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Sample records for hans-dieter pilz siegfried

  1. Editorial: Siegfried Hoyer's concept of Alzheimer pathophysiology.

    PubMed

    Frölich, Lutz; Müller, Walter E; Riederer, Peter

    2015-04-01

    The concept of central insulin resistance and dysfunctional insulin signaling in Alzheimer's Disease (AD) has been developed by Siegfried Hoyer in 1985-2000. It is widely recognized that the mechanisms underlying neuronal energy deficiency and in particular to elucidate insulin/insulin receptor cascade deficiencies are some of the most relevant proximate characteristics of sporadic AD. The imbalance between cerebral oxygen utilization and cerebral glucose utilization may cause rise in reactive oxygen species production and this might be causal for synapse degeneration. This concept has been substantiated by work on postmortem Alzheimer brains and has been translated back into the streptozotozin animal model, which has stimulated much further research by other researchers. Finally, the insulin hypothesis of Alzheimer's disease has currently advanced into a potential therapeutic avenue.

  2. 78 FR 32458 - Manufacturer of Controlled Substances; Notice of Application; Siegfried USA, LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Siegfried USA, LLC... April 18, 2013, Siegfried USA, LLC., 33 Industrial Park Road, Pennsville, New Jersey 08070,...

  3. 77 FR 70825 - Manufacturer of Controlled Substances; Notice of Application; Siegfried (USA), LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-27

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Siegfried (USA), LLC... November 5, 2012, Siegfried (USA) LLC, 33 Industrial Park Road, Pennsville, New Jersey 08070,...

  4. 78 FR 5500 - Manufacturer of Controlled Substances, Notice of Application; Siegfried (USA)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances, Notice of Application; Siegfried (USA... 19, 2012, Siegfried (USA), 33 Industrial Park Road, Pennsville, New Jersey 08070, made application...

  5. 78 FR 46613 - Manufacturer of Controlled Substances; Notice of Application; Siegfried (USA), LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-01

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Siegfried (USA), LLC... 10, 2013, Siegfried (USA), LLC., 33 Industrial Park Road, Pennsville, New Jersey 08070,...

  6. The Structural Basis of Cyclic Diguanylate Signal Transduction by PilZ Domains

    SciTech Connect

    Benach,J.; Swaminathan, S.; Tamayo, R.; Handelman, S.; Folta-Stogniew, E.; Ramos, J.; Forouhar, F.; Neely, H.; Seetharaman, J.; et al

    2007-01-01

    The second messenger cyclic diguanylate (c-di-GMP) controls the transition between motile and sessile growth in eubacteria, but little is known about the proteins that sense its concentration. Bioinformatics analyses suggested that PilZ domains bind c-di-GMP and allosterically modulate effector pathways. We have determined a 1.9 Angstroms crystal structure of c-di-GMP bound to VCA0042/PlzD, a PilZ domain-containing protein from Vibrio cholerae. Either this protein or another specific PilZ domain-containing protein is required for V. cholerae to efficiently infect mice. VCA0042/PlzD comprises a C-terminal PilZ domain plus an N-terminal domain with a similar beta-barrel fold. C-di-GMP contacts seven of the nine strongly conserved residues in the PilZ domain, including three in a seven-residue long N-terminal loop that undergoes a conformational switch as it wraps around c-di-GMP. This switch brings the PilZ domain into close apposition with the N-terminal domain, forming a new allosteric interaction surface that spans these domains and the c-di-GMP at their interface. The very small size of the N-terminal conformational switch is likely to explain the facile evolutionary diversification of the PilZ domain.

  7. C. G. Jung's Dream of Siegfried: A Psychobiographical Study.

    PubMed

    Kovary, Zoltan

    2015-08-01

    During the past decades, besides Sigmund Freud, C.G. Jung has been a subject of modern psychobiographical investigations. The revealed documents of Jung and Sabina Speielrein's relationship remarkably changed the narratives of this outstanding story, and it also bears important theoretical consequences. This article focuses on Jung's Siegfried-dream found in his autobiography, since it is closely related to the Freud-Jung-Spielrein triangle, and can be associated with some significant aspects of intellectual history. The text of the dream is treated as an Allportian "first-person document" that can be a starting point of a psychobiographical investigation. PMID:26290943

  8. The riddle of Siegfried: exploring methods and psychological perspectives in analytical psychology.

    PubMed

    Barreto, Marco Heleno

    2016-02-01

    Jung's dream of the killing of Siegfried poses a riddle: why did the unconscious choose precisely Siegfried as the hero to be murdered? Jung himself declares that he does not know. This paper attempts to decipher this riddle using three distinct methodological approaches accepted by Jung, two of them in fact grounded in his theories of dream interpretation. Besides presenting some possible answers to the riddle of Siegfried, this interpretative reflection brings to light the discrepancy of the psychological perspectives created by the heterogeneity of methods within analytical psychology.

  9. The riddle of Siegfried: exploring methods and psychological perspectives in analytical psychology.

    PubMed

    Barreto, Marco Heleno

    2016-02-01

    Jung's dream of the killing of Siegfried poses a riddle: why did the unconscious choose precisely Siegfried as the hero to be murdered? Jung himself declares that he does not know. This paper attempts to decipher this riddle using three distinct methodological approaches accepted by Jung, two of them in fact grounded in his theories of dream interpretation. Besides presenting some possible answers to the riddle of Siegfried, this interpretative reflection brings to light the discrepancy of the psychological perspectives created by the heterogeneity of methods within analytical psychology. PMID:26785416

  10. Functional divergence of FimX in PilZ binding and type IV pilus regulation.

    PubMed

    Qi, Yaning; Xu, Linghui; Dong, Xueming; Yau, Yin Hoe; Ho, Chun Loong; Koh, Siew Lee; Shochat, Susana Geifman; Chou, Shan-Ho; Tang, Kai; Liang, Zhao-Xun

    2012-11-01

    Type IV pili (T4P) are polar surface structures that play important roles in bacterial motility, biofilm formation, and pathogenicity. The protein FimX and its orthologs are known to mediate T4P formation in the human pathogen Pseudomonas aeruginosa and some other bacterial species. It was reported recently that FimX(XAC2398) from Xanthomonas axonopodis pv. citri interacts with PilZ(XAC1133) directly through the nonenzymatic EAL domain of FimX(XAC2398). Here we present experimental data to reveal that the strong interaction between FimX(XAC2398) and PilZ(XAC1133) is not conserved in P. aeruginosa and likely other Pseudomonas species. In vitro and in vivo binding experiments showed that the interaction between FimX and PilZ in P. aeruginosa is below the measurable limit. Surface plasmon resonance assays further confirmed that the interaction between the P. aeruginosa proteins is at least more than 3 orders of magnitude weaker than that between the X. axonopodis pv. citri pair. The N-terminal lobe region of FimX(XAC2398) was identified as the binding surface for PilZ(XAC1133) by amide hydrogen-deuterium exchange and site-directed mutagenesis studies. Lack of several key residues in the N-terminal lobe region of the EAL domain of FimX is likely to account for the greatly reduced binding affinity between FimX and PilZ in P. aeruginosa. All together, the results suggest that the interaction between PilZ and FimX in Xanthomonas species is not conserved in P. aeruginosa due to the evolutionary divergence among the FimX orthologs. The precise roles of FimX and PilZ in bacterial motility and T4P biogenesis are likely to vary among bacterial species. PMID:22942245

  11. The PilZ domain is a receptor for the second messenger c-di-GMP: the PilZ domain protein YcgR controls motility in enterobacteria.

    PubMed

    Ryjenkov, Dmitri A; Simm, Roger; Römling, Ute; Gomelsky, Mark

    2006-10-13

    The ubiquitous bacterial second messenger c-di-GMP controls exopolysaccharide synthesis, flagella- and pili-based motility, gene expression, and interactions of bacteria with eukaryotic hosts. With the exception of bacterial cellulose synthases, the identities of c-di-GMP receptors and end targets have remained unknown. Recently, Amikam and Galperin (Amikam, D., and Galperin, M. (2006) Bioinformatics 22, 3-6) hypothesized that the PilZ domains present in the BcsA subunits of bacterial cellulose synthases function in c-di-GMP binding. This hypothesis has been tested here using the Escherichia coli PilZ domain protein YcgR, its individual PilZ domain and the PilZ domain from Gluconacetobacter xylinus BcsA. YcgR was purified and found to bind c-di-GMP tightly and specifically, Kd 0.84 microm. Individual PilZ domains from YcgR and BcsA also bound c-di-GMP, albeit with lesser affinity, indicating that PilZ is sufficient for binding. The site-directed mutagenesis performed on YcgR implicated the most conserved residues in the PilZ domain directly in c-di-GMP binding. It is suggested that c-di-GMP binding to PilZ brings about conformational changes in the protein that stabilize the bound ligand and initiate the downstream signal transduction cascade. While the identity of the downstream partner(s) of YcgR remains unknown, it is shown that YcgR regulates flagellum-based motility in a c-di-GMP-dependent manner. The inactivation of ycgR improves swimming and swarming motility of the poorly motile yhjH mutants of Salmonella enterica serovar Typhimurium UMR1. Therefore, biochemical and genetic evidence presented here establishes PilZ as a long sought after c-di-GMP-binding domain and YcgR as a c-di-GMP receptor affecting motility in enterobacteria. PMID:16920715

  12. 78 FR 64020 - Manufacturer of Controlled Substances, Notice of Registration, Siegfried USA, LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-25

    ... The Notice dated July 23, 2013, and published in the Federal Register on August 1, 2013, 78 FR 46613... registration as a Bulk Manufacturer of drug codes Opium, raw (9600), and Poppy Straw Concentrate (9670). On August 6, 2013, Siegfried (USA), LLC., subsequently withdrew this request for drug code Opium, raw...

  13. Invite the Magic of Siegfried and Roy into Your Torts Discussion

    ERIC Educational Resources Information Center

    Ludlum, M. P.

    2008-01-01

    Magic is exciting, but dangerous. David Copperfield explained "of all the performers on stage, no one courts disaster, no one flirts with danger as much as the magician." On October 3, 2003, Siegfried and Roy experienced that danger firsthand when Roy was attacked by one of his tigers while performing before a live audience. This tragic event can…

  14. 78 FR 64020 - Manufacturer of Controlled Substances; Notice of Registration; Siegfried USA, LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-25

    ... public interest at this time. DEA has investigated Siegfried USA, LLC., to ensure that the company's... By Notice dated May 22, 2013, and published in the Federal Register on May 30, 2013, 78 FR 32458... (9630), a basic class of controlled substance listed in schedule II. The company plans to...

  15. 77 FR 30027 - Manufacturer of Controlled Substances; Notice of Registration; Siegfried (USA)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-21

    ... interest at this time. DEA has investigated Siegfried (USA), to ensure that the company's registration is consistent with the public interest. The investigation has included inspection and testing of the company's... Notice dated January 6, 2012, and published in the Federal Register on January 17, 2012, 77 FR...

  16. Siegfried the Dragonslayer Meets the Web: Using Digital Media for Developing Historical Awareness and Advanced Language and Critical Thinking Skills

    ERIC Educational Resources Information Center

    Rasmussen, Ann Marie

    2011-01-01

    This article describes an undergraduate, German-language course that aimed to improve students' language skills, critical thinking, and declarative knowledge of German history and culture by studying multiple manifestations of the legend of Siegfried the Dragonslayer. The course used web-based e-learning tools to address two major learning…

  17. Molekulare Methoden zum Nachweis, zur Quantifizierung und zum Monitoring der Mykotoxinbildung lebensmittelrelevanter Pilze

    NASA Astrophysics Data System (ADS)

    Geisen, Rolf

    Schimmelpilze kommen ubiquitär vor und spielen besonders bei pflanzlichen Lebensmitteln und Rohprodukten eine besondere Rolle als Verderbsorganismen. Es wird geschätzt, dass 20-25 % der jährlichen Produktion an pflanzlichen Produkten durch Schimmelpilze verdorben werden (Smith et al., 1994). Viele der lebensmittelrelevanten Schimmelpilze sind zudem in der Lage, Mykotoxine, toxische Sekundärmetabolite, zu bilden, was das Ausmaß des Problems deutlich macht. Die wichtigsten mykotoxinbildenden Spezies gehören zu den Fusarien (Trichothecene, Fumonisine, Zearalenon), Aspergillen (Aflatoxin, Ochratoxin, Cyclopiazonsäure) und Penicillien (Patulin, Ochratoxin). Für viele Mykotoxine, wie die Aflatoxine, Ochratoxin, Fumonisine und Trichothecene sind Grenzwerte erlassen worden, die die Verkehrsfähigkeit betroffener Produkte regeln. Die Einhaltung der Grenzwerte kann sehr genau durch offizielle chemisch-analytische Methoden, wie HPLC, GC-MS etc. kontrolliert werden. Diese analytischen Methoden sind aber für die Anwendung eines HACCP-Ansatzes zur Kontrolle der Mykotoxinbildung nur bedingt geeignet, da sie Endpunktkontrollen darstellen und nur das über eine längere Zeit gebildete Mykotoxin bestimmen. Sie sagen daher nichts über die biologischen Bedingungen zur Zeit der Bildung durch den Pilz aus.

  18. The Xanthomonas oryzae pv. oryzae PilZ Domain Proteins Function Differentially in Cyclic di-GMP Binding and Regulation of Virulence and Motility.

