases confirm those obtained in the EMBL and misfolded globin databases concerning predictive accuracy, the energetic advantage of misfolded proteins regarding the solvation component, and the improved correlation between energy

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. IMGT, the international ImMunoGeneTics database.

    PubMed Central

    Giudicelli, V; Chaume, D; Bodmer, J; Müller, W; Busin, C; Marsh, S; Bontrop, R; Marc, L; Malik, A; Lefranc, M P

    1997-01-01

    IMGT, the international ImMunoGeneTics database, is an integrated database specializing in immunoglobulins, T-cell receptors (TcR) and major histocompatibility complex (MHC) of all vertebrate species, initiated and co-ordinated by Marie-Paule Lefranc, CNRS, Montpellier II University, Montpellier, France (lefranc@ligm.crbm.cnrs-mop.fr). IMGT includes two databases: LIGM-DB (for immunoglobulins and TcR) and MHC/HLA-DB. IMGT comprises expertly annotated sequences and alignment tables. LIGM-DB contains more than 19 000 immunoglobulin and TcR sequences from 78 species. MHC/HLA-DB contains class I and class II human leukocyte antigen alignment tables. An IMGT tool, DNAPLOT, developed for immunoglobulins, TcR and MHC sequence alignments, is also available. IMGT works in close collaboration with the EMBL database. IMGT goals are to establish a common data access to all immunogenetics data, including sequences, oligonucleotide primers, gene maps and other genetic data of immunoglobulins, TcR and MHC molecules, and to provide a graphical user-friendly data access. IMGT will have important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas), therapeutical approaches (antibody engineering), genome diversity and genome evolution studies. IMGT can be accessed at http://imgt.cnusc.fr:8104 and http://www.ebi.ac.uk/IMGT PMID:9016537

  16. Compilation and physicochemical classification analysis of a diverse hERG inhibition database

    NASA Astrophysics Data System (ADS)

    Didziapetris, Remigijus; Lanevskij, Kiril

    2016-12-01

    A large and chemically diverse hERG inhibition data set comprised of 6690 compounds was constructed on the basis of ChEMBL bioactivity database and original publications dealing with experimental determination of hERG activities using patch-clamp and competitive displacement assays. The collected data were converted to binary format at 10 µM activity threshold and subjected to gradient boosting machine classification analysis using a minimal set of physicochemical and topological descriptors. The tested parameters involved lipophilicity (log P), ionization (p K a ), polar surface area, aromaticity, molecular size and flexibility. The employed approach allowed classifying the compounds with an overall 75-80 % accuracy, even though it only accounted for non-specific interactions between hERG and ligand molecules. The observed descriptor-response profiles were consistent with common knowledge about hERG ligand binding site, but also revealed several important quantitative trends, as well as slight inter-assay variability in hERG inhibition data. The results suggest that even weakly basic groups (p K a < 6) might substantially contribute to hERG inhibition potential, whereas the role of lipophilicity depends on the compound's ionization state, and the influence of log P decreases in the order of bases > zwitterions > neutrals > acids. Given its robust performance and clear physicochemical interpretation, the proposed model may provide valuable information to direct drug discovery efforts towards compounds with reduced risk of hERG-related cardiotoxicity.

  17. 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.

  18. STITCH 4: integration of protein-chemical interactions with user data.

    PubMed

    Kuhn, Michael; Szklarczyk, Damian; Pletscher-Frankild, Sune; Blicher, Thomas H; von Mering, Christian; Jensen, Lars J; Bork, Peer

    2014-01-01

    STITCH is a database of protein-chemical interactions that integrates many sources of experimental and manually curated evidence with text-mining information and interaction predictions. Available at http://stitch.embl.de, the resulting interaction network includes 390 000 chemicals and 3.6 million proteins from 1133 organisms. Compared with the previous version, the number of high-confidence protein-chemical interactions in human has increased by 45%, to 367 000. In this version, we added features for users to upload their own data to STITCH in the form of internal identifiers, chemical structures or quantitative data. For example, a user can now upload a spreadsheet with screening hits to easily check which interactions are already known. To increase the coverage of STITCH, we expanded the text mining to include full-text articles and added a prediction method based on chemical structures. We further changed our scheme for transferring interactions between species to rely on orthology rather than protein similarity. This improves the performance within protein families, where scores are now transferred only to orthologous proteins, but not to paralogous proteins. STITCH can be accessed with a web-interface, an API and downloadable files.

  19. 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

    SciTech Connect

    Von Lindern, M.; Fornerod, M.; Van Baal, S.; Jaegle, M.; De Wit, T.; Buijs, A.; Grosveld, G. )

    1992-04-01

    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. 50 refs., 8 figs.

  20. Histidine biosynthesis genes in Lactococcus lactis subsp. lactis.

    PubMed Central

    Delorme, C; Ehrlich, S D; Renault, P

    1992-01-01

    The genes of Lactococcus lactis subsp. lactis involved in histidine biosynthesis were cloned and characterized by complementation of Escherichia coli and Bacillus subtilis mutants and DNA sequencing. Complementation of E. coli hisA, hisB, hisC, hisD, hisF, hisG, and hisIE genes and the B. subtilis hisH gene (the E. coli hisC equivalent) allowed localization of the corresponding lactococcal genes. Nucleotide sequence analysis of the 11.5-kb lactococcal region revealed 14 open reading frames (ORFs), 12 of which might form an operon. The putative operon includes eight ORFs which encode proteins homologous to enzymes involved in histidine biosynthesis. The operon also contains (i) an ORF encoding a protein homologous to the histidyl-tRNA synthetases but lacking a motif implicated in synthetase activity, which suggests that it has a role different from tRNA aminoacylation, and (ii) an ORF encoding a protein that is homologous to the 3'-aminoglycoside phosphotransferases but does not confer antibiotic resistance. The remaining ORFs specify products which have no homology with proteins in the EMBL and GenBank data bases. PMID:1400209

  1. The Complete Mitochondrial Genome of Yarrowia Lipolytica

    PubMed Central

    Durstewitz, Gregor; Casaregola, Serge; Gaillardin, Claude; Brandt, Ulrich

    2001-01-01

    We here report the complete nucleotide sequence of the 47.9 kb mitochondrial (mt) genome from the obligate aerobic yeast Yarrowia lipolytica. It encodes, all on the same strand, seven subunits of NADH: ubiquinone oxidoreductase (ND1-6, ND4L), apocytochrome b (COB), three subunits of cytochrome oxidase (COX1, 2, 3), three subunits of ATP synthetase (ATP6, 8 and 9), small and large ribosomal RNAs and an incomplete set of tRNAs. The Y. lipolytica mt genome is very similar to the Hansenula wingei mt genome, as judged from blocks of conserved gene order and from sequence homology. The extra DNA in the Y. lipolytica mt genome consists of 17 group 1 introns and stretches of A+Trich sequence, interspersed with potentially transposable GC clusters. The usual mould mt genetic code is used. Interestingly, there is no tRNA able to read CGN (arginine) codons. CGN codons could not be found in exonic open reading frames, whereas they do occur in intronic open reading frames. However, several of the intronic open reading frames have accumulated mutations and must be regarded as pseudogenes. We propose that this may have been triggered by the presence of untranslatable CGN codons. This sequence is available under EMBL Accession No. AJ307410. PMID:18628906

  2. Isolation and identification of a novel tandemly repeated DNA sequence in the centromeric region of human chromosome 8.

    PubMed

    Lin, C C; Sasi, R; Lee, C; Fan, Y S; Court, D

    1993-05-01

    EcoRI subclones, designated as 50E1 and 50E4, were independently obtained from a cosmid clone previously mapped to the centromeric region of human chromosome 8. Southern blot hybridization analyses suggested that both subclones contain repetitive DNA sequences different from the chromosome 8 specific alphoid DNA. DNA sequence analysis of the 704 bp insert of 50E1 and the 1,962 bp insert of 50E4 revealed that both inserts contained tandemly repeated units of approximately 220 bp. Fluorescence in situ hybridization studies confirmed these two subclones to be specifically located on the centromeric region of chromosome 8. A 220 bp consensus sequence, derived from nine monomeric repeats, showed no significant homology to alphoid consensus sequences or to other currently known human centromeric DNA sequence. Furthermore, no significant homology was found with any other DNA sequence deposited in the EMBL or GenBank databases, indicating that this chromosome 8 specific repetitive DNA sequence is novel. From slot blot experiments it was estimated that 0.013% of the human genome comprises 1,750 of these monomeric repeats, residing on the centromeric region of chromosome 8 in tandem array(s).

  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.

  4. Molecular characterization and evaluation of plant litter-associated fungi from the spring 'grazing corridor' of a sheep herd vulnerable to alveld disease.

    PubMed

    Mysterud, Ivar; Høiland, Klaus; Koller, Gry; Stensrud, Øyvind

    2007-11-01

    This study sample and identify species of fungi on withered vegetation in the spring 'grazing corridor' from infields to Narthecium bogs for a sheep herd almost chronically vulnerable to phototoxic disease. Hepatogen photosensitizing disorders like alveld attack grazing sheep, especially lambs, in various parts of the world. It has been hypothesized that saponin metabolites in the monocotyledonous plant Narthecium ossifragum causes the disorder in Norway, however, this has not been verified. Thus, the search for other causal agents or saponin cofactors (the cofactor hypothesis) has been intensified, and endophytic poisonous fungi associated with dead N. ossifragum leaves and grasses are among the prime suspects. The fungal diversity was targeted by obtaining axenic cultures from surface-sterilized plant material, with subsequent DNA isolation, PCR, and sequencing of the ITS nrDNA region. The taxonomic affinities of the obtained sequences were thereafter explored by similarity searches against the public access sequence database EMBL/GenBank/DDBJ. Among the spectrum of identified taxa were representatives of Cladosporium, Fusarium, Penicillium, and Trichoderma, all of which are well known as potential producers of toxins. A possible involvement of these toxic species in the etiology of alveld is evaluated and discussed.

  5. [Diversity of polyketide synthase genes (PKS) in metagenomic community of the freshwater sponge].

    PubMed

    Kaliuzhnaia, O V; Kulakova, N V; Itskovich, B V

    2012-01-01

    Screening of metagenomic DNA of microbial community, associated with Baikalian sponge Lubomirskia baicalensis, was made to show the presence of polyketide synthase genes (PKS). PKS enzymatic systems take part in synthesis of a great number of biologically-active substances. Cloning and sequencing of amplified products of the ketosynthase domain section of PKS gene cluster has revealed 15 fragments of PKS genes differing from each other's on 35-65% by aminoacid sequences. BLASTX analysis has shown that all these sequences belong to the KS-domains identified in various groups of microorganisms: alpha-, beta-, delta-Proteobacteria, Verrucomicrobia, Cyanobacteria, Chlorophyta. Some sequences were related to the genes which are taking part in biosynthesis of curacin A (CurI, CurJ), stigmatellin (StiC, StiG), nostophycin (NpnB), and cryptophycins (CrpB). The homology of the found sequences with those of the EMBL database varies within 50-82% confirming the presence in fresh-water sponge community the genes for synthesis of the new, yet not studied polyketide substances, possessing the biotechnological potential.

  6. 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.

  7. Prediction of Chemical-Protein Interactions Network with Weighted Network-Based Inference Method

    PubMed Central

    Cheng, Feixiong; Zhou, Yadi; Li, Weihua; Liu, Guixia; Tang, Yun

    2012-01-01

    Chemical-protein interaction (CPI) is the central topic of target identification and drug discovery. However, large scale determination of CPI is a big challenge for in vitro or in vivo experiments, while in silico prediction shows great advantages due to low cost and high accuracy. On the basis of our previous drug-target interaction prediction via network-based inference (NBI) method, we further developed node- and edge-weighted NBI methods for CPI prediction here. Two comprehensive CPI bipartite networks extracted from ChEMBL database were used to evaluate the methods, one containing 17,111 CPI pairs between 4,741 compounds and 97 G protein-coupled receptors, the other including 13,648 CPI pairs between 2,827 compounds and 206 kinases. The range of the area under receiver operating characteristic curves was 0.73 to 0.83 for the external validation sets, which confirmed the reliability of the prediction. The weak-interaction hypothesis in CPI network was identified by the edge-weighted NBI method. Moreover, to validate the methods, several candidate targets were predicted for five approved drugs, namely imatinib, dasatinib, sertindole, olanzapine and ziprasidone. The molecular hypotheses and experimental evidence for these predictions were further provided. These results confirmed that our methods have potential values in understanding molecular basis of drug polypharmacology and would be helpful for drug repositioning. PMID:22815915

  8. Design and generation of highly diverse fluorinated fragment libraries and their efficient screening with improved (19) F NMR methodology.

    PubMed

    Vulpetti, Anna; Dalvit, Claudio

    2013-12-01

    Fragment screening performed with (19) F NMR spectroscopy is becoming increasingly popular in drug discovery projects. With this approach, libraries of fluorinated fragments are first screened using the direct-mode format of the assay. The choice of fluorinated motifs present in the library is fundamental in order to ensure a large coverage of chemical space and local environment of fluorine (LEF). Mono- and poly-fluorinated fragments to be included in the libraries for screening are selected from both in-house and commercial collections, and those that are ad hoc designed and synthesized. Additional fluorinated motifs to be included in the libraries derive from the fragmentation of compounds in development and launched on the market, and compounds contained in other databases (such as Integrity, PDB and ChEMBL). Complex mixtures of highly diverse fluorine motifs can be rapidly screened and deconvoluted in the same NMR tube with a novel on the fly combined procedure for the identification of the active molecule(s). Issues and problems encountered in the design, generation and screening of diverse fragment libraries of fluorinated compounds with (19) F NMR spectroscopy are analyzed and technical solutions are provided to overcome them. The versatile screening methodology described here can be efficiently applied in laboratories with limited NMR setup and could potentially lead to the increasing role of (19) F NMR in the hit identification and lead optimization phases of drug discovery projects.

  9. Identification of genes associated with copper tolerance in an adhesion-defective mutant of Aeromonas veronii biovar sobria.

    PubMed

    Francki, K T; Chang, B J; Mee, B J; Collignon, P J; Susai, V; Keese, P K

    2000-10-01

    TnphoA mutagenesis was used to identify adhesins of Aeromonas veronii biovar sobria 3767, a strain isolated from a diarrhoeal stool specimen. Six mutants, from a library of 154, exhibited significantly reduced levels of adhesion to HEp-2 cells. Primers to the terminal regions of TnphoA were used for inverse PCR and the product from one mutant was cloned into pBluescript and partial sequence data obtained. Scanning GenBank and EMBL data bases revealed DNA sequence similarity to the copA gene of Pseudomonas syringae pv. tomato which confers resistance to copper and other heavy metals. The transposon was located within the copA gene and the mutant exhibited a reduced tolerance to copper. Primer walking, using the inverse PCR product as a template, revealed three open reading frames (ORFs) copA, B and C in A. veronii biovar sobria 3767. The predicted amino acid sequences of ORFs A and B had significant homology (55 and 34% respectively) to the copA and B proteins of P. syringae. No amino acid or DNA sequence homology existed between ORF C of strain 3767 and any other gene in the data bases scanned. Further analysis of the nucleotide sequence failed to reveal the presence of typical copper regulatory genes within the vicinity of the Aeromonas sequence. The association between copper tolerance and adhesion in A. veronii biovar sobria requires further study.

  10. The human DEPhOsphorylation database DEPOD: a 2015 update

    PubMed Central

    Duan, Guangyou; Li, Xun; Köhn, Maja

    2015-01-01

    Phosphatases are crucial enzymes in health and disease, but the knowledge of their biological roles is still limited. Identifying substrates continues to be a great challenge. To support the research on phosphatase–kinase–substrate networks we present here an update on the human DEPhOsphorylation Database: DEPOD (http://www.depod.org or http://www.koehn.embl.de/depod). DEPOD is a manually curated open access database providing human phosphatases, their protein and non-protein substrates, dephosphorylation sites, pathway involvements and external links to kinases and small molecule modulators. All internal data are fully searchable including a BLAST application. Since the first release, more human phosphatases and substrates, their associated signaling pathways (also from new sources), and interacting proteins for all phosphatases and protein substrates have been added into DEPOD. The user interface has been further optimized; for example, the interactive human phosphatase–substrate network contains now a ‘highlight node’ function for phosphatases, which includes the visualization of neighbors in the network. PMID:25332398

  11. 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.

  12. Reactome Pathway Analysis to Enrich Biological Discovery in Proteomics Datasets

    PubMed Central

    Haw, Robin; Hermjakob, Henning; D’Eustachio, Peter; Stein, Lincoln

    2012-01-01

    Reactome (http://www.reactome.org) is an open source, expert-authored, peer-reviewed, manually curated database of reactions, pathways and biological processes. We provide an intuitive web-based user interface to pathway knowledge and a suite of data analysis tools. The Pathway Browser is a Systems Biology Graphical Notation (SBGN)-like visualization system that supports manual navigation of pathways by zooming, scrolling and event highlighting, and that exploits PSI Common Query Interface (PSIQUIC) web services to overlay pathways with molecular interaction data from the Reactome Functional Interaction (FI) Network and interaction databases such as IntAct, ChEMBL, and BioGRID. Pathway and Expression Analysis tools employ web services to provide ID mapping, pathway assignment and over-representation analysis of user-supplied datasets. By applying Ensembl Compara to curated human proteins and reactions, Reactome generates pathway inferences for 20 other species. The Species Comparison tool provides a summary of results for each of these species as a table showing numbers of orthologous proteins found by pathway from which users can navigate to inferred details for specific proteins and reactions. Reactome’s diverse pathway knowledge and suite of data analysis tools provide a platform for data mining, modeling and the analysis of large-scale proteomics datasets. PMID:21751369

  13. High polymorphism in Plasmodium vivax merozoite surface protein-5 (MSP5).

    PubMed

    Gomez, A; Suarez, C F; Martinez, P; Saravia, C; Patarroyo, M A

    2006-12-01

    A key issue relating to developing multi-component anti-malarial vaccines, lies in studying Plasmodium vivax surface proteins' genetic variation. The present work was aimed at amplifying, cloning and sequencing the gene encoding P. vivax merozoite surface protein 5 (PvMSP5) in samples obtained from infected patients from Colombian areas having varying malaria transmission rates. Nucleotide sequence data reported in this paper are available in the GenBank, EMBL and DDBJ databases under Accessions numbers DQ341586 to DQ341601. Our results have revealed that PvMSP5 is one of the P. vivax surface proteins having greater polymorphism, this being restricted to specific protein regions. The intron and exon II (which includes the GPI anchor and EGF-like domain) were both highly conserved when compared to exon I; exon I displayed the greatest variation and most of the recombination events occurred within it. No geographical grouping was observed. The Nei-Gojobori test revealed significant positive selection in the samples analysed here, whereas Tajima and Fu and Li tests presented a neutral selection pattern. The results reflected a localized variation pattern, recombination between PvMSP5 alleles and also functional and immune pressures, where stronger selective forces might be acting on exon I than on exon II, suggesting that the latter could be an important region to be included in an anti-malarial vaccine.

  14. 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

  15. 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.

  16. A Leaf Lipoxygenase of Potato Induced Specifically by Pathogen Infection1

    PubMed Central

    Kolomiets, Michael V.; Chen, Hao; Gladon, Richard J.; Braun, E.J.; Hannapel, David J.

    2000-01-01

    Lipoxygenase (LOX) activity has been identified consistently during pathogen-induced defense responses. Here we report the involvement of a specific leaf LOX gene of potato (Solanum tuberosum), designated POTLX-3 (GenBank/EMBL accession no. U60202), in defense responses against pathogens. The sequence of POTLX-3 does not match any other LOX genes of potato and has the greatest match to a tobacco LOX gene that contributes to a resistance mechanism against Phytophthora parasitica var nicotianae. POTLX-3 transcript accumulation was not detected in untreated, healthy potato organs or in wounded mature leaves. POTLX-3 mRNA accumulation was induced in potato leaves treated with ethylene or methyl jasmonate or infected with either virulent or avirulent strains of Phytophthora infestans, the causal agent of late blight. During the resistance response, POTLX-3 was induced within 6 hours, increased steadily through 24 hours, and its mRNA continued to accumulate for a week after inoculation. In contrast, when a plant was susceptible to P. infestans, induction of mRNA accumulation in response to inoculation was inconsistent and delayed. LOX activity assayed during an incompatible interaction in leaves peaked 3 days earlier than during a compatible interaction. POTLX-3 mRNA accumulation also was induced during hypersensitive response development caused by the incompatible pathogen Pseudomonas syringae pv phaseolicola. Our results show that POTLX-3 may be involved specifically in defense responses against pathogen infection. PMID:11080289

  17. 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.

  18. 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.

  19. Database of patterns PROF_PAT for detecting local similarities.

    PubMed

    Nizolenko, Lily P; Bachinsky, Alexander G; Naumochkin, Andrey N; Yarigin, Andrey A; Grigorovich, Dmitry A

    2003-01-01

    We have developed PROF_PAT, a database of patterns, constructed for groups of related proteins and designed to maximize representation of amino acid sequences from the SWISS-PROT database. The purpose of the current study was to demonstrate that PROT_PAT is not only as good as known analogs but surpasses them in some features. 10938 new amino acid sequences from the SWISS-PROT bank were compared with patterns constructed for protein families in the PROF_PAT 1.10 bank. The aim of the comparisons was to estimate some threshold values of "Score" parameter to distinguish random similarities from significant ones. From the 10938 new sequences, 638 did not reveal any similarities with PROF_PAT patterns. Cases of found similarities were divided into three sets: 'positive', 'putative' (or 'unknown'), and 'false positive', containing 7719, 2297 and 284 sequences respectively. Using 20 amino acid sequences from the TrEMBL bank that have no descriptions, PROF_PAT demonstrated specificity at a level that was as good as the best-known "secondary" banks. At the same time, its pattern content and variety of included proteins was significantly richer, and its search speed was 3-10 times higher than those of any other protein family bank used for comparison.

  20. Isolation and characterization of marsupial IL5 genes.

    PubMed

    Hawken, R J; Maccarone, P; Toder, R; Marshall Graves, J A; Maddox, J F

    1999-10-01

    The genomic nucleotide sequence and chromosomal position of the interleukin 5 (IL5) gene has been described for the model marsupial Macropus eugenii (tammar wallaby). A 272 base pair genomic IL5 polymerase chain reaction (PCR) product spanning exon 3, intron 3, and exon 4 was generated using stripe-faced dunnart (Sminthopsis macroura) DNA. This PCR product was used to isolate a genomic lambda clone containing the complete IL5 gene from a tammar wallaby EMBL3 lambda library. Sequencing revealed that the tammar wallaby IL5 gene consists of four exons separated by three introns. Comparison of the marsupial coding sequence with coding sequences from eutherian species revealed 61 to 69% identity at the nucleotide level and 48 to 63% identity at the amino acid (aa) level. A polymorphic complex compound microsatellite was identified within intron 2 of the tammar wallaby IL5 gene. This microsatellite was also found in other marsupials including the swamp wallaby, tree kangaroo, stripe-faced dunnart, South American opossum, brushtail possum, and koala. Fluorescence in situ hybridization using DNA from the IL5 clone on tammar wallaby chromosomes indicated that the IL5 gene is located on Chromosome 1.

  1. Genomic Analysis of a Marine Bacterium: Bioinformatics for Comparison, Evaluation, and Interpretation of DNA Sequences

    PubMed Central

    Khobragade, Chandrahasya N.

    2016-01-01

    A total of five highly related strains of an unidentified marine bacterium were analyzed through their short genome sequences (AM260709–AM260713). Genome-to-Genome Distance (GGDC) showed high similarity to Pseudoalteromonas haloplanktis (X67024). The generated unique Quick Response (QR) codes indicated no identity to other microbial species or gene sequences. Chaos Game Representation (CGR) showed the number of bases concentrated in the area. Guanine residues were highest in number followed by cytosine. Frequency of Chaos Game Representation (FCGR) indicated that CC and GG blocks have higher frequency in the sequence from the evaluated marine bacterium strains. Maximum GC content for the marine bacterium strains ranged 53-54%. The use of QR codes, CGR, FCGR, and GC dataset helped in identifying and interpreting short genome sequences from specific isolates. A phylogenetic tree was constructed with the bootstrap test (1000 replicates) using MEGA6 software. Principal Component Analysis (PCA) was carried out using EMBL-EBI MUSCLE program. Thus, generated genomic data are of great assistance for hierarchical classification in Bacterial Systematics which combined with phenotypic features represents a basic procedure for a polyphasic approach on unambiguous bacterial isolate taxonomic classification. PMID:27882328

  2. The newly characterized Pl-jun is specifically expressed in skeletogenic cells of the Paracentrotus lividus sea urchin embryo.

    PubMed

    Russo, Roberta; Pinsino, Annalisa; Costa, Caterina; Bonaventura, Rosa; Matranga, Valeria; Zito, Francesca

    2014-09-01

    Growing evidence suggests that the transcription factors belonging to the Jun family are involved in many important cellular events, such as the control of bone development in mammalians. We have characterized, for the first time, a member of the Jun family from embryos of the sea urchin Paracentrotus lividus. The Pl-jun protein sequence includes all the functional domains characteristic of members of the Jun family (i.e. the basic leucine zipper, the basic DNA-binding and the c-Jun N-terminal kinase docking-like domains), which are evolutionarily conserved. Moreover, all the key serine and threonine residues, which are phosphorylation targets for different kinases necessary for jun activation, appear to be well preserved. A model of the monomeric protein provides a simulation of the three-dimensional structure and shows the potential sites for dimerization and DNA binding. Pl-jun mRNA is expressed in the unfertilized egg and throughout sea urchin embryo development. As the development proceeds, Pl-jun mRNA becomes exclusively expressed in the skeletogenic cells. Intriguingly, these cells contain significant amounts of the phosphorylated active protein entirely localized into their nuclei. These findings strengthen our hypothesis that suggests an active role for Pl-jun in skeletogenic cells, thus indicating that this transcription factor is a novel component of the gene regulatory networks controlling skeletogenesis. Database: Nucleotide sequence data have been deposited in the EMBL databases under the accession number: HE817756.

  3. The human DEPhOsphorylation database DEPOD: a 2015 update.

    PubMed

    Duan, Guangyou; Li, Xun; Köhn, Maja

    2015-01-01

    Phosphatases are crucial enzymes in health and disease, but the knowledge of their biological roles is still limited. Identifying substrates continues to be a great challenge. To support the research on phosphatase-kinase-substrate networks we present here an update on the human DEPhOsphorylation Database: DEPOD (http://www.depod.org or http://www.koehn.embl.de/depod). DEPOD is a manually curated open access database providing human phosphatases, their protein and non-protein substrates, dephosphorylation sites, pathway involvements and external links to kinases and small molecule modulators. All internal data are fully searchable including a BLAST application. Since the first release, more human phosphatases and substrates, their associated signaling pathways (also from new sources), and interacting proteins for all phosphatases and protein substrates have been added into DEPOD. The user interface has been further optimized; for example, the interactive human phosphatase-substrate network contains now a 'highlight node' function for phosphatases, which includes the visualization of neighbors in the network.

  4. SledgeHMMER: a web server for batch searching the Pfam database.

    PubMed

    Chukkapalli, Giridhar; Guda, Chittibabu; Subramaniam, Shankar

    2004-07-01

    The SledgeHMMER web server is intended for genome-scale searching of the Pfam database without having to install this database and the HMMER software locally. The server implements a parallelized version of hmmpfam, the program used for searching the Pfam HMM database. Pfam search results have been calculated for the entire Swiss-Prot and TrEmbl database sequences (approximately 1.2 million) on 256 processors of IA64-based teragrid machines. The Pfam database can be searched in local, glocal or merged mode, using either gathering or E-value thresholds. Query sequences are first matched against the pre-calculated entries to retrieve results, and those without matches are processed through a new search process. Results are emailed in a space-delimited tabular format upon completion of the search. While most other Pfam-searching web servers set a limit of one sequence per query, this server processes batch sequences with no limit on the number of input sequences. The web server and downloadable data are accessible from http://SledgeHmmer.sdsc.edu.

  5. Leucémie à plasmocytes primitive: à propos de 03 cas

    PubMed Central

    Miloudi, Mouhcine; Messaoudi, Nezha

    2016-01-01

    La leucémie à plasmocytes est une hémopathie maligne rare définie par la présence de plus de 20 % de plasmocytes de la formule leucocytaire ou un nombre de plasmocytes circulants supérieur à 2 × 109/L (2G/L). Elle peut être primitive, dans 60% des cas, et se manifeste d'emblée sur un mode leucémique ou secondaire, dans 40% des cas, compliquant un myélome multiple connu. Vu la rareté de cette affection, seuls quelques cas ont été rapportés dans la littérature. Elle est caractérisée par son agressivité et son mauvais pronostic. A travers 03 cas diagnostiqués au laboratoire d'hématologie de l'hôpital militaire Mohammed V les auteurs présentent les particularités cliniques, biologiques et pronostic de cette affection. PMID:27795764

  6. 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.

  7. The mouse proline-rich protein MP6 promoter binds isoprenaline-inducible parotid nuclear proteins via a highly conserved NFkB/rel-like site.

    PubMed

    Roberts, S G; Layfield, R; McDonald, C J

    1991-10-11

    Proline-rich protein (PRP) gene MP6 was isolated from a mouse BALB/c genomic DNA library in lambda EMBL3, characterised by hybridisation and restriction mapping and the promoter region, from -162 to +72 around the PRP consensus cap-site, was sequenced. In gel shift assays this region formed complexes C1 and C2 with parotid nuclear proteins which were induced by the beta-adrenergic agonist isoprenaline. DNA competition studies and direct binding assays of promoter subfragments showed that it was the sequence from -157 to -91 that was forming the isoprenaline-dependent complexes. All PRP genes conserve a 23bp. sequence, termed PRP Box1, with ets and NFkB/rel binding site-like elements, upstream of their promoters. In the MP6 promoter, PRP Box1 was within the region forming the complexes. Further gel shift assays using PRP Box1 oligonucleotides as competitors and targets indicated that the NFkB/rel binding site-like element was important in formation of the isoprenaline-inducible complexes. HeLa nuclear extracts also formed complexes with PRP Box1 similar to C1 and C2 but nuclear extracts from spleen, submandibular gland and liver did not. These complexes are thus candidate regulators for the isoprenaline-dependent and tissue-specific transcription of PRP genes.

  8. Molecular defect in factor IXBm Lake Elsinore. Substitution of Ala390 by Val in the catalytic domain.

    PubMed

    Spitzer, S G; Pendurthi, U R; Kasper, C K; Bajaj, S P

    1988-08-05

    Earlier studies with factor IXBm Lake Elsinore (IXBmLE), a nonfunctional variant of factor IX, suggested that the defect in this protein may reside in the catalytic domain of the molecule (Usharani, P., Warn-Cramer, B. J., Kasper, C. K., and Bajaj, S. P. (1985) J. Clin. Invest. 75, 76-83). In this report, genomic DNA fragments from normal IX and IXBmLE alleles were cloned into phage lambda EMBL3 and the recombinant phage identified using normal IX cDNA and synthetic oligonucleotides. Exons VI, VII, and VIII of normal IX and IXBmLE gene were also amplified using a newly developed primer-directed polymerase chain reaction method. All eight exons and flanking regions of the normal IX and IXBmLE gene were sequenced by the dideoxy chain termination method. Comparison of the normal IX and IXBmLE sequences revealed a single base substitution (C----T) in the exon VIII of the BmLE variant, which results in the replacement of Ala390 by Val in the variant molecule. Although this mutation is in the catalytic domain of the molecule, purified factor IXaBmLE is indistinguishable from normal IXa in its activity toward a small synthetic substrate, L-tosylarginine methyl ester. These data, coupled with the previous data, identify a region (around residue 390) in the normal factor IXa which appears to play a major role in the extended macromolecular substrate binding site.

  9. Proteome-pI: proteome isoelectric point database

    PubMed Central

    Kozlowski, Lukasz P.

    2017-01-01

    Proteome-pI is an online database containing information about predicted isoelectric points for 5029 proteomes calculated using 18 methods. The isoelectric point, the pH at which a particular molecule carries no net electrical charge, is an important parameter for many analytical biochemistry and proteomics techniques, especially for 2D gel electrophoresis (2D-PAGE), capillary isoelectric focusing, liquid chromatography–mass spectrometry and X-ray protein crystallography. The database, available at http://isoelectricpointdb.org allows the retrieval of virtual 2D-PAGE plots and the development of customised fractions of proteome based on isoelectric point and molecular weight. Moreover, Proteome-pI facilitates statistical comparisons of the various prediction methods as well as biological investigation of protein isoelectric point space in all kingdoms of life. For instance, using Proteome-pI data, it is clear that Eukaryotes, which evolved tight control of homeostasis, encode proteins with pI values near the cell pH. In contrast, Archaea living frequently in extreme environments can possess proteins with a wide range of isoelectric points. The database includes various statistics and tools for interactive browsing, searching and sorting. Apart from data for individual proteomes, datasets corresponding to major protein databases such as UniProtKB/TrEMBL and the NCBI non-redundant (nr) database have also been precalculated and made available in CSV format. PMID:27789699

  10. 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

  11. 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).

  12. Quickly Getting the Best Data from Your Macromolecular Crystals with a New Generation of Beamline Instruments

    SciTech Connect

    Cipriani, Florent; Felisaz, Franck; Lavault, Bernard; Brockhauser, Sandor; Ravelli, Raimond; Launer, Ludovic

    2007-01-19

    While routine Macromolecular x-ray (MX) crystallography has relied on well established techniques for some years all the synchrotrons around the world are improving the throughput of their MX beamlines. Third generation synchrotrons provide small intense beams that make data collection of 5-10 microns sized crystals possible. The EMBL/ESRF MX Group in Grenoble has developed a new generation of instruments to easily collect data on 10 {mu}m size crystals in an automated environment. This work is part of the Grenoble automation program that enables FedEx like crystallography using fully automated data collection and web monitored experiments. Seven ESRF beamlines and the MRC BM14 ESRF/CRG beamline are currently equipped with these latest instruments. We describe here the main features of the MD2x diffractometer family and the SC3 sample changer robot. Although the SC3 was primarily designed to increase the throughput of MX beamlines, it has also been shown to be efficient in improving the quality of the data collected. Strategies in screening a large number of crystals, selecting the best, and collecting a full data set from several re-oriented micro-crystals can now be run with minimum time and effort. The MD2x and SC3 instruments are now commercialised by the company ACCEL GmbH.

  13. 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.

  14. 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.

  15. A manual curation strategy to improve genome annotation: application to a set of haloarchael genomes.

    PubMed

    Pfeiffer, Friedhelm; Oesterhelt, Dieter

    2015-06-02

    Genome annotation errors are a persistent problem that impede research in the biosciences. A manual curation effort is described that attempts to produce high-quality genome annotations for a set of haloarchaeal genomes (Halobacterium salinarum and Hbt. hubeiense, Haloferax volcanii and Hfx. mediterranei, Natronomonas pharaonis and Nmn. moolapensis, Haloquadratum walsbyi strains HBSQ001 and C23, Natrialba magadii, Haloarcula marismortui and Har. hispanica, and Halohasta litchfieldiae). Genomes are checked for missing genes, start codon misassignments, and disrupted genes. Assignments of a specific function are preferably based on experimentally characterized homologs (Gold Standard Proteins). To avoid overannotation, which is a major source of database errors, we restrict annotation to only general function assignments when support for a specific substrate assignment is insufficient. This strategy results in annotations that are resistant to the plethora of errors that compromise public databases. Annotation consistency is rigorously validated for ortholog pairs from the genomes surveyed. The annotation is regularly crosschecked against the UniProt database to further improve annotations and increase the level of standardization. Enhanced genome annotations are submitted to public databases (EMBL/GenBank, UniProt), to the benefit of the scientific community. The enhanced annotations are also publically available via HaloLex.

  16. SNP Profile within the Human Major Histocompatibility Complex Reveals an Extreme and Interrupted Level of Nucleotide Diversity

    PubMed Central

    Gaudieri, Silvana; Dawkins, Roger L.; Habara, Kaori; Kulski, Jerzy K.; Gojobori, Takashi

    2000-01-01

    The human major histocompatibility complex (MHC) is characterized by polymorphic multicopy gene families, such as HLA and MIC (PERB11); duplications; insertions and deletions (indels); and uneven rates of recombination. Polymorphisms at the antigen recognition sites of the HLA class I and II genes and at associated neutral sites have been attributed to balancing selection and a hitchhiking effect, respectively. We, and others, have previously shown that nucleotide diversity between MHC haplotypes at non-HLA sites is unusually high (>10%) and up to several times greater than elsewhere in the genome (0.08%–0.2%). We report here the most extensive analysis of nucleotide diversity within a continuous sequence in the genome. We constructed a single nucleotide polymorphism (SNP) profile that reveals a pattern of extreme but interrupted levels of nucleotide diversity by comparing a continuous sequence within haplotypes in three genomic subregions of the MHC. A comparison of several haplotypes within one of the genomic subregions containing the HLA-B and -C loci suggests that positive selection is operating over the whole subgenomic region, including HLA and non-HLA genes. [The sequence data for the multiple haplotype comparisons within the class I region have been submitted to DDBJ/EMBL/GenBank under accession nos. AF029061, AF029062, and AB031005–AB031010. Additional sequence data have been submitted to the DDBJ data library under accession nos. AB031005–AB03101 and AF029061–AF029062.] PMID:11042155

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

    PubMed Central

    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

  18. The SUPERFAMILY database in 2004: additions and improvements.

    PubMed

    Madera, Martin; Vogel, Christine; Kummerfeld, Sarah K; Chothia, Cyrus; Gough, Julian

    2004-01-01

    The SUPERFAMILY database provides structural assignments to protein sequences and a framework for analysis of the results. At the core of the database is a library of profile Hidden Markov Models that represent all proteins of known structure. The library is based on the SCOP classification of proteins: each model corresponds to a SCOP domain and aims to represent an entire superfamily. We have applied the library to predicted proteins from all completely sequenced genomes (currently 154), the Swiss-Prot and TrEMBL databases and other sequence collections. Close to 60% of all proteins have at least one match, and one half of all residues are covered by assignments. All models and full results are available for download and online browsing at http://supfam.org. Users can study the distribution of their superfamily of interest across all completely sequenced genomes, investigate with which other superfamilies it combines and retrieve proteins in which it occurs. Alternatively, concentrating on a particular genome as a whole, it is possible first, to find out its superfamily composition, and secondly, to compare it with that of other genomes to detect superfamilies that are over- or under-represented. In addition, the webserver provides the following standard services: sequence search; keyword search for genomes, superfamilies and sequence identifiers; and multiple alignment of genomic, PDB and custom sequences.

  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. 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

  1. Expression and properties of the recombinant lumazine (riboflavin) protein from Photobacterium leiognathi.

    PubMed

    Illarionov, B; Illarionova, V; Lee, J; van Dongen, W; Vervoort, J

    1994-11-11

    Photobacterium leiognathi lumazine protein has been expressed in Escherichia coli in high yield, 30 mg/l. The cloned gene was one previously reported by Illarionov (EMBL X56534), that had a similar sequence and was located in the same position as the lumazine protein gene in P. phosphoreum. This gene was placed downstream of the T7 gene 10 promoter of the plasmid pT7-7. When the E. coli are grown at 37 degrees C the protein accumulates in inclusion bodies but solubilization can be achieved in 6 M urea. By a simple procedure of dialysis in the presence of riboflavin and centrifugation, without any chromatography, the recombinant holoprotein is purified to 95% homogeneity. The spectral properties of this recombinant riboflavin protein are the same as those of a fluorescent riboflavin-bound protein produced by many strains of P. leiognathi. The absorption spectrum has the same maxima, 276, 386, 464 nm, the circular dichroism is also the same, and both absorption spectrum and CD are the same as that of apo-lumazine protein having riboflavin bound. The riboflavin on the recombinant can be easily replaced by 6,7-dimethyl-8-ribityllumazine. The absorption and fluorescence spectra, fluorescence yield, and bioluminescence properties of this rebound protein identify it as authentic lumazine protein.

  2. The lumazine protein-encoding gene in Photobacterium leiognathi is linked to the lux operon.

    PubMed

    Lin, J W; Chao, Y F; Weng, S F

    1993-04-15

    The nucleotide (nt) sequence of the lumP (EMBL accession No. X65612) gene of Photobacterium leiognathi PL741 was determined and the amino acid (aa) sequence deduced. The encoded aa sequence of lumP was identified as that of the lumazine protein (LumP) by homology with that of Photobacterium phosphoreum (56%). This small protein has a calculated M(r) of 19,997 and comprises 186 aa residues. Biochemical studies suggested that LumP is the protein which, when combined with luciferase, is responsible for the bioluminescent spectrum shift from blue-green light (490-505 nm) to blue (470 nm) in P. leiognathi. The nt sequence of the flanking region showed that lumP is linked to the lux operon but runs in the opposite direction. The gene order of the lumP and lux operon is as follows: <--lumP-R&R-luxC-luxD-luxA-luxB-luxN-lu xE-->; the R&R regulatory region sequence included two promoter systems, PR for the lux operon and PL for the lumP or the lum operon.

  3. Regulatory region with putA gene of proline dehydrogenase that links to the lum and the lux operons in Photobacterium leiognathi.

    PubMed

    Lin, J W; Yu, K Y; Chen, H Y; Weng, S F

    1996-02-27

    Nucleotide sequence of regulatory region (R & R) with putA gene (EMBL Accession No. U39227) from Photobacterium leiognathi PL741 has been determined, and the putA gene encoded amino acid sequence of proline dehydrogenase is deduced. Alignment and comparison of proline dehydrogenase of P. leiognathi with the proline dehydrogenase domain in the PutA protein of Escherichia coli and Salmonella typhimurium show that they are homologous. Nucleotide sequence reveals that regulatory region with the putA gene is linked to the lum and lux operons in genome; the gene order is <--putA--R & R(I)<--ter-lumQ-lumP-R & R-luxC-luxD-luxA-luxB-luxE--> (R & R: regulatory region; ter:transcriptional terminator), whereas the R & R is the regulatory region for the lum and the lux operons, ter is the transcriptional terminator for the lum operon, and R & R(I) apparently is the regulatory region for the putA and related genes. Nucleotide sequence analysis illustrates the specific inverted repeat (SIR), cAMP-CRP consensus sequence, canonical -10/-35 promoter, putative operator and Shine-Dalgarno (SD) sequence on the regulatory region R & R(I) for the putA and related genes; it suggests that the putA and related genes are simply linked to the lum and the lux operons in genome, the regulatory region R & R(I) is independent for the putA and related genes.

  4. 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.

  5. MODBASE, a database of annotated comparative protein structure models.

    PubMed

    Pieper, Ursula; Eswar, Narayanan; Stuart, Ashley C; Ilyin, Valentin A; Sali, Andrej

    2002-01-01

    MODBASE (http://guitar.rockefeller.edu/modbase) is a relational database of annotated comparative protein structure models for all available protein sequences matched to at least one known protein structure. The models are calculated by MODPIPE, an automated modeling pipeline that relies on PSI-BLAST, IMPALA and MODELLER. MODBASE uses the MySQL relational database management system for flexible and efficient querying, and the MODVIEW Netscape plugin for viewing and manipulating multiple sequences and structures. It is updated regularly to reflect the growth of the protein sequence and structure databases, as well as improvements in the software for calculating the models. For ease of access, MODBASE is organized into different datasets. The largest dataset contains models for domains in 304 517 out of 539 171 unique protein sequences in the complete TrEMBL database (23 March 2001); only models based on significant alignments (PSI-BLAST E-value < 10(-4)) and models assessed to have the correct fold are included. Other datasets include models for target selection and structure-based annotation by the New York Structural Genomics Research Consortium, models for prediction of genes in the Drosophila melanogaster genome, models for structure determination of several ribosomal particles and models calculated by the MODWEB comparative modeling web server.

  6. MOCAT: A Metagenomics Assembly and Gene Prediction Toolkit

    PubMed Central

    Li, Junhua; Chen, Weineng; Chen, Hua; Mende, Daniel R.; Arumugam, Manimozhiyan; Pan, Qi; Liu, Binghang; Qin, Junjie; Wang, Jun; Bork, Peer

    2012-01-01

    MOCAT is a highly configurable, modular pipeline for fast, standardized processing of single or paired-end sequencing data generated by the Illumina platform. The pipeline uses state-of-the-art programs to quality control, map, and assemble reads from metagenomic samples sequenced at a depth of several billion base pairs, and predict protein-coding genes on assembled metagenomes. Mapping against reference databases allows for read extraction or removal, as well as abundance calculations. Relevant statistics for each processing step can be summarized into multi-sheet Excel documents and queryable SQL databases. MOCAT runs on UNIX machines and integrates seamlessly with the SGE and PBS queuing systems, commonly used to process large datasets. The open source code and modular architecture allow users to modify or exchange the programs that are utilized in the various processing steps. Individual processing steps and parameters were benchmarked and tested on artificial, real, and simulated metagenomes resulting in an improvement of selected quality metrics. MOCAT can be freely downloaded at http://www.bork.embl.de/mocat/. PMID:23082188

  7. ZOONET: perspectives on the evolution of animal form. Meeting report.

    PubMed

    Fischer, Antje H L; Arboleda, Enrique; Egger, Bernhard; Hilbrant, Maarten; McGregor, Alistair P; Cole, Alison G; Daley, Allison C

    2009-11-15

    What drives evolution? This was one of the main questions raised at the final ZOONET meeting in Budapest, Hungary, in November 2008. The meeting marked the conclusion of ZOONET, an EU-funded Marie-Curie Research Training Network comprising nine research groups from all over Europe (Max Telford, University College London; Michael Akam, University of Cambridge; Detlev Arendt, EMBL Heidelberg; Maria Ina Arnone, Stazione Zoologica Anton Dohrn Napoli; Michalis Averof, IMBB Heraklion; Graham Budd, Uppsala University; Richard Copley, University of Oxford; Wim Damen, University of Cologne; Ernst Wimmer, University of Göttingen). ZOONET meetings and practical courses held during the past four years provided researchers from diverse backgrounds--bioinformatics, phylogenetics, embryology, palaeontology, and developmental and molecular biology--the opportunity to discuss their work under a common umbrella of evolutionary developmental biology (Evo Devo). The Budapest meeting emphasized in-depth discussions of the key concepts defining Evo Devo, and bringing together ZOONET researchers with external speakers who were invited to present their views on the evolution of animal form. The discussion sessions addressed four main topics: the driving forces of evolution, segmentation, fossils and phylogeny, and the future of Evo Devo.

  8. Carcinome neuroendocrine à grandes cellules primitif du sein: une tumeur rare chez l’homme

    PubMed Central

    Safini, Fatima; Bouchbika, Zineb; Bennani, Zineb; Belkheiri, Sara; Attar, Hicham El; Benchakroun, Nadia; Jouhadi, Hassan; Tawfiq, Nezha; Sahraoui, Souha; Benider, Abdellatif

    2016-01-01

    Le carcinome neuroendocrine à grandes cellules primitif du sein est une entité extrêmement rare. Moins de dix cas ont été rapportés dans la littérature. Nous présentons un nouveau cas survenu chez un homme de 61 ans qui s’est présenté pour une tumeur localement avancée du sein droit d’emblée métastatique aux poumons et à la plèvre, classée cT4bN1M1. Le patient avait reçu huit cycles de chimiothérapie à base de Docetaxel tous les 21 jours, avec une bonne réponse clinique et radiologique (>50%), puis mis sous hormonothérapie à base de tamoxifène avec une stabilisation pendant 18 mois. L’étude immuni-histochimique reste indispensable pour déterminer la nature neuroendocrine de cette tumeur. Le traitement n’est pas bien codifié vu la rareté de ce type de cancer. PMID:28292162

  9. Assessment of the food habits of the Moroccan dorcas gazelle in M'Sabih Talaa, west central Morocco, using the trnL approach.

    PubMed

    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.

  10. Genenames.org: the HGNC and VGNC resources in 2017

    PubMed Central

    Yates, Bethan; Braschi, Bryony; Gray, Kristian A.; Seal, Ruth L.; Tweedie, Susan; Bruford, Elspeth A.

    2017-01-01

    The HUGO Gene Nomenclature Committee (HGNC) based at the European Bioinformatics Institute (EMBL-EBI) assigns unique symbols and names to human genes. Currently the HGNC database contains almost 40 000 approved gene symbols, over 19 000 of which represent protein-coding genes. In addition to naming genomic loci we manually curate genes into family sets based on shared characteristics such as homology, function or phenotype. We have recently updated our gene family resources and introduced new improved visualizations which can be seen alongside our gene symbol reports on our primary website http://www.genenames.org. In 2016 we expanded our remit and formed the Vertebrate Gene Nomenclature Committee (VGNC) which is responsible for assigning names to vertebrate species lacking a dedicated nomenclature group. Using the chimpanzee genome as a pilot project we have approved symbols and names for over 14 500 protein-coding genes in chimpanzee, and have developed a new website http://vertebrate.genenames.org to distribute these data. Here, we review our online data and resources, focusing particularly on the improvements and new developments made during the last two years. PMID:27799471

  11. Gene sequence of mouse B-type proline-rich protein MP4. Transcriptional start point and an upstream phylogenetic footprint with ets-like and rel/NFkB-like elements.

    PubMed

    Roberts, S G; Layfield, R; Bannister, A J; McDonald, C J

    1991-12-18

    A mouse genomic B-type proline-rich protein (PRP) cosmid clone was isolated by cDNA hybridisation and mapped, the gene region was subcloned and 3770 bp were sequenced. This gene (MP4) contained three introns and encoded a 1020-nt (nt, nucleotide) mRNA for a PRP precursor 300 amino acids long arranged with 11 imperfect 18-residue proline-rich repeats. The transcriptional start point was determined by S1 nuclease mapping and primer extension to be 26 bp downstream of a TATAA sequence. Sequence comparisons revealed that only two regions from positions -650 bp - -30 bp were highly conserved in all other PRP genes, PRP boxes 1 and 2. Box 1 at positions -112 to -135 contained ets-like and rel/NFkB-like elements and was 74% conserved over 23 bp. Box 2 at positions -33 - -51 was 53% conserved over 19 bp. A search of the EMBL and GenBank sequence libraries indicated that PRP box 1 was only present upstream of the known mammalian PRP gene sequences and was absent from other genes. These conserved sequences may thus be relevant to the tissue-specific and beta-adrenergic regulation of PRP gene transcription.

  12. Computational Drug Target Screening through Protein Interaction Profiles

    PubMed Central

    Vilar, Santiago; Quezada, Elías; Uriarte, Eugenio; Costanzi, Stefano; Borges, Fernanda; Viña, Dolores; Hripcsak, George

    2016-01-01

    The development of computational methods to discover novel drug-target interactions on a large scale is of great interest. We propose a new method for virtual screening based on protein interaction profile similarity to discover new targets for molecules, including existing drugs. We calculated Target Interaction Profile Fingerprints (TIPFs) based on ChEMBL database to evaluate drug similarity and generated new putative compound-target candidates from the non-intersecting targets in each pair of compounds. A set of drugs was further studied in monoamine oxidase B (MAO-B) and cyclooxygenase-1 (COX-1) enzyme through molecular docking and experimental assays. The drug ethoxzolamide and the natural compound piperlongumine, present in Piper longum L, showed hMAO-B activity with IC50 values of 25 and 65 μM respectively. Five candidates, including lapatinib, SB-202190, RO-316233, GW786460X and indirubin-3′-monoxime were tested against human COX-1. Compounds SB-202190 and RO-316233 showed a IC50 in hCOX-1 of 24 and 25 μM respectively (similar range as potent inhibitors such as diclofenac and indomethacin in the same experimental conditions). Lapatinib and indirubin-3′-monoxime showed moderate hCOX-1 activity (19.5% and 28% of enzyme inhibition at 25 μM respectively). Our modeling constitutes a multi-target predictor for large scale virtual screening with potential in lead discovery, repositioning and drug safety. PMID:27845365

  13. Computational and biophysical approaches to protein-protein interaction inhibition of Plasmodium falciparum AMA1/RON2 complex

    NASA Astrophysics Data System (ADS)

    Pihan, Emilie; Delgadillo, Roberto F.; Tonkin, Michelle L.; Pugnière, Martine; Lebrun, Maryse; Boulanger, Martin J.; Douguet, Dominique

    2015-06-01

    Invasion of the red blood cell by Plasmodium falciparum parasites requires formation of an electron dense circumferential ring called the Moving Junction (MJ). The MJ is anchored by a high affinity complex of two parasite proteins: Apical Membrane Antigen 1 ( PfAMA1) displayed on the surface of the parasite and Rhoptry Neck Protein 2 that is discharged from the parasite and imbedded in the membrane of the host cell. Structural studies of PfAMA1 revealed a conserved hydrophobic groove localized to the apical surface that coordinates RON2 and invasion inhibitory peptides. In the present work, we employed computational and biophysical methods to identify competitive P. falciparum AMA1-RON2 inhibitors with the goal of exploring the `druggability' of this attractive antimalarial target. A virtual screen followed by molecular docking with the PfAMA1 crystal structure was performed using an eight million compound collection that included commercial molecules, the ChEMBL malaria library and approved drugs. The consensus approach resulted in the selection of inhibitor candidates. We also developed a fluorescence anisotropy assay using a modified inhibitory peptide to experimentally validate the ability of the selected compounds to inhibit the AMA1-RON2 interaction. Among those, we identified one compound that displayed significant inhibition. This study offers interesting clues to improve the throughput and reliability of screening for new drug leads.

  14. WONKA and OOMMPPAA: analysis of protein–ligand interaction data to direct structure-based drug design

    PubMed Central

    Deane, Charlotte M.; Wall, Ian D.; Green, Darren V. S.; Marsden, Brian D.; Bradley, Anthony R.

    2017-01-01

    In this work, two freely available web-based interactive computational tools that facilitate the analysis and interpretation of protein–ligand interaction data are described. Firstly, WONKA, which assists in uncovering interesting and unusual features (for example residue motions) within ensembles of protein–ligand structures and enables the facile sharing of observations between scientists. Secondly, OOMMPPAA, which incorporates protein–ligand activity data with protein–ligand structural data using three-dimensional matched molecular pairs. OOMMPPAA highlights nuanced structure–activity relationships (SAR) and summarizes available protein–ligand activity data in the protein context. In this paper, the background that led to the development of both tools is described. Their implementation is outlined and their utility using in-house Structural Genomics Consortium (SGC) data sets and openly available data from the PDB and ChEMBL is described. Both tools are freely available to use and download at http://wonka.sgc.ox.ac.uk/WONKA/ and http://oommppaa.sgc.ox.ac.uk/OOMMPPAA/. PMID:28291763

  15. The human-induced pluripotent stem cell initiative-data resources for cellular genetics.

    PubMed

    Streeter, Ian; Harrison, Peter W; Faulconbridge, Adam; Flicek, Paul; Parkinson, Helen; Clarke, Laura

    2017-01-04

    The Human Induced Pluripotent Stem Cell Initiative (HipSci) isf establishing a large catalogue of human iPSC lines, arguably the most well characterized collection to date. The HipSci portal enables researchers to choose the right cell line for their experiment, and makes HipSci's rich catalogue of assay data easy to discover and reuse. Each cell line has genomic, transcriptomic, proteomic and cellular phenotyping data. Data are deposited in the appropriate EMBL-EBI archives, including the European Nucleotide Archive (ENA), European Genome-phenome Archive (EGA), ArrayExpress and PRoteomics IDEntifications (PRIDE) databases. The project will make 500 cell lines from healthy individuals, and from 150 patients with rare genetic diseases; these will be available through the European Collection of Authenticated Cell Cultures (ECACC). As of August 2016, 238 cell lines are available for purchase. Project data is presented through the HipSci data portal (http://www.hipsci.org/lines) and is downloadable from the associated FTP site (ftp://ftp.hipsci.ebi.ac.uk/vol1/ftp). The data portal presents a summary matrix of the HipSci cell lines, showing available data types. Each line has its own page containing descriptive metadata, quality information, and links to archived assay data. Analysis results are also available in a Track Hub, allowing visualization in the context of public genomic annotations (http://www.hipsci.org/data/trackhubs).

  16. The human-induced pluripotent stem cell initiative—data resources for cellular genetics

    PubMed Central

    Streeter, Ian; Harrison, Peter W.; Faulconbridge, Adam; Flicek, Paul; Parkinson, Helen; Clarke, Laura

    2017-01-01

    The Human Induced Pluripotent Stem Cell Initiative (HipSci) isf establishing a large catalogue of human iPSC lines, arguably the most well characterized collection to date. The HipSci portal enables researchers to choose the right cell line for their experiment, and makes HipSci's rich catalogue of assay data easy to discover and reuse. Each cell line has genomic, transcriptomic, proteomic and cellular phenotyping data. Data are deposited in the appropriate EMBL-EBI archives, including the European Nucleotide Archive (ENA), European Genome-phenome Archive (EGA), ArrayExpress and PRoteomics IDEntifications (PRIDE) databases. The project will make 500 cell lines from healthy individuals, and from 150 patients with rare genetic diseases; these will be available through the European Collection of Authenticated Cell Cultures (ECACC). As of August 2016, 238 cell lines are available for purchase. Project data is presented through the HipSci data portal (http://www.hipsci.org/lines) and is downloadable from the associated FTP site (ftp://ftp.hipsci.ebi.ac.uk/vol1/ftp). The data portal presents a summary matrix of the HipSci cell lines, showing available data types. Each line has its own page containing descriptive metadata, quality information, and links to archived assay data. Analysis results are also available in a Track Hub, allowing visualization in the context of public genomic annotations (http://www.hipsci.org/data/trackhubs). PMID:27733501

  17. 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

  18. A dataset of fishes in and around Inle Lake, an ancient lake of Myanmar, with DNA barcoding, photo images and CT/3D models

    PubMed Central

    Kano, Yuichi; Musikasinthorn, Prachya; Iwata, Akihisa; Tun, Sein; Yun, LKC; Win, Seint Seint; Matsui, Shoko; Tabata, Ryoichi; Yamasaki, Takeshi

    2016-01-01

    Abstract Background Inle (Inlay) Lake, an ancient lake of Southeast Asia, is located at the eastern part of Myanmar, surrounded by the Shan Mountains. Detailed information on fish fauna in and around the lake has long been unknown, although its outstanding endemism was reported a century ago. New information Based on the fish specimens collected from markets, rivers, swamps, ponds and ditches around Inle Lake as well as from the lake itself from 2014 to 2016, we recorded a total of 948 occurrence data (2120 individuals), belonging to 10 orders, 19 families, 39 genera and 49 species. Amongst them, 13 species of 12 genera are endemic or nearly endemic to the lake system and 17 species of 16 genera are suggested as non-native. The data are all accessible from the document “A dataset of Inle Lake fish fauna and its distribution (http://ipt.pensoft.net/resource.do?r=inle_fish_2014-16)”, as well as DNA barcoding data (mitochondrial COI) for all species being available from the DDBJ/EMBL/GenBank (Accession numbers: LC189568–LC190411). Live photographs of almost all the individuals and CT/3D model data of several specimens are also available at the graphical fish biodiversity database (http://ffish.asia/INLE2016; http://ffish.asia/INLE2016-3D). The information can benefit the clarification, public concern and conservation of the fish biodiversity in the region. PMID:27932926

  19. QSAR studies, synthesis and antibacterial assessment of new inhibitors against multidrug-resistant Mycobacterium tuberculosis.