    PubMed

    Yang, Fenghuan; Tian, Fang; Chen, Huamin; Hutchins, William; Yang, Ching-Hong; He, Chenyang

    2015-07-01

    The PilZ domain proteins have been demonstrated to be one of the major types of receptors mediating cyclic di-GMP (c-di-GMP) signaling pathways in several pathogenic bacteria. However, little is known about the function of PilZ domain proteins in c-di-GMP regulation of virulence in the bacterial blight pathogen of rice Xanthomonas oryzae pv. oryzae. Here, the roles of PilZ domain proteins PXO_00049 and PXO_02374 in c-di-GMP binding, regulation of virulence and motility, and subcellular localization were characterized in comparison with PXO_02715, identified previously as an interactor with the c-di-GMP receptor Filp to regulate virulence. The c-di-GMP binding motifs in the PilZ domains were conserved in PXO_00049 and PXO_02374 but were less well conserved in PXO_02715. PXO_00049 and PXO_02374 but not PXO_02715 proteins bound to c-di-GMP with high affinity in vitro, and the R(141) and R(10) residues in the PilZ domains of PXO_00049 and PXO_02374, respectively, were crucial for c-di-GMP binding. Gene deletion of PXO_00049 and PXO_02374 resulted in significant increases in virulence and hrp gene transcription, indicating their negative regulation of virulence via type III secretion system expression. All mutants showed significant changes in sliding motility but not exopolysaccharide production and biofilm formation. In trans expression of the full-length open reading frame (ORF) of each gene in the relevant mutants led to restoration of the phenotype to wild-type levels. Moreover, PXO_00049 and PXO_02374 displayed mainly multisite subcellular localizations, whereas PXO_02715 showed nonpolar distributions in the X. oryzae pv. oryzae cells. Therefore, this study demonstrated the different functions of the PilZ domain proteins in mediation of c-di-GMP regulation of virulence and motility in X. oryzae pv. oryzae.

  19. The Arabidopsis PILZ group genes encode tubulin-folding cofactor orthologs required for cell division but not cell growth.

    PubMed

    Steinborn, Katharina; Maulbetsch, Christoph; Priester, Bianca; Trautmann, Susanne; Pacher, Tobias; Geiges, Bernd; Küttner, Frank; Lepiniec, Loic; Stierhof, York-Dieter; Schwarz, Heinz; Jürgens, Gerd; Mayer, Ulrike

    2002-04-15

    Plant microtubules are organized into specific cell cycle-dependent arrays that have been implicated in diverse cellular processes, including cell division and organized cell expansion. Mutations in four Arabidopsis genes collectively called the PILZ group result in lethal embryos that consist of one or a few grossly enlarged cells. The mutant embryos lack microtubules but not actin filaments. Whereas the cytokinesis-specific syntaxin KNOLLE is not localized properly, trafficking of the putative auxin efflux carrier PIN1 to the plasma membrane is normal. The four PILZ group genes were isolated by map-based cloning and are shown to encode orthologs of mammalian tubulin-folding cofactors (TFCs) C, D, and E, and associated small G-protein Arl2 that mediate the formation of alpha/beta-tubulin heterodimers in vitro. The TFC C ortholog, PORCINO, was detected in cytosolic protein complexes and did not colocalize with microtubules. Another gene with a related, although weaker, embryo-lethal phenotype, KIESEL, was shown to encode a TFC A ortholog. Our genetic ablation of microtubules shows their requirement in cell division and vesicle trafficking during cytokinesis, whereas cell growth is mediated by microtubule-independent vesicle trafficking to the plasma membrane during interphase.

  20. The Arabidopsis PILZ group genes encode tubulin-folding cofactor orthologs required for cell division but not cell growth

    PubMed Central

    Steinborn, Katharina; Maulbetsch, Christoph; Priester, Bianca; Trautmann, Susanne; Pacher, Tobias; Geiges, Bernd; Küttner, Frank; Lepiniec, Loic; Stierhof, York-Dieter; Schwarz, Heinz; Jürgens, Gerd; Mayer, Ulrike

    2002-01-01

    Plant microtubules are organized into specific cell cycle-dependent arrays that have been implicated in diverse cellular processes, including cell division and organized cell expansion. Mutations in four Arabidopsis genes collectively called the PILZ group result in lethal embryos that consist of one or a few grossly enlarged cells. The mutant embryos lack microtubules but not actin filaments. Whereas the cytokinesis-specific syntaxin KNOLLE is not localized properly, trafficking of the putative auxin efflux carrier PIN1 to the plasma membrane is normal. The four PILZ group genes were isolated by map-based cloning and are shown to encode orthologs of mammalian tubulin-folding cofactors (TFCs) C, D, and E, and associated small G-protein Arl2 that mediate the formation of α/β-tubulin heterodimers in vitro. The TFC C ortholog, PORCINO, was detected in cytosolic protein complexes and did not colocalize with microtubules. Another gene with a related, although weaker, embryo-lethal phenotype, KIESEL, was shown to encode a TFC A ortholog. Our genetic ablation of microtubules shows their requirement in cell division and vesicle trafficking during cytokinesis, whereas cell growth is mediated by microtubule-independent vesicle trafficking to the plasma membrane during interphase. PMID:11959844

  1. Aftermath: the implicit processes of integrating traumatic experience in the poetry of Siegfried Sassoon.

    PubMed

    Saks, Paul S

    2007-01-01

    The creation of narratives often allows individuals to bear witness to traumatic events. This study looked at connections between the processing of traumatic, affect laden experience and levels of symbolization and symmetry within the context of poetic expression. The sample for this pilot study is composed of selected works by Siegfried Sassoon (1886-1967), a British soldier-poet of the Great War. The language of the poems reflected the deepening trauma of the war experience by showing a progression toward paranoid (concrete)/symmetrical experiences. As the years passed and the poet was able to process the memory of the events, the poetry reflected a more balanced shift toward integration of depressive (symbolic)/asymmetrical experience. In terms of affect, the most significant changes were seen after Sassoon left the front and witnessed the flagrant dichotomy between civilian and military life. The results suggest a way in which traumatic events are processed. The routine horror and brutality of the Western Front initially lay outside of the realm of language and symbols and were thus highly concrete and unprocessed experiences. Time, place, and identity collapsed in on itself, leading to the increase of symmetrical experience, while the extreme "us versus them experience" of the trenches can be seen in the balance of asymmetrical experience. The study has implications for the treatment of war trauma, suggesting that writing provides a vehicle through which events can be processed and an internal sense of balance can be approached. PMID:18335612

  2. NMR structure and binding studies confirm that PA4608 from Pseudomonas aeruginosa is a PilZ domain and a c-di-GMP binding protein

    SciTech Connect

    Ramelot, Theresa A; Yee, Adelinda; Cort, John R; Semesi, Anthony; Arrowsmith, Cheryl H; Kennedy, Michael A

    2007-02-01

    PA4608 is a 125 residue protein with a proposed identification as a PilZ domain and c-di-GMP adaptor protein that plays a role in bacterial second-messenger regulated processes. The NMR structure of PA4608 has been determined and c-di-GMP binding has been confirmed by NMR titration studies. The monomeric structure of PA4608 contains a six-stranded anti-parallel β barrel flanked by three helices. Conserved surface residues among PA4608 homologs suggest the the c-di-GMP binding site is at one end of the barrel and includes residues in the helices as well as in the unstructured N-terminus. Chemical shift changes upon binding to c-di-GMP confirm that PA4608 binds to c-di-GMP. This evidence supports the hypothesis that proteins containing PilZ domains are the long-sought c-di-GMP adaptor proteins.

  3. Structures of the activator of K. pneumonia biofilm formation, MrkH, indicates PilZ domains involved in c-di-GMP and DNA binding.

    PubMed

    Schumacher, Maria A; Zeng, Wenjie

    2016-09-01

    The pathogenesis of Klebsiella pneumonia is linked to the bacteria's ability to form biofilms. Mannose-resistant Klebsiella-like (Mrk) hemagglutinins are critical for K pneumonia biofilm development, and the expression of the genes encoding these proteins is activated by a 3',5'-cyclic diguanylic acid (c-di-GMP)-regulated transcription factor, MrkH. To gain insight into MrkH function, we performed structural and biochemical analyses. Data revealed MrkH to be a monomer with a two-domain architecture consisting of a PilZ C-domain connected to an N domain that unexpectedly also harbors a PilZ-like fold. Comparison of apo- and c-di-GMP-bound MrkH structures reveals a large 138° interdomain rotation that is induced by binding an intercalated c-di-GMP dimer. c-di-GMP interacts with PilZ C-domain motifs 1 and 2 (RxxxR and D/NxSxxG) and a newly described c-di-GMP-binding motif in the MrkH N domain. Strikingly, these c-di-GMP-binding motifs also stabilize an open state conformation in apo MrkH via contacts from the PilZ motif 1 to residues in the C-domain motif 2 and the c-di-GMP-binding N-domain motif. Use of the same regions in apo structure stabilization and c-di-GMP interaction allows distinction between the states. Indeed, domain reorientation by c-di-GMP complexation with MrkH, which leads to a highly compacted structure, suggests a mechanism by which the protein is activated to bind DNA. To our knowledge, MrkH represents the first instance of specific DNA binding mediated by PilZ domains. The MrkH structures also pave the way for the rational design of inhibitors that target K pneumonia biofilm formation. PMID:27551088

  4. Structures of the activator of K. pneumonia biofilm formation, MrkH, indicates PilZ domains involved in c-di-GMP and DNA binding

    PubMed Central

    Schumacher, Maria A.; Zeng, Wenjie

    2016-01-01

    The pathogenesis of Klebsiella pneumonia is linked to the bacteria’s ability to form biofilms. Mannose-resistant Klebsiella-like (Mrk) hemagglutinins are critical for K. pneumonia biofilm development, and the expression of the genes encoding these proteins is activated by a 3′,5′-cyclic diguanylic acid (c-di-GMP)–regulated transcription factor, MrkH. To gain insight into MrkH function, we performed structural and biochemical analyses. Data revealed MrkH to be a monomer with a two-domain architecture consisting of a PilZ C-domain connected to an N domain that unexpectedly also harbors a PilZ-like fold. Comparison of apo- and c-di-GMP–bound MrkH structures reveals a large 138° interdomain rotation that is induced by binding an intercalated c-di-GMP dimer. c-di-GMP interacts with PilZ C-domain motifs 1 and 2 (RxxxR and D/NxSxxG) and a newly described c-di-GMP–binding motif in the MrkH N domain. Strikingly, these c-di-GMP–binding motifs also stabilize an open state conformation in apo MrkH via contacts from the PilZ motif 1 to residues in the C-domain motif 2 and the c-di-GMP–binding N-domain motif. Use of the same regions in apo structure stabilization and c-di-GMP interaction allows distinction between the states. Indeed, domain reorientation by c-di-GMP complexation with MrkH, which leads to a highly compacted structure, suggests a mechanism by which the protein is activated to bind DNA. To our knowledge, MrkH represents the first instance of specific DNA binding mediated by PilZ domains. The MrkH structures also pave the way for the rational design of inhibitors that target K. pneumonia biofilm formation. PMID:27551088

  5. Solution structure of the PilZ domain protein PA4608 complex with cyclic di-GMP identifies charge clustering as molecular readout.

    PubMed

    Habazettl, Judith; Allan, Martin G; Jenal, Urs; Grzesiek, Stephan

    2011-04-22

    Cyclic diguanosine monophosphate (c-di-GMP) is a ubiquitous bacterial second messenger that controls the switch from a single-cell lifestyle to surface-attached, multicellular communities called biofilms. PilZ domain proteins are a family of bacterial c-di-GMP receptors, which control various cellular processes. We have solved the solution structure of the Pseudomonas aeruginosa single-domain PilZ protein PA4608 in complex with c-di-GMP by NMR spectroscopy. Isotope labeling by (13)C and (15)N of both the ligand and the protein made it possible to define the structure of c-di-GMP in the complex at high precision by a large number of intermolecular and intraligand NOEs and by two intermolecular hydrogen bond scalar couplings. Complex formation induces significant rearrangements of the C- and N-terminal parts of PA4608. c-di-GMP binds as an intercalated, symmetric dimer to one side of the β-barrel, thereby displacing the C-terminal helix of the apo state. The N-terminal RXXXR PilZ domain motif, which is flexible in the apo state, wraps around the ligand and in turn ties the displaced C terminus in a loose manner by a number of hydrophobic contacts. The recognition of the dimeric ligand is achieved by numerous H-bonds and stacking interactions involving residues Arg(8), Arg(9), Arg(10), and Arg(13) of the PilZ motif, as well as β-barrel residues Asp(35) and Trp(77). As a result of the rearrangement of the N and C termini, a highly negative surface is created on one side of the protein complex. We propose that the movement of the termini and the resulting negative surface form the basis for downstream signaling. PMID:21310957

  6. Structures of the activator of K. pneumonia biofilm formation, MrkH, indicates PilZ domains involved in c-di-GMP and DNA binding.

    PubMed

    Schumacher, Maria A; Zeng, Wenjie

    2016-09-01

    The pathogenesis of Klebsiella pneumonia is linked to the bacteria's ability to form biofilms. Mannose-resistant Klebsiella-like (Mrk) hemagglutinins are critical for K pneumonia biofilm development, and the expression of the genes encoding these proteins is activated by a 3',5'-cyclic diguanylic acid (c-di-GMP)-regulated transcription factor, MrkH. To gain insight into MrkH function, we performed structural and biochemical analyses. Data revealed MrkH to be a monomer with a two-domain architecture consisting of a PilZ C-domain connected to an N domain that unexpectedly also harbors a PilZ-like fold. Comparison of apo- and c-di-GMP-bound MrkH structures reveals a large 138° interdomain rotation that is induced by binding an intercalated c-di-GMP dimer. c-di-GMP interacts with PilZ C-domain motifs 1 and 2 (RxxxR and D/NxSxxG) and a newly described c-di-GMP-binding motif in the MrkH N domain. Strikingly, these c-di-GMP-binding motifs also stabilize an open state conformation in apo MrkH via contacts from the PilZ motif 1 to residues in the C-domain motif 2 and the c-di-GMP-binding N-domain motif. Use of the same regions in apo structure stabilization and c-di-GMP interaction allows distinction between the states. Indeed, domain reorientation by c-di-GMP complexation with MrkH, which leads to a highly compacted structure, suggests a mechanism by which the protein is activated to bind DNA. To our knowledge, MrkH represents the first instance of specific DNA binding mediated by PilZ domains. The MrkH structures also pave the way for the rational design of inhibitors that target K pneumonia biofilm formation.

  7. Identification of flgZ as a flagellar gene encoding a PilZ domain protein that regulates swimming motility and biofilm formation in Pseudomonas.