    PubMed

    Kovalishyn, Vasyl; Brovarets, Volodymyr; Blagodatnyi, Volodymyr; Kopernyk, Iryna; Hodyna, Diana; Chumachenko, Svitlana; Shablykin, Oleg; Kozachenko, Oleksandr; Vovk, Myhailo; Barus, Marianna; Bratenko, Myhailo; Metelytsia, Larysa

    2016-11-08

    This paper describes Quantitative Structure-Activity Relationships (QSAR) studies using Artificial Neural Networks (ANN), synthesis and in vitro antitubercular activity of several potent compounds against H37Rv and resistant Mycobacterium tuberculosis (Mtb) strains. Eight QSAR models were built using various types of descriptors with four publicly available structurally diverse datasets, including recent data from PubChem and ChEMBL. The predictive power of the obtained QSAR models was evaluated with a cross-validation procedure, giving a q2=0.74-0.78 for regression models and overall accuracy 78.9-94.4% for classification models. The external test sets were predicted with accuracies in the range of 84.1-95.0% (for the active/inactive classifications) and q2=0.80-0.83 for regressions. The 15 synthesized compounds showed inhibitory activity against H37Rv strain whereas the compounds 1-7 were also active against resistant Mtb strain (resistant to isoniazid and rifampicin). The results indicated that compounds 1-7 could serve as promising leads for further optimization as novel antibacterial inhibitors, in particular, for the treatment of drug resistance of Mtb forms.

  20. 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.

  1. Prediction of acute toxicity of phenol derivatives using multiple linear regression approach for Tetrahymena pyriformis contaminant identification in a median-size database.

    PubMed

    Dieguez-Santana, Karel; Pham-The, Hai; Villegas-Aguilar, Pedro J; Le-Thi-Thu, Huong; Castillo-Garit, Juan A; Casañola-Martin, Gerardo M

    2016-12-01

    In this article, the modeling of inhibitory grown activity against Tetrahymena pyriformis is described. The 0-2D Dragon descriptors based on structural aspects to gain some knowledge of factors influencing aquatic toxicity are mainly used. Besides, it is done by some enlarged data of phenol derivatives described for the first time and composed of 358 chemicals. It overcomes the previous datasets with about one hundred compounds. Moreover, the results of the model evaluation by the parameters in the training, prediction and validation give adequate results comparable with those of the previous works. The more influential descriptors included in the model are: X3A, MWC02, MWC10 and piPC03 with positive contributions to the dependent variable; and MWC09, piPC02 and TPC with negative contributions. In a next step, a median-size database of nearly 8000 phenolic compounds extracted from ChEMBL was evaluated with the quantitative-structure toxicity relationship (QSTR) model developed providing some clues (SARs) for identification of ecotoxicological compounds. The outcome of this report is very useful to screen chemical databases for finding the compounds responsible of aquatic contamination in the biomarker used in the current work.

  2. 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.

  3. PCR amplification and sequencing of ITS1 rDNA of Culicoides arakawae.

    PubMed

    Li, G Q; Hu, Y L; Kanu, S; Zhu, X Q

    2003-02-28

    The first internal transcribed spacer (ITS1) of nuclear ribosomal DNA from Culicoides arakawae was amplified by PCR, cloned and sequenced. The wDNAsis software was used to analyze the ITS1 sequences of C. arakawae and other nine species of Culicoides, which were obtained from GenBank and EMBL databases. For all species, the lengths of the ITS1 were 316-469 bp, and the G+C contents were 26.79-34.53%. Based on the lengths of the ITS1 sequences, the 10 Culicoides species could be divided into two groups. The first group consisted of C. arakawae, C. albicans, C. cubitalis, C. pulicaris and C. punctatus, and the second group comprised C. impunctatus, C. nubeculosus, C. variipennis, C. grisescens and C. imicola. The lengths for the first group were 316-347 bp and the second group were 457-469 bp. C. arakawae belonged to the first group by its ITS1 sequence length. Sequence analysis revealed that C. arakawae was genetically more similar to the first group than it was to the second group, consistent with results based on sequence length. The alignment of ITS1 (the alignment length was 500 bp including the gaps) sequences showed that there was a highly conserved region, which was between 288 and 388 bp, except for a few insertions and substitutions. These findings have important implications for the molecular identification of C. arakawae, for studying its molecular genetics and epidemiology, and for studying the molecular systematics of Culicoides.

  4. 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

    2016-01-04

    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.

  5. Detection of Porphyromonas gingivalis and Streptococcus intermedius in chronic periodontitis patients by multiplex PCR.

    PubMed

    De La Garza-Ramos, Myriam A; Galán-Wong, Luis J; Caffesse, Raúl G; González-Salazar, Francisco; Pereyra-Alférez, Benito

    2008-01-01

    A Multiplex PCR assay for the detection of Porphyromonas gingivalis and Streptococcus intermedius in chronic periodontitis is presented. A total of 180 samples from 65 adults with untreated periodontitis and 17 healthy volunteers were taken and processed in a simple boiling step. Cell lysates were used as DNA source for multiplex PCR assays. Primers were designed from 16S rRNA gene sequences from the GenBank-EMBL database showing specificity for target pathogens. This multiplex PCR system could detect 8.2 P gingivalis and S. intermedius cells. In untreated periodontitis patients, only 78.5% were positive for one or both bacteria; 37% were positive for P gingivalis only, 17% for S. intermedius and 24.5% for both. P. gingivalis was detected in 23.5% of healthy volunteers, while S. intermedius was not detected in the same patients. The distribution of these bacteria was related to the periodontal probing depth, while 95.23% of patients with pockets wih 6 to 7 mm deep were positive for either or both, only 70.45% of of them with 4 to 5 mm pockets were positive.

  6. Screening, Isolation and Identification of Probiotic Producing Lactobacillus acidophilus Strains EMBS081 & EMBS082 by 16S rRNA Gene Sequencing.

    PubMed

    Chandok, Harshpreet; Shah, Pratik; Akare, Uday Raj; Hindala, Maliram; Bhadoriya, Sneha Singh; Ravi, G V; Sharma, Varsha; Bandaru, Srinivas; Rathore, Pragya; Nayarisseri, Anuraj

    2015-09-01

    16S rDNA sequencing which has gained wide popularity amongst microbiologists for the molecular characterization and identification of newly discovered isolates provides accurate identification of isolates down to the level of sub-species (strain). Its most important advantage over the traditional biochemical characterization methods is that it can provide an accurate identification of strains with atypical phenotypic characters as well. The following work is an application of 16S rRNA gene sequencing approach to identify a novel species of Probiotic Lactobacillus acidophilus. The sample was collected from pond water samples of rural and urban areas of Krishna district, Vijayawada, Andhra Pradesh, India. Subsequently, the sample was serially diluted and the aliquots were incubated for a suitable time period following which the suspected colony was subjected to 16S rDNA sequencing. The sequence aligned against other species was concluded to be a novel, Probiotic L. acidophilus bacteria, further which were named L. acidophilus strain EMBS081 & EMBS082. After the sequence characterization, the isolate was deposited in GenBank Database, maintained by the National Centre for Biotechnology Information NCBI. The sequence can also be retrieve from EMBL and DDBJ repositories with accession numbers JX255677 and KC150145.

  7. Comparative Analysis of Noncoding Regions of 77 Orthologous Mouse and Human Gene Pairs

    PubMed Central

    Jareborg, Niclas; Birney, Ewan; Durbin, Richard

    1999-01-01

    A data set of 77 genomic mouse/human gene pairs has been compiled from the EMBL nucleotide database, and their corresponding features determined. This set was used to analyze the degree of conservation of noncoding sequences between mouse and human. A new alignment algorithm was developed to cope with the fact that large parts of noncoding sequences are not alignable in a meaningful way because of genetic drift. This new algorithm, DNA Block Aligner (DBA), finds colinear-conserved blocks that are flanked by nonconserved sequences of varying lengths. The noncoding regions of the data set were aligned with DBA. The proportion of the noncoding regions covered by blocks >60% identical was 36% for upstream regions, 50% for 5′ UTRs, 23% for introns, and 56% for 3′ UTRs. These blocks of high identity were more or less evenly distributed across the length of the features, except for upstream regions in which the first 100 bp upstream of the transcription start site was covered in up to 70% of the gene pairs. This data set complements earlier sets on the basis of cDNA sequences and will be useful for further comparative studies. [This paper contains supplementary data that can be found at http://www.genome.com.] PMID:10508839

  8. 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/.

  9. 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

  10. A Phylogeny-Based Benchmarking Test for Orthology Inference Reveals the Limitations of Function-Based Validation

    PubMed Central

    Larsson, Tomas; Powell, Sean; Doerks, Tobias; von Mering, Christian

    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

  11. 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.

  12. Role of Chemical Reactivity and Transition State Modeling for Virtual Screening.

    PubMed

    Karthikeyan, Muthukumarasamy; Vyas, Renu; Tambe, Sanjeev S; Radhamohan, Deepthi; Kulkarni, Bhaskar D

    2015-01-01

    Every drug discovery research program involves synthesis of a novel and potential drug molecule utilizing atom efficient, economical and environment friendly synthetic strategies. The current work focuses on the role of the reactivity based fingerprints of compounds as filters for virtual screening using a tool ChemScore. A reactant-like (RLS) and a product- like (PLS) score can be predicted for a given compound using the binary fingerprints derived from the numerous known organic reactions which capture the molecule-molecule interactions in the form of addition, substitution, rearrangement, elimination and isomerization reactions. The reaction fingerprints were applied to large databases in biology and chemistry, namely ChEMBL, KEGG, HMDB, DSSTox, and the Drug Bank database. A large network of 1113 synthetic reactions was constructed to visualize and ascertain the reactant product mappings in the chemical reaction space. The cumulative reaction fingerprints were computed for 4000 molecules belonging to 29 therapeutic classes of compounds, and these were found capable of discriminating between the cognition disorder related and anti-allergy compounds with reasonable accuracy of 75% and AUC 0.8. In this study, the transition state based fingerprints were also developed and used effectively for virtual screening in drug related databases. The methodology presented here provides an efficient handle for the rapid scoring of molecular libraries for virtual screening.

  13. The SCR1 gene from Schwanniomyces occidentalis encodes a highly hydrophobic polypeptide, which confers ribosomal resistance to cycloheximide.

    PubMed

    Hoenicka, Janet; Fernández Lobato, María; Marín, Dolores; Jiménez, Antonio

    2002-06-30

    In Saccharomyces cerevisiae, the SCR1 gene from Schwanniomyces occidentalis is known to induce ribosomal resistance to cycloheximide (cyh). A 2.8 kb DNA fragment encoding this gene was sequenced. Its EMBL Accession No. is AJ419770. It disclosed a putative tRNA(Asn) (GUU) sequence located downstream of an open reading frame (ORF) of 1641 nucleotides. This ORF was shown to correspond to SCR1. It would encode a highly hydrophobic polypeptide (SCR1) with 12 transmembrane domains. SCR1 is highly similar to a variety of yeast proteins of the multidrug-resistance (MDR) family. However, SCR1 only conferred resistance to cyh but not to benomyl or methotrexate. The cyh-resistance phenotype induced by SCR1 was confirmed in several S. cerevisiae strains that expressed this gene to reside at the ribosomal level. In contrast, a beta-galacosidase-tagged SCR1 was found to be integrated in the endoplasmic reticulum (ER). It is proposed that the ribosomes of yeast cells expressing SCR1 undergo a conformational change during their interaction with the ER, which lowers their affinity for cyh-binding. If so, these findings would disclose a novel ribosomal resistance mechanism.

  14. STRING: a database of predicted functional associations between proteins.

    PubMed

    von Mering, Christian; Huynen, Martijn; Jaeggi, Daniel; Schmidt, Steffen; Bork, Peer; Snel, Berend

    2003-01-01

    Functional links between proteins can often be inferred from genomic associations between the genes that encode them: groups of genes that are required for the same function tend to show similar species coverage, are often located in close proximity on the genome (in prokaryotes), and tend to be involved in gene-fusion events. The database STRING is a precomputed global resource for the exploration and analysis of these associations. Since the three types of evidence differ conceptually, and the number of predicted interactions is very large, it is essential to be able to assess and compare the significance of individual predictions. Thus, STRING contains a unique scoring-framework based on benchmarks of the different types of associations against a common reference set, integrated in a single confidence score per prediction. The graphical representation of the network of inferred, weighted protein interactions provides a high-level view of functional linkage, facilitating the analysis of modularity in biological processes. STRING is updated continuously, and currently contains 261 033 orthologs in 89 fully sequenced genomes. The database predicts functional interactions at an expected level of accuracy of at least 80% for more than half of the genes; it is online at http://www.bork.embl-heidelberg.de/STRING/.

  15. '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.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. Direct selection of conserved cDNAs from the DiGeorge critical region: isolation of a novel CDC45-like gene.

    PubMed

    McKie, J M; Wadey, R B; Sutherland, H F; Taylor, C L; Scambler, P J

    1998-08-01

    We have used a modified direct selection technique to detect transcripts that are both evolutionary conserved and developmentally expressed. The enrichment for homologous mouse cDNAs by use of human genomic DNA as template is shown to be an efficient and rapid approach for generating transcript maps. Deletions of human 22q11 are associated with several clinical syndromes, with overlapping phenotypes, for example, velocardiofacial syndrome (VCFS) and DiGeorge syndrome (DGS). A large number of transcriptional units exist within the defined critical region, many of which have been identified previously by direct selection. However, no single obvious candidate gene for the VCFS/DGS phenotype has yet been found. Our technique has been applied to the DiGeorge critical region and has resulted in the isolation of a novel candidate gene, Cdc45l2, similar to yeast Cdc45p. [The sequence data described in this paper have been submitted to the EMBL data library under accession nos. AJ0223728 and AF0223729.

  1. 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

  2. Construction of a genomic library of the food spoilage yeast Zygosaccharomyces bailii and isolation of the beta-isopropylmalate dehydrogenase gene (ZbLEU2).

    PubMed

    Rodrigues, F; Zeeman, A M; Alves, C; Sousa, M J; Steensma, H Y; Côrte-Real, M; Leão, C

    2001-04-01

    A genomic library of the yeast Zygosaccharomyces bailii ISA 1307 was constructed in pRS316, a shuttle vector for Saccharomyces cerevisiae and Escherichia coli. The library has an average insert size of 6 kb and covers the genome more than 20 times assuming a genome size similar to that of S. cerevisiae. This new tool has been successfully used, by us and others, to isolate Z. bailii genes. One example is the beta-isopropylmalate dehydrogenase gene (ZbLEU2) of Z. bailii, which was cloned by complementation of a leu2 mutation in S. cerevisiae. An open reading frame encoding a protein with a molecular mass of 38.7 kDa was found. The nucleotide sequence of ZbLEU2 and the deduced amino acid sequence showed a significant degree of identity to those of beta-isopropylmalate dehydrogenases from several other yeast species. The sequence of ZbLEU2 has been deposited in the EMBL data library under accession number AJ292544.

  3. Cardioprotection Effects of Sevoflurane by Regulating the Pathway of Neuroactive Ligand-Receptor Interaction in Patients Undergoing Coronary Artery Bypass Graft Surgery

    PubMed Central

    Wang, Jinquan; Cheng, Jian; Zhang, Chao

    2017-01-01

    This study was designed to identify attractor modules and further reveal the potential biological processes involving in sevoflurane-induced anesthesia in patients treated with coronary artery bypass graft (CABG) surgery. Microarray profile data (ID: E-GEOD-4386) on atrial samples obtained from patients receiving anesthetic gas sevoflurane prior to and following CABG procedure were downloaded from EMBL-EBI database for further analysis. Protein-protein interaction (PPI) networks of baseline and sevoflurane groups were inferred and reweighted according to Spearman correlation coefficient (SCC), followed by systematic modules inference using clique-merging approach. Subsequently, attract method was utilized to explore attractor modules. Finally, pathway enrichment analyses for genes in the attractor modules were implemented to illuminate the biological processes in sevoflurane group. Using clique-merging approach, 27 and 36 modules were obtained from the PPI networks of baseline and sevoflurane-treated samples, respectively. By comparing with the baseline condition, 5 module pairs with the same gene composition were identified. Subsequently, 1 out of 5 modules was identified as an attractor based on attract method. Additionally, pathway analysis indicated that genes in the attractor module were associated with neuroactive ligand-receptor interaction. Accordingly, sevoflurane might exert important functions in cardioprotection in patients following CABG, partially through regulating the pathway of neuroactive ligand-receptor interaction. PMID:28348638

  4. AVCpred: an integrated web server for prediction and design of antiviral compounds.

    PubMed

    Qureshi, Abid; Kaur, Gazaldeep; Kumar, Manoj

    2017-01-01

    Viral infections constantly jeopardize the global public health due to lack of effective antiviral therapeutics. Therefore, there is an imperative need to speed up the drug discovery process to identify novel and efficient drug candidates. In this study, we have developed quantitative structure-activity relationship (QSAR)-based models for predicting antiviral compounds (AVCs) against deadly viruses like human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), human herpesvirus (HHV) and 26 others using publicly available experimental data from the ChEMBL bioactivity database. Support vector machine (SVM) models achieved a maximum Pearson correlation coefficient of 0.72, 0.74, 0.66, 0.68, and 0.71 in regression mode and a maximum Matthew's correlation coefficient 0.91, 0.93, 0.70, 0.89, and 0.71, respectively, in classification mode during 10-fold cross-validation. Furthermore, similar performance was observed on the independent validation sets. We have integrated these models in the AVCpred web server, freely available at http://crdd.osdd.net/servers/avcpred. In addition, the datasets are provided in a searchable format. We hope this web server will assist researchers in the identification of potential antiviral agents. It would also save time and cost by prioritizing new drugs against viruses before their synthesis and experimental testing.

  5. proGenomes: a resource for consistent functional and taxonomic annotations of prokaryotic genomes

    PubMed Central

    Mende, Daniel R.; Letunic, Ivica; Huerta-Cepas, Jaime; Li, Simone S.; Forslund, Kristoffer; Sunagawa, Shinichi; Bork, Peer

    2017-01-01

    The availability of microbial genomes has opened many new avenues of research within microbiology. This has been driven primarily by comparative genomics approaches, which rely on accurate and consistent characterization of genomic sequences. It is nevertheless difficult to obtain consistent taxonomic and integrated functional annotations for defined prokaryotic clades. Thus, we developed proGenomes, a resource that provides user-friendly access to currently 25 038 high-quality genomes whose sequences and consistent annotations can be retrieved individually or by taxonomic clade. These genomes are assigned to 5306 consistent and accurate taxonomic species clusters based on previously established methodology. proGenomes also contains functional information for almost 80 million protein-coding genes, including a comprehensive set of general annotations and more focused annotations for carbohydrate-active enzymes and antibiotic resistance genes. Additionally, broad habitat information is provided for many genomes. All genomes and associated information can be downloaded by user-selected clade or multiple habitat-specific sets of representative genomes. We expect that the availability of high-quality genomes with comprehensive functional annotations will promote advances in clinical microbial genomics, functional evolution and other subfields of microbiology. proGenomes is available at http://progenomes.embl.de. PMID:28053165

  6. Bioinformatics training: selecting an appropriate learning content management system--an example from the European Bioinformatics Institute.

    PubMed

    Wright, Victoria Ann; Vaughan, Brendan W; Laurent, Thomas; Lopez, Rodrigo; Brooksbank, Cath; Schneider, Maria Victoria

    2010-11-01

    Today's molecular life scientists are well educated in the emerging experimental tools of their trade, but when it comes to training on the myriad of resources and tools for dealing with biological data, a less ideal situation emerges. Often bioinformatics users receive no formal training on how to make the most of the bioinformatics resources and tools available in the public domain. The European Bioinformatics Institute, which is part of the European Molecular Biology Laboratory (EMBL-EBI), holds the world's most comprehensive collection of molecular data, and training the research community to exploit this information is embedded in the EBI's mission. We have evaluated eLearning, in parallel with face-to-face courses, as a means of training users of our data resources and tools. We anticipate that eLearning will become an increasingly important vehicle for delivering training to our growing user base, so we have undertaken an extensive review of Learning Content Management Systems (LCMSs). Here, we describe the process that we used, which considered the requirements of trainees, trainers and systems administrators, as well as taking into account our organizational values and needs. This review describes the literature survey, user discussions and scripted platform testing that we performed to narrow down our choice of platform from 36 to a single platform. We hope that it will serve as guidance for others who are seeking to incorporate eLearning into their bioinformatics training programmes.

  7. 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.

  8. 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.

  9. Human ethanol-inducible P450IIE1: complete gene sequence, promoter characterization, chromosome mapping, and cDNA-directed expression

    SciTech Connect

    Umeno, M.; McBride, W.; Yang, C.S.; Gelboin, H.V.; Gonzalez, F.J.

    1988-12-13

    The human P450IIE1 gene, coding for an ethanol-inducible nitrosamine-metabolizing P-450, was isolated from a lambdaEMBL3 genomic library and completely sequenced. The human gene spanned 11413 base pairs and contained nine exons and a typical TATA box. Upstream and downstream DNAs of 2788 and 559 base pairs were also sequenced and compared to the rat gene. Significant areas of sequence similarity were observed within 140 base pairs upstream of the transcription start site in the rat and human genes. Human DNA 539 base pairs upstream of the transcription start site was inserted into the expression vector pSVOAL..delta..5', and luciferase activity was detected when the constructs were introduced into a rat hepatoma cell line. The activity was over 100-fold lower than that of pRSVL, a Rous sarcoma virus LTR-driven luciferase gene. By use of panel of rodent-human cell hybrids, the gene was mapped to chromosome 10 (CYP2E locus). A full-length cDNA, constructed with the first exon of the genomic clone and a partial cDNA clone, was expressed in COS cells and found to code for N-nitrosodimethylamine demethylase activity.

  10. Predicted metal binding sites for phytoremediation.

    PubMed

    Sharma, Ashok; Roy, Sudeep; Tripathi, Kumar Parijat; Roy, Pratibha; Mishra, Manoj; Khan, Feroz; Meena, Abha

    2009-09-05

    Metal ion binding domains are found in proteins that mediate transport, buffering or detoxification of metal ions. The objective of the study is to design and analyze metal binding motifs against the genes involved in phytoremediation. This is being done on the basis of certain pre-requisite amino-acid residues known to bind metal ions/metal complexes in medicinal and aromatic plants (MAP's). Earlier work on MAP's have shown that heavy metals accumulated by aromatic and medicinal plants do not appear in the essential oil and that some of these species are able to grow in metal contaminated sites. A pattern search against the UniProtKB/Swiss-Prot and UniProtKB/TrEMBL databases yielded true positives in each case showing the high specificity of the motifs designed for the ions of nickel, lead, molybdenum, manganese, cadmium, zinc, iron, cobalt and xenobiotic compounds. Motifs were also studied against PDB structures. Results of the study suggested the presence of binding sites on the surface of protein molecules involved. PDB structures of proteins were finally predicted for the binding sites functionality in their respective phytoremediation usage. This was further validated through CASTp server to study its physico-chemical properties. Bioinformatics implications would help in designing strategy for developing transgenic plants with increased metal binding capacity. These metal binding factors can be used to restrict metal update by plants. This helps in reducing the possibility of metal movement into the food chain.

  11. Cloning and expression of human tyrosine aminotransferase cDNA.

    PubMed

    Séralini, G E; Luu-Thé, V; Labrie, F

    1995-01-02

    Complementary DNA clones encoding human tyrosine aminotransferase (TAT) were isolated by screening a normal adult woman liver lambda gt11 library with rat TAT cDNA. The largest isolated cDNA is 2051 bp long (EMBL accession number X55675). This cDNA was subcloned downstream of the cytomegalovirus promoter in the pCMV vector for transfection into human cervical carcinoma HeLa cells. Expression of the TAT cDNA resulted in the synthesis of a protein with a molecular mass of approximately 50 kDa, as assessed by Western analysis, a value which is in close agreement with the predicted molecular weight of 50,399, for a deduced sequence of 454 amino acids. The expressed protein catalyzed specifically the conversion of L-[14C]tyrosine into p-[14C]hydroxyphenylpyruvate. The availability of a functional TAT cDNA provides a useful tool for detailed study of the structure-function relationship of the enzyme and its mutated derivatives.

  12. Development and evaluation of two novel oligonucleotide probes based on 16S rRNA sequence for the identification of Salmonella in foods.

    PubMed

    Lin, C K; Tsen, H Y

    1995-05-01

    DNA sequence in the V3 to V6 region of the 16S rRNA gene of Salmonella enteritidis was determined. By comparison of this sequence with those of Escherichia coli and Proteus vulgaris obtained from GenBank/EMBL database, three oligonucleotides termed as 16S I, 16S II and 16S III were synthesized. Hybridization of these oligonucleotides with 325 Salmonella isolates and some non-Salmonella isolates including the Salmonella closely related species of the family of Enterobacteriaceae showed that 16S II could not be used as a Salmonella specific-probe. 16S I and 16S III hybridized with all the Salmonella isolates tested, the former also hybridizing with Citrobacter spp. and the latter hybridizing with Klebsiella pneumoniae as well as Serratia marcescens. Since enrichment of the target cells in food samples was usually required prior to the DNA hybridization assay, the interference from those non-Salmonella isolates could be prevented by enrichment by culturing in lactose-combined tetrathionate (CTET) broth followed by Gram-negative (GN) broth at 37 degrees C and/or 43 degrees C. Such a culture step could inhibit the growth of Klebsiella spp., Ser. marcescens and/or Citrobacter spp. and allowed the specific detection of Salmonella.

  13. Bioinformatics approach of salt tolerance gene in mangrove plant Rhizophora stylosa

    NASA Astrophysics Data System (ADS)

    Basyuni, M.; Sumardi

    2017-01-01

    This study descibes bioinformatics approach on the analyze of the salt tolerance genes in mangrove plant, Rhizophora stylosa on DDBJ/EMBL/GenBank as well as similarity, phylogenetic, potential peptide, and subcellular localization. The DNA sequence between salt tolerance gene from R. stylosa exhibited 42-11% between themselves The target peptide value of mitochondria varied from 0.163 to 0.430, indicated it was possible to exist. These results suggested the importance of understanding the diversity and functional of properties of the different amino acids in mangrove OSC genes. To clarify the relationship among the salt-tolerant genes in R. stylosa, a phylogenetic tree was constructed. The phylogenetic tree shows that there are three clusters, first branch of Cu/Zn SOD and reverse transcriptase genes, the second branch consists of the majority genes and the last group was MAP3K alpha protein kinase only. The present study, therefore, suggested that salt tolerance genes form distinct clusters in the tree.

  14. Bioinformatics study of the mangrove actin genes

    NASA Astrophysics Data System (ADS)

    Basyuni, M.; Wasilah, M.; Sumardi

    2017-01-01

    This study describes the bioinformatics methods to analyze eight actin genes from mangrove plants on DDBJ/EMBL/GenBank as well as predicted the structure, composition, subcellular localization, similarity, and phylogenetic. The physical and chemical properties of eight mangroves showed variation among the genes. The percentage of the secondary structure of eight mangrove actin genes followed the order of a helix > random coil > extended chain structure for BgActl, KcActl, RsActl, and A. corniculatum Act. In contrast to this observation, the remaining actin genes were random coil > extended chain structure > a helix. This study, therefore, shown the prediction of secondary structure was performed for necessary structural information. The values of chloroplast or signal peptide or mitochondrial target were too small, indicated that no chloroplast or mitochondrial transit peptide or signal peptide of secretion pathway in mangrove actin genes. These results suggested the importance of understanding the diversity and functional of properties of the different amino acids in mangrove actin genes. To clarify the relationship among the mangrove actin gene, a phylogenetic tree was constructed. Three groups of mangrove actin genes were formed, the first group contains B. gymnorrhiza BgAct and R. stylosa RsActl. The second cluster which consists of 5 actin genes the largest group, and the last branch consist of one gene, B. sexagula Act. The present study, therefore, supported the previous results that plant actin genes form distinct clusters in the tree.

  15. Bioinformatics analysis of the oxidosqualene cyclase gene and the amino acid sequence in mangrove plants

    NASA Astrophysics Data System (ADS)

    Basyuni, M.; Wati, R.

    2017-01-01

    This study described the bioinformatics methods to analyze seven oxidosqualene cyclase (OSC) genes from mangrove plants on DDBJ/EMBL/GenBank as well as predicted the structure, composition, similarity, subcellular localization and phylogenetic. The physical and chemical properties of seven mangrove OSC showed variation among the genes. The percentage of the secondary structure of seven mangrove OSC genes followed the order of a helix > random coil > extended chain structure. The values of chloroplast or signal peptide were too low, indicated that no chloroplast transit peptide or signal peptide of secretion pathway in mangrove OSC genes. The target peptide value of mitochondria varied from 0.163 to 0.430, indicated it was possible to exist. These results suggested the importance of understanding the diversity and functional of properties of the different amino acids in mangrove OSC genes. To clarify the relationship among the mangrove OSC gene, a phylogenetic tree was constructed. The phylogenetic tree shows that there are three clusters, Kandelia KcMS join with Bruguiera BgLUS, Rhizophora RsM1 was close to Bruguiera BgbAS, and Rhizophora RcCAS join with Kandelia KcCAS. The present study, therefore, supported the previous results that plant OSC genes form distinct clusters in the tree.