    PubMed

    Martínez-Granero, Francisco; Navazo, Ana; Barahona, Emma; Redondo-Nieto, Miguel; González de Heredia, Elena; Baena, Irene; Martín-Martín, Irene; Rivilla, Rafael; Martín, Marta

    2014-01-01

    Diguanylate cyclase and phosphodiesterase enzymatic activities control c-di-GMP levels modulating planktonic versus sessile lifestyle behavior in bacteria. The PilZ domain is described as a sensor of c-di-GMP intracellular levels and the proteins containing a PilZ domain represent the best studied class of c-di-GMP receptors forming part of the c-di-GMP signaling cascade. In P. fluorescens F113 we have found two diguanylate cyclases (WspR, SadC) and one phosphodiesterase (BifA) implicated in regulation of swimming motility and biofilm formation. Here we identify a flgZ gene located in a flagellar operon encoding a protein that contains a PilZ domain. Moreover, we show that FlgZ subcellular localization depends on the c-di-GMP intracellular levels. The overexpression analysis of flgZ in P. fluorescens F113 and P. putida KT2440 backgrounds reveal a participation of FlgZ in Pseudomonas swimming motility regulation. Besides, the epistasis of flgZ over wspR and bifA clearly shows that c-di-GMP intracellular levels produced by the enzymatic activity of the diguanylate cyclase WspR and the phosphodiesterase BifA regulates biofilm formation through FlgZ.

  8. 78 FR 49546 - Importer of Controlled Substances; Notice of Application; Siegfried USA, LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-14

    ... import narcotic raw material are not appropriate. 72 FR 3417 (2007). As noted in a previous notice published in the Federal Register on September 23, 1975, 40 FR 43745, all applicants for registration to... importer of the following basic classes of controlled substances: Drug Schedule Opium, raw (9600) II...

  9. 78 FR 64015 - Importer of Controlled Substances, Notice of Registration, Siegfried (USA), LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-25

    ... Notice dated August 2, 2013, and published in the Federal Register on ] August 14, 2013, 78 FR 49546... appropriate. 72 FR 3417 (2007). DEA has considered the factors in 21 U.S.C. 823(a) and 952(a), and determined... classes of controlled substances: Drug Schedule Opium, raw (9600) II Poppy Straw Concentrate (9670) II...

  10. 78 FR 30333 - Manufacturer of Controlled Substances; Notice of Registration; Siegfried (Usa), Llc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-22

    .... By Notice dated November 19, 2012, and published in the Federal Register on November 27, 2012, 77 FR...-dosage forms) II (9273). Morphine (9300) II Oripavine (9330) II Oxymorphone (9652) II The company...

  11. Bacterial Morphologies Supporting Cometary Panspermia: a Reappraisal

    NASA Astrophysics Data System (ADS)

    Wickramasinghe, Chandra

    It is nearly 30 years since the first decisive evidence of microbial morphologies in carbonaceous chondrites was discovered and reported by Hans Dieter Pflug. In addition to morphology other data, notably laser mass spectroscopy, served to confirm the identification of such structures as putative bacterial fossils. Recent examinations of cometary dust collected in the stratosphere and further studies of carbonaceous meteorites reaffirm the presence of putative microbial fossils. Since carbonaceous chondrites (particularly Type 1 chondrites) are thought to be extinct comets the data reviewed in this article provide strong support for theories of cometary panspermia.

  12. Bacterial morphologies supporting cometary panspermia: a reappraisal

    NASA Astrophysics Data System (ADS)

    Wickramasinghe, Chandra

    2011-01-01

    It is nearly 30 years since the first decisive evidence of microbial morphologies in carbonaceous chondrites was discovered and reported by Hans Dieter Pflug. In addition to morphology, other data, notably laser mass spectroscopy, served to confirm the identification of such structures as putative bacterial fossils. Recent examinations of cometary dust collected in the stratosphere and further studies of carbonaceous meteorites reaffirm the presence of putative microbial fossils. Since carbonaceous chondrites (particularly Type 1 chondrites) are thought to be extinct comets the data reviewed in this article provide strong support for theories of cometary panspermia.

  13. Bacterial morphologies in carbonaceous meteorites and comet dust

    NASA Astrophysics Data System (ADS)

    Wickramasinghe, Chandra; Wallis, Max K.; Gibson, Carl H.; Wallis, Jamie; Al-Mufti, Shirwan; Miyake, Nori

    2010-09-01

    Three decades ago the first convincing evidence of microbial fossils in carbonaceous chondrites was discovered and reported by Hans Dieter Pflug and his collaborators. In addition to morphology, other data, notably laser mass spectroscopy, confirmed the identification of such structures as putative bacterial fossils. Balloon-borne cryosampling of the stratosphere enables recovery of fragile cometary dust aggregates with their structure and carbonaceous matter largely intact. SEM studies of texture and morphology of particles in the Cardiff collection, together with EDX identifications, show two main types of putative bio-fossils - firstly organic-walled hollow spheres around 10μm across, secondly siliceous diatom skeletons similar to those found in carbonaceous chondrites and terrestrial sedimentary rocks and termed 'acritarchs'. Since carbonaceous chondrites (particularly Type 1 chondrites) are thought to be extinct comets the data reviewed in this article provide strong support for theories of cometary panspermia.

  14. 76 FR 21916 - Manufacturer of Controlled Substances; Notice of Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-19

    ... December 20, 2010, and published in the Federal Register on December 29, 2010, 75 FR 82073, Siegfried (USA... ] Methadone (9250) II Methadone intermediate (9254) II Dextropropoxyphene, bulk (non-dosage forms) II...

  15. A Cyclic di-GMP-binding Adaptor Protein Interacts with Histidine Kinase to Regulate Two-component Signaling.

    PubMed

    Xu, Linghui; Venkataramani, Prabhadevi; Ding, Yichen; Liu, Yang; Deng, Yinyue; Yong, Grace Lisi; Xin, Lingyi; Ye, Ruijuan; Zhang, Lianhui; Yang, Liang; Liang, Zhao-Xun

    2016-07-29

    The bacterial messenger cyclic di-GMP (c-di-GMP) binds to a diverse range of effectors to exert its biological effect. Despite the fact that free-standing PilZ proteins are by far the most prevalent c-di-GMP effectors known to date, their physiological function and mechanism of action remain largely unknown. Here we report that the free-standing PilZ protein PA2799 from the opportunistic pathogen Pseudomonas aeruginosa interacts directly with the hybrid histidine kinase SagS. We show that PA2799 (named as HapZ: histidine kinase associated PilZ) binds directly to the phosphoreceiver (REC) domain of SagS, and that the SagS-HapZ interaction is further enhanced at elevated c-di-GMP concentration. We demonstrate that binding of HapZ to SagS inhibits the phosphotransfer between SagS and the downstream protein HptB in a c-di-GMP-dependent manner. In accordance with the role of SagS as a motile-sessile switch and biofilm growth factor, we show that HapZ impacts surface attachment and biofilm formation most likely by regulating the expression of a large number of genes. The observations suggest a previously unknown mechanism whereby c-di-GMP mediates two-component signaling through a PilZ adaptor protein.

  16. A Cyclic di-GMP-binding Adaptor Protein Interacts with Histidine Kinase to Regulate Two-component Signaling.

    PubMed

    Xu, Linghui; Venkataramani, Prabhadevi; Ding, Yichen; Liu, Yang; Deng, Yinyue; Yong, Grace Lisi; Xin, Lingyi; Ye, Ruijuan; Zhang, Lianhui; Yang, Liang; Liang, Zhao-Xun

    2016-07-29

    The bacterial messenger cyclic di-GMP (c-di-GMP) binds to a diverse range of effectors to exert its biological effect. Despite the fact that free-standing PilZ proteins are by far the most prevalent c-di-GMP effectors known to date, their physiological function and mechanism of action remain largely unknown. Here we report that the free-standing PilZ protein PA2799 from the opportunistic pathogen Pseudomonas aeruginosa interacts directly with the hybrid histidine kinase SagS. We show that PA2799 (named as HapZ: histidine kinase associated PilZ) binds directly to the phosphoreceiver (REC) domain of SagS, and that the SagS-HapZ interaction is further enhanced at elevated c-di-GMP concentration. We demonstrate that binding of HapZ to SagS inhibits the phosphotransfer between SagS and the downstream protein HptB in a c-di-GMP-dependent manner. In accordance with the role of SagS as a motile-sessile switch and biofilm growth factor, we show that HapZ impacts surface attachment and biofilm formation most likely by regulating the expression of a large number of genes. The observations suggest a previously unknown mechanism whereby c-di-GMP mediates two-component signaling through a PilZ adaptor protein. PMID:27231351

  17. Our Youngest Learners: The Bereiter-Engelmann Experiment

    ERIC Educational Resources Information Center

    Grade Teacher, 1969

    1969-01-01

    Method of instruction developed by Carl Bereiter and Siegfried Engelmann which is based upon "repetitive drills in language development. Part of a longer special report available from: Grade Teacher Reprints, 23 Leroy Ave., Darien, Conn. 06820. (No. 91291, 75J) (Author/AP)

  18. Stockpile Stewardship's 20th Anniversary

    SciTech Connect

    Hecker, Siegfried; Gottemoeller, Rose; Reis, Victor H.; McMillan, Charles; Rohlfing, Joan; Hurricane, Omar; Hagengruber, Roger; Taylor, John

    2015-10-22

    A short oral history of the NNSA's Stockpile Stewardship Program, produced in association with the 20th anniversary of the program. It features Siegfried Hecker, Rose Gottemoeller, Victor Reis, Charles McMillan, Joan Rohlfing, Omar Hurricane, Roger Hagengruber, and John Taylor.

  19. 78 FR 68476 - Notice of Lodging of Proposed Consent Decree Under the Comprehensive Environmental Response...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-14

    ... Settling Defendants, consisting of Air Products and Chemicals, Inc., Akzo Nobel Coatings, Inc., Alcatel..., Rohm and Haas Company, Seagrave Coatings Corp. (NJ), SI Group, Inc., Siegfried (USA), Inc., Simon....usdoj.gov/enrd/Consent_Decrees.html . We will provide a paper copy of the consent decree upon...

  20. European Influences on the Theory and Philosophy of Viktor Lowenfeld.

    ERIC Educational Resources Information Center

    Michael, John A.; Morris, Jerry W.

    1985-01-01

    Discusses how the work of art theorists, art educators, psychologists, and anthropologists who were predecessors or contemporaries of Viktor Lowenfeld influenced Lowenfeld's philosophy and theory of art education. Included are Friedrich Froebel, James Sully, Franz Cizek, Siegfried Levinstein, Max Verworn, Walter Krotzsch, George Luquet, and Karl…

  1. 75 FR 36683 - Manufacturer of Controlled Substances Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-28

    ..., Siegfried (USA), 33 Industrial Park Road, Pennsville, New Jersey 08070, made application by letter to the... Acid (2010), a basic class of controlled substance listed in schedule I. The company plans to manufacture the listed controlled substance in bulk for sale to its customers. Any other such applicant,...

  2. 75 FR 62570 - Manufacturer of Controlled Substances; Notice of Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-12

    ... 17, 2010, and published in the Federal Register on June 28, 2010 (75 FR 36683), Siegfried (USA), 33 Industrial Park Road, Pennsville, New Jersey 08070, made application by letter to the Drug Enforcement... of controlled substance listed in schedule I. The company plans to manufacture the listed...

  3. 75 FR 75497 - Manufacturer of Controlled Substances; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-03

    ..., Siegfried (USA), Inc., 33 Industrial Park Road, Pennsville, New Jersey 08070, made application by letter to... (9301), a basic class of controlled substance listed in schedule I. The company plans to manufacture small quantities of the listed controlled substance in bulk for distribution to its customers for use...

  4. Why Has CAI Not Been More Successful in Economic Education: A Note.

    ERIC Educational Resources Information Center

    Schenk, Robert; Silvia, John E.

    1984-01-01

    The negative judgment about computers reached by Siegfried and Fels in their article, "Teaching College Economics: A Survey" (Journal of Economic Literature, September 1979) is questioned. There are research questions in need of answers before economists reject the generally positive picture across disciplines of the efficacy of computer related…

  5. Trends in Undergraduate Economics Degrees, 1991-2014

    ERIC Educational Resources Information Center

    Siegfried, John J.

    2016-01-01

    The number of undergraduate economics degrees awarded by colleges and universities in the United States rose by 18 percent from 2007 to 2010. The upward trend ended abruptly in 2010 and was followed by three years of virtual stagnation (Siegfried 2014). In 2013-14, undergraduate economics degrees began to accelerate again, rising about 5 percent…

  6. Engaging Undergraduates in Economics

    ERIC Educational Resources Information Center

    Gajwani, Kiran; Miron, Jeffrey

    2015-01-01

    Siegfried and Stock (2007) explore the undergraduate training of PhD economists. Their findings show that among U.S. undergraduate economics programs, the Harvard University Economics Department produces many eventual economics PhD recipients. In this article, the authors discuss Harvard's undergraduate economics program and highlight some key…

  7. 75 FR 44287 - Manufacturer of Controlled Substances; Notice of Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-28

    ... 16, 2010, and published in the Federal Register on March 24, 2010, (75 FR 14189), Siegfried (USA), 33... Codeine (9050) II Oxycodone (9143) II Hydromorphone (9150) II Hydrocodone (9193) II Methadone (9250) II Methadone intermediate (9254) II Dextropropoxyphene, bulk (non-dosage forms) II (9273). Morphine (9300)...

  8. 76 FR 21407 - Manufacturer of Controlled Substances Notice of Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-15

    ... ensure that the company's registration is consistent with the public interest. The investigation has... November 19, 2010, and published in the Federal Register on December 3, 2010, 75 FR 75497, Siegfried (USA... class of controlled substance in schedule I. The company plans to manufacture small quantities of...

  9. Comet C/2011 J2 (LINEAR)

    NASA Astrophysics Data System (ADS)

    Carrillo, J.; Kadota, K.; Pilz, U.; Paradowski, M. L.; The, A.

    2014-09-01

    J. Carrillo obtained images on Sept. 15.9 UT with a 0.36-m f/5 reflector at Fuensanta de Martos, Spain, that show component B to be 4 mag fainter than component A. Total-magnitude and coma-diameter estimates for component A: Feb. 22.45 UT, 14.0, -- (K. Kadota, Ageo, Japan, 0.25-m reflector + CCD); 28.78, 13.2, 0'.3 (U. Pilz, Leipzig, Germany, 32-cm reflector; visual); May 2.77, 14.1, -- (Kadota); 30.72, 14.4, -- (Kadota); July 28.65, 14.1, -- (Kadota); Aug. 1.03, 13.2, 1'.2 (Pilz); 3.01, 13.5, 0'.93 (M. L. Paradowski, Dabrowa, Poland, 0.30-m reflector; visual); 18.63, 14.0, -- (Kadota). The total brightness has remained fairly close to the prediction in the ICQ's 2014 Comet Handbook, with no obvious large outburst associated with an outburst seen in these data reported to the ICQ and the Central Bureau.

  10. Kafka's uncle: scenes from a world of trust infected by suspicion.

    PubMed

    Bamforth, I

    2000-12-01

    What happens when we heed a call? Few writers have been as suspicious of their vocation as Franz Kafka (1883-1924). His story, A Country Doctor, (1919) ostensibly about a night visit to a patient that goes badly wrong, suggests a modern writer's journey to the heart of his work. There he discovers that trust, like the tradition which might sustain him, is blighted. This essay also examines Kafka's attitude to illness and the medical profession, and his close relationship with his uncle, Siegfried Löwy (1867-1942), a country doctor in Moravia.

  11. The recognition of the anatomical artists in the works of Vesalius, Albinus, and Hunter.

    PubMed

    Rudakewich, M

    1998-01-01

    Medical illustrators offer a unique and valuable contribution to scientific, medical, and health publications. However, they are not always properly acknowledged. This issue existed in the 16th century when Andreas Vesalius produced his revolutionary atlas the Fabrica and failed to recognize his artistic colleagues. This essay examines the atlases by Vesalius, Bernhard Siegfried Albinus, and William Hunter and the historical contexts in which they were produced, in order to reach some understanding of why the creators of the timeless illustrations contained in these atlases did not receive greater recognition. PMID:9842501

  12. ["Dr Breuer will care for him with utmost attention." A plan for Nietzsche's neuropathological treatment in Vienna].

    PubMed

    Müller-Buck, Renate

    2007-01-01

    This essay is about a plan for the treatment of Friedrich Nietzsche by Josef Breuer in the spring of 1878. The plan was developed by Siegfried Lipiner, a philosphy student from Galicia and an admirer of Nietzsche, who was acquainted with Breuer as well as with Freud. Lipiner was convinced that Nietzsche could be treated by the Viennese specialists and tried his best to arrange this. However all his endeavors were frustrated by the opposition of Nietzsche's advisors in Basel, as well as his docters, and ultimately of Nietzsche himself who preferred the cold-water therapy in Baden-Baden.

  13. The recognition of the anatomical artists in the works of Vesalius, Albinus, and Hunter.

    PubMed

    Rudakewich, M

    1998-01-01

    Medical illustrators offer a unique and valuable contribution to scientific, medical, and health publications. However, they are not always properly acknowledged. This issue existed in the 16th century when Andreas Vesalius produced his revolutionary atlas the Fabrica and failed to recognize his artistic colleagues. This essay examines the atlases by Vesalius, Bernhard Siegfried Albinus, and William Hunter and the historical contexts in which they were produced, in order to reach some understanding of why the creators of the timeless illustrations contained in these atlases did not receive greater recognition.

  14. Predicting the Operating Behavior of Ceramic Filters from Thermo-Mechanical Ash Properties

    SciTech Connect

    Hemmer, G.; Kasper, G.

    2002-09-19

    Stable operation, in other words the achievement of a succession of uniform filtration cycles of reasonable length is a key issue in high-temperature gas filtration with ceramic media. Its importance has rather grown in recent years, as these media gain in acceptance due to their excellent particle retention capabilities. Ash properties have been known for some time to affect the maximum operating temperature of filters. However, softening and consequently ''stickiness'' of the ash particles generally depend on composition in a complex way. Simple and accurate prediction of critical temperature ranges from ash analysis--and even more so from coal analysis--is still difficult without practical and costly trials. In general, our understanding of what exactly happens during break-down of filtration stability is still rather crude and general. Early work was based on the concept that ash particles begin to soften and sinter near the melting temperatures of low-melting, often alkaline components. This softening coincides with a fairly abrupt increase of stickiness, that can be detected with powder mechanical methods in a Jenicke shear cell as first shown by Pilz (1996) and recently confirmed by others (Kamiya et al. 2001 and 2002, Kanaoka et al. 2001). However, recording {sigma}-{tau}-diagrams is very time consuming and not the only off-line method of analyzing or predicting changes in thermo-mechanical ash behavior. Pilz found that the increase in ash stickiness near melting was accompanied by shrinkage attributed to sintering. Recent work at the University of Karlsruhe has expanded the use of such thermo-analytical methods for predicting filtration behavior (Hemmer 2001). Demonstrating their effectiveness is one objective of this paper. Finally, our intent is to show that ash softening at near melting temperatures is apparently not the only phenomenon causing problems with filtration, although its impact is certainly the ''final catastrophe''. There are other

  15. A Signaling Pathway Involving the Diguanylate Cyclase CelR and the Response Regulator DivK Controls Cellulose Synthesis in Agrobacterium tumefaciens

    PubMed Central

    Barnhart, D. Michael; Su, Shengchang

    2014-01-01

    The production of cellulose fibrils is involved in the attachment of Agrobacterium tumefaciens to its plant host. Consistent with previous studies, we reported recently that a putative diguanylate cyclase, celR, is required for synthesis of this polymer in A. tumefaciens. In this study, the effects of celR and other components of the regulatory pathway of cellulose production were explored. Mutational analysis of celR demonstrated that the cyclase requires the catalytic GGEEF motif, as well as the conserved aspartate residue of a CheY-like receiver domain, for stimulating cellulose production. Moreover, a site-directed mutation within the PilZ domain of CelA, the catalytic subunit of the cellulose synthase complex, greatly reduced cellulose production. In addition, deletion of divK, the first gene of the divK-celR operon, also reduced cellulose production. This requirement for divK was alleviated by expression of a constitutively active form of CelR, suggesting that DivK acts upstream of CelR activation. Based on bacterial two-hybrid assays, CelR homodimerizes but does not interact with DivK. The mutation in divK additionally affected cell morphology, and this effect was complementable by a wild-type copy of the gene, but not by the constitutively active allele of celR. These results support the hypothesis that CelR is a bona fide c-di-GMP synthase and that the nucleotide signal produced by this enzyme activates CelA via the PilZ domain. Our studies also suggest that the DivK/CelR signaling pathway in Agrobacterium regulates cellulose production independent of cell cycle checkpoint systems that are controlled by divK. PMID:24443526

  16. Adolph Barkan (1845-1935), European ophthalmologist in San Francisco.

    PubMed

    Muirhead, J Fraser

    2014-03-01

    Adolph Barkan, a mid-19th century Central European-born and -trained ophthalmologist, spent almost half his nearly 91 years in a very successful career on the West Coast of the United States. His activities included intimate involvement in the development of a private medical school and with this school's acquisition by Stanford University as its medical school. In retirement, he founded, financed, and stocked a large medical history library at that university. In the 1890s, Siegfried Czapski, the developer of the Carl Zeiss corneal biomicroscope, the direct precursor of today's slitlamp, incorporated Barkan's suggestion that Czapski replace the planned monoscopic binocular microscope with a stereoscopic binocular one, an essential modification of the device. This Zeiss invention lacked only the slit illumination of today's instrument. Comments he wrote in a memoir-diary during World War I explain how he came to the decision to stray and to stay so far from his roots.

  17. Science fiction and the history of the astro-department of Carl Zeiss Jena (German Title: Science Fiction und die Geschichte der Astroabteilung von Carl Zeiss Jena)

    NASA Astrophysics Data System (ADS)

    Beck, Hans G.

    This contribution uses the literary form of science fiction in retrospect, in order to display the initial conditions given in the run-up of the founding of the astro-department of the Zeiss factory. Written minutes (supposedly found during restoration works in the people's house in Jena) introduce the participants of a sort of founding party of the main actors Ernst Abbe, Otto Schott, Siegfried Czapski, Hans Harting, Albert König, Franz Meyer and Walter Villiger. Their contributions to the discussion yield a market analysis, based on the past development of the technology of astronomical instruments, the international competitors' state of the art, and the assessment of the future development in astronomy and especially of astrophysics. The contribution presents a piece of modern history of the year 1987; it was presented as a talk on May 13 of the same year, when Rolf Riekher celebrated his 65th birthday.

  18. Evolution of one-handed piano compositions.

    PubMed

    Drozdov, Ignat; Kidd, Mark; Modlin, Irvin M

    2008-01-01

    Electronic searches were performed to investigate the evolution of one-handed piano compositions and one-handed music techniques, and to identify individuals responsible for the development of music meant for playing with one hand. Particularly, composers such as Liszt, Ravel, Scriabin, and Prokofiev established a new model in music by writing works to meet the demands of a variety of pianist-amputees that included Count Géza Zichy (1849-1924), Paul Wittgenstein (1887-1961), and Siegfried Rapp (b. 1915). Zichy was the first to amplify the scope of the repertoire to improve the variety of one-handed music; Wittgenstein developed and adapted specific and novel performance techniques to accommodate one-handedness; and Rapp sought to promote the stature of one-handed pianists among a musically sophisticated public able to appreciate the nuances of such maestros.

  19. W. H. R. Rivers and the war neuroses.

    PubMed

    Young, A

    1999-01-01

    W. H. R. Rivers was the most famous member of the Cambridge Expedition to the Torres Strait. At the time, he was a physician and had an international reputation as a researcher in physiological psychology. The expedition signaled the beginning of his career in social anthropology, but also a long hiatus in his activities in medicine. His clinical interests revived during World War I. As an officer in the Royal Army Medical Corps (RAMC), Rivers became a leading proponent of "psychological medicine." Today, his war-time psychiatry is remembered mainly in association with his patient, Siegfried Sassoon. This article focuses on his wartime activities, his clinical practices, and his theories concerning the war neuroses and the unconscious. The currently popular view of Rivers as a quasi-Freudian humanist is challenged. PMID:10531561

  20. W. H. R. Rivers and the war neuroses.

    PubMed

    Young, A

    1999-01-01

    W. H. R. Rivers was the most famous member of the Cambridge Expedition to the Torres Strait. At the time, he was a physician and had an international reputation as a researcher in physiological psychology. The expedition signaled the beginning of his career in social anthropology, but also a long hiatus in his activities in medicine. His clinical interests revived during World War I. As an officer in the Royal Army Medical Corps (RAMC), Rivers became a leading proponent of "psychological medicine." Today, his war-time psychiatry is remembered mainly in association with his patient, Siegfried Sassoon. This article focuses on his wartime activities, his clinical practices, and his theories concerning the war neuroses and the unconscious. The currently popular view of Rivers as a quasi-Freudian humanist is challenged.

  1. Evolution of one-handed piano compositions.

    PubMed

    Drozdov, Ignat; Kidd, Mark; Modlin, Irvin M

    2008-01-01

    Electronic searches were performed to investigate the evolution of one-handed piano compositions and one-handed music techniques, and to identify individuals responsible for the development of music meant for playing with one hand. Particularly, composers such as Liszt, Ravel, Scriabin, and Prokofiev established a new model in music by writing works to meet the demands of a variety of pianist-amputees that included Count Géza Zichy (1849-1924), Paul Wittgenstein (1887-1961), and Siegfried Rapp (b. 1915). Zichy was the first to amplify the scope of the repertoire to improve the variety of one-handed music; Wittgenstein developed and adapted specific and novel performance techniques to accommodate one-handedness; and Rapp sought to promote the stature of one-handed pianists among a musically sophisticated public able to appreciate the nuances of such maestros. PMID:18590863

  2. Adolph Barkan (1845-1935), European ophthalmologist in San Francisco.

    PubMed

    Muirhead, J Fraser

    2014-03-01

    Adolph Barkan, a mid-19th century Central European-born and -trained ophthalmologist, spent almost half his nearly 91 years in a very successful career on the West Coast of the United States. His activities included intimate involvement in the development of a private medical school and with this school's acquisition by Stanford University as its medical school. In retirement, he founded, financed, and stocked a large medical history library at that university. In the 1890s, Siegfried Czapski, the developer of the Carl Zeiss corneal biomicroscope, the direct precursor of today's slitlamp, incorporated Barkan's suggestion that Czapski replace the planned monoscopic binocular microscope with a stereoscopic binocular one, an essential modification of the device. This Zeiss invention lacked only the slit illumination of today's instrument. Comments he wrote in a memoir-diary during World War I explain how he came to the decision to stray and to stay so far from his roots. PMID:24626825

  3. Cyclic Di-GMP Regulates Multiple Cellular Functions in the Symbiotic Alphaproteobacterium Sinorhizobium meliloti

    PubMed Central

    Schäper, Simon; Krol, Elizaveta; Skotnicka, Dorota; Kaever, Volkhard; Hilker, Rolf; Søgaard-Andersen, Lotte