  16. 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.

  17. 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.

  18. Using GenBank.

    PubMed

    Wheeler, David

    2007-01-01

    GenBank(R) is a comprehensive database of publicly available DNA sequences for more than 205,000 named organisms and for more than 60,000 within the embryophyta, obtained through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Daily data exchange with the European Molecular Biology Laboratory (EMBL) in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through the National Center for Biotechnology Information (NCBI) retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases with taxonomy, genome, mapping, protein structure, and domain information and the biomedical journal literature through PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available through FTP. GenBank usage scenarios ranging from local analyses of the data available through FTP to online analyses supported by the NCBI Web-based tools are discussed. To access GenBank and its related retrieval and analysis services, go to the NCBI Homepage at http://www.ncbi.nlm.nih.gov.

  19. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Wheeler, David L

    2007-01-01

    GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for more than 240 000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage (www.ncbi.nlm.nih.gov).

  20. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Wheeler, David L

    2006-01-01

    GenBank (R) is a comprehensive database that contains publicly available DNA sequences for more than 205 000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the Web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, go to the NCBI Homepage at www.ncbi.nlm.nih.gov.

  1. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Wheeler, David L

    2005-01-01

    GenBank is a comprehensive database that contains publicly available DNA sequences for more than 165,000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in the UK and the DNA Data Bank of Japan helps to ensure worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, go to the NCBI Homepage at http://www.ncbi.nlm.nih.gov.

  2. 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

  3. 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.

  4. 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.

  5. Conservation of the Conformation and Positive Charges of Hepatitis C Virus E2 Envelope Glycoprotein Hypervariable Region 1 Points to a Role in Cell Attachment

    PubMed Central

    Penin, François; Combet, Christophe; Germanidis, Georgios; Frainais, Pierre-Olivier; Deléage, Gilbert; Pawlotsky, Jean-Michel

    2001-01-01

    Chronic hepatitis C virus (HCV) infection is a major cause of liver disease. The HCV polyprotein contains a hypervariable region (HVR1) located at the N terminus of the second envelope glycoprotein E2. The strong variability of this 27-amino-acid region is due to its apparent tolerance of amino acid substitutions together with strong selection pressures exerted by anti-HCV immune responses. No specific function has so far been attributed to HVR1. However, its presence at the surface of the viral particle suggests that it might be involved in viral entry. This would imply that HVR1 is not randomly variable. We sequenced 460 HVR1 clones isolated at various times from six HCV-infected patients receiving alpha interferon therapy (which exerts strong pressure towards quasispecies genetic evolution) and analyzed their amino acid sequences together with those of 1,382 nonredundant HVR1 sequences collected from the EMBL database. We found that (i) despite strong amino acid sequence variability related to strong pressures towards change, the chemicophysical properties and conformation of HVR1 were highly conserved, and (ii) HVR1 is a globally basic stretch, with the basic residues located at specific sequence positions. This conservation of positively charged residues indicates that HVR1 is involved in interactions with negatively charged molecules such as lipids, proteins, or glycosaminoglycans (GAGs). As with many other viruses, possible interaction with GAGs probably plays a role in host cell recognition and attachment. PMID:11356980

  6. LigDig: a web server for querying ligand–protein interactions

    PubMed Central

    Fuller, Jonathan C.; Martinez, Michael; Henrich, Stefan; Stank, Antonia; Richter, Stefan

    2015-01-01

    Summary: LigDig is a web server designed to answer questions that previously required several independent queries to diverse data sources. It also performs basic manipulations and analyses of the structures of protein–ligand complexes. The LigDig webserver is modular in design and consists of seven tools, which can be used separately, or via linking the output from one tool to the next, in order to answer more complex questions. Currently, the tools allow a user to: (i) perform a free-text compound search, (ii) search for suitable ligands, particularly inhibitors, of a protein and query their interaction network, (iii) search for the likely function of a ligand, (iv) perform a batch search for compound identifiers, (v) find structures of protein–ligand complexes, (vi) compare three-dimensional structures of ligand binding sites and (vii) prepare coordinate files of protein–ligand complexes for further calculations. Availability and implementation: LigDig makes use of freely available databases, including ChEMBL, PubChem and SABIO-RK, and software programs, including cytoscape.js, PDB2PQR, ProBiS and Fconv. LigDig can be used by non-experts in bio- and chemoinformatics. LigDig is available at: http://mcm.h-its.org/ligdig. Contact: jonathan.fuller@h-its.org, rebecca.wade@h-its.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25433696

  7. 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

    2016-01-04

    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.

  8. proGenomes: a resource for consistent functional and taxonomic annotations of prokaryotic genomes.

    PubMed

    Mende, Daniel R; Letunic, Ivica; Huerta-Cepas, Jaime; Li, Simone S; Forslund, Kristoffer; Sunagawa, Shinichi; Bork, Peer

    2017-01-04

    The availability of microbial genomes has opened many new avenues of research within microbiology. This has been driven primarily by comparative genomics approaches, which rely on accurate and consistent characterization of genomic sequences. It is nevertheless difficult to obtain consistent taxonomic and integrated functional annotations for defined prokaryotic clades. Thus, we developed proGenomes, a resource that provides user-friendly access to currently 25 038 high-quality genomes whose sequences and consistent annotations can be retrieved individually or by taxonomic clade. These genomes are assigned to 5306 consistent and accurate taxonomic species clusters based on previously established methodology. proGenomes also contains functional information for almost 80 million protein-coding genes, including a comprehensive set of general annotations and more focused annotations for carbohydrate-active enzymes and antibiotic resistance genes. Additionally, broad habitat information is provided for many genomes. All genomes and associated information can be downloaded by user-selected clade or multiple habitat-specific sets of representative genomes. We expect that the availability of high-quality genomes with comprehensive functional annotations will promote advances in clinical microbial genomics, functional evolution and other subfields of microbiology. proGenomes is available at http://progenomes.embl.de.

  9. 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

    2016-03-24

    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.

  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. Gene order in a 10 275 bp fragment of Yarrowia lipolytica, including adjacent YlURA5 and YlSEC65 genes conserved in four yeast species.

    PubMed

    Sánchez, M; Domínguez, A

    2001-06-30

    We have determined the sequence of a 10275 bp DNA segment of Yarrowia lipolytica located on chromosome VI. The sequence contains six complete open reading frames (ORFs) longer than 100 amino acids and two more partial ORFs at both ends. Two of the ORFs encode for the well-characterized genes YlURA5 (orotate phosphoribosyltransferase) and YlSEC65 (encoding a subunit of the signal recognition particle). These two genes show an identical organization-located on opposite strands and in opposite orientations-in four yeast species: Saccharomyces cerevisiae, Kluyveromyces lactis, Candida albicans and Y. lipolytica. One ORF and the two partial ORFs code for putative proteins showing significant homology with proteins from other organisms. YlVI-108w (partial) and YlVI-103w show 39% and 54% identity, respectively, with YDR430c and YHR088w from S. cerevisiae. YlVI-102c (partial) shows significant homology with a matrix protein, lustrin A from Haliotis rufescens, and with the PGRS subfamily (Gly-rich proteins) of Mycobacterium tuberculosis. The three remaining ORFs show weak or non-significant homology with previously sequenced genes. The nucleotide sequence has been submitted to the EMBL database under Accession No. AI006754.

  12. 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

  13. Desulfovibrio brasiliensis sp. nov., a moderate halophilic sulfate-reducing bacterium from Lagoa Vermelha (Brazil) mediating dolomite formation.

    PubMed

    Warthmann, Rolf; Vasconcelos, Crisogono; Sass, Henrik; McKenzie, Judith A

    2005-06-01

    A novel halotolerant sulfate-reducing bacterium, Desulfovibrio brasiliensis strain LVform1, was isolated from sediments of a dolomite-forming hypersaline coastal lagoon, Lagoa Vermelha, in the state of Rio de Janeiro, Brazil. The cells are vibrio-shaped and 0.30 to 0.45 microm by 1.0 to 3.5 microm in size. These bacteria mediate the precipitation of dolomite [CaMg(CO3)2] in culture experiments. The strain was identified as a member of the genus Desulfovibrio in the delta-subclass of the Proteobacteria on the basis of its 16S rRNA gene sequence, its physiological and morphological properties. Strain LVform1 is obligate sodium-dependent and grows at NaCl concentrations of up to 15%. The 16S rRNA sequence revealed that this strain is closely related to Desulfovibrio halophilus (96.2% similarity) and to Desulfovibrio oxyclinae (96.8% similarity), which were both isolated from Solar Lake, a hypersaline coastal lake in the Sinai, Egypt. Strain LVform1 is barotolerant, growing under pressures of up to 370 bar (37 MPa). We propose strain LVform1 to be the type strain of a novel species of the genus Desulfovibrio, Desulfovibrio brasiliensis (type strain LVform1 = DSMZ No. 15816 and JCM No. 12178). The GenBank/EMBL accession number for the 16S rDNA sequence of strain LVform1 is AJ544687.

  14. Structure and chemical reactivity of the polar three-fold surfaces of GaPd: A density-functional study

    NASA Astrophysics Data System (ADS)

    Krajčí, M.; Hafner, J.

    2013-03-01

    The polar threefold surfaces of the GaPd compound crystallizing in the B20 (FeSi-type) structure (space group P213) 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 (bar{1}bar{1}bar{1}) 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

  15. Hepatitis B Virus of Genotype B with or without Recombination with Genotype C over the Precore Region plus the Core Gene

    PubMed Central

    Sugauchi, Fuminaka; Orito, Etsuro; Ichida, Takafumi; Kato, Hideaki; Sakugawa, Hiroshi; Kakumu, Shinichi; Ishida, Takafumi; Chutaputti, Anuchit; Lai, Ching-Ling; Ueda, Ryuzo; Miyakawa, Yuzo; Mizokami, Masashi

    2002-01-01

    The entire nucleotide sequences of 70 hepatitis B virus (HBV) isolates of genotype B (HBV/B), including 38 newly determined and 32 retrieved from the international DNA database (DDBJ/EMBL/GenBank), were compared phylogenetically. Two subgroups of HBV/B were identified based on sequence divergence in the precore region plus the core gene, one with the recombination with genotype C and the other without it. The analysis over the entire genome of HBV/B by the SimPlot program located the recombination with genotype C in the precore region plus the core gene spanning nucleotide positions from 1740 to 1838 to 2443 to 2485. Within this genomic area, HBV/B strains with the recombination had higher nucleotide and amino acid homology to genotype C than those without the recombination (96.9 versus 91.1% in nucleotides and 97.0 versus 92.9% in amino acids). There were 29 HBV/B strains without the recombination, and they were all recovered from carriers in Japan. The remaining 41 HBV/B isolates having the recombination with genotype C were from carriers in China (12 strains), Hong Kong (3 strains), Indonesia (4 strains), Japan (3 strains), Taiwan (4 strains), Thailand (3 strains), and Vietnam (12 strains). Due to the frequency of the distribution of HBV/B without the recombination (29 of 32 isolates, or 91%) and the fact that it was exclusive to Japan, it was provisionally classified into the Bj (j standing for Japan) subgroup, and HBV/B with the recombination was classified into the Ba (a for Asia) subgroup. Virological differences between HBV/Bj and HBV/Ba may be reflected in the severity of clinical disease in the patients infected with HBV of genotype B, which seems to be under strong geographic influences in Asia. PMID:12021331

  16. 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

  17. 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).

  18. 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.

  19. Molecular detection of Culicoides spp. and Culicoides imicola, the principal vector of bluetongue (BT) and African horse sickness (AHS) in Africa and Europe.

    PubMed

    Cêtre-Sossah, Catherine; Baldet, Thierry; Delécolle, Jean-Claude; Mathieu, Bruno; Perrin, Aurélie; Grillet, Colette; Albina, Emmanuel

    2004-01-01

    Bluetongue (BT) and African Horse Sickness (AHS) are infectious arthropod-borne viral diseases affecting ruminants and horses, respectively. Culicoides imicola Kieffer, 1913, a biting midge, is the principal vector of these livestock diseases in Africa and Europe. Recently bluetongue disease has re-emerged in the Mediterranean Basin and has had a devastating effect on the sheep industry in Italy and on the islands of Sicily, Sardinia, Corsica and the Balearics, but fortunately, has not penetrated onto mainland France and Spain. To survey for the presence of C. imicola, an extensive light-trap network for the collection of Culicoides, was implemented in 2002 in southern mainland France. The morphological identification of Culicoides can be both tedious and time-consuming because its size ranges from 1.5 to 3 mm. Therefore, an ITS1 rDNA polymerase chain reaction (PCR)-based diagnostic assay was developed to rapidly and reliably identify Culicoides spp. and C. imicola. The aim of this work was to set up a rapid test for the detection of C. imicola amongst a pool of insects collected in areas at risk for BT. The sequence similarity of the rDNA (nuclear ribosomal DNA), which is greater within species than between species, is the foundation of its utilisation in species-diagnostic assays. The alignment of the 11 ITS1 sequences of Culicoides obtained from Genbank and EMBL databases helped us to identify one region in the 5' end and one in the 3' end that appear highly conserved. PCR primers were designed within these regions to amplify genus-specific fragments. In order to set up a C. imicola-specific PCR, another forward primer was designed and used in combination with the previously designed reverse primer. These primers proved to be highly specific and sensitive and permitted a rapid diagnostic separation of C. imicola from Culicoides spp.

  20. 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.

  1. Characterization of three genomic loci encoding Rhizobium sp. strain ORS571 N2 fixation genes.

    PubMed

    Donald, R G; Nees, D W; Raymond, C K; Loroch, A I; Ludwig, R A

    1986-01-01

    Sixty-five independent, N2 fixation-defective (Nif-) vector insertion (Vi) mutants were selected, cloned, and mapped to the ORS571 genome. The recombinant Nif::Vi plasmids obtained in this way were used as DNA hybridization probes to isolate homologous phages from a genomic library of ORS571 constructed in lambda EMBL3. Genomic maps were drawn for three ORS571 Nif gene loci. Forty-five Nif::Vi mutants in genomic Nif locus 1 defined two gene clusters separated by 8 kilobase pairs (kb) of DNA. In the first cluster, 36 Nif::Vi mutants mapped to a 7-kb DNA segment that showed DNA homology with Klebsiella pneumoniae nifHDKE and encoded at least two Nif operons. In the other cluster, nine Nif::Vi mutants mapped to a 1.5-kb DNA segment that showed homology with K. pneumoniae and Rhizobium meliloti nifA; this DNA segment encoded a separate Nif operon. Fifteen Nif::Vi mutants mapped to a 3.5-kb DNA segment defined as Nif locus 2 and showed DNA homology with the R. meliloti P2 fixABC operon. Nif locus 2 carries a second nifH (nifH2) gene. Four Nif::Vi mutants mapped to a 2-kb DNA segment defined as Nif locus 3 and showed DNA homology with K. pneumoniae nifB. DNA from lambda Nif phages comprising all three genomic Nif loci was subcloned in plasmid vectors able to stably replicate in ORS571. These plasmid subclones were introduced into ORS571 strains carrying physically mapped Nif::Vi insertions, and genetic complementations were conducted. With the exception of certain mutants mapping to the nifDK genes, all mutants could be complemented to Nif+ when they carried plasmid subclones of defined genomic DNA regions. Conversely, most nifDK mutants behaved as pseudodominant alleles.

  2. Genome sequence of three Psychrobacter sp. strains with potential applications in bioremediation.

    PubMed

    Lasa, Aide; Romalde, Jesús L

    2017-06-01

    To date, the genus Psychrobacter consists of 37 recognized species isolated from different sources, however they are more frequently found in cold and other non-polar environments of low water activity. Some strains belonging to the genus have shown different enzymatic activities with potential applications in bioremediation or food industry. In the present study, the whole genome sequences of three Psychrobacter-like strains (C 20.9, Cmf 22.2 and Rd 27.2) isolated from reared clams in Galicia (Spain) are described. The sequenced genomes resulted in an assembly size of 3,143,782 bp for C 20.9 isolate, 3,168,467 bp for Cmf 22.2 isolate and 3,028,386 bp for Rd 27.2 isolate. Among the identified coding sequences of the genomes, mercury detoxification and biogeochemistry genes were found, as well as genes related to heavy metals and antibiotic resistance. Also virulence-related features were identified such as the siderophore vibrioferrin or an aerobactin-like siderophore. The phylogenetic analysis of the 16S rRNA gene suggested that these strains may represent novel species of the Psychrobacter genus. The genome sequences of the Psychrobacter sp. strains have been deposited at DDBJ/EMBL/GenBank under the accession numbers MRYA00000000 (Cmf 22.2), MRYB00000000 (Rd 27.2) and MRYC00000000 (C 20.9), and the sequences could be found at the site https://www.ncbi.nlm.nih.gov/bioproject/PRJNA353858.

  3. 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

  4. Cloning and characterization of the major promoter of the human protein kinase C beta gene. Regulation by phorbol esters.

    PubMed

    Obeid, L M; Blobe, G C; Karolak, L A; Hannun, Y A

    1992-10-15

    The expression of the beta isoenzyme for protein kinase C is regulated developmentally and in response to inducers of cell differentiation (such as phorbol esters and 1 alpha,25-dihydroxyvitamin D3). The 5' segment of the gene for protein kinase C beta was cloned from a human leukocyte genomic library in EMBL3 bacteriophage. This segment of the gene (greater than 54 kilobases in length) encompassed the coding sequence for the amino-terminal regulatory domain of the enzyme, the 5'-untranslated region, and the 5'-flanking region. Initiation of transcription was identified by S1 nuclease analysis and confirmed by RNase protection analysis at 197 base pairs 5' of the initiator ATG. Sequence analysis of the 5'-flanking region revealed it to be extremely G+C-rich (> 80%) with many features of a CpG island. Comparison of sequence with known cis-regulatory motifs disclosed a number of potential regulatory elements including an octamer binding motif at -76, Sp1-binding sites at -94 and -63, E boxes at -110, -26, and +18, an AP-1 site at -442, and an AP-2 site at -330. To demonstrate promoter activity, a 630-base pair fragment extending from -587 to +43 was subcloned in front of a promoterless luciferase gene. This fragment was able to drive the expression of luciferase in transient transfections of human hematopoietic cells. Deletion analysis demonstrated that a fragment -111 to +43 was necessary and sufficient for promoter activity; this fragment did not contain TATA or CAAT motifs. The promoter was stimulated 8-20-fold by phorbol esters accounting for the previously observed transcriptional activation of protein kinase C beta. This phorbol ester responsiveness was conferred by the basal promoter (-111 to +43) and was independent of the AP-1 site. These results define a novel mechanism of protein kinase C autoregulation at a transcriptional level.

  5. The Bioperl Toolkit: Perl Modules for the Life Sciences

    PubMed Central

    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

    2002-01-01

    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. [Supplemental material is available online at www.genome.org. Bioperl is available as open-source software free of charge and is licensed under the Perl Artistic License (http://www.perl.com/pub/a/language/misc/Artistic.html). It is available for download at http://www.bioperl.org. Support inquiries should be addressed to bioperl-l@bioperl.org.] PMID:12368254

  6. 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.

  7. 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

  8. Diversity in VP3, NSP3, and NSP4 of rotavirus B detected from Japanese cattle.

    PubMed

    Hayashi-Miyamoto, Michiko; Murakami, Toshiaki; Minami-Fukuda, Fujiko; Tsuchiaka, Shinobu; Kishimoto, Mai; Sano, Kaori; Naoi, Yuki; Asano, Keigo; Ichimaru, Toru; Haga, Kei; Omatsu, Tsutomu; Katayama, Yukie; Oba, Mami; Aoki, Hiroshi; Shirai, Junsuke; Ishida, Motohiko; Katayama, Kazuhiko; Mizutani, Tetsuya; Nagai, Makoto

    2017-04-01

    Bovine rotavirus B (RVB) is an etiological agent of diarrhea mostly in adult cattle. Currently, a few sequences of viral protein (VP)1, 2, 4, 6, and 7 and nonstructural protein (NSP)1, 2, and 5 of bovine RVB are available in the DDBJ/EMBL/GenBank databases, and none have been reported for VP3, NSP3, and NSP4. In order to fill this gap in the genetic characterization of bovine RVB strains, we used a metagenomics approach and sequenced and analyzed the complete coding sequences (CDS) of VP3, NSP3, and NSP4 genes, as well as the partial or complete CDS of other genes of RVBs detected from Japanese cattle. VP3, NSP3, and NSP4 of bovine RVBs shared low nucleotide sequence identities (63.3-64.9% for VP3, 65.9-68.2% for NSP3, and 52.6-56.2% for NSP4) with those of murine, human, and porcine RVBs, suggesting that bovine RVBs belong to a novel genotype. Furthermore, significantly low amino acid sequence identities were observed for NSP4 (36.1-39.3%) between bovine RVBs and the RVBs of other species. In contrast, hydrophobic plot analysis of NSP4 revealed profiles similar to those of RVBs of other species and rotavirus A (RVA) strains. Phylogenetic analyses of all gene segments revealed that bovine RVB strains formed a cluster that branched distantly from other RVBs. These results suggest that bovine RVBs have evolved independently from other RVBs but in a similar manner to other rotaviruses. These findings provide insights into the evolution and diversity of RVB strains.

  9. Molecular cloning of a mouse DNA repair gene that complements the defect of group-A xeroderma pigmentosum

    SciTech Connect

    Tanaka, K.; Satokata, I.; Ogita, Z.; Uchida, T.; Okada, Y.

    1989-07-01

    For isolation of the gene responsible for xeroderma pigmentosum (XP) complementation group A, plasmid pSV2gpt and genomic DNA from a mouse embryo were cotransfected into XP2OSSV cells, a group-A XP cell line. Two primary UV-resistant XP transfectants were isolated from about 1.6 X 10(5) pSV2gpt-transformed XP colonies. pSV2gpt and genomic DNA from the primary transfectants were again cotransfected into XP2OSSV cells and a secondary UV-resistant XP transfectant was obtained by screening about 4.8 X 10(5) pSV2gpt-transformed XP colonies. The secondary transfectant retained fewer mouse repetitive sequences. A mouse gene that complements the defect of XP2OSSV cells was cloned into an EMBL3 vector from the genome of a secondary transfectant. Transfections of the cloned DNA also conferred UV resistance on another group-A XP cell line but not on XP cell lines of group C, D, F, or G. Northern blot analysis of poly(A)+ RNA with a subfragment of cloned mouse DNA repair gene as the probe revealed that an approximately 1.0 kilobase mRNA was transcribed in the donor mouse embryo and secondary transfectant, and approximately 1.0- and approximately 1.3-kilobase mRNAs were transcribed in normal human cells, but none of these mRNAs was detected in three strains of group-A XP cells. These results suggest that the cloned DNA repair gene is specific for group-A XP and may be the mouse homologue of the group-A XP human gene.

  10. 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

  11. Heterologous expression of the flavonoid 3',5'-hydroxylase gene of Vinca major alters flower color in transgenic Petunia hybrida.

    PubMed

    Mori, S; Kobayashi, H; Hoshi, Y; Kondo, M; Nakano, M

    2004-01-01

    Flavonoid 3',5'-hydroxylase (F3'5'H) is the key enzyme for the expression of blue or purple flower color. A full-length cDNA for the F3'5'H gene was cloned from petals of Vinca major, and its genomic clone, designated VmFH1 (accession number AB078781 in the GenBank/EMBL/DDBJ databases), was isolated from leaves by a PCR-based strategy. Nucleotide sequence analysis revealed that VmFH1 contains one intron and an open reading frame encoding a polypeptide of 506 amino acid residues. The deduced amino acid sequence shows between 51% and 83% identity with those of previously reported F3'5'H genes. Southern blot analysis showed that there are 3-4 copies of the F3'5'H gene in the genome of V. major. Transcripts of the F3'5'H gene were detected in young flower petals but not in leaves as revealed by RT-PCR analysis. When VmFH1 was expressed in transgenic Petunia hybrida under the control of the cauliflower mosaic virus 35S promoter, some transgenic plants showed drastic flower color alteration from red to deep red with deep purple sectors. These transgenic plants accumulated 3',5'-hydroxylated anthocyanins in their petals, which were never detected in non-transgenic plants by high-performance liquid chromatography analysis. These results indicate that VmFH1 isolated from V. major encodes F3'5'H and is active in a heterologous plant species.

  12. 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

  13. 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.

  14. [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.

  15. 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.

  16. Structural and functional analysis of the nor-1 gene involved in the biosynthesis of aflatoxins by Aspergillus parasiticus.

    PubMed Central

    Trail, F; Chang, P K; Cary, J; Linz, J E

    1994-01-01

    The nor-1 gene was cloned previously by complementation of a mutation (nor-1) in Aspergillus parasiticus SU-1 which blocked aflatoxin B1 biosynthesis, resulting in the accumulation of norsolorinic acid (NA). In this study, the nucleotide sequences of the cDNA and genomic DNA clones encompassing the coding region of the nor-1 gene were determined. The transcription initiation and polyadenylation sites of nor-1 were located by primer extension and RNase protection analyses and by comparison of the nucleotide sequences of the nor-1 genomic and cDNA clones. A plasmid, pNA51-82, was created for one-step disruption of the nor-1 gene by inserting a functional copy of the nitrate reductase (niaD) gene from A. parasiticus into the coding region of the nor-1 gene. Transformation of A. parasiticus NR-3 (niaD Afl+) with pNA51-82 resulted in niaD+ transformants that accumulated NA and produced reduced levels of aflatoxin as determined by thin-layer chromatography and enzyme-linked immunosorbent assay analyses of extracts from mycelia and the growth medium. Southern analysis of genomic DNA isolated from the NA-accumulating transformants indicated that the wild-type nor-1 gene in the chromosome had been replaced by the nonfunctional allele carried on pNA51-82. This recombinational inactivation event provides direct evidence that the nor-1 gene is functionally involved in aflatoxin biosynthesis. Comparison of the predicted nor-1 amino acid sequence with sequences in the GenBank and EMBL databases suggested that the protein is a member of the family of short-chain alcohol dehydrogenases, consistent with its proposed function as a keto reductase. Images PMID:7993094

  17. Molecular characterization of a conserved 20-kilodalton membrane-associated lipoprotein antigen of Helicobacter pylori.

    PubMed Central

    Kostrzynska, M; O'Toole, P W; Taylor, D E; Trust, T J

    1994-01-01

    Antisera raised in rabbits to whole cells of Helicobacter pylori recognized as a major antigen a protein with an apparent molecular weight of 20,000. The antigen was purified by differential solubilization with N-octyl-beta-D-glucopyranoside, urea, and sodium dodecyl sulfate followed by molecular sieving. The mass of the protein, Lpp20, was 18,283 Da as determined by mass spectrometry. The lpp20 gene encoding this protein was cloned in Escherichia coli by using the vector lambda EMBL3, and plasmid subclones expressed the full-length protein from the native H. pylori promoter. lpp20 was mapped to the same 358-kb NruI fragment as flaB. DNA sequence analysis showed that the gene was 525 bp long and encoded a 175-amino-acid protein with a molecular weight of 19,094 containing a 21-residue typical lipoprotein signal peptide and consensus prolipoprotein processing site. The mass of the deduced 154-residue mature protein was 16,865 Da. Growth of E. coli cells expressing the cloned H. pylori lpp20 gene in the presence of [3H]palmitic acid resulted in radiolabelled Lpp20 while treatment of the E. coli cells with globomycin caused accumulation of unprocessed Lpp20, consistent with Lpp20 being a lipoprotein. Lpp20 cofractionated with the cytoplasmic membrane fraction, although a proportion of the protein was also found in the outer membrane. A mutant generated by mutant-allele exchange displayed normal viability, showing that Lpp20 belonged to the nonessential class of lipoproteins. Images PMID:7928954

  18. 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 .

  19. 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

  20. LabDisk for SAXS: a centrifugal microfluidic sample preparation platform for small-angle X-ray scattering.

    PubMed

    Schwemmer, Frank; Blanchet, Clement E; Spilotros, Alessandro; Kosse, Dominique; Zehnle, Steffen; Mertens, Haydyn D T; Graewert, Melissa A; Rössle, Manfred; Paust, Nils; Svergun, Dmitri I; von Stetten, Felix; Zengerle, Roland; Mark, Daniel

    2016-04-07

    We present a centrifugal microfluidic LabDisk for protein structure analysis via small-angle X-ray scattering (SAXS) on synchrotron beamlines. One LabDisk prepares 120 different measurement conditions, grouped into six dilution matrices. Each dilution matrix: (1) features automatic generation of 20 different measurement conditions from three input liquids and (2) requires only 2.5 μl of protein solution, which corresponds to a tenfold reduction in sample volume in comparison to the state of the art. Total hands on time for preparation of 120 different measurement conditions is less than 5 min. Read-out is performed on disk within the synchrotron beamline P12 at EMBL Hamburg (PETRA III, DESY). We demonstrate: (1) aliquoting of 40 nl aliquots for five different liquids typically used in SAXS and (2) confirm fluidic performance of aliquoting, merging, mixing and read-out from SAXS experiments (2.7-4.4% CV of protein concentration). We apply the LabDisk for SAXS for basic analysis methods, such as measurement of the radius of gyration, and advanced analysis methods, such as the ab initio calculation of 3D models. The suitability of the LabDisk for SAXS for protein structure analysis under different environmental conditions is demonstrated for glucose isomerase under varying protein and NaCl concentrations. We show that the apparent radius of gyration of the negatively charged glucose isomerase decreases with increasing protein concentration at low salt concentration. At high salt concentration the radius of gyration (Rg) does not change with protein concentrations. Such experiments can be performed by a non-expert, since the LabDisk for SAXS does not require attachment of tubings or pumps and can be filled with regular pipettes. The new platform has the potential to introduce routine high-throughput SAXS screening of protein structures with minimal input volumes to the regular operation of synchrotron beamlines.

  1. Diversity Analysis of Bacterial Community from Permafrost Soil of Mo-he in China.

    PubMed

    Dan, Dong; Zhang, Dian-Peng; Liu, Wei-Cheng; Lu, Cai-Ge; Zhang, Tao-Tao

    2014-03-01

    The permafrost soil of Mo-he in Northeast China presents a typical cold environment colonized by psychrophilic microorganisms. This study is aimed at assessing the bacterial communities of permafrost soil of Mo-he in China by sequencing the 16S rRNA genes and Mothur analysis. PCR products with universal 16S rRNA gene primers were cloned and partially sequenced, and bacterial identification at the species was performed by comparative analysis with the GenBank/EMBL/DDBJ database. A total of 266 clones were obtained with the average length of 1,050 bp. Mothur analysis showed that the coverage value of clone library was 53.78 %, Shannon diversity (H) was 4.03, Simpson diversity value was 0.018, and 74 operational taxonomic units were generated. Through phylogenetic assignment using BLASTN by more than 97 % similarity, a total of 87 tentative taxa were identified. The majority of bacterial sequences recovered in this study belonged to the Acidobacteria, Proteobacteria, Verrucomicrobia, Bacteroidetes, Chloroflexi and Chlorobi. Among them, Acidobacteria are dominant community, accounting for 30.1 % of total bacteria, followed by Proteobacteria which accounted for 22.2 %. This result reflected the acidic characteristics of the permafrost soil of which pH value was 6.0. Our study indicated that the permafrost soil of Mo-he in China has a high diversity of bacteria and represents a vast potential resource of novel bacteria. As far as we knew, this is the first report on bacterial diversity of permafrost soil of Mo-he in China.

  2. Historeceptomic Fingerprints for Drug-Like Compounds.

    PubMed

    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.

  3. Diopatra neapolitana and Diopatra marocensis from the Portuguese coast: Morphological and genetic comparison

    NASA Astrophysics Data System (ADS)

    Rodrigues, Ana Maria; Pires, Adília; Mendo, Sónia; Quintino, Victor

    2009-12-01

    This paper reports the presence of Diopatra marocensis in European waters, for which Diopatra neapolitana was the only species recognized until recently. Both species coexist in transitional waters, where D. marocensis may be mistaken for young specimens of D. neapolitana. The population of D. marocensis studied in the coastal shelf can be traced back to 1997 and is increasing in density, apparently benefiting from a local anthropogenic organic enrichment source. This study emphasizes the main morphological characteristics that allow discriminating the two species and uses a molecular approach through the mitochondrial DNA genes 16S rDNA and COI (cytochrome c oxidase subunit I) analysis to confirm their distinction. The percentage of nucleotides divergence of the 16S and COI genes between the two species was 14% and 17%, respectively. The nucleotide sequence was conserved among all specimens of the same species for 16S gene, and the differences observed between individuals of the same species for the COI gene always corresponded to a silent alteration with no amino acid change. The nucleotide sequences of the two genes of both species were also compared to the sequences of Diopatra aciculata deposited in the EMBL database. The divergence values between Diopatra marocensis and D. aciculata were 14% and 18% for 16S and COI, respectively whereas between Diopatra neapolitana and D. aciculata were 1% and 5% for 16S and COI, respectively. Phylogenetic analysis was performed to deduce relationships among the Diopatra species studied. This analysis showed that D. marocensis and D. neapolitana are in different clades and thus could be considered different species, whereas D. aciculata and D. neapolitana are in sister clades thus emphasising their similarities, already noticed at a morphological level.

  4. Characterization of attached bacterial populations in deep granitic groundwater from the Stripa research mine by 16S rRNA gene sequencing and scanning electron microscopy.

    PubMed

    Ekendahl, S; Arlinger, J; Ståhl, F; Pedersen, K

    1994-07-01

    This paper presents the molecular characterization of attached bacterial populations growing in slowly flowing artesian groundwater from deep crystalline bed-rock of the Stripa mine, south central Sweden. Bacteria grew on glass slides in laminar flow reactors connected to the anoxic groundwater flowing up through tubing from two levels of a borehole, 812-820 m and 970-1240 m. The glass slides were collected, the bacterial DNA was extracted and the 16S rRNA genes were amplified by PCR using primers matching universally conserved positions 519-536 and 1392-1405. The resulting PCR fragments were subsequently cloned and sequenced. The sequences were compared with each other and with 16S rRNA gene sequences in the EMBL database. Three major groups of bacteria were found. Signature bases placed the clones in the appropriate systematic groups. All belonged to the proteobacterial groups beta and gamma. One group was found only at the 812-820 m level, where it constituted 63% of the sequenced clones, whereas the second group existed almost exclusively at the 970-1240 m level, where it constituted 83% of the sequenced clones. The third group was equally distributed between the levels. A few other bacteria were also found. None of the 16S rRNA genes from the dominant bacteria showed more than 88% similarity to any of the others, and none of them resembled anything in the database by more than 96%. Temperature did not seem to have any effect on species composition at the deeper level. SEM images showed rods appearing in microcolonies.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. 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.

  6. Virus-like particles in Eimeria nieschulzi are associated with multiple RNA segments.

    PubMed

    Roditi, I; Wyler, T; Smith, N; Braun, R

    1994-02-01

    RNA preparations from sporulated oocysts of Eimeria nieschulzi were found to contain 2 double-stranded RNA segments of 5.0 kb and 5.7 kb that were not present in other species of Eimeria. Treatment of crude lysates with RNase A revealed that in addition to these two segments, 3 other segments of 0.57 kb, 0.72 kb and 11.5 kb were protected from digestion, suggesting that they were enclosed within particles. Virus-like particles with a diameter of approximately 39 nm were purified by caesium chloride buoyant density centrifugation. Four of the five RNA segments copurified with these particles. In keeping with the nomenclature generally adopted for protozoan viruses, we have named this new isolate ENV 1. The largest RNA segment does not cosediment with ENV 1 particles and may be derived from another RNA-protein complex that is unstable under the conditions used. The particle size and genome structure of ENV 1 both differ from that of the Eimeria stiedae virus (ESV), which is the only other virus to have been isolated from Eimeria to date. Short cDNA clones derived from ENV 1 show significant homology to a region of the Leishmania virus (LRV 1) genome that encodes an RNA-dependent RNA polymerase. The polymerase sequences from ENV 1 and LRV 1 are more closely related to each other than to any other protein sequences in the GenEMBL Database. This raises intriguing questions about the origins of the two viruses, since Eimeria and Leishmania normally infect different hosts and also show different cell tropisms within these hosts.

  7. Properties of recombinant fluorescent proteins from Photobacterium leiognathi and their interaction with luciferase intermediates.

    PubMed

    Petushkov, V N; Gibson, B G; Lee, J

    1995-03-14

    Ligand binding and luciferase interaction properties of the recombinant protein corresponding to the lumazine protein gene (EMBL X56534) of Photobacterium leiognathi have been determined by fluorescence dynamics, circular dichroism, gel filtration, and SDS-PAGE. Scatchard analysis of a fluorescence titration shows that the apoprotein possess one binding site, and at 30 degrees C the KdS (microM) are as follows: 6,7-dimethyl-8-ribityllumazine, 0.26; riboflavin, 0.53; and much more weakly bound FMN, 30. All holoproteins are highly fluorescent and have absorption spectra distinct from each other and from the free ligands. The longest wavelength absorption maxima are, respectively (nm, 2 degrees C), 420, 463, and 458. Ligand binding produces no change in the far-UV circular dichroism; all have mean residual ellipticity at 210 nm of -6500 deg cm2 dmol-1, the same as the native protein. However, in the bioluminescence reaction only the lumazine holoprotein shows a bioluminescence effect. Fluorescence emission anisotropy decay was used to establish that none of these holoproteins complexed with native luciferase and that the lumazine protein alone formed a 1:1 complex with the luciferase hydroxyflavin fluorescent transient and the luciferase peroxyflavin intermediates, revealed by a dominant channel of anisotropy loss, with rotational correlation time of 2.5 ns, and attributed to excitation transfer from the luciferase flavin donor to the acceptor, the lumazine ligand. The complex stability was sufficient to allow its isolation by FPLC gel filtration and verification by SDS-PAGE. These methods also confirmed the absence of interaction of the holoflavoproteins.

  8. The lumQ gene is linked to the lumP gene and the lux operon in Photobacterium leiognathi.

    PubMed

    Lin, J W; Yu, K Y; Chao, Y F; Weng, S F

    1995-12-14

    The nucleotide sequence of the designated lumQ gene (EMBL accession No. U35231) from Photobacterium leiognathi PL741 has been determined, and the encoded amino acid sequence is deduced. The LumQ protein has a calculated M(r) of 28,416 and comprises 248 amino acid residues. The lumQ gene is identified as the envY-like gene by significant similarity of the encoded protein with the EnvY and AdiY proteins of E. coli; there the envY gene encodes the porin thermoregulatory protein EnvY, and the adiY gene encodes the putative transcriptional regulator protein AdiY. It suggests that the lumQ gene of P. leiognathi is orthologous to the envY and adiY genes of E. coli. The function of the protein encoded by the lumQ gene from P. leiognathi is not really defined yet, it is likely to be the DNA-binding protein related to the araC and xylS family of transcriptional regulators. The lumQ and lumP genes form the lum operon which linked to the lux operon, but run in the opposite direction. The gene order of the lum and the lux operon is < -ter-lumQ-lumP-R&R-luxC-luxD-luxA-luxB- luxN-luxE- > (R&R: regulatory region; ter: transcriptional terminator); whereas the regulatory region (R&R) includes two promoter systems, PR-promoter for the lux operon and PL-promoter for the lum operon; ter is the transcriptional terminator of the lum operon.

  9. 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

  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. Nitric oxide and cGMP signaling in calcium-dependent development of cell polarity in Ceratopteris richardii.

    PubMed

    Salmi, Mari L; Morris, Kacey E; Roux, Stanley J; Porterfield, D Marshall

    2007-05-01

    Single-celled spores of the fern Ceratopteris richardii undergo gravity-directed cell polarity development that is driven by polar calcium currents. Here we present results that establish a role for nitric oxide (NO)/cGMP signaling in transducing the stimulus of gravity to directed polarization of the spores. Application of specific NO donors and scavengers inhibited the calcium-dependent gravity response in a dose-dependent manner. The effects of NO donor exposure were antagonized by application of NO scavenger compounds. Similarly, the guanylate cyclase inhibitors 6-anilino-5,8-quinolinedione and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin, and the phosphodiesterase inhibitor Viagra, which modulate NO-dependent cGMP levels in the cells, disrupted gravity-directed cell polarity in a dose-dependent manner. Viagra effects were antagonized by application of NO scavengers, consistent with the postulate that NO and cGMP are linked in the signaling pathway. To identify other components of the signaling system we analyzed gene expression changes induced by Viagra treatment using microarrays and quantitative real-time reverse transcription-polymerase chain reaction. Preliminary microarray analysis revealed several genes whose expression was significantly altered by Viagra treatment. Three of these genes had strong sequence similarity to key signal transduction or stress response genes and quantitative real-time reverse transcription-polymerase chain reaction was used to more rigorously quantify the effects of Viagra on their expression in spores and to test how closely these effects could be mimicked by treatment with dibutyryl cGMP. Taken together our results implicate NO and cGMP as downstream effectors that help link the gravity stimulus to polarized growth in C. richardii spores. Sequence data from this article can be found in the GenBank/EMBL data libraries under accession numbers BE 640669 to BE 643506, BQ 086920 to BQ 087668, and CV 734654 to CV 736151.

  12. MHC-Linked Olfactory Receptor Loci Exhibit Polymorphism and Contribute to Extended HLA/OR-Haplotypes

    PubMed Central

    Ehlers, Anke; Beck, Stephan; Forbes, Simon A.; Trowsdale, John; Volz, Armin; Younger, Ruth; Ziegler, Andreas

    2000-01-01

    Clusters of olfactory receptor (OR) genes are found on most human chromosomes. They are one of the largest mammalian multigene families. Here, we report a systematic study of polymorphism of OR genes belonging to the largest fully sequenced OR cluster. The cluster contains 36 OR genes, of which two belong to the vomeronasal 1 (V1-OR) family. The cluster is divided into a major and a minor region at the telomeric end of the HLA complex on chromosome 6. These OR genes could be involved in MHC-related mate preferences. The polymorphism screen was carried out with 13 genes from the HLA-linked OR cluster and three genes from chromosomes 7, 17, and 19 as controls. Ten human cell lines, representing 18 different chromosome 6s, were analyzed. They were from various ethnic origins and exhibited different HLA haplotypes. All OR genes tested, including those not linked to the HLA complex, were polymorphic. These polymorphisms were dispersed along the coding region and resulted in up to seven alleles for a given OR gene. Three polymorphisms resulted either in stop codons (genes hs6M1-4P, hs6M1-17) or in a 16–bp deletion (gene hs6M1-19P), possibly leading to lack of ligand recognition by the respective receptors in the cell line donors. In total, 13 HLA-linked OR haplotypes could be defined. Therefore, allelic variation appears to be a general feature of human OR genes. [The sequence data reported in this paper have been submitted to EMBL under accession nos. AC006137, AC004178, AJ132194, AL022727, AL031983, AL035402, AL035542, Z98744, CAB55431, AL050339, AL035402, AL096770, AL133267, AL121944, Z98745, AL021808, and AL021807.] PMID:11116091

  13. Digestion of rice straw and oil palm fronds by microflora from rumen and termite bacteria, in vitro.

    PubMed

    Ramin, M; Alimon, A R; Panandam, J M; Sijam, K; Javanmard, A; Abdullah, N

    2008-02-15

    The digestion and Volatile Fatty Acid (VFA) production from rice straw and oil palm fronds by cellulolytic bacteria isolated from the termite Coptotermes curvignathus were investigated. The bacteria were Acinetobacter strain Raminalimon, Enterobacter aerogenes strain Razmin C, Enterobacter cloacae strain Razmin B, Bacillus cereus strain Razmin A and Chryseobacterium kwangyangense strain Cb. Acinetobacter strain Raminalimon is an aerobic bacterium, while the other species are facultative anaerobes. There were significant differences (p<0.05) among the bacteria for Dry Matter (DM) lost and acetic acid production from rice straw and Acinetobacter strain Raminalimon showed the highest activity. The facultative bacteria C. kwangyangense strain Cb (cfu mL(-1) 231 x 10(-6), OD: 0.5), E. cloacae (cfu mL(-1) 68 x 10(-7), OD: 0.5) and E. aerogenes (cfu mL(-1) 33 x 10(-7), OD: 0.5) were used for digestion study with the rumen fluid microflora. The in vitro gas production technique was applied for the comparative study and the parameters measured were pH, gas (volume), dry matter lost, acetic acid, propionic acid and butyric acid concentrations. pH was not significantly (p<0.05) different among the five treatments. The bacterium C. kwangyangense strain Cb showed the highest activity (p<0.05) for DM lost, acetic acid, propionic acid and butyric acid production from rice straw when compared to the other bacterial activities. There was no significance (p<0.05) difference between the three bacteria for the dry matter lost of oil palm fronds but the production of Volatile Fatty Acids (VFA) was significantly (p<0.05) high in the treatment which was inoculated with C. kwangyangense strain Cb. The Gen Bank NCBI/EMBL accession numbers for the bacterial strains are EU332791, EU305608, EU305609, EU294508 and EU169201.

  14. 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

  15. 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.

  16. 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

  17. Human-specific amino acid changes found in 103 protein-coding genes.

    PubMed

    Kitano, Takashi; Liu, Yu-Hua; Ueda, Shintaroh; Saitou, Naruya

    2004-05-01

    We humans have many characteristics that are different from those of the great apes. These human-specific characters must have arisen through mutations accumulated in the genome of our direct ancestor after the divergence of the last common ancestor with chimpanzee. Gene trees of human and great apes are necessary for extracting these human-specific genetic changes. We conducted a systematic analysis of 103 protein-coding genes for human, chimpanzee, gorilla, and orangutan. Nucleotide sequences for 18 genes were newly determined for this study, and those for the remaining genes were retrieved from the DDBJ/EMBL/GenBank database. The total number of amino acid changes in the human lineage was 147 for 26,199 codons (0.56%). The total number of amino acid changes in the human genome was, thus, estimated to be about 80,000. We applied the acceleration index test and Fisher's synonymous/nonsynonymous exact test for each gene tree to detect any human-specific enhancement of amino acid changes compared with ape branches. Six and two genes were shown to have significantly higher nonsynonymous changes at the human lineage from the acceleration index and exact tests, respectively. We also compared the distribution of the differences of the nonsynonymous substitutions on the human lineage and those on the great ape lineage. Two genes were more conserved in the ape lineage, whereas one gene was more conserved in the human lineage. These results suggest that a small proportion of protein-coding genes started to evolve differently in the human lineage after it diverged from the ape lineage.

  18. 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.

  19. Organisation and structural evolution of the rice glutathione S-transferase gene family.

    PubMed

    Soranzo, N; Sari Gorla, M; Mizzi, L; De Toma, G; Frova, C

    2004-06-01

    Glutathione S-transferases (GSTs) comprise a large family of key defence enzymes against xenobiotic toxicity. Here we describe the comprehensive characterisation of this important multigene family in the model monocot species rice [ Oryza sativa(L.)]. Furthermore, we investigate the molecular evolution of the family based on the analysis of (1) the patterns of within-genome duplication, and (2) the phylogenetic relationships and evolutionary divergence among rice, Arabidopsis, maize and soybean GSTs. By in-silico screening of the EST and genome divisions of the Genbank/EMBL/DDBJ database we have isolated 59 putative genes and two pseudogenes, making this the largest plant GST family characterised to date. Of these, 38 (62%) are represented by genomic and EST sequences and 23 (38%) are known only from their genomic sequences. A preliminary survey of EST collections shows a large degree of variability in gene expression between different tissues and environmental conditions, with a small number of genes (13) accounting for 80% of all ESTs. Rice GSTs are organised in four main phylogenetic classes, with 91% of all rice genes belonging to the two plant-specific classes Tau (40 genes) and Phi (16 genes). Pairwise identity scores range between 17 and 98% for proteins of the same class, and 7 and 21% for interclass comparisons. Rapid evolution by gene duplication is suggested by the discovery of two large clusters of 7 and 23 closely related genes on chromosomes 1 and 10, respectively. A comparison of the complete GST families in two monocot and two dicot species suggests a monophyletic origin for all Theta and Zeta GSTs, and no more than three common ancestors for all Phi and Tau genes.

  20. Data standards can boost metabolomics research, and if there is a will, there is a way.

    PubMed

    Rocca-Serra, Philippe; Salek, Reza M; Arita, Masanori; Correa, Elon; Dayalan, Saravanan; Gonzalez-Beltran, Alejandra; Ebbels, Tim; Goodacre, Royston; Hastings, Janna; Haug, Kenneth; Koulman, Albert; Nikolski, Macha; Oresic, Matej; Sansone, Susanna-Assunta; Schober, Daniel; Smith, James; Steinbeck, Christoph; Viant, Mark R; Neumann, Steffen

    Thousands of articles using metabolomics approaches are published every year. With the increasing amounts of data being produced, mere description of investigations as text in manuscripts is not sufficient to enable re-use anymore: the underlying data needs to be published together with the findings in the literature to maximise the benefit from public and private expenditure and to take advantage of an enormous opportunity to improve scientific reproducibility in metabolomics and cognate disciplines. Reporting recommendations in metabolomics started to emerge about a decade ago and were mostly concerned with inventories of the information that had to be reported in the literature for consistency. In recent years, metabolomics data standards have developed extensively, to include the primary research data, derived results and the experimental description and importantly the metadata in a machine-readable way. This includes vendor independent data standards such as mzML for mass spectrometry and nmrML for NMR raw data that have both enabled the development of advanced data processing algorithms by the scientific community. Standards such as ISA-Tab cover essential metadata, including the experimental design, the applied protocols, association between samples, data files and the experimental factors for further statistical analysis. Altogether, they pave the way for both reproducible research and data reuse, including meta-analyses. Further incentives to prepare standards compliant data sets include new opportunities to publish data sets, but also require a little "arm twisting" in the author guidelines of scientific journals to submit the data sets to public repositories such as the NIH Metabolomics Workbench or MetaboLights at EMBL-EBI. In the present article, we look at standards for data sharing, investigate their impact in metabolomics and give suggestions to improve their adoption.

  1. Molecular cloning and structural characterization of the human histidase gene (HAL)

    SciTech Connect

    Suchi, Mariko; Sano, Hirofumi; Mizuno, Haruo; Wada, Yoshiro

    1995-09-01

    Histidase (EC 4.3.1.3) is a cytosolic enzyme that catalyzes the nonoxidative determination of histidine to urocanic acid. Histidinemia, resulting from reduced histidase activity as reported in Cambridge stock his/her mice and in humans, is the most frequent inborn metabolic error in Japan. The histidase chromosomal gene (HAL) was isolated from a {lambda}EMBL-3 human genomic library using the human histidase cDNA as a probe. Restriction mapping and Southern blot analysis of the isolated clones reveal a single-copy gene spanning approximately 25 kb and consisting of 21 exons. Exon 1 encodes only 5{prime} untranslated sequence of liver histidase mRNA, with protein coding beginning in exon 2. A rarely observed 5{prime}GC, similar to that reported in the human P-450(SCC) gene, is present in intron 20. All other splicing junctions adhere to the canonical GT/AG rule. A TATA box sequence is located 25 bp upstream of the liver histidase transcription initiation site determined by S1 nuclease protection analysis. Several liver- and epidermis-specific transcription factor binding sites, including C/EBP, NFIL6, HNF5, AP2/ KER1, MNF, and others, are also identified in the 5{prime} flanking region. Consistent with the hepatic and epidermal expression of histidase, this finding suggests that histidase transcription may be regulated by these factors. We further identify a polymorphism (A to G transition) in the histidase coding region of exon 16. The human histidase genomic structure presented here should facilitate the molecular investigation of symptomatic and asymptomatic forms of histidinemia. 69 refs., 4 figs., 1 tab.

  2. 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.

  3. "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/

  4. The very large amplifiable element AUD2 from Streptomyces lividans 66 has insertion sequence-like repeats at its ends.

    PubMed Central

    Eichenseer, C; Altenbuchner, J

    1994-01-01

    In a spontaneous, chloramphenicol-sensitive (Cms), arginine-auxotrophic (Arg-) mutant of Streptomyces lividans 1326, two amplified DNA sequences were found. One of them was the well-characterized 5.7-kb ADS1 sequence, amplified to about 300 copies per chromosome. The second one was a 92-kb sequence called ADS2. ADS2 encoding the previously isolated mercury resistance genes of S. lividans was amplified to around 20 copies per chromosome. The complete ADS2 sequence was isolated from a genomic library of the mutant S. lividans 1326.32, constructed in the phage vector lambda EMBL4. In addition, the DNA sequences flanking the corresponding amplifiable element called AUD2 in the wild-type strain were isolated by using another genomic library prepared from S. lividans 1326 DNA. Analysis of the ends of AUD2 revealed the presence of an 846-bp sequence on both sides repeated in the same orientation. Each of the direct repeats ended with 18-bp inverted repeated sequences. This insertion sequence-like structure was confirmed by the DNA sequence determined from the amplified copy of the direct repeats which demonstrated a high degree of similarity of 65% identity in nucleic acid sequence to IS112 from Streptomyces albus. The recombination event leading to the amplification of AUD2 occurred within these direct repeats, as shown by DNA sequence analysis. The amplification of AUD2 was correlated with a deletion on one side of the flanking chromosomal region beginning very near or in the amplified DNA. Strains of S. lividans like TK20 and TK21 which are mercury sensitive have completely lost AUD2 together with flanking chromosomal DNA on one or both sides. Images PMID:7961479

  5. Purification and Characterization of a Surface Protein from Lactobacillus fermentum 104R That Binds to Porcine Small Intestinal Mucus and Gastric Mucin

    PubMed Central

    Rojas, Maurilia; Ascencio, Felipe; Conway, Patricia L.

    2002-01-01

    An adhesion-promoting protein involved in the binding of Lactobacillus fermentum strain 104R to small intestinal mucus from piglets and to partially purified gastric mucin was isolated and characterized. Spent culture supernatant fluid and bacterial cell wall extracts were fractionated by ammonium sulfate precipitation and gel filtration. The active fraction was purified by affinity chromatography. The adhesion-promoting protein was detected in the fractions by adhesion inhibition and dot blot assays and visualized by polyacrylamide gel electrophoresis (PAGE), sodium dodecyl sulfate-PAGE, and Western blotting with horseradish peroxidase-labeled mucus and mucin. The active fraction was characterized by estimating the relative molecular weight and by assessing the presence of carbohydrates in, and heat sensitivity of, the active region of the adhesion-promoting protein. The purified protein was digested with porcine trypsin, and the peptides were purified in a SMART system. The peptides were tested for adhesion to horseradish peroxidase-labeled mucin by using the dot blot adhesion assay. Peptides which bound mucin were sequenced. It was shown that the purified adhesion-promoting protein on the cell surface of L. fermentum 104R is extractable with 1 M LiCl and low concentrations of lysozyme but not with 0.2 M glycine. The protein could be released to the culture supernatant fluid after 24 h of growth and had affinity for both small intestinal mucus and gastric mucin. In the native state this protein was variable in size, and it had a molecular mass of 29 kDa when denatured. The denatured protein did not contain carbohydrate moieties and was not heat sensitive. Alignment of amino acids of the adhering peptides with sequences deposited in the EMBL data library showed poor homology with previously published sequences. The protein represents an important molecule for development of probiotics. PMID:11976105

  6. Molecular cloning of a mouse DNA repair gene that complements the defect of group-A xeroderma pigmentosum.

    PubMed Central

    Tanaka, K; Satokata, I; Ogita, Z; Uchida, T; Okada, Y

    1989-01-01

    For isolation of the gene responsible for xeroderma pigmentosum (XP) complementation group A, plasmid pSV2gpt and genomic DNA from a mouse embryo were cotransfected into XP2OSSV cells, a group-A XP cell line. Two primary UV-resistant XP transfectants were isolated from about 1.6 X 10(5) pSV2gpt-transformed XP colonies. pSV2gpt and genomic DNA from the primary transfectants were again cotransfected into XP2OSSV cells and a secondary UV-resistant XP transfectant was obtained by screening about 4.8 X 10(5) pSV2gpt-transformed XP colonies. The secondary transfectant retained fewer mouse repetitive sequences. A mouse gene that complements the defect of XP2OSSV cells was cloned into an EMBL3 vector from the genome of a secondary transfectant. Transfections of the cloned DNA also conferred UV resistance on another group-A XP cell line but not on XP cell lines of group C, D, F, or G. Northern blot analysis of poly(A)+ RNA with a subfragment of cloned mouse DNA repair gene as the probe revealed that an approximately 1.0 kilobase mRNA was transcribed in the donor mouse embryo and secondary transfectant, and approximately 1.0- and approximately 1.3-kilobase mRNAs were transcribed in normal human cells, but none of these mRNAs was detected in three strains of group-A XP cells. These results suggest that the cloned DNA repair gene is specific for group-A XP and may be the mouse homologue of the group-A XP human gene. Images PMID:2748601

  7. Evaluating the impact of different sequence databases on metaproteome analysis: insights from a lab-assembled microbial mixture.

    PubMed

    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

  8. Duplicates, redundancies and inconsistencies in the primary nucleotide databases: a descriptive study.

    PubMed

    Chen, Qingyu; Zobel, Justin; Verspoor, Karin

    2017-01-01

    GenBank, the EMBL European Nucleotide Archive and the DNA DataBank of Japan, known collectively as the International Nucleotide Sequence Database Collaboration or INSDC, are the three most significant nucleotide sequence databases. Their records are derived from laboratory work undertaken by different individuals, by different teams, with a range of technologies and assumptions and over a period of decades. As a consequence, they contain a great many duplicates, redundancies and inconsistencies, but neither the prevalence nor the characteristics of various types of duplicates have been rigorously assessed. Existing duplicate detection methods in bioinformatics only address specific duplicate types, with inconsistent assumptions; and the impact of duplicates in bioinformatics databases has not been carefully assessed, making it difficult to judge the value of such methods. Our goal is to assess the scale, kinds and impact of duplicates in bioinformatics databases, through a retrospective analysis of merged groups in INSDC databases. Our outcomes are threefold: (1) We analyse a benchmark dataset consisting of duplicates manually identified in INSDC-a dataset of 67 888 merged groups with 111 823 duplicate pairs across 21 organisms from INSDC databases - in terms of the prevalence, types and impacts of duplicates. (2) We categorize duplicates at both sequence and annotation level, with supporting quantitative statistics, showing that different organisms have different prevalence of distinct kinds of duplicate. (3) We show that the presence of duplicates has practical impact via a simple case study on duplicates, in terms of GC content and melting temperature. We demonstrate that duplicates not only introduce redundancy, but can lead to inconsistent results for certain tasks. Our findings lead to a better understanding of the problem of duplication in biological databases.Database URL: the merged records are available at https

  9. 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

    • 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

      2016-01-04

      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.