    2015-01-01

    ABSTRACT Sinorhizobium meliloti undergoes major lifestyle changes between planktonic states, biofilm formation, and symbiosis with leguminous plant hosts. In many bacteria, the second messenger 3′,5′-cyclic di-GMP (c-di-GMP, or cdG) promotes a sessile lifestyle by regulating a plethora of processes involved in biofilm formation, including motility and biosynthesis of exopolysaccharides (EPS). Here, we systematically investigated the role of cdG in S. meliloti Rm2011 encoding 22 proteins putatively associated with cdG synthesis, degradation, or binding. Single mutations in 21 of these genes did not cause evident changes in biofilm formation, motility, or EPS biosynthesis. In contrast, manipulation of cdG levels by overproducing endogenous or heterologous diguanylate cyclases (DGCs) or phosphodiesterases (PDEs) affected these processes and accumulation of N-Acyl-homoserine lactones in the culture supernatant. Specifically, individual overexpression of the S. meliloti genes pleD, SMb20523, SMb20447, SMc01464, and SMc03178 encoding putative DGCs and of SMb21517 encoding a single-domain PDE protein had an impact and resulted in increased levels of cdG. Compared to the wild type, an S. meliloti strain that did not produce detectable levels of cdG (cdG0) was more sensitive to acid stress. However, it was symbiotically potent, unaffected in motility, and only slightly reduced in biofilm formation. The SMc01790-SMc01796 locus, homologous to the Agrobacterium tumefaciens uppABCDEF cluster governing biosynthesis of a unipolarly localized polysaccharide, was found to be required for cdG-stimulated biofilm formation, while the single-domain PilZ protein McrA was identified as a cdG receptor protein involved in regulation of motility. IMPORTANCE We present the first systematic genome-wide investigation of the role of 3′,5′-cyclic di-GMP (c-di-GMP, or cdG) in regulation of motility, biosynthesis of exopolysaccharides, biofilm formation, quorum sensing, and symbiosis in a

  4. Dimeric c-di-GMP is required for post-translational regulation of alginate production in Pseudomonas aeruginosa

    SciTech Connect

    Whitney, John C.; Robinson, Howard; Whitfield, Gregory B.; Marmont, Lindsey S.; Yip, Patrick; Neculai, A. Mirela; Lobsanov, Yuri D.; Ohman, Dennis E.; Howell, P. Lynne

    2015-05-15

    Pseudomonas aeruginosa is an opportunistic human pathogen that secretes the exopolysaccharide alginate during infection of the respiratory tract of individuals afflicted with cystic fibrosis and chronic obstructive pulmonary disease. Among the proteins required for alginate production, Alg44 has been identified as an inner membrane protein whose bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP) binding activity post-translationally regulates alginate secretion. In this study, we report the 1.8 Å crystal structure of the cytoplasmic region of Alg44 in complex with dimeric self-intercalated c-di-GMP and characterize its dinucleotide-binding site using mutational analysis. The structure shows that the c-di-GMP binding region of Alg44 adopts a PilZ domain fold with a dimerization mode not previously observed for this family of proteins. Moreover, calorimetric binding analysis of residues in the c-di-GMP binding site demonstrate that mutation of Arg-17 and Arg-95 alters the binding stoichiometry between c-di-GMP and Alg44 from 2:1 to 1:1. Introduction of these mutant alleles on the P. aeruginosa chromosome show that the residues required for binding of dimeric c-di-GMP in vitro are also required for efficient alginate production in vivo. Our results suggest that the dimeric form of c-di-GMP represents the biologically active signaling molecule needed for the secretion of an important virulence factor produced by P. aeruginosa.

  5. A sex difference in interference between identity and expression judgments with static but not dynamic faces.

    PubMed

    Stoesz, Brenda M; Jakobson, Lorna S

    2013-04-26

    Facial motion cues facilitate identity and expression processing (Pilz, Thornton, & Bülthoff, 2006). To explore this dynamic advantage, we used Garner's speeded classification task (Garner, 1976) to investigate whether adding dynamic cues alters the interactions between the processing of identity and expression. We also examined whether facial motion affected women and men differently, given that women show an advantage for several aspects of static face processing (McClure, 2000). Participants made speeded identity or expression judgments while the irrelevant cue was held constant or varied. Significant interference occurred with both tasks when static stimuli were used (as in Ganel & Goshen-Gottstein, 2004), but interference was minimal with dynamic displays. This suggests that adult viewers are either better able to selectively attend to relevant cues, or better able to integrate multiple facial cues, when viewing moving as opposed to static faces. These gains, however, come with a cost in processing time. Only women showed asymmetrical interference with static faces, with variations in identity affecting expression judgments more than the opposite. This finding may reflect sex differences in global-local processing biases (Godard & Fiori, 2012). Our findings stress the importance of using dynamic displays and of considering sex distributions when characterizing typical face processing mechanisms.

  6. Exploring the relationship between object realism and object-based attention effects.

    PubMed

    Roque, Nelson; Boot, Walter R

    2015-09-01

    Visual attention prioritizes processing of locations in space, and evidence also suggests that the benefits of attention can be shaped by the presence of objects (object-based attention). However, the prevalence of object-based attention effects has been called into question recently by evidence from a large-sampled study employing classic attention paradigms (Pilz et al., 2012). We conducted two experiments to explore factors that might determine when and if object-based attention effects are observed, focusing on the degree to which the concreteness and realism of objects might contribute to these effects. We adapted the classic attention paradigm first reported by Egly, Driver, and Rafal (1994) by replacing abstract bar stimuli in some conditions with objects that were more concrete and familiar to participants: items of silverware. Furthermore, we varied the realism of these items of silverware, presenting either cartoon versions or photo-realistic versions. Contrary to predictions, increased realism did not increase the size of object-based effects. In fact, no clear object-based effects were observed in either experiment, consistent with previous failures to replicate these effects in similar paradigms. While object-based attention may exist, and may have important influences on how we parse the visual world, these and other findings suggest that the two-object paradigm typically relied upon to study object-based effects may not be the best paradigm to investigate these issues.

  7. Targeting cyclic di-GMP signalling: a strategy to control biofilm formation?

    PubMed

    Caly, Delphine L; Bellini, Domenico; Walsh, Martin A; Dow, J Maxwell; Ryan, Robert P

    2015-01-01

    Cyclic di-GMP is a second messenger found in almost all eubacteria that acts to regulate a wide range of functions including developmental transitions, adhesion and biofilm formation. Cyclic di-GMP is synthesised from two GTP molecules by diguanylate cyclases that have a GGDEF domain and is degraded by phosphodiesterases with either an EAL or an HD-GYP domain. Proteins with these domains often contain additional signal input domains, suggesting that their enzymatic activity may be modulated as a response to different environmental or cellular cues. Cyclic di-GMP exerts a regulatory action through binding to diverse receptors that include a small protein domain called PilZ, enzymatically inactive GGDEF, EAL or HD-GYP domains, transcription factors and riboswitches. In many bacteria, high cellular levels of cyclic di-GMP are associated with a sessile, biofilm lifestyle, whereas low levels of the nucleotide promote motility and virulence factor synthesis in pathogens. Elucidation of the roles of cyclic di-GMP signalling in biofilm formation has suggested strategies whereby modulation of the levels of the nucleotide or interference with signalling pathways may lead to inhibition of biofilm formation or promotion of biofilm dispersal. In this review we consider these approaches for the control of biofilm formation, beginning with an overview of cyclic di-GMP signalling and the different ways that it can act in regulation of biofilm dynamics.

  8. Dimeric c-di-GMP is required for post-translational regulation of alginate production in Pseudomonas aeruginosa.

    PubMed

    Whitney, John C; Whitfield, Gregory B; Marmont, Lindsey S; Yip, Patrick; Neculai, A Mirela; Lobsanov, Yuri D; Robinson, Howard; Ohman, Dennis E; Howell, P Lynne

    2015-05-15

    Pseudomonas aeruginosa is an opportunistic human pathogen that secretes the exopolysaccharide alginate during infection of the respiratory tract of individuals afflicted with cystic fibrosis and chronic obstructive pulmonary disease. Among the proteins required for alginate production, Alg44 has been identified as an inner membrane protein whose bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP) binding activity post-translationally regulates alginate secretion. In this study, we report the 1.8 Å crystal structure of the cytoplasmic region of Alg44 in complex with dimeric self-intercalated c-di-GMP and characterize its dinucleotide-binding site using mutational analysis. The structure shows that the c-di-GMP binding region of Alg44 adopts a PilZ domain fold with a dimerization mode not previously observed for this family of proteins. Calorimetric binding analysis of residues in the c-di-GMP binding site demonstrate that mutation of Arg-17 and Arg-95 alters the binding stoichiometry between c-di-GMP and Alg44 from 2:1 to 1:1. Introduction of these mutant alleles on the P. aeruginosa chromosome show that the residues required for binding of dimeric c-di-GMP in vitro are also required for efficient alginate production in vivo. These results suggest that the dimeric form of c-di-GMP represents the biologically active signaling molecule needed for the secretion of an important virulence factor produced by P. aeruginosa.

  9. Capture compound mass spectrometry--a powerful tool to identify novel c-di-GMP effector proteins.

    PubMed

    Laventie, Benoît-Joseph; Nesper, Jutta; Ahrné, Erik; Glatter, Timo; Schmidt, Alexander; Jenal, Urs

    2015-01-01

    Considerable progress has been made during the last decade towards the identification and characterization of enzymes involved in the synthesis (diguanylate cyclases) and degradation (phosphodiesterases) of the second messenger c-di-GMP. In contrast, little information is available regarding the molecular mechanisms and cellular components through which this signaling molecule regulates a diverse range of cellular processes. Most of the known effector proteins belong to the PilZ family or are degenerated diguanylate cyclases or phosphodiesterases that have given up on catalysis and have adopted effector function. Thus, to better define the cellular c-di-GMP network in a wide range of bacteria experimental methods are required to identify and validate novel effectors for which reliable in silico predictions fail. We have recently developed a novel Capture Compound Mass Spectrometry (CCMS) based technology as a powerful tool to biochemically identify and characterize c-di-GMP binding proteins. This technique has previously been reported to be applicable to a wide range of organisms(1). Here we give a detailed description of the protocol that we utilize to probe such signaling components. As an example, we use Pseudomonas aeruginosa, an opportunistic pathogen in which c-di-GMP plays a critical role in virulence and biofilm control. CCMS identified 74% (38/51) of the known or predicted components of the c-di-GMP network. This study explains the CCMS procedure in detail, and establishes it as a powerful and versatile tool to identify novel components involved in small molecule signaling.

  10. Dimeric c-di-GMP Is Required for Post-translational Regulation of Alginate Production in Pseudomonas aeruginosa*

    PubMed Central

    Whitney, John C.; Whitfield, Gregory B.; Marmont, Lindsey S.; Yip, Patrick; Neculai, A. Mirela; Lobsanov, Yuri D.; Robinson, Howard; Ohman, Dennis E.; Howell, P. Lynne

    2015-01-01

    Pseudomonas aeruginosa is an opportunistic human pathogen that secretes the exopolysaccharide alginate during infection of the respiratory tract of individuals afflicted with cystic fibrosis and chronic obstructive pulmonary disease. Among the proteins required for alginate production, Alg44 has been identified as an inner membrane protein whose bis-(3′,5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) binding activity post-translationally regulates alginate secretion. In this study, we report the 1.8 Å crystal structure of the cytoplasmic region of Alg44 in complex with dimeric self-intercalated c-di-GMP and characterize its dinucleotide-binding site using mutational analysis. The structure shows that the c-di-GMP binding region of Alg44 adopts a PilZ domain fold with a dimerization mode not previously observed for this family of proteins. Calorimetric binding analysis of residues in the c-di-GMP binding site demonstrate that mutation of Arg-17 and Arg-95 alters the binding stoichiometry between c-di-GMP and Alg44 from 2:1 to 1:1. Introduction of these mutant alleles on the P. aeruginosa chromosome show that the residues required for binding of dimeric c-di-GMP in vitro are also required for efficient alginate production in vivo. These results suggest that the dimeric form of c-di-GMP represents the biologically active signaling molecule needed for the secretion of an important virulence factor produced by P. aeruginosa. PMID:25817996

  11. Correalism and Equipoise: Kiesler and Giedion on the sustainable

    SciTech Connect

    Braham, W.W.

    1997-12-31

    This paper inquires about standards for the sustainable that are not strictly bound to the principles of conservation or scarcity. In particular, two earlier contributions to this discussion offer alternate views of sustainability: the architect Frederick Kiesler and the critic-historian Siegfried Giedion both explored the human and social consequences of technological constructions. Their work participates in the long, nineteenth- and twentieth-century discourse about mechanization, that examined the many consequences of industrialization. In a sequence of published and unpublished works in the 1930`s Kieler evolved a theory about the relationship between buildings and nature that he called Correalism. While at the end Mechanization Takes Command of 1948, Giedion examined the loss of public and regenerative bathing habits and the rise of the private, forms of cleansing still largely practiced today. He concluded that work with a plea for a dynamic balance that he called Equipoise. Both works develop from ideas of interconnection that he now associates with systems theory and which are properly integral to modern ecology. Their critical questions revolve around the social dimensions of everyday constructions like buildings and bathtubs. The distinction between instrumental criteria and social ones is everywhere present in modern environmentalism, which can be traced to fundamental concerns about either resource use or about health. These two issues are wholly intertwined in most environmental practices, but the assumptions on which they rest are themselves historically changeable. The complex interaction between measurable environmental features and human concerns or desires is the subject of Kiesler`s Correalism.

  12. The papal anatomist: Eustachius in renaissance Rome.

    PubMed

    Simpson, Donald

    2011-12-01

    Bartholomeo Eustachi, usually latinized as Eustachius, was an important anatomist in the 16th century, arguably second only to his contemporary and rival Andreas Vesalius. He was the first to identify several important anatomical structures, including the suprarenal glands, though he was probably not the first to describe the Eustachian tube. However, it has been hard to evaluate his achievements, because during his lifetime he published only some short monographs, and his career as a teacher in Rome is not well documented. He and his assistant P.M. Pini were the first to use copper plate engravings to illustrate human and animal anatomy, but most of their engravings were not published in their time, and the original plates were lost for some 140 years after the death of Eustachius. Early in the 18th century, these plates were rediscovered by the anatomist and papal physician G.M. Lancisi; he published the engravings in a book which aroused much interest and many reprintings. In 1744, Bernhard Siegfried Albinus of Leiden University published a version of these engravings, with commentaries by himself. The engraved illustrations prepared by Eustachius and Pini are clear and largely accurate. They idealize the findings of actual dissections, and have a diagrammatic quality that facilitates understanding and memory. They are the ancestors of later anatomical atlases, which have helped generations of surgeons in teaching and in planning operations. PMID:22507418

  13. ['Anatomia actuosa et apta'. The mechanist 'proto'-physiology of B.S. Albinus].

    PubMed

    van der Korst, J K

    1993-01-01

    Already during his tenure as professor of anatomy and surgery (1721-1746) and before he became a professor of physiology and medicine at the University of Leiden, Bernard Siegfried Albinus held private lecture courses on physiology. In these lectures he pleaded for a separation of physiology from theoretical medicine, which was still its customary place in the medical curriculum of the first half of the eighteenth century. According to Albinus, physiology was a science in its own right and should be solely based on the careful observation of forms and structures of the human body. From the 'fabrica', the function ('aptitudo') could be derived by careful reasoning. As shown by a set of lecture notes, which recently came to light, Albinus adhered, initially, to a strictly mechanistic explanatory model, which was almost completely based on the physiological concepts of Herman Boerhaave. However, in contrast to the latter, he even rejected the involvement of chemical processes in digestion. Although his lectures were highly acclaimed as demonstrations of minute anatomy, Albinus met with little or no direct response in regard to his concept of physiology.

  14. Historical aspects of the study of malformations in The Netherlands.

    PubMed

    Baljet, B; Oostra, R J

    1998-05-01

    The collection of malformed ("teratological") specimens of man and other mammals of Gerardus Vrolik (1775-1859) and his son Willem Vrolik (1801-1863), dating from the beginning of the 19th century, continues to function as a central part of the Department of Anatomy and Embryology in the Academic Medical Center at the University of Amsterdam. Recently, many specimens in the collection were reexamined, using radiographic, CT scan, and MRI methods. In order to provide background information concerning Dutch teratological research and anatomical cabinets, some aspects of the history of Dutch morphology during the 17th-19th centuries are briefly described in this paper. Special attention is paid to the scientific work and cabinet of Frederik Ruijsch (1638-1731), who sold this cabinet to Czar Peter the Great; Bernard Siegfried Albinus (1697-1770); Wouter van Doeveren (1733-1783), Andreas Bonn (1738-1818), and Sebald Justinus Brugmans (1763-1819), who sold or donated parts of their collections of malformed specimens to Leiden University; Petrus Camper (1722-1789) and Jan Bleuland (1756-1838), whose collections are still in the Department of Anatomy at Groningen University and the Departments of Anatomy and Pathology of Utrecht University; and Gerard and Willem Vrolik.

  15. PSHAe (Probabilistic Seismic Hazard enhanced): the case of Istanbul.

    NASA Astrophysics Data System (ADS)

    Stupazzini, Marco; Allmann, Alexander; Infantino, Maria; Kaeser, Martin; Mazzieri, Ilario; Paolucci, Roberto; Smerzini, Chiara

    2016-04-01

    The Probabilistic Seismic Hazard Analysis (PSHA) only relying on GMPEs tends to be insufficiently constrained at short distances and data only partially account for the rupture process, seismic wave propagation and three-dimensional (3D) complex configurations. Given a large and representative set of numerical results from 3D scenarios, analysing the resulting database from a statistical point of view and implementing the results as a generalized attenuation function (GAF) into the classical PSHA might be an appealing way to deal with this problem (Villani et al., 2014). Nonetheless, the limited amount of computational resources or time available tend to pose substantial constrains in a broad application of the previous method and, furthermore, the method is only partially suitable for taking into account the spatial correlation of ground motion as modelled by each forward physics-based simulation (PBS). Given that, we envision a streamlined and alternative implementation of the previous approach, aiming at selecting a limited number of scenarios wisely chosen and associating them a probability of occurrence. The experience gathered in the past year regarding 3D modelling of seismic wave propagation in complex alluvial basin (Pilz et al., 2011, Guidotti et al., 2011, Smerzini and Villani, 2012) allowed us to enhance the choice of simulated scenarios in order to explore the variability of ground motion, preserving the full spatial correlation necessary for risk modelling, on one hand and on the other the simulated losses for a given location and a given building stock. 3D numerical modelling of scenarios occurring the North Anatolian Fault in the proximity of Istanbul are carried out through the spectral element code SPEED (http://speed.mox.polimi.it). The results are introduced in a PSHA, exploiting the capabilities of the proposed methodology against a traditional approach based on GMPE. References Guidotti R, M Stupazzini, C Smerzini, R Paolucci, P Ramieri

  16. Inactivation of Cyclic Di-GMP Binding Protein TDE0214 Affects the Motility, Biofilm Formation, and Virulence of Treponema denticola

    PubMed Central

    Bian, Jiang; Liu, Xiangyang; Cheng, Yi-Qiang

    2013-01-01

    As a ubiquitous second messenger, cyclic dimeric GMP (c-di-GMP) has been studied in numerous bacteria. The oral spirochete Treponema denticola, a periodontal pathogen associated with human periodontitis, has a complex c-di-GMP signaling network. However, its function remains unexplored. In this report, a PilZ-like c-di-GMP binding protein (TDE0214) was studied to investigate the role of c-di-GMP in the spirochete. TDE0214 harbors a PilZ domain with two signature motifs: RXXXR and DXSXXG. Biochemical studies showed that TDE0214 binds c-di-GMP in a specific manner, with a dissociation constant (Kd) value of 1.73 μM, which is in the low range compared to those of other reported c-di-GMP binding proteins. To reveal the role of c-di-GMP in T. denticola, a TDE0214 deletion mutant (TdΔ214) was constructed and analyzed in detail. First, swim plate and single-cell tracking analyses showed that TdΔ214 had abnormal swimming behaviors: the mutant was less motile and reversed more frequently than the wild type. Second, we found that biofilm formation of TdΔ214 was substantially repressed (∼6.0-fold reduction). Finally, in vivo studies using a mouse skin abscess model revealed that the invasiveness and ability to induce skin abscesses and host humoral immune responses were significantly attenuated in TdΔ214, indicative of the impact that TDE0214 has on the virulence of T. denticola. Collectively, the results reported here indicate that TDE0214 plays important roles in motility, biofilm formation, and virulence of the spirochete. This report also paves a way to further unveil the roles of the c-di-GMP signaling network in the biology and pathogenicity of T. denticola. PMID:23794624

  17. Costs and deaths of landslides in Europe

    NASA Astrophysics Data System (ADS)

    Haque, Ubydul; Blum, Philipp

    2016-04-01

    Landslides cause human and large economic losses worldwide and also in Europe. However, the quantification of associated costs and deaths is highly underestimated and still incomplete, thus the estimation of landslide costs and risk is still rather ambitious. Hence, in this study a spatio-temporal analysis of fatal landslides is presented for 27 European countries from 1995-2014. These landslides are mainly concentrated in mountainous areas. A total of 1370 fatalities are reported resulting from 476 landslides. The highest fatalities with 335 are observed in Turkey. In general, an increasing trend of fatal landslides is recognized starting in 2008. The latter is almost certainly triggered by an increase in natural extreme events such as storms (i.e. heavy rainfall) and floods. The highest annual economic loss is observed in Italy with 3.9 billion Euro per year. In contrast, in Germany the annual total loss is only about 0.3 billion Euro. The results of this study serves as an initial baseline information for further risk studies integrating landslide locations, local land use data, cost data, and will therefore certainly support the studied countries to better protect their citizens and assets. Acknowledgements We would like to acknowledge the valuable contributions by Paula F. da Silva, Peter Andersen, Jürgen Pilz, Ali Ardalan, Sergey R. Chalov, Jean-Philippe Malet, Mateja Jemec Auflič, Norina Andres, Eleftheria Poyiadji, Pedro C. Lamas, Wenyi Zhang, Igor Pesevski, Halldór G. Pétursson, Tayfun Kurt, Nikolai Dobrev, Juan Carlos García Davalillo, Matina Halkia, Stefano Ferri, George Gaprindashvili, Johanna Engström and David Keellings.

  18. Impact of a Cross-Kingdom Signaling Molecule of Candida albicans on Acinetobacter baumannii Physiology

    PubMed Central

    Kostoulias, Xenia; Murray, Gerald L.; Cerqueira, Gustavo M.; Kong, Jason B.; Bantun, Farkad; Mylonakis, Eleftherios; Khoo, Chen Ai

    2015-01-01

    Multidrug-resistant (MDR) Acinetobacter baumannii is an opportunistic human pathogen that has become highly problematic in the clinical environment. Novel therapies are desperately required. To assist in identifying new therapeutic targets, the antagonistic interactions between A. baumannii and the most common human fungal pathogen, Candida albicans, were studied. We have observed that the C. albicans quorum-sensing molecule, farnesol, has cross-kingdom interactions, affecting the viability of A. baumannii. To gain an understanding of its mechanism, the transcriptional profile of A. baumannii exposed to farnesol was examined. Farnesol caused dysregulation of a large number of genes involved in cell membrane biogenesis, multidrug efflux pumps (AcrAB-like and AdeIJK-like), and A. baumannii virulence traits such as biofilm formation (csuA, csuB, and ompA) and motility (pilZ and pilH). We also observed a strong induction in genes involved in cell division (minD, minE, ftsK, ftsB, and ftsL). These transcriptional data were supported by functional assays showing that farnesol disrupts A. baumannii cell membrane integrity, alters cell morphology, and impairs virulence characteristics such as biofilm formation and twitching motility. Moreover, we showed that A. baumannii uses efflux pumps as a defense mechanism against this eukaryotic signaling molecule. Owing to its effects on membrane integrity, farnesol was tested to see if it potentiated the activity of the membrane-acting polymyxin antibiotic colistin. When coadministered, farnesol increased sensitivity to colistin for otherwise resistant strains. These data provide mechanistic understanding of the antagonistic interactions between diverse pathogens and may provide important insights into novel therapeutic strategies. PMID:26482299

  19. The Anatomische Gesellschaft and National Socialism: an analysis based on newly available archival material.

    PubMed

    Winkelmann, Andreas

    2015-09-01

    The newly available scientific estate of Heinrich von Eggeling (1869-1954), long-time secretary of the Anatomische Gesellschaft (AG), allows a more profound analysis of how this scientific association went through the period of the "Third Reich". At the first meeting under the new rulers in 1934, von Eggeling and Siegfried Mollier prevented their board colleague Martin Heidenhain from giving an introductory talk because they (not unjustly) feared anti-Jewish protests, but also because many anatomy professors, like other German scholars, were fervent nationalists who welcomed Hitler and largely accepted the expulsion of Jewish and other colleagues as 'inevitable' for national renewal. Many persecuted members nevertheless remained on the membership lists and the AG never officially introduced anti-Jewish bylaws. Eggeling and his like-minded colleagues successfully defended the international status of the AG, though not so much against the Nazi authorities but against a younger generation of anatomists who were willing to benefit from the new political situation and strived for their own German anatomical association. The available archival material suggests that the motivation of the established leading members of the AG to take this specific path was not rooted in opposition to the new rulers but rather in defence of their traditional status of reputed professors running a time-honoured, world leading society. This made international reputation an important guideline for many decisions. While they did ward off attempts by the younger generation to politicise the AG, their post-war calls for an apolitical science remain ambivalent, as their own stance had not always been apolitical.

  20. The Anatomische Gesellschaft and National Socialism: an analysis based on newly available archival material.

    PubMed

    Winkelmann, Andreas

    2015-09-01

    The newly available scientific estate of Heinrich von Eggeling (1869-1954), long-time secretary of the Anatomische Gesellschaft (AG), allows a more profound analysis of how this scientific association went through the period of the "Third Reich". At the first meeting under the new rulers in 1934, von Eggeling and Siegfried Mollier prevented their board colleague Martin Heidenhain from giving an introductory talk because they (not unjustly) feared anti-Jewish protests, but also because many anatomy professors, like other German scholars, were fervent nationalists who welcomed Hitler and largely accepted the expulsion of Jewish and other colleagues as 'inevitable' for national renewal. Many persecuted members nevertheless remained on the membership lists and the AG never officially introduced anti-Jewish bylaws. Eggeling and his like-minded colleagues successfully defended the international status of the AG, though not so much against the Nazi authorities but against a younger generation of anatomists who were willing to benefit from the new political situation and strived for their own German anatomical association. The available archival material suggests that the motivation of the established leading members of the AG to take this specific path was not rooted in opposition to the new rulers but rather in defence of their traditional status of reputed professors running a time-honoured, world leading society. This made international reputation an important guideline for many decisions. While they did ward off attempts by the younger generation to politicise the AG, their post-war calls for an apolitical science remain ambivalent, as their own stance had not always been apolitical. PMID:26117073

  1. Well-based stable carbon isotope leakage monitoring of an aquifer overlying the CO2 storage reservoir at the Ketzin pilot site, Germany

    NASA Astrophysics Data System (ADS)

    Nowak, Martin; Myrttinen, Anssi; Zimmer, Martin; van Geldern, Robert; Barth, Johannes A. C.

    2014-05-01

    Isotopes at the Ketzin Pilot Site, Germany. Energy Procedia 40, 346-354. Wiese, B., Zimmer, M., Nowak, M., Pellizzari, L., Pilz, P., 2013. Well-based hydraulic and geochemical monitoring of the above zone of the CO2 reservoir at Ketzin, Germany. Environmental Earth Sciences, 1-18.