    • 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.

    • 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.

    • Incidence and clinical implication of TT virus in patients with hepatitis and its frequency in blood donors in India

      PubMed Central

      Magu, S.K.; Kalghatgi, A.T.; Bhagat, M.R.

      2015-01-01

      Background Transfusion Transmitted Virus (TTV), also known as Torque Teno Virus is a new novel viral agent which appears to correlate with some acute and chronic hepatitis cases and may produce liver damage under specific circumstances. Aim of this study was to detect TT virus by real-time PCR, study its clinical implications and effects of its co-infection in HBV and HCV chronic liver diseases. Methods The study population comprised 50 acute hepatitis, 50 chronic hepatitis patients and 100 voluntary blood donors. All samples were tested for serum bilirubin, AST, ALT and alkaline phosphatase levels and for all available viral markers for hepatitis. The detection of TT viral genome was carried out by real-time PCR using TTV sequences as reported by Takahashi et al with modifications on the basis of database of the DDBJ/EMBL/GenBank (GenBank accession no. AB008394). Result Serum was positive for TTV in 72% of volunteer blood donors, 77.4% (24/31) of hepatitis A cases, 87.6% (36/41) of HBV-positive, 77% (10/13) of HCV-positive, and 92.8% (13/14) of non-B, non-C cases. Co-infection of TTV with other hepatitis viruses was detected in some patients. Conclusion TTV is a frequent virus detected in patients with various types of viral hepatitis, in cases of hepatitis without obvious viral agent, and from the healthy population in India. Rate of TTV was found to be significantly higher (92.8%) for Non A–E hepatitis group. PMID:26663961

    • Differentiation of Bacillus pumilus and Bacillus safensis using MALDI-TOF-MS.

      PubMed

      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.

    • A microsatellite marker for studying the ecology and diversity of fungal endophytes (Epichloë spp.) in grasses.

      PubMed Central

      Groppe, K; Sanders, I; Wiemken, A; Boller, T

      1995-01-01

      Randomly amplified polymorphic DNA fingerprinting, which is based on PCR with arbitrary 10-nucleotide primers, were used to analyze genetic diversity among isolates of the endophytic ascomycete Epichloë typhina, which were collected at a single field site from a population of one of its hosts, the grass Bromus erectus. One of the polymorphic randomly amplified polymorphic DNA PCR products occurred in all isolates as single bands with different but closely related sizes. Two of the size variants of this product were cloned and sequenced, and they were found to represent the same DNA sequence, except for a stretch of tandem repeats of the trinucleotide AAG.TTC, which differed in size, consisting of 8 and 18 repeats, respectively. Tandem repeats of this type are called microsatellites. Oligonucleotides were synthesized corresponding to portions of the sequence flanking the microsatellite and were used for PCR amplification of the loci from the genomic DNAs of different Epichloë isolates. A single PCR product was found for most isolates, indicating that the sequence represented a single genetic locus. Five alleles that could clearly be distinguished in size were found in a population of 91 field isolates. PCR with (AAC)8 and (AAG)8 as primers yielded a number of amplified bands from genomic DNA of Epichloë isolates, indicating that these types of microsatellites occur frequently in the genome of this fungus. A survey of all fungal DNA sequences currently deposited in the DNA sequence databases of EMBL and GenBank revealed that microsatellites of different repeating units are widespread in fungi.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8526508

    • Development of a Macroarray To Specifically Analyze Immunological Gene Expression in Swine

      PubMed Central

      Ledger, Terence N.; Pinton, Philippe; Bourges, Dorothée; Roumi, Patrick; Salmon, Henri; Oswald, Isabelle P.

      2004-01-01

      DNA arrays are useful tools for simultaneously studying the expressions of a large number of genes. Herein, we describe the construction and the optimization of conditions for a low-density DNA macroarray specific for the porcine immune system. This specific DNA macroarray contains 63 gene products, including 20 cytokines, 11 chemokines, and 12 immunologically relevant receptors. It was constructed by designing gene-specific oligonucleotide primers from porcine sequences available in the EMBL or TIGR expressed sequence tag data bank and using primers from conserved regions of aligned sequences from other species for sequences unavailable for swine. Amplicons produced by reverse transcription-PCR were cloned, sequenced, and spotted onto nylon filters. A trial DNA array was first produced to optimize the intensity, specificity, and variability of signals from amplicons amplified with either gene-specific or universal primers. The DNA macroarray was then validated by comparing the gene expression profile of nonstimulated peripheral blood mononuclear cells (PBMCs) to that of phorbol 12-myristate 13-acetate and ionomycin (PMA-Iono)-stimulated PBMCs from three different animals over a 48-h time period. As already described for more conventional techniques, we showed that certain genes, such as those for CD40, gamma interferon, interleukin 2 (IL-2), the IL-2 receptor, and tumor necrosis factor alpha, were upregulated in PMA-Iono-stimulated PBMCs. A detailed analysis also indicated a downregulation of several genes which are expressed mainly by macrophages (IL-1, IL-8, AMCF-1, natural-resistance-associated macrophage protein, neutrophil chemotactic protein, DAP-12, and monocyte chemoattractant protein) in samples stimulated for 24 h with PMA-Iono compared to their levels of expression in control samples. These results indicate that the DNA macroarray that we constructed can be a useful tool for simultaneously monitoring the mRNA expression of immunologically relevant genes

    • 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

    • Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families.

      PubMed Central

      Suchi, M; Mizuno, H; Kawai, Y; Tsuboi, T; Sumi, S; Okajima, K; Hodgson, M E; Ogawa, H; Wada, Y

      1997-01-01

      Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC). Loss of either enzymatic activity results in hereditary orotic aciduria, a rare autosomal recessive disorder characterized by retarded growth, anemia, and excessive urinary excretion of orotic acid. We have isolated the UMP synthase chromosomal gene from a lambdaEMBL-3 human genomic library and report a single-copy gene spanning approximately 15 kb. The UMP synthase genomic structure encodes six exons ranging in size from 115 bp to 672 bp, and all splicing junctions adhere to the canonical GT/AG rule. Cognate promoter elements implicated in glucocorticoid- and cAMP-mediated regulation as well as in liver-, myeloid-, and lymphocyte-specific expression are located within the 5' flanking sequence. Molecular investigation of UMP synthase deficiency in a Japanese orotic aciduria patient revealed mutations R96G (A-to-G transition; nt 286) and G429R (G-to-C transversion; nt 1285) in one allele and V109G (T-to-G transversion; nt 326) in the other allele. Expression of human UMP synthase cDNAs containing these mutations in pyrimidine auxotrophic Escherichia coli and in recombinant baculovirus-infected Sf21 cells demonstrates impaired activity presumably associated with the urinary orotic acid substrate accumulations observed in vivo. We further establish the identity of two polymorphisms, G213A (v = .26) and 440Gpoly (v = .27) located in exons 3 and 6, respectively, which did not significantly compromise either OPRT or ODC function. Images Figure 1 Figure 4 Figure 5 PMID:9042911

    • 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.

    • Predicting targets of compounds against neurological diseases using cheminformatic methodology

      NASA Astrophysics Data System (ADS)

      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).

  1. Use of 18S rRNA gene-based PCR assay for diagnosis of acanthamoeba keratitis in non-contact lens wearers in India.

    PubMed

    Pasricha, Gunisha; Sharma, Savitri; Garg, Prashant; Aggarwal, Ramesh K

    2003-07-01

    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.

  2. 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

  3. RiboaptDB: A Comprehensive Database of Ribozymes and Aptamers

    PubMed Central

    Thodima, Venkata; Pirooznia, Mehdi; Deng, Youping

    2006-01-01

    Background Catalytic RNA molecules are called ribozymes. The aptamers are DNA or RNA molecules that have been selected from vast populations of random sequences, through a combinatorial approach known as SELEX. The selected oligo-nucleotide sequences (~200 bp in length) have the ability to recognize a broad range of specific ligands by forming binding pockets. These novel aptamer sequences can bind to nucleic acids, proteins or small organic and inorganic chemical compounds and have many potential uses in medicine and technology. Results The comprehensive sequence information on aptamers and ribozymes that have been generated by in vitro selection methods are included in this RiboaptDB database. Such types of unnatural data generated by in vitro methods are not available in the public 'natural' sequence databases such as GenBank and EMBL. The amount of sequence data generated by in vitro selection experiments has been accumulating exponentially. There are 370 artificial ribozyme sequences and 3842 aptamer sequences in the total 4212 sequences from 423 citations in this RiboaptDB. We included general search feature, and individual feature wise search, user submission form for new data through online and also local BLAST search. Conclusion This database, besides serving as a storehouse of sequences that may have diagnostic or therapeutic utility in medicine, provides valuable information for computational and theoretical biologists. The RiboaptDB is extremely useful for garnering information about in vitro selection experiments as a whole and for better understanding the distribution of functional nucleic acids in sequence space. The database is updated regularly and is publicly available at . PMID:17118149

  4. Molecular Cloning, Genomic Organization, Developmental Regulation, and a Knock-out Mutant of a Novel Leu-rich Repeats-containing G Protein-coupled Receptor (DLGR-2) from Drosophila melanogaster

    PubMed Central

    Eriksen, Kathrine Krageskov; Hauser, Frank; Schiøtt, Morten; Pedersen, Karen-Marie; Søndergaard, Leif; Grimmelikhuijzen, Cornelis J.P.

    2000-01-01

    After screening the Berkeley Drosophila Genome Project database with sequences from a recently characterized Leu-rich repeats-containing G protein-coupled receptor (LGR) from Drosophila (DLGR-1), we identified a second gene for a different LGR (DLGR-2) and cloned its cDNA. DLGR-2 is 1360 amino acid residues long and shows a striking structural homology with members of the glycoprotein hormone [thyroid-stimulating hormone (TSH); follicle-stimulating hormone (FSH); luteinizing hormone/choriogonadotropin (LH/CG)] receptor family from mammals and with two additional, recently identified mammalian orphan LGRs (LGR-4 and LGR-5). This homology includes the seven transmembrane region (e.g., 49% amino acid identity with the human TSH receptor) and the very large extracellular amino terminus. This amino terminus contains 18 Leu-rich repeats—in contrast with the 3 mammalian glycoprotein hormone receptors and DLGR-1 that contain 9 Leu-rich repeats, but resembling the mammalian LGR-4 and LGR-5 that each have 17 Leu-rich repeats in their amino termini. The DLGR-2 gene is >18.6 kb pairs long and contains 15 exons and 14 introns. Four intron positions coincide with the intron positions of the three mammalian glycoprotein hormone receptors and have the same intron phasing, showing that DLGR-2 is evolutionarily related to these mammalian receptors. The DLGR-2 gene is located at position 34E-F on the left arm of the second chromosome and is expressed in embryos and pupae but not in larvae and adult flies. Homozygous knock-out mutants, where the DLGR-2 gene is interrupted by a P element insertion, die around the time of hatching. This finding, together with the expression data, strongly suggests that DLGR-2 is exclusively involved in development. [The nucleotide sequence(s) reported in this paper has been submitted to the GenBank/EMBL database with accession no. AF142343.] PMID:10899142

  5. Structural-functional characterization of the cathodic haemoglobin of the conger eel Conger conger: molecular modelling study of an additional phosphate-binding site.

    PubMed Central

    Pellegrini, Mariagiuseppina; Giardina, Bruno; Verde, Cinzia; Carratore, Vito; Olianas, Alessandra; Sollai, Luigi; Sanna, Maria T; Castagnola, Massimo; di Prisco, Guido

    2003-01-01

    The protein sequence data for the alpha- and beta-chains have been deposited in the SWISS-PROT and TrEMBL protein knowledgebase under the accession numbers P83479 and P83478 respectively. The Conger conger (conger eel) haemoglobin (Hb) system is made of three components, one of which, the so-called cathodic Hb, representing approx. 20% of the total pigment, has been purified and characterized from both a structural and functional point of view. Stripped Hb showed a reverse Bohr effect, high oxygen affinity and slightly low cooperativity in the absence of any effector. Addition of saturating GTP strongly influences the pH dependence of the oxygen affinity, since the reverse Bohr effect, observed under stripped conditions, is converted into a small normal Bohr effect. A further investigation of the GTP effect on oxygen affinity, carried out by fitting its titration curve, demonstrated the presence of two independent binding sites. Therefore, on the basis of the amino acid sequence of the alpha- and beta-chains, which have been determined, a computer modelling study has been performed. The data suggest that C. conger cathodic Hb may bind organic phosphates at two distinct binding sites located along the central cavity of the tetramer by hydrogen bonds and/or electrostatic interactions with amino acid residues of both chains, which have been identified. Among these residues, the two Lys-alpha(G6) (where the letter refers to the haemoglobin helix and the number to the amino acid position in the helix) appear to have a key role in the GTP movement from the external binding region to the internal central cavity of the tetrameric molecule. PMID:12646043

  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. Finding new human minisatellite sequences in the vicinity of long CA-rich sequences.

    PubMed

    Giraudeau, F; Petit, E; Avet-Loiseau, H; Hauck, Y; Vergnaud, G; Amarger, V

    1999-07-01

    Microsatellites and minisatellites are two classes of tandem repeat sequences differing in their size, mutation processes, and chromosomal distribution. The boundary between the two classes is not defined. We have developed a convenient, hybridization-based human library screening procedure able to detect long CA-rich sequences. Analysis of cosmid clones derived from a chromosome 1 library show that cross-hybridizing sequences tested are imperfect CA-rich sequences, some of them showing a minisatellite organization. All but one of the 13 positive chromosome 1 clones studied are localized in chromosomal bands to which minisatellites have previously been assigned, such as the 1pter cluster. To test the applicability of the procedure to minisatellite detection on a larger scale, we then used a large-insert whole-genome PAC library. Altogether, 22 new minisatellites have been identified in positive PAC and cosmid clones and 20 of them are telomeric. Among the 42 positive PAC clones localized within the human genome by FISH and/or linkage analysis, 25 (60%) are assigned to a terminal band of the karyotype, 4 (9%) are juxtacentromeric, and 13 (31%) are interstitial. The localization of at least two of the interstitial PAC clones corresponds to previously characterized minisatellite-containing regions and/or ancestrally telomeric bands, in agreement with this minisatellite-like distribution. The data obtained are in close agreement with the parallel investigation of human genome sequence data and suggest that long human (CA)s are imperfect CA repeats belonging to the minisatellite class of sequences. This approach provides a new tool to efficiently target genomic clones originating from subtelomeric domains, from which minisatellite sequences can readily be obtained. [The sequence data described in this paper have been submitted to the EMBL data library under accession nos. AJ000377-AJ000383.

  8. Duplicates, redundancies and inconsistencies in the primary nucleotide databases: a descriptive study

    PubMed Central

    Chen, Qingyu; Zobel, Justin; Verspoor, Karin

    2017-01-01

    GenBank, the EMBL European Nucleotide Archive and the DNA DataBank of Japan, known collectively as the International Nucleotide Sequence Database Collaboration or INSDC, are the three most significant nucleotide sequence databases. Their records are derived from laboratory work undertaken by different individuals, by different teams, with a range of technologies and assumptions and over a period of decades. As a consequence, they contain a great many duplicates, redundancies and inconsistencies, but neither the prevalence nor the characteristics of various types of duplicates have been rigorously assessed. Existing duplicate detection methods in bioinformatics only address specific duplicate types, with inconsistent assumptions; and the impact of duplicates in bioinformatics databases has not been carefully assessed, making it difficult to judge the value of such methods. Our goal is to assess the scale, kinds and impact of duplicates in bioinformatics databases, through a retrospective analysis of merged groups in INSDC databases. Our outcomes are threefold: (1) We analyse a benchmark dataset consisting of duplicates manually identified in INSDC—a dataset of 67 888 merged groups with 111 823 duplicate pairs across 21 organisms from INSDC databases – in terms of the prevalence, types and impacts of duplicates. (2) We categorize duplicates at both sequence and annotation level, with supporting quantitative statistics, showing that different organisms have different prevalence of distinct kinds of duplicate. (3) We show that the presence of duplicates has practical impact via a simple case study on duplicates, in terms of GC content and melting temperature. We demonstrate that duplicates not only introduce redundancy, but can lead to inconsistent results for certain tasks. Our findings lead to a better understanding of the problem of duplication in biological databases. Database URL: the merged records are available at https

  9. 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

  10. Etude critique de la prise en charge de 159 personnes âgées en consultation de psychiatrie

    PubMed Central

    Ben Thabet, Jihène; Ammar, Yousra; Charfi, Nada; Zouari, Lobna; Zouari, Nasreddine; Gaha, Lotfi; Maalej, Mohamed

    2014-01-01

    Introduction Le phénomène de vieillissement des populations est associé à une augmentation de la prévalence de la morbidité liée à l’âge. La prescription des psychotropes chez le sujet âgé est de plus en plus fréquente dans les institutions, les doses sont de plus en plus élevées, avec un recours fréquent à une poly pharmacothérapie. Nous nous sommes proposé de décrire les conduites thérapeutiques chez le sujet âgé consultant en psychiatrie, en vue de les confronter aux dernières recommandations en la matière. Méthodes L’étude était de type rétrospectif et descriptif. Elle a concerné les sujets âgés d'au moins 60 ans ayant consulté pour la première fois en psychiatrie, au CHU Hédi Chaker à Sfax, en 2010 ou 2011. Résultats Nous avons colligé 159 dossiers. L’âge moyen était de 73 ans. La démence et les troubles de l'humeur étaient les diagnostics les plus fréquents. Sur le plan thérapeutique, une poly thérapie faite d'au moins deux psychotropes de familles différentes a été prescrite pour 55,9%. Chez 60.3% des sujets, le traitement a été prescrit d'emblée à dose complète. Aucun dossier ne faisait état d'une prise en charge psychothérapeutique. Conclusion La prise en charge des malades de notre étude n’était pas conforme aux recommandations, notamment en matière d'association médicamenteuse, de progression des doses et d'association de la psychothérapie à la pharmacothérapie. L'information des médecins et leur sensibilisation aux particularités du sujet âgé contribuerait à optimiser les soins qui leur sont prodigués, y compris en psychiatrie. PMID:25120873

  11. Benchmarks for measurement of duplicate detection methods in nucleotide databases.

    PubMed

    Chen, Qingyu; Zobel, Justin; Verspoor, Karin

    2017-01-08

    Duplication of information in databases is a major data quality challenge. The presence of duplicates, implying either redundancy or inconsistency, can have a range of impacts on the quality of analyses that use the data. To provide a sound basis for research on this issue in databases of nucleotide sequences, we have developed new, large-scale validated collections of duplicates, which can be used to test the effectiveness of duplicate detection methods. Previous collections were either designed primarily to test efficiency, or contained only a limited number of duplicates of limited kinds. To date, duplicate detection methods have been evaluated on separate, inconsistent benchmarks, leading to results that cannot be compared and, due to limitations of the benchmarks, of questionable generality. In this study, we present three nucleotide sequence database benchmarks, based on information drawn from a range of resources, including information derived from mapping to two data sections within the UniProt Knowledgebase (UniProtKB), UniProtKB/Swiss-Prot and UniProtKB/TrEMBL. Each benchmark has distinct characteristics. We quantify these characteristics and argue for their complementary value in evaluation. The benchmarks collectively contain a vast number of validated biological duplicates; the largest has nearly half a billion duplicate pairs (although this is probably only a tiny fraction of the total that is present). They are also the first benchmarks targeting the primary nucleotide databases. The records include the 21 most heavily studied organisms in molecular biology research. Our quantitative analysis shows that duplicates in the different benchmarks, and in different organisms, have different characteristics. It is thus unreliable to evaluate duplicate detection methods against any single benchmark. For example, the benchmark derived from UniProtKB/Swiss-Prot mappings identifies more diverse types of duplicates, showing the importance of expert curation, but

  12. 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

  13. A type II protein secretory pathway required for levansucrase secretion by Gluconacetobacter diazotrophicus.

    PubMed

    Arrieta, Juan G; Sotolongo, Mailin; Menéndez, Carmen; Alfonso, Dubiel; Trujillo, Luis E; Soto, Melvis; Ramírez, Ricardo; Hernández, Lázaro

    2004-08-01

    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 Cys(162) 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.

  14. 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

  15. The Glucuronic Acid Utilization Gene Cluster from Bacillus stearothermophilus T-6

    PubMed Central

    Shulami, Smadar; Gat, Orit; Sonenshein, Abraham L.; Shoham, Yuval

    1999-01-01

    A λ-EMBL3 genomic library of Bacillus stearothermophilus T-6 was screened for hemicellulolytic activities, and five independent clones exhibiting β-xylosidase activity were isolated. The clones overlap each other and together represent a 23.5-kb chromosomal segment. The segment contains a cluster of xylan utilization genes, which are organized in at least three transcriptional units. These include the gene for the extracellular xylanase, xylanase T-6; part of an operon coding for an intracellular xylanase and a β-xylosidase; and a putative 15.5-kb-long transcriptional unit, consisting of 12 genes involved in the utilization of α-d-glucuronic acid (GlcUA). The first four genes in the potential GlcUA operon (orf1, -2, -3, and -4) code for a putative sugar transport system with characteristic components of the binding-protein-dependent transport systems. The most likely natural substrate for this transport system is aldotetraouronic acid [2-O-α-(4-O-methyl-α-d-glucuronosyl)-xylotriose] (MeGlcUAXyl3). The following two genes code for an intracellular α-glucuronidase (aguA) and a β-xylosidase (xynB). Five more genes (kdgK, kdgA, uxaC, uxuA, and uxuB) encode proteins that are homologous to enzymes involved in galacturonate and glucuronate catabolism. The gene cluster also includes a potential regulatory gene, uxuR, the product of which resembles repressors of the GntR family. The apparent transcriptional start point of the cluster was determined by primer extension analysis and is located 349 bp from the initial ATG codon. The potential operator site is a perfect 12-bp inverted repeat located downstream from the promoter between nucleotides +170 and +181. Gel retardation assays indicated that UxuR binds specifically to this sequence and that this binding is efficiently prevented in vitro by MeGlcUAXyl3, the most likely molecular inducer. PMID:10368143

  16. MitoPhAST, a new automated mitogenomic phylogeny tool in the post-genomic era with a case study of 89 decapod mitogenomes including eight new freshwater crayfish mitogenomes.

    PubMed

    Tan, Mun Hua; Gan, Han Ming; Schultz, Mark B; Austin, Christopher M

    2015-04-01

    The increased rate at which complete mitogenomes are being sequenced and their increasing use for phylogenetic studies have resulted in a bioinformatic bottleneck in preparing and utilising such data for phylogenetic analysis. Hence, we present MitoPhAST, an automated tool that (1) identifies annotated protein-coding gene features and generates a standardised, concatenated and partitioned amino acid alignment directly from complete/partial GenBank/EMBL-format mitogenome flat files, (2) generates a maximum likelihood phylogenetic tree using optimised protein models and (3) reports various mitochondrial genes and sequence information in a table format. To demonstrate the capacity of MitoPhAST in handling a large dataset, we used 81 publicly available decapod mitogenomes, together with eight new complete mitogenomes of Australian freshwater crayfishes, including the first for the genus Gramastacus, to undertake an updated test of the monophyly of the major groups of the order Decapoda and their phylogenetic relationships. The recovered phylogenetic trees using both Bayesian and ML methods support the results of studies using fragments of mtDNA and nuclear markers and other smaller-scale studies using whole mitogenomes. In comparison to the fragment-based phylogenies, nodal support values are generally higher despite reduced taxon sampling suggesting there is value in utilising more fully mitogenomic data. Additionally, the simple table output from MitoPhAST provides an efficient summary and statistical overview of the mitogenomes under study at the gene level, allowing the identification of missing or duplicated genes and gene rearrangements. The finding of new mtDNA gene rearrangements in several genera of Australian freshwater crayfishes indicates that this group has undergone an unusually high rate of evolutionary change for this organelle compared to other major families of decapod crustaceans. As a result, freshwater crayfishes are likely to be a useful model for

  17. ReRep: Computational detection of repetitive sequences in genome survey sequences (GSS)

    PubMed Central

    Otto, Thomas D; Gomes, Leonardo HF; Alves-Ferreira, Marcelo; de Miranda, Antonio B; Degrave, Wim M

    2008-01-01

    Background Genome survey sequences (GSS) offer a preliminary global view of a genome since, unlike ESTs, they cover coding as well as non-coding DNA and include repetitive regions of the genome. A more precise estimation of the nature, quantity and variability of repetitive sequences very early in a genome sequencing project is of considerable importance, as such data strongly influence the estimation of genome coverage, library quality and progress in scaffold construction. Also, the elimination of repetitive sequences from the initial assembly process is important to avoid errors and unnecessary complexity. Repetitive sequences are also of interest in a variety of other studies, for instance as molecular markers. Results We designed and implemented a straightforward pipeline called ReRep, which combines bioinformatics tools for identifying repetitive structures in a GSS dataset. In a case study, we first applied the pipeline to a set of 970 GSSs, sequenced in our laboratory from the human pathogen Leishmania braziliensis, the causative agent of leishmaniosis, an important public health problem in Brazil. We also verified the applicability of ReRep to new sequencing technologies using a set of 454-reads of an Escheria coli. The behaviour of several parameters in the algorithm is evaluated and suggestions are made for tuning of the analysis. Conclusion The ReRep approach for identification of repetitive elements in GSS datasets proved to be straightforward and efficient. Several potential repetitive sequences were found in a L. braziliensis GSS dataset generated in our laboratory, and further validated by the analysis of a more complete genomic dataset from the EMBL and Sanger Centre databases. ReRep also identified most of the E. coli K12 repeats prior to assembly in an example dataset obtained by automated sequencing using 454 technology. The parameters controlling the algorithm behaved consistently and may be tuned to the properties of the dataset, in particular

  18. Cloning, expression, and nucleotide sequence of the Lactobacillus helveticus 481 gene encoding the bacteriocin helveticin J.

    PubMed Central

    Joerger, M C; Klaenhammer, T R

    1990-01-01

    Lactobacillus helveticus 481 produces a 37-kDa bacteriocin called helveticin J. Libraries of chromosomal DNA from L. helveticus were prepared in lambda gt11 and probed for phage-producing fusion proteins that could react with polyclonal helveticin J antibody. Two recombinant phage, HJ1 and HJ4, containing homologous inserts of 350 and 600 bp, respectively, produced proteins that reacted with antibody. These two phage clones specifically hybridized to L. helveticus 481 total genomic DNA but not to DNA from strains that did not produce helveticin J or strains producing unrelated bacteriocins. HJ1 and HJ4 lysogens produced beta-galactosidase fusion proteins that shared similar epitopes with each other and helveticin J. The intact helveticin J gene (hlv) was isolated by screening a library of L. helveticus chromosomal DNA in lambda EMBL3 with the insert DNA from phage HJ4 as a probe. The DNA sequence of a contiguous 3,364-bp region was determined. Two complete open reading frames (ORF), designated ORF2 and ORF3, were identified within the sequenced fragment. The 3' end of another open reading frame, ORF1, was located upstream of ORF2. A noncoding region and a putative promoter were located between ORF1 and ORF2. ORF2 could encode an 11,808-Da protein. The L. helveticus DNA inserts of the HJ1 and HJ4 clones reside within ORF3, which begins 30 bp downstream from the termination codon of ORF2. ORF3 could encode a 37,511-Da protein. Downstream from ORF3, the 5' end of another ORF (ORF4) was found. A Bg/II fragment containing ORF2 and ORF3 was cloned into pGK12, and the recombinant plasmid, pTRK135, was transformed into Lactobacillus acidophilus via electroporation. Transformants carrying pTRK135 produced a bacteriocin that was heat labile and exhibited an acitivity spectrum that was the same as that of helveticin J. Images PMID:2228964

  19. 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

  20. Differential gene expression profile of the hepatopancreas of white spot syndrome virus infected Fenneropenaeus indicus by suppression subtractive hybridization.

    PubMed

    James, Roswin; Thampuran, Nirmala; Lalitha, K V; Rajan, Lawrance Anbu; Joseph, Toms C

    2010-11-01

    Suppression Subtractive Hybridization was employed in order to identify the differentially expressed genes in the hepatopancreas of white spot syndrome virus infected Fenneropenaeus indicus. A forward subtracted cDNA library generated 356 clones following a white spot syndrome virus infection. A total of 345 clones with more than 100 nucleotides were selected for further analysis using bioinformatics tools after vector screening. Twenty-three contigs and 111 singletons were generated from a total of 134 consensuses. The consensuses, on a sequence homology search using BLASTX (NCBI), revealed that 74 (55%) of them had no significant match to reported sequences in the database, suggesting that they were found for the first time and are probably associated with shrimp immune function. Out of the remaining 60 (45%) consensuses, 43 had significant homology to known protein sequences in the database while 17 consensuses are homologous to unknown proteins in the database which are considered novel. The most abundant genes in the subtracted library were antimicrobial peptides accounting for 56 clones; among which one is a member of SNF2 family of proteins and another belonged to PfP1 family of proteins on analysis using Antimicrobial peptide predictor software. The other predicted genes in the subtracted library include signal transduction molecules (GTPase, Serine threonine kinase, Armadillo repeats etc), antioxidant enzymes (Cytochrome oxidase, Monomeric sarcosine oxidase and Catalase), active transporters (Nuclear Localization Signal [NLS], calcium ATPase, sodium glutamate symporter, Store-Operated Calcium Entry [SOCE] and ribonucleoprotein [RNP]) contributing to 19, 14 and 5 clones respectively. Three clones are homologous to reverse transcriptase; a first time report in shrimp and one each belong to cell adhesion molecule and Proteinase. InterProScan at EMBL, when used for an integrated search at PROSITE predicted; signal sequences and transmembrane regions for 13

  1. La grossesse extra-utérine dans une région semi-rurale en Afrique: Aspects épidémiologiques, cliniques et thérapeutiques à propos d'une série de 74 cas traités à l'Hôpital de District de Sangmelima au Sud-Cameroun

    PubMed Central

    Kenfack, Bruno; Noubom, Michel; Bongoe, Adamo; Tsatedem, Faustin Atemkeng; Ngono, Modeste; Tsague, Georges Nguefack; Mboudou, Emile

    2012-01-01

    La grossesse extra-utérine (GEU) constitue une cause fréquente de morbidité et parfois de mortalité chez les femmes en âge de procréation. Son étiologie n'est pas clairement précisée. Son tableau clinique est polymorphe et ses méthodes thérapeutiques très diversifiées. C'est dans le but d’étudier les aspects épidémiologiques cliniques et thérapeutiques dans une zone rurale à ressources limitées d'Afrique que ce travail a été réalisé. Il s'agit d'une étude descriptive transversale sur une durée de trois ans, portant sur 74 cas de GEU traités à l'Hôpital de District de Sangmelima. Le matériel utilisé était constitué d'une fiche anonyme de collecte des données, des dossiers du malade, et du registre opératoire. Au cours de la période d’étude, 2142 naissances vivantes ont été enregistrées, soit un taux de GEU de 3,45%. Les femmes non mariées et celles ayant les antécédents d'IST étaient les plus atteintes. Le délai moyen entre le début des symptômes et l'admission était de132h. L’âge gestationnel moyen au moment du diagnostic était de 8,14 semaines. Le diagnostic était clinique dans 61% des cas. L'annexe controlatérale était cliniquement normale dans 53% des cas. Le traitement était chirurgical d'emblée chez 97% des cas. Aucun décès n'a été observé. La GEU est fréquente dans cette zone rurale, les malades consultent à un stade tardif, le diagnostic est surtout clinique, et le traitement chirurgical par laparotomie. PMID:23396682

  2. 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

  3. Age-Specific Anti-Hepatitis A Virus Seroepidemiology in Italian Travelers: Indications for Anti-Hepatitis A Vaccination.

    PubMed

    Castelli; Carosi; Tebaldi; Pizzocolo; Pisani; Rossitto; Boffelli; Crevatin; Pettoello; Fausti; Messino; Brunelli; Costa; Ronca

    1996-12-01

    Background: Hepatitis A virus (HAV) circulation in the environment is decreasing in most industrialized Western countries. This decrease has lead to low seroprevalence rates in adults. As a consequence, many nonimmune unprotected travelers from areas of low prevalence are considered at risk of acquiring HAV infection when traveling to high HAV endemic areas in developing countries. The recent HAV inactivated vaccine has proved safe and effective, and its use in different geographic areas should be guided by local age-specific HAV seroprevalence rates. The aim of this paper is to describe the age-specific sero-epidemiology of HAV infection in travelers from a highly industrialized region in Northern Italy (Lombardy). Methods: Seven hundred and forty-four consecutive travelers aged from 20 to 59 years, subdivided in 10-year age groups, gave blood samples in the collaborative Health Centers in the Lombardy region and sera were tested for HAV IgG antibodies. A questionnaire was given to travelers that investigated alimentary habits and a history of previous travel. Results: Anti-HAV seroprevalence was 18.0%, 58.0%, 75.8%, and 89.5% in the 20-29, 30-39, 40-49, and 50-59 age groups, respectively. Age was the single most important determinant of anti-HAV seroprevalence. The influence of previous travels, eating shellfish, or ingestion of self-cultivated vegetables was ruled out by multivariate analysis. Conclusions: In the Lombardy region (Northern Italy), age specific anti-HAV seroprevalence rates are much higher than those reported in other Western European countries. The cost-benefit analysis suggested that travelers born after 1960 do not need serologic screening before vaccination. Whenever possible, however, HAV serologic screening is advisable for travelers born before 1960. However, the severity of the disease in older subjects, and the proved safety of HAV vaccination in immune subjects, may advise d'emblée HAV vaccination without prior screening, when serologic

  4. Sequential Application of Ligand and Structure Based Modeling Approaches to Index Chemicals for Their hH4R Antagonism

    PubMed Central

    Basile, Livia; Milardi, Danilo; Zeidan, Mouhammed; Raiyn, Jamal; Guccione, Salvatore; Rayan, Anwar

    2014-01-01

    The human histamine H4 receptor (hH4R), a member of the G-protein coupled receptors (GPCR) family, is an increasingly attractive drug target. It plays a key role in many cell pathways and many hH4R ligands are studied for the treatment of several inflammatory, allergic and autoimmune disorders, as well as for analgesic activity. Due to the challenging difficulties in the experimental elucidation of hH4R structure, virtual screening campaigns are normally run on homology based models. However, a wealth of information about the chemical properties of GPCR ligands has also accumulated over the last few years and an appropriate combination of these ligand-based knowledge with structure-based molecular modeling studies emerges as a promising strategy for computer-assisted drug design. Here, two chemoinformatics techniques, the Intelligent Learning Engine (ILE) and Iterative Stochastic Elimination (ISE) approach, were used to index chemicals for their hH4R bioactivity. An application of the prediction model on external test set composed of more than 160 hH4R antagonists picked from the chEMBL database gave enrichment factor of 16.4. A virtual high throughput screening on ZINC database was carried out, picking ∼4000 chemicals highly indexed as H4R antagonists' candidates. Next, a series of 3D models of hH4R were generated by molecular modeling and molecular dynamics simulations performed in fully atomistic lipid membranes. The efficacy of the hH4R 3D models in discrimination between actives and non-actives were checked and the 3D model with the best performance was chosen for further docking studies performed on the focused library. The output of these docking studies was a consensus library of 11 highly active scored drug candidates. Our findings suggest that a sequential combination of ligand-based chemoinformatics approaches with structure-based ones has the potential to improve the success rate in discovering new biologically active GPCR drugs and increase the

  5. 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

  6. 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

  7. cDNA cloning reveals the molecular structure of a sperm surface protein, PH-20, involved in sperm-egg adhesion and the wide distribution of its gene among mammals

    PubMed Central

    1990-01-01

    Sperm binding to the egg zona pellucida in mammals is a cell-cell adhesion process that is generally species specific. The guinea pig sperm protein PH-20 has a required function in sperm adhesion to the zona pellucida of guinea pig eggs. PH-20 is located on both the sperm plasma membrane and acrosomal membrane. We report here the isolation and sequence of a full-length cDNA for PH-20 (available from EMBL/GenBank/DDBJ under accession number X56332). The derived amino acid sequence shows a mature protein of 468 amino acids containing six N-linked glycosylation sites and twelve cysteines, eight of which are tightly clustered near the COOH terminus. The sequence indicates PH-20 is a novel protein with no relationship to the mouse sperm adhesion protein galactosyl transferase and no significant homology with other known proteins. The two PH-20 populations, plasma membrane and acrosomal membrane, could arise because one form of PH-20 is encoded and differentially targeted at different spermatogenic stages. Alternatively, two different forms of PH-20 could be encoded. Our evidence thus far reveals only one sequence coding for PH-20: Southern blots of guinea pig genomic DNA indicated there is a single PH-20 gene, Northern blots showed a single size PH-20 message (approximately 2.2 kb), and no sequence variants were found among the sequenced cDNA clones. Cross-species Southern blots reveal the presence of a homologue of the PH-20 gene in mouse, rat, hamster, rabbit, bovine, monkey, and human genomic DNA, showing the PH-20 gene is conserved among mammals. Since genes for zona glycoproteins are also conserved among mammals, the general features of sperm and zona proteins involved in mammalian sperm-egg adhesion may have been evolutionarily maintained. Species specificity may result from limited changes in these molecules, either in their binding domains or in other regions that affect the ability of the binding domains to interact. PMID:2269661

  8. 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.

  9. Le lymphangiome kystique rétropéritonéal: à propos de 5 cas et revue de la littérature

    PubMed Central

    Saadi, Ahmed; Ayed, Haroun; Karray, Omar; Kerkeni, Walid; Bouzouita, Abderrazak; Cherif, Mohamed; Slama, Riadh Ben; Derouiche, Amine; Chebil, Mohamed

    2016-01-01

    Le lymphangiome kystique est une tumeur bénigne malformative rare des vaisseaux lymphatiques à localisations diverses. La localisation rétropéritonéale est moins fréquente comparée à celle mésentérique. Sa présentation clinique est polymorphe. Le diagnostic est évoqué par l'imagerie mais il nécessite une confirmation histologique. Le traitement de choix est chirurgical. Notre objectif est d'étudier les manifestations cliniques, les complications, les aspects diagnostiques et thérapeutiques de cette tumeur. Nous rapportons une série de 5 cas de lymphangiomes kystiques rétropéritonéaux (4 femmes et un homme) opérés dans notre service entre les années 2004 et 2014. Leurs dossiers ont été examinés rétrospectivement. Le suivi était basé sur l'examen clinique et l'échographie abdominale. L´âge moyen était de 45 ans. Le suivi moyen était de 32,6 mois. La symptomatologie révélatrice la plus fréquente était les douleurs et/ou une masse abdominale. Le scanner abdominal était l'examen le plus utile au diagnostic. Une exérèse complète était réalisée d'emblée chez quatre patients et elle était différée après cinq ans de surveillance par une échographie annuelle chez un. Dans un cas, on a eu recours à une néphrectomie. Aucune récidive ni complication n´ont été notées chez les 5 patients. le lymphangiome kystique à localisation rétropéritonéale est une affection rare. Sa prise en charge thérapeutique repose sur une exérèse complète, de cas de lésions symptomatiques ou de complications, pour limiter le risque de récidive. Cette dernière peut être différée chez les patients asymptomatiques. PMID:28292036

  10. Characterization of Clustered MHC-Linked Olfactory Receptor Genes in Human and Mouse

    PubMed Central

    Younger, Ruth M.; Amadou, Claire; Bethel, Graeme; Ehlers, Anke; Lindahl, Kirsten Fischer; Forbes, Simon; Horton, Roger; Milne, Sarah; Mungall, Andrew J.; Trowsdale, John; Volz, Armin; Ziegler, Andreas; Beck, Stephan

    2001-01-01

    Olfactory receptor (OR) loci frequently cluster and are present on most human chromosomes. They are members of the seven transmembrane receptor (7-TM) superfamily and, as such, are part of one of the largest mammalian multigene families, with an estimated copy number of up to 1000 ORs per haploid genome. As their name implies, ORs are known to be involved in the perception of odors and possibly also in other, nonolfaction-related, functions. Here, we report the characterization of ORs that are part of the MHC-linked OR clusters in human and mouse (partial sequence only). These clusters are of particular interest because of their possible involvement in olfaction-driven mate selection. In total, we describe 50 novel OR loci (36 human, 14 murine), making the human MHC-linked cluster the largest sequenced OR cluster in any organism so far. Comparative and phylogenetic analyses confirm the cluster to be MHC-linked but divergent in both species and allow the identification of at least one ortholog that will be useful for future regulatory and functional studies. Quantitative feature analysis shows clear evidence of duplications of blocks of OR genes and reveals the entire cluster to have a genomic environment that is very different from its neighboring regions. Based on in silico transcript analysis, we also present evidence of extensive long-distance splicing in the 5′-untranslated regions and, for the first time, of alternative splicing within the single coding exon of ORs. Taken together with our previous finding that ORs are also polymorphic, the presented data indicate that the expression, function, and evolution of these interesting genes might be more complex than previously thought. [The sequence data described in this paper have been submitted to the EMBL nucleotide data library under accession nos. Z84475, Z98744, Z98745, AL021807, AL021808, AL022723, AL022727, AL031893, AL035402, AL035542, AL050328, AL050339, AL078630, AL096770, AL121944, AL133160, and AL

  11. Place de la chirurgie dans la prise en charge des cancers du sein chez la femme au Centre Hospitalier Universitaire Yalgado Ouedraogo: à propos de 81 cas

    PubMed Central

    Zongo, Nayi; Millogo-Traore, Timonga Françoise Danielle; Bagre, Sidpawalmdé Carine; Bagué, Abdoul-Halim; Ouangre, Edgar; Zida, Maurice; Bambara, Aboubacar; Bambara, Tozoula Augustin; Traoré, Si Simon

    2015-01-01

    Etudier la place de la chirurgie dans la prise en charge des cancers du sein au centre hospitalier universitaire Yalgado Ouédraogo. Nous avons réalisé une étude prospective et descriptive sur dix (10) mois portant sur la place de la chirurgie dans le cancer du sein. Elle a eu pour cadre les services de gynécologie-obstétrique et de chirurgie viscérale et digestive du centre hospitalier universitaire Yalgado Ouédraogo. Ont été pris en compte les indications, les gestes et les résultats de la chirurgie. Nous avons colligé 81 cancers mammaires. Le délai moyen de consultation a été de 14,26 mois. Les tumeurs T3 à T4 représentaient 82,71% des cas. Trente-huit patientes (46,91%) ont été opérées. La chimiothérapie néo adjuvante a été réalisée dans 29,63% des cas. Trente-quatre patientes (41,97%) étaient opérables d'emblée. Il s'agissait de mastectomie selon Madden dans 94,74% des cas et de chirurgie de propreté dans 2 cas (5,26% des cas). Une chimiothérapie adjuvante a été réalisée chez 52,63% des patientes opérées. Des complications à type de lymphocèle ont été notées dans 23,68% des cas. Leur traitement a consisté en des ponctions évacuatrices. Les indications de la chirurgie sont limitées par le retard diagnostique corollaire de stades avancés des cancers du sein. L'absence de la radiothérapie rend délicate la pratique de la chirurgie conservatrice et la mastectomie occupe toujours une place importante. Un diagnostic précoce permettrait d'augmenter les indications chirurgicales. PMID:26848364

  12. Small and Wide Angle X-ray Scattering studies of biological macromolecules in solution.

    PubMed

    Liu, Li; Boldon, Lauren; Urquhart, Melissa; Wang, Xiangyu

    2013-01-08

    In this paper, Small and Wide Angle X-ray Scattering (SWAXS) analysis of macromolecules is demonstrated through experimentation. SWAXS is a technique where X-rays are elastically scattered by an inhomogeneous sample in the nm-range at small angles (typically 0.1 - 5°) and wide angles (typically > 5°). This technique provides information about the shape, size, and distribution of macromolecules, characteristic distances of partially ordered materials, pore sizes, and surface-to-volume ratio. Small Angle X-ray Scattering (SAXS) is capable of delivering structural information of macromolecules between 1 and 200 nm, whereas Wide Angle X-ray Scattering (WAXS) can resolve even smaller Bragg spacing of samples between 0.33 nm and 0.49 nm based on the specific system setup and detector. The spacing is determined from Bragg's law and is dependent on the wavelength and incident angle. In a SWAXS experiment, the materials can be solid or liquid and may contain solid, liquid or gaseous domains (so-called particles) of the same or another material in any combination. SWAXS applications are very broad and include colloids of all types: metals, composites, cement, oil, polymers, plastics, proteins, foods, and pharmaceuticals. For solid samples, the thickness is limited to approximately 5 mm. Usage of a lab-based SWAXS instrument is detailed in this paper. With the available software (e.g., GNOM-ATSAS 2.3 package by D. Svergun EMBL-Hamburg and EasySWAXS software) for the SWAXS system, an experiment can be conducted to determine certain parameters of interest for the given sample. One example of a biological macromolecule experiment is the analysis of 2 wt% lysozyme in a water-based aqueous buffer which can be chosen and prepared through numerous methods. The preparation of the sample follows the guidelines below in the Preparation of the Sample section. Through SWAXS experimentation, important structural parameters of lysozyme, e.g. the radius of gyration, can be analyzed.

  13. Facteurs liés au diagnostic tardif du cancer du sein: expérience du CHU Mohammed VI Marrakech

    PubMed Central

    Aloulou, Sofia; El Mahfoudi, Amal; El Omrani, Abdelhamid; Khouchani, Mouna

    2015-01-01

    Le cancer du sein est le premier cancer féminin en termes d'incidence et de mortalité. Au Maroc, il vient au premier rang des cancers de la femme avant celui du col utérin Il constitue un problème de santé publique. Son pronostic est étroitement lié au stade auquel le diagnostic est posé. Il s'agit d'une pathologie dont les moyens diagnostiques sont de nos jours développés, allant de la détection précoce à la mise en évidence de lésions infra-cliniques, ce qui a nettement amélioré le pronostic dans les pays développés. Ce travail que nous présentons a pour objectif d'identifier dans notre pratique quotidienne, les facteurs qui amènent les patientes à consulter à des stades tardifs. Une étude rétrospective a été menée de janvier 2012 à janvier 2013 portant sur 130 patientes porteuses d'un cancer du sein au sein du service d'onco-radiotherapie CHU Mohammed VI Marrakech. Un questionnaire a été élaboré et dument renseigné en ayant recours aux dossiers des malades. Ainsi 63,07% des patientes consultaient au-delà de six mois avec un délai moyen de consultation de 8,47 mois avec comme motif de consultation des lésions classées T4 dans 27,69%, et des tumeurs d'emblée métastatiques dans 13,84%. Les facteurs retrouvés à l'interrogatoire étaient le manque de moyens financiers 40%, l’éloignement des structures sanitaires dans 23%, les habitudes socioculturelles avec les traitements traditionnels en première intention 20%, et l'insuffisance de prise en charge thérapeutique 7%. Cependant, pris individuellement, aucune concordance significative n’était retrouvée entre ces facteurs et le long délai diagnostique. Dans notre pratique, c'est la conjonction de la triade ignorance, indigence et habitudes socioculturelles qui constituent le facteur essentiel du diagnostic tardif des cancers du sein. PMID:26327999

  14. 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

  15. Inner core biosynthesis of lipooligosaccharide (LOS) in Neisseria meningitidis serogroup B: identification and role in LOS assembly of the alpha1,2 N-acetylglucosamine transferase (RfaK).

    PubMed Central

    Kahler, C M; Carlson, R W; Rahman, M M; Martin, L E; Stephens, D S

    1996-01-01

    A lipooligosaccharide (LOS) mutant of Neisseria meningitidis serogroup B strain NMB (immunotype L3,7,9) was identified in a Tn916 (tetM) mutant bank by loss of reactivity with monoclonal antibody 3F11, which recognizes the terminal Galbeta1-->4GlcNAc epitope in the lacto-N-neotetraose moiety of the wild-type LOS structure. The mutant, designated 559, was found to express a truncated LOS of 3.0 kDa. Southern and PCR analyses demonstrated that there was a single intact Tn916 insertion (class I) in the mutant 559 chromosome. Linkage of the LOS phenotype and the Tn916 insertion was confirmed by transformation of the wild-type parent. Nucleotide sequence analysis of the region surrounding the transposition site revealed a 1,065-bp open reading frame (ORF). A homology search of the GenBank/EMBL database revealed that the amino acid sequence of this ORF had 46.8% similarity and 21.2% identity with the alpha1,2 N-acetylglucosamine transferase (RfaK) from Salmonella typhimurium. Glycosyl composition and linkage analysis of the LOS produced by mutant 559 revealed that the lacto-N-neotetraose group which is attached to heptose I (HepI) and the N-acetylglucosamine and glucose residues that are attached to HepII in the inner core of the parental LOS were absent. These analyses also showed that the HepII residue in both the parent and the mutant LOS molecules was phosphorylated, presumably by a phosphoethanolamine substituent. The insertion of nonpolar and polar antibiotic resistance cartridges into the parental rfaK gene resulted in the expression of LOS with the same mobility as that produced by mutant 559. This result indicated that the inability to add the lacto-N-neotetraose group to the 559 LOS is not due to a polar effect on a gene(s) downstream of rfaK. Our data indicate that we have identified the meningococcal alpha1,2 N-acetylglucosamine transferase responsible for the addition of N-acetylglucosamine to HepII. We propose that the lack of alpha-chain extension from Hep

  16. 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

  17. Profil évolutif et pronostic des tumeurs urothéliales de la vessie chez le sujet jeune

    PubMed Central

    Bouzouita, Abderrazak; Saadi, Ahmed; Kerkeni, Walid; Chakroun, Marouene; Cherif, Mohamed; Ayed, Haroun; Selmi, Selim; Derouiche, Amine; Benslama, Riadh Mohamed; Chebil, Mohamed

    2016-01-01

    Résumé But: Les tumeurs urothéliales de la vessie sont rares chez le jeune adulte. Leur profil évolutif et leur pronostic restent matière à contro-verse. Nous rapportons notre expérience à propos de 54 patients. Méthodologie: Entre 1990 et 2010, 54 patients de moins de 40 ans au moment du diagnostic ont été traités pour carcinome à cellules transitionnelles de la vessie. Nous avons étudié le profil évolutif de ces tumeurs en séparant les patients en deux groupes (moins de 30 ans, et 30 à 40 ans). Résultats: La tumeur n’infiltrait pas le muscle vésical dans 37 cas et l’infiltrait dans 17 cas. Pour les tumeurs n’infiltrant pas le muscle vésical, elles étaient de stade Ta dans 20 cas et de grade I–II dans 36 cas. Le pronostic de ces tumeurs était meilleur avant l’âge de 30 ans avec un taux de récidive de 15,3 % sans progression. Pour les patients de 30 à 40 ans, le taux de récidive était de 33,3 %, et 25 % des tumeurs qui ont récidivé ont présenté une progression du stade. Pour les tumeurs infiltrant le muscle vésical, le pronostic était sombre (localement avancées dans neuf cas et métastatiques d’emblée dans cinq cas). Conclusion: Le profil évolutif des tumeurs n’infiltrant pas le muscle vésical a semblé meilleur avant l’âge de 30 ans. Entre 30 et 40 ans, le profil évolutif s’est approché de celui des sujets âgés. Les tumeurs infiltrantes étaient souvent évoluées et agressives, évoquant un potentiel évolutif particulier. PMID:27330577

  18. 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).

  19. 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

  20. 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

  1. 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

  2. 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.

  3. Antitubercular specific activity of ibuprofen and the other 2-arylpropanoic acids using the HT-SPOTi whole-cell phenotypic assay

    PubMed Central

    Guzman, Juan D; Evangelopoulos, Dimitrios; Gupta, Antima; Birchall, Kristian; Mwaigwisya, Solomon; Saxty, Barbara; McHugh, Timothy D; Gibbons, Simon; Malkinson, John; Bhakta, Sanjib

    2013-01-01

    Objectives Lead antituberculosis (anti-TB) molecules with novel mechanisms of action are urgently required to fuel the anti-TB drug discovery pipeline. The aim of this study was to validate the use of the high-throughput spot culture growth inhibition (HT-SPOTi) assay for screening libraries of compounds against Mycobacterium tuberculosis and to study the inhibitory effect of ibuprofen (IBP) and the other 2-arylpropanoic acids on the growth inhibition of M tuberculosis and other mycobacterial species. Methods The HT-SPOTi method was validated not only with known drugs but also with a library of 47 confirmed anti-TB active compounds published in the ChEMBL database. Three over-the-counter non-steroidal anti-inflammatory drugs were also included in the screening. The 2-arylpropanoic acids, including IBP, were comprehensively evaluated against phenotypically and physiologically different strains of mycobacteria, and their cytotoxicity was determined against murine RAW264.7 macrophages. Furthermore, a comparative bioinformatic analysis was employed to propose a potential mycobacterial target. Results IBP showed antitubercular properties while carprofen was the most potent among the 2-arylpropanoic class. A 3,5-dinitro-IBP derivative was found to be more potent than IBP but equally selective. Other synthetic derivatives of IBP were less active, and the free carboxylic acid of IBP seems to be essential for its anti-TB activity. IBP, carprofen and the 3,5-dinitro-IBP derivative exhibited activity against multidrug-resistant isolates and stationary phase bacilli. On the basis of the human targets of the 2-arylpropanoic analgesics, the protein initiation factor infB (Rv2839c) of M tuberculosis was proposed as a potential molecular target. Conclusions The HT-SPOTi method can be employed reliably and reproducibly to screen the antimicrobial potency of different compounds. IBP demonstrated specific antitubercular activity, while carprofen was the most selective agent among the

  4. 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

  5. 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

  6. Sequential application of ligand and structure based modeling approaches to index chemicals for their hH4R antagonism.

    PubMed

    Pappalardo, Matteo; Shachaf, Nir; Basile, Livia; Milardi, Danilo; Zeidan, Mouhammed; Raiyn, Jamal; Guccione, Salvatore; Rayan, Anwar

    2014-01-01

    The human histamine H4 receptor (hH4R), a member of the G-protein coupled receptors (GPCR) family, is an increasingly attractive drug target. It plays a key role in many cell pathways and many hH4R ligands are studied for the treatment of several inflammatory, allergic and autoimmune disorders, as well as for analgesic activity. Due to the challenging difficulties in the experimental elucidation of hH4R structure, virtual screening campaigns are normally run on homology based models. However, a wealth of information about the chemical properties of GPCR ligands has also accumulated over the last few years and an appropriate combination of these ligand-based knowledge with structure-based molecular modeling studies emerges as a promising strategy for computer-assisted drug design. Here, two chemoinformatics techniques, the Intelligent Learning Engine (ILE) and Iterative Stochastic Elimination (ISE) approach, were used to index chemicals for their hH4R bioactivity. An application of the prediction model on external test set composed of more than 160 hH4R antagonists picked from the chEMBL database gave enrichment factor of 16.4. A virtual high throughput screening on ZINC database was carried out, picking ∼ 4000 chemicals highly indexed as H4R antagonists' candidates. Next, a series of 3D models of hH4R were generated by molecular modeling and molecular dynamics simulations performed in fully atomistic lipid membranes. The efficacy of the hH4R 3D models in discrimination between actives and non-actives were checked and the 3D model with the best performance was chosen for further docking studies performed on the focused library. The output of these docking studies was a consensus library of 11 highly active scored drug candidates. Our findings suggest that a sequential combination of ligand-based chemoinformatics approaches with structure-based ones has the potential to improve the success rate in discovering new biologically active GPCR drugs and increase the

  7. Mapping of the first preferentially expressed cDNA in human fetal cochlea to human 14q11.2-12 and to a region of homologous synteny on mouse chromosome 12

    SciTech Connect

    Robertson, N.G.; Weremowicz, S.; Kovatch, K.A.

    1994-09-01

    We have isolated a cDNA, Coch-5B2 (D14S564E) from a human fetal cochlear cDNA library by subtractive hybridization and differential screening methods. This is the first cDNA to date shown to be expressed preferentially in human fetal cochlea (membranous labyrinth). On Northern blot of a panel of 14 human fetal tissue RNAs including cochlea, brain, liver, spleen, skeletal muscle, kidney, lung, skin, thymus, adrenal, small intestine, eye, sternal cartilage, and cultured fibroblasts, very high level expression of D14S564E is seen only in cochlea; very faint bands are discernible in brain and eye. Sequence comparison of this clone to sequences in GenBank/EMBL data bases shows no match to any known genes, indicating that it represents a novel cochlear sequence. Chromosome localization of this cochlear cDNA may provide insight into a region of the human genome to which human deafness disorders may map. We have assigned D14S564E to human chromosome 14 using the NIGMS human/rodent somatic cell hybrid mapping panel 1, and regionally to q11.2-q12 by fluorescence in situ hybridization (FISH). Besides detection of the human genomic band on the hybrid panel, genomic bands were seen for mouse and hamster, demonstrating evolutionary conservation of D14S564E. By FISH, signal was detected on human 14q11.2-q12 in 20 metaphases. In 3 metaphases, signal was present on both chromosome 14s. The mouse homolog of this cochlear cDNA was also used to probe human metaphases by FISH: signal was detected in the same region, 14q11.2-12, as the human clone in 5 metaphases, confirming human mapping data and homology to the human cDNA. The human cochlear D14S564E was genetically mapped in the mouse to chromosome 12, in a region of homology with human 14q11.2-q12. This region on mouse 12 contains the asp-1 (audiogenic seizure prone) locus and future studies will be directed at determining whether D14S564E is a candidate gene for this disorder.