  2. Structure of the Cellulose Synthase Complex of Gluconacetobacter hansenii at 23.4 Å Resolution.

    PubMed

    Du, Juan; Vepachedu, Venkata; Cho, Sung Hyun; Kumar, Manish; Nixon, B Tracy

    2016-01-01

    Bacterial crystalline cellulose is used in biomedical and industrial applications, but the molecular mechanisms of synthesis are unclear. Unlike most bacteria, which make non-crystalline cellulose, Gluconacetobacter hansenii extrudes profuse amounts of crystalline cellulose. Its cellulose synthase (AcsA) exists as a complex with accessory protein AcsB, forming a 'terminal complex' (TC) that has been visualized by freeze-fracture TEM at the base of ribbons of crystalline cellulose. The catalytic AcsAB complex is embedded in the cytoplasmic membrane. The C-terminal portion of AcsC is predicted to form a translocation channel in the outer membrane, with the rest of AcsC possibly interacting with AcsD in the periplasm. It is thus believed that synthesis from an organized array of TCs coordinated with extrusion by AcsC and AcsD enable this bacterium to make crystalline cellulose. The only structural data that exist for this system are the above mentioned freeze-fracture TEM images, fluorescence microscopy images revealing that TCs align in a row, a crystal structure of AcsD bound to cellopentaose, and a crystal structure of PilZ domain of AcsA. Here we advance our understanding of the structural basis for crystalline cellulose production by bacterial cellulose synthase by determining a negative stain structure resolved to 23.4 Å for highly purified AcsAB complex that catalyzed incorporation of UDP-glucose into β-1,4-glucan chains, and responded to the presence of allosteric activator cyclic diguanylate. Although the AcsAB complex was functional in vitro, the synthesized cellulose was not visible in TEM. The negative stain structure revealed that AcsAB is very similar to that of the BcsAB synthase of Rhodobacter sphaeroides, a non-crystalline cellulose producing bacterium. The results indicate that the crystalline cellulose producing and non-crystalline cellulose producing bacteria share conserved catalytic and membrane translocation components, and support the

  3. Systematic Identification of Cyclic-di-GMP Binding Proteins in Vibrio cholerae Reveals a Novel Class of Cyclic-di-GMP-Binding ATPases Associated with Type II Secretion Systems.

    PubMed

    Roelofs, Kevin G; Jones, Christopher J; Helman, Sarah R; Shang, Xiaoran; Orr, Mona W; Goodson, Jonathan R; Galperin, Michael Y; Yildiz, Fitnat H; Lee, Vincent T

    2015-10-01

    Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial signaling molecule that regulates a variety of complex processes through a diverse set of c-di-GMP receptor proteins. We have utilized a systematic approach to identify c-di-GMP receptors from the pathogen Vibrio cholerae using the Differential Radial Capillary Action of Ligand Assay (DRaCALA). The DRaCALA screen identified a majority of known c-di-GMP binding proteins in V. cholerae and revealed a novel c-di-GMP binding protein, MshE (VC0405), an ATPase associated with the mannose sensitive hemagglutinin (MSHA) type IV pilus. The known c-di-GMP binding proteins identified by DRaCALA include diguanylate cyclases, phosphodiesterases, PilZ domain proteins and transcription factors VpsT and VpsR, indicating that the DRaCALA-based screen of open reading frame libraries is a feasible approach to uncover novel receptors of small molecule ligands. Since MshE lacks the canonical c-di-GMP-binding motifs, a truncation analysis was utilized to locate the c-di-GMP binding activity to the N-terminal T2SSE_N domain. Alignment of MshE homologs revealed candidate conserved residues responsible for c-di-GMP binding. Site-directed mutagenesis of these candidate residues revealed that the Arg9 residue is required for c-di-GMP binding. The ability of c-di-GMP binding to MshE to regulate MSHA dependent processes was evaluated. The R9A allele, in contrast to the wild type MshE, was unable to complement the ΔmshE mutant for the production of extracellular MshA to the cell surface, reduction in flagella swimming motility, attachment to surfaces and formation of biofilms. Testing homologs of MshE for binding to c-di-GMP identified the type II secretion ATPase of Pseudomonas aeruginosa (PA14_29490) as a c-di-GMP receptor, indicating that type II secretion and type IV pili are both regulated by c-di-GMP. PMID:26506097

  4. Structure of the cellulose synthase complex of Gluconacetobacter hansenii at 23.4 Å resolution

    DOE PAGES

    Du, Juan; Vepachedu, Venkata; Cho, Sung Hyun; Kumar, Manish; Nixon, B. Tracy; Lai, Hsin -Chih

    2016-05-23

    Bacterial crystalline cellulose is used in biomedical and industrial applications, but the molecular mechanisms of synthesis are unclear. Unlike most bacteria, which make non-crystalline cellulose, Gluconacetobacter hansenii extrudes profuse amounts of crystalline cellulose. Its cellulose synthase (AcsA) exists as a complex with accessory protein AcsB, forming a 'terminal complex' (TC) that has been visualized by freeze-fracture TEM at the base of ribbons of crystalline cellulose. The catalytic AcsAB complex is embedded in the cytoplasmic membrane. The C-terminal portion of AcsC is predicted to form a translocation channel in the outer membrane, with the rest of AcsC possibly interacting with AcsDmore » in the periplasm. It is thus believed that synthesis from an organized array of TCs coordinated with extrusion by AcsC and AcsD enable this bacterium to make crystalline cellulose. The only structural data that exist for this system are the above mentioned freeze-fracture TEM images, fluorescence microscopy images revealing that TCs align in a row, a crystal structure of AcsD bound to cellopentaose, and a crystal structure of PilZ domain of AcsA. Here we advance our understanding of the structural basis for crystalline cellulose production by bacterial cellulose synthase by determining a negative stain structure resolved to 23.4 angstrom for highly purified AcsAB complex that catalyzed incorporation of UDP-glucose into β-1,4-glucan chains, and responded to the presence of allosteric activator cyclic diguanylate. Although the AcsAB complex was functional in vitro, the synthesized cellulose was not visible in TEM. The negative stain structure revealed that AcsAB is very similar to that of the BcsAB synthase of Rhodobacter sphaeroides, a non-crystalline cellulose producing bacterium. Furthermore, the results indicate that the crystalline cellulose producing and non-crystalline cellulose producing bacteria share conserved catalytic and membrane translocation

  5. Application of Synthetic Peptide Arrays To Uncover Cyclic Di-GMP Binding Motifs

    PubMed Central

    Düvel, Juliane; Bense, Sarina; Möller, Stefan; Bertinetti, Daniela; Schwede, Frank; Morr, Michael; Eckweiler, Denitsa; Genieser, Hans-Gottfried; Jänsch, Lothar; Herberg, Friedrich W.; Frank, Ronald

    2015-01-01

    ABSTRACT High levels of the universal bacterial second messenger cyclic di-GMP (c-di-GMP) promote the establishment of surface-attached growth in many bacteria. Not only can c-di-GMP bind to nucleic acids and directly control gene expression, but it also binds to a diverse array of proteins of specialized functions and orchestrates their activity. Since its development in the early 1990s, the synthetic peptide array technique has become a powerful tool for high-throughput approaches and was successfully applied to investigate the binding specificity of protein-ligand interactions. In this study, we used peptide arrays to uncover the c-di-GMP binding site of a Pseudomonas aeruginosa protein (PA3740) that was isolated in a chemical proteomics approach. PA3740 was shown to bind c-di-GMP with a high affinity, and peptide arrays uncovered LKKALKKQTNLR to be a putative c-di-GMP binding motif. Most interestingly, different from the previously identified c-di-GMP binding motif of the PilZ domain (RXXXR) or the I site of diguanylate cyclases (RXXD), two leucine residues and a glutamine residue and not the charged amino acids provided the key residues of the binding sequence. Those three amino acids are highly conserved across PA3740 homologs, and their singular exchange to alanine reduced c-di-GMP binding within the full-length protein. IMPORTANCE In many bacterial pathogens the universal bacterial second messenger c-di-GMP governs the switch from the planktonic, motile mode of growth to the sessile, biofilm mode of growth. Bacteria adapt their intracellular c-di-GMP levels to a variety of environmental challenges. Several classes of c-di-GMP binding proteins have been structurally characterized, and diverse c-di-GMP binding domains have been identified. Nevertheless, for several c-di-GMP receptors, the binding motif remains to be determined. Here we show that the use of a synthetic peptide array allowed the identification of a c-di-GMP binding motif of a putative c

  6. Systematic Identification of Cyclic-di-GMP Binding Proteins in Vibrio cholerae Reveals a Novel Class of Cyclic-di-GMP-Binding ATPases Associated with Type II Secretion Systems

    PubMed Central

    Shang, Xiaoran; Orr, Mona W.; Goodson, Jonathan R.; Galperin, Michael Y.; Yildiz, Fitnat H.; Lee, Vincent T.

    2015-01-01

    Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial signaling molecule that regulates a variety of complex processes through a diverse set of c-di-GMP receptor proteins. We have utilized a systematic approach to identify c-di-GMP receptors from the pathogen Vibrio cholerae using the Differential Radial Capillary Action of Ligand Assay (DRaCALA). The DRaCALA screen identified a majority of known c-di-GMP binding proteins in V. cholerae and revealed a novel c-di-GMP binding protein, MshE (VC0405), an ATPase associated with the mannose sensitive hemagglutinin (MSHA) type IV pilus. The known c-di-GMP binding proteins identified by DRaCALA include diguanylate cyclases, phosphodiesterases, PilZ domain proteins and transcription factors VpsT and VpsR, indicating that the DRaCALA-based screen of open reading frame libraries is a feasible approach to uncover novel receptors of small molecule ligands. Since MshE lacks the canonical c-di-GMP-binding motifs, a truncation analysis was utilized to locate the c-di-GMP binding activity to the N-terminal T2SSE_N domain. Alignment of MshE homologs revealed candidate conserved residues responsible for c-di-GMP binding. Site-directed mutagenesis of these candidate residues revealed that the Arg9 residue is required for c-di-GMP binding. The ability of c-di-GMP binding to MshE to regulate MSHA dependent processes was evaluated. The R9A allele, in contrast to the wild type MshE, was unable to complement the ΔmshE mutant for the production of extracellular MshA to the cell surface, reduction in flagella swimming motility, attachment to surfaces and formation of biofilms. Testing homologs of MshE for binding to c-di-GMP identified the type II secretion ATPase of Pseudomonas aeruginosa (PA14_29490) as a c-di-GMP receptor, indicating that type II secretion and type IV pili are both regulated by c-di-GMP. PMID:26506097

  7. Structure of the Cellulose Synthase Complex of Gluconacetobacter hansenii at 23.4 Å Resolution

    PubMed Central

    Du, Juan; Vepachedu, Venkata; Cho, Sung Hyun; Kumar, Manish; Nixon, B. Tracy

    2016-01-01

    Bacterial crystalline cellulose is used in biomedical and industrial applications, but the molecular mechanisms of synthesis are unclear. Unlike most bacteria, which make non-crystalline cellulose, Gluconacetobacter hansenii extrudes profuse amounts of crystalline cellulose. Its cellulose synthase (AcsA) exists as a complex with accessory protein AcsB, forming a 'terminal complex' (TC) that has been visualized by freeze-fracture TEM at the base of ribbons of crystalline cellulose. The catalytic AcsAB complex is embedded in the cytoplasmic membrane. The C-terminal portion of AcsC is predicted to form a translocation channel in the outer membrane, with the rest of AcsC possibly interacting with AcsD in the periplasm. It is thus believed that synthesis from an organized array of TCs coordinated with extrusion by AcsC and AcsD enable this bacterium to make crystalline cellulose. The only structural data that exist for this system are the above mentioned freeze-fracture TEM images, fluorescence microscopy images revealing that TCs align in a row, a crystal structure of AcsD bound to cellopentaose, and a crystal structure of PilZ domain of AcsA. Here we advance our understanding of the structural basis for crystalline cellulose production by bacterial cellulose synthase by determining a negative stain structure resolved to 23.4 Å for highly purified AcsAB complex that catalyzed incorporation of UDP-glucose into β-1,4-glucan chains, and responded to the presence of allosteric activator cyclic diguanylate. Although the AcsAB complex was functional in vitro, the synthesized cellulose was not visible in TEM. The negative stain structure revealed that AcsAB is very similar to that of the BcsAB synthase of Rhodobacter sphaeroides, a non-crystalline cellulose producing bacterium. The results indicate that the crystalline cellulose producing and non-crystalline cellulose producing bacteria share conserved catalytic and membrane translocation components, and support the

  8. Systematic Identification of Cyclic-di-GMP Binding Proteins in Vibrio cholerae Reveals a Novel Class of Cyclic-di-GMP-Binding ATPases Associated with Type II Secretion Systems.

    PubMed

    Roelofs, Kevin G; Jones, Christopher J; Helman, Sarah R; Shang, Xiaoran; Orr, Mona W; Goodson, Jonathan R; Galperin, Michael Y; Yildiz, Fitnat H; Lee, Vincent T

    2015-10-01

    Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial signaling molecule that regulates a variety of complex processes through a diverse set of c-di-GMP receptor proteins. We have utilized a systematic approach to identify c-di-GMP receptors from the pathogen Vibrio cholerae using the Differential Radial Capillary Action of Ligand Assay (DRaCALA). The DRaCALA screen identified a majority of known c-di-GMP binding proteins in V. cholerae and revealed a novel c-di-GMP binding protein, MshE (VC0405), an ATPase associated with the mannose sensitive hemagglutinin (MSHA) type IV pilus. The known c-di-GMP binding proteins identified by DRaCALA include diguanylate cyclases, phosphodiesterases, PilZ domain proteins and transcription factors VpsT and VpsR, indicating that the DRaCALA-based screen of open reading frame libraries is a feasible approach to uncover novel receptors of small molecule ligands. Since MshE lacks the canonical c-di-GMP-binding motifs, a truncation analysis was utilized to locate the c-di-GMP binding activity to the N-terminal T2SSE_N domain. Alignment of MshE homologs revealed candidate conserved residues responsible for c-di-GMP binding. Site-directed mutagenesis of these candidate residues revealed that the Arg9 residue is required for c-di-GMP binding. The ability of c-di-GMP binding to MshE to regulate MSHA dependent processes was evaluated. The R9A allele, in contrast to the wild type MshE, was unable to complement the ΔmshE mutant for the production of extracellular MshA to the cell surface, reduction in flagella swimming motility, attachment to surfaces and formation of biofilms. Testing homologs of MshE for binding to c-di-GMP identified the type II secretion ATPase of Pseudomonas aeruginosa (PA14_29490) as a c-di-GMP receptor, indicating that type II secretion and type IV pili are both regulated by c-di-GMP.

  9. Web-based interactive access, analysis and comparison of remotely sensed and in situ measured temperature data

    NASA Astrophysics Data System (ADS)

    Eberle, Jonas; Urban, Marcel; Hüttich, Christian; Schmullius, Christiane

    2014-05-01

    Temperature from Meteorological Stations on the Pan-Arctic Scale." Remote Sens. 5, no. 5: 2348-2367. Further materials: Eberle, Jonas; Clausnitzer, Siegfried; Hüttich, Christian; Schmullius, Christiane. 2013. "Multi-Source Data Processing Middleware for Land Monitoring within a Web-Based Spatial Data Infrastructure for Siberia." ISPRS Int. J. Geo-Inf. 2, no. 3: 553-576.

  10. Science versus News: On the Cutting Edge

    NASA Astrophysics Data System (ADS)

    Kinney, A. L.; French, V.; Villard, R.; Maran, S. P.

    1998-12-01

    Washington, Mr. Thomas Siegfried, from The Dallas Daily News, Ms. Kathy Sawyer, from The Washington Post, Mr. John Noble Wilford from The New York Times, and Ms. Ann Kellan from CNN.

  11. The use of historical maps for reconstructing landforms before river damming. The case of the Swiss Rhone River

    NASA Astrophysics Data System (ADS)

    Reynard, E.; Laigre, L.; Baud, D.

    2012-04-01

    The Swiss Rhone River was systematically embanked during the period 1864-1893. The Swiss Rhone River valley is a glacial valley filled by glaciolacustrine, fluvioglacial and fluvial sediments. Torrential tributaries contribute to a large extent to the sedimentation in the valley and have built large alluvial fans in the main valley. The period before the river damming corresponds to the Little Ice Age, and it is supposed that the torrential behaviour of the river and its tributaries was very active during that period. In parallel to a large hydraulic project (Third Rhone River Correction), aiming at enlarging the river for security and environmental reasons, this project aims at reconstructing the palaeogeomorphology of the river floodplain before and also during the 30-year long embankment project developed during the last decades of the 19th century. The objective is to better know the geomorphological behaviour of the river, and also to localize palaolandforms (meanders, braided patterns, sandstone dunes, wetlands, etc.), present in the floodplain in the first part of the 19th century and that have now totally disappeared. The project is carried out in close collaboration with the Cantonal Archives of Valais and with a group of historians working on the relations between the river and the communities. It should contribute to a better knowledge of the Swiss Rhone River history (Reynard et al., 2009). Both published official maps (Dufour maps, Siegfried maps) and unpublished maps and plans are systematically collected, digitized, and organised in a database managed by a Geographical Information System. Other data are collected (place names, geomorphological, hydrological and hydraulic data, information about land-use and vegetation, paintings and photographs, etc.) and localised. A high-resolution digital terrain model and areal photographs are also used and allow us to map palaeolandforms (meanders, filled oxbow lakes, former channels, etc.). In a second step

  12. An Extended Cyclic Di-GMP Network in the Predatory Bacterium Bdellovibrio bacteriovorus

    PubMed Central

    Rotem, Or; Nesper, Jutta; Borovok, Ilya; Gorovits, Rena; Kolot, Mikhail; Pasternak, Zohar; Shin, Irina; Glatter, Timo; Pietrokovski, Shmuel; Jenal, Urs

    2015-01-01

    specificity to c-di-GMP binding were confirmed using microscale thermophoresis with a hypothetical protein bearing a PilZ domain, an acyl coenzyme A dehydrogenase, and a two-component system response regulator, indicating that additional c-di-GMP binding candidates may be bona fide novel effectors. IMPORTANCE In this study, 84 putative c-di-GMP binding proteins were identified in B. bacteriovorus, an obligate predatory bacterium whose lifestyle and reproduction are dependent on c-di-GMP signaling, using a c-di-GMP capture compound precipitation approach. This predicted complement covers metabolic, energy, transport, motility and regulatory pathways, and most of it is phase specific, i.e., 62 candidates bind the capture compound at defined modes of B. bacteriovorus lifestyle. Three of the putative binders further demonstrated specificity and high affinity to c-di-GMP via microscale thermophoresis, lending support for the presence of additional bona fide c-di-GMP effectors among the pulled-down protein repertoire. PMID:26324450

  13. Mercury: a final prediction for internal thermal and physical structure, prior to MESSENGER data

    NASA Astrophysics Data System (ADS)

    Prentice, A. J.

    2008-05-01

    The confirmation by the NASA MESSENGER spacecraft that Mercury has an internal magnetic field that is well described by a dipole nearly aligned with the spin axis strongly suggests that the planet may have an outer core of molten metal (S. Solomon, MESSENGER news release of 30 January 2008). The existence of an internal layer of liquid has also been invoked to explain radar measurements of the large amplitude of the longitudinal libration of Mercury relative to the value expected for a wholly solid planet (J.L. Margot et al 2007 Science 316 710). The existence of molten metal in the planet`s interior is surprising since previous numerical models for the thermal evolution of the planet, calculated on the basis of the heat released by the decay of the radioactive isotopes of U and Th, indicated that the present temperature at the edge of the metal core is only ~ 1200 K (cf. Siegfried & Solomon 1974 Icarus 23 192) . This value is well below the melting temperature Tm = 2030 K of Fe-Ni alloy at the core/mantle boundary (CMB) pressure of ~ 70 kbar. Those earlier thermal calculations were, however, based on low abundances of U and Th found in lunar samples. Prentice (2008 LPSC 2008 abs. # 1945.pdf - see URL below) has put forward a new model for the bulk chemical composition of Mercury. It is based on the idea that this planet condensed from a gas ring that was cast off by the protosolar cloud close to the planet`s present orbit. The temperature of the gas ring Tn at the moment of detachment from the cloud is 1628 K and the pressure on the mean orbit of the ring is 0.168 bar. Because Tn is so high, the condensate contains a much reduced proportion of magnesium silicates relative to metals. This is because metals have a much lower vapour pressure than those silicates. The condensate consists mostly of Fe-Ni-Cr-Co-V (mass fraction 0.671), gehlenite (0.190) and Mg-silicates (0.081). What is really important in the gas ring model of solar system origin, however, is that the

  14. STEM Education in Jordan Applicable to Developing Future Geophysicists: An Example Combining Electrical Engineering and Medical Research

    NASA Astrophysics Data System (ADS)

    Fraiwan, A.; Khadra, L.; Shahab, W.; Olgaard, D. L.

    2010-12-01

    the three arrhythmias used a Back-propagation neural network whose input is the energy level calculated from the wavelet transform. The network was trained using 13 different patterns (3 for AF, 5 for VT and 5 for VF) and blind tested on 25 records. The classification scheme correctly identified all 9 VF records, 5 of 6 VT records, and 9 of 10 AF records. Manual interpretation of time-frequency seismic data is computationally intensive because large volumes of data are generated during the time-frequency analysis process. The proposed NWA method has the potential to partially automate the interpretation of seismic data. Also, a relatively straight-forward adaptation of the proposed NWA-based classification scheme may help identify hydrocarbon-laden reservoirs, which have been observed to contain enhanced low-frequency content in the time-frequency domain (Castagna, Sun, & Siegfried, 2003).

  15. Geodiversity and the natural history of landforms

    NASA Astrophysics Data System (ADS)

    Giusti, Christian

    2014-05-01

    For a long time, landforms were studied according to the criteria exposed in the theory of the geographical cycle, at least for geomorphologists claiming a Davisian approach. In this context, particular importance was attached, concerning landforms, to the remains of "peneplains". At this point, it must be remembered that Davis has never been followed unanimously, including the United States, but it was the German geomorphologists who by far developed the strongest criticism of Davisian ideas: scientists such as Albrecht Penck, Siegfried Passarge or Johannes Walther could not be satisfied with views so different of concepts and methods used by German naturalists in geology, geography and geomorphology. This intellectual opposition, however, leads Davis to constantly improve the model of the geographical cycle depending on climatic conditions (arid cycle, glacial cycle…), thick formations of limestones (karstic cycle), or a peculiar geographical position (coastal cycle, coral reef problem). After 1950, Davisian conceptions were, either abruptly given up (Strahler), or severely criticized (Tricart, Hack, Chorley), or deeply modified (King, Baulig, Klein), in particular to make them compatible with situations where it is not possible to identify in the topography the remains of several geographic cycles. For example, in the case of the Appalachians, Hack's originality is to reason exactly at the opposite to Davis and Johnson. Where the latter would select in the topographic continuum supposed elements of successive cycles, in order to interpret current landscape with the hypothetical lights of a theoretical past, Hack starts by a comprehensive analysis of landforms, patterned reliefs and soils of the present mountain chain, leading to the famous conclusion that the Appalachians are not evolving under decay conditions but are in situation of steady state through dynamic equilibrium. So the question becomes now to understand how far it is relevant and how it is

  16. LFSTAT - Low-Flow Analysis in R

    NASA Astrophysics Data System (ADS)

    Koffler, Daniel; Laaha, Gregor

    2013-04-01

    objects are usual R-data-frames including date, flow, hydrological year and possibly baseflow information. Once these objects are created, analysis can be performed by mouse-click and a script can be saved to make the analysis easily reproducible. At the moment we are offering implementation of all major methods proposed in the WMO manual on Low-flow Estimation and Predictions [1]. Future plans include a dynamic low flow report in odt-file format using odf-weave which allows automatic updates if data or analysis change. We hope to offer a tool to ease and structure the analysis of stream flow data focusing on low-flows and to make analysis transparent and communicable. The package can also be used in teaching students the first steps in low-flow hydrology. The software packages can be installed from CRAN (latest stable) and R-Forge: http://r-forge.r-project.org (development version). References: [1] Gustard, Alan; Demuth, Siegfried, (eds.) Manual on Low-flow Estimation and Prediction. Geneva, Switzerland, World Meteorological Organization, (Operational Hydrology Report No. 50, WMO-No. 1029).

  17. PREFACE: EmerQuM 11: Emergent Quantum Mechanics 2011 (Heinz von Foerster Congress)

    NASA Astrophysics Data System (ADS)

    Grössing, Gerhard

    2012-05-01

    These proceedings comprise the plenary lectures and poster contributions of the 'Heinz von Foerster Conference 2011' on Emergent Quantum Mechanics (EmerQuM11), which was held at the University of Vienna, 11-13 November 2011. With the 5th International Heinz von Foerster Conference convened at the occasion of von Foerster's 100th birthday, the organizers opted for a twin conference to take place at the Large and Small Ceremonial Halls of the University's main building, respectively. The overall topic was chosen as 'Self-Organization and Emergence', a topic to which von Foerster was an early contributor. While the first conference ('Self-Organization and Emergence in Nature and Society') addressed a more general audience, the second one ('Emergent Quantum Mechanics') was intended as a specialist meeting with a contemporary topic that could both serve as an illustration of von Foerster's intellectual heritage and, more generally, point towards future directions in physics. We thus intended to bring together many of those physicists who are interested in or are working on attempts to understand quantum mechanics as emerging from a suitable classical (or, more generally, deeper level) physics. EmerQuM11 was organized by the Austrian Institute for Nonlinear Studies (AINS), with essential support from the Wiener Institute for Social Science Documentation and Methodology (WISDOM), the Department of Contemporary History at the University of Vienna, and the Heinz von Foerster-Gesellschaft. There were a number of individuals who contributed to the smooth course of our meeting and whom I would like to sincerely thank: Christian Bischof, Thomas Elze, Marianne Ertl, Gertrud Hafner, Werner Korn, Angelika Krawanja, Florian Krug and his team, Sonja Lang, Albert Müller, Ilse Müller, Irene Müller, Karl Müller, Armin Reautschnig, Marion Schirrmacher, Anton Staudinger, Roman Zlabinger, and, last but not least, my AINS colleagues Siegfried Fussy, Herbert Schwabl and Johannes Mesa

  18. PREFACE: EmQM13: Emergent Quantum Mechanics 2013

    NASA Astrophysics Data System (ADS)

    2014-04-01

    these proceedings represent the talks of the invited speakers as written immediately after the symposium. The volume starts with a contribution by organizers Jan Walleczek and Gerhard Grössing, essentially explaining why emergent quantum mechanics, and other deterministic approaches to quantum theory, must be considered viable approaches in quantum foundations today. This is followed by the exposition of Stephen Adler's talk who introduced to a general audience key questions at the current frontiers of quantum mechanics during the opening evening (with the contents of his conference talk appearing elsewhere). The conference proceedings then continues with the presentations as given in their chronological order i.e. starting with the opening talk of the scientific program by Gerard 't Hooft. While the page number was restricted for all invited speakers, the paper by Jeff Tollaksen was given more space, as his invited collaborator Yakir Aharonov was unable to deliver a separate talk, in order to represent both contributions in one paper. Note that the talks of all speakers, including the talks of those who could not be represented in this volume (M. Arndt, B. Braverman, C. Brukner, S. Colin, Y. Couder, B. Poirier, A. Steinberg, G. Weihs and H. Wiseman) are freely available on the conference website as video presentations (http://www.emqm13.org). The organizers wish to express their gratitude to Siegfried Fussy and Herbert Schwabl from AINS for the organizational support. The organizers also wish to thank Bruce Fetzer, President and CEO, John E. Fetzer Memorial Trust, and the Members of the Board of Trustees, for their strong support and for funding this symposium. We also wish to thank the Austrian Academy of Sciences for allowing the symposium to be held on their premises, and Anton Zeilinger, President of the Austrian Academy of Sciences, for his welcome address. The expertise of the Members of the Scientific Advisory Board of the EmQM13 symposium, Ana Maria Cetto

  19. Limits to the availability of groundwater in Africa

    NASA Astrophysics Data System (ADS)

    Edmunds, W. Mike

    2012-06-01

    recharge in semi-arid and arid regions Hydrol. Process. 20 3335-70 Zammouri M, Siegfried T, El-Fahem T, Kriâa S and Kinzelbach W 2007 Salinization of groundwater in the Nefzawaoases region, Tunisia: results of a regional-scale hydrogeologic approach Hydrogeol. J. 15 1357-75