  8. Mappability of drug-like space: towards a polypharmacologically competent map of drug-relevant compounds

    NASA Astrophysics Data System (ADS)

    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

  9. 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

  10. Intermolecular Vibrations of Hydrophobic Amino Acids

    NASA Astrophysics Data System (ADS)

    Williams, Michael Roy Casselman

    -TDS) was used to measure the absorption spectra of low-frequency vibrational modes for a variety of hydrophobic amino acids in the solid (polycrystalline) state. The THz-TDS technique uses ultrafast (<50 fs) pulses of light from a visible/near-IR laser to generate single-cycle pulses of THz (far-IR) light. Pulses from the ultrafast laser are also used to coherently gate a THz detector, allowing phase-sensitive measurements of the THz electric field. In some cases, Raman scattering spectra of some of the polycrystalline hydrophobic amino acid samples were measured as well, in this case using an Ar+ laser and a triple monochromator to detect signals at the low Raman-shift values corresponding to the far-IR. THz-TDS was used to measure the low-frequency vibrational absorption spectra of pure L- and pure D-valine crystals as well as the racemic cocrystal, DL-valine. As expected, the Land D-valine THz-TDS absorption spectra are identical to one another (they are enantiomorphous crystals) but very different from the spectrum of DL-valine. In the process of these experiments, it was discovered that it was possible to prepare two distinct polymorphs (different crystalline arrangements) of DL-valine by varying the conditions under which stock material was recrystallized. Once crystallized in a particular form, both polymorphs remained (meta)stable at all temperatures investigated (from 80 K to room temperature), i.e., no phase transformation was observed. The THz-TDS and Raman spectra of the two polymorphs of DL-valine were measured. In addition, THz-TDS and Raman spectra of DL-leucine were measured; this substance has a crystal structure closely analagous to one of the DL-valine polymorphs. The temperature-dependence of the THz-TDS spectrum of each material was also measured. At lower temperatures, it is generally expected that intermolecular vibration frequencies increase (blueshift) due to a shrinking unit cell (effectively squeezing the oscillator potential into a smaller space

  11. Les abcès orbitaires: à propos de 7 cas

    PubMed Central

    Ouaissi, Laila; El Khiati, Rhizlane; Serghini, Salma; Abada, Redallah; Rouadi, Sami; Mahtar, Mohamed; Roubal, Mohamed; Essaadi, Mustapha; Kadiri, Fatmi

    2014-01-01

    L'abcès orbitaire correspond à une infection collectée bien limitée située dans l'orbite, généralement due à une cellulite orbitaire. Nous rapportons notre expérience à propos de 7 cas d'abcès orbitaires opérés dans le service d'ORL est de chirurgie cervico-faciale de l'hôpital 20 aout de Casablanca entre juin 2007 et juin 2008. L’âge moyen est de 11 ans avec des extrêmes de 5 et 22 ans. On note une prédominance masculine avec un sex-ratio de 3. On retrouve une exophtalmie inflammatoire, avec tuméfaction palpébrale et une porte d'entrée sinusienne chez tous nos patients. L'ophtalmoplégie est notée dans 5 cas, la baisse de l'acuité visuelle dans 4 cas, et la cécité dans 2 cas. La tomodensitométrie a été réalisée chez tous nos patients. Elle a permit de confirmer l'abcès et sa localisation: interne (4 cas), supéro-interne (2 cas), et inférieure (1 cas). L'imagerie par résonnance magnétique a été faite dans 3 cas, et a permis de préciser les limites de l'infection. Le traitement médical a été instauré d'emblée, associant une triple antibiothérapie par voie parentérale. Le traitement chirurgical a été réalisé chez 5 patients devant la non amélioration clinique. Un drainage externe a été pratiqué et la cure de la sinusite était différée. On note une évolution défavorable dans 3 cas: cécité par névrite optique (2 cas) et ophtalmoplégie (1 cas). Elle a été favorable dans les autres cas. En conclusion, l'abcès orbitaire est une affection rare et grave du sujet jeune, engageant le pronostic visuel voire même le pronostic vital, et constitue de ce fait une urgence ophtalmologique et ORL. Le traitement se base sur une poly-antibiothérapie avec des drainages de la collection le plus rapidement possible. La prévention passe par un diagnostic et un traitement appropriés des sinusites. PMID:25722783

  12. From First Base: The Sequence of the Tip of the X Chromosome of Drosophila melanogaster, a Comparison of Two Sequencing Strategies

    PubMed Central

    Benos, Panayiotis V.; Gatt, Melanie K.; Murphy, Lee; Harris, David; Barrell, Bart; Ferraz, Concepcion; Vidal, Sophie; Brun, Christine; Demaille, Jacques; Cadieu, Edouard; Dreano, Stephane; Gloux, Stéphanie; Lelaure, Valerie; Mottier, Stephanie; Galibert, Francis; Borkova, Dana; Miñana, Belen; Kafatos, Fotis C.; Bolshakov, Slava; Sidén-Kiamos, Inga; Papagiannakis, George; Spanos, Lefteris; Louis, Christos; Madueño, Encarnación; de Pablos, Beatriz; Modolell, Juan; Peter, Annette; Schöttler, Petra; Werner, Meike; Mourkioti, Fotini; Beinert, Nicole; Dowe, Gordon; Schäfer, Ulrich; Jäckle, Herbert; Bucheton, Alain; Callister, Debbie; Campbell, Lorna; Henderson, Nadine S.; McMillan, Paul J.; Salles, Cathy; Tait, Evelyn; Valenti, Phillipe; Saunders, Robert D.C.; Billaud, Alain; Pachter, Lior; Glover, David M.; Ashburner, Michael

    2001-01-01

    We present the sequence of a contiguous 2.63 Mb of DNA extending from the tip of the X chromosome of Drosophila melanogaster. Within this sequence, we predict 277 protein coding genes, of which 94 had been sequenced already in the course of studying the biology of their gene products, and examples of 12 different transposable elements. We show that an interval between bands 3A2 and 3C2, believed in the 1970s to show a correlation between the number of bands on the polytene chromosomes and the 20 genes identified by conventional genetics, is predicted to contain 45 genes from its DNA sequence. We have determined the insertion sites of P-elements from 111 mutant lines, about half of which are in a position likely to affect the expression of novel predicted genes, thus representing a resource for subsequent functional genomic analysis. We compare the European Drosophila Genome Project sequence with the corresponding part of the independently assembled and annotated Joint Sequence determined through “shotgun” sequencing. Discounting differences in the distribution of known transposable elements between the strains sequenced in the two projects, we detected three major sequence differences, two of which are probably explained by errors in assembly; the origin of the third major difference is unclear. In addition there are eight sequence gaps within the Joint Sequence. At least six of these eight gaps are likely to be sites of transposable elements; the other two are complex. Of the 275 genes in common to both projects, 60% are identical within 1% of their predicted amino-acid sequence and 31% show minor differences such as in choice of translation initiation or termination codons; the remaining 9% show major differences in interpretation. [All of the sequences analyzed in this paper have been deposited in the EMBL-Bank database under the following accession nos.: AL009146, AL009147, AL009171, AL009188–AL009196, AL021067, AL021086, AL021106–AL021108, AL021726, AL

  13. "Life in the Universe" Final Event Video Now Available

    NASA Astrophysics Data System (ADS)

    2002-02-01

    associated with the programme, e.g., the European Molecular Biology Laboratory (EMBL) and the European Synchrotron Radiation Facility (ESRF). Detailed information about the "Life in the Universe" programme can be found at the website b>http://www.lifeinuniverse.org and a webcast of this 90-min closing session in one of the large experimental halls at CERN is available on the web via that page. Most of the ESO PR Video Clips at the ESO website provide "animated" illustrations of the ongoing work and events at the European Southern Observatory. The most recent clip was: ESO PR Video Clips 08a-b/01 about The Eagle's EGGs (20 December 2001) . General information is available on the web about ESO videos.

  14. Helix Nebula - the Science Cloud: a public-private partnership to build a multidisciplinary cloud platform for data intensive science

    NASA Astrophysics Data System (ADS)

    Jones, Bob; Casu, Francesco

    2013-04-01

    The feasibility of using commercial cloud services for scientific research is of great interest to research organisations such as CERN, ESA and EMBL, to the suppliers of cloud-based services and to the national and European funding agencies. Through the Helix Nebula - the Science Cloud [1] initiative and with the support of the European Commission, these stakeholders are driving a two year pilot-phase during which procurement processes and governance issues for a framework of public/private partnership will be appraised. Three initial flagship use cases from high energy physics, molecular biology and earth-observation are being used to validate the approach, enable a cost-benefit analysis to be undertaken and prepare the next stage of the Science Cloud Strategic Plan [2] to be developed and approved. The power of Helix Nebula lies in a shared set of services for initially 3 very different sciences each supporting a global community and thus building a common e-Science platform. Of particular relevance is the ESA sponsored flagship application SuperSites Exploitation Platform (SSEP [3]) that offers the global geo-hazard community a common platform for the correlation and processing of observation data for supersites monitoring. The US-NSF Earth Cube [4] and Ocean Observatory Initiative [5] (OOI) are taking a similar approach for data intensive science. The work of Helix Nebula and its recent architecture model [6] has shown that is it technically feasible to allow publicly funded infrastructures, such as EGI [7] and GEANT [8], to interoperate 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 of choice" over the type of computing resources to be consumed and the manner in which they can be obtained. But to offer such freedom-of choice across a spectrum of suppliers, various issues such as intellectual property, legal responsibility

  15. Probing the origins of human acetylcholinesterase inhibition via QSAR modeling and molecular docking

    PubMed Central

    Shoombuatong, Watshara; Malik, Aijaz Ahmad; Prachayasittikul, Virapong; Wikberg, Jarl E.S.

    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 R2, \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${Q}_{\\mathrm{CV }}^{2}$\\end{document}QCV2 and \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${Q}_{\\mathrm{Ext}}^{2}$\\end{document}QExt2 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 R2, \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage

  16. Abcès encéphaliques: prise en charge, à propos d'une série de 82 cas

    PubMed Central

    Hassani, Fahd Derkaoui; El Fatemi, Nizare; Moufid, Faycal; YassadOudrhiri, Mohammed; Gana, Rachid; El Maaqili, Rachid; Bellakhdar, Fouad

    2014-01-01

    Les auteurs proposent des options thérapeutiques dans la prise en charge des abcès encéphaliques, en fonction des paramètres cliniques et radiologiques des patients, en dégageant des facteurs pronostiques à long terme. Il s'agit d'une étude rétrospective incluant tous les abcès encéphaliques pris en charge, sur une période 13 ans, au service de Neurochirurgie de l'Hôpital Ibn Sina de Rabat. L'analyse a porté sur: le Glasgow coma scale (GCS), la présence de déficit neurologique, l'imagerie cérébrale avec contraste, et la recherche d'une porte d'entrée; le traitement a compris chirurgie et antibiothérapie, et le pronostic a été évalué à long terme. 82 cas d'abcès ont été analysés, un score de GCS inférieur à 12 a été trouvé dans 24%. La porte d'entrée a été d'origine ORL dans 45%. La trépanoponction seule a été décidée dans 34% des cas en situation d'urgence avec troubles de conscience. Elle a été suivie d'une exérèse de la coque dans 16% des cas lors de persistance ou récidive de la collection. La ponction stéréotaxiques a été réalisée dans 10% des cas lors de localisations éloquentes et l'exérèse d'emblée dans 38% des cas avec abcès collecté non menaçant. La mortalité opératoire a été de 1,22%, la morbidité de 19,30%. Les facteurs de bon pronostic à long terme ont été l’âge jeune, un GCS supérieur à 12 à l'admission, et la trépanoponction suivie de l'exérèse da la coque. L'amélioration du pronostic passe par le diagnostic précoce, un geste neurochirurgical précis et antibiothérapie adaptée, et le traitement des portes d'entrée. PMID:25404970

  17. Life in the Universe

    NASA Astrophysics Data System (ADS)

    2001-10-01

    Live Webcast from Europe's Leading Research Organisations Summary Is there life elsewhere in the Universe? Are we alone? These questions have always fascinated humanity and for more than 50 years, physicists, biologists, chemists, cosmologists, astronomers and other scientists have worked tirelessly to answer these fundamental questions. And now this November via webcast, all the world will have the opportunity to see and hear the latest news on extraterrestrial life from the most prestigious research centers and how for the past three months, European students have had the chance to jump into the scientists' shoes and explore these questions for themselves. The event is being sponsored by the European Organisation for Nuclear Research (CERN) , the European Space Agency (ESA) and the European Southern Observatory (ESO) , in cooperation with the European Molecular Biology Laboratory (EMBL) and the European Synchrotron Radiation Facility (ESRF) and the European Association for Astronomy Education (EAAE). "Life in the Universe" is being mounted in collaboration with the Research Directorate-General of the European Commission for the European Week of Science and Technology in November 2001 . "Life in the Universe" competitions are already underway in 23 European countries to find the best projects from school students between 14 and 18. Two winning teams from each country will be invited to a final event at CERN in Geneva on 8-11 November 2001 to present their projects and discuss them with a panel of International Experts at a special three-day event. They will also compete for the "Super Prize" - a free visit to ESA's and ESO's research and technology facilities at Kourou and Paranal in South America. Students participating in the programme are encouraged to present their views on extraterrestrial life creatively. The only requirement is that the views be based upon scientific evidence. Many projects are being submitted just now - among them are scientific essays

  18. How Consistent are Publicly Reported Cytotoxicity Data? Large-Scale Statistical Analysis of the Concordance of Public Independent Cytotoxicity Measurements.

    PubMed

    Cortés-Ciriano, Isidro; Bender, Andreas

    2016-01-05

    While increased attention is being paid to the impact of data quality in cell-line sensitivity and toxicology modeling, to date, no systematic study has evaluated the comparability of independent cytotoxicity measurements on a large-scale. Here, we estimate the experimental uncertainty of public cytotoxicity data from ChEMBL version 19. We applied stringent filtering criteria to assemble a curated data set comprised of pIC50 data for compound-cell line systems measured in independent laboratories. The estimated experimental uncertainty calculated was a mean unsigned error (MUE) value of 0.61-0.76, a median unsigned error (MedUE) value of 0.51-0.58, and a standard deviation of 0.76-1.00 pIC50 units. The experimental uncertainty (σE) estimated from all pairs of cytotoxicity measurements with a ΔpIC50 value lower than 2.5 was found to be 0.59-0.77 pIC50 units, and thus 21-60% and 21-26% higher than that of pKi and pIC50 data for ligand-protein data (σE =0.47-0.48 pKi units and σE =0.57-0.61 pIC50 units, respectively). The estimated σE value from the pairs of pIC50 values measured with metabolic assays was 0.98, whereas the σE value was found to be 0.69 when using the 1388 pIC50 pairs measured using exactly the same experimental setup. The maximum achievable Pearson correlation coefficient (RPearsonmax.2) of in silico models trained on cytotoxicity data from different laboratories was estimated to be 0.51-0.85, which is considerably different from the value of 1 corresponding to perfect predictions, hinting at the maximum performance one can expect also from computational cytotoxicity predictions. The lowest concordance between pairs of measurements was found for the drugs paclitaxel, methotrexate, zidovudine, and docetaxel, and for the cell lines HepG2, NCI-H460, L1210, and CCRF-CEM, hinting at particular sensitivity of those systems to experimental setups. The highest concordance was estimated for the compound-cell line system HL-60-etoposide (σE =0

  19. Les pyélonephrites aigues de la femme enceinte: place du traitement médical et indications d'un drainage de la voie excrétrice supérieure (y'a-t-il des facteurs prédictifs cliniques, biologiques et radiologiques pour rendre le drainage licite?)

    PubMed Central

    El Bahri, Abdessamad; Janane, Abdellatif; Chafiki, Jaouad; Arnaud, Tayiri; Ghadouane, Mohammed; Ameur, Ahmed; Abbar, Mohammed

    2015-01-01

    Les pyélonéphrites aigues gravidiques (PNAg) sont fréquentes et peuvent avoir des conséquences maternelles et fœtales graves. Le but de notre étude était de déterminer les facteurs prédictifs cliniques, biologiques et radiologiques qui permettent de se limiter au traitement médical ou d'associer un drainage de la voie excrétrice supérieure dans la prise en charge des PNAg. Nous rapportons, de façon rétrospective une série de 26 cas dans les services d'Urologie et de Gynécologie de l'Hôpital Militaire d'Instruction Mohamed V de Rabat (Maroc) sur une période allant du 1er Janvier 2010 au 30 Aout 2012. Toutes les patientes avaient une PNAg symptomatique objectivée par l'ECBU et/ou l’échographie rénale. La fréquence de la pyélonéphrite aigue gravidique par rapport aux pyélonéphrites aigues en général a été de 27,95% avec une prédominance chez les primipares de 53,84%. Son pic de fréquence se situe à 73,08% pour les gestantes âgées de 19 à 37 ans ainsi qu'au troisième trimestre (77%) de la grossesse. La triade clinique fièvre, lombalgie, troubles mictionnels et l’échographie rénale sont les éléments importants du diagnostic. L'antibiothérapie probabiliste a été débuté d'emblée et adaptée en fonctions des résultats de l'examen cytobactériologique des urines. Sa durée est de trois à six semaines en fonction de l’évolution clinique. La protéine C réactive est un marqueur de progression de la maladie ou de l'efficacité thérapeutique. Les principaux facteurs prédictifs du drainage de la voie excrétrice supérieure sont: persistance de la symptomatologie clinique, du syndrome infectieux et des anomalies visibles à l’échographie rénale ainsi que l'altération de la fonction rénale. La montée de la sonde JJ est le principal traitement urologique. Le traitement médical repose sur l'antibiothérapie probabiliste qui sera adaptée Ultérieurement en fonction des résultats de l'antibiogramme. Les facteurs pr

  20. Structure and regulation of the mDot1 gene, a mouse histone H3 methyltransferase.

    PubMed Central

    Zhang, Wenzheng; Hayashizaki, Yoshihide; Kone, Bruce C

    2004-01-01

    The nucleotide sequence data reported have been deposited in the DDBJ, EMBL, GenBank(R) and GSDB Nucleotide Sequence Databases under accession numbers AY196089, AY196090, AY376663, AY377920 and AY376664. Recently, a new class of histone methyltransferases that plays an indirect role in chromatin silencing by targeting a conserved lysine residue in the nucleosome core was described, namely the Dot1 (disruptor of telomeric silencing) family [Feng, Wang, Ng, Erdjument-Bromage, Tempst, Struhl and Zhang (2002) Curr. Biol. 12, 1052-1058; van Leeuwen, Gafken and Gottschling (2002) Cell (Cambridge, Mass.) 109, 745-756; Ng, Feng, Wang, Erdjument-Bromage, Tempst, Zhang and Struhl (2002) Genes Dev. 16, 1518-1527]. In the present study, we report the isolation, genomic organization and in vivo expression of a mouse Dot1 homologue (mDot1). Expressed sequence tag analysis identified five mDot1 mRNAs (mDot1a-mDot1e) derived from alternative splicing. mDot1a and mDot1b encode 1540 and 1114 amino acids respectively, whereas mDot1c-mDot1e are incomplete at the 5'-end. mDot1a is closest to its human counterpart (hDot1L), sharing 84% amino acid identity. mDot1b is truncated at its N- and C-termini and contains an internal deletion. The five mDot1 isoforms are encoded by 28 exons on chromosome 10qC1, with exons 24 and 28 further divided into two and four sections respectively. Alternative splicing occurs in exons 3, 4, 12, 24, 27 and 28. Northern-blot analysis with probes corresponding to the methyltransferase domain or the mDot1a-coding region detected 7.6 and 9.5 kb transcripts in multiple tissues, but only the 7.6 kb transcript was evident in mIMCD3-collecting duct cells. Transfection of mDot1a-EGFP constructs (where EGFP stands for enhanced green fluorescent protein) into human embryonic kidney (HEK)-293T or mIMCD3 cells increased the methylation of H3-K79 but not H3-K4, -K9 or -K36. Furthermore, DMSO induced mDot1 gene expression and methylation specifically at H3-K79 in mIMCD3

  1. "Sci-Tech - Couldn't be without it !"

    NASA Astrophysics Data System (ADS)

    2002-03-01

    it! will be launched on Friday 22 March at 18:30 at the Technopolis Science Museum in Brussels , coinciding with the official inauguration of CERN's travelling exhibition "E=mc 2 - When energy becomes matter". The exhibition will stay at Technopolis until 21 July. CERN Director General, Luciano Maiani , and European Commissioner for Research, Philippe Busquin , will open the event with speeches underlining the importance of joining efforts for science education and outreach in Europe. A tour of the exhibition and a demonstration of the project's hot site for cool science will follow, and the event will be brought to a close with a "Science in the Pub" discussion on the subject of modern physics and philosophy, complete with musical intermezzo and buffet. * Access the Couldn't be without it! online voting and web resources at: www.cern.ch/sci-tech * Confirm your presence at the Technopolis event before Wed. March 20 by fax to: +32-(0)15-34 20 10 * To reach Technopolis take exit 10 (Mechelen-Zuid) on motorway E19 (Bruxelles-Anvers). * For more information on the exhibition, contact Veronique de Man: veronique@technopolis.be; Tel. +32-15-34 2020 * For more information on Couldn't be without it! contact the executive coordinator: monica.de.pasquale@cern.ch; Tel. +41 22 767 3586 Note [1] CERN , the European Organisation for Nuclear Research, ESA , the European Space Agency, ESO , the European Southern Observatory, EMBL , the European Molecular Biology Laboratory, EFDA , the European Fusion Development Agreement, ESRF , the European Synchrotron Radiation Facility and ILL , Institut Laue-Langevin. These organizations have recently teamed up to form EIROFORUM (cf. ESO PR 12/01 ), whose Working Group on Outreach and Education is working with the European Union to provide a bridge between the organisations, the European Union and the citizens of Europe. The activities of the Working Group also contribute to the creation of the European Research Area.

  2. Something going on in Milan: a review of the 4th International PhD Student Cancer Conference.

    PubMed

    Segré, C

    2010-01-01

    with other prestigious research centres and to create connections for future post docs or job experiences. And last but not least, it is a golden chance for penniless PhD students to spend a couple of extra days visiting a foreign country (this motivation will of course never be voiced to supervisors).The network of participating institutes has a three-nation core, made up of the Netherlands Cancer Institute, the Italian European School of Molecular Medicine (SEMM) and five UK Cancer Research Institutes (The London Research Institute, The Cambridge Research Institute, The Beatson Institute for Cancer Research in Glasgow, The Patterson Institute for Cancer Research in Manchester and the MRC Gray Institute for Radiation Oncology and Biology in Oxford).The conference is hosted and organised every year by one of the core institutes; the first was in Cambridge in 2007, Amsterdam in 2008 and London in 2009, this year was the turn of Milan.In addition to the core institutes, PhD students from several other high-profile institutes are invited to attend the conference. This year participants applied from the Spanish National Cancer Centre (CNIO, Madrid), the German Cancer Research Centre (DKFZ, Heidelberg), the European Molecular Biology Labs (EMBL, Heidelberg) and the San Raffaele Institute (HSR, Milan). Moreover four 'special guests' from the National Centre for Biological Sciences of Bangalore (India) attended the conference in Milan. This represents a first step in widening the horizons beyond Europe into a global worldwide network of talented PhD students in life sciences.The conference spread over two and a half days (Wednesday 19th to Friday 21st May) and touched on a broad spectrum of topics: from basic biology to development, from cancer therapies to modelling and top-down new generation global approaches. The final selection of presentations has been a tough task for us organisers (Chiara Segré, Federica Castellucci, Francesca Milanesi, Gianluca Varetti and Gian

  3. "Physics and Life" - Teachers Meet Scientists at Major EIROforum Event [

    NASA Astrophysics Data System (ADS)

    2003-11-01

    More than 400 selected delegates from 22 European countries will take part in "Physics on Stage 3" , organised by the EIROforum [1] research organisations (CERN, EFDA, EMBL, ESA, ESO, ESRF, ILL) at the ESA ESTEC site (Noordwijk, The Netherlands). It is the culmination of a year-long educational programme and is a central event during the EC-sponsored European Science and Technology Week (November 8-15, 2003). Following the vastly successful preceeding events in 2000 and 2002, the main theme this year is "Physics and Life", reflecting the decision to broaden the Physics on Stage activities to encompass more of the natural sciences within an interdisciplinary approach. As before, European teachers, scientists, curricula organisers and others connected to the national education systems in Europe will gather with the main goal of exploring solutions to stimulate the interest of young people in science, by means of exciting and innovative teaching methods and materials. The rich one-week programme has many components: spectacular and original performances by students and professional actors, intensive encounters at a central fair where each country will present the latest developments from its teaching community at their stands, workshops about a host of crucial themes related to the central mission of this programme, seminars where EIROforum scientists and experienced high school teachers get together to discuss new teaching opportunities based on the latest results from front-line research projects at Europe's leading science centres, as well as a publishers fair that will also serve as an international exchange for new educational materials. A mystery cultural event will surprise everyone with its originality. And last but not least, the annual European Science Teaching Awards - the highest distinction in this field - will be presented at the end of the meeting. "Physics on Stage" is a joint project organised by EIROforum, together with the European Physical Society

  4. Life in the Universe - Is there anybody out there?

    NASA Astrophysics Data System (ADS)

    2001-07-01

    The Universe is indescribably huge. Can it be possible that Humanity is the only form of intelligent life which exists in all this immensity? Are we really alone ? Throughout history there have been sightings of creatures from elsewhere. Science fiction novels and films with flying saucers and bizarre looking aliens are part of our general culture. Perhaps the Earth is really only an experiment designed by mice and soon we will all be destroyed to make way for a new interstellar highway ! The possibility that there is life in the Universe has always excited the general public and scientists are equally enthusiastic. Physicists, biologists, chemists, cosmologists, astronomers are researching all over Europe to try to answer this age-old question : Is there life in the Universe ? Our current understanding What is our understanding at the beginning of the 21st century? Is there any scientific evidence for other forms of life? How can you define life? What signs are they looking for? What would the reaction be if other forms of life were discovered? The European Organisation for Nuclear Research (CERN) , the European Space Agency (ESA) and the European Southern Observatory (ESO) , in cooperation with the European Association for Astronomy Education (EAAE) have organised a competition to find out what the young people in Europe think. The European Molecular Biology Laboratory (EMBL) and the European Synchrotron Radiation Facility (ESRF) are also associated with the programme. The "Life in the Universe" programme ESO PR Video Clip 05/01 [192x144 pix MPEG-version] ESO PR Video Clip 05/01 (13300 frames/8:52 min) [MPEG Video+Audio; 192x144 pix; 12.1Mb] [RealMedia; streaming; 56kps] ESO Video Clip 05/01 is a trailer for the Europe-wide "Life in the Universe" programme. It touches upon some of the main issues and includes statements by members of the Experts' Panel. The "Life in the Universe" programme is being mounted in collaboration with the research directorate of the

  5. PREFACE Proceedings of the XIV International Conference on Small-Angle Scattering, SAS-2009

    NASA Astrophysics Data System (ADS)

    King, Stephen; Terrill, Nicholas

    2010-10-01

    scientific heart of the conference comprised 10 plenary sessions, interspersed by 39 'themed' parallel sessions, 2 poster sessions, an afternoon tour of Diamond and ISIS, and a week-long exhibition. There were 144 contributed oral presentations and 308 poster presentations across a total of 21 themes. Over half of all presentations fell under 6 themes: biological systems, colloids and solutions, instrumentation, kinetic and time-resolved measurements, polymers, and surfaces and interfaces. The importance of SAS techniques to the study of biology, materials science and soft matter/nanoscience is clear. The plenary presentations, which covered topics as diverse as advanced analysis techniques, biology, green chemistry, materials science and surfaces, were delivered by Frank Bates, Minnesota, USA, Peter Fratzl, MPI Golm, Germany, Buxing Han, Bejing, China, Julia Kornfield, CIT, USA, Jan Skov Pedersen, Aarhus, Denmark, Moonhor Ree, Pohang, Korea, Mitsuhiro Shibayama, Tokyo, Japan, Robert Thomas, Oxford, UK, Jill Trewhella, Sydney, Australia, and Thomas Zemb, ICSM Bagnols, France. Instigated by representatives of the Belgian and Dutch SAS communities one parallel session was dedicated to a tribute for Michel Koch, the pioneer of so many novel applications of SAXS, who retired after 30 years at the EMBL Hamburg in late 2006. With a supporting cast that included Wim Bras, ESRF, France, Tony Ryan, Sheffield, UK and Joe Zaccai, ILL,France, and watched by former colleague André Gabriel, Michel treated the audience to a fascinating - and at times light-hearted - retrospective of the evolution of synchrotron SAXS. Another parallel session was devoted to the work of the canSAS (Collective Action for Nomadic Small-Angle Scatterers) network of large-facility representatives and instrument scientists in areas such as data file formats, intensity calibration and software development. For further information see http://www.smallangles.net/wgwiki/index.php/canSAS_Working_Groups. A total of

  6. The ESO Educational Office Reaches Out towards Europe's Teachers

    NASA Astrophysics Data System (ADS)

    2001-12-01

    participation of more than one hundred physics teachers from different European countries. Other educational projects include the highly successful "Sea and Space" (in 1998; with ESA), "Physics on Stage" (2000; with CERN and ESA), and "Life in the Universe" (2001; with CERN, ESA, EMBL and ESRF), all in close collaboration with EAAE. Astronomy and Astrophysics at the frontline of education The subject of Astronomy and Astrophysics plays an increasingly important role within education. This is not coincidental - this particular field of basic science is very attractive to young people. Its exploratory nature tickles youthful minds and the vast expanse of the Universe harbours many unknown secrets that are waiting to be discovered. The beautiful and intriguing images brought back by high-tech telescopes and instruments from the enormous terra incognita out there are natural works of art that invite comtemplation as well as interpretation. Astronomy and Astrophysics is a broadly interdisciplinary field, providing ample opportunities for interesting educational angles into many different fields of fundamental science, from physics, chemistry and mathematics, to applied research in opto-mechanics, detectors and data handling, and onwards into the humanities. The ESO Educational Office In order to further enhance the educational potential of the numerous scientific endeavours now carried out by Europe's astronomers with ESO front-line facilities, it has been decided to set up an Educational Office within the ESO EPR Department. It will from now on work closely with astronomy-oriented teachers, in particular at the high-school level , providing support, inspiration and new materials. Beginning next year, it will arrange meetings for teachers to inform about new results and trends in modern astrophysics, while facilitating the efficient exchange of the teachers' educational experience at different levels within the different curricula at Europe's schools. These initiatives will